KR101379808B1 - Pyrazolopyrimidine derivatives for inhibiting nitric oxide - Google Patents

Abstract

본 발명은 피라졸로피리미딘 유도체 화합물을 포함하는 산화질소 생성 억제용 조성물 및 뇌신경 질환 예방 및 치료용 약학적 조성물에 관한 것으로서, 생체 내 산화질소의 생성을 억제할 수 있고, 산화질소의 과다생성에 따른 신경 세포의 기능장애 및 사멸로 인하여 야기되는 뇌신경 질환, 특히 파킨슨병, 알츠하이머 치매, 헌팅턴병, 루게릭병, 간질, 우울증, 불면증, 불안증 및 퇴행성 뇌신경 질환 등을 치료하는데 사용할 수 있다.The present invention relates to a composition for inhibiting nitric oxide production and a pharmaceutical composition for preventing and treating cerebral neurological diseases, comprising a pyrazolopyrimidine derivative compound, which can inhibit the production of nitric oxide in vivo and to prevent overproduction of nitric oxide. Can be used to treat neurological diseases caused by dysfunction and death of nerve cells, in particular Parkinson's disease, Alzheimer's dementia, Huntington's disease, Lou Gehrig's disease, epilepsy, depression, insomnia, anxiety and degenerative brain neurological diseases.

Description

산화질소 생성 억제용 피라졸로피리미딘 유도체 화합물{Pyrazolopyrimidine derivatives for inhibiting nitric oxide}Pyrazolopyrimidine derivatives for inhibiting nitric oxide

본 발명은 산화질소 생성 억제용 조성물 및 뇌신경 질환 예방 및 치료용 약학적 조성물에 관한 것으로서, 더욱 상세하게는 피라졸로피리미딘 유도체 화합물를 포함하는 산화질소 생성 억제용 조성물 및 뇌신경 질환 예방 및 치료용 약학적 조성물에 관한 것이다.The present invention relates to a composition for inhibiting nitric oxide production and a pharmaceutical composition for preventing and treating cerebral neurological diseases, and more particularly, a composition for inhibiting nitric oxide production and a pharmaceutical composition for preventing and treating cerebral neurological diseases, including pyrazolopyrimidine derivative compounds. It relates to a composition.

지속적인 생활수준의 향상과 보건 및 의료 기술의 발달로 국민들의 평균수명연장과 함께 노인 인구가 급증하였다. 따라서 인구 구조가 고령화되면서 필연적으로 야기되는 국민 보건 문제 가운데 노년층에서 흔히 관찰되는 퇴행성 신경질환인 노인성 치매와 파킨슨병 (Parkinson's disease)은 심각한 현안으로 대두되고 있다.With the continuous improvement of living standards and the development of health and medical technology, the elderly population increased rapidly with the average life expectancy of the people. As a result, aging dementia and Parkinson's disease, a degenerative neurological disease commonly observed in older people, are a serious problem among the public health problems inevitably caused by aging population.

파킨슨병은 60세 이상에서 1%, 70세 이상에서 3.4%, 80세 이상에서 4%의 발병률을 보이며 일차적인 증상으로는 느린 움직임, 정지시 떨림, 자세의 불안정, 근육경직이 특징적으로 나타나고, 병의 진행에 따라 우울증, 불면증, 치매 등의 2차적 증상을 동반한다 [1) de Lau et al., Lancet Neurol. 2006, 5, 525-535; 2) Chaudhuri et al., Lancet Neurol. 2009, 8, 464-474; 3) Fahn, In Handbook Exp. Pharmacol, 1989, 8, Calne, D.B., (Ed.) pp. 386-409]. 매해 50,000명 이상이 새롭게 진단을 받고 있으나 그 동안의 많은 연구에도 불구하고 병인의 기전에 대한 명확한 원인을 규명하지 못하였다 [Arevalo et al., Mov. Disord. 1997, 12, 277 284].The incidence of Parkinson's disease is 1% in patients over 60 years old, 3.4% in patients over 70 years old, and 4% in patients over 80 years old. The primary symptoms are slow motion, tremor at rest, instability of posture, It is associated with secondary symptoms such as depression, insomnia, and dementia as the disease progresses. [1] de Lau et al., Lancet Neurol. 2006, 5, 525-535; 2) Chaudhuri et al., Lancet Neurol. 2009, 8, 464-474; 3) Fahn, In Handbook Exp. Pharmacol, 1989, 8, Calne, D. B., (Ed.) Pp. 386-409]. More than 50,000 patients are diagnosed each year, but despite many studies, no clear cause for the pathogenesis has been identified [Arevalo et al., Mov. Disord. 1997, 12, 277 284.

그로 인해 현재 치료방법은 대증적 치료제를 이용하고 있고, 대표적으로는 도파민(dopamine)의 전구체인 L-3,4-dihydroxyphenylalanine (L-DOPA), monoamine oxidase inhibitor 그리고 dopamine receptor agonist 등이 있다. 그러나 이러한 방법들은 병의 진행을 지연시켜 줄 뿐 근원적인 치료가 되지 않으며, 장기간의 복용에 따른 부작용과 합병증을 동반한다. 따라서 최근에는 neuroprotection을 통한 병의 진행방향을 바꾸려는 노력이 활발히 진행되고 있다.As a result, current therapeutic methods use symptomatic therapeutic agents, such as L-3,4-dihydroxyphenylalanine (L-DOPA), a monoamine oxidase inhibitor, and dopamine receptor agonist, which are precursors of dopamine. However, these methods delay the progression of the disease but do not lead to the underlying treatment, and are associated with long-term side effects and complications. Recently, efforts have been actively made to change the path of disease progression through neuroprotection.

파킨슨병은 주로 흑질(substantia nigra pars compacta)로 불리는 중뇌 부위에서 신경전달물질(neurotransmitter)인 도파민을 포함하고 있는 도파민성 신경세포(dopaminergic neurons)의 손실에 의해 일어난다고 알려졌다. 파킨슨병의 원인을 규명하기 위하여 활발한 연구가 진행되고 있으며, 제초제나 살충제의 사용이 파킨슨병의 위험성을 증가시킨다는 보고, 바이러스성 뇌염등의 감염설, 선천적으로 발병한다는 유전설 등이 있으나 정확한 원인은 규명되지 않았다 [1) Corrigan et al., Exp. Neurol. 1998, 150, 339-342; 2) Schapira et al., Mov. Disord. 2011, 26, 1049-1055; 3) Ascherio et al., Annal. Neurol. 2001, 50, 56-63; 4) Warner et al., Annal. Neurol. 2003, 53 Suppl 3, S16-23].Parkinson's disease is known to be caused by the loss of dopaminergic neurons containing dopamine, a neurotransmitter, mainly in the middle brain, called the substantia nigra pars compacta. Active research is underway to determine the cause of Parkinson's disease, and reports of the use of herbicides and insecticides increase the risk of Parkinson's disease, infections such as viral encephalitis, and the heredity of congenital incidence. [1] Corrigan et al., Exp. Neurol. 1998, 150, 339-342; 2) Schapira et al., Mov. Disord. 2011, 26, 1049-1055; 3) Ascherio et al., Annal. Neurol. 2001, 50, 56-63; 4) Warner et al., Annal. Neurol. 2003, 53 Suppl 3, S16-23].

또한, 파킨슨병 환자의 10-15 %는 가족력을 가지고 있으며 현재까지 이들로부터 SNCA, PARKIN, UCHL1, PINK1, DJ-1, LRRK2, Omi/HtrA2 유전자 변이가 가족성 파킨슨병을 일으키는 것으로 밝혀졌다 [1) Paisan-Ruiz et al., Neuron 2004, 44, 595-600; 2) Zimprich et al., Neuron 2004, 44, 601-607; 3) Bonifati et al., Neurol. Sci. 2003, 24, 159-160; 4) Andres-Mateos et al., Proc. Natl. Acad. Sci. USA. 2007, 104, 14807-14812]. 상기 유전자로부터 밝혀진 파킨슨병의 환경요인 및 병인에는 1) 비정상적인 삼차원 구조를 가진 단백질 (a-synuclein)의 응집, 2) 미토콘드리아 이상, 3) Ubiquitin 단백분해 시스템 이상, 4) 산화성 스트레스 (oxidative stress), 5) 흥분성독성 (excitotoxicity), 6) 신경염증 (neuroinflammation)등이 관여하는 것으로 알려져 있다.In addition, 10-15% of Parkinson's disease patients have a family history, and to date, it has been shown that SNCA, PARKIN, UCHL1, PINK1, DJ-1, LRRK2, and Omi / HtrA2 gene mutations cause familial Parkinson's disease [1 ) Paisan-Ruiz et al., Neuron 2004, 44, 595-600; 2) Zimprich et al., Neuron 2004, 44, 601-607; 3) Bonifati et al., Neurol. Sci. 2003, 24, 159-160; 4) Andres-Mateos et al., Proc. Natl. Acad. Sci. USA. 2007, 104, 14807-14812. The environmental factors and etiology of Parkinson's disease revealed by the gene include 1) agglutination of a-synuclein with abnormal three-dimensional structure, 2) mitochondrial abnormalities, 3) ubiquitin proteolytic system abnormalities, 4) oxidative stress, 5) Excitotoxicity, 6) Neuroinflammation is known to be involved.

산화성 스트레스는 활성산소(reactive oxygen species; ROS)와 세포내의 항산화 활성간의 불균형으로 일어나며, 이는 파킨슨병에서 신경세포의 기능장애나 사멸을 야기하는 근본적인 이유로 생각되고 있다. 도파민의 대사과정이 산화성 스트레스와 관련되어 세포의 생장에 중요한 역할을 하는 세포 내 고분자들(macromolecules)의 변성(modification)을 일으킨다고 알려져 있다. 이러한 또한 활성화된 소교세포(microglia)에 의한 신경염증 반응과정에서 생성된 활성산소는 도파민성 신경세포가 분비하는 물질들에 의해 더욱 가속화되고, 신경세포의 사멸을 야기한다고 보고되었다 [1) Andersen et al., Nat. Med. 2004, 10 Suppl, S18-25; 2) Jenner et al., Annal. Neurol. 2003, 53 Suppl3, S26-36].Oxidative stress arises from an imbalance between reactive oxygen species (ROS) and the antioxidant activity in cells, which is thought to be a fundamental reason for causing neuronal dysfunction or death in Parkinson's disease. Dopamine metabolism is known to cause the modification of macromolecules (macromolecules) that play an important role in cell growth associated with oxidative stress. It has also been reported that free radicals generated during neuroinflammatory reactions by activated microglia are further accelerated by substances secreted by dopaminergic neurons and cause neuronal death [1] Andersen et. al., Nat. Med. 2004, 10 Suppl, S18-25; 2) Jenner et al., Annal. Neurol. 2003, 53 Suppl3, S26-36].

이러한 활성산소 가운데 산화질소 (nitric oxide, NO)는 생체 내에 존재하는 가스성 물질로써, nitrate (NO₃ ^-), nitrite (NO₂ ^-), peroxynitrite (ONOO^-), 3-nitrotyrosine 등 매우 반응성이 높은 중간체로 쉽게 전환된다. NO가 과다 생성될 경우, NO나 그 중간체들은 세포를 구성하고 있는 DNA, 단백질 및 지질의 변형을 일으키는 nitrooxidative 스트레스를 유발한다. 특히 세포의 생존에 필요한 다양한 단백질들의 기능 장애로 인해 결과적으로 세포 기능장애와 세포사멸이 일어난다.These free radicals of nitrogen oxides (nitric oxide, NO) is as a gaseous substance existing in the living ^{_{body, nitrate (NO 3 -),}} nitrite (NO 2 -), peroxynitrite (ONOO -), 3-nitrotyrosine , such as highly reactive with the high Easily converted to intermediate When NO is produced excessively, NO and its intermediates induce nitrooxidative stress that causes DNA, protein and lipid changes that make up the cells. In particular, the dysfunction of various proteins required for cell survival results in cell dysfunction and apoptosis.

신경세포는 특히 NO에 대해 취약하다. 그 이유는 첫째, NO가 신경세포에서 흥분성독성을 유발하고, 둘째, 소교세포가 만들어내는 superoxide와 함께 존재할 때 그 세포독성이 상승되기 때문이다. 그러므로 NO의 과다생성은 신경세포의 사멸을 초래하여 다양한 퇴행성 뇌질환의 발병에 기여할 수 있다. 실제로 파킨슨병의 경우 nitrite 농도가 척수액에서 증가하고 [Qureshi et al., Neuroreport 1995, 6(12), 1642-1644], 뇌병변 부위와 Lewy body에 존재하는 a-synuclein에서 3-nitrotyrosine이 증가하며 [Good et al., J Neuropathol. Exp. Neurol. 1998, 57(4), 338-342], 세포생존에 중요한 parkin, XIAP 등이 S-nitrosylation화 되어 있음이 발견되었다 [1)Yao et al., Proc. Natl. Acad. Sci. USA. 2004, 101(29), 10810-10814; 2) Tsang et al., Proc. Natl. Acad. Sci. USA. 2009, 106(12), 4900-4905; 3) Pathak et al., Biochim. Biophys. Acta 2008, 1777(7-8), 777-782). 또한, NO 과생산은 파킨슨병뿐만 아니라 알츠하이머치매, 헌팅턴병, 루게릭병, 뇌졸중 후에 나타나는 신경퇴행과도 관계가 있는 것으로 알려져 있다.Neurons are particularly vulnerable to NO. This is because, first, NO causes excitatory toxicity in neurons, and second, the cytotoxicity is enhanced when coexists with superoxide produced by microglia. Thus, overproduction of NO can lead to the death of neurons and contribute to the development of various degenerative brain diseases. Indeed, in Parkinson's disease, nitrite levels increase in spinal fluid (Qureshi et al., Neuroreport 1995, 6 (12), 1642-1644), and 3-nitrotyrosine in a-synuclein in brain lesions and in the Lewy body. Good et al., J Neuropathol. Exp. Neurol. 1998, 57 (4), 338-342], Parkin, XIAP, etc. important for cell survival was found to be S-nitrosylation [1) Yao et al., Proc. Natl. Acad. Sci. USA. 2004, 101 (29), 10810-10814; 2) Tsang et al., Proc. Natl. Acad. Sci. USA. 2009, 106 (12), 4900-4905; 3) Pathak et al., Biochim. Biophys. Acta 2008, 1777 (7-8), 777-782). In addition, NO overproduction is known to be associated with Parkinson's disease as well as Alzheimer's dementia, Huntington's disease, Lou Gehrig's disease, and neurodegeneration following stroke.

따라서, 파킨슨병의 예방 및 치료를 위해 NO의 생성을 효과적으로 억제할 수 있는 화합물이 절실히 요구되고 있다.Therefore, there is an urgent need for compounds that can effectively inhibit the production of NO for the prevention and treatment of Parkinson's disease.

따라서, 본 발명이 해결하고자 하는 과제는 생체 내에서 산화질소의 생성을 억제할 수 있고, 이에 의해서 산화질소의 과다 생성으로 인한 뇌신경 세포의 사멸을 방지할 수 있으며 각종 뇌신경 질환 치료용으로 활용할 수 있는 피라졸로피리미딘 유도체 화합물 또는 이의 약학적으로 수용 가능한 염을 제공하는 것이다.Therefore, the problem to be solved by the present invention can suppress the production of nitric oxide in vivo, thereby preventing the death of neuronal cells due to the excessive production of nitric oxide can be utilized for the treatment of various brain neurological diseases It is to provide a pyrazolopyrimidine derivative compound or a pharmaceutically acceptable salt thereof.

또한, 본 발명이 해결하고자 하는 과제는 약학적 수용 가능한 담체 또는 희석제와 함께 활성성분으로서 피라졸로피리미딘 유도체 화합물을 함유하는 산화질소 생성 억제용 약학 조성물과 뇌신경 질환의 예방 및 치료용 약학 조성물을 제공하는 것이다.In addition, the problem to be solved by the present invention provides a pharmaceutical composition for inhibiting nitric oxide production containing a pyrazolopyrimidine derivative compound as an active ingredient with a pharmaceutically acceptable carrier or diluent and a pharmaceutical composition for the prevention and treatment of cerebral neurological diseases. It is.

본 발명은 상기 과제를 해결하기 위하여,In order to solve the above problems,

하기 [화학식 Ⅰ] 내지 [화학식 Ⅶ]로 표시되는 피라졸로피리미딘 유도체 화합물 또는 이의 약학적으로 수용 가능한 염을 제공한다.Provided is a pyrazolopyrimidine derivative compound represented by the following [formula I] to [formula VII], or a pharmaceutically acceptable salt thereof.

[화학식 Ⅰ] [화학식 Ⅱ] [화학식 Ⅲ][Formula (I)] [Formula (II)] [Formula (III)

[화학식 Ⅳ] [화학식 Ⅴ][Formula Ⅳ] [Formula Ⅴ]

[화학식 Ⅵ] [화학식 Ⅶ][Formula VI] [Formula VII]

상기 [화학식 Ⅰ] 내지 [화학식 Ⅶ]에서,In [Formula I] to [Formula VII],

상기 R₁은 수소, 치환 또는 비치환된 탄소수 1 내지 12의 알킬기, 치환 또는 비치환된 탄소수 1 내지 12의 알릴기, 치환 또는 비치환된 탄소수 1 내지 10의 알콜기, 치환 또는 비치환된 탄소수 1 내지 10의 알콕시기, 치환 또는 비치환된 탄소수 6 내지 18의 아릴기, 치환 또는 비치환된 탄소수 6 내지 18의 아릴옥시기 및 치환 또는 비치환된 탄소수 1 내지 5의 알킬카바메이트기 중에서 선택되는 어느 하나이고,R ₁ is hydrogen, a substituted or unsubstituted C1-C12 alkyl group, a substituted or unsubstituted C1-C12 allyl group, a substituted or unsubstituted C1-C10 alcohol group, a substituted or unsubstituted carbon number Selected from an alkoxy group having 1 to 10, a substituted or unsubstituted aryl group having 6 to 18 carbon atoms, a substituted or unsubstituted aryloxy group having 6 to 18 carbon atoms, and a substituted or unsubstituted alkyl carbamate group having 1 to 5 carbon atoms Which one is

상기 R₂는 수소, 할로젠기, 치환 또는 비치환된 탄소수 1 내지 10의 알콕시기, 치환 또는 비치환된 탄소수 1 내지 12의 알릴기, 치환 또는 비치환된 탄소수 1 내지 10의 알콜기, 치환 또는 비치환된 탄소수 6 내지 18의 아릴기, 치환 또는 비치환된 탄소수 3 내지 18의 헤테로아릴기, 치환 또는 비치환된 탄소수 1 내지 12의 알킬아민기, 치환 또는 비치환된 탄소수 6 내지 18의 아릴아민기, 치환 또는 비치환된 탄소수 3 내지 18의 헤테로아릴아민기, 치환 또는 비치환된 탄소수 1 내지 10의 알킬티올기, 치환 또는 비치환된 탄소수 6 내지 18의 아릴티올기 및 치환 또는 비치환된 탄소수 6 내지 18의 아릴옥시기 중에서 선택되는 어느 하나이며,R ₂ is hydrogen, a halogen group, a substituted or unsubstituted C1-C10 alkoxy group, a substituted or unsubstituted C1-C12 allyl group, a substituted or unsubstituted C1-C10 alcohol group, substituted Or an unsubstituted aryl group having 6 to 18 carbon atoms, a substituted or unsubstituted heteroaryl group having 3 to 18 carbon atoms, a substituted or unsubstituted alkylamine group having 1 to 12 carbon atoms, a substituted or unsubstituted carbon group having 6 to 18 carbon atoms Arylamine group, substituted or unsubstituted heteroarylamine group having 3 to 18 carbon atoms, substituted or unsubstituted alkylthiol group having 1 to 10 carbon atoms, substituted or unsubstituted arylthiol group having 6 to 18 carbon atoms, and substituted or unsubstituted Any one selected from an aryloxy group having 6 to 18 ring carbon atoms,

상기 R₃는 O 또는 S이고,R ₃ is O or S,

상기 R₄는 수소, 치환 또는 비치환된 탄소수 1 내지 6의 알킬설파이닐기, 치환 또는 비치환된 탄소수 1 내지 6의 알킬설포닐기, 치환 또는 비치환된 탄소수 1 내지 12의 알킬아민기, 치환 또는 비치환된 탄소수 1 내지 10의 알콕시기 및 치환 또는 비치환된 탄소수 6 내지 18의 아릴아민기 중에서 선택되는 어느 하나이며,R ₄ is hydrogen, a substituted or unsubstituted C1-C6 alkylsulfinyl group, a substituted or unsubstituted C1-C6 alkylsulfonyl group, a substituted or unsubstituted C1-C12 alkylamine group, substituted or It is any one selected from an unsubstituted alkoxy group having 1 to 10 carbon atoms and a substituted or unsubstituted arylamine group having 6 to 18 carbon atoms,

상기 X₁은 수소, 할로젠기 및 치환 또는 비치환된 탄소수 6 내지 18의 아릴기 중에서 선택되는 어느 하나이다.X ₁ is any one selected from hydrogen, a halogen group, and a substituted or unsubstituted aryl group having 6 to 18 carbon atoms.

본 발명의 일 실시예에 의하면, 상기 R₁, R₂ 및 R₄는 각각 독립적으로 탄소수 1 내지 6의 알킬기, 탄소수 1 내지 12의 알콕시기, 탄소수 1 내지 12의 알킬아민기, 탄소수 3 내지 18의 헤테로아릴기, 탄소수 3 내지 18의 헤테로아릴아민기, 시아노기 및 할로겐원자로 이루어지는 군으로부터 1종 이상 선택되어 치환될 수 있다.According to an embodiment of the present invention, the R ₁ , R ₂ And R ₄ is each independently an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, an alkylamine group having 1 to 12 carbon atoms, a heteroaryl group having 3 to 18 carbon atoms, a heteroarylamine group having 3 to 18 carbon atoms, One or more selected from the group consisting of a cyano group and a halogen atom may be substituted.

본 발명의 일 실시예에 의하면, 상기 피라졸로피리미딘 유도체 화합물은 약학적으로 수용 가능한 염을 형성할 수 있으며, 상기 약학적으로 수용 가능한 염은 염산, 브롬화수소산, 요오드화수소산, 황산, 질산, 인산, 메탄설폰산, 벤젠설폰산, 포름산, 아세트산, 트리플루오로 아세트산, 프로피온산, 옥살산, 말론산, 숙신산, 푸마르산, 말레산, 젖산, 말산, 타르타르산, 시트르산, 에탄설폰산, 아스파르트산 및 글루탐산으로 구성된 군에서 선택된 1종 이상일 수 있다.
According to an embodiment of the present invention, the pyrazolopyrimidine derivative compound may form a pharmaceutically acceptable salt, the pharmaceutically acceptable salt is hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid , Consisting of methanesulfonic acid, benzenesulfonic acid, formic acid, acetic acid, trifluoro acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, ethanesulfonic acid, aspartic acid and glutamic acid It may be one or more selected from the group.

본 발명은 상기 과제를 해결하기 위하여,In order to solve the above problems,

약학적 수용 가능한 담체 또는 희석제와 함께 활성성분으로서 상기 피라졸로피리미딘 유도체 화합물을 함유하는 산화질소 생성 억제용 약학 조성물을 제공한다.It provides a pharmaceutical composition for inhibiting nitric oxide production containing the pyrazolopyrimidine derivative compound as an active ingredient together with a pharmaceutically acceptable carrier or diluent.

또한, 본 발명은 약학적 수용 가능한 담체 또는 희석제와 함께 활성성분으로서 상기 피라졸로피리미딘 유도체 화합물을 함유하는 뇌신경 질환 치료용 조성물을 제공한다.In addition, the present invention provides a composition for treating neurological diseases comprising the pyrazolopyrimidine derivative compound as an active ingredient together with a pharmaceutically acceptable carrier or diluent.

본 발명의 일 실시예에 의하면, 상기 뇌신경 질환은 파킨슨병, 알츠하이머 치매, 헌팅턴병, 루게릭병, 간질, 우울증, 통증 불안증 및 퇴행성 뇌신경 질환 중에서 선택되는 어느 하나일 수 있다.
According to an embodiment of the present invention, the neurological disease may be selected from Parkinson's disease, Alzheimer's disease, Huntington's disease, Lou Gehrig's disease, epilepsy, depression, pain anxiety, and degenerative brain disease.

본 발명에 따른 [화학식 ] 내지 [화학식 ]로 표시되는 피라졸로피리미딘 유도체 화합물의 치환기 및 용어에 대한 정의에서,In the definition of the substituents and terms of the pyrazolopyrimidine derivative compounds represented by [Formula] to [Formula] according to the present invention,

용어 '알콕시'는 달리 정의하지 않는 한 1 내지 10 개의 탄소 원자를 가지는 알킬옥시를 말하고, 바람직하게는 1 내지 3개의 탄소 원자를 가지는 알콕시기일 수 있다.The term "alkoxy" refers to alkyloxy having 1 to 10 carbon atoms unless otherwise defined, and preferably may be an alkoxy group having 1 to 3 carbon atoms.

용어 '알킬'은 지방족 탄화수소 라디칼을 의미한다. 알킬은 알케닐이나 알키닐 부위를 포함하지 않는 '포화(saturated alkyl)알킬'이거나, 적어도 하나의 알케닐 또는 알키닐 부위를 포함하는 '불포화(unsaturated alkyl)알킬'일 수 있다. '알케닐(alkenyl)'은 적어도 하나의 탄소-탄소 이중결합을 포함하는 그룹을 의미하며, '알키닐(alkynyl)'은 적어도 하나의 탄소-탄소 삼중결합을 포함하는 그룹을 의미한다. 알킬은 단독으로 또는 알콕시와 같이 조합하여 사용되는 경우에 각각 분지형 또는 직쇄형일 수 있다.The term " alkyl " means an aliphatic hydrocarbon radical. Alkyl may be 'saturated alkylalkyl' containing no alkenyl or alkynyl moieties, or 'unsaturated alkylalkyl' containing at least one alkenyl or alkynyl moieties. 'Alkenyl' refers to a group containing at least one carbon-carbon double bond, and 'alkynyl' refers to a group containing at least one carbon-carbon triple bond. Alkyl may be branched or straight chain, respectively, when used alone or in combination, such as alkoxy.

알킬 그룹은 달리 정의하지 않는 한 1 내지 12 개의 탄소 원자들을 가지는 알킬일 수도 있고, 바람직하게는 1 내지 6개의 탄소원자를 가지는 저급 알킬기일 수 있다. 전형적인 알킬 그룹에는 메틸, 에틸, 프로필, 이소프로필, n-부틸, 이소부틸, t-부틸, 펜틸, 헥실, 에테닐, 프로페닐, 부테닐 등이 포함되지만, 이들만으로 한정되는 것은 아니다. 예를 들어, 탄소수 1 내지 4의 알킬은 알킬쇄에 1 내지 4 개의 탄소 원자를 가지며, 메틸, 에틸, 프로필, 이소-프로필, n-부틸, 이소-부틸, sec-부틸 및 t-부틸로 이루어진 그룹에서 선택된다.The alkyl group may be an alkyl having 1 to 12 carbon atoms, and preferably a lower alkyl group having 1 to 6 carbon atoms unless otherwise defined. Typical alkyl groups include but are not limited to methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, t-butyl, pentyl, hexyl, ethenyl, propenyl, butenyl and the like. For example, alkyl having 1 to 4 carbon atoms has 1 to 4 carbon atoms in the alkyl chain and consists of methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl and t-butyl Is selected from the group.

용어 '아릴(aryl)'은 공유 파이 전자계를 가지는 적어도 하나의 환을 포함하며, 예를들어 모노사이클릭 또는 융합환 폴리사이클릭(즉, 탄소 원자들의 인접한 쌍들을 나눠가지는 링들)그룹을 포함한다. 즉, 본 명세서에서 아릴은 달리 정의하지 않는 한 페닐, 나프틸 등과 바이아릴을 포함할 수 있다.The term 'aryl' includes at least one ring having a shared pi electron field and includes, for example, a monocyclic or fused polycyclic (ie, rings which divide adjacent pairs of carbon atoms) groups. . That is, in the present specification, aryl may include phenyl, naphthyl, etc., and a biaryl, unless otherwise defined.

용어 '헤테로아릴'은 달리 정의하지 않는 한 N, O 및 S로 이루어진 그룹에서 선택된 1 내지 4개의 헤테로 원자를 포함하고, 바람직하게는 N을 1개 이상 포함하는 헤테로아릴일 수 있다. 모노사이클릭 헤테로아릴의 예로는 티아졸, 옥사졸, 티오펜, 퓨란, 피롤, 이미다졸, 이소옥사졸, 이소티아졸, 피라졸, 트리아졸, 트리아진, 티아디아졸, 테트라졸, 옥사디아졸, 피리딘, 피리다진, 피리미딘, 피라진 및 이와 유사한 그룹을 들 수 있으나, 이들로 제한되는 것은 아니다. 비사이클릭 헤테로아릴의 예로는 인돌, 인돌린, 벤조티오펜, 벤조퓨란, 벤즈이미다졸, 벤족사졸, 벤즈이속사졸, 벤즈티아졸, 벤즈티아디아졸, 벤즈트리아졸, 퀴놀린, 이소퀴놀린, 퓨린, 퓨로피리딘 및 이와 유사한 그룹을 들 수 있으나 이들로 제한되는 것은 아니다.The term 'heteroaryl' may be heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of N, O and S, preferably including one or more N, unless otherwise defined. Examples of monocyclic heteroaryl include thiazole, oxazole, thiophene, furan, pyrrole, imidazole, isoxazole, isothiazole, pyrazole, triazole, triazine, thiadiazole, tetrazole, oxadia Sol, pyridine, pyridazine, pyrimidine, pyrazine and similar groups, but is not limited to these. Examples of bicyclic heteroaryls include indole, indoline, benzothiophene, benzofuran, benzimidazole, benzoxazole, benzisoxazole, benzthiazole, benzthiadiazole, benztriazole, quinoline, isoquinoline, purine , Furopyridine, and similar groups.

용어 '할로겐기'의 구체적인 예로는 플루오르(F), 클로린(Cl), 브롬(Br) 등을들수있고, 바람직하게는 플루오르(F) 및 클로린(Cl)일 수 있다.Specific examples of the term 'halogen group' include fluorine (F), chlorine (Cl), bromine (Br), and the like, and preferably fluorine (F) and chlorine (Cl).

용어 '아릴옥시'는 R-O-로 표시되는 원자단으로서, 산소에 단일 결합으로 연결된 비치환 또는 치환된 알킬, 아릴 및 헤테로아릴을 포함한다.The term 'aryloxy' is an atomic group represented by R-O- and includes unsubstituted or substituted alkyl, aryl and heteroaryl linked by a single bond to oxygen.

용어 '카바메이트'는 일반적인 구조로 RNH (CO) OR'로 의미하며, R'는 알킬기일 수 있다.The term 'carbamate' is a general structure, meaning RNH (CO) OR ', and R' may be an alkyl group.

본 발명에 있어서, '치환 또는 비치환된' 이라는 용어는 알킬기, 알콕시기, 알킬아민기, 헤테로아릴기, 헤테로아릴아민기, 시아노기 및 할로겐원자로 이루어진 군에서 선택된 1개 이상의 치환기로 치환 또는 비치환되는 것을 의미한다.In the present invention, the term "substituted or unsubstituted" is substituted or unsubstituted with one or more substituents selected from the group consisting of an alkyl group, an alkoxy group, an alkylamine group, a heteroaryl group, a heteroarylamine group, a cyano group and a halogen atom It means that the ring.

상기 '치료'라 함은 발병 증상을 보이는 객체에 사용될 때 질병의 진행을 중단 또는 지연시키는 것을 의미한다.The term " treatment " refers to stopping or delaying the progress of a disease when used in an object having an onset symptom.

상기 '약학적 조성물'은 본 발명의 화합물과 함께 필요에 따라 약학적으로 허용되는 담체, 희석제, 부형제, 또는 이들의 조합을 포함할 수 있다.The 'pharmaceutical composition' may include, if necessary, a pharmaceutically acceptable carrier, diluent, excipient, or a combination thereof together with the compound of the present invention.

상기 '담체(carrier)'라 함은 세포 또는 조직 내로 화합물의 부가를 용이하게 하는 물질을 의미한다.The term "carrier" refers to a substance that facilitates the addition of a compound into a cell or tissue.

상기 '희석제(diluent)'라 함은 대상 화합물의 생물학적 활성 형태를 안정화시킬 뿐만 아니라, 화합물을 용해시키는 물에서 희석되는 물질로 정의된다.The term 'diluent' is defined as a substance that not only stabilizes the biologically active form of the compound of interest but also dilutes in water to dissolve the compound.

상기 '약학적으로 허용되는'이라 함은 화합물의 생물학적 활성과 물성을 손상시키지 않는 성질을 의미한다.The term " pharmaceutically acceptable " means a property that does not impair the biological activity and physical properties of the compound.

기타 본 명세서에서 사용된 용어와 약어들은 달리 정의되지 않는 한 본 발명이 속하는 기술 분야의 당업자에게 통상적으로 이해되는 의미로서 해석될 수 있다.Other terms and abbreviations used herein can be interpreted as commonly understood by a person skilled in the art to which the present invention belongs, unless otherwise defined.

본 발명에 따른 피라졸로피리미딘 유도체 화합물을 활성성분으로 함유하는 약학적 조성물은 생체 내 산화질소의 생성을 억제할 수 있고, 산화질소의 과다생성에 따른 신경 세포의 기능장애 및 사멸로 인하여 야기되는 뇌신경 질환, 특히 파킨슨병, 알츠하이머 치매, 헌팅턴병, 루게릭병, 간질, 우울증, 불면증, 불안증 및 퇴행성 뇌신경 질환 등을 치료하는데 사용할 수 있다.The pharmaceutical composition containing the pyrazolopyrimidine derivative compound according to the present invention as an active ingredient can inhibit the production of nitric oxide in vivo, and is caused by dysfunction and death of nerve cells due to overproduction of nitric oxide. It can be used to treat cranial nerve diseases, especially Parkinson's disease, Alzheimer's dementia, Huntington's disease, Lou Gehrig's disease, epilepsy, depression, insomnia, anxiety and degenerative neurodegenerative diseases.

이하, 본 발명을 더욱 상세하게 설명한다.Hereinafter, the present invention will be described in more detail.

산화질소(NO)는 세포 내에서 nitric oxide synthase (NOS) 효소에 의해 생성된다. 특히 inducible NOS (iNOS)는 뇌에 존재하는 소교세포와 성상세포에서 작용하는 효소이다. 평소에는 매우 낮은 농도로 존재하다가 세포가 활성될 경우 발현되고, 결과적으로 뇌 NO 농도를 현저히 (약 100 배) 증가시킨다. 퇴행성뇌질환 환자의 뇌에서는 이렇게 증가된 iNOS의 발현이 휴식상태로 되돌아가지 못하고 NO를 장기적, 지속적으로 생성한다. 그러므로 iNOS를 제어하는 것은 파킨슨병을 비롯한 퇴행성뇌질환의 예방 및 치료에 사용될 수 있을 것이다. 특히, 타 NOS (neuronal, endothelial type)의 활성에 영향을 주지 않으면서 iNOS의 발현을 휴식상태 수준으로 억제하는 방법은 NO의 정상기능에는 영향을 주지 않으므로 관련 부작용을 최소화할 수 있다.Nitric oxide (NO) is produced by the nitric oxide synthase (NOS) enzyme in the cell. In particular, inducible NOS (iNOS) is an enzyme that acts on microglia and astrocytes in the brain. It is usually present at very low concentrations and is expressed when cells are activated, resulting in a significant increase in brain NO concentration (about 100 times). In the brains of patients with degenerative brain diseases, this increased expression of iNOS does not return to rest and produces NO in the long term. Therefore, controlling iNOS may be used to prevent and treat degenerative brain diseases including Parkinson's disease. In particular, the method of inhibiting the expression of iNOS to a resting level without affecting the activity of other NOS (neuronal, endothelial type) does not affect the normal function of NO, so the related side effects can be minimized.

따라서, 본 발명은 iNOS의 발현을 휴식상태 수준으로 억제하여 뇌에서 산화질소의 과생산을 억제할 수 있는 약학 조성물로 적용할 수 있고, 이에 따라 뇌신경 질환을 치료할 수 있는 하기 [화학식 Ⅰ] 내지 [화학식 Ⅶ]로 표시되는 신규의 피라졸로피리미딘 유도체 화합물 또는 이의 약학적으로 수용 가능한 염을 제공한다.Therefore, the present invention can be applied as a pharmaceutical composition capable of inhibiting the expression of iNOS to the resting state level, thereby inhibiting the overproduction of nitric oxide in the brain, and thus can treat the neurological diseases of the following formula [I] to [ It provides a novel pyrazolopyrimidine derivative compound represented by the formula (VII) or a pharmaceutically acceptable salt thereof.

[화학식 Ⅰ] [화학식 Ⅱ] [화학식 Ⅲ][Formula (I)] [Formula (II)] [Formula (III)

[화학식 Ⅳ] [화학식 Ⅴ][Formula Ⅳ] [Formula Ⅴ]

[화학식 Ⅵ] [화학식 Ⅶ][Formula VI] [Formula VII]

상기 [화학식 Ⅰ] 내지 [화학식 Ⅶ]에서,In [Formula I] to [Formula VII],

상기 R₁은 하기 [구조식 1]로 표시되는 군으로부터 선택되는 어느 하나일 수 있고,R ₁ may be any one selected from the group represented by the following [Formula 1],

[구조식 1][Structural formula 1]

상기 R₂는 하기 [구조식 2]로 표시되는 군으로부터 선택되는 어느 하나일 수 있으며,R ₂ may be any one selected from the group represented by the following [Formula 2],

[구조식 2][Structural formula 2]

상기 R₄는 하기 [구조식 3]으로 표시되는 군으로부터 선택되는 어느 하나일 수 있다.R ₄ may be any one selected from the group represented by the following [Formula 3].

[구조식 3][Structural Formula 3]

또한, 본 발명의 범위가 이에 의해서 제한되지 않는다는 것은 당업계의 통상의 지식을 가진 자에게 자명할 것이나, 본 발명의 바람직한 실시예에 의하면, 본 발명에 따른 상기 [화학식 Ⅰ] 내지 [화학식 Ⅶ]의 화합물은 구체적으로 특허청구범위에 기재된 [화학식 4] 내지 [화학식 31k]로 표시되는 화합물들 중 어느 하나일 수 있다.In addition, it will be obvious to those skilled in the art that the scope of the present invention is not limited by this, but according to a preferred embodiment of the present invention, the above-mentioned [Formula I] to [Formula VII] The compound of may be specifically any one of the compounds represented by [Formula 4] to [Formula 31k] described in the claims.

본 발명에서 약학적으로 수용 가능한 염은 약학적으로 허용되는 음이온을 함유하는 무독성 산부가염을 형성하는 산, 예를 들어,황산, 염산, 질산, 인산, 브롬화수소산, 요오드화수소산 등과 같은 무기산과, 타르타르산, 포름산, 시트르산, 아세트산, 트리플루오로아세트산, 글루콘산, 벤조산, 락트산, 푸마르산, 젖산, 말론산, 말산, 살리실산, 숙신산, 옥살산, 프로피온산, 아스파르탄산, 글루탐산, 구연산 등과 같은 유기산과, 메탄설폰산, 에탄설폰산, 벤젠설폰산, p-톨루엔설폰산, 나프탈렌설폰산 등과 같은 설폰산 등에 의해 형성된 산부가염일 수 있고, 유리 카르복시 치환체를 포함하는 본 발명에 따르는 [화학식 Ⅰ] 내지 [화학식 Ⅶ]로 표시되는 피라졸로피리미딘 유도체 화합물은 상기의 산 부가염 및 나트륨, 칼슘 및 암모늄의 염일 수 있으며, 약학적으로 수용 가능한 염기 부가염, 예를 들어, 리튬, 나트륨, 칼륨, 칼슘, 마그네슘 등에 의해 형성된 알칼리 금속 또는 알칼리 토금속 염과, 라이신,아르기닌, 구아니딘 등의 아미노산 염과, 디사이클로헥실아민, N-메틸-D-글루카민, 트리스 (하이드록시메틸)메틸아민, 디에탄올아민, 콜린, 트리에틸 아민 등과 같은 유기염일 수 있다.Pharmaceutically acceptable salts herein include acids that form non-toxic acid addition salts containing pharmaceutically acceptable anions, such as inorganic acids such as sulfuric acid, hydrochloric acid, nitric acid, phosphoric acid, hydrobromic acid, hydroiodic acid, and tartaric acid. Organic acids such as formic acid, citric acid, acetic acid, trifluoroacetic acid, gluconic acid, benzoic acid, lactic acid, fumaric acid, lactic acid, malonic acid, malic acid, salicylic acid, succinic acid, oxalic acid, propionic acid, aspartic acid, glutamic acid, citric acid, It may be an acid addition salt formed by sulfonic acids such as phenolic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, and the like, and includes the free carboxyl substituents according to the present invention. The pyrazolopyrimidine derivative compounds represented by] may be the above acid addition salts and salts of sodium, calcium and ammonium, Base addition salts which are acceptable, for example, alkali or alkaline earth metal salts formed by lithium, sodium, potassium, calcium, magnesium, and the like, amino acid salts such as lysine, arginine, guanidine, dicyclohexylamine, N-methyl Organic salts such as -D-glucamine, tris (hydroxymethyl) methylamine, diethanolamine, choline, triethyl amine and the like.

본 발명에 따른 피라졸로피리미딘 화합물은 통상적인 방법에 의해 그의 염으로 전환될 수 있으며, 염의 제조는 별도의 설명이 없이도 상기 [화학식 Ⅰ] 내지 [화학식 Ⅶ]의 구조를 바탕으로 당업자에 의해 용이하게 수행될 수 있을 것이다.The pyrazolopyrimidine compounds according to the present invention can be converted to their salts by conventional methods, and the preparation of the salts can be easily carried out by those skilled in the art based on the structures of the above Chemical Formulas I to XII without further explanation. May be performed.

이하에서 별도의 설명이 없는 한, 피라졸로피리미딘 유도체 화합물에는 약학적으로 수용 가능한 그의 염이 포함되며, 이들은 모두 본 발명의 범주에 포함되는 것으로 해석되어야 한다.Unless otherwise stated below, pyrazolopyrimidine derivative compounds include pharmaceutically acceptable salts thereof, all of which are to be construed as being within the scope of the present invention.

본 발명에 따른 피라졸로피리미딘 유도체 화합물은 뇌에서 산화질소의 과다 생성을 억제할 수 있는 저해제로서, 산화질소의 과다 생성으로 야기되는 파킨슨병, 알츠하이머 치매, 헌팅턴병, 루게릭병, 간질, 우울증, 통증 불안증 및 퇴행성 뇌신경 질환 등 다양한 뇌신경 질환을 예방 또는 치료제로 사용할 수 있다.The pyrazolopyrimidine derivative compounds according to the present invention are inhibitors capable of inhibiting the overproduction of nitric oxide in the brain and are caused by Parkinson's disease, Alzheimer's dementia, Huntington's disease, Lou Gehrig's disease, epilepsy, depression and pain caused by the overproduction of nitric oxide. Various neurological disorders such as anxiety and degenerative neurological disorders can be used as a prophylactic or therapeutic agent.

본 발명의 바람직한 일 실시예에 의하면, 버퍼 용액에 용해되어 있는 염을 희석제로 사용하고, 통상 사용되는 버퍼 용액은 인간 용액의 염 형태를 모방하고 있는 포스페이트 버퍼 식염수일 수 있다. 버퍼 염은 낮은 농도에서 용액의 pH를 제어할 수 있기 때문에, 버퍼 희석제가 화합물의 생물학적 활성을 변형시키지 않는다.According to a preferred embodiment of the present invention, the salt dissolved in the buffer solution is used as a diluent, and the buffer solution usually used may be phosphate buffer saline that mimics the salt form of the human solution. Since buffer salts can control the pH of the solution at low concentrations, the buffer diluent does not alter the biological activity of the compound.

본 발명의 화합물은 약학적으로 또는 수의학적으로 수용가능한 담체 또는 희석제를 또한 함유하는 약학적 또는 수의학적 조성물로 사용하기 위해 제형화할 수 있다. 본 발명에 따른 조성물은 통상적인 방법에 따라 일반적으로 제조하여, 약학적으로 또는 수의학적으로 적절한 형태로 투여할 수 있다.The compounds of the present invention may be formulated for use as pharmaceutical or veterinary compositions also containing a pharmaceutically or veterinarily acceptable carrier or diluent. The composition according to the present invention can be generally prepared according to a conventional method, and can be administered in a pharmaceutically or veterinarily appropriate form.

본 발명의 바람직한 실시예에 의하면, 정제, 캡슐, 당-코팅, 필름-코팅정제, 액체 용액 또는 현탁액의 형태와 같은 경구적으로 투여할 수 있고, 또는 피하나 근육내로 또는 정맥 내로 주사 또는 주입의 방법을 통하여 비경구적으로 투여할 수도 있다.According to a preferred embodiment of the invention, it can be administered orally, such as in the form of tablets, capsules, sugar-coated, film-coated tablets, liquid solutions or suspensions, or by injection or infusion subcutaneously or intramuscularly or intravenously. It can also be administered parenterally via the method.

환자의 연령, 체중 및 상태와 투여경로를 비롯한 각종 요인에 따라 투여량은 결정될 수 있다. 1일 투여용량은 광범위한 한도치 내에서 변할 수 있으며, 각각의 개별 경우에서 개인적 요건에 맞게 조정될 수 있다. 그러나 일반적으로, 본 화합물을 성인에게 단독 투여하는 경우, 투여 경로별로 채택된 투여용량은 0.0001 내지 50 ㎎/㎏ 체중이며, 0.001 내지 10 ㎎/㎏ 체중의 범위에서 예를 들면 0.01 내지 1 ㎎/㎏ 체중으로 할 수 있다.The dosage can be determined according to various factors including the patient's age, body weight and condition and administration route. The daily dose can vary within wide limits and can be tailored to individual requirements in each individual case. In general, however, when the present compound is administered alone to an adult, the dosages adopted by the route of administration are 0.0001 to 50 mg / kg body weight, for example 0.01 to 1 mg / kg in the range of 0.001 to 10 mg / kg body weight. You can do it by weight.

이러한 투여 용량은 예를 들면 1일 1 내지 5 회 제공할 수 있다. 정맥 내 주사의 경우, 적절한 1일 용량은 0.0001 내지 1 ㎎/㎏ 체중, 바람직하게는 0.0001 내지 0.1 ㎎/㎏ 체중이다. 1일 투여용량은 단일 투여분으로서 또는 분할용량 스케줄에 따라 투여할 수 있다.
Such dosage can be provided, for example, 1 to 5 times per day. For intravenous injection, the appropriate daily dose is 0.0001 to 1 mg / kg body weight, preferably 0.0001 to 0.1 mg / kg body weight. The daily dose may be administered as a single dose or according to a divided dose schedule.

이하, 바람직한 실시예를 들어 본 발명을 더욱 상세하게 설명한다. 그러나, 이들 실시예는 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 범위가 이에 의하여 제한되지 않고, 본 발명의 범주 및 기술사상 범위 내에서 다양한 변경 및 수정이 가능함은 당업계의 통상의 지식을 가진 자에게 자명할 것이다.Hereinafter, the present invention will be described in more detail with reference to preferred examples. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. It will be clear to those who have knowledge.

또한, 본 발명이 속한 기술분야에서 통상의 지식을 가진 자라면 [화학식 Ⅰ] 내지 [화학식 Ⅶ]의 구조를 바탕으로 다양한 방법에 의해 [화학식 Ⅰ] 내지 [화학식 Ⅶ]의 화합물을 제조할 수 있으며, 이러한 방법들은 모두 본 발명의 범주에 포함되는 것으로 해석되어야 한다.In addition, a person having ordinary knowledge in the technical field to which the present invention belongs may prepare the compounds of [Formula I] to [Formula VII] by various methods based on the structure of [Formula I] to [Formula VII]. All these methods should be construed as being included in the scope of the present invention.

즉, 이하의 실시예에 구체적으로 기재된 합성방법 또는 선행기술에 개시된 여러 합성법들을 임의로 조합하여 [화학식 Ⅰ] 내지 [화학식 Ⅶ]의 화합물을 제조할 수 있고, 이는 본 발명의 범위에 속하는 것으로 이해되고, [화학식 Ⅰ] 내지 [화학식 Ⅶ] 화합물의 제조방법이 하기 설명된 것으로 제한되는 것은 아니다.
That is, the compound of [Formula I] to [Formula X] can be prepared by arbitrarily combining the synthesis method described in the following Examples or various synthesis methods disclosed in the prior art, which is understood to be within the scope of the present invention. , And the method for preparing the compound of Formula I to Compound VIII is not limited to those described below.

<실시예><Examples>

합성예 1. [화학식 A] 및 [화학식 B]의 합성Synthesis Example 1. Synthesis of [Formula A] and [Formula B]

하기 [반응식 1](반응조건 POCl₃, DMF, 100 , 23 h)에 따라 [화학식 A], [화학식 B]로 표시되는 화합물을 합성하였다.Compounds represented by [Formula A] and [Formula B] were synthesized according to the following [Scheme 1] (reaction conditions POCl ₃ , DMF, 100, 23 h).

[반응식 1][Reaction Scheme 1]

[화학식 A] [화학식 B][Formula A] [Formula B]

반응기에 POCl₃ (6 eq, 7.07 mL)을 넣고 ice bath를 사용하여 0 ℃로 냉각 시킨 후 DMF(dimethylformamide, 2.1 eq. 2.03 mL)를 천천히 넣어주고 상온에서 1 시간 동안 교반하였다. 이후, 4,6-디하이드록시-2-(메틸티오)피리미딘 (2 g, 12.6 mmol)을 천천히 투여하고 23 시간 동안 100 ℃ 가열 교반하였다. 반응 종료 후 반응물을 상온으로 냉각시키고, 얼음물에 반응 혼합물을 붓고 6 시간 동안 정체시켰다. 이때 생성된 갈색 침전물은 여과를 통해서 분리하고 여액은 포화 NaHCO₃ 수용액과 EtOAc (2×30 mL)를 사용해서 추출하고 유기층은 무수 MgSO₄을 사용하여 소량의 물을 제거하였으며, 감압 증류하여 용매를 제거하고 진공 건조한 후 EtOAc/hexanes을 이용한 결정화 방법으로 갈색의 고체상 화합물 [화학식 A], [화학식 B]을 얻었다.
POCl _{3 in the} reactor (6 eq, 7.07 mL) was added and the mixture was cooled to 0 ° C. using an ice bath. Then, DMF (dimethylformamide, 2.1 eq. 2.03 mL) was slowly added thereto and stirred at room temperature for 1 hour. Thereafter, 4,6-dihydroxy-2- (methylthio) pyrimidine (2 g, 12.6 mmol) was slowly administered and stirred with heating at 100 ° C. for 23 hours. After the reaction was completed, the reaction was cooled to room temperature, the reaction mixture was poured into iced water and held for 6 hours. The resulting brown precipitate is separated by filtration and the filtrate is saturated with NaHCO _3. Aqueous solution was extracted with EtOAc (2 × 30 mL) and the organic layer was removed with a small amount of water using anhydrous MgSO ₄ , distilled under reduced pressure to remove the solvent, dried in vacuo and crystallized with EtOAc / hexanes to give a brown solid phase. The compound [Formula A] and [Formula B] were obtained.

(1) [화학식 A] 4,6-디클로로-2-(메틸티오)피리미딘-5-카바알데하이드(1) 4,6-dichloro-2- (methylthio) pyrimidine-5-carbaaldehyde

Yield: 65%; ¹H NMR (400 MHz, CDCl₃) δ 2.71 (s, 3H), 10.43 (s, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 14.7, 119.0, 162.3, 177.0, 185.3.
Yield: 65%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 2.71 (s, 3H), 10.43 (s, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 14.7, 119.0, 162.3, 177.0, 185.3.

(2) [화학식 B] 4,6-디클로로-2-(메틸티오)피리미딘(2) 4,6-dichloro-2- (methylthio) pyrimidine

Yield: 42%; ¹H NMR (400 MHz, CDCl₃) δ 2.57 (s, 3H), 7.04 (s, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 14.4, 115.6, 161.2, 174.4.
Yield: 42%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 2.57 (s, 3H), 7.04 (s, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 14.4, 115.6, 161.2, 174.4.

실시예 1. 4-클로로-6-(메틸티오)피라졸로[3,4-d]피리미딘, [4]Example 1. 4-chloro-6- (methylthio) pyrazolo [3,4-d] pyrimidine, [4]

하기 [반응식 2](반응조건 PPh₃, DIAD, R₁OH, THF, N₂, 0 ℃-상온, 6 h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [4]를 합성하였다.The pyrazolopyrimidine derivative compound [4] according to the present invention was synthesized by the following [Scheme 2] (reaction conditions PPh ₃ , DIAD, R ₁ OH, THF, N ₂ , 0 ° C.-room temperature, 6 h).

[반응식 2][Reaction Scheme 2]

[화학식 A] [4]Formula A] [4]

4,6-디클로로-2-(메틸티오)피리미딘-5-카바알데하이드(1.2 g, 5.38 mmol)를 THF/H₂O(3:1, 24 mL)에 넣고 교반하는 상태에서 H₂O(4 mL)에 하이드라진 하이드레이트(1.5 eq, 0.39 mL)을 섞은 것을 가하고, 상온에서 4 시간을 교반하였다. 그 후 반응 용매의 부피를 줄인 후에 디에틸에테르를 가하였다. 그 후 유기층만을 따로 분리하여 무수 MgSO₄로 수분을 제거한 후 감압증류를 하였다. 여기서 얻은 반응 혼합물을 flash chromatography (hexanes : EtOAc = 4:1)로 분리하여 옅은 노란색 고체상의 화합물, 4-클로로-6-(메틸티오)피라졸로[3,4-d]피리미딘 [4]를 얻었다.4,6-Dichloro-2- (methylthio) pyrimidine-5-carbaaldehyde (1.2 g, 5.38 mmol) was added to THF / H ₂ O (3: 1, 24 mL) and stirred with H ₂ O ( 4 mL) was added to the mixture of hydrazine hydrate (1.5 eq, 0.39 mL), followed by stirring at room temperature for 4 hours. Thereafter, the volume of the reaction solvent was reduced and then diethyl ether was added. Thereafter, only the organic layer was separated, and water was removed with anhydrous MgSO ₄ , followed by distillation under reduced pressure. The reaction mixture obtained here was separated by flash chromatography (hexanes: EtOAc = 4: 1) to give 4-chloro-6- (methylthio) pyrazolo [3,4-d] pyrimidine [4] as a pale yellow solid. Got it.

Yield: 76%; ¹H NMR (400 MHz, CDCl₃) δ 2.67 (s, 3H), 8.13 (s, 1H), 11.45 (s, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 14.6, 110.2, 134.0, 154.4, 155.5, 171.1.
Yield: 76%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 2.67 (s, 3H), 8.13 (s, 1H), 11.45 (s, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 14.6, 110.2, 134.0, 154.4, 155.5, 171.1.

실시예 2. [5a] 내지 [5d]의 합성Example 2. Synthesis of [5a] to [5d]

하기 [반응식 3](반응조건 R₁-N₂H₄, Hunig base, THF, 상온, 24 h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [5a] 내지 [5k]를 합성하였다.The pyrazolopyrimidine derivative compounds [5a] to [5k] were synthesized by the following Reaction Scheme 3 (reaction conditions R ₁ -N ₂ H ₄ , Hunig base, THF, room temperature, 24 h).

[반응식 3]Scheme 3

[4] [5a] ~ [5d][4] [5a]-[5d]

상기 실시예 1에서 합성한 [4]와 Ph₃P (1.5 eq)를 THF에 넣고 0 ℃로 낮추어 15분 동안 교반하였다. 그 후, R₁OH (1.1 eq)을 넣고 다이아이소프로필 아조디카르복실레이트(1.5 eq)를 2 분간 천천히 가해준 후 2 시간 동안을 0 ℃로 유지한 상태에서 교반시켜준 후 4 시간을 상온에서 교반시켰다. 반응 혼합물을 감압증류를 시킨 후, flash chromatography (hexanes : EtOAc = 9:1)을 통하여 분리하여 원하는 화합물 [5a] 내지 [5d]를 얻었다.[4] and Ph ₃ P (1.5 eq) synthesized in Example 1 were added to THF, and the mixture was stirred at 0 ° C. for 15 minutes. Then, R ₁ OH (1.1 eq) was added and diisopropyl azodicarboxylate (1.5 eq) was added slowly for 2 minutes, and stirred for 2 hours at 0 ° C., followed by 4 hours at room temperature. Stirred at. The reaction mixture was evaporated under reduced pressure, and then separated through flash chromatography (hexanes: EtOAc = 9: 1) to obtain desired compounds [5a] to [5d].

[5a] 내지 [5d]에서 R₁은 각각 하기 [표 1]과 같다.R ₁ in [5a] to [5d] is as shown in the following [Table 1], respectively.

구분division R₁ R ₁ 구분division R₁ R ₁ 5a5a CH₃ CH ₃ 5c5c

5b5b

5d5d

(1) 1-메틸-4-클롤로-6-(메틸티오)피라졸로[3,4-d]피리미딘, [5a](1) 1-methyl-4-chloro-6- (methylthio) pyrazolo [3,4-d] pyrimidine, [5a]

Yield: 79%; ¹H NMR (400 MHz, DMSO-d₆) δ 2.64 (s, 3H), 3.98 (s, 3H), 8.31 (s, 1H).
Yield: 79%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.64 (s, 3H), 3.98 (s, 3H), 8.31 (s, 1H).

(2) 1-알릴-4-클로로-6-(메틸티오)피라졸로[3,4-d]피리미딘 [5b](2) 1-allyl-4-chloro-6- (methylthio) pyrazolo [3,4-d] pyrimidine [5b]

Yield: 70%; ¹H NMR (400 MHz, CDCl₃) δ 2.61 (s, 3H), 5.03 (d, J = 5.9Hz, 2H), 5.29 (d, J = 11.3 Hz, 2H), 5.98-6.08 (m, 1H), 8.07 (s, 1H).
Yield: 70%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 2.61 (s, 3H), 5.03 (d, J = 5.9 Hz, 2H), 5.29 (d, J = 11.3 Hz, 2H), 5.98-6.08 (m, 1H) , 8.07 (s, 1 H).

(3) 1-[2-(테트라하이드로피란-2-일옥시)에틸]-4-클로로-6-(메틸티오)피라졸로[3,4-d]피리미딘 [5c](3) 1- [2- (tetrahydropyran-2-yloxy) ethyl] -4-chloro-6- (methylthio) pyrazolo [3,4-d] pyrimidine [5c]

Yield: 78%; ¹H NMR (400 MHz, DMSO-d₆) δ 2.61 (s, 3H), 3.86 (quar, J = 5.2 Hz, 2H), 4.43 (t, J = 5.6 Hz, 2H), 4.86 (t, J = 5.3 Hz, 1H), 8.34 (s, 1H).
Yield: 78%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.61 (s, 3H), 3.86 (quar, J = 5.2 Hz, 2H), 4.43 (t, J = 5.6 Hz, 2H), 4.86 (t, J = 5.3 Hz, 1H), 8.34 (s, 1H).

(4) 1-[N-t-Boc-(2-아미노에틸)]-4-클로로-6-(m메틸티오)피라졸로[3,4-d]피리미딘 [5d](4) 1- [N-t-Boc- (2-aminoethyl)]-4-chloro-6- (mmethylthio) pyrazolo [3,4-d] pyrimidine [5d]

Yield: 77%; ¹H NMR (400 MHz, DMSO-d₆) δ 1.23 (s, 9H), 2.62 (s, 3H), 3.37 (quar, J = 5.8 Hz, 2H), 4.42 (t, J = 5.4 Hz, 2H), 6.87 (t, J = 5.8 Hz, 1H), 8.33 (s, 1H).
Yield: 77%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.23 (s, 9H), 2.62 (s, 3H), 3.37 (quar, J = 5.8 Hz, 2H), 4.42 (t, J = 5.4 Hz, 2H) , 6.87 (t, J = 5.8 Hz, 1H), 8.33 (s, 1H).

실시예 3. [5e] 내지 [5k]의 합성Example 3. Synthesis of [5e] to [5k]

하기 [반응식 4]에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [5a] 내지 [5k]를 합성하였다.The pyrazolopyrimidine derivative compounds [5a] to [5k] according to the present invention were synthesized by the following [Scheme 4].

[반응식 4][Reaction Scheme 4]

[화학식 A] [5e] ~ [5k]   [Formula A] [5e]-[5k]

[5a] 내지 [5d]에서 R₁은 각각 하기 [표 2]와 같다.R ₁ in [5a] to [5d] is as shown in the following [Table 2], respectively.

구분division R₁ R ₁ 구분division R₁ R ₁ 5e5e

5i5i

5f5f

5j5j

5g5g

5k5k

5h5h

(1) 1-페닐-4-클로로-6-(메틸티오)피라졸로[3,4-d]피리미딘 [5e](1) 1-phenyl-4-chloro-6- (methylthio) pyrazolo [3,4-d] pyrimidine [5e]

4,6-디클로로-2-(메틸티오)피리미딘-5-카바알데하이드 (1.3 g, 5.83 mmol)과 Hunig base (1 eq, 1.02 mL)를 THF/H₂O (3:1, 20 mL)에 넣고 교반하는 상태에서 페닐하이드라진 (1.1 eq, 0.63 mL)을 가하고, 상온에서 4 시간을 교반하였다. 그 후 반응 용매의 부피를 줄인 후에 EtOAc를 가하였다. 유기층만을 따로 분리하여 무수 MgSO₄로 수분을 제거한 후에 evaporation을 하였다. 여기서 얻은 반응 혼합물을 flash chromatography (hexanes : EtOAc = 8:1)로 분리하여 하얀색 고체상 화합물 [5e]를 얻었다.4,6-dichloro-2- (methylthio) pyrimidine-5-carbaaldehyde (1.3 g, 5.83 mmol) and Hunig base (1 eq, 1.02 mL) were mixed with THF / H ₂ O (3: 1, 20 mL). Phenylhydrazine (1.1 eq, 0.63 mL) was added to the mixture, and stirred for 4 hours at room temperature. The volume of reaction solvent was then reduced and then EtOAc was added. Only the organic layer was separated and removed with anhydrous MgSO ₄ , and then evaporated. The reaction mixture thus obtained was separated by flash chromatography (hexanes: EtOAc = 8: 1) to obtain a white solid compound [5e].

Yield: 61%; ¹H NMR (400 MHz, DMSO-d₆) δ 2.63 (s, 3H), 7.43 (t, J = 9.1 Hz, 1H), 7.60 (t, J = 8.0 Hz, 2H), 8.15 (d, J = 7.7 Hz, 2H), 8.60 (s, 1H); ¹³C NMR (100 MHz, DMSO-d₆) δ 14.5, 112.1, 121.3, 127.6, 129.9, 134.9, 138.3, 153.5, 153.9, 170.6.
Yield: 61%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.63 (s, 3H), 7.43 (t, J = 9.1 Hz, 1H), 7.60 (t, J = 8.0 Hz, 2H), 8.15 (d, J = 7.7 Hz, 2H), 8.60 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.5, 112.1, 121.3, 127.6, 129.9, 134.9, 138.3, 153.5, 153.9, 170.6.

(2) 1-벤질-4-클로로-6-(메틸티오)피라졸로[3,4-d]피리미딘 [5f](2) 1-benzyl-4-chloro-6- (methylthio) pyrazolo [3,4-d] pyrimidine [5f]

상기 실시예 3-(1)과 동일한 방법으로 합성하고, 4,6-디클로로-2-(메틸티오)피리미딘-5-카바알데하이드와 벤질 하이드라진 모노하이드로클로라이드로부터 연한 노란색의 고체상 화합물 [5f]를 얻었다.Synthesis was carried out in the same manner as in Example 3- (1), and a pale yellow solid compound [5f] was obtained from 4,6-dichloro-2- (methylthio) pyrimidine-5-carbaaldehyde and benzyl hydrazine monohydrochloride. Got it.

Yield: 63%; ¹H NMR (400 MHz, CDCl₃) δ 2.62 (s, 3H), 5.57 (s, 2H), 7.25-7.36 (m, 5H), 8.01 (s, 1H).
Yield: 63%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 2.62 (s, 3H), 5.57 (s, 2H), 7.25-7.36 (m, 5H), 8.01 (s, 1H).

(3) 1-t-뷰틸-4-클로로-6-(메틸티오)피라졸로[3,4-d]피리미딘 [5g](3) 1-t-butyl-4-chloro-6- (methylthio) pyrazolo [3,4-d] pyrimidine [5 g]

상기 실시예 3-(1)과 동일한 방법으로 합성하고, 4,6-디클로로-2-(메틸티오)피리미딘-5-카바알데하이드와 t-뷰틸하이드라진 디하이드로클로라이드로부터 연한 노란색의 고체상 화합물 [5g]를 얻었다.Synthesis was carried out in the same manner as in Example 3- (1), and was pale yellow solid compound from 4,6-dichloro-2- (methylthio) pyrimidine-5-carbaaldehyde and t-butylhydrazine dihydrochloride [5 g ] Was obtained.

Yield: 42%; ¹H NMR (400 MHz, DMSO-d₆) δ 1.65 (s, 9H), 2.54 (s, 3H), 8.82 (s, 1H); ¹³C NMR (100 MHz, DMSO-d₆) δ 14.3, 29.6, 62.4, 109.7, 124.5, 155.2, 159.7, 167.8.
Yield: 42%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.65 (s, 9H), 2.54 (s, 3H), 8.82 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.3, 29.6, 62.4, 109.7, 124.5, 155.2, 159.7, 167.8.

(4) 1-(4-플루오로페닐)-4-클로로-6-(메틸티오)피라졸로[3,4-d]피리미딘 [5h](4) 1- (4-fluorophenyl) -4-chloro-6- (methylthio) pyrazolo [3,4-d] pyrimidine [5h]

상기 실시예 3-(1)과 동일한 방법으로 합성하고, 4,6-디클로로-2-(메틸티오)피리미딘-5-카바알데하이드와 4-플루오로페닐하이드라진 하이드로클로라이드로부터 연한 오렌지색의 고체상 화합물 [5h]를 얻었다.It was synthesized in the same manner as in Example 3- (1), and was pale orange solid compound from 4,6-dichloro-2- (methylthio) pyrimidine-5-carbaaldehyde and 4-fluorophenylhydrazine hydrochloride [ 5h].

Yield: 64%; ¹H NMR (400 MHz, DMSO-d₆) δ 2.63 (s, 3H), 7.46 (t, J = 8 Hz, 2H), 8.17 (dd, J = 4 Hz, 3 Hz, 2H), 8.61 (s, 1H)
Yield: 64%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.63 (s, 3H), 7.46 (t, J = 8 Hz, 2H), 8.17 (dd, J = 4 Hz, 3 Hz, 2H), 8.61 (s , 1H)

(5) 1-(4-메틸페닐)-4-클로로-6-(메틸티오)피라졸로[3,4-d]피리미딘 [5i](5) 1- (4-methylphenyl) -4-chloro-6- (methylthio) pyrazolo [3,4-d] pyrimidine [5i]

상기 실시예 3-(1)과 동일한 방법으로 합성하고, 4,6-디클로로-2-(메틸티오)피리미딘-5-카바알데하이드와 4-메틸페닐하이드라진 하이드로클로라이드로부터 연한 노란색의 고체상 화합물 [5i]를 얻었다.It was synthesized in the same manner as in Example 3- (1), and was pale yellow solid compound from 4,6-dichloro-2- (methylthio) pyrimidine-5-carbaaldehyde and 4-methylphenylhydrazine hydrochloride [5i] Got.

Yield: 57%; ¹H NMR (400 MHz, DMSO-d₆) δ 2.43 (s, 3H), 2.61 (s, 3H), 7.37 (d, J = 8 Hz, 2H), 7.97 (d, J = 8 Hz, 2H), 8.56 (s, 1H); ¹³C NMR (400 MHz, DMSO-d₆) δ 14.5, 21.0, 111.9, 121.2, 130.2, 134.5, 135.9, 137.0, 153.3, 153.8, 170.4.
Yield: 57%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.43 (s, 3H), 2.61 (s, 3H), 7.37 (d, J = 8 Hz, 2H), 7.97 (d, J = 8 Hz, 2H) , 8.56 (s, 1 H); ¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 14.5, 21.0, 111.9, 121.2, 130.2, 134.5, 135.9, 137.0, 153.3, 153.8, 170.4.

(6) 1-(3-메톡시펜에틸)-4-클로로-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘 [5j](6) 1- (3-methoxyphenethyl) -4-chloro-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidine [5j]

상기 실시예 3-(1)과 동일한 방법으로 합성하고, 4,6-디클로로-2-(메틸티오)피리미딘-5-카바알데하이드와 3-메톡시펜에틸하이드라진 하이드로클로라이드로부터 연한 노란색의 고체상 화합물 [5j]를 얻었다.It was synthesized in the same manner as in Example 3- (1), and was pale yellow solid compound from 4,6-dichloro-2- (methylthio) pyrimidine-5-carbaaldehyde and 3-methoxyphenethylhydrazine hydrochloride. [5j] was obtained.

Yield: 76.46%; ¹H NMR (400 MHz, DMSO-d₆) δ 3.10 (t, J = 6.8 Hz, 2H), 3.30 (s, 3H), 3.61 (s, 3H), 4.59 (t, J = 6.8 Hz, 2H), 6.56-6.66 (m, 3H), 7.03 (t, J = 7.8 Hz, 1H), 8.27 (s, 1H); ¹³C NMR (100 MHz, DMSO-d₆) δ 14.2, 35.2, 48.6, 55.2, 100.8, 110.1, 112.3, 114.6, 121.2, 129.6, 132.9, 139.8, 153.1, 154.0, 159.5, 169.0.
Yield: 76.46%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 3.10 (t, J = 6.8 Hz, 2H), 3.30 (s, 3H), 3.61 (s, 3H), 4.59 (t, J = 6.8 Hz, 2H) , 6.56-6.66 (m, 3H), 7.03 (t, J = 7.8 Hz, 1H), 8.27 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.2, 35.2, 48.6, 55.2, 100.8, 110.1, 112.3, 114.6, 121.2, 129.6, 132.9, 139.8, 153.1, 154.0, 159.5, 169.0.

