反应详情

To a solution of [(2R,5R)-5-(5-amino-2-fluoro-phenyl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester (step p Example 1) (2.2 g, 5.43 mmol) in DMF (20 ml) was added at 0-5° C. 5-cyano-3-methyl-pyridine-2-carboxylic acid (0.968 g, 5.97 mmol), EDC (1.095 g, 7.05 mmol), HOAt (1.182 g, 8.68 mmol) and the reaction mixture was stirred at 25° C. for 16 h. The reaction mixture was added to cold saturated NaHCO3 solution and the product was extracted with TBME. Combined TBME layers were washed with H2O and brine, dried over MgSO4, filtered and concentrated to obtain after crystallization from diisopropylether the title compound as colorless crystals: UPLC RtH5=1.472 min); ESIMS: 550; [(M+H)+]; 1H NMR (400 MHz, CDCl3): δ 11.11 (s, 1H), 10.11 (s, 1H), 8.79 (br s, 1H), 8.01 (s, 1H), 7.84 (m, 1H), 7.68 (dd, 1H), 7.21 (dd, 1H), 4.49 (d, 1H), 4.16 (d, 1H), 1.76 (s, 3H), 1.64 (s, 3H), 1.62 (s, 9H).

1. extractionthe product was extracted with TBME
2. washCombined TBME layers were washed with H2O and brine
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated
6. customto obtain
7. customafter crystallization from diisopropylether the title compound as colorless crystals
8. customUPLC RtH5=1.472 min