Patent ID: 7060825

Claim:
In a process for synthesizing a compound of formula Ib: wherein R 1 and R 2 are each individually amino or N-alkyl substituted amino; hydroxy; alkoxy; keto; lower alkyl; R 3 is hydrogen; hydroxy; alkoxy; trifluoromethyl alkoxy; halo; sulfhydryl or alkylthio; R 4 is —C(O)—X; X is alkoxy; or γ-methylene glutamic acid, glutamic acid, aspartic acid or γ-methylene glutamate 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; the improvement comprising: reacting a bromo-alkyl-p-benzoic acid moiety with triethyl phosphite to form a 4-R 4 -carbonyloxyalkyl-phenyl-alkyldiethylphosphonate; and reacting the 2,4-diamino-6-formyl-quinazoline with the 4-R 4 -carbonyloxyalkyl-phenyl-alkyldiethylphosphonate to form a product with an unsaturated bond; and reducing said product to form the compound of formula Ib.