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 1807214ノート

反応式

HRID 1807214 の反応式
[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]

参加物

5

反応物 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

生成物 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)-amide収率 82.6%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-edb5743748c44d9f883a77599ce2b825
出典データセット
uspto-grants-2013_01
特許番号
US08354444B2

反応ノート

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