反应详情

A mixture of (R)-7-bromo-4-methyl-6-(3-methyl-azetidin-3-ylamino)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (4.0 g, 10.4 mmol) and polyformaldehyde (0.78 g, 26 mmol) in MeOH (10 mL) was stirred at ambient temperature for 10 min followed by the addition of AcOH (0.5 mL). The mixture was stirred at ambient temperature for 30 min before the addition of sodium cyanoborohydride (1.4 g, 22.8 mmol). The mixture was stirred at 40° C. overnight. The mixture was cooled to ambient temperature and concentrated in vacuo to give the residue, which was purified by chromatography on silica gel (eluting with 1% methanol in dichloromethane) to give (R)-7-bromo-6-(1,3-dimethyl-azetidin-3-ylamino)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (2.8 g, 62%). 1H NMR (400 MHz, CDCl3) δ=8.77 (s, 1H), 7.14 (s, 1H), 6.01 (s, 1H), 4.63 (q, J=6.8 Hz, 1H), 4.56 (d, J=12.8, 2H), 4.46 (s, 1H), 3.87 (m, 2H), 3.46 (m, 2H), 2.57 (s, 3H), 1.65 (s, 3H), 1.55 (d, J=6.8 Hz, 3H). LC/MS (Table 1, Method 25) Rt=0.659 min.; MS m/z: 394 [M+H]+ and 396 [M+H+2]+.

1. stirringThe mixture was stirred at 40° C. overnight
2. temperatureThe mixture was cooled to ambient temperature
3. concentrationconcentrated in vacuo
4. customto give the residue, which
5. customwas purified by chromatography on silica gel (eluting with 1% methanol in dichloromethane)