UNEXPECTED INTRAMOLECULAR CYCLIZATION AND PHOSPHONATION OF A PYRAZOLO[3,4-b]QUINOLINE

Abstract

The pyrazoloquinolines are an extensively studied group of compounds which present a large number of applications in medicinal chemistry, such as anticancer, antianxiety, anti-inflammatory, antiasthmatic and antiviral activities.[1,2] Also, they have been classified as a promising material for optoelectronics due to their highly fluorescent properties.[2] Bisphophonates (BPs) are potent antiresorptive agents used in the treatment of several bone diseases associated to bone resorption, such Paget’s disease, and osteoporosis. It has been also shown that these compounds were able to inhibit metastases proliferation in bone, prostate and breast cancers. In addition, functional BPs have been used as novel ligands for well-defined radioactive metal complexes for both imaging and radiotherapy applications and in the treatment of metal intoxications.[3] The aim of this work is to extend the previous studies on indazolebisphosphonates [4] to other condensed pyrazole derivatives. During these studies to achieve new BPs derived from pyrazolo[3,4-b]quinolines, a new and unexpected cyclization, followed by a phosphonation of C4 of pyrazolo[3,4-b]quinolines, were achieved, despite the different methods of synthesis used. The new compound shows a six-member lactone ring, formed from the reaction between the acyl chloride side chain and the aromatic N9 of pyrazolo[3,4-b]quinolines. It also shows an unexpected phosphonation of C4 position of pyrazolo[3,4-b]quinolines, with the change of the hybridization of this carbon