One-Step Synthesis of Fully Functionalized Pyrazolo[3,4-b]pyridines via Isobenzofuranone Ring Opening

Abstract

A novel series of fully substituted pyrazolo[3,4-b]pyridines 4 has been prepared in a regioselective manner by the microwave-assisted reaction between N-substituted 5-aminopyrazoles 1 and 3-(3-oxo-2-benzofuran-1(3H)-ylidene)pentane-2,4-dione (2). This is the second reported example of a cyclocondensation reaction using substrate 2 as a 1,3-bis-electrophilic reagent. Remarkably, this synthesis offers functionalized products with acetyl and carboxyl groups in one step, in good yields, and with short reaction times. Additionally, the cyclization intermediate 3 was isolated, allowing us to postulate a mechanism for this reaction, which is initiated via isobenzofuranone ring opening of 2 in a Michael-type reaction. The structures of the products and regioselectivity of the reactions were determined on the basis of NMR measurements and X-ray diffraction. For this new reaction using substrate 2, the optimal reaction conditions and its scope were investigated.

Synthesis and in vitro Antifungal Evaluation of Novel N‐Substituted 4‐Aryl‐2‐methylimidazoles

“…These methods have some operational drawbacks; hence, development of alternative and efficient protocols for the preparation of novel imidazoles from inexpensive substrates is of prime importance. Currently, microwave‐assisted reactions are being intensely studied due to their resemblance to the ideal synthesis criteria, since several steps can be developed in parallel and in different reaction sites leading to a unique structural assembly ,. Additionally, multicomponent reactions (MCRs) are useful synthetic tools in organic synthesis since they are efficient and proceed with high atomic economy, quickly and simultaneously generating molecular complexity.…”

“…Although this protocol is reliable, many of the syntheses suffer from several drawbacks, including harsh reaction conditions, prolonged reaction times, moderate yields and limited scope; therefore, few works have reported its use. All these facts, along with our interest in developing efficient methods for intramolecular C–N bond formation,,,,, have led us to propose a microwave‐assisted method to synthesize 2‐methyl‐ NH ‐imidazoles starting from acetamidine (poorly soluble in organic solvents) and α‐bromoacetophenones. These NH ‐imidazoles could be used as precursors of their N ‐substituted products, which have structural similarity to some azole drugs in clinical use (Scheme c).…”

Synthesis and structural elucidation of a phthalide analog using NMR analysis and DFT calculations

“…Phthalides can be found in nature as secondary metabolites of several species of fungi, and in the last years, much research has been done on their synthesis, [3] physicochemical properties, and bioactivities of phthalides and their derivatives. [4] Among the strategies to synthesize phthalides analogs, the Diels-Alder (DA) reaction is one of the most useful strategies that chemists have in their disposal. [5] Phthalides and other complex molecules can be synthesized using DA reaction, once this reaction enables the formation of two new σ-bonds and up to four stereogenic centers in a single step, [6] having control of the stereoisomerism of the final product.…”

Synthesis and in vitro evaluation of novel tetralin‐pyrazolo[3,4‐b]pyridine hybrids as potential anticancer agents

“…Moreover, pyrazolo[3,4‐ b ]pyridine system is considered as the main component in many medicinally important compounds. Some pyrazolo[3,4‐ b ]pyridine derivatives are currently used as drugs like etazolate I and tracazolate II (Figure ).…”