反应详情

Phosphorous oxychloride (0.81 ml, 0.0086 mol) was added to a solution of 1-acetyl-4-(4-morpholinecarbonyl)-1,4-diazepane (4.02 g, 0.0157 mol) in dichloromethane (25 ml) and the mixture stirred for 30 minutes at room temperature. A solution of 2-amino-5-benzyloxy-4-methoxybenzonitrile (2 g, 0.0078 mol) in dichloromethane (25 ml) was then added and the reaction stirred for 18 hours at 40° C. On cooling, the reaction mixture was poured carefully in to ice/water (100 ml) and extracted with dichloromethane (2×100 ml). The combined organic layers were dried (MgSO4), filtered and evaporated under reduced pressure to give a brown oil. The crude product was purified on silica gel eluting with a solvent gradient of methanol:dichloromethane (2:98 to 10:90 v/v) to give the subtitle compound. Rf 0.67 (0.880 aqueous ammonia:methanol:dichloromethane 1:7:92, v/v). MS m/z 492 (MH)+.

1. stirringthe reaction stirred for 18 hours at 40° C
2. temperatureOn cooling
3. extractionextracted with dichloromethane (2×100 ml)
4. dry with materialThe combined organic layers were dried (MgSO4)
5. filtrationfiltered
6. customevaporated under reduced pressure
7. customto give a brown oil
8. customThe crude product was purified on silica gel eluting with a solvent gradient of methanol:dichloromethane (2:98 to 10:90 v/v)