Phosgene → HCID 178442227, compound

HRID 909032Notes

Reaction equation

HRID 909032 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.[NH:40]1[C:44]([C:45]2[CH:46]=[C:47]([NH2:51])[CH:48]=[CH:49][CH:50]=2)=[N:43][N:42]=[N:41]1>C(Cl)Cl>[NH:43]1[C:44]([C:45]2[CH:46]=[C:47]([NH:51][C:29]([N:9]3[CH2:10][CH:11]([CH2:23][C:24]([CH3:25])([CH3:27])[CH3:26])[C:12]([C:15]4[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=4[F:22])([C:13]#[N:14])[CH:8]3[C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=3[F:28])=[O:30])[CH:48]=[CH:49][CH:50]=2)=[N:40][N:41]=[N:42]1

Participants

6

Reactant 4

HCID 6371PhosgeneHCID 8471TriethylamineHCID 67095372rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrileHCID 178507542HCID 178507542, compound

Product 1

HCID 178442227HCID 178442227, compoundYield 41.4%

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, 90 mg, 0.90 mmol) in CH2Cl2 (2 mL) followed by reacting with 3-(1H-tetrazol-5-yl)-phenylamine (48.3 mg, 0.30 mmol) at rt for 30 min 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 [3-(1H-tetrazol-5-yl)-phenyl]amide (25.3 mg, 41.4%) as a white amorphous. HRMS (ES+) m/z Calcd for C30H27Cl2F2N7O+H [(M+H)+]: 610.1695. found: 610.1695

Sources & evidence

ORD record
ord-469bd4d5bc364ec88fe2f7241dc6b637
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

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