Selective method for the preparation of isomeric N-alkyl and N-aryl-3(5)-amino-5(3)-hydroxy-1H-pyrazole-1-carboxamides

As part of a program to develop novel mechanism based skeletal muscle relaxants we identified 5-amino-3-hydroxy-1H-pyrazole-1-carboxamide (1) as a potential structural lead. This highly functionalized pyrazole was prepared via a published procedure 1] (Scheme 1, R¹ = R¹ = H), which utilized 3,5-dimethyl-1H-pyrazole-1-carboxamide as an aminocarbonyl transfer reagent, to give with cyanoacethydrazide the semicarbazide intermediate 6 . Base catalyzed cyclization of 6 afforded the initial lead compound. This reaction scheme was extended to the synthesis of additional 4-alkyl- and 4-aryl-5-amino-3-hydroxy-1H-pyrazole-1-carboxamides (Table 1).