WO2007116265A1 - Procede de fabrication d'un compose de tetrahydro-pyridoazepin-8-one - Google Patents

Procede de fabrication d'un compose de tetrahydro-pyridoazepin-8-one Download PDF

Info

Publication number
WO2007116265A1
WO2007116265A1 PCT/IB2007/000762 IB2007000762W WO2007116265A1 WO 2007116265 A1 WO2007116265 A1 WO 2007116265A1 IB 2007000762 W IB2007000762 W IB 2007000762W WO 2007116265 A1 WO2007116265 A1 WO 2007116265A1
Authority
WO
WIPO (PCT)
Prior art keywords
reaction
potassium
sodium
triaza
butoxy
Prior art date
Application number
PCT/IB2007/000762
Other languages
English (en)
Inventor
Michael Huai Gu Chen
Javier Magano
Kenneth Earl Mennen
Original Assignee
Pfizer Products Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Pfizer Products Inc. filed Critical Pfizer Products Inc.
Publication of WO2007116265A1 publication Critical patent/WO2007116265A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system

Definitions

  • This invention relates to process for preparing 2- ⁇ 4-[4-(7-fluoro-naphthalen- 1 -yl)- piperazin-l-yl]-butoxy ⁇ -5,6,7,94etrahydro-l,7,9-triaza-benzocyclohepten-8-one, which is represented by formula (I) below:
  • WO 2006/103559 discloses 2- ⁇ 4-[4-(7-fluoro-na ⁇ hthalen-l-yl)- ⁇ iperazin-l-yl]-butoxy ⁇ - 5,6,7,9-tetrahydro-l,7,9-triaza-benzocyclohepten-8-one, its property of binding to dopamine D2 receptors, a method of making this compound, and uses of this compound for treating certain central nervous system (CNS) disorders, such as schizophrenia.
  • CNS central nervous system
  • the present invention provides a process for preparing 2- ⁇ 4- [4-(7-fluoro-naphthalen- 1 - y ⁇ -piperazin-l-yy-butoxyl-S j ⁇ -tetrahydro-l ⁇ -triaza-benzocyclohepten-S-one, which comprises reacting a compound of formula (II)
  • a "leaving group” refers to a group that can be replaced in a chemical reaction by a nucleophile such as an amine, an alkoxy (RO ' ), or thio (RS " ) compound.
  • a nucleophile such as an amine, an alkoxy (RO ' ), or thio (RS " ) compound.
  • Examples of specific leaving group that may be used in the process include chloro (Cl), bromo (Br), iodo (I), mesylate (MsO), and triflate (TfO).
  • reaction of l-(7-fluoro-naphthalen-l-yl)-piperazine hydrochloride with a compound of formula (II) is generally carried out in a solvent and in the presence of a base.
  • One mole of 1 - (7-fluoro-naphthalen-l-yl)-piperazine hydrochloride is theoretically needed based on one mole of the compound of formula (II), but the ratio may be slightly different.
  • Suitable base examples include potassium or sodium te/t-butoxides, potassium or sodium hydrides, lithium diisopropylamide (LDA), lithium, sodium or potassium bis(trimiethylsilyl)amides, potassium or sodium carbonates, and potassium or sodium bicarbonates.
  • the amount of the base is usually in the range of 0.1 to 10 moles, preferably one mole or more in the view of the reaction rate, based on one mole of the compound offormula ( ⁇ ) or ( ⁇ i).
  • Suitable solvents include tetrahydrofuran (THF), dioxane, diethylether, tert-buty ⁇ methylether, dimethylformamide (DMF), dimethyl phthalate (NMP), dimethylsulfoxide (DMSO), and acetonitrile (MeCN).
  • THF tetrahydrofuran
  • dioxane diethylether
  • tert-buty ⁇ methylether dimethylformamide
  • DMF dimethyl phthalate
  • NMP dimethylsulfoxide
  • MeCN acetonitrile
  • a single solvent or a mixture of two or more solvents may be used in the reaction.
  • the reaction temperature is usually in the range of about 20 0 C to 120 0 C, typically at the range of about 25 0 C to 100 0 C, and more desirably at the range of about 60 0 C to 80 0 C.
  • the reaction time is usually in the range of about 1 hour to 5 hours.
  • the reaction may be run
  • the end point of the reaction can be detected by sampling a part of the reaction mixture, analyzing the sample by conventional analytical means such as liquid chromatography, thin-layer chromatography, and so on, and measuring the remaining amount of one or both starting materials.
  • the obtained product 2- ⁇ 4-[4-(7-Fluoro-naphthalen-l-yl)-piperazin-l-yl]-butoxy ⁇ -
  • 5,6,7,9-te1xahydro-l,7,9-triaza-benzocyclohepten-8-one (I) can be purified by a known procedure such as chromatography , recrystallization, and son on.
  • a solution of sodium t-butoxide (3eq., 3.41mmol/ml DMF) was prepared over a temperature range of 5 0 C to 20 0 C.
  • a solution of 4-Benzyloxy- butan-1-ol leq., 2.39mmole/inl DMF
  • N-(6-cMoro-3-foimyl-pyridm-2-yl)-2,2-dimethyl-propionamide 1.3eq., 2.29mmol/ml DMF
  • Toluene (883.38 g, 1000 mL, 10 mL/g) was added to the reaction mixture.
  • the system was filled with N 2 (Note 1).
  • the dark solution was heated tol05 0 C (internal temperature) from 20.5 0 C in 45 minutes with a heating mental with mechanical stirring. After 2 h at 105 0 C, HPLC analysis showed the product peak (86.6%) and no starting material 1 -bromo-7-fluoronaphthalene.
  • the heating mental was removed and the reaction mixture was cooled to 25 0 C with a cold water bath with stirring.
  • the dark reaction mixture was filtered through celite (1 inch thick, packed with water and sucked dry), washed with MTBE (500 g) (Note 2).
  • HCl gas (105.5 g) was introduced to the reaction via the Teflon tube to the top surface of the solution for 1 h. Solid formed after 20 min. The mixture was stirred at ambient temperature over night (18 h) after HCl was stopped. HPLC analysis showed no starting material Boc-piperazine. The solid was filtered, washed with MTBE (200 g), and dried at 45 0 C vacuum oven for 20 h, to give a light brown solid 117.24 g, (98.9%). The solid was suspended in MeOH (300 g) + MTBE (150 g) and stirred for 2 h.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Neurology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

