Oxalyl chloride → 3-(1-methyl-1H-indol-3-yl)-4-(1-methyl-6-morpholin-4-yl-1H-indol-3-yl)pyrrole 2,5-dione

Participants

Reaction Conditions

Reaction Steps

A solution of 1-methyl-6-morpholin-4-yl-1H-indole (0.50 g, 2.31 mmol) in CH2Cl2 (5 mL) (dried over 3A° molecular sieves) was cooled to 0° C. Oxalyl chloride (0.4 mL, 4.62 mmol), was added dropwise over 5 min. The mixture was stirred at 0° C. for 4 h and evaporated. The residual solid was triturated with ether, filtered, washed with ether and dried under vacuum for 30 min. 1-Methyl -3-indoleacetimidic acid isopropyl ester hydrochloride (0.58 g, 2.20 mmol) and CH2Cl2 (9 mL) were added to the yellow solid at 0° C. Et3N (dried over 3A° molecular sieve) (1.8 mL) was added dropwise over 10 min. and then the orange-red mixture was stirred at room temperature overnight. The mixture was diluted with EtOAc, washed with 1 N NaOH and the aqueous layer was back-extracted with EtOAc. The combined organic extracts were washed with brine, dried (K2CO3) and evaporated. The residue was dissolved in MeOH (100 mL) containing TsOH.H2O (3.30 g, 17.3 mmol ) and the mixture was stirred at room temperature for 4 h. After the solvents were removed under reduced pressure the residue was diluted with EtOAc (500 mL) and made basic using aqueous NaHCO3. The organic layer was separated and the aqueous layer was back extracted with EtOAc. The combined organic extracts were washed with brine, dried (MgSO4), and evaporated. Chromatography of the residue over silica gel using 30-70% EtOAc/hexanes gave 3-(1-methyl-1H-indol-3-yl)-4-(1-methyl-6-morpholin-4-yl-1H-indol-3-yl)pyrrole 2,5-dione (0.30 g, 30%) as an orange solid.

Provenance & Evidence