An unexpected formation of pyrazolopyrimidines during the attempted to obtain 5-substituted tetrazoles from carbonitriles

In this Letter, we described the synthesis of new 5-(5-amino-1-aryl-1H-pyrazole-4-yl)-1H-tetrazoles 2a–c from 5-amino-1-aryl-1H-pyrazole-4-carbonitriles 1a–c as well as the unexpected 1H-pyrazolo[3,4-d]pyrimidine derivatives 6a–c from 5-amino-1-aryl-3-methyl-1H-pyrazole-4-carbonitriles 4a–c, instead of 5-(5-amino-1-aryl-3-methyl-1H-pyrazole-4-yl)-1H-tetrazoles 5a–c as desired. In an attempt to obtain these tetrazole derivatives containing the methyl group at C3-position in the pyrazole ring, the amino group in 5-amino-1-(4-methoxyphenyl)-3-methyl-1H-pyrazole-4-carbonitrile 4c was protected by the reaction with sodium hydride and di-tert-butyl-dicarbonate (Boc). The tetrazole derivative 5c was synthesized from the protected compound 7c using analogue methodology to obtain 2a–c and 6a–c.     

The first total synthesis of novel human chymase inhibitor SPF32629A

The first total synthesis of SPF32629A, a novel human chymase inhibitor, has been accomplished from the readily available precursor 4-nitropyridine N-oxide, following an efficient strategy with a sequence of eight straightforward steps.     

The first total synthesis of potent human chymase inhibitor SPF32629B via regioselective bromination and O-acylation strategy

An efficient total synthesis of (±)-SPF32629B is described. The key features of the synthesis include regioselective bromination followed by carboxylation at C-3 and protecting-group-free regioselective acylation of hydroxyl group present at C7. Structure was determined by X-ray analysis.