(7) 1-(2-메톡시펜에틸)-4-클로로-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘 [5k](7) 1- (2-methoxyphenethyl) -4-chloro-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidine [5k]

상기 실시예 3-(1)과 동일한 방법으로 합성하고, 4,6-디클로로-2-(메틸티오)피리미딘-5-카바알데하이드와 2-메톡시펜에틸하이드라진 하이드로클로라이드로부터 연한 노란색의 고체상 화합물 [5k]를 얻었다.It was synthesized in the same manner as in Example 3- (1), and was pale yellow solid compound from 4,6-dichloro-2- (methylthio) pyrimidine-5-carbaaldehyde and 2-methoxyphenethylhydrazine hydrochloride. [5k] was obtained.

Yield: 72.51%; ¹H NMR (400 MHz, DMSO-d₆) δ 2.51 (s, 3H), 3.10 (t, J = 6.8 Hz, 2H), 3.71 (s, 3H), 4.59 (t, J = 6.8 Hz, 2H), 6.70 (t, J = 7.3 Hz, 1H), 6.84-6.90 (m, 2H), 7.14 (t, J = 7.0Hz, 1H), 8.29 (s, 1H); ¹³C NMR (100 MHz, DMSO-d₆) δ 14.1, 30.7, 47.4, 55.6, 110.1, 110.9, 120.5, 126.0, 128.5, 130.5, 132.7, 153.1, 153.9, 157.7, 168.9.
Yield: 72.51%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.51 (s, 3H), 3.10 (t, J = 6.8 Hz, 2H), 3.71 (s, 3H), 4.59 (t, J = 6.8 Hz, 2H) , 6.70 (t, J = 7.3 Hz, 1H), 6.84-6.90 (m, 2H), 7.14 (t, J = 7.0 Hz, 1H), 8.29 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.1, 30.7, 47.4, 55.6, 110.1, 110.9, 120.5, 126.0, 128.5, 130.5, 132.7, 153.1, 153.9, 157.7, 168.9.

실시예 4. [6a] 내지 [6y]의 합성Example 4. Synthesis of [6a] to [6y]

하기 [반응식 5](반응조건 R₂N(1.1 eq), 1,4-dioxane, reflux, 8h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [6a] 내지 [6y]를 합성하였다.The pyrazolopyrimidine derivative compounds [6a] to [6y] were synthesized according to the following Reaction Scheme 5 (reaction conditions R ₂ N (1.1 eq), 1,4-dioxane, reflux, 8h).

[반응식 5][Reaction Scheme 5]

[4] [6a] ~ [6y][4] [6a] to [6y]

[6a] 내지 [6y]에서 R₁은 각각 하기 [표 3]과 같다.In [6a] to [6y], each R ₁ is as shown in Table 3 below.

구분division NR₂ NR ₂ 구분division NR₂ NR ₂ 6a6a

6n6n

6b6b

6o6o

6c6c

6p6p

6d6d

6q6q

6e6e

6r6r

6f6f

6s6s

6g6g

6t6t

6h6h

6u6u

6i6i

6v6v

6j6j

6w6w

6k6k

6x6x

6l6l

6y6y

6m6m

(1) 4-벤질아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [6a](1) 4-benzylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [6a]

상기 [4] (430 mg, 2.14 mmol)과 벤질아민 (1.1 eq, 0.26 mL)을 1,4-dioxane (5 mL)에 넣고 8 시간 동안 reflux를 하였다. 반응 혼합물을 EtOAc/H₂O 혼합용매로 층 분리를 한 다음 유기층만 따로 분리하여 무수 MgSO₄로 수분을 제거하고 감압증류 하였다. 반응 혼합물을 flash chromatography (CH₂Cl₂ : CH₃OH = 10 : 1)로 분리하여 옅은 노란색의 고체상 화합물 [6a]를 얻었다.[4] (430 mg, 2.14 mmol) and benzylamine (1.1 eq, 0.26 mL) were added to 1,4-dioxane (5 mL) and refluxed for 8 hours. The reaction mixture was separated by EtOAc / H ₂ O mixed solvent, and then the organic layer was separated and the water was removed with anhydrous MgSO ₄ and distilled under reduced pressure. The reaction mixture was separated by flash chromatography (CH ₂ Cl ₂ : CH ₃ OH = 10: 1) to give a pale yellow solid compound [6a].

Yield: 84%; ¹H NMR (400 MHz, CD₃OD-d₄) δ 2.49 (s, 3H), 4.78 (s, 2H), 7.23 (t, J = 7 Hz, 1H), 7.31 (t, J = 7 Hz, 2H), 7.36 (d, J = 7 Hz, 2H), 7.97 (s, 1H) ; ¹³C NMR (100 MHz, CD₃OD-d₄) δ 12.8, 43.7, 97.8, 126.7, 127.3, 128.1, 132.0, 138.9, 155.3, 155.8, 170.2.
Yield: 84%; ¹ H NMR (400 MHz, CD ₃ OD-d ₄ ) δ 2.49 (s, 3H), 4.78 (s, 2H), 7.23 (t, J = 7 Hz, 1H), 7.31 (t, J = 7 Hz, 2H), 7.36 (d, J = 7 Hz, 2H), 7.97 (s, 1H); ¹³ C NMR (100 MHz, CD ₃ OD-d ₄ ) δ 12.8, 43.7, 97.8, 126.7, 127.3, 128.1, 132.0, 138.9, 155.3, 155.8, 170.2.

(2) 4-알릴아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [6b](2) 4-allylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [6b]

상기 [4]와 알릴아민으로부터 옅은 노란색의 고체상 화합물 [6b]를 얻었다.A pale yellow solid compound [6b] was obtained from the above [4] and allylamine.

Yield: 78%; ¹H NMR (400 MHz, DMSO-d₆) δ 2.43 (s, 3H), 4.10 (t, J = 4.7 Hz, 2H), 5.12 (d, J = 10.2 Hz, 2H), 5.21 (d, J = 17.2 Hz, 2H), 5.89-5.98 (m, 1H), 8.02 (s, 1H), 8.39 (s, 1H), 13.20 (s, 1H).
Yield: 78%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.43 (s, 3H), 4.10 (t, J = 4.7 Hz, 2H), 5.12 (d, J = 10.2 Hz, 2H), 5.21 (d, J = 17.2 Hz, 2H), 5.89-5.98 (m, 1H), 8.02 (s, 1H), 8.39 (s, 1H), 13.20 (s, 1H).

(3) 4-펜에틸아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [6c](3) 4-phenethylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [6c]

상기 [4]와 펜에틸아민으로부터 옅은 노란색의 고체상 화합물 [6c]를 얻었다.A pale yellow solid compound [6c] was obtained from the above [4] and phenethylamine.

Yield: 56%; ¹H NMR (400 MHz, DMSO-d₆) δ 2.46 (s, 3H), 2.91 (t, J = 7.4 Hz, 2H), 3.65 (quar, J = 6.8 Hz, 2H), 7.17-7.31 (m, 5H), 7.98 (s, 1H), 8.34 (t, J = 5.2 Hz, 1H), 13.18 (s, 1H); ¹³C NMR (100 MHz, DMSO-d₆) δ 14.0, 35.2, 42.0, 98.1, 126.6, 128.8, 129.1, 132.8, 139.8, 155.5, 155.7, 168.6.
Yield: 56%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.46 (s, 3H), 2.91 (t, J = 7.4 Hz, 2H), 3.65 (quar, J = 6.8 Hz, 2H), 7.17-7.31 (m, 5H), 7.98 (s, 1 H), 8.34 (t, J = 5.2 Hz, 1 H), 13.18 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 35.2, 42.0, 98.1, 126.6, 128.8, 129.1, 132.8, 139.8, 155.5, 155.7, 168.6.

(4) 4-(4-플루오로벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [6d] (4) 4- (4-fluorobenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [6d]

상기 [4]와 4-플루오로벤질아민으로부터 옅은 노란색의 고체상 화합물 [6d]를 얻었다.A pale yellow solid compound [6d] was obtained from the above [4] and 4-fluorobenzylamine.

Yield: 72%; ¹H NMR (400 MHz, DMSO-d₆) δ 2.42 (s, 3H), 4.66 (d, J = 5.6 Hz, 2H), 7.15 (t, J = 8.3 Hz, 2H), 7.38 (t, J = 6.7 Hz, 2H), 8.02 (s, 1H), 8.73 (t, J = 5.3 Hz, 1H), 13.24 (s, 1H); ¹³C NMR (400 MHz, DMSO-d₆) δ 14.0, 42.9, 98.1, 115.4, 115.6, 129.9, 130.0, 132.9, 135.9, 155.6, 160.5, 162.9, 168.6.
Yield: 72%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.42 (s, 3H), 4.66 (d, J = 5.6 Hz, 2H), 7.15 (t, J = 8.3 Hz, 2H), 7.38 (t, J = 6.7 Hz, 2H), 8.02 (s, 1 H), 8.73 (t, J = 5.3 Hz, 1 H), 13.24 (s, 1 H); ¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 14.0, 42.9, 98.1, 115.4, 115.6, 129.9, 130.0, 132.9, 135.9, 155.6, 160.5, 162.9, 168.6.

(5) 4-n-뷰틸아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [6e](5) 4-n-butylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [6e]

상기 [4]와 n-뷰틸아민으로부터 옅은 노란색의 고체상 화합물 [6e]를 얻었다.A pale yellow solid compound [6e] was obtained from the above [4] and n-butylamine.

Yield: 91%; ¹H NMR (400 MHz, DMSO-d₆) δ 0.90 (t, J = 7.3 Hz, 3H), 1.30-1.39 (m, 2H), 1.52-1.59 (m, 2H), 2.44 (s, 3H), 3.44 (quar, J = 6.5 Hz, 2H), 7.99 (s, 1H), 8.16 (s, 1H), 13.1 (s, 1H); ¹³C NMR (400 MHz, DMSO-d₆) δ 13.9, 14.1, 20.1, 31.3, 98.1, 132.9, 155.4, 155.7, 168.6.
Yield: 91%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.90 (t, J = 7.3 Hz, 3H), 1.30-1.39 (m, 2H), 1.52-1.59 (m, 2H), 2.44 (s, 3H), 3.44 (quar, J = 6.5 Hz, 2H), 7.99 (s, 1H), 8.16 (s, 1H), 13.1 (s, 1H); ¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 13.9, 14.1, 20.1, 31.3, 98.1, 132.9, 155.4, 155.7, 168.6.

(6) 4-(1-하이드록시에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [6f](6) 4- (1-hydroxyethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [6f]

상기 [4]와 1-하이드록시에틸아민으로부터 옅은 노란색의 고체상 화합물 [6f]를 얻었다.The pale yellow solid compound [6f] was obtained from the above [4] and 1-hydroxyethylamine.

Yield: 84%; ¹H NMR (400 MHz, DMSO-d₆) δ 2.44 (s, 3H), 3.48-3.57 (m, 4H), 4.83 (t, J = 4.5 Hz, 1H), 8.02 (s, 1H), 8.25 (s, 1H), 13.16 (s, 1H); ¹³C NMR (100 MHz, DMSO-d₆) δ 13.9, 43.1, 59.9, 98.2, 133.0, 155.5, 155.9, 168.5.
Yield: 84%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.44 (s, 3H), 3.48-3.57 (m, 4H), 4.83 (t, J = 4.5 Hz, 1H), 8.02 (s, 1H), 8.25 ( s, 1 H), 13.16 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 43.1, 59.9, 98.2, 133.0, 155.5, 155.9, 168.5.

(7) 4-(2-피페리딘-1-일)에틸아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [6g](7) 4- (2-piperidin-1-yl) ethylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [6g]

상기 [4]와 2-(피페리딘-1-일)에틸아민으로부터 옅은 노란색의 고체상 화합물 [6g]를 얻었다.A pale yellow solid compound [6 g] was obtained from the above [4] and 2- (piperidin-1-yl) ethylamine.

Yield: 44%; ¹H NMR (400 MHz, DMSO-d₆) δ 1.36 (d, J = 5.0Hz, 2H), 1.47 (quin, J = 5.3 Hz, 4H), 2.37 (s, 4H), 2.44 (s, 3H), 3.54 (quar, J = 6.4 Hz, 2H), 7.99 (s, 1H), 8.16 (s, 1H), 13.19 (s, 1H); ¹³C NMR (100 MHz, DMSO-d₆) δ 13.9, 24.5, 26.0, 37.9, 54.6, 58.0, 98.2, 132.7, 155.6, 155.8, 168.5.
Yield: 44%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.36 (d, J = 5.0 Hz, 2H), 1.47 (quin, J = 5.3 Hz, 4H), 2.37 (s, 4H), 2.44 (s, 3H) , 3.54 (quar, J = 6.4 Hz, 2H), 7.99 (s, 1H), 8.16 (s, 1H), 13.19 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 24.5, 26.0, 37.9, 54.6, 58.0, 98.2, 132.7, 155.6, 155.8, 168.5.

(8) 4-(피리딘-2-일)메틸아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [6h](8) 4- (pyridin-2-yl) methylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [6h]

상기 [4]와 (피리딘-2-일)메틸아민으로부터 옅은 노란색의 고체상 화합물 [6h]를 얻었다.A pale yellow solid compound [6h] was obtained from the above [4] and (pyridin-2-yl) methylamine.

Yield: 49%; ¹H NMR (400 MHz, DMSO-d₆) δ 2.31 (s, 3H), 4.76 (d, J = 5.7 Hz, 2H), 7.26 (t, J = 6.1 Hz, 1H), 7.34 (d, J = 7.8 Hz, 1H), 7.74 (t, J = 7.5 Hz, 1H), 8.07 (s, 1H), 8.52 (d, J = 7.5 Hz, 1H), 8.86 (s, 1H), 13.2 (s, 1H).
Yield: 49%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.31 (s, 3H), 4.76 (d, J = 5.7 Hz, 2H), 7.26 (t, J = 6.1 Hz, 1H), 7.34 (d, J = 7.8 Hz, 1H), 7.74 (t, J = 7.5 Hz, 1H), 8.07 (s, 1H), 8.52 (d, J = 7.5 Hz, 1H), 8.86 (s, 1H), 13.2 (s, 1H) .

(9) 4-(3-메톡시벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [6i](9) 4- (3-methoxybenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [6i]

상기 [4]와 3-메톡시벤질아민으로부터 옅은 노란색의 고체상 화합물 [6i]를 얻었다.A pale yellow solid compound [6i] was obtained from the above [4] and 3-methoxybenzylamine.

Yield: 59%; ¹H NMR (400 MHz, DMSO-d₆) δ 2.43 (s, 3H), 3.71 (s, 3H), 4.65 (d, J = 5.7Hz, 2H), 6.82 (d, J = 7.0Hz, 1H), 6.89 (d, J = 9.4Hz, 2H), 7.24 (t, J = 7.8Hz, 1H), 8.03 (s, 1H), 8.72 (t, J = 5.3Hz, 1H), 13.23 (s, 1H).
Yield: 59%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.43 (s, 3H), 3.71 (s, 3H), 4.65 (d, J = 5.7 Hz, 2H), 6.82 (d, J = 7.0 Hz, 1H) , 6.89 (d, J = 9.4 Hz, 2H), 7.24 (t, J = 7.8 Hz, 1H), 8.03 (s, 1H), 8.72 (t, J = 5.3 Hz, 1H), 13.23 (s, 1H) .

(10) 4-(1-사이클로헥실에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [6j](10) 4- (1-cyclohexylethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [6j]

상기 [4]와 1-사이클로헥실에틸아민으로부터 옅은 노란색의 고체상 화합물 [6j]를 얻었다.A pale yellow solid compound [6j] was obtained from the above [4] and 1-cyclohexylethylamine.

Yield: 59%; ¹H NMR (400MHz, DMSO-d₆) δ 0.94-1.00 (m, 2H), 1.13 (d, J = 6.2Hz, 3H), 1.13 (br s, 3H), 1.43-1.76 (m, 6H), 2.42 (s, 3H), 4.17 (quar, J = 6.8Hz, 1H), 7.91 (d, J = 8.4Hz, 1H), 8.04 (s, 1H), 13.12 (s, 1H).
Yield: 59%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.94-1.00 (m, 2H), 1.13 (d, J = 6.2 Hz, 3H), 1.13 (br s, 3H), 1.43-1.76 (m, 6H), 2.42 (s, 3H), 4.17 (quar, J = 6.8 Hz, 1H), 7.91 (d, J = 8.4 Hz, 1H), 8.04 (s, 1H), 13.12 (s, 1H).

(11) (R)-4-(1-페닐에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [6k](11) (R) -4- (1-phenylethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [6k]

상기 [4]와 (R)-1-페닐에틸아민으로부터 옅은 노란색의 고체상 화합물 [6k]를 얻었다.A pale yellow solid compound [6k] was obtained from the above [4] and (R) -1-phenylethylamine.

Yield: 77%; ¹H NMR (400 MHz, DMSO-d₆) δ 1.51 (d, J = 7.0Hz, 3H), 2.37 (s, 3H), 5.42 (t, J = 7.1Hz, 1H), 7.21 (t, J = 7.2Hz, 1H), 7.31 (t, J = 7.5Hz, 2H), 7.38 (d, J = 7.4Hz, 2H), 8.09 (s, 1H), 8.59 (d, J = 7.5Hz, 1H), 13.1 (s, 1H); ¹³C NMR (100 MHz, DMSO-d₆) δ 13.9, 22.8, 49.4, 98.1, 126.5, 127.1, 128.7, 133.1, 145.1, 154.8, 155.6, 168.4.
Yield: 77%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.51 (d, J = 7.0 Hz, 3H), 2.37 (s, 3H), 5.42 (t, J = 7.1 Hz, 1H), 7.21 (t, J = 7.2 Hz, 1H), 7.31 (t, J = 7.5 Hz, 2H), 7.38 (d, J = 7.4 Hz, 2H), 8.09 (s, 1H), 8.59 (d, J = 7.5 Hz, 1H), 13.1 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 22.8, 49.4, 98.1, 126.5, 127.1, 128.7, 133.1, 145.1, 154.8, 155.6, 168.4.

(12) 4-(2-하이드록시-1-다이메틸에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [6l](12) 4- (2-hydroxy-1-dimethylethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [6l]

상기 [4]와 1-하이드록시-2-다이메틸에틸아민으로부터 옅은 노란색의 고체상 화합물 [6l]을 얻었다.A pale yellow solid compound [6l] was obtained from the above [4] and 1-hydroxy-2-dimethylethylamine.

Yield: 72%; ¹H NMR (400MHz, DMSO-d₆) δ 1.38 (s, 6H), 2.44 (s, 3H), 3.65 (d, J = 5.7Hz, 2H), 4.93 (t, J = 5.4Hz, 1H), 7.40 (s, 1H), 8.12 (s, 1H), 13.11 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.1, 24.5, 56.4, 67.1, 98.7, 133.4, 155.4, 155.7, 167.8.
Yield: 72%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.38 (s, 6H), 2.44 (s, 3H), 3.65 (d, J = 5.7 Hz, 2H), 4.93 (t, J = 5.4 Hz, 1H), 7.40 (s, 1 H), 8.12 (s, 1 H), 13.11 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.1, 24.5, 56.4, 67.1, 98.7, 133.4, 155.4, 155.7, 167.8.

(13) 4-(3-이미다졸-1-일)프로판아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [6m](13) 4- (3-imidazol-1-yl) propanamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [6m]

상기 [4]와 (3-이미다졸-1-일)프로판아민으로부터 옅은 노란색의 고체상 화합물 [6m]을 얻었다.A pale yellow solid compound [6m] was obtained from the above [4] and (3-imidazol-1-yl) propanamine.

Yield: 18%; ¹H NMR (400MHz, DMSO-d₆) δ 2.02 (t, J = 6.9Hz, 2H), 2.42 (s, 3H), 3.40 (quar, J = 6.2Hz, 2H), 4.04 (t, J = 6.7Hz, 2H), 6.88 (s, 1H), 7.20 (s, 1H), 7.64 (s, 1H), 8.23 (s, 1H).
Yield: 18%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.02 (t, J = 6.9 Hz, 2H), 2.42 (s, 3H), 3.40 (quar, J = 6.2 Hz, 2H), 4.04 (t, J = 6.7 Hz, 2H), 6.88 (s, 1H), 7.20 (s, 1H), 7.64 (s, 1H), 8.23 (s, 1H).

(14) 4-(4-메틸피페라지노)-6-(메틸티오)피라졸로[3,4-d]피리미딘 [6n](14) 4- (4-methylpiperazino) -6- (methylthio) pyrazolo [3,4-d] pyrimidine [6n]

상기 [4]와 4-메틸피페라진으로부터 옅은 노란색의 고체상 화합물 [6n]을 얻었다.A pale yellow solid compound [6n] was obtained from the above [4] and 4-methylpiperazine.

Yield: 93%; ¹H NMR (400MHz, CDCl₃) δ 2.39 (s, 3H), 2.59 (d, J = 5.0Hz, 4H), 2.60 (s, 3H), 4.02 (m, 4H), 7.93 (s, 1H); ¹³C NMR (100MHz, CDCl₃) δ 14.2, 45.9, 50.4, 54.5, 97.8, 133.7, 155.8, 156.8, 168.9.
Yield: 93%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 2.39 (s, 3H), 2.59 (d, J = 5.0 Hz, 4H), 2.60 (s, 3H), 4.02 (m, 4H), 7.93 (s, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 14.2, 45.9, 50.4, 54.5, 97.8, 133.7, 155.8, 156.8, 168.9.

(15) 4-(디-2-하이드로에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [6o](15) 4- (di-2-hydroethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [6o]

상기 [4]와 디에탄올아민으로부터 하얀색의 고체상 화합물 [6o]를 얻었다.From the above [4] and diethanolamine, a white solid compound [6o] was obtained.

Yield: 92%; ¹H NMR (400MHz, DMSO-d₆) δ 2.44 (s, 3H), 3.66 (br s, 4H), 3.79 (br s, 4H), 4.78 (s, 1H), 4.97 (s, 1H), 7.97 (s, 1H), 13.26 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.9, 52.0, 53.1, 58.9, 97.4, 134.5, 155.9, 156.5, 167.5.
Yield: 92%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.44 (s, 3H), 3.66 (br s, 4H), 3.79 (br s, 4H), 4.78 (s, 1H), 4.97 (s, 1H), 7.97 (s, 1 H), 13.26 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 52.0, 53.1, 58.9, 97.4, 134.5, 155.9, 156.5, 167.5.

(16) 4-(4-클로로벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [6p](16) 4- (4-chlorobenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [6p]

상기 [4]와 4-클로로벤질아민으로부터 옅은 노란색의 고체상 화합물 [6p]를 얻었다.A pale yellow solid compound [6p] was obtained from the above [4] and 4-chlorobenzylamine.

Yield: 93%; ¹H NMR (400MHz, DMSO-d₆) δ 2.41 (s, 3H), 4.67 (d, J = 5.7Hz, 2H), 7.34-7.39 (m, 3H), 8.02 (s, 1H), 8.76 (t, J = 5.3Hz, 1H), 13.24 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 42.9, 98.1, 128.7, 129.7, 131.9, 132.9, 138.8, 155.6, 168.6.
Yield: 93%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.41 (s, 3H), 4.67 (d, J = 5.7 Hz, 2H), 7.34-7.39 (m, 3H), 8.02 (s, 1H), 8.76 (t , J = 5.3 Hz, 1H), 13.24 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 42.9, 98.1, 128.7, 129.7, 131.9, 132.9, 138.8, 155.6, 168.6.

(17) 4-(4-메틸벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [6q](17) 4- (4-methylbenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [6q]

상기 [4]와 4-메틸벤질아민으로부터 하얀색의 고체상 화합물 [6q]를 얻었다.White solid compound [6q] was obtained from the above [4] and 4-methylbenzylamine.

Yield: 75%; ¹H NMR (400MHz, DMSO-d₆) δ 2.20 (s, 3H), 2.42 (s, 3H), 4.63 (d, J = 5.6Hz, 2H), 7.13 (d, J = 7.8Hz, 2H), 7.23 (t, J = 7.9Hz, 2H), 8.02 (s, 1H), 8.68 (s, 1H), 13.21 (s, 1H).
Yield: 75%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.20 (s, 3H), 2.42 (s, 3H), 4.63 (d, J = 5.6 Hz, 2H), 7.13 (d, J = 7.8 Hz, 2H), 7.23 (t, J = 7.9 Hz, 2H), 8.02 (s, 1H), 8.68 (s, 1H), 13.21 (s, 1H).

(18) 4-(2-메틸벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [6r](18) 4- (2-methylbenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [6r]

상기 [4]와 2-메틸벤질아민으로부터 하얀색의 고체상 화합물 [6r]을 얻었다.White solid compound [6r] was obtained from the above [4] and 2-methylbenzylamine.

Yield: 80%; ¹H NMR (400MHz, DMSO-d₆) δ 2.32 (s, 3H), 2.42 (s, 3H), 4.65 (d, J = 5.4Hz, 2H), 7.14-7.17 (m, 3H), 7.28 (d, J = 5.9Hz, 1H), 8.06 (s, 1H), 8.56 (s, 1H), 13.2 (s, 1H).
Yield: 80%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.32 (s, 3H), 2.42 (s, 3H), 4.65 (d, J = 5.4 Hz, 2H), 7.14-7.17 (m, 3H), 7.28 (d , J = 5.9 Hz, 1H), 8.06 (s, 1H), 8.56 (s, 1H), 13.2 (s, 1H).

(19) 4-피페리디노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [6s](19) 4-piperidino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [6s]

상기 [4]와 피페리딘으로부터 옅은 노란색의 고체상 화합물 [6s]를 얻었다.A pale yellow solid compound [6s] was obtained from [4] and piperidine.

Yield: 98%; ¹H NMR (400MHz, DMSO-d₆) δ 1.59 (d, J = 3.5Hz, 4H), 1.66 (d, J = 4.4Hz, 2H), 2.44 (s, 3H), 3.85 (d, J = 5.2Hz, 4H), 8.14 (s, 1H), 13.3 (br s, 1H); ¹³C NMR (400MHz, DMSO-d₆) δ 13.9, 24.3, 25.8, 97.4, 134,2, 155.5, 156.9, 167.6.
Yield: 98%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.59 (d, J = 3.5 Hz, 4H), 1.66 (d, J = 4.4 Hz, 2H), 2.44 (s, 3H), 3.85 (d, J = 5.2 Hz, 4H), 8.14 (s, 1 H), 13.3 (br s, 1 H); ¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 13.9, 24.3, 25.8, 97.4, 134,2, 155.5, 156.9, 167.6.

(20) 4-사이클로헥실아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [6t](20) 4-cyclohexylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [6t]

상기 [4]와 사이클로헥실아민으로부터 하얀색의 고체상 화합물 [6t]를 얻었다.From the above [4] and cyclohexylamine, a white solid compound [6t] was obtained.

Yield: 57%; ¹H NMR (400MHz, DMSO-d₆) δ 1.13-1.37 (m, 6H), 1.61 (d, J = 12.5Hz, 1H), 1.74 (d, J = 10.0Hz, 2H), 1.93 (d, J = 9.9Hz, 2H), 2.43 (s, 3H), 3.98 (br s, 1H), 7.98 (d, J = 7.6Hz, 1H), 8.02 (s, 1H), 13.14 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.9, 25.2, 25.7, 32.8, 49.2, 99.1, 133.0, 154.9, 155.5, 168.9.
Yield: 57%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.13-1.37 (m, 6H), 1.61 (d, J = 12.5 Hz, 1H), 1.74 (d, J = 10.0 Hz, 2H), 1.93 (d, J = 9.9 Hz, 2H), 2.43 (s, 3H), 3.98 (br s, 1H), 7.98 (d, J = 7.6 Hz, 1H), 8.02 (s, 1H), 13.14 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 25.2, 25.7, 32.8, 49.2, 99.1, 133.0, 154.9, 155.5, 168.9.

(21) 4-다이에틸아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [6u](21) 4-diethylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [6u]

상기 [4]와 다이에틸아민으로부터 옅은 노란색의 고체상 화합물 [6u]를 얻었다.A pale yellow solid compound [6u] was obtained from the above [4] and diethylamine.

Yield: 85%; ¹H NMR (400MHz, CDCl₃) δ 1.27 (br s, 6H), 2.63 (s, 3H), 3.66 (br s, 4H), 7.84 (s, 1H), 12.72 (br s, 1H); ¹³C NMR (100MHz, CDCl₃) δ 13.0, 14.2, 43.8, 97.4, 134.3, 155.1, 156.5, 168.9.
Yield: 85%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 1.27 (br s, 6H), 2.63 (s, 3H), 3.66 (br s, 4H), 7.84 (s, 1H), 12.72 (br s, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 13.0, 14.2, 43.8, 97.4, 134.3, 155.1, 156.5, 168.9.

(22) 4-(2-메톡시벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [6v](22) 4- (2-methoxybenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [6v]

상기 [4]와 2-메톡시벤질아민으로부터 옅은 노란색의 고체상 화합물 [6v]를 얻었다.A pale yellow solid compound [6v] was obtained from the above [4] and 2-methoxybenzylamine.

Yield: 66%; ¹H NMR (400MHz, DMSO-d₆) δ 2.40 (s, 3H), 3.81 (s, 3H), 4.63 (d, J = 5.5Hz, 2H), 6.88 (t, J = 7.3Hz, 1H), 7.00 (d, J = 7.3Hz, 2H), 7.21-7.26 (m, 2H), 8.06 (s, 1H), 8.54 (s, 1H), 13.2 (s, 1H).
Yield: 66%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.40 (s, 3H), 3.81 (s, 3H), 4.63 (d, J = 5.5 Hz, 2H), 6.88 (t, J = 7.3 Hz, 1H), 7.00 (d, J = 7.3 Hz, 2H), 7.21-7.26 (m, 2H), 8.06 (s, 1H), 8.54 (s, 1H), 13.2 (s, 1H).

(23) N-(2-클로로벤질)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [6w](23) N- (2-chlorobenzyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [6w]

상기 [4]와 2-클로로벤질아민으로부터 하얀색의 고체상 화합물 [6w]를 얻었다.White solid compound [6w] was obtained from the above [4] and 2-chlorobenzylamine.

Yield: 92.03%; ¹H NMR (400MHz, DMSO-d₆) δ 2.40 (s, 3H), 4.76 (d, J = 5.5Hz, 2H), 7.30-7.33 (m, 2H), 7.40-7.42 (m, 1H), 7.47-7.49 (m, 1H), 8.09 (s, 1H), 8.75 (s, 1H), 13.28 (s, 1H); ₁₃C NMR (100MHz, DMSO-d₆) δ 13.3, 23.9, 33.2, 43.0, 97.6, 127.1, 128.7, 129.1, 132.1, 136.0, 155.1, 168.0, 174.2.
Yield: 92.03%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.40 (s, 3H), 4.76 (d, J = 5.5 Hz, 2H), 7.30-7.33 (m, 2H), 7.40-7.42 (m, 1H), 7.47 -7.49 (m, 1 H), 8.09 (s, 1 H), 8.75 (s, 1 H), 13.28 (s, 1 H); ₁₃ C NMR (100 MHz, DMSO-d ₆ ) δ 13.3, 23.9, 33.2, 43.0, 97.6, 127.1, 128.7, 129.1, 132.1, 136.0, 155.1, 168.0, 174.2.

(24) N-(4-메톡시벤질)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [6x](24) N- (4-methoxybenzyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [6x]

상기 [4]와 4-메톡시벤질아민으로부터 옅은 노란색의 고체상 화합물 [6x]를 얻었다.A pale yellow solid compound [6x] was obtained from the above [4] and 4-methoxybenzylamine.

Yield: 95.44%; ¹H NMR (400MHz, DMSO-d₆) δ 2.47 (s, 3H), 3.73 (s, 3H), 4.64 (d, J = 5.0 Hz, 2H), 6.91 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.0Hz, 2H), 8.06 (s, 1H), 8.68 (s, 1H), 13.25 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 13.9, 20.6, 42.6, 54.9, 59.6, 97.6, 113.7, 128.8, 131.0, 132.4, 155.0, 158.3, 168.1.
Yield: 95.44%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.47 (s, 3H), 3.73 (s, 3H), 4.64 (d, J = 5.0 Hz, 2H), 6.91 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 8.06 (s, 1H), 8.68 (s, 1H), 13.25 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 13.9, 20.6, 42.6, 54.9, 59.6, 97.6, 113.7, 128.8, 131.0, 132.4, 155.0, 158.3, 168.1.

(25) 6-(메틸티오)-N-((피리딘-2-일)메틸)-1H-피라졸로[3,4-d]피리미딘-4-아민 [6y](25) 6- (methylthio) -N-((pyridin-2-yl) methyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [6y]

상기 [4]와 (피리딘-2-일)메탄아민으로부터 노란색의 고체상 화합물 [6y]를 얻었다.The yellow solid compound [6y] was obtained from the above [4] and (pyridin-2-yl) methanamine.

Yield: 96.02%; ¹H NMR (400MHz, DMSO-d₆) δ 2.39 (s, 3H), 4.79 (d, J = 5.5Hz, 2H), 7.32 (dd, J = 7.1Hz, 29.0Hz, 2H), 7.75 (t, J = 5.6Hz, 1H), 8.09 (s, 1H), 8.54 (d, J = 2.8Hz, 1H), 8.88 (s, 1H), 13.26 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 45.1, 97.7, 98.6, 121.3, 122.1, 132.5, 136.6, 148.9, 155.1, 155.2, 158.4, 168.0.
Yield: 96.02%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.39 (s, 3H), 4.79 (d, J = 5.5 Hz, 2H), 7.32 (dd, J = 7.1 Hz, 29.0 Hz, 2H), 7.75 (t, J = 5.6 Hz, 1H), 8.09 (s, 1H), 8.54 (d, J = 2.8 Hz, 1H), 8.88 (s, 1H), 13.26 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 45.1, 97.7, 98.6, 121.3, 122.1, 132.5, 136.6, 148.9, 155.1, 155.2, 158.4, 168.0.

실시예 5. [7a] 내지 [7b]의 합성Example 5. Synthesis of [7a] to [7b]

(1) 6-(메틸티오)피라졸로[3,4-d]피리미딘 [7a](1) 6- (methylthio) pyrazolo [3,4-d] pyrimidine [7a]

하기 [반응식 6](반응조건 10% Pd/C, NH₄OH, abs. EtOH, H₂(g), 상온, 24 h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [7a]를 합성하였다. (R=H)Synthesized pyrazolopyrimidine derivative compounds [7a] according to the present invention by the following Reaction Scheme 6 (reaction conditions 10% Pd / C, NH ₄ OH, abs.EtOH, H ₂ (g), room temperature, 24 h) It was. (R = H)

[반응식 6][Reaction Scheme 6]

[4] [7a][4] [7a]

ethanol (6 mL)에 상기 [4] (80 mg, 0.398 mmol)와 10% Pd/C (1 eq. 31 mg)을 넣은 후, NH₄OH (5.5%, 0.33 mL)를 가하였다. 수분이 제거된 용기에 H_{2 (g)}를 연결한 후 24 시간 동안 상온에서 교반하였다. 24 시간 후에는 H_{2 (g)}를 제거하고, 반응 혼합물을 celite 545에 여과하여 10% Pd/C을 제거한 후에, 여과액의 부피를 줄였다. 이렇게 얻은 반응 혼합물을 flash chromatography (hexanes : EtOAc = 4 : 1)로 분리하면 옅은 노란색의 고체상 화합물 [7a]를 얻었다.To ethanol (6 mL) [4] (80 mg, 0.398 mmol) and 10% Pd / C (1 eq. 31 mg) were added, followed by NH ₄ OH (5.5%, 0.33 mL). H _{2 (g)} was connected to the vessel from which the water was removed, followed by stirring at room temperature for 24 hours. After 24 hours, H _{2 (g)} was removed and the reaction mixture was filtered through celite 545 to remove 10% Pd / C, after which the volume of the filtrate was reduced. The reaction mixture thus obtained was separated by flash chromatography (hexanes: EtOAc = 4: 1) to obtain a pale yellow solid compound [7a].

Yield: 33%; ¹H NMR (400MHz, DMSO-d₆) δ 2.55 (s, 3H), 8.23 (s, 1H), 9.11 (s, 1H), 13.88 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.1, 111.0, 134.5, 153.3, 155.0, 169.0.
Yield: 33%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.55 (s, 3H), 8.23 (s, 1H), 9.11 (s, 1H), 13.88 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.1, 111.0, 134.5, 153.3, 155.0, 169.0.

(2) 1-페닐-6-(메틸티오)피라졸로[3,4-d]피리미딘 [7b](2) 1-phenyl-6- (methylthio) pyrazolo [3,4-d] pyrimidine [7b]

하기 [반응식 7](반응조건 10% Pd/C, NH₄OH, abs. EtOH, H₂(g), 상온, 24 h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [7b]를 합성하였다. (R=Ph)The pyrazolopyrimidine derivative compound [7b] according to the present invention was synthesized by the following [Scheme 7] (reaction conditions 10% Pd / C, NH ₄ OH, abs.EtOH, H ₂ (g), room temperature, 24 h). It was. (R = Ph)

[반응식 7][Reaction Scheme 7]

[5e] [7b][5e] [7b]

상기 [5e]를 이용하여 옅은 노란색의 고체상 화합물 [7b]를 얻었다.Using [5e], a pale yellow solid compound [7b] was obtained.

Yield: 25%; ¹H NMR (400MHz, DMSO-d₆) δ 2.49 (s, 3H), 7.37 (t, J = 6.9Hz, 1H), 7.58 (t, J = 8.0Hz, 2H), 8.19 (d, J = 7.7Hz, 2H), 8.51 (s, 1H), 9.20 (s, 1H); ¹³C NMR (400MHz, DMSO-d₆) δ 14.3, 29.4, 113.1, 121.0, 127.0, 129.8, 136.1, 138.6, 152.8, 154.1, 170.5.
Yield: 25%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.49 (s, 3H), 7.37 (t, J = 6.9 Hz, 1H), 7.58 (t, J = 8.0 Hz, 2H), 8.19 (d, J = 7.7 Hz, 2H), 8.51 (s, 1 H), 9.20 (s, 1 H); ¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 14.3, 29.4, 113.1, 121.0, 127.0, 129.8, 136.1, 138.6, 152.8, 154.1, 170.5.

실시예 6. [8a] 내지 [8b]의 합성Example 6. Synthesis of [8a] to [8b]

하기 [반응식 8](반응조건 10% Pd/C, NH₄OH, abs. EtOH, H₂(g), 상온, 24 h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [8a] 내지 [8d]를 합성하였다. ([8a] R=H; [8b] R=Ph)Pyrazolopyrimidine derivative compounds [8a] to [following scheme 8] (reaction conditions 10% Pd / C, NH ₄ OH, abs.EtOH, H ₂ (g), room temperature, 24 h) 8d] was synthesized. ([8a] R = H; [8b] R = Ph)

[반응식 8][Reaction Scheme 8]

[4], [5e] [8a] ~ [8b]     [4], [5e] [8a]-[8b]

(1) 6-(메틸티오)피라졸로[3,4-d]피리미딘-4-온 [8a](1) 6- (methylthio) pyrazolo [3,4-d] pyrimidin-4-one [8a]

상기 [4] (100 mg, 0.498 mmol)을 2N NaOH 수용액 (10 mL)에 넣은 후, 24 시간 동안 reflux를 시켰다. 24 시간 후 상온으로 냉각을 시키고, 진한 염산으로 pH 5로 조절하면 침전물이 형성되었다. 그 침전물을 여과하여 모은 후 물로 여러 번 씻어주고, 옅은 노란색의 고체상 화합물 [8a]를 얻었다.[4] (100 mg, 0.498 mmol) was added to a 2N NaOH aqueous solution (10 mL), followed by reflux for 24 hours. After 24 hours, the mixture was cooled to room temperature, and adjusted to pH 5 with concentrated hydrochloric acid to form a precipitate. The precipitate was collected by filtration and washed several times with water to obtain a pale yellow solid compound [8a].

Yield: 63%; ¹H NMR (400MHz, DMSO-d₆) δ 2.51 (s, 3H), 8.23 (s, 1H), 12.24 (s, 1H), 13.56 (s, 1H); ¹³C NMR (400MHz, DMSO-d₆) δ 13.3, 103.1, 134.5, 153.3, 158.6, 160.3.
Yield: 63%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.51 (s, 3H), 8.23 (s, 1H), 12.24 (s, 1H), 13.56 (s, 1H); ¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 13.3, 103.1, 134.5, 153.3, 158.6, 160.3.

(2) 1-페닐-6-(메틸티오)피라졸로[3,4-d]피리미딘-4-온 [8b](2) 1-phenyl-6- (methylthio) pyrazolo [3,4-d] pyrimidin-4-one [8b]

상기 [5e]를 이용하여 옅은 노란색의 고체상 화합물 [8b]를 얻었다.Using [5e], a pale yellow solid compound [8b] was obtained.

Yield: 84%; ¹H NMR (400MHz, DMSO-d₆) δ 2.57 (s, 3H), 7.36 (t, J = 7.9Hz, 1H), 7.54 (t, J = 7.8Hz, 2H), 8.08 (d, J = 8.5Hz, 2H), 8.22 (d, J = 1.0Hz, 1H), 12.7 (s, 1H); ¹³C NMR (400MHz, DMSO-d₆) δ 13.6, 104.9, 121.6, 127.2, 129.6, 136.5, 138.8, 151.9, 157.8, 162.1.
Yield: 84%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.57 (s, 3H), 7.36 (t, J = 7.9 Hz, 1H), 7.54 (t, J = 7.8 Hz, 2H), 8.08 (d, J = 8.5 Hz, 2H), 8.22 (d, J = 1.0 Hz, 1H), 12.7 (s, 1H); ¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 13.6, 104.9, 121.6, 127.2, 129.6, 136.5, 138.8, 151.9, 157.8, 162.1.

실시예 7. [9a] 내지 [9d]의 합성Example 7. Synthesis of [9a] to [9d]

하기 [반응식 9](반응조건 Thiourea, abs. EtOH, reflux, 4h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [9a] 내지 [9d]를 합성하였다. ([9a] R=H; [9b] R=Ph, [9c] R=Bn; [9d] R=t-Butyl)The pyrazolopyrimidine derivative compounds [9a] to [9d] were synthesized according to the following Reaction Scheme 9 (reaction conditions Thiourea, abs. EtOH, reflux, 4h). ([9a] R = H; [9b] R = Ph, [9c] R = Bn; [9d] R = t-Butyl)

[반응식 9][Reaction Scheme 9]

[4], [5e], [5f], [5g] [9a] ~ [9d][4], [5e], [5f], [5g] [9a]-[9d]

(1) 6-(메틸티오)피라졸로[3,4-d]피리미딘-4-티온 [9a](1) 6- (methylthio) pyrazolo [3,4-d] pyrimidin-4-thione [9a]

상기 [4] (100 mg, 0.498 mmol)와 Thiourea (1.1 eq, 41 mg)를 ethanol (10 mL)에 넣고 4 시간 동안 reflux를 하였다. 4 시간 후에는 반응 혼합물의 용매는 감압기화를 시켜서 제거하였고, 남아있는 고체는 물로 여러 번 씻어내어 황토색의 고체상 화합물 [9a]를 얻었다.[4] (100 mg, 0.498 mmol) and Thiourea (1.1 eq, 41 mg) were added to ethanol (10 mL) and refluxed for 4 hours. After 4 hours, the solvent of the reaction mixture was removed by evaporation under reduced pressure, and the remaining solid was washed several times with water to obtain an ocher solid compound [9a].

Yield: 73%; ¹H NMR (400MHz, DMSO-d₆) δ 2.53 (s, 3H), 8.05 (s, 1H), 13.73 (s, 1H), 13.80 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.5, 114.6, 137.9, 148.6, 160.5, 180.3.
Yield: 73%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.53 (s, 3H), 8.05 (s, 1H), 13.73 (s, 1H), 13.80 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.5, 114.6, 137.9, 148.6, 160.5, 180.3.

(2) 1-페닐-6-(메틸티오)피라졸로[3,4-d]피리미딘-4-티온 [9b](2) 1-phenyl-6- (methylthio) pyrazolo [3,4-d] pyrimidin-4-thione [9b]

상기 [5e]와 Thiourea으로부터 옅은 갈색의 고체상 화합물 [15a]를 얻었다.A pale brown solid compound [15a] was obtained from [5e] and Thiourea.

Yield: 85%; ¹H NMR (400MHz, DMSO-d₆) δ 2.59 (s, 3H), 7.39 (t, J = 7.4Hz, 1H), 7.56 (t, J = 7.2Hz, 2H), 8.07 (d, J = 8.6Hz, 2H), 8.32 (s, 1H), 14.05 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.7, 99.1, 116.5, 121.6, 127.5, 129.7, 138.4, 138.5, 161.9, 180.3.
Yield: 85%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.59 (s, 3H), 7.39 (t, J = 7.4 Hz, 1H), 7.56 (t, J = 7.2 Hz, 2H), 8.07 (d, J = 8.6 Hz, 2H), 8.32 (s, 1 H), 14.05 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.7, 99.1, 116.5, 121.6, 127.5, 129.7, 138.4, 138.5, 161.9, 180.3.

(3) 1-벤질-6-(메틸티오)피라졸로[3,4-d]피리미딘-4-티온 [9c](3) 1-benzyl-6- (methylthio) pyrazolo [3,4-d] pyrimidin-4-thione [9c]

상기 [5f]와 Thiourea로부터 옅은 갈색의 고체상 화합물 [9c]를 얻었다.Light brown solid compound [9c] was obtained from [5f] and Thiourea.

Yield: 85%; ¹H NMR (400MHz, DMSO-d₆) δ 2.58 (s, 3H), 5.45 (s, 2H), 7.27-7.35 (m, 4H), 13.85 (s, 1H).
Yield: 85%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.58 (s, 3H), 5.45 (s, 2H), 7.27-7.35 (m, 4H), 13.85 (s, 1H).

(4) 1-t-뷰틸-6-(메틸티오)피라졸로[3,4-d]피리미딘-4-티온 [9d](4) 1-t-butyl-6- (methylthio) pyrazolo [3,4-d] pyrimidin-4-thione [9d]

상기 [5g]와 Thiourea로부터 옅은 갈색의 고체상 화합물 [9d]를 얻었다.A light brown solid compound [9d] was obtained from [5 g] and Thiourea.

Yield: 71%; ¹H NMR (400MHz, DMSO-d₆) δ 1.57 (s, 9H), 2.51 (s, 3H), 8.51 (s, 1H), 13.43 (s, 1H); ¹³C NMR (400MHz, DMSO-d₆) δ 13.4, 29.5, 61.2, 115.0, 128.6, 153.1, 158.0, 182.7.
Yield: 71%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.57 (s, 9H), 2.51 (s, 3H), 8.51 (s, 1H), 13.43 (s, 1H); ¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 13.4, 29.5, 61.2, 115.0, 128.6, 153.1, 158.0, 182.7.

실시예 8. [10a] 내지 [10b]의 합성Example 8. Synthesis of [10a] to [10b]

하기 [반응식 10](반응조건 1M. NaOR/ROH, reflux, 6h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [10a] 내지 [10b]를 합성하였다. ([10a] R=Me; [10b] R=Et)The pyrazolopyrimidine derivative compounds [10a] to [10b] were synthesized according to the following Reaction Scheme 10 (reaction conditions 1 M. NaOR / ROH, reflux, 6h). ([10a] R = Me; [10b] R = Et)

[반응식 10][Reaction Scheme 10]

(1) 4-메톡시-6-(메틸티오)피라졸로[3,4-d]피리미딘 [10a](1) 4-methoxy-6- (methylthio) pyrazolo [3,4-d] pyrimidine [10a]

1M sodium methoxide/methanol (10 mL)에 상기 [4] (100 mg, 0.498 mmol)을 넣은 후 6 시간 동안 reflux를 하였다. 시간이 지나면 상온으로 냉각을 시키고 Et₂O (7 mL)를 가하였다. 반응 혼합물에 있는 고체는 필터하여 제거하고, acetic acid를 사용하여 중성으로 조절한 후 용매를 농축하였다. 이렇게 얻은 고체는 물을 이용하여 씻어주고 하얀색의 고체상 화합물 [10a]를 얻었다.[4] (100 mg, 0.498 mmol) was added to 1M sodium methoxide / methanol (10 mL), followed by reflux for 6 hours. After the time was cooled to room temperature and Et ₂ O (7 mL) was added. The solid in the reaction mixture was filtered off, neutralized with acetic acid and the solvent was concentrated. The solid thus obtained was washed with water to obtain a white solid compound [10a].

Yield: 81%; ¹H NMR (400MHz, DMSO-d₆) δ 2.55 (s, 3H), 4.05 (s, 3H), 8.10 (s, 1H), 13.77 (s, 1H); ¹³C NMR (400MHz, DMSO-d₆) δ 14.1, 54.6, 132.4, 157.3, 162.8, 168.8.
Yield: 81%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.55 (s, 3H), 4.05 (s, 3H), 8.10 (s, 1H), 13.77 (s, 1H); ¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 14.1, 54.6, 132.4, 157.3, 162.8, 168.8.

(2) 4-에톡시-6-(메틸티오)피라졸로[3,4-d]피리미딘 [10b](2) 4-ethoxy-6- (methylthio) pyrazolo [3,4-d] pyrimidine [10b]

상기 [4]와 1M sodium ethoxide/ethanol (10 mL)를 사용하면 하얀색의 고체상 화합물 [10b]를 얻었다.[4] and 1M sodium ethoxide / ethanol (10 mL) were used to obtain a white solid compound [10b].

Yield: 57%; ¹H NMR (400MHz, DMSO-d₆) δ 1.39 (t, J = 7.3Hz, 3H), 2.52 (s, 3H), 4.52 (quar, J = 7.1Hz, 2H), 8.06 (s, 1H), 13.73 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.1, 14.6, 63.3, 99.3, 132.4, 157.4, 162.4, 168.8.
Yield: 57%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.39 (t, J = 7.3 Hz, 3H), 2.52 (s, 3H), 4.52 (quar, J = 7.1 Hz, 2H), 8.06 (s, 1H), 13.73 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.1, 14.6, 63.3, 99.3, 132.4, 157.4, 162.4, 168.8.

실시예 9. [11a] 내지 [11d]의 합성Example 9 Synthesis of [11a] to [11d]

하기 [반응식 11](반응조건 NIS, DMF, reflux, 30h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [11a] 내지 [11b]를 합성하였다.The pyrazolopyrimidine derivative compounds [11a] to [11b] according to the present invention were synthesized by the following Reaction Scheme 11 (reaction conditions NIS, DMF, reflux, 30h).

또한, 하기 [반응식 10](반응조건 NIS, ClCH₂CH₂Cl, reflux)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [11c] 내지 [11d]를 합성하였다.Further, pyrazolopyrimidine derivative compounds [11c] to [11d] according to the present invention were synthesized by the following Reaction Scheme 10 (reaction conditions NIS, ClCH ₂ CH ₂ Cl, reflux).

[반응식 11][Reaction Scheme 11]

[6a], [6f], [6u], [10a] [11a] ~ [11d][6a], [6f], [6u], [10a] [11a] to [11d]

[11a] 내지 [11d]에서 R은 각각 하기 [표 4]와 같다.R in [11a] to [11d] is as shown in Table 4 below, respectively.

구분division RR 구분division RR 11a11a

11c11c

11b11b

11d11d CH₃OCH ₃ O

(1) 3-아이오도-4-벤질아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [11a](1) 3-iodo-4-benzylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [11a]

상기 [6a] (70 mg, 0.258 mmol)와 N-iodosuccimide (2 eq, 116 mg)를 DMF (10 mL)에 넣고 reflux를 하였고, 12시간 후, 6시간 후 N-iodosuccimide (2 eq, 116 mg)을 더 넣어주고, 18 시간을 더 reflux를 하였다. 그 후에 용매를 감압증류하고, 남아있는 고체를 물로 여러 번 씻어준 다음 flash chromatography(hexanes : EtOAc = 1 : 1)로 분리하여 옅은 노란색의 고체상 화합물 [11a]를 얻었다.[6a] (70 mg, 0.258 mmol) and N-iodosuccimide (2 eq, 116 mg) were added to DMF (10 mL) and refluxed. After 12 hours, 6 hours later, N-iodosuccimide (2 eq, 116 mg). ), And refluxed for 18 hours. Thereafter, the solvent was distilled under reduced pressure, and the remaining solid was washed several times with water, and then separated by flash chromatography (hexanes: EtOAc = 1: 1) to obtain a pale yellow solid compound [11a].

Yield: 75%; ¹H NMR (400MHz, DMSO-d₆) δ 2.39 (s, 3H), 4.77 (d, J = 5.9Hz, 2H), 7.22-7.36 (m, 5H), 13.67 (br s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 43.9, 89.7, 100.9, 127.3, 127.7, 128.8, 139.6, 155.2, 155.9, 169.3.
Yield: 75%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.39 (s, 3H), 4.77 (d, J = 5.9 Hz, 2H), 7.22-7.36 (m, 5H), 13.67 (br s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 43.9, 89.7, 100.9, 127.3, 127.7, 128.8, 139.6, 155.2, 155.9, 169.3.

(2) 3-아이오도-4-(1-하이드록시에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [11b](2) 3-iodo-4- (1-hydroxyethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [11b]

상기 [6f]와 N-iodosuccimide으로부터 옅은 노란색의 고체상 화합물 [11b]를 얻었다.A pale yellow solid compound [11b] was obtained from [6f] and N-iodosuccimide.

Yield: 33%; ¹H NMR (400MHz, DMSO-d₆) δ 2.44 (s, 3H), 3.37 (s, 2H), 3.59 (s, 2H), 4.95 (s, 1H), 6.77 (s, 1H), 13.62 (br s, 1H).
Yield: 33%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.44 (s, 3H), 3.37 (s, 2H), 3.59 (s, 2H), 4.95 (s, 1H), 6.77 (s, 1H), 13.62 (br s, 1 H).

(3) 3-아이오도-4-다이에틸아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [11c](3) 3-iodo-4-diethylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [11c]

상기 [6u] (40 mg, 0.169 mmol)와 N-iodosuccimide (1.5 eq, 57 mg)를 1,2-dichloroethane (10 mL)에 넣고 37 시간 동안 reflux를 하였다. 그 후에 용매를 가압증류하고, 남아있는 고체를 물로 여러 번 씻어 준 다음 flash chromatography (hexanes : EtOAc = 1:1)로 분리하여 옅은 갈색의 고체상 화합물 [11c]를 얻었다.[6u] (40 mg, 0.169 mmol) and N-iodosuccimide (1.5 eq, 57 mg) were added to 1,2-dichloroethane (10 mL) and refluxed for 37 hours. Thereafter, the solvent was distilled under pressure, the remaining solid was washed several times with water, and then separated by flash chromatography (hexanes: EtOAc = 1: 1) to obtain a pale brown solid compound [11c].

Yield: 19%; ¹H NMR (400MHz, CDCl₃) δ 1.31 (t, J = 7Hz, 6H), 2.56 (s, 3H), 3.86 (quar, J = 7Hz, 4H), 11.19 (br s, 1H).
Yield: 19%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 1.31 (t, J = 7 Hz, 6H), 2.56 (s, 3H), 3.86 (quar, J = 7 Hz, 4H), 11.19 (br s, 1H).

(4) 3-아이오도-4-메톡시-6-(메틸티오)피라졸로[3,4-d]피리미딘 [11d](4) 3-iodo-4-methoxy-6- (methylthio) pyrazolo [3,4-d] pyrimidine [11d]

상기 [10a]와 N-iodosuccimide으로부터 하얀색의 고체상 화합물 [11d]를 얻었다.A white solid compound [11d] was obtained from [10a] and N-iodosuccimide.

Yield: 67%; ¹H NMR (400MHz, CD₃CD-d₄) δ 2.59 (s, 3H), 4.13 (s, 3H); ¹³C NMR (100MHz, CD₃CD-d₄) δ 12.8, 53.4, 87.6, 103.0, 157.1, 162.5, 170.7.
Yield: 67%; ¹ H NMR (400 MHz, CD ₃ CD-d ₄ ) δ 2.59 (s, 3H), 4.13 (s, 3H); ¹³ C NMR (100 MHz, CD ₃ CD-d ₄ ) δ 12.8, 53.4, 87.6, 103.0, 157.1, 162.5, 170.7.

실시예 10. [12a] 내지 [12o]의 합성Example 10. Synthesis of [12a] to [12o]

하기 [반응식 12](R₂N, 1,4-dioxane, reflux, 8h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [12a] 내지 [12o]를 합성하였다.The pyrazolopyrimidine derivative compounds [12a] to [12o] according to the present invention were synthesized by the following Scheme 12 (R ₂ N, 1,4-dioxane, reflux, 8h).

[반응식 12][Reaction Scheme 12]

[5a] [12a] ~ [12o][5a] [12a] to [12o]

[12a] 내지 [12o]에서 NR₂은 각각 하기 [표 5]와 같다.In [12a] to [12o], NR ₂ is shown in Table 5 below, respectively.

구분division NR₂ NR ₂ 구분division NR₂ NR ₂ 12a12a

12i12i

12b12b

12j12j

12c12c

12k12k

12d12d

12l12l

12e12e

12m12m

12f12f

12n12n

12g12g

12o12o

12h12h

(1) 1-메틸-4-벤질아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [12a](1) 1-methyl-4-benzylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [12a]

상기 [5a] (60 mg, 0.279 mmol)과 benzylamine (1.1 eq, 0.04 mL)을 1,4-dioxane (5 mL)에 넣고 8 시간 동안 reflux를 하였다. 반응 혼합물을 EtOAc/H₂O 혼합용매로 층 분리를 한 다음 유기층만 따로 분리하여 MgSO₄로 수분을 제거하고 감압증류를 하였다. 반응혼합물을 flash chromatography (hexanes : EtOAc = 4:1)로 분리하여 옅은 노란색의 고체상 화합물 [12a]를 얻었다.[5a] (60 mg, 0.279 mmol) and benzylamine (1.1 eq, 0.04 mL) were added to 1,4-dioxane (5 mL) and refluxed for 8 hours. The reaction mixture was separated by EtOAc / H ₂ O mixed solvent, and then the organic layer was separated and the water was removed with MgSO ₄ and distilled under reduced pressure. The reaction mixture was separated by flash chromatography (hexanes: EtOAc = 4: 1) to give a pale yellow solid compound [12a].

Yield: 76%; ¹H NMR (400MHz, DMSO-d₆) δ 2.48 (s, 3H), 3.81 (s, 3H), 4.70 (d, J = 5.7Hz, 2H), 7.25 (d, J = 6.2Hz, 1H), 7.33 (s, 4H), 8.02 (s, 1H), 8.85 (t, J = 5.3Hz, 1H).
Yield: 76%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.48 (s, 3H), 3.81 (s, 3H), 4.70 (d, J = 5.7 Hz, 2H), 7.25 (d, J = 6.2 Hz, 1H), 7.33 (s, 4 H), 8.02 (s, 1 H), 8.85 (t, J = 5.3 Hz, 1 H).

(2) 1-메틸-4-[(1-하이드록시-2,2-다이메틸)에틸]아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [12b](2) 1-methyl-4-[(1-hydroxy-2,2-dimethyl) ethyl] amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [12b]

상기 [5a]와 (1-hydroxy-2,2-dimethyl)ethylamine으로부터 하얀색의 고체상 화합물 [12b]를 얻었다.A white solid compound [12b] was obtained from the above [5a] and (1-hydroxy-2,2-dimethyl) ethylamine.

Yield: 45%; ¹H NMR (400MHz, DMSO-d₆) δ 1.39 (s, 6H), 2.48 (s, 3H), 3.66 (d, J = 5.7Hz, 2H), 3.78 (s, 3H), 4.91 (t, J = 5.8Hz, 1H), 7.47 (s, 1H), 8.12 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.1, 24.4, 33.6, 56.5, 67.0, 99.1, 132.4, 153.6, 155.7, 168.0.
Yield: 45%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.39 (s, 6H), 2.48 (s, 3H), 3.66 (d, J = 5.7 Hz, 2H), 3.78 (s, 3H), 4.91 (t, J = 5.8 Hz, 1 H), 7.47 (s, 1 H), 8.12 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.1, 24.4, 33.6, 56.5, 67.0, 99.1, 132.4, 153.6, 155.7, 168.0.

(3) 1-메틸-4-비스(1-하이드록시에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [12c](3) 1-methyl-4-bis (1-hydroxyethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [12c]

상기 [5a]와 diethanolamine으로부터 하얀색의 고체상 화합물 [12c]를 얻었다.A white solid compound [12c] was obtained from [5a] and diethanolamine.

Yield: 77%; ¹H NMR (400MHz, DMSO-d₆) δ 2.47 (s, 3H), 3.79 (d, J = 5.9Hz, 3H), 3.81 (s, 4H), 4.80 (s, 1H), 4.98 (s, 1H), 7.96 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 33.8, 52.1, 43.0, 58.8, 97.8, 133.6, 154.6, 156.0, 167.7.
Yield: 77%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.47 (s, 3H), 3.79 (d, J = 5.9 Hz, 3H), 3.81 (s, 4H), 4.80 (s, 1H), 4.98 (s, 1H ), 7.96 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 33.8, 52.1, 43.0, 58.8, 97.8, 133.6, 154.6, 156.0, 167.7.

(4) 1-메틸-4-[3-(이미다졸-1-일)]프로필아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [12d](4) 1-methyl-4- [3- (imidazol-1-yl)] propylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [12d]

상기 [5a]와 3-(imidazol-1yl)propylamine으로부터 노란색의 고체상 화합물 [12d]를 얻었다.A yellow solid compound [12d] was obtained from the above [5a] and 3- (imidazol-1yl) propylamine.

Yield: 82%; ¹H NMR (400MHz, DMSO-d₆) δ 2.03 (quin, J = 6.8Hz, 2H), 2.45 (s, 3H), 3.42 (quar, J = 6.1Hz, 2H), 3.80 (s, 3H), 4.04 (t, J = 6.7Hz, 2H), 6.82 (s, 1H), 7.19 (s, 1H), 7.64 (s, 1H), 7.97 (s, 1H), 8.37 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.9, 30.8, 33.7, 37.6, 44.2, 98.5, 119.7, 128.8, 131.9, 137.7, 153.7, 155.8, 168.7.
Yield: 82%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.03 (quin, J = 6.8 Hz, 2H), 2.45 (s, 3H), 3.42 (quar, J = 6.1 Hz, 2H), 3.80 (s, 3H), 4.04 (t, J = 6.7 Hz, 2H), 6.82 (s, 1H), 7.19 (s, 1H), 7.64 (s, 1H), 7.97 (s, 1H), 8.37 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 30.8, 33.7, 37.6, 44.2, 98.5, 119.7, 128.8, 131.9, 137.7, 153.7, 155.8, 168.7.

(5) 1-메틸-4-(1-하이드록시에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [12e](5) 1-methyl-4- (1-hydroxyethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [12e]

상기 [5a]와 1-hydroxyethylamine으로부터 하얀색의 고체상 화합물 [12e]를 얻었다.White solid compound [12e] was obtained from [5a] and 1-hydroxyethylamine.

Yield: 91%; ¹H NMR (400MHz, DMSO-d₆) δ 2.48 (s, 3H), 3.53 (d, J = 5.3Hz, 2H), 3.57 (br s, 2H), 3.80 (s, 3H), 4.81 (s, 1H), 8.01 (s, 1H), 8.32 (br s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.9, 33.7, 43.2, 59.9, 98.6, 132.1, 153.7, 155.9, 168.6.
Yield: 91%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.48 (s, 3H), 3.53 (d, J = 5.3 Hz, 2H), 3.57 (br s, 2H), 3.80 (s, 3H), 4.81 (s, 1H), 8.01 (s, 1 H), 8.32 (br s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 33.7, 43.2, 59.9, 98.6, 132.1, 153.7, 155.9, 168.6.

(6) 1-메틸-4-(4-플루오로벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [12f](6) 1-methyl-4- (4-fluorobenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [12f]

상기 [5a]와 4-fluorobenzylamine으로부터 옅은 노란색의 고체상 화합물 [12f]를 얻었다.The pale yellow solid compound [12f] was obtained from the above [5a] and 4-fluorobenzylamine.

Yield: 81%; ¹H NMR (400MHz, DMSO-d₆) δ 2.45 (s, 3H), 3.81 (s, 3H), 4.67 (d, J = 5.7Hz, 2H), 7.15 (t, J = 8.9Hz, 2H), 7.38 (quar, J = 4.7Hz, 2H), 8.00 (s, 1H), 8.80 (t, J = 5.6Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 33.7, 43.0, 98.5, 115.4, 115.6, 129.9, 130.0, 131.9, 135.8, 153.8, 155.6, 160.5, 162.9, 168.7.
Yield: 81%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.45 (s, 3H), 3.81 (s, 3H), 4.67 (d, J = 5.7 Hz, 2H), 7.15 (t, J = 8.9 Hz, 2H), 7.38 (quar, J = 4.7 Hz, 2H), 8.00 (s, 1H), 8.80 (t, J = 5.6 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 33.7, 43.0, 98.5, 115.4, 115.6, 129.9, 130.0, 131.9, 135.8, 153.8, 155.6, 160.5, 162.9, 168.7.

(7) 1-메틸-4-(2-페닐에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [12g](7) 1-methyl-4- (2-phenylethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [12g]

상기 [5a]와 2-phenylethylamine으로 옅은 노란색의 고체상 화합물 [12g]를 얻었다.The pale yellow solid compound [12g] was obtained from [5a] and 2-phenylethylamine.

Yield: 79%; ¹H NMR (400MHz, DMSO-d₆) δ 2.50 (s, 3H), 2.90 (t, J = 9.8Hz, 2H), 3.67 (quar, J = 6.8Hz, 2H), 3.80 (s, 3H), 7.16-7.21 (m, 1H), 7.27 (quin, J = 7.2Hz, 3H), 7.94 (s, 1H), 8.42 (t, J = 5.4Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 33.7, 35.2, 42.1, 98.5, 126.6, 128.8,129.1, 131.9, 139.8, 153.7, 155.7, 168.7.
Yield: 79%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.50 (s, 3H), 2.90 (t, J = 9.8 Hz, 2H), 3.67 (quar, J = 6.8 Hz, 2H), 3.80 (s, 3H), 7.16-7.21 (m, 1 H), 7.27 (quin, J = 7.2 Hz, 3H), 7.94 (s, 1H), 8.42 (t, J = 5.4 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 33.7, 35.2, 42.1, 98.5, 126.6, 128.8,129.1, 131.9, 139.8, 153.7, 155.7, 168.7.

(8) 1-메틸-4-(4-메톡시벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [12h](8) 1-methyl-4- (4-methoxybenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [12h]

상기 [5a]와 4-methoxybenzylamine으로 옅은 노란색의 고체상 화합물 [12h]를 얻었다.A pale yellow solid compound [12h] was obtained from [5a] and 4-methoxybenzylamine.

Yield: 91%; ¹H NMR (400MHz, DMSO-d₆) δ 2.49 (s, 3H), 3.72 (s, 3H), 3.83 (s, 3H), 4.64 (d, J = 5.6Hz, 2H), 6.90 (d, J = 8.5Hz, 2H), 7.29 (d, J = 8.5Hz, 2H), 8.02 (s, 1H), 8.75 (t, J = 5.5Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 33.7, 43.2, 55.5, 98.5, 114.2, 129.3, 131.4, 132.0, 153.8, 155.6, 158.8, 168.7.
Yield: 91%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.49 (s, 3H), 3.72 (s, 3H), 3.83 (s, 3H), 4.64 (d, J = 5.6 Hz, 2H), 6.90 (d, J = 8.5 Hz, 2H), 7.29 (d, J = 8.5 Hz, 2H), 8.02 (s, 1H), 8.75 (t, J = 5.5 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 33.7, 43.2, 55.5, 98.5, 114.2, 129.3, 131.4, 132.0, 153.8, 155.6, 158.8, 168.7.

(9) 1-메틸-4-알릴아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [12i](9) 1-methyl-4-allylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [12i]

상기 [5a]와 allylamine으로 옅은 노란색의 고체상 화합물 12i를 얻었다.A pale yellow solid compound 12i was obtained from [5a] and allylamine.

Yield: 73%; ¹H NMR (400MHz, DMSO-d₆) δ 2.47 (s, 3H), 3.80 (s, 3H), 4.11 (t, J = 5.5Hz, 2H), 5.12 (dd, J = 1.5Hz, 10.2Hz, 1H), 5.21 (dd, J = 1.5Hz, 17.2Hz, 1H), 5.89-5.98 (m, 1H), 7.99 (s, 1H), 8.46 (t, J = 5.3Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.9, 33.7, 42.6, 98.5, 116.3, 131.9, 135.4, 153.8, 155.6, 168.7.
Yield: 73%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.47 (s, 3H), 3.80 (s, 3H), 4.11 (t, J = 5.5 Hz, 2H), 5.12 (dd, J = 1.5 Hz, 10.2 Hz, 1H), 5.21 (dd, J = 1.5 Hz, 17.2 Hz, 1H), 5.89-5.98 (m, 1H), 7.99 (s, 1H), 8.46 (t, J = 5.3 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 33.7, 42.6, 98.5, 116.3, 131.9, 135.4, 153.8, 155.6, 168.7.

(10) 1-메틸-4-(2-메톡시벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [12j](10) 1-methyl-4- (2-methoxybenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [12j]

상기 [5a]와 2-methoxybenzylamine으로 옅은 노란색의 고체상 화합물 12j를 얻었다.A pale yellow solid compound 12j was obtained from [5a] and 2-methoxybenzylamine.

