Potassium Phosphate, Tribasic → HCID 118324058, compound

HRID 1778289Notes

Reaction equation

HRID 1778289 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]1[CH:28]=[C:29](/[CH:33]=[CH:34]/B(O)O)[CH:30]=[CH:31][CH:32]=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:34]=[CH:33]/[C:29]2[CH:30]=[CH:31][CH:32]=[C:27]([F:26])[CH:28]=2)=[CH:19][CH:20]=1

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 16217749B-[(1E)-2-(3-Fluorophenyl)ethenyl]boronic acidHCID 1183240034-bromo-6-((4-chlorophenyl)(thiazol-2-yl)methyl)quinolin-2(1H)-one

Product 1

HCID 118324058HCID 118324058, compound

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 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-(3-fluorophenyl)vinylboronic acid (61.5 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 72 h. 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 and the fractions were lyophilized. The lyophilized product was washed with hot hexanes to remove residual SPhos, filtered, and dried under vacuum to yield (E)-6-((4-chlorophenyl)(thiazol-2-yl)methyl)-4-(3-fluorostyryl)quinolin-2(1H)-one as an off-white solid.

Workup

  1. customthe layers were separated
  2. washThe organic phase was washed with saturated sodium bicarbonate
  3. dry with materialwater, dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by RP-HPLC
  7. washThe lyophilized product was washed with hot hexanes
  8. customto remove residual SPhos
  9. filtrationfiltered
  10. customdried under vacuum

Sources & evidence

ORD record
ord-8a20ae385f27443e8602a9166b3bbf25
Source dataset
uspto-grants-2016_02
Patent number
US09266835B2

Reaction notes

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