Methanesulfonyl chloride → rac-(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid [4-(methanesulfonylamino-methyl)-phenyl]-amide

HRID 1807297Notes

Reaction equation

HRID 1807297 reaction equation
[NH2:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([CH:12]2[CH:16]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=3[F:24])[C:15]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:28]=3[F:34])([C:25]#[N:26])[CH:14]([CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[NH:13]2)=[O:11])=[CH:5][CH:4]=1.[CH3:40][S:41](Cl)(=[O:43])=[O:42]>C(Cl)Cl>[CH3:40][S:41]([NH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([CH:12]2[CH:16]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=3[F:24])[C:15]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:28]=3[F:34])([C:25]#[N:26])[CH:14]([CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[NH:13]2)=[O:11])=[CH:5][CH:4]=1)(=[O:43])=[O:42]

Participants

4

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 67369526HCID 67369526, compound

Product 1

HCID 76022068rac-(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid [4-(methanesulfonylamino-methyl)-phenyl]-amideYield 36,515.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of rac-(2R,3S,4R,5S)—N-(4-(aminomethyl)phenyl)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamide (21.0 mg, 0.0367 mmol, example XJ-2) in CH2Cl2 (4 ml) was treated with METHANESULFONYL CHLORIDE (8.5 mg, 5.78 μl, 0.0742 μmol) and the reaction was stirred at 0 C for 1 hr. The reaction mixture was diluted with CH2Cl2 (80 mL), washed with sat Na2CO3 (2×15 mL), water (2×15 mL) and evaporated. The crude material was purified by flash chromatography (silica gel, 4 g, 1% to 10% MeOH/CH2Cl2) to give rac-(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid [4-(methanesulfonylamino-methyl)-phenyl]-amide as off-white solid (17.6 mg, 73%). MS (ES+) m/z Calcd: [(M+H)+]: 649. found: 649.

Workup

  1. washwashed
  2. customevaporated
  3. customThe crude material was purified by flash chromatography (silica gel, 4 g, 1% to 10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-73125242d22546c093ef913e1b7bb0af
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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