The condensation of L-glutamic acid diethyl ester (I) with 4-nitrophthalic anhydride (II) by means of DIEA in refluxing toluene gives the 4-nitrophthalimide (III), which is reduced with H2 over Pd/C to yield the 4-aminophthalimide (IV). The reduction of (IV) with Zn/HCl in ethanol affords a 3:1 mixture of the 5-aminoisoindolinone (V) and 6-aminoisoindolinone (VI) that is separated by chromatography. The desired isomer (V) is condensed with 9-(bromomethyl)-3-methylbenzo[f]quinazolin-1(2H)-one (VII) (obtained by bromination of 3,9-dimethylbenzo[f]quinazolin-1(2H)-one (VIII) with NBS) in DMF at 110?C to provide the precursor (IX). Finally, the ester groups of (IX) are hydrolyzed with NaOH in methanol.

The condensation of L-glutamic acid diethyl ester (I) with 4-nitrophthalic anhydride (II) by means of DIEA in refluxing toluene gives the 4-nitrophthalimide (III), which is reduced with H2 over Pd/C to yield the 4-aminophthalimide (IV). The reduction of (IV) with Zn/HCl in ethanol affords a 3:1 mixture of the 5-aminoisoindolinone (V) and 6-aminoisoindolinone (VI) that is separated by chromatography. The desired isomer (V) is condensed with 9-(bromomethyl)-3-methylbenzo[f]quinazolin-1(2H)-one (VII) (obtained by bromination of 3,9-dimethylbenzo[f]quinazolin-1(2H)-one (VIII) with NBS) in DMF at 110?C to provide the precursor (IX). Finally, the ester groups of (IX) are hydrolyzed with NaOH in methanol.