1-Hydroxybenzotriazole → HCID 68504999, compound

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Reaction Steps

N-(4-chloro-2-fluorophenyl)-6,7-dimethoxy-2-[4-(methylamino)piperidin-1-yl]quinazoline-4-amine (445 mg), 1-(tert-butoxycarbonyl)-L-proline (323 mg), HOBt (135 mg) and EDCI hydrochloride (290 mg) were added in that order to DMF (10 mL), followed by stirring at room temperature for 24 hours. Ethyl acetate and a saturated sodium bicarbonate aqueous solution were added to the reaction solution, and the organic layer was separated. Next, the organic layer was washed with saturated brine, dried over magnesium sulfate and then filtered. The solvent was evaporated under a reduced pressure. By purifying the residue by silica gel flash column chromatography (chloroform-MeOH), N-(1-{4-[(4-chloro-2-fluorophenyl)amino]-6,7-dimethoxyquinazolin-2-yl}piperidin-4-yl)-N-methyl-L-prolinamide was obtained. This was dissolved in ethyl acetate (10 mL), and 4 M HCl/ethyl acetate solution (0.5 mL) was added thereto. By evaporating the solvent under a reduced pressure and recrystallizing the resulting residue from EtOH-diethyl ether, N-(1-{4-[(4-chloro-2-fluorophenyl)amino]-6,7-dimethoxyquinazolin-2-yl}piperidin-4-yl)-N-methyl-L-prolinamide dihydrochloride (481 mg) was obtained as pale yellow powder.

Provenance & Evidence