反应详情

温度

90 °C

To a suspension of 7-chloro-2-methyl-5,10-dihydro-11H-pyrrolo[2,1-c][1,4]benzodiazepin-11-one (40.6 g, 164.58 mmoles) in methoxybenzene (250 mL) at 70° C. add N,N-dimethylaniline (2.8 equiv; 58.59 mL, 460.8 mmoles) in one portion followed by phosphoryl chloride (2.3 equiv (molar); 35.18 mL, 378.52 mmoles) over 20 minutes, controlling the exotherm by addition. Heat the resultant dark solution at 90° C. for 1.5 h. Add additional phosphoryl chloride (0.33 equiv; 5.05 mL, 54.31 mmoles) and heat the mixture at 90° C. for a further 1 h to give complete conversion. Evaporate to near dryness and partition the residue between water (500 mL) and ethyl acetate (2×500 mL). Combine organic layers and wash with water (500 mL) then brine. Dry over Na2SO4, filter and evaporate onto silica. Pass through a silica gel pad with iso-hexane/ethyl acetate (gradient elution 5 to 25%). Combine product fractions and evaporate to a small amount of solvent. Add iso-hexane (150 mL) and collect the resulting yellow powder by filtration, to give 7,11-dichloro-2-methyl-5H-pyrrolo[2,1-c][1,4]benzodiazepine (34.0 g, 78% yield). MS (m/z): 265.1 (M+1).

1. additionby addition
2. temperatureheat the mixture at 90° C. for a further 1 h
3. customto give complete conversion
4. customEvaporate
5. custompartition the residue between water (500 mL) and ethyl acetate (2×500 mL)
6. washCombine organic layers and wash with water (500 mL)
7. dry with materialDry over Na2SO4
8. filtrationfilter
9. customevaporate onto silica
10. customCombine product fractions and evaporate to a small amount of solvent
11. customAdd iso-hexane (150 mL) and collect the resulting yellow powder
12. filtrationby filtration