反应详情

温度

-30 °C

A suspension of 2,4-bis(4-methyl-1-piperazinyl)-3H-[1,5]benzodiazepine (1.702 g, 5 mmol) in tetrahydrofuran (20 ml) under constant flow of argon was cooled to −30° C. A solution of lithium diisopropylamide (LDA) (2 M, 3.75 ml, 7.5 mmol) was added dropwise. Thus obtained dark brown suspension was allowed to warm to −5° C. until dissolved and then again cooled to −30° C. Propionaldehyd (0.54 ml, 7.5 mmol) was added during 5 min. The resulting clear yellow solution was allowed to warm to −5° C., triethylamine (5.55 ml, 40 mmol) and pyridine (0.040 ml, 0.5 mmol) were added. A solution of trifluoroacetic anhydride (4.2 ml, 30 mmol) in tetrahydrofuran (6 ml) was added dropwise maintaining the temperature at −5° C. The reaction mixture was stirred for another hour. Methanol (5 ml) and while strongly agitated NaOH (1 M, 35 ml) were added dropwise. The reaction mixture was stirred for four hours while slowly warming to room temperature. The solution was made acidic at ph of 1 and extracted with dichloromethane (3×25 ml). The water phase was made alkalic at a pH of 10 and extracted with diethyl ether (15×25 ml). After each extraction water phase was adjusted to pH of 10. The ether phase was dried over anhydrous Na2SO4 and ether was evaporated at reduced pressure to give 1, 701 g (89%) of the title compound as a yellow resin.

1. temperatureto warm to −5° C.
2. dissolutionuntil dissolved
3. temperatureagain cooled to −30° C
4. temperatureto warm to −5° C.
5. temperaturemaintaining the temperature at −5° C
6. stirringThe reaction mixture was stirred for four hours
7. temperaturewhile slowly warming to room temperature
8. extractionextracted with dichloromethane (3×25 ml)
9. extractionextracted with diethyl ether (15×25 ml)
10. extractionAfter each extraction water phase
11. dry with materialThe ether phase was dried over anhydrous Na2SO4 and ether
12. customwas evaporated at reduced pressure