反应详情

A suspension of 4-iodo-2-methoxybenzoic acid of Step B (2.5 g, 9.0 mmol) in thionyl chloride (10 mL) was heated at reflux for 1 hour. 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 brown solid. The acid chloride was then dissolved in dichloromethane (10 mL) and slowly added to a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (1.75 g, 9.5 mmol) and N,N-diisopropylethyl amine (3.4 mL, 19.5 mmol) in dichloromethane (20 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, filtered and concentrated in vacuo to give a yellow foam. Purification by flash chromatography on silica gel using a solvent gradient of 15 to 25% ethyl acetate in hexane provided 3.6 g of title product as a white foam, which was redissolved in dichloromethane and evaporated to dryness prior to use in the next step.

1. temperaturewas heated
2. temperatureat reflux for 1 hour
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 brown solid
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. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customto give a yellow foam
14. customPurification by flash chromatography on silica gel using a solvent gradient of 15 to 25% ethyl acetate in hexane