Sodium Bicarbonate → HCID 178483094, compound

Participants

Reaction Steps

A mixture of (2-chloro-quinazolin-4-yl)-dimethyl-amine obtained in step B of example 1 (3.00 g, 14.4 mmol) and cis-(4-amino-cyclohexyl)-carbamic acid tert-butyl ester (3.72 g, 17.4 mmol) in 2-propanol (10 mL) was stirred at reflux for 5.5 days, poured into saturated aqueous NaHCO3, and the aqueous layer was extracted with CHCl3 (three times). The combined organic layer was dried over MgSO4, filtered, concentrated, and purified by flash chromatography (NH-silica, 20% EtOAc in hexane) to give cis-[4-(4-dimethylamino-quinazolin-2-ylamino)-cyclohexyl]-carbamic acid tert-butyl ester including solvent (5.44 g) as a colorless oil. To a solution of the above material (5.44 g) in EtOAc (10 mL) was added 4 M hydrogen chloride in EtOAc (50 mL). The reaction mixture was stirred at ambient temperature for 2 hr, and concentrated. The residue was alkalized with saturated aqueous NaHCO3, and the precipitate was collected by filtration to give cis-N2-(4-amino-cyclohexyl)-N4,N4-dimethyl-quinazoline-2,4-diamine (2.26 g, 55%) as a white solid. The aqueous layer was extracted CHCl3 (three times). The combined organic layer was dried over MgSO4, filtered, and concentrated to give cis-N2-(4-amino-cyclohexyl)-N4,N4-diethyl-quinazoline-2,4-diamine (687 mg, 17%) as a white solid.

Provenance & Evidence