La présente invention concerne un procédé de préparation de 2-{4-[4-(7-fluoro-naphtalèn-1-yl)-pipérazin-1-yl]-butoxy}-5,6,7,9-tétrahydro-1,7,9-triaza-benzocycloheptèn-8-one. Le procédé comprend la mise en réaction d'hydrochlorure de 1-(7-fluoro-naphtalèn-1-yl)-pipérazine avec un composé de formule (II) dans laquelle L est un groupe partant.
PCT/IB2007/000762 2006-03-31 2007-03-15 Procede de fabrication d'un compose de tetrahydro-pyridoazepin-8-one WO2007116265A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US78784306P 2006-03-31 2006-03-31
US60/787,843 2006-03-31

Publications (1)

Publication Number Publication Date
WO2007116265A1 true WO2007116265A1 (fr) 2007-10-18

Family

ID=38335626

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2007/000762 WO2007116265A1 (fr) 2006-03-31 2007-03-15 Procede de fabrication d'un compose de tetrahydro-pyridoazepin-8-one

Country Status (4)

Country Link
JP (1) JP2007269796A (fr)
AR (1) AR060219A1 (fr)
TW (1) TW200815435A (fr)
WO (1) WO2007116265A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS57193461A (en) * 1981-05-22 1982-11-27 Otsuka Pharmaceut Co Ltd Benzazepine derivative
WO2005019215A1 (fr) * 2003-08-22 2005-03-03 Warner-Lambert Company Llc [1,8]naphtyridin-2-ones et composes apparentes destines au traitement de la schizophrenie
WO2006103559A1 (fr) * 2005-04-01 2006-10-05 Warner-Lambert Company Llc Tetrahydro-pyridoazepin-8-ones et composes voisins utiles pour le traitement de la schizophrenie