Yield: 73%; ¹H NMR (400MHz, DMSO-d₆) δ 2.45 (s, 3H), 3.83 (s, 3H), 3.83 (s, 3H), 4.66 (d, J = 5.4Hz, 2H), 6.90 (t, J = 7.4Hz, 1H), 7.02 (d, J = 8.1Hz, 1H), 7.25 (t, J = 6.4Hz, 2H), 8.06 (s, 1H), 8.63 (t, J = 5.1Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 33.2, 38.2, 55.2, 98.0, 110.5, 120.0, 126.2, 128.1, 128.2, 131.5, 153.2, 155.2, 156.7, 168.1.
Yield: 73%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.45 (s, 3H), 3.83 (s, 3H), 3.83 (s, 3H), 4.66 (d, J = 5.4 Hz, 2H), 6.90 (t, J = 7.4 Hz, 1H), 7.02 (d, J = 8.1 Hz, 1H), 7.25 (t, J = 6.4 Hz, 2H), 8.06 (s, 1H), 8.63 (t, J = 5.1 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 33.2, 38.2, 55.2, 98.0, 110.5, 120.0, 126.2, 128.1, 128.2, 131.5, 153.2, 155.2, 156.7, 168.1.

(11) 1-메틸-4-(3-메톡시벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [12k](11) 1-methyl-4- (3-methoxybenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [12k]

상기 [5a]와 3-methoxybenzylamine으로 옅은 노란색의 고체상 화합물 12k를 얻었다.12k of pale yellow solid compound was obtained with [5a] and 3-methoxybenzylamine.

Yield: 30%; ¹H NMR (400MHz, DMSO-d₆) δ 2.46 (s, 3H), 3.71 (s, 3H), 3.81 (s, 3H), 4.66 (d, J = 5.8Hz, 2H), 6.82 (d, J = 7.7Hz, 1H), 6.91 (s, 2H), 7.24 (t, J = 7.8Hz, 1H), 8.79 (t, J = 5.6Hz, 1H); ¹³C NMR (400MHz, DMSO-d₆) δ 14.0, 33.7, 43.7, 55.4, 98.5, 112.7, 113.7, 120.1, 129.9, 132.0, 141.2, 153.8, 155.7, 159.7, 168.7.
Yield: 30%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.46 (s, 3H), 3.71 (s, 3H), 3.81 (s, 3H), 4.66 (d, J = 5.8 Hz, 2H), 6.82 (d, J = 7.7 Hz, 1H), 6.91 (s, 2H), 7.24 (t, J = 7.8 Hz, 1H), 8.79 (t, J = 5.6 Hz, 1H); ¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 14.0, 33.7, 43.7, 55.4, 98.5, 112.7, 113.7, 120.1, 129.9, 132.0, 141.2, 153.8, 155.7, 159.7, 168.7.

(12) 1-메틸-4-(2-메틸벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [12l](12) 1-methyl-4- (2-methylbenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [12l]

상기 [5a]와 2-methybenzylamine으로 옅은 노란색의 고체상 화합물 12l를 얻었다.12l of a pale yellow solid compound was obtained from [5a] and 2-methybenzylamine.

Yield: 73%; ¹H NMR (400MHz, DMSO-d₆) δ 2.31 (s, 3H), 2.45 (s, 3H), 3.81 (s, 3H), 4.66 (d, J = 5.4Hz, 2H), 7.14-7.16 (m, 3H), 7.27 (d, J = 6.6Hz, 1H), 8.03 (s, 1H), 8.63 (t, J = 4.9Hz, 1H); ¹³C NMR (400MHz, DMSO-d₆) δ 13.9, 19.2, 33.7, 42.0, 98.5, 126.3, 127.6, 128.5, 130.5, 132.1, 136.4, 137.0, 153.8, 155.6, 168.7.
Yield: 73%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.31 (s, 3H), 2.45 (s, 3H), 3.81 (s, 3H), 4.66 (d, J = 5.4 Hz, 2H), 7.14-7.16 (m , 3H), 7.27 (d, J = 6.6 Hz, 1 H), 8.03 (s, 1 H), 8.63 (t, J = 4.9 Hz, 1 H); ¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 13.9, 19.2, 33.7, 42.0, 98.5, 126.3, 127.6, 128.5, 130.5, 132.1, 136.4, 137.0, 153.8, 155.6, 168.7.

(13) 1-메틸-4-(4-클로로벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [12m](13) 1-methyl-4- (4-chlorobenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [12m]

상기 [5a]와 4-chlorobenzylamine으로 옅은 노란색의 고체상 화합물 12m을 얻었다.12m of pale yellow solid compound was obtained from [5a] and 4-chlorobenzylamine.

Yield: 44%; ¹H NMR (400MHz, DMSO-d₆) δ 2.45 (s, 3H), 3.83 (s, 3H), 4.70 (d, J = 5.8Hz, 2H), 7.35-7.41 (m, 4H), 8.02 (s, 1H), 8.85 (t, J = 5.6Hz, 1H).
Yield: 44%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.45 (s, 3H), 3.83 (s, 3H), 4.70 (d, J = 5.8 Hz, 2H), 7.35-7.41 (m, 4H), 8.02 (s , 1H), 8.85 (t, J = 5.6 Hz, 1H).

(14) N-벤질-1-메틸-6-(메틸티오)피라졸로[3,4-d]피리미딘-4-아민 [12n](14) N-benzyl-1-methyl-6- (methylthio) pyrazolo [3,4-d] pyrimidin-4-amine [12n]

상기 [5a]와 benzylamine으로 노란색의 고체상 화합물 12n을 얻었다.The yellow solid compound 12n was obtained from [5a] and benzylamine.

Yield: 82%; ¹H NMR (400MHz, DMSO-d₆) δ 2.25 (s, 3H), 2.45 (s, 3H), 3.81 (s, 3H), 4.64 (d, J = 5.8Hz, 2H), 7.12 (d, J = 7.9Hz, 2H), 7.22 (d, J = 8.0Hz, 2H), 8.00 (s, 1H), 8.75 (t, J = 5.7Hz, 1H); ¹³C NMR (400MHz, DMSO-d₆) δ 14.01, 21.1, 33.7, 43.5, 60.6, 98.5, 127.9, 129.3, 132.0, 136.5, 153.8, 155.6, 168.7.
Yield: 82%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.25 (s, 3H), 2.45 (s, 3H), 3.81 (s, 3H), 4.64 (d, J = 5.8 Hz, 2H), 7.12 (d, J = 7.9 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 8.00 (s, 1H), 8.75 (t, J = 5.7 Hz, 1H); ¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 14.01, 21.1, 33.7, 43.5, 60.6, 98.5, 127.9, 129.3, 132.0, 136.5, 153.8, 155.6, 168.7.

(15) 1-메틸-6-(메틸티오)-N-(1-페닐에틸)-1H-피라졸로[3,4-d]피리미딘-4-아민 [12o](15) 1-methyl-6- (methylthio) -N- (1-phenylethyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [12o]

상기 [5a]와 (R)-phenylethylamine으로 노란색의 고체상 화합물 12o을 얻었다.The yellow solid compound 12o was obtained from [5a] and (R) -phenylethylamine.

Yield: 74%; ¹H NMR (400MHz, DMSO-d₆) δ 1.53 (d, J = 7.0Hz, 3H), 2.41 (s, 2H), 3.85 (s, 3H), 7.23 (t, J = 7.1Hz, 1H), 7.33 (t, J = 7.5Hz, 2H), 7.40 (d, J = 7.4Hz, 2H), 8.10 (s, 1H), 8.67 (d, J = 7.7Hz, 1H); ¹³C NMR (400MHz, DMSO-d₆) δ 14.0, 22.8, 33.7, 98.5, 126.4, 127.2, 128.7, 132.1, 145.1, 153.9, 154.9, 168.6.
Yield: 74%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.53 (d, J = 7.0 Hz, 3H), 2.41 (s, 2H), 3.85 (s, 3H), 7.23 (t, J = 7.1 Hz, 1H), 7.33 (t, J = 7.5 Hz, 2H), 7.40 (d, J = 7.4 Hz, 2H), 8.10 (s, 1H), 8.67 (d, J = 7.7 Hz, 1H); ¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 14.0, 22.8, 33.7, 98.5, 126.4, 127.2, 128.7, 132.1, 145.1, 153.9, 154.9, 168.6.

실시예 11. [13a] 내지 [13o]의 합성Example 11. Synthesis of [13a] to [13o]

하기 [반응식 13](R₂N, 1,4-dioxane, reflux, 8h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [13a] 내지 [13o]를 합성하였다.The pyrazolopyrimidine derivative compounds [13a] to [13o] were synthesized according to the following Reaction Scheme 13 (R ₂ N, 1,4-dioxane, reflux, 8h).

[반응식 13][Reaction Scheme 13]

[5b] [13a] ~ [13o][5b] [13a] to [13o]

[13a] 내지 [13o]에서 NR₂은 각각 하기 [표 6]과 같다.In [13a] to [13o], NR ₂ is shown in Table 6 below, respectively.

구분division NR₂ NR ₂ 구분division NR₂ NR ₂ 13a13a

13i13i

13b13b

13j13j

13c13c

13k13k

13d13d

13l13l

13e13e

13m13m

13f13f

13n13n

13g13g

13o13o

13h13h

(1) 1-알릴-4-벤질아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [13a](1) 1-allyl-4-benzylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [13a]

상기 [5b]와 benzylamine으로 옅은 노란색의 고체상 화합물 13a를 얻었다.A pale yellow solid compound 13a was obtained from [5b] and benzylamine.

Yield: 85%; ¹H NMR (400MHz, DMSO-d₆) δ 2.46 (s, 3H), 4.72 (d, J = 5.6Hz, 2H), 4.85 (d, J = 4.7Hz, 2H), 5.01 (d, J = 17.1Hz, 1H), 5.15 (d, J = 10.3Hz, 1H), 5.94-6.03 (m, 1H), 7.24-7.27 (m, 1H), 7.32-7.37 (m, 4H), 8.08 (s, 1H), 8.85 (t, J = 5.4Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 43.2, 48.3, 97.9, 117.0, 126.9, 127.4, 128.3, 131.9, 133.3, 139.0, 153.2, 155.1, 168.3.
Yield: 85%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.46 (s, 3H), 4.72 (d, J = 5.6 Hz, 2H), 4.85 (d, J = 4.7 Hz, 2H), 5.01 (d, J = 17.1 Hz, 1H), 5.15 (d, J = 10.3 Hz, 1H), 5.94-6.03 (m, 1H), 7.24-7.27 (m, 1H), 7.32-7.37 (m, 4H), 8.08 (s, 1H) , 8.85 (t, J = 5.4 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 43.2, 48.3, 97.9, 117.0, 126.9, 127.4, 128.3, 131.9, 133.3, 139.0, 153.2, 155.1, 168.3.

(2) 1-알릴-4-알릴아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [13b](2) 1-allyl-4-allylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [13b]

상기 [5b]와 allyllamine으로 옅은 노란색의 고체상 화합물 13b를 얻었다.[5b] and allyllamine were obtained as a pale yellow solid compound 13b.

Yield: 88%; ¹H NMR (400MHz, DMSO-d₆) δ 2.48 (s, 3H), 4.14 (t, J = 5.5Hz, 2H), 4.85 (dd, J = 1.4Hz, 4.0Hz, 2H), 5.01 (dd, J = 1.3Hz, 17.1Hz, 1H), 5.12-5.17 (m, 2H), 5.24 (dd, J = 1.6Hz, 17.2Hz, 1H), 5.91-6.04 (m, 2H), 8.07 (s, 1H), 8.52 (t, J = 5.1Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 42.6, 48.9, 98.5, 116.3, 117.6, 132.4, 133.9, 135.3, 153.7, 155.6, 168.8.
Yield: 88%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.48 (s, 3H), 4.14 (t, J = 5.5 Hz, 2H), 4.85 (dd, J = 1.4 Hz, 4.0 Hz, 2H), 5.01 (dd, J = 1.3 Hz, 17.1 Hz, 1H), 5.12-5.17 (m, 2H), 5.24 (dd, J = 1.6 Hz, 17.2 Hz, 1H), 5.91-6.04 (m, 2H), 8.07 (s, 1H) , 8.52 (t, J = 5.1 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 42.6, 48.9, 98.5, 116.3, 117.6, 132.4, 133.9, 135.3, 153.7, 155.6, 168.8.

(3) 1-알릴-4-(1-하이드록시에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [13c](3) 1-allyl-4- (1-hydroxyethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [13c]

상기 [5b]와 benzylamine으로 하얀색의 고체상 화합물 13c를 얻었다.White solid compound 13c was obtained from [5b] and benzylamine.

Yield: 91%; ¹H NMR (400MHz, DMSO-d₆) δ 2.48 (s, 3H), 3.57 (dt, J = 5.2Hz, 17.3Hz, 4H), 4.81-4.85 (m, 2H), 4.99 (dd, J = 1.2Hz, 17.1Hz, 1H), 5.15 (dd, J = 1.1Hz, 10.3Hz, 1H), 5.94-6.03 (m, 1H), 8.07 (s, 1H), 8.38 (t, J = 5.1Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 42.7, 48.3, 59.3, 98.0, 116.9, 132.0, 133.4, 153.1, 155.4, 168.2.
Yield: 91%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.48 (s, 3H), 3.57 (dt, J = 5.2 Hz, 17.3 Hz, 4H), 4.81-4.85 (m, 2H), 4.99 (dd, J = 1.2 Hz, 17.1 Hz, 1H), 5.15 (dd, J = 1.1 Hz, 10.3 Hz, 1H), 5.94-6.03 (m, 1H), 8.07 (s, 1H), 8.38 (t, J = 5.1 Hz, 1H) ; ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 42.7, 48.3, 59.3, 98.0, 116.9, 132.0, 133.4, 153.1, 155.4, 168.2.

(4) 1-알릴-4-(4-플루오로벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [13d](4) 1-allyl-4- (4-fluorobenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [13d]

상기 [5b]와 benzylamine으로 옅은 노란색의 고체상 화합물 13d를 얻었다.The pale yellow solid compound 13d was obtained from [5b] and benzylamine.

Yield: 82%; ¹H NMR (400MHz, DMSO-d₆) δ 2.46 (s, 3H), 4.69 (d, J = 5.6Hz, 2H), 4.85 (d, J = 5.3Hz, 2H), 5.01 (dd, J = 1.4Hz, 17.1Hz, 1H), 5.15 (dd, J = 1.4Hz, 10.3Hz, 1H), 5.94-6.03 (m, 1H), 7.14-7.20 (m, 2H), 7.41 (quar, J = 4.7Hz, 2H), 8.07 (s, 1H), 8.87 (t, J = 5.6Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 42.5, 48.3, 98.0, 114.9, 115.1, 117.0, 129.3, 129.4, 131.9, 133.3, 135.2, 153.2, 155.1, 159.9, 162.4, 168.3.
Yield: 82%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.46 (s, 3H), 4.69 (d, J = 5.6 Hz, 2H), 4.85 (d, J = 5.3 Hz, 2H), 5.01 (dd, J = 1.4 Hz, 17.1 Hz, 1H), 5.15 (dd, J = 1.4 Hz, 10.3 Hz, 1H), 5.94-6.03 (m, 1H), 7.14-7.20 (m, 2H), 7.41 (quar, J = 4.7 Hz, 2H), 8.07 (s, 1 H), 8.87 (t, J = 5.6 Hz, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 42.5, 48.3, 98.0, 114.9, 115.1, 117.0, 129.3, 129.4, 131.9, 133.3, 135.2, 153.2, 155.1, 159.9, 162.4, 168.3.

(5) N-(2-메톡시벤질)-1-알릴-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [13e](5) N- (2-methoxybenzyl) -1-allyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [13e]

상기 [5b]와 2-methoxybenzylamine으로 하얀색의 고체상 화합물 13e를 얻었다.White solid compound 13e was obtained from [5b] and 2-methoxybenzylamine.

Yield: 89.04%; ¹H NMR (400MHz, DMSO-d₆) δ 2.44 (s, 3H), 3.83 (s, 3H), 4.67 (s, 2H), 4.85 (s, 2H), 4.99-5.16 (m, 2H), 5.99 (s, 1H), 6.91 (s, 1H), 7.02 (s, 1H), 7.26 (s, 2H), 8.11 (s, 1H), 8.66 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.9, 38.8, 48.9, 55.8, 98.6, 111.1, 117.6, 120.6, 126.7, 128.7, 132.6, 133.9, 153.7, 155.8, 157.3, 168.8.
Yield: 89.04%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.44 (s, 3H), 3.83 (s, 3H), 4.67 (s, 2H), 4.85 (s, 2H), 4.99-5.16 (m, 2H), 5.99 (s, 1H), 6.91 (s, 1H), 7.02 (s, 1H), 7.26 (s, 2H), 8.11 (s, 1H), 8.66 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 38.8, 48.9, 55.8, 98.6, 111.1, 117.6, 120.6, 126.7, 128.7, 132.6, 133.9, 153.7, 155.8, 157.3, 168.8.

(6) N-(4-클로로벤질)-1-알릴-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [13f](6) N- (4-chlorobenzyl) -1-allyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [13f]

상기 [5b]와 4-chlorobenzylamine으로 하얀색의 고체상 화합물 13f를 얻었다.White solid compound 13f was obtained from [5b] and 4-chlorobenzylamine.

Yield: 88.54%; ¹H NMR (400MHz, DMSO-d₆) δ 2.47 (s, 3H), 4.73 (d, J = 5.5Hz, 2H), 4.88 (d, J = 4.3Hz, 2H), 5.04 (d, J = 17.1Hz, 1H), 5.18 (d, J = 10.2Hz, 1H), 5.98-6.01 (m, 1H), 7.41 (s, 4H), 8.01 (s, 1H), 8.90 (d, J = 5.3Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 43.0, 48.9, 98.5, 117.6, 128.7, 129.7, 131.9, 132.4, 133.9, 138.7, 153.7, 155.7, 168.8.
Yield: 88.54%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.47 (s, 3H), 4.73 (d, J = 5.5 Hz, 2H), 4.88 (d, J = 4.3 Hz, 2H), 5.04 (d, J = 17.1 Hz, 1H), 5.18 (d, J = 10.2 Hz, 1H), 5.98-6.01 (m, 1H), 7.41 (s, 4H), 8.01 (s, 1H), 8.90 (d, J = 5.3 Hz, 1H ); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 43.0, 48.9, 98.5, 117.6, 128.7, 129.7, 131.9, 132.4, 133.9, 138.7, 153.7, 155.7, 168.8.

(7) N-(4-메틸벤질)-1-알릴-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 (13g)(7) N- (4-methylbenzyl) -1-allyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine (13 g)

상기 [5b]와 4-methylbenzylamine으로 하얀색의 고체상 화합물 13g를 얻었다.13g of white solid compound was obtained from [5b] and 4-methylbenzylamine.

Yield: 83.65%; ¹H NMR (400MHz, DMSO-d₆) δ 2.27 (s, 3H), 2.46 (s, 3H), 4.66 (d, J = 5.6Hz, 2H), 4.92 (d, J = 4.5Hz, 2H), 5.08 (dd, J = 1.4Hz, 44.4Hz, 1H), 5.16 (d, J = 8.7Hz, 1H), 5.94-6.02 (m, 1H), 7.20 (dd, J = 7.9Hz, 41.9Hz, 4H), 8.07 (s, 1H), 8.80 (t, J = 5.5Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 21.1, 43.5, 48.9, 98.5, 117.6, 128.0, 129.3, 132.5, 133.9, 136.5, 153.7, 155.7, 168.8.
Yield: 83.65%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.27 (s, 3H), 2.46 (s, 3H), 4.66 (d, J = 5.6 Hz, 2H), 4.92 (d, J = 4.5 Hz, 2H), 5.08 (dd, J = 1.4 Hz, 44.4 Hz, 1H), 5.16 (d, J = 8.7 Hz, 1H), 5.94-6.02 (m, 1H), 7.20 (dd, J = 7.9 Hz, 41.9 Hz, 4H) , 8.07 (s, 1 H), 8.80 (t, J = 5.5 Hz, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 21.1, 43.5, 48.9, 98.5, 117.6, 128.0, 129.3, 132.5, 133.9, 136.5, 153.7, 155.7, 168.8.

(8) N-(2-메틸벤질)-1-알릴-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [13h](8) N- (2-methylbenzyl) -1-allyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [13h]

상기 [5b]와 2-methylbenzylamine으로 하얀색의 고체상 화합물 13h를 얻었다.The white solid compound 13h was obtained from [5b] and 2-methylbenzylamine.

Yield: 86.42%; ¹H NMR (400MHz, DMSO-d₆) δ 2.37 (s, 3H), 2.46 (s, 3H), 4.72 (d, J = 5.2Hz, 2H), 4.89 (d, J = 4.7Hz, 2H), 5.05 (dd, J = 1.0Hz, 17.1Hz, 1H), 5.19 (d, J = 9.5Hz, 1H), 5.99-6.06 (m, 1H), 7.21 (s, 3H), 7.33 (d, J = 5.8Hz, 1H), 8.14 (s, 1H), 8.70 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.9, 19.2, 42.0, 48.9, 98.5, 117.6, 126.3, 127.6, 128.6, 130.5, 132.6, 133.9, 136.4, 137.0, 153.7, 155.6, 168.8.
Yield: 86.42%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.37 (s, 3H), 2.46 (s, 3H), 4.72 (d, J = 5.2 Hz, 2H), 4.89 (d, J = 4.7 Hz, 2H), 5.05 (dd, J = 1.0 Hz, 17.1 Hz, 1H), 5.19 (d, J = 9.5 Hz, 1H), 5.99-6.06 (m, 1H), 7.21 (s, 3H), 7.33 (d, J = 5.8 Hz, 1H), 8.14 (s, 1H), 8.70 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 19.2, 42.0, 48.9, 98.5, 117.6, 126.3, 127.6, 128.6, 130.5, 132.6, 133.9, 136.4, 137.0, 153.7, 155.6, 168.8.

(9) 1-알릴-6-(메틸티오)-N-(1-페닐에틸)-1H-피라졸로[3,4-d]피리미딘-4-아민 [13i](9) 1-allyl-6- (methylthio) -N- (1-phenylethyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [13i]

상기 [5b]와 (S)-phenylethylamine으로 하얀색의 고체상 화합물 13i를 얻었다.A white solid compound 13i was obtained from the above [5b] and (S) -phenylethylamine.

Yield: 84.44%; ¹H NMR (400MHz, DMSO-d₆) δ 1.54 (d, J = 6.8Hz, 3H), 2.41 (s, 3H), 4.82 (s, 2H), 4.99 (d, J = 17.1Hz, 1H), 5.14 (d, J = 10.2Hz, 1H), 5.45 (t, J = 6.9Hz, 1H), 5.93-6.01 (m, 1H), 7.23 (t, J = 6.7Hz, 1H), 7.33 (t, J = 7.5Hz, 2H), 7.41 (d, J = 7.4Hz, 2H), 8.16 (s, 1H), 8.71 (d, J = 7.4Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 22.8, 48.8, 49.6, 98.5, 99.1, 117.5, 126.5, 127.2, 128.7, 132.6, 133.9, 145.0, 153.8, 154.9, 168.7.
Yield: 84.44%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.54 (d, J = 6.8 Hz, 3H), 2.41 (s, 3H), 4.82 (s, 2H), 4.99 (d, J = 17.1 Hz, 1H), 5.14 (d, J = 10.2 Hz, 1H), 5.45 (t, J = 6.9 Hz, 1H), 5.93-6.01 (m, 1H), 7.23 (t, J = 6.7 Hz, 1H), 7.33 (t, J = 7.5 Hz, 2H), 7.41 (d, J = 7.4 Hz, 2H), 8.16 (s, 1 H), 8.71 (d, J = 7.4 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 22.8, 48.8, 49.6, 98.5, 99.1, 117.5, 126.5, 127.2, 128.7, 132.6, 133.9, 145.0, 153.8, 154.9, 168.7.

(10) N-(3-메톡시벤질)-1-알릴-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [13j](10) N- (3-methoxybenzyl) -1-allyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [13j]

상기 [5b]와 3-methoxybenzylamine으로 하얀색의 고체상 화합물 13j를 얻었다.White solid compound 13j was obtained from [5b] and 3-methoxybenzylamine.

Yield: 82.44%; ¹H NMR (400MHz, DMSO-d₆) δ 1.42 (s, 3H), 2.49 (s, 3H), 3.69 (d, J = 5.8Hz, 2H), 4.83 (d, J = 5.3Hz, 2H), 4.91-5.00 (m, 2H), 5.15 (dd, J = 1.4Hz, 10.3Hz, 1H), 5.95-5.99 (m, 1H), 7.25-7.57 (m, 2H), 7.61-7.64 (m, 2H), 8.20 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.6, 23.9, 48.2, 56.0, 66.4, 98.6, 116.9, 128.6, 128.7, 131.3, 131.4, 131.9, 132.1, 132.4, 133.1, 133.4, 153.0, 155.2, 167.5.
Yield: 82.44%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.42 (s, 3H), 2.49 (s, 3H), 3.69 (d, J = 5.8 Hz, 2H), 4.83 (d, J = 5.3 Hz, 2H), 4.91-5.00 (m, 2H), 5.15 (dd, J = 1.4 Hz, 10.3 Hz, 1H), 5.95-5.99 (m, 1H), 7.25-7.57 (m, 2H), 7.61-7.64 (m, 2H) , 8.20 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.6, 23.9, 48.2, 56.0, 66.4, 98.6, 116.9, 128.6, 128.7, 131.3, 131.4, 131.9, 132.1, 132.4, 133.1, 133.4, 153.0, 155.2, 167.5.

(11) 2-(1-알릴-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-일아미노)-2-메틸프로판-1-올 [13k](11) 2- (1-allyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-ylamino) -2-methylpropan-1-ol [13k]

상기 [5b]와 1-hydroxy-2-methylpropan-2-amine으로 하얀색의 고체상 화합물 13k를 얻었다.13k was obtained from the above [5b] and 1-hydroxy-2-methylpropan-2-amine.

Yield: 80.35%; ¹H NMR (400MHz, DMSO-d₆) δ 2.47 (s, 3H), 3.74 (s, 3H), 4.69 (d, J = 5.7Hz, 2H), 4.86 (d, J = 5.3Hz, 2H), 5.02 (dd, J = 1.4Hz, 17.1Hz, 1H), 5.16 (dd, J = 1.3Hz, 10.3Hz, 1H), 5.96-6.00 (m, 1H), 6.84 (dd, J = 2.0Hz, 8.1Hz, 1H), 6.93-6.95 (m, 2H), 7.26 (t, J = 7.8Hz, 1H), 8.09 (s, 1H), 8.83 (d, J = 5.7Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.5, 43.2, 48.4, 54.9, 98.0, 112.2, 113.3, 117.1, 119.7, 129.4, 132.0, 133.4, 140.7, 153.3, 155.2, 159.2, 168.3.
Yield: 80.35%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.47 (s, 3H), 3.74 (s, 3H), 4.69 (d, J = 5.7 Hz, 2H), 4.86 (d, J = 5.3 Hz, 2H), 5.02 (dd, J = 1.4 Hz, 17.1 Hz, 1H), 5.16 (dd, J = 1.3 Hz, 10.3 Hz, 1H), 5.96-6.00 (m, 1H), 6.84 (dd, J = 2.0 Hz, 8.1 Hz , 1H), 6.93-6.95 (m, 2H), 7.26 (t, J = 7.8 Hz, 1H), 8.09 (s, 1H), 8.83 (d, J = 5.7 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.5, 43.2, 48.4, 54.9, 98.0, 112.2, 113.3, 117.1, 119.7, 129.4, 132.0, 133.4, 140.7, 153.3, 155.2, 159.2, 168.3.

(12) 1-알릴-N-뷰틸-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [13l](12) 1-allyl-N-butyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [13l]

상기 [5b]와 n-butylamine으로 하얀색의 고체상 화합물 13l를 얻었다.13l of a white solid compound was obtained from [5b] and n-butylamine.

Yield: 92.56%; ¹H NMR (400MHz, DMSO-d₆) δ 0.92 (t, J = 7.4Hz, 3H), 1.34-1.39 (m, 2H), 1.55-1.62 (m, 2H), 2.49 (s, 3H), 3.45-3.50 (m, 2H), 4.85 (d, J = 5.1Hz, 2H), 5.01 (d, J = 17.1Hz, 1H), 5.16 (d, J = 10.2Hz, 1H), 5.95-6.02 (m, 1H), 8.04 (s, 1H), 8.28 (t, J = 5.0Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.9, 14.1, 20.1, 31.3, 48.8, 98.5, 117.5, 132.4, 133.9, 153.6, 155.8, 168.8.
Yield: 92.56%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.92 (t, J = 7.4 Hz, 3H), 1.34-1.39 (m, 2H), 1.55-1.62 (m, 2H), 2.49 (s, 3H), 3.45 -3.50 (m, 2H), 4.85 (d, J = 5.1 Hz, 2H), 5.01 (d, J = 17.1 Hz, 1H), 5.16 (d, J = 10.2 Hz, 1H), 5.95-6.02 (m, 1H), 8.04 (s, 1H), 8.28 (t, J = 5.0 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 14.1, 20.1, 31.3, 48.8, 98.5, 117.5, 132.4, 133.9, 153.6, 155.8, 168.8.

(13) N-(4-메톡시벤질)-1-알릴-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [13m](13) N- (4-methoxybenzyl) -1-allyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [13m]

상기 [5b]와 4-methoxybenzylamine으로 하얀색의 고체상 화합물 13m를 얻었다.13m of a white solid compound was obtained from [5b] and 4-methoxybenzylamine.

Yield: 81.38%; ¹H NMR (400MHz, DMSO-d₆) δ 2.50 (s,3H), 3.74 (s, 3H), 4.66 (d, J = 5.6Hz, 2H), 4.87 (d, J = 5.2Hz, 2H), 5.02 (dd, J = 1.2Hz, 17.1Hz, 1H), 5.17 (dd, J = 1.3Hz, 10.3Hz, 1H), 6.00-6.01 (m, 1H), 6.92 (d, J = 8.6Hz, 2H), 7.32 (d, J = 8.6Hz, 2H), 8.09 (s, 1H), 8.78 (t, J = 5.5Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 43.2, 48.9, 55.5, 98.5, 114.2, 117.6, 129.4, 131.4, 131.9, 132.0, 132.5, 133.5, 153.7, 155.6, 158.8, 168.8.
Yield: 81.38%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.50 (s, 3H), 3.74 (s, 3H), 4.66 (d, J = 5.6 Hz, 2H), 4.87 (d, J = 5.2 Hz, 2H), 5.02 (dd, J = 1.2 Hz, 17.1 Hz, 1H), 5.17 (dd, J = 1.3 Hz, 10.3 Hz, 1H), 6.00-6.01 (m, 1H), 6.92 (d, J = 8.6 Hz, 2H) , 7.32 (d, J = 8.6 Hz, 2H), 8.09 (s, 1H), 8.78 (t, J = 5.5 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 43.2, 48.9, 55.5, 98.5, 114.2, 117.6, 129.4, 131.4, 131.9, 132.0, 132.5, 133.5, 153.7, 155.6, 158.8, 168.8.

(14) 1-알릴-6-(메틸티오)-N-((피리딘-2-일)메틸)-1H-피라졸로[3,4-d]피리미딘-4-아민 [13n](14) 1-allyl-6- (methylthio) -N-((pyridin-2-yl) methyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [13n]

상기 [5b]와 (pyridin-2-yl)methanamine으로 하얀색의 고체상 화합물 13n를 얻었다.White solid compound 13n was obtained from [5b] and (pyridin-2-yl) methanamine.

Yield: 90.84%; ¹H NMR (400MHz, DMSO-d₆) δ 2.40 (s, 3H), 4.80-4.95 (m, 4H), 5.02 (dd, J = 1.0Hz, 17.2Hz, 1H), 5.16 (d, J = 10.2Hz, 1H), 5.99-6.03 (m, 1H), 7.26-7.75 (m, 4H), 8.13 (s, 1H), 8.54 (d, J = 4.4Hz, 1H), 8.99 (t, J = 5.5Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 45.2, 48.4, 98.1, 117.1, 121.3, 122.2, 125.2, 128.6, 128.7, 131.4, 131.5, 132.0, 133.2, 133.4, 136.7, 148.9, 153.3, 155.3, 158.3, 168.3.
Yield: 90.84%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.40 (s, 3H), 4.80-4.95 (m, 4H), 5.02 (dd, J = 1.0 Hz, 17.2 Hz, 1H), 5.16 (d, J = 10.2 Hz, 1H), 5.99-6.03 (m, 1H), 7.26-7.75 (m, 4H), 8.13 (s, 1H), 8.54 (d, J = 4.4 Hz, 1H), 8.99 (t, J = 5.5 Hz , 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 45.2, 48.4, 98.1, 117.1, 121.3, 122.2, 125.2, 128.6, 128.7, 131.4, 131.5, 132.0, 133.2, 133.4, 136.7, 148.9, 153.3, 155.3, 158.3, 168.3.

(15) N-(2-클로로벤질)-1-알릴-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [13o](15) N- (2-chlorobenzyl) -1-allyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [13o]

상기 [5b]와 2-chlorobenzylamine으로 하얀색의 고체상 화합물 13o를 얻었다.White solid compound 13o was obtained by using [5b] and 2-chlorobenzylamine.

Yield: 81.39%; ¹H NMR (400MHz, DMSO-d₆) δ 2.45 (s, 3H), 4.86 (dd, J = 5.3Hz, 30.0Hz, 4H), 5.05 (dd, J = 1.4Hz, 17.1Hz, 1H), 5.19 (dd, J = 1.3Hz, 17.2Hz, 1H), 5.99-6.07 (m, 1H), 7.33-7.52 (m, 4H), 8.15 (s, 1H), 8.89 (d, J = 5.0Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.9, 41.7, 48.9, 98.6, 117.7, 127.7, 129.3, 129.7, 132.5, 132.7, 133.9, 136.5, 153.8, 155.7, 168.8.
Yield: 81.39%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.45 (s, 3H), 4.86 (dd, J = 5.3 Hz, 30.0 Hz, 4H), 5.05 (dd, J = 1.4 Hz, 17.1 Hz, 1H), 5.19 (dd, J = 1.3 Hz, 17.2 Hz, 1H), 5.99-6.07 (m, 1H), 7.33-7.52 (m, 4H), 8.15 (s, 1H), 8.89 (d, J = 5.0 Hz, 1H) ; ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 41.7, 48.9, 98.6, 117.7, 127.7, 129.3, 129.7, 132.5, 132.7, 133.9, 136.5, 153.8, 155.7, 168.8.

실시예 12. [14a] 내지 [14l]의 합성Example 12. Synthesis of [14a] to [14l]

하기 [반응식 14](R₂N, 1,4-dioxane, reflux, 8h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [14a] 내지 [14l]를 합성하였다.The pyrazolopyrimidine derivative compounds [14a] to [14l] were synthesized according to the following Scheme 14 (R ₂ N, 1,4-dioxane, reflux, 8h).

[반응식 14][Reaction Scheme 14]

[5d] [14a] ~ [14l][5d] [14a] to [14l]

[14a] 내지 [14l]에서 NR₂은 각각 하기 [표 7]과 같다.NR ₂ in [14a] to [14l] are as shown in the following [Table 7].

구분division NR₂ NR ₂ 구분division NR₂ NR ₂ 14a14a

14g14 g

14b14b

14h14h

14c14c

14i14i

14d14d

14j14j

14e14e

14k14k

14f14f

14l14l

(1) 1-(N-t-Boc-아미노에틸)-4-벤질아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [14a](1) 1- (N-t-Boc-aminoethyl) -4-benzylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [14a]

상기 [5d]와 benzylamine으로 옅은 노란색의 고체상 화합물 14a를 얻었다.A pale yellow solid compound 14a was obtained from [5d] and benzylamine.

Yield: 94%; ¹H NMR (400MHz, DMSO-d₆) δ 1.31 (s, 9H), 2.49 (s, 3H), 3.31 (t, J = 6.0Hz, 2H), 4.25 (t, J = 5.9Hz, 2H), 4.71 (d, J = 5.8Hz, 2H), 6.85 (t, J = 5.7Hz, 1H), 7.24-7.27 (m, 1H), 7.31-7.34 (m, 4H), 8.03 (s, 1H), 8.79 (t, J = 5.5Hz, 1H).
Yield: 94%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.31 (s, 9H), 2.49 (s, 3H), 3.31 (t, J = 6.0 Hz, 2H), 4.25 (t, J = 5.9 Hz, 2H), 4.71 (d, J = 5.8 Hz, 2H), 6.85 (t, J = 5.7 Hz, 1H), 7.24-7.27 (m, 1H), 7.31-7.34 (m, 4H), 8.03 (s, 1H), 8.79 (t, J = 5.5 Hz, 1H).

(2) 1-(N-t-Boc-아미노에틸)-4-(1-하이드록시에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [14b](2) 1- (N-t-Boc-aminoethyl) -4- (1-hydroxyethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [14b]

상기 [5d]와 1-hydroxyethylamine으로 옅은 노란색의 고체상 화합물 14b를 얻었다.A pale yellow solid compound 14b was obtained from [5d] and 1-hydroxyethylamine.

Yield: 68%; ¹H NMR (400MHz, DMSO-d₆) δ 1.32 (s, 9H), 2.49 (s, 3H), 3.31 (t, J = 6.0Hz, 2H), 3.56 (dt, J = 5.2Hz, 16.5Hz, 4H), 4.24 (t, J = 5.9Hz, 2H), 4.81 (t, J = 5.1Hz, 1H), 6.84 (t, J = 5.4Hz, 1H), 8.03 (s, 1H), 8.31 (s, 1H).
Yield: 68%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.32 (s, 9H), 2.49 (s, 3H), 3.31 (t, J = 6.0 Hz, 2H), 3.56 (dt, J = 5.2 Hz, 16.5 Hz, 4H), 4.24 (t, J = 5.9 Hz, 2H), 4.81 (t, J = 5.1 Hz, 1H), 6.84 (t, J = 5.4 Hz, 1H), 8.03 (s, 1H), 8.31 (s, 1H).

(3) 1-(N-t-Boc-아미노에틸)-4-(2-메톡시벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [14c](3) 1- (N-t-Boc-aminoethyl) -4- (2-methoxybenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [14c]

상기 [5d]와 2-mehoxybenzylamine으로 옅은 노란색 고체상 화합물 14c를 얻었다.A pale yellow solid compound 14c was obtained from [5d] and 2-mehoxybenzylamine.

Yield: 68%; ¹H NMR (400MHz, DMSO-d₆) δ 1.31 (s, 9H), 2.45 (s, 3H), 3.31 (t, J = 6.0Hz, 2H), 3.83 (s, 3H), 4.25 (t, J = 5.9Hz, 2H), 4.66 (d, J = 5.5Hz, 2H), 6.87 (dt, J = 6.5Hz, 20.5Hz, 2H), 7.02 (d, J = 8.1Hz, 1H), 7.25 (quar, J = 7.4Hz, 2H), 8.07 (s, 1H), 8.60 (t, J = 5.2Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.9, 28.5, 38.8, 46.7, 55.8, 78.1, 98.6, 111.1, 120.6, 126.7, 128.6, 128.7, 132.4, 154.1, 155.8, 157.3, 168.6.
Yield: 68%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.31 (s, 9H), 2.45 (s, 3H), 3.31 (t, J = 6.0 Hz, 2H), 3.83 (s, 3H), 4.25 (t, J = 5.9 Hz, 2H), 4.66 (d, J = 5.5 Hz, 2H), 6.87 (dt, J = 6.5 Hz, 20.5 Hz, 2H), 7.02 (d, J = 8.1 Hz, 1H), 7.25 (quar, J = 7.4 Hz, 2H), 8.07 (s, 1 H), 8.60 (t, J = 5.2 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 28.5, 38.8, 46.7, 55.8, 78.1, 98.6, 111.1, 120.6, 126.7, 128.6, 128.7, 132.4, 154.1, 155.8, 157.3, 168.6.

(4) 1-(N-t-Boc-아미노에틸)-4-(3-메톡시벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [14d](4) 1- (N-t-Boc-aminoethyl) -4- (3-methoxybenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [14d]

상기 [5d]와 3-mehoxybenzylamine으로 하얀색 고체상 화합물 14d를 얻었다.The white solid compound 14d was obtained from [5d] and 3-mehoxybenzylamine.

Yield: 90%; ¹H NMR (400MHz, DMSO-d₆) δ 1.31 (s, 9H), 2.47 (s, 3H), 3.31 (t, J = 5.9Hz, 2H), 3.73 (s, 3H), 4.25 (t, J = 5.8Hz, 2H), 4.67 (d, J = 5.7Hz, 2H), 6.82-6.93 (m, 3H), 7.25 (t, J = 7.8Hz, 1H), 8.03 (s, 1H), 8.78 (t, J = 5.3Hz, 1H).
Yield: 90%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.31 (s, 9H), 2.47 (s, 3H), 3.31 (t, J = 5.9 Hz, 2H), 3.73 (s, 3H), 4.25 (t, J = 5.8 Hz, 2H), 4.67 (d, J = 5.7 Hz, 2H), 6.82-6.93 (m, 3H), 7.25 (t, J = 7.8 Hz, 1H), 8.03 (s, 1H), 8.78 (t , J = 5.3 Hz, 1H).

(5) 2-(4-(4-클로로벤질아미노)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-1-일)에틸카바메이트 (14e)(5) 2- (4- (4-chlorobenzylamino) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) ethylcarbamate (14e)

상기 [5d]와 4-chlorobenzylamine으로 하얀색 고체상 화합물 14e를 얻었다.The white solid compound 14e was obtained from [5d] and 4-chlorobenzylamine.

Yield: 80.75%; ¹H NMR (400MHz, DMSO-d₆) δ 1.31 (s, 9H), 2.45 (s, 3H), 3.30-3.34 (m, 1H), 4.25 (t, J = 5.9Hz, 2H), 4.69 (d, J = 5.7Hz, 2H), 6.84 (s, 1H), 7.35-7.41 (m, 4H), 8.03 (s, 1H), 8.82 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 28.5, 43.0, 46.7, 78.1, 98.6, 128.7, 129.7, 131.9, 132.2, 138.8, 154.1, 155.6, 155.8, 168.6.
Yield: 80.75%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.31 (s, 9H), 2.45 (s, 3H), 3.30-3.34 (m, 1H), 4.25 (t, J = 5.9 Hz, 2H), 4.69 (d , J = 5.7 Hz, 2H), 6.84 (s, 1H), 7.35-7.41 (m, 4H), 8.03 (s, 1H), 8.82 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 28.5, 43.0, 46.7, 78.1, 98.6, 128.7, 129.7, 131.9, 132.2, 138.8, 154.1, 155.6, 155.8, 168.6.

(6) 2-(4-(4-플루오로벤질아미노)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-1-일)에틸카바메이트 [14f](6) 2- (4- (4-fluorobenzylamino) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) ethylcarbamate [14f]

상기 [5d]와 4-fluorobenzylamine으로 하얀색 고체상 화합물 14f를 얻었다.The white solid compound 14f was obtained from [5d] and 4-fluorobenzylamine.

Yield: 87.44%; ¹H NMR (400MHz, DMSO-d₆) δ 1.31 (s, 9H), 1.51 (d, J = 6.7Hz, 2H), 2.43 (s, 3H), 3.27-3.35 (m, 2H), 4.19-4.23 (m, 2H), 5.41-5.44 (m, 1H), 6.80 (s, 1H), 7.20-7.42 (m, 5H), 8.12 (s, 1H), 8.61 (d, J = 7.3Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.5, 28.2, 42.1, 46.4, 77.3, 98.0, 114.7, 115.0, 129.2, 131.3, 135.1, 153.5, 154.9, 155.1, 159.7, 162.6, 168.3.
Yield: 87.44%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.31 (s, 9H), 1.51 (d, J = 6.7 Hz, 2H), 2.43 (s, 3H), 3.27-3.35 (m, 2H), 4.19-4.23 (m, 2H), 5.41-5.44 (m, 1H), 6.80 (s, 1H), 7.20-7.42 (m, 5H), 8.12 (s, 1H), 8.61 (d, J = 7.3 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.5, 28.2, 42.1, 46.4, 77.3, 98.0, 114.7, 115.0, 129.2, 131.3, 135.1, 153.5, 154.9, 155.1, 159.7, 162.6, 168.3.

(7) 2-(4-(1-페닐에틸아미노)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-1-일)에틸카바메이트 [14g](7) 2- (4- (1-phenylethylamino) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) ethylcarbamate [14 g]

상기 [5d]와 (S)-phenylethylamine으로 하얀색 고체상 화합물 14g를 얻었다.14g of a white solid compound was obtained from the [5d] and (S) -phenylethylamine.

Yield: 92.88%; ¹H NMR (400MHz, DMSO-d₆) δ 1.30 (s, 9H), 1.53 (d, J = 6.9Hz, 2H), 2.41 (s, 3H), 3.29-3.34 (m, 2H), 4.21-4.24 (m, 2H), 5.42-5.46 (m, 1H), 6.83 (s, 1H), 7.22-7.40 (m, 5H), 8.10 (s, 1H), 8.64 (d, J = 7.6Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 28.0, 42.4, 46.2, 77.5, 98.1, 114.9, 115.1, 129.4, 131.7, 135.3, 153.6, 155.1, 155.3, 159.9, 162.4, 168.1.
Yield: 92.88%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.30 (s, 9H), 1.53 (d, J = 6.9 Hz, 2H), 2.41 (s, 3H), 3.29-3.34 (m, 2H), 4.21-4.24 (m, 2H), 5.42-5.46 (m, 1H), 6.83 (s, 1H), 7.22-7.40 (m, 5H), 8.10 (s, 1H), 8.64 (d, J = 7.6 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 28.0, 42.4, 46.2, 77.5, 98.1, 114.9, 115.1, 129.4, 131.7, 135.3, 153.6, 155.1, 155.3, 159.9, 162.4, 168.1.

(8) 2-(4-(1-하이드록시-2-메틸프로판-2-일아미노)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-1-일)에틸카바메이트 [14h](8) 2- (4- (1-hydroxy-2-methylpropan-2-ylamino) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) Ethyl carbamate [14h]

상기 [5d]와 1-hydroxy-2-methylpropan-2-amine으로 하얀색 고체상 화합물 14h를 얻었다.The white solid compound 14h was obtained from [5d] and 1-hydroxy-2-methylpropan-2-amine.

Yield: 78.26%; ¹H NMR (400MHz, DMSO-d₆) δ 1.32 (s, 9H), 1.40 (s, 6H), 2.49 (s, 3H), 3.29-3.36 (m, 2H), 3.67 (d, J = 5.7Hz, 2H), 4.22 (t, J = 5.9Hz, 2H), 4.94 (t, J = 5.8Hz, 1H), 6.84 (s, 1H), 7.46 (s, 1H), 8.14 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.6, 23.9, 28.0, 46.0, 55.9, 66.6, 77.5, 98.6, 132.2, 153.3, 154.5, 155.1, 155.3, 167.3, 170.2.
Yield: 78.26%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.32 (s, 9H), 1.40 (s, 6H), 2.49 (s, 3H), 3.29-3.36 (m, 2H), 3.67 (d, J = 5.7 Hz , 2H), 4.22 (t, J = 5.9 Hz, 2H), 4.94 (t, J = 5.8 Hz, 1H), 6.84 (s, 1H), 7.46 (s, 1H), 8.14 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.6, 23.9, 28.0, 46.0, 55.9, 66.6, 77.5, 98.6, 132.2, 153.3, 154.5, 155.1, 155.3, 167.3, 170.2.

(9) 2-(4-(뷰틸아미노)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-1-일)에틸카바메이트 [14i](9) 2- (4- (butylamino) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) ethylcarbamate [14i]

상기 [5d]와 n-butylamine으로 하얀색 고체상 화합물 14i를 얻었다.The white solid compound 14i was obtained from [5d] and n-butylamine.

Yield: 89.55%; ¹H NMR (400MHz, DMSO-d₆) δ 0.92 (d, J = 4.6Hz, 3H), 1.27 (s, 3H), 1.31 (s, 9H), 1.57 (s, 2H), 3.46 (s, 2H), 4.24 (s, 2H), 6.85 (d, J = 3.6Hz, 1H), 8.00 (d, J = 4.2Hz, 1H), 8.23 (d, J = 3.6Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 13.4, 19.5, 28.0, 30.8, 46.1, 77.5, 98.0, 131.7, 153.4, 155.2, 168.0.
Yield: 89.55%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.92 (d, J = 4.6 Hz, 3H), 1.27 (s, 3H), 1.31 (s, 9H), 1.57 (s, 2H), 3.46 (s, 2H ), 4.24 (s, 2H), 6.85 (d, J = 3.6 Hz, 1H), 8.00 (d, J = 4.2 Hz, 1H), 8.23 (d, J = 3.6 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 13.4, 19.5, 28.0, 30.8, 46.1, 77.5, 98.0, 131.7, 153.4, 155.2, 168.0.

(10) 2-(4-(4-메톡시벤질아미노)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-1-일)에틸카바메이트 [14j](10) 2- (4- (4-methoxybenzylamino) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) ethylcarbamate [14j]

상기 [5d]와 4-methoxybenzylamine으로 하얀색 고체상 화합물 14j를 얻었다.The white solid compound 14j was obtained from [5d] and 4-methoxybenzylamine.

Yield: 87.48%; ¹H NMR (400MHz, DMSO-d₆) δ 1.31 (s, 9H), 2.49 (s, 3H), 3.72 (s, 3H), 4.25 (t, J = 6.0Hz, 2H), 4.63 (d, J = 5.7Hz, 2H), 6.84-6.91 (m, 4H), 7.28 (d, J = 8.4Hz, 2H), 8.02 (s, 1H), 8.71 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 28.5, 43.1, 46.7, 55.5, 78.1, 98.6, 114.2, 129.3, 131.5, 132.3, 154.1, 155.6, 155.9, 158.8, 168.6.
Yield: 87.48%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.31 (s, 9H), 2.49 (s, 3H), 3.72 (s, 3H), 4.25 (t, J = 6.0 Hz, 2H), 4.63 (d, J = 5.7 Hz, 2H), 6.84-6.91 (m, 4H), 7.28 (d, J = 8.4 Hz, 2H), 8.02 (s, 1H), 8.71 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 28.5, 43.1, 46.7, 55.5, 78.1, 98.6, 114.2, 129.3, 131.5, 132.3, 154.1, 155.6, 155.9, 158.8, 168.6.

(11) 2-(4-((피리딘-2-일)메틸아미노)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-1-일)에틸카바메이트 [14k](11) 2- (4-((pyridin-2-yl) methylamino) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) ethylcarbamate [14k ]

상기 [5d]와 (pyridin-2-yl)methanamine으로 하얀색 고체상 화합물 14k를 얻었다.14k of white solid compound was obtained from [5d] and (pyridin-2-yl) methanamine.

Yield: 79.40%; ¹H NMR (400MHz, DMSO-d₆) δ 1.31 (s, 9H), 2.40 (s, 3H), 4.26 (d, J = 5.6Hz, 2H), 4.79 (d, J = 5.8Hz, 2H), 6.87 (d, J = 5.2Hz, 1H), 7.26-7.35 (m, 2H), 7.73-7.77 (m, 1H), 8.08 (s, 1H), 8.53 (d, J = 4.4Hz, 1H), 8.94 (d, J = 5.2Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.9, 28.5, 45.7, 46.7, 78.1, 98.7, 121.7, 122.6, 132.3, 137.1, 149.4, 154.1, 155.7, 155.8, 158.9, 168.5.
Yield: 79.40%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.31 (s, 9H), 2.40 (s, 3H), 4.26 (d, J = 5.6 Hz, 2H), 4.79 (d, J = 5.8 Hz, 2H), 6.87 (d, J = 5.2 Hz, 1H), 7.26-7.35 (m, 2H), 7.73-7.77 (m, 1H), 8.08 (s, 1H), 8.53 (d, J = 4.4 Hz, 1H), 8.94 (d, J = 5.2 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 28.5, 45.7, 46.7, 78.1, 98.7, 121.7, 122.6, 132.3, 137.1, 149.4, 154.1, 155.7, 155.8, 158.9, 168.5.

(12) 2-(4-(2-클로로벤질아미노)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-1-일)에틸카바메이트 (14l)(12) 2- (4- (2-chlorobenzylamino) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) ethylcarbamate (14l)

상기 [5d]와 2-chlorobenzylamine으로 하얀색 고체상 화합물 14l를 얻었다.14l of a white solid compound was obtained from [5d] and 2-chlorobenzylamine.

Yield: 83.42%; ¹H NMR (400MHz, DMSO-d₆) δ 1.30 (s, 9H), 2.42 (s, 3H), 4.26 (t, J = 5.7Hz, 2H), 4.77 (d, J = 5.5Hz, 2H), 6.86 (d, J = 5.2Hz, 1H), 7.30-7.33 (m, 2H), 7.38-7.41 (m, 1H), 7.46-7.49 (m, 1H), 8.07 (s, 1H), 8.79 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.9, 28.5, 41.6, 46.7, 78.1, 127.6, 129.3, 129.7, 132.4, 132.7, 136.5, 155.6, 155.8, 168.5.
Yield: 83.42%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.30 (s, 9H), 2.42 (s, 3H), 4.26 (t, J = 5.7 Hz, 2H), 4.77 (d, J = 5.5 Hz, 2H), 6.86 (d, J = 5.2 Hz, 1H), 7.30-7.33 (m, 2H), 7.38-7.41 (m, 1H), 7.46-7.49 (m, 1H), 8.07 (s, 1H), 8.79 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 28.5, 41.6, 46.7, 78.1, 127.6, 129.3, 129.7, 132.4, 132.7, 136.5, 155.6, 155.8, 168.5.

실시예 13. [15a] 내지 [15zc]의 합성Example 13. Synthesis of [15a] to [15zc]

하기 [반응식 115](R₂N, 1,4-dioxane, reflux, 8h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [15a] 내지 [15zc]를 합성하였다.The pyrazolopyrimidine derivative compounds [15a] to [15zc] were synthesized according to the following Scheme 115 (R ₂ N, 1,4-dioxane, reflux, 8h).

[반응식 15][Reaction Scheme 15]

[5e] [15a] ~ [15zc][5e] [15a] to [15zc]

[15a] 내지 [15zc]에서 NR₂은 각각 하기 [표 8]과 같다.NR ₂ in [15a] to [15zc] are as shown in [Table 8], respectively.

구분division NR₂ NR ₂ 구분division NR₂ NR ₂ 15a15a

15p15p

15b15b

15q15q

15c15c

15r15r

15d15d

15s15s CH₃OCH ₃ O 15e15e

15t15 t

15f15f

15u15 u

15g15g

15v15v

15h15h

15w15w

15i15i

15x15x

15j15j

15y15y

15k15k

15z15z

15l15l

15za15za

15m15m

15zb15zb

15n15n

15zc15zc

15o15o

(1) 1-페닐-4-벤질아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15a](1) 1-phenyl-4-benzylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15a]

상기 [5e]와 benzylamine으로 하얀색 고체상 화합물 15a를 얻었다.[5e] and benzylamine gave a white solid compound 15a.

Yield: 96%; ¹H NMR (400MHz, DMSO-d₆) δ 2.49 (s, 3H), 4.73 (d, J = 5.7Hz, 2H), 7.24-7.38 (m, 6H), 7.53 (t, J = 7.7Hz, 2H), 8.17 (d, J = 8.4Hz, 2H), 8.32 (s, 1H), 9.00 (t, J = 5.6Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.2, 43.8, 99.9, 120.7, 126.4, 127.5, 128.0, 128.9, 129.6, 134.4, 139.4, 153.8, 155.8, 170.2.
Yield: 96%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.49 (s, 3H), 4.73 (d, J = 5.7 Hz, 2H), 7.24-7.38 (m, 6H), 7.53 (t, J = 7.7 Hz, 2H ), 8.17 (d, J = 8.4 Hz, 2H), 8.32 (s, 1H), 9.00 (t, J = 5.6 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.2, 43.8, 99.9, 120.7, 126.4, 127.5, 128.0, 128.9, 129.6, 134.4, 139.4, 153.8, 155.8, 170.2.

(2) 1-페닐-4-(2-페닐에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15b](2) 1-phenyl-4- (2-phenylethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15b]

상기 [5e]와 2-phenylethylamine으로 옅은 노란색의 고체상 화합물 15b를 얻었다.A pale yellow solid compound 15b was obtained from [5e] and 2-phenylethylamine.

Yield: 70%; ¹H NMR (400MHz, DMSO-d₆) δ 2.53 (s, 3H), 2.93 (t, J = 7.3Hz, 2H), 3.71 (quar, J = 6.6Hz, 2H), 7.18-7.31 (m, 7H), 7.52 (t, J = 7.5Hz, 2H), 8.18 (d, J = 8.2Hz, 2H), 8.27 (s, 1H), 8.62 (t, J = 5.1Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.1, 100.0, 116.5, 120.7, 126.3, 129.5, 134.4, 135.2, 139.4, 153.8, 155.7, 170.1.
Yield: 70%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.53 (s, 3H), 2.93 (t, J = 7.3 Hz, 2H), 3.71 (quar, J = 6.6 Hz, 2H), 7.18-7.31 (m, 7H ), 7.52 (t, J = 7.5 Hz, 2H), 8.18 (d, J = 8.2 Hz, 2H), 8.27 (s, 1H), 8.62 (t, J = 5.1 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.1, 100.0, 116.5, 120.7, 126.3, 129.5, 134.4, 135.2, 139.4, 153.8, 155.7, 170.1.

(3) 1-페닐-4-(4-메톡시벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15c](3) 1-phenyl-4- (4-methoxybenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15c]

상기 [5e]와 4-methoxybenzylamine으로 옅은 노란색의 고체상 화합물 15c를 얻었다.The pale yellow solid compound 15c was obtained from [5e] and 4-methoxybenzylamine.

Yield: 75%; ¹H NMR (400MHz, DMSO-d₆) δ 2.51 (s, 3H), 3.71 (s, 3H), 4.65 (d, J = 5.5Hz, 2H), 6.91 (d, J = 8.2Hz, 2H), 7.29-7.32 (m, 3H), 7.53 (t, J = 7.7Hz, 2H), 8.18 (d, J = 8.3Hz, 2H), 8.31 (s, 1H), 8.91 (t, J = 5.5Hz, 1H).
Yield: 75%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.51 (s, 3H), 3.71 (s, 3H), 4.65 (d, J = 5.5 Hz, 2H), 6.91 (d, J = 8.2 Hz, 2H), 7.29-7.32 (m, 3H), 7.53 (t, J = 7.7 Hz, 2H), 8.18 (d, J = 8.3 Hz, 2H), 8.31 (s, 1H), 8.91 (t, J = 5.5 Hz, 1H ).

(4) 1-페닐-4-(1-하이드록식에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15d](4) 1-phenyl-4- (1-hydroxyethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15d]

상기 [5e]와 1-hydroxyethylamine으로 옅은 노란색의 고체상 화합물 15d를 얻었다.A pale yellow solid compound 15d was obtained from [5e] and 1-hydroxyethylamine.

Yield: 61%; ¹H NMR (400MHz, DMSO-d₆) δ 2.51 (s,3H), 3.55-3.61 (m, 4H), 4.85 (t, J = 5.1Hz, 1H), 7.31 (t, J = 7.4Hz, 1H), 7.53 (t, J = 7.9Hz, 2H), 8.18 (d, J = 8.5Hz, 2H), 8.32 (s, 1H), 8.55 (t, J = 5.1Hz, 1H).
Yield: 61%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.51 (s, 3H), 3.55-3.61 (m, 4H), 4.85 (t, J = 5.1 Hz, 1H), 7.31 (t, J = 7.4 Hz, 1H ), 7.53 (t, J = 7.9 Hz, 2H), 8.18 (d, J = 8.5 Hz, 2H), 8.32 (s, 1H), 8.55 (t, J = 5.1 Hz, 1H).

(5) 1-페닐-4-(4-플루오로벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15e](5) 1-phenyl-4- (4-fluorobenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15e]

상기 [5e]와 4-fluorobenzylamine으로 옅은 노란색의 고체상 화합물 15e를 얻었다.The pale yellow solid compound 15e was obtained from [5e] and 4-fluorobenzylamine.

Yield: 94%; ¹H NMR (400MHz, DMSO-d₆) δ 2.49 (s, 3H), 4.71 (d, J = 5.4Hz, 2H), 7.17 (t, J = 8.2Hz, 2H), 7.32 (t, J = 7.0Hz, 1H), 7.41 (t, J = 6.5Hz, 2H), 7.53 (t, J = 7.3Hz, 2H), 8.17 (d, J = 8.3Hz, 2H), 8.30 (s, 1H), 9.00 (t, J = 5.3Hz, 1H).
Yield: 94%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.49 (s, 3H), 4.71 (d, J = 5.4 Hz, 2H), 7.17 (t, J = 8.2 Hz, 2H), 7.32 (t, J = 7.0 Hz, 1H), 7.41 (t, J = 6.5 Hz, 2H), 7.53 (t, J = 7.3 Hz, 2H), 8.17 (d, J = 8.3 Hz, 2H), 8.30 (s, 1H), 9.00 ( t, J = 5.3 Hz, 1H).

(6) 1-페닐-4-알릴아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15f](6) 1-phenyl-4-allylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15f]

상기 [5e]와 4-fluorobenzylamine으로 옅은 노란색의 고체상 화합물 15f를 얻었다.The pale yellow solid compound 15f was obtained from [5e] and 4-fluorobenzylamine.

Yield: 91%; ¹H NMR (400MHz, DMSO-d₆) δ 2.51 (s, 3H), 4.15 (t, J = 4.8Hz, 2H), 5.15 (dd, J = 1.2Hz, 10.3Hz, 1H), 5.25 (dd, J = 1.2Hz, 17.2Hz, 1H), 5.92-6.01 (m, 1H), 7.30 (t, J = 7.8Hz, 1H), 7.52 (t, J = 7.5Hz, 2H), 8.18 (d, J = 8.5Hz, 2H), 8.31 (s, 1H), 8.66 (t, J = 5.2Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.1, 100.0, 116.5, 120.7, 126.3, 129.5, 134.4, 135.2, 139.4, 153.8, 155.7, 170.1.
Yield: 91%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.51 (s, 3H), 4.15 (t, J = 4.8 Hz, 2H), 5.15 (dd, J = 1.2 Hz, 10.3 Hz, 1H), 5.25 (dd, J = 1.2 Hz, 17.2 Hz, 1H), 5.92-6.01 (m, 1H), 7.30 (t, J = 7.8 Hz, 1H), 7.52 (t, J = 7.5 Hz, 2H), 8.18 (d, J = 8.5 Hz, 2H), 8.31 (s, 1H), 8.66 (t, J = 5.2 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.1, 100.0, 116.5, 120.7, 126.3, 129.5, 134.4, 135.2, 139.4, 153.8, 155.7, 170.1.

(7) 1-페닐-4-[2-(피페리딘-1-일)]에틸아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15g](7) 1-phenyl-4- [2- (piperidin-1-yl)] ethylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15g]

상기 [5e]와 2-(piperidin-1-yl)ethylamine으로 옅은 노란색의 고체상 화합물 15g를 얻었다.15 g of a pale yellow solid compound was obtained from [5e] and 2- (piperidin-1-yl) ethylamine.

Yield: 74%; ¹H NMR (400MHz, DMSO-d₆) δ 1.63 (br s, 4H), 1.68 (br s, 3H), 2.51 (s, 3H), 3.90 (s, 4H), 7.33 (t, J = 7.4Hz, 1H), 7.54 (t, J = 7.7Hz, 2H), 8.16 (d, J = 8.5Hz, 2H), 8.46 (s, 1H).
Yield: 74%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.63 (br s, 4H), 1.68 (br s, 3H), 2.51 (s, 3H), 3.90 (s, 4H), 7.33 (t, J = 7.4 Hz , 1H), 7.54 (t, J = 7.7 Hz, 2H), 8.16 (d, J = 8.5 Hz, 2H), 8.46 (s, 1H).

(8) (R)-1-페닐-4-(1-페닐에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15h](8) (R) -1-phenyl-4- (1-phenylethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15h]

상기 [5e]와 (R)-1-phenylethylamine으로 옅은 노란색의 고체상 화합물 15h를 얻었다.A pale yellow solid compound 15h was obtained from [5e] and (R) -1-phenylethylamine.

Yield: 89%; ¹H NMR (400MHz, DMSO-d₆) δ 1.55 (d, J = 5Hz, 2H), 2.44 (s, 3H), 5.47 (m, 1H), 7.22 (m, 1H), 7.30 (m, 3H), 7.40 (m, 2H), 7.52 (m, 2H), 8.14 (d, J = 7Hz, 2H), 8.39 (s, 1H), 8.64 (d, J = 7Hz, 1H).
Yield: 89%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.55 (d, J = 5 Hz, 2H), 2.44 (s, 3H), 5.47 (m, 1H), 7.22 (m, 1H), 7.30 (m, 3H) , 7.40 (m, 2H), 7.52 (m, 2H), 8.14 (d, J = 7 Hz, 2H), 8.39 (s, 1H), 8.64 (d, J = 7 Hz, 1H).

(9) 1-페닐-4-비스(1-하이드록시에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15i](9) 1-phenyl-4-bis (1-hydroxyethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15i]

상기 [5e]와 diethanolamine으로 하얀색의 고체상 화합물 15i를 얻었다.White solid compound 15i was obtained from [5e] and diethanolamine.

Yield: 74%; ¹H NMR (400MHz, DMSO-d₆) δ 2.50 (s, 3H), 3.67-3.73 (m, 4H), 3.84 (br s, 4H), 4.82 (s, 1H), 5.02 (s, 1H), 7.32 (t, J = 7.1Hz, 1H), 7.53 (t, J = 7.3Hz, 2H), 8.15 (d, J = 8.2Hz, 2H), 8.28 (d, J = 1.1Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.1, 52.4, 53.1, 58.8, 99.1, 121.2, 126.5, 129.5, 136.0, 139.2, 154.7, 156.0, 168.9.
Yield: 74%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.50 (s, 3H), 3.67-3.73 (m, 4H), 3.84 (br s, 4H), 4.82 (s, 1H), 5.02 (s, 1H), 7.32 (t, J = 7.1 Hz, 1H), 7.53 (t, J = 7.3 Hz, 2H), 8.15 (d, J = 8.2 Hz, 2H), 8.28 (d, J = 1.1 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.1, 52.4, 53.1, 58.8, 99.1, 121.2, 126.5, 129.5, 136.0, 139.2, 154.7, 156.0, 168.9.

(10) 1-페닐-4-[(피리딘-2-일)메틸]아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15j](10) 1-phenyl-4-[(pyridin-2-yl) methyl] amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15j]

상기 [5e]와 (pyrindin-2-yl)methylamine으로 옅은 노란색의 고체상 화합물 15j를 얻었다.The light yellow solid compound 15j was obtained from [5e] and (pyrindin-2-yl) methylamine.

Yield: 62%; ¹H NMR (400MHz, DMSO-d₆) δ 2.43 (s, 3H), 4.82 (d, J = 5.7Hz, 2H), 7.26-7.32 (m, 1H), 7.38 (d, J = 7.8Hz, 1H), 7.53 (t, J = 7.6Hz, 2H), 7.76 (t, J = 7.6Hz, 1H), 8.17 (d, J = 8.4Hz, 2H), 8.36 (s, 1H), 8.53 (d, J = 4.4Hz, 1H), 9.13 (t, J = 5.7Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.1, 45.7, 100.0, 120.8, 121.9, 122.7, 126.4, 129.6, 134.4, 137.2, 139.4, 149.5, 153.8, 155.9, 158.6, 170.1.
Yield: 62%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.43 (s, 3H), 4.82 (d, J = 5.7 Hz, 2H), 7.26-7.32 (m, 1H), 7.38 (d, J = 7.8 Hz, 1H ), 7.53 (t, J = 7.6 Hz, 2H), 7.76 (t, J = 7.6 Hz, 1H), 8.17 (d, J = 8.4 Hz, 2H), 8.36 (s, 1H), 8.53 (d, J = 4.4 Hz, 1H), 9.13 (t, J = 5.7 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.1, 45.7, 100.0, 120.8, 121.9, 122.7, 126.4, 129.6, 134.4, 137.2, 139.4, 149.5, 153.8, 155.9, 158.6, 170.1.

(11) 1-페닐-4-[(1-하이드록시-2,2-다이메틸)에틸]아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15k](11) 1-phenyl-4-[(1-hydroxy-2,2-dimethyl) ethyl] amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15k]

상기 [5e]와 (1-hydroxy-2,2-dimethyl)ethylamine으로 하얀색의 고체상 화합물 15k를 얻었다.The white solid compound 15k was obtained from [5e] and (1-hydroxy-2,2-dimethyl) ethylamine.

Yield: 77%; ¹H NMR (400MHz, DMSO-d₆) δ 1.42 (s, 6H), 2.51 (s, 3H), 3.70 (d, J = 5.6Hz, 2H), 4.91 (t, J = 5.6Hz, 1H), 7.30 (t, J = 7.8Hz, 1H), 7.52 (t, J = 7.5Hz, 2H), 7.67 (s, 1H), 8.16 (d, J = 8.5Hz, 2H), 8.45 (d, J = 1.1Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.3, 24.4, 56.7, 66.8, 100.5, 120.7, 126.3, 129.5, 134.8, 139.4, 153.7, 155.8, 169.4.
Yield: 77%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.42 (s, 6H), 2.51 (s, 3H), 3.70 (d, J = 5.6 Hz, 2H), 4.91 (t, J = 5.6 Hz, 1H), 7.30 (t, J = 7.8 Hz, 1H), 7.52 (t, J = 7.5 Hz, 2H), 7.67 (s, 1H), 8.16 (d, J = 8.5 Hz, 2H), 8.45 (d, J = 1.1 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.3, 24.4, 56.7, 66.8, 100.5, 120.7, 126.3, 129.5, 134.8, 139.4, 153.7, 155.8, 169.4.

