KR100731469B1 - Oxazolidinone derivatives containing pyridine moiety and process for the preparation thereof - Google Patents

Oxazolidinone derivatives containing pyridine moiety and process for the preparation thereof Download PDF

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KR100731469B1
KR100731469B1 KR1020000056035A KR20000056035A KR100731469B1 KR 100731469 B1 KR100731469 B1 KR 100731469B1 KR 1020000056035 A KR1020000056035 A KR 1020000056035A KR 20000056035 A KR20000056035 A KR 20000056035A KR 100731469 B1 KR100731469 B1 KR 100731469B1
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oxo
fluorophenyl
compound
oxazolidinyl
methyl acetamide
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KR1020000056035A
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KR20010110057A (en
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이재걸
임원빈
조종환
최성학
이종진
김동구
박상국
이태호
성현정
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동아제약주식회사
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Priority to AU5889701A priority patent/AU5889701A/en
Priority to CN01810697A priority patent/CN1433413A/en
Priority to BR0111280-5A priority patent/BR0111280A/en
Priority to CA002411859A priority patent/CA2411859A1/en
Priority to EP01932368A priority patent/EP1289984A4/en
Priority to JP2002501891A priority patent/JP2003535860A/en
Priority to US10/296,896 priority patent/US6689779B2/en
Priority to NZ522990A priority patent/NZ522990A/en
Priority to MXPA02012045A priority patent/MXPA02012045A/en
Priority to PCT/KR2001/000821 priority patent/WO2001094342A1/en
Priority to HU0301562A priority patent/HUP0301562A2/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D263/18—Oxygen atoms
    • C07D263/20—Oxygen atoms attached in position 2
    • C07D263/22—Oxygen atoms attached in position 2 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to other ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

Abstract

본 발명은 신규 옥사졸리디논 (oxazolidinone) 유도체와 약학적으로 허용되는 그의 염, 그의 제조방법 및 그를 포함하는 약학적 조성물에 관한 것으로서, 하기 화학식 1로 표시되는 피리딘 고리를 포함하는 옥사졸리디논 유도체는 항균 스펙트럼이 넓고, 우수한 항균효과를 나타내며 독성이 낮아 항생제로서 유용하게 사용될 수 있다.The present invention relates to a novel oxazolidinone derivative, a pharmaceutically acceptable salt thereof, a preparation method thereof, and a pharmaceutical composition comprising the same, wherein an oxazolidinone derivative including a pyridine ring represented by Chemical Formula 1 is Wide antimicrobial spectrum, excellent antimicrobial effect and low toxicity can be usefully used as antibiotic.

Figure 112000019986940-pat00001
Figure 112000019986940-pat00001

상기 화학식 1에서, R1 및 R2는 명세서에 기재된 바와 같다.In Formula 1, R 1 and R 2 are as described in the specification.

Description

피리딘 고리를 포함하는 옥사졸리디논 유도체 및 그의 제조방법 {Oxazolidinone derivatives containing pyridine moiety and process for the preparation thereof}Oxazolidinone derivatives containing a pyridine ring and a method for preparing the same {Oxazolidinone derivatives containing pyridine moiety and process for the preparation

본 발명은 공지의 페닐 옥사졸리디논 유도체와 다양한 치환기를 갖는 피리딘 유도체와 화학적인 결합을 통하여 얻은 하기 화학식 1의 신규 옥사졸리디논 (oxazolidinone) 유도체와 약학적으로 허용되는 그의 염, 이를 제조하는 방법 및 이들 화합물을 유효성분으로 하는 항균제용 약학적 조성물에 관한 것이다.The present invention provides a novel oxazolidinone derivative of the general formula (1) obtained through chemical bonding with a known phenyl oxazolidinone derivative and a pyridine derivative having various substituents, and a pharmaceutically acceptable salt thereof, and a method for preparing the same. It relates to a pharmaceutical composition for antimicrobial agents comprising these compounds as an active ingredient.

화학식 1Formula 1

Figure 112000019986940-pat00002
Figure 112000019986940-pat00002

(상기식에서, R1 및 R2는 명세서에 기재된 바와 같다.)
(Wherein R 1 and R 2 are as described in the specification).

옥사졸리디논(oxazolidinone) 화합물은 발효 산물이 아닌 경구 투여가 가능한 새로운 합성 항생제로서 다양한 구조의 유도체가 알려져 있다. 예를 들면 하나 또는 두개의 치환기를 가진 3-페닐-2-옥사졸리디논 유도체는 USP 4,948,801, USP 4,461,773, USP 4,340,606, USP 4,476,136, USP 4,250,318, USP 4,128,654에 기술되어 있으며, 하기 화학식 2로 표시되는 3-[(모노치환된)페닐]-2-옥사졸리디논 유도체들은 EP 0312000, J. Med. Chem. 32, 1673(1989), J. Med. Chem. 33, 2569 (1990), Tetrahedron. 45,123(1989) 등에 언급되어 있다.Oxazolidinone compounds are known as new synthetic antibiotics that can be administered orally rather than as fermentation products, and derivatives of various structures are known. For example, 3-phenyl-2-oxazolidinone derivatives having one or two substituents are described in USP 4,948,801, USP 4,461,773, USP 4,340,606, USP 4,476,136, USP 4,250,318, USP 4,128,654, and are represented by the following Chemical Formula 2 -[(Monosubstituted) phenyl] -2-oxazolidinone derivatives are described in EP 0312000, J. Med. Chem . 32, 1673 ( 1989 ), J. Med. Chem . 33, 2569 ( 1990 ), Tetrahedron . 45,123 ( 1989 ) and the like.

Figure 112000019986940-pat00003
Figure 112000019986940-pat00003

또한 파마시아 앤 업존 (Pharmacia & Upjohn)에서는 하기 화학식 3 및 화학식 4의 옥사졸리디논 유도체를 합성하였으며 (WO 93/23384, WO 95/14684, WO 95/07271), 현재 화학식 3의 화합물은 미국 식품의약품국 (FDA, Food and Drug Administration)의 허가를 얻어 발매를 앞두고 있다. 그러나 종래 합성된 옥사졸리디논 화합물들은 항균 스펙트럼이 광범위하지 못하고 독성이 있을 뿐만 아니라 생체내 (in vivo)에서 그 치료효과가 감소하는 단점을 가지고 있다. In addition, Pharmacia & Upjohn synthesized oxazolidinone derivatives of the following Chemical Formulas 3 and 4 (WO 93/23384, WO 95/14684, WO 95/07271). It is being released with permission from the Food and Drug Administration (FDA). However, conventionally synthesized oxazolidinone compounds are disadvantageous in that the antimicrobial spectrum is not broad and toxic, and their therapeutic effect is reduced in vivo .

Figure 112000019986940-pat00004
Figure 112000019986940-pat00004

Figure 112000019986940-pat00005
Figure 112000019986940-pat00005

또한 WO 93/09103에는 상기 화학식 1과 같이 페닐기의 4번 위치에 피리딘을 포함한 싸이아졸, 인돌, 옥사졸, 퀴놀 등과 같은 헤테로고리를 갖는 페닐 옥사졸리디논 유도체가 알려져 있으나, 헤테로고리의 치환기들이 단순한 알킬기 또는 아미노기에 그치고 약효 또한 충분히 뛰어나지 않은 것으로 알려져 있다.
WO 93/09103 also discloses phenyl oxazolidinone derivatives having heterocycles such as thiazole, indole, oxazole, quinol and the like containing pyridine at position 4 of the phenyl group as shown in Formula 1, but the substituents of the heterocycle are simple It is known that not only the alkyl group or the amino group but also the effect is not sufficiently excellent.

이에 본 발명자들은 상기 문제점을 해결하기 위해 노력한 결과, 화학식 1에 나타낸 바와 같이 페닐기의 4번 위치에 다양한 피리딘 유도체를 갖는 페닐 옥사졸리디논 유도체를 합성하였고, 상기 합성된 화합물들의 항균력을 측정한 결과 그 항균 스펙트럼이 넓고, 본 발명의 화합물들은 항균효과도 탁월함을 밝혀 본 발명을 완성하였다.
Accordingly, the present inventors have tried to solve the above problems, as shown in the formula 1 synthesized a phenyl oxazolidinone derivative having a variety of pyridine derivatives at the position 4 of the phenyl group, and measured the antibacterial activity of the synthesized compounds The antimicrobial spectrum is broad, and the compounds of the present invention have been found to be excellent in antimicrobial effects, thus completing the present invention.

본 발명의 목적은 강한 항균력을 갖는 화학식 1로 표시되는, 다양한 피리딘 유도체를 포함하는 옥사졸리디논 (oxazolidinone)유도체와 약학적으로 허용되는 그의 염 및 그들의 제조방법을 제공하는 것이다. It is an object of the present invention to provide an oxazolidinone derivative including various pyridine derivatives, pharmaceutically acceptable salts thereof, and a method for preparing the same, which are represented by the general formula (1) having strong antibacterial activity.

또한 본 발명의 목적은 화학식 1로 표시되는 옥사졸리디논 (oxazolidinone)유도체 또는 약학적으로 허용되는 그의 염을 유효성분으로 하는 항생제용 약학적 조성물을 제공하는 것이다.
It is also an object of the present invention to provide a pharmaceutical composition for antibiotics comprising an oxazolidinone derivative represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

상기 목적을 달성하기 위하여, 본 발명에서는 하기 화학식 1로 표시되는 피리딘 고리를 포함하는 옥사졸리디논 (oxazolidinone) 유도체 및 약학적으로 허용되는 그들의 염을 제공한다.In order to achieve the above object, the present invention provides an oxazolidinone derivative and a pharmaceutically acceptable salt thereof containing a pyridine ring represented by the following formula (1).

화학식 1Formula 1

Figure 112000019986940-pat00006
Figure 112000019986940-pat00006

상기 화학식 1에서,In Chemical Formula 1,

R1은 수소 또는 불소이고, R 1 is hydrogen or fluorine,

R2는 수소; 아지도;

Figure 112000019986940-pat00007
; -NR4R5; -(CH2)m-R6; -OR7; 또는 R8 및 R9이 치환된 헤테로고리이고 (이때, l은 1 내지 2의 정수이고, m은 1 내지 4의 정수이다.),R 2 is hydrogen; Azido;
Figure 112000019986940-pat00007
; -NR 4 R 5 ; -(CH 2 ) m -R 6 ; -OR 7 ; or R 8 and R 9 are substituted heterocycles, where l is an integer from 1 to 2 and m is an integer from 1 to 4,

R3은 수소, C1∼C3의 알콕시, 아미노, C1∼C3의 알킬아미노 또는 C1∼C3의 히드록시알킬아미노기이고,R 3 is hydrogen, C 1 -C 3 alkoxy, amino, C 1 -C 3 alkylamino or C 1 -C 3 hydroxyalkylamino group,

R4와 R5는 서로 같거나 또는 다르며,R 4 and R 5 are the same as or different from each other,

(a) 수소, (a) hydrogen,

(b) 하나 또는 그 이상의 페닐기로 치환된 또는 치환되지 않은 알킬기(C1∼C4), C1∼C3의 알킬아미노기로 치환된 알케닐기(C 1∼C4),(b) one or or unsubstituted alkyl group substituted by a further phenyl group (C 1 ~C 4), an alkenyl group (C 1 ~C 4) alkyl substituted by an amino group of the C 1 ~C 3,

(c) 치환 또는 치환되지않은 아세틸기 (이때, 치환된 아세틸기는 아세톡시아세틸, 히드록시아세틸, C1∼C3의 알킬아미노아세톡시아세틸, C1∼C 3의 알콕시아세틸, 아미노아세틸, 아지도아세틸, 아세틸아미노아세틸, C1∼C3의 알킬아미노아세틸, 아미노프로피오닐 또는 히드록시프로피오닐기이다.),(c) an acetyl group (where the substituted acetyl group is unsubstituted or substituted acetoxy, acetyl, hydroxy, acetyl, alkoxy, acetyl, amino acetyl in C 1 ~C 3 alkyl-amino-acetoxy acetyl, C 1 ~C 3 a, ah map acetyl, acetylamino, acetyl, alkyl, amino, acetyl, propionyl amino or hydroxy propionyl group of the C 1 ~C 3.),

또는 (d) 니코티노일기이고,Or (d) a nicotinoyl group,

R6은 수소; 아지도; 히드록시; C1∼C3의 알킬아미노아세톡시; 아세틸싸이오; 머캅토; 시아노; 할로겐 원소; 또는 5원 또는 6원 헤테로고리이고,R 6 is hydrogen; Azido; Hydroxy; Alkylamino acetoxy of C 1 ~C 3; Acetylthio; Mercapto; Cyano; Halogen element; Or 5- or 6-membered heterocycle,

R7은 수소, C1∼C3의 알킬, 아세틸, 알콕시알킬 또는 메탄술포닐기이고, R 7 is hydrogen, C 1 -C 3 alkyl, acetyl, alkoxyalkyl or methanesulfonyl group,

R8 및 R9는 서로 같거나 다르고, R 8 and R 9 are the same as or different from each other,

(a) 수소; (a) hydrogen;

(b) 치환 또는 치환되지 않은 알킬(이때, 치환된 알킬기는 히드록시알킬, 알콕시카보닐알킬, 트리페닐알킬, 아세톡시알킬 또는 메탄술포닐옥시알킬기이다); (b) substituted or unsubstituted alkyl, wherein the substituted alkyl group is a hydroxyalkyl, alkoxycarbonylalkyl, triphenylalkyl, acetoxyalkyl or methanesulfonyloxyalkyl group;

(c)

Figure 112000019986940-pat00008
;(c)
Figure 112000019986940-pat00008
;

(d) 아미노; 치환 또는 치환되지 않은 이미노(이때, 치환된 이미노기는 히드록시이미노, 알킬이미노 또는 메탄술포닐옥시이미노기이다.); 또는 알콕시카보닐기로 치환 또는 치환되지 않은 히드라지노;(d) amino; Substituted or unsubstituted imino, wherein the substituted imino group is a hydroxyimino, alkylimino or methanesulfonyloxyimino group; Or hydrazino unsubstituted or substituted with an alkoxycarbonyl group;

(e) 히드록시; 시아노기; 또는(e) hydroxy; Cyano group; or

(f) 5원 또는 6원 헤테로고리이고,(f) a 5 or 6 membered heterocycle,

R10은 (a) C1∼C6의 알킬, C1∼C3의 알킬기로 치환 또는 치환되지않은 알케닐 ,R 10 is (a) C 1 -C 6 alkyl, C 1 -C 3 alkyl group unsubstituted or substituted with alkenyl,

(b) 알콕시카보닐,(b) alkoxycarbonyl,

(c) 아세톡시메틸, 벤질옥시메틸, 히드록시메틸, C1∼C3의 알킬아미노아세톡시메틸, 할로메틸, C1∼C3의 알콕시메틸, 몰포리닐메틸, C1∼C3 의 알콕시카보닐메틸아미노메틸, 메탄술포닐옥시메틸, C1∼C3의 알콕시옥소메틸, 니코티노일옥시메틸, C1∼C3의 알콕시페닐메틸, 벤질, 트리할로메틸, (c) of the acetoxymethyl, benzyloxy-methyl, hydroxymethyl, C 1 ~C 3 alkyl amino acetoxymethyl, halomethyl, C 1 ~C 3 alkoxy-methyl, morpholinyl-methyl, C 1 ~C 3 alkoxycarbonyl methylaminomethyl, methanesulfonyloxy methyl, C 1 ~C 3 alkoxy-oxo-methyl, nicotinoyl-oxy-methyl, methyl-alkoxyphenyl, benzyl, trihalomethyl of the C 1 ~C 3,

(d) C1∼C3의 알콕시, 페닐옥시, 알릴옥시, C1∼C3의 할로알킬옥시; 니트로기로 치환 또는 치환되지않은 벤질옥시 또는 9-플루오레닐메틸옥시,(d) C 1 -C 3 alkoxy, phenyloxy, allyloxy, C 1 -C 3 haloalkyloxy; Benzyloxy or 9-fluorenylmethyloxy, unsubstituted or substituted with a nitro group,

(e) 니코티노일메틸기, 또는(e) nicotinoylmethyl groups, or

(f) 5원 또는 6원 헤테로고리이다.
(f) 5- or 6-membered heterocycles.

R2에 치환된 헤테로고리는 피롤, 피페라진, 피페리딘, 1,4-디아제팬 (1,4-diazepan), 이미다졸, 1,2,4-트리아졸, 1,2,3-트리아졸, 피라졸, 피롤리딘, 옥사졸, 이소옥사졸, 피리딘, 피리미딘, 또는 피라진이 바람직하다.
The heterocycle substituted in R 2 is pyrrole, piperazine, piperidine, 1,4-diazepan (1,4-diazepan), imidazole, 1,2,4-triazole, 1,2,3-tria Preference is given to sol, pyrazole, pyrrolidine, oxazole, isoxazole, pyridine, pyrimidine, or pyrazine.

상기 화학식 1의 화합물들 중 특히 바람직한 화합물로는 구체적으로 하기와 같다.Particularly preferred compounds among the compounds of Formula 1 are as follows.

1) (S)-[N-3-(4-피리딘-2-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 1의 화합물)1) (S)-[N-3- (4-pyridin-2-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (compound of Example 1)

2) (S)-[N-3-(4-(2-아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 2의 화합물)2) (S)-[N-3- (4- (2-aminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (from Example 2 compound)

3) (S)-[N-3-(4-(3-메톡시카르보닐피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 3의 화합물)3) (S)-[N-3- (4- (3-methoxycarbonylpyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (implemented Compound of Example 3)

4) (S)-[N-3-(4-(2-아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 4의 화합물) 4) (S)-[N-3- (4- (2-acetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 4 Compound of                     

5) (S)-[N-3-(4-(2-아세톡시아세틸아미노피리딘-5-일)-3-플로로페닐) -2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 5의 화합물)5) (S)-[N-3- (4- (2-acetoxyacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (implemented Compound of Example 5)

6) (S)-[N-3-(4-(2-히드록시아세틸아미노피리딘-5-일)-3-플로로페닐) -2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 6의 화합물)6) (S)-[N-3- (4- (2-hydroxyacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (implemented Compound of Example 6)

7) (S)-[N-3-(4-(2-이미다졸-1-일-피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 7의 화합물)7) (S)-[N-3- (4- (2-imidazol-1-yl-pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acet Amide (Compound of Example 7)

8) (S)-[N-3-(4-(2-몰포린-4-일-피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 8의 화합물)8) (S)-[N-3- (4- (2-morpholin-4-yl-pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acet Amide (Compound of Example 8)

9) (S)-[N-3-(4-(2-트리페닐메틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 9의 화합물)9) (S)-[N-3- (4- (2-triphenylmethylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (implemented Compound of Example 9)

10) (S)-[N-3-(4-(2-메톡시피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 10의 화합물)10) (S)-[N-3- (4- (2-methoxypyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 10 Compound of

11) (S)-[N-3-(4-(2-메톡시아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조 (실시예 11의 화합물)11) Preparation of (S)-[N-3- (4- (2-methoxyacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Compound of Example 11)

12) (S)-[N-3-(4-(2-(4-트리페닐메틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 12의 화합물)12) (S)-[N-3- (4- (2- (4-triphenylmethylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5- Oxazolidinyl] methyl acetamide (Compound of Example 12)

13) (S)-[N-3-(4-(2-트리페닐메틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 염산염 (실시예 13의 화합물)13) (S)-[N-3- (4- (2-triphenylmethylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide hydrochloride ( Compound of Example 13)

14) (S)-[N-3-(4-(2-아지도피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 14의 화합물) 14) (S)-[N-3- (4- (2-azidopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 14 Compound of                     

15) (S)-[N-3-(4-(2-히드록시메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 15의 화합물)15) (S)-[N-3- (4- (2-hydroxymethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 15 compounds)

16) (S)-[N-3-(4-(2-메톡시카보닐피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 16의 화합물)16) (S)-[N-3- (4- (2-methoxycarbonylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (implemented Compound of Example 16)

17) (S)-[N-3-(4-(2-디메틸아미노카보닐피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 17의 화합물)17) (S)-[N-3- (4- (2-dimethylaminocarbonylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (implemented Compound of Example 17)

18) (S)-[N-3-(4-(2-히드록시피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 18의 화합물)18) (S)-[N-3- (4- (2-hydroxypyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 18 Compound of

19) (S)-[N-3-(4-(N-2-디메틸아미노아세톡시아세틸아미노피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 19의 화합물)19) (S)-[N-3- (4- (N-2-dimethylaminoacetoxyacetylaminopyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl Acetamide (compound of Example 19)

20) (S)-[N-3-(4-(2-메틸아미노피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 20의 화합물)20) (S)-[N-3- (4- (2-methylaminopyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 20 Compound of

21) (S)-[N-3-(4-(2-디메틸아미노피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 21의 화합물)21) (S)-[N-3- (4- (2-dimethylaminopyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 21 Compound of

22) (S)-[N-3-(4-(2-히드록시아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 염산염 (실시예 22의 화합물)22) (S)-[N-3- (4- (2-hydroxyacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide hydrochloride ( Compound of Example 22)

23) (S)-[N-3-(4-(2-히드록시아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 히드록시프로필메틸셀룰로스 (HPMC, hydroxypropylmethylcellulose) 배산체 (실시예 23의 화합물)23) (S)-[N-3- (4- (2-hydroxyacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide hydroxy Propylmethylcellulose (HPMC, Hydroxypropylmethylcellulose) Dispersant (Compound of Example 23)

24) (S)-[N-3-(4-(2-아세톡시피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리 딘일]메틸 아세트아마이드 (실시예 24의 화합물)24) (S)-[N-3- (4- (2-acetoxypyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 24 Compound of

25) (S)-[N-3-(4-(2-메톡시메틸옥시피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 25의 화합물)25) (S)-[N-3- (4- (2-methoxymethyloxypyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (implemented Compound of Example 25)

26) (S)-[N-3-(4-(2-메탄술포닐옥시피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 26의 화합물)26) (S)-[N-3- (4- (2-methanesulfonyloxypyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (implemented Compound of Example 26)

27) (S)-[N-3-(4-(2-아미노카보닐피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 27의 화합물)27) (S)-[N-3- (4- (2-aminocarbonylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 27 compounds)

28) (S)-[N-3-(4-(2-디메틸아미노아세톡시메틸피리딘-4-일)-3-플로로페닐)-2 -옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 28의 화합물)28) (S)-[N-3- (4- (2-dimethylaminoacetoxymethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide ( Compound of Example 28)

29) (S)-[N-3-(4-(2-(2-히드록시에틸)아미노카보닐피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 29의 화합물)29) (S)-[N-3- (4- (2- (2-hydroxyethyl) aminocarbonylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl ] Methyl Acetamide (Compound of Example 29)

30) (S)-[N-3-(4-(2-N,N-디(2-히드록시에틸)아미노카보닐피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 30의 화합물)30) (S)-[N-3- (4- (2-N, N-di (2-hydroxyethyl) aminocarbonylpyridin-4-yl) -3-fluorophenyl) -2-oxo- 5-oxazolidinyl] methyl acetamide (compound of Example 30)

31) (S)-[N-3-(4-(2-피페라진-1-일피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 31의 화합물)31) (S)-[N-3- (4- (2-piperazin-1-ylpyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Compound of Example 31)

32) (S)-[N-3-(4-(2-(4-아세톡시아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 32의 화합물)32) (S)-[N-3- (4- (2- (4-acetoxyacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5- Oxazolidinyl] methyl acetamide (Compound of Example 32)

33) (S)-[N-3-(4-(2-(4-벤질옥시아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 33의 화합물)33) (S)-[N-3- (4- (2- (4-benzyloxyacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5- Oxazolidinyl] methyl acetamide (Compound of Example 33)

34) (S)-[N-3-(4-(2-(4-히드록시아세틸피페라진-1-일)피리딘-5-일)-3-플로로 페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 34의 화합물)34) (S)-[N-3- (4- (2- (4-hydroxyacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5- Oxazolidinyl] methyl acetamide (Compound of Example 34)

35) (S)-[N-3-(4-(2-(4-디메틸아미노아세톡시아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 35의 화합물)35) (S)-[N-3- (4- (2- (4-dimethylaminoacetoxyacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo- 5-oxazolidinyl] methyl acetamide (compound of Example 35)

36) (S)-[N-3-(4-(2-(4-클로로아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 36의 화합물)36) (S)-[N-3- (4- (2- (4-chloroacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxa Zolidinyl] methyl acetamide (compound of Example 36)

37) (S)-[N-3-(4-(2-(4-아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 37의 화합물)37) (S)-[N-3- (4- (2- (4-acetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazoli Dinyl] methyl acetamide (compound of Example 37)

38) (S)-[N-3-(4-(2-(4-메톡시아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 38의 화합물)38) (S)-[N-3- (4- (2- (4-methoxyacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5- Oxazolidinyl] methyl acetamide (Compound of Example 38)

39) (S)-[N-3-(4-(2-(4-몰포리닐아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 39의 화합물)39) (S)-[N-3- (4- (2- (4-morpholinylacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5 -Oxazolidinyl] methyl acetamide (compound of Example 39)

40) (S)-[N-3-(4-(2-(4-메톡시카보닐메틸아미노아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 40의 화합물)40) (S)-[N-3- (4- (2- (4-methoxycarbonylmethylaminoacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2- Oxo-5-oxazolidinyl] methyl acetamide (compound of Example 40)

41) (S)-[N-3-(4-(2-(4-에톡시카보닐피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 41의 화합물)41) (S)-[N-3- (4- (2- (4-ethoxycarbonylpiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5 -Oxazolidinyl] methyl acetamide (compound of Example 41)

42) (S)-[N-3-(4-(2-아지도메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 42의 화합물)42) (S)-[N-3- (4- (2-azidomethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example Compound of 42)

43) (S)-[N-3-(4-(2-이미다졸-1-일)메틸피리딘-4-일)-3-플로로페닐)-2-옥소- 5-옥사졸리딘일]메틸 아세트아마이드 (실시예 43의 화합물)43) (S)-[N-3- (4- (2-imidazol-1-yl) methylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl Acetamide (compound of Example 43)

44) (S)-[N-3-(4-(2-몰포린-4-일)메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 44의 화합물)44) (S)-[N-3- (4- (2-morpholin-4-yl) methylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl Acetamide (compound of Example 44)

45) (S)-[N-3-(4-(2-아세틸싸이오메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 45의 화합물)45) (S)-[N-3- (4- (2-acetylthiomethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (implemented Compound of Example 45)

46) (S)-[N-3-(4-(2-머캅토메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 46의 화합물)46) (S)-[N-3- (4- (2-mercaptomethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example Compound of 46)

47) (S)-[N-3-(4-(2-(4-메탄술포닐옥시아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 47의 화합물)47) (S)-[N-3- (4- (2- (4-methanesulfonyloxyacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo- 5-oxazolidinyl] methyl acetamide (compound of Example 47)

48) (S)-[N-3-(4-(2-(4-아크릴로일피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 48의 화합물)48) (S)-[N-3- (4- (2- (4-acryloylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5- Oxazolidinyl] methyl acetamide (Compound of Example 48)

49) (S)-[N-3-(4-(2-(4-에톡시옥소아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 49의 화합물)49) (S)-[N-3- (4- (2- (4-ethoxyoxoacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5 -Oxazolidinyl] methyl acetamide (compound of Example 49)

50) (S)-[N-3-(4-(2-(4-니코티노일피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 50의 화합물)50) (S)-[N-3- (4- (2- (4-nicotinoylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5- Oxazolidinyl] methyl acetamide (Compound of Example 50)

51) (S)-[N-3-(4-(2-(4-피발로일피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 51의 화합물)51) (S)-[N-3- (4- (2- (4-pivaloylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5- Oxazolidinyl] methyl acetamide (Compound of Example 51)

52) (S)-[N-3-(4-(2-(4-테트라부틸아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 52의 화합물)52) (S)-[N-3- (4- (2- (4-tetrabutylacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5- Oxazolidinyl] methyl acetamide (Compound of Example 52)

53) (S)-[N-3-(4-(2-(4-니코티노일옥시아세틸피페라진-1-일)피리딘-5-일)-3- 플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 53의 화합물)53) (S)-[N-3- (4- (2- (4-nicotinoyloxyacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo- 5-oxazolidinyl] methyl acetamide (compound of Example 53)

54) (S)-[N-3-(4-(2-(4-(2,5-디메톡시페닐아세틸)피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 54의 화합물)54) (S)-[N-3- (4- (2- (4- (2,5-dimethoxyphenylacetyl) piperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (compound of Example 54)

55) (S)-[N-3-(4-(2-(4-(3,3-디메틸아크릴로일)피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 55의 화합물)55) (S)-[N-3- (4- (2- (4- (3,3-dimethylacryloyl) piperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (compound of Example 55)

56) (S)-[N-3-(4-(2-(4-(2,6-디메톡시벤조일)피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 56의 화합물)56) (S)-[N-3- (4- (2- (4- (2,6-dimethoxybenzoyl) piperazin-1-yl) pyridin-5-yl) -3-fluorophenyl)- 2-oxo-5-oxazolidinyl] methyl acetamide (compound of Example 56)

57) (S)-[N-3-(4-(2-(4-(2-트리플로로메틸)벤조일)피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 57의 화합물)57) (S)-[N-3- (4- (2- (4- (2-trifluoromethyl) benzoyl) piperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (compound of Example 57)

