The invention claimed herein relates to an improvement in a process for synthesizing a compound of formula Ib:wherein R1 and R2 are each individually amino or N-
alkyl substituted amino; hydroxy; alkoxy; keto; lower
alkyl; or a
nitrogen or
oxygen protecting group;R3 is
hydrogen; hydroxy; alkoxy;
trifluoromethyl alkoxy; halo; sulfhydryl or alkylthio;R4 is —C(O)—X;X is hydroxy; alkoxy; or an
amino acid residue;in which process a 2-amino-5-nitro-
benzonitrile starting
reagent is cyclized to form 2,4-diamino-6-nitro-
quinazoline, which is converted to 2,4,6-triamino-
quinazoline, which is converted to 2,4-diamino-6-cyano-
quinazoline, which is converted to 2,4-diamino-6-formyl-quinazoline;in which the improvement includes:reacting an R4-p-
benzoic acid alkylene
moiety with triethyl phosphite to form a 4-R4-carbonyloxyalkyl-phenyl-alkyldiethylphosphite; andreacting the 2,4-diamino-6-formyl-quinazoline with the 4-R4-carbonyloxyalkyl-phenyl-alkyldiethylphosphite to form the compound of formula Ib.