反应详情

A suspension of 11-(chloroacetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one (276 g, 0.959 mol), and 2-[(diethylamino)methyl]piperidine dihydrochloride (244.95 g, 100.7 mol), of sodium carbonate (223.9 g, 2.112 mol) and acetonitrile (1.92 liters) are stirred for 6 hours at a reaction temperature of 70° C. After this time, the 11-(chloroacetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one has 95-97% reacted (TLC). The mixture is left to stand overnight at ambient temperature, then suction filtered. The contents of the filter are washed three times, each time with acetonitrile (60 ml). The dark colored filtrates are discarded. The remaining solid is stirred for a further 2 hours with water (1.5 liters), suction filtered again and washed with another water (300 ml) and finally dried at 40° C. in a circulating air drier. The crude product thus obtained (390 g) is transferred into a 10 liter flask, taken up in 1-propanol (5.14 liters) and, after the addition of 2-[(diethylamino)methyl]piperidine dihydrochloride (13.5 g, 0.0555 mol) and anhydrous sodium carbonate (11.8 g, 0.1113 mol), refluxed for 16 hours. After the addition of activated charcoal (39 g) the mixture is heated to boiling for a further 30 minutes and the boiling hot mixture is then forced through a SEITZ filter. Clarification is repeated twice more in the same way using activated charcoal (20 g). The filtrate is left to stand for 12 hours at ambient temperature, the precipitated crystals are suction filtered and washed twice, each time with 1-propanol (50 ml). The product is again stirred with cold 1-propanol (0.5 liters), suction filtered and again washed twice, each time with 1-propanol (50 ml). It is then dried in a circulating air drier at 40° C. and almost colorless crystals (263 g) are obtained, mp. 226°-227° C.

1. customreacted (TLC)
2. waitThe mixture is left
3. filtrationsuction filtered
4. washThe contents of the filter are washed three times
5. filtrationfiltered again
6. washwashed with another water (300 ml)
7. customfinally dried at 40° C. in a circulating air drier
8. customThe crude product thus obtained (390 g)
9. customis transferred into a 10 liter flask
10. temperaturerefluxed for 16 hours
11. temperatureis heated
12. waitto boiling for a further 30 minutes
13. filtrationfilter
14. waitThe filtrate is left
15. waitto stand for 12 hours at ambient temperature
16. filtrationfiltered
17. washwashed twice
18. stirringThe product is again stirred with cold 1-propanol (0.5 liters), suction
19. filtrationfiltered
20. washagain washed twice
21. customIt is then dried in a circulating air drier at 40° C.