1) The cyclization of 2-(benzyloxycarbonylamino)-4-chlorobenzoic acid (I) by means of PBr3 in refluxing ethyl ether gives 7-chloro-2H-3,1-benzoxazine-2,4(1H)-dione (II), which is condensed with 4-bromo-2-fluorobenzylamine (III) in refluxing THF yielding 2-amino-N-(4-bromo-2-fluorobenzyl)-4-chloro-benzamide (IV). The cyclization of (IV) with carbonyldiimidazole (CDI) in refluxing dioxane affords 3-(4-bromo-2-fluorobenzyl)-7-chloro-1,2,3,4-tetrahydroquinazoline-2,4-dione (V), which is alkylated with ethyl bromoacetate (VI) by means of NaH in DMF to give ethyl 3-(4-bromo-2-fluorobenzyl)-7-chloro-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-1-acetate (VII). Finally, this compound is hydrolyzed with NaOH in refluxing methanol.
2) The condensation of 4-chloro-2-nitrobenzoic acid (VIII) with benzylamine (III) by means of CDI in THF gives the corresponding amide (IX), which is reduced with Fe in acetic acid to the 2-aminobenzamide (IV). The cyclization of (IV) with carbonyldiimidazole (CDI) in refluxing dioxane affords 3-(4-bromo-2-fluorobenzyl)-7-chloro-1,2,3,4-tetrahydroquinazoline-2,4-dione (V), which is alkylated with ethyl bromoacetate (VI) by means of NaH in DMF to give ethyl 3-(4-bromo-2-fluorobenzyl)-7-chloro-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-1-acetate (VII). Finally, this compound is hydrolyzed with NaOH in refluxing methanol.
3) The alkylation of 2-amino-4-chlorobenzamide (X) with ethyl bromoacetate (VI) by means of K2CO3 in hot DMF gives ethyl 2-(2-carbamoyl-4-chlorophenylamino)acetate (XI), which is cyclized with CDI at 150 C yielding ethyl 7-chloro-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-1-acetate (XII). Finally, this compound is alkylated with 4-bromo-2-fluorobenzyl chloride (XIII) by means of NaH in DMF to afford quinazoline (VII) already obtained.