4-[(Imidazole-1-carbonyl)-amino]-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}-2-methoxy-benzoic acid methyl ester

HRID 909087Notes

Reaction equation

HRID 909087 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:48])[C:32]1[CH:37]=[CH:36][C:35]([NH:38][C:39](N2C=CN=C2)=[O:40])=[CH:34][C:33]=1[O:46][CH3:47]>C(Cl)Cl>[CH3:29][O:30][C:31](=[O:48])[C:32]1[CH:37]=[CH:36][C:35]([NH:38][C:39]([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:40])=[CH:34][C:33]=1[O:46][CH3:47]

Participants

4

Reactant 2

HCID 670951714-[(Imidazole-1-carbonyl)-amino]-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 51357251rac-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}-2-methoxy-benzoic acid methyl esterYield 64.6%

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 (50.5 mg, 0.119 mmol) and 4-[(imidazole-1-carbonyl)-amino]-2-methoxy-benzoic acid methyl ester (325.2 mg, 1.181 mmol) in CH2Cl2 (8 mL) was stirred at reflux 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}-2-methoxy-benzoic acid methyl ester (48.5 mg, 64.6%). HRMS (ES+) m/z Calcd for C32H31Cl2F2N3O4+H [(M+H)+]: 630.1733; Found: 630.1738.

Workup

  1. temperatureat reflux for 16 hrs
  2. customThe reaction mixture was then purified by flash column

Sources & evidence

ORD record
ord-b2bcd7b5373c4c75bb749b0b125099a5
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

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