4-Isocyanatopyridine → 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 pyridin-4-ylamide

HRID 909065Notes

Reaction equation

HRID 909065 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.[N:29]([C:32]1[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=1)=[C:30]=[O:31]>C(Cl)Cl>[N:35]1[CH:36]=[CH:37][C:32]([NH:29][C:30]([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:31])=[CH:33][CH:34]=1

Participants

4

Reactant 2

HCID 116367964-Isocyanatopyridine2×HCID 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 67095544rac-(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 pyridin-4-ylamideYield 89.6%

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 (39.4 mg, 0.093 mmol) and 4-isocyanatopyridine (Princeton, 27.8 mg, 0.231 mmol) in CH2Cl2 (5 mL) was stirred at rt for 7.5 hrs then more 4-isocyanatopyridine (Princeton, 23.6 mg, 0.196 mmol) was added. After and additions 16 hrs, the reaction mixture was then concentrated and 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 pyridin-4-ylamide (45.3 mg, 89.5%). HRMS (ES+) m/z Calcd for C28H26Cl2F2N4O+H [(M+H)+]: 543.1525; Found: 543.1525.

Workup

  1. concentrationAfter and additions 16 hrs, the reaction mixture was then concentrated
  2. custompurified by flash column

Sources & evidence

ORD record
ord-2b6f19f19be3417d9da08705e4f4dbdc
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

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