Trifluoroacetic acid → N-[3-[(3R)-5-Amino-3-(difluoromethyl)-3,6-dihydro-2H-1,4-oxazin-3-yl]-4-fluorophenyl]-5-cyano-3-methyl-2-pyridinecarboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of ((R)-5-{5-[(5-cyano-3-methyl-pyridine-2-carbonyl)-amino]-2-fluoro-phenyl}-5-difluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl)-carbamic acid tert-butyl ester (23 g, 45.77 mmol) in DCM (615 ml) was added under argon TFA (23 ml, 302.27 mmol) below 25° C. After stirring for 18 h at 25° C., another TFA (12 ml, 151.13 mmol) was added. After stirring at 25° C. for another 6 h, cooled down to −5° C., quenched by 12.5% NH3 aqueous solution (110 ml). The DCM phase was collected and water (100 ml) was added. The DCM of the diphase solution was removed to provide a yellowish suspension. Filtered and dried to provide the title compound as yellowish crystals. ESIMS: 404 [(M+H)+]; 1H NMR (400 MHz, DMSO-d6): 10.72 (s, 1H), 8.96 (s, 1H), 8.38 (s, 1H), 7.99 (dd, 1H), 7.81 (m, 1H), 7.18 (d, 1H), 6.17 (br s, 2H), 6.15 (t, 1H), 3.98 (m, 4H), 2.53 (s, 3H).

Provenance & Evidence