Imidazole-1-carboxylic acid (1-methanesulfonyl-piperidin-4-yl)-amide → rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidine-1-carboxylic acid (1-methanesulfonyl-piperidin-4-yl)-amide

HRID 909075Notes

Reaction equation

HRID 909075 reaction equation
[Cl:1][C:2]1[C:3]([F:28])=[C:4]([CH:8]2[C:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[CH:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:10][NH:9]2)[CH:5]=[CH:6][CH:7]=1.[CH3:29][S:30]([N:33]1[CH2:38][CH2:37][CH:36]([NH:39][C:40](N2C=CN=C2)=[O:41])[CH2:35][CH2:34]1)(=[O:32])=[O:31]>C(Cl)Cl>[CH3:29][S:30]([N:33]1[CH2:38][CH2:37][CH:36]([NH:39][C:40]([N:9]2[CH2:10][CH:11]([CH2:23][C:24]([CH3:25])([CH3:27])[CH3:26])[C:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[CH:8]2[C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=2[F:28])=[O:41])[CH2:35][CH2:34]1)(=[O:32])=[O:31]

Participants

4

Reactant 2

HCID 67095364Imidazole-1-carboxylic acid (1-methanesulfonyl-piperidin-4-yl)-amideHCID 67095372rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile

Product 1

HCID 75631467rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidine-1-carboxylic acid (1-methanesulfonyl-piperidin-4-yl)-amideYield 34.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile (30.5 mg, 0.072 mmol) and imidazole-1-carboxylic acid (1-methanesulfonyl-piperidin-4-yl)-amide (75.4 mg, 0.277 mmol) in CH2Cl2 (4 mL) was stirred at rt for 72 hrs. The reaction mixture was then purified by flash column to give rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidine-1-carboxylic acid (1-methanesulfonyl-piperidin-4-yl)-amide (15.7 mg, 34.7%). HRMS (ES+) m/z Calcd for C29H34Cl2F2N4O3S+H [(M+H)+]: 627.1770; Found: 627.1770.

Workup

  1. customThe reaction mixture was then purified by flash column

Sources & evidence

ORD record
ord-cb22f63340794dad94dde5423db779b7
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

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