合成路线1

Condensation of N-benzyloxycarbonyl-D-serine (I) with 3-methylbenzylamine (II) in the presence of 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide.HCl (EDC) afforded amide (III). Reduction of this amide with borane gave amine (IV), which was then protected as the tert-butyl carbamate (V) with Boc2O. Subsequent treatment of (V) with methanesulfonyl chloride produced the corresponding mesylate (VI) which, without purification, was treated with methylamine in refluxing EtOH to provide triamine (VII). Alkylation of (VII) with methyl bromoacetate gave aminoacetate (VIII), and then, the tert-butoxycarbonyl protecting group was removed using HCl in EtOH. The resulting (IX) was treated with diisobutyl aluminum hydride in THF at -70 C to give aldehyde (X), and further reduction with NaBH4 of iminium salt (XI), derived from aldehyde (X), provided the optically active diazepine (XII). Deprotection of the benzyloxycarbonyl group, followed by coupling of the resulting amine (XIII) with indazole-3-carboxylic acid (XIV) in the presence of EDC gave the target amide, which was then converted to the dihydrochloride.