Sodium methanesulfonate → (s)-2-[(s)-1-(4-Bromo-phenyl)-2,2,2-trifluoro-ethylamino]-4-methyl-pentanoic acid [(s)-1-cyano-2-(4-methanesulfonyl-phenyl)-ethyl]-amide

HRID 239862

Reaction equation

HRID 239862 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:13][C@H:14]([C:19]([NH:21][C@H:22]([C:31]#[N:32])[CH2:23][C:24]2[CH:29]=[CH:28][C:27](I)=[CH:26][CH:25]=2)=[O:20])[CH2:15][CH:16]([CH3:18])[CH3:17])[C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=1.[Na+].[CH3:34][S:35]([O-])(=[O:37])=[O:36]>CS(C)=O.CCOC(C)=O.[Cu](I)I>[C:31]([C@@H:22]([NH:21][C:19](=[O:20])[C@@H:14]([NH:13][C@@H:8]([C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=1)[C:9]([F:12])([F:11])[F:10])[CH2:15][CH:16]([CH3:18])[CH3:17])[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([S:35]([CH3:34])(=[O:37])=[O:36])=[CH:26][CH:25]=1)#[N:32]

Participants

6

Reactant 2

HCID 638112Sodium methanesulfonateHCID 68779205N2-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N-[(1S)-1-cyano-2-(4-iodophenyl)ethyl]-L-leucinamide

Product 1

HCID 42633519(s)-2-[(s)-1-(4-Bromo-phenyl)-2,2,2-trifluoro-ethylamino]-4-methyl-pentanoic acid [(s)-1-cyano-2-(4-methanesulfonyl-phenyl)-ethyl]-amide

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To N2-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N-[(1S)-1-cyano-2-(4-iodophenyl)ethyl]-L-leucinamide (1 eq) in DMSO (0.3 M) were added methane sulfonic acid sodium salt (2 eq) and copper iodide (3 eq) and the mixture was stirred at 100° C. for 2 h. The reaction mixture was cooled and diluted with EtOAc. The organic layer was washed with brine and water, dried over Na2SO4, filtered and concentrated. The crude compound was purified by automated SiO2 flash chromatography system using solvent gradient of 40% EtOAc/Hex to 100% EtOAc/Hex.

Workup

  1. temperatureThe reaction mixture was cooled
  2. washThe organic layer was washed with brine and water
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude compound was purified by automated SiO2 flash chromatography system

Sources & evidence

ORD record
ord-53f846116d2044d497afa95b5c656f0a
Source dataset
uspto-grants-2014_02
Patent number
US08642799B2

Linked notes

Loading…