The reaction of 4-aminophthalimide (I) with NaNO2/HCl and then with CuCl/KCN gives 4-cyanophthalimide (II), which is treated with hydrazone in ethanol, yielding 6-cyanophthalazine-2,3(1H,4H)-dione (III). The reaction of (III) with refluxing POCl3 affords 1,4-dichlorophthalazine-6-carbonitrile (IV), which is condensed with 3-chloro-4-methoxybenzylamine (V) by means of TEA in THF to provide the secondary amine (VI). Finally, this compound is condensed with 4-hydroxypiperidine (VII) by means of DIEA in N-methyl-2-pyrrolidone to furnish the target phthalazine.

The reaction of 4-aminophthalimide (I) with NaNO2/HCl and then with CuCl/KCN gives 4-cyanophthalimide (II), which is treated with hydrazone in ethanol, yielding 6-cyanophthalazine-2,3(1H,4H)-dione (III). The reaction of (III) with refluxing POCl3 affords 1,4-dichlorophthalazine-6-carbonitrile (IV), which is condensed with 3-chloro-4-methoxybenzylamine (V) by means of TEA in THF to provide the secondary amine (VI). Finally, this compound is condensed with 4-hydroxypiperidine (VII) by means of DIEA in N-methyl-2-pyrrolidone to furnish the target phthalazine.

The condensation of the commercially available (Amersham) 14C-labeled 1-chloro-4-(3-chloro-4-methoxybenzylamino)phthalazine-6-carbonitrile (I) with 4-hydroxypiperidine (II) by means of K2CO3 and N-methyl-2-pyrrolidinone at 170 C yields the target phthalazine derivative.