As part of the structure-activity relationship of the dopamine D 2 and serotonin 5-HT 3 receptors antagonist 1, which is a clinical candidate with a broad antiemetic activity, the synthesis and dopamine D 2 and serotonin 5-HT 3 receptors binding affinity of (R)-5-bromo-N-(1-ethyl-3-methylhexahydro-1,3-diazin-5-yl)-and (R)-5bromo-N- (1-ethyl-5-methyloctahydro-1,5-diazocin-3-yl)-2-methoxy-6-methylaminopyridine-3-carboxamides (2 and3) are described. Treatment of 1-ethyl-2-(p-toluenesulfonyl)amino-3-methylaminopropane dihydrochloride (4a) with paraformaldehyde and successive deprotection gave the 5-aminohexahydro-1,3diazine 6 in excellent yield. 3-Amino-1-ethyl-5-methyloctahydro-1,5-diazocine (15) was prepared from 2-(benzyloxycarbonyl)amino-3-[[N-(tert-butoxycarbonyl)-N-methyl]amino]-1-ethylaminopropane ( 9) through the intramolecular amidation of (R)-3-[N-[(2-benzyloxycarbonylamino-3-methylamino)propyl]-Nethyl]aminopropionic acid trifluoroacetate (12), followed by lithium aluminum hydride reduction of the resulting 6-oxo-1-ethyl-5-methyloctahydrodiazocine (13) in 41% yield. Reaction of the amines 6 and 15 with 5-bromo-2-methoxy-6-methylaminopyridine-3-carboxylic acid furnished the desired 2 and 3, which showed much less potent affinity for dopamine D 2 receptors than 1.