(12) 1-페닐-4-(3-메톡시벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15l](12) 1-phenyl-4- (3-methoxybenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15l]

상기 [5e]와 3-methoxybenzylamine으로 옅은 노란색의 고체상 화합물 15l를 얻었다.15l of a pale yellow solid compound was obtained from [5e] and 3-methoxybenzylamine.

Yield: 70%; ¹H NMR (400MHz, DMSO-d₆) δ 2.50 (s, 3H), 3.72 (s, 3H), 4.69 (s, 2H), 6.83 (d, J = 7.8Hz, 1H), 6.95 (s, 2H), 7.23-7.32 (m, 2H), 7.53 (t, J = 7.7Hz, 2H), 8.17 (d, J = 8.2Hz, 2H), 8.33 (s, 1H), 9.02 (br s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.1, 43.7, 55.4, 99.9, 112.8, 113.8, 120.1, 120.8, 126.5, 129.6, 130.0, 134.3, 139.3, 141.0, 153.8, 155.8, 159.7, 170.2.
Yield: 70%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.50 (s, 3H), 3.72 (s, 3H), 4.69 (s, 2H), 6.83 (d, J = 7.8 Hz, 1H), 6.95 (s, 2H ), 7.23-7.32 (m, 2H), 7.53 (t, J = 7.7 Hz, 2H), 8.17 (d, J = 8.2 Hz, 2H), 8.33 (s, 1H), 9.02 (br s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.1, 43.7, 55.4, 99.9, 112.8, 113.8, 120.1, 120.8, 126.5, 129.6, 130.0, 134.3, 139.3, 141.0, 153.8, 155.8, 159.7, 170.2.

(13) 1-페닐-4-피페리디노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15m](13) 1-phenyl-4-piperidino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15m]

상기 [5e]와 piperidine으로 옅은 노란색의 고체상 화합물 15m을 얻었다.15m of a pale yellow solid compound was obtained from [5e] and piperidine.

Yield: 93%; ¹H NMR (400MHz, DMSO-d₆) δ 1.62 (br s, 4H), 1.67 (br s, 2H), 2.50 (s, 3H), 3.88 (br s, 4H), 7.32 (t, J = 7.4Hz, 1H), 7.53 (t, J = 7.3Hz, 2H), 8.15 (d, J = 8.1Hz, 2H), 8.44 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.1, 24.2, 25.8, 46.2, 99.1, 121.2, 126.5, 129.5, 135.8, 139.2, 154.9, 155.5, 169.0.
Yield: 93%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.62 (br s, 4H), 1.67 (br s, 2H), 2.50 (s, 3H), 3.88 (br s, 4H), 7.32 (t, J = 7.4 Hz, 1H), 7.53 (t, J = 7.3 Hz, 2H), 8.15 (d, J = 8.1 Hz, 2H), 8.44 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.1, 24.2, 25.8, 46.2, 99.1, 121.2, 126.5, 129.5, 135.8, 139.2, 154.9, 155.5, 169.0.

(14) 1-페닐-4-(4-클로로벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15n](14) 1-phenyl-4- (4-chlorobenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15n]

상기 [5e]와 4-chloro-benzylamine으로 옅은 노란색의 고체상 화합물 15n을 얻었다.A pale yellow solid compound 15n was obtained from [5e] and 4-chloro-benzylamine.

Yield: 82%; ¹H NMR (400MHz, DMSO-d₆) δ 2.48 (s, 3H), 4.71 (d, J = 5.7Hz, 2H), 7.31 (t, J = 7.4Hz, 1H), 7.39 (s, 4H), 7.53 (t, J = 7.8Hz, 2H), 8.17 (d, J = 8.2Hz, 2H), 8.31 (s, 1H), 9.02 (t, J = 5.7Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.2, 43.1, 100.0, 120.8, 126.4, 128.8, 129.6, 129.8, 132.0, 134.3, 138.5, 139.4, 153.8, 155.8, 170.2.
Yield: 82%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.48 (s, 3H), 4.71 (d, J = 5.7 Hz, 2H), 7.31 (t, J = 7.4 Hz, 1H), 7.39 (s, 4H), 7.53 (t, J = 7.8 Hz, 2H), 8.17 (d, J = 8.2 Hz, 2H), 8.31 (s, 1H), 9.02 (t, J = 5.7 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.2, 43.1, 100.0, 120.8, 126.4, 128.8, 129.6, 129.8, 132.0, 134.3, 138.5, 139.4, 153.8, 155.8, 170.2.

(15) 1-페닐-4-(2-메틸벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15o](15) 1-phenyl-4- (2-methylbenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15o]

상기 [5e]와 2-methylbenzylamine으로 옅은 노란색의 고체상 화합물 15o를 얻었다.A pale yellow solid compound 15o was obtained from [5e] and 2-methylbenzylamine.

Yield: 67%; ¹H NMR (400MHz, DMSO-d₆) δ 2.33 (s, 3H), 2.49 (s, 3H), 4.70 (d, J = 5.1Hz, 2H), 7.18 (br s, 3H), 7.30 (t, J = 6.9Hz, 2H), 7.52 (t, J = 7.6Hz, 2H), 8.18 (d, J = 8.1Hz, 2H), 8.35 (s, 1H), 8.81 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.1, 19.2, 42.1, 99.9, 120.7, 126.3, 126.3, 127.7, 128.7, 129.6, 130.5, 134.5, 136.5, 136.8, 139.4, 153.8, 155.7, 170.1.
Yield: 67%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.33 (s, 3H), 2.49 (s, 3H), 4.70 (d, J = 5.1 Hz, 2H), 7.18 (br s, 3H), 7.30 (t, J = 6.9 Hz, 2H), 7.52 (t, J = 7.6 Hz, 2H), 8.18 (d, J = 8.1 Hz, 2H), 8.35 (s, 1H), 8.81 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.1, 19.2, 42.1, 99.9, 120.7, 126.3, 126.3, 127.7, 128.7, 129.6, 130.5, 134.5, 136.5, 136.8, 139.4, 153.8, 155.7, 170.1.

(16) 1-페닐-4-(4-메틸벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15p](16) 1-phenyl-4- (4-methylbenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15p]

상기 [5e]와 4-methylbenzylamine으로 옅은 노란색의 고체상 화합물 15p를 얻었다.15p was obtained as a pale yellow solid compound using [5e] and 4-methylbenzylamine.

Yield: 46%; ¹H NMR (400MHz, DMSO-d₆) δ 2.26 (s, 3H), 2.50 (s, 3H), 4.68 (d, J = 5.7Hz, 2H), 7.14 (d, J = 7.9Hz, 2H), 7.25 (d, J = 11.9Hz, 2H), 7.31 (t, J = 7.4Hz, 1H), 7.53 (t, J = 8.0Hz, 2H), 8.17 (d, J = 7.7Hz, 2H), 8.31 (s, 1H), 8.95 (t, J = 5.7Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.2, 21.1, 43.5, 99.9, 120.7, 126.4, 128.0, 129.4, 129.6, 134.4, 136.3, 136.6, 139.4, 153.8, 155.7, 170.1.
Yield: 46%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.26 (s, 3H), 2.50 (s, 3H), 4.68 (d, J = 5.7 Hz, 2H), 7.14 (d, J = 7.9 Hz, 2H), 7.25 (d, J = 11.9 Hz, 2H), 7.31 (t, J = 7.4 Hz, 1H), 7.53 (t, J = 8.0 Hz, 2H), 8.17 (d, J = 7.7 Hz, 2H), 8.31 ( s, 1 H), 8.95 (t, J = 5.7 Hz, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.2, 21.1, 43.5, 99.9, 120.7, 126.4, 128.0, 129.4, 129.6, 134.4, 136.3, 136.6, 139.4, 153.8, 155.7, 170.1.

(17) 1-페닐-4-사이클로헥실아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15q](17) 1-phenyl-4-cyclohexylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15q]

상기 [5e]와 4-methylbenzylamine으로 옅은 노란색의 고체상 화합물 15q를 얻었다.The pale yellow solid compound 15q was obtained from [5e] and 4-methylbenzylamine.

Yield: 96%; ¹H NMR (400MHz, DMSO-d₆) δ 1.15-1.35 (m, 5H), 1.60-1.63 (m, 1H), 1.74 (br s, 2H), 1.96 (br s, 2H), 2.50 (s, 3H), 4.03 (br s, 1H), 7.29 (t, J = 7.4Hz, 1H), 7.51 (t, J = 7.9Hz, 2H), 8.17 (d, J = 8.5Hz, 2H), 8.27 (d, J = 7.4Hz, 1H), 8.31 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.1, 25.2, 25.7, 32.7, 49.5, 99.8, 120.7, 126.3, 129.5, 134.5, 139.4, 153.8, 155.0, 170.1.
Yield: 96%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.15-1.35 (m, 5H), 1.60-1.63 (m, 1H), 1.74 (br s, 2H), 1.96 (br s, 2H), 2.50 (s, 3H), 4.03 (br s, 1H), 7.29 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.9 Hz, 2H), 8.17 (d, J = 8.5 Hz, 2H), 8.27 (d , J = 7.4 Hz, 1 H), 8.31 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.1, 25.2, 25.7, 32.7, 49.5, 99.8, 120.7, 126.3, 129.5, 134.5, 139.4, 153.8, 155.0, 170.1.

(18) (R)-1-페닐-4-(1-사이클로헥실에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15r](18) (R) -1-phenyl-4- (1-cyclohexylethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15r]

상기 [5e]와 (R)-1-cyclohexylethylamine으로 옅은 노란색의 고체상 화합물 15r을 얻었다.The pale yellow solid compound 15r was obtained from [5e] and (R) -1-cyclohexylethylamine.

Yield: 92%; ¹H NMR (400MHz, DMSO-d₆) δ 0.94-1.03 (m, 2H), 1.08-1.20 (m, 3H), 1.16 (d, J = 6.7Hz, 4H), 1.47 (m, 1H), 1.44-1.51 (m, 1H), 1.58-1.61 (m, 1H), 1.68-1.78 (m, 4H), 2.50 (s, 3H), 4.17-4.30 (m, 1H), 7.30 (t, J = 7.4Hz, 1H), 7.52 (t, J = 8.0Hz, 2H), 8.16 (d, J = 7.9Hz, 2H), 8.19 (s, 1H), 8.34 (s, 1H).
Yield: 92%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.94-1.03 (m, 2H), 1.08-1.20 (m, 3H), 1.16 (d, J = 6.7 Hz, 4H), 1.47 (m, 1H), 1.44 -1.51 (m, 1H), 1.58-1.61 (m, 1H), 1.68-1.78 (m, 4H), 2.50 (s, 3H), 4.17-4.30 (m, 1H), 7.30 (t, J = 7.4 Hz , 1H), 7.52 (t, J = 8.0 Hz, 2H), 8.16 (d, J = 7.9 Hz, 2H), 8.19 (s, 1H), 8.34 (s, 1H).

(19) 1-페닐-4-메톡시-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15s](19) 1-phenyl-4-methoxy-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15s]

1 M sodium methoxide/methanol(10 mL)에 상기 [5e] (70 mg, 0.252 mmol)을 넣은 후 6 시간 동안 reflux를 하였다. 시간이 지나면 상온으로 냉각을 시키고 diethyl ether (7 mL)를 가하였다. 반응 혼합물에 있는 고체는 필터하여 제거하고, acetic acid를 이용하여 중성으로 조절한 후 용매를 제거한다. 이렇게 얻은 고체는 물을 이용하여 씻어 내주면 옅은 갈색의 고체상 화합물 15s를 얻었다.[5e] (70 mg, 0.252 mmol) was added to 1 M sodium methoxide / methanol (10 mL), followed by reflux for 6 hours. After the time was cooled to room temperature and diethyl ether (7 mL) was added. Solids in the reaction mixture are removed by filtration, neutralized with acetic acid and solvent removed. The solid thus obtained was washed with water to obtain a light brown solid compound 15s.

Yield: 95%; ¹H NMR (400MHz, DMSO-d₆) δ 2.60 (s, 3H), 4.09 (s, 3H), 7.37 (t, J = 7.4Hz, 1H), 7.57 (t, J = 7.9Hz, 2H), 8.17 (d, J = 7.9Hz, 2H), 8.38 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.4, 54.9, 100.8, 121.0, 127.0, 129.7, 133.8, 138.9, 163.0, 170.5.
Yield: 95%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.60 (s, 3H), 4.09 (s, 3H), 7.37 (t, J = 7.4 Hz, 1H), 7.57 (t, J = 7.9 Hz, 2H), 8.17 (d, J = 7.9 Hz, 2H), 8.38 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.4, 54.9, 100.8, 121.0, 127.0, 129.7, 133.8, 138.9, 163.0, 170.5.

(20) 1-페닐-4-n-뷰틸아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15t](20) 1-phenyl-4-n-butylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15t]

상기 [5e]와 n-butylamine으로 옅은 노란색의 고체상 화합물 15t를 얻었다.15t of pale yellow solid compound was obtained using [5e] and n-butylamine.

Yield: 63%; ¹H NMR (400MHz, DMSO-d₆) δ 0.91 (t, J = 7.3Hz, 3H), 1.31-1.45 (m, 2H), 1.55-1.62 (m, 2H), 2.51 (s, 3H), 3.48 (quar, J = 6.5Hz, 2H), 7.30 (t, J = 7.4Hz, 1H), 7.52 (t, J = 7.9Hz, 2H), 8.17 (d, J = 7.8Hz, 2H), 8.27 (s, 1H), 8.42 (t, J = 5.4Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) d 14.1, 20.1, 31.2, 99.9, 120.7, 126.3, 129.5, 134.3, 139.4, 153.8, 155.9, 170.1.
Yield: 63%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.91 (t, J = 7.3 Hz, 3H), 1.31-1.45 (m, 2H), 1.55-1.62 (m, 2H), 2.51 (s, 3H), 3.48 (quar, J = 6.5 Hz, 2H), 7.30 (t, J = 7.4 Hz, 1H), 7.52 (t, J = 7.9 Hz, 2H), 8.17 (d, J = 7.8 Hz, 2H), 8.27 (s , 1H), 8.42 (t, J = 5.4 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) d 14.1, 20.1, 31.2, 99.9, 120.7, 126.3, 129.5, 134.3, 139.4, 153.8, 155.9, 170.1.

(21) 1-페닐-4-(4-메틸)피페라지노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15u](21) 1-phenyl-4- (4-methyl) piperazino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15u]

상기 [5e]와 4-methylpiperazine으로 옅은 노란색의 고체상 화합물 15u를 얻었다.15u of a pale yellow solid compound was obtained from [5e] and 4-methylpiperazine.

Yield: 63%; ¹H NMR (400MHz, DMSO-d₆) δ 2.22 (s, 3H), 2.44-2.45 (m, 4H), 2.50 (s, 3H), 3.91 (t, J = 4.7Hz, 4H), 7.33 (t, J = 7.9Hz, 1H), 7.48 (t, J = 8.0Hz, 2H), 8.15 (d, J = 8.5Hz, 2H), 8.48 (s, 1H).
Yield: 63%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.22 (s, 3H), 2.44-2.45 (m, 4H), 2.50 (s, 3H), 3.91 (t, J = 4.7 Hz, 4H), 7.33 (t , J = 7.9 Hz, 1H), 7.48 (t, J = 8.0 Hz, 2H), 8.15 (d, J = 8.5 Hz, 2H), 8.48 (s, 1H).

(22) 1-페닐-4-(2-메톡시벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15v](22) 1-phenyl-4- (2-methoxybenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15v]

상기 [5e]와 2-methylbenzylamine으로 옅은 노란색의 고체상 화합물 15v를 얻었다.A pale yellow solid compound 15v was obtained from [5e] and 2-methylbenzylamine.

Yield: 69%; ¹H NMR (400MHz, DMSO-d₆) δ 2.50 (s, 3H), 3.84 (s, 3H), 4.70 (d, J = 5.4Hz, 2H), 6.93 (t, J = 7.4Hz, 1H), 7.04 (d, J = 7.4Hz, 1H), 7.30 (quin, J = 8.0Hz, 3H), 7.54 (t, J = 7.4Hz, 2H), 8.20 (d, J = 8.4Hz, 2H), 8.38 (d, J = 1.1Hz, 1H), 8.82 (t, J = 5.3Hz, 1H); ¹³C NMR (400MHz, DMSO-d₆) δ 14.1, 55.8, 100.0, 111.1, 120.6, 120.7, 126.4, 126.5, 128.8, 129.6, 134.5, 139.4, 155.9, 157.4, 170.1.
Yield: 69%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.50 (s, 3H), 3.84 (s, 3H), 4.70 (d, J = 5.4 Hz, 2H), 6.93 (t, J = 7.4 Hz, 1H), 7.04 (d, J = 7.4 Hz, 1H), 7.30 (quin, J = 8.0 Hz, 3H), 7.54 (t, J = 7.4 Hz, 2H), 8.20 (d, J = 8.4 Hz, 2H), 8.38 ( d, J = 1.1 Hz, 1H), 8.82 (t, J = 5.3 Hz, 1H); ¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 14.1, 55.8, 100.0, 111.1, 120.6, 120.7, 126.4, 126.5, 128.8, 129.6, 134.5, 139.4, 155.9, 157.4, 170.1.

(23) 1-페닐-4-다이에틸아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [15w](23) 1-phenyl-4-diethylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [15w]

상기 [5e]와 diethylamine으로 옅은 투명한 액체상 화합물 15w를 얻었다.15 W of a light transparent liquid compound was obtained using [5e] and diethylamine.

Yield: 72%; ¹H NMR (400MHz, CDCl₃) δ 1.32 (s, 6H), 2.59 (s, 3H), 3.76 (d, J = 6.8Hz, 4H), 7.29 (t, J = 7.9Hz, 1H), 7.49 (t, J = 8.0Hz, 2H), 7.92 (s, 1H), 8.25 (dd, J = 0.9Hz, 8.6Hz, 2H); ¹³C NMR (100MHz, CDCl₃) δ 12.9, 14.2, 43.6, 98.8, 121.2, 125.9, 128.8, 134.4, 139.3, 154.9, 155.1, 169.5.
Yield: 72%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 1.32 (s, 6H), 2.59 (s, 3H), 3.76 (d, J = 6.8 Hz, 4H), 7.29 (t, J = 7.9 Hz, 1H), 7.49 ( t, J = 8.0 Hz, 2H), 7.92 (s, 1H), 8.25 (dd, J = 0.9 Hz, 8.6 Hz, 2H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 12.9, 14.2, 43.6, 98.8, 121.2, 125.9, 128.8, 134.4, 139.3, 154.9, 155.1, 169.5.

(24) N-(2-클로로벤질)-6-(메틸티오)-1-페닐-1H-피라졸로[3,4-d]피리미딘-4-아민 [15x](24) N- (2-chlorobenzyl) -6- (methylthio) -1-phenyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [15x]

상기 [5e]와 2-chlorobenzylamine으로 옅은 투명한 액체상 화합물 15x를 얻었다.15x was obtained as a light transparent liquid compound with [5e] and 2-chlorobenzylamine.

Yield: 82.61%; ¹H NMR (400MHz, DMSO-d₆) δ 2.48 (s, 3H), 4.82 (d, J = 5.6Hz, 2H), 7.31-7.35 (m, 3H), 7.45-7.57 (m, 5H), 8.21 (d, J = 8.3Hz, 2H), 8.39 (s, 1H), 9.02 (t, J = 5.4Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.1, 41.8, 100.0, 120.8, 126.4, 127.7, 129.3, 129.6, 129.7, 129.8, 132.8, 134.4, 136.3, 139.4, 153.8, 155.8, 170.1.
Yield: 82.61%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.48 (s, 3H), 4.82 (d, J = 5.6 Hz, 2H), 7.31-7.35 (m, 3H), 7.45-7.57 (m, 5H), 8.21 (d, J = 8.3 Hz, 2H), 8.39 (s, 1 H), 9.02 (t, J = 5.4 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.1, 41.8, 100.0, 120.8, 126.4, 127.7, 129.3, 129.6, 129.7, 129.8, 132.8, 134.4, 136.3, 139.4, 153.8, 155.8, 170.1.

(25) 4-(p-톨릴티오)-6-(메틸티오)-1-페닐-1H-피라졸로[3,4-d]피리미딘 [15y](25) 4- (p-tolylthio) -6- (methylthio) -1-phenyl-1H-pyrazolo [3,4-d] pyrimidine [15y]

상기 [5e]와 p-tolylthiol으로 하얀색의 고체상 화합물 15y를 얻었다.The white solid compound 15y was obtained from [5e] and p-tolylthiol.

Yield: 92.47%; ¹H NMR (400MHz, DMSO-d₆) δ 2.44 (s, 6H), 7.24 (s, 1H), 7.35-7.40 (m, 3H), 7.55 (t, J = 7.9Hz, 2H), 7.62 (d, J = 8.0Hz, 2H), 8.09 (d, J = 7.8Hz, 2H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.7, 20.9, 109.5, 120.6, 122.5, 126.6, 129.1, 130.5, 133.1, 135.8, 137.9, 140.8, 151.8, 166.8, 168.7.
Yield: 92.47%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.44 (s, 6H), 7.24 (s, 1H), 7.35-7.40 (m, 3H), 7.55 (t, J = 7.9 Hz, 2H), 7.62 (d , J = 8.0 Hz, 2H), 8.09 (d, J = 7.8 Hz, 2H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.7, 20.9, 109.5, 120.6, 122.5, 126.6, 129.1, 130.5, 133.1, 135.8, 137.9, 140.8, 151.8, 166.8, 168.7.

(26) N-((4-클로로페닐)(페닐)메틸)-6-(메틸티오)-1-페닐-1H-피라졸로[3,4-d]피리미딘-4-아민 [15z](26) N-((4-chlorophenyl) (phenyl) methyl) -6- (methylthio) -1-phenyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [15z]

상기 [5e]와 (4-chlorophenyl)(phenyl)methanamine으로 하얀색의 고체상 화합물 15z를 얻었다.White solid compound 15z was obtained from [5e] and (4-chlorophenyl) (phenyl) methanamine.

Yield: 94.25%; ¹H NMR (400MHz, DMSO-d₆) δ 2.44 (s, 3H), 6.69 (d, J = 7.6Hz, 1H), 7.31-7.56 (m, 12H), 8.16 (d, J = 7.8Hz, 2H), 8.48 (s, 1H), 9.26 (d, J = 7.5Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.7, 28.9, 56.6, 99.5, 100.3, 120.3, 126.0, 127.4, 127.7, 128.4, 128.5, 129.1, 129.4, 131.7, 134.2, 138.8, 140.8, 141.2, 153.5, 154.5, 169.5.
Yield: 94.25%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.44 (s, 3H), 6.69 (d, J = 7.6 Hz, 1H), 7.31-7.56 (m, 12H), 8.16 (d, J = 7.8 Hz, 2H ), 8.48 (s, 1 H), 9.26 (d, J = 7.5 Hz, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.7, 28.9, 56.6, 99.5, 100.3, 120.3, 126.0, 127.4, 127.7, 128.4, 128.5, 129.1, 129.4, 131.7, 134.2, 138.8, 140.8, 141.2, 153.5, 154.5, 169.5.

(27) N-(1-사이클로헥실에틸)-6-(메틸티오)-1-페닐-1H-피라졸로[3,4-d]피리미딘-4-아민 [15za](27) N- (1-cyclohexylethyl) -6- (methylthio) -1-phenyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [15za]

상기 [5e]와 (S)-cyclohexylethylamine으로 하얀색의 고체상 화합물 15za를 얻었다.White solid compound 15za was obtained from the above [5e] and (S) -cyclohexylethylamine.

Yield; 92.44%; ¹H NMR (400MHz, DMSO-d₆) δ 0.98-1.02 (m, 2H), 1.13-1.19 (m, 5H), 1.60-1.78 (m, 6H), 2.52 (s, 3H), 4.23-4.25 (m, 1H), 7.29-7.33 (m, 1H), 7.54 (t, J = 7.9Hz, 2H), 8.17-8.25 (m, 3H), 8.35 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.6, 17.3, 25.7, 25.9, 28.6, 29.1, 42.5, 49.8, 120.2, 125.8, 129.0, 134.0, 139.0, 153.4, 155.0, 161.2, 169.5.
Yield; 92.44%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.98-1.02 (m, 2H), 1.13-1.19 (m, 5H), 1.60-1.78 (m, 6H), 2.52 (s, 3H), 4.23-4.25 ( m, 1H), 7.29-7.33 (m, 1H), 7.54 (t, J = 7.9 Hz, 2H), 8.17-8.25 (m, 3H), 8.35 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.6, 17.3, 25.7, 25.9, 28.6, 29.1, 42.5, 49.8, 120.2, 125.8, 129.0, 134.0, 139.0, 153.4, 155.0, 161.2, 169.5.

(28) 6-(메틸티오)-1-페닐-N-(1-p-톨릴에틸)-1H-피라졸로[3,4-d]피리미딘-4-아민 [15zb](28) 6- (methylthio) -1-phenyl-N- (1-p-tolylethyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [15zb]

상기 [5e]와 1-p-tolylethanamine으로 하얀색의 고체상 화합물 15zb를 얻었다.15zb of a white solid compound was obtained using [5e] and 1-p-tolylethanamine.

Yield: 92.70%; ¹H NMR (400MHz, DMSO-d₆) δ 1.54 (d, J = 6.9Hz, 3H), 2.26 (s, 3H), 2.47 (s, 3H), 5.44 (t, J = 7.1Hz, 1H), 7.15 (d, J = 7.9Hz, 2H), 7.32 (t, J = 7.1Hz, 3H), 7.54 (t, J = 7.9Hz, 1H), 8.18 (d, J = 8.4Hz, 2H), 8.40 (s, 1H), 8.82 (d, J = 7.7Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.7, 20.5, 22.2, 48.9, 99.4, 120.2, 125.8, 125.9, 128.8, 129.0, 134.0, 135.8, 138.9, 141.3, 153.4, 154.4, 169.5.
Yield: 92.70%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.54 (d, J = 6.9 Hz, 3H), 2.26 (s, 3H), 2.47 (s, 3H), 5.44 (t, J = 7.1 Hz, 1H), 7.15 (d, J = 7.9 Hz, 2H), 7.32 (t, J = 7.1 Hz, 3H), 7.54 (t, J = 7.9 Hz, 1H), 8.18 (d, J = 8.4 Hz, 2H), 8.40 ( s, 1 H), 8.82 (d, J = 7.7 Hz, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.7, 20.5, 22.2, 48.9, 99.4, 120.2, 125.8, 125.9, 128.8, 129.0, 134.0, 135.8, 138.9, 141.3, 153.4, 154.4, 169.5.

(29) N-((S)-1-(4-메톡시페닐)에틸)-6-(메틸티오))-1-페닐-1H-피라졸로[3,4-d]피리미딘-4-아민 [15zc](29) N-((S) -1- (4-methoxyphenyl) ethyl) -6- (methylthio))-1-phenyl-1H-pyrazolo [3,4-d] pyrimidine-4- Amine [15zc]

상기 [5e]와 (R)-4-(methoxyphenyl)ethylamine으로 하얀색의 고체상 화합물 15zc를 얻었다.White solid compound 15zc was obtained from [5e] and (R) -4- (methoxyphenyl) ethylamine.

Yield: 94.56%; ¹H NMR (400MHz, DMSO-d₆) δ 1.55 (d, J = 6.9Hz, 3H), 2.49 (s, 3H), 3.73 (s, 3H), 5.45-5.46 (m, 1H), 6.91 (d, J = 8.6Hz, 2H), 7.30-7.36 (m, 3H), 7.54 (t, J = 7.9Hz, 2H), 8.19 (d, J = 8.3Hz, 1H), 8.40 (s, 1H), 8.80 (d, J = 7.7Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.6, 22.1, 48.5, 54.9, 99.4, 113.6, 120.2, 125.8, 127.2, 129.0, 133.9, 136.1, 138.9, 153.3, 154.4, 158.0, 169.5.
Yield: 94.56%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.55 (d, J = 6.9 Hz, 3H), 2.49 (s, 3H), 3.73 (s, 3H), 5.45-5.46 (m, 1H), 6.91 (d , J = 8.6Hz, 2H), 7.30-7.36 (m, 3H), 7.54 (t, J = 7.9Hz, 2H), 8.19 (d, J = 8.3Hz, 1H), 8.40 (s, 1H), 8.80 (d, J = 7.7 Hz, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.6, 22.1, 48.5, 54.9, 99.4, 113.6, 120.2, 125.8, 127.2, 129.0, 133.9, 136.1, 138.9, 153.3, 154.4, 158.0, 169.5.

실시예 14. [16a] 내지 [16zi]의 합성Example 14 Synthesis of [16a] to [16zi]

하기 [반응식 16](R₂N, 1,4-dioxane, reflux, 8h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [16a] 내지 [16zi]를 합성하였다.The pyrazolopyrimidine derivative compounds [16a] to [16zi] were synthesized according to the following Reaction Scheme 16 (R ₂ N, 1,4-dioxane, reflux, 8h).

[반응식 16][Reaction Scheme 16]

[5f] [16a] ~ [16zi][5f] [16a]-[16zi]

[16a] 내지 [16zi]에서 NR₂은 각각 하기 [표 9]와 같다.NR ₂ in [16a] to [16zi] are as shown in Table 9 below, respectively.

구분division NR₂ NR ₂ 구분division NR₂ NR ₂ 16a16a

16s16s

16b16b

16t16t

16c16c

16u16u

16d16d

16v16v

16e16e

16w16w

16f16f

16x16x

16g16g

16y16y

16h16h

16z16z

16i16i

16za16za

16j16j

16zb16zb

16k16k

16zc16zc

16l16l

16zd16zd

16m16m

16ze16ze

16n16n

16zf16zf

16o16o

16zg16zg

16p16p

16zh16zh

16q16q

16zi16zi

16r16r

(1) 1-벤질-4-벤질아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [16a](1) 1-benzyl-4-benzylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [16a]

상기 [5f]와 benzylamine으로 옅은 노란색의 고체상 화합물 16a를 얻었다[5f] and benzylamine gave pale yellow solid compound 16a.

Yield: 71%; ¹H NMR (400MHz, DMSO-d₆) δ 2.46 (s, 3H), 4.70 (d, J = 5.8Hz, 2H), 5.43 (s, 2H), 7.22-7.31 (m, 6H), 7.36-7.41 (m, 4H), 8.07 (s, 1H), 8.90 (t, J = 5.8Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 43.1, 50.2, 98.6, 127.9, 128.0, 128.8, 128.9, 129.7, 131.9, 132.6, 137.7, 138.7, 153.9, 155.7, 169.1.
Yield: 71%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.46 (s, 3H), 4.70 (d, J = 5.8 Hz, 2H), 5.43 (s, 2H), 7.22-7.31 (m, 6H), 7.36-7.41 (m, 4H), 8.07 (s, 1 H), 8.90 (t, J = 5.8 Hz, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 43.1, 50.2, 98.6, 127.9, 128.0, 128.8, 128.9, 129.7, 131.9, 132.6, 137.7, 138.7, 153.9, 155.7, 169.1.

(2) 1-벤질-4-(1-하이드록시에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [16b](2) 1-benzyl-4- (1-hydroxyethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [16b]

상기 [5f]와 1-hydroxyethylamine 으로 하얀색의 고체상 화합물 16a를 얻었다.[5f] and 1-hydroxyethylamine gave a white solid compound 16a.

Yield: 84%; ¹H NMR (400MHz, DMSO-d₆) δ 2.48 (s, 3H), 3.55 (dt, J = 5.2Hz, 16.8Hz, 4H), 4.81 (t, J = 5.0Hz, 1H), 5.41 (s, 2H), 7.18-7.31 (m, 5H), 8.06 (s, 1H), 8.39 (t, J = 4.9Hz, 1H).
Yield: 84%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.48 (s, 3H), 3.55 (dt, J = 5.2 Hz, 16.8 Hz, 4H), 4.81 (t, J = 5.0 Hz, 1H), 5.41 (s, 2H), 7.18-7.31 (m, 5H), 8.06 (s, 1H), 8.39 (t, J = 4.9 Hz, 1H).

(3) 1-벤질-4-(4-플루오로벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [16c](3) 1-benzyl-4- (4-fluorobenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [16c]

상기 [5f]와 4-fluorobenzylamine으로 옅은 노란색의 고체상 화합물 16c를 얻었다.A pale yellow solid compound 16c was obtained from [5f] and 4-fluorobenzylamine.

Yield: 64%; ¹H NMR (400MHz, DMSO-d₆) δ 2.46 (s, 3H), 4.68 (d, J = 5.7Hz, 2H), 5.42 (s, 2H), 7.15 (t, J = 8.8Hz, 2H), 7.22 (t, J = 8.3Hz, 3H), 7.29 (quar, J = 7.5Hz, 3H), 7.39 (t, J = 4.7Hz, 2H), 8.05 (s, 1H), 8.86 (t, J = 5.6Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 43.0, 50.1, 98.6, 115.4, 115.7, 127.9, 128.0, 128.9, 129.9, 130.0, 132.6, 135.7, 137.7, 153.9, 155.6, 169.1.
Yield: 64%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.46 (s, 3H), 4.68 (d, J = 5.7 Hz, 2H), 5.42 (s, 2H), 7.15 (t, J = 8.8 Hz, 2H), 7.22 (t, J = 8.3 Hz, 3H), 7.29 (quar, J = 7.5 Hz, 3H), 7.39 (t, J = 4.7 Hz, 2H), 8.05 (s, 1H), 8.86 (t, J = 5.6 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 43.0, 50.1, 98.6, 115.4, 115.7, 127.9, 128.0, 128.9, 129.9, 130.0, 132.6, 135.7, 137.7, 153.9, 155.6, 169.1.

(4) 1-벤질-4-(2-페닐에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [16d](4) 1-benzyl-4- (2-phenylethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [16d]

상기 [5f]와 2-phenylethylamine으로 옅은 노란색의 고체상 화합물 16d를 얻었다.16d was obtained as a pale yellow solid compound using [5f] and 2-phenylethylamine.

Yield: 77%; ¹H NMR (400MHz, DMSO-d₆) δ 2.50 (s, 3H), 2.91 (t, J = 7.4Hz, 2H), 3.67 (quar, J = 6.7Hz, 2H), 5.41 (s, 2H), 7.19 (d, J = 6.3Hz, 3H), 7.21-7.32 (m, 8H), 8.01 (s, 1H), 8.48 (t, J = 5.2Hz, 1H); ¹³C NMR (400MHz, DMSO-d₆) δ 14.1, 42.1, 50.1, 98.6, 126.6, 127.9, 128.0, 128.8, 128.9, 129.1, 132.6, 137.7, 153.9, 155.7, 169.0.
Yield: 77%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.50 (s, 3H), 2.91 (t, J = 7.4 Hz, 2H), 3.67 (quar, J = 6.7 Hz, 2H), 5.41 (s, 2H), 7.19 (d, J = 6.3 Hz, 3H), 7.21-7.32 (m, 8H), 8.01 (s, 1H), 8.48 (t, J = 5.2 Hz, 1H); ¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 14.1, 42.1, 50.1, 98.6, 126.6, 127.9, 128.0, 128.8, 128.9, 129.1, 132.6, 137.7, 153.9, 155.7, 169.0.

(5) (R)-1-벤질-4-(1-페닐에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [16e](5) (R) -1-benzyl-4- (1-phenylethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [16e]

상기 [5f]와 (R)-1-phenylethylamine으로 옅은 노란색의 고체상 화합물 16e를 얻었다.The pale yellow solid compound 16e was obtained from [5f] and (R) -1-phenylethylamine.

Yield: 83.68%; ¹H NMR (400MHz, DMSO-d₆) δ 1.52 (d, J = 6.9Hz, 3H), 2.40 (s, 3H), 5.40 (s, 2H), 5.44 (t, J = 6.9Hz, 1H), 7.19 (t, J = 6.4Hz, 3H), 7.24 (d, J = 7.0Hz, 1H), 7.30 (quar, J = 8.0Hz, 4H), 7.39 (t, J = 7.6Hz, 2H), 8.13 (s, 1H), 8.71 (d, J = 7.6Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.5, 22.3, 49.1, 49.6, 98.0, 126.0, 126.7, 127.4, 127.5, 128.3, 128.4, 132.3, 137.2, 144.5, 153.5, 154.4, 168.4.
Yield: 83.68%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.52 (d, J = 6.9 Hz, 3H), 2.40 (s, 3H), 5.40 (s, 2H), 5.44 (t, J = 6.9 Hz, 1H), 7.19 (t, J = 6.4 Hz, 3H), 7.24 (d, J = 7.0 Hz, 1H), 7.30 (quar, J = 8.0 Hz, 4H), 7.39 (t, J = 7.6 Hz, 2H), 8.13 ( s, 1 H), 8.71 (d, J = 7.6 Hz, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.5, 22.3, 49.1, 49.6, 98.0, 126.0, 126.7, 127.4, 127.5, 128.3, 128.4, 132.3, 137.2, 144.5, 153.5, 154.4, 168.4.

(6) 1-벤질-4-(2-메틸벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [16f](6) 1-benzyl-4- (2-methylbenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [16f]

상기 [5f]와 2-methylbenzylamine으로 옅은 노란색의 고체상 화합물 16f를 얻었다.16f was obtained as a pale yellow solid compound using [5f] and 2-methylbenzylamine.

Yield: 64%; ¹H NMR (400MHz, DMSO-d₆) δ 2.32 (s, 3H), 2.45 (s, 3H), 4.66 (d, J = 5.5Hz, 2H), 5.42 (s, 2H), 7.14-7.48 (m, 9H), 8.09 (s, 1H), 8.69 (t, J = 5.4Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 19.2, 42.0, 50.1, 98.5, 126.3, 127.6, 127.9, 128.1, 128.6, 128.9, 130.5, 132.8, 136.4, 137.0, 137.7, 153.9, 155.6, 169.0.
Yield: 64%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.32 (s, 3H), 2.45 (s, 3H), 4.66 (d, J = 5.5 Hz, 2H), 5.42 (s, 2H), 7.14-7.48 (m , 9H), 8.09 (s, 1 H), 8.69 (t, J = 5.4 Hz, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 19.2, 42.0, 50.1, 98.5, 126.3, 127.6, 127.9, 128.1, 128.6, 128.9, 130.5, 132.8, 136.4, 137.0, 137.7, 153.9, 155.6, 169.0.

(7) 1-벤질-4-(4-메톡시벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [16g](7) 1-benzyl-4- (4-methoxybenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [16 g]

상기 [5f]와 4-methoxybenzylamine으로 옅은 노란색의 고체상 화합물 16g를 얻었다.16 g of a pale yellow solid compound was obtained using [5f] and 4-methoxybenzylamine.

Yield: 64%; ¹H NMR (400MHz, DMSO-d₆) d 2.47 (s, 3H), 3.71 (s, 3H), 4.62 (d, J = 5.6Hz, 2H), 5.41 (s, 2H), 6.89 (d, J = 8.5Hz, 2H), 7.19-7.31 (m, 7H), 8.05 (s, 1H), 8.78 (t, J = 5.6Hz, 1H).
Yield: 64%; ¹ H NMR (400 MHz, DMSO-d ₆ ) d 2.47 (s, 3H), 3.71 (s, 3H), 4.62 (d, J = 5.6 Hz, 2H), 5.41 (s, 2H), 6.89 (d, J = 8.5 Hz, 2H), 7.19-7.31 (m, 7H), 8.05 (s, 1H), 8.78 (t, J = 5.6 Hz, 1H).

(8) 1-벤질-4-알릴아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [16h](8) 1-benzyl-4-allylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [16h]

상기 [5f]와 allylamine으로 옅은 노란색의 액체상 화합물 16h를 얻었다.16h was obtained as a pale yellow liquid compound using [5f] and allylamine.

Yield: 65%; ¹H NMR (400MHz, CDCl₃) δ 2.58 (s, 3H), 4.21 (s, 2H), 5.18 (d, J = 10.0Hz, 1H), 5.27 (d, J = 17.1Hz, 1H), 5.48 (s, 2H), 5.89-5.99 (m, 1H), 7.21-7.32 (m, 5H), 7.76 (s, 1H); ¹³C NMR (400MHz, CDCl₃) δ 14.2, 43.3, 50.5, 60.4, 117.2, 127.7, 128.1, 128.5, 133.6, 136.7, 154.3, 169.6.
Yield: 65%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 2.58 (s, 3H), 4.21 (s, 2H), 5.18 (d, J = 10.0 Hz, 1H), 5.27 (d, J = 17.1 Hz, 1H), 5.48 ( s, 2H), 5.89-5.99 (m, 1 H), 7.21-7.32 (m, 5H), 7.76 (s, 1H); ¹³ C NMR (400 MHz, CDCl ₃ ) δ 14.2, 43.3, 50.5, 60.4, 117.2, 127.7, 128.1, 128.5, 133.6, 136.7, 154.3, 169.6.

(9) 1-벤질-4-비스(1-하이드록시에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [16i](9) 1-benzyl-4-bis (1-hydroxyethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [16i]

상기 [5f]와 diethanolamine으로 하얀색의 고체상 화합물 16i를 얻었다.[5f] and diethanolamine yielded a white solid compound 16i.

Yield: 68%; ¹H NMR (400MHz, DMSO-d₆) δ 2.49 (s, 3H), 3.66 (br s, 4H), 3.81 (s, 4H), 4.80 (br s, 1H), 4.99 (br s, 1H), 5.44 (s, 2H), 7.20-7.33 (m, 5H), 8.03 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.5, 49.5, 51.5, 52.5, 58.2, 97.3, 127.3, 127.4, 128.3, 133.7, 137.1, 154.2, 155.4, 167.3.
Yield: 68%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.49 (s, 3H), 3.66 (br s, 4H), 3.81 (s, 4H), 4.80 (br s, 1H), 4.99 (br s, 1H), 5.44 (s, 2 H), 7.20-7.33 (m, 5 H), 8.03 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.5, 49.5, 51.5, 52.5, 58.2, 97.3, 127.3, 127.4, 128.3, 133.7, 137.1, 154.2, 155.4, 167.3.

(10) 1-벤질-4-[(1-하이드록시-2,2-다이메틸)에틸]아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [16j](10) 1-benzyl-4-[(1-hydroxy-2,2-dimethyl) ethyl] amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [16j]

상기 [5f]와 1-hydroxy-2,2-dimethylethylamine으로 하얀색의 고체상 화합물 16j를 얻었다.White solid compound 16j was obtained from [5f] and 1-hydroxy-2,2-dimethylethylamine.

Yield: 68%; ¹H NMR (400MHz, DMSO-d₆) δ 1.40 (s, 6H), 2.49 (s, 3H), 3.68 (d, J = 5.8Hz, 2H), 4.92 (t, J = 5.9Hz, 1H), 5.41 (s, 2H), 7.19-7.33 (m, 5H), 7.54 (s, 1H), 8.19 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.2, 24.4, 50.0, 56.5, 66.9, 99.2, 127.9, 127.9, 128.9, 133.1, 137.8, 153.7, 155.7, 168.3.
Yield: 68%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.40 (s, 6H), 2.49 (s, 3H), 3.68 (d, J = 5.8 Hz, 2H), 4.92 (t, J = 5.9 Hz, 1H), 5.41 (s, 2 H), 7.19-7.33 (m, 5 H), 7.54 (s, 1 H), 8.19 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.2, 24.4, 50.0, 56.5, 66.9, 99.2, 127.9, 127.9, 128.9, 133.1, 137.8, 153.7, 155.7, 168.3.

(11) 1-벤질-6-(메틸티오)-N-(1-페닐에틸)-1H-피라졸로[3,4-d]피리미딘-4-아민 [16k](11) 1-benzyl-6- (methylthio) -N- (1-phenylethyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [16k]

상기 [5f]와 1-phenylethylamine으로 얇은 노란색의 고체상 화합물 16k를 얻었다.The thin yellow solid compound 16k was obtained from [5f] and 1-phenylethylamine.

Yield: 90.24%; ¹H NMR (400MHz, DMSO-d₆) δ 1.54 (d, J = 7.0Hz, 3H), 2.42 (s, 3H), 5.42-5.45 (m, 3H), 7.20-7.34 (m, 8H), 7.41 (d, J = 7.2Hz, 2H), 8.17 (s, 1H), 8.74 (d, J = 7.6Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.5, 22.3, 49.1, 49.6, 98.0, 126.0, 126.7, 127.4, 127.5, 128.2, 128.4, 132.3, 137.2, 144.5, 153.5, 154.4, 168.4.
Yield: 90.24%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.54 (d, J = 7.0 Hz, 3H), 2.42 (s, 3H), 5.42-5.45 (m, 3H), 7.20-7.34 (m, 8H), 7.41 (d, J = 7.2 Hz, 2H), 8.17 (s, 1 H), 8.74 (d, J = 7.6 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.5, 22.3, 49.1, 49.6, 98.0, 126.0, 126.7, 127.4, 127.5, 128.2, 128.4, 132.3, 137.2, 144.5, 153.5, 154.4, 168.4.

(12) 1-벤질-4-(에틸티오)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘 [16l](12) 1-benzyl-4- (ethylthio) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidine [16l]

상기 [5f]와 ethylthiol으로 노란색의 고체상 화합물 16l를 얻었다.16l of a yellow solid compound was obtained from [5f] and ethylthiol.

Yield: 90.58%; ¹H NMR (400MHz, DMSO-d₆) δ 1.36 (t, J = 7.3Hz, 3H), 2.60 (s, 3H), 3.34 (t, J = 7.3Hz, 2H), 5.54 (s, 2H), 7.24-7.33 (m, 5H), 8.19 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.7, 14.4, 23.0, 50.0, 108.8, 127.6, 128.5, 132.0, 136.6, 151.3, 164.3, 168.0.
Yield: 90.58%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.36 (t, J = 7.3 Hz, 3H), 2.60 (s, 3H), 3.34 (t, J = 7.3 Hz, 2H), 5.54 (s, 2H), 7.24-7.33 (m, 5 H), 8.19 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.7, 14.4, 23.0, 50.0, 108.8, 127.6, 128.5, 132.0, 136.6, 151.3, 164.3, 168.0.

(13) 1-벤질-4-(뷰틸티오)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘 [16m](13) 1-benzyl-4- (butylthio) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidine [16m]

상기 [5f]와 n-butylthiol으로 노란색의 고체상 화합물 16m를 얻었다.16m of a yellow solid compound was obtained from [5f] and n-butylthiol.

Yield: 93.10%; ¹H NMR (400MHz, DMSO-d₆) δ 0.91 (t, J = 7.3Hz, 3H), 1.39-1.46 (m, 2H), 1.67-1.72 (m, 2H), 2.60 (s, 3H), 3.33 (t, J = 7.2Hz, 2H), 5.54 (s, 2H), 7.25-7.34 (m, 5H), 8.19 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 13.7, 21.3, 27.9, 30.8, 50.0, 108.9, 127.6, 128.5, 132.0, 136.6, 151.3, 164.3, 168.0.
Yield: 93.10%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.91 (t, J = 7.3 Hz, 3H), 1.39-1.46 (m, 2H), 1.67-1.72 (m, 2H), 2.60 (s, 3H), 3.33 (t, J = 7.2 Hz, 2H), 5.54 (s, 2H), 7.25-7.34 (m, 5H), 8.19 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 13.7, 21.3, 27.9, 30.8, 50.0, 108.9, 127.6, 128.5, 132.0, 136.6, 151.3, 164.3, 168.0.

(14) 1-벤질-4-(이소부틸티오)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘 [16n](14) 1-benzyl-4- (isobutylthio) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidine [16n]

상기 [5f]와 isobutylthiol으로 노란색의 액체상 화합물 16n를 얻었다.[5f] and isobutylthiol yielded a yellow liquid compound 16n.

Yield: 79.30% ¹H NMR (400MHz, DMSO-d₆) δ 1.01 (d, J = 6.6Hz, 6H), 1.96-1.99 (m, 1H), 2.61 (s, 3H), 3.26 (d, J = 6.6Hz, 2H), 5.54 (s, 2H), 7.25-7.34 (m, 5H), 8.20 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.7, 21.4, 28.0, 36.3, 50.0, 108.9, 127.6, 128.5, 132.0, 136.5, 151.3, 164.3, 167.9.
Yield: 79.30% ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.01 (d, J = 6.6 Hz, 6H), 1.96-1.99 (m, 1H), 2.61 (s, 3H), 3.26 (d, J = 6.6 Hz, 2H), 5.54 (s, 2H), 7.25-7.34 (m, 5H), 8.20 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.7, 21.4, 28.0, 36.3, 50.0, 108.9, 127.6, 128.5, 132.0, 136.5, 151.3, 164.3, 167.9.

(15) 4-(3-클로로프로필티오)-1-벤질-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘 [16o](15) 4- (3-chloropropylthio) -1-benzyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidine [16o]

상기 [5f]와 4-chloropropylthiol으로 노란색의 액체상 화합물 16o를 얻었다.[5f] and 4-chloropropylthiol to obtain a yellow liquid compound 16o.

Yield: 83.40%; ¹H NMR (400MHz, DMSO-d₆) δ 2.17-2.22 (m, 2H), 2.61 (s, 3H), 3.45 (t, J = 7.1Hz, 2H), 3.77 (t, J = 6.4Hz, 2H), 5.54 (s, 2H), 7.25-7.34 (m, 5H), 8.20 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.9, 25.8, 31.7, 44.0, 50.1, 109.0, 127.7, 128.6, 132.1, 136.6, 151.4, 163.8, 168.2.
Yield: 83.40%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.17-2.22 (m, 2H), 2.61 (s, 3H), 3.45 (t, J = 7.1 Hz, 2H), 3.77 (t, J = 6.4 Hz, 2H ), 5.54 (s, 2H), 7.25-7.34 (m, 5H), 8.20 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 25.8, 31.7, 44.0, 50.1, 109.0, 127.7, 128.6, 132.1, 136.6, 151.4, 163.8, 168.2.

(16) 4-(p-톨릴티오)-1-벤질-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘 [16p](16) 4- (p-tolylthio) -1-benzyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidine [16p]

상기 [5f]와 p-Tolylthiol으로 노란색의 고체상 화합물 16p를 얻었다.The yellow solid compound 16p was obtained by the above [5f] and p-Tolylthiol.

Yield: 94.59%; ¹H NMR (400MHz, DMSO-d₆) δ 2.44 (d, J = 12.8Hz, 6H), 5.49 (s, 2H), 6.92 (s, 1H), 7.23-7.33 (m, 5H), 7.38 (d, J = 7.9Hz, 2H), 7.62 (d, J = 7.9Hz, 2H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.6, 20.8, 49.9, 108.1, 122.6, 127.6, 127.7, 128.5, 130.4, 131.7, 135.9, 136.3, 140.8, 152.0, 166.7, 167.7.
Yield: 94.59%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.44 (d, J = 12.8 Hz, 6H), 5.49 (s, 2H), 6.92 (s, 1H), 7.23-7.33 (m, 5H), 7.38 (d , J = 7.9 Hz, 2H), 7.62 (d, J = 7.9 Hz, 2H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.6, 20.8, 49.9, 108.1, 122.6, 127.6, 127.7, 128.5, 130.4, 131.7, 135.9, 136.3, 140.8, 152.0, 166.7, 167.7.

(17) 4-(4-메톡시페닐티오)-1-벤질-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘 [16q](17) 4- (4-methoxyphenylthio) -1-benzyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidine [16q]

상기 [5f]와 4-methoxyphenylthiol으로 노란색의 고체상 화합물 16q를 얻었다.The yellow solid compound 16q was obtained from [5f] and 4-methoxyphenylthiol.

Yield: 85.22%; ¹H NMR (400MHz, DMSO-d₆) δ 2.46 (s, 3H), 3.85 (s, 3H), 5.49 (s, 2H), 6.87 (s, 1H), 7.12 (d, J = 8.8Hz, 2H), 7.22-7.30 (m, 5H), 7.65 (d, J = 8.8Hz, 2H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.6, 49.9, 55.4, 108.0, 115.4, 116.4, 127.6, 127.7, 128.4, 131.7, 136.3, 137.7, 152.1, 161.3, 167.5, 167.7.
Yield: 85.22%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.46 (s, 3H), 3.85 (s, 3H), 5.49 (s, 2H), 6.87 (s, 1H), 7.12 (d, J = 8.8 Hz, 2H ), 7.22-7.30 (m, 5H), 7.65 (d, J = 8.8 Hz, 2H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.6, 49.9, 55.4, 108.0, 115.4, 116.4, 127.6, 127.7, 128.4, 131.7, 136.3, 137.7, 152.1, 161.3, 167.5, 167.7.

(18) 4-(4-클로로페닐티오)-1-벤질-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘 [16r](18) 4- (4-chlorophenylthio) -1-benzyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidine [16r]

상기 [5f]와 4-chlorophenylthiol으로 노란색의 고체상 화합물 16r를 얻었다.[5f] and 4-chlorophenylthiol to give a yellow solid compound 16r.

Yield: 97.03%; ¹H NMR (400MHz, DMSO-d₆) δ 2.39 (s, 3H), 5.52 (s, 2H), 7.23-7.31 (m, 5H), 7.54 (s, 1H), 7.62 (d, J = 8.5Hz, 2H), 7.74 (d,J = 8.3Hz, 2H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.7, 50.1, 108.4, 125.1, 127.8, 128.6, 129.8, 131.9, 135.7, 136.5, 137.6, 152.1, 164.8, 168.1.
Yield: 97.03%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.39 (s, 3H), 5.52 (s, 2H), 7.23-7.31 (m, 5H), 7.54 (s, 1H), 7.62 (d, J = 8.5 Hz , 2H), 7.74 (d, J = 8.3 Hz, 2H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.7, 50.1, 108.4, 125.1, 127.8, 128.6, 129.8, 131.9, 135.7, 136.5, 137.6, 152.1, 164.8, 168.1.

(19) 4-(2-클로로벤질티오)-1-벤질-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘 [16s](19) 4- (2-chlorobenzylthio) -1-benzyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidine [16s]

상기 [5f]와 2-chlorobenzylthiol으로 노란색의 고체상 화합물 16s를 얻었다.The yellow solid compound 16s was obtained from [5f] and 2-chlorobenzylthiol.

Yield: 93.86%; ¹H NMR (400MHz, DMSO-d₆) δ 2.61 (s, 3H), 4.71 (s, 2H), 5.54 (s, 2H), 7.25-7.34 (m, 7H), 7.47-7.50 (m, 1H), 7.62-7.65 (m, 1H), 8.22 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.7, 30.1, 50.0, 108.4, 127.3, 127.7, 128.5, 129.1, 131.4, 132.0, 133.3, 134.4, 136.5, 151.4, 163.0, 168.1.
Yield: 93.86%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.61 (s, 3H), 4.71 (s, 2H), 5.54 (s, 2H), 7.25-7.34 (m, 7H), 7.47-7.50 (m, 1H) , 7.62-7.65 (m, 1 H), 8.22 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.7, 30.1, 50.0, 108.4, 127.3, 127.7, 128.5, 129.1, 131.4, 132.0, 133.3, 134.4, 136.5, 151.4, 163.0, 168.1.

(20) 4-(2,6-다이클로로페닐티오)-1-벤질-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘 [16t](20) 4- (2,6-dichlorophenylthio) -1-benzyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidine [16t]

상기 [5f]와 2,6-dichlorophenylthiol으로 노란색의 고체상 화합물 16t를 얻었다.16t of a yellow solid compound was obtained from [5f] and 2,6-dichlorophenylthiol.

Yield: 95.31%; ¹H NMR (400MHz, DMSO-d₆) δ 2.29 (s, 3H), 5.54 (s, 2H), 7.26-7.35 (m, 5H), 7.64-7.68 (m, 1H), 7.76 (d, J = 7.8Hz, 2H), 7.84 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 50.1, 98.5, 108.1, 125.1, 127.7, 128.5, 129.1, 131.5, 133.4, 136.3, 141.0, 151.9, 161.9, 168.0.
Yield: 95.31%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.29 (s, 3H), 5.54 (s, 2H), 7.26-7.35 (m, 5H), 7.64-7.68 (m, 1H), 7.76 (d, J = 7.8 Hz, 2H), 7.84 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 50.1, 98.5, 108.1, 125.1, 127.7, 128.5, 129.1, 131.5, 133.4, 136.3, 141.0, 151.9, 161.9, 168.0.

(21) 4-(4-플루오로페닐티오)-1-벤질-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘 [16u](21) 4- (4-fluorophenylthio) -1-benzyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidine [16u]

상기 [5f]와 4-Fluorophenylthiol으로 노란색의 고체상 화합물 16u를 얻었다.The yellow solid compound 16u was obtained from [5f] and 4-Fluorophenylthiol.

Yield: 92.42%, ¹H NMR (400MHz, DMSO-d₆) δ 2.39 (s, 3H), 5.52 (s, 2H), 7.24-7.31 (m, 5H), 7.39-7.43 (m, 3H), 7.77-7.79 (m, 3H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.6, 50.1, 108.2, 116.7, 116.9, 121.7, 127.6, 128.5, 131.7, 136.3, 138.3, 138.4, 151.9, 162.2, 164.7, 165.4, 167.8.
Yield: 92.42%, ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.39 (s, 3H), 5.52 (s, 2H), 7.24-7.31 (m, 5H), 7.39-7.43 (m, 3H), 7.77 -7.79 (m, 3 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.6, 50.1, 108.2, 116.7, 116.9, 121.7, 127.6, 128.5, 131.7, 136.3, 138.3, 138.4, 151.9, 162.2, 164.7, 165.4, 167.8.

(22) 1-벤질-6-(메틸티오)-4-(옥틸티오)-1H-피라졸로[3,4-d]피리미딘 [16v](22) 1-benzyl-6- (methylthio) -4- (octylthio) -1H-pyrazolo [3,4-d] pyrimidine [16v]

상기 [5f]와 n-octylthiol으로 노란색의 고체상 화합물 16v를 얻었다.The yellow solid compound 16v was obtained from [5f] and n-octylthiol.

Yield: 78.35%; ¹H NMR (400MHz, DMSO-d₆) δ 0.83 (t, J = 6.8Hz, 3H), 1.22-1.26 (m, 8H), 1.36-1.40 (m, 2H), 1.67-1.71 (m, 2H), 2.59 (s, 3H), 3.31 (t, J = 7.3Hz, 2H), 5.53 (s, 2H), 7.24-7.33 (m, 5H), 8.18 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.7, 13.8, 22.0, 28.1, 28.2, 28.4, 28.4, 28.7, 31.1, 49.9, 108.8, 127.6, 128.4, 132.0, 136.5, 151.3, 164.3, 168.0.
Yield: 78.35%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.83 (t, J = 6.8 Hz, 3H), 1.22-1.26 (m, 8H), 1.36-1.40 (m, 2H), 1.67-1.71 (m, 2H) , 2.59 (s, 3H), 3.31 (t, J = 7.3 Hz, 2H), 5.53 (s, 2H), 7.24-7.33 (m, 5H), 8.18 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.7, 13.8, 22.0, 28.1, 28.2, 28.4, 28.4, 28.7, 31.1, 49.9, 108.8, 127.6, 128.4, 132.0, 136.5, 151.3, 164.3, 168.0.

(23) 1-벤질-4-(도데실티오)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘(16w)(23) 1-benzyl-4- (dodecylthio) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidine (16w)

상기 [5f]와 n-dodecylthiol으로 노란색의 액체상 화합물 16w를 얻었다.[5f] and n-dodecylthiol gave a yellow liquid compound 16w.

Yield: 91.66%; ¹H NMR (400MHz, DMSO-d₆) δ 0.85 (t, J = 3.4Hz, 3H), 1.24 (s, 16H), 1.42 (s, 2H), 1.71-1.74 (m, 2H), 2.59 (s, 3H), 3.31 (t, J = 7.2Hz, 2H), 5.52 (s, 2H), 7.23-7.32 (m, 5H), 8.02 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.9, 22.2, 28.3, 28.4, 28.6, 28.8, 28.9, 29.0, 29.1, 31.4, 50.1, 78.4, 78.7, 79.0, 109.0, 127.6, 127.7, 128.4, 131.7, 136.4, 151.4, 164.3, 168.1.
Yield: 91.66%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.85 (t, J = 3.4 Hz, 3H), 1.24 (s, 16H), 1.42 (s, 2H), 1.71-1.74 (m, 2H), 2.59 (s , 3H), 3.31 (t, J = 7.2 Hz, 2H), 5.52 (s, 2H), 7.23-7.32 (m, 5H), 8.02 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 22.2, 28.3, 28.4, 28.6, 28.8, 28.9, 29.0, 29.1, 31.4, 50.1, 78.4, 78.7, 79.0, 109.0, 127.6, 127.7, 128.4, 131.7, 136.4, 151.4, 164.3, 168.1.

(24) 1-벤질-6-(메틸티오)-N-(1-페닐에틸)-1H-피라졸로[3,4-d]피리미딘-4-아민 [16x](24) 1-benzyl-6- (methylthio) -N- (1-phenylethyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [16x]

상기 [5f]와 (S)-phenylethylamine으로 얇은 노란색의 액체상 화합물 16x를 얻었다.[5f] and (S) -phenylethylamine afforded a thin yellow liquid compound 16x.

Yield: 92.02%; ¹H NMR (400MHz, DMSO-d₆) δ 1.54 (d, J = 6.5Hz, 3H), 2.42 (s, 3H), 5.42 (s, 3H), 7.19-7.41 (m, 8H), 7.41 (d, J = 7.1Hz, 2H), 8.15 (s, 1H), 8.74 (d, J = 7.1Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.5, 22.3, 49.1, 49.6, 98.0, 126.0, 126.7, 127.4, 127.5, 128.3, 128.4, 132.3, 137.2, 144.5, 153.5, 154.4, 168.4.
Yield: 92.02%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.54 (d, J = 6.5 Hz, 3H), 2.42 (s, 3H), 5.42 (s, 3H), 7.19-7.41 (m, 8H), 7.41 (d , J = 7.1 Hz, 2H), 8.15 (s, 1H), 8.74 (d, J = 7.1 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.5, 22.3, 49.1, 49.6, 98.0, 126.0, 126.7, 127.4, 127.5, 128.3, 128.4, 132.3, 137.2, 144.5, 153.5, 154.4, 168.4.

(25) 1-벤질-N-((4-클로로페닐)(페닐)메틸)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [16y](25) 1-benzyl-N-((4-chlorophenyl) (phenyl) methyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [16y]

상기 [5f]와 4-(chlorophenyl)(phenyl)methylamine으로 하얀색의 고체상 화합물 16y를 얻었다.White solid compound 16y was obtained from [5f] and 4- (chlorophenyl) (phenyl) methylamine.

Yield: 91.08%; ¹H NMR (400MHz, DMSO-d₆) δ 2.41 (s, 3H), 5.43 (s, 2H), 6.67 (d, J = 7.6Hz, 1H), 7.20-7.44 (m, 14H), 8.23 (s, 1H), 9.14 (d, J = 7.6Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) d 13.6, 14.0, 28.9, 49.6, 56.6, 98.1, 127.3, 127.4, 127.5, 127.6, 128.3, 138.4, 128.5, 129.3, 131.7, 132.6, 137.2, 140.9, 141.3, 153.6, 154.4, 168.4.
Yield: 91.08%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.41 (s, 3H), 5.43 (s, 2H), 6.67 (d, J = 7.6 Hz, 1H), 7.20-7.44 (m, 14H), 8.23 (s , 1H), 9.14 (d, J = 7.6 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) d 13.6, 14.0, 28.9, 49.6, 56.6, 98.1, 127.3, 127.4, 127.5, 127.6, 128.3, 138.4, 128.5, 129.3, 131.7, 132.6, 137.2, 140.9, 141.3, 153.6, 154.4, 168.4.

(26) 1-벤질-N-(1-사이클로헥실에틸)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [16z](26) 1-benzyl-N- (1-cyclohexylethyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [16z]

상기 [5f]와 (S)-cyclohexylethylamine으로 노란색의 고체상 화합물 16z를 얻었다.The yellow solid compound 16z was obtained from the above [5f] and (S) -cyclohexylethylamine.

Yield: 93.22%; ¹H NMR (400MHz, DMSO-d₆) δ 0.94-1.02 (m, 2H), 1.15 (d, J = 6.8Hz, 3H), 1.17-1.22 (m, 2H), 1.46-1.61 (m, 2H), 1.68-1.77 (m, 4H), 2.48 (s, 3H), 4.18-4.23 (m, 1H), 5.44-5.41 (m, 2H), 7.21-7.33 (m, 5H), 8.05 (d, J = 8.5Hz, 1H), 8.10 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.5, 17.2, 25.6, 25.7, 25.8, 28.6, 29.1, 42.4, 49.5, 49.7, 97.9, 127.3, 127.5, 128.4, 132.2, 137.2, 153.4, 154.9, 168.3.
Yield: 93.22%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.94-1.02 (m, 2H), 1.15 (d, J = 6.8 Hz, 3H), 1.17-1.22 (m, 2H), 1.46-1.61 (m, 2H) , 1.68-1.77 (m, 4H), 2.48 (s, 3H), 4.18-4.23 (m, 1H), 5.44-5.41 (m, 2H), 7.21-7.33 (m, 5H), 8.05 (d, J = 8.5 Hz, 1 H), 8.10 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.5, 17.2, 25.6, 25.7, 25.8, 28.6, 29.1, 42.4, 49.5, 49.7, 97.9, 127.3, 127.5, 128.4, 132.2, 137.2, 153.4, 154.9, 168.3.

(27) 1-벤질-6-(메틸티오)-N-(1-p-톨릴에틸)-1H-피라졸로[3,4-d]피리미딘-4-아민 [16za](27) 1-benzyl-6- (methylthio) -N- (1-p-tolylethyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [16za]

상기 [5f]와 p-tolylethylamine으로 하얀색의 고체상 화합물 16za를 얻었다.The solid solid compound 16za was obtained from the above [5f] and p-tolylethylamine.

Yield: 93.78%; ¹H NMR (400MHz, DMSO-d₆) δ 1.52 (d, J = 6.9Hz, 3H), 2.25 (s, 3H), 2.43 (s, 3H), 5.42 (s, 3H), 7.13 (d, J = 7.6Hz, 2H), 7.19-7.31 (m, 8H), 8.15 (s, 1H), 8.68 (d, J = 7.6Hz, 1H); ¹³C NMR(100MHz, DMSO-d₆) δ 13.5, 20.5, 22.2, 48.8, 49.6, 98.0, 125.9, 127.4, 127.5, 128.4, 128.8, 132.3, 135.7, 137.2, 141.5, 153.5, 154.4, 168.4.
Yield: 93.78%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.52 (d, J = 6.9 Hz, 3H), 2.25 (s, 3H), 2.43 (s, 3H), 5.42 (s, 3H), 7.13 (d, J = 7.6 Hz, 2H), 7.19-7.31 (m, 8H), 8.15 (s, 1H), 8.68 (d, J = 7.6 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.5, 20.5, 22.2, 48.8, 49.6, 98.0, 125.9, 127.4, 127.5, 128.4, 128.8, 132.3, 135.7, 137.2, 141.5, 153.5, 154.4, 168.4.

(28) 1-벤질-N-((S)-1-(4-메톡시페닐)에틸)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [16zb](28) 1-benzyl-N-((S) -1- (4-methoxyphenyl) ethyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [16zb]

상기 [5f]와 (R)-4-methoxyphenylethylamine으로 얇은 노란색의 고체상 화합물 16zb를 얻었다.The thin yellow solid compound 16zb was obtained from [5f] and (R) -4-methoxyphenylethylamine.

Yield: 96.33%; ¹H NMR (400MHz, DMSO-d₆) δ 1.52 (d, J = 6.8Hz, 3H), 2.45 (s, 3H), 3.71 (s, 3H), 5.42 (s, 3H), 6.89 (d, J = 8.5Hz, 2H), 7.19-7.33 (m, 8H), 8.14 (s, 1H), 8.65 (d, J = 7.6Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.6, 22.2, 38.8, 48.4, 49.6, 54.9, 98.0, 113.6, 127.2, 127.4, 127.5, 128.4, 132.3, 136.3, 137.2, 153.5, 154.3, 158.0, 168.4.
Yield: 96.33%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.52 (d, J = 6.8 Hz, 3H), 2.45 (s, 3H), 3.71 (s, 3H), 5.42 (s, 3H), 6.89 (d, J = 8.5 Hz, 2H), 7.19-7.33 (m, 8H), 8.14 (s, 1H), 8.65 (d, J = 7.6 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.6, 22.2, 38.8, 48.4, 49.6, 54.9, 98.0, 113.6, 127.2, 127.4, 127.5, 128.4, 132.3, 136.3, 137.2, 153.5, 154.3, 158.0, 168.4.

(29) N-(2-메톡시벤질)-1-벤질-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [16zc](29) N- (2-methoxybenzyl) -1-benzyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [16zc]

상기 [5f]와 2-Methoxybenzylamine으로 하얀색의 고체상 화합물 16zc를 얻었다.White solid compound 16zc was obtained from [5f] and 2-Methoxybenzylamine.

Yield: 88.82%; ¹H NMR (400MHz, DMSO-d₆) δ 2.47 (s, 3H), 3.83 (s, 3H), 4.69 (d, J = 4.4Hz, 2H), 5.44 (s, 2H), 6.91 (t, J = 7.0Hz, 1H), 7.01 (d, J = 8.0Hz, 1H), 7.25-7.31 (m, 7H), 8.14 (s, 1H), 8.69 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 38.3, 49.6, 55.2, 98.1, 110.5, 120.1, 126.2, 127.3, 127.5, 128.2, 128.4, 132.3, 137.2, 153.3, 155.3, 156.8, 168.5.
Yield: 88.82%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.47 (s, 3H), 3.83 (s, 3H), 4.69 (d, J = 4.4 Hz, 2H), 5.44 (s, 2H), 6.91 (t, J = 7.0 Hz, 1H), 7.01 (d, J = 8.0 Hz, 1H), 7.25-7.31 (m, 7H), 8.14 (s, 1H), 8.69 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 38.3, 49.6, 55.2, 98.1, 110.5, 120.1, 126.2, 127.3, 127.5, 128.2, 128.4, 132.3, 137.2, 153.3, 155.3, 156.8, 168.5.

