Potassium Carbonate → HCID 67298406, compound

HRID 1880543Notes

Reaction equation

HRID 1880543 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:13][C@H:14]([C:18]([NH:20][C:21]2([C:24]#[N:25])[CH2:23][CH2:22]2)=[O:19])[CH2:15][CH2:16][CH3:17])[C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=1.[CH3:26][S:27]([C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1)(=[O:29])=[O:28].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C(OCC)(=O)C>[C:24]([C:21]1([NH:20][C:18](=[O:19])[C@H:14]([CH2:15][CH2:16][CH3:17])[NH:13][C@@H:8]([C:5]2[CH:6]=[CH:7][C:2]([C:33]3[CH:34]=[CH:35][C:30]([S:27]([CH3:26])(=[O:29])=[O:28])=[CH:31][CH:32]=3)=[CH:3][CH:4]=2)[C:9]([F:12])([F:11])[F:10])[CH2:23][CH2:22]1)#[N:25]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27343644-(Methanesulfonyl)phenylboronic acidHCID 59715504HCID 59715504, compound

Product 1

HCID 67298406HCID 67298406, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
82.5 °C

Procedure

A mixture of N2-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N1-(1-cyanocyclopropyl)-L-norvalinamide (6.46 g, 15.44 mmol), 4-methanesulfonylphenyl-boronic acid (3.40 g, 16.98 mmol), and 2M K2CO3 (19.3 mL) was dissolved in DMF (75 mL) in a thick-walled flask. The reaction mixture was degassed, and [1,1′-bis(diphenyl-phosphino)ferrocene]dichloropalladium(II), dichloromethane complex (0.678 g, 0.926 mmol) was added. The flask was sealed, heated at 80-85° C. for 3 hours, cooled, and diluted with ethyl acetate (300 mL). The solution was washed with 1:1 water/brine (200 mL), brine (200 mL), filtered through a three-layered plug of silica (bottom) DARCO, and MgSO4 (top), concentrated in vacuo, and purified on a plug of silica gel (50-70% ethyl acetate/hexane elution). The product was then further purified by recrystallization from ethyl acetate/hexanes to yield the title compound.

Workup

  1. customThe reaction mixture was degassed
  2. customThe flask was sealed
  3. temperaturecooled
  4. washThe solution was washed with 1:1 water/brine (200 mL), brine (200 mL)
  5. filtrationfiltered through a three-layered plug of silica (bottom) DARCO, and MgSO4 (top)
  6. concentrationconcentrated in vacuo
  7. custompurified on a plug of silica gel (50-70% ethyl acetate/hexane elution)
  8. customThe product was then further purified by recrystallization from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-6cb99e762b6a416b8b8e04b08d5fd7c5
Source dataset
uspto-grants-2012_11
Patent number
US08318748B2

Reaction notes

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