Dimethyl Sulfide → HCID 53357741, compound

HRID 1807279Notes

Reaction equation

HRID 1807279 reaction equation
[Cl:1][C:2]1[C:3]([F:42])=[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[N:32]=[CH:33][C:34]([C:37]([O:39]CC)=[O:38])=[N:35][CH:36]=2)=[O:29])[CH:5]=[CH:6][CH:7]=1.CSC.[Br-].[Al+3].[Br-].[Br-]>ClCCl.C(#N)C.CCOC(C)=O.O>[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])([CH3:27])[CH3:25])[NH:10][C@@H:9]([C:28]([NH:30][C:31]3[N:32]=[CH:33][C:34]([C:37]([OH:39])=[O:38])=[N:35][CH:36]=3)=[O:29])[C@@H:8]2[C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=2[F:42])=[C:16]([F:22])[CH:17]=1

Participants

8

Reactant 3

HCID 1068Dimethyl SulfideHCID 166749BromhydrolHCID 67380471ethyl 5-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)pyrazine-2-carboxylate

Product 1

HCID 53357741HCID 53357741, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of ethyl 5-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)pyrazine-2-carboxylate (27.6 mg, 0.0448 mmol) in dichloromethane (2 ml) were added DIMETHYL SULFIDE (846 mg, 0.0136 mmol) and ALUMINUM BROMIDE (64.5 mg, 0.242 mmol). The mixture was stirred under argon for 5 hrs. The reaction mixture was diluted with acetonitrile (2 ml), EtOAc (10 ml) and water (10 ml) and stirred for several minutes. After more ethyl acetate (50 ml) was added, the organic layer was separated and washed with saturated ammonium chloride (10 ml), water (10 ml) and sat. sodium chloride (10 ml). The organic layers were dried over Na2SO4 and concentrated and purified by silica gel chromatography with methanol and dichloromethane to give chiral 5-{[(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}-pyrazine-2-carboxylic acid as an off-white lyophilized solid (19.7 mg, 74%). MS (ES+) m/z Calcd: [(M+H)+]: 588.13. found: 588.0

Workup

  1. stirringstirred for several minutes
  2. customthe organic layer was separated
  3. washwashed with saturated ammonium chloride (10 ml), water (10 ml) and sat. sodium chloride (10 ml)
  4. dry with materialThe organic layers were dried over Na2SO4
  5. concentrationconcentrated
  6. custompurified by silica gel chromatography with methanol and dichloromethane

Sources & evidence

ORD record
ord-fdf8215591dc406f8a1e9a8fae36c7e4
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

Loading…