(30) N-(4-클로로벤질)-1-벤질-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [16zd](30) N- (4-chlorobenzyl) -1-benzyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [16zd]

상기 [5f]와 4-chlorobenzylamine으로 하얀색의 고체상 화합물 16zd를 얻었다.The solid solid compound 16zd was obtained from [5f] and 4-chlorobenzylamine.

Yield: 92.77%; ¹H NMR (400MHz, DMSO-d₆) δ 2.47 (s, 3H), 4.71 (d, J = 4.5Hz, 2H), 5.45 (s, 2H), 7.25-7.31 (m, 5H), 7.39 (s, 4H), 8.10 (s, 1H), 8.91 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 43.1, 50.2, 98.6, 127.9, 128.0, 128.8, 128.9, 139.7, 132.0, 132.6, 137.7, 138.6, 153.9, 155.7, 169.1.
Yield: 92.77%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.47 (s, 3H), 4.71 (d, J = 4.5 Hz, 2H), 5.45 (s, 2H), 7.25-7.31 (m, 5H), 7.39 (s , 4H), 8.10 (s, 1 H), 8.91 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 43.1, 50.2, 98.6, 127.9, 128.0, 128.8, 128.9, 139.7, 132.0, 132.6, 137.7, 138.6, 153.9, 155.7, 169.1.

(31) N-(4-메틸벤질)-1-벤질-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [16ze](31) N- (4-methylbenzyl) -1-benzyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [16ze]

상기 [5f]와 4-methylbenzylamine으로 하얀색의 고체상 화합물 16ze를 얻었다.White solid compound 16ze was obtained from [5f] and 4-methylbenzylamine.

Yield: 85.30%; ¹H NMR (400MHz, DMSO-d₆) δ 2.27 (s, 3H), 2.48 (s, 3H), 4.66 (d, J = 5.0Hz, 2H), 5.43 (s, 2H), 7.14 (d, J = 7.4Hz, 2H), 7.21-7.32 (m, 7H), 8.08 (s, 1H), 8.82 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.8, 29.7, 37.9, 42.9, 49.6, 98.0, 110.5, 120.1, 127.4, 128.4, 128.8, 131.4, 132.1, 135.9, 137.2, 153.4, 155.1, 168.5.
Yield: 85.30%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.27 (s, 3H), 2.48 (s, 3H), 4.66 (d, J = 5.0 Hz, 2H), 5.43 (s, 2H), 7.14 (d, J = 7.4 Hz, 2H), 7.21-7.32 (m, 7H), 8.08 (s, 1H), 8.82 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.8, 29.7, 37.9, 42.9, 49.6, 98.0, 110.5, 120.1, 127.4, 128.4, 128.8, 131.4, 132.1, 135.9, 137.2, 153.4, 155.1, 168.5.

(32) N-(3-메톡시벤질)-1-벤질-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [16zf](32) N- (3-methoxybenzyl) -1-benzyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [16zf]

상기 [5f]와 3-methoxybenzylamine으로 얇은 노란색의 고체상 화합물 16zf를 얻었다.The thin yellow solid compound 16zf was obtained from [5f] and 3-methoxybenzylamine.

Yield: 86.37%; ¹H NMR (400MHz, DMSO-d₆) δ 2.49 (s, 3H), 3.73 (s, 3H), 4.70 (d, J = 5.6Hz, 2H), 5.45 (s, 2H), 6.84 (d, J = 8.0Hz, 1H), 6.96 (t, J = 6.3Hz, 2H), 7.22-7.33 (m, 6H), 8.11 (s, 1H), 8.87 (t, J = 5.6Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.5, 43.2, 49.6, 54.8, 98.1, 112.2, 113.3, 119.6, 127.4, 127.5, 128.4, 129.4, 132.2, 137.2, 140.6, 153.4, 155.2, 159.2, 168.5.
Yield: 86.37%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.49 (s, 3H), 3.73 (s, 3H), 4.70 (d, J = 5.6 Hz, 2H), 5.45 (s, 2H), 6.84 (d, J = 8.0 Hz, 1H), 6.96 (t, J = 6.3 Hz, 2H), 7.22-7.33 (m, 6H), 8.11 (s, 1H), 8.87 (t, J = 5.6 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.5, 43.2, 49.6, 54.8, 98.1, 112.2, 113.3, 119.6, 127.4, 127.5, 128.4, 129.4, 132.2, 137.2, 140.6, 153.4, 155.2, 159.2, 168.5.

(33) 1-벤질-N-뷰틸-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [16zg](33) 1-benzyl-N-butyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [16zg]

상기 [5f]와 n-butylamine으로 얇은 노란색의 고체상 화합물 16zg를 얻었다.16zg of a thin yellow solid compound was obtained using [5f] and n-butylamine.

Yield: 97.04%; ¹H NMR (400MHz, DMSO-d₆) δ 0.92 (t, J = 7.3Hz, 3H), 1.34-1.41 (m, 2H), 1.55.-1.62 (m, 2H), 2.51 (s, 3H), 3.45-3.50 (m, 2H), 5.43 (s, 2H), 7.22-7.33 (m, 5H), 8.06 (s, 1H), 8.31 (t, J = 5.2Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.6, 13.7, 19.6, 30.9, 49.7, 98.1, 100.4, 127.4, 127.6, 128.5, 132.2, 137.3, 153.4, 155.4, 168.6.
Yield: 97.04%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.92 (t, J = 7.3 Hz, 3H), 1.34-1.41 (m, 2H), 1.55.-1.62 (m, 2H), 2.51 (s, 3H), 3.45-3.50 (m, 2H), 5.43 (s, 2H), 7.22-7.33 (m, 5H), 8.06 (s, 1H), 8.31 (t, J = 5.2 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.6, 13.7, 19.6, 30.9, 49.7, 98.1, 100.4, 127.4, 127.6, 128.5, 132.2, 137.3, 153.4, 155.4, 168.6.

(34) 1-벤질-6-(메틸티오)-N-((피리딘-2-일)메틸)-1H-피라졸로[3,4-d]피리미딘-4-아민 [16zh](34) 1-benzyl-6- (methylthio) -N-((pyridin-2-yl) methyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [16zh]

상기 [5f]와 (pyridin-2-yl)methanamine으로 하얀색의 고체상 화합물 16zh를 얻었다.The white solid compound 16zh was obtained from [5f] and (pyridin-2-yl) methanamine.

Yield: 89.26%; ¹H NMR (400MHz, DMSO-d₆) δ 2.41 (s, 3H), 4.80 (d, J = 5.7Hz, 2H), 5.44 (s, 2H), 7.22-7.36 (m, 7H), 7.75 (t, J = 7.6Hz, 1H), 8.12 (s, 1H), 8.53 (d, J = 4.4Hz, 1H), 9.00 (t, J = 5.6Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 45.1, 49.6, 98.1, 121.3, 122.1, 127.3, 127.5, 128.4, 132.2, 136.6, 137.1, 148.8, 153.4, 155.2, 158.2, 168.4.
Yield: 89.26%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.41 (s, 3H), 4.80 (d, J = 5.7 Hz, 2H), 5.44 (s, 2H), 7.22-7.36 (m, 7H), 7.75 (t , J = 7.6 Hz, 1H), 8.12 (s, 1H), 8.53 (d, J = 4.4 Hz, 1H), 9.00 (t, J = 5.6 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 45.1, 49.6, 98.1, 121.3, 122.1, 127.3, 127.5, 128.4, 132.2, 136.6, 137.1, 148.8, 153.4, 155.2, 158.2, 168.4.

(35) N-(2-클로로벤질)-1-벤질-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [16zi](35) N- (2-chlorobenzyl) -1-benzyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [16zi]

상기 [5f]와 2-chlorobenzylamine으로 하얀색의 고체상 화합물 16zi를 얻었다.White solid compound 16zi was obtained from [5f] and 2-chlorobenzylamine.

Yield: 92.44%; ¹H NMR (400MHz, DMSO-d₆) δ 2.44 (s, 3H), 4.79 (d, J = 5.4Hz, 2H), 5.45 (s, 2H), 7.23-7.33 (m, 7H), 7.43 (t, J = 4.4Hz, 1H), 7.48 (t, J = 4.5Hz, 1H), 8.13 (s, 1H), 8.88 (t, J = 5.3Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 41.2, 49.6, 98.1, 126.8, 127.1, 127.4, 127.5, 128.0, 128.4, 128.7, 129.1, 129.2, 132.2, 135.9, 137.1, 153.4, 155.1, 168.5.
Yield: 92.44%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.44 (s, 3H), 4.79 (d, J = 5.4 Hz, 2H), 5.45 (s, 2H), 7.23-7.33 (m, 7H), 7.43 (t , J = 4.4 Hz, 1H), 7.48 (t, J = 4.5 Hz, 1H), 8.13 (s, 1H), 8.88 (t, J = 5.3 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 41.2, 49.6, 98.1, 126.8, 127.1, 127.4, 127.5, 128.0, 128.4, 128.7, 129.1, 129.2, 132.2, 135.9, 137.1, 153.4, 155.1, 168.5.

실시예 15. [17a] 내지 [17q]의 합성Example 15. Synthesis of [17a] to [17q]

하기 [반응식 17](R₂N, 1,4-dioxane, reflux, 8h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [17a] 내지 [17q]를 합성하였다.The pyrazolopyrimidine derivative compounds [17a] to [17q] according to the present invention were synthesized by the following Scheme 17 (R ₂ N, 1,4-dioxane, reflux, 8h).

[반응식 17][Reaction Scheme 17]

[5g] [17a] ~ [17q][5g] [17a]-[17q]

[17a] 내지 [17q]에서 NR₂은 각각 하기 [표 10]과 같다.NR ₂ in [17a] to [17q] are as shown in Table 10 below, respectively.

구분division NR₂ NR ₂ 구분division NR₂ NR ₂ 17a17a

17j17j

17b17b

17k17k

17c17c

17l17l

17d17d

17m17 m

17e17e

17n17n

17f17f

17o17o

17g17g

17p17p

17h17h

17q17q

17i17i

(1) 1-t-뷰틸-4-벤질아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [17a](1) 1-t-butyl-4-benzylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [17a]

상기 [5g]와 benzylamine으로 옅은 노란색의 고체상 화합물 17a를 얻었다.The pale yellow solid compound 17a was obtained from [5 g] and benzylamine.

Yield: 85%; ¹H NMR (400MHz, DMSO-d₆) δ 1.57 (s, 9H), 2.40 (s, 3H), 4.66 (d, J = 5.4Hz, 2H), 7.25-7.34 (m, 5H), 8.38 (s, 1H), 8.57 (t, J = 5.3Hz, 1H).
Yield: 85%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.57 (s, 9H), 2.40 (s, 3H), 4.66 (d, J = 5.4 Hz, 2H), 7.25-7.34 (m, 5H), 8.38 (s , 1H), 8.57 (t, J = 5.3 Hz, 1H).

(2) (R)-1-t-뷰틸-4-(1-페닐에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [17b](2) (R) -1-t-butyl-4- (1-phenylethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [17b]

상기 [5g]와 (R)-1-phenylethylamine으로 옅은 노란색의 고체상 화합물 17b를 얻었다.The pale yellow solid compound 17b was obtained from [5 g] and (R) -1-phenylethylamine.

Yield: 69%; ¹H NMR (400MHz, DMSO-d₆) δ 1.50 (d, J = 6.9Hz, 3H), 1.58 (s, 9H), 2.36 (s, 3H), 5.37-5.44 (m, 1H), 7.22 (t, J = 7.1Hz, 1H), 7.32 (d, J = 7.5Hz, 2H), 7.39 (d, J = 7.6Hz, 2H), 8.46 (d, J = 9.1Hz, 1H).
Yield: 69%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.50 (d, J = 6.9 Hz, 3H), 1.58 (s, 9H), 2.36 (s, 3H), 5.37-5.44 (m, 1H), 7.22 (t , J = 7.1 Hz, 1H), 7.32 (d, J = 7.5 Hz, 2H), 7.39 (d, J = 7.6 Hz, 2H), 8.46 (d, J = 9.1 Hz, 1H).

(3) 1-t-뷰틸-4-(4-플루오로벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [17c](3) 1-t-butyl-4- (4-fluorobenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [17c]

상기 [5g]와 4-fluorobenzylamine으로 옅은 노란색의 고체상 화합물 17c를 얻었다.The pale yellow solid compound 17c was obtained from [5 g] and 4-fluorobenzylamine.

Yield: 63%; ¹H NMR (400MHz, DMSO-d₆) δ 1.57 (s, 9H), 2.40 (s, 3H), 4.64 (d, J = 5.5Hz, 2H), 7.16 (d, J = 8.8Hz, 2H), 7.39 (quar, J = 8.8Hz, 2H), 8.37 (s, 1H), 8.58 (t, J = 5.4Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.8, 29.6, 43.0, 60.2, 99.5, 115.4, 121.8, 130.1, 135.7, 156.7, 160.0, 168.9.
Yield: 63%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.57 (s, 9H), 2.40 (s, 3H), 4.64 (d, J = 5.5 Hz, 2H), 7.16 (d, J = 8.8 Hz, 2H), 7.39 (quar, J = 8.8 Hz, 2H), 8.37 (s, 1 H), 8.58 (t, J = 5.4 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.8, 29.6, 43.0, 60.2, 99.5, 115.4, 121.8, 130.1, 135.7, 156.7, 160.0, 168.9.

(4) 1-t-뷰틸-4-(1-하이드록시에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [17d](4) 1-t-butyl-4- (1-hydroxyethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [17d]

상기 [5g]와 4-fluorobenzylamine으로 하얀색의 고체상 화합물 17d를 얻었다.[5g] and 4-fluorobenzylamine gave white solid compound 17d.

Yield: 77%; ¹H NMR (400MHz, DMSO-d₆) δ 1.57 (s, 9H), 2.40 (s, 3H), 3.53 (dt, J = 5.3Hz, 21.2Hz, 4H), 4.81 (t, J = 5.2Hz, 1H), 8.14 (t, J = 5.0Hz, 1H), 8.41 (s, 1H).
Yield: 77%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.57 (s, 9H), 2.40 (s, 3H), 3.53 (dt, J = 5.3 Hz, 21.2 Hz, 4H), 4.81 (t, J = 5.2 Hz, 1H), 8.14 (t, J = 5.0 Hz, 1H), 8.41 (s, 1H).

(5) 1-t-뷰틸-4-(4-메톡시벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [17e](5) 1-t-butyl-4- (4-methoxybenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [17e]

상기 [5g]와 4-methoxybenzylamine으로 갈색의 고체상 화합물 17e를 얻었다.[5g] and 4-methoxybenzylamine gave brown solid compound 17e.

Yield: 98%; ¹H NMR (400MHz, CDCl₃) δ 1.58 (s, 9H), 2.54 (s, 3H), 3.75 (s, 3H), 4.66 (s, 2H), 6.27 (br s, 1H), 6.79 (d, J = 8.1Hz, 2H), 7.23 (d, J = 8.4Hz, 2H), 7.96 (s, 1H).
Yield: 98%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 1.58 (s, 9H), 2.54 (s, 3H), 3.75 (s, 3H), 4.66 (s, 2H), 6.27 (br s, 1H), 6.79 (d, J = 8.1 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 7.96 (s, 1H).

(6) 1-t-뷰틸-4-알릴아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [17f](6) 1-t-butyl-4-allylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [17f]

상기 [5g]와 4-methoxybenzylamine으로 옅은 노란색의 고체상 화합물 17f를 얻었다.The pale yellow solid compound 17f was obtained from [5 g] and 4-methoxybenzylamine.

Yield: 92%; ¹H NMR (400MHz, DMSO-d₆) δ 1.58 (s, 9H), 2.40 (s, 3H), 4.08 (t, J = 4.9Hz, 2H), 5.13 (dd, J = 1.3Hz, 10.3Hz, 1H), 5.23 (dd, J = 1.5Hz, 17.2Hz, 1H), 5.88-5.97 (m, 1H), 8.25 (t, J = 5.1Hz, 1H), 8.38 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.8, 29.6, 42.5, 60.1, 99.6, 116.3, 121.8, 135.3, 156.7, 160.0, 168.0.
Yield: 92%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.58 (s, 9H), 2.40 (s, 3H), 4.08 (t, J = 4.9 Hz, 2H), 5.13 (dd, J = 1.3 Hz, 10.3 Hz, 1H), 5.23 (dd, J = 1.5 Hz, 17.2 Hz, 1H), 5.88-5.97 (m, 1H), 8.25 (t, J = 5.1 Hz, 1H), 8.38 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.8, 29.6, 42.5, 60.1, 99.6, 116.3, 121.8, 135.3, 156.7, 160.0, 168.0.

(7) (R)-1-t-뷰틸-4-(1-페닐에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [17g](7) (R) -1-t-butyl-4- (1-phenylethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [17 g]

상기 [5g]와 (R)-1-phenylethylamine으로 갈색의 고체상 화합물 17g를 얻었다.17g of the brown solid compound was obtained from the above [5g] and (R) -1-phenylethylamine.

Yield: 63%; ¹H NMR (400MHz, CDCl₃) d 1.62 (s, 9H), 2.58 (s, 3H), 2.95 (t, J = 7.0Hz, 2H), 3.84 (t, J = 6.5Hz, 2H), 5.84 (br s, 1H), 7.18-7.33 (m, 5H), 7.86 (s, 1H).
Yield: 63%; ¹ H NMR (400 MHz, CDCl ₃ ) d 1.62 (s, 9H), 2.58 (s, 3H), 2.95 (t, J = 7.0 Hz, 2H), 3.84 (t, J = 6.5 Hz, 2H), 5.84 ( br s, 1 H), 7.18-7.33 (m, 5 H), 7.86 (s, 1 H).

(8) 1-t-뷰틸-4-(2-페닐에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [17h](8) 1-t-butyl-4- (2-phenylethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [17h]

상기 [5g]와 2-phenylethylamine으로 갈색의 고체상 화합물 17h를 얻었다.[5g] and 2-phenylethylamine gave 17h of a brown solid compound.

Yield: 63%; ¹H NMR (400MHz, CDCl₃) δ 1.50 (d, J = 6.9Hz, 3H), 1.58 (s, 9H), 2.36 (s, 3H), 5.41 (d, J = 7.0Hz, 1H), 7.22 (t, J = 7.1Hz, 1H), 7.32 (d, J = 7.5Hz, 2H), 7.39 (d, J = 7.6Hz, 2H), 8.44 (s, 1H), 8.47 (s, 1H).
Yield: 63%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 1.50 (d, J = 6.9 Hz, 3H), 1.58 (s, 9H), 2.36 (s, 3H), 5.41 (d, J = 7.0 Hz, 1H), 7.22 ( t, J = 7.1 Hz, 1H), 7.32 (d, J = 7.5 Hz, 2H), 7.39 (d, J = 7.6 Hz, 2H), 8.44 (s, 1H), 8.47 (s, 1H).

(9) N-(2-메톡시벤질)-1-t-뷰틸-6-(methylthio)-1H-피라졸로[3,4-d]피리미딘-4-아민 [17i](9) N- (2-methoxybenzyl) -1-t-butyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [17i]

상기 [5g]와 2-methoxybenzylamine으로 하얀색의 고체상 화합물 17i를 얻었다.White solid compound 17i was obtained from [5g] and 2-methoxybenzylamine.

Yield: 89.25%; ¹H NMR (400MHz, DMSO-d₆) δ 1.59 (s, 9H), 2.41 (s, 3H), 3.83 (s, 3H), 4.63 (d, J = 4.4Hz, 2H), 6.97 (dd, J = 7.8Hz, 39.9Hz, 2H), 7.27 (t, J = 3.2Hz, 2H), 8.43 (d, J = 23.0Hz, 2H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 29.2, 55.4, 59.7, 99.2, 110.7, 120.2, 121.6, 126.2, 128.5, 128.6, 156.5, 157.0, 159.6, 167.6.
Yield: 89.25%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.59 (s, 9H), 2.41 (s, 3H), 3.83 (s, 3H), 4.63 (d, J = 4.4 Hz, 2H), 6.97 (dd, J = 7.8 Hz, 39.9 Hz, 2H), 7.27 (t, J = 3.2 Hz, 2H), 8.43 (d, J = 23.0 Hz, 2H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 29.2, 55.4, 59.7, 99.2, 110.7, 120.2, 121.6, 126.2, 128.5, 128.6, 156.5, 157.0, 159.6, 167.6.

(10) N-(4-클로로벤질)-1-t-뷰틸-6-(methylthio)-1H-피라졸로[3,4-d]피리미딘-4-아민 [17j](10) N- (4-chlorobenzyl) -1-t-butyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [17j]

상기 [5g]와 4-chlorobenzylamine으로 하얀색의 고체상 화합물 17j를 얻었다.[5g] and 4-chlorobenzylamine to obtain a white solid compound 17j.

Yield: 92.44%; ¹H NMR (400MHz, DMSO-d₆) δ 1.59 (s, 9H), 2.41 (s, 3H), 4.67 (d, J = 5.5Hz, 2H), 7.36-7.41 (m, 4H), 8.39 (s, 1H), 8.63 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 29.1, 42.5, 59.7, 99.0, 121.4, 128.3, 129.4, 131.5, 138.1, 156.3, 159.6, 167.6.
Yield: 92.44%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.59 (s, 9H), 2.41 (s, 3H), 4.67 (d, J = 5.5 Hz, 2H), 7.36-7.41 (m, 4H), 8.39 (s , 1H), 8.63 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 29.1, 42.5, 59.7, 99.0, 121.4, 128.3, 129.4, 131.5, 138.1, 156.3, 159.6, 167.6.

(11) N-(3-메톡시벤질)-1-t-뷰틸-6-(methylthio)-1H-피라졸로[3,4-d]피리미딘-4-아민 [17k](11) N- (3-methoxybenzyl) -1-t-butyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [17k]

상기 [5g]와 3-methoxybenzylamine으로 하얀색의 고체상 화합물 17k를 얻었다.17k was obtained as a white solid compound using [5g] and 3-methoxybenzylamine.

Yield: 90.86%; ¹H NMR (400MHz, DMSO-d₆) δ 1.61 (s, 9H), 2.44 (s, 3H), 3.75 (s, 3H), 4.66 (d, J = 4.4Hz, 2H), 6.91 (dd, J = 9.4Hz, 38.5Hz, 3H), 7.28 (t, J = 7.1Hz, 1H), 8.42 (s, 1H), 8.59 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.9, 29.6, 43.7, 55.4, 60.1, 99.5, 112.8, 114.0, 120.3, 121.9, 129.9, 141.0, 156.8, 159.7, 160.1, 168.0.
Yield: 90.86%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.61 (s, 9H), 2.44 (s, 3H), 3.75 (s, 3H), 4.66 (d, J = 4.4 Hz, 2H), 6.91 (dd, J = 9.4 Hz, 38.5 Hz, 3H), 7.28 (t, J = 7.1 Hz, 1H), 8.42 (s, 1H), 8.59 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 29.6, 43.7, 55.4, 60.1, 99.5, 112.8, 114.0, 120.3, 121.9, 129.9, 141.0, 156.8, 159.7, 160.1, 168.0.

(12) 1-t-뷰틸-N-뷰틸-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [17l](12) 1-t-butyl-N-butyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [17l]

상기 [5g]와 n-buthylamine으로 하얀색의 고체상 화합물 17l를 얻었다.17 L of white solid compound was obtained from [5 g] and n-buthylamine.

Yield: 91.22%; ¹H NMR (400MHz, DMSO-d₆) δ 0.92 (t, J = 6.3Hz, 3H), 1.34-1.39 (m, 2H), 1.59 (s, 9H), 2.42 (s, 3H), 3.44 (d, J = 4.6Hz, 2H), 8.04 (s, 1H), 8.36 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.3, 13.6, 19.5, 29.0, 30.7, 59.5, 99.0, 121.1, 156.3, 159.4, 167.5.
Yield: 91.22%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.92 (t, J = 6.3 Hz, 3H), 1.34-1.39 (m, 2H), 1.59 (s, 9H), 2.42 (s, 3H), 3.44 (d , J = 4.6 Hz, 2H), 8.04 (s, 1H), 8.36 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.3, 13.6, 19.5, 29.0, 30.7, 59.5, 99.0, 121.1, 156.3, 159.4, 167.5.

(13) 1-t-뷰틸-6-(메틸티오)-N-((피리딘-2-일)메틸)-1H-피라졸로[3,4-d]피리미딘-4-아민 [17m](13) 1-t-butyl-6- (methylthio) -N-((pyridin-2-yl) methyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [17m]

상기 [5g]와 (pyridin-2-yl)methanamine으로 하얀색의 고체상 화합물 17m를 얻었다.17 m of a white solid compound was obtained from [5 g] and (pyridin-2-yl) methanamine.

Yield: 93.44%; ¹H NMR (400MHz, DMSO-d₆) δ 1.60 (s, 9H), 2.38 (s, 3H), 4.77 (d, J = 5.6Hz, 2H), 7.29 (t, J = 6.1Hz, 1H), 7.36 (d, J = 7.8Hz, 1H), 7.76 (t, J = 5.6Hz, 1H), 8.45 (s, 1H), 8.54 (d, J = 4.3Hz, 1H), 8.71 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.2, 29.0, 45.0, 59.6, 99.0, 120.9, 121.4, 121.8, 122.1, 126.3, 136.6, 137.7, 148.4, 148.8, 156.3, 158.1, 159.5, 167.4.
Yield: 93.44%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.60 (s, 9H), 2.38 (s, 3H), 4.77 (d, J = 5.6 Hz, 2H), 7.29 (t, J = 6.1 Hz, 1H), 7.36 (d, J = 7.8 Hz, 1H), 7.76 (t, J = 5.6 Hz, 1H), 8.45 (s, 1H), 8.54 (d, J = 4.3 Hz, 1H), 8.71 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.2, 29.0, 45.0, 59.6, 99.0, 120.9, 121.4, 121.8, 122.1, 126.3, 136.6, 137.7, 148.4, 148.8, 156.3, 158.1, 159.5, 167.4.

(14) N-(2-클로로벤질)-1-t-뷰틸-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [17n](14) N- (2-chlorobenzyl) -1-t-butyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [17n]

상기 [5g]와 2-chlorobenzylamine으로 하얀색의 고체상 화합물 17n를 얻었다.White solid compound 17n was obtained from [5 g] and 2-chlorobenzylamine.

Yield: 85.40%; ¹H NMR (400MHz, DMSO-d₆) δ 1.62 (s, 9H), 2.42 (s, 3H), 4.76 (s, 2H), 7.34-7.49 (m, 4H), 8.46 (s, 1H), 8.60 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.2, 29.0, 41.2, 59.6, 98.9, 121.4, 127.1, 128.8, 129.1, 129.5, 132.4, 135.8, 156.2, 159.5, 167.4.
Yield: 85.40%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.62 (s, 9H), 2.42 (s, 3H), 4.76 (s, 2H), 7.34-7.49 (m, 4H), 8.46 (s, 1H), 8.60 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.2, 29.0, 41.2, 59.6, 98.9, 121.4, 127.1, 128.8, 129.1, 129.5, 132.4, 135.8, 156.2, 159.5, 167.4.

(15) 2-(1-t-뷰틸-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-일아미노)-2-메틸프로판-1-올 [17o](15) 2- (1-t-butyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-ylamino) -2-methylpropan-1-ol [17o]

상기 [5g]와 2-amino-2-methylpropan-1-ol으로 하얀색의 고체상 화합물 17o를 얻었다.The white solid compound 17o was obtained from [5g] and 2-amino-2-methylpropan-1-ol.

Yield: 95.36%; ¹H NMR (400MHz, DMSO-d₆) δ 1.40 (s, 6H), 1.60 (s, 9H), 2.44 (s, 3H), 3.67 (d, J = 4.3Hz, 2H), 5.0 (s, 1H), 7.38 (m, 1H), 8.57 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 23.9, 29.1, 56.0, 59.5, 66.7, 99.6, 121.9, 156.1, 159.4, 166.7.
Yield: 95.36%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.40 (s, 6H), 1.60 (s, 9H), 2.44 (s, 3H), 3.67 (d, J = 4.3 Hz, 2H), 5.0 (s, 1H ), 7.38 (m, 1 H), 8.57 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 23.9, 29.1, 56.0, 59.5, 66.7, 99.6, 121.9, 156.1, 159.4, 166.7.

(16) 1-t-뷰틸-N-(1-사이클로헥실에틸)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [17p](16) 1-t-butyl-N- (1-cyclohexylethyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [17p]

상기 [5g]와 (R)-cyclohexylethylamine으로 하얀색의 고체상 화합물 17p를 얻었다.White solid compound 17p was obtained from the above [5g] and (R) -cyclohexylethylamine.

Yield: 90.52%; ¹H NMR (400MHz, DMSO-d₆) δ 0.97-1.04 (m, 2H), 1.15 (d, J = 7.1Hz, 3H), 1.42-1.46 (m, 2H), 1.59 (s, 9H), 1.62 (s, 2H), 1.69-1.75 (m, 4H), 2.40 (s, 3H), 4.16 (d, J = 7.1Hz, 1H), 7.79 (d, J = 8.5Hz, 1H), 8.42 (s, 1H)
Yield: 90.52%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.97-1.04 (m, 2H), 1.15 (d, J = 7.1 Hz, 3H), 1.42-1.46 (m, 2H), 1.59 (s, 9H), 1.62 (s, 2H), 1.69-1.75 (m, 4H), 2.40 (s, 3H), 4.16 (d, J = 7.1 Hz, 1H), 7.79 (d, J = 8.5 Hz, 1H), 8.42 (s, 1H)

(17) 1-t-뷰틸-N-(1-사이클로헥실에틸)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [17q](17) 1-t-butyl-N- (1-cyclohexylethyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [17q]

상기 [5g]와 (S)-cyclohexylethylamine으로 하얀색의 고체상 화합물 17q를 얻었다.The white solid compound 17q was obtained from the above [5g] and (S) -cyclohexylethylamine.

Yield: 88.20%; ¹H NMR (400MHz, DMSO-d₆) δ 0.98-1.04 (m, 2H), 1.14 (d, J = 7.1Hz, 3H), 1.19-1.22 (m, 2H), 1.43-1.44 (m, 2H), 1.60 (s, 9H), 1.70-1.75 (m, 4H), 2.42 (s, 3H), 4.17 (d, J = 7.3Hz, 1H), 7.80 (d, J = 8.5Hz, 1H), 8.44 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.8, 17.9, 26.2, 26.4, 29.1, 29.6, 43.0, 49.9, 60.0, 99.5, 121.9, 156.5, 160.1, 168.0.
Yield: 88.20%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.98-1.04 (m, 2H), 1.14 (d, J = 7.1 Hz, 3H), 1.19-1.22 (m, 2H), 1.43-1.44 (m, 2H) , 1.60 (s, 9H), 1.70-1.75 (m, 4H), 2.42 (s, 3H), 4.17 (d, J = 7.3 Hz, 1H), 7.80 (d, J = 8.5 Hz, 1H), 8.44 ( s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.8, 17.9, 26.2, 26.4, 29.1, 29.6, 43.0, 49.9, 60.0, 99.5, 121.9, 156.5, 160.1, 168.0.

실시예 16. [18a] 내지 [18i]의 합성Example 16. Synthesis of [18a] to [18i]

하기 [반응식 18](R₂N, 1,4-dioxane, reflux, 8h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [18a] 내지 [18i]를 합성하였다.The pyrazolopyrimidine derivative compounds [18a] to [18i] were synthesized according to the following Reaction Scheme 18 (R ₂ N, 1,4-dioxane, reflux, 8h).

[반응식 18][Reaction Scheme 18]

[5j] [18a] ~ [18i][5j] [18a] to [18i]

[18a] 내지 [18i]에서 NR₂은 각각 하기 [표 11]과 같다.In [18a] to [18i], NR ₂ is shown in Table 11 below, respectively.

구분division NR₂ NR ₂ 구분division NR₂ NR ₂ 18a18a

18f18f

18b18b

18g18g

18c18c

18h18h

18d18d

18i18i

18e18e

(1) N-(2-클로로벤질)-1-(3-메톡시펜에틸)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [18a](1) N- (2-chlorobenzyl) -1- (3-methoxyphenethyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [18a]

상기 [5j]와 2-chlorobenzylamine으로 노란색의 고체상 화합물 18a를 얻었다.The yellow solid compound 18a was obtained from [5j] and 2-chlorobenzylamine.

Yield: 79.53%; ¹H NMR (400MHz, DMSO-d₆) δ 2.38 (s, 3H), 3.10 (t, J = 6.9Hz, 2H), 3.65 (s, 3H), 4.46 (t, J = 7.0Hz, 2H), 4.75 (d, J = 5.6Hz, 2H), 6.70 (t, J = 6.3Hz, 3H), 7.12 (t, J = 7.8Hz, 1H), 7.30 (t, J = 4.6Hz, 2H), 7.39 (t, J = 4.5Hz, 1H), 7.46 (t, J = 4.5Hz, 1H), 8.07 (s, 1H), 8.78 (t, J = 5.3Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.9, 35.3, 41.7, 47.6, 55.2, 98.5, 112.4, 114.5, 121.3, 127.7, 129.3, 129.7, 132.2, 132.7, 136.5, 140.3, 153.8, 155.6, 159.6, 168.6.
Yield: 79.53%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.38 (s, 3H), 3.10 (t, J = 6.9 Hz, 2H), 3.65 (s, 3H), 4.46 (t, J = 7.0 Hz, 2H), 4.75 (d, J = 5.6 Hz, 2H), 6.70 (t, J = 6.3 Hz, 3H), 7.12 (t, J = 7.8 Hz, 1H), 7.30 (t, J = 4.6 Hz, 2H), 7.39 ( t, J = 4.5 Hz, 1H), 7.46 (t, J = 4.5 Hz, 1H), 8.07 (s, 1H), 8.78 (t, J = 5.3 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 35.3, 41.7, 47.6, 55.2, 98.5, 112.4, 114.5, 121.3, 127.7, 129.3, 129.7, 132.2, 132.7, 136.5, 140.3, 153.8, 155.6, 159.6, 168.6.

(2) N-(2-메톡시벤질)-1-(3-메톡시펜에틸)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [18b](2) N- (2-methoxybenzyl) -1- (3-methoxyphenethyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [18b ]

상기 [5j]와 2-methoxybenzylamine으로 하얀색의 고체상 화합물 18b를 얻었다.The white solid compound 18b was obtained from [5j] and 2-methoxybenzylamine.

Yield: 84.95%; ¹H NMR (400MHz, DMSO-d₆) δ 2.41 (s, 3H), 3.10 (t, J = 7.0Hz, 2H), 3.65 (s, 3H), 3.90 (s, 3H), 4.45 (t, J = 7.0Hz, 2H), 4.63 (d, J = 5.5Hz, 2H), 6.70 (t, J = 5.9Hz, 3H), 6.89 (t, J = 7.4Hz, 1H), 7.00 (d, J = 8.1Hz, 1H), 7.12 (t, J = 7.8Hz, 1H), 7.24 (quar, J = 7.3Hz, 2H), 8.07 (s, 1H), 8.58 (t, J = 5.5Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.8, 35.3, 38.8, 47.6, 55.2, 55.8, 98.5, 111.1, 112.3, 114.5, 120.6, 121.3, 126.7, 128.8, 129.7, 132.3, 140.3, 153.8, 155.7, 157.3, 159.6, 168.5.
Yield: 84.95%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.41 (s, 3H), 3.10 (t, J = 7.0 Hz, 2H), 3.65 (s, 3H), 3.90 (s, 3H), 4.45 (t, J = 7.0 Hz, 2H), 4.63 (d, J = 5.5 Hz, 2H), 6.70 (t, J = 5.9 Hz, 3H), 6.89 (t, J = 7.4 Hz, 1H), 7.00 (d, J = 8.1 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 7.24 (quar, J = 7.3 Hz, 2H), 8.07 (s, 1H), 8.58 (t, J = 5.5 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.8, 35.3, 38.8, 47.6, 55.2, 55.8, 98.5, 111.1, 112.3, 114.5, 120.6, 121.3, 126.7, 128.8, 129.7, 132.3, 140.3, 153.8, 155.7, 157.3, 159.6, 168.5.

(3) N-(2-메틸벤질)-1-(3-메톡시펜에틸)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [18c](3) N- (2-methylbenzyl) -1- (3-methoxyphenethyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [18c]

상기 [5j]와 2-methylbenzylamine으로 하얀색의 고체상 화합물 18c를 얻었다.The white solid compound 18c was obtained from [5j] and 2-methylbenzylamine.

Yield: 80.21%; ¹H NMR (400MHz, DMSO-d₆) δ 2.31 (s, 3H), 2.42 (s, 3H), 3.10 (t, J = 6.6Hz, 2H), 3.64 (s, 3H), 4.45 (t, J = 6.7Hz, 2H), 4.65 (d, J = 5.2Hz, 2H), 6.69 (t,J = 6.7Hz, 3H), 7.09-7.17 (m, 4H), 7.27 (d, J = 5.9Hz, 1H), 8.07 (s, 1H), 8.60 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.9, 19.2, 35.3, 42.0, 47.6, 55.2, 98.5, 112.3, 114.5, 121.3, 126.3, 127.6, 128.6, 129.7, 130.5, 132.3, 136.4, 137.0, 140.3, 153.8, 155.5, 159.6, 168.6.
Yield: 80.21%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.31 (s, 3H), 2.42 (s, 3H), 3.10 (t, J = 6.6 Hz, 2H), 3.64 (s, 3H), 4.45 (t, J = 6.7 Hz, 2H), 4.65 (d, J = 5.2 Hz, 2H), 6.69 (t, J = 6.7 Hz, 3H), 7.09-7.17 (m, 4H), 7.27 (d, J = 5.9 Hz, 1H ), 8.07 (s, 1 H), 8.60 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 19.2, 35.3, 42.0, 47.6, 55.2, 98.5, 112.3, 114.5, 121.3, 126.3, 127.6, 128.6, 129.7, 130.5, 132.3, 136.4, 137.0, 140.3, 153.8, 155.5, 159.6, 168.6.

(4) N-(3-메톡시벤질)-1-(3-메톡시펜에틸)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [18d](4) N- (3-methoxybenzyl) -1- (3-methoxyphenethyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [18d ]

상기 [5j]와 3-methoxybenzylamine으로 노란색의 고체상 화합물 18d를 얻었다.The yellow solid compound 18d was obtained from [5j] and 3-methoxybenzylamine.

Yield: 94.66%; ¹H NMR (400MHz, DMSO-d₆) δ 2.45 (s, 3H), 3.12 (t, J = 6.6Hz, 2H), 3.67 (s, 3H), 3.74 (s, 3H), 4.48 (t, J = 6.6Hz, 2H), 4.68 (d, J = 4.9Hz, 2H), 6.71 (t, J = 6.2Hz, 2H), 6.84 (d, J = 8.1Hz, 1H), 6.94 (d, J = 9.3Hz, 2H), 7.13 (t, J = 7.17Hz, 1H), 7.26 (t, J = 5.2Hz, 1H), 8.07 (s, 1H), 8.78 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 14.0, 19.7, 34.8, 43.2, 47.1, 54.7, 54.9, 59.7, 98.0, 100.3, 111.8, 112.2, 113.3, 114.0, 119.6, 120.8, 129.2, 129.4, 131.6, 139.8, 140.7, 153.3, 155.1, 159.1, 159.2, 168.1.
Yield: 94.66%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.45 (s, 3H), 3.12 (t, J = 6.6 Hz, 2H), 3.67 (s, 3H), 3.74 (s, 3H), 4.48 (t, J = 6.6 Hz, 2H), 4.68 (d, J = 4.9 Hz, 2H), 6.71 (t, J = 6.2 Hz, 2H), 6.84 (d, J = 8.1 Hz, 1H), 6.94 (d, J = 9.3 Hz, 2H), 7.13 (t, J = 7.17 Hz, 1H), 7.26 (t, J = 5.2 Hz, 1H), 8.07 (s, 1H), 8.78 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 14.0, 19.7, 34.8, 43.2, 47.1, 54.7, 54.9, 59.7, 98.0, 100.3, 111.8, 112.2, 113.3, 114.0, 119.6, 120.8, 129.2, 129.4, 131.6, 139.8, 140.7, 153.3, 155.1, 159.1, 159.2, 168.1.

(5) 1-(3-메톡시펜에틸)-N-(4-메톡시벤질)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [18e](5) 1- (3-methoxyphenethyl) -N- (4-methoxybenzyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [18e ]

상기 [5j]와 4-methoxybenzylamine으로 노란색의 고체상 화합물 18e를 얻었다.The yellow solid compound 18e was obtained from [5j] and 4-methoxybenzylamine.

Yield: 76.44%; ¹H NMR (400MHz, DMSO-d₆) δ 2.49 (s, 3H), 3.15 (t, J = 7.1Hz, 2H), 3.70 (s, 3H), 3.76 (s, 3H), 4.50 (t, J = 7.1Hz, 2H), 4.66 (d, J = 5.7Hz, 2H), 6.73-6.77 (m, 3H), 6.94 (d, J = 6.8Hz, 2H), 7.17 (t, J = 7.8Hz, 1H), 7.34 (t, J = 10.4Hz, 2H), 8.08 (s, 3H), 8.75 (t, J = 5.7Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 14.0, 19.7, 34.8, 42.7, 47.1, 54.7, 55.0, 59.7, 98.0, 111.8, 113.7, 114.0, 120.8, 128.9, 129.2, 130.9, 131.6, 139.8, 153.3, 155.0, 158.3, 159.1, 168.1.
Yield: 76.44%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.49 (s, 3H), 3.15 (t, J = 7.1 Hz, 2H), 3.70 (s, 3H), 3.76 (s, 3H), 4.50 (t, J = 7.1 Hz, 2H), 4.66 (d, J = 5.7 Hz, 2H), 6.73-6.77 (m, 3H), 6.94 (d, J = 6.8 Hz, 2H), 7.17 (t, J = 7.8 Hz, 1H ), 7.34 (t, J = 10.4 Hz, 2H), 8.08 (s, 3H), 8.75 (t, J = 5.7 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 14.0, 19.7, 34.8, 42.7, 47.1, 54.7, 55.0, 59.7, 98.0, 111.8, 113.7, 114.0, 120.8, 128.9, 129.2, 130.9, 131.6, 139.8, 153.3, 155.0, 158.3, 159.1, 168.1.

(6) 1-(3-메톡시펜에틸)-N-(4-메틸벤질)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [18f](6) 1- (3-methoxyphenethyl) -N- (4-methylbenzyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [18f]

상기 [5j]와 4-methylbenzylamine으로 노란색의 고체상 화합물 18f를 얻었다.The yellow solid compound 18f was obtained by using [5j] and 4-methylbenzylamine.

Yield: 88.47%; ¹H NMR (400MHz, DMSO-d₆) δ 2.27 (s, 3H), 2.44 (s, 3H), 3.11 (t, J = 7.0Hz, 2H), 3.66 (s, 3H), 4.46 (t, J = 7.0Hz, 2H), 4.65 (d, J = 5.6Hz, 2H), 6.69-6.72 (m, 3H), 7.13 (t, J = 7.9Hz, 3H), 7.24 (d, J = 7.8Hz, 2H), 8.05 (s, 1H), 8.74 (t, J = 5.6Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 19.6, 34.8, 43.0, 47.1, 54.7, 98.0, 111.8, 114.0, 120.8, 127.4, 129.8, 129.2, 131.6, 136.0, 139.8, 153.3, 155.1, 159.1, 168.1.
Yield: 88.47%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.27 (s, 3H), 2.44 (s, 3H), 3.11 (t, J = 7.0 Hz, 2H), 3.66 (s, 3H), 4.46 (t, J = 7.0 Hz, 2H), 4.65 (d, J = 5.6 Hz, 2H), 6.69-6.72 (m, 3H), 7.13 (t, J = 7.9 Hz, 3H), 7.24 (d, J = 7.8 Hz, 2H ), 8.05 (s, 1 H), 8.74 (t, J = 5.6 Hz, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 19.6, 34.8, 43.0, 47.1, 54.7, 98.0, 111.8, 114.0, 120.8, 127.4, 129.8, 129.2, 131.6, 136.0, 139.8, 153.3, 155.1, 159.1, 168.1.

(7) 1-(3-메톡시펜에틸)-N-(4-플루오로벤질)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [18g](7) 1- (3-methoxyphenethyl) -N- (4-fluorobenzyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [18 g ]

상기 [5j]와 4-fluorobenzylamine으로 하얀색의 고체상 화합물 18g를 얻었다.18g of a white solid compound was obtained from [5j] and 4-fluorobenzylamine.

Yield: 87.04%; ¹H NMR (400MHz, DMSO-d₆) δ 2.44 (s, 3H), 3.12 (t, J = 7.0Hz, 2H), 3.66 (s, 3H), 4.47 (t, J = 7.0Hz, 2H), 4.68 (d, J = 5.6Hz, 2H), 4.76-4.80 (m, 1H), 6.70-6.73 (m, 3H), 7.13-7.19 (m, 3H), 7.37-7.41 (m, 2H), 8.04 (s, 1H), 8.79 (t, J = 5.2Hz, 1H), 8.90 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 21.8, 34.7, 42.4, 47.1, 54.7, 98.0, 111.8, 113.9, 114.9, 115.1, 120.7, 129.1, 129.4, 131.6, 135.2, 139.7, 153.3, 155.0, 156.1, 159.0, 162.4, 168.1.
Yield: 87.04%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.44 (s, 3H), 3.12 (t, J = 7.0 Hz, 2H), 3.66 (s, 3H), 4.47 (t, J = 7.0 Hz, 2H), 4.68 (d, J = 5.6 Hz, 2H), 4.76-4.80 (m, 1H), 6.70-6.73 (m, 3H), 7.13-7.19 (m, 3H), 7.37-7.41 (m, 2H), 8.04 ( s, 1 H), 8.79 (t, J = 5.2 Hz, 1 H), 8.90 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 21.8, 34.7, 42.4, 47.1, 54.7, 98.0, 111.8, 113.9, 114.9, 115.1, 120.7, 129.1, 129.4, 131.6, 135.2, 139.7, 153.3, 155.0, 156.1, 159.0, 162.4, 168.1.

(8) 1-(3-메톡시펜에틸)-N-벤질-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [18h](8) 1- (3-methoxyphenethyl) -N-benzyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [18h]

상기 [5j]와 benzylamine으로 하얀색의 고체상 화합물 18h를 얻었다.The white solid compound 18h was obtained from [5j] and benzylamine.

Yield: 89.45%; ¹H NMR (400MHz, DMSO-d₆) δ 2.44 (s, 3H), 3.12 (t, J = 7.0Hz, 2H), 3.66 (s, 3H), 4.47 (t, J = 7.0Hz, 2H), 4.71 (d, J = 5.6Hz, 2H), 4.75-4.80 (m, 1H), 6.71 (t, J = 6.1Hz, 3H), 7.13 (t, J = 7.8Hz, 1H), 7.24-7.35 (m, 5H), 8.06 (s, 1H), 8.80 (d, J = 5.5Hz, 1H), 8.90 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.9, 22.3, 35.3, 43.7, 47.6, 55.2, 98.5, 112.3, 114.5, 121.3, 127.4, 128.0, 128.8, 129.7, 132.2, 139.6, 140.3, 153.8, 155.6, 156.6, 159.6, 168.6.
Yield: 89.45%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.44 (s, 3H), 3.12 (t, J = 7.0 Hz, 2H), 3.66 (s, 3H), 4.47 (t, J = 7.0 Hz, 2H), 4.71 (d, J = 5.6 Hz, 2H), 4.75-4.80 (m, 1H), 6.71 (t, J = 6.1 Hz, 3H), 7.13 (t, J = 7.8 Hz, 1H), 7.24-7.35 (m , 5H), 8.06 (s, 1H), 8.80 (d, J = 5.5 Hz, 1H), 8.90 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 22.3, 35.3, 43.7, 47.6, 55.2, 98.5, 112.3, 114.5, 121.3, 127.4, 128.0, 128.8, 129.7, 132.2, 139.6, 140.3, 153.8, 155.6, 156.6, 159.6, 168.6.

(9) 1-(3-메톡시펜에틸)-N-알릴-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [18i](9) 1- (3-methoxyphenethyl) -N-allyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [18i]

상기 [5j]와 allylamine으로 하얀색의 고체상 화합물 18i를 얻었다.White solid compound 18i was obtained from [5j] and allylamine.

Yield: 90.21%; ¹H NMR (400MHz, DMSO-d₆) δ 2.46 (s, 3H), 3.12 (t, J = 6.9Hz, 2H), 3.67 (s, 3H), 4.11 (s, 2H), 4.47 (t, J = 6.9Hz, 2H), 4.76-4.81 (m, 1H), 5.12-5.25 (m, 2H), 5.92-5.99 (m, 1H), 6.72 (t, J = 5.7Hz, 2H), 7.13 (t, J = 7.7Hz, 1H), 8.04 (s, 1H), 8.45 (s, 1H), 8.89 (s, 1H), 8.89 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 21.8, 34.7, 42.0, 47.0, 54.7, 98.0, 111.8, 113.9, 115.8, 120.7, 129.1, 131.6, 134.8, 139.7, 153.2, 155.0, 159.0, 168.0.
Yield: 90.21%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.46 (s, 3H), 3.12 (t, J = 6.9 Hz, 2H), 3.67 (s, 3H), 4.11 (s, 2H), 4.47 (t, J = 6.9 Hz, 2H), 4.76-4.81 (m, 1H), 5.12-5.25 (m, 2H), 5.92-5.99 (m, 1H), 6.72 (t, J = 5.7 Hz, 2H), 7.13 (t, J = 7.7 Hz, 1H), 8.04 (s, 1H), 8.45 (s, 1H), 8.89 (s, 1H), 8.89 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 21.8, 34.7, 42.0, 47.0, 54.7, 98.0, 111.8, 113.9, 115.8, 120.7, 129.1, 131.6, 134.8, 139.7, 153.2, 155.0, 159.0, 168.0.

실시예 17. [19a] 내지 [19i]의 합성Example 17. Synthesis of [19a] to [19i]

하기 [반응식 19](R₂N, 1,4-dioxane, reflux, 8h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [19a] 내지 [19i]를 합성하였다.The pyrazolopyrimidine derivative compounds [19a] to [19i] were synthesized according to the following Reaction Scheme 19 (R ₂ N, 1,4-dioxane, reflux, 8h).

[반응식 19]Scheme 19

[5k] [19a] ~ [19i][5k] [19a]-[19i]

[19a] 내지 [19i]에서 NR₂은 각각 하기 [표 12]와 같다.NR ₂ in [19a] to [19i] are as shown in Table 12 below, respectively.

구분division NR₂ NR ₂ 구분division NR₂ NR ₂ 19a19a

19f19f

19b19b

19g19 g

19c19c

19h19h

19d19d

19i19i

19e19e

(1) 1-(2-메톡시펜에틸)-N-(3-메톡시벤질)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [19a](1) 1- (2-methoxyphenethyl) -N- (3-methoxybenzyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [19a ]

상기 [5k]와 3-methoxybenzylamine으로 하얀색의 고체상 화합물 19a를 얻었다.White solid compound 19a was obtained by using [5k] and 3-methoxybenzylamine.

Yield: 96.88%; ¹H NMR (400MHz, DMSO-d₆) δ 2.45 (s, 3H), 3.09 (t, J = 6.6Hz, 2H), 3.73 (s, 3H), 3.78 (s, 3H), 4.44 (t, J = 6.6Hz, 2H), 4.67 (d, J = 4.6Hz, 2H), 6.77 (t, J = 7.3Hz, 1H), 6.84 (d, J = 8.1Hz, 1H), 6.95 (t, J = 10.8Hz, 4H), 7.17 (t, J = 7.7Hz, 1H), 7.26 (t, J = 7.8Hz, 1H), 8.04 (s, 1H), 8.75 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 30.2, 43.2, 45.9, 54.9, 55.2, 98.0, 110.5, 112.2, 113.3, 119.6, 120.1, 125.9, 127.8, 129.4, 129.9, 131.5, 140.7, 153.2, 155.1, 157.3, 159.2, 168.0.
Yield: 96.88%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.45 (s, 3H), 3.09 (t, J = 6.6 Hz, 2H), 3.73 (s, 3H), 3.78 (s, 3H), 4.44 (t, J = 6.6 Hz, 2H), 4.67 (d, J = 4.6 Hz, 2H), 6.77 (t, J = 7.3 Hz, 1H), 6.84 (d, J = 8.1 Hz, 1H), 6.95 (t, J = 10.8 Hz, 4H), 7.17 (t, J = 7.7 Hz, 1H), 7.26 (t, J = 7.8 Hz, 1H), 8.04 (s, 1H), 8.75 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 30.2, 43.2, 45.9, 54.9, 55.2, 98.0, 110.5, 112.2, 113.3, 119.6, 120.1, 125.9, 127.8, 129.4, 129.9, 131.5, 140.7, 153.2, 155.1, 157.3, 159.2, 168.0.

(2) 1-(2-메톡시펜에틸)-N-(4-메톡시벤질)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [19b](2) 1- (2-methoxyphenethyl) -N- (4-methoxybenzyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [19b ]

상기 [5k]와 4-methoxybenzylamine으로 얇은 노란색의 고체상 화합물 19b를 얻었다.The thin yellow solid compound 19b was obtained from [5k] and 4-methoxybenzylamine.

Yield: 93.57%; ¹H NMR (400MHz, DMSO-d₆) δ 2.45 (s, 3H), 3.08 (t, J = 6.8Hz, 2H), 3.72 (s, 3H), 3.78 (s, 3H), 4.43 (t, J = 6.8Hz, 2H), 4.62 (d, J = 5.2Hz, 2H), 6.76 (t, J = 7.3Hz, 1H), 6.89-6.97 (m, 4H), 7.16 (t, J = 7.7Hz, 1H), 7.28 (d, J = 8.3Hz, 2H), 8.02 (s, 1H), 8.68 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 30.2, 42.7, 45.8, 55.0, 55.2, 97.9, 110.5, 113.7, 120.1, 125.9, 127.8, 128.9, 129.9, 130.9, 131.5, 153.2, 155.0, 157.3, 158.3, 168.0.
Yield: 93.57%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.45 (s, 3H), 3.08 (t, J = 6.8 Hz, 2H), 3.72 (s, 3H), 3.78 (s, 3H), 4.43 (t, J = 6.8 Hz, 2H), 4.62 (d, J = 5.2 Hz, 2H), 6.76 (t, J = 7.3 Hz, 1H), 6.89-6.97 (m, 4H), 7.16 (t, J = 7.7 Hz, 1H ), 7.28 (d, J = 8.3 Hz, 2H), 8.02 (s, 1H), 8.68 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 30.2, 42.7, 45.8, 55.0, 55.2, 97.9, 110.5, 113.7, 120.1, 125.9, 127.8, 128.9, 129.9, 130.9, 131.5, 153.2, 155.0, 157.3, 158.3, 168.0.

(3) 1-(2-메톡시펜에틸)-N-(4-메톡시벤질)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [19c](3) 1- (2-methoxyphenethyl) -N- (4-methoxybenzyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [19c ]

상기 [5k]와 4-methylbenzylamine으로 하얀색의 고체상 화합물 19c를 얻었다.[5k] and 4-methylbenzylamine gave white solid compound 19c.

Yield: 90.54%; ¹H NMR (400MHz, DMSO-d₆) δ 2.27 (s, 3H), 2.44 (s, 3H), 3.08 (t, J = 7.1Hz, 2H), 3.78 (s, 3H), 4.43 (t, J = 7.2Hz, 2H), 4.64 (d, J = 5.7Hz, 2H), 6.76 (t, J = 7.2Hz, 1H), 6.92-6.97 (m, 2H), 7.13-7.16 (m, 3H), 7.24 (d,J = 8.0Hz, 2H), 8.03 (s, 1H), 8.71 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.9, 21.1, 30.7, 43.4, 46.3, 55.7, 98.5, 111.0, 120.6, 126.4, 128.0, 128.3, 129.3, 130.4,132.0, 136.5, 153.7, 155.6, 157.8, 168.5.
Yield: 90.54%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.27 (s, 3H), 2.44 (s, 3H), 3.08 (t, J = 7.1 Hz, 2H), 3.78 (s, 3H), 4.43 (t, J = 7.2 Hz, 2H), 4.64 (d, J = 5.7 Hz, 2H), 6.76 (t, J = 7.2 Hz, 1H), 6.92-6.97 (m, 2H), 7.13-7.16 (m, 3H), 7.24 (d, J = 8.0 Hz, 2H), 8.03 (s, 1H), 8.71 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 21.1, 30.7, 43.4, 46.3, 55.7, 98.5, 111.0, 120.6, 126.4, 128.0, 128.3, 129.3, 130.4,132.0, 136.5, 153.7, 155.6, 157.8, 168.5.

(4) 1-(2-메톡시펜에틸)-N-(4-플루오로벤질)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [19d](4) 1- (2-methoxyphenethyl) -N- (4-fluorobenzyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [19d ]

상기 [5k]와 4-fluorobenzylamine으로 갈색의 고체상 화합물 19d를 얻었다.[5k] and 4-fluorobenzylamine obtained the brown solid compound 19d.

Yield: 84.37%; ¹H NMR (400MHz, DMSO-d₆) δ 2.44 (s, 3H), 3.08 (t, J = 7.0Hz, 2H), 3.78 (s, 3H), 4.43 (t, J = 7.0Hz, 2H), 4.67 (d, J = 5.4Hz, 2H), 4.76-4.80 (m, 1H), 6.77 (t, J = 7.3Hz, 1H), 6.95 (t, J = 9.5Hz, 2H), 7.17 (t, J = 8.1Hz, 3H), 7.37-7.40 (m, 2H), 8.01 (s, 1H), 8.76 (t, J = 5.3Hz, 1H), 8.89 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.3, 21.8, 30.1, 42.4, 45.8, 55.1, 97.9, 100.3, 110.5, 114.9, 115.1, 120.0, 125.8, 127.8, 129.4, 129.9, 131.4, 135.2, 155.0, 156.0, 157.2, 167.9.
Yield: 84.37%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.44 (s, 3H), 3.08 (t, J = 7.0 Hz, 2H), 3.78 (s, 3H), 4.43 (t, J = 7.0 Hz, 2H), 4.67 (d, J = 5.4 Hz, 2H), 4.76-4.80 (m, 1H), 6.77 (t, J = 7.3 Hz, 1H), 6.95 (t, J = 9.5 Hz, 2H), 7.17 (t, J = 8.1 Hz, 3H), 7.37-7.40 (m, 2H), 8.01 (s, 1H), 8.76 (t, J = 5.3 Hz, 1H), 8.89 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.3, 21.8, 30.1, 42.4, 45.8, 55.1, 97.9, 100.3, 110.5, 114.9, 115.1, 120.0, 125.8, 127.8, 129.4, 129.9, 131.4, 135.2, 155.0, 156.0, 157.2, 167.9.

(5) 1-(2-메톡시펜에틸)-N-벤질-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [19e](5) 1- (2-methoxyphenethyl) -N-benzyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [19e]

상기 [5k]와 benzylamine으로 갈색의 고체상 화합물 19e를 얻었다.[5k] and benzylamine gave brown solid compound 19e.

Yield: 81.24%, ¹H NMR (400MHz, DMSO-d₆) δ 2.44 (s, 3H), 3.08 (t, J = 7.1Hz, 2H), 3.79 (s, 3H), 4.43 (t, J = 7.1Hz, 2H), 4.70 (d, J = 5.7Hz, 2H), 4.76-4.80 (m, 1H), 6.77 (t, J = 7.2Hz, 1H), 6.95 (t, J = 9.1Hz, 2H), 7.26 (t, J = 7.9Hz, 3H), 7.32-7.36 (m, 3H), 8.03 (s, 1H), 8.76 (t, J = 5.2Hz, 1H), 8.89 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.8, 21.8, 30.2, 43.2, 45.8, 55.1, 97.9, 101.3, 110.5, 114.9, 115.1, 120.0, 125.8, 127.8, 129.4, 129.9, 131.4, 135.2, 155.1, 156.1, 157.2, 168.0.
Yield: 81.24%, ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.44 (s, 3H), 3.08 (t, J = 7.1 Hz, 2H), 3.79 (s, 3H), 4.43 (t, J = 7.1 Hz, 2H), 4.70 (d, J = 5.7 Hz, 2H), 4.76-4.80 (m, 1H), 6.77 (t, J = 7.2 Hz, 1H), 6.95 (t, J = 9.1 Hz, 2H), 7.26 (t, J = 7.9 Hz, 3H), 7.32-7.36 (m, 3H), 8.03 (s, 1 H), 8.76 (t, J = 5.2 Hz, 1H), 8.89 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.8, 21.8, 30.2, 43.2, 45.8, 55.1, 97.9, 101.3, 110.5, 114.9, 115.1, 120.0, 125.8, 127.8, 129.4, 129.9, 131.4, 135.2, 155.1, 156.1, 157.2, 168.0.

(6) 1-(2-메톡시펜에틸)-N-알릴-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 (19f)(6) 1- (2-methoxyphenethyl) -N-allyl-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine (19f)

상기 [5k]와 allylamine으로 하얀색의 고체상 화합물 19f를 얻었다.White solid compound 19f was obtained from [5k] and allylamine.

Yield: 78.53%; ¹H NMR (400MHz, DMSO-d₆) δ 2.45 (s, 3H), 3.08 (t, J = 7.1Hz, 2H), 3.78 (s, 3H), 4.09-4.12 (m, 2H), 4.43 (t, J = 7.2Hz, 2H), 4.76-4.81 (m, 1H), 5.11-5.24 (m, 2H), 5.94-5.97 (m, 1H), 6.76 (t, J = 7.3Hz, 1H), 6.95 (t, J = 8.6Hz, 2H), 7.14-7.18 (m, 1H), 8.02 (s, 1H), 8.43 (d, J = 5.2Hz, 1H), 8.89 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.3, 30.1, 42.0, 55.1, 97.9, 110.4, 115.7, 120.0, 125.9, 127.8, 129.9, 131.4, 134.8, 153.1, 155.0, 156.0, 157.2, 167.9.
Yield: 78.53%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.45 (s, 3H), 3.08 (t, J = 7.1 Hz, 2H), 3.78 (s, 3H), 4.09-4.12 (m, 2H), 4.43 (t , J = 7.2 Hz, 2H), 4.76-4.81 (m, 1H), 5.11-5.24 (m, 2H), 5.94-5.97 (m, 1H), 6.76 (t, J = 7.3 Hz, 1H), 6.95 ( t, J = 8.6 Hz, 2H), 7.14-7.18 (m, 1H), 8.02 (s, 1H), 8.43 (d, J = 5.2 Hz, 1H), 8.89 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.3, 30.1, 42.0, 55.1, 97.9, 110.4, 115.7, 120.0, 125.9, 127.8, 129.9, 131.4, 134.8, 153.1, 155.0, 156.0, 157.2, 167.9.

(7) N-(2-메톡시벤질)-1-(2-메톡시펜에틸)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [19g](7) N- (2-methoxybenzyl) -1- (2-methoxyphenethyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [19 g ]

상기 [5k]와 2-methylbenzylamine으로 하얀색의 고체상 화합물 19g를 얻었다.19g of white solid compound was obtained by using [5k] and 2-methylbenzylamine.

Yield: 89.52%; ¹H NMR (400MHz, DMSO-d₆) δ 2.33 (s, 3H), 2.44 (s, 3H), 3.09 (t, J = 6.3Hz, 2H), 3.78 (s, 3H), 4.44 (t, J = 6.5Hz, 2H), 4.67 (d, J = 4.8Hz, 2H), 6.77 (t, J = 5.2Hz, 1H), 6.92-6.99 (m, 2H), 7.18 (m, 4H), 7.30 (d, J = 5.6Hz, 1H), 8.07 (s, 1H), 8.60 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.3, 18.7, 30.2, 41.5, 45.8, 55.1, 97.9, 110.5, 120.0, 125.7, 125.9, 127.0, 127.8, 128.0, 129.9, 129.9, 131.6, 135.9, 136.5, 153.2, 155.0, 157.2, 167.9.
Yield: 89.52%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.33 (s, 3H), 2.44 (s, 3H), 3.09 (t, J = 6.3 Hz, 2H), 3.78 (s, 3H), 4.44 (t, J = 6.5 Hz, 2H), 4.67 (d, J = 4.8 Hz, 2H), 6.77 (t, J = 5.2 Hz, 1H), 6.92-6.99 (m, 2H), 7.18 (m, 4H), 7.30 (d , J = 5.6 Hz, 1H), 8.07 (s, 1H), 8.60 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.3, 18.7, 30.2, 41.5, 45.8, 55.1, 97.9, 110.5, 120.0, 125.7, 125.9, 127.0, 127.8, 128.0, 129.9, 129.9, 131.6, 135.9, 136.5, 153.2, 155.0, 157.2, 167.9.

(8) N-(2-클로로벤질)-1-(2-메톡시펜에틸)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [19h](8) N- (2-chlorobenzyl) -1- (2-methoxyphenethyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [19h]

상기 [5k]와 2-chlorobenzylamine으로 하얀색의 고체상 화합물 19h를 얻었다.A white solid compound 19h was obtained from [5k] and 2-chlorobenzylamine.

Yield: 86.02%; ¹H NMR (400MHz, DMSO-d₆) δ 2.40 (s, 3H), 3.09 (t, J = 7.0Hz, 2H), 3.78 (s, 3H), 4.44 (t, J = 7.0Hz, 2H), 4.76 (d, J = 5.5Hz, 2H), 6.77 (t, J = 7.3Hz, 1H), 6.92-6.98 (m, 2H), 7.17 (t, J = 7.7Hz, 1H), 7.32 (t, J = 4.5Hz, 2H), 7.41 (t, J = 4.2Hz, 1H), 7.48 (t, J = 4.4Hz, 1H), 8.08 (s, 1H), 8.77 (t, J = 5.0Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.8, 30.7, 41.7, 46.4, 55.7, 98.5, 111.0, 120.6, 126.4, 127.7, 128.4, 129.3, 129.7, 130.4, 132.1, 132.8, 136.5, 153.8, 155.6, 157.8, 168.4.
Yield: 86.02%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.40 (s, 3H), 3.09 (t, J = 7.0 Hz, 2H), 3.78 (s, 3H), 4.44 (t, J = 7.0 Hz, 2H), 4.76 (d, J = 5.5 Hz, 2H), 6.77 (t, J = 7.3 Hz, 1H), 6.92-6.98 (m, 2H), 7.17 (t, J = 7.7 Hz, 1H), 7.32 (t, J = 4.5 Hz, 2H), 7.41 (t, J = 4.2 Hz, 1H), 7.48 (t, J = 4.4 Hz, 1H), 8.08 (s, 1H), 8.77 (t, J = 5.0 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.8, 30.7, 41.7, 46.4, 55.7, 98.5, 111.0, 120.6, 126.4, 127.7, 128.4, 129.3, 129.7, 130.4, 132.1, 132.8, 136.5, 153.8, 155.6, 157.8, 168.4.

(9) N-(2-메톡시벤질)-1-(2-메톡시펜에틸)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [19i](9) N- (2-methoxybenzyl) -1- (2-methoxyphenethyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [19i ]

상기 [5k]와 2-methoxybenzylamine으로 하얀색의 고체상 화합물 19i를 얻었다.White solid compound 19i was obtained from [5k] and 2-methoxybenzylamine.

Yield: 88.34%; ¹H NMR (400MHz, DMSO-d₆) δ 2.42 (s, 3H), 3.08 (t, J = 7.1Hz, 2H), 3.78 (s, 3H), 3.83 (s, 3H), 4.43 (t, J = 7.2Hz, 2H), 4.65 (d, J = 5.6Hz, 2H), 6.77 (t, J = 7.3Hz, 1H), 6.88-7.02 (m, 4H), 7.14-7.28 (m, 3H), 8.07 (s, 1H), 8.57 (t, J = 5.5Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.3, 30.2, 38.3, 45.8, 55.2, 55.3, 98.0, 110.5, 110.6, 120.1, 125.9, 126.2, 127.8, 128.2, 128.3, 129.9, 131.6, 153.2, 155.3, 156.8, 157.3, 167.9.
Yield: 88.34%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.42 (s, 3H), 3.08 (t, J = 7.1 Hz, 2H), 3.78 (s, 3H), 3.83 (s, 3H), 4.43 (t, J = 7.2 Hz, 2H), 4.65 (d, J = 5.6 Hz, 2H), 6.77 (t, J = 7.3 Hz, 1H), 6.88-7.02 (m, 4H), 7.14-7.28 (m, 3H), 8.07 (s, 1 H), 8.57 (t, J = 5.5 Hz, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.3, 30.2, 38.3, 45.8, 55.2, 55.3, 98.0, 110.5, 110.6, 120.1, 125.9, 126.2, 127.8, 128.2, 128.3, 129.9, 131.6, 153.2, 155.3, 156.8, 157.3, 167.9.

실시예 18. [20a] 내지 [20f]의 합성Example 18. Synthesis of [20a] to [20f]

하기 [반응식 20](R₂N, 1,4-dioxane, reflux, 8h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [20a] 내지 [20f]를 합성하였다.The pyrazolopyrimidine derivative compounds [20a] to [20f] were synthesized according to the following Reaction Scheme 20 (R ₂ N, 1,4-dioxane, reflux, 8h).

[반응식 20][Reaction Scheme 20]

[5h] [20a] ~ [20f][5h] [20a] to [20f]

[20a] 내지 [20f]에서 NR₂은 각각 하기 [표 13]과 같다.In [20a] to [20f], NR ₂ is shown in the following [Table 13].

구분division NR₂ NR ₂ 구분division NR₂ NR ₂ 20a20a

20d20d

20b20b

20e20e

20c20c

20f20f

(1) N-(2-클로로벤질)-1-(4-플루오로페닐)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [20a](1) N- (2-chlorobenzyl) -1- (4-fluorophenyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [20a]

상기 [5h]와 2-chlorobenzylamine으로 하얀색의 고체상 화합물 20a를 얻었다.[5h] and 2-chlorobenzylamine to obtain a white solid compound 20a.