58) (S)-[N-3-(4-(2-(4-(4-트리플로로메틸)벤조일)피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 58의 화합물)58) (S)-[N-3- (4- (2- (4- (4-trifluoromethyl) benzoyl) piperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (compound of Example 58)

59) (S)-[N-3-(4-(2-(4-벤질카보닐피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 59의 화합물)59) (S)-[N-3- (4- (2- (4-benzylcarbonylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5- Oxazolidinyl] methyl acetamide (Compound of Example 59)

60) (S)-[N-3-(4-(2-(4-크로토닐피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 60의 화합물)60) (S)-[N-3- (4- (2- (4-crotonylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxa Zolidinyl] methyl acetamide (compound of Example 60)

61) (S)-[N-3-(4-(2-(4-트리플로로메틸카보닐피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 61의 화합물) 61) (S)-[N-3- (4- (2- (4-trifluoromethylcarbonylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo -5-oxazolidinyl] methyl acetamide (compound of Example 61)                     

62) (S)-[N-3-(4-(2-(4-n-발레릴피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 62의 화합물)62) (S)-[N-3- (4- (2- (4-n- valerylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5 -Oxazolidinyl] methyl acetamide (compound of Example 62)

63) (S)-[N-3-(4-(2-(4-페닐옥시카보닐피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 63의 화합물)63) (S)-[N-3- (4- (2- (4-phenyloxycarbonylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5 -Oxazolidinyl] methyl acetamide (compound of Example 63)

64) (S)-[N-3-(4-(2-(4-알릴옥시카보닐피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 64의 화합물)64) (S)-[N-3- (4- (2- (4-allyloxycarbonylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5 -Oxazolidinyl] methyl acetamide (compound of Example 64)

65) (S)-[N-3-(4-(2-(4-(1-클로로에틸)옥시카보닐피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 65의 화합물)65) (S)-[N-3- (4- (2- (4- (1-chloroethyl) oxycarbonylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl)- 2-oxo-5-oxazolidinyl] methyl acetamide (compound of Example 65)

66) (S)-[N-3-(4-(2-(4-(4-니트로벤질)옥시카보닐피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 66의 화합물)66) (S)-[N-3- (4- (2- (4- (4-nitrobenzyl) oxycarbonylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl)- 2-oxo-5-oxazolidinyl] methyl acetamide (compound of Example 66)

67) (S)-[N-3-(4-(2-(4-벤질옥시카보닐피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 67의 화합물)67) (S)-[N-3- (4- (2- (4-benzyloxycarbonylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5 -Oxazolidinyl] methyl acetamide (compound of Example 67)

68) (S)-[N-3-(4-(2-(4-(9-플루오레닐메틸옥시카보닐)피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 68의 화합물)68) (S)-[N-3- (4- (2- (4- (9-fluorenylmethyloxycarbonyl) piperazin-1-yl) pyridin-5-yl) -3-fluorophenyl ) -2-oxo-5-oxazolidinyl] methyl acetamide (compound of Example 68)

69) (S)-[N-3-(4-(2-(4-(2-피리미디닐)피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 69의 화합물)69) (S)-[N-3- (4- (2- (4- (2-pyrimidinyl) piperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2- Oxo-5-oxazolidinyl] methyl acetamide (compound of Example 69)

70) (S)-[N-3-(4-(2-(4-메톡시카보닐메틸피페라진-1-일)피리딘-5-일)-3-플로 로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 70의 화합물)70) (S)-[N-3- (4- (2- (4-methoxycarbonylmethylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo- 5-oxazolidinyl] methyl acetamide (compound of Example 70)

71) (S)-[N-3-(4-(2-플로로메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 71의 화합물)71) (S)-[N-3- (4- (2-fluoromethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 71 compounds)

72) (S)-[N-3-(4-(2-시아노메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 72의 화합물)72) (S)-[N-3- (4- (2-cyanomethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 72 compounds)

73) (S)-[N-3-(4-(2-메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 73의 화합물)73) (S)-[N-3- (4- (2-methylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (from Example 73 compound)

74) (S)-[N-3-(4-(2-(4-(2-히드록시)에틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 74의 화합물)74) (S)-[N-3- (4- (2- (4- (2-hydroxy) ethylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2- Oxo-5-oxazolidinyl] methyl acetamide (compound of Example 74)

75) (S)-[N-3-(4-(2-(4-(2-아세톡시)에틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 75의 화합물)75) (S)-[N-3- (4- (2- (4- (2-acetoxy) ethylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2- Oxo-5-oxazolidinyl] methyl acetamide (compound of Example 75)

76) (S)-[N-3-(4-(2-(4-메톡시카보닐피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 76의 화합물)76) (S)-[N-3- (4- (2- (4-methoxycarbonylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5 -Oxazolidinyl] methyl acetamide (compound of Example 76)

77) (S)-[N-3-(4-(2-(4-(2-메탄술포닐옥시)에틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 77의 화합물)77) (S)-[N-3- (4- (2- (4- (2-methanesulfonyloxy) ethylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl)- 2-oxo-5-oxazolidinyl] methyl acetamide (compound of Example 77)

78) (S)-[N-3-(4-(2-(4-히드록시메틸)이미다졸-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 78의 화합물)78) (S)-[N-3- (4- (2- (4-hydroxymethyl) imidazol-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5 -Oxazolidinyl] methyl acetamide (compound of Example 78)

79) (S)-[N-3-(4-(2-아미노아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 79의 화합물)79) (S)-[N-3- (4- (2-aminoacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example Compound of 79)

80) (S)-[N-3-(4-(2-(4-시아노피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2- 옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 80의 화합물)80) (S)-[N-3- (4- (2- (4-cyanopiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxa Zolidinyl] methyl acetamide (compound of Example 80)

81) (S)-[N-3-(4-(2-(4-카르복스아마이드옥심피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 81의 화합물)81) (S)-[N-3- (4- (2- (4-carboxamide oximepiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5 -Oxazolidinyl] methyl acetamide (compound of Example 81)

82) (S)-[N-3-(4-(2-(4-옥소피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 82의 화합물)82) (S)-[N-3- (4- (2- (4-oxopiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxa Zolidinyl] methyl acetamide (compound of Example 82)

83) (S)-[N-3-(4-(2-아지도아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 83의 화합물)83) (S)-[N-3- (4- (2-azidoacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (implemented Compound of Example 83)

84) (S)-[N-3-(4-(2-(1,2,3,4,6,7-헥사히드로-5-옥소-1,4-디아제팬-1-일)-피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 84의 화합물)84) (S)-[N-3- (4- (2- (1,2,3,4,6,7-hexahydro-5-oxo-1,4-diazepane-1-yl) -pyridine -5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (compound of Example 84)

85) (S)-[N-3-(4-(2-N-(디메틸아미노메틸렌)아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 85의 화합물)85) (S)-[N-3- (4- (2-N- (dimethylaminomethylene) aminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl Acetamide (Compound of Example 85)

86) (S)-[N-3-(4-(2-(4-히드록시이미노피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 86의 화합물)86) (S)-[N-3- (4- (2- (4-hydroxyiminopiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5 -Oxazolidinyl] methyl acetamide (compound of Example 86)

87) (S)-[N-3-(4-(2-(4-메탄술포닐옥시이미노피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 87의 화합물)87) (S)-[N-3- (4- (2- (4-methanesulfonyloxyiminopiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo -5-oxazolidinyl] methyl acetamide (compound of Example 87)

88) (S)-[N-3-(4-(2-(4-메틸이미노피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 88의 화합물)88) (S)-[N-3- (4- (2- (4-methyliminopiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5 -Oxazolidinyl] methyl acetamide (compound of Example 88)

89) (S)-[N-3-(4-(2-(4-메톡시카보닐히드라지노피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 89의 화합물) 89) (S)-[N-3- (4- (2- (4-methoxycarbonylhydrazinopiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2- Oxo-5-oxazolidinyl] methyl acetamide (compound of Example 89)                     

90) (S)-[N-3-(4-(2-N-(L-알라닐)아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 90의 화합물)90) (S)-[N-3- (4- (2-N- (L-alanyl) aminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] Methyl Acetamide (Compound of Example 90)

91) (S)-[N-3-(4-(2-아세틸아미노아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 91의 화합물)91) (S)-[N-3- (4- (2-acetylaminoacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (implemented Compound of Example 91)

92) (S)-[N-3-(4-(2-디메틸아미노아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 92의 화합물)92) (S)-[N-3- (4- (2-dimethylaminoacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (implemented Compound of Example 92)

93) (S)-[N-3-(4-(2-니코티노일아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 93의 화합물)93) (S)-[N-3- (4- (2-nicotinoylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (implemented Compound of Example 93)

94) (S)-[N-3-(4-(2-(1,2,4-트리아졸-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 94의 화합물)94) (S)-[N-3- (4- (2- (1,2,4-triazol-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5 -Oxazolidinyl] methyl acetamide (compound of Example 94)

95) (S)-[N-3-(4-(2-(4-히드록시피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 95의 화합물)95) (S)-[N-3- (4- (2- (4-hydroxypiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5- Oxazolidinyl] methyl acetamide (Compound of Example 95)

96) (S)-[N-3-(4-(2-N,N-(히드록시아세틸)메틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 96의 화합물)96) (S)-[N-3- (4- (2-N, N- (hydroxyacetyl) methylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazoli Dinyl] methyl acetamide (compound of Example 96)

97) (S)-[N-3-(4-(2-(4-메틸이미다졸-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 97의 화합물)97) (S)-[N-3- (4- (2- (4-methylimidazol-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxa Zolidinyl] methyl acetamide (compound of Example 97)

98) (S)-[N-3-(4-(2-(2-히드록시프로피오닐)아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 98의 화합물)98) (S)-[N-3- (4- (2- (2-hydroxypropionyl) aminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] Methyl Acetamide (Compound of Example 98)

99) (S)-[N-3-(4-(2-(3-아미노-1,2,4-트리아졸-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 99의 화합물) 99) (S)-[N-3- (4- (2- (3-amino-1, 2,4-triazol-1-yl) pyridin-5-yl) -3-fluorophenyl) -2 -Oxo-5-oxazolidinyl] methyl acetamide (compound of Example 99)                     

100) (S)-[N-3-(4-(2-(4-에톡시카보닐이미다졸-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 100의 화합물)
100) (S)-[N-3- (4- (2- (4-ethoxycarbonylimidazol-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo- 5-oxazolidinyl] methyl acetamide (compound of Example 100)

더욱 바람직하게는 상기 화학식 1의 화합물은 More preferably, the compound of Formula 1

1) (S)-[N-3-(4-(2-히드록시아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소 -5-옥사졸리딘일]메틸 아세트아마이드,1) (S)-[N-3- (4- (2-hydroxyacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide,

2) (S)-[N-3-(4-(2-메톡시피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드,2) (S)-[N-3- (4- (2-methoxypyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide,

3) (S)-[N-3-(4-(2-메틸아미노피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드,3) (S)-[N-3- (4- (2-methylaminopyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide,

4) (S)-[N-3-(4-(2-디메틸아미노피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드,4) (S)-[N-3- (4- (2-dimethylaminopyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide,

5) (S)-[N-3-(4-(2-아미노아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드, 5) (S)-[N-3- (4- (2-aminoacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide,

6) (S)-[N-3-(4-(2-(1,2,4-트리아졸-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드,6) (S)-[N-3- (4- (2- (1,2,4-triazol-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5 Oxazolidinyl] methyl acetamide,

7) (S)-[N-3-(4-(2-(4-히드록시피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드, 또는7) (S)-[N-3- (4- (2- (4-hydroxypiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5- Oxazolidinyl] methyl acetamide, or

8) (S)-[N-3-(4-(2-(4-메틸이미다졸-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드이다. 8) (S)-[N-3- (4- (2- (4-methylimidazol-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxa Zolidinyl] methyl acetamide.                     

9) (S)-[N-3-(4-(2-이미다졸-1-일-피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 9) (S)-[N-3- (4- (2-imidazol-1-yl-pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acet Amide

상기 화학식 1로 표시되는 옥사졸리디논 화합물들의 화학식을 하기 표 1에 나타내었다. The chemical formulas of the oxazolidinone compounds represented by Chemical Formula 1 are shown in Table 1 below.

<표 1>TABLE 1

Figure 112000019986940-pat00009
Figure 112000019986940-pat00009

Figure 112000019986940-pat00010
Figure 112000019986940-pat00010

Figure 112000019986940-pat00011
Figure 112000019986940-pat00011

Figure 112000019986940-pat00012

Figure 112000019986940-pat00012

Figure 112000019986940-pat00013



Figure 112000019986940-pat00013



상기 화학식 1로 표시되는 본 발명의 옥사졸리디논 화합물은 약학적으로 허용 가능한 염의 형태로 사용할 수 있으며, 염으로는 약학적으로 허용가능한 유리산 (free acid)에 의해 형성된 산부가염이 유용하다. 유리산으로는 무기산과 유기산을 사용할 수 있다. 무기산으로는 염산, 브롬산, 황산, 인산 등을 사용할 수 있고, 유기산으로는 구연산, 초산, 젖산, 말레인산, 우마린산, 글루콘산, 메탄술폰산, 글리콘산, 숙신산, 4-톨루엔술폰산, 갈룩투론산, 엠본산, 글루탐산, 또는 아스파르트산 등을 사용할 수 있다. The oxazolidinone compound of the present invention represented by Chemical Formula 1 may be used in the form of a pharmaceutically acceptable salt, and acid addition salts formed by pharmaceutically acceptable free acid are useful as salts. Inorganic acids and organic acids can be used as the free acid. Hydrochloric acid, bromic acid, sulfuric acid, phosphoric acid and the like can be used as the inorganic acid, and citric acid, acetic acid, lactic acid, maleic acid, umarin acid, gluconic acid, methanesulfonic acid, glyconic acid, succinic acid, 4-toluenesulfonic acid, and gallic acid are used as the organic acid. Luteuronic acid, embonic acid, glutamic acid, aspartic acid and the like can be used.

또한 화학식 1의 화합물은 염기로 인해 형성된 약학적으로 허용 가능한 금속염 특히 알칼리 금속염일 수도 있다. 이들의 예로는 나트륨염 및 칼륨염이 있다.
The compound of formula 1 may also be a pharmaceutically acceptable metal salt, in particular an alkali metal salt, formed due to the base. Examples of these are sodium salts and potassium salts.

또한 본 발명에서는 하기 반응식 1로 표시되는 화학식 1의 옥사졸리디논(oxazolidinone) 유도체의 제조방법을 제공한다.In another aspect, the present invention provides a method for preparing an oxazolidinone derivative of the formula (1) represented by Scheme 1.

Figure 112000019986940-pat00014
Figure 112000019986940-pat00014

상기 반응식에서 R1 및 R2는 화학식 1에서 정의한 바와 같으며, X는 할로겐 원소이다.
R 1 and in the above scheme R 2 is as defined in Formula 1, and X is a halogen element.

화학식 1의 화합물의 제조방법은Method for preparing a compound of formula 1

1) 히드록시메틸옥사졸리디논 유도체(2)의 히드록시기를 아민기로 변환시켜 아미노메틸옥사졸리디논 유도체(3)을 제조하는 단계 (제 1 단계);1) preparing an aminomethyloxazolidinone derivative (3) by converting the hydroxy group of the hydroxymethyloxazolidinone derivative (2) to an amine group (first step);

2) 상기 제 1 단계에서 제조된 아미노메틸옥사졸리디논 유도체(3)의 화합물을 아세틸화 반응시켜 화합물(4)를 얻는 단계 (제 2 단계); 2) acetylating the compound of the aminomethyloxazolidinone derivative (3) prepared in the first step to obtain a compound (4) (second step);

3) 화합물(4)를 할로겐화 반응시켜 화합물(5)를 얻는 단계 (제 3 단계);3) halogenating the compound (4) to obtain the compound (5) (third step);

4) 화합물(5)를 스텐닐화시켜 화합물(6)을 얻는 단계 (제 4 단계);4) stenylating compound (5) to obtain compound (6) (fourth step);

5) 화합물(6)과 화학식 1로 표시되는 화합물의 적절한 치환기에 대응하는 브롬 또는 요오드로 치환된 피리딘 유도체와 반응시켜 화학식 1의 피리딘 고리를 포함하는 옥사졸리디논 유도체를 얻는 단계 (제 5단계)로 이루어진다.
5) reacting compound (6) with a pyridine derivative substituted with bromine or iodine corresponding to an appropriate substituent of compound represented by formula (1) to obtain an oxazolidinone derivative comprising a pyridine ring of formula (I) Is done.

상기 반응에서 출발물질로 사용되는 화학식 2의 히드록시메틸옥사졸리디논 유도체는 공지의 방법으로 간단히 합성할 수 있다. 예를들면, 아닐린의 아민기에 Cbz (Benzyloxycarbonyl)기를 도입한 다음 글라시딜부티레이트와 강염기 하에서 반응시켜 얻을 수 있다.
The hydroxymethyloxazolidinone derivative of the formula (2) used as a starting material in the reaction can be simply synthesized by a known method. For example, a Cbz (Benzyloxycarbonyl) group may be introduced into an amine group of aniline and then reacted with glacidyl butyrate under a strong base.

제 1 단계에서는 화학식 (2)의 화합물의 하이드록시기를 아자이드로 쉽게 치환하기위해 우선 하이드록시기에 메탄술포닐기, 파라톨루엔술포닐기 또는 할로겐을 도입한 후, 소디움아자이드와 반응시키고 생성된 아자이드를 팔라디움이나 트리페닐 포스핀을 사용하여 환원시켜 화학식 (3)의 화합물을 얻는다. In the first step, methanesulfonyl group, paratoluenesulfonyl group or halogen is first introduced into the hydroxy group to easily replace the hydroxy group of the compound of formula (2) with azide, and then reacted with sodium azide and the resulting azide Is reduced using palladium or triphenyl phosphine to obtain the compound of formula (3).

상기 화학식 (2)로 표시되는 화합물의 히드록시기에 메탄술포닐기, 파라톨루엔술포닐기 또는 할로겐을 도입할 경우에는 반응온도 0℃에서 실시하는 것이 바람직하다. When introducing methanesulfonyl group, paratoluenesulfonyl group or halogen into the hydroxy group of the compound represented by the above formula (2), it is preferable to carry out at a reaction temperature of 0 ° C.

상기 메탄술포닐기, 파라톨루엔술포닐기 또는 할로겐이 도입된 화합물에 아자이드기를 도입하기 위해 소디움아자이드는 약 1∼3 당량 첨가하는 것이 바람직하다. 또한 반응온도는 90∼110℃ 범위가 바람직하며, 1∼2시간동안 반응시키는 것이 바람직하다. 반응용매로는 디메틸포름아마이드, 디메틸설프옥사이드 또는 1,4-디옥산 등을 사용할 수 있다.Sodium azide is preferably added in an amount of about 1 to 3 equivalents to introduce an azide group into the compound into which the methanesulfonyl group, paratoluenesulfonyl group, or halogen is introduced. In addition, the reaction temperature is preferably in the range of 90 to 110 ° C, and preferably for 1 to 2 hours. Dimethyl formamide, dimethyl sulfoxide or 1,4-dioxane can be used as the reaction solvent.

팔라디움을 사용하여 상기 아자이드 화합물을 환원할 경우에는 상온에서 수소 하에 반응을 실시하는 것이 바람직하다. 이때 반응용매는 테트라하이드로퓨란, 메탄올 등을 단독으로 또는 혼합하여 사용할 수 있다. 또한 트리페닐 포스핀을 사용하여 아자이드 화합물을 환원할 경우에는 테트라하이드로퓨란에 물을 소량 첨가한 후 2시간 가량 환류한다.
When the azide compound is reduced using palladium, it is preferable to carry out the reaction under hydrogen at room temperature. At this time, the reaction solvent may be used alone or mixed with tetrahydrofuran, methanol. In addition, when triphenyl phosphine is used to reduce the azide compound, it is refluxed for about 2 hours after adding a small amount of water to tetrahydrofuran.

제 2 단계는 제 1 단계에서 얻은 화학식(3)의 아민 화합물을 염기 하에 무수 아세트산과 반응시켜 아세틸화 반응시키는 단계로, 이때 적당한 염기로는 트리에틸 아민, 피리딘, 디이소프로필에틸아민 등이 사용될 수 있다.
In the second step, the amine compound of formula (3) obtained in the first step is reacted with acetic anhydride under a base to be acetylated. In this case, triethyl amine, pyridine, diisopropylethylamine, etc. may be used as a suitable base. Can be.

제 3 단계에서는 화학식(4)의 화합물의 페닐기의 4번 위치에 할로겐화 반응시키는 단계로, 페닐기에 치환될 할로겐은 요오드가 바람직하다. 요오드화 반응은 아이오딘 모노클로라이드 (ICl), 또는 트리플루오아세트산 은염 (CF3COOAg)과 요오드 존재 하에서 반응시키는 것이 바람직하다. 반응은 상온에서 실시하는 것이 바람직하다.
In the third step, halogenation reaction is carried out at position 4 of the phenyl group of the compound of formula (4), and the halogen to be substituted for the phenyl group is preferably iodine. The iodide reaction is preferably reacted with iodine monochloride (ICl) or trifluoroacetic acid silver salt (CF 3 COOAg) in the presence of iodine. It is preferable to perform reaction at normal temperature.

제 4단계에서는 화학식 (5)의 화합물을 팔라디움 촉매 하에 헥사메틸디틴과 반응시켜 요오드기가 트리메틸스테닐기로 치환된 화합물을 얻을 수 있다. 팔라디움 촉매로는 디클로로비스트리페닐포스핀팔라디움(II) 또는 테트라키스트리페닐포스핀팔라디움(0)을 사용할 수 있다. 반응용매로는 1,4-디옥산, 디메틸포름아마이드, 테트라하이드로퓨란 등을 사용할 수 있고 반응온도는 90∼120℃에서 실시하는 것이 바람직하다.
In the fourth step, the compound of formula (5) may be reacted with hexamethylditin under a palladium catalyst to obtain a compound in which an iodine group is substituted with a trimethylstenyl group. As the palladium catalyst, dichlorobistriphenylphosphinepalladium (II) or tetrakistriphenylphosphinepalladium (0) can be used. As a reaction solvent, 1, 4- dioxane, dimethylformamide, tetrahydrofuran, etc. can be used, It is preferable to carry out reaction temperature at 90-120 degreeC.

화학식 1로 표시되는 본 발명의 옥사졸리디논 화합물들은 트리메틸스테닐기를 도입한 화학식 (6)의 화합물과 브롬 또는 아이오딘으로 치환된 피리딘 유도체를 팔라디움(0) 또는 팔라디움(II) 하에 반응시켜 얻는다. 상기 팔라디움 촉매로는 디클로로비스트리페닐포스핀 팔라디움(II) 또는 테트라키스트리페닐포스핀 팔라디움(0)을 사용할 수 있다. 반응온도는 60∼150 ℃ 범위에서 실시하는 것이 바람직하며, 반응시간은 약 30분∼12시간이 바람직하다. 또한 반응용매로는 디메틸포름아마이드, 1,4-디옥산, 테트라히드로퓨란을 단독으로 또는 혼합하여 사용할 수 있다.
The oxazolidinone compounds of the present invention represented by the formula (1) are obtained by reacting a compound of the formula (6) having a trimethylstenyl group with a pyridine derivative substituted with bromine or iodine under palladium (0) or palladium (II). As the palladium catalyst, dichlorobistriphenylphosphine palladium (II) or tetrakistriphenylphosphine palladium (0) may be used. The reaction temperature is preferably carried out in the range of 60 to 150 ° C., and the reaction time is preferably about 30 minutes to 12 hours. As the reaction solvent, dimethylformamide, 1,4-dioxane and tetrahydrofuran may be used alone or in combination.

또한 본 발명에서는 화학식 1의 화합물을 유효성분으로 함유하는 항생제용 약학적 조성물을 제공한다.In another aspect, the present invention provides a pharmaceutical composition for antibiotics containing the compound of formula (1) as an active ingredient.

본 발명은 비독성, 불활성, 제약상 적합한 부형제 이외에, 본 발명에 따른 1종 이상의 화합물을 함유하거나, 또는 본 발명에 따른 1종 이상의 유효 화합물로 이루어지는 제약 조성물 및 이 조성물의 제조 방법을 제공한다.The present invention provides, in addition to non-toxic, inert, pharmaceutically suitable excipients, a pharmaceutical composition containing at least one compound according to the invention or consisting of at least one active compound according to the invention and a process for preparing the composition.

화학식 1의 화합물은 임상투여시에 경구 또는 비경구로 투여가 가능하며 일반적인 의약품제제의 형태로 사용될 수 있다.The compound of formula 1 may be administered orally or parenterally during clinical administration and may be used in the form of a general pharmaceutical preparation.

즉, 본 발명의 화학식 1의 화합물은 실제 임상투여시에 경구 및 비경구의 여러 가지 제형으로 투여될 수 있는데, 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 하나 이상의 화학식 1의 화합물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트 (Calcium carbonate), 수크로스 (Sucrose) 또는 락토오스 (Lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다. 비수성용제, 현탁용제로는 프로필렌글리콜 (Propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔 (witepsol), 마크로골, 트윈 (tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.
That is, the compound of Formula 1 of the present invention may be administered in various oral and parenteral dosage forms during actual clinical administration, and when formulated, the commonly used fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc. Prepared using diluents or excipients. Solid form preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which form at least one excipient such as starch, calcium carbonate, It is prepared by mixing sucrose or lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

일반적으로 의약품에 있어서, 본 발명에 의한 화학식 1로 표시되는 화합물의 유효 용량은 성인기준 1.2g/day 이고 하루 2~3회 투여될 수 있다. 그러나, 상기 투약량은 변화시킬 필요가 있으며, 특히 치료할 객체의 체질 특이성 및 체중, 질병의 종류 및 심도, 제형의 성질, 의약품 투여의 성질, 및 투여 기간 또는 간격을 고려해서 변화시킬 수 있다.
In general, in medicine, the effective dose of the compound represented by the formula (1) according to the present invention is 1.2 g / day for adults and may be administered 2-3 times a day. However, the dosage may need to be changed, and in particular, may be changed in consideration of the constitution specificity and weight of the subject to be treated, the type and depth of the disease, the nature of the formulation, the nature of the drug administration, and the duration or interval of administration.

본 발명에 의한 화학식 1로 표시되는 옥사졸리디논 화합물의 항균력을 측정한 결과 항균 스펙트럼이 넓고 일부 화합물들은 생체내 (in vivo) 효과도 탁월한 것이 확인되었다. 또한 본 발명의 화합물은 기존 항생제에 내성을 가지는 스타필로코카이(Staphylococci), 엔테로코카이(Enterococci), 스트렙토코카이(Streptococci )와 같은 그람양성 호기성 박테리아뿐만 아니라, 박테로이데스 종(Bacteroides), 클로스티리디아 종(Clostridia)과 같은 혐기성 생물과 마이코박테리움 투베르쿨로시스(Mycobacterium tuberculosis), 마이코 박테리움 아비움(Mycobacterium avium) 등의 마이코 박테리움 종(Mycobacterium)과 같은 항산성 미생물들을 포함하여 각종 사람 및 동물 병원균에 강한 항균효과를 나타내었다.
As a result of measuring the antimicrobial activity of the oxazolidinone compound represented by Chemical Formula 1 according to the present invention, it was confirmed that the antimicrobial spectrum was wide and some compounds also had excellent in vivo effects. In addition, compounds of the present invention are Staphylococcus Kokai (Staphylococci), those resistant to existing antibiotics, Enterobacter Kokai (Enterococci), streptomycin Kokai (Streptococci) Gram-positive aerobic bacteria teroyi, as well as foil des species (Bacteroides), such as a Claus tea Lydia Humans , including anaerobic organisms such as Clostridia , and acidic microorganisms such as Mycobacterium species such as Mycobacterium tuberculosis and Mycobacterium avium And showed strong antibacterial effect on animal pathogens.

이하 제조예와 실시예에 의하여 본 발명을 상세히 설명한다. 단 하기 실시예는 발명을 예시하는 것일 뿐 본 발명이 실시예에 의하여 한정되는 것은 아니다.
Hereinafter, the present invention will be described in detail by preparation examples and examples. However, the following examples are merely to illustrate the invention and the present invention is not limited by the examples.

<제조예 1> N-카보벤질옥시-3-플로로아닐린의 제조 Preparation Example 1 Preparation of N-Carbobenzyloxy-3-fluoroaniline

3-플로로아닐린 100g(0.90 mole)을 1L의 테트라하이드로퓨란(Tetrahydrofuran, THF)에 용해시키고 탄산수소나트륨(NaHCO3) 150g(1.8mol)을 첨가한 후 0℃로 냉각시킨 다음 상기 용액에 카보벤질옥시 크로라이드 (CbzCl, N-carbobenzyloxy chloride) 154ml(1.08mol)를 천천히 가하였다. 상기 반응 혼합물은 0℃를 유지시키면서 2시간 동안 교반시킨 다음 에틸아세테이트(ethylacetate) 0.5L를 가하여 추출하였다. 추출된 유기층은 소금물로 세척하고 무수 황산마그네슘 (MgSO4)으로 탈수한 후 감압농축하였다. 잔유물은 n-헥산으로 2번 세척하여 백색결정 132g (85%)의 표제 화합물을 얻었다.
Dissolve 100 g (0.90 mole) of 3-fluoroaniline in 1 L of tetrahydrofuran (THF), add 150 g (1.8 mol) of sodium hydrogen carbonate (NaHCO 3 ), cool to 0 ° C., and then cabo to the solution. 154 ml (1.08 mol) of benzyloxy chloride (CbzCl, N- carbobenzyloxy chloride) was slowly added. The reaction mixture was stirred for 2 hours while maintaining 0 ℃ and extracted by adding 0.5L ethylacetate (ethylacetate). The extracted organic layer was washed with brine, dehydrated with anhydrous magnesium sulfate (MgSO 4 ), and concentrated under reduced pressure. The residue was washed twice with n- hexane to give 132 g (85%) of the title compound as white crystals.

