Cesium carbonate → 6-[2-(4-Cyano-phenyl)-2H-pyrazol-3-yl]-5-methyl-3-oxo-4-(3-trifluoromethyl-phenyl)-3,4-dihydro-pyrazine-2-carboxylic acid methylamide

HRID 1958293Notes

Reaction equation

HRID 1958293 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]([NH:10][CH3:11])=[O:9])[C:5](=[O:12])[N:4]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=2)[C:3]=1[CH3:23].[C:24]([C:26]1[CH:31]=[CH:30][C:29]([N:32]2[C:36](B(O)O)=[CH:35][CH:34]=[N:33]2)=[CH:28][CH:27]=1)#[N:25].C([O-])([O-])=O.[Cs+].[Cs+]>COCCOC>[CH3:11][NH:10][C:8]([C:6]1[C:5](=[O:12])[N:4]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=2)[C:3]([CH3:23])=[C:2]([C:36]2[N:32]([C:29]3[CH:30]=[CH:31][C:26]([C:24]#[N:25])=[CH:27][CH:28]=3)[N:33]=[CH:34][CH:35]=2)[N:7]=1)=[O:9]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 667386596-Bromo-N,5-dimethyl-3-oxo-4-[3-(trifluoromethyl)phenyl]-3,4-dihydropyrazine-2-carboxamideHCID 66738661[1-(4-cyanophenyl)-1H-pyrazol-5-yl]boronic acid

Product 1

HCID 248901406-[2-(4-Cyano-phenyl)-2H-pyrazol-3-yl]-5-methyl-3-oxo-4-(3-trifluoromethyl-phenyl)-3,4-dihydro-pyrazine-2-carboxylic acid methylamideYield 20%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
110 °C

Procedure

6-Bromo-N,5-dimethyl-3-oxo-4-[3-(trifluoromethyl)phenyl]-3,4-dihydropyrazine-2-carboxamide (SM2, 0.05 g, 0.128 mmol), 1-(4-cyanophenyl)-1H-pyrazol-5-boronic acid (SM4, 0.062 g, 0256 mmol), Cs2CO3 (0.125 g, 0.384 mmol) and DME (3 ml) were added to a glass tube for microwave synthesis. The mixture was degassed with nitrogen and Pd(PBut3)2 (0.010 g) was added. The tube was sealed and heated with stirring at 110° C. (150 W) in a microwave heater for 10 minutes. The mixture was diluted with EtOAc (5 ml), and filtered. The solution was concentrated in vacuo and was purified by chromatography on silica to give a reasonably pure material that was further purified by preparative HPLC to give 0.012 g (20%) of the title compound as a white solid.

Workup

  1. customThe mixture was degassed with nitrogen and Pd(PBut3)2 (0.010 g)
  2. additionwas added
  3. customThe tube was sealed
  4. temperatureheated
  5. additionThe mixture was diluted with EtOAc (5 ml)
  6. filtrationfiltered
  7. concentrationThe solution was concentrated in vacuo
  8. customwas purified by chromatography on silica
  9. customto give a reasonably pure material that
  10. customwas further purified by preparative HPLC

Sources & evidence

ORD record
ord-df7ee117c403476dbd09ebe02fc25446
Source dataset
uspto-grants-2013_04
Patent number
US08410114B2

Reaction notes

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