Dimethyl Sulfide → 4-{[(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-carbonyl]-amino}-2,5-difluoro-benzoic acid

HRID 1807323Notes

Reaction equation

HRID 1807323 reaction equation
[Cl:1][C:2]1[C:3]([F:43])=[C:4]([C@@H: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])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][C@H:9]2[C:28]([NH:30][C:31]2[C:40]([F:41])=[CH:39][C:34]([C:35]([O:37]C)=[O:36])=[C:33]([F:42])[CH:32]=2)=[O:29])[CH:5]=[CH:6][CH:7]=1.[Al](Br)(Br)Br.CSC>C(Cl)Cl>[Cl:21][C:18]1[CH:19]=[CH:20][C:15]([C@@:12]2([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:26])([CH3:25])[CH3:27])[NH:10][C@@H:9]([C:28]([NH:30][C:31]3[C:40]([F:41])=[CH:39][C:34]([C:35]([OH:37])=[O:36])=[C:33]([F:42])[CH:32]=3)=[O:29])[C@@H:8]2[C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=2[F:43])=[C:16]([F:22])[CH:17]=1

Participants

5

Reactant 3

HCID 1068Dimethyl SulfideHCID 24409Aluminum bromideHCID 53357230methyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-2,5-difluorobenzoate

Product 1

HCID 533572314-{[(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-carbonyl]-amino}-2,5-difluoro-benzoic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of methyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-2,5-difluorobenzoate (75 mg, 0.118 mmol) in methylene chloride (10 ml), AlBr3 (Aldrich, 59 mg, 0.94 mmol) was added followed by dimethyl sulfide (Aldrich, 0.2 ml, 0.63 mmol). The mixture was stirred at rt for 2 hrs. The solvent was removed and the residue was treated with 3 ml of acetonitrile and 10 ml of water. The mixture was then extracted with ethyl acetate. Removal of solvent gave an off white solid. 72 mg. (ES+) m/z Calcd: [(M+H)+]: 622. found: 622.

Workup

  1. customThe solvent was removed
  2. additionthe residue was treated with 3 ml of acetonitrile and 10 ml of water
  3. extractionThe mixture was then extracted with ethyl acetate
  4. customRemoval of solvent
  5. customgave an off white solid

Sources & evidence

ORD record
ord-0e3b82fdc277414e8352f6eda7ccef34
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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