Pyrazole 3-amino-, ring synthesis

The aromatic acid is available and we need consider only the pyrazole (core pyrazole ring in black in the diagram). The aromatic amino group can be put in by nitration and reduction and the amide can be made from the corresponding ester. This leaves a carbon skeleton, which must be made by ring synthesis. 

Similar ring systems were prepared <97JHC1693> by Coppo and Fawzi from the reaction of substituted ethyl 5-[methyl(methylsulfonyl)amino]-l 7/-pyrazole-4-carboxylates 119 with sodium hydride. This gave the 7-substitued 1,7-dihydro-l-methylpyrazolo[3,4-c][l, 2]thiazin-4(37/)-one 2,2-dioxides 120 in fair to good yield (Scheme 30). They also extended this synthesis by treating methyl 2-[methyl(methylsulfonyl)amino]-6-(trifluoromethyl)-3-pyridinecarboxylate 121 with sodium hydride in dimethylformamide to yield l-methyl-7-(trifhioromethyl)-l//-pyrido[2,3-c][l,2]thiazin-4(3//)-one 2,2-dioxide 122 in 79% yield (Scheme 31) <98JHC499>. 

Synthesis of a pyrazole derivative with an amino group in position 3 in the B-ring was described by Ohsumi et al. [50]. Phenylacetronitrile (35)... 

Studies on the potential of the electrochemical approach to pyrazolotriazoles 117 showed that under the conditions of bicycle synthesis from 3-amino-4-hydrazonopyrazoles the N-l-unsubstituted triazole ring of 117 was further oxidized in a one-electron peak, followed by proton removal to yield the bis-(l,l )-2-phenylpyrazolo[3,4-i/][l,2,3]triazoles 118. This observation is significant, since in spite of pronounced pharmaceutical applications of pyrazoles, the redox characteristics of substituted pyrazoles have received limited attention (Scheme 13) <2001MI1022>. 

Several methods for the synthesis of 5-imino-2-pyrazolines depend upon the amination of a pyrazole ring. 5-Chloropyrazoles react with aniline to give the corresponding 5-amino compound.826,1002 The chloropyrazoles can be prepared and amination accomplished in one... 

The synthesis of pyrazolo[5,1 -6]purin-2-ones 261 started from ethyl 7-amino-pyrazolo[l,5-a]pyrimidine-6-carboxylates 262, following hydrazinolysis and reaction with HN02 gave the corresponding azide and the modified Curtius reaction closed the third pyrazole ring of 261. The final tricyclic 261 can be hydrolyzed to 6,7-diamino-pyrazolo[l, 5-a]purines (68CPB2195) (Scheme 77). 

The most commonly used strategy for the synthesis of this class of C-nucleosides was the annulation of the 1,3,5-triazine ring onto suitably substituted pyrazol-4-yl C-nucleosides. Thus, the C-nucleosides 836, related to adenosine and formycin, was prepared by reacting the 3-aminopyrazol-4-yl C-nucleoside 832 with ethoxy V-cyanoformimidate (76JHC1305 96MI2) or by reacting the 3-amino-2-carbamimidoylpyrazol-4-yl C-nucleoside 835 with triethyl orthoformate [84H(22)345] (Scheme 218). 

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