<제조예 2> (R)-[N-3-(3-플로로페닐)-2-옥소-5-옥사졸리딘일]메탄올의 제조 Preparation Example 2 Preparation of (R)-[N-3- (3-fluorophenyl) -2-oxo-5-oxazolidinyl] methanol

상기 제조예 1에서 얻은 N-카보벤질옥시-3-플로로아닐린 132g(0.54mol)을 1.3L의 테트라하이드로퓨란에 용해시키고 -78℃로 냉각시켰다. 질소 하에 n-부틸리튬(n-BuLi, 1.6M /n-헥산, 0.59mol) 370ml를 천천히 가한 다음 약 10분간 교반시켰다. 상기 용액에 (R)-(-)-글리시딜부티레이트 84ml(1.1mol)를 천천히 가하고 반응혼합물을 동일 온도에서 2시간 교반시킨 후 상온에서 24시간 반응시켰다. 반응이 완결된 후 상온에서 반응용액에 암모늄 클로라이드(NH4CI) 용액을 가한 후 에틸아세테이트(0.5L)로 추출하였다. 추출된 유기 층은 소금물로 세척한 다음 무수 황산마그네슘으로 탈수하고 감압 증류하였다. 잔유물은 에틸아세테이트(100ml)로 용해시킨 후 n-헥산을 가하여 백색결정을 얻었다. 상기 백색 결정을 걸러내어 원하는 표제 화합물 80g(70%)을 얻었다. 132 g (0.54 mol) of N-carbenzyloxy-3-fluoroaniline obtained in Preparation Example 1 was dissolved in 1.3 L of tetrahydrofuran and cooled to -78 ° C. 370 ml of n -butyllithium ( n- BuLi, 1.6M / n -hexane, 0.59mol) was slowly added under nitrogen, followed by stirring for about 10 minutes. 84 ml (1.1 mol) of (R)-(-)-glycidyl butyrate was slowly added to the solution, and the reaction mixture was stirred at the same temperature for 2 hours and then reacted at room temperature for 24 hours. After the reaction was completed, ammonium chloride (NH 4 CI) solution was added to the reaction solution at room temperature, and extracted with ethyl acetate (0.5L). The extracted organic layer was washed with brine, dehydrated with anhydrous magnesium sulfate and distilled under reduced pressure. The residue was dissolved in ethyl acetate (100 ml) and n- hexane was added to give white crystals. The white crystals were filtered off to afford 80 g (70%) of the title compound.

1H NMR(DMSO-d6) 7.85(t,1H), 7.58(dd,1H), 7.23(dd,1H), 4.69(m,1H), 4.02(t,1H), 3.80(dd,1H), 3.60(br dd,2H).
 1 H NMR (DMSO-d 6 ) 7.85 (t, 1H), 7.58 (dd, 1H), 7.23 (dd, 1H), 4.69 (m, 1H), 4.02 (t, 1H), 3.80 (dd, 1H) , 3.60 (br dd, 2H).

<제조예 3> (R)-[N-3-(3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 메탄술폰네이트의 제조 Preparation Example 3 Preparation of (R)-[N-3- (3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl methanesulfonate

(R)-[N-3-(3-플로로페닐)-2-옥소-5-옥사졸리딘일]메탄올 55.1g(0.26mol)을 메틸렌 클로라이드(300ml)에 녹이고 0℃에서 트리에틸아민 54.4ml(0.39mol)와 메탄술포닐 클로라이드 24ml(0.312mol)를 천천히 적가하였다. 0℃에서 약 40분가량 반응 혼합물을 교반한 후 물을 첨가하고 클로로포름으로 추출한 다음 무수 황산마그 네슘으로 탈수하고 감압농축한 후 건조하여 표제 화합물 78.3g을 얻었다.
55.1 g (0.26 mol) of (R)-[N-3- (3-fluorophenyl) -2-oxo-5-oxazolidinyl] methanol is dissolved in methylene chloride (300 ml) and 54.4 ml of triethylamine at 0 ° C. (0.39 mol) and 24 ml (0.312 mol) of methanesulfonyl chloride were slowly added dropwise. After stirring the reaction mixture at 0 ° C. for about 40 minutes, water was added, extracted with chloroform, dehydrated with anhydrous magnesium sulfate, concentrated under reduced pressure, and dried to obtain 78.3 g of the title compound.

<제조예 4> (R)-[N-3-(3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아자이드의 제조 Preparation Example 4 Preparation of (R)-[N-3- (3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl azide

(R)-[N-3-(3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 메탄술폰네이트 78g(0.27mol)을 디메틸포름아마이드 800ml에 녹이고 소듐아자이드 26.3g (0.41mol)을 가한 후 100℃에서 2시간 교반하였다. 상기 반응 혼합물에 물을 첨가한 다음 에틸아세테이트로 추출하고 탈수한 후 감압 농축하고 건조하여 표제 화합물 70g을 얻었다.
78 g (0.27 mol) of (R)-[N-3- (3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl methanesulfonate was dissolved in 800 ml of dimethylformamide and 26.3 g (0.41) of sodium azide mol) was added and stirred at 100 ° C. for 2 hours. Water was added to the reaction mixture, which was then extracted with ethyl acetate, dehydrated, concentrated under reduced pressure and dried to give 70 g of the title compound.

<제조예 5> (S)-[N-3-(3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아민의 제조 Preparation Example 5 Preparation of (S)-[N-3- (3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl amine

(R)-[N-3-(3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아자이드 70g을 테트라히드로퓨란 400ml와 메탄올 80ml의 혼합용매에 녹인 후 팔라듐 카본(Pd/C) 8g을 가하고 실온에서 수소 하에 24시간동안 교반한 다음 여과하고 감압농축하여 표제 화합물 54.6g을 얻었다.
70 g of (R)-[N-3- (3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl azide was dissolved in a mixed solvent of 400 ml of tetrahydrofuran and 80 ml of methanol, followed by palladium carbon (Pd / C) 8 g was added, stirred at room temperature under hydrogen for 24 hours, filtered and concentrated under reduced pressure to give 54.6 g of the title compound.

<제조예 6> (S)-[N-3-(3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조 Preparation Example 6 Preparation of (S)-[N-3- (3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide

(S)-[N-3-(3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아민 54.6g(0.26mol)을 메틸렌 클로라이드 500ml에 녹인 후 0℃에서 트리에틸아민 72.4ml(0.52mol)와 무수아세트산 36.8ml(0.39mol)을 가한 후 반응온도 0℃를 유지하면서 반응 혼합물을 1시간 교반한 다음 물을 가하고 클로로포름으로 추출하였다. 추출된 유기층은 소금물로 세척하고 탈수한 후 감압 농축하여 미색 분말을 얻었다. 생성된 미색 분말을 n-헥산으로 세 번 세척하여 표제 화합물 49.6g(76%)를 얻었다.
54.6 g (0.26 mol) of (S)-[N-3- (3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl amine was dissolved in 500 ml of methylene chloride, and then 72.4 ml of triethylamine at 0 ° C. (0.52 mol) and 36.8 ml (0.39 mol) of acetic anhydride were added thereto, the reaction mixture was stirred for 1 hour while maintaining the reaction temperature at 0 ° C., and water was added thereto, followed by extraction with chloroform. The extracted organic layer was washed with brine, dehydrated and concentrated under reduced pressure to obtain an off-white powder. The resulting off-white powder was washed three times with n- hexane to give 49.6 g (76%) of the title compound.

<제조예 7> (S)-[N-3-(4-아이오도-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조 Preparation Example 7 Preparation of (S)-[N-3- (4-iodo-3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide

(S)-[N-3-(3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 54.5g(0.22mol)을 아세트산 2.5L와 트리플로로아세트산 700ml의 혼합용매에 녹이고 아세트산 300ml에 녹인 아이오딘 모노클로라이드(ICl) 455.7g(2.8mol)을 실온에서 천천히 적가하였다. 실온에서 15시간동안 상기 반응 혼합물을 교반한 후 디에틸에테르를 첨가하여 고체를 생성시키고 이를 여과한 후 얻어진 고체를 클로로포름과 메탄올 혼합용매에 녹인 다음 소듐치오설패이트 용액과 탄산수소나트륨(NaHCO3)용액으로 세척하고 탈수하였다. 잔유물은 감압 농축한 후 건조하여 표제 화합물 59.5g(80.4%)을 얻었다.54.5 g (0.22 mol) of (S)-[N-3- (3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide was added to a mixed solvent of 2.5 L acetic acid and 700 ml of trifluoroacetic acid. 455.7 g (2.8 mol) of iodine monochloride (ICl) dissolved in 300 ml of acetic acid was slowly added dropwise at room temperature. After stirring the reaction mixture at room temperature for 15 hours, diethyl ether was added to form a solid, and the resultant solid was dissolved in a mixed solvent of chloroform and methanol, followed by sodium thiosulfate solution and sodium hydrogen carbonate (NaHCO 3 Washed with solution and dehydrated. The residue was concentrated under reduced pressure and dried to give 59.5 g (80.4%) of the title compound.

1H NMR(DMSO-d6) 8.23(t,1H), 7.82(dd,1H), 7.56(dd,1H), 7.18(dd,1H). 4.74(m,1H), 4.10(t,1H), 3.73(dd,1H), 3.40(br dd,2H), 1.83(s,3H)
 1 H NMR (DMSO-d 6 ) 8.23 (t, 1H), 7.82 (dd, 1H), 7.56 (dd, 1H), 7.18 (dd, 1H). 4.74 (m, 1H), 4.10 (t, 1H), 3.73 (dd, 1H), 3.40 (br dd, 2H), 1.83 (s, 3H)

<제조예 8> (S)-[N-3-(4-트리메틸스테닐-3-플로로페닐)-2-옥소-5-옥사졸리딘일] 메틸 아세트아마이드의 제조 Preparation Example 8 Preparation of (S)-[N-3- (4-trimethylstenyl-3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide

(S)-[N-3-(4-아이오도-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 50g을 1,4-디옥산 660ml에 녹이고 헥사메틸디틴 ((Me3Sn)2) 52g과 디클로로비스트리페닐포스핀팔라디움(II) 9.3g을 가한 후 2시간 동안 환류하였다. 셀라이트(celite)를 사용하여 여과한 후 감압 농축하고 잔유물을 컬럼크로마토그래피로 정제하여 표제 화합물 45g을 분리하였다.
50 g of (S)-[N-3- (4-iodo-3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide was dissolved in 660 ml of 1,4-dioxane and hexamethylditin ( 52 g of (Me 3 Sn) 2 ) and 9.3 g of dichlorobistriphenylphosphinepalladium (II) were added and refluxed for 2 hours. Filtration was carried out using celite, concentrated under reduced pressure, and the residue was purified by column chromatography to separate 45 g of the titled compound.

<제조예 9> 2-아세틸아미노-5-부로모피리딘의 제조Preparation Example 9 Preparation of 2-Acetylamino-5-Bromopyridine

2-아미노-5-부로모피리딘 1g을 피리딘 29ml에 녹이고 실온에서 아세틸클로라이드 0.61ml를 가한 후 15시간동안 실온에서 교반하였다. 상기 반응물에 물을 가하고 에틸아세테이트로 추출한 다음 유기층은 소금물로 세척하였다. 상기 유기층을 탈수, 여과, 감압 농축하여 얻은 고체를 에탄올과 헥산로 재결정하여 표제 화합물 1.06g(85%)을 얻었다.1 g of 2-amino-5-bromopyridine was dissolved in 29 ml of pyridine, 0.61 ml of acetyl chloride was added at room temperature, followed by stirring at room temperature for 15 hours. Water was added to the reaction, extracted with ethyl acetate, and the organic layer was washed with brine. The organic layer was dehydrated, filtered, and concentrated under reduced pressure. The solid obtained was recrystallized from ethanol and hexane to obtain 1.06 g (85%) of the title compound.

1H NMR(CDCl3) 8.60(s,1H), 8.34(d,1H), 8.18(d,1H), 7.79(dd,1H), 2.18(s,3H)
 1 H NMR (CDCl 3 ) 8.60 (s, 1H), 8.34 (d, 1H), 8.18 (d, 1H), 7.79 (dd, 1H), 2.18 (s, 3H)

<제조예 10> 2-아세톡시아세틸아미노-5-부로모피리딘의 제조Preparation Example 10 Preparation of 2-acetoxyacetylamino-5-bromopyridine

2-아미노-5-부로모피리딘 1g을 메틸렌클로라이드 29ml에 녹이고 실온에서 아세톡시아세틸클로라이드 0.93ml와 트리에틸아민 1.61ml를 가한 후 같은 온도에서 1시간 동안 교반하였다. 상기 반응 혼합물에 물을 가한 후 메틸렌클로라이드로 추출 하고 추출된 유기층은 소금물로 세척한 후 탈수 및 여과하고 감압농축한 다음 에틸에테르로 재결정하여 표제 화합물 615mg을 얻었다.1 g of 2-amino-5-bromopyridine was dissolved in 29 ml of methylene chloride, 0.93 ml of acetoxyacetyl chloride and 1.61 ml of triethylamine were added at room temperature, followed by stirring at the same temperature for 1 hour. Water was added to the reaction mixture, followed by extraction with methylene chloride. The extracted organic layer was washed with brine, dehydrated and filtered, concentrated under reduced pressure, and recrystallized with ethyl ether to obtain 615 mg of the title compound.

1H NMR(CDCl3) 8.57(s,1H), 8.32(d,1H), 8.15(d,1H), 7.82(dd,1H), 4.73(s,2H), 2.21(s,3H)
 1 H NMR (CDCl 3 ) 8.57 (s, 1H), 8.32 (d, 1H), 8.15 (d, 1H), 7.82 (dd, 1H), 4.73 (s, 2H), 2.21 (s, 3H)

<실시예 1> (S)-[N-3-(4-피리딘-2-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 1 Preparation of (S)-[N-3- (4-pyridin-2-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide

(S)-[N-3-(4-트리메틸스테닐-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 300mg을 디메틸포름아마이드 4ml에 녹이고 실온에서 2-부로모피리딘 0.14ml, 트리에틸아민 0.25ml와 디클로로비스트리페닐포스핀팔라디움(II) 0.2g을 각각 가한 후 4시간동안 100℃에서 교반하였다. 상기 반응 혼합물에 물을 가한 다음 에틸아세테이트로 추출하고 추출된 유기층은 소금물로 세척한 후 탈수, 여과 및 감압농축한 다음 컬럼크로마토그래피로 정제하여 표제 화합물 50mg을 얻었다.
300 mg of (S)-[N-3- (4-trimethylstenyl-3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide was dissolved in 4 ml of dimethylformamide and 2-bromo at room temperature. 0.14 ml of pyridine, 0.25 ml of triethylamine, and 0.2 g of dichlorobistriphenylphosphinepalladium (II) were added, followed by stirring at 100 ° C. for 4 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The extracted organic layer was washed with brine, dehydrated, filtered and concentrated under reduced pressure, and then purified by column chromatography to obtain 50 mg of the title compound.

<실시예 2> (S)-[N-3-(4-(2-아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 2 Preparation of (S)-[N-3- (4- (2-aminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide

출발물질로 2-부로모피리딘 대신 2-아미노-5-아이오도피리딘을 5.0g 첨가하는 것을 제외하고 상기 실시예 1과 동일한 방법으로 표제 화합물 1.5g (45 %) 을 얻었다. 1.5 g (45%) of the title compound was obtained in the same manner as in Example 1, except that 5.0 g of 2-amino-5-iodopyridine was added instead of 2-bromopyridine as a starting material.                     

1H NMR(DMSO-d6) 8.26(t,1H), 8.08(s,1H), 7.52(m,3H), 7.32(dd,1H), 8.51(d,1H), 6.14(s,2H), 4.74(m,1H), 4.14(t,1H), 3.75(dd,1H), 3.41(m,2H), 1.85(s,3H)
 1 H NMR (DMSO-d 6 ) 8.26 (t, 1H), 8.08 (s, 1H), 7.52 (m, 3H), 7.32 (dd, 1H), 8.51 (d, 1H), 6.14 (s, 2H) , 4.74 (m, 1H), 4.14 (t, 1H), 3.75 (dd, 1H), 3.41 (m, 2H), 1.85 (s, 3H)

<실시예 3> (S)-[N-3-(4-(3-메톡시카르보닐피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 3 (S)-[N-3- (4- (3-methoxycarbonylpyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acet Preparation of Amide

(S)-[N-3-(4-트리메틸스테닐-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 200mg을 디메틸포름아마이드 2.4ml에 녹이고 실온에서 메틸 5-부로모피리딘-3-카르복실레이트 260.3mg, 트리에틸아민 0.17ml과 디클로로비스트리페닐포스핀팔라디움(II) 135mg을 각각 가한 후 3시간동안 100℃에서 교반하였다. 상기 반응 혼합물에 물을 가하고 에틸아세테이트로 추출한 후 유기층을 소금물로 세척하고 탈수 및 여과하여 감압 농축한 다음 컬럼크로마토그래피로 정제하여 표제 화합물 60mg을 얻었다.200 mg of (S)-[N-3- (4-trimethylstenyl-3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide in 2.4 ml of dimethylformamide and methyl 5- at room temperature 260.3 mg of bromopyridine-3-carboxylate, 0.17 ml of triethylamine and 135 mg of dichlorobistriphenylphosphinepalladium (II) were added, followed by stirring at 100 ° C. for 3 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with brine, dehydrated and filtered, concentrated under reduced pressure, and purified by column chromatography to obtain 60 mg of the title compound.

1H NMR(CDCl3) 9.16(d,1H), 8.90(t,1H), 8.42(m,1H), 7.60(dd,1H), 7.45(t,1H), 7.30(dd,1H), 6.16(bt,1H), 4.81(m,1H), 4.10(t,1H), 3.96(s,3H), 3.81(dd,1H), 3.70(m,2H), 2.02(s,3H)
 1 H NMR (CDCl 3 ) 9.16 (d, 1H), 8.90 (t, 1H), 8.42 (m, 1H), 7.60 (dd, 1H), 7.45 (t, 1H), 7.30 (dd, 1H), 6.16 (bt, 1H), 4.81 (m, 1H), 4.10 (t, 1H), 3.96 (s, 3H), 3.81 (dd, 1H), 3.70 (m, 2H), 2.02 (s, 3H)

<실시예 4> (S)-[N-3-(4-(2-아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 4 of (S)-[N-3- (4- (2-acetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide Produce

메틸 5-부로모피리딘-3-카르복실레이트 대신 2-아세틸아미노-5-부로모피리딘 260mg을 사용한 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물 48mg을 얻었다.48 mg of the title compound was obtained in the same manner as in Example 3, except that 260 mg of 2-acetylamino-5-bromopyridine was used instead of methyl 5-bromopyridine-3-carboxylate.

1H NMR(DMSO-d6) 8.48(s,1H), 8.28(t,1H), 8.15(d,1H), 7.98(d,1H), 7.64(m,1H), 7.43(m,1H), 4.76(m,1H), 4.18(t,1H), 3.79(t,1H), 3.42(t,2H), 2.10(s,3H), 1.82(s,3H)
 1 H NMR (DMSO-d 6 ) 8.48 (s, 1H), 8.28 (t, 1H), 8.15 (d, 1H), 7.98 (d, 1H), 7.64 (m, 1H), 7.43 (m, 1H) , 4.76 (m, 1H), 4.18 (t, 1H), 3.79 (t, 1H), 3.42 (t, 2H), 2.10 (s, 3H), 1.82 (s, 3H)

<실시예 5> (S)-[N-3-(4-(2-아세톡시아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 5 (S)-[N-3- (4- (2-acetoxyacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acet Preparation of Amide

(S)-[N-3-(4-트리메틸스테닐-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 467mg을 디메틸포름아마이드 5.6ml에 녹이고 실온에서 2-아세톡시아세틸아미노-5-부로모피리딘 615mg, 트리에틸아민 0.39ml 및 디클로로비스트리페닐포스핀팔라디움(II) 237mg을 각각 가한 후 4시간동안 100℃에서 교반하였다. 상기 반응물에 물을 가하고 에틸아세테이트로 추출한 후 유기층을 소금물로 세척한 다음 탈수, 여과, 감압농축한 후 컬럼크로마토그래피로 정제하여 표제 화합물 218mg을 얻었다.467 mg of (S)-[N-3- (4-trimethylstenyl-3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide was dissolved in 5.6 ml of dimethylformamide and 2-acetated at room temperature. 615 mg of oxyacetylamino-5-buromopyridine, 0.39 ml of triethylamine and 237 mg of dichlorobistriphenylphosphinepalladium (II) were added respectively, followed by stirring at 100 ° C. for 4 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with brine, dehydrated, filtered, and concentrated under reduced pressure, and then purified by column chromatography to obtain 218 mg of the title compound.

1H NMR(DMSO-d6) 8.50(s,1H), 8.28(t,1H), 8.12(d,1H), 8.00(d,1H), 7.64(m,2H), 7.39(m,1H), 4.76(m,4H), 4.15(t,1H), 3.78(dd,1H), 3.42(t,2H), 2.10(s,3H), 1.82(s,3H)
 1 H NMR (DMSO-d 6 ) 8.50 (s, 1H), 8.28 (t, 1H), 8.12 (d, 1H), 8.00 (d, 1H), 7.64 (m, 2H), 7.39 (m, 1H) , 4.76 (m, 4H), 4.15 (t, 1H), 3.78 (dd, 1H), 3.42 (t, 2H), 2.10 (s, 3H), 1.82 (s, 3H)

<실시예 6> (S)-[N-3-(4-(2-히드록시아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 6 (S)-[N-3- (4- (2-hydroxyacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acet Preparation of Amide

상기 실시예 5에서 제조한 (S)-[N-3-(4-(2-아세톡시아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 100mg을 메탄올 1ml와 클로로포름 1ml의 혼합용매에 녹이고 실온에서 1N KOH 용액을 적가하였다. 실온에서 1시간동안 반응 혼합물을 교반한 다음 물을 가하고 에틸아세테이트로 추출하였다. 추출된 유기층을 소금물로 세척한 후 탈수, 여과, 감압농축하여 얻은 고체를 메틸렌클로라이드와 헥산으로 재결정하여 표제 화합물 50mg을 얻었다.(S)-[N-3- (4- (2-acetoxyacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] prepared in Example 5 above; 100 mg of methyl acetamide was dissolved in a mixed solvent of 1 ml of methanol and 1 ml of chloroform, and a 1N KOH solution was added dropwise at room temperature. The reaction mixture was stirred for 1 hour at room temperature, then water was added and extracted with ethyl acetate. The extracted organic layer was washed with brine, dehydrated, filtered and concentrated under reduced pressure. The solid obtained was recrystallized with methylene chloride and hexane to obtain 50 mg of the title compound.

1H NMR(DMSO-d6) 8.50(s,1H), 8.28(d,1H), 8.17(d,1H), 7.99(d,1H), 7.64(m,2H), 7.42(dd,1H), 5.75(t,1H0, 4.76(m,1H), 4.13(t,1H), 4.05(d,2H), 3.79(dd,1H), 3.42(t,2H), 1.83(s,3H)
 1 H NMR (DMSO-d 6 ) 8.50 (s, 1H), 8.28 (d, 1H), 8.17 (d, 1H), 7.99 (d, 1H), 7.64 (m, 2H), 7.42 (dd, 1H) , 5.75 (t, 1H0, 4.76 (m, 1H), 4.13 (t, 1H), 4.05 (d, 2H), 3.79 (dd, 1H), 3.42 (t, 2H), 1.83 (s, 3H)

<실시예 7> (S)-[N-3-(4-(2-이미다졸-1-일피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 7 (S)-[N-3- (4- (2-imidazol-1-ylpyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] Preparation of Methyl Acetamide

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 2-이미다졸릴-5-부로모피리딘을 사용한 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물 을 얻었다. The title compound was obtained in the same manner as in Example 3, except that 2-imidazolyl-5-butromopyridine was used as a starting material instead of methyl 5-bromopyridine-3-carboxylate.                     

1H NMR(CDCl3) 8.61(s,1H), 8.39(s,1H), 8.00(dd,1H), 7.87(s,1H), 7.61(dd,1H), 7.49(m,2H), 7.32(dd,1H), 7.21(s,1H), 6.13(t,1H), 4.80(m,1H), 4.08(t,1H), 3.81(dd,1H), 3.61(m,2H), 2.02(s,3H)
 1 H NMR (CDCl 3 ) 8.61 (s, 1H), 8.39 (s, 1H), 8.00 (dd, 1H), 7.87 (s, 1H), 7.61 (dd, 1H), 7.49 (m, 2H), 7.32 (dd, 1H), 7.21 (s, 1H), 6.13 (t, 1H), 4.80 (m, 1H), 4.08 (t, 1H), 3.81 (dd, 1H), 3.61 (m, 2H), 2.02 ( s, 3H)

<실시예 8> (S)-[N-3-(4-(2-몰포린-4-일피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 8 (S)-[N-3- (4- (2-morpholin-4-ylpyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] Preparation of Methyl Acetamide

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 2-몰포리노-4-일-5-부로모피리딘을 첨가하는 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물 을 얻었다.The title compound was obtained in the same manner as in Example 3, except that 2-morpholino-4-yl-5-butromopyridine was added as a starting material instead of methyl 5-bromopyridine-3-carboxylate.

1H NMR(CDCl3) 8.31(s,1H), 7.87(dd,1H), 7.50(dd,1H), 7.38(t,1H), 7.20(dd,1H), 6.65(d,1H), 6.55(t,1H), 4.79(m,1H), 4.04(t,1H), 3.81(m,5H), 3.62(m,2H), 3.52(m,4H), 2.00(s,3H)
 1 H NMR (CDCl 3 ) 8.31 (s, 1H), 7.87 (dd, 1H), 7.50 (dd, 1H), 7.38 (t, 1H), 7.20 (dd, 1H), 6.65 (d, 1H), 6.55 (t, 1H), 4.79 (m, 1H), 4.04 (t, 1H), 3.81 (m, 5H), 3.62 (m, 2H), 3.52 (m, 4H), 2.00 (s, 3H)

<실시예 9> (S)-[N-3-(4-(2-트리페닐메틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 9 (S)-[N-3- (4- (2-triphenylmethylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acet Preparation of Amide

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 2-트리페닐메틸아미노-5-부로모피리딘을 첨가하는 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물 을 얻었다.
The title compound was obtained in the same manner as in Example 3, except that 2-triphenylmethylamino-5-butromopyridine was added instead of methyl 5-bromopyridine-3-carboxylate as a starting material.

<실시예 10> (S)-[N-3-(4-(2-메톡시피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 10 of (S)-[N-3- (4- (2-methoxypyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide Produce

(S)-[N-3-(4-트리메틸스테닐-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 430mg을 디메틸포름아마이드 5ml에 녹이고 실온에서 2-메톡시-5-아이오도피리딘 610mg, 트리에틸아민 0.36ml, 디클로로비스트리페닐포스핀팔라디움(II) 292mg을 각각 가한 후 2시간동안 100℃에서 교반하였다. 상기 반응물에 물을 가하고 에틸아세테이트로 추출한 후 유기층을 소금물로 세척하고 탈수, 여과, 감압농축한 후 컬럼크로마토그래피로 정제하여 표제 화합물 200mg을 얻었다.430 mg of (S)-[N-3- (4-trimethylstenyl-3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide was dissolved in 5 ml of dimethylformamide and 2-methoxy at room temperature. 610 mg of 5-5-iodopyridine, 0.36 ml of triethylamine, and 292 mg of dichlorobistriphenylphosphinepalladium (II) were added thereto, followed by stirring at 100 ° C. for 2 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with brine, dehydrated, filtered and concentrated under reduced pressure, and then purified by column chromatography to obtain 200 mg of the title compound.