Yield: 82.17%; ¹H NMR (400MHz, DMSO-d₆) δ 2.35 (s, 3H), 4.63 (d, J = 4.9Hz, 2H), 6.36 (s, 1H), 7.31-7.37 (m, 3H), 7.47 (t, J = 4.2Hz, 1H), 8.28 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.3, 41.6, 99.3, 127.2, 128.8, 129.2, 132.2, 135.8, 156.6, 162.3, 171.2.
Yield: 82.17%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.35 (s, 3H), 4.63 (d, J = 4.9 Hz, 2H), 6.36 (s, 1H), 7.31-7.37 (m, 3H), 7.47 (t , J = 4.2 Hz, 1 H), 8.28 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.3, 41.6, 99.3, 127.2, 128.8, 129.2, 132.2, 135.8, 156.6, 162.3, 171.2.

(2) N-(2-메톡시벤질)-1-(4-플루오로페닐)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [20b](2) N- (2-methoxybenzyl) -1- (4-fluorophenyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [20b]

상기 [5h]와 2-methoxybenzylamine으로 하얀색의 고체상 화합물 20b를 얻었다.The white solid compound 20b was obtained from [5h] and 2-methoxybenzylamine.

Yield: 88.32%; ¹H NMR (400MHz, DMSO-d₆) δ 2.47 (s, 3H), 3.82 (s, 3H), 4.68 (d, J = 5.2Hz, 2H), 6.90 (t, J = 7.3Hz, 1H), 7.00 (d, J = 7.9Hz, 1H), 7.25 (t, J = 7.8Hz, 2H), 7.36 (t, J = 8.7Hz, 2H), 8.16-8.19 (m, 2H), 8.34 (s, 1H), 8.81 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.1, 39.0, 55.8, 99.9, 111.1, 116.2, 116.4, 120.6, 122.6, 126.5, 128.8, 134.5, 135.8, 153.6, 155.8, 157.3, 170.2.
Yield: 88.32%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.47 (s, 3H), 3.82 (s, 3H), 4.68 (d, J = 5.2 Hz, 2H), 6.90 (t, J = 7.3 Hz, 1H), 7.00 (d, J = 7.9 Hz, 1H), 7.25 (t, J = 7.8 Hz, 2H), 7.36 (t, J = 8.7 Hz, 2H), 8.16-8.19 (m, 2H), 8.34 (s, 1H ), 8.81 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.1, 39.0, 55.8, 99.9, 111.1, 116.2, 116.4, 120.6, 122.6, 126.5, 128.8, 134.5, 135.8, 153.6, 155.8, 157.3, 170.2.

(3) N-(2-메틸벤질)-1-(4-프루오로페닐)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [20c](3) N- (2-methylbenzyl) -1- (4-fluorofluoro) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [20c]

상기 [5h]와 2-methylbenzylamine으로 하얀색의 고체상 화합물 20c를 얻었다.The white solid compound 20c was obtained from [5h] and 2-methylbenzylamine.

Yield: 77.24%; ¹H NMR (400MHz, DMSO-d₆) δ 2.29 (s, 3H), 2.39 (s, 3H), 4.52 (s, 2H), 6.30 (s, 1H), 7.16-7.24 (m, 5H), 8.12 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.3, 18.6, 39.9, 99.2, 125.8, 127.1, 128.1, 130.0, 135.9, 136.3, 156.5, 162.2, 171.2.
Yield: 77.24%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.29 (s, 3H), 2.39 (s, 3H), 4.52 (s, 2H), 6.30 (s, 1H), 7.16-7.24 (m, 5H), 8.12 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.3, 18.6, 39.9, 99.2, 125.8, 127.1, 128.1, 130.0, 135.9, 136.3, 156.5, 162.2, 171.2.

(4) N-(3-메톡시벤질)-1-(4-플루오로페닐)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [20d](4) N- (3-methoxybenzyl) -1- (4-fluorophenyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [20d]

상기 [5h]와 3-methoxybenzylamine으로 노란색의 고체상 화합물 20d를 얻었다.The yellow solid compound 20d was obtained from [5h] and 3-methoxybenzylamine.

Yield: 96.53%; ¹H NMR (400MHz, DMSO-d₆) δ 2.51 (s, 3H), 3.75 (s, 3H), 4.72 (d, J = 5.6Hz, 2H), 6.86 (d, J = 7.0Hz, 1H), 6.97 (d, J = 8.3Hz, 2H), 7.28 (t, J = 7.8Hz, 1H), 7.39 (t, J = 8.7Hz, 2H), 8.18-8.22 (m, 2H), 8.33 (s, 1H), 9.01 (t, J = 5.5Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.7, 43.3, 54.9, 99.3, 112.3, 113.3, 115.7, 115.9, 119.7, 122.1, 122.2, 129.4, 133.9, 135.3, 140.4, 153.2, 155.3, 158.6, 159.3, 161.0, 169.7.
Yield: 96.53%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.51 (s, 3H), 3.75 (s, 3H), 4.72 (d, J = 5.6 Hz, 2H), 6.86 (d, J = 7.0 Hz, 1H), 6.97 (d, J = 8.3 Hz, 2H), 7.28 (t, J = 7.8 Hz, 1H), 7.39 (t, J = 8.7 Hz, 2H), 8.18-8.22 (m, 2H), 8.33 (s, 1H ), 9.01 (t, J = 5.5 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.7, 43.3, 54.9, 99.3, 112.3, 113.3, 115.7, 115.9, 119.7, 122.1, 122.2, 129.4, 133.9, 135.3, 140.4, 153.2, 155.3, 158.6, 159.3, 161.0, 169.7.

(5) N-(4-메톡시벤질)-1-(4-플루오로페닐)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [20e](5) N- (4-methoxybenzyl) -1- (4-fluorophenyl) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [20e]

상기 [5h]와 3-methoxybenzylamine으로 얇은 노란색의 고체상 화합물 20e를 얻었다.The thin yellow solid compound 20e was obtained from [5h] and 3-methoxybenzylamine.

Yield: 92.58%; ¹H NMR (400MHz, DMSO-d₆) δ 2.52 (s, 3H), 3.74 (s, 3H), 4.68 (d, J = 5.5Hz, 2H), 6.93 (d, J = 8.4Hz, 2H), 7.33 (d, J = 8.4Hz, 2H), 7.39 (t, J = 8.8Hz, 2H), 8.19-8.22 (m, 2H), 8.32 (s, 1H), 8.95 (t, J = 5.5Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.7, 42.8, 55.0, 99.3, 113.7, 115.7, 115.9, 122.1, 122.1, 128.9, 130.6, 133.9, 135.3, 153.2, 155.1, 158.4, 158.5, 161.0, 169.7.
Yield: 92.58%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.52 (s, 3H), 3.74 (s, 3H), 4.68 (d, J = 5.5 Hz, 2H), 6.93 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 7.39 (t, J = 8.8 Hz, 2H), 8.19-8.22 (m, 2H), 8.32 (s, 1H), 8.95 (t, J = 5.5 Hz, 1H ); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.7, 42.8, 55.0, 99.3, 113.7, 115.7, 115.9, 122.1, 122.1, 128.9, 130.6, 133.9, 135.3, 153.2, 155.1, 158.4, 158.5, 161.0, 169.7.

(6) N-(4-메틸벤질)-1-(4-프루오로페닐)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-4-아민 [20f](6) N- (4-methylbenzyl) -1- (4-fluorofluoro) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [20f]

상기 [5h]와 4-methylbenzylamine으로 노란색의 고체상 화합물 20f를 얻었다.The yellow solid compound 20f was obtained from [5h] and 4-methylbenzylamine.

Yield: 86.42%; ¹H NMR (400MHz, DMSO-d₆) δ 2.19 (d, J = 6.3Hz, 3H), 3.29 (s, 3H), 4.57 (dd, J = 5.1Hz, 38.1Hz, 2H), 7.03-7.12 (m, 3H), 7.20 (d, J = 7.3Hz, 1H), 7.30 (t, J = 8.7Hz, 1H), 8.11-8.25 (m, 2H), 8.89 (s, 1H), 9.95 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.7, 20.6, 43.1, 92.0, 99.3, 115.7, 115.9, 122.1, 127.5, 128.8, 128.9, 133.9, 135.7, 136.1, 153.2, 155.2, 158.5, 160.9, 169.8, 174.9, 186.0.
Yield: 86.42%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.19 (d, J = 6.3 Hz, 3H), 3.29 (s, 3H), 4.57 (dd, J = 5.1 Hz, 38.1 Hz, 2H), 7.03-7.12 ( m, 3H), 7.20 (d, J = 7.3 Hz, 1H), 7.30 (t, J = 8.7 Hz, 1H), 8.11-8.25 (m, 2H), 8.89 (s, 1H), 9.95 (s, 1H ); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.7, 20.6, 43.1, 92.0, 99.3, 115.7, 115.9, 122.1, 127.5, 128.8, 128.9, 133.9, 135.7, 136.1, 153.2, 155.2, 158.5, 160.9, 169.8, 174.9, 186.0.

실시예 19. [21a] 내지 [21j]의 합성Example 19. Synthesis of [21a] to [21j]

하기 [반응식 21](R₂N, 1,4-dioxane, reflux, 8h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [21a] 내지 [21j]를 합성하였다.The pyrazolopyrimidine derivative compounds [21a] to [21j] were synthesized according to the following Reaction Scheme 21 (R ₂ N, 1,4-dioxane, reflux, 8h).

[반응식 21][Reaction Scheme 21]

[5i] [21a] ~ [21j][5i] [21a]-[21j]

[21a] 내지 [21j]에서 NR₂은 각각 하기 [표 14]와 같다.NR ₂ in [21a] to [21j] are as shown in Table 14 below, respectively.

구분division NR₂ NR ₂ 구분division NR₂ NR ₂ 21a21a

21f21f

21b21b

21g21g

21c21c

21h21h

21d21d

21i21i

21e21e

21j21j

(1) N-(2-클로로벤질)-6-(메틸티오)-1-p-톨릴-1H-피라졸로[3,4-d]피리미딘-4-아민 [21a](1) N- (2-chlorobenzyl) -6- (methylthio) -1-p-tolyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [21a]

상기 [5i]와 2-chlorobenzylamine으로 얇은 노란색의 고체상 화합물 21a를 얻었다.The thin yellow solid compound 21a was obtained from [5i] and 2-chlorobenzylamine.

Yield: 80.05%; ¹H NMR (400MHz, DMSO-d₆) δ 2.31 (s, 3H), 2.43 (s, 3H), 4.78 (d, J = 5.3Hz, 2H), 7.29 (d, J = 7.7Hz, 4H), 7.42-7.45 (m, 2H), 8.02 (d, J = 8.0Hz, 2H), 8.32 (s, 1H), 8.95 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.1, 20.9, 41.7, 99.9, 116.8, 120.7, 127.7, 129.0, 129.3, 129.7, 129.7, 129.9, 132.4, 132.8, 134.1, 135.7, 136.3, 137.0, 153.6, 155.8, 161.2, 169.9, 173.6.
Yield: 80.05%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.31 (s, 3H), 2.43 (s, 3H), 4.78 (d, J = 5.3 Hz, 2H), 7.29 (d, J = 7.7 Hz, 4H), 7.42-7.45 (m, 2H), 8.02 (d, J = 8.0 Hz, 2H), 8.32 (s, 1H), 8.95 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.1, 20.9, 41.7, 99.9, 116.8, 120.7, 127.7, 129.0, 129.3, 129.7, 129.7, 129.9, 132.4, 132.8, 134.1, 135.7, 136.3, 137.0, 153.6, 155.8, 161.2, 169.9, 173.6.

(2) N-(2-메톡시벤질)-6-(메틸티오)-1-p-톨릴-1H-피라졸로[3,4-d]피리미딘-4-아민 [21b](2) N- (2-methoxybenzyl) -6- (methylthio) -1-p-tolyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [21b]

상기 [5i]와 2-methoxybenzylamine으로 얇은 노란색의 고체상 화합물 21b를 얻었다.The thin yellow solid compound 21b was obtained from [5i] and 2-methoxybenzylamine.

Yield: 79.84%; ¹H NMR (400MHz, DMSO-d₆) δ 2.32 (s, 3H), 2.46 (s, 3H), 3.81 (s, 3H), 4.67 (d, J = 4.4Hz, 2H), 6.90 (t, J = 7.0Hz, 1H), 7.00 (d, J = 7.8Hz, 1H), 7.28 (dd, J = 7.5Hz, 18.6Hz, 4H), 8.02 (d, J = 7.7Hz, 2H), 8.32 (s, 1H), 8.77 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 20.9, 55.8, 99.9, 111.1, 120.6, 120.7, 126.5, 128.8, 128.8, 129.9, 134.2, 135.6, 137.0, 153.6, 155.9, 157.3, 169.9.
Yield: 79.84%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.32 (s, 3H), 2.46 (s, 3H), 3.81 (s, 3H), 4.67 (d, J = 4.4 Hz, 2H), 6.90 (t, J = 7.0 Hz, 1H), 7.00 (d, J = 7.8 Hz, 1H), 7.28 (dd, J = 7.5 Hz, 18.6 Hz, 4H), 8.02 (d, J = 7.7 Hz, 2H), 8.32 (s, 1H), 8.77 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 20.9, 55.8, 99.9, 111.1, 120.6, 120.7, 126.5, 128.8, 128.8, 129.9, 134.2, 135.6, 137.0, 153.6, 155.9, 157.3, 169.9.

(3) N-(2-메틸벤질)-6-(메틸티오)-1-p-톨릴-1H-피라졸로[3,4-d]피리미딘-4-아민 [21c](3) N- (2-methylbenzyl) -6- (methylthio) -1-p-tolyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [21c]

상기 [5i]와 2-methylbenzylamine으로 갈색의 고체상 화합물 21c를 얻었다.[5i] and 2-methylbenzylamine obtained the brown solid compound 21c.

Yield: 82.33%; ¹H NMR (400MHz, DMSO-d₆) δ 2.35 (s, 6H), 2.50 (s, 3H), 4.71 (d, J = 4.7Hz, 2H), 7.26 (dd, J = 8.1Hz, 56.7Hz, 7H), 8.05 (d, J = 7.9Hz, 2H), 8.34 (s, 1H), 8.81 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.6, 18.7, 20.4, 41.6, 99.3, 120.3, 125.8, 127.1, 128.1, 129.4, 130.0, 133.6, 135.2, 136.0, 136.3, 136.5, 153.1, 155.2, 165.5.
Yield: 82.33%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.35 (s, 6H), 2.50 (s, 3H), 4.71 (d, J = 4.7 Hz, 2H), 7.26 (dd, J = 8.1 Hz, 56.7 Hz, 7H), 8.05 (d, J = 7.9 Hz, 2H), 8.34 (s, 1H), 8.81 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.6, 18.7, 20.4, 41.6, 99.3, 120.3, 125.8, 127.1, 128.1, 129.4, 130.0, 133.6, 135.2, 136.0, 136.3, 136.5, 153.1, 155.2, 165.5.

(4) N-(3-메톡시벤질)-6-(메틸티오)-1-p-톨릴-1H-피라졸로[3,4-d]피리미딘-4-아민 [21d](4) N- (3-methoxybenzyl) -6- (methylthio) -1-p-tolyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [21d]

상기 [5i]와 3-methoxybenzylamine으로 갈색의 고체상 화합물 21d를 얻었다.[5i] and 3-methoxybenzylamine were obtained as a brown solid compound 21d.

Yield: 75.89%; ¹H NMR (400MHz, DMSO-d₆) δ 2.35 (s, 3H), 2.51 (s, 3H), 3.74 (s, 3H), 4.72 (d, J = 4.8Hz, 2H), 6.91 (dd, J = 8.9Hz, 45.0Hz, 3H), 7.25-7.34 (m, 3H), 8.05 (d, J = 7.7Hz, 2H), 8.31 (s, 1H), 8.97 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.6, 20.4, 43.3, 54.9, 99.3, 112.3, 113.3, 119.7, 120.3, 129.4, 133.5, 135.2, 136.5, 140.5, 153.1, 155.3, 159.3, 169.5.
Yield: 75.89%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.35 (s, 3H), 2.51 (s, 3H), 3.74 (s, 3H), 4.72 (d, J = 4.8 Hz, 2H), 6.91 (dd, J = 8.9 Hz, 45.0 Hz, 3H), 7.25-7.34 (m, 3H), 8.05 (d, J = 7.7 Hz, 2H), 8.31 (s, 1H), 8.97 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.6, 20.4, 43.3, 54.9, 99.3, 112.3, 113.3, 119.7, 120.3, 129.4, 133.5, 135.2, 136.5, 140.5, 153.1, 155.3, 159.3, 169.5.

(5) N-(4-메톡시벤질)-6-(메틸티오)-1-p-톨릴-1H-피라졸로[3,4-d]피리미딘-4-아민 [21e](5) N- (4-methoxybenzyl) -6- (methylthio) -1-p-tolyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [21e]

상기 [5i]와 4-methoxybenzylamine으로 하얀색의 고체상 화합물 21e를 얻었다.White solid compound 21e was obtained from [5i] and 4-methoxybenzylamine.

Yield: 92.46%; ¹H NMR (400MHz, DMSO-d₆) δ 2.35 (s, 3H), 2.52 (s, 3H), 3.74 (s, 3H), 4.67 (d, J = 5.4Hz, 2H), 6.92 (d, J = 8.4Hz, 2H), 7.31-7.34 (m, 4H), 8.05 (d, J = 8.2Hz, 2H), 8.30 (s, 1H), 8.91 (t, J = 5.2Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.6, 20.4, 42.8, 55.0, 99.3, 113.7, 120.2, 128.9, 129.4, 130.7, 13 3.6, 135.1, 136.5, 153.1, 155.2, 158.4, 169.5.
Yield: 92.46%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.35 (s, 3H), 2.52 (s, 3H), 3.74 (s, 3H), 4.67 (d, J = 5.4 Hz, 2H), 6.92 (d, J = 8.4 Hz, 2H), 7.31-7.34 (m, 4H), 8.05 (d, J = 8.2 Hz, 2H), 8.30 (s, 1H), 8.91 (t, J = 5.2 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.6, 20.4, 42.8, 55.0, 99.3, 113.7, 120.2, 128.9, 129.4, 130.7, 13 3.6, 135.1, 136.5, 153.1, 155.2, 158.4, 169.5.

(6) N-(4-메틸벤질)-6-(메틸티오)-1-p-톨릴-1H-피라졸로[3,4-d]피리미딘-4-아민 [21f](6) N- (4-methylbenzyl) -6- (methylthio) -1-p-tolyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [21f]

상기 [5i]와 4-methylbenzylamine으로 얇은 붉은색의 고체상 화합물 21f를 얻었다.The thin red solid compound 21f was obtained from [5i] and 4-methylbenzylamine.

Yield: 81.85%; ¹H NMR (400MHz, DMSO-d₆) δ 2.26 (s, 3H), 2.34 (s, 3H), 2.50 (s, 3H), 4.69 (d, J = 5.4Hz, 2H), 7.13-7.18 (m, 2H), 7.27 (d, J = 7.7Hz, 2H), 7.33 (d, J = 8.2Hz, 2H), 8.04 (d, J = 8.3Hz, 2H), 8.30 (s, 1H), 8.94 (t, J = 5.4Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.6, 20.5, 20.6, 43.0, 99.3, 120.2, 127.2, 127.5, 128.9, 129.4, 133.9, 135.2, 135.8, 136.1, 136.5, 153.1, 155.2, 169.5.
Yield: 81.85%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.26 (s, 3H), 2.34 (s, 3H), 2.50 (s, 3H), 4.69 (d, J = 5.4 Hz, 2H), 7.13-7.18 (m , 2H), 7.27 (d, J = 7.7 Hz, 2H), 7.33 (d, J = 8.2 Hz, 2H), 8.04 (d, J = 8.3 Hz, 2H), 8.30 (s, 1H), 8.94 (t , J = 5.4 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.6, 20.5, 20.6, 43.0, 99.3, 120.2, 127.2, 127.5, 128.9, 129.4, 133.9, 135.2, 135.8, 136.1, 136.5, 153.1, 155.2, 169.5.

(7) N-((4-클로로페닐)(페닐)메틸)-6-(메틸티오)-1-p-톨릴-1H-피라졸로[3,4-d]피리미딘-4-아민 [21g](7) N-((4-chlorophenyl) (phenyl) methyl) -6- (methylthio) -1-p-tolyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [21 g ]

상기 [5i]와 (4-chlorophenyl)(phenyl)methanamine으로 하얀색의 고체상 화합물 21g를 얻었다.21 g of a white solid compound was obtained from [5i] and (4-chlorophenyl) (phenyl) methanamine.

Yield: 89.42%; ¹H NMR (400MHz, DMSO-d₆) δ 2.35 (s, 3H), 2.42 (s, 3H), 6.68 (d, J = 7.5Hz, 1H), 7.32-7.45 (m, 11H), 8.00 (d, J = 8.0Hz, 2H), 8.44 (s, 1H), 9.23 (d, J = 7.8Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.6, 20.4, 56.5, 99.3, 120.3, 127.3, 127.6, 128.3, 128.4, 129.4, 131.7, 133.9, 135.2, 136.4, 140.8, 141.2, 153.2, 154.4, 169.3.
Yield: 89.42%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.35 (s, 3H), 2.42 (s, 3H), 6.68 (d, J = 7.5 Hz, 1H), 7.32-7.45 (m, 11H), 8.00 (d , J = 8.0 Hz, 2H), 8.44 (s, 1H), 9.23 (d, J = 7.8 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.6, 20.4, 56.5, 99.3, 120.3, 127.3, 127.6, 128.3, 128.4, 129.4, 131.7, 133.9, 135.2, 136.4, 140.8, 141.2, 153.2, 154.4, 169.3.

(8) N-(1-사이클로헥실에틸)-6-(메틸티오)-1-p-톨릴-1H-피라졸로[3,4-d]피리미딘-4-아민 [21h](8) N- (1-cyclohexylethyl) -6- (methylthio) -1-p-tolyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [21h]

상기 [5i]와 (S)-cyclohexylethylamine으로 하얀색의 고체상 화합물 21h를 얻었다.The white solid compound 21h was obtained from [5i] and (S) -cyclohexylethylamine.

Yield: 94.28%; ¹H NMR (400MHz, DMSO-d₆) δ 0.99-1.04 (m, 2H), 1.12-1.20 (m, 5H), 1.48-1.69 (m, 6H), 2.35 (s, 3H), 2.52 (s, 3H), 4.21-4.27 (m, 1H), 7.33 (d, J = 8.4Hz, 2H), 8.04 (d, J = 8.4Hz, 2H), 8.17 (d, J = 8.4Hz, 1H), 8.34 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.6, 17.3, 20.4, 25.6, 25.7, 25.9, 28.6, 29.1, 42.4, 49.8, 98.6, 99.2, 120.2, 129.4, 133.6, 135.0, 136.6, 153.1, 155.0, 169.3.
Yield: 94.28%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.99-1.04 (m, 2H), 1.12-1.20 (m, 5H), 1.48-1.69 (m, 6H), 2.35 (s, 3H), 2.52 (s, 3H), 4.21-4.27 (m, 1H), 7.33 (d, J = 8.4 Hz, 2H), 8.04 (d, J = 8.4 Hz, 2H), 8.17 (d, J = 8.4 Hz, 1H), 8.34 ( s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.6, 17.3, 20.4, 25.6, 25.7, 25.9, 28.6, 29.1, 42.4, 49.8, 98.6, 99.2, 120.2, 129.4, 133.6, 135.0, 136.6, 153.1, 155.0, 169.3.

(9) 6-(메틸티오)-1-p-톨릴-N-(1-p-톨릴에틸)-1H-피라졸로[3,4-d]피리미딘-4-아민 [21i](9) 6- (methylthio) -1-p-tolyl-N- (1-p-tolylethyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [21i]

상기 [5i]와 p-tolylethylamine으로 하얀색의 고체상 화합물 21i를 얻었다.White solid compound 21i was obtained from [5i] and p-tolylethylamine.

Yield: 91.97%; ¹H NMR (400MHz, DMSO-d₆) δ 1.54 (d, J = 6.8Hz, 3H), 2.26 (s, 3H), 2.34 (s, 3H), 2.46 (s, 3H), 5.45 (t, J = 7.0Hz, 1H), 7.14 (d, J = 7.8Hz, 2H), 7.31 (t, J = 6.2Hz, 4H), 8.03 (d, J = 8.2Hz, 2H), 8.38 (s, 1H), 8.79 (d, J = 7.6Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.6, 20.4, 20.5, 22.1, 48.8, 99.2, 120.2, 125.9, 128.8, 129.4, 133.6, 135.1, 135.7, 136.5, 141.3, 153.1, 154.4, 169.3.
Yield: 91.97%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.54 (d, J = 6.8 Hz, 3H), 2.26 (s, 3H), 2.34 (s, 3H), 2.46 (s, 3H), 5.45 (t, J = 7.0 Hz, 1H), 7.14 (d, J = 7.8 Hz, 2H), 7.31 (t, J = 6.2 Hz, 4H), 8.03 (d, J = 8.2 Hz, 2H), 8.38 (s, 1H), 8.79 (d, J = 7.6 Hz, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.6, 20.4, 20.5, 22.1, 48.8, 99.2, 120.2, 125.9, 128.8, 129.4, 133.6, 135.1, 135.7, 136.5, 141.3, 153.1, 154.4, 169.3.

(10) N-((S)-1-(4-메톡시페닐)에틸)-6-(메틸티오)-1-p-톨릴-1H-피라졸로[3,4-d]피리미딘-4-아민 [21j](10) N-((S) -1- (4-methoxyphenyl) ethyl) -6- (methylthio) -1-p-tolyl-1H-pyrazolo [3,4-d] pyrimidine-4 Amines [21j]

상기 [5i]와 (R)-4-(methoxyphenyl)ethylamine으로 하얀색의 고체상 화합물 21j를 얻었다.White solid compound 21j was obtained from [5i] and (R) -4- (methoxyphenyl) ethylamine.

Yield: 88.03%; ¹H NMR (400MHz, DMSO-d₆) δ 1.54 (d, J = 6.7Hz, 3H), 2.34 (s, 3H), 2.47 (s, 3H), 2.73 (s, 3H), 5.44 (t, J = 6.9Hz, 1H), 6.91 (d, J = 8.2Hz, 2H), 7.34 (t, J = 8.9Hz, 4H), 8.03 (d, J = 8.0Hz, 2H), 8.37 (s, 1H), 8.76 (d, J = 7.5Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.6, 20.4, 22.1, 48.4, 54.9, 99.2, 113.6, 120.2, 127.1, 129.4, 133.6, 135.1, 136.1, 136.5, 153.1, 154.4, 158.0, 169.3.
Yield: 88.03%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.54 (d, J = 6.7 Hz, 3H), 2.34 (s, 3H), 2.47 (s, 3H), 2.73 (s, 3H), 5.44 (t, J = 6.9 Hz, 1H), 6.91 (d, J = 8.2 Hz, 2H), 7.34 (t, J = 8.9 Hz, 4H), 8.03 (d, J = 8.0 Hz, 2H), 8.37 (s, 1H), 8.76 (d, J = 7.5 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.6, 20.4, 22.1, 48.4, 54.9, 99.2, 113.6, 120.2, 127.1, 129.4, 133.6, 135.1, 136.1, 136.5, 153.1, 154.4, 158.0, 169.3.

실시예 20. [22a] 내지 [22p]의 합성Example 20. Synthesis of [22a] to [22p]

하기 [반응식 22](mCPBA, CH₂Cl_{2 ,} 0 ℃, 2h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [22a] 내지 [22p]를 합성하였다.The pyrazolopyrimidine derivative compounds [22a] to [22p] according to the present invention were synthesized by the following Reaction Scheme 22 (mCPBA, CH ₂ Cl _{2 ,} 0 ° C, 2h).

[반응식 22][Reaction Scheme 22]

[22a] ~ [22p][22a] to [22p]

[22a] 내지 [22p]에서 NR₂는 각각 하기 [표 15]와 같다.In [22a] to [22p], NR ₂ is shown in Table 15 below, respectively.

(R₁은 [5e], [5f], [5h]~[5k]에서와 동일하고, R₃는

이다.)(R ₁ is the same as in [5e], [5f], [5h] to [5k], and R ₃ is

to be.)

구분division NR₂ NR ₂ 구분division NR₂ NR ₂ 22a22a

22i22i

22b22b

22j22j

22c22c

22k22k

22d22d

22l22l

22e22e

22m22 m

22f22f

22n22n

22g22 g

22o22o

22h22h

22p22p

(1) N-(2-클로로벤질)-6-(메틸설파이닐)-1-페닐-1H-피라졸로[3,4-d]피리미딘-4-아민 [22a](1) N- (2-chlorobenzyl) -6- (methylsulfinyl) -1-phenyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [22a]

상기 [15x]를 CH₂Cl₂ 5 mL에 녹인 후 0 ℃에서 천천히 2.4 eq mCPBA를 투여하였다. 반응은 0 ℃에서 3 시간 진행시켰다. 반응 종료 후 반응물은 0 ℃에서 포화 NaHCO₃ 수용액을 천천히 투여하고 CH₂Cl₂ (2×30 mL)를 이용하여 추출하고 유기층은 무수 MgSO₄을 사용하여 소량의 물을 제거하였으며, 감압 증류하여 용매를 제거하였다. 여기서 얻은 반응 혼합물을 flash chromatography (hexanes : EtOAc = 1 : 1)로 분리하여 하얀색의 고체상 화합물 22a를 얻었다.The [15x] was dissolved in 5 mL of CH ₂ Cl ₂ and slowly administered 2.4 eq mCPBA at 0 ° C. The reaction proceeded at 0 ° C. for 3 hours. After completion of reaction the reaction was saturated with NaHCO ₃ at 0 ° C. Slowly administer the aqueous solution and CH ₂ Cl ₂ Extracted using (2 x 30 mL) and the organic layer was removed a small amount of water using anhydrous MgSO ₄ , the solvent was removed by distillation under reduced pressure. The reaction mixture obtained here was separated by flash chromatography (hexanes: EtOAc = 1: 1) to obtain a white solid compound 22a.

Yield: 85.94%; ¹H NMR (400MHz, DMSO-d₆) δ 2.78 (s, 3H), 4.86 (t, J = 6.7Hz, 2H), 7.32-7.41 (m, 3H), 7.49-7.60 (m, 4H), 8.18 (d, J = 7.6Hz, 2H), 8.53 (s, 1H), 9.46 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 41.7, 101.8, 120.9, 126.6, 127.2, 129.1, 129.2, 129.9, 132.5, 134.1, 135.3, 138.4, 152.6, 171.4.
Yield: 85.94%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.78 (s, 3H), 4.86 (t, J = 6.7 Hz, 2H), 7.32-7.41 (m, 3H), 7.49-7.60 (m, 4H), 8.18 (d, J = 7.6 Hz, 2H), 8.53 (s, 1H), 9.46 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 41.7, 101.8, 120.9, 126.6, 127.2, 129.1, 129.2, 129.9, 132.5, 134.1, 135.3, 138.4, 152.6, 171.4.

(2) N-(2-메톡시벤질)-6-(메틸설파이닐)-1-페닐-1H-피라졸로[3,4-d]피리미딘-4-아민 [22b](2) N- (2-methoxybenzyl) -6- (methylsulfinyl) -1-phenyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [22b]

상기 [15v]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 22b를 얻었다.[15v] was reacted with 2.4 eq mCPBA to obtain a white solid compound 22b.

Yield: 88.05%; ¹H NMR (400MHz, DMSO-d₆) δ 2.83 (s, 3H), 3.85 (s, 3H), 4.76 (d, J = 5.4Hz, 2H), 6.93 (t, J = 7.3Hz, 1H), 7.05 (d, J = 8.2Hz, 1H), 7.29-7.40 (m, 3H), 7.58 (t, J = 6.0Hz, 2H), 8.19 (d, J = 6.8Hz, 2H), 8.54 (s, 1H), 9.28 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 20.7, 55.4, 59.7, 101.7, 110.7, 120.1, 120.8, 125.5, 126.5, 128.6, 128.8, 129.2, 134.2, 138.5, 152.6, 156.4, 157.0, 171.4.
Yield: 88.05%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.83 (s, 3H), 3.85 (s, 3H), 4.76 (d, J = 5.4 Hz, 2H), 6.93 (t, J = 7.3 Hz, 1H), 7.05 (d, J = 8.2 Hz, 1H), 7.29-7.40 (m, 3H), 7.58 (t, J = 6.0 Hz, 2H), 8.19 (d, J = 6.8 Hz, 2H), 8.54 (s, 1H ), 9.28 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 20.7, 55.4, 59.7, 101.7, 110.7, 120.1, 120.8, 125.5, 126.5, 128.6, 128.8, 129.2, 134.2, 138.5, 152.6, 156.4, 157.0, 171.4.

(3) N-(2-메톡시벤질)-6-(메틸설파이닐)-1-페닐-1H-피라졸로[3,4-d]피리미딘-4-아민 [22c](3) N- (2-methoxybenzyl) -6- (methylsulfinyl) -1-phenyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [22c]

상기 [15o]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 22c를 얻었다.The reaction of [15o] with 2.4 eq mCPBA afforded a white solid compound 22c.

Yield: 91.77%; ¹H NMR (400MHz, DMSO-d₆) δ 2.36 (s, 3H), 2.82 (s, 3H), 4.76 (t, J = 5.0Hz, 2H), 7.18-7.22 (m, 3H), 7.35-7.38 (m, 2H), 7.58 (t, J = 7.2Hz, 2H), 8.18 (d, J = 8.2Hz, 2H), 8.51 (s, 1H), 9.31 (s, 1H).
Yield: 91.77%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.36 (s, 3H), 2.82 (s, 3H), 4.76 (t, J = 5.0 Hz, 2H), 7.18-7.22 (m, 3H), 7.35-7.38 (m, 2H), 7.58 (t, J = 7.2 Hz, 2H), 8.18 (d, J = 8.2 Hz, 2H), 8.51 (s, 1H), 9.31 (s, 1H).

(4) N-뷰틸-6-(메틸설파이닐)-1-페닐-1H-피라졸로[3,4-d]피리미딘-4-아민 [22d](4) N-butyl-6- (methylsulfinyl) -1-phenyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [22d]

상기 [15t]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 22d를 얻었다.[15t] was reacted with 2.4 eq mCPBA to obtain a white solid compound 22d.

Yield: 63.15% ¹H NMR (400MHz, DMSO-d₆) δ 0.94 (t, J = 7.1Hz, 3H), 1.37-1.42 (m, 2H), 1.63 (t, J = 7.0Hz, 2H), 2.88 (s, 3H), 3.55 (s, 2H), 7.39 (t, J = 7.0Hz, 1H), 7.58 (t, J = 7.5Hz, 2H), 8.19 (d, J = 7.6Hz, 2H), 8.45 (s, 1H), 8.92 (s, 1H), ¹³C NMR (100MHz,DMSO-d₆) δ 13.6, 19.5, 30.6, 100.3, 101.7, 120.8, 121.0, 126.5, 129.2, 134.0, 138.5, 152.5, 156.4, 171.4.
Yield: 63.15% ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.94 (t, J = 7.1 Hz, 3H), 1.37-1.42 (m, 2H), 1.63 (t, J = 7.0 Hz, 2H), 2.88 (s, 3H), 3.55 (s, 2H), 7.39 (t, J = 7.0 Hz, 1H), 7.58 (t, J = 7.5 Hz, 2H), 8.19 (d, J = 7.6 Hz, 2H), 8.45 (s, 1H), 8.92 (s, 1H), ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.6, 19.5, 30.6, 100.3, 101.7, 120.8, 121.0, 126.5, 129.2, 134.0, 138.5, 152.5, 156.4 , 171.4.

(5) N-(2-메톡시벤질)-1-(4-플루오로페닐)-6-(메틸설파이닐)-1-페닐-1H-피라졸로[3,4-d]피리미딘-4-아민 [22e](5) N- (2-methoxybenzyl) -1- (4-fluorophenyl) -6- (methylsulfinyl) -1-phenyl-1H-pyrazolo [3,4-d] pyrimidine-4 Amines [22e]

상기 [20b]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 22e를 얻었다.The reaction of [20b] with 2.4 eq mCPBA afforded a white solid compound 22e.

Yield: 85.63%; ¹H NMR (400MHz, DMSO-d₆) δ 2.81 (s, 3H), 3.84 (s, 3H), 4.74 (t, J = 6.3Hz, 2H), 6.99 (dd, J = 7.8Hz, 44.7Hz, 2H), 7.27-7.45 (m, 4H), 8.17-8.21 (m, 2H), 8.52 (s, 1H), 9.29 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 55.4, 98.6, 101.6, 110.7, 115.9, 116.1, 120.1, 122.8, 122.9, 125.4, 128.6, 128.8, 134.2, 134.9, 152.5, 157.0, 171.5.
Yield: 85.63%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.81 (s, 3H), 3.84 (s, 3H), 4.74 (t, J = 6.3 Hz, 2H), 6.99 (dd, J = 7.8 Hz, 44.7 Hz, 2H), 7.27-7.45 (m, 4H), 8.17-8.21 (m, 2H), 8.52 (s, 1H), 9.29 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 55.4, 98.6, 101.6, 110.7, 115.9, 116.1, 120.1, 122.8, 122.9, 125.4, 128.6, 128.8, 134.2, 134.9, 152.5, 157.0, 171.5.

(6) N-(2-클로로벤질)-6-(메틸설파이닐)-1-페닐-1H-피라졸로[3,4-d]피리미딘-4-아민 [22f](6) N- (2-chlorobenzyl) -6- (methylsulfinyl) -1-phenyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [22f]

상기 [21a]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 22f를 얻었다.[21a] was reacted with 2.4 eq mCPBA to obtain a white solid compound 22f.

Yield: 94.27%; ¹H NMR (400MHz, DMSO-d₆) δ 2.37 (s, 3H), 2.77 (s, 3H), 4.85 (t, J = 6.7Hz, 2H), 7.32-7.39 (m, 4H), 7.49-7.52 (m, 2H), 8.02 (d, J = 8.4Hz, 2H), 8.50 (s, 1H), 9.43 (s, 1H).
Yield: 94.27%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.37 (s, 3H), 2.77 (s, 3H), 4.85 (t, J = 6.7 Hz, 2H), 7.32-7.39 (m, 4H), 7.49-7.52 (m, 2H), 8.02 (d, J = 8.4 Hz, 2H), 8.50 (s, 1H), 9.43 (s, 1H).

(7) N-(2-메톡시벤질)-6-(메틸설파이닐)-1-p-톨릴-1H-피라졸로[3,4-d]피리미딘-4-아민 [22g](7) N- (2-methoxybenzyl) -6- (methylsulfinyl) -1-p-tolyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [22g]

상기 [21b]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 22g를 얻었다.[21b] was reacted with 2.4 eq mCPBA to obtain 22 g of a white solid compound.

Yield; 89.35%; ¹H NMR (400MHz, DMSO-d₆) δ 2.37 (s, 3H), 2.80 (s, 3H), 3.84 (s, 3H), 4.73 (t, J = 6.3Hz, 2H), 6.98 (dd, J = 7.8Hz, 46.0Hz, 2H), 7.28-7.38 (m, 4H), 8.02 (d, J = 8.1Hz, 2H), 8.49 (s, 1H), 9.25 (s, 1H)
Yield; 89.35%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.37 (s, 3H), 2.80 (s, 3H), 3.84 (s, 3H), 4.73 (t, J = 6.3 Hz, 2H), 6.98 (dd, J = 7.8 Hz, 46.0 Hz, 2H), 7.28-7.38 (m, 4H), 8.02 (d, J = 8.1 Hz, 2H), 8.49 (s, 1H), 9.25 (s, 1H)

(8) 1-벤질-6-(메틸설파이닐)-N-(1-페닐에틸)-1H-피라졸로[3,4-d]피리미딘-4-아민 [22h](8) 1-benzyl-6- (methylsulfinyl) -N- (1-phenylethyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [22h]

상기 [16x]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 22h를 얻었다.[16x] was reacted with 2.4 eq mCPBA to obtain a white solid compound 22h.

Yield: 28.59%; ¹H NMR (400MHz, DMSO-d₆) δ 1.58 (d, J = 6.5Hz, 3H), 2.82 (s, 3H), 5.39 (t, J = 6.8Hz, 1H), 5.54 (s, 2H), 7.22-7.36 (m, 8H), 7.46 (d, J = 7.2Hz, 2H), 8.35 (s, 1H), 9.23 (d, J = 7.2Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 21.8, 49.4, 49.9, 100.1, 126.0, 126.2, 126.9, 127.4, 128.3, 128.5, 132.8, 136.8, 143.8, 144.1, 152.9, 155.4, 162.6.
Yield: 28.59%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.58 (d, J = 6.5 Hz, 3H), 2.82 (s, 3H), 5.39 (t, J = 6.8 Hz, 1H), 5.54 (s, 2H), 7.22-7.36 (m, 8H), 7.46 (d, J = 7.2 Hz, 2H), 8.35 (s, 1H), 9.23 (d, J = 7.2 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 21.8, 49.4, 49.9, 100.1, 126.0, 126.2, 126.9, 127.4, 128.3, 128.5, 132.8, 136.8, 143.8, 144.1, 152.9, 155.4, 162.6.

(9) 1-벤질-6-(메틸설파이닐)-N-(1-페닐에틸)-1H-피라졸로[3,4-d]피리미딘-4-아민 [22i](9) 1-benzyl-6- (methylsulfinyl) -N- (1-phenylethyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [22i]

상기 [16e]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 22i를 얻었다.The reaction of [16e] with 2.4 eq mCPBA afforded a white solid compound 22i.

Yield: 78.32%; ¹H NMR (400MHz, DMSO-d₆) δ 1.57 (d, J = 6.9Hz, 3H), 2.81 (s, 3H), 5.36-5.53 (m, 3H), 7.22-7.45 (m, 8H), 7.49 (d, J = 7.6Hz, 2H), 8.34 (s, 1H), 9.24 (d, J = 7.5Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 21.8, 49.4, 49.9, 100.2, 126.0, 126.2, 126.8, 127.4, 127.5, 128.3, 128.5, 132.8, 136.8, 143.8, 152.8, 155.2, 170.6.
Yield: 78.32%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.57 (d, J = 6.9 Hz, 3H), 2.81 (s, 3H), 5.36-5.53 (m, 3H), 7.22-7.45 (m, 8H), 7.49 (d, J = 7.6 Hz, 2H), 8.34 (s, 1H), 9.24 (d, J = 7.5 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 21.8, 49.4, 49.9, 100.2, 126.0, 126.2, 126.8, 127.4, 127.5, 128.3, 128.5, 132.8, 136.8, 143.8, 152.8, 155.2, 170.6.

(10) 1-벤질-6-(메틸설파이닐)-N-(1-페닐에틸)-1H-피라졸로[3,4-d]피리미딘-4-아민 [22j](10) 1-benzyl-6- (methylsulfinyl) -N- (1-phenylethyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [22j]

상기 [16k]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 22j를 얻었다.[16k] was reacted with 2.4 eq mCPBA to obtain a white solid compound 22j.

Yield: 74.55%; ¹H NMR (400MHz, DMSO-d₆) δ 1.57 (d, J = 6.5Hz, 3H), 2.81 (s, 3H), 5.39-5.54 (m, 3H), 7.22-7.31 (m, 8H), 7.42 (d, J = 6.6Hz, 2H), 8.34 (s, 1H), 9.21 (d, J = 7.3Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.6, 21.8, 49.4, 49.9, 100.2, 126.1, 126.9, 127.5, 127.6, 128.4, 128.5, 132.9, 136.6, 143.7, 151.9, 155.4, 170.4.
Yield: 74.55%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.57 (d, J = 6.5 Hz, 3H), 2.81 (s, 3H), 5.39-5.54 (m, 3H), 7.22-7.31 (m, 8H), 7.42 (d, J = 6.6 Hz, 2H), 8.34 (s, 1H), 9.21 (d, J = 7.3 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.6, 21.8, 49.4, 49.9, 100.2, 126.1, 126.9, 127.5, 127.6, 128.4, 128.5, 132.9, 136.6, 143.7, 151.9, 155.4, 170.4.

(11) N-(2-클로로벤질)-1-(3-메톡시펜에틸)-6-(메틸설파이닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [22k](11) N- (2-chlorobenzyl) -1- (3-methoxyphenethyl) -6- (methylsulfinyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [22k ]

상기 [18a]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 22k를 얻었다.[18a] was reacted with 2.4 eq mCPBA to give a white solid compound 22k.

Yield: 78.69%; ¹H NMR (400MHz, DMSO-d₆) δ 2.69 (s, 3H), 3.16 (t, J = 7.0Hz, 2H), 3.65 (s, 3H), 4.58 (t, J = 7.0Hz, 2H), 4.81 (t, J = 6.7Hz, 1H), 6.66-6.72 (m, 3H), 7.11 (t, J = 7.8Hz, 1H), 7.33 (t, J = 4.6Hz, 2H), 7.46-7.49 (m, 2H), 7.68-7.72 (m, 1H), 8.28 (s, 1H), 9.26 (s, 1H)
Yield: 78.69%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.69 (s, 3H), 3.16 (t, J = 7.0 Hz, 2H), 3.65 (s, 3H), 4.58 (t, J = 7.0 Hz, 2H), 4.81 (t, J = 6.7 Hz, 1H), 6.66-6.72 (m, 3H), 7.11 (t, J = 7.8 Hz, 1H), 7.33 (t, J = 4.6 Hz, 2H), 7.46-7.49 (m , 2H), 7.68-7.72 (m, 1H), 8.28 (s, 1H), 9.26 (s, 1H)

(12) N-(2-메톡시벤질)-1-(3-메톡시펜에틸)-6-(메틸설파이닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [22l](12) N- (2-methoxybenzyl) -1- (3-methoxyphenethyl) -6- (methylsulfinyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [ 22l]

상기 [18b]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 22l를 얻었다.The reaction of [18b] with 2.4 eq mCPBA afforded 22 l of a white solid compound.

Yield: 83.66%; ¹H NMR (400MHz, DMSO-d₆) δ 2.71 (s, 3H), 3.15 (t, J = 7.0Hz, 2H), 3.65 (s, 3H), 3.82 (s, 3H), 4.57 (t, J = 7.0Hz, 2H), 4.70 (t, J = 6.1Hz, 2H), 6.66-6.71 (m, 3H), 6.91 (t, J = 7.4Hz, 1H), 7.02 (d, J = 8.4Hz, 1H), 7.11 (t,J = 7.8Hz, 1H), 7.27 (t, J = 7.3Hz, 2H), 8.26 (s, 1H), 9.07 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 34.8, 47.4, 54.7, 55.3, 59.7, 100.1, 110.6, 111.9, 113.9, 120.1, 120.8, 125.7, 128.5, 128.7, 129.2, 132.2, 139.6, 152.7, 156.3, 156.9, 159.0, 170.2.
Yield: 83.66%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.71 (s, 3H), 3.15 (t, J = 7.0 Hz, 2H), 3.65 (s, 3H), 3.82 (s, 3H), 4.57 (t, J = 7.0 Hz, 2H), 4.70 (t, J = 6.1 Hz, 2H), 6.66-6.71 (m, 3H), 6.91 (t, J = 7.4 Hz, 1H), 7.02 (d, J = 8.4 Hz, 1H ), 7.11 (t, J = 7.8 Hz, 1H), 7.27 (t, J = 7.3 Hz, 2H), 8.26 (s, 1H), 9.07 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 34.8, 47.4, 54.7, 55.3, 59.7, 100.1, 110.6, 111.9, 113.9, 120.1, 120.8, 125.7, 128.5, 128.7, 129.2, 132.2, 139.6, 152.7, 156.3, 156.9, 159.0, 170.2.

(13) N-(2-메틸벤질)-1-(3-메톡시펜에틸)-6-(메틸설포닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [22m](13) N- (2-methylbenzyl) -1- (3-methoxyphenethyl) -6- (methylsulfonyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [22m ]

상기 [18c]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 22m를 얻었다.The reaction of [18c] with 2.4 eq mCPBA afforded 22m of a white solid compound.

Yield: 89.17%; ¹H NMR (400MHz, DMSO-d₆) δ 2.34 (s, 3H), 3.16 (t, J = 6.7Hz, 2H), 3.26 (s, 3H), 3.65 (s, 3H), 4.59 (t, J = 6.7Hz, 2H), 4.75 (t, J = 4.9Hz, 2H), 6.70 (t,J = 7.6Hz, 3H), 7.11 (t, J = 7.8Hz, 2H), 7.18-7.21 (m, 2H), 7.35 (d, J = 6.6Hz, 1H), 8.30 (s, 1H), 9.26 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 18.7, 34.8, 42.1, 47.7, 54.7, 100.3, 100.6, 111.9, 114.0, 120.8, 125.8, 127.4, 128.5, 129.2, 130.1, 132.4, 135.8, 136.2, 139.5, 151.7, 156.4, 159.1, 162.5.
Yield: 89.17%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.34 (s, 3H), 3.16 (t, J = 6.7 Hz, 2H), 3.26 (s, 3H), 3.65 (s, 3H), 4.59 (t, J = 6.7 Hz, 2H), 4.75 (t, J = 4.9 Hz, 2H), 6.70 (t, J = 7.6 Hz, 3H), 7.11 (t, J = 7.8 Hz, 2H), 7.18-7.21 (m, 2H ), 7.35 (d, J = 6.6 Hz, 1 H), 8.30 (s, 1 H), 9.26 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 18.7, 34.8, 42.1, 47.7, 54.7, 100.3, 100.6, 111.9, 114.0, 120.8, 125.8, 127.4, 128.5, 129.2, 130.1, 132.4, 135.8, 136.2, 139.5, 151.7, 156.4, 159.1, 162.5.

(14) 1-(2-메톡시펜에틸)-N-(3-메톡시벤질)-6-(메틸설파이닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [22n](14) 1- (2-methoxyphenethyl) -N- (3-methoxybenzyl) -6- (methylsulfinyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [ 22n]

상기 [19a]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 22n를 얻었다.[19a] was reacted with 2.4 eq mCPBA to obtain a white solid compound 22n.

Yield: 88.04%; ¹H NMR (400MHz, DMSO-d₆) δ 2.73 (s, 3H), 3.11 (t, J = 6.4Hz, 2H), 3.73 (s, 3H), 3.79 (s, 3H), 4.55 (t, J = 6.5Hz, 2H), 4.70 (d, J = 4.6Hz, 2H), 6.71 (t, J = 7.2Hz, 1H), 6.83-6.96 (m, 5H), 7.14 (t, J = 7.5Hz, 1H), 7.25 (t, J = 7.9Hz, 1H), 8.20 (s, 1H), 9.20 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 30.6, 43.8, 46.4, 55.2, 55.5, 98.9, 100.3, 110.8, 112.8, 113.6, 120.1, 120.2, 126.0, 128.1, 129.7, 130.1, 132.2, 140.4, 152.9, 156.4, 157.6, 159.6, 170.3.
Yield: 88.04%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.73 (s, 3H), 3.11 (t, J = 6.4 Hz, 2H), 3.73 (s, 3H), 3.79 (s, 3H), 4.55 (t, J = 6.5 Hz, 2H), 4.70 (d, J = 4.6 Hz, 2H), 6.71 (t, J = 7.2 Hz, 1H), 6.83-6.96 (m, 5H), 7.14 (t, J = 7.5 Hz, 1H ), 7.25 (t, J = 7.9 Hz, 1 H), 8.20 (s, 1 H), 9.20 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 30.6, 43.8, 46.4, 55.2, 55.5, 98.9, 100.3, 110.8, 112.8, 113.6, 120.1, 120.2, 126.0, 128.1, 129.7, 130.1, 132.2, 140.4, 152.9, 156.4, 157.6, 159.6, 170.3.

(15) 1-(2-메톡시펜에틸)-N-(4-메톡시벤질)-6-(메틸설파이닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [22o](15) 1- (2-methoxyphenethyl) -N- (4-methoxybenzyl) -6- (methylsulfinyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [ 22o]

상기 [19b]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 22o를 얻었다.[19b] was reacted with 2.4 eq mCPBA to obtain a white solid compound 22o.

Yield: 82.07%; ¹H NMR (400MHz, DMSO-d₆) δ 2.74 (s, 3H), 3.10 (t, J = 6.7Hz, 2H), 3.72 (s, 3H), 3.79 (s, 3H), 4.54 (t, J = 6.7Hz, 2H), 4.65 (d, J = 4.8Hz, 2H), 6.72 (t, J = 7.1Hz, 1H), 6.91 (t, J = 6.9Hz, 4H), 7.14 (t, J = 7.5Hz, 1H), 7.30 (d, J = 8.0Hz, 2H), 8.17 (s, 1H), 9.12 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 30.8, 43.5, 46.6, 55.5, 55.7, 99.1, 100.5, 111.1, 114.2, 120.5, 126.2, 128.4, 129.6, 130.3, 130.9, 132.4, 153.1, 156.5, 157.8, 158.9, 170.6.
Yield: 82.07%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.74 (s, 3H), 3.10 (t, J = 6.7 Hz, 2H), 3.72 (s, 3H), 3.79 (s, 3H), 4.54 (t, J = 6.7 Hz, 2H), 4.65 (d, J = 4.8 Hz, 2H), 6.72 (t, J = 7.1 Hz, 1H), 6.91 (t, J = 6.9 Hz, 4H), 7.14 (t, J = 7.5 Hz, 1H), 7.30 (d, J = 8.0 Hz, 2H), 8.17 (s, 1H), 9.12 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 30.8, 43.5, 46.6, 55.5, 55.7, 99.1, 100.5, 111.1, 114.2, 120.5, 126.2, 128.4, 129.6, 130.3, 130.9, 132.4, 153.1, 156.5, 157.8, 158.9, 170.6.

(16) 1-(2-메톡시펜에틸)-N-(4-메틸벤질)-6-(메틸설파이닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [22p](16) 1- (2-methoxyphenethyl) -N- (4-methylbenzyl) -6- (methylsulfinyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [22p ]

상기 [19c]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 22p를 얻었다.[19c] was reacted with 2.4 eq mCPBA to obtain a white solid compound 22p.

Yield: 80.25%; ¹H NMR (400MHz, DMSO-d₆) δ 2.27 (s, 3H), 2.74 (s, 3H), 3.12 (t, J = 6.4Hz, 2H), 3.79 (s, 3H), 4.55 (t, J = 6.3Hz, 2H), 4.69 (d, J = 4.0Hz, 2H), 6.72 (t, J = 6.9Hz, 1H), 6.91 (t, J = 5.5Hz, 2H), 7.14 (d, J = 7.1Hz, 3H), 7.26 (d, J = 7.4Hz, 2H), 8.20 (s, 1H), 9.16 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 20.6, 30.3, 43.3, 46.1, 46.4, 55.2, 100.0, 110.5, 119.9, 125.7, 127.6, 127.8, 128.8, 129.8, 131.9, 135.4, 136.1, 152.6, 156.1, 157.3, 170.1.
Yield: 80.25%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.27 (s, 3H), 2.74 (s, 3H), 3.12 (t, J = 6.4 Hz, 2H), 3.79 (s, 3H), 4.55 (t, J = 6.3 Hz, 2H), 4.69 (d, J = 4.0 Hz, 2H), 6.72 (t, J = 6.9 Hz, 1H), 6.91 (t, J = 5.5 Hz, 2H), 7.14 (d, J = 7.1 Hz, 3H), 7.26 (d, J = 7.4 Hz, 2H), 8.20 (s, 1 H), 9.16 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 20.6, 30.3, 43.3, 46.1, 46.4, 55.2, 100.0, 110.5, 119.9, 125.7, 127.6, 127.8, 128.8, 129.8, 131.9, 135.4, 136.1, 152.6, 156.1, 157.3, 170.1.

실시예 21. [23a] 내지 [23zh]의 합성Example 21.Synthesis of [23a] to [23zh]

하기 [반응식 23](mCPBA, CH₂Cl_{2 ,} 0 ℃, 2h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [23a] 내지 [23zh]를 합성하였다.The pyrazolopyrimidine derivative compounds [23a] to [23zh] were synthesized according to Scheme 23 (mCPBA, CH ₂ Cl _{2 ,} 0 ° C., 2h).

[반응식 23][Reaction Scheme 23]

[23a] ~ [23zh][23a]-[23zh]

[23a] 내지 [23zh]에서 NR₂는 각각 하기 [표 16]과 같다.NR ₂ in [23a] to [23zh] are as shown in Table 16 below, respectively.

(R₁은 [5e]~[5k]에서와 동일하고, R₃는

이다.)(R ₁ is the same as in [5e] to [5k], and R ₃ is

to be.)

구분division NR₂ NR ₂ 구분division NR₂ NR ₂ 23a23a

23r23r

23b23b

23s23s

23c23c

23t23 t

23d23d

23u23u

23e23e

23v23v

23f23f

23w23w

23g23 g

23x23x

23h23h

23y23y

23i23i

23z23z

23j23j

23za23za

23k23k

23zb23zb

23l23l

23zc23zc

23m23m

23zd23zd

23n23n

23ze23ze

23o23o

23zf23zf

23p23p

23zg23zg

23q23q

23zh23zh

(1) N-뷰틸-6-(메틸설포닐)-1-페닐-1H-피라졸로[3,4-d]피리미딘-4-아민 [23a](1) N-butyl-6- (methylsulfonyl) -1-phenyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [23a]

상기 [15t]를 CH₂Cl₂ 5 mL에 녹인 후 0 ℃에서 천천히 2.4 eq mCPBA를 투여하였다. 반응은 상온에서 4 시간 진행시켰다. 반응 종료 후 반응물은 0 ℃에서 포화 NaHCO₃ 수용액을 천천히 투여하고 CH₂Cl₂ (2×10 mL)를 이용하여 추출하고 유기층은 무수 MgSO₄을 사용하여 소량의 물을 제거하였으며, 감압 증류하여 용매를 제거하였다. 여기서 얻은 반응 혼합물을 flash chromatography (hexanes : EtOAc = 1 : 1)로 하여 분리하면 하얀색의 고체상 화합물 23a를 얻었다.After dissolving [15t] in 5 mL of CH ₂ Cl ₂ , 2.4 eq mCPBA was slowly administered at 0 ° C. The reaction was carried out at room temperature for 4 hours. After completion of reaction the reaction was saturated with NaHCO ₃ at 0 ° C. Slowly administer the aqueous solution and CH ₂ Cl ₂ (2 × 10 mL) was used to extract the organic layer, and a small amount of water was removed using anhydrous MgSO ₄ , and the solvent was distilled off under reduced pressure. The reaction mixture obtained here was separated by flash chromatography (hexanes: EtOAc = 1: 1) to give a white solid compound 23a.

Yield: 95.27%; ¹H NMR (400MHz, DMSO-d₆) δ 0.98 (t, J = 7.3Hz, 3H), 1.41-1.48 (m, 2H), 1.66-1.71 (m, 2H), 3.42, (s, 3H), 3.59-3.64 (m, 2H), 7.43 (t, J = 7.0Hz, 1H), 7.63 (t, J = 7.9Hz, 2H), 8.16 (d, J = 8.5Hz, 2H), 8.54 (s, 1H), 9.15 (s, 1H); ¹³C NMR(100MHz,DMSO-d₆) δ 13.6, 19.5, 30.5, 102.5, 120.9, 121.1, 126.8, 129.3, 134.1, 138.2, 151.5, 156.8, 163.4.
Yield: 95.27%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.98 (t, J = 7.3 Hz, 3H), 1.41-1.48 (m, 2H), 1.66-1.71 (m, 2H), 3.42, (s, 3H), 3.59-3.64 (m, 2H), 7.43 (t, J = 7.0 Hz, 1H), 7.63 (t, J = 7.9 Hz, 2H), 8.16 (d, J = 8.5 Hz, 2H), 8.54 (s, 1H ), 9.15 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.6, 19.5, 30.5, 102.5, 120.9, 121.1, 126.8, 129.3, 134.1, 138.2, 151.5, 156.8, 163.4.

(2) N-(2-클로로벤질)-6-(메틸설포닐)-1-페닐-1H-피라졸로[3,4-d]피리미딘-4-아민 [23b](2) N- (2-chlorobenzyl) -6- (methylsulfonyl) -1-phenyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [23b]

상기 [15x]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23b를 얻었다.[15x] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23b.

Yield: 93.28%; ¹H NMR (400MHz, DMSO-d₆) δ 3.32 (s, 3H), 4.90 (s, 2H), 7.34-7.43 (m, 3H), 7.50-7.62 (m, 4H), 8.13 (d, J = 8.4Hz, 2H), 8.58 (s, 1H), 9.64 (s, 1H)
Yield: 93.28%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 3.32 (s, 3H), 4.90 (s, 2H), 7.34-7.43 (m, 3H), 7.50-7.62 (m, 4H), 8.13 (d, J = 8.4 Hz, 2H), 8.58 (s, 1H), 9.64 (s, 1H)

(3) N-(2-메톡시벤질)-6-(메틸설포닐)-1-페닐-1H-피라졸로[3,4-d]피리미딘-4-아민 [23c](3) N- (2-methoxybenzyl) -6- (methylsulfonyl) -1-phenyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [23c]

상기 [15v]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23c를 얻었다.The reaction of [15v] with 2.4 eq mCPBA afforded a white solid compound 23c.

Yield: 96.45%; ¹H NMR (400MHz, DMSO-d₆) δ 3.35 (s, 3H), 3.84 (s, 3H), 4.78 (d, J = 5.2Hz, 2H), 6.94 (t, J = 7.4Hz, 1H), 7.06 (d, J = 8.2Hz, 1H), 7.28-7.42 (m, 3H), 7.60 (t, J = 7.1Hz, 2H), 8.13 (d, J = 7.6Hz, 2H), 8.58 (s, 1H), 9.47 (s, 1H)
Yield: 96.45%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 3.35 (s, 3H), 3.84 (s, 3H), 4.78 (d, J = 5.2 Hz, 2H), 6.94 (t, J = 7.4 Hz, 1H), 7.06 (d, J = 8.2 Hz, 1H), 7.28-7.42 (m, 3H), 7.60 (t, J = 7.1 Hz, 2H), 8.13 (d, J = 7.6 Hz, 2H), 8.58 (s, 1H ), 9.47 (s, 1 H)

(4) N-(2-메톡시벤질)-6-(메틸설포닐)-1-페닐-1H-피라졸로[3,4-d]피리미딘-4-아민 [23d](4) N- (2-methoxybenzyl) -6- (methylsulfonyl) -1-phenyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [23d]

상기 [15o]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23d를 얻었다.The reaction of [15o] with 2.4 eq mCPBA afforded a white solid compound 23d.

Yield: 93.48%; ¹H NMR (400MHz, DMSO-d₆) δ 2.37 (s, 3H), 2.50 (s, 3H), 4.80 (s, 2H), 7.20-7.23 (m, 3H), 7.38-7.42 (m, 2H), 7.60 (t, J = 7.1Hz, 2H), 8.13 (d, J = 6.8Hz, 2H), 8.57 (s, 1H), 9.50 (s,1H).
Yield: 93.48%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.37 (s, 3H), 2.50 (s, 3H), 4.80 (s, 2H), 7.20-7.23 (m, 3H), 7.38-7.42 (m, 2H) , 7.60 (t, J = 7.1 Hz, 2H), 8.13 (d, J = 6.8 Hz, 2H), 8.57 (s, 1H), 9.50 (s, 1H).

(5) N-((4-클로로페닐)(페닐)메틸)-6-(메틸설포닐)-1-페닐-1H-피라졸로[3,4-d]피리미딘-4-아민 [23e](5) N-((4-chlorophenyl) (phenyl) methyl) -6- (methylsulfonyl) -1-phenyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [23e]

상기 [15z]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23e를 얻었다.[15z] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23e.

Yield: 91.43%; ¹H NMR (400MHz, DMSO-d₆) δ 3.26 (s, 3H), 6.75 (d, J = 7.4Hz, 1H), 7.34-7.92 (m, 12H), 8.13 (d, J = 7.7Hz, 2H), 8.71 (s, 1H), 9.94 (d, J = 7.3Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.7, 28.9, 56.6, 99.5, 102.8, 120.3, 126.0, 127.4, 127.7, 128.4, 128.5, 129.1, 129.4, 131.0, 133.8, 135.1, 140.6, 141.2, 151.9, 155.8, 166.0.
Yield: 91.43%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 3.26 (s, 3H), 6.75 (d, J = 7.4 Hz, 1H), 7.34-7.92 (m, 12H), 8.13 (d, J = 7.7 Hz, 2H ), 8.71 (s, 1 H), 9.94 (d, J = 7.3 Hz, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.7, 28.9, 56.6, 99.5, 102.8, 120.3, 126.0, 127.4, 127.7, 128.4, 128.5, 129.1, 129.4, 131.0, 133.8, 135.1, 140.6, 141.2, 151.9, 155.8, 166.0.

(6) N-(1-사이클로헥실에틸)-6-(메틸설포닐)-1-페닐-1H-피라졸로[3,4-d]피리미딘-4-아민 [23f](6) N- (1-cyclohexylethyl) -6- (methylsulfonyl) -1-phenyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [23f]

상기 [15za]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23f를 얻었다.[15za] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23f.

Yield: 90.97%; ¹H NMR (400MHz, DMSO-d₆) δ 1.01-1.07 (m, 2H), 1.13-1.24 (m,5H), 1.60-1.80 (m, 6H), 3.39 (s, 3H), 4.28-4.29 (m, 1H), 7.39-7.42 (m, 1H), 7.53-7.61 (m, 3H), 8.12-8.14 (m, 2H), 8.58 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 17.7, 26.1, 26.3, 29.2, 29.5, 42.9, 51.3, 121.4, 127.2, 129.2, 134.8, 139.8, 152.1, 156.8, 163.9, 166.5.
Yield: 90.97%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.01-1.07 (m, 2H), 1.13-1.24 (m, 5H), 1.60-1.80 (m, 6H), 3.39 (s, 3H), 4.28-4.29 ( m, 1H), 7.39-7.42 (m, 1H), 7.53-7.61 (m, 3H), 8.12-8.14 (m, 2H), 8.58 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 17.7, 26.1, 26.3, 29.2, 29.5, 42.9, 51.3, 121.4, 127.2, 129.2, 134.8, 139.8, 152.1, 156.8, 163.9, 166.5.

(7) 6-(메틸설포닐)-1-페닐-N-(1-p-톨릴에틸)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23g](7) 6- (methylsulfonyl) -1-phenyl-N- (1-p-tolylethyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [23 g]

상기 [15zb]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23g를 얻었다.[15zb] was reacted with 2.4 eq mCPBA to obtain 23 g of a white solid compound.

Yield: 95.39%; ¹H NMR (400MHz, DMSO-d₆) δ 1.61 (d, J = 6.8Hz, 3H), 2.26 (s, 3H), 3.32 (s, 3H), 5.50 (t, J = 7.0Hz, 1H), 7.17 (d, J = 7.6Hz, 2H), 7.36 (t, J = 7.2Hz, 3H), 7.57 (t, J = 7.5Hz, 1H), 8.13 (d, J = 8.0Hz, 2H), 8.61 (s, 1H), 9.48 (d, J = 7.4Hz, 1H); ¹³C NMR(100MHz, DMSO-d₆) δ 14.0, 20.5, 21.8, 49.6, 99.4, 120.7, 126.6, 127.3, 128.3, 129.2, 133.7, 134.8, 138.7, 141.0, 151.7, 155.7, 163.2.
Yield: 95.39%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.61 (d, J = 6.8 Hz, 3H), 2.26 (s, 3H), 3.32 (s, 3H), 5.50 (t, J = 7.0 Hz, 1H), 7.17 (d, J = 7.6 Hz, 2H), 7.36 (t, J = 7.2 Hz, 3H), 7.57 (t, J = 7.5 Hz, 1H), 8.13 (d, J = 8.0 Hz, 2H), 8.61 ( s, 1 H), 9.48 (d, J = 7.4 Hz, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 20.5, 21.8, 49.6, 99.4, 120.7, 126.6, 127.3, 128.3, 129.2, 133.7, 134.8, 138.7, 141.0, 151.7, 155.7, 163.2.

(8) N-((S)-1-(4-메톡시페닐)에틸)-6-(메틸설포닐)-1-페닐-1H-피라졸로[3,4-d]피리미딘-4-아민 [23h](8) N-((S) -1- (4-methoxyphenyl) ethyl) -6- (methylsulfonyl) -1-phenyl-1H-pyrazolo [3,4-d] pyrimidine-4- Amines [23h]

상기 [15zc]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23h를 얻었다.[15zc] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23h.

Yield: 91.88%; ¹H NMR (400MHz, DMSO-d₆) δ 1.61 (d, J = 6.4Hz, 3H), 3.33 (s, 3H), 3.73 (s, 3H), 5.49-5.51 (m, 1H), 6.93 (d, J = 8.0Hz, 2H), 7.40-7.53 (m, 3H), 7.59 (t, J = 7.7Hz, 2H), 8.14 (d, J = 8.8Hz, 1H), 8.60 (s, 1H), 9.45 (d, J = 7.2Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 22.2, 49.8, 55.5, 99.1, 114.2, 121.4, 127.3, 127.9, 128.3, 129.2, 133.1, 134.8, 138.7, 156.2, 158.8, 163.7, 166.5.
Yield: 91.88%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.61 (d, J = 6.4 Hz, 3H), 3.33 (s, 3H), 3.73 (s, 3H), 5.49-5.51 (m, 1H), 6.93 (d , J = 8.0 Hz, 2H), 7.40-7.53 (m, 3H), 7.59 (t, J = 7.7 Hz, 2H), 8.14 (d, J = 8.8 Hz, 1H), 8.60 (s, 1H), 9.45 (d, J = 7.2 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 22.2, 49.8, 55.5, 99.1, 114.2, 121.4, 127.3, 127.9, 128.3, 129.2, 133.1, 134.8, 138.7, 156.2, 158.8, 163.7, 166.5.

