Modifications and extensions of the Pschorr reaction in pyrazole series. Access to the [2]benzopyrano[4,3-c]pyrazole system of pharmaceutical interest

Abstract

The Pschorr reaction performed under non-classical reaction conditions on the diazonium chloride derived from 2-amino-N-methyl-N-(3-methyl-1-phenyl-1H-pyrazol-5-yl)benzamide 1 afforded the epimers (3′R,4′S)- and (3′R,4′R)-4′-chloro-2′,4′-dihydro-2,5′-dimethyl-2′-phenylspiro[isoindoline1,3′-3′H-pyrazol]-3-one 4a and 4b together with the related enantiomers. The epimers were easily converted under acid conditions into both 4-chloro-3-methyl-5-[2-(methylcarbamoyl)phenyl]-1-phenyl-1H-pyrazole 5 and the potentially pharmacologically active 3-methyl-1-phenyl-1H-[2]benzopyrano[4,3-c]pyrazol-5-one 3, whereas under base conditions, as well as thermally, only compound 5 was obtained.

The molecular structure of epimer 4a and that of the derivative 5 were confirmed by single-crystal X-ray analysis. The crystal of compound 5 is characterized by the presence of two conformational isomers in the unit cell.