An efficient synthesis of 6-substituted aminohexahydro-1H-1,4-diazepines from 2-substituted aminopropenals

Abstract

Swern oxidation of 2-substituted amino-1,3-propanediols 20a - d, 38, 41, and 42 smoothly proceeded to give the oxidative dehydration products, 2-substituted aminopropenals 17a - d, 43, 45 and 46, respectively. Reaction of the intriguing 2-substituted aminopropenals 17a - d with N-benzyl-N′-methyl- or N,N′-dimethylethylenediamine (12o or 12p) followed by NaBH4 reduction of the iminium salt intermediates afforded the corresponding 6-substituted aminohexahydro-1H-1,4-diazepines 16 and 24-28. The similar ring formation of 1H-indazole derivatives 43 and 45 employing 12o directly furnished the 1H-indazole-3-carboxamide 4, which showed a potent serotonin-3 (5-HT3) receptor antagonistic activity.