4-({[(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-methyl)-2-fluoro-benzoic acid → 4-(((2S,3R,4S,5R)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)methyl)-2-fluorobenzoic acid

HRID 1807283Notes

Reaction equation

HRID 1807283 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]2([C:40]#[N:41])[C@H:12]([CH2:13][C:14]([CH3:17])([CH3:16])[CH3:15])[NH:11][C@@H:10]([C:18]([NH:20][CH2:21][C:22]3[CH:30]=[CH:29][C:25]([C:26]([OH:28])=[O:27])=[C:24]([F:31])[CH:23]=3)=[O:19])[C@@H:9]2[C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([Cl:38])[C:33]=2[F:39])=[C:4]([F:42])[CH:3]=1>CO>[Cl:38][C:34]1[C:33]([F:39])=[C:32]([C@H:9]2[C@@:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=3[F:42])([C:40]#[N:41])[C@@H:12]([CH2:13][C:14]([CH3:17])([CH3:16])[CH3:15])[NH:11][C@@H:10]2[C:18]([NH:20][CH2:21][C:22]2[CH:30]=[CH:29][C:25]([C:26]([OH:28])=[O:27])=[C:24]([F:31])[CH:23]=2)=[O:19])[CH:37]=[CH:36][CH:35]=1

Participants

3

Reactant 1

HCID 533570944-({[(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-methyl)-2-fluoro-benzoic acid

Product 1

HCID 533577344-(((2S,3R,4S,5R)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)methyl)-2-fluorobenzoic acidYield 41.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The mixture 4-({[(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-methyl)-2-fluoro-benzoic acid (71.1 mg. 0.115 mmol) was separated by SFC, 40% CH3OH on a Whelk-01 R,R prep column to give chiral-4-(((2S,3R,4S,5R)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)methyl)-2-fluorobenzoic acid (29.4 mg., 41.4%) as a white lyophilized solid. MS (ES+) m/z Calcd: [(M+H)+]: 618.15. found: 618.2 and chiral 4-(((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)methyl)-2-fluorobenzoic acid (29.7 mg., 41.8%) as a white lyophilized solid. MS (ES+) m/z Calcd: [(M+H)+]: 618.15. found: 618.2.

Sources & evidence

ORD record
ord-4c1b92c6894a4f9cba25e81da2b8a91c
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

Loading…