Solid-phase synthesis of 3-alkyl-2-arylamino-3,4-dihydroquinazolines

The solid-phase synthesis of 3-alkyl-2-arylamino-3,4-dihydroquinazolines using an N-Fmoc-β-amino-2-nitrobenzenepropanoic acid scaffold is described. The resin-bound scaffold was reductively alkylated with aldehydes or ketones after Fmoc deprotection, followed by reduction of the nitro group with tin(II) chloride. Subsequent cyclization of the 1,3-diamine intermediates with aryl isothiocyanates in the presence of 1,3-diisopropylcarbodiimide (DIC) afforded the desired products in high purity with moderate to good yield after trifluoroacetic acid (TFA) cleavage.