反应详情

To a solution of ((2R,5R)-5-{5-[(5-cyano-3-methyl-pyridine-2-carbonyl)-amino]-2-fluoro-phenyl}-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl)-carbamic acid tert-butyl ester in CH2Cl2 (0.3 ml) was added TFA (0.6 ml) and the reaction mixture was kept at 25° C. for 2 h. The reaction was added to cold 10% aqueous K2CO3 solution and the product extracted with EtOAc. Combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated to provide 5-cyano-3-methyl-pyridine-2-carboxylic acid [3-((3R,6R)-5-amino-3,6-dimethyl-6-trifluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-4-fluoro-phenyl]-amide as a colorless foam. The title compound was converted into its hydrochloride salt by dissolving the free base in CH2Cl2, adding 1 eq of 2N HCl in Et2O, evaporation to dryness, followed by crystallization from CH2Cl2-Et2O to provide the title compound as a white solid: HPLC RtH5=0.957 min; ESIMS: 450 [(M+H)+]; 1H NMR (600 MHz, DMSO-d6): 11.0 (s, 1H), 9.60 (d, 2H), 9.04 (s, 1H), 8.41 (s, 1H), 7.96 (m, 1H), 7.83 (dd, 1H), 7.33 (dd, 1H), 4.37 (d, 1H), 4.11 (d, 1H), 2.56 (s, 3H), 1.73 (s, 3H), 1.70 (s, 3H).

1. extractionthe product extracted with EtOAc
2. washCombined organic layers were washed with brine
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated