1,3-Benzenediamine, 5-chloro- → (3-Amino-5-chlorophenyl)-(6,7-dimethoxyquinazolin-4-yl)amine hydrochloride

Participants

Reaction Conditions

Reaction Steps

4-Chloro-6,7-dimethoxyquinazoline (200 mg, 0.89 mmol) and 5-amino-3-chloroaniline (253 mg, 1.78 mmol) were combined in isopropanol (3 mL) and heated to reflux for 16 hours under an atmosphere of dry nitrogen. After cooling to 20° C. the mixture was diluted with methanol (5 mL) and the resulting precipitate was filtered and dried, in vacuo, to afford 252 mg (77%) of (3-amino-5-chlorophenyl)-(6,7-dimethoxyquinazolin-4-yl)amine hydrochloride (mp. 298°-301° C.; LC-MS: 331 (MH+)). A portion of this product (175 mg, 0.476 mmol) was dissolved in 80% acetic acid/H2O (12 mL), cooled to 0° C., and a solution of NaNO2 (36 mg, 0.516 mmol) in H2O (300 μL) was added. The solution was stirred for 10 minutes at 0° C. and NaN3 (33 mg, 0.50 mmol) in H2O (300 μL) was added. The reaction mixture was allowed to warm to 20° C. and stirred 16 hours. The resulting precipitate was filtered and dissolved in 10% methanol in CHCl3 and the solution was washed with saturated aqueous NaHCO3, and brine, dried over Na2SO4, filtered and concentrated in vacuo to yield 59 mg (35%) of the title product as a yellow solid; mp 205°-206° C.

Provenance & Evidence