4-{[(Imidazole-1-carbonyl)-amino]-methyl}-2-methoxy-benzoic acid methyl ester → rac-4-({[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]-amino}-methyl)-2-methoxy-benzoic acid methyl ester

HRID 909107Notes

Reaction equation

HRID 909107 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][O:30][C:31](=[O:49])[C:32]1[CH:37]=[CH:36][C:35]([CH2:38][NH:39][C:40](N2C=CN=C2)=[O:41])=[CH:34][C:33]=1[O:47][CH3:48]>C(Cl)Cl>[CH3:29][O:30][C:31](=[O:49])[C:32]1[CH:37]=[CH:36][C:35]([CH2:38][NH:39][C:40]([N:9]2[CH2:10][C@@H: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])[C@H:8]2[C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=2[F:28])=[O:41])=[CH:34][C:33]=1[O:47][CH3:48]

Participants

4

Reactant 2

HCID 670953264-{[(Imidazole-1-carbonyl)-amino]-methyl}-2-methoxy-benzoic acid methyl esterHCID 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 51353869rac-4-({[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]-amino}-methyl)-2-methoxy-benzoic acid methyl esterYield 82.8%

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 (49.2 mg, 0.116 mmol) and 4-{[(imidazole-1-carbonyl)-amino]-methyl}-2-methoxy-benzoic acid methyl ester (224.3 mg, 0.775 mmol) in CH2Cl2 (8 mL) was stirred rt for 16 hrs. The reaction mixture was then purified by flash column to give rac-4-({[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]-amino}-methyl)-2-methoxy-benzoic acid methyl ester (61.9 mg, 82.8%). HRMS (ES+) m/z Calcd for C33H33Cl2F2N3O4: 644.1889; Found: 644.1888

Workup

  1. customThe reaction mixture was then purified by flash column

Sources & evidence

ORD record
ord-8a4777a405cd48e5b2c95bf82b5df0e9
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

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