合成路线1

The reaction of N-methyl-N'-(3-methylbenzyl)ethylene-1,2-diamine (VIII) with (Boc)2O in chloroform gives N-(tert-butoxycarbonyl)-N-methyl-N'-(3-methylbenzyl)ethylene-1,2-diamine (IX), which is condensed with the chiral aziridine (X) by heating at 80 C to yield the diaminobutyric ester (XI). Selective elimination of the Boc protecting group of (XI) with HCl in methanol affords the methylamino intermediate (XII), which is treated with NaOH in ethanol/water to provide the carboxylic acid (XIII). The cyclization of (XIII) by means of DEC gives the perhydro-1,4-diazepin-5-one derivative (XIV), which is debenzylated by means of 1-chloroethyl chloroformate to yield the 6(S)-(benzyloxycarbonylamino)-4-methylperhydro-1,4-diazepin-5-one (XV). The reductive alkylation of (XV) with acetaldehyde, NaBH4 and TEA in methanol affords the 1-ethyl derivative (XVI), which is deprotected by means of conc. HBr to provide 6(S)-amino-1-ethyl-4-methylperhydro-1,4-diazepin-5-one (XVII). The reduction of (XVII) with BH3/THF gives 1-ethyl-4-methylperhydro-1,4-diazepin-6(R)-amine (XVIII), which is condensed with 5-bromo-2-methoxy-6-(methylamino)pyridine-3-carboxylic acid (VII) by means of ethyl chloroformate and TEA to yield the target amide (XIX). Finally, this compound is treated with fumaric acid (XX) in ethanol to afford the desired fumarate salt.