Methyl 4-aminobenzoate → rac-4-{2-[(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-acetylamino}-benzoic acid methyl ester

HRID 909053노트

반응식

HRID 909053 반응식
[Cl:1][C:2]1[C:3]([F:32])=[C:4]([C@H:8]2[CH2:12][N:11]([CH2:13][C:14](O)=[O:15])[C@@H:10]([CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])[C@@:9]2([C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=2[F:31])[C:22]#[N:23])[CH:5]=[CH:6][CH:7]=1.[NH2:33][C:34]1[CH:43]=[CH:42][C:37]([C:38]([O:40][CH3:41])=[O:39])=[CH:36][CH:35]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:41][O:40][C:38](=[O:39])[C:37]1[CH:36]=[CH:35][C:34]([NH:33][C:14](=[O:15])[CH2:13][N:11]2[CH2:12][C@H:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=3[F:32])[C@:9]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=3[F:31])([C:22]#[N:23])[C@@H:10]2[CH2:17][C:18]([CH3:20])([CH3:19])[CH3:21])=[CH:43][CH:42]=1

참가 물질

6

반응물 4

HCID 12082Methyl 4-aminobenzoateHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 51355303rac-[(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-acetic acid

생성물 1

HCID 51355304rac-4-{2-[(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-acetylamino}-benzoic acid methyl ester수율 81%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

A mixture of rac-[(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-acetic acid (0.5 g, 1.04 mmol), methyl 4-aminobenzoate (Aldrich) (0.3 g, 1.99 mmol), HATU (0.4 g, 1.05 mmol) and iPr2NEt (0.3 g, 2.33 mmol) in CH2Cl2 (30 mL) was stirred at room temperature for 20 h. The mixture was then diluted with CH2Cl2 and washed with water, brine. The organic phase was separated, filtered and dried over Na2SO4. The mixture was then concentrated and purified by chromatography (EtOAc:hexanes=1:5) to give rac-4-{2-[(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-acetylamino}-benzoic acid methyl ester as a white solid (0.5 g, 81%).

후처리

  1. washwashed with water, brine
  2. customThe organic phase was separated
  3. filtrationfiltered
  4. dry with materialdried over Na2SO4
  5. concentrationThe mixture was then concentrated
  6. custompurified by chromatography (EtOAc:hexanes=1:5)

출처 및 근거

ORD 기록
ord-2bc5ddd193fa421d84e9480248956cae
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08017607B2

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