A convenient synthesis of pyrazolo[3,4-b]pyridine nucleosides by convenient ring-closure procedures. X-Ray crystal and molecular structure of 4-amino-1 -(β-D-ribofuranosyl)-1,7-dihydropyrazolo[3,4-b]pyridin-6-one

Abstract

Practical syntheses of 1 -(~-~-ribofuranosyl)pyrazolo[3,4-b] pyridines as purine antagonists, related to isoguanosine, guanosine, and xanthosine, are described for the first time. Ethyl 5-amino-l-(2,3-0isopropylidene-p-D-ri bofuranosyl) -1 H-pyrarole-4-carboxylate (1 0 ) was converted into 5-amino-1 -(~,3-O-isopropylidene-~-o-ribofuranosy~) -1 H-pyrazole (1 2), which was in turn converted into 6amino-l-(p-D-ribofuranosyt) -1,7-dihydropyrazolo[3,4-b]pyridin-4-one (4) in four steps. 4-Amino-1 -(p-D-ribofuranosyl) -1,7-dihydropyrazolo[3,4-b] pyridin-6-one (3) was obtained in satisfactory overall yield from compound (12), prepared in four steps via a ring-closure procedure. The structure of compound (3) was established by a single-crystal X-ray study. 4-Hydroxy-1 -(P-D-ribofuranosyl

Interrogating the mechanism of a tight binding inhibitor of AIR carboxylase

“…The nucleoside precursors, 4-NIRs ( 11 )15, 3-NPyRs ( 12 )16, 4-NPzRs ( 13 )17, and CAPzRs ( 14 )18 are either known compounds or could be readily prepared from known compounds. Thus, their syntheses were carried out following the reported procedure.…”

Synthesis of Pyrazolo[3,4‐b]pyridin‐6‐ones

“…In ref. 91, the authors studied the possibility of synthesizing the derivative of pyrazolo[3,4‐ b ]pyridin‐6‐one ( 199 ) as the analog of the isomeric guanosine. Condensation of aminopyrazole ( 194 ) with diethyl ester of malonic acid in glacial acetic acid, and the subsequent reaction of the condensed compound ( 195 ) with hydrazine hydrate led to hydrazide ( 196 ) that was converted into azido derivative ( 197 ).…”

“…The latter, in the course of the Curtius rearrangement [92] in acetic acid, was converted into nucleoside ( 198 ), the hydrolysis of which resulted in the desired product ( 199 ), in a 50% yield. Unfortunately, the authors [91] did not investigate the stereochemistry of obtained compounds (Scheme 46).…”

“…It was demonstrated that the treatment of amine ( 293 ) with diethyl malonate in ethanol, in the presence of sodium ethoxide led to the formation of the ester ( 294 ) in a 62% yield. The product ( 295 ) was synthesized in a similar manner as the analog of isoguanosine ( 199 ) [91] and subjected to alkaline hydrolysis. The, decarboxylation with the formation of 4‐hydroxy derivative of pyrazolo[3,4‐ b ]pyridine‐6‐one ( 296 ) was observed, in a 42% yield but authors did not describe stereochemistry of the substitute (Scheme 73).…”