Phosgene → HCID 67095081, compound

HRID 909019Notes

Reaction equation

HRID 909019 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.[C:29](Cl)(Cl)=[O:30].C(N(CC)CC)C.[CH2:40]([N:42]1[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]1)[CH3:41]>C(Cl)Cl>[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]([CH3:25])([CH3:27])[CH3:26])[CH2:10][N:9]2[C:29]([N:45]2[CH2:46][CH2:47][N:42]([CH2:40][CH3:41])[CH2:43][CH2:44]2)=[O:30])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6371PhosgeneHCID 8471TriethylamineHCID 791961-EthylpiperazineHCID 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 67095081HCID 67095081, compoundYield 36.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a manner similar to the method described in Example 4, rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile (42.3 mg, 0.10 mmol) was reacted with phosgene solution (Aldrich, 20% in toluene, 0.12 mL, 0.12 mmol), in the presence of triethylamine (TEA, 30.0 mg, 0.30 mmol) in CH2Cl2 (2 mL) followed by reacting with 1-ethyl-piperazine (17.2 mg, 0.15 mmol) at rt for 30 min to give rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-1-(4-ethyl-piperazine-1-carbonyl)-pyrrolidine-3-carbonitrile (20.6 mg, 30.4%, as TFA salt) as a white amorphous. HRMS (ES+) m/z Calcd for C29H34Cl2F2N4O+H [(M+H)+]: 563.2151, found: 563.2151.

Sources & evidence

ORD record
ord-3b89e49039ca405597a1a205a6759ccd
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

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