4-(Trifluoromethyl)aniline → Methyl 3-methyl-2-(3-(4-(3-(4-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoate

Participants

Reaction Conditions

Reaction Steps

To Methyl 2-(3-(4-aminophenyl)isoxazole-5-carboxamido)-3-methylbutanoate (example 151, step 3, 500 mg) dissolved in THF (10 ml) were added 4-(trifluoromethyl)aniline (254 mg) and carbonyl diimidazole (283 mg) and heated to reflux at 65° C. overnight. THF was removed completely under reduced pressure to get pale brown residue which was purified by silica gel column chromatography in 3:7 EtOAc: CHCl3 to get off white solid which was crystallized from methylene chloride to yield 375 mg (47%) off white solid. MS (ES+): m/z 505 (M+1); 1HNMR (DMSO-d6, 300 MHz): δ 9.19 (s, 1H), 9.18 (d, 1H), 9.09 (s, 1H), 7.85 (d, 2H), 7.67 (s, 1H), 7.65 (d, 2H), 7.63 (d, 2H), 7.6 (d, 2H), 4.29 (m, 1H), 3.66 (s, 3H), 2.2 (m, 1H), 0.95 (d, 6H).

Provenance & Evidence