1H NMR(CDCl3) 8.25(s,1H), 7.70(m,1H), 7.51(dd,1H), 7.38(t,1H), 7.22(m,1H), 6.78(d,1H), 6.65(t,1H), 4.80(m,1H), 4.08(t,1H), 3.97(s,3H), 3.81(dd,1H), 3.65(m,2H), 2.00(s,3H)
 1 H NMR (CDCl 3 ) 8.25 (s, 1H), 7.70 (m, 1H), 7.51 (dd, 1H), 7.38 (t, 1H), 7.22 (m, 1H), 6.78 (d, 1H), 6.65 (t, 1H), 4.80 (m, 1H), 4.08 (t, 1H), 3.97 (s, 3H), 3.81 (dd, 1H), 3.65 (m, 2H), 2.00 (s, 3H)

<실시예 11> (S)-[N-3-(4-(2-메톡시아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 11 (S)-[N-3- (4- (2-methoxyacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acet Preparation of Amide

(S)-[N-3-(4-트리메틸스테닐-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 200mg을 디메틸포름아마이드 2.5ml에 녹이고 실온에서 2-메톡시아세틸아미노-5-부로모피리딘 295mg, 트리에틸아민 0.17ml, 디클로로비스트리페닐포스핀팔라디움(II) 135mg을 각각 가한 후 2시간동안 100℃에서 교반하였다. 상기 반응 물에 물을 가하고 에틸아세테이트로 추출한 후 유기층을 소금물로 세척하고 탈수, 여과, 감압농축한 후 컬럼크로마토그래피로 정제하여 표제 화합물 47mg을 얻었다.Dissolve 200 mg of (S)-[N-3- (4-trimethylstenyl-3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide in 2.5 ml of dimethylformamide and store 2-meth at room temperature. 295 mg of oxyacetylamino-5-buromopyridine, 0.17 ml of triethylamine, and 135 mg of dichlorobistriphenylphosphinepalladium (II) were added thereto, followed by stirring at 100 ° C. for 2 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with brine, dehydrated, filtered and concentrated under reduced pressure, and then purified by column chromatography to obtain 47 mg of the title compound.

1H NMR(DMSO-d6) 8.50(s,1H), 8.20(t,1H), 8.15(d,1H), 7.97(d,1H), 7.64(m,2H), 7.42(m,1H), 4.78(m,1H), 4.16(t,1H), 4.09(s,3H), 3.79(dd,1H), 3.42(t,2H), 3.37(s,3H), 1.83(s,3H)
 1 H NMR (DMSO-d 6 ) 8.50 (s, 1H), 8.20 (t, 1H), 8.15 (d, 1H), 7.97 (d, 1H), 7.64 (m, 2H), 7.42 (m, 1H) , 4.78 (m, 1H), 4.16 (t, 1H), 4.09 (s, 3H), 3.79 (dd, 1H), 3.42 (t, 2H), 3.37 (s, 3H), 1.83 (s, 3H)

<실시예 12> (S)-[N-3-(4-(2-(4-트리페닐메틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 12 (S)-[N-3- (4- (2- (4-triphenylmethylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo Preparation of -5-oxazolidinyl] methyl acetamide

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 4-트리페닐메틸피페라진-1-일-5-부로모피리딘을 첨가하는 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물을 얻었다.
The title compound was prepared in the same manner as in Example 3, except that 4-triphenylmethylpiperazin-1-yl-5-bromopyridine was added instead of methyl 5-bromopyridine-3-carboxylate as a starting material. Got it.

<실시예 13> (S)-[N-3-(4-(2-트리페닐메틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 염산염의 제조Example 13 (S)-[N-3- (4- (2-triphenylmethylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acet Preparation of Amide Hydrochloride

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 2-트리페닐메틸아미노-5-부로모피리딘을 첨가하는 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물 을 얻었다.
The title compound was obtained in the same manner as in Example 3, except that 2-triphenylmethylamino-5-butromopyridine was added instead of methyl 5-bromopyridine-3-carboxylate as a starting material.

<실시예 14> (S)-[N-3-(4-(2-아지도피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸 리딘일]메틸 아세트아마이드의 제조Example 14 (S)-[N-3- (4- (2-azidopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide Manufacture

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 2-아지도-5-부로모피리딘을 첨가하는 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 3, except that 2-azido-5-butromopyridine was added instead of methyl 5-bromopyridine-3-carboxylate as a starting material.

<실시예 15> (S)-[N-3-(4-(2-히드록시메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 15 (S)-[N-3- (4- (2-hydroxymethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide Manufacture

(S)-[N-3-(4-(2-메톡시카보닐피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 100mg을 에탄올 3ml와 테트라히드로퓨란 1.3ml의 혼합용매에 녹이고 실온에서 소듐보로하이드라이드 29.3mg 및 리튬클로라이드 32.8mg을 첨가하였다. 상기 반응 혼합물을 실온에서 2시간 교반한 후 에틸아세테이트를 가한 후 유기층을 탄산수소나트륨(NaHCO3)용액과 소금물로 세척하였다. 상기 유기층을 탈수, 여과 및 감압농축한 후 에틸에테르로 정제하여 표제 화합물 35mg을 얻었다.100 ml of (S)-[N-3- (4- (2-methoxycarbonylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide 3 ml of ethanol It was dissolved in a mixed solvent of 1.3 ml of tetrahydrofuran and 29.3 mg of sodium borohydride and 32.8 mg of lithium chloride were added at room temperature. After the reaction mixture was stirred at room temperature for 2 hours, ethyl acetate was added, and the organic layer was washed with sodium hydrogen carbonate (NaHCO 3 ) solution and brine. The organic layer was dehydrated, filtered and concentrated under reduced pressure, and then purified by ethyl ether to obtain 35 mg of the title compound.

1H NMR(DMSO-d6) 8.54(d,1H), 8.28(t,1H), 7.70(m,3H), 7.45(m,2H), 5.52(t,1H), 4.76(m,1H), 4.62(d,2H), 4.17(t,1H), 3.79(dd,1H), 3.42(t,2H), 1.83(s,3H)
 1 H NMR (DMSO-d 6 ) 8.54 (d, 1H), 8.28 (t, 1H), 7.70 (m, 3H), 7.45 (m, 2H), 5.52 (t, 1H), 4.76 (m, 1H) , 4.62 (d, 2H), 4.17 (t, 1H), 3.79 (dd, 1H), 3.42 (t, 2H), 1.83 (s, 3H)

<실시예 16> (S)-[N-3-(4-(2-메톡시카보닐피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 16 (S)-[N-3- (4- (2-methoxycarbonylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acet Preparation of Amide

(S)-[N-3-(4-트리메틸스테닐-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아 세트아마이드 790mg을 디메틸포름아마이드 9.5ml에 녹이고 실온에서 메틸 4-아이오도피리딘-2-카르복실레이트 1g, 트리에틸아민 0.67ml 및 디클로로비스트리페닐포스핀팔라디움(II) 533mg을 각각 가한 후 3시간동안 100℃에서 교반하였다. 상기 반응 혼합물에 물을 가하고 에틸아세테이트로 추출한 후 유기층을 소금물로 세척하고 탈수, 여과 및 감압농축한 후 컬럼크로마토그래피로 정제하여 표제 화합물 394mg을 얻었다.790 mg of (S)-[N-3- (4-trimethylstenyl-3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide was dissolved in 9.5 ml of dimethylformamide and methyl 4 at room temperature. -1 g of iodopyridine-2-carboxylate, 0.67 ml of triethylamine and 533 mg of dichlorobistriphenylphosphinepalladium (II) were added, followed by stirring at 100 ° C. for 3 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with brine, dehydrated, filtered and concentrated under reduced pressure, and then purified by column chromatography to obtain 394 mg of the title compound.

1H NMR(DMSO-d6) 8.78(d,1H), 8.27(m,2H), 7.70(m,3H), 7.47(dd,2H), 4.76(m,1H), 4.20(t,1H), 4.18(s,3H), 3.90(dd,1H), 3.43(t,2H), 1.83(s,3H)
 1 H NMR (DMSO-d 6 ) 8.78 (d, 1H), 8.27 (m, 2H), 7.70 (m, 3H), 7.47 (dd, 2H), 4.76 (m, 1H), 4.20 (t, 1H) , 4.18 (s, 3H), 3.90 (dd, 1H), 3.43 (t, 2H), 1.83 (s, 3H)

<실시예 17> (S)-[N-3-(4-(2-디메틸아미노카보닐피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 17 (S)-[N-3- (4- (2-dimethylaminocarbonylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acet Preparation of Amide

(S)-[N-3-(4-트리메틸스테닐-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 380mg을 디메틸포름아마이드 5ml에 녹이고 실온에서 N,N-2-디메틸아미노카보닐-4-아이오도피리딘 300mg, 트리에틸아민 0.32ml 및 디클로로비스트리페닐포스핀팔라디움(II) 255mg을 각각 가한 후 2시간동안 100℃에서 교반하였다. 상기 반응 혼합물에 물을 가하고 에틸아세테이트로 추출한 후 유기층을 소금물로 세척하고 탈수, 여과 및 감압농축한 후 컬럼크로마토그래피로 정제하여 표제 화합물 91mg을 얻었다. 380 mg of (S)-[N-3- (4-trimethylstenyl-3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide was dissolved in 5 ml of dimethylformamide and N, N- at room temperature. 300 mg of 2-dimethylaminocarbonyl-4-iodopyridine, 0.32 ml of triethylamine and 255 mg of dichlorobistriphenylphosphinepalladium (II) were added respectively, followed by stirring at 100 ° C. for 2 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with brine, dehydrated, filtered and concentrated under reduced pressure, and then purified by column chromatography to obtain 91 mg of the title compound.                     

1H NMR(DMSO-d6) 8.63(d,1H), 8.27(t,1H), 7.70(m,4H), 7.45(dd,1H), 4.76(m,1H), 4.17(t,1H), 3.79(dd,1H), 3.42(t,2H), 3.01(s,3H), 2.96(s,3H), 1.83(s,3H)
 1 H NMR (DMSO-d 6 ) 8.63 (d, 1H), 8.27 (t, 1H), 7.70 (m, 4H), 7.45 (dd, 1H), 4.76 (m, 1H), 4.17 (t, 1H) , 3.79 (dd, 1H), 3.42 (t, 2H), 3.01 (s, 3H), 2.96 (s, 3H), 1.83 (s, 3H)

<실시예 18> (S)-[N-3-(4-(2-히드록시피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 18 of (S)-[N-3- (4- (2-hydroxypyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide Produce

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 2-히드록시-5-부로모피리딘을 첨가하는 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 3, except that 2-hydroxy-5-bromopyridine was added instead of methyl 5-bromopyridine-3-carboxylate as a starting material.

<실시예 19> (S)-[N-3-(4-(N-2-디메틸아미노아세톡시아세틸아미노피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 19 (S)-[N-3- (4- (N-2-dimethylaminoacetoxyacetylaminopyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazoli Dinyl] Preparation of methyl acetamide

(S)-[N-3-(4-(N-2-히드록시아세틸아미노피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 200mg을 피리딘 2.5ml에 녹이고 실온에서 N,N-디메틸글리신 205mg, 1-(3-디메틸아미노프로필)-3-에틸카보디이미드 염산염 381mg 및 4-디메틸아미노피리딘 91mg을 각각 적가한 후 15시간동안 실온에서 교반하였다. 상기 반응 혼합물에 물을 가하고 에틸아세테이트로 추출한 후 유기층을 소금물로 세척하고 탈수, 여과 및 감압농축하여 컬럼크로마토그라피로 정제하여 표제 화합물 110mg을 얻었다.
200 mg of (S)-[N-3- (4- (N-2-hydroxyacetylaminopyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide It was dissolved in 2.5 ml of pyridine and 205 mg of N, N-dimethylglycine, 381 mg of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and 91 mg of 4-dimethylaminopyridine were added dropwise at room temperature for 15 hours at room temperature. Stirred. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with brine, dehydrated, filtered and concentrated under reduced pressure, and purified by column chromatography to obtain 110 mg of the title compound.

<실시예 20> (S)-[N-3-(4-(2-메틸아미노피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 20 of (S)-[N-3- (4- (2-methylaminopyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide Produce

(S)-[N-3-(4-트리메틸스테닐-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 500mg을 테트라히드로퓨란 6ml에 녹이고 실온에서 2-메틸아미노-5-아이오도피리딘 564mg, 리튬클로라이드 153mg 및 테트라키스트리페닐포스핀 팔라디움(II) 278mg을 각각 가한 후 48시간 동안 환류하였다. 상기 반응 혼합물에 물을 가하고 에틸아세테이트로 추출한 후 추출된 유기층을 소금물로 세척하고 탈수, 여과 및 감압농축한 후 컬럼크로마토그래피로 정제하여 표제 화합물 181mg을 얻었다.500 mg of (S)-[N-3- (4-trimethylstenyl-3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide in 6 ml of tetrahydrofuran and 2-methylamino at room temperature 564 mg of 5-5-iodopyridine, 153 mg of lithium chloride and 278 mg of tetrakistriphenylphosphine palladium (II) were added, respectively, and refluxed for 48 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The extracted organic layer was washed with brine, dehydrated, filtered and concentrated under reduced pressure, and then purified by column chromatography to obtain 181 mg of the title compound.

1H NMR(DMSO-d6) 8.26(t,1H), 8.16(s,1H), 7.58(m,2H), 7.35(dd,1H), 6.70(dd,1H), 6.50(d,1H), 4.74(m,1H), 4.17(t,1H), 3.79(dd,1H), 3.43(t,2H), 2.78(d,3H), 1.82(s,3H)
 1 H NMR (DMSO-d 6 ) 8.26 (t, 1H), 8.16 (s, 1H), 7.58 (m, 2H), 7.35 (dd, 1H), 6.70 (dd, 1H), 6.50 (d, 1H) , 4.74 (m, 1H), 4.17 (t, 1H), 3.79 (dd, 1H), 3.43 (t, 2H), 2.78 (d, 3H), 1.82 (s, 3H)

<실시예 21> (S)-[N-3-(4-(2-디메틸아미노피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 21 of (S)-[N-3- (4- (2-dimethylaminopyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide Produce

2-메틸아미노-5-아이오도피리딘 대신 2-디메틸아미노-5-아이오도피리딘을 사용하는 것을 제외하고 상기 실시예 20과 동일한 방법으로 표제 화합물을 얻었다.The title compound was obtained in the same manner as in Example 20, except for using 2-dimethylamino-5-iodopyridine instead of 2-methylamino-5-iodopyridine.

1H NMR(DMSO-d6) 8.31(m,2H), 7.71(dd,1H), 7.60(m,3H), 7.34(dd,1H), 6.73(d,1H), 4.73(m,1H), 4.14(t,1H), 3.76(dd,1H), 3.42(t,2H), 3.05(s,6H), 1.82(s,3H)
 1 H NMR (DMSO-d 6 ) 8.31 (m, 2H), 7.71 (dd, 1H), 7.60 (m, 3H), 7.34 (dd, 1H), 6.73 (d, 1H), 4.73 (m, 1H) , 4.14 (t, 1H), 3.76 (dd, 1H), 3.42 (t, 2H), 3.05 (s, 6H), 1.82 (s, 3H)

<실시예 22> (S)-[N-3-(4-(2-히드록시아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 염산염의 제조Example 22 (S)-[N-3- (4- (2-hydroxyacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acet Preparation of Amide Hydrochloride

(S)-[N-3-(4-(2-히드록시아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 500mg을 메탄올과 클로로포름의 혼합용매에 녹이고 실온에서 염산 0.5ml를 가하고 1시간 교반하였다. 상기 반응물을 감압농축하여 생성된 고체를 에틸에테르로 여러번 정제하여 원하는 표제 화합물 520mg을 얻었다.500 mg of (S)-[N-3- (4- (2-hydroxyacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide with methanol It was dissolved in a mixed solvent of chloroform and 0.5 ml of hydrochloric acid was added at room temperature, followed by stirring for 1 hour. The reaction was concentrated under reduced pressure, and the resulting solid was purified several times with ethyl ether to obtain 520 mg of the title compound.

1H NMR(DMSO-d6) 10.01(s,1H), 8.53(s,1H), 4.75(m,1H), 4.18(t,1H), 4.08(s,2H), 3.78(dd,1H), 3.42(t,2H), 1.83(s,3H)
 1 H NMR (DMSO-d 6 ) 10.01 (s, 1H), 8.53 (s, 1H), 4.75 (m, 1H), 4.18 (t, 1H), 4.08 (s, 2H), 3.78 (dd, 1H) , 3.42 (t, 2H), 1.83 (s, 3H)

<실시예 23> (S)-[N-3-(4-(2-히드록시아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 히드록시프로필메틸셀룰로스 배산체의 제조Example 23 (S)-[N-3- (4- (2-hydroxyacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acet Preparation of Amide Hydroxypropylmethylcellulose Dispersion

(S)-[N-3-(4-(2-히드록시아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드와 히드록시프로필메틸셀룰로스 (HPMC, Hydroxypropylmethylcellulose)를 무게비 2:1의 비율로 에탄올과 메틸렌 클로라이드 혼합용매에 서서히 녹이고 2시간동안 교반한 후 스프레이 드라이법을 사용하여 용매를 휘발시키고 표제 배산물을 얻었다.
(S)-[N-3- (4- (2-hydroxyacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide and hydroxypropyl Methyl cellulose (HPMC, Hydroxypropylmethylcellulose) was slowly dissolved in a mixed solvent of ethanol and methylene chloride at a ratio of 2: 1 by weight, stirred for 2 hours, and then the solvent was evaporated by spray drying to obtain the title product.

<실시예 24> (S)-[N-3-(4-(2-아세톡시피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 24 of (S)-[N-3- (4- (2-acetoxypyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide Produce

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 2-아세톡시-5-부로모피리딘을 첨가하는 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물 을 얻었다.
The title compound was obtained in the same manner as in Example 3, except that 2-acetoxy-5-butromopyridine was added instead of methyl 5-bromopyridine-3-carboxylate as a starting material.

<실시예 25> (S)-[N-3-(4-(2-메톡시메틸옥시피리딘-5-일)-3-플로로페닐)-2-옥소 -5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 25 (S)-[N-3- (4- (2-methoxymethyloxypyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acet Preparation of Amide

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 2-메톡시메틸옥시-5-부로모피리딘을 첨가하는 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 3, except that 2-methoxymethyloxy-5-butromopyridine was added instead of methyl 5-bromopyridine-3-carboxylate as a starting material.

<실시예 26> (S)-[N-3-(4-(2-메탄술포닐옥시피리딘-5-일)-3-플로로페닐)-2- 옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 26 (S)-[N-3- (4- (2-methanesulfonyloxypyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acet Preparation of Amide

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 2-메탄술포닐옥시-5-부로모피리딘을 첨가하는 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물 을 얻었다.
The title compound was obtained in the same manner as in Example 3, except that 2-methanesulfonyloxy-5-butromopyridine was added instead of methyl 5-bromopyridine-3-carboxylate as a starting material.

<실시예 27> (S)-[N-3-(4-(2-아미노카보닐피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 27 (S)-[N-3- (4- (2-aminocarbonylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide Manufacture

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 2-아미노카보닐-4-부로모피리딘을 첨가하는 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물 을 얻었다.
The title compound was obtained in the same manner as in Example 3, except that 2-aminocarbonyl-4-bromopyridine was added instead of methyl 5-bromopyridine-3-carboxylate as a starting material.

<실시예 28> (S)-[N-3-(4-(2-디메틸아미노아세톡시메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 28 (S)-[N-3- (4- (2-dimethylaminoacetoxymethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl Preparation of Acetamide

(S)-[N-3-(4-(2-히드록시메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 155mg을 피리딘 2ml에 녹이고 실온에서 N,N-디메틸글리신 318mg, 1-(3-디메틸아미노프로필)-3-에틸카보디이미드 염산염 662mg 및 4-디메틸아미노피리딘 158mg을 각각 적가한 후 15시간동안 실온에서 교반하였다. 상기 반응 혼합물에 물을 가하고 에틸아세테이트로 추출한 후 유기층을 소금물로 세척한 다음 탈수, 여과 및 감압농축하고 컬럼크로마토그라피로 정제하여 표제 화합물 113mg을 얻었다.155 mg of (S)-[N-3- (4- (2-hydroxymethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide in 2 ml of pyridine After dissolving, 318 mg of N, N-dimethylglycine, 662 mg of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, and 158 mg of 4-dimethylaminopyridine were respectively added dropwise and stirred at room temperature for 15 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with brine, dehydrated, filtered and concentrated under reduced pressure and purified by column chromatography to obtain 113 mg of the title compound.

1H NMR(CDCl3) 8.48(d,1H), 5.18(s,2H), 4.75(m,1H), 4.00(t,1H), 3.76(dd,1H), 3.60(bs,2H), 3.19(s,2H), 2.25(s,6H), 1.93(s,3H)
 1 H NMR (CDCl 3 ) 8.48 (d, 1H), 5.18 (s, 2H), 4.75 (m, 1H), 4.00 (t, 1H), 3.76 (dd, 1H), 3.60 (bs, 2H), 3.19 (s, 2H), 2.25 (s, 6H), 1.93 (s, 3H)

<실시예 29> (S)-[N-3-(4-(2-(2-히드록시에틸)아미노카보닐피리딘-4-일)-3-플로 로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 29 (S)-[N-3- (4- (2- (2-hydroxyethyl) aminocarbonylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5- Preparation of oxazolidinyl] methyl acetamide

(S)-[N-3-(4-트리메틸스테닐-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 245mg을 디메틸포름아마이드 3ml에 녹이고 실온에서 2-(2-히드록시에틸)아미노카보닐-4-아이오도피리딘 345mg, 트리에틸아민 0.21ml 및 디클로로비스트리페닐포스핀팔라디움(II) 166mg을 가한 후 3시간동안 100℃에서 교반하였다. 상기 반응물에 물을 가하고 에틸아세테이트로 추출한 후 유기층을 소금물로 세척하고 탈수, 여과 및 감압농축한 후 컬럼크로마토그래피로 정제하여 표제 화합물 60mg을 얻었다.245 mg of (S)-[N-3- (4-trimethylstenyl-3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide was dissolved in 3 ml of dimethylformamide and 2- (2) at room temperature. 345 mg of hydroxyethyl) aminocarbonyl-4-iodopyridine, 0.21 ml of triethylamine and 166 mg of dichlorobistriphenylphosphinepalladium (II) were added and stirred at 100 ° C. for 3 hours. Water was added to the reaction, followed by extraction with ethyl acetate. The organic layer was washed with brine, dehydrated, filtered and concentrated under reduced pressure, and then purified by column chromatography to obtain 60 mg of the title compound.

1H NMR(DMSO-d6) 8.69(d,1H), 8.27(t,1H), 8.19(s,1H), 7.81(m,1H), 7.70(m,1H), 7.45(dd,2H), 4.79(m,1H), 4.17(t,1H), 3.79(dd,1H), 3.51(t,2H), 3.43(m,4H), 1.83(s,3H)
 1 H NMR (DMSO-d 6 ) 8.69 (d, 1H), 8.27 (t, 1H), 8.19 (s, 1H), 7.81 (m, 1H), 7.70 (m, 1H), 7.45 (dd, 2H) , 4.79 (m, 1H), 4.17 (t, 1H), 3.79 (dd, 1H), 3.51 (t, 2H), 3.43 (m, 4H), 1.83 (s, 3H)

<실시예 30> (S)-[N-3-(4-(2-N,N-디(2-히드록시에틸)아미노카보닐피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 30 (S)-[N-3- (4- (2-N, N-di (2-hydroxyethyl) aminocarbonylpyridin-4-yl) -3-fluorophenyl) -2 -Oxo-5-oxazolidinyl] methyl acetamide

출발물질로 (2-히드록시에틸)아미노카보닐-4-아이오도피리딘 대신 N,N-디(2-히드록시에틸)아미노카보닐-4-아이오도피리딘을 첨가하는 것을 제외하고 상기 실시예 29과 동일한 방법으로 표제 화합물을 얻었다.The above example except adding N, N-di (2-hydroxyethyl) aminocarbonyl-4-iodopyridine as a starting material instead of (2-hydroxyethyl) aminocarbonyl-4-iodopyridine In the same manner as in 29, the title compound was obtained.

1H NMR(DMSO-d6) 8.60(d,1H), 8.26(t,1H), 7.64(m,4H), 7.45(m,1H), 4.80(m,3H), 4.17(t,1H), 3.79(dd,1H), 3.54(m,10H), 1.83(s,3H)
1 H NMR (DMSO-d 6 ) 8.60 (d, 1H), 8.26 (t, 1H), 7.64 (m, 4H), 7.45 (m, 1H), 4.80 (m, 3H), 4.17 (t, 1H) , 3.79 (dd, 1H), 3.54 (m, 10H), 1.83 (s, 3H)

<실시예 31> (S)-[N-3-(4-(2-피페라진-1-일피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 31 (S)-[N-3- (4- (2-piperazin-1-ylpyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] Preparation of Methyl Acetamide

(S)-[N-3-(4-(2-(4-트리페닐메틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 200mg을 테트라히드로퓨란에 녹이고 1N HCl 용액을 1ml 가한다음 실온에서 하루동안 교반하여 생성된 고체를 여과하고 테트라히드로퓨란과 에테르로 세척하여 표제의 화합물 110mg(88%)를 얻었다.
(S)-[N-3- (4- (2- (4-triphenylmethylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazoli 200 mg of dinyl] methyl acetamide was dissolved in tetrahydrofuran, 1 ml of 1N HCl solution was added, followed by stirring at room temperature for 1 day. The resulting solid was filtered and washed with tetrahydrofuran and ether to obtain 110 mg (88%) of the title compound.

<실시예 32> (S)-[N-3-(4-(2-(4-아세톡시아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 32 (S)-[N-3- (4- (2- (4-acetoxyacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo Preparation of -5-oxazolidinyl] methyl acetamide

(S)-[N-3-(4-(2-피페라진-1-일피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 30mg을 테트라히드로퓨란에 녹이고 트리에틸아민 30ul와 아세톡시아세틸클로라이드 16ul를 가한 후 20분동안 실온에서 교반하였다. 상기 반응물에 물을 가한 후 클로로포름으로 추출하고 유기층을 소금물로 세척한 후 탈수, 여과, 감압 농축한 다음 컬럼크로마토그라피로 정제하여 표제의 화합물 23mg을 얻었다.
30 mg of (S)-[N-3- (4- (2-piperazin-1-ylpyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide It was dissolved in tetrahydrofuran and 30ul of triethylamine and 16ul of acetoxyacetyl chloride were added, followed by stirring at room temperature for 20 minutes. Water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with brine, dehydrated, filtered and concentrated under reduced pressure, and then purified by column chromatography to obtain 23 mg of the title compound.

<실시예 33> (S)-[N-3-(4-(2-(4-벤질옥시아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 33 (S)-[N-3- (4- (2- (4-benzyloxyacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo Preparation of -5-oxazolidinyl] methyl acetamide

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 벤질옥시아세틸피페 라지닐-5-부로모피리딘을 첨가하는 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 3, except that benzyloxyacetylpiperazinyl-5-bromopyridine was added instead of methyl 5-bromopyridine-3-carboxylate as a starting material.

<실시예 34> (S)-[N-3-(4-(2-(4-히드록시아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 34 (S)-[N-3- (4- (2- (4-hydroxyacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo Preparation of -5-oxazolidinyl] methyl acetamide

실시예 33으로부터 얻은 화합물 220mg을 메탄올에 녹이고 1N KOH 용액을 1ml 가한 후 실온에서 1시간동안 교반하였다. 과량의 메탄올을 감압농축한 후 물을 가하고 클로로포름으로 추출한 다음 유기층을 탈수, 여과, 감압농축하고 컬럼크로마토그라피로 정제하여 표제화합물 189mg을 얻었다. 220 mg of the compound obtained in Example 33 was dissolved in methanol, 1 ml of 1N KOH solution was added, followed by stirring at room temperature for 1 hour. Excess methanol was concentrated under reduced pressure, water was added, extraction was performed with chloroform, and the organic layer was dehydrated, filtered, and concentrated under reduced pressure and purified by column chromatography to obtain 189 mg of the title compound.

1H NMR(CDCl3) 8.35(s,1H), 7.70(d,1H), 7.50(dd,1H), 7.37(t,1H), 7.27(dd,1H), 6.70(d,1H), 4.74(m,1H), 4.21(d,2H), 4.06(t,1H), 3.80(m,3H), 3.62(m,6H), 3.39(m,2H), 2.01(s,3H)
 1 H NMR (CDCl 3 ) 8.35 (s, 1H), 7.70 (d, 1H), 7.50 (dd, 1H), 7.37 (t, 1H), 7.27 (dd, 1H), 6.70 (d, 1H), 4.74 (m, 1H), 4.21 (d, 2H), 4.06 (t, 1H), 3.80 (m, 3H), 3.62 (m, 6H), 3.39 (m, 2H), 2.01 (s, 3H)

<실시예 35> (S)-[N-3-(4-(2-(4-디메틸아미노아세톡시아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 35 (S)-[N-3- (4- (2- (4-dimethylaminoacetoxyacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2 -Oxo-5-oxazolidinyl] methyl acetamide

출발물질로 (S)-[N-3-(4-(2-히드록시메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 대신 (S)-[N-3-(4-(2-(4-히드록시아세틸피페라진-1-일 피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드를 첨가하 는 것을 제외하고 상기 실시예 28과 동일한 방법으로 표제 화합물을 얻었다.Instead of (S)-[N-3- (4- (2-hydroxymethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide as starting material ( S)-[N-3- (4- (2- (4-hydroxyacetylpiperazin-1-yl pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] The title compound was obtained in the same manner as in Example 28, except for adding methyl acetamide.

