Potassium Phosphate, Tribasic → (E)-6-((4-chlorophenyl)(thiazol-2-yl)methyl)-4-(4-(trifluoromethyl)styryl)quinolin-2(1H)-one

HRID 1778288Notes

Reaction equation

HRID 1778288 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH:12]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=3)[C:13]3[S:14][CH:15]=[CH:16][N:17]=3)[CH:10]=2)[NH:5][C:4](=[O:25])[CH:3]=1.[F:26][C:27]([F:40])([F:39])[C:28]1[CH:33]=[CH:32][C:31](/[CH:34]=[CH:35]/B(O)O)=[CH:30][CH:29]=1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[Cl:24][C:21]1[CH:22]=[CH:23][C:18]([CH:12]([C:13]2[S:14][CH:15]=[CH:16][N:17]=2)[C:9]2[CH:10]=[C:11]3[C:6](=[CH:7][CH:8]=2)[NH:5][C:4](=[O:25])[CH:3]=[C:2]3/[CH:35]=[CH:34]/[C:31]2[CH:30]=[CH:29][C:28]([C:27]([F:26])([F:39])[F:40])=[CH:33][CH:32]=2)=[CH:19][CH:20]=1

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, Tribasic2×HCID 6153620trans-2-[4-(Trifluoromethyl)phenyl]vinylboronic acid2×HCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl2×HCID 1183240034-bromo-6-((4-chlorophenyl)(thiazol-2-yl)methyl)quinolin-2(1H)-one

Product 1

HCID 118324066(E)-6-((4-chlorophenyl)(thiazol-2-yl)methyl)-4-(4-(trifluoromethyl)styryl)quinolin-2(1H)-one

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalyst2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

4-Bromo-6-((4-chlorophenyl)(thiazol-2-yl)methyl)quinolin-2(1H)-one (80 mg, 0.185 mol, 1 equip), trans-2-[4-(trifluoromethyl)phenyl]vinylboronic acid (80 mg, 0.371 mmol, 2 equip), SPhos (15.5 mg, 0.037 mmol, 0.2 equip), tripotassium phosphate (78.7 mg, 0.371 mmol, 2 equip), and palladium acetate (4.2 mg, 0.019 mmol, 0.1 equip) were added to 1,4-dioxane (5 mL) and the resulting mixture stirred for 2 h. Additional trans-2-[4-(trifluoromethyl)phenyl]vinylboronic acid (80 mg, 0.371 mmol, 2 equip), SPhos (15.5 mg, 0.037 mmol, 0.2 equip), tripotassium phosphate (78.7 mg, 0.371 mmol, 2 equip), and palladium acetate (4.2 mg, 0.019 mmol, 0.1 equip) were added and the resulting mixture was stirred overnight. The reaction mixture was diluted with water and ethyl acetate and the layers were separated. The organic phase was washed with saturated sodium bicarbonate, then water, dried over Na2SO4, filtered and concentrated. The residue was purified by RP-HPLC to yield (E)-6-((4-chlorophenyl)(thiazol-2-yl)methyl)-4-(4-(trifluoromethyl)styryl)quinolin-2(1H)-one.

Workup

  1. stirringthe resulting mixture was stirred overnight
  2. customthe layers were separated
  3. washThe organic phase was washed with saturated sodium bicarbonate
  4. dry with materialwater, dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by RP-HPLC

Sources & evidence

ORD record
ord-d389f57f50104ae3866d0c36da0921a3
Source dataset
uspto-grants-2016_02
Patent number
US09266835B2

Reaction notes

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