(9) N-(2-메톡시벤질)-1-(4-플루오로페닐)-6-(메틸설포닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23i](9) N- (2-methoxybenzyl) -1- (4-fluorophenyl) -6- (methylsulfonyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [23i ]

상기 [20b]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23i를 얻었다.The reaction of [20b] with 2.4 eq mCPBA afforded a white solid compound 23i.

Yield: 93.25%; ¹H NMR (400MHz, DMSO-d₆) δ 3.35 (s, 3H), 3.85 (s, 3H), 4.78 (d, J = 5.1Hz, 2H), 7.00 (dd, J = 7.7Hz, 43.2Hz, 2H), 7.31-7.47 (m, 4H), 8.13-8.16 (m, 2H), 8.57 (s, 1H), 9.48 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 55.4, 102.1, 110.8, 116.0, 116.2, 120.2, 123.0, 123.1, 125.2, 128.8, 129.0, 134.4, 134.6, 151.5, 156.8, 157.0, 159.1, 163.3.
Yield: 93.25%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 3.35 (s, 3H), 3.85 (s, 3H), 4.78 (d, J = 5.1 Hz, 2H), 7.00 (dd, J = 7.7 Hz, 43.2 Hz, 2H), 7.31-7.47 (m, 4H), 8.13-8.16 (m, 2H), 8.57 (s, 1H), 9.48 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 55.4, 102.1, 110.8, 116.0, 116.2, 120.2, 123.0, 123.1, 125.2, 128.8, 129.0, 134.4, 134.6, 151.5, 156.8, 157.0, 159.1, 163.3.

(10) N-(2-클로로벤질)-1-(4-플루오로페닐)-6-(메틸설포닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23j](10) N- (2-chlorobenzyl) -1- (4-fluorophenyl) -6- (methylsulfonyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [23j]

상기 [20a]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23j를 얻었다.The reaction of [20a] with 2.4 eq mCPBA afforded a white solid compound 23j.

Yield: 73.29%; ¹H NMR (400MHz, DMSO-d₆) δ 3.26 (s, 3H), 4.64 (t, J = 25.2Hz, 2H), 6.86 (d, J = 22.1Hz, 1H), 7.34 (t, J = 4.1Hz, 2H), 7.47 (s, 2H), 8.91 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 20.7, 42.1, 42.8, 59.7, 102.3, 106.2, 127.3, 129.2, 129.3, 130.0, 132.5, 134.9, 157.2, 163.3, 165.2.
Yield: 73.29%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 3.26 (s, 3H), 4.64 (t, J = 25.2 Hz, 2H), 6.86 (d, J = 22.1 Hz, 1H), 7.34 (t, J = 4.1 Hz, 2H), 7.47 (s, 2H), 8.91 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 20.7, 42.1, 42.8, 59.7, 102.3, 106.2, 127.3, 129.2, 129.3, 130.0, 132.5, 134.9, 157.2, 163.3, 165.2.

(11) N-(2-메틸벤질)-1-(4-플루오로페닐)-6-(메틸설포닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23k](11) N- (2-methylbenzyl) -1- (4-fluorophenyl) -6- (methylsulfonyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [23k]

상기 [20c]를 2.4 eq mCPBA로 반응시켜 하얀색의 액체상 화합물 23k를 얻었다.[20c] was reacted with 2.4 eq mCPBA to obtain a white liquid compound 23k.

Yield: 71.48%; ¹H NMR (400MHz, DMSO-d₆) δ 2.31 (s, 3H), 3.28 (s, 3H), 4.52 (dd, J = 5.4Hz, 41.8Hz, 2H), 6.80 (d, J = 20.5Hz, 1H), 7.19 (t, J = 5.3Hz, 2H), 7.31 (d, J = 6.9Hz, 2H), 8.76 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 18.7, 20.7, 42.3, 42.8, 59.7, 102.3, 106.0, 125.8, 126.2, 127.1, 127.5, 128.5, 130.1, 134.7, 135.5, 136.2, 157.0, 163.2, 165.2.
Yield: 71.48%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.31 (s, 3H), 3.28 (s, 3H), 4.52 (dd, J = 5.4 Hz, 41.8 Hz, 2H), 6.80 (d, J = 20.5 Hz, 1H), 7.19 (t, J = 5.3 Hz, 2H), 7.31 (d, J = 6.9 Hz, 2H), 8.76 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 18.7, 20.7, 42.3, 42.8, 59.7, 102.3, 106.0, 125.8, 126.2, 127.1, 127.5, 128.5, 130.1, 134.7, 135.5, 136.2, 157.0, 163.2, 165.2.

(12) N-(2-클로로벤질)-6-(메틸설포닐)-1-p-톨릴-1H-피라졸로[3,4-d]피리미딘-4-아민 [23l](12) N- (2-chlorobenzyl) -6- (methylsulfonyl) -1-p-tolyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [23l]

상기 [21a]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23l를 얻었다.[21a] was reacted with 2.4 eq mCPBA to obtain 23 l of a white solid compound.

Yield: 92.18%; ¹H NMR (400MHz, DMSO-d₆) δ 2.37 (s, 3H), 3.32 (s, 3H), 4.89 (d, J = 5.3Hz, 2H), 7.34-7.40 (m, 4H), 7.50-7.56 (m, 2H), 7.98 (d, J = 8.2Hz, 2H), 8.56 (s, 1H), 9.61 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 20.5, 39.9, 102.2, 121.0, 127.3, 129.2, 129.3, 129.7, 130.0, 132.5, 134.0, 135.0, 135.8, 136.4, 151.4, 156.7, 163.1.
Yield: 92.18%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.37 (s, 3H), 3.32 (s, 3H), 4.89 (d, J = 5.3 Hz, 2H), 7.34-7.40 (m, 4H), 7.50-7.56 (m, 2H), 7.98 (d, J = 8.2 Hz, 2H), 8.56 (s, 1H), 9.61 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 20.5, 39.9, 102.2, 121.0, 127.3, 129.2, 129.3, 129.7, 130.0, 132.5, 134.0, 135.0, 135.8, 136.4, 151.4, 156.7, 163.1.

(13) N-(2-메톡시벤질)-6-(메틸설포닐)-1-p-톨릴-1H-피라졸로[3,4-d]피리미딘-4-아민 [23m](13) N- (2-methoxybenzyl) -6- (methylsulfonyl) -1-p-tolyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [23m]

상기 [21b]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23m를 얻었다.[21b] was reacted with 2.4 eq mCPBA to obtain 23m of a white solid compound.

Yield: 96.42%; ¹H NMR (400MHz, DMSO-d₆) δ 2.37 (s, 3H), 3.34 (s, 3H), 3.85 (s, 3H), 4.78 (d, J = 5.0Hz, 2H), 7.00 (dd, J = 7.8Hz, 42.1Hz, 2H), 7.30-7.39 (m, 4H), 7.98 (d, J = 8.2Hz, 2H), 8.55 (s, 1H), 9.44 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 20.5, 55.4, 102.1, 110.7, 120.2, 120.9, 125.3, 128.7, 129.0, 129.6, 134.0, 135.8, 136.2, 151.4, 156.8, 157.0, 163.2.
Yield: 96.42%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.37 (s, 3H), 3.34 (s, 3H), 3.85 (s, 3H), 4.78 (d, J = 5.0 Hz, 2H), 7.00 (dd, J = 7.8 Hz, 42.1 Hz, 2H), 7.30-7.39 (m, 4H), 7.98 (d, J = 8.2 Hz, 2H), 8.55 (s, 1H), 9.44 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 20.5, 55.4, 102.1, 110.7, 120.2, 120.9, 125.3, 128.7, 129.0, 129.6, 134.0, 135.8, 136.2, 151.4, 156.8, 157.0, 163.2.

(14) N-(2-메틸벤질)-1-(4-메틸페닐)-6-(메틸설포닐)-1-p-톨릴-1H-피라졸로[3,4-d]피리미딘-4-아민 [23n](14) N- (2-methylbenzyl) -1- (4-methylphenyl) -6- (methylsulfonyl) -1-p-tolyl-1H-pyrazolo [3,4-d] pyrimidine-4- Amines [23n]

상기 [21c]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23n를 얻었다.[21c] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23n.

Yield: 91.04%; ¹H NMR (400MHz, DMSO-d₆) δ 2.37 (s, 6H), 3.35 (s, 3H), 4.80 (d, J = 5.3Hz, 2H), 7.17-7.23 (m, 4H), 7.39 (d, J = 8.0Hz, 2H), 7.98 (d, J = 8.3Hz, 2H), 8.54 (s, 1H), 9.45 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 18.8, 20.5, 42.2, 102.1, 121.0, 125.9, 127.4, 128.6, 129.7, 130.1, 134.0, 135.6, 135.8, 136.2, 151.4, 156.6, 163.2.
Yield: 91.04%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.37 (s, 6H), 3.35 (s, 3H), 4.80 (d, J = 5.3 Hz, 2H), 7.17-7.23 (m, 4H), 7.39 (d , J = 8.0 Hz, 2H), 7.98 (d, J = 8.3 Hz, 2H), 8.54 (s, 1H), 9.45 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 18.8, 20.5, 42.2, 102.1, 121.0, 125.9, 127.4, 128.6, 129.7, 130.1, 134.0, 135.6, 135.8, 136.2, 151.4, 156.6, 163.2.

(15) N-(4-메톡시벤질)-6-(메틸설포닐)-1-p-톨릴-1H-피라졸로[3,4-d]피리미딘-4-아민 [23o](15) N- (4-methoxybenzyl) -6- (methylsulfonyl) -1-p-tolyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine [23o]

상기 [21e]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23o를 얻었다.[21e] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23o.

Yield: 88.45%; ¹H NMR (400MHz, DMSO-d₆) δ 1.21 (s, 4H), 2.37 (s, 3H), 3.73 (s, 3H), 4.74 (d, J = 5.6Hz, 2H), 6.93 (d, J = 8.6Hz, 2H), 7.35-7.40 (m, 4H), 7.89-7.97 (m, 3H), 8.49 (s, 1H), 9.55 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 20.5, 28.9, 43.3, 55.0, 102.1, 113.8, 121.0, 127.8, 128.7, 129.2, 129.7, 130.0, 133.9, 135.8, 136.3, 151.4, 156.5, 158.5, 163.3.
Yield: 88.45%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.21 (s, 4H), 2.37 (s, 3H), 3.73 (s, 3H), 4.74 (d, J = 5.6 Hz, 2H), 6.93 (d, J = 8.6 Hz, 2H), 7.35-7.40 (m, 4H), 7.89-7.97 (m, 3H), 8.49 (s, 1H), 9.55 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 20.5, 28.9, 43.3, 55.0, 102.1, 113.8, 121.0, 127.8, 128.7, 129.2, 129.7, 130.0, 133.9, 135.8, 136.3, 151.4, 156.5, 158.5, 163.3.

(16) 1-벤질-6-(메틸설포닐)-N-(1-페닐에틸)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23p](16) 1-benzyl-6- (methylsulfonyl) -N- (1-phenylethyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [23p]

상기 [16x]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23p를 얻었다.[16x] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23p.

Yield: 70.78%; ¹H NMR (400MHz, DMSO-d₆) δ 1.60 (d, J = 6.5Hz, 3H), 3.26 (s, 3H), 5.49 (t, J = 6.8Hz, 1H), 5.55 (s, 2H), 7.22-7.36 (m, 8H), 7.46 (d, J = 7.2Hz, 2H), 8.39 (s, 1H), 9.39 (d, J = 7.2Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 21.9, 49.9, 50.1, 100.7, 125.6, 126.1, 126.9, 127.5, 127.6, 128.4, 128.5, 132.9, 136.6, 143.7, 151.9, 155.6, 162.8.
Yield: 70.78%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.60 (d, J = 6.5 Hz, 3H), 3.26 (s, 3H), 5.49 (t, J = 6.8 Hz, 1H), 5.55 (s, 2H), 7.22-7.36 (m, 8H), 7.46 (d, J = 7.2 Hz, 2H), 8.39 (s, 1H), 9.39 (d, J = 7.2 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 21.9, 49.9, 50.1, 100.7, 125.6, 126.1, 126.9, 127.5, 127.6, 128.4, 128.5, 132.9, 136.6, 143.7, 151.9, 155.6, 162.8.

(17) 1-벤질-6-(메틸설포닐)-N-(1-페닐에틸)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23q](17) 1-benzyl-6- (methylsulfonyl) -N- (1-phenylethyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [23q]

상기 [16e]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23q를 얻었다.[16e] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23q.

Yield: 87.44%; ¹H NMR (400MHz, DMSO-d₆) δ 1.59 (d, J = 6.9Hz, 3H), 3.24 (s, 3H), 5.47-5.54 (m, 3H), 7.20-7.36 (m, 8H), 7.45 (d, J = 7.6Hz, 2H), 8.37 (s, 1H), 9.37 (d, J = 7.6Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 21.9, 49.8, 50.1, 100.7, 126.1, 126.9, 127.5, 127.6, 128.4, 128.5, 132.9, 136.6, 143.7, 151.9, 155.6, 162.8.
Yield: 87.44%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.59 (d, J = 6.9 Hz, 3H), 3.24 (s, 3H), 5.47-5.54 (m, 3H), 7.20-7.36 (m, 8H), 7.45 (d, J = 7.6 Hz, 2H), 8.37 (s, 1 H), 9.37 (d, J = 7.6 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 21.9, 49.8, 50.1, 100.7, 126.1, 126.9, 127.5, 127.6, 128.4, 128.5, 132.9, 136.6, 143.7, 151.9, 155.6, 162.8.

(18) 1-벤질-6-(메틸설포닐)-N-(1-페닐에틸)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23r](18) 1-benzyl-6- (methylsulfonyl) -N- (1-phenylethyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [23r]

상기 [16k]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23r를 얻었다.[16k] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23r.

Yield: 90.37%; ¹H NMR (400MHz, DMSO-d₆) δ 1.60 (d, J = 6.6Hz, 3H), 3.25 (s, 3H), 5.47-5.55 (m, 3H), 7.21-7.36 (m, 8H), 7.46 (d, J = 6.8Hz, 2H), 8.38 (s, 1H), 9.39 (d, J = 7.1Hz, 1H); ¹³C NMR 100MHz, DMSO-d₆) δ 13.5, 21.9, 49.8, 50.1, 100.7, 126.1, 126.9, 127.5, 127.6, 128.4, 128.5, 132.9, 136.6, 143.7, 151.9, 155.6, 162.8.
Yield: 90.37%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.60 (d, J = 6.6 Hz, 3H), 3.25 (s, 3H), 5.47-5.55 (m, 3H), 7.21-7.36 (m, 8H), 7.46 (d, J = 6.8 Hz, 2H), 8.38 (s, 1 H), 9.39 (d, J = 7.1 Hz, 1H); ¹³ C NMR 100 MHz, DMSO-d ₆ ) δ 13.5, 21.9, 49.8, 50.1, 100.7, 126.1, 126.9, 127.5, 127.6, 128.4, 128.5, 132.9, 136.6, 143.7, 151.9, 155.6, 162.8.

(19) 1-벤질-N-((4-클로로페닐)(페닐)메틸)-6-(메틸설포닐)-N-(1-페닐에틸)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23s](19) 1-benzyl-N-((4-chlorophenyl) (phenyl) methyl) -6- (methylsulfonyl) -N- (1-phenylethyl) -1H-pyrazolo [3,4-d] Pyrimidin-4-amine [23s]

상기 [16y]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23s를 얻었다.[16y] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23s.

Yield: 97.05%; ¹H NMR (400MHz, DMSO-d₆) δ 3.23 (s, 3H), 5.56 (s, 2H), 6.70 (d, J = 7.4Hz, 1H), 7.22-7.57 (m, 14H), 8.23 (s, 1H), 9.79 (d, J = 7.2Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.6, 14.0, 28.9, 50.6, 57.7, 101.3, 128.0, 128.1, 128.3, 128.9, 129.0, 129.2, 129.9, 131.0, 133.1, 133.3, 133.8, 137.0, 141.2, 156.1, 163.1, 166.6.
Yield: 97.05%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 3.23 (s, 3H), 5.56 (s, 2H), 6.70 (d, J = 7.4 Hz, 1H), 7.22-7.57 (m, 14H), 8.23 (s , 1H), 9.79 (d, J = 7.2 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.6, 14.0, 28.9, 50.6, 57.7, 101.3, 128.0, 128.1, 128.3, 128.9, 129.0, 129.2, 129.9, 131.0, 133.1, 133.3, 133.8, 137.0, 141.2, 156.1, 163.1, 166.6.

(20) 1-벤질-N-(1-사이클로헥실에틸)-6-(메틸설포닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23t](20) 1-benzyl-N- (1-cyclohexylethyl) -6- (methylsulfonyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [23t]

상기 [16z]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23t를 얻었다.[16z] was reacted with 2.4 eq mCPBA to give a white solid compound 23t.

Yield: 96.20%; ¹H NMR (400MHz, DMSO-d₆) δ 0.98-1.01 (m, 2H), 1.15 (d, J = 6.8Hz, 3H), 1.17-1.22 (m, 2H), 1.46-1.61 (m, 2H), 1.70-1.77 (m, 4H), 2.48 (s, 3H), 4.19-4.24 (m, 1H), 5.54 (s, 2H), 7.21-7.33 (m, 5H), 8.05 (d, J = 8.5Hz, 1H), 8.10 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 17.7, 26.2, 26.3, 29.1, 29.5, 42.9, 50.6, 51.2, 128.1, 128.3, 129.0, 129.2, 131.0, 133.1, 133.4, 133.7, 152.3, 166.5.
Yield: 96.20%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.98-1.01 (m, 2H), 1.15 (d, J = 6.8 Hz, 3H), 1.17-1.22 (m, 2H), 1.46-1.61 (m, 2H) , 1.70-1.77 (m, 4H), 2.48 (s, 3H), 4.19-4.24 (m, 1H), 5.54 (s, 2H), 7.21-7.33 (m, 5H), 8.05 (d, J = 8.5 Hz , 1H), 8.10 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 17.7, 26.2, 26.3, 29.1, 29.5, 42.9, 50.6, 51.2, 128.1, 128.3, 129.0, 129.2, 131.0, 133.1, 133.4, 133.7, 152.3, 166.5.

(21) 1-벤질-6-(메틸설포닐)-N-(1-p-톨릴에틸)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23u](21) 1-benzyl-6- (methylsulfonyl) -N- (1-p-tolylethyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [23u]

상기 [16za]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23u를 얻었다.[16za] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23u.

Yield: 95.68%; ¹H NMR (400MHz, DMSO-d₆) δ 1.57 (d, J = 6.8Hz, 3H), 2.26 (s, 3H), 3.28 (s, 3H), 5.43-5.55 (m, 3H), 7.15 (d, J = 7.4Hz, 2H), 7.21-7.91 (m, 8H), 8.37 (s, 1H), 9.35 (d, J = 7.4Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 21.0, 22.3, 50.0, 50.6, 101.2, 126.6, 128.0, 127.5, 128.3, 129.0, 131.0, 133.4, 136.6, 137.1, 141.1, 152.4, 156.1, 166.5.
Yield: 95.68%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.57 (d, J = 6.8 Hz, 3H), 2.26 (s, 3H), 3.28 (s, 3H), 5.43-5.55 (m, 3H), 7.15 (d , J = 7.4 Hz, 2H), 7.21-7.91 (m, 8H), 8.37 (s, 1H), 9.35 (d, J = 7.4 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 21.0, 22.3, 50.0, 50.6, 101.2, 126.6, 128.0, 127.5, 128.3, 129.0, 131.0, 133.4, 136.6, 137.1, 141.1, 152.4, 156.1, 166.5.

(22) 1-벤질-N-((S)-1-(4-메톡시페닐)에틸)-6-(메틸설포닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23v](22) 1-benzyl-N-((S) -1- (4-methoxyphenyl) ethyl) -6- (methylsulfonyl) -1H-pyrazolo [3,4-d] pyrimidine-4- Amine [23v]

상기 [16zb]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23v를 얻었다.The [16zb] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23v.

Yield: 93.22%; ¹H NMR (400MHz, DMSO-d₆) δ 1.57 (d, J = 6.8Hz, 3H), 3.30 (s, 3H), 3.72 (s, 3H), 5.44-5.55 (s, 3H), 6.91 (d, J = 8.5Hz, 2H), 7.21-7.91 (m, 8H), 8.36 (s, 1H), 9.32 (d, J = 7.5Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 21.7, 49.1, 50.1, 54.9, 100.6, 113.9, 127.3, 127.4, 127.6, 128.5, 130.5, 132.9, 135.4, 136.6, 151.9, 155.5, 158.2, 162.8.
Yield: 93.22%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.57 (d, J = 6.8 Hz, 3H), 3.30 (s, 3H), 3.72 (s, 3H), 5.44-5.55 (s, 3H), 6.91 (d , J = 8.5 Hz, 2H), 7.21-7.91 (m, 8H), 8.36 (s, 1H), 9.32 (d, J = 7.5 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 21.7, 49.1, 50.1, 54.9, 100.6, 113.9, 127.3, 127.4, 127.6, 128.5, 130.5, 132.9, 135.4, 136.6, 151.9, 155.5, 158.2, 162.8.

(23) N-(2-클로로벤질)-1-(3-메톡시펜에틸)-6-(메틸설포닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23w](23) N- (2-chlorobenzyl) -1- (3-methoxyphenethyl) -6- (methylsulfonyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [23w ]

상기 [18a]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23w를 얻었다.[18a] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23w.

Yield: 89.11%; ¹H NMR (400MHz, DMSO-d₆) δ 2.39 (s, 3H), 3.11 (t, J = 6.9Hz, 2H), 3.66 (s, 3H), 4.47 (t, J = 7.0Hz, 2H), 4.76 (d, J = 5.6Hz, 2H), 6.71 (t, J = 6.9Hz, 3H), 7.13 (t, J = 7.8Hz, 1H), 7.30-7.33 (m, 2H), 7.39 (t, J = 4.5Hz, 1H), 7.48 (t, J = 4.5Hz, 1H), 8.08 (s, 1H), 8.79 (s, 1H).
Yield: 89.11%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.39 (s, 3H), 3.11 (t, J = 6.9 Hz, 2H), 3.66 (s, 3H), 4.47 (t, J = 7.0 Hz, 2H), 4.76 (d, J = 5.6 Hz, 2H), 6.71 (t, J = 6.9 Hz, 3H), 7.13 (t, J = 7.8 Hz, 1H), 7.30-7.33 (m, 2H), 7.39 (t, J = 4.5 Hz, 1H), 7.48 (t, J = 4.5 Hz, 1H), 8.08 (s, 1H), 8.79 (s, 1H).

(24) N-(2-메톡시벤질)-1-(3-메톡시펜에틸)-6-(메틸설포닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23x](24) N- (2-methoxybenzyl) -1- (3-methoxyphenethyl) -6- (methylsulfonyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [ 23x]

상기 [18b]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23x를 얻었다.[18b] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23x.

Yield: 90.88%; ¹H NMR (400MHz, DMSO-d₆) δ 2.42 (s, 3H), 3.11 (t, J = 7.0Hz, 2H), 3.66 (s, 3H), 3.82 (s, 3H), 4.46 (t, J = 7.0Hz, 2H), 4.65 (d, J = 5.5Hz, 2H), 6.71 (t, J = 6.0Hz, 3H), 6.90 (t, J = 4.5Hz, 1H), 7.02 (d, J = 8.1Hz, 1H), 7.13 (t, J = 4.5Hz, 1H), 7.22-7.26 (m, 2H), 8.08 (s, 1H), 8.59 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.3, 34.8, 38.3, 47.1, 54.7, 55.3, 98.0, 110.6, 111.8, 114.0, 120.1, 120.8, 126.2, 128.2, 128.3, 129.2, 131.8, 139.8, 153.3, 155.2, 156.8, 159.1, 168.0.
Yield: 90.88%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.42 (s, 3H), 3.11 (t, J = 7.0 Hz, 2H), 3.66 (s, 3H), 3.82 (s, 3H), 4.46 (t, J = 7.0 Hz, 2H), 4.65 (d, J = 5.5 Hz, 2H), 6.71 (t, J = 6.0 Hz, 3H), 6.90 (t, J = 4.5 Hz, 1H), 7.02 (d, J = 8.1 Hz, 1H), 7.13 (t, J = 4.5 Hz, 1H), 7.22-7.26 (m, 2H), 8.08 (s, 1H), 8.59 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.3, 34.8, 38.3, 47.1, 54.7, 55.3, 98.0, 110.6, 111.8, 114.0, 120.1, 120.8, 126.2, 128.2, 128.3, 129.2, 131.8, 139.8, 153.3, 155.2, 156.8, 159.1, 168.0.

(25) N-(2-메틸벤질)-1-(3-메톡시펜에틸)-6-(메틸설포닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23y](25) N- (2-methylbenzyl) -1- (3-methoxyphenethyl) -6- (methylsulfonyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [23y ]

상기 [18c]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23y를 얻었다.[18c] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23y.

Yield: 89.17%; ¹H NMR (400MHz, DMSO-d₆) δ 2.34 (s, 3H), 3.16 (t, J = 6.7Hz, 2H), 3.26 (s, 3H), 3.65 (s, 3H), 4.59 (t, J = 6.7Hz, 2H), 4.75 (t, J = 4.9Hz, 2H), 6.70 (t,J = 7.6Hz, 3H), 7.11 (t, J = 7.8Hz, 2H), 7.18-7.21 (m, 2H), 7.35 (d, J = 6.6Hz, 1H), 8.30 (s, 1H), 9.26 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 18.7, 34.8, 42.1, 47.7, 54.7, 100.3, 100.6, 111.9, 114.0, 120.8, 125.8, 127.4, 128.5, 129.2, 130.1, 132.4, 135.8, 136.2, 139.5, 151.7, 156.4, 159.1, 162.5.
Yield: 89.17%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.34 (s, 3H), 3.16 (t, J = 6.7 Hz, 2H), 3.26 (s, 3H), 3.65 (s, 3H), 4.59 (t, J = 6.7 Hz, 2H), 4.75 (t, J = 4.9 Hz, 2H), 6.70 (t, J = 7.6 Hz, 3H), 7.11 (t, J = 7.8 Hz, 2H), 7.18-7.21 (m, 2H ), 7.35 (d, J = 6.6 Hz, 1 H), 8.30 (s, 1 H), 9.26 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 18.7, 34.8, 42.1, 47.7, 54.7, 100.3, 100.6, 111.9, 114.0, 120.8, 125.8, 127.4, 128.5, 129.2, 130.1, 132.4, 135.8, 136.2, 139.5, 151.7, 156.4, 159.1, 162.5.

(26) 1-(2-메톡시펜에틸)-N-(3-메톡시벤질)-6-(메틸설포닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23z](26) 1- (2-methoxyphenethyl) -N- (3-methoxybenzyl) -6- (methylsulfonyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [ 23z]

상기 [19a]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23z를 얻었다.[19a] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23z.

Yield: 79.38%, ¹H NMR (400MHz, DMSO-d₆) δ 3.11 (t, J = 6.9Hz, 2H), 3.26 (s, 3H), 3.73 (s, 3H), 3.76 (s, 3H), 4.55 (t, J = 6.9Hz, 2H), 4.73 (d, J = 5.6Hz, 2H), 6.73 (t, J = 7.4Hz, 1H), 6.83-6.99 (m, 5H), 7.21 (dd, J=7.8Hz, 47.4Hz, 2H), 8.24 (s, 1H), 9.39 (t, J = 5.6Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 30.8, 44.2, 46.9, 55.4, 55.7, 99.1, 101.1, 111.0, 113.2, 113.9, 120.4, 120.5, 126.1, 128.4, 130.0, 130.4, 132.6, 140.4, 152.2, 157.0, 157.8, 159.8, 162.9.
Yield: 79.38%, ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 3.11 (t, J = 6.9 Hz, 2H), 3.26 (s, 3H), 3.73 (s, 3H), 3.76 (s, 3H), 4.55 (t, J = 6.9 Hz, 2H), 4.73 (d, J = 5.6 Hz, 2H), 6.73 (t, J = 7.4 Hz, 1H), 6.83-6.99 (m, 5H), 7.21 (dd, J = 7.8 Hz, 47.4 Hz, 2H), 8.24 (s, 1H), 9.39 (t, J = 5.6 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 30.8, 44.2, 46.9, 55.4, 55.7, 99.1, 101.1, 111.0, 113.2, 113.9, 120.4, 120.5, 126.1, 128.4, 130.0, 130.4, 132.6, 140.4, 152.2, 157.0, 157.8, 159.8, 162.9.

(27) 1-(2-메톡시펜에틸)-N-(4-메톡시벤질)-6-(메틸설포닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23za](27) 1- (2-methoxyphenethyl) -N- (4-methoxybenzyl) -6- (methylsulfonyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [ 23za]

상기 [19b]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23za를 얻었다.[19b] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23za.

Yield: 84.88%; ¹H NMR (400MHz, DMSO-d₆) δ 3.12 (t, J = 6.6Hz, 2H), 3.28 (s, 3H), 3.73 (s, 3H), 3.77 (s, 3H), 4.55 (t, J = 6.7Hz, 2H), 4.69 (d, J = 5.2Hz, 2H), 6.73 (t, J = 7.2Hz, 1H), 6.92 (d, J = 8.0Hz, 4H), 7.15 (t, J = 7.3Hz, 1H), 7.34 (d, J = 8.2Hz, 2H), 8.24 (s, 1H), 9.34 (d, J = 5.1Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 30.8, 43.7, 46.9, 55.5, 55.7, 101.1, 111.0, 114.3, 120.5, 126.1, 128.4, 129.7, 130.4, 130.7, 132.6, 152.2, 156.8, 157.8, 159.0, 163.0.
Yield: 84.88%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 3.12 (t, J = 6.6 Hz, 2H), 3.28 (s, 3H), 3.73 (s, 3H), 3.77 (s, 3H), 4.55 (t, J = 6.7 Hz, 2H), 4.69 (d, J = 5.2 Hz, 2H), 6.73 (t, J = 7.2 Hz, 1H), 6.92 (d, J = 8.0 Hz, 4H), 7.15 (t, J = 7.3 Hz, 1H), 7.34 (d, J = 8.2 Hz, 2H), 8.24 (s, 1H), 9.34 (d, J = 5.1 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 30.8, 43.7, 46.9, 55.5, 55.7, 101.1, 111.0, 114.3, 120.5, 126.1, 128.4, 129.7, 130.4, 130.7, 132.6, 152.2, 156.8, 157.8, 159.0, 163.0.

(28) 1-(2-메톡시펜에틸)-N-(4-메톡시벤질)-6-(메틸설포닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23zb](28) 1- (2-methoxyphenethyl) -N- (4-methoxybenzyl) -6- (methylsulfonyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [ 23zb]

상기 [19c]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23zb를 얻었다.[19c] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23zb.

Yield: 90.32%; ¹H NMR (400MHz, DMSO-d₆) δ 2.27 (s, 3H), 3.11 (t, J = 7.0Hz, 2H), 3.26 (s, 3H), 3.77 (s, 3H), 4.55 (t, J = 7.0Hz, 2H), 4.71 (d, J = 5.6Hz, 2H), 6.73 (t, J = 5.8Hz, 1H), 6.92 (d, J = 7.6Hz, 2H), 7.13-7.16 (m, 3H), 7.28 (d, J = 7.8Hz, 2H), 8.23 (s, 1H), 9.35 (t, J = 5.3Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 21.1, 30.8, 44.0, 46.9, 55.7, 101.1, 111.0, 120.5, 126.1, 127.0, 128.2, 128.4, 129.4, 130.4, 132.6, 135.7, 136.8, 152.2, 156.9, 157.8, 163.0.
Yield: 90.32%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.27 (s, 3H), 3.11 (t, J = 7.0 Hz, 2H), 3.26 (s, 3H), 3.77 (s, 3H), 4.55 (t, J = 7.0 Hz, 2H), 4.71 (d, J = 5.6 Hz, 2H), 6.73 (t, J = 5.8 Hz, 1H), 6.92 (d, J = 7.6 Hz, 2H), 7.13-7.16 (m, 3H ), 7.28 (d, J = 7.8 Hz, 2H), 8.23 (s, 1H), 9.35 (t, J = 5.3 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 21.1, 30.8, 44.0, 46.9, 55.7, 101.1, 111.0, 120.5, 126.1, 127.0, 128.2, 128.4, 129.4, 130.4, 132.6, 135.7, 136.8, 152.2, 156.9, 157.8, 163.0.

(29) N-(4-메톡시벤질)-1-t-뷰틸-6-(메틸설포닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23zc](29) N- (4-methoxybenzyl) -1-t-butyl-6- (methylsulfonyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [23zc]

상기 [17e]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23zc를 얻었다.[17e] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23zc.

Yield: 83.33%; ¹H NMR (400MHz, DMSO-d₆) δ 1.63 (s, 9H), 3.28 (s, 3H), 3.73 (s, 3H), 4.69 (d, J = 5.4Hz, 2H), 6.91 (t, J = 4.3Hz, 2H), 7.34 (d, J = 8.5Hz, 2H), 8.60 (s, 1H), 9.18 (s, 1H).
Yield: 83.33%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.63 (s, 9H), 3.28 (s, 3H), 3.73 (s, 3H), 4.69 (d, J = 5.4 Hz, 2H), 6.91 (t, J = 4.3 Hz, 2H), 7.34 (d, J = 8.5 Hz, 2H), 8.60 (s, 1H), 9.18 (s, 1H).

(30) N-(4-클로로벤질)-1-t-뷰틸-6-(메틸설포닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23zd](30) N- (4-chlorobenzyl) -1-t-butyl-6- (methylsulfonyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [23zd]

상기 [17j]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23zd를 얻었다.[17j] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23zd.

Yield: 89.06%; ¹H NMR (400MHz, DMSO-d₆) δ 1.64 (s, 9H), 3.26 (s, 3H), 4.76 (d, J = 5.7Hz, 2H), 7.43 (t, J = 5.6Hz, 4H), 8.60 (s, 1H), 9.29 (s, 1H)
Yield: 89.06%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.64 (s, 9H), 3.26 (s, 3H), 4.76 (d, J = 5.7 Hz, 2H), 7.43 (t, J = 5.6 Hz, 4H), 8.60 (s, 1 H), 9.29 (s, 1 H)

(31) N-(2-클로로벤질)-1-t-뷰틸-6-(메틸설포닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23ze](31) N- (2-chlorobenzyl) -1-t-butyl-6- (methylsulfonyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [23ze]

상기 [17n]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23ze를 얻었다.[17n] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23ze.

Yield: 90.89%; ¹H NMR (400MHz, DMSO-d₆) δ 1.60 (s, 9H), 4.79 (d, J = 5.5Hz, 2H), 6.92 (d, J = 8.4Hz, 2H), 7.37 (d, J = 8.3Hz, 2H), 8.63 (s, 1H), 9.20 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 28.7, 43.7, 55.0, 98.4, 113.8, 126.6, 129.2, 149.4, 155.1, 158.5, 165.5.
Yield: 90.89%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.60 (s, 9H), 4.79 (d, J = 5.5 Hz, 2H), 6.92 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.3 Hz, 2H), 8.63 (s, 1 H), 9.20 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 28.7, 43.7, 55.0, 98.4, 113.8, 126.6, 129.2, 149.4, 155.1, 158.5, 165.5.

(32) 1-t-뷰틸-N-(1-사이클로헥실에틸)-6-(메틸설포닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23zf](32) 1-t-butyl-N- (1-cyclohexylethyl) -6- (methylsulfonyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [23zf]

상기 [17q]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23zf를 얻었다.[17q] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23zf.

Yield: 83.95%; ¹H NMR (400MHz, DMSO-d₆) δ 0.99-1.05 (m, 2H), 1.18 (d, J = 7.1Hz, 3H), 1.17-1.19 (m, 2H), 1.44-1.48 (m, 2H), 1.64 (s, 9H), 1.71-1.78 (m, 4H), 3.27 (s, 3H), 4.24 (d, J = 6.9Hz, 1H), 7.90 (s, 1H), 8.51 (s, 1H).
Yield: 83.95%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.99-1.05 (m, 2H), 1.18 (d, J = 7.1 Hz, 3H), 1.17-1.19 (m, 2H), 1.44-1.48 (m, 2H) , 1.64 (s, 9H), 1.71-1.78 (m, 4H), 3.27 (s, 3H), 4.24 (d, J = 6.9 Hz, 1H), 7.90 (s, 1H), 8.51 (s, 1H).

(33) 1-t-뷰틸-N-(1-사이클로헥실에틸)-6-(메틸설포닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23zh](33) 1-t-butyl-N- (1-cyclohexylethyl) -6- (methylsulfonyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [23zh]

상기 [17p]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23zh를 얻었다.[17p] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23zh.

Yield: 86.27%; ¹H NMR (400MHz, DMSO-d₆) δ 0.99-1.03 (m, 2H), 1.16 (d, J = 7.1Hz, 3H), 1.17-1.19 (m, 2H), 1.44-1.48 (m, 2H), 1.64 (s, 9H), 1.69-1.77 (m, 4H), 3.27 (s, 3H), 4.25 (d, J = 6.7Hz, 1H), 7.90 (s, 1H), 8.50 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 17.2, 25.6, 25.8, 28.6, 28.8, 29.0, 42.6, 50.3, 60.6, 100.9, 122.5, 127.7, 128.7, 130.5, 132.5, 133.2, 157.5, 163.2, 165.9.
Yield: 86.27%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.99-1.03 (m, 2H), 1.16 (d, J = 7.1 Hz, 3H), 1.17-1.19 (m, 2H), 1.44-1.48 (m, 2H) , 1.64 (s, 9H), 1.69-1.77 (m, 4H), 3.27 (s, 3H), 4.25 (d, J = 6.7 Hz, 1H), 7.90 (s, 1H), 8.50 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 17.2, 25.6, 25.8, 28.6, 28.8, 29.0, 42.6, 50.3, 60.6, 100.9, 122.5, 127.7, 128.7, 130.5, 132.5, 133.2, 157.5, 163.2, 165.9.

(34) 1-t-뷰틸-N-뷰틸-6-(메틸설포닐)-1H-피라졸로[3,4-d]피리미딘-4-아민 [23zi](34) 1-t-butyl-N-butyl-6- (methylsulfonyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine [23zi]

상기 [17l]를 2.4 eq mCPBA로 반응시켜 하얀색의 고체상 화합물 23zi를 얻었다.[17l] was reacted with 2.4 eq mCPBA to obtain a white solid compound 23zi.

Yield: 90.10%; ¹H NMR (400MHz, DMSO-d₆) δ 0.93 (t, J = 7.3Hz, 3H), 1.36-1.41 (m, 2H), 1.59-1.61 (m, 2H), 1.64 (s, 9H), 3.28 (s, 3H), 3.52-3.56 (m, 2H), 8.59 (s, 1H), 8.75 (t, J = 5.1Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.5, 19.4, 29.0, 30.5, 60.6, 101.1, 122.3, 157.4 , 158.3, 163.2.
Yield: 90.10%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.93 (t, J = 7.3 Hz, 3H), 1.36-1.41 (m, 2H), 1.59-1.61 (m, 2H), 1.64 (s, 9H), 3.28 (s, 3H), 3.52-3.56 (m, 2H), 8.59 (s, 1H), 8.75 (t, J = 5.1 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.5, 19.4, 29.0, 30.5, 60.6, 101.1, 122.3, 157.4, 158.3, 163.2.

실시예 22. [24a] 내지 [24j]의 합성Example 22. Synthesis of [24a] to [24j]

하기 [반응식 24](R_{3 ,} n-BuOH : DMSO = 4 : 1, 90 ℃)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [24a] 내지 [24j]를 합성하였다.The pyrazolopyrimidine derivative compounds [24a] to [24j] were synthesized according to the following Reaction Scheme 24 (R _{3 ,} n-BuOH: DMSO = 4: 1, 90 ° C).

[반응식 24][Reaction Scheme 24]

[24a] ~ [24j][24a] to [24j]

[24a] 내지 [24j]에서 R₃는 각각 하기 [표 17]과 같다.In [24a] to [24j], each of R ₃ is shown in Table 17 below.

(NR₂은 [16e], [16x]에서와 동일하다.)(NR ₂ is the same as in [16e], [16x].)

구분division R₃ R ₃ 구분division R₃ R ₃ 24a24a

24f24f

24b24b

24g24 g

24c24c

24h24h

24d24d

24i24i

24e24e

24j24j

(1) 2-(4-(1-페닐에틸아미노)-1-벤질-1H-피라졸로[3,4-d]피리미딘-6-일아미노)에탄올 [24a](1) 2- (4- (1-phenylethylamino) -1-benzyl-1H-pyrazolo [3,4-d] pyrimidin-6-ylamino) ethanol [24a]

상기 [23p]를 용매 (n-BuOH : DMSO = 4 : 1)비율로 녹인 다음 1.2 eq 2-aminoethanol을 상온에서 넣어주고 90 ℃에서 overnight 반응으로 진행시킨다. 반응종료 후 반응물은 CH₂Cl₂ (2×30 mL), H₂O를 이용하여 추출하고 유기층은 무수 MgSO₄을 사용하여 소량의 물을 제거하였으며, 감압 증류하여 용매를 제거하였다. 여기서 얻은 반응 혼합물을 flash chromatography (hexanes : EtOAc = 1 : 1)로 하여 분리하면 하얀색의 고체상 화합물 24a를 얻었다.[23p] was dissolved in a solvent (n-BuOH: DMSO = 4: 1) ratio, and then 1.2 eq 2-aminoethanol was added at room temperature, followed by overnight reaction at 90 ° C. After completion of reaction, the reactant is CH ₂ Cl ₂ (2 × 30 mL), extracted with H ₂ O, and the organic layer was removed with a small amount of water using anhydrous MgSO ₄ , the solvent was removed by distillation under reduced pressure. The reaction mixture obtained here was separated by flash chromatography (hexanes: EtOAc = 1: 1) to give a white solid compound 24a.

Yield: 66.57%; ¹H NMR (400MHz, DMSO-d₆) δ 1.51 (d, J = 6.9Hz, 3H), 3.32 (s, 2H), 3.48 (s, 2H), 4.65 (s, 1H), 5.27-5.43 (m, 3H), 6.48 (s, 1H), 7.19-7.33 (m, 8H), 7.41 (d, J = 7.5Hz, 2H), 7.94 (s, 1H), 8.15 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 22.8, 44.2, 49.5, 60.6, 95.8, 126.6, 127.0, 127.6, 128.7, 128.8, 132.6, 138.3, 156.0, 161.9.
Yield: 66.57%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.51 (d, J = 6.9 Hz, 3H), 3.32 (s, 2H), 3.48 (s, 2H), 4.65 (s, 1H), 5.27-5.43 (m , 3H), 6.48 (s, 1H), 7.19-7.33 (m, 8H), 7.41 (d, J = 7.5 Hz, 2H), 7.94 (s, 1H), 8.15 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 22.8, 44.2, 49.5, 60.6, 95.8, 126.6, 127.0, 127.6, 128.7, 128.8, 132.6, 138.3, 156.0, 161.9.

(2) 3-(4-(1-페닐에틸아미노)-1-벤질-1H-피라졸로[3,4-d]피리미딘-6-일아미노)프로판-1-올 [24b](2) 3- (4- (1-phenylethylamino) -1-benzyl-1H-pyrazolo [3,4-d] pyrimidin-6-ylamino) propan-1-ol [24b]

상기 [23q]를 3-aminopropan-1-ol으로 하얀색의 고체상 화합물 24b를 얻었다.[23q] was obtained as white solid compound 24b as 3-aminopropan-1-ol.

Yield: 71.235; ¹H NMR (400MHz, DMSO-d₆) δ 1.51 (d, J = 6.9Hz, 3H), 1.64 (s, 2H), 3.29 (s, 2H), 3.45 (s, 2H), 4.47 (s, 1H), 5.27-5.44 (m, 3H), 6.58 (s, 1H), 7.19-7.33 (m, 8H), 7.42 (d, J = 7.5Hz, 2H), 7.93 (s, 1H), 8.13 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 22.9, 49.5, 59.3, 99.1, 126.6, 126.5, 127.1, 128.1, 128.3, 132.1, 137.9, 155.5, 161.4.
Yield: 71.235; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.51 (d, J = 6.9 Hz, 3H), 1.64 (s, 2H), 3.29 (s, 2H), 3.45 (s, 2H), 4.47 (s, 1H ), 5.27-5.44 (m, 3H), 6.58 (s, 1H), 7.19-7.33 (m, 8H), 7.42 (d, J = 7.5 Hz, 2H), 7.93 (s, 1H), 8.13 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 22.9, 49.5, 59.3, 99.1, 126.6, 126.5, 127.1, 128.1, 128.3, 132.1, 137.9, 155.5, 161.4.

(3) 4-(4-(1-페닐에틸아미노)-1-벤질-1H-피라졸로[3,4-d]피리미딘-6-일아미노)부탄-1-올 [24c](3) 4- (4- (1-phenylethylamino) -1-benzyl-1H-pyrazolo [3,4-d] pyrimidin-6-ylamino) butan-1-ol [24c]

상기 [23q]와 4-aminobutan-1-ol으로 하얀색의 고체상 화합물 24c를 얻었다.The white solid compound 24c was obtained from [23q] and 4-aminobutan-1-ol.

Yield: 61.44%; ¹H NMR (400MHz, DMSO-d₆) δ 1.43 (s, 4H), 1.51 (d, J = 6.9Hz, 3H), 3.21 (s, 2H), 3.43 (s, 2H), 4.37 (t, J = 5.1Hz, 1H), 5.26-5.43 (m, 3H), 6.61 (s, 1H), 7.20-7.33 (m, 8H), 7.41 (d, J = 7.4Hz, 2H), 7.92 (s, 1H), 8.12 (s, 1H); ¹³C NMR 100MHz, DMSO-d₆) δ 22.6, 26.4, 30.6, 49.5, 61.1, 95.6, 126.5, 126.4, 127.1, 1281, 128.3, 132.0, 137.9, 155.5, 161.4.
Yield: 61.44%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.43 (s, 4H), 1.51 (d, J = 6.9 Hz, 3H), 3.21 (s, 2H), 3.43 (s, 2H), 4.37 (t, J = 5.1 Hz, 1H), 5.26-5.43 (m, 3H), 6.61 (s, 1H), 7.20-7.33 (m, 8H), 7.41 (d, J = 7.4 Hz, 2H), 7.92 (s, 1H) , 8.12 (s, 1 H); ¹³ C NMR 100 MHz, DMSO-d ₆ ) δ 22.6, 26.4, 30.6, 49.5, 61.1, 95.6, 126.5, 126.4, 127.1, 1281, 128.3, 132.0, 137.9, 155.5, 161.4.

(4) 2-(2-(4-(1-페닐에틸아미노)-1-벤질-1H-피라졸로[3,4-d]피리미딘-6-일아미노)에톡시)에탄올 [24d](4) 2- (2- (4- (1-phenylethylamino) -1-benzyl-1H-pyrazolo [3,4-d] pyrimidin-6-ylamino) ethoxy) ethanol [24d]

상기 [23q]와 2-(2-aminoethoxy)ethanol으로 하얀색의 고체상 화합물 24d를 얻었다.The white solid compound 24d was obtained from [23q] and 2- (2-aminoethoxy) ethanol.

Yield: 59.76%; ¹H NMR (400MHz, DMSO-d₆) δ 1.51 (d, J = 6.5Hz, 3H), 3.48 (s, 4H), 3.49 (s, 4H), 3.60 (s, 1H), 5.27-5.43 (m, 3H), 6.55 (s, 1H), 7.20-7.34 (m, 8H), 7.41 (d, J = 6.6Hz, 2H), 7.94 (s, 1H), 8.11 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 22.5, 49.0, 60.1, 69.1, 72.0, 98.6, 126.0, 126.5, 127.1, 128.2, 128.3, 132.1, 137.9, 155.6, 161.2.
Yield: 59.76%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.51 (d, J = 6.5 Hz, 3H), 3.48 (s, 4H), 3.49 (s, 4H), 3.60 (s, 1H), 5.27-5.43 (m , 3H), 6.55 (s, 1H), 7.20-7.34 (m, 8H), 7.41 (d, J = 6.6 Hz, 2H), 7.94 (s, 1H), 8.11 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 22.5, 49.0, 60.1, 69.1, 72.0, 98.6, 126.0, 126.5, 127.1, 128.2, 128.3, 132.1, 137.9, 155.6, 161.2.

(5) N⁶,1-디벤질-N⁴-(1-페닐에틸)-1-벤질-1H-피라졸로[3,4-d]피리미딘-4,6-디아민 [24e](5) N ⁶ , 1-dibenzyl-N ^4- (1-phenylethyl) -1-benzyl-1H-pyrazolo [3,4-d] pyrimidine-4,6-diamine [24e]

상기 [23p]와 benzylamine으로 하얀색의 고체상 화합물 24e를 얻었다.[23p] and benzylamine gave a white solid compound 24e.

Yield: 48.39%; ¹H NMR (400MHz, DMSO-d₆) δ 1.48 (d, J = 6.6Hz, 3H), 4.41-4.45 (m, 2H), 5.25-5.41 (m, 3H), 7.16-7.35 (m, 15H), 7.93 (s, 1H), 8.1 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 22.3, 44.3, 49.0, 95.4, 98.6, 126.0, 126.2, 126.5, 127.1, 127.3, 127.9, 128.1, 128.3, 132.1, 137.8, 141.1, 144.8, 155.6, 161.2.
Yield: 48.39%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.48 (d, J = 6.6 Hz, 3H), 4.41-4.45 (m, 2H), 5.25-5.41 (m, 3H), 7.16-7.35 (m, 15H) , 7.93 (s, 1 H), 8.1 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 22.3, 44.3, 49.0, 95.4, 98.6, 126.0, 126.2, 126.5, 127.1, 127.3, 127.9, 128.1, 128.3, 132.1, 137.8, 141.1, 144.8, 155.6, 161.2.

(6) 1-벤질-N⁶-뷰틸-N⁴-(1-페닐에틸)-1H-피라졸로[3,4-d]피리미딘-4,6-디아민 [24f](6) 1-benzyl-N ⁶ -butyl-N ^4- (1-phenylethyl) -1H-pyrazolo [3,4-d] pyrimidine-4,6-diamine [24f]

상기 [23p]와 n-butylamine으로 하얀색의 고체상 화합물 24f를 얻었다.[23p] and n-butylamine gave a white solid compound 24f.

Yield: 62.49%; ¹H NMR (400MHz, DMSO-d₆) δ 0.86 (t, J = 6.4Hz, 3H), 1.15-1.23 (m, 4H), 1.51 (d, J = 6.9Hz, 3H), 3.24 (s, 2H), 5.26-5.43 (m, 3H), 6.60 (s, 1H), 7.18-7.32 (m, 8H), 7.40 (d, J = 6.9Hz, 2H), 7.93 (s, 1H), 8.12 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.2, 20.1, 22.9, 29.4, 31.9, 49.5, 126.5, 126.9, 127.6, 128.6, 128.8, 132.5, 138.4, 156.0, 161.9.
Yield: 62.49%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.86 (t, J = 6.4 Hz, 3H), 1.15-1.23 (m, 4H), 1.51 (d, J = 6.9 Hz, 3H), 3.24 (s, 2H ), 5.26-5.43 (m, 3H), 6.60 (s, 1H), 7.18-7.32 (m, 8H), 7.40 (d, J = 6.9 Hz, 2H), 7.93 (s, 1H), 8.12 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.2, 20.1, 22.9, 29.4, 31.9, 49.5, 126.5, 126.9, 127.6, 128.6, 128.8, 132.5, 138.4, 156.0, 161.9.

(7) 1-벤질-N⁶,N⁶-디메틸-N⁴-(1-페닐에틸)-1H-피라졸로[3,4-d]피리미딘-4,6-디아민 [24g](7) 1-benzyl-N ⁶ , N ⁶ -dimethyl-N ^4- (1-phenylethyl) -1H-pyrazolo [3,4-d] pyrimidine-4,6-diamine [24 g]

상기 [23p]와 dimethylamine으로 하얀색의 고체상 화합물 24g를 얻었다.24g of a white solid compound was obtained using [23p] and dimethylamine.

Yield: 87.34%; ¹H NMR (400MHz, DMSO-d₆) δ 1.51 (d, J = 7.0Hz, 3H), 3.03 (s, 6H), 5.28-5.35 (m, 3H), 7.19-7.31 (m, 8H), 7.40 (d, J = 7.4Hz, 2H), 7.94 (s, 1H), 8.21 (d, J = 7.3Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 23.0, 37.1, 49.5, 49.7, 95.0, 126.4, 126.9, 127.6, 128.0, 128.6, 128.8, 132.5, 138.4, 146.0, 155.6, 156.2, 161.5.
Yield: 87.34%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.51 (d, J = 7.0 Hz, 3H), 3.03 (s, 6H), 5.28-5.35 (m, 3H), 7.19-7.31 (m, 8H), 7.40 (d, J = 7.4 Hz, 2H), 7.94 (s, 1H), 8.21 (d, J = 7.3 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 23.0, 37.1, 49.5, 49.7, 95.0, 126.4, 126.9, 127.6, 128.0, 128.6, 128.8, 132.5, 138.4, 146.0, 155.6, 156.2, 161.5.

(8) 1-벤질-N⁶-(2-메톡시에틸)-N⁴-(1-페닐에틸)-1H-피라졸로[3,4-d]피리미딘-4,6-디아민 [24h](8) 1-benzyl-N ^6- (2-methoxyethyl) -N ^4- (1-phenylethyl) -1H-pyrazolo [3,4-d] pyrimidine-4,6-diamine [24h]

상기 [23p]와 2-methoxyethanamine으로 하얀색의 고체상 화합물 24h를 얻었다.The white solid compound 24h was obtained from [23p] and 2-methoxyethanamine.

Yield: 67.29%; ¹H NMR (400MHz, DMSO-d₆) δ 1.23 (S, 3H), 1.51 (d, J = 6.9Hz, 3H), 3.18-3.24 (m, 4H), 5.27-5.43 (m, 3H), 6.54 (s, 1H), 7.18-7.33 (m, 8H), 7.40 (d, J = 7.1Hz, 2H), 7.94 (s, 1H), 8.12 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.9, 22.0, 22.4, 25.2, 28.6, 29.0, 31.2, 35.2, 38.2, 49.0, 57.7, 70.7, 95.3, 126.0, 126.5, 127.1, 127.3, 128.1, 128.3, 132.1, 137.9, 145.1, 155.6, 161.2.
Yield: 67.29%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.23 (S, 3H), 1.51 (d, J = 6.9 Hz, 3H), 3.18-3.24 (m, 4H), 5.27-5.43 (m, 3H), 6.54 (s, 1H), 7.18-7.33 (m, 8H), 7.40 (d, J = 7.1 Hz, 2H), 7.94 (s, 1H), 8.12 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.9, 22.0, 22.4, 25.2, 28.6, 29.0, 31.2, 35.2, 38.2, 49.0, 57.7, 70.7, 95.3, 126.0, 126.5, 127.1, 127.3, 128.1, 128.3, 132.1, 137.9, 145.1, 155.6, 161.2.

(9) 1-벤질-N⁶-(3-에톡시프로필)-N⁴-(1-페닐에틸)-1H-피라졸로[3,4-d]피리미딘-4,6-디아민 [24j](9) 1-benzyl-N ^6- (3-ethoxypropyl) -N ^4- (1-phenylethyl) -1H-pyrazolo [3,4-d] pyrimidine-4,6-diamine [24j]

상기 [23p]와 3-ethoxypropan-1-amine으로 하얀색의 고체상 화합물 24j를 얻었다.The white solid compound 24j was obtained from [23p] and 3-ethoxypropan-1-amine.

Yield: 69.36%; ¹H NMR (400MHz, DMSO-d₆) δ 1.09 (t, J = 7.0Hz, 3H), 1.23 (s, 3H), 1.51 (d, J = 7.0Hz, 3H), 1.60-1.69 (m, 2H), 3.29 (t, J = 7.2Hz, 3H), 5.27-5.43 (m, 3H), 6.60 (s, 1H), 7.18-7.32 (m, 8H), 7.41 (d, J = 7.3Hz, 2H), 7.94 (s, 1H), 8.13 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.4, 15.6, 22.5, 22.9, 25.7, 29.1, 29.1, 29.9, 31.7, 35.8, 36.1, 38.8, 49.5, 65.7, 67.9, 68.4, 95.7, 126.5, 126.9, 127.6, 128.6, 128.8, 130.1, 132.6, 138.4, 145.6, 156.0, 161.9.
Yield: 69.36%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.09 (t, J = 7.0 Hz, 3H), 1.23 (s, 3H), 1.51 (d, J = 7.0 Hz, 3H), 1.60-1.69 (m, 2H ), 3.29 (t, J = 7.2 Hz, 3H), 5.27-5.43 (m, 3H), 6.60 (s, 1H), 7.18-7.32 (m, 8H), 7.41 (d, J = 7.3 Hz, 2H) , 7.94 (s, 1 H), 8.13 (s, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.4, 15.6, 22.5, 22.9, 25.7, 29.1, 29.1, 29.9, 31.7, 35.8, 36.1, 38.8, 49.5, 65.7, 67.9, 68.4, 95.7, 126.5, 126.9, 127.6, 128.6, 128.8, 130.1, 132.6, 138.4, 145.6, 156.0, 161.9.

(10) 1-벤질-N⁶-뷰틸-N⁴-(1-페닐에틸)-1H-피라졸로[3,4-d]피리미딘-4,6-디아민 [24i](10) 1-benzyl-N ⁶ -butyl-N ^4- (1-phenylethyl) -1H-pyrazolo [3,4-d] pyrimidine-4,6-diamine [24i]

상기 [23q]와 n-butylamine으로 하얀색의 고체상 화합물 24d를 얻었다.The white solid compound 24d was obtained from [23q] and n-butylamine.

Yield: 58.56%; ¹H NMR (400MHz, DMSO-d₆) δ 0.86 (t, J = 7.0Hz, 3H), 1.28 (s, 2H), 1.42 (s, 2H), 1.51 (d, J = 7.0Hz, 3H), 3.24 (s, 2H), 5.24-5.27 (m, 3H), 6.60 (s, 1H), 7.18-7.40 (m, 9H), 7.93 (s, 1H), 8.12 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.7, 19.6, 22.3, 31.4, 48.9, 95.1, 125.9, 126.4, 127.0, 128.0, 128.2, 132.0, 137.9, 155.5, 161.3.
Yield: 58.56%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 0.86 (t, J = 7.0 Hz, 3H), 1.28 (s, 2H), 1.42 (s, 2H), 1.51 (d, J = 7.0 Hz, 3H), 3.24 (s, 2H), 5.24-5.27 (m, 3H), 6.60 (s, 1H), 7.18-7.40 (m, 9H), 7.93 (s, 1H), 8.12 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.7, 19.6, 22.3, 31.4, 48.9, 95.1, 125.9, 126.4, 127.0, 128.0, 128.2, 132.0, 137.9, 155.5, 161.3.

실시예 23. [25a] 내지 [25b]의 합성Example 23. Synthesis of [25a] to [25b]

하기 [반응식 25](alkyl halide, KOH, EtOH, reflux, 4h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [24a] 내지 [25b]를 합성하였다.The pyrazolopyrimidine derivative compounds [24a] to [25b] were synthesized according to Scheme 25 (alkyl halide, KOH, EtOH, reflux, 4h).

[반응식 25][Reaction Scheme 25]

[9b] [25a] ~ [25b][9b] [25a]-[25b]

[25a] 내지 [25b]에서 SR₂는 각각 하기 [표 18]과 같다.SR ₂ in [25a] to [25b] is as follows.

구분division SR₂ SR ₂ 구분division SR₂ SR ₂ 25a25a

25b25b

(1) 1-페닐-4-벤질티오-6-(메틸티오)피라졸로[3,4-d]피리미딘 [25a](1) 1-phenyl-4-benzylthio-6- (methylthio) pyrazolo [3,4-d] pyrimidine [25a]

상기 [9b] (50 mg, 0.182 mmol)와 KOH (1 eq, 10 mg), benzyl chloride (1,1 eq, 0.02 mL)를 ethanol (10 mL)에 넣고 4 시간 동안 reflux를 하였다. 4 시간 후에는 반응 혼합물의 용매는 감압기화를 시켜서 제거하였고, 남아있는 반응 혼합물은 flash chromatography (hexanes : EtOAc = 4 : 1)로 분리하여 옅은 노란색의 고체상 화합물 25a를 얻었다.[9b] (50 mg, 0.182 mmol), KOH (1 eq, 10 mg) and benzyl chloride (1,1 eq, 0.02 mL) were added to ethanol (10 mL) and refluxed for 4 hours. After 4 hours, the solvent of the reaction mixture was removed by evaporation under reduced pressure, and the remaining reaction mixture was separated by flash chromatography (hexanes: EtOAc = 4: 1) to obtain a pale yellow solid compound 25a.

Yield: 85%; ¹H NMR (400MHz, DMSO-d₆) δ 2.61 (s, 3H), 4.64 (s, 2H), 7.27 (quar, J = 6.6Hz, 2H), 7.31-7.38 (m, 3H), 7.47 (d, J = 7.5Hz, 2H), 7.57 (t, J = 7.6Hz, 3H), 8.14 (d, J = 8.6Hz, 2H), 8.44 (s, 1H).
Yield: 85%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.61 (s, 3H), 4.64 (s, 2H), 7.27 (quar, J = 6.6 Hz, 2H), 7.31-7.38 (m, 3H), 7.47 (d , J = 7.5 Hz, 2H), 7.57 (t, J = 7.6 Hz, 3H), 8.14 (d, J = 8.6 Hz, 2H), 8.44 (s, 1H).

(2) 1-페닐-4-알릴티오-6-(메틸티오)피라졸로[3,4-d]피리미딘 [25b](2) 1-phenyl-4-allylthio-6- (methylthio) pyrazolo [3,4-d] pyrimidine [25b]

상기 [9b] (50 mg, 0.182 mmol)와 allyll iodide를 이용하여 옅은 노란색의 고체상 화합물 25b를 얻었다.Light yellow solid compound 25b was obtained using [9b] (50 mg, 0.182 mmol) and allyll iodide.

Yield: 55%; ¹H NMR (400MHz, CDCl₃) δ 2.64 (s, 3H), 4.03 (dd, J = 0.7Hz, 6.9Hz, 2H), 5.20 (d, J = 10.0Hz, 1H), 5.38 (dd, J = 1.1Hz, 16.9Hz, 1H), 5.94-6.04 (m, 1H), 7.31 (t, J = 7.8Hz, 1H), 7.50 (t, J = 7.7Hz, 2H), 8.08 (s, 1H), 8.22 (dd, J = 0.8Hz, 7.8Hz, 2H); ¹³C NMR (100MHz, CDCl₃) δ 14.4, 31.6, 110.6, 118.7, 120.9, 126.4, 129.0, 132.6, 133.0, 138.8, 151.7, 164.1, 169.6.
Yield: 55%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 2.64 (s, 3H), 4.03 (dd, J = 0.7 Hz, 6.9 Hz, 2H), 5.20 (d, J = 10.0 Hz, 1H), 5.38 (dd, J = 1.1Hz, 16.9Hz, 1H), 5.94-6.04 (m, 1H), 7.31 (t, J = 7.8Hz, 1H), 7.50 (t, J = 7.7Hz, 2H), 8.08 (s, 1H), 8.22 (dd, J = 0.8 Hz, 7.8 Hz, 2H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 14.4, 31.6, 110.6, 118.7, 120.9, 126.4, 129.0, 132.6, 133.0, 138.8, 151.7, 164.1, 169.6.

실시예 24. [26a] 내지 [26b]의 합성Example 24. Synthesis of [26a] to [26b]

하기 [반응식 26](chloromethyl pivalate, K₂CO₃, THF, rt, 2h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [26a] 내지 [26b]를 합성하였다.Pyrazolopyrimidine derivative compounds [26a] to [26b] were synthesized by the following Reaction Scheme 26 (chloromethyl pivalate, K ₂ CO ₃ , THF, rt, 2h).

[반응식 26][Reaction Scheme 26]

[4], [10a] [26a] ~ [26b]    [4], [10a] [26a]-[26b]

[26a] 내지 [26b]에서 R₂는 각각 하기 [표 19]와 같다.In [26a] to [26b], each of R ₂ is shown in Table 19 below.

구분division R₂ R ₂ 구분division R₂ R ₂ 26a26a

26b26b

(1) (4-클로로-6-(메틸티오)피라졸로[3,4-d]피리미딘-1-일)메틸피발레이트 [26a](1) (4-chloro-6- (methylthio) pyrazolo [3,4-d] pyrimidin-1-yl) methylpivalate [26a]

상기 [4] (50 mg, 0.249 mmol)와 chloromethyl pivalate (1.2 eq, 0.04 mL), K₂CO₃ (1.2 eq, 41 mg)을 THF (7 mL)에 넣고 상온에서 48 시간 동안 교반하였다. 그 후 용매는 감압기화시키고, flash chromatography (hexanes : EtOAc = 4 : 1)로 분리하면 하얀색의 고체상 화합물 26a를 얻었다.[4] (50 mg, 0.249 mmol), chloromethyl pivalate (1.2 eq, 0.04 mL) and K ₂ CO ₃ (1.2 eq, 41 mg) were added to THF (7 mL) and stirred at room temperature for 48 hours. The solvent was then evaporated under reduced pressure and separated by flash chromatography (hexanes: EtOAc = 4: 1) to obtain a white solid compound 26a.

Yield: 26%; ¹H NMR (400MHz, CDCl₃) δ 1.18 (s, 9H), 2.64 (s, 3H), 6.35 (s, 2H), 8.08 (s, 1H); ¹³C NMR (100MHz, CDCl₃) δ 14.6, 26.9, 38.9, 68.3, 110.8, 134.3, 154.1, 155.0, 171.4, 177.2.
Yield: 26%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 1.18 (s, 9H), 2.64 (s, 3H), 6.35 (s, 2H), 8.08 (s, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 14.6, 26.9, 38.9, 68.3, 110.8, 134.3, 154.1, 155.0, 171.4, 177.2.

(2) (4-메톡시-(메틸티오)피라졸로[3,4-d]피리미딘-1-일)메틸피발레이트 [26b](2) (4-methoxy- (methylthio) pyrazolo [3,4-d] pyrimidin-1-yl) methylpivalate [26b]

상기 [10a]와 chloromethyl pivalate으로 하얀색 고체상 화합물 26b를 얻었다.[10a] and chloromethyl pivalate to obtain a white solid compound 26b.

Yield: 51%; ¹H NMR (400MHz, CD₃OD-d₄) δ 1.15 (s, 9H), 2.62 (s, 3H), 4.13 (s, 3H), 6.31 (s, 2H), 8.05 (s, 1H); ¹³C NMR (100MHz, CD₃OD-d₄) δ 12.9, 25.8, 38.4, 53.6, 68.0, 99.9, 133.2, 156.2, 156.4, 162.9, 171.3, 177.2.
Yield: 51%; ¹ H NMR (400 MHz, CD ₃ OD-d ₄ ) δ 1.15 (s, 9H), 2.62 (s, 3H), 4.13 (s, 3H), 6.31 (s, 2H), 8.05 (s, 1H); ¹³ C NMR (100 MHz, CD ₃ OD-d ₄ ) δ 12.9, 25.8, 38.4, 53.6, 68.0, 99.9, 133.2, 156.2, 156.4, 162.9, 171.3, 177.2.

실시예 25. [27a] 내지 [27i]의 합성Example 25. Synthesis of [27a] to [27i]

하기 [반응식 27]((i) R₂N, 1,4-dioxane, reflux, 8h, (ⅱ) p-TsOH, MeOH, rt, 24h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [27a] 내지 [27b]를 합성하였다.The pyrazolopyrimidine derivative compounds according to the present invention [27a] by the following Reaction Scheme 27 ((i) R ₂ N, 1,4-dioxane, reflux, 8h, (ii) p-TsOH, MeOH, rt, 24h) ] To [27b] were synthesized.

[반응식 27][Reaction Scheme 27]

[5c] [27a] ~ [27i]     [5c] [27a] to [27i]

[27a] 내지 [27i]에서 NR₂는 각각 하기 [표 20]과 같다.In [27a] to [27i], NR ₂ is shown in Table 20 below, respectively.

구분division NR₂ NR ₂ 구분division NR₂ NR ₂ 27a27a

27f27f CH₃OCH ₃ O 27b27b

27g27g

27c27c

27h27h

27d27d

27i27i

27e27e

(1) 1-(1-하이드록시에틸)-4-벤질아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [27a](1) 1- (1-hydroxyethyl) -4-benzylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [27a]

상기 [5c] (57 mg, 0.178 mmol)과 benzylamine을 1,4-dioxane (7 mL)에 넣은 후 8 시간 동안 reflux를 하였다. 그 후 용매를 감압증류하여 얻게 된 반응 혼합물을 EtOAc/H₂O로 희석한 후 유기층만 따로 분리하고, 분리된 유기층은 무수 MgSO₄로 수분을 제거하고 감압증류 하여 무색의 액체상 화합물을 얻었다. 이 화합물을 p-toluenesulfonic acid monohydrate (1 eq)와 함께 methanol (7 mL)에 넣고 24 시간 동안 상온에서 교반하였다. 그 후 1M NaOH 수용액으로 pH 7~8 사이로 조절한 후 감압증류한 후 EtOAc/H₂O로 희석시킨 후 유기층만 따로 분리하였다. 분리된 유기층은 무수 MgSO₄로 수분을 제거하고 감압증류 하고, 이렇게 얻게 된 반응 혼합물을 flash chromatography (hexanes : EtOAc = 1 : 1)로 분리하여 하얀색 고체상 화합물 27a를 얻었다.[5c] (57 mg, 0.178 mmol) and benzylamine were added to 1,4-dioxane (7 mL), followed by reflux for 8 hours. Thereafter, the reaction mixture obtained by distillation of the solvent under reduced pressure was diluted with EtOAc / H ₂ O, and then the organic layer was separated separately. The separated organic layer was distilled under reduced pressure with anhydrous MgSO ₄ to obtain a colorless liquid compound. The compound was added to methanol (7 mL) with p-toluenesulfonic acid monohydrate (1 eq) and stirred at room temperature for 24 hours. Thereafter, the mixture was adjusted to pH 7-8 with 1M aqueous NaOH solution, distilled under reduced pressure, diluted with EtOAc / H ₂ O, and only an organic layer was separated. The separated organic layer was dried with anhydrous MgSO ₄ , distilled under reduced pressure, and the reaction mixture was separated by flash chromatography (hexanes: EtOAc = 1: 1) to obtain a white solid compound 27a.