1H NMR(DMSO-d6) 8.34(s,1H), 7.53(m,1H), 7.37(dd,1H), 7.33(t,1H), 7.26(dd,1H), 6.72(d,1H), 5.80(t,1H), 4.83(m,3H), 3.79(m,7H), 3.54(t,4H), 3.33(d,2H), 2.40(s,6H), 2.01(s,3H)
 1 H NMR (DMSO-d 6 ) 8.34 (s, 1H), 7.53 (m, 1H), 7.37 (dd, 1H), 7.33 (t, 1H), 7.26 (dd, 1H), 6.72 (d, 1H) , 5.80 (t, 1H), 4.83 (m, 3H), 3.79 (m, 7H), 3.54 (t, 4H), 3.33 (d, 2H), 2.40 (s, 6H), 2.01 (s, 3H)

<실시예 36> (S)-[N-3-(4-(2-(4-클로로아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 36 (S)-[N-3- (4- (2- (4-chloroacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo- Preparation of 5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 클로로아세틸클로라이드를 첨가하는 것을 제외하고 상기 실시예 32과 동일한 방법으로 표제 화합물을 얻었다.The title compound was obtained in the same manner as in Example 32, except that chloroacetyl chloride was added instead of acetoxyacetyl chloride as a starting material.

1H NMR(CDCl3) 8.35(s,1H), 7.72(m,1H), 7.50(dd,1H), 7.41(t,1H), 6.74(d,1H), 6.16(t,1H), 4.79(m,1H), 3.79(m,13H), 2.02(s,3H)
 1 H NMR (CDCl 3 ) 8.35 (s, 1H), 7.72 (m, 1H), 7.50 (dd, 1H), 7.41 (t, 1H), 6.74 (d, 1H), 6.16 (t, 1H), 4.79 (m, 1H), 3.79 (m, 13H), 2.02 (s, 3H)

<실시예 37> (S)-[N-3-(4-(2-(4-아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 37 (S)-[N-3- (4- (2- (4-acetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5 -Oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 아세틸클로라이드를 첨가하는 것을 제외하고 상기 실시예 33과 동일한 방법으로 표제 화합물 을 얻었다.
The title compound was obtained in the same manner as in Example 33, except for adding acetyl chloride instead of acetoxyacetyl chloride as a starting material.

<실시예 38> (S)-[N-3-(4-(2-(4-메톡시아세틸피페라진-1-일)피리딘-5-일)-3-플로 로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 38 (S)-[N-3- (4- (2- (4-methoxyacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo Preparation of -5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 메톡시아세틸클로라이드를 첨가하는 것을 제외하고 상기 실시예 32과 동일한 방법으로 표제 화합물 을 얻었다.
The title compound was obtained in the same manner as in Example 32, except that methoxyacetyl chloride was added instead of acetoxyacetyl chloride as a starting material.

<실시예 39> (S)-[N-3-(4-(2-(4-몰포리닐아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 39 (S)-[N-3- (4- (2- (4-morpholinylacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2- Preparation of oxo-5-oxazolidinyl] methyl acetamide

실시예 37로부터 얻은 화합물 30mg을 테트라히드로퓨란에 녹이고 트리에틸아민 25ul와 몰포린 10.4ul를 실온에서 가한 후 2시간동안 교반하였다. 상기 반응물을 감압농축하고 컬럼크로마토그라피로 정제하여 표제화합물 30mg을 얻었다.
30 mg of the compound obtained in Example 37 was dissolved in tetrahydrofuran, 25ul of triethylamine and 10.4ul of morpholine were added at room temperature, followed by stirring for 2 hours. The reaction was concentrated under reduced pressure and purified by column chromatography to obtain 30 mg of the title compound.

<실시예 40> (S)-[N-3-(4-(2-(4-메톡시카보닐메틸아미노아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 40 (S)-[N-3- (4- (2- (4-methoxycarbonylmethylaminoacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) Preparation of 2-oxo-5-oxazolidinyl] methyl acetamide

출발물질로 몰포린 대신 메톡시카보닐메틸아미노 하이드로클로라이드를 첨가하는 것을 제외하고 상기 실시예 39과 동일한 방법으로 표제 화합물을 얻었다.The title compound was obtained in the same manner as in Example 39, except that methoxycarbonylmethylamino hydrochloride was added instead of morpholine as a starting material.

1H NMR(CDCl3) 8.34(s,1H), 7.70(dd,1H), 7.54(dd,1H), 7.37(t,1H), 7.27(dd,1H), 6.68(d,1H), 5.98(m,1H), 4.76(m,1H), 4.06(t,1H), 3.90(m,1H), 3.782(m,8H), 3.63(m,3H), 3.52(m,5H) 3.39(m,1H), 2.01(s,3H)
 1 H NMR (CDCl 3 ) 8.34 (s, 1H), 7.70 (dd, 1H), 7.54 (dd, 1H), 7.37 (t, 1H), 7.27 (dd, 1H), 6.68 (d, 1H), 5.98 (m, 1H), 4.76 (m, 1H), 4.06 (t, 1H), 3.90 (m, 1H), 3.782 (m, 8H), 3.63 (m, 3H), 3.52 (m, 5H) 3.39 (m , 1H), 2.01 (s, 3H)

<실시예 41> (S)-[N-3-(4-(2-(4-에톡시카보닐피페리딘-1-일)피리딘-5-일)-3-플로 로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 41 (S)-[N-3- (4- (2- (4-ethoxycarbonylpiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2- Preparation of oxo-5-oxazolidinyl] methyl acetamide

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 (4-에톡시카보닐피페리딘-1-일)-5-부로모피리딘을 첨가하는 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물을 얻었다.
In the same manner as in Example 3, except that (4-ethoxycarbonylpiperidin-1-yl) -5-butromopyridine was added instead of methyl 5-bromopyridine-3-carboxylate as starting material. The title compound was obtained.

<실시예 42> (S)-[N-3-(4-(2-아지도메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 42 (S)-[N-3- (4- (2-azidomethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide Manufacture

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 2-아지도메틸-4-부로모피리딘을 첨가하는 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물을 얻었다.The title compound was obtained in the same manner as in Example 3, except that 2-azidomethyl-4-bromopyridine was added instead of methyl 5-bromopyridine-3-carboxylate as a starting material.

1H NMR(DMSO-d6) 8.67(d,1H), 8.27(t,1H), 7.72(d,1H), 7.68(dd,1H), 7.62(s,1H), 7.57(d,1H), 7.44(dd,1H), 4.76(m,1H), 4.56(s,3H), 4.17(t,1H), 3.79(dd,1H), 3.42(t,2H), 1.82(s,3H)
 1 H NMR (DMSO-d 6 ) 8.67 (d, 1H), 8.27 (t, 1H), 7.72 (d, 1H), 7.68 (dd, 1H), 7.62 (s, 1H), 7.57 (d, 1H) , 7.44 (dd, 1H), 4.76 (m, 1H), 4.56 (s, 3H), 4.17 (t, 1H), 3.79 (dd, 1H), 3.42 (t, 2H), 1.82 (s, 3H)

<실시예 43> (S)-[N-3-(4-(2-이미다졸-1-일)메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 43 (S)-[N-3- (4- (2-imidazol-1-yl) methylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazoli Dinyl] Preparation of methyl acetamide

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 2-이미다졸릴메틸-4-부로모피리딘을 첨가하는 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물을 얻었다. The title compound was obtained in the same manner as in Example 3, except that 2-imidazolylmethyl-4-buromopyridine was added instead of methyl 5-bromopyridine-3-carboxylate as a starting material.                     

1H NMR(DMSO-d6) 8.55(d,1H), 8.18(t,1H), 7.68(s,1H), 7.58(m,2H), 7.40(m,2H), 7.28(s,1H), 7.16(s,1H), 6.81(s,1H), 5.22(s,2H), 4.68(m,1H), 4.16(t,1H), 3.69(dd,1H), 3.38(t,2H), 1.73(s,3H)
 1 H NMR (DMSO-d 6 ) 8.55 (d, 1H), 8.18 (t, 1H), 7.68 (s, 1H), 7.58 (m, 2H), 7.40 (m, 2H), 7.28 (s, 1H) , 7.16 (s, 1H), 6.81 (s, 1H), 5.22 (s, 2H), 4.68 (m, 1H), 4.16 (t, 1H), 3.69 (dd, 1H), 3.38 (t, 2H), 1.73 (s, 3H)

<실시예 44> (S)-[N-3-(4-(2-몰포린-4-일)메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 44 (S)-[N-3- (4- (2-morpholin-4-yl) methylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazoli Dinyl] Preparation of methyl acetamide

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 몰포리닐메틸-4-부로모피리딘을 첨가하는 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물을 얻었다.The title compound was obtained in the same manner as in Example 3, except that morpholinylmethyl-4-buromopyridine was added instead of methyl 5-bromopyridine-3-carboxylate as a starting material.

1H NMR(DMSO-d6) 8.56(d,1H), 8.28(t,1H), 7.60(m,3H), 7.45(m,2H), 4.78(m,1H), 4.17(t,1H), 3.77(dd,1H), 3.57(m,4H), 3.42(m,2H), 2.43(m,4H), 1.82(s,3H)
 1 H NMR (DMSO-d 6 ) 8.56 (d, 1H), 8.28 (t, 1H), 7.60 (m, 3H), 7.45 (m, 2H), 4.78 (m, 1H), 4.17 (t, 1H) , 3.77 (dd, 1H), 3.57 (m, 4H), 3.42 (m, 2H), 2.43 (m, 4H), 1.82 (s, 3H)

<실시예 45> (S)-[N-3-(4-(2-아세틸싸이오메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 45 (S)-[N-3- (4- (2-acetylthiomethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acet Preparation of Amide

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 아세틸싸이오메틸-4-부로모피리딘을 첨가하는 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물 을 얻었다.The title compound was obtained in the same manner as in Example 3, except for adding acetylthiomethyl-4-bromopyridine instead of methyl 5-bromopyridine-3-carboxylate as a starting material.

1H NMR(CDCl3) 8.56(d,1H), 7.58(dd,1H), 7.49(m,2H), 7.32(m,2H), 6.03(t,1H), 4.81(m,1H), 4.28(s,2H), 4.09(t,1H), 3.81(dd,1H), 3.69(m,2H), 2.35(s,3H), 2.01(s,3H)
 1 H NMR (CDCl 3 ) 8.56 (d, 1H), 7.58 (dd, 1H), 7.49 (m, 2H), 7.32 (m, 2H), 6.03 (t, 1H), 4.81 (m, 1H), 4.28 (s, 2H), 4.09 (t, 1H), 3.81 (dd, 1H), 3.69 (m, 2H), 2.35 (s, 3H), 2.01 (s, 3H)

<실시예 46> (S)-[N-3-(4-(2-머캅토메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 46 (S)-[N-3- (4- (2-mercaptomethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide Manufacture

실시예 47에서 얻은 화합물 58mg을 메탄올에 녹이고 1N NaOH 용액을 실온에서 가한 후 5분동안 교반하였다. 상기 반응물에 물을 가하고 에틸아세테이트로 추출한 후 유기층을 탈수, 여과, 감압농축하고 컬럼크로마토그라피로 정제하여 표제화합물 15mg을 얻었다.58 mg of the compound obtained in Example 47 was dissolved in methanol, 1N NaOH solution was added at room temperature, and stirred for 5 minutes. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dehydrated, filtered, concentrated under reduced pressure, and purified by column chromatography to obtain 15 mg of the title compound.

1H NMR(CDCl3) 8.54(d,1H), 6.18(t,1H), 4.81(m,1H), 4.10(t,1H), 3.85(d,2H), 3.65(dd,2H), 2.01(s,3H)
 1 H NMR (CDCl 3 ) 8.54 (d, 1H), 6.18 (t, 1H), 4.81 (m, 1H), 4.10 (t, 1H), 3.85 (d, 2H), 3.65 (dd, 2H), 2.01 (s, 3H)

<실시예 47> (S)-[N-3-(4-(2-(4-메탄술포닐옥시아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 47 (S)-[N-3- (4- (2- (4-methanesulfonyloxyacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2 -Oxo-5-oxazolidinyl] methyl acetamide

실시예35로부터 얻은 화합물 30mg을 테트라히드로퓨란에 녹이고 메탄술포닐클로라이드 15ul와 트리에틸아민 30ul를 실온에서 적가한 후 1시간동안 교반하였다. 상기 반응물에 물을 가하고 에틸아세테이트로 추출한 후 유기층을 탈수, 여과, 감압농축하고 컬럼크로마토그라피로 정제하여 표제화합물 20mg을 얻었다. 30 mg of the compound obtained in Example 35 was dissolved in tetrahydrofuran, and 15ul of methanesulfonylchloride and 30ul of triethylamine were added dropwise at room temperature, followed by stirring for 1 hour. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dehydrated, filtered, concentrated under reduced pressure, and purified by column chromatography to obtain 20 mg of the title compound.                     

1H NMR(CDCl3) 8.34(s,1H), 7.42(dd,1H), 7.52(dd,1H), 7.38(t,1H), 7.27(dd,1H), 6.72(d,1H), 6.17(t,1H), 4.94(s,1H), 4.81(m,1H), 4.10(t,1H), 3.75(m,13H), 3.24(s,3H), 2.01(s,3H)
 1 H NMR (CDCl 3 ) 8.34 (s, 1H), 7.42 (dd, 1H), 7.52 (dd, 1H), 7.38 (t, 1H), 7.27 (dd, 1H), 6.72 (d, 1H), 6.17 (t, 1H), 4.94 (s, 1H), 4.81 (m, 1H), 4.10 (t, 1H), 3.75 (m, 13H), 3.24 (s, 3H), 2.01 (s, 3H)

<실시예 48> (S)-[N-3-(4-(2-(4-아크릴로일피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 48 (S)-[N-3- (4- (2- (4-acryloylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo Preparation of -5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 아크릴로일클로라이드을 첨가하는 것을 제외하고 상기 실시예 33과 동일한 방법으로 표제 화합물 을 얻었다.
The title compound was obtained in the same manner as in Example 33, except for adding acryloyl chloride instead of acetoxyacetyl chloride as a starting material.

<실시예 49> (S)-[N-3-(4-(2-(4-에톡시옥소아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 49 (S)-[N-3- (4- (2- (4-ethoxyoxoacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2- Preparation of oxo-5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 에톡시옥소아세틸클로라이드를 첨가하는 것을 제외하고 상기 실시예 32과 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 32, except that ethoxyoxoacetylchloride was added instead of acetoxyacetyl chloride as a starting material.

<실시예 50> (S)-[N-3-(4-(2-(4-니코티노일피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 50 (S)-[N-3- (4- (2- (4-nicotinoylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo Preparation of -5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 니코티노일클로라이드를 첨가하는 것을 제외하고 상기 실시예 32와 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 32, except that nicotinoyl chloride was added instead of acetoxyacetyl chloride as a starting material.

<실시예 51> (S)-[N-3-(4-(2-(4-피발로일피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 51 (S)-[N-3- (4- (2- (4-pivaloylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo Preparation of -5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 피발로일클로라이드를 첨가하는 것을 제외하고 상기 실시예 32와 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 32, except that pivaloyl chloride was added instead of acetoxyacetyl chloride as a starting material.

<실시예 52> (S)-[N-3-(4-(2-(4-테트라부틸아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 52 (S)-[N-3- (4- (2- (4-tetrabutylacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo Preparation of -5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 테트라부틸아세틸클로라이드를 첨가하는 것을 제외하고 상기 실시예 32와 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 32, except that tetrabutylacetylchloride was added instead of acetoxyacetyl chloride as a starting material.

<실시예 53> (S)-[N-3-(4-(2-(4-니코티노일옥시아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 53 (S)-[N-3- (4- (2- (4-nicotinoyloxyacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2 -Oxo-5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 니코티노일옥시아세틸클로라이드를 첨가하는 것을 제외하고 상기 실시예 32와 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 32, except that nicotinoyloxyacetylchloride was added instead of acetoxyacetylchloride as a starting material.

<실시예 54> (S)-[N-3-(4-(2-(4-(2,5-디메톡시페닐아세틸)피페라진-1-일)피리딘 -5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 54 (S)-[N-3- (4- (2- (4- (2,5-dimethoxyphenylacetyl) piperazin-1-yl) pyridin-5-yl) -3-flo Rophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 2,5-디메톡시페닐아세틸클로라이드를 첨가하는 것을 제외하고 상기 실시예 32와 동일한 방법으로 표제 화합물을 얻 었다.
The title compound was obtained in the same manner as in Example 32, except that 2,5-dimethoxyphenylacetylchloride was added instead of acetoxyacetylchloride as a starting material.

<실시예 55> (S)-[N-3-(4-(2-(4-(3,3-디메틸아크릴로일)피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 55 (S)-[N-3- (4- (2- (4- (3,3-dimethylacryloyl) piperazin-1-yl) pyridin-5-yl) -3-flo Rophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 3,3-디메틸아크릴로일클로라이드를 첨가하는 것을 제외하고 상기 실시예 32와 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 32, except that 3,3-dimethylacryloyl chloride was added instead of acetoxyacetyl chloride as a starting material.

<실시예 56> (S)-[N-3-(4-(2-(4-(2,6-디메톡시벤조일)피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 56 (S)-[N-3- (4- (2- (4- (2,6-dimethoxybenzoyl) piperazin-1-yl) pyridin-5-yl) -3-fluoro Phenyl) -2-oxo-5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 2,6-디메톡시벤조일클로라이드를 첨가하는 것을 제외하고 상기 실시예 32와 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 32, except that 2,6-dimethoxybenzoyl chloride was added instead of acetoxyacetyl chloride as a starting material.

<실시예 57> (S)-[N-3-(4-(2-(4-(2-트리플로로메틸)벤조일)피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 57 (S)-[N-3- (4- (2- (4- (2-trifluoromethyl) benzoyl) piperazin-1-yl) pyridin-5-yl) -3-flo Rophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 2-트리플로로메틸벤조일클로라이드를 첨가하는 것을 제외하고 상기 실시예 32와 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 32, except that 2-trifluoromethylbenzoyl chloride was added instead of acetoxyacetyl chloride as a starting material.

<실시예 58> (S)-[N-3-(4-(2-(4-(4-트리플로로메틸)벤조일)피페라진-1-일)피리딘 -5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 58 (S)-[N-3- (4- (2- (4- (4-trifluoromethyl) benzoyl) piperazin-1-yl) pyridin-5-yl) -3-flo Rophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 4-트리플로로메틸벤조일클로라이드를 첨가하는 것을 제외하고 상기 실시예 32와 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 32, except that 4-trifluoromethylbenzoyl chloride was added instead of acetoxyacetyl chloride as a starting material.

<실시예 59> (S)-[N-3-(4-(2-(4-벤질카보닐피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 59 (S)-[N-3- (4- (2- (4-benzylcarbonylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo Preparation of -5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 페닐아세틸클로라이드를 첨가하는 것을 제외하고 상기 실시예 32와 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 32, except that phenylacetyl chloride was added instead of acetoxyacetyl chloride as a starting material.

<실시예 60> (S)-[N-3-(4-(2-(4-크로토닐피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 60 (S)-[N-3- (4- (2- (4-crotonylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo- Preparation of 5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 크로토닐클로라이드를 첨가하는 것을 제외하고 상기 실시예 32와 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 32, except that crotonyl chloride was added instead of acetoxyacetyl chloride as a starting material.

<실시예 61> (S)-[N-3-(4-(2-(4-트리플로로메틸카보닐피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 61 (S)-[N-3- (4- (2- (4-trifluoromethylcarbonylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl)- Preparation of 2-oxo-5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 트리플로로아세틸클로라이드를 첨가하는 것을 제외하고 상기 실시예 32와 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 32, except that trifluoroacetyl chloride was added instead of acetoxyacetyl chloride as a starting material.

<실시예 62> (S)-[N-3-(4-(2-(4-n-발레릴피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 62 (S)-[N-3- (4- (2- (4-n-Valerylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2- Preparation of oxo-5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 발레릴클로라이드를 첨가하는 것을 제외하고 상기 실시예 32와 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 32, except that valeryl chloride was added instead of acetoxyacetyl chloride as a starting material.

<실시예 63> (S)-[N-3-(4-(2-(4-페닐옥시카보닐피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 63 (S)-[N-3- (4- (2- (4-phenyloxycarbonylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2- Preparation of oxo-5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 페닐옥시카보닐클로라이드를 첨가하는 것을 제외하고 상기 실시예 32와 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 32, except that phenyloxycarbonyl chloride was added instead of acetoxyacetyl chloride as a starting material.

<실시예 64> (S)-[N-3-(4-(2-(4-알릴옥시카보닐피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 64 (S)-[N-3- (4- (2- (4-allyloxycarbonylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2- Preparation of oxo-5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 알릴옥시카보닐클로라이드를 첨가하는 것을 제외하고 상기 실시예 32와 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 32, except that allyloxycarbonyl chloride was added instead of acetoxyacetyl chloride as a starting material.

<실시예 65> (S)-[N-3-(4-(2-(4-(1-클로로에틸)옥시카보닐피페라진-1-일)피리딘 -5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 65 (S)-[N-3- (4- (2- (4- (1-chloroethyl) oxycarbonylpiperazin-1-yl) pyridin-5-yl) -3-fluoro Phenyl) -2-oxo-5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 1-클로로에틸옥시카보닐클로라이드를 첨가하는 것을 제외하고 상기 실시예 32와 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 32, except that 1-chloroethyloxycarbonyl chloride was added instead of acetoxyacetyl chloride as a starting material.

<실시예 66> (S)-[N-3-(4-(2-(4-(4-니트로벤질)옥시카보닐피페라진-1-일)피리딘 -5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 66 (S)-[N-3- (4- (2- (4- (4-nitrobenzyl) oxycarbonylpiperazin-1-yl) pyridin-5-yl) -3-fluoro Phenyl) -2-oxo-5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 4-니트로벤질옥시카보닐클로라이드를 첨가하는 것을 제외하고 상기 실시예 32와 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 32, except that 4-nitrobenzyloxycarbonyl chloride was added instead of acetoxyacetyl chloride as a starting material.

<실시예 67> (S)-[N-3-(4-(2-(4-벤질옥시카보닐피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 67 (S)-[N-3- (4- (2- (4-benzyloxycarbonylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2- Preparation of oxo-5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 벤질옥시카보닐클로라이드를 첨가하는 것을 제외하고 상기 실시예 32와 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 32, except that benzyloxycarbonyl chloride was added instead of acetoxyacetyl chloride as a starting material.

<실시예 68> (S)-[N-3-(4-(2-(4-(9-플루오레닐메틸옥시카보닐)피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 68 (S)-[N-3- (4- (2- (4- (9-fluorenylmethyloxycarbonyl) piperazin-1-yl) pyridin-5-yl) -3- Florophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 9-플루오레닐메틸옥시카보닐클로라이드를 첨가하는 것을 제외하고 상기 실시예 32와 동일한 방법으로 표제 화합물 을 얻었다.
The title compound was obtained in the same manner as in Example 32, except that 9-fluorenylmethyloxycarbonyl chloride was added instead of acetoxyacetyl chloride as a starting material.

<실시예 69> (S)-[N-3-(4-(2-(4-(2-피리미디닐)피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 69 (S)-[N-3- (4- (2- (4- (2-pyrimidinyl) piperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) Preparation of 2-oxo-5-oxazolidinyl] methyl acetamide

(S)-[N-3-(4-(2-피페라진-1-일피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 20mg을 디메틸아세트아마이드에 녹이고 2-부로모피리미딘 38mg과 디이소프로필에틸아민 63ul를 가한 후 50℃에서 20시간 교반한 후 컬럼크로마토그라피로 정제하여 표제화합물 39mg을 얻었다.
20 mg of (S)-[N-3- (4- (2-piperazin-1-ylpyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide It was dissolved in dimethylacetamide, 38 mg of 2-buromopyrimidine and 63 ul of diisopropylethylamine were added thereto, and the resultant was stirred at 50 ° C. for 20 hours and purified by column chromatography to obtain 39 mg of the title compound.

<실시예 70> (S)-[N-3-(4-(2-(4-메톡시카보닐메틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 70 (S)-[N-3- (4- (2- (4-methoxycarbonylmethylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2 -Oxo-5-oxazolidinyl] methyl acetamide

출발물질로 아세톡시아세틸클로라이드 대신 메톡시카보닐메틸클로라이드를 첨가하는 것을 제외하고 상기 실시예 32와 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 32, except that methoxycarbonylmethylchloride was added instead of acetoxyacetylchloride as a starting material.

<실시예 71> (S)-[N-3-(4-(2-플로로메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 71 (S)-[N-3- (4- (2-fluoromethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide Manufacture

(S)-[N-3-(4-(2-히드록시메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 68mg을 메틸렌클로라이드에 녹이고 트리에틸아민 0.04ml와 디에틸아미노설퍼트리플루오라이드(DAST) 0.03ml를 0℃에서 가한후 2시간동안 교반하였다. 상기 반응물에 물을 가하고 메틸렌클로라이드로 추출한 다음 유기층을 탈수,여과,감압농축하고 컬럼크로마토그라피로 정제하여 표제화합물 20mg을 얻었다.68 mg of (S)-[N-3- (4- (2-hydroxymethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide in methylene chloride After dissolving, 0.04 ml of triethylamine and 0.03 ml of diethylaminosulfur trifluoride (DAST) were added at 0 ° C. and stirred for 2 hours. Water was added to the reaction mixture, followed by extraction with methylene chloride. The organic layer was dehydrated, filtered, and concentrated under reduced pressure and purified by column chromatography to obtain 20 mg of the title compound.

1H NMR(CDCl3) 8.45(d,1H), 5.25(dd,1H), 5.02(dd,1H), 4.93(m,1H), 4.02(t,1H), 4.17(t,1H), 3.87(m,1H), 3.63(m,2H), 2.04(s,3H)
 1 H NMR (CDCl 3 ) 8.45 (d, 1H), 5.25 (dd, 1H), 5.02 (dd, 1H), 4.93 (m, 1H), 4.02 (t, 1H), 4.17 (t, 1H), 3.87 (m, 1H), 3.63 (m, 2H), 2.04 (s, 3H)

<실시예 72> (S)-[N-3-(4-(2-시아노메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 72 (S)-[N-3- (4- (2-cyanomethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide Manufacture

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 2-시아노메틸-4-부로모피리딘을 첨가하는 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물 을 얻었다.The title compound was obtained in the same manner as in Example 3, except that 2-cyanomethyl-4-bromopyridine was added instead of methyl 5-bromopyridine-3-carboxylate as a starting material.

1H NMR(CDCl3) 8.59(d,1H), 6.10(t,1H), 4.82(m,1H), 4.13(t,1H), 3.98(s,2H), 3.79(dd,1H), 3.83(dd,2H), 3.68(m,2H), 2.02(s,3H)
 1 H NMR (CDCl 3 ) 8.59 (d, 1H), 6.10 (t, 1H), 4.82 (m, 1H), 4.13 (t, 1H), 3.98 (s, 2H), 3.79 (dd, 1H), 3.83 (dd, 2H), 3.68 (m, 2H), 2.02 (s, 3H)

<실시예 73> (S)-[N-3-(4-(2-메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 73 Preparation of (S)-[N-3- (4- (2-methylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 2-메틸-4-부로모피리딘을 첨가하는 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물을 얻었다.The title compound was obtained in the same manner as in Example 3, except that 2-methyl-4-bromopyridine was added instead of methyl 5-bromopyridine-3-carboxylate as a starting material.

1H NMR(DMSO-d6) 8.54(d,1H), 8.27(t,1H), 4.78(m,1H), 4.17(t,1H), 3.80(dd,1H), 3.42(t,2H), 2.54(s,3H), 1.83(s,3H)
 1 H NMR (DMSO-d 6 ) 8.54 (d, 1H), 8.27 (t, 1H), 4.78 (m, 1H), 4.17 (t, 1H), 3.80 (dd, 1H), 3.42 (t, 2H) , 2.54 (s, 3H), 1.83 (s, 3H)

<실시예 74> (S)-[N-3-(4-(2-(4-(2-히드록시)에틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 74 (S)-[N-3- (4- (2- (4- (2-hydroxy) ethylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) Preparation of 2-oxo-5-oxazolidinyl] methyl acetamide

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 2-히드록시에틸피페라지닐-5-부로모피리딘을 첨가하는 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 3, except that 2-hydroxyethylpiperazinyl-5-bromopyridine was added instead of methyl 5-bromopyridine-3-carboxylate as a starting material.

<실시예 75> (S)-[N-3-(4-(2-(4-(2-아세톡시)에틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 75 (S)-[N-3- (4- (2- (4- (2-acetoxy) ethylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) Preparation of 2-oxo-5-oxazolidinyl] methyl acetamide

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 2-아세톡시에틸피페라지닐-5-부로모피리딘을 첨가하는 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 3, except that 2-acetoxyethylpiperazinyl-5-bromopyridine was added instead of methyl 5-bromopyridine-3-carboxylate as a starting material.

<실시예 76> (S)-[N-3-(4-(2-(4-메톡시카보닐피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 76 (S)-[N-3- (4- (2- (4-methoxycarbonylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2- Preparation of oxo-5-oxazolidinyl] methyl acetamide

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 4-메톡시카보닐피페라지닐-5-부로모피리딘을 첨가하는 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물을 얻었다.
The title compound was obtained in the same manner as in Example 3, except that 4-methoxycarbonylpiperazinyl-5-bromopyridine was added instead of methyl 5-bromopyridine-3-carboxylate as a starting material.

