合成路线1

Reaction of 2-carboxybenzaldehye (I) with dimethyl phosphite in the presence of MeONa in MeOH affords the isobenzofuranylphosphonate (II), which is condensed with 2-fluoro-5-formylbenzonitrile (III) by means of triethylamine in THF to give the benzylidene-isobenzofuranone (IV). Basic hydrolysis of the nitrile group of compound (IV) followed by treatment with hydrazine hydrate leads to the phthalazinone-carboxylic acid (V) (1-3), which can also be obtained by treatment of isobenzofuranone (IV) first with hydrazine hydrate in THF, followed by hydrolysis of the resulting phthalazinone nitrile (VI) with aqueous NaOH (2). Coupling of carboxylic acid (V) with N-Boc-piperazine (VII) by means of HBTU and DIEA in dimethylacetamide yields the Boc-protected amide (VIII), which is then deprotected to compound (IX) by treatment with HCl in EtOH or MeOH. Finally, piperazine-phthalazinone (IX) is acylated with cyclopropanecarbonyl chloride (X) in the presence of triethylamine or DIEA in CH2Cl2 (1, 2). Alternatively, condensation of piperazine (XI) with cyclopropanecarbonyl chloride (X) in AcOH solution gives N-(cyclopropylcarbonyl)piperazine (XII) (2), which is then coupled with the phthalazinone-carboxylic acid (V) by means of HBTU and DIEA in acetonitrile or dimethylacetamide (2, 3). Scheme 1.