反应详情

A suspension of 3′-methyl-[1,1′-biphenyl]-4-carboxylic acid of Step B (0.50 g, 2.36 mmol) in thionyl chloride (3 mL) was heated at reflux for 30 minutes. After cooling, the thionyl chloride was removed in vacuo. The residue was dissolved in toluene and concentrated in vacuo to give the crude acid chloride as a yellow oil. The acid chloride was then dissolved in dichloromethane (5 mL) and slowly added to a solution of the 10,11-dihydro-5H-pyrrolo [2,1-c][1,4]benzodiazepine (0.65 g, 3.53 mmol) and N,N-diisopropylethyl amine (0.90 mL, 5.17 mmol) in dichloromethane (15 mL). After stirring for 2 hours, the reaction was quenched with water. The organic layer was washed with 1 N hydrochloric acid, 1 N sodium hydroxide and brine, dried over anhydrous sodium sulfate, and concentrated in vacuo to give a white foam. Purification of the residue by flash chromatography using a solvent gradient from 15% to 25% of ethyl acetate in hexane gave a white foam which was crystallized by sonication from ethyl acetate/hexane to provide the title compound (0.74 g, 82.8%) as a white solid, m.p. 128-130° C.

1. temperaturewas heated
2. temperatureat reflux for 30 minutes
3. temperatureAfter cooling
4. customthe thionyl chloride was removed in vacuo
5. dissolutionThe residue was dissolved in toluene
6. concentrationconcentrated in vacuo
7. customto give the crude acid chloride as a yellow oil
8. customthe reaction was quenched with water
9. washThe organic layer was washed with 1 N hydrochloric acid, 1 N sodium hydroxide and brine
10. dry with materialdried over anhydrous sodium sulfate
11. concentrationconcentrated in vacuo
12. customto give a white foam
13. customPurification of the residue by flash chromatography
14. customgave a white foam which
15. customwas crystallized by sonication from ethyl acetate/hexane