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.