rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile → HCID 51357532, compound

HRID 909094Notes

Reaction equation

HRID 909094 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.[CH2:29]([O:31][C:32](=[O:47])[CH2:33][CH:34]1[CH2:39][CH2:38][N:37]([C:40](N2C=CN=C2)=[O:41])[CH2:36][CH2:35]1)[CH3:30]>C(Cl)Cl>[CH2:29]([O:31][C:32](=[O:47])[CH2:33][CH:34]1[CH2:35][CH2:36][N:37]([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])[CH2:38][CH2:39]1)[CH3:30]

Participants

4

Reactant 2

HCID 67095372rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrileHCID 67095615HCID 67095615, compound

Product 1

HCID 51357532HCID 51357532, compoundYield 53.4%

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 (51.6 mg, 0.122 mmol) and [1-(imidazole-1-carbonyl)-piperidin-4-yl]-acetic acid ethyl ester (293.3 mg, 1.10 mmol) in CH2Cl2 (8 mL) was stirred at reflux for 16 hrs then 1 h at 140° C. in a microwave tube and finally at 160° C. for 1 hr. The reaction mixture was then purified by flash column to give rac-{1-[(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]-piperidin-4-yl}-acetic acid ethyl ester (40.4 mg, 53.4%). HRMS (ES+) m/z Calcd for C32H37Cl2F2N3O3+H [(M+H)+]: 620.2253; Found: 620.2254.

Workup

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

Sources & evidence

ORD record
ord-5998b8cb65824abc91ed71eef648c3f7
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

Loading…