Sodium hydride → 1-(4-Amino-5-fluoro-7-quinazolinyl)-1,5,6,7-tetrahydro-3,6,6-trimethyl-4H-indol-4-one

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Reaction Steps

3,6,6-Trimethyl-1,5,6,7-tetrahydro-indol-4-one (0.61 mmol, 107.6 mg) is dissolved in 5 mL DMF. To this solution is added sodium hydride (60% suspension in mineral oil) (0.77 mmol, 30.8 mg) and the mixture is stirred at rt for 5 min. and then 5,7-Difluoro-quinazolin-4-ylamine (0.55 mmol, 100 mg) is added. The reaction is stirred at 50° C. for 22 h. The reaction is cooled and quenched by pouring into 100 ml sat. NH4Cl aq. and extracted 3 times with 20 mL CH2Cl2. The combined organics are dried with Na2SO4, concentrated, and purified by silica gel chromatography on Biotage using a gradient of 0-15% MeOH in CH2Cl2. 1-(4-Amino-5-fluoro-quinazolin-7-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one is isolated (35 mg, LC/MS m/z=339 [M+H]+) as a white powder.

Provenance & Evidence