反应详情

A stirred mixture of 7-chloro-1,3-dihydro-3-methyl-5-phenyl-2H-1,4 -benzodiazepine-2-thione (3.0 g, 0.01 mol), phenyl acetic acid hydrazide (4.95 g, 0.033 mol) and butanol (150 ml) was refluxed for 16 hours while N2 was being bubbled through the mixture. The reaction mixture was concentrated under high vacuum, and the residue mixed with iced H2O. The product was filtered and dissolved in CH2Cl2. The CH2Cl2 was washed with dilute HCl and brine, dried over Na2SO4 and concentrated in vacuo. At this point it appeared that complete cyclization had not been achieved. Therefore, the residue was combined with acetic acid (100 ml) and refluxed for 2 hours under N2. The reaction mixture was concentrated in vacuo and the residue mixed with CH2Cl2 and H2O. The CH2Cl2 was washed with NaHCO3 and brine, dried over Na2SO4 and concentrated in vacuo. The material was crystallized from EtOAc-Skelly B to give 1.55 g, mp 195°-197° of the subtitled intermediate, which had a C:H:N:Cl ratio of 72.38:4.85:14.16:8.81. Calculated for C24H19N4Cl: 72.26:4.80:14.05:8.89.

1. customwas being bubbled through the mixture
2. concentrationThe reaction mixture was concentrated under high vacuum
3. additionthe residue mixed with iced H2O
4. filtrationThe product was filtered
5. dissolutiondissolved in CH2Cl2
6. washThe CH2Cl2 was washed with dilute HCl and brine
7. dry with materialdried over Na2SO4
8. concentrationconcentrated in vacuo
9. temperaturerefluxed for 2 hours under N2
10. concentrationThe reaction mixture was concentrated in vacuo
11. additionthe residue mixed with CH2Cl2 and H2O
12. washThe CH2Cl2 was washed with NaHCO3 and brine
13. dry with materialdried over Na2SO4
14. concentrationconcentrated in vacuo
15. customThe material was crystallized from EtOAc-Skelly B