反应详情

A mixture of 1,2-dihydro-7-(2-propynyl)-benzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepin-6-one (4.45 gm, 16.2 mmole), paraformaldehyde (3.6 gm), 4-methylpiperidine (1.93 gm, 1.2 eq) and copper(I) chloride (300 mg), in dioxane (75 ml) was stirred for 16 hours at room temperature. After the reaction was complete, the mixture was diluted with dichloromethane (DCM, 300 ml). The insolubles were filtered off through a pad of celite. The solution was concentrated on a rotary evaporator to an oil (48 gm). The desired product was purified by flash chromatography over a silica gel column (100 gm, SiO2, eluted with 1% CH3OH:1% diethylamine:98% DCM, 1.5 l). The material obtained as a yellow syrup was dissolved in ether (50 ml) and filtered once. The ethereal solution was added to a solution of fumaric acid (1.9 gm, 1.0 eq) in ether (30 ml) with fast stirring. The salt crashed out as a thick gum. This mixture was diluted with ether (300 ml) and stirred for i hour, while the gum turned slowly to a solid. The solid was collected and recrystallized once from hot ethanol to afford yellow crystals: 3.9 gm, m.p. 157°-158° C.

1. filtrationThe insolubles were filtered off through a pad of celite
2. concentrationThe solution was concentrated on a rotary evaporator to an oil (48 gm)
3. customThe desired product was purified by flash chromatography over a silica gel column (100 gm, SiO2, eluted with 1% CH3OH:1% diethylamine:98% DCM, 1.5 l)
4. customThe material obtained as a yellow syrup
5. filtrationfiltered once
6. stirringstirred for i hour, while the gum
7. customThe solid was collected
8. customrecrystallized once from hot ethanol
9. customto afford yellow crystals