Yield: 51%; ¹H NMR (400MHz, DMSO-d₆) δ 2.46 (s, 3H), 3.78 (quar, J = 5.8Hz, 2H), 4.26 (t, J = 6.0Hz, 2H), 4.71 (d, J = 5.8Hz, 2H), 4.83 (t, J = 5.6Hz, 1H), 7.23-7.27 (m, 1H), 7.31-7.39 (m, 4H), 8.04 (s, 1H), 8.81 (t, J = 5.7Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 43.7, 49.3, 59.6, 98.6, 127.4, 127.9, 128.8, 132.1, 139.6, 154.1, 155.7, 168.5.
Yield: 51%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.46 (s, 3H), 3.78 (quar, J = 5.8 Hz, 2H), 4.26 (t, J = 6.0 Hz, 2H), 4.71 (d, J = 5.8 Hz, 2H), 4.83 (t, J = 5.6 Hz, 1H), 7.23-7.27 (m, 1H), 7.31-7.39 (m, 4H), 8.04 (s, 1H), 8.81 (t, J = 5.7 Hz , 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 43.7, 49.3, 59.6, 98.6, 127.4, 127.9, 128.8, 132.1, 139.6, 154.1, 155.7, 168.5.

(2) 1-(1-하이드록시에틸)-4-(4-플루오로벤질)벤질아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [27b](2) 1- (1-hydroxyethyl) -4- (4-fluorobenzyl) benzylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [27b]

상기 [5c]와 4-fluorobenzylamine으로 하얀색 고체상 화합물 27b를 얻었다.[5c] and 4-fluorobenzylamine gave white solid compound 27b.

Yield: 41%; ¹H NMR (400MHz, DMSO-d₆) δ 2.46 (s, 3H), 3.78 (t, J = 5.9Hz, 2H), 4.25 (t, J = 6.0Hz, 2H), 4.69 (d, J = 5.6Hz, 2H), 4.83 (br s, 1H), 7.16 (t, J = 8.9Hz, 2H), 7.39 (quar, J = 4.7Hz, 2H), 8.03 (s, 1H), 8.82 (t, J = 5.6Hz, 1H).
Yield: 41%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.46 (s, 3H), 3.78 (t, J = 5.9 Hz, 2H), 4.25 (t, J = 6.0 Hz, 2H), 4.69 (d, J = 5.6 Hz, 2H), 4.83 (br s, 1H), 7.16 (t, J = 8.9 Hz, 2H), 7.39 (quar, J = 4.7 Hz, 2H), 8.03 (s, 1H), 8.82 (t, J = 5.6 Hz, 1H).

(3) 1-(1-하이드록시에틸)-4-알릴아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [27d](3) 1- (1-hydroxyethyl) -4-allylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [27d]

상기 [5c]와 allylamine으로 하얀색 고체상 화합물 27c를 얻었다.The white solid compound 27c was obtained from [5c] and allylamine.

Yield: 72%; ¹H NMR (400MHz, DMSO-d₆) δ 2.48 (s, 3H), 3.78 (quar, J = 5.6Hz, 2H), 4.13 (t, J = 5.5Hz, 2H), 4.25 (t, J = 6.1Hz, 2H), 4.84 (t, J = 5.2Hz, 1H), 5.13 (dd, J = 1.5Hz, 10.3Hz, 1H), 5.22 (dd, J = 1.6Hz, 17.2Hz, 1H), 5.90-6.00 (m, 1H), 8.03 (s, 1H), 8.47 (t, J = 5.4Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.0, 42.6, 49.3, 59.6, 98.6, 116.3, 132.1, 135.4, 154.1, 155.6, 168.5.
Yield: 72%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.48 (s, 3H), 3.78 (quar, J = 5.6 Hz, 2H), 4.13 (t, J = 5.5 Hz, 2H), 4.25 (t, J = 6.1 Hz, 2H), 4.84 (t, J = 5.2 Hz, 1H), 5.13 (dd, J = 1.5 Hz, 10.3 Hz, 1H), 5.22 (dd, J = 1.6 Hz, 17.2 Hz, 1H), 5.90-6.00 (m, 1 H), 8.03 (s, 1 H), 8.47 (t, J = 5.4 Hz, 1 H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.0, 42.6, 49.3, 59.6, 98.6, 116.3, 132.1, 135.4, 154.1, 155.6, 168.5.

(4) 1-(1-하이드록시에틸)-4-(3-메톡시벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [27d](4) 1- (1-hydroxyethyl) -4- (3-methoxybenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [27d]

상기 [5c]와 3-methoxybenzylamine으로 하얀색 고체상 화합물 27d를 얻었다.A white solid compound 27d was obtained from [5c] and 3-methoxybenzylamine.

Yield: 76%; ¹H NMR (400MHz, DMSO-d₆) δ 2.46 (s, 3H), 3.73 (s, 3H), 3.78 (quar, J = 5.6Hz, 2H), 4.26 (t, J = 5.9Hz, 2H), 4.68 (d, J = 5.7Hz, 2H), 4.83 (t, J = 5.2Hz, 1H), 6.83 (d, J = 7.8Hz, 1H), 6.92 (d, J = 8.3Hz, 2H), 7.25 (t, J = 7.8Hz, 1H), 8.04 (s, 1H), 8.79 (t, J = 5.6Hz, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.4, 43.1, 48.7, 54.8, 59.1, 98.0, 112.1, 113.2, 119.5, 129.3, 131.5, 140.7, 155.1, 159.2, 167.9.
Yield: 76%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.46 (s, 3H), 3.73 (s, 3H), 3.78 (quar, J = 5.6 Hz, 2H), 4.26 (t, J = 5.9 Hz, 2H), 4.68 (d, J = 5.7 Hz, 2H), 4.83 (t, J = 5.2 Hz, 1H), 6.83 (d, J = 7.8 Hz, 1H), 6.92 (d, J = 8.3 Hz, 2H), 7.25 ( t, J = 7.8 Hz, 1H), 8.04 (s, 1H), 8.79 (t, J = 5.6 Hz, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.4, 43.1, 48.7, 54.8, 59.1, 98.0, 112.1, 113.2, 119.5, 129.3, 131.5, 140.7, 155.1, 159.2, 167.9.

(5) 1-(1-하이드록시에틸)-4-(4-메톡시벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [27e](5) 1- (1-hydroxyethyl) -4- (4-methoxybenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [27e]

상기 [5c]와 4-methoxybenzylamine으로 하얀색 고체상 화합물 27e를 얻었다.The white solid compound 27e was obtained from [5c] and 4-methoxybenzylamine.

Yield: 72%; ¹H NMR (400MHz, DMSO-d₆) δ 2.48 (s, 3H), 3.72 (s, 3H), 3.77 (br s, 2H), 4.25 (t, J = 6.1Hz, 2H), 4.63 (d, J = 5.7Hz, 2H), 4.83 (br s, 1H), 6.90 (dt, J = 2.4Hz, 9.3Hz, 2H), 7.28 (d, J = 8.6Hz, 2H), 8.03 (s, 1H), 8.74 (t, J = 5.6Hz, 1H); ¹³C NMR (400MHz, DMSO-d₆) δ 14.0, 43.2, 49.3, 55.5, 59.6, 98.6, 114.2, 129.3, 131.5, 132.1, 154.1, 155.6, 158.8, 168.5.
Yield: 72%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.48 (s, 3H), 3.72 (s, 3H), 3.77 (br s, 2H), 4.25 (t, J = 6.1 Hz, 2H), 4.63 (d, J = 5.7 Hz, 2H), 4.83 (br s, 1H), 6.90 (dt, J = 2.4 Hz, 9.3 Hz, 2H), 7.28 (d, J = 8.6 Hz, 2H), 8.03 (s, 1H), 8.74 (t, J = 5.6 Hz, 1H); ¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 14.0, 43.2, 49.3, 55.5, 59.6, 98.6, 114.2, 129.3, 131.5, 132.1, 154.1, 155.6, 158.8, 168.5.

(6) 2-(4-메톡시-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-1-일)에탄올 [27f](6) 2- (4-methoxy-6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) ethanol [27f]

상기 [5c]와 sodium methoxide으로 하얀색 고체상 화합물 27f를 얻었다.[5c] and sodium methoxide afforded a white solid compound 27f.

Yield: 32%; ¹H NMR (400MHz, DMSO-d₆) δ 2.59 (s, 3H), 3.83 (quar, J = 5.8Hz, 2H), 4.07 (s, 3H), 4.36 (t, J = 5.8Hz, 2H), 4.85 (t, J = 5.6Hz, 1H), 8.11 (s, 1H); ¹³C NMR (400MHz, DMSO-d₆) δ 0.56, 14.2, 49.8, 54.7, 59.5, 99.7, 131.6, 155.8, 162.8, 168.8.
Yield: 32%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.59 (s, 3H), 3.83 (quar, J = 5.8 Hz, 2H), 4.07 (s, 3H), 4.36 (t, J = 5.8 Hz, 2H), 4.85 (t, J = 5.6 Hz, 1 H), 8.11 (s, 1 H); ¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 0.56, 14.2, 49.8, 54.7, 59.5, 99.7, 131.6, 155.8, 162.8, 168.8.

(7) 2-(4-(2-메틸벤질아미노)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-1-일)에탄올 [27g](7) 2- (4- (2-methylbenzylamino) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) ethanol [27 g]

상기 [5c]와 2-methylbenzylamine으로 하얀색 고체상 화합물 27g를 얻었다.27g of a white solid compound was obtained from [5c] and 2-methylbenzylamine.

Yield: 67.77%; ¹H NMR (400MHz, DMSO-d₆) δ 1.24 (d, J = 5.8Hz, 3H), 2.47 (s, 3H), 3.82 (t, J = 5.5Hz, 2H), 4.30 (t, J = 5.9Hz, 2H), 4.81-4.86 (m, 2H), 7.72 (s, 2H), 8.02 (s, 2H), 9.19 (s, 1H), 9.85 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.8, 22.3, 49.5, 59.5, 69.0, 96.9, 125.9, 128.5, 131.7, 132.4, 154.3, 155.1, 156.4, 156.8, 160.0, 168.2.
Yield: 67.77%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.24 (d, J = 5.8 Hz, 3H), 2.47 (s, 3H), 3.82 (t, J = 5.5 Hz, 2H), 4.30 (t, J = 5.9 Hz, 2H), 4.81-4.86 (m, 2H), 7.72 (s, 2H), 8.02 (s, 2H), 9.19 (s, 1H), 9.85 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.8, 22.3, 49.5, 59.5, 69.0, 96.9, 125.9, 128.5, 131.7, 132.4, 154.3, 155.1, 156.4, 156.8, 160.0, 168.2.

(8) 2-(4-(2-클로로벤질아미노)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-1-일)에탄올 [27h](8) 2- (4- (2-chlorobenzylamino) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) ethanol [27h]

상기 [5c]와 2-chlorobenzylamine으로 하얀색 고체상 화합물 27h를 얻었다.The white solid compound 27h was obtained from [5c] and 2-chlorobenzylamine.

Yield: 71.29%; ¹H NMR (400MHz, DMSO-d₆) δ 2.51 (s, 3H), 3.78-3.83 (m, 2H), 4.30 (t, J = 5.9Hz, 2H), 4.82-4.87 (m, 2H), 7.72 (s, 2H), 8.01 (s, 2H), 9.22 (s, 1H), 9.84 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.2, 21.8, 48.8, 58.9, 59.0, 68.0, 68.4, 96.3, 131.1, 131.8, 154.5, 155.8, 167.6.
Yield: 71.29%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.51 (s, 3H), 3.78-3.83 (m, 2H), 4.30 (t, J = 5.9 Hz, 2H), 4.82-4.87 (m, 2H), 7.72 (s, 2H), 8.01 (s, 2H), 9.22 (s, 1H), 9.84 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.2, 21.8, 48.8, 58.9, 59.0, 68.0, 68.4, 96.3, 131.1, 131.8, 154.5, 155.8, 167.6.

(9) 2-(4-(2-메톡시벤질아미노)-6-(메틸티오)-1H-피라졸로[3,4-d]피리미딘-1-일)에탄올 [27i](9) 2- (4- (2-methoxybenzylamino) -6- (methylthio) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) ethanol [27i]

상기 [5c]와 2-methoxybenzylamine으로 하얀색 고체상 화합물 27i를 얻었다.A white solid compound 27i was obtained from [5c] and 2-methoxybenzylamine.

Yield: 69.47%; ¹H NMR (400MHz, DMSO-d₆) δ 1.24 (S, 3H), 2.51 (s, 3H), 3.81 (s, 2H), 4.30 (d, J = 4.5Hz, 2H), 4.84-4.88 (m, 2H), 7.71 (s, 2H), 8.04 (s, 2H), 9.27 (s, 1H), 9.83 (s, 1H); ¹³C NMR (100MHz, DMSO-d₆) δ 13.2, 21.8, 48.8, 58.9, 59.0, 68.0, 68.4, 96.3, 131.1, 131.8, 154.5, 155.8, 167.6.
Yield: 69.47%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.24 (S, 3H), 2.51 (s, 3H), 3.81 (s, 2H), 4.30 (d, J = 4.5 Hz, 2H), 4.84-4.88 (m , 2H), 7.71 (s, 2H), 8.04 (s, 2H), 9.27 (s, 1H), 9.83 (s, 1H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 13.2, 21.8, 48.8, 58.9, 59.0, 68.0, 68.4, 96.3, 131.1, 131.8, 154.5, 155.8, 167.6.

실시예 26. [Ⅵ] 내지 [Ⅶ]의 합성Example 26. Synthesis of [VI] to [VII]

하기 [반응식 28]((i) Benzaldehyde, LDA, N₂, THF, -78 ℃, 2h; (ⅱ) CrO₃, acetone, N₂, 0 ℃, 3h; (ⅲ) Benzoyl chloride, LDA, N₂, THF, -78 ℃, 6h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [Ⅵ] 내지 [Ⅶ]를 합성하였다.(Scheme 28) ((i) Benzaldehyde, LDA, N ₂ , THF, -78 ° C, 2h; (ii) CrO ₃ , acetone, N ₂ , 0 ° C, 3h; (iii) Benzoyl chloride, LDA, N ₂ , THF, -78 ° C, 6h) to synthesize pyrazolopyrimidine derivative compounds [VI] to [VII] according to the present invention.

[반응식 28][Reaction Scheme 28]

[3] [Ⅵ] [Ⅶ]
[3] [Ⅵ] [Ⅶ]

(1) 1-[(4,6-다이클로로-2-(메틸티오)피리미딘)-5-일]-벤질알콜 [Ⅵ](1) 1-[(4,6-dichloro-2- (methylthio) pyrimidin) -5-yl] -benzyl alcohol [VI]

상기 [3] (100 mg, 0.513 mmol)이 녹아있는 THF (5 mL)를 N_{2 (g)}하에 -78 ℃로 냉각시킨 다음 lithium diisopropylamide (1.8 eq, 0.5 mL)을 천천히 넣어주었다. 20 분간 교반한 후, benzaldehyde (2 eq, 0.1 mL)를 천천히 넣어주었다. 그리고 2 시간을 교반한 후, 상온으로 온도를 올리고 포화 NH₄Cl 수용액 (5 mL)으로 여분의 lithium diisopropylamide를 제거하였다. 그리고 EtOAc (5 mL)을 가하여 30 분을 교반한 후, 유기층만을 분리하여 무수 MgSO₄로 수분을 제거하였다. 분리된 유기층은 감압증류하고 생성된 혼합물은 flash chromatography (hexanes : EtOAc = 5 : 1)로 분리하여 갈색의 액체상 화합물 [Ⅵ]를 얻었다.THF (5 mL) in which [3] (100 mg, 0.513 mmol) was dissolved was cooled to −78 ° C. under N _{2 (g)} , and lithium diisopropylamide (1.8 eq, 0.5 mL) was slowly added thereto. After stirring for 20 minutes, benzaldehyde (2 eq, 0.1 mL) was added slowly. After stirring for 2 hours, the temperature was raised to room temperature and excess lithium diisopropylamide was removed with a saturated NH ₄ Cl aqueous solution (5 mL). Then, EtOAc (5 mL) was added, the mixture was stirred for 30 minutes, and only the organic layer was separated, and water was removed with anhydrous MgSO ₄ . The separated organic layer was distilled under reduced pressure and the resulting mixture was separated by flash chromatography (hexanes: EtOAc = 5: 1) to obtain a brown liquid compound [VI].

Yield: 32%; ¹H NMR (400MHz, CDCl₃) δ 2.57 (s, 3H), 3.19 (d, J = 6.7Hz, 1H), 6.49 (d, J = 5.4Hz, 1H), 7.34 (m, 5H); ¹³C NMR (100MHz, CDCl₃) δ 14.4, 70.6, 125.2, 126.8, 127.8, 128.5, 139.8, 161.0, 172.4.
Yield: 32%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 2.57 (s, 3H), 3.19 (d, J = 6.7 Hz, 1H), 6.49 (d, J = 5.4 Hz, 1H), 7.34 (m, 5H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 14.4, 70.6, 125.2, 126.8, 127.8, 128.5, 139.8, 161.0, 172.4.

(2) 1-[(4,6-다이클로로-2-(메틸티오)피리미딘)-5-일]-페닐케톤 [Ⅶ](2) 1-[(4,6-dichloro-2- (methylthio) pyrimidin) -5-yl] -phenylketone [Ⅶ]

상기 [3] (100 mg, 0.513 mmol)을 N_{2 (g)}하에서 chromic oxide(V) (3 eq, 50 mg)을 aetone (5 mL)에 녹인 후 0 ℃로 냉각시켰다. 냉각이 되어 있는 반응 용기에 acetone (2 mL)에 녹인 상기 [Ⅵ] (50 mg, 0.166 mmol)을 넣어주고 3 시간 동안 교반하였다. 과량의 chromic oxide(V)은 포화 NaHCO₃ 수용액을 가하면 침전되는데, 이 침전물은 여과하여 제거하고, 여과액에 Et₂O를 가하여 추출하였다. 유기층만을 분리하여 무수 MgSO₄로 수분을 제거하고, 감압증류 시켜서 옅은 노란색의 고체상 화합물 [Ⅶ]를 얻었다.[3] (100 mg, 0.513 mmol) was dissolved in chromic oxide (V) (3 eq, 50 mg) in aetone (5 mL) under N _{2 (g)} and cooled to 0 ° C. [VI] (50 mg, 0.166 mmol) dissolved in acetone (2 mL) was added to a cooled reaction vessel, followed by stirring for 3 hours. Excess chromic oxide (V) was precipitated by addition of saturated aqueous NaHCO ₃ solution. The precipitate was filtered off and extracted by adding Et ₂ O to the filtrate. Only the organic layer was separated, the water was removed with anhydrous MgSO ₄ , and distilled under reduced pressure to obtain a pale yellow solid compound [VIII].

Yield: 82%; ¹H NMR (400MHz, CDCl₃) δ 2.62 (s, 3H), 7.53 (t, J = 7.7Hz, 2H), 7.68 (quar, J = 7.7Hz, 1H), 7.85 (d, J = 7.9Hz, 2H); ¹³C NMR (100MHz, CDCl₃) δ 14.5, 125.7, 129.2, 129.5, 134.9, 157.9, 174.3, 189.3.
Yield: 82%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 2.62 (s, 3H), 7.53 (t, J = 7.7 Hz, 2H), 7.68 (quar, J = 7.7 Hz, 1H), 7.85 (d, J = 7.9 Hz, 2H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 14.5, 125.7, 129.2, 129.5, 134.9, 157.9, 174.3, 189.3.

실시예 27. [30a] 내지 [30c]의 합성Example 27. Synthesis of [30a] to [30c]

하기 [반응식 29](R₁-N₂H₄, Hunig base, THF, rt, 24h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [30a] 내지 [30c]를 합성하였다.The pyrazolopyrimidine derivative compounds [30a] to [30c] were synthesized according to the following Reaction Scheme 29 (R ₁ -N ₂ H ₄ , Hunig base, THF, rt, 24h).

[반응식 29][Reaction Scheme 29]

[Ⅶ] [30a] ~ [30c]       [Ⅶ] [30a] ~ [30c]

[30a] 내지 [30c]에서 R₁은 각각 하기 [표 21]과 같다.In [30a] to [30c], R ₁ is as shown in Table 21 below.

구분division R₁ R ₁ 구분division R₁ R ₁ 30a30a

30c30c

30b30b

(1) 1-페닐-3-페닐-4-클로로-6-(메틸티오)피라졸로[3,4-d]피리미딘 [30a](1) 1-phenyl-3-phenyl-4-chloro-6- (methylthio) pyrazolo [3,4-d] pyrimidine [30a]

상기 [Ⅶ] (200 mg, 0.668 mmol)과 Hunig base (1 eg, 0.02 mL)을 THF에 넣고 교반 중에 phenylhydrazine을 천천히 가하면서, 모두 가한 후에 24 시간 동안 상온에서 교반한 후 용매를 감압증류 하여 감소시키고 EtOAc/H₂O로 희석시킨 후 유기층만 따로 분리하였다. 분리된 유기층은 무수 MgSO₄로 수분을 제거하고 여기서 얻게 된 반응 혼합물을 flash chromatography (hexanes : EtOAc = 8 : 1)로 하여 분리하여 옅은 노란색의 고체상 화합물 30a을 얻었다.Add [iii] (200 mg, 0.668 mmol) and Hunig base (1 eg, 0.02 mL) to THF, slowly add phenylhydrazine while stirring, and after adding all, stir at room temperature for 24 hours, and then reduce the solvent by distillation under reduced pressure. And diluted with EtOAc / H ₂ O, only the organic layer was separated. The separated organic layer was dried with anhydrous MgSO ₄ , and the obtained reaction mixture was separated by flash chromatography (hexanes: EtOAc = 8: 1) to obtain a pale yellow solid compound 30a.

Yield: 72%; ¹H NMR (400MHz, DMSO-d₆) δ 2.59 (s, 3H), 7.40-7.68 (m, 10H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.4, 109.2, 126.6, 127.6, 128.7, 129.5, 129.8, 130.5, 131.6, 138.9, 139.4, 156.2, 159.7, 168.7.
Yield: 72%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.59 (s, 3H), 7.40-7.68 (m, 10H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.4, 109.2, 126.6, 127.6, 128.7, 129.5, 129.8, 130.5, 131.6, 138.9, 139.4, 156.2, 159.7, 168.7.

(2) 1-벤질-3-페닐-4-클로로-6-(메틸티오)피라졸로[3,4-d]피리미딘 [30b](2) 1-benzyl-3-phenyl-4-chloro-6- (methylthio) pyrazolo [3,4-d] pyrimidine [30b]

상기 [Ⅶ]와 benzylhydrazine dihydrochloride으로 옅은 노란색의 고체상 화합물 30b를 얻었다.[B] and benzylhydrazine dihydrochloride were obtained as a pale yellow solid compound 30b.

Yield: 61%; ¹H NMR (400MHz, DMSO-d₆) δ 2.63 (s, 3H), 5.64 (s, 2H), 7.28-7.36 (m, 5H), 7.48-7.50 (m, 3H), 7.71-7.73 (m, 2H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.4, 51.0, 107.9, 128.3, 128.4, 128.6, 129.1, 129.6, 130.6, 131.2, 136.6, 145.1, 153.9, 154.9, 169.4.
Yield: 61%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.63 (s, 3H), 5.64 (s, 2H), 7.28-7.36 (m, 5H), 7.48-7.50 (m, 3H), 7.71-7.73 (m, 2H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.4, 51.0, 107.9, 128.3, 128.4, 128.6, 129.1, 129.6, 130.6, 131.2, 136.6, 145.1, 153.9, 154.9, 169.4.

(3) 1-t-뷰틸-3-페닐-4-클로로-6-(메틸티오)피라졸로[3,4-d]피리미딘 [30c](3) 1-t-butyl-3-phenyl-4-chloro-6- (methylthio) pyrazolo [3,4-d] pyrimidine [30c]

상기 [Ⅶ]와 t-butylhydrazine hydrochloride으로 옅은 노란색의 고체상 화합물 30c를 얻었다.A pale yellow solid compound 30c was obtained from [K] and t-butylhydrazine hydrochloride.

Yield: 8%; ¹H NMR (400MHz, CDCl₃) δ 1.60 (s, 9H), 2.66 (s, 3H), 7.40 (d, J = 7.9Hz, 2H), 7.47-7.56 (m, 3H).
Yield: 8%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 1.60 (s, 9H), 2.66 (s, 3H), 7.40 (d, J = 7.9 Hz, 2H), 7.47-7.56 (m, 3H).

실시예 28. [31a] 내지 [31k]의 합성Example 28. Synthesis of [31a] to [31k]

하기 [반응식 30](R₂N, 1,4-dioxane, reflux, 8h)에 의해서 본 발명에 따른 피라졸로피리미딘 유도체 화합물 [31a] 내지 [31k]를 합성하였다.The pyrazolopyrimidine derivative compounds [31a] to [31k] were synthesized according to the following Reaction Scheme 30 (R ₂ N, 1,4-dioxane, reflux, 8h).

[반응식 30][Reaction Scheme 30]

[30a] ~ [30c] [31a] ~ [31k]   [30a] to [30c] [31a] to [31k]

[31a] 내지 [31k]에서 R₂는 각각 하기 [표 22]와 같다.R ₂ in [31a] to [31k] is as shown in [Table 22], respectively.

구분division R₁ R ₁ 구분division R₁ R ₁ 31a31a

31g31 g

31b31b

31h31h

31c31c

31i31i

31d31d

31j31j

31e31e

31k31k

31f31f

(1) 1-페닐-3-페닐-4-벤질아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [31a](1) 1-phenyl-3-phenyl-4-benzylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [31a]

상기 [30a](28 mg, 0.079 mmol)와 benzylamine (1.1 eq, 0.01 mL)을 1,4-dioxane에 넣고, 8시간동안 reflux 하였다. 그 후 용매는 감압증류를 하여 얻은 반응혼합물은 EA/H₂O로 희석을 한 후 유기층만 따로 분리하였다. 분리된 유기층은 무수 MgSO₄로 수분을 제거한 후, flash chromatography (MC : MeOH = 10 : 1)로 분리하여 옅은 갈색의 고체상 화합물 31a를 얻었다.[30a] (28 mg, 0.079 mmol) and benzylamine (1.1 eq, 0.01 mL) were added to 1,4-dioxane and refluxed for 8 hours. After that, the solvent was distilled under reduced pressure, and the reaction mixture was diluted with EA / H ₂ O, and only the organic layer was separated. The separated organic layer was dried with anhydrous MgSO ₄ , and then separated by flash chromatography (MC: MeOH = 10: 1) to give a pale brown solid compound 31a.

Yield: 95%; ¹H NMR (400MHz, CDCl₃) δ 2.62 (s, 3H), 4.69 (d, J = 5.3Hz, 2H), 5.29 (br s, 1H), 7.18 (d, J = 6.9Hz, 2H), 7.24-7.41 (m, 13H); ¹³C NMR (100MHz, CDCl₃) δ 14.2, 44.6, 100.2, 125.3, 127.4, 127.4, 128.1, 128.2, 128.6, 128.8, 129.4, 129.5, 129.7, 130.7, 135.8, 137.8, 139.0, 156.7, 160.7, 161.9, 170.6.
Yield: 95%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 2.62 (s, 3H), 4.69 (d, J = 5.3 Hz, 2H), 5.29 (br s, 1H), 7.18 (d, J = 6.9 Hz, 2H), 7.24 -7.41 (m, 13 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 14.2, 44.6, 100.2, 125.3, 127.4, 127.4, 128.1, 128.2, 128.6, 128.8, 129.4, 129.5, 129.7, 130.7, 135.8, 137.8, 139.0, 156.7, 160.7, 161.9, 170.6.

(2) 1-페닐-3-페닐-4-(1-하이드록시에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [31b](2) 1-phenyl-3-phenyl-4- (1-hydroxyethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [31b]

상기 [30a]와 1-hydroxyethylamine으로 하얀색의 고체상 화합물 31b를 얻었다.White solid compound 31b was obtained by using [30a] and 1-hydroxyethylamine.

Yield: 90%; ¹H NMR (400MHz, DMSO-d₆) δ 2.48 (s, 3H), 3.44 (s, 4H), 4.71 (br s, 1H), 5.85 (br s, 1H), 7.29-7.48 (m, 10H).
Yield: 90%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.48 (s, 3H), 3.44 (s, 4H), 4.71 (br s, 1H), 5.85 (br s, 1H), 7.29-7.48 (m, 10H) .

(3) 1-페닐-3-페닐-4-(4-플루오로벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [31c](3) 1-phenyl-3-phenyl-4- (4-fluorobenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [31c]

상기 [30a]와 4-fluorobenzylamine으로 옅은 노란색의 고체상 화합물 31c를 얻었다.A pale yellow solid compound 31c was obtained from [30a] and 4-fluorobenzylamine.

Yield: 97%; ¹H NMR (400MHz, DMSO-d₆) δ 2.44 (s, 3H), 4.59 (d, J = 5.7Hz, 2H), 6.36 (t, J = 5.8Hz, 1H), 7.12 (t, J = 8.9Hz, 2H), 7.27-7.30 (m, 4H), 7.34-7.48 (m, 8H).
Yield: 97%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.44 (s, 3H), 4.59 (d, J = 5.7 Hz, 2H), 6.36 (t, J = 5.8 Hz, 1H), 7.12 (t, J = 8.9 Hz, 2H), 7.27-7.30 (m, 4H), 7.34-7.48 (m, 8H).

(4) 1-페닐-3-페닐-4-[2-(피페리딘-1-일)]에칠아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [31d](4) 1-phenyl-3-phenyl-4- [2- (piperidin-1-yl)] ethylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [31d]

상기 [30a]와 2-(piperidin-1-yl)ethylamine으로 옅은 노란색의 고체상 화합물 31d를 얻었다.A pale yellow solid compound 31d was obtained from [30a] and 2- (piperidin-1-yl) ethylamine.

Yield: 52%; ¹H NMR (400MHz, DMSO-d₆) δ 1.26 (br s, 6H), 2.15 (br s, 4H), 2.33 (t, J = 5.6Hz, 2H), 2.49 (s, 3H), 3.42-3.43 (m, 2H), 5.96 (s, 1H), 7.28-7.50 (m, 10H).
Yield: 52%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.26 (br s, 6H), 2.15 (br s, 4H), 2.33 (t, J = 5.6 Hz, 2H), 2.49 (s, 3H), 3.42-3.43 (m, 2H), 5.96 (s, 1H), 7.28-7.50 (m, 10H).

(5) 1-페닐-3-페닐-4-(2-페닐에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [31e](5) 1-phenyl-3-phenyl-4- (2-phenylethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [31e]

상기 [30a]와 2-phenylethylamine으로 옅은 노란색의 고체상 화합물 31e를 얻었다.A pale yellow solid compound 31e was obtained from [30a] and 2-phenylethylamine.

Yield: 90%; ¹H NMR (400MHz, DMSO-d₆) δ 2.50 (s, 3H), 2.78 (t, J = 6.7Hz, 2H), 3.63 (quar, J = 6.3Hz, 2H), 5.66 (t, J = 5.2Hz, 1H), 7.09 (d, J = 7.7Hz, 2H), 7.18-7.27 (m, 7H), 7.35-7.38 (m, 5H), 7.44-7.47 (m, 1H).
Yield: 90%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.50 (s, 3H), 2.78 (t, J = 6.7 Hz, 2H), 3.63 (quar, J = 6.3 Hz, 2H), 5.66 (t, J = 5.2 Hz, 1H), 7.09 (d, J = 7.7 Hz, 2H), 7.18-7.27 (m, 7H), 7.35-7.38 (m, 5H), 7.44-7.47 (m, 1H).

(6) 1-페닐-3-페닐-4-(피리딘-2-일)메틸아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [31f](6) 1-phenyl-3-phenyl-4- (pyridin-2-yl) methylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [31f]

상기 [30a]와 (pyridin-2-yl)methylamine으로 옅은 노란색의 고체상 화합물 31f를 얻었다.A pale yellow solid compound 31f was obtained from [30a] and (pyridin-2-yl) methylamine.

Yield: 99%; ¹H NMR (400MHz, DMSO-d₆) δ 2.47 (s, 3H), 4.67 (d, J = 4.2Hz, 2H), 7.06 (t, J = 4.2Hz, 1H), 7.26 (t, J = 6.1Hz, 1H), 7.36-7.41 (m, 6H), 7.47-7.57 (m, 6H), 7.75 (t, J = 6.9Hz, 1H), 8.31 (d, J = 4.7Hz, 1H).
Yield: 99%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.47 (s, 3H), 4.67 (d, J = 4.2 Hz, 2H), 7.06 (t, J = 4.2 Hz, 1H), 7.26 (t, J = 6.1 Hz, 1H), 7.36-7.41 (m, 6H), 7.47-7.57 (m, 6H), 7.75 (t, J = 6.9 Hz, 1H), 8.31 (d, J = 4.7 Hz, 1H).

(7) 1-페닐-3-페닐-4-알릴아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [31g](7) 1-phenyl-3-phenyl-4-allylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [31 g]

상기 [30a]와 allylamine으로 옅은 노란색의 고체상 화합물 31g를 얻었다.31 g of a pale yellow solid compound was obtained using [30a] and allylamine.

Yield: 98%; ¹H NMR (400MHz, DMSO-d₆) δ 2.47 (s, 3H), 4.03 (s, 2H), 4.99-5.04 (m, 2H), 5.79-5.88 (m, 2H), 7.28-7.30 (m, 2H), 7.36-7.49 (m, 8H).
Yield: 98%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.47 (s, 3H), 4.03 (s, 2H), 4.99-5.04 (m, 2H), 5.79-5.88 (m, 2H), 7.28-7.30 (m, 2H), 7.36-7.49 (m, 8H).

(8) 1-벤질-3-페닐-4-벤질아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [31h](8) 1-benzyl-3-phenyl-4-benzylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [31h]

상기 [30b]와 benzylamine으로 옅은 노란색의 고체상 화합물 31h를 얻었다.31h was obtained as a pale yellow solid compound using [30b] and benzylamine.

Yield: 78%; ¹H NMR (400MHz, DMSO-d₆) δ 2.46 (s, 3H), 4.68 (d, J = 5.7Hz, 2H), 5.49 (s, 2H), 6.98 (t, J = 5.6Hz, 1H), 7.08-7.39 (m, 9H), 7.42-7.51 (m, 4H), 7.65 (d, J = 7.8Hz, 2H); ¹³C NMR (100MHz, DMSO-d₆) δ 14.1, 44.4, 50.2, 95.8, 127.2, 127.6, 128.0, 128.2, 128.6, 128.7, 129.0, 133.2, 137.5, 139.6, 144.4, 155.2, 156.0, 169.0.
Yield: 78%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.46 (s, 3H), 4.68 (d, J = 5.7 Hz, 2H), 5.49 (s, 2H), 6.98 (t, J = 5.6 Hz, 1H), 7.08-7.39 (m, 9H), 7.42-7.51 (m, 4H), 7.65 (d, J = 7.8 Hz, 2H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 14.1, 44.4, 50.2, 95.8, 127.2, 127.6, 128.0, 128.2, 128.6, 128.7, 129.0, 133.2, 137.5, 139.6, 144.4, 155.2, 156.0, 169.0.

(9) 1-벤질-3-페닐-4-(1-하이드록시에틸)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [31i](9) 1-benzyl-3-phenyl-4- (1-hydroxyethyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [31i]

상기 [30b]와 1-hydroxyethylamine으로 하얀색의 고체상 화합물 31i를 얻었다.White solid compound 31i was obtained from [30b] and 1-hydroxyethylamine.

Yield: 79%; ¹H NMR (400MHz, CDCl₃) δ 2.57 (s, 3H), 3.70 (dt, J = 4.6Hz, 34.4Hz, 4H), 5.53 (s, 2H), 5.79 (t, J = 5.1Hz, 1H), 7.22-7.31 (m, 3H), 7.37-7.48 (m, 5H), 7.62 (d, J = 7.0Hz, 2H); ¹³C NMR (100MHz, CDCl₃) δ 14.2, 43.8, 50.6, 62.6, 96.2, 127.7, 128.2, 128.3, 128.5, 129.0, 129.3, 133.3, 136.7, 144.4, 154.8, 156.5, 169.6.
Yield: 79%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 2.57 (s, 3H), 3.70 (dt, J = 4.6 Hz, 34.4 Hz, 4H), 5.53 (s, 2H), 5.79 (t, J = 5.1 Hz, 1H) , 7.22-7.31 (m, 3H), 7.37-7.48 (m, 5H), 7.62 (d, J = 7.0 Hz, 2H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 14.2, 43.8, 50.6, 62.6, 96.2, 127.7, 128.2, 128.3, 128.5, 129.0, 129.3, 133.3, 136.7, 144.4, 154.8, 156.5, 169.6.

(10) 1-벤질-3-페닐-4-(4-플루오로벤질)아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [31j](10) 1-benzyl-3-phenyl-4- (4-fluorobenzyl) amino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [31j]

상기 [30b]와 4-fluorobenzylamine으로 옅은 노란색의 고체상 화합물 31j를 얻었다.A pale yellow solid compound 31j was obtained from [30b] and 4-fluorobenzylamine.

Yield: 77%; ¹H NMR (400MHz, DMSO-d₆) δ 2.45 (s, 3H), 4.63 (d, J = 5.6Hz, 2H), 5.48 (s, 2H), 7.01-7.18 (m, 4H), 7.23-7.39 (m, 8H), 7.64 (d, J = 7.8Hz, 2H).
Yield: 77%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.45 (s, 3H), 4.63 (d, J = 5.6 Hz, 2H), 5.48 (s, 2H), 7.01-7.18 (m, 4H), 7.23-7.39 (m, 8H), 7.64 (d, J = 7.8 Hz, 2H).

(11) 1-벤질-3-페닐-4-알릴아미노-6-(메틸티오)피라졸로[3,4-d]피리미딘 [31k](11) 1-benzyl-3-phenyl-4-allylamino-6- (methylthio) pyrazolo [3,4-d] pyrimidine [31k]

상기 [30b]와 allylamine으로 옅은 노란색의 고체상 화합물 31k를 얻었다.31k of pale yellow solid compound was obtained using [30b] and allylamine.

Yield: 69%; ¹H NMR (400MHz, CDCl₃) δ 2.59 (s, 3H), 4.19 (t, J = 5.4Hz, 2H), 5.10-5.12 (m, 1H), 5.15 (s, 1H), 5.38 (t, J = 5.1Hz, 1H), 5.54 (s, 2H), 5.84-5.94 (m, 1H), 7.22-7.31 (m, 3H), 7.38-7.51 (m, 5H), 7.64 (d, J = 7.9Hz, 2H); ¹³C NMR (100MHz, CDCl₃) δ 14.3, 43.0, 50.6, 96.3, 116.3, 127.7, 128.2, 128.4, 128.5, 129.0, 129.3, 133.5, 133.9, 136.9, 144.2, 155.1, 155.7, 169.8.
Yield: 69%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 2.59 (s, 3H), 4.19 (t, J = 5.4 Hz, 2H), 5.10-5.12 (m, 1H), 5.15 (s, 1H), 5.38 (t, J = 5.1 Hz, 1H), 5.54 (s, 2H), 5.84-5.94 (m, 1H), 7.22-7.31 (m, 3H), 7.38-7.51 (m, 5H), 7.64 (d, J = 7.9 Hz, 2H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 14.3, 43.0, 50.6, 96.3, 116.3, 127.7, 128.2, 128.4, 128.5, 129.0, 129.3, 133.5, 133.9, 136.9, 144.2, 155.1, 155.7, 169.8.

실험예 1. Nitric oxide(NO) 정량Experimental Example 1. Determination of Nitric oxide (NO)

BV-2 세포를 96 well plate에 2×10⁴ cells/well씩 넣고 배양한 후 lipopolysaccharide(LPS) (0.2 ㎍/mL)로 처리하여 활성을 유도하였다. 이때 적절 농도의 시험대상 화합물을 공동처리였다. 24 시간 후에 배양액에 존재하는 nitrite, 즉 NO 산화물질을 다음 Griess reaction 방법으로 정량하였다. 각 well에서 200 ㎕의 배양액을 취하여 새 96 well plate로 옮기고 100 ㎕의 Griess reagent (1% sulphanilamide, 0.1% naphthylethylenediamine dihydrochloride, 2.5% H₃PO₄)를 첨가한 후 상온에서 10 분간 반응시켰다. SpectraMax Plus microplate spectrophotometer (Molecular Devices)를 사용하여 540 ㎚ 파장에서 흡광도를 측정한다. NaNO₂ 에 대한 표준 곡선을 매번 작성하고, 이를 기준으로 Nitrite를 정량하였다.본 발명에 따른 피라졸로피리미딘 유도체 화합물의 NO 생성에 대한 %억제율 결과는 하기 [표 23] 내지 [표 30]에 나타내었다.BV-2 cells were incubated in 96 well plates at 2 × 10 ⁴ cells / well and incubated with lipopolysaccharide (LPS) (0.2 ㎍ / mL) to induce activity. Appropriate concentration of the test subject compound was cotreated. After 24 hours, the nitrite, ie NO oxide, present in the culture was quantified by the following Griess reaction method. 200 μl of the culture solution was taken from each well, transferred to a new 96 well plate, and 100 μl of Griess reagent (1% sulphanilamide, 0.1% naphthylethylenediamine dihydrochloride, 2.5% H ₃ PO ₄ ) was added and allowed to react at room temperature for 10 minutes. Absorbance is measured at a wavelength of 540 nm using a SpectraMax Plus microplate spectrophotometer (Molecular Devices). NaNO ₂ And a standard curve for Nitrite was quantified. The% inhibition rate results for NO production of the pyrazolopyrimidine derivative compounds according to the present invention are shown in the following Tables 23 to 30.

화합물compound NO (% of LPS)NO (% of LPS) 화합물compound NO (% of LPS)NO (% of LPS) 20 μM20 μM 30 μM30 μM 20 μM20 μM 30 μM30 μM 4
(KST004076)4
(KST004076) 19±4.119 ± 4.1 6i
(KKC080087)6i
(KKC080087) 48±1048 ± 10 5a
(KKC080055)5a
(KKC080055) 51±251 ± 2 6j
(KKC080062)6j
(KKC080062) 66±1066 ± 10 5b
(KKC080071)5b
(KKC080071) 63±863 ± 8 6k
(KKC080070)6k
(KKC080070) 16±1716 ± 17 5c
(KKC080164)5c
(KKC080164) 49±949 ± 9 6l
(KKC080041)6l
(KKC080041) 125±14125 ± 14 5d
(KKC080165)5d
(KKC080165) 48±448 ± 4 6m
(KKC080094)6m
(KKC080094) 97±697 ± 6 5e
(KKC080090)5e
(KKC080090) 50±750 ± 7 6n
(KKC080036)6n
(KKC080036) 114±9114 ± 9 5f
(KKC080053)5f
(KKC080053) 69±369 ± 3 6o
(KKC080035)6o
(KKC080035) 106±10106 ± 10 5g
(KKC080056)5g
(KKC080056) 15±1815 ± 18 6p
(KKC080039)6p
(KKC080039) 50±2350 ± 23 5h
(KKC080173)5h
(KKC080173) 9±42.29 ± 42.2 59.6359.63 6q
(KKC080042)6q
(KKC080042) 90±1590 ± 15 5i
(KKC080174)5i
(KKC080174) 54±2.754 ± 2.7 6r
(KKC080043)6r
(KKC080043) 64±364 ± 3 5j
(KKC080175)5j
(KKC080175) 5±49.75 ± 49.7 6s
(KKC080044)6s
(KKC080044) 85±1585 ± 15 5k
(KKC080188)5k
(KKC080188) 5±62.95 ± 62.9 6t
(KKC080046)6t
(KKC080046) 106±5106 ± 5 6a
(KST004077)6a
(KST004077) 35±4
(50 μM)35 ± 4
(50 [mu] M) 6u
(KKC080048)6u
(KKC080048) 87±887 ± 8 6b
(KKC080038)6b
(KKC080038) 100±4100 ± 4 6v
(KKC080102)6v
(KKC080102) 36±736 ± 7 6c
(KKC080045)6c
(KKC080045) 91±491 ± 4 6w
(KKC080287)6w
(KKC080287) 46±2.946 ± 2.9 6d
(KKC080040)6d
(KKC080040) 84±884 ± 8 6x
(KKC080288)6x
(KKC080288) 115±3.2115 ± 3.2 6e
(KKC080037)6e
(KKC080037) 83±983 ± 9 6y
(KKC080289)6y
(KKC080289) 90±2.990 ± 2.9 6f
(KKC080049)6f
(KKC080049) 87±687 ± 6 7a
(KKC080027)7a
(KKC080027) 79±179 ± 1 6g
(KKC080034)6 g
(KKC080034) 102±6102 ± 6 7b
(KKC080132)7b
(KKC080132) 78±478 ± 4 6h
(KKC080033)6h
(KKC080033) 97±597 ± 5 8a
(KKC08032)8a
(KKC08032) 75±0.975 ± 0.9

화합물compound NO (% of LPS)NO (% of LPS) 화합물compound NO (% of LPS)NO (% of LPS) 20 μM20 μM 30 μM30 μM 20 μM20 μM 30 μM30 μM 8b
(KKC080125)8b
(KKC080125) 75±375 ± 3 12h
(KKC080152)12h
(KKC080152) 33±1033 ± 10 9a
(KKC080031)9a
(KKC080031) 98±5.598 ± 5.5 12i
(KKC080140)12i
(KKC080140) 101±3101 ± 3 9b
(KKC080078)9b
(KKC080078) 94±794 ± 7 12j
(KKC080144)12j
(KKC080144) 40±540 ± 5 9c
(KKC080100)9c
(KKC080100) 79±579 ± 5 12k
(KKC080134)12k
(KKC080134) 94±594 ± 5 9d
(KKC080067)9d
(KKC080067) 108±5108 ± 5 12l
(KKC080141)12l
(KKC080141) 69±069 ± 0 10a
(KKC0800028)10a
(KKC0800028) 91±2.491 ± 2.4 12m
(KKC080153)12m
(KKC080153) 53±653 ± 6 10b
(KKC080047)10b
(KKC080047) 93±993 ± 9 12n
(KKC080138)12n
(KKC080138) 51±151 ± 1 11a
(KKC080050)11a
(KKC080050) II 27±1127 ± 11 12o
(KKC080156)12o
(KKC080156) 70±570 ± 5 11b
(KKC080051)11b
(KKC080051) II 82±782 ± 7 13a
(KKC080161)13a
(KKC080161) 15±2515 ± 25 11c11c II 13b
(KKC080157)13b
(KKC080157) 86±986 ± 9 11d
(KKC080086)11d
(KKC080086) II 91±391 ± 3 13c
(KKC080158)13c
(KKC080158) 77±777 ± 7 11e
(KKC080083)11e
(KKC080083) BrBr 98±998 ± 9 13d
(KKC080160)13d
(KKC080160) 14±3914 ± 39 11f
(KKC080190)11f
(KKC080190) BrBr -1±165.5-1 ± 165.5 13e
(KKC080311)13e
(KKC080311) 22.4±0.422.4 ± 0.4 12a
(KKC080116)12a
(KKC080116) 77±277 ± 2 13f
(KKC080312)13f
(KKC080312) 11.0±2.911.0 ± 2.9 12b
(KKC080118)12b
(KKC080118) 90±790 ± 7 13g
(KKC080313)13 g
(KKC080313) 12.2±3.812.2 ± 3.8 12c
(KKC080119)12c
(KKC080119) 115±6115 ± 6 13h
(KKC080314)13h
(KKC080314) 25.0±0.325.0 ± 0.3 12d
(KKC080120)12d
(KKC080120) 75±175 ± 1 13i
(KKC080315)13i
(KKC080315) 9.5±3.89.5 ± 3.8 12e
(KKC080124)12e
(KKC080124) 91±291 ± 2 13j
(KKC080316)13j
(KKC080316) 87.0±0.287.0 ± 0.2 12f
(KKC080133)12f
(KKC080133) 72±272 ± 2 13k
(KKC080317)13k
(KKC080317) 15.9±0.615.9 ± 0.6 12g
(KKC080136)12g
(KKC080136) 92±192 ± 1 13l
(KKC080318)13l
(KKC080318) 43.3±1.143.3 ± 1.1

화합물compound NO (% of LPS)NO (% of LPS) 화합물compound NO (% of LPS)NO (% of LPS) 20 μM20 μM 30 μM30 μM 20 μM20 μM 30 μM30 μM 13m
(KKC080319)13m
(KKC080319) 8.6±2.78.6 ± 2.7 15f
(KKC080079)15f
(KKC080079) 60±1760 ± 17 13n
(KKC080320)13n
(KKC080320) 17.6±0.717.6 ± 0.7 15g
(KKC080088)15g
(KKC080088) 64±764 ± 7 13o
(KKC080321)13o
(KKC080321) 17.5±1.517.5 ± 1.5 15h
(KKC080305)15h
(KKC080305) 29±4.629 ± 4.6 14a
(KKC080146)14a
(KKC080146) 58±658 ± 6 15i
(KKC080114)15i
(KKC080114) 90±390 ± 3 14b
(KKC080147)14b
(KKC080147) 102±4102 ± 4 15j
(KKC080117)15j
(KKC080117) 30±1430 ± 14 14c
(KKC080149)14c
(KKC080149) 54±554 ± 5 15k
(KKC080121)15k
(KKC080121) 70±370 ± 3 14d
(KKC080163)14d
(KKC080163) 49±1249 ± 12 15l
(KKC080122)15l
(KKC080122) 50±950 ± 9 14e
(KKC080323)14e
(KKC080323) 26.8±0.126.8 ± 0.1 15m
(KKC080123)15m
(KKC080123) 92±492 ± 4 14f
(KKC080324)14f
(KKC080324) 38.3±1.338.3 ± 1.3 15n
(KKC080126)15n
(KKC080126) 63±663 ± 6 14g
(KKC080325)14 g
(KKC080325) 33.5±1.333.5 ± 1.3 15o
(KKC080127)15o
(KKC080127) 57±157 ± 1 14h
(KKC080326)14h
(KKC080326) 78.9±1.678.9 ± 1.6 15p
(KKC080128)15p
(KKC080128) 71±571 ± 5 14i
(KKC080327)14i
(KKC080327) 54.2±2.354.2 ± 2.3 15q
(KKC080129)15q
(KKC080129) 54±154 ± 1 14j
(KKC080328)14j
(KKC080328) 25.8±3.025.8 ± 3.0 15r
(KKC080130)15r
(KKC080130) 41±141 ± 1 14k
(KKC080329)14k
(KKC080329) 61.0±0.861.0 ± 0.8 15s
(KKC080131)15s
(KKC080131) 93±293 ± 2 14l
(KKC080330)14l
(KKC080330) 24.2±1.724.2 ± 1.7 15t
(KKC080135)15 t
(KKC080135) 48±848 ± 8 15a
(KKC080084)15a
(KKC080084) 53±1253 ± 12 15u
(KKC080139)15 u
(KKC080139) 64±064 ± 0 15b
(KKC080081)15b
(KKC080081) 72±872 ± 8 15v
(KKC080142)15v
(KKC080142) 41±241 ± 2 15c
(KKC080069)15c
(KKC080069) 61±661 ± 6 15w
(KKC080143)15w
(KKC080143) 79±379 ± 3 15d
(KKC080072)15d
(KKC080072) 68±768 ± 7 15x
(KKC080179)15x
(KKC080179) 15e
(KKC080073)15e
(KKC080073) 46±1046 ± 10 15y
(KKC080241)15y
(KKC080241) 85±2.385 ± 2.3

화합물compound NO (% of LPS)NO (% of LPS) 화합물compound NO (% of LPS)NO (% of LPS) 20 μM20 μM 30 μM30 μM 20 μM20 μM 30 μM30 μM 15z
(KKC080263)15z
(KKC080263) 46±.646 ± .6 16q
(KKC080247)16q
(KKC080247) 40±1.840 ± 1.8 15za
(KKC080264)15za
(KKC080264) 36±.736 ± .7 16r
(KKC080248)16r
(KKC080248) 20±1.920 ± 1.9 15zb
(KKC080267)15zb
(KKC080267) 51±.151 ± .1 16s
(KKC080249)16s
(KKC080249) 66±2.666 ± 2.6 15zc
(KKC080268)15zc
(KKC080268) 42±.942 ± .9 16t
(KKC080250)16t
(KKC080250) 43±1.243 ± 1.2 16a
(KKC080306)16a
(KKC080306) 35±.535 ± .5 16u
(KKC080251)16 u
(KKC080251) 28±1.828 ± 1.8 16b
(KKC080074)16b
(KKC080074) 83±683 ± 6 16v
(KKC080252)16v
(KKC080252) 95±4.095 ± 4.0 16c
(KKC080103)16c
(KKC080103) 32.3±332.3 ± 3 16w
(KKC080253)16w
(KKC080253) 16d
(KKC080104)16d
(KKC080104) 54±154 ± 1 16x
(KKC080254)16x
(KKC080254) 34±1.434 ± 1.4 16e
(KKC080106)16e
(KKC080106) 36±436 ± 4 16y
(KKC080257)16y
(KKC080257) 41±0.941 ± 0.9 16f
(KKC080137)16f
(KKC080137) 35±635 ± 6 16z
(KKC080258)16z
(KKC080258) 26±2.426 ± 2.4 16g
(KKC080166)16g
(KKC080166) 37±637 ± 6 16za
(KKC080265)16za
(KKC080265) 40±1.340 ± 1.3 16h
(KKC080167)16h
(KKC080167) 66±966 ± 9 16zb
(KKC080266)16zb
(KKC080266) 49±2.449 ± 2.4 16i
(KKC080145)16i
(KKC080145) 79±379 ± 3 16zc
(KKC080290)16zc
(KKC080290) 50±1.150 ± 1.1 16j
(KKC080154)16j
(KKC080154) 48±848 ± 8 16zd
(KKC080291)16zd
(KKC080291) 46±1.946 ± 1.9 16k
(KKC080228)16k
(KKC080228) 31±0.531 ± 0.5 16ze
(KKC080292)16ze
(KKC080292) 51±3.451 ± 3.4 16l
(KKC080242)16l
(KKC080242) 48±5.148 ± 5.1 16zf
(KKC080293)16zf
(KKC080293) 49±0.649 ± 0.6 16m
(KKC080243)16m
(KKC080243) 58±1.958 ± 1.9 16zg
(KKC080294)16zg
(KKC080294) 55±1.955 ± 1.9 16n
(KKC080244)16n
(KKC080244) 56±4.556 ± 4.5 16zh
(KKC080295)16zh
(KKC080295) 53±7.253 ± 7.2 16o
(KKC080245)16o
(KKC080245) 43±4.643 ± 4.6 16zi
(KKC080296)16zi
(KKC080296) 39±3.139 ± 3.1 16p
(KKC080246)16p
(KKC080246) 34±1.734 ± 1.7 17a
(KKC080109)17a
(KKC080109) 73±373 ± 3

화합물compound NO (% of LPS)NO (% of LPS) 화합물compound NO (% of LPS)NO (% of LPS) 20 μM20 μM 30 μM30 μM 20 μM20 μM 30 μM30 μM 17b
(KKC080107)17b
(KKC080107) 61±161 ± 1 18e
(KKC080220)18e
(KKC080220) 44±1.344 ± 1.3 17c
(KKC080110)17c
(KKC080110) 59±259 ± 2 18f
(KKC080221)18f
(KKC080221) 56±3.156 ± 3.1 17d
(KKC080091)17d
(KKC080091) 93±293 ± 2 18g
(KKC080284)18g
(KKC080284) 58±4.858 ± 4.8 17e
(KKC080096)17e
(KKC080096) 21±2721 ± 27 18h
(KKC080285)18h
(KKC080285) 56±3.156 ± 3.1 17f
(KKC080099)17f
(KKC080099) 89±889 ± 8 18i
(KKC080286)18i
(KKC080286) 78±4.478 ± 4.4 17g
(KKC080108)17 g
(KKC080108) 42±1842 ± 18 19a
(KKC080222)19a
(KKC080222) 32±1.132 ± 1.1 17h
(KKC080107)17h
(KKC080107) 61±161 ± 1 19b
(KKC080223)19b
(KKC080223) 27±6.827 ± 6.8 17i
(KKC080298)17i
(KKC080298) 45±5.945 ± 5.9 19c
(KKC080224)19c
(KKC080224) 25±1.925 ± 1.9 17j
(KKC080299)17j
(KKC080299) 19±3.919 ± 3.9 19d
(KKC080281)19d
(KKC080281) 40±1.140 ± 1.1 17k
(KKC080300)17k
(KKC080300) 51±551 ± 5 19e
(KKC080282)19e
(KKC080282) 60±5.960 ± 5.9 17l
(KKC080301)17l
(KKC080301) 82±9.582 ± 9.5 19f
(KKC080283)19f
(KKC080283) 75±8.775 ± 8.7 17m
(KKC080302)17m
(KKC080302) 92±6.692 ± 6.6 19g
(KKC080332)19 g
(KKC080332) 27.4±0.727.4 ± 0.7 17n
(KKC080303)17n
(KKC080303) 38±2.938 ± 2.9 19h
(KKC080333)19h
(KKC080333) 18.0±1.218.0 ± 1.2 17o
(KKC080322)17o
(KKC080322) 73.6±2.473.6 ± 2.4 19i
(KKC080334)19i
(KKC080334) 23.1±0.523.1 ± 0.5 17p
(KKC080345)17p
(KKC080345) 20a
(KKC080182)20a
(KKC080182) 48±17.248 ± 17.2 17q
(KKC080346)17q
(KKC080346) 20b
(KKC080183)20b
(KKC080183) 48±27.148 ± 27.1 18a
(KKC080176)18a
(KKC080176) 43±18.143 ± 18.1 20c
(KKC080184)20c
(KKC080184) 47±8.047 ± 8.0 18b
(KKC080177)18b
(KKC080177) 37±17.637 ± 17.6 20d
(KKC080213)20d
(KKC080213) 43±5.943 ± 5.9 18c
(KKC080178)18c
(KKC080178) 37±7.937 ± 7.9 20e
(KKC080214)20e
(KKC080214) 235±235 ± 18d
(KKC080219)18d
(KKC080219) 39±4.839 ± 4.8 20f
(KKC080215)20f
(KKC080215) 62±3.862 ± 3.8

화합물compound NO (% of LPS)NO (% of LPS) 화합물compound NO (% of LPS)NO (% of LPS) 20 μM20 μM 30 μM30 μM 20 μM20 μM 30 μM30 μM 21a
(KKC080185)21a
(KKC080185) 37±10.737 ± 10.7 22k
(KKC080192)22k
(KKC080192) 58±258 ± 2 21b
(KKC080186)21b
(KKC080186) 44±25.244 ± 25.2 22l
(KKC080194)22l
(KKC080194) 60±3.360 ± 3.3 21c
(KKC080187)21c
(KKC080187) 47±6.847 ± 6.8 22m
(KKC080195)22 m
(KKC080195) 62±2.862 ± 2.8 21d
(KKC080216)21d
(KKC080216) 42±5.242 ± 5.2 22n
(KKC080338)22n
(KKC080338) 21e
(KKC080217)21e
(KKC080217) 39±3.039 ± 3.0 22o
(KKC080339)22o
(KKC080339) 21f
(KKC080218)21f
(KKC080218) 49±5.949 ± 5.9 22p
(KKC080340)22p
(KKC080340) 21g
(KKC080277)21 g
(KKC080277) 79±1.879 ± 1.8 23a
(KKC080189)23a
(KKC080189) 40±7.140 ± 7.1 21h
(KKC080278)21h
(KKC080278) 73±2.673 ± 2.6 23b
(KKC080197)23b
(KKC080197) 93±293 ± 2 21i
(KKC080279)21i
(KKC080279) 57±157 ± 1 23c
(KKC080199)23c
(KKC080199) 41±2.341 ± 2.3 21j
(KKC080280)21j
(KKC080280) 52±1.752 ± 1.7 23d
(KKC080201)23d
(KKC080201) 35±7.435 ± 7.4 22a
(KKC080198)22a
(KKC080198) 24±12.924 ± 12.9 23e
(KKC080271)23e
(KKC080271) 36±3.636 ± 3.6 22b
(KKC080200)22b
(KKC080200) 28±4.128 ± 4.1 23f
(KKC080272)23f
(KKC080272) 23±0.623 ± 0.6 22c
(KKC080202)22c
(KKC080202) 55±455 ± 4 23g
(KKC080275)23 g
(KKC080275) 46±3.946 ± 3.9 22d
(KKC080209)22d
(KKC080209) 46±8.346 ± 8.3 23h
(KKC080276)23h
(KKC080276) 41±5.741 ± 5.7 22e
(KKC080204)22e
(KKC080204) 31±6.931 ± 6.9 23i
(KKC080203)23i
(KKC080203) 35±7.335 ± 7.3 22f
(KKC080206)22f
(KKC080206) 58±3.758 ± 3.7 23j
(KKC080210)23j
(KKC080210) 28±19.328 ± 19.3 22g
(KKC080208)22g
(KKC080208) 42±2.342 ± 2.3 23k
(KKC080211)23k
(KKC080211) 35±4.635 ± 4.6 22h
(KKC080226)22h
(KKC080226) 59±1.459 ± 1.4 23l
(KKC080205)23l
(KKC080205) 30±37.430 ± 37.4 22i
(KKC080230)22i
(KKC080230) 81±7.581 ± 7.5 23m
(KKC080207)23m
(KKC080207) 35±3.335 ± 3.3 22j
(KKC080232)22j
(KKC080232) 70±3.970 ± 3.9 23n
(KKC080212)23n
(KKC080212) 82±3.182 ± 3.1

화합물compound NO (% of LPS)NO (% of LPS) 화합물compound NO (% of LPS)NO (% of LPS) 20 μM20 μM 30 μM30 μM 20 μM20 μM 30 μM30 μM 23o
(KKC080259)23o
(KKC080259) 30±2.430 ± 2.4 24a
(KKC080233)24a
(KKC080233) 78±1.478 ± 1.4 23p
(KKC080225)23p
(KKC080225) 40±4.940 ± 4.9 24b
(KKC080234)24b
(KKC080234) 137±5.7137 ± 5.7 23q
(KKC080229)23q
(KKC080229) 122±2.8122 ± 2.8 24c
(KKC080235)24c
(KKC080235) 123±5.4123 ± 5.4 23r
(KKC080231)23r
(KKC080231) 87±7.187 ± 7.1 24d
(KKC080236)24d
(KKC080236) 130±1.8130 ± 1.8 23s
(KKC080269)23 s
(KKC080269) 54±2.354 ± 2.3 24e
(KKC080237)24e
(KKC080237) 41±16.341 ± 16.3 23t
(KKC080270)23 t
(KKC080270) 42±2.642 ± 2.6 24f
(KKC080238)24f
(KKC080238) 9±19 ± 1 23u
(KKC080273)23u
(KKC080273) 120±3.1120 ± 3.1 24g
(KKC080239)24g
(KKC080239) 63±2.663 ± 2.6 23v
(KKC080274)23v
(KKC080274) 59±359 ± 3 24h
(KKC080255)24h
(KKC080255) 44±4.244 ± 4.2 23w
(KKC080191)23w
(KKC080191) 54±2.354 ± 2.3 24i
(KKC080256)24i
(KKC080256) 42±0.842 ± 0.8 23x
(KKC080193)23x
(KKC080193) 35±4.335 ± 4.3 24j
(KKC080344)24j
(KKC080344) 23y
(KKC080195)23y
(KKC080195) 54±3.554 ± 3.5 25a
(KKC080068)25a
(KKC080068) 23z
(KKC080260)23z
(KKC080260) 51±3.551 ± 3.5 25b
(KKC080098)25b
(KKC080098) 89±689 ± 6 23za
(KKC080261)23za
(KKC080261) 56±3.656 ± 3.6 26a
(KKC080063)26a
(KKC080063) 23zb
(KKC080262)23zb
(KKC080262) 49±2.949 ± 2.9 26b
(KKC080052)26b
(KKC080052) 23zc
(KKC080341)23zc
(KKC080341) 27a
(KKC080148)27a
(KKC080148) 77±577 ± 5 23zd
(KKC080342)23zd
(KKC080342) 27b
(KKC080151)27b
(KKC080151) 73±1073 ± 10 23ze
(KKC080343)23ze
(KKC080343) 27c
(KKC080155)27c
(KKC080155) 98±698 ± 6 23zf
(KKC080347)23zf
(KKC080347) 27d
(KKC080162)27d
(KKC080162) 49±1249 ± 12 23zg
(KKC080348)23zg
(KKC080348) 27e
(KKC080159)27e
(KKC080159) 56±656 ± 6 23zh
(KKC080349)23zh
(KKC080349) 27f
(KKC080150)27f
(KKC080150) 86±386 ± 3

화합물compound NO (% of LPS)NO (% of LPS) 화합물compound NO (% of LPS)NO (% of LPS) 20 μM20 μM 30 μM30 μM 20 μM20 μM 30 μM30 μM 27g
(KKC080335)27g
(KKC080335) 82±2.582 ± 2.5 31c
(KKC080065)31c
(KKC080065) 100±4100 ± 4 27h
(KKC080336)27h
(KKC080336) 87.4±1.287.4 ± 1.2 31d
(KKC080089)31d
(KKC080089) 27i
(KKC080337)27i
(KKC080337) 83.5±3.183.5 ± 3.1 31e
(KKC080066)31e
(KKC080066) 105±10105 ± 10 2828 31f
(KKC080064)31f
(KKC080064) 100±5100 ± 5 29
(KKC080093)29
(KKC080093) 35±1235 ± 12 31g
(KKC080077)31 g
(KKC080077) 71±371 ± 3 30a
(KKC080076)30a
(KKC080076) 13±1813 ± 18 32a
(KKC080115)32a
(KKC080115) 53±353 ± 3 30b
(KKC080054)30b
(KKC080054) 31±1931 ± 19 32b
(KKC080111)32b
(KKC080111) 49±949 ± 9 30c
(KKC080085)30c
(KKC080085) 21±2221 ± 22 32c
(KKC080112)32c
(KKC080112) 69±869 ± 8 31a
(KKC080075)31a
(KKC080075) 68±2868 ± 28 32d
(KKC080113)32d
(KKC080113) 46±246 ± 2 31b
(KKC080082)31b
(KKC080082) 55±555 ± 5

Claims (10)

삭제delete 삭제delete 삭제delete 삭제delete 삭제delete 하기 [화학식 5e] 내지 [화학식 31f]로 표시되는 군에서 선택되는 어느 하나인 것을 특징으로 하는 산화질소 생성 억제용 피라졸로피리미딘 유도체 화합물:
[화학식 5e] [화학식 5f] [화학식 5i]

[화학식 6b] [화학식 6c]

[화학식 6e] [화학식 6f] [화학식 6g]

[화학식 6l] [화학식 6m]

[화학식 6n] [화학식 6o] [화학식 6s]

[화학식 6t] [화학식 6u]

[화학식 7a] [화학식 7b] [화학식 8a]

[화학식 8b] [화학식 9a] [화학식 9b]

[화학식 9c] [화학식 9d]

[화학식 11b] [화학식 11c] [화학식 11d]

[화학식 12b] [화학식 12c]

[화학식 12e] [화학식 12g] [화학식 12i]

[화학식 13b] [화학식 13c]

[화학식 14a] [화학식 14b] [화학식 14h]

[화학식 15i] [화학식 15m]

[화학식 15s]

[화학식 15w] [ 화학식 15y]

[화학식 16b] [화학식 16i]

[화학식 16v] [화학식 17d]

[화학식 17f] [화학식 17l] [화학식 17m]

[화학식 18i] [화학식 20e]

[화학식 22i]

[화학식 23b] [화학식 23n]

[화학식 23q] [화학식 23r] [화학식 23u]

[화학식 24b] [화학식 24c]

[화학식 24d] [화학식 25b]

[화학식 27c] [화학식 27f] [화학식 27i]

[화학식 31c] [화학식 31e]

[화학식 31f]

A pyrazolopyrimidine derivative compound for inhibiting nitric oxide production, which is any one selected from the group represented by the following [Formula 5e] to [Formula 31f]:
[Formula 5e] [Formula 5f] [Formula 5i]

[Formula 6b] [Formula 6c]

[Formula 6e] [Formula 6f] [Formula 6g]

[Formula 6l] [Formula 6m]

[Formula 6n] [Formula 6o] [Formula 6s]

[Formula 6t] [Formula 6u]

[Formula 7a] [Formula 7b] [Formula 8a]

[Formula 8b] [Formula 9a] [Formula 9b]

[Formula 9c] [Formula 9d]

[Formula 11b] [Formula 11c] [Formula 11d]

[Formula 12b] [Formula 12c]

[Formula 12e] [Formula 12g] [Formula 12i]

[Formula 13b] [Formula 13c]

[Formula 14a] [Formula 14b] [Formula 14h]

[Formula 15i] [Formula 15m]

[Formula 15s]

[Formula 15w] [Formula 15y]

[Formula 16b] [Formula 16i]

[Formula 16v] [Formula 17d]

[Formula 17f] [Formula 17l] [Formula 17m]

[Formula 18i] [Formula 20e]

[Formula 22i]

[Formula 23b] [Formula 23n]

[Formula 23q] [Formula 23r] [Formula 23u]

[Formula 24b] [Formula 24c]

[Formula 24d] [Formula 25b]

[Formula 27c] [Formula 27f] [Formula 27i]

[Formula 31c] [Formula 31e]

[Formula 31f]

삭제delete 삭제delete 삭제delete 삭제delete