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS57193461A (en) * 1981-05-22 1982-11-27 Otsuka Pharmaceut Co Ltd Benzazepine derivative
WO2005019215A1 (fr) * 2003-08-22 2005-03-03 Warner-Lambert Company Llc [1,8]naphtyridin-2-ones et composes apparentes destines au traitement de la schizophrenie
WO2006103559A1 (fr) * 2005-04-01 2006-10-05 Warner-Lambert Company Llc Tetrahydro-pyridoazepin-8-ones et composes voisins utiles pour le traitement de la schizophrenie

Also Published As

Publication number Publication date
TW200815435A (en) 2008-04-01
AR060219A1 (es) 2008-06-04
JP2007269796A (ja) 2007-10-18

Similar Documents

Publication Publication Date Title
KR20210057032A (ko) 메틸 6-(2,4-디클로로페닐)-5-[4-[(3s)-1-(3-플루오로프로필)피롤리딘-3-일]옥시페닐]-8,9-디히드로-7h-벤조[7]아눌렌-2-카르복실레이트의 염 및 이의 제조 방법
EP2451786B1 (fr) Procédé amélioré de préparation d'ambrisentan et nouveaux intermédiaires associés
CA2646795A1 (fr) Procede de preparation du bosentan
JPWO2014042176A1 (ja) 縮合複素環誘導体の製造方法およびその製造中間体
JP2021098744A (ja) 新規な４−ベンゾアゾニン誘導体の製造方法
US8466318B2 (en) Method of preparing chiral cyclic β-aminocarboxamides
US20090247755A1 (en) Process for Preparing a Substituted Imidazopyridine Compound
FI91064C (fi) Menetelmä terapeuttisesti vaikuttavien 3-(N-asyylietyyli-aminoalkyyli)-kromaanien ja -1,4-dioksaanien valmistamiseksi
JP2560358B2 (ja) イミダゾール誘導体およびその製法
IL182439A (en) Intermediates useful for the preparation of aripiprazole and methods for the preparation of the intermediates and aripiprazole
EP1551839B1 (fr) Procede de preparation de 9-¬4-acetoxy-3-(acetoxymethyl)but-1-yl -2-aminopurine
US20050080072A1 (en) Process for the preparation of a thiazepine derivative
WO2007116265A1 (fr) Procede de fabrication d'un compose de tetrahydro-pyridoazepin-8-one
JP4026233B2 (ja) ４，５−ジクロロ−６−（α−フルオロアルキル）ピリミジンの製法
CN110894186B (zh) 匹莫范色林及其中间体的制备方法
KR102441327B1 (ko) 다이아미노피리미딘 유도체 또는 이의 산부가염의 신규의 제조방법
JPWO2006083010A1 (ja) ４−アセチルピリミジン化合物の製造方法およびその結晶
BRPI0712608A2 (pt) Oxindoldioxianos, síntese dos mesmos e intermediários dos mesmos
US6818777B2 (en) Intermediates for synthesis of vinblastine compound and method for synthesizing the intermediate
CN113302192A (zh) 用于制备四氢吡啶并嘧啶的方法
US20040039013A1 (en) Process for preparing a substituted imidazopyridine compound
JP4055246B2 (ja) ５−クロロ−６−（α−フルオロアルキル）−４−ピリミドン及びその製法
CN116655520A (zh) 6，6-二甲基-3-氮杂[3.1.0]己烷-2-羧酸类衍生物的制备方法
KR100355756B1 (ko) Ｓ－오플로삭신의 제조방법
KR920003690B1 (ko) 퀴놀린 유도체의 제조방법

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 07734089

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 07734089

Country of ref document: EP

Kind code of ref document: A1