Carbamate → 4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione

A stirred solution of 770 mg (2.25 mmol) of tert.butyl [1(R or S)-[6,7,8,9-tetrahydropyrido[1,2-a]indol-8(R or S)-yl]-2-methylpropyl]carbamate (diastereomer A) in 30 ml of dichloromethane at 0° C. was treated dropwise with 287 mg (2.4 mmol) of oxalyl chloride. After 5 minutes, the solvent was removed under reduced pressure and the residue was dissolved in 30 ml of dichloromethane and treated with 686 mg (2.57 mmol) of isopropyl 1-methyl-3-indoleacetimidate hydrochloride and 1.02 g (10 mmol) of triethylamine at 0° C. under nitrogen. After warming to room temperature, the solution was stirred for 18 hours, washed with 50 ml of water and dried over magnesium sulfate. The solvent was removed by evaporation and the residue was dissolved in 10 ml of pyridine. The stirred solution was cooled to ice bath temperature and treated dropwise with 664 μl (4.8 mmol) of trifluoroacetic anhydride. After 15 minutes, 50 ml of ethyl acetate was added and the organic phase was washed with water and 2M hydrochloric acid, 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 460 mg of 3-[8(R or S)-[1(R or S)-tert.butoxyformamido-2-methylpropyl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione (diastereomer A) as a red solid of melting point 223°-224° C.

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

ORD record

ord-29cd225414aa4b2ab184d8520f4109cc

Source dataset

uspto-grants-1998_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05721230