反应详情

温度

90 °C

A mixture of (R)-6-amino-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (50 g, 172 mmol), methansulfonic acid 1-benzhydryl-3-methylazetidin-3-yl ester (Preparation #14, Step B, 95 g, 258 mmol) and K2CO3 (47.6 g, 344 mmol) in iPrOH (1 L) was stirred at 90° C. for 16 h. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was dissolved in water (1 L) and extracted with EtOAc (3×500 mL). The combined organic phase was dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated and the residue was purified by column chromatography on silica gel (eluting with 30-60% EtOAc in petroleum ether) to give (R)-6-(1-benzhydryl-3-methyl-azetidin-3-ylamino)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (31 g, 38%) as a yellow solid. 1H NMR (CDCl3, 400 MHz): δ 8.47 (s, 1H), 7.45-7.40 (m, 4H), 7.30-7.26 (m, 4H), 7.22-7.16 (m, 2H), 6.78 (d, J=9.0 Hz, 1H), 6.08-6.02 (m, 2H), 4.64-4.57 (t, J=6.8 Hz, 1H), 4.53-4.41 (d, J=14.8 Hz, 3H), 3.30 (m, 2H), 3.15 (m, 2H), 1.65 (s, 3H), 1.46 (d, J=6.8 Hz, 3H). SFC (Table 1, Method 1) Rt=4.36 min.

1. temperatureThe reaction mixture was cooled to ambient temperature
2. concentrationconcentrated in vacuo
3. dissolutionThe residue was dissolved in water (1 L)
4. extractionextracted with EtOAc (3×500 mL)
5. dry with materialThe combined organic phase was dried over anhydrous Na2SO4
6. filtrationfiltered
7. concentrationThe filtrate was concentrated
8. customthe residue was purified by column chromatography on silica gel (eluting with 30-60% EtOAc in petroleum ether)