Expedient Synthesis of 3-Alkoxymethyl- and 3-Aminomethyl-Pyrazolo[3,4-b]pyridines

Abstract

An effective strategy has been developed for the preparation of 3-alkoxymethyl-pyrazolo[3,4-b]pyridines, compounds that are currently not readily accessible by existing synthetic methods. Further manipulation of these compounds allows for access to 3-alkoxymethyl-pyrazolo[3,4-b]pyridines with a variety of substitution patterns as well as 3-aminomethyl-pyrazolo[3,4-b]pyridines.

Facile Three‐Component Synthesis of Macrocyclane‐Fused Pyrazolo[3,4‐b]pyridine Derivatives

“…[4,5] Nitrogen-containing heterocycles are abundant in nature and exhibit diverse and important biological properties. The pyrazolo[3,4-b]pyridine system as a key heterocycle represents the core skeleton of a pharmaceutically important class of heterocyclic compounds that possess a broad range of biological activities, [6] such as anxiolytic activity, [7] and can be used in the inhibition of xanthine oxidases [8] and cholesterol formation [9] and in the treatment of Alzheimer's disease, gastrointestinal diseases, anorexia nervosa, drug and alcohol withdrawal symptoms, drug addiction and in- [ consuming and costly syntheses, tedious work-ups and purifications of precursors as well as protection/deprotection of functional groups. This method is very efficient due to short reaction times and easy work-up and provides an efficient and promising synthetic strategy for the construction of the macrocyclane-fused pyrazolo[3,4-b]pyridine skeleton.…”

“…When aliphatic aldehydes replaced their aromatic counterparts in the above multicomponent reaction, the reaction was found to proceed along another pathway leading to the formation of multifunctionalized tricyclo[6.2.2.0 1,6 ]dodecanes.…”

Synthesis of new fluorine-containing pyrazolo[3,4-b]pyridinones as promising drug precursors

“…1 In the last de cade, some heterocycles of this class have been found to regulate the cardiovascular system 2 and possess antiviral, 3 antitumor, 4 antiinflammatory, 5 antimicrobial, 6 and anti parasitic properties. 7 Fluoroalkyl containing pyrazolo [3,4 b]pyridines are also believed to be candidates for med ications and considered to be potential inhibitors of ade nosine deaminase and inosine 5´ monophosphate dehy drogenase.…”

“…R 1 = Ph, R 2 = Me (3a); R1 = 4 FC 6 H 4 , R 2 = Me (3b); R 1 = 4 MeOC 6 H 4 CH 2 , R 2 = H (3c) MW denotes microwave irradiationWith ethyl 4 fluoro 4 phenylthioacetoacetate 4b, all our attempts to obtain the target 4 ArSCHF 6,7 dihydro 1H pyrazolo[3,4 b]pyridin 6 ones 3 from oxo ester 4b and pyrazoles 5a-c, including heating in acetic acid under microwave irradiation, were unsuccessful. Ethyl 4 bromo 4,4 difluoroacetoacetate (4c) reacts with aminopyrazoles 5a-c in boiling acetic acid for 3 h to give pyrazolo[3,4 b]pyridines 6a-c in high yields.…”

“…Keto form 1. H NMR (CDCl 3 ), δ: 1.31 (t, 3 H, CH 3 CH 2 O, J = 7.5 Hz); 3.50 (AB system, 2 H, COCH 2 ); 4.22 (q, 2 H, OCH 2 CH 3 , J = 7.5 Hz); 6.27 (d, 1 H, CHFSPh, J = 51.7 Hz); 7.37-7.62 (m, 5 H, Ph).…”