<실시예 77> (S)-[N-3-(4-(2-(4-(2-메탄술포닐옥시)에틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 77 (S)-[N-3- (4- (2- (4- (2-methanesulfonyloxy) ethylpiperazin-1-yl) pyridin-5-yl) -3-fluoro Phenyl) -2-oxo-5-oxazolidinyl] methyl acetamide

실시예 76으로부터 얻은 화합물 30mg을 테트라히드로퓨란에 녹이고 메탄술포닐클로라이드 15ul와 트리에틸아민 30ul를 실온에서 적가한 후 1시간동안 교반하였다. 상기 반응물에 물을 가하고 에틸아세테이트로 추출한 후 유기층을 탈수, 여과, 감압농축하고 컬럼크로마토그라피로 정제하여 표제화합물 20mg을 얻었다.
30 mg of the compound obtained in Example 76 was dissolved in tetrahydrofuran and 15ul of methanesulfonylchloride and 30ul of triethylamine were added dropwise at room temperature, followed by stirring for 1 hour. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dehydrated, filtered, concentrated under reduced pressure, and purified by column chromatography to obtain 20 mg of the title compound.

<실시예 78> (S)-[N-3-(4-(2-(4-히드록시메틸이미다졸-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 78 (S)-[N-3- (4- (2- (4-hydroxymethylimidazol-1-yl) pyridin-5-yl) -3-fluorophenyl) -2- Preparation of oxo-5-oxazolidinyl] methyl acetamide

출발물질로 메틸 5-부로모피리딘-3-카르복실레이트 대신 3-히드록시메틸이미다졸릴-5-부로모피리딘을 첨가하는 것을 제외하고 상기 실시예 3과 동일한 방법으로 표제 화합물을 얻었다.The title compound was obtained in the same manner as in Example 3, except that 3-hydroxymethylimidazolyl-5-bromopyridine was added instead of methyl 5-bromopyridine-3-carboxylate as a starting material.

1H NMR(DMSO-d6) 9.80(s,1H), 8.79(s.1H), 8.31(m,3H), 8.11(d,1H), 7.64(m,2H), 7.45(dd,1H), 4.77(m,1H), 4.59(s,2H), 4.18(t,1H), 3.81(dd,1H), 3.43(t,2H), 1.83(s,3H)
 1 H NMR (DMSO-d 6 ) 9.80 (s, 1H), 8.79 (s.1H), 8.31 (m, 3H), 8.11 (d, 1H), 7.64 (m, 2H), 7.45 (dd, 1H) , 4.77 (m, 1H), 4.59 (s, 2H), 4.18 (t, 1H), 3.81 (dd, 1H), 3.43 (t, 2H), 1.83 (s, 3H)

<실시예 79> (S)-[N-3-(4-(2-아미노아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 79 (S)-[N-3- (4- (2-aminoacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide Manufacture

N-t-부톡시카보닐글리신(10.13g)을 피리딘 100ml에 녹이고 실온에서 2-아미노-5-부로모피리딘(5g), 1-(3-디메틸아미노프로필)-3-에틸카보디이미드 염산염(13.85g)및 4-디메틸아미노피리딘(7.06g)을 각각 가한 후 15시간동안 실온에 서 교반하였다. 상기 반응 혼합물에 물을 가하고 에틸아세테이트로 추출한 후 유기층을 소금물로 세척하고 탈수, 여과 및 감압농축하여 2-(N-t-부톡시카보닐글리시닐아미노)-5-부로모피리딘(5.58g)을 얻었다. 위 화합물과 (S)-[N-3-(4-트리메틸스테닐-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드(5.82g)를 디메틸포름아마이드(70ml)에 녹이고 실온에서 트리에틸아민(4.9ml)과 디클로로비스트리페닐포스핀팔라디움(II) 2.97g을 각각 가한 후 4시간동안 100℃에서 교반하였다. 상기 반응 혼합물에 물을 가한 다음 에틸아세테이트로 추출하고 추출된 유기층은 소금물로 세척한 후 탈수, 여과 및 감압농축한 다음 재결정방법으로 정제하여 (S)-[N-3-(4-(2-(N-t-부톡시카보닐글리시닐아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드(5.13g)을 얻었다. 위 화합물을 클로로포름에 녹이고 트리메틸실릴아이오다이드(1.65ml)를 질소하에서 가하고 실온에서 30분 교반한다. 클로로포름을 가하고 유기층을 소금물로 세척한 후 탈수, 여과, 감압농축하고 컬럼크로마토그라피로 정제하여 표제화합물(550mg)을 얻었다.N- t -butoxycarbonylglycine (10.13 g) was dissolved in 100 ml of pyridine and 2-amino-5-butromopyridine (5 g), 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride at room temperature (13.85 g) and 4-dimethylaminopyridine (7.06 g) were added, followed by stirring at room temperature for 15 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with brine, dehydrated, filtered and concentrated under reduced pressure to give 2- (Nt-butoxycarbonylglycinylamino) -5-butromopyridine (5.58 g). Got it. The above compound and (S)-[N-3- (4-trimethylstenyl-3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (5.82 g) were dimethylformamide (70 ml). It was dissolved in and triethylamine (4.9ml) and 2.97g of dichlorobistriphenylphosphinepalladium (II) were added at room temperature, followed by stirring at 100 ° C for 4 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The extracted organic layer was washed with brine, dehydrated, filtered and concentrated under reduced pressure, and then purified by recrystallization (S)-[N-3- (4- (2- (Nt-butoxycarbonylglycinylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (5.13 g) was obtained. After dissolving, trimethylsilyl iodide (1.65 ml) was added under nitrogen and stirred at room temperature for 30 minutes, chloroform was added, the organic layer was washed with brine, dehydrated, filtered, concentrated under reduced pressure and purified by column chromatography to obtain the title compound (550 mg). Got it.

1H NMR(DMSO-d6) 8.49(s,1H), 8.23(m.2H), 8.00(m,1H), 7.64(m,2H), 7.40(dd,1H), 4.75(m,1H), 4.16(t,1H), 3.77(dd,1H), 3.42(t,2H), 3.32(s,2H), 1.83(s,3H)
 1 H NMR (DMSO-d 6 ) 8.49 (s, 1H), 8.23 (m.2H), 8.00 (m, 1H), 7.64 (m, 2H), 7.40 (dd, 1H), 4.75 (m, 1H) , 4.16 (t, 1H), 3.77 (dd, 1H), 3.42 (t, 2H), 3.32 (s, 2H), 1.83 (s, 3H)

<실시예 80> (S)-[N-3-(4-(2-(4-시아노피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 80 (S)-[N-3- (4- (2- (4-cyanopiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo- Preparation of 5-oxazolidinyl] methyl acetamide

(S)-[N-3-(4-(2-피페라진-1-일피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸 리딘일]메틸 아세트아마이드 히드로클로라이드(500mg)를 메탄올에 녹이고 시아노부로마이드(192mg)와 소듐아세테이트(295mg)을 가하고 실온에서 3시간 교반한다. 클로로포름을 가하고 유기층을 소금물로 세척한 후 탈수, 여과, 감압농축하고 컬럼크로마토그라피로 정제하여 표제화합물 480mg(90%)을 얻었다.
(S)-[N-3- (4- (2-piperazin-1-ylpyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide hydro Chloride (500 mg) is dissolved in methanol, cyanobromide (192 mg) and sodium acetate (295 mg) are added, and the mixture is stirred at room temperature for 3 hours. Chloroform was added, the organic layer was washed with brine, dehydrated, filtered, concentrated under reduced pressure and purified by column chromatography to obtain 480 mg (90%) of the title compound.

<실시예 81> (S)-[N-3-(4-(2-(4-카르복스아마이드옥심피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 81 (S)-[N-3- (4- (2- (4-carboxamide oxime piperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2- Preparation of oxo-5-oxazolidinyl] methyl acetamide

(S)-[N-3-(4-(2-(4-시아노피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드(250mg)를 에탄올에 녹이고 히드록시아민 염산염(79mg)과 소듐카보네이트(211mg)를 가하고 3시간 환류한다. 클로로포름을 가하고 유기층을 소금물로 세척하고 탈수 및 여과하여 감압 농축한 다음 컬럼크로마토그래피로 정제하여 표제 화합물 150mg(39%)을 얻었다.
(S)-[N-3- (4- (2- (4-cyanopiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl ] Methyl acetamide (250 mg) is dissolved in ethanol, hydroxyamine hydrochloride (79 mg) and sodium carbonate (211 mg) are added and refluxed for 3 hours. Chloroform was added, the organic layer was washed with brine, dehydrated and filtered, concentrated under reduced pressure, and purified by column chromatography to obtain 150 mg (39%) of the title compound.

<실시예 82> (S)-[N-3-(4-(2-(4-옥소피페리딘-1-일)피리딘-5-일)-3-플로로페닐) -2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 82 (S)-[N-3- (4- (2- (4-oxopiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo- Preparation of 5-oxazolidinyl] methyl acetamide

(S)-[N-3-(4-(2-(1,4-디옥사-8-아자스피로(4,5)데칸-8-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드(3.3g)을 아세톤(3ml)과 물(1ml)의 혼합용매에 녹이고 p-톨루엔술폰산(4g)을 가한 한 24시간동안 환류하다. 에틸아세테이트를 가하고 유기층을 소금물로 세척한 후 탈수, 여과, 감압농축한 후 컬럼크로마토그라피로 정제하여 표제 화합물 1.2g(40%)을 얻었다.(S)-[N-3- (4- (2- (1,4-dioxa-8-azaspiro (4,5) decan-8-yl) pyridin-5-yl) -3-fluorophenyl ) -2-oxo-5-oxazolidinyl] methyl acetamide (3.3 g) is dissolved in a mixed solvent of acetone (3 ml) and water (1 ml) and refluxed for 24 hours as long as p-toluenesulfonic acid (4 g) is added. Ethyl acetate was added, the organic layer was washed with brine, dehydrated, filtered, and concentrated under reduced pressure and purified by column chromatography to obtain 1.2 g (40%) of the title compound.

1H NMR(CDCl3) 8.35(s,1H), 7.73(m,1H), 7.53(dd,1H), 7.42(t,1H), 7.25(m,1H), 6.80(d,1H), 6.12(t,1H), 4.79(m,1H), 4.09(t,1H), 3.98(t,4H), 3.78(m,1H), 3.67(m,2H), 2.52(t,4H), 2.01(s,3H)
 1 H NMR (CDCl 3 ) 8.35 (s, 1H), 7.73 (m, 1H), 7.53 (dd, 1H), 7.42 (t, 1H), 7.25 (m, 1H), 6.80 (d, 1H), 6.12 (t, 1H), 4.79 (m, 1H), 4.09 (t, 1H), 3.98 (t, 4H), 3.78 (m, 1H), 3.67 (m, 2H), 2.52 (t, 4H), 2.01 ( s, 3H)

<실시예 83> (S)-[N-3-(4-(2-아지도아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 83 (S)-[N-3- (4- (2-azidoacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acet Preparation of Amide

(S)-[N-3-(4-(2-히드록시아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드(500mg)를 메틸렌클로라이드(6.2ml)에 녹이고 메탄술포닐클로라이드(0.144ml)와 트리에틸아민(0.35ml)를 0℃에서 가하고 같은 온도에서 1시간 교반한다. 메틸렌클로라이드를 가하고 유기층을 소금물로 세척한 후 탈수, 여과, 감압농축하여 (S)-[N-3-(4-(2-메탄술포닐옥시아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드(0.47g)를 얻는다. 위 물질을 디메틸포름아마이드(5ml)에 녹이고 실온에서 소듐아자이드(1.5g)를 가한 후 2시간동안 100℃에서 교반하다. 에틸아세테이트를 가하고 유기층을 소금물로 세척한 후 탈수, 여과, 감압농축하고 컬럼크로마토그라피로 정제하여 표제화합물(180mg, 34%)을 얻었다.(S)-[N-3- (4- (2-hydroxyacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (500 mg) Dissolve in methylene chloride (6.2 ml), methanesulfonyl chloride (0.144 ml) and triethylamine (0.35 ml) are added at 0 ° C. and stirred at the same temperature for 1 hour. Methylene chloride was added, the organic layer was washed with brine, dehydrated, filtered, and concentrated under reduced pressure, followed by (S)-[N-3- (4- (2-methanesulfonyloxyacetylaminopyridin-5-yl) -3-fluoro. Phenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (0.47 g) is obtained. The above material is dissolved in dimethylformamide (5 ml), sodium azide (1.5 g) is added at room temperature, and then stirred at 100 ° C. for 2 hours. Ethyl acetate was added, the organic layer was washed with brine, dehydrated, filtered, concentrated under reduced pressure and purified by column chromatography to obtain the title compound (180mg, 34%).

1H NMR(DMSO-d6) 10.83(s,1H), 8.51(s,1H), 8.28(t,1H), 8.18(d,1H), 8.00(dd,1H), 7.64(m,2H), 7.40(dd,1H), 4.76(m,4H), 4.21(t,1H), 4.13(s,2H), 3.78(dd,1H), 3.42(t,2H), 1.83(s,3H)
 1 H NMR (DMSO-d 6 ) 10.83 (s, 1H), 8.51 (s, 1H), 8.28 (t, 1H), 8.18 (d, 1H), 8.00 (dd, 1H), 7.64 (m, 2H) , 7.40 (dd, 1H), 4.76 (m, 4H), 4.21 (t, 1H), 4.13 (s, 2H), 3.78 (dd, 1H), 3.42 (t, 2H), 1.83 (s, 3H)

<실시예 84> (S)-[N-3-(4-(2-(1,2,3,4,6,7-헥사히드로-5-옥소-1,4-디아제팬-1-일)-피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 84 (S)-[N-3- (4- (2- (1,2,3,4,6,7-hexahydro-5-oxo-1,4-diazepane-1-yl) ) -Pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide

상기 실시예 82에서 제조한 (S)-[N-3-(4-(2-(4-옥소피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드(1.2g)를 포름산(20ml)에 녹이고 히드록실아미노-O-술폰산(1.6g)을 가한 후 8시간동안 100℃에서 교반한다. 가성소다로 산성용액을 중성화시키고 메틸렌클로라이드로 추출한 후 유기층을 소금물로 세척하고 탈수, 여과, 감압농축한 후 컬럼크로마토그라피로 정제하여 표제의 화합물(120mg)을 얻었다.(S)-[N-3- (4- (2- (4-oxopiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) prepared in Example 82 above. Dissolve oxo-5-oxazolidinyl] methyl acetamide (1.2 g) in formic acid (20 ml), add hydroxylamino-O-sulfonic acid (1.6 g) and stir at 100 ° C. for 8 hours. The acidic solution was neutralized with caustic soda and extracted with methylene chloride. The organic layer was washed with brine, dehydrated, filtered and concentrated under reduced pressure, and then purified by column chromatography to obtain the title compound (120 mg).

1H NMR(DMSO-d6) 8.30(s,1H), 8.26(t,1H), 7.74(m,1H), 7.59(m,3H), 7.38(dd,1H), 6.80(d,1H), 4.76(m,1H), 4.16(t,1H), 3.77(m,6H), 3.47(t,2H), 3.19(m,2H), 1.83(s,3H)
 1 H NMR (DMSO-d 6 ) 8.30 (s, 1H), 8.26 (t, 1H), 7.74 (m, 1H), 7.59 (m, 3H), 7.38 (dd, 1H), 6.80 (d, 1H) , 4.76 (m, 1H), 4.16 (t, 1H), 3.77 (m, 6H), 3.47 (t, 2H), 3.19 (m, 2H), 1.83 (s, 3H)

<실시예 85> (S)-[N-3-(4-(2-N-(디메틸아미노메틸렌)아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 85 (S)-[N-3- (4- (2-N- (dimethylaminomethylene) aminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazoli Dinyl] Preparation of methyl acetamide

(S)-[N-3-(4-(2-아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일] 메틸 아세트아마이드(50mg)를 메탄올에 녹이고 N,N-디메틸아미노디메톡시메탄(58ml)을 실온에서 가한 후 24시간동안 환류한다. 메틸렌클로라이드를 가하고 소금물로 유기층을 세척한 후 탈수, 여과, 감압농축하고 컬럼크로마토그라피로 정제하여 표제화합물(52mg, 90%)을 얻었다.Dissolve (S)-[N-3- (4- (2-aminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (50 mg) in methanol N, N-dimethylaminodimethoxymethane (58 ml) is added at room temperature and refluxed for 24 hours. Methylene chloride was added, the organic layer was washed with brine, dehydrated, filtered, concentrated under reduced pressure, and purified by column chromatography to obtain the title compound (52 mg, 90%).

1H NMR(CDCl3) 8.46(s,1H), 8.39(s,1H), 7.73(m,1H), 7.53(dd,1H), 7.47(d,1H), 7.27(m,1H), 7.00(d,1H), 6.04(t,1H), 4.80(m,1H), 4.08(t,1H), 3.81(dd,1H), 3.61(m,2H), 3.10(s,6H), 2.02(s,3H)
 1 H NMR (CDCl 3 ) 8.46 (s, 1H), 8.39 (s, 1H), 7.73 (m, 1H), 7.53 (dd, 1H), 7.47 (d, 1H), 7.27 (m, 1H), 7.00 (d, 1H), 6.04 (t, 1H), 4.80 (m, 1H), 4.08 (t, 1H), 3.81 (dd, 1H), 3.61 (m, 2H), 3.10 (s, 6H), 2.02 ( s, 3H)

<실시예 86> (S)-[N-3-(4-(2-(4-히드록시이미노피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 86 (S)-[N-3- (4- (2- (4-hydroxyiminopiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2- Preparation of oxo-5-oxazolidinyl] methyl acetamide

상기 실시예 82에서 제조한 (S)-[N-3-(4-(2-(4-옥소피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드(600mg)를 에탄올에 녹이고 히드록실아민 염산염(200mg)과 피리딘(250mg)을 가한 후 2시간동안 환류한다. 에틸아세테이트를 가하고 유기층을 소금물로 세척한 후 탈수, 여과, 감압농축하고 재결정(클로로포름/메탄올/에틸에테르)하여 표제화합물(600mg, 96%)을 얻었다.(S)-[N-3- (4- (2- (4-oxopiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) prepared in Example 82 above. Dissolve oxo-5-oxazolidinyl] methyl acetamide (600 mg) in ethanol, add hydroxylamine hydrochloride (200 mg) and pyridine (250 mg), and reflux for 2 hours. Ethyl acetate was added, the organic layer was washed with brine, dehydrated, filtered, concentrated under reduced pressure and recrystallized (chloroform / methanol / ethyl ether) to obtain the title compound (600 mg, 96%).

1H NMR(DMSO-d6) 10.42(s,1H), 8.31(m,2H), 7.75(m,1H), 7.55(d,1H), 7.51(m,1H), 7.38(dd,1H), 6.95(d,1H), 4.79(m,1H), 4.14(t,1H), 3.75(m,5H), 3.41(t,2H), 2.49(t,2H), 2.36(t,2H), 1.82(s,3H)
 1 H NMR (DMSO-d 6 ) 10.42 (s, 1H), 8.31 (m, 2H), 7.75 (m, 1H), 7.55 (d, 1H), 7.51 (m, 1H), 7.38 (dd, 1H) , 6.95 (d, 1H), 4.79 (m, 1H), 4.14 (t, 1H), 3.75 (m, 5H), 3.41 (t, 2H), 2.49 (t, 2H), 2.36 (t, 2H), 1.82 (s, 3H)

<실시예 87> (S)-[N-3-(4-(2-(4-메탄술포닐옥시이미노피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 87 (S)-[N-3- (4- (2- (4-methanesulfonyloxyiminopiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl)- Preparation of 2-oxo-5-oxazolidinyl] methyl acetamide

상기 실시예 86에서 제조한 (S)-[N-3-(4-(2-(4-히드록시이미노피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드(50mg)를 테트라히드로퓨란에 녹이고 실온에서 메탄술포닐클로라이드(14mg)와 트리에틸아민(50mg)을 가한 후 30분동안 교반한다. 에틸아세테이트를 가하고 유기층을 소금물로 세척한 후 탈수, 여과, 감압농축하고 컬럼크로마토그라피로 정제하여 표제화합물(40mg, 65%)을 얻었다.
(S)-[N-3- (4- (2- (4-hydroxyiminopiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) -prepared in Example 86 above- 2-oxo-5-oxazolidinyl] methyl acetamide (50 mg) is dissolved in tetrahydrofuran and methanesulfonyl chloride (14 mg) and triethylamine (50 mg) are added at room temperature, followed by stirring for 30 minutes. Ethyl acetate was added, the organic layer was washed with brine, dehydrated, filtered, concentrated under reduced pressure, and purified by column chromatography to obtain the title compound (40 mg, 65%).

<실시예 88> (S)-[N-3-(4-(2-(4-메틸이미노피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 88 (S)-[N-3- (4- (2- (4-methyliminopiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2- Preparation of oxo-5-oxazolidinyl] methyl acetamide

상기 실시예 82에서 제조한 (S)-[N-3-(4-(2-(4-옥소피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드(50mg)를 에탄올에 녹이고 메틸아민 염산염(16mg)과 피리딘(28mg)을 가한 후 3시간동안 환류한다. 에틸아세테이트를 가하고 유기층을 소금물로 세척한 후 탈수, 여과, 감압농축하고 컬럼크로마토그래피로 정제하여 표제 화합물(10mg, 20%)을 얻었다.
(S)-[N-3- (4- (2- (4-oxopiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) prepared in Example 82 above. Oxo-5-oxazolidinyl] methyl acetamide (50 mg) is dissolved in ethanol and methylamine hydrochloride (16 mg) and pyridine (28 mg) are added and refluxed for 3 hours. Ethyl acetate was added, the organic layer was washed with brine, dehydrated, filtered, concentrated under reduced pressure and purified by column chromatography to obtain the title compound (10mg, 20%).

<실시예 89> (S)-[N-3-(4-(2-(4-메톡시카보닐히드라지노피페리딘-1-일)피리딘- 5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 89 (S)-[N-3- (4- (2- (4-methoxycarbonylhydrazinopiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) Preparation of 2-oxo-5-oxazolidinyl] methyl acetamide

상기 실시예 82에서 제조한 (S)-[N-3-(4-(2-(4-옥소피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드(100mg)를 에탄올에 녹이고 메톡시카보닐히드라진(106mg)을 가한 후 3시간동안 환류한다. 에틸아세테이트를 가하고 유기층을 소금물로 세척한 후 탈수, 여과, 감압농축하고 컬럼크로마토그래피로 정제하여 표제 화합물(80mg, 70%)을 얻었다.(S)-[N-3- (4- (2- (4-oxopiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) prepared in Example 82 above. Oxo-5-oxazolidinyl] methyl acetamide (100 mg) is dissolved in ethanol and methoxycarbonylhydrazine (106 mg) is added and refluxed for 3 hours. Ethyl acetate was added, the organic layer was washed with brine, dehydrated, filtered, concentrated under reduced pressure, and purified by column chromatography to obtain the title compound (80 mg, 70%).

1H NMR(DMSO-d6) 9.94(s,1H), 8.27(m,2H), 7.78(d,1H), 7.64(m,2H), 7.38(dd,1H), 7.00(d,1H), 4.78(m,1H), 4.16(t,1H), 3.79(m,5H), 3.63(s,3H), 3.42(t,4H), 2.49(t,2H), 1.83(s,3H)
 1 H NMR (DMSO-d 6 ) 9.94 (s, 1H), 8.27 (m, 2H), 7.78 (d, 1H), 7.64 (m, 2H), 7.38 (dd, 1H), 7.00 (d, 1H) , 4.78 (m, 1H), 4.16 (t, 1H), 3.79 (m, 5H), 3.63 (s, 3H), 3.42 (t, 4H), 2.49 (t, 2H), 1.83 (s, 3H)

<실시예 90> (S)-[N-3-(4-(2-N-(L-알라닐)아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 90 (S)-[N-3- (4- (2-N- (L-alanyl) aminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxa Preparation of Zolidinyl] methyl Acetamide

N-t-부톡시카보닐-L-알라닌(2.19g)을 피리딘 20ml에 녹이고 실온에서 2-아미노-5-부로모피리딘(1g), 1-(3-디메틸아미노프로필)-3-에틸카보디이미드 염산염(2.77g)및 4-디메틸아미노피리딘(1.41g)을 각각 가한 후 15시간동안 실온에서 교반하였다. 상기 반응 혼합물에 물을 가하고 에틸아세테이트로 추출한 후 유기층을 소금물로 세척하고 탈수, 여과 및 감압농축하여 2-(N-t-부톡시카보닐-L-알라닐아미노)-5-부로모피리딘(0.713g)을 얻었다. 위 화합물과 (S)-[N-3-(4-트리메틸스테닐-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드(0.714g)를 디메틸 포름아마이드(20ml)에 녹이고 실온에서 트리에틸아민(0.6ml)과 디클로로비스트리페닐포스핀팔라디움(II) 0.36g을 각각 가한 후 4시간동안 100℃에서 교반하였다. 상기 반응 혼합물에 물을 가한 다음 에틸아세테이트로 추출하고 추출된 유기층은 소금물로 세척한 후 탈수, 여과 및 감압농축한 다음 재결정방법으로 정제하여 (S)-[N-3-(4-(2-(N-t-부톡시카보닐-L-알라닐아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드(0.27g)을 얻었다. 위 화합물을 클로로포름에 녹이고 트리메틸실릴아이오다이드(0.15ml)를 질소하에서 가하고 실온에서 30분 교반한다. 클로로포름을 가하고 유기층을 소금물로 세척한 후 탈수, 여과, 감압농축하고 컬럼크로마토그라피로 정제하여 표제화합물(50mg)을 얻었다.Nt-butoxycarbonyl-L-alanine (2.19 g) was dissolved in 20 ml of pyridine and 2-amino-5-buromopyridine (1 g), 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide at room temperature Hydrochloride (2.77 g) and 4-dimethylaminopyridine (1.41 g) were each added and then stirred at room temperature for 15 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with brine, dehydrated, filtered and concentrated under reduced pressure. 2- (Nt-butoxycarbonyl-L-alanylamino) -5-bromopyridine (0.713 g ) The above compound and (S)-[N-3- (4-trimethylstenyl-3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (0.714 g) was diluted with dimethyl formamide (20 ml). It was dissolved in and triethylamine (0.6ml) and dichlorobistriphenylphosphinepalladium (II) 0.36g at room temperature were added, and the mixture was stirred at 100 ° C for 4 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The extracted organic layer was washed with brine, dehydrated, filtered and concentrated under reduced pressure, and then purified by recrystallization (S)-[N-3- (4- (2- (Nt-butoxycarbonyl-L-alanylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (0.27 g) was obtained. It is dissolved in chloroform and trimethylsilyl iodide (0.15 ml) is added under nitrogen and stirred at room temperature for 30 minutes, chloroform is added, the organic layer is washed with brine, dehydrated, filtered, concentrated under reduced pressure and purified by column chromatography to obtain the title compound (50 mg). )

1H NMR(DMSO-d6) 8.50(s,1H), 8.27(t,1H), 8.20(d,1H), 8.01(m,1H), 7.63(m,2H), 7.40(dd,1H), 4.78(m,1H), 4.16(t,1H), 3.78(dd,1H), 3.51(q,1H), 3.42(t,2H), 1.83(s,3H), 1.20(d,3H)
 1 H NMR (DMSO-d 6 ) 8.50 (s, 1H), 8.27 (t, 1H), 8.20 (d, 1H), 8.01 (m, 1H), 7.63 (m, 2H), 7.40 (dd, 1H) , 4.78 (m, 1H), 4.16 (t, 1H), 3.78 (dd, 1H), 3.51 (q, 1H), 3.42 (t, 2H), 1.83 (s, 3H), 1.20 (d, 3H)

<실시예 91> (S)-[N-3-(4-(2-아세틸아미노아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 91 (S)-[N-3- (4- (2-acetylaminoacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acet Preparation of Amide

상기 실시예 79에서 제조한 (S)-[N-3-(4-(2-아미노아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드(50mg)를 메틸렌클로라이드(10ml)에 녹이고 무수아세트산(0.018ml)와 트리에틸아민(0.035ml)를 가한다. 실온에서 30분동안 교 반한 후 메틸렌 클로라이드를 가하고 소금물로 유기층을 세척한 후 탈수, 여과, 감압농축하고 컬럼크로마토그라피로 정제하여 표제화합물(15mg, 27%)을 얻었다. (S)-[N-3- (4- (2-aminoacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl prepared in Example 79 above. Acetamide (50 mg) is dissolved in methylene chloride (10 ml) and acetic anhydride (0.018 ml) and triethylamine (0.035 ml) are added. After stirring at room temperature for 30 minutes, methylene chloride was added, the organic layer was washed with brine, dehydrated, filtered, concentrated under reduced pressure, and purified by column chromatography to obtain the title compound (15 mg, 27%).

1H NMR(DMSO-d6) 10.60(s,1H), 8.49(s.1H), 8.20(m,3H), 7.99(m,1H), 7.64(m,2H), 7.43(dd,1H), 4.78(m,1H), 4.16(t,1H), 3.95(d,2H), 3.79(m,1H), 3.42(t,2H), 1.88(s,3H), 1.83(s,3H)
 1 H NMR (DMSO-d 6 ) 10.60 (s, 1H), 8.49 (s.1H), 8.20 (m, 3H), 7.99 (m, 1H), 7.64 (m, 2H), 7.43 (dd, 1H) , 4.78 (m, 1H), 4.16 (t, 1H), 3.95 (d, 2H), 3.79 (m, 1H), 3.42 (t, 2H), 1.88 (s, 3H), 1.83 (s, 3H)

<실시예 92> (S)-[N-3-(4-(2-디메틸아미노아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 92 (S)-[N-3- (4- (2-dimethylaminoacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acet Preparation of Amide

N,N-디메틸글리신(5.96g)을 피리딘 100ml에 녹이고 실온에서 2-아미노-5-부로모피리딘(5g), 1-(3-디메틸아미노프로필)-3-에틸카보디이미드 염산염(13.85g)및 4-디메틸아미노피리딘(7.06g)을 각각 가한 후 15시간동안 실온에서 교반하였다. 상기 반응 혼합물에 물을 가하고 에틸아세테이트로 추출한 후 유기층을 소금물로 세척하고 탈수, 여과 및 감압농축하여 2-(N,N-디메틸아미노아세틸아미노)-5-부로모피리딘(1.0g)을 얻었다. 위 화합물과 (S)-[N-3-(4-트리메틸스테닐-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드(1.34g)를 디메틸포름아마이드(14ml)에 녹이고 실온에서 트리에틸아민(0.68ml)과 디클로로비스트리페닐포스핀팔라디움(II) 0.68g을 각각 가한 후 4시간동안 100℃에서 교반하였다. 상기 반응 혼합물에 물을 가한 다음 에틸아세테이트로 추출하고 추출된 유기층은 소금물로 세척한 후 탈수, 여과 및 감압농축한 다음 컬럼크로마토그라피로 정제하여 표제화합물(430mg)을 얻 었다.N, N-dimethylglycine (5.96 g) was dissolved in 100 ml of pyridine and 2-amino-5-bromopyridine (5 g), 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (13.85 g) at room temperature ) And 4-dimethylaminopyridine (7.06 g) were added respectively, followed by stirring at room temperature for 15 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with brine, dehydrated, filtered and concentrated under reduced pressure to obtain 2- (N, N-dimethylaminoacetylamino) -5-bromopyridine (1.0 g). The above compound and (S)-[N-3- (4-trimethylstenyl-3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (1.34 g) were dimethylformamide (14 ml). It was dissolved in and triethylamine (0.68ml) and dichlorobistriphenylphosphinepalladium (II) 0.68g were added at room temperature, and the mixture was stirred at 100 ° C for 4 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The extracted organic layer was washed with brine, dehydrated, filtered and concentrated under reduced pressure, and then purified by column chromatography to obtain the title compound (430 mg).

1H NMR(DMSO-d6) 10.03(s,1H), 8.49(s,1H), 8.27(m,2H), 7.99(m,1H), 7.64(m,2H), 7.38(dd,1H), 4.78(m,1H), 4.16(t,1H), 3.79(dd,1H), 3.42(t,2H), 3.16(s,2H), 2.31(s,6H), 1.83(s,3H)
 1 H NMR (DMSO-d 6 ) 10.03 (s, 1H), 8.49 (s, 1H), 8.27 (m, 2H), 7.99 (m, 1H), 7.64 (m, 2H), 7.38 (dd, 1H) , 4.78 (m, 1H), 4.16 (t, 1H), 3.79 (dd, 1H), 3.42 (t, 2H), 3.16 (s, 2H), 2.31 (s, 6H), 1.83 (s, 3H)

<실시예 93> (S)-[N-3-(4-(2-니코티노일아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 93 (S)-[N-3- (4- (2-nicotinoylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acet Preparation of Amide

출발물질로 N,N-디메틸글리신 대신 니코틴산을 첨가하는 것을 제외하고 상기 실시예 92과 동일한 방법으로 표제 화합물을 얻었다The title compound was obtained in the same manner as in Example 92, except for adding nicotinic acid instead of N, N-dimethylglycine as starting material.

1H NMR(DMSO-d6) 11.21(s,1H), 9.15(d,1H), 8.77(dd,1H), 8.59(s,1H), 8.38(m,1H), 8.28(m,1H), 8.02(m,1H), 7.67(m,1H), 7.59(m,3H), 7.43(m,1H), 4.76(m,1H), 4.17(t,1H), 3.81(dd,1H), 3.42(t,2H), 1.83(s,3H)
 1 H NMR (DMSO-d 6 ) 11.21 (s, 1H), 9.15 (d, 1H), 8.77 (dd, 1H), 8.59 (s, 1H), 8.38 (m, 1H), 8.28 (m, 1H) , 8.02 (m, 1H), 7.67 (m, 1H), 7.59 (m, 3H), 7.43 (m, 1H), 4.76 (m, 1H), 4.17 (t, 1H), 3.81 (dd, 1H), 3.42 (t, 2H), 1.83 (s, 3H)

<실시예 94> (S)-[N-3-(4-(2-(1,2,4-트리아졸-1-일)피리딘-5-일)-3-플로로페닐) -2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 94 (S)-[N-3- (4- (2- (1,2,4-triazol-1-yl) pyridin-5-yl) -3-fluorophenyl) -2- Preparation of oxo-5-oxazolidinyl] methyl acetamide

2,5-디부로모피리딘(1g)과 1,2,4-트리아진 나트륨염(0.58g)을 디메틸포름아미드(20ml)에 녹이고 80℃에서 10시간 교반한다. 에틸아세테이트를 가하고 유기층을 소금물로 세척한 후 탈수, 여과, 감압농축하면 2-(1,2,4-트리아졸-1-일)-5-부로 모피리딘(880mg)을 얻을 수 있다. 위 화합물과 (S)-[N-3-(4-트리메틸스테닐-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드(1.4g)을 디메틸포름아마이드 50ml에 녹이고 실온에서 트리에틸아민(1.2ml) 및 디클로로비스트리페닐포스핀팔라디움(II) (1.1g)을 각각 가한 후 3시간동안 100℃에서 교반하였다. 상기 반응 혼합물에 물을 가하고 에틸아세테이트로 추출한 후 유기층을 소금물로 세척하고 탈수, 여과 및 감압농축한 후 컬럼크로마토그래피로 정제하여 표제 화합물(320mg, 23%)을 얻었다.2,5-dibromopyridine (1 g) and 1,2,4-triazine sodium salt (0.58 g) are dissolved in dimethylformamide (20 ml) and stirred at 80 ° C for 10 hours. Ethyl acetate was added, the organic layer was washed with brine, dehydrated, filtered, and concentrated under reduced pressure to obtain 2- (1,2,4-triazol-1-yl) -5- mofurridine (880 mg). Dissolve the above compound and (S)-[N-3- (4-trimethylstenyl-3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (1.4 g) in 50 ml of dimethylformamide. Triethylamine (1.2 ml) and dichlorobistriphenylphosphinepalladium (II) (1.1 g) were each added at room temperature and then stirred at 100 ° C. for 3 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with brine, dehydrated, filtered and concentrated under reduced pressure, and then purified by column chromatography to obtain the title compound (320 mg, 23%).

1H NMR(DMSO-d6) 9.41(s,1H), 8.72(s,1H), 8.33(s,1H), 8.25(m,2H), 7.96(d,1H), 7.72(m,2H), 7.47(dd,1H), 4.76(m,1H), 4.18(t,1H), 3.43(t,2H), 1.83(s,3H)
 1 H NMR (DMSO-d 6 ) 9.41 (s, 1H), 8.72 (s, 1H), 8.33 (s, 1H), 8.25 (m, 2H), 7.96 (d, 1H), 7.72 (m, 2H) , 7.47 (dd, 1H), 4.76 (m, 1H), 4.18 (t, 1H), 3.43 (t, 2H), 1.83 (s, 3H)

<실시예 95> (S)-[N-3-(4-(2-(4-히드록시피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 95 (S)-[N-3- (4- (2- (4-hydroxypiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo Preparation of -5-oxazolidinyl] methyl acetamide

상기 실시예 82에서 제조한 (S)-[N-3-(4-(2-(4-옥소피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드(300mg)를 에탄올과 테트라히드로퓨란 혼합용매에 녹이고 실온에서 소듐보로하이드라이드(106mg)을 가한 후 1시간 교반하다. 유기층을 감압농축하고 메탄올과 클로로포름, 에틸에테르를 사용하여 재결정으로 정제하여 표제 화합물(270mg, 90%)을 얻었다.(S)-[N-3- (4- (2- (4-oxopiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) prepared in Example 82 above. Oxo-5-oxazolidinyl] methyl acetamide (300 mg) is dissolved in a mixed solvent of ethanol and tetrahydrofuran, and sodium borohydride (106 mg) is added at room temperature, followed by stirring for 1 hour. The organic layer was concentrated under reduced pressure and purified by recrystallization using methanol, chloroform and ethyl ether to obtain the title compound (270 mg, 90%).

1H NMR(DMSO-d6) 8.27(m,2H), 7.70(m,1H), 7.52(m,2H), 7.34(m,1H), 6.90(d,1H), 4.76(m,1H), 4.69(d,1H), 4.17(t,1H), 4.07(m,2H), 3.79(m,2H), 3.42(t,2H), 3.12(m,2H), 1.83(s,3H), 1.75(m,2H), 1.41(m,2H)
 1 H NMR (DMSO-d 6 ) 8.27 (m, 2H), 7.70 (m, 1H), 7.52 (m, 2H), 7.34 (m, 1H), 6.90 (d, 1H), 4.76 (m, 1H) , 4.69 (d, 1H), 4.17 (t, 1H), 4.07 (m, 2H), 3.79 (m, 2H), 3.42 (t, 2H), 3.12 (m, 2H), 1.83 (s, 3H), 1.75 (m, 2H), 1.41 (m, 2H)

<실시예 96> (S)-[N-3-(4-(2-N,N-(히드록시아세틸)메틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 96 (S)-[N-3- (4- (2-N, N- (hydroxyacetyl) methylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5 -Oxazolidinyl] methyl acetamide

(S)-[N-3-(4-(2-N,N-(아세톡시아세틸)메틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드(470mg)를 메탄올과 클로로포름의 혼합용매에 녹이고 1N KOH 수용액(1.5ml)을 실온에서 가한 후 15분 교반한다. 감압농축한 후 에틸아세테이트를 가하고 유기층을 소금물로 세척한 후 탈수, 여과, 감압농축하고 컬럼크로마토그라피로 정제하여 표제화합물(64mg)을 얻었다.(S)-[N-3- (4- (2-N, N- (acetoxyacetyl) methylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] Methyl acetamide (470 mg) is dissolved in a mixed solvent of methanol and chloroform, and 1N aqueous KOH solution (1.5 ml) is added at room temperature, followed by stirring for 15 minutes. After concentration under reduced pressure, ethyl acetate was added, the organic layer was washed with brine, dehydrated, filtered, and concentrated under reduced pressure and purified by column chromatography to obtain the title compound (64 mg).

1H NMR(DMSO-d6) 8.61(s,1H), 8.26(t,1H), 8.06(m,1H), 7.62(m,3H), 7.47(dd,1H), 4.85(t,1H), 4.78(m,1H), 4.21(d,2H), 4.16(t,1H), 3.79(t,1H), 3.42(t,2H), 3.32(s.3H), 1.83(s,3H)
 1 H NMR (DMSO-d 6 ) 8.61 (s, 1H), 8.26 (t, 1H), 8.06 (m, 1H), 7.62 (m, 3H), 7.47 (dd, 1H), 4.85 (t, 1H) , 4.78 (m, 1H), 4.21 (d, 2H), 4.16 (t, 1H), 3.79 (t, 1H), 3.42 (t, 2H), 3.32 (s.3H), 1.83 (s, 3H)

<실시예 97> (S)-[N-3-(4-(2-(4-메틸이미다졸-1-일)피리딘-5-일)-3-플로로페닐) -2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 97 (S)-[N-3- (4- (2- (4-methylimidazol-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo- Preparation of 5-oxazolidinyl] methyl acetamide

출발물질로 1,2,4-트리아진 나트륨염 대신 4-메틸이미다졸을 첨가하는 것을 제외하고 상기 실시예 94과 동일한 방법으로 표제 화합물을 얻었다 The title compound was obtained in the same manner as in Example 94, except that 4-methylimidazole was added instead of 1,2,4-triazine sodium salt as a starting material.                     

1H NMR(DMSO-d6) 8.64(s,1H), 8.45(s,1H), 8.30(t,1H), 8.17(m,1H), 7.81(d,1H), 7.64(m,3H), 7.38(dd,1H), 4.78(m,1H), 4.16(t,1H), 3.79(m,1H), 3.42(t,2H), 2.18(s,3H), 1.83(s,3H)
 1 H NMR (DMSO-d 6 ) 8.64 (s, 1H), 8.45 (s, 1H), 8.30 (t, 1H), 8.17 (m, 1H), 7.81 (d, 1H), 7.64 (m, 3H) , 7.38 (dd, 1H), 4.78 (m, 1H), 4.16 (t, 1H), 3.79 (m, 1H), 3.42 (t, 2H), 2.18 (s, 3H), 1.83 (s, 3H)

<실시예 98> (S)-[N-3-(4-(2-(2-히드록시프로피오닐)아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 98 (S)-[N-3- (4- (2- (2-hydroxypropionyl) aminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxa Preparation of Zolidinyl] methyl Acetamide

출발물질로 (S)-[N-3-(4-(2-N,N-(아세톡시아세틸)메틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 대신 (S)-[N-3-(4-(2-(2-아세톡시프로피오닐)아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드을 첨가하는 것을 제외하고 상기 실시예 96과 동일한 방법으로 표제 화합물을 얻었다(S)-[N-3- (4- (2-N, N- (acetoxyacetyl) methylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxa as starting material (S)-[N-3- (4- (2- (2-acetoxypropionyl) aminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5 instead of zolidinyl] methyl acetamide The title compound was obtained in the same manner as in Example 96, except for adding -oxazolidinyl] methyl acetamide.

1H NMR(DMSO-d6) 9.73(s,1H), 8.50(s,1H), 8.26(t,1H), 8.16(d,1H), 8.03(d,1H), 7.63(m,2H), 7.40(dd,1H), 5.90(d,1H), 4.75(m,1H), 4.20(m,2H), 3.79(dd,1H), 3.43(t,2H), 1.82(s,3H), 1.31(d,3H)
 1 H NMR (DMSO-d 6 ) 9.73 (s, 1H), 8.50 (s, 1H), 8.26 (t, 1H), 8.16 (d, 1H), 8.03 (d, 1H), 7.63 (m, 2H) , 7.40 (dd, 1H), 5.90 (d, 1H), 4.75 (m, 1H), 4.20 (m, 2H), 3.79 (dd, 1H), 3.43 (t, 2H), 1.82 (s, 3H), 1.31 (d, 3H)

<실시예 99> (S)-[N-3-(4-(2-(3-아미노-1,2,4-트리아졸-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 99 (S)-[N-3- (4- (2- (3-amino-1, 2,4-triazol-1-yl) pyridin-5-yl) -3-fluorophenyl ) -2-oxo-5-oxazolidinyl] methyl acetamide

출발물질로 1,2,4-트리아진 나트륨염 대신 3-아미노-1,2,4-트리아진을 첨가 하는 것을 제외하고 상기 실시예 94과 동일한 방법으로 표제 화합물을 얻었다The title compound was obtained in the same manner as in Example 94, except that 3-amino-1,2,4-triazine was added instead of 1,2,4-triazine sodium salt as a starting material.

1H NMR(DMSO-d6) 8.64(s,1H), 8.24(m,2H), 7.83(d,1H), 7.61(m,5H), 7.43(dd,1H), 4.77(m,1H), 4.17(t,1H), 3.76(dd,1H), 3.42(t,2H), 1.82(s,3H)
 1 H NMR (DMSO-d 6 ) 8.64 (s, 1H), 8.24 (m, 2H), 7.83 (d, 1H), 7.61 (m, 5H), 7.43 (dd, 1H), 4.77 (m, 1H) , 4.17 (t, 1H), 3.76 (dd, 1H), 3.42 (t, 2H), 1.82 (s, 3H)

<실시예 100> (S)-[N-3-(4-(2-(4-에톡시카보닐이미다졸-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조Example 100 (S)-[N-3- (4- (2- (4-ethoxycarbonylimidazol-1-yl) pyridin-5-yl) -3-fluorophenyl) -2 -Oxo-5-oxazolidinyl] methyl acetamide

출발물질로 1,2,4-트리아진 나트륨염 대신 4-에톡시카보닐이미다졸을 첨가하는 것을 제외하고 상기 실시예 94과 동일한 방법으로 표제 화합물을 얻었다

The title compound was obtained in the same manner as in Example 94, except for adding 4-ethoxycarbonylimidazole instead of 1,2,4-triazine sodium salt as a starting material.

본 발명의 화학식 1의 화합물을 유효성분으로 하는 약학적 조성물은 비경구 및 경구로 투여될 수 있으며, 하기에 일례로 실시예 1의 화합물을 비경구용 제형으로 주사제, 경구용 제형으로 시럽제 및 정제로 제조하였다.
A pharmaceutical composition comprising the compound of formula 1 as an active ingredient of the present invention may be administered parenterally and orally. For example, the compound of Example 1 may be used as a parenteral formulation as an injection, oral formulation as a syrup and a tablet. Prepared.

<제제예 1> 주사액제의 제조방법Preparation Example 1 Preparation of Injection Solution

유효성분 10 mg을 함유하는 주사액제는 다음과 같은 방법으로 제조하였다. Injection solution containing 10 mg of the active ingredient was prepared by the following method.

실시예 1의 화합물 1 g, 염화나트륨 0.6 g 및 아스코르브산 0.1 g을 증류수에 용해시켜서 100 ㎖을 만들었다. 이 용액을 병에 넣고 20℃에서 30 분간 가열하여 멸균시켰다. 1 g of the compound of Example 1, 0.6 g of sodium chloride and 0.1 g of ascorbic acid were dissolved in distilled water to make 100 ml. The solution was bottled and sterilized by heating at 20 ° C. for 30 minutes.                     

상기 주사액제의 구성성분은 다음과 같다.
The components of the injection solution are as follows.

실시예 1의 화합물················1 gCompound of Example 1 ... 1 g

염화나트륨···················0.6 gSodium Chloride ・ ・ ・ ・ 0.6 g

아스코르브산··················0.1 g0.1 g of ascorbic acid

증류수·····················정량
Distilled water ··················

<제제예 2> 시럽제의 제조방법Preparation Example 2 Preparation of Syrup

본 발명의 화합물의 산부가염 및 약학적으로 허용되는 그의 염을 유효성분 2%(중량/부피)로 함유하는 시럽은 다음과 같은 방법으로 제조한다. Syrups containing an acid addition salt of the compound of the present invention and a pharmaceutically acceptable salt thereof as an active ingredient of 2% (weight / volume) are prepared by the following method.

실시예 1의 화합물의 산부가염, 사카린, 당을 온수 80 g에 용해시켰다. 이 용액을 냉각시킨 후, 여기에 글리세린, 사카린, 향미료, 에탄올, 소르브산 및 증류수로 이루어진 용액을 제조하여 혼합하였다. 이 혼합물에 물을 첨가하여 100 ㎖가 되게 하였다.
Acid addition salt, saccharin and sugar of the compound of Example 1 were dissolved in 80 g of warm water. After the solution was cooled, a solution consisting of glycerin, saccharin, spices, ethanol, sorbic acid and distilled water was prepared and mixed thereto. Water was added to this mixture to 100 ml.

상기 시럽제의 구성성분은 다음과 같다.The components of the syrup are as follows.

실시예 1의 화합물의 산부가염············ 2 gAcid addition salts of the compound of Example 1 2 g

사카린 ····· ·················0.8 gSaccharin: 0.8 g ················

당 ························ 25.4 g25.4 g of sugar

글리세린······················ 8.0 g Glycerin ... 8.0 g                     

향미료 ······················ 0.04 gSpices ··················· 0.04 g

에탄올 ·······················4.0 gEthanol 4.0 g

소르브산 ······················0.4 g0.4 g of sorbic acid

증류수 ·······················정량
Distilled water ···················

<제제예 3> 정제의 제조방법Preparation Example 3 Manufacturing Method

유효성분 15 mg이 함유된 정제는 다음과 같은 방법으로 제조한다.A tablet containing 15 mg of active ingredient is prepared by the following method.

실시예 1의 화합물 250 g을 락토오스 175.9 g, 감자전분 180 g 및 콜로이드성 규산 32 g과 혼합하였다. 이 혼합물에 10% 젤라틴 용액을 첨가시킨 후, 분쇄해서 14 메쉬체를 통과시켰다. 이것을 건조시키고 여기에 감자전분 160 g, 활석 50 g 및 스테아린산 마그네슘 5 g을 첨가해서 얻은 혼합물을 정제로 만들었다.
250 g of the compound of Example 1 were mixed with 175.9 g of lactose, 180 g of potato starch and 32 g of colloidal silicic acid. 10% gelatin solution was added to the mixture, which was then ground and passed through a 14 mesh sieve. It was dried and the mixture obtained by adding 160 g of potato starch, 50 g of talc and 5 g of magnesium stearate was made into a tablet.

상기 정제의 구성성분은 다음과 같다. The components of the tablet are as follows.

실시예 1의 화합물··············· 250 gCompound of Example 1 ... 250 g

락토오스 ···················175.9 gLactose ···················· 175.9 g

감자전분 ····················180 gPotato starch ·············· 180 g

콜로이드성 규산 ················ 32 gColloidal silicic acid 32 g

10% 젤라틴 용액10% gelatin solution

감자전분 ····················160 gPotato starch · 160 g

활석 ······················ 50 g Talc · 50 g                     

스테아르산 마그네슘 ··············· 5
Magnesium stearate ·········· 5

<실험예 1> 시험관내 항균활성 측정Experimental Example 1 Measurement of In Vitro Antimicrobial Activity

본 발명에 의한 화합물의 항균력을 알아보기 위하여, 문헌에 기재된 한천희석법(agar dilution)을 이용하여 메티실린에 내성을 가지는 스타필로코커스 아우레우스 (MRSA, methicillin resistant Staphylococcus aureus)와 반코마이신에 내성을 가지는 엔테로코카이 (VRE, vancomycin resistant Enterococci)에 대한 항균력을 최소 발육저지 농도 (MIC, ㎍/㎖)로 나타내었으며 이때 화학식 3의 U-100766 화합물을 대조물질로 하여 항균 활성을 비교하였다(Chemotheraphy, 29(1), 76, (1981)). 그 결과는 하기 표 2에 나타낸 바와 같다. In order to examine the antimicrobial activity of the compounds according to the present invention, agar dilution described in the literature is resistant to methicillin and methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant The antimicrobial activity against enterocokai (VRE, vancomycin resistant Enterococci ) was expressed as the minimum growth inhibitory concentration (MIC, μg / ml), and the antimicrobial activity was compared with U-100766 compound of formula 3 as a control ( Chemotheraphy , 29 ( 1), 76, ( 1981 )). The results are as shown in Table 2 below.

<표 2>TABLE 2

화합물compound 항균력 (MIC50, μg/ml)Antimicrobial Activity (MIC 50 , μg / ml) 화합물compound 항균력 (MIC50, μg/ml)Antimicrobial Activity (MIC 50 , μg / ml) MRSAMRSA VREVRE MRSAMRSA VREVRE U-100766U-100766 3.133.13 1.561.56 1One 1.561.56 0.780.78 2121 0.390.39 0.20.2 22 0.780.78 0.20.2 2222 0.780.78 NANA 33 1.561.56 0.390.39 2323 0.780.78 NANA 44 0.780.78 0.20.2 2424 3.133.13 1.561.56 55 0.780.78 0.20.2 2525 12.512.5 3.133.13 66 0.390.39 0.10.1 2626 0.780.78 0.390.39 77 0.780.78 0.20.2 2727 1.561.56 0.780.78 88 1.561.56 0.390.39 2828 1.561.56 0.780.78 99 1.561.56 0.20.2 2929 1.561.56 0.390.39 1010 0.390.39 0.20.2 3030 >25> 25 12.512.5 1111 0.780.78 0.20.2 3131 3.133.13 0.780.78 1212 1.561.56 0.20.2 3232 1.561.56 0.780.78 1313 0.780.78 0.780.78 3333 >100> 100 6.256.25 1414 0.780.78 0.780.78 3434 0.780.78 0.390.39 1515 1.561.56 0.390.39 3535 0.780.78 0.390.39 1616 1.561.56 0.390.39 3636 0.780.78 0.390.39 1717 6.256.25 0.780.78 3737 1.561.56 0.780.78 1818 3.133.13 0.20.2 3838 1.561.56 0.390.39 1919 0.780.78 NANA 3939 3.133.13 0.780.78 2020 0.390.39 0.20.2 4040 1.561.56 0.390.39 NA : 측정안함 (Not determined) MRSA: 메티실린에 내성을 가지는 스타필로코커스 아우레우스 (methicillin resistantStaphylococcus aureus) VRE : 반코마이신에 내성을 가지는 엔테로코카이 (vancomycin resistantEnterococci) NA: Not determined MRSA: methicillin resistant Staphylococcus aureus VRE: vancomycin resistant Enterococci resistant to vancomycin

화합물compound 항균력 (MIC50, μg/ml)Antimicrobial Activity (MIC 50 , μg / ml) 화합물compound 항균력 (MIC50, μg/ml)Antimicrobial Activity (MIC 50 , μg / ml) MRSAMRSA VREVRE MRSAMRSA VREVRE 3.133.13 1.561.56 U-100766U-100766 4141 1.561.56 0.780.78 7171 12.512.5 6.256.25 4242 0.780.78 0.390.39 7272 1.561.56 0.780.78 4343 12.512.5 1.561.56 7373 1.561.56 0.390.39 4444 6.256.25 1.561.56 7474 1.561.56 0.780.78 4545 3.133.13 0.780.78 7575 3.133.13 0.780.78 4646 6.256.25 3.133.13 7676 3.133.13 0.780.78 4747 0.780.78 0.780.78 7777 6.256.25 1.561.56 4848 1.561.56 0.780.78 7878 0.780.78 0.390.39 4949 3.133.13 1.561.56 7979 0.780.78 0.20.2 5050 3.133.13 1.561.56 8080 0.780.78 0.20.2 5151 3.133.13 1.561.56 8181 1.561.56 0.20.2 5252 6.256.25 1.561.56 8282 0.780.78 0.390.39 5353 3.133.13 0.780.78 8383 0.20.2 0.20.2 5454 6.256.25 3.133.13 8484 0.390.39 0.20.2 5555 6.256.25 1.561.56 8585 0.390.39 0.20.2 5656 6.256.25 1.561.56 8686 0.780.78 0.390.39 5757 6.256.25 3.133.13 8787 1.561.56 0.390.39 5858 >25> 25 12.512.5 8888 0.780.78 0.20.2 5959 3.133.13 0.780.78 8989 0.780.78 0.390.39 6060 1.561.56 0.390.39 9090 0.780.78 0.20.2 6161 >25> 25 3.133.13 9191 1.561.56 0.780.78 6262 3.133.13 1.561.56 9292 0.780.78 0.390.39 6363 >25> 25 2525 9393 0.780.78 0.20.2 6464 3.133.13 1.561.56 9494 0.780.78 0.20.2 6565 3.133.13 0.390.39 9595 1.561.56 0.780.78 6666 >25> 25 2525 9696 1.561.56 0.390.39 6767 >25> 25 >25> 25 9797 1.561.56 0.390.39 6868 >25> 25 >25> 25 9898 0.780.78 0.20.2 6969 1.561.56 0.780.78 9999 1.561.56 0.390.39 7070 3.133.13 1.561.56 100100 12.512.5 0.780.78 NA : 측정안함 (Not determined) MRSA: 메티실린에 내성을 가지는 스타필로코커스 아우레우스 (methicillin resistantStaphylococcus aureus) VRE : 반코마이신에 내성을 가지는 엔테로코카이 (vancomycin resistantEnterococci) NA: Not determined MRSA: methicillin resistant Staphylococcus aureus VRE: vancomycin resistant Enterococci resistant to vancomycin

상기 표 2에서 볼 수 있듯이, 본 발명의 화합물들이 미국 식품의약품국의 허가를 얻은 화학식 3의 U-100766 화합물에 비하여 훨씬 낮은 농도에서 기존 항생제에 내성을 갖는 스타틸로코커스와 엔테로코카이에 대해 강한 항균력을 보임을 알 수 있었다.
As can be seen in Table 2 , the compounds of the present invention are resistant to staphylococcus and enterocokai that are resistant to conventional antibiotics at much lower concentrations than the U-100766 compound of Formula 3, which is licensed by the US Food and Drug Administration. It can be seen that the antimicrobial activity.

<실험예 2> 마우스에 대한 경구투여 급성독성 실험 Experimental Example 2 Oral Acute Toxicity in Mice

본 발명에 의한 화합물의 급성 독성을 알아보기 위하여 하기와 같은 실험을 수행하였다. 실시예 6, 10, 20, 21, 79, 94, 95 및 97의 화합물 각각 200mg을 1%의 히드록시프로필메틸셀룰로스 배산체를 조제하여 5주령의 웅성 ICR계 마우스(20g ± 2g) 5마리에 1g/10ml/kg으로 경구투여하고 2주간 사망율, 체중, 임상증상 등을 관찰하여 최소치사량(MLD, mg/kg)을 조사하였다. 그 결과는 하기 표 3에 나타내었다.In order to determine the acute toxicity of the compound according to the present invention was carried out the following experiment. 200 mg of each of the compounds of Examples 6, 10, 20, 21, 79, 94, 95, and 97 were prepared with 1% hydroxypropylmethylcellulose embryoids, and 5 male ICR mice (20 g ± 2 g) at 5 weeks of age were prepared. The minimum lethal dose (MLD, mg / kg) was investigated by oral administration at 1g / 10ml / kg and observation of mortality, body weight, and clinical symptoms for 2 weeks. The results are shown in Table 3 below.

<표 3>TABLE 3

화합물compound 최소치사량(MLD, mg/kg)Minimum lethal dose (MLD, mg / kg) U-100766U-100766 > 1000> 1000 실시예 6Example 6 > 1000> 1000 실시예 10Example 10 > 1000> 1000 실시예 20Example 20 > 1000> 1000 실시예 21Example 21 > 1000> 1000 실시예 79Example 79 > 1000> 1000 실시예 94Example 94 > 1000> 1000 실시예 95Example 95 > 1000> 1000 실시예 97Example 97 > 1000> 1000

경구투여 급성독성시험 결과, 상기 조제한 본 발명에 의한 시험 물질을 투여한 모든 마우스에서 특기할만한 임상증상은 없었고 폐사된 동물도 없었으며, 또한 체중변화, 혈액검사, 혈액생화학검사, 부검소견 등에서도 독성변화는 관찰되지 않았다. 상기 표 3에서 볼 수 있듯이, 화학식 1로 표시되는 본 발명의 화합물들은 항균효과가 뛰어날 뿐만 아니라 경구투여 최소치사량이 1g/kg 이상으로 안전한 물질로 판단되었다.
As a result of oral acute toxicity test, all mice administered the test substance according to the present invention had no clinical symptoms and no dead animals, and also toxicity in weight change, blood test, blood biochemical test, autopsy findings, etc. No change was observed. As can be seen in Table 3 , the compounds of the present invention represented by the formula (1) was not only excellent in the antimicrobial effect but also determined to be a safe substance with a minimum lethal dose of 1 g / kg or more.

이상에서 살펴본 바와 같이, 본 발명의 화학식 1로 표시되는 옥사졸리디논 화합물들은 항균 스펙트럼이 넓을 뿐만 아니라 기존 항생제에 내성을 가지는 스타필로코카이, 엔테로코카이, 스트렙토코카이와 같은 그람양성 호기성 박테리아 뿐만 아니라, 박테로이데스 종, 클로스티리디아 종과 같은 혐기성 생물과 마이코박테리움 투메르쿨로시스, 마이코 박테리움 아비움 등의 마아코 박테리움 종과 같은 항산성 미생물들을 포함하여 각종 사람 및 동물 병원균에 우수한 항균 효과를 나타내고 독성이 낮아 본 발명의 옥사졸리디논 화합물들은 항생제로 유용하게 사용될 수 있다.As described above, the oxazolidinone compounds represented by Chemical Formula 1 of the present invention not only have a broad antibacterial spectrum but also have resistance to conventional antibiotics, as well as Gram-positive aerobic bacteria such as Staphylocokai, Enterocokai, and Streptocokai, Excellent antimicrobial against a variety of human and animal pathogens, including anaerobic organisms such as the Teroides species and Clostridia species, and anti-acidic microorganisms such as the Mako bacterium species such as Mycobacterium Tumerculosis and Mycobacterium avium The oxazolidinone compounds of the present invention can be usefully used as antibiotics because of their low toxicity and low toxicity.

Claims (4)

하기 화학식 1로 표시되는 피리딘 고리를 포함하는 옥사졸리디논(oxazolidinone) 유도체 및 약학적으로 허용되는 그의 염.An oxazolidinone derivative including a pyridine ring represented by the following formula (1) and a pharmaceutically acceptable salt thereof. 화학식 1Formula 1
Figure 112007008478503-pat00015
Figure 112007008478503-pat00015
 상기 화학식 1에서,In Chemical Formula 1, R1은 수소 또는 불소이고,R 1 is hydrogen or fluorine, R2는 아지도;
Figure 112007008478503-pat00019
; -NR4R5; -(CH2)m-R6; -OR7; 또는 R8 및 R9이 치환된 헤테로고리이고 (이때, l은 1 내지 2의 정수이고, m은 1 내지 4의 정수이다.),R 2 is azido;
Figure 112007008478503-pat00019
; -NR 4 R 5 ; -(CH 2 ) m -R 6 ; -OR 7 ; or R 8 and R 9 are substituted heterocycles, where l is an integer from 1 to 2 and m is an integer from 1 to 4, R3은 수소, C1∼C3의 알콕시, 아미노, C1∼C3의 알킬아미노 또는 C1∼C3의 히드록시알킬아미노기이고,R 3 is hydrogen, C 1 -C 3 alkoxy, amino, C 1 -C 3 alkylamino or C 1 -C 3 hydroxyalkylamino group, R4와 R5는 서로 같거나 또는 다르며,R 4 and R 5 are the same as or different from each other, (a) 수소, (a) hydrogen, (b) 하나 또는 그 이상의 페닐기로 치환된 또는 치환되지 않은 알킬기(C1∼C4), C1∼C3의 알킬아미노기로 치환된 알케닐기(C1∼C4),(b) one or or unsubstituted alkyl group substituted by a further phenyl group (C 1 ~C 4), an alkenyl group (C 1 ~C 4) alkyl substituted by an amino group of the C 1 ~C 3, (c) 치환 또는 치환되지않은 아세틸기 (이때, 치환된 아세틸기는 아세톡시아세틸, 히드록시아세틸, C1∼C3의 알킬아미노아세톡시아세틸, C1∼C3의 알콕시아세틸, 아미노아세틸, 아지도아세틸, 아세틸아미노아세틸, C1∼C3의 알킬아미노아세틸, 아미노프로피오닐 또는 히드록시프로피오닐기이다.),(c) an acetyl group (where the substituted acetyl group is unsubstituted or substituted acetoxy, acetyl, hydroxy, acetyl, alkoxy, acetyl, amino acetyl in C 1 ~C 3 alkyl-amino-acetoxy acetyl, C 1 ~C 3 a, ah map acetyl, acetylamino, acetyl, alkyl, amino, acetyl, propionyl amino or hydroxy propionyl group of the C 1 ~C 3.), 또는 (d) 니코티노일기이고,Or (d) a nicotinoyl group, R6은 수소; 아지도; 히드록시; C1∼C3의 알킬아미노아세톡시; 아세틸싸이오; 머캅토; 시아노; 할로겐 원소; 또는 5원 또는 6원 헤테로고리이고,R 6 is hydrogen; Azido; Hydroxy; Alkylamino acetoxy of C 1 ~C 3; Acetylthio; Mercapto; Cyano; Halogen element; Or 5- or 6-membered heterocycle, R7은 수소, C1∼C3의 알킬, 아세틸, 알콕시알킬 또는 메탄술포닐기이고,R 7 is hydrogen, C 1 -C 3 alkyl, acetyl, alkoxyalkyl or methanesulfonyl group, R8 및 R9는 서로 같거나 다르고,R 8 and R 9 are the same as or different from each other, (a) 수소; (a) hydrogen; (b) 치환 또는 치환되지 않은 알킬(이때, 치환된 알킬기는 히드록시알킬, 알콕시카보닐알킬, 트리페닐알킬, 아세톡시알킬 또는 메탄술포닐옥시알킬기이다); (b) substituted or unsubstituted alkyl, wherein the substituted alkyl group is a hydroxyalkyl, alkoxycarbonylalkyl, triphenylalkyl, acetoxyalkyl or methanesulfonyloxyalkyl group; (c)
Figure 112007008478503-pat00020
;(c)
Figure 112007008478503-pat00020
; (d) 아미노; 치환 또는 치환되지 않은 이미노(이때, 치환된 이미노기는 히드록시이미노, 알킬이미노 또는 메탄술포닐옥시이미노기이다.); 또는 알콕시카보닐기로 치환 또는 치환되지 않은 히드라지노;(d) amino; Substituted or unsubstituted imino, wherein the substituted imino group is a hydroxyimino, alkylimino or methanesulfonyloxyimino group; Or hydrazino unsubstituted or substituted with an alkoxycarbonyl group; (e) 히드록시; 시아노기; 또는(e) hydroxy; Cyano group; or (f) 5원 또는 6원 헤테로고리이고,(f) a 5 or 6 membered heterocycle, R10은 (a) C1∼C6의 알킬, C1∼C3의 알킬기로 치환 또는 치환되지않은 알케닐 ,R 10 is (a) C 1 -C 6 alkyl, C 1 -C 3 alkyl group unsubstituted or substituted with alkenyl, (b) 알콕시카보닐,(b) alkoxycarbonyl, (c) 아세톡시메틸, 벤질옥시메틸, 히드록시메틸, C1∼C3의 알킬아미노아세톡시메틸, 할로메틸, C1∼C3의 알콕시메틸, 몰포리닐메틸, C1∼C3의 알콕시카보닐메틸아미노메틸, 메탄술포닐옥시메틸, C1∼C3의 알콕시옥소메틸, 니코티노일옥시메틸, C1∼C3의 알콕시페닐메틸, 벤질, 트리할로메틸, (c) of the acetoxymethyl, benzyloxy-methyl, hydroxymethyl, C 1 ~C 3 alkyl amino acetoxymethyl, halomethyl, C 1 ~C 3 alkoxy-methyl, morpholinyl-methyl, C 1 ~C 3 alkoxycarbonyl methylaminomethyl, methanesulfonyloxy methyl, C 1 ~C 3 alkoxy-oxo-methyl, nicotinoyl-oxy-methyl, methyl-alkoxyphenyl, benzyl, trihalomethyl of the C 1 ~C 3, (d) C1∼C3의 알콕시, 페닐옥시, 알릴옥시, C1∼C3의 할로알킬옥시; 니트로기로 치환 또는 치환되지않은 벤질옥시 또는 9-플루오레닐메틸옥시,(d) C 1 -C 3 alkoxy, phenyloxy, allyloxy, C 1 -C 3 haloalkyloxy; Benzyloxy or 9-fluorenylmethyloxy, unsubstituted or substituted with a nitro group, (e) 니코티노일메틸기, 또는(e) nicotinoylmethyl groups, or (f) 5원 또는 6원 헤테로고리이다.(f) 5- or 6-membered heterocycles. 제 1항에 있어서, 화학식 1로 표시되는 피리딘 고리를 포함하는 옥사졸리디논 유도체는 The oxazolidinone derivative of claim 1, wherein the oxazolidinone derivative includes a pyridine ring represented by Chemical Formula 1. (S)-[N-3-(4-(2-아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 2의 화합물),(S)-[N-3- (4- (2-aminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (compound of Example 2) , (S)-[N-3-(4-(3-메톡시카르보닐피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 3의 화합물),(S)-[N-3- (4- (3-methoxycarbonylpyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 3 Compound), (S)-[N-3-(4-(2-아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 4의 화합물),(S)-[N-3- (4- (2-acetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Compound of Example 4 ), (S)-[N-3-(4-(2-아세톡시아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소 -5-옥사졸리딘일]메틸 아세트아마이드 (실시예 5의 화합물),(S)-[N-3- (4- (2-acetoxyacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 5 Compound), (S)-[N-3-(4-(2-히드록시아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소 -5-옥사졸리딘일]메틸 아세트아마이드 (실시예 6의 화합물),(S)-[N-3- (4- (2-hydroxyacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 6 Compound), (S)-[N-3-(4-(2-이미다졸-1-일-피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 7의 화합물),(S)-[N-3- (4- (2-imidazol-1-yl-pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide ( Compound of Example 7), (S)-[N-3-(4-(2-몰포린-4-일-피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 8의 화합물),(S)-[N-3- (4- (2-morpholin-4-yl-pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide ( Compound of Example 8), (S)-[N-3-(4-(2-트리페닐메틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 9의 화합물),(S)-[N-3- (4- (2-triphenylmethylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 9 Compound), (S)-[N-3-(4-(2-메톡시피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 10의 화합물),(S)-[N-3- (4- (2-methoxypyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Compound of Example 10 ), (S)-[N-3-(4-(2-메톡시아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드의 제조 (실시예 11의 화합물),Preparation of (S)-[N-3- (4- (2-methoxyacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide Compound of Example 11), (S)-[N-3-(4-(2-(4-트리페닐메틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 12의 화합물),(S)-[N-3- (4- (2- (4-triphenylmethylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazoli Dinyl] methyl acetamide (compound of Example 12), (S)-[N-3-(4-(2-트리페닐메틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 염산염 (실시예 13의 화합물),(S)-[N-3- (4- (2-triphenylmethylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide hydrochloride (Example 13 compounds), (S)-[N-3-(4-(2-아지도피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 14의 화합물),(S)-[N-3- (4- (2-azidopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Compound of Example 14 ), (S)-[N-3-(4-(2-히드록시메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 15의 화합물),(S)-[N-3- (4- (2-hydroxymethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (from Example 15 compound), (S)-[N-3-(4-(2-메톡시카보닐피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 16의 화합물),(S)-[N-3- (4- (2-methoxycarbonylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 16 Compound), (S)-[N-3-(4-(2-디메틸아미노카보닐피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 17의 화합물),(S)-[N-3- (4- (2-dimethylaminocarbonylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 17 Compound), (S)-[N-3-(4-(2-히드록시피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 18의 화합물),(S)-[N-3- (4- (2-hydroxypyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Compound of Example 18 ), (S)-[N-3-(4-(N-2-디메틸아미노아세톡시아세틸아미노피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 19의 화합물),(S)-[N-3- (4- (N-2-dimethylaminoacetoxyacetylaminopyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Compound of Example 19), (S)-[N-3-(4-(2-메틸아미노피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 20의 화합물),(S)-[N-3- (4- (2-methylaminopyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Compound of Example 20 ), (S)-[N-3-(4-(2-디메틸아미노피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 21의 화합물),(S)-[N-3- (4- (2-dimethylaminopyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Compound of Example 21 ), (S)-[N-3-(4-(2-히드록시아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 염산염 (실시예 22의 화합물),(S)-[N-3- (4- (2-hydroxyacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide hydrochloride (Example 22 compounds), (S)-[N-3-(4-(2-히드록시아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 히드록시프로필메틸셀룰로스 (HPMC, hydroxypropylmethylcellulose) 배산체 (실시예 23의 화합물),(S)-[N-3- (4- (2-hydroxyacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide hydroxypropylmethyl Cellulose (HPMC, hydroxypropylmethylcellulose) dispersion (compound of Example 23), (S)-[N-3-(4-(2-아세톡시피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 24의 화합물),(S)-[N-3- (4- (2-acetoxypyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Compound of Example 24 ), (S)-[N-3-(4-(2-메탄술포닐옥시피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 26의 화합물),(S)-[N-3- (4- (2-methanesulfonyloxypyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 26 Compound), (S)-[N-3-(4-(2-아미노카보닐피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 27의 화합물),(S)-[N-3- (4- (2-aminocarbonylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (from Example 27 compound), (S)-[N-3-(4-(2-디메틸아미노아세톡시메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 28의 화합물),(S)-[N-3- (4- (2-dimethylaminoacetoxymethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 28 compounds), (S)-[N-3-(4-(2-(2-히드록시에틸)아미노카보닐피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 29의 화합물),(S)-[N-3- (4- (2- (2-hydroxyethyl) aminocarbonylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl Acetamide (compound of Example 29), (S)-[N-3-(4-(2-피페라진-1-일피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 31의 화합물),(S)-[N-3- (4- (2-piperazin-1-ylpyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (implemented Compound of Example 31), (S)-[N-3-(4-(2-(4-아세톡시아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 32의 화합물),(S)-[N-3- (4- (2- (4-acetoxyacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazoli Dinyl] methyl acetamide (compound of Example 32), (S)-[N-3-(4-(2-(4-히드록시아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 34의 화합물),(S)-[N-3- (4- (2- (4-hydroxyacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazoli Dinyl] methyl acetamide (compound of Example 34), (S)-[N-3-(4-(2-(4-디메틸아미노아세톡시아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 35의 화합물),(S)-[N-3- (4- (2- (4-dimethylaminoacetoxyacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5- Oxazolidinyl] methyl acetamide (compound of Example 35), (S)-[N-3-(4-(2-(4-클로로아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 36의 화합물),(S)-[N-3- (4- (2- (4-chloroacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl ] Methyl acetamide (compound of Example 36), (S)-[N-3-(4-(2-(4-아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 37의 화합물),(S)-[N-3- (4- (2- (4-acetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] Methyl acetamide (compound of Example 37), (S)-[N-3-(4-(2-(4-메톡시아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 38의 화합물),(S)-[N-3- (4- (2- (4-methoxyacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazoli Dinyl] methyl acetamide (compound of Example 38), (S)-[N-3-(4-(2-(4-몰포리닐아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 39의 화합물),(S)-[N-3- (4- (2- (4-morpholinylacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxa Zolidinyl] methyl acetamide (compound of Example 39), (S)-[N-3-(4-(2-(4-메톡시카보닐메틸아미노아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 40의 화합물),(S)-[N-3- (4- (2- (4-methoxycarbonylmethylaminoacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo- 5-oxazolidinyl] methyl acetamide (compound of Example 40), (S)-[N-3-(4-(2-(4-에톡시카보닐피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 41의 화합물),(S)-[N-3- (4- (2- (4-ethoxycarbonylpiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxa Zolidinyl] methyl acetamide (compound of Example 41), (S)-[N-3-(4-(2-아지도메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 42의 화합물),(S)-[N-3- (4- (2-azidomethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (from Example 42 compound), (S)-[N-3-(4-(2-아세틸싸이오메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 45의 화합물),(S)-[N-3- (4- (2-acetylthiomethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 45 Compound), (S)-[N-3-(4-(2-머캅토메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 46의 화합물),(S)-[N-3- (4- (2-mercaptomethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (from Example 46 compound), (S)-[N-3-(4-(2-(4-메탄술포닐옥시아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 47의 화합물),(S)-[N-3- (4- (2- (4-methanesulfonyloxyacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5- Oxazolidinyl] methyl acetamide (compound of Example 47), (S)-[N-3-(4-(2-(4-아크릴로일피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 48의 화합물),(S)-[N-3- (4- (2- (4-acryloylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazoli Dinyl] methyl acetamide (compound of Example 48), (S)-[N-3-(4-(2-(4-에톡시옥소아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 49의 화합물),(S)-[N-3- (4- (2- (4-ethoxyoxoacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxa Zolidinyl] methyl acetamide (compound of Example 49), (S)-[N-3-(4-(2-(4-니코티노일피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 50의 화합물),(S)-[N-3- (4- (2- (4-nicotinoylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazoli Dinyl] methyl acetamide (compound of Example 50), (S)-[N-3-(4-(2-(4-피발로일피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 51의 화합물),(S)-[N-3- (4- (2- (4-pivaloylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazoli Dinyl] methyl acetamide (compound of Example 51), (S)-[N-3-(4-(2-(4-니코티노일옥시아세틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 53의 화합물),(S)-[N-3- (4- (2- (4-nicotinoyloxyacetylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5- Oxazolidinyl] methyl acetamide (compound of Example 53), (S)-[N-3-(4-(2-(4-벤질카보닐피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 59의 화합물),(S)-[N-3- (4- (2- (4-benzylcarbonylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazoli Dinyl] methyl acetamide (compound of Example 59), (S)-[N-3-(4-(2-(4-크로토닐피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 60의 화합물),(S)-[N-3- (4- (2- (4-crotonylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl ] Methyl acetamide (compound of Example 60), (S)-[N-3-(4-(2-(4-n-발레릴피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 62의 화합물),(S)-[N-3- (4- (2- (4-n- valerylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxa Zolidinyl] methyl acetamide (compound of Example 62), (S)-[N-3-(4-(2-(4-알릴옥시카보닐피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 64의 화합물),(S)-[N-3- (4- (2- (4-allyloxycarbonylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxa Zolidinyl] methyl acetamide (compound of Example 64), (S)-[N-3-(4-(2-(4-(1-클로로에틸)옥시카보닐피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 65의 화합물),(S)-[N-3- (4- (2- (4- (1-chloroethyl) oxycarbonylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2- Oxo-5-oxazolidinyl] methyl acetamide (compound of Example 65), (S)-[N-3-(4-(2-(4-(2-피리미디닐)피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 69의 화합물),(S)-[N-3- (4- (2- (4- (2-pyrimidinyl) piperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo- 5-oxazolidinyl] methyl acetamide (compound of Example 69), (S)-[N-3-(4-(2-(4-메톡시카보닐메틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 70의 화합물),(S)-[N-3- (4- (2- (4-methoxycarbonylmethylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5- Oxazolidinyl] methyl acetamide (compound of Example 70), (S)-[N-3-(4-(2-시아노메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 72의 화합물),(S)-[N-3- (4- (2-cyanomethylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (from Example 72 compound), (S)-[N-3-(4-(2-메틸피리딘-4-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 73의 화합물),(S)-[N-3- (4- (2-methylpyridin-4-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Compound of Example 73) , (S)-[N-3-(4-(2-(4-(2-히드록시)에틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 74의 화합물),(S)-[N-3- (4- (2- (4- (2-hydroxy) ethylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo- 5-oxazolidinyl] methyl acetamide (compound of Example 74), (S)-[N-3-(4-(2-(4-(2-아세톡시)에틸피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 75의 화합물),(S)-[N-3- (4- (2- (4- (2-acetoxy) ethylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo- 5-oxazolidinyl] methyl acetamide (compound of Example 75), (S)-[N-3-(4-(2-(4-메톡시카보닐피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 76의 화합물),(S)-[N-3- (4- (2- (4-methoxycarbonylpiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxa Zolidinyl] methyl acetamide (compound of Example 76), (S)-[N-3-(4-(2-(4-히드록시메틸이미다졸-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 78의 화합물),(S)-[N-3- (4- (2- (4-hydroxymethylimidazol-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxa Zolidinyl] methyl acetamide (compound of Example 78), (S)-[N-3-(4-(2-아미노아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 79의 화합물),(S)-[N-3- (4- (2-aminoacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (from Example 79 compound), (S)-[N-3-(4-(2-(4-시아노피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 80의 화합물),(S)-[N-3- (4- (2- (4-cyanopiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl ] Methyl acetamide (compound of Example 80), (S)-[N-3-(4-(2-(4-카르복스아마이드옥심피페라진-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 81의 화합물),(S)-[N-3- (4- (2- (4-carboxamide oximepiperazin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxa Zolidinyl] methyl acetamide (compound of Example 81), (S)-[N-3-(4-(2-(4-옥소피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 82의 화합물),(S)-[N-3- (4- (2- (4-oxopiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl ] Methyl acetamide (compound of Example 82), (S)-[N-3-(4-(2-아지도아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 83의 화합물),(S)-[N-3- (4- (2-azidoacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 83 Compound), (S)-[N-3-(4-(2-(1,2,3,4,6,7-헥사히드로-5-옥소-1,4-디아제팬-1-일)-피리딘 -5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 84의 화합물),(S)-[N-3- (4- (2- (1,2,3,4,6,7-hexahydro-5-oxo-1,4-diazepane-1-yl) -pyridine-5 -Yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (compound of Example 84), (S)-[N-3-(4-(2-N-(디메틸아미노메틸렌)아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 85의 화합물),(S)-[N-3- (4- (2-N- (dimethylaminomethylene) aminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Compound of Example 85), (S)-[N-3-(4-(2-(4-히드록시이미노피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 86의 화합물),(S)-[N-3- (4- (2- (4-hydroxyiminopiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxa Zolidinyl] methyl acetamide (compound of Example 86), (S)-[N-3-(4-(2-(4-메탄술포닐옥시이미노피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 87의 화합물),(S)-[N-3- (4- (2- (4-methanesulfonyloxyiminopiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5 -Oxazolidinyl] methyl acetamide (compound of Example 87), (S)-[N-3-(4-(2-(4-메틸이미노피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 88의 화합물),(S)-[N-3- (4- (2- (4-methyliminopiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxa Zolidinyl] methyl acetamide (compound of Example 88), (S)-[N-3-(4-(2-(4-메톡시카보닐히드라지노피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 89의 화합물),(S)-[N-3- (4- (2- (4-methoxycarbonylhydrazinopiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo- 5-oxazolidinyl] methyl acetamide (compound of Example 89), (S)-[N-3-(4-(2-N-(L-알라닐)아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5- 옥사졸리딘일]메틸 아세트아마이드 (실시예 90의 화합물),(S)-[N-3- (4- (2-N- (L-alanyl) aminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acet Amide (compound of Example 90), (S)-[N-3-(4-(2-아세틸아미노아세틸아미노피리딘-5-일)-3-플로로페닐)-2- 옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 91의 화합물),(S)-[N-3- (4- (2-acetylaminoacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 91 Compound), (S)-[N-3-(4-(2-디메틸아미노아세틸아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 92의 화합물),(S)-[N-3- (4- (2-dimethylaminoacetylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 92 Compound), (S)-[N-3-(4-(2-니코티노일아미노피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 93의 화합물),(S)-[N-3- (4- (2-nicotinoylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] methyl acetamide (Example 93 Compound), (S)-[N-3-(4-(2-(1,2,4-트리아졸-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 94의 화합물),(S)-[N-3- (4- (2- (1,2,4-triazol-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxa Zolidinyl] methyl acetamide (compound of Example 94), (S)-[N-3-(4-(2-(4-히드록시피페리딘-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 95의 화합물),(S)-[N-3- (4- (2- (4-hydroxypiperidin-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazoli Dinyl] methyl acetamide (compound of Example 95), (S)-[N-3-(4-(2-N,N-(히드록시아세틸)메틸아미노피리딘-5-일)-3-플로로페닐) -2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 96의 화합물),(S)-[N-3- (4- (2-N, N- (hydroxyacetyl) methylaminopyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl] Methyl acetamide (compound of Example 96), (S)-[N-3-(4-(2-(4-메틸이미다졸-1-일)피리딘-5-일)-3-플로로페닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 97의 화합물),(S)-[N-3- (4- (2- (4-methylimidazol-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo-5-oxazolidinyl ] Methyl acetamide (compound of Example 97), (S)-[N-3-(4-(2-(2-히드록시프로피오닐)아미노피리딘-5-일)-3-플로로페(닐)-2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 98의 화합물) 또는(S)-[N-3- (4- (2- (2-hydroxypropionyl) aminopyridin-5-yl) -3-fluoro ((yl) -2-oxo-5-oxazolidinyl] Methyl acetamide (compound of Example 98) or (S)-[N-3-(4-(2-(3-아미노-1,2,4-트리아졸-1-일)피리딘-5-일)-3-플로로페닐) -2-옥소-5-옥사졸리딘일]메틸 아세트아마이드 (실시예 99의 화합물)인 것을 특징으로 하는 옥사졸리디논 유도체 및 약학적으로 허용되는 그의 염.(S)-[N-3- (4- (2- (3-amino-1, 2,4-triazol-1-yl) pyridin-5-yl) -3-fluorophenyl) -2-oxo -Oxazolidinyl] methyl acetamide (compound of Example 99), and an pharmaceutically acceptable salt thereof. 1) 히드록시메틸옥사졸리디논 유도체(2)의 히드록시기를 아민기로 변환시켜 아미노메틸옥사졸리디논 유도체(3)을 제조하는 단계 (제 1 단계);1) preparing an aminomethyloxazolidinone derivative (3) by converting the hydroxy group of the hydroxymethyloxazolidinone derivative (2) to an amine group (first step); 3) 상기 제 1 단계에서 제조된 아미노메틸옥사졸리디논 유도체(3)의 화합물을 아세틸화 반응시켜 화합물(4)를 얻는 단계 (제 2 단계); 3) acetylating the compound of the aminomethyloxazolidinone derivative (3) prepared in the first step to obtain a compound (4) (second step); 4) 화합물(4)를 할로겐화 반응시켜 화합물(5)를 얻는 단계 (제 3 단계);4) halogenating the compound (4) to obtain the compound (5) (third step); 5) 화합물(5)를 스텐닐화시켜 화합물(6)을 얻는 단계 (제 4 단계);5) Stenylation of compound (5) to obtain compound (6) (fourth step); 6) 화합물(6)과 화학식 1로 표시되는 화합물의 적절한 치환기에 대응하는 브롬 또는 요오드로 치환된 피리딘 유도체와 반응시켜 화학식 1의 피리딘 고리를 포함하는 옥사졸리디논 유도체를 얻는 단계 (제 5단계)로 이루어지는 것을 특징으로 하는 제 1항의 옥사졸리디논 유도체의 제조방법.6) reacting compound (6) with a pyridine derivative substituted with bromine or iodine corresponding to an appropriate substituent of compound represented by formula (1) to obtain an oxazolidinone derivative comprising a pyridine ring of formula (1) A method for producing the oxazolidinone derivative according to claim 1, comprising: 반응식 1Scheme 1
Figure 112000019986940-pat00018
Figure 112000019986940-pat00018
 상기 반응식에서 R1 및 R2는 화학식 1에서 정의한 바와 같으며, X는 할로겐 원소이다.R 1 and in the above scheme R 2 is as defined in Formula 1, and X is a halogen element. 제 1항의 옥사졸리디논 화합물 및 이들의 약학적으로 허용되는 그의 염을 유효성분으로 함유하는 항생제용 약학적 조성물. The pharmaceutical composition for antibiotics containing the oxazolidinone compound of claim 1 and their pharmaceutically acceptable salts as an active ingredient.
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