2-Dimethylaminopyridine → rac-(2R,3R,4R,5s)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (3-methanesulfonylamino-propyl)-amide

HRID 1807214노트

반응식

HRID 1807214 반응식
[NH2:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]([CH:8]1[CH:12]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)[C:11]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=2)([C:20]#[N:21])[CH:10]([CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[NH:9]1)=[O:7].[CH3:34][S:35](Cl)(=[O:37])=[O:36].CN(C1C=CC=CN=1)C>C(Cl)Cl>[CH3:34][S:35]([NH:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]([CH:8]1[CH:12]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)[C:11]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=2)([C:20]#[N:21])[CH:10]([CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[NH:9]1)=[O:7])(=[O:37])=[O:36]

참가 물질

5

반응물 3

HCID 218852-DimethylaminopyridineHCID 31297Methanesulfonyl chlorideHCID 75095855Rac-(2r,3r,4r,5s)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid(3-amino-propyl)-amide

생성물 1

HCID 72243932rac-(2R,3R,4R,5s)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (3-methanesulfonylamino-propyl)-amide수율 82.6%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A mixture of rac (2R,3R,4R,5S)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (3-amino-propyl)-amide (120 mg, 0.24 mmol), methane sulfonyl chloride (49 μL, 0.6 mmol) and dimethylaminopyridine (97.6 mg, 0.8 mmol) in CH2Cl2 (8 mL) was stirred for 5 h at rt. The mixture was then extracted with NaHCO3(s), water and the organic layer dried with MgSO4, filtered and the solvent was evaporated under reduced pressure. diluted with CH2Cl2 and washed with water, brine. The organic phase was separated, filtered and dried over Na2SO4. The mixture was then purified by reverse phase chromatography (20-95% of ACN/water) to give rac-(2R,3R,4R,5S)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (3-methanesulfonylamino-propyl)-amide (112.1 mg, 80.5%) as an off-white powder. HRMS (ES+) m/z Calcd for C27H34Cl2N4O3S+H [(M+H)+]: 565.1802. found: 565.1800.

후처리

  1. extractionThe mixture was then extracted with NaHCO3(s), water
  2. dry with materialthe organic layer dried with MgSO4
  3. filtrationfiltered
  4. customthe solvent was evaporated under reduced pressure
  5. additiondiluted with CH2Cl2
  6. washwashed with water, brine
  7. customThe organic phase was separated
  8. filtrationfiltered
  9. dry with materialdried over Na2SO4
  10. customThe mixture was then purified by reverse phase chromatography (20-95% of ACN/water)

출처 및 근거

ORD 기록
ord-edb5743748c44d9f883a77599ce2b825
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08354444B2

반응 노트

불러오는 중…