反应详情

温度

25 °C

To a solution of [(2R*,5R*)-5-(3-amino-phenyl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester (0.1 g, 0.253 mmol) in DMF (2.5 ml) was added 5-bromo-pyridine-2-carboxylic acid (78 mg, 0.379 mmol), EDC (0.074 g, 0.379 mmol), HOAt (0.053 g, 0.379 mmol) and DIPEA (0.083 g, 0.632 mmol) and the reaction mixture was stirred for 2 h at 25° C. After evaporation of the DMF the residue was taken up in NaH2PO4 solution and extracted with EtOAc. Combined organic layers were washed with 5% NaHCO3 solution and brine, dried over MgSO4, filtered and concentrated. The crude product was crystallized from diisopropylether to provide the title compound as a white crystalline solid: TLC (hexane/EtOAc 1:1): Rf=0.61; HPLC RtH5=1.565 min; 1H NMR (360 MHz, CDCl3): ): δ 11.01 (s, 1H), 9.92 (s, 1H), 8.71 (dd, 1H), 8.21 (d, 1H), 8.10 (dd, 1H), 7.87 (s, 1H), 7.73 (d, 1H), 7.46 (t, 1H), 7.18 (d, 1H), 4.10 (m, 2H), 1.75 (s, 3H), 1.67 (s, 3H), 1.58 (s, 9H); ESIMS: 571, 573 [(M+H)+].

1. customAfter evaporation of the DMF the residue
2. extractionextracted with EtOAc
3. washCombined organic layers were washed with 5% NaHCO3 solution and brine
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe crude product was crystallized from diisopropylether