Potassium Phosphate, Tribasic → 1-[6-fluoro-2'-(trifluoromethoxy)-1,1'-biphenyl-3-yl]-5-methyl-1H-pyrazole-3-carboxamide

HRID 733149Notes

Reaction equation

Cl[C:2]1[CH:3]=[C:4]([N:9]2[C:13]([CH3:14])=[CH:12][C:11]([C:15]([NH2:17])=[O:16])=[N:10]2)[CH:5]=[CH:6][C:7]=1[F:8].[F:18][C:19]([F:31])([F:30])[O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1>[F:8][C:7]1[C:2]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=2[O:20][C:19]([F:18])([F:31])[F:30])=[CH:3][C:4]([N:9]2[C:13]([CH3:14])=[CH:12][C:11]([C:15]([NH2:17])=[O:16])=[N:10]2)=[CH:5][CH:6]=1

Participants

Conditions

Temperature: 95 °C

Procedure

To a solution of the carboxamide (from step 2) (0.063 g, 0.2 mmol) and 2-trifluromethoxyphenyl boronic acid (0.076 g, 0.37 mmol) in dioxane (1 mL) were added NiCl2(dppf)2 (0.002 g, 1 mole %) and potassium phosphate (0.158 g, 0.74 mmol) and the mixture was stirred at 95° C. for 16 hours. After cooling, the reaction was partitioned between EtOAc and water. The organic phase was washed with saturated sodium bicarbonate, brine and then dried over sodium sulfate. The crude product, obtained upon concentration of the organic phase, was purified by reverse phase HPLC (acetonitrile/water system) (gradient: 10% to 90% acetonitrile over 10 minutes) to yield the titled product (0.009 g, 9.5%).

Workup

temperatureAfter cooling
customthe reaction was partitioned between EtOAc and water
washThe organic phase was washed with saturated sodium bicarbonate, brine
dry with materialdried over sodium sulfate
customThe crude product, obtained upon concentration of the organic phase
customwas purified by reverse phase HPLC (acetonitrile/water system) (gradient: 10% to 90% acetonitrile over 10 minutes)

Sources & evidence

ORD record: ord-3a43a05f902d4f589d5cd50b77abe14a
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07589116B2

Reaction notes

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