反应详情

A stirred solution of 3.0 g (9.57 mmol) of tert.butyl[1(R or S)-(6,7,8,9-tetrahydropyrido[1,2-a]indol-8(R or S)-yl)ethyl]carbamate in 150 ml of dichloromethane was treated dropwise at 0° C. with 1.28 g (10.3 mmol) of oxalyl chloride. After 5 minutes, the solvent was removed under reduced pressure and the residue was dissolved in 150 ml of dichloromethane and treated with 2.94 g (11 mmol) of isopropyl 1-methyl-3-indoleacetimidate hydrochloride and 4.38 g (43 mmol) of triethylamine at 0° C. under nitrogen. After warming to room temperature, the solution was stirred for 24 hours, washed with water and dried over magnesium sulfate. The solvent was removed by evaporation and the residue was dissolved in 30 ml of pyridine. The resulting solution was cooled to ice bath temperature and treated dropwise with 1.5 ml (10.8 mmol) of trifluoroacetic anhydride. After 15 minutes, the solvent was removed under reduced pressure and the residue was partitioned between 200 ml of ethyl acetate and 200 ml of 0.2M hydrochloric acid. The organic layer was washed with 50 ml of sodium bicarbonate solution, dried over magnesium sulfate and evaporated to dryness. The residue was purified by flash chromatography on silica gel using ethyl acetate/petroleum ether (1:2) for the elution to give 1.35 g of 3-[8(R or S)-[1(R or S)-tert.butoxyformamidoethyl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione (diastereomer A) in the form of a red solid of melting point 255°-7° C. Further elution gave 1.38 g of diastereomer B as a red solid of melting point 230°-233° C.

1. customthe solvent was removed under reduced pressure
2. dissolutionthe residue was dissolved in 150 ml of dichloromethane
3. washwashed with water
4. dry with materialdried over magnesium sulfate
5. customThe solvent was removed by evaporation
6. dissolutionthe residue was dissolved in 30 ml of pyridine
7. temperatureThe resulting solution was cooled to ice bath temperature
8. waitAfter 15 minutes
9. customthe solvent was removed under reduced pressure
10. customthe residue was partitioned between 200 ml of ethyl acetate and 200 ml of 0.2M hydrochloric acid
11. washThe organic layer was washed with 50 ml of sodium bicarbonate solution
12. dry with materialdried over magnesium sulfate
13. customevaporated to dryness
14. customThe residue was purified by flash chromatography on silica gel
15. washfor the elution