Methylamine → HCID 178485520, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one hydrogen chloride (0.20 g, 0.41 mmol) and 7-amino-4,4-dimethyl-6-(methyloxy)-3,4-dihydro-2(1H)-quinolinone (0.10 g, 0.45 mmol) was taken in tetrahydrofuran (7.0 mL) and refluxed for 3 h. The reaction was cooled, diluted with saturated aqueous sodium bicarbonate and extracted with dichloromethane. The organic layer was separated, dried over magnesium sulfate, filtered, concentrated, diluted with tetrahydrofuran (10 mL) and treated with excess methyl amine (10 mL, 20 mmol, 2M in THF). The reaction was stirred for 16 h and then heated in a sealed tube at 50° C. for another 6 h. The reaction was cooled, diluted with water, and extracted with ethyl acetate. The organic layer was separated, dried over sodium sulfate and concentrated. The crude material was dissolved in tetrahydrofuran (5.0 mL), diluted with methanol (5.0 mL) and treated with sodium methoxide (700 mg, 28.5 mmol) and stirred at 50° C. for 3 h. The reaction was cooled, diluted with water, and extracted with ethyl acetate. The organic layer was separated, dried over sodium sulfate, and purified by flash silica gel column chromatography (dichloromethane to 8:1:1 mixture of dichloromethane:methanol:2M ammonia in methanol) to provide 2-[(2-{[4,4-dimethyl-6-(methyloxy)-2-oxo-1,2,3,4-tetrahydro-7-quinolinyl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluoro-N-methylbenzamide (0.100 g, 0.195 mmol, 43% over 3 steps).

Provenance & Evidence