Sodium hydride → N-(3-Methyl-5-isoxazolyl)-4-(trifluoromethyl)nicotinamide

HRID 1744262Notes

Reaction equation

[NH2:1][C:2]1[O:6][N:5]=[C:4]([CH3:7])[CH:3]=1.[H-].[Na+].[F:10][C:11]([F:22])([F:21])[C:12]1[C:17]([C:18](Cl)=[O:19])=[CH:16][N:15]=[CH:14][CH:13]=1.C(OCC)(=O)C.CCCCCC>CN(C)C=O>[CH3:7][C:4]1[CH:3]=[C:2]([NH:1][C:18](=[O:19])[C:17]2[C:12]([C:11]([F:22])([F:10])[F:21])=[CH:13][CH:14]=[N:15][CH:16]=2)[O:6][N:5]=1

Participants

Conditions

Temperature: 80 °C

Procedure

5-Amino-3-methylisoxazole (147 mg, 1.5 mmol) was dissolved in dimethylformamide (5 ml), sodium hydride (60% dispersion in mineral oil, 72 mg, 1.8 mmol) was added and subsequently, 4-trifluoromethylnicotinic acid chloride (314 mg, 1.5 mmol) was added under ice-cooling. The mixture was stirred under heating at 80° C. for 2 hours. The reaction mixture was poured into ice-water and extracted with ethyl acetate. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and the resulting residue was purified by thin layer chromatography (a developing solvent: ethyl acetate/hexane=1/1) to obtain the title compound (181 mg, yield 44%).

Workup

temperaturecooling
extractionextracted with ethyl acetate
washThe organic layer was washed with brine
dry with materialdried over anhydrous magnesium sulfate
customThe solvent was removed by distillation under reduced pressure
customthe resulting residue was purified by thin layer chromatography (a developing solvent

Sources & evidence

ORD record: ord-8b56b414d1c944f58a9ca45012b7cc37
Source dataset: uspto-grants-2006_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07015236B2

Reaction notes

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