合成路线1

An improved synthesis of the title compound has been developed. Methyl ester (XX) was prepared from the known indazolylbenzoate sodium salt (XIX) by alkylation with iodomethane and K2CO3. Benzylic bromination of (XX) using NBS in the presence of AIBN as the radical initiator furnished the bromomethyl derivative (XXI). The brominated ester (XXI) was cyclized with trifluoromethanesulfonic acid at 100 C to provide the pyrazoloacridone (XXII) along with some phenol analogue (XXIII). Complete cleavage of the methyl ether of (XXII) was then accomplished with HBr in AcOH at 70 C. Further bromination of (XXIII) with elemental bromine in dichloroethane gave the ortho-bromophenol (XXIV). Introduction of the hydroxy group at C-10 was carried out by a two step sequence involving oxidation of (XXIV) to quinone (XXV) with (diacetoxy)iodobenzene, followed by its reduction to the corresponding hydroquinone (XXVI) with tetrabutylammonium triacetoxyborohydride. Condensation of (XXVI) with N-benzylethanolamine (XXVII) yielded the tertiary amine (XXVIII). Further bromine displacement in (XXVIII) with 1,3-propanediamine (XVI) provided (XXIX). The remaining bromine and the N-benzyl protecting groups of (XXIX) were finally subjected to hydrogenolysis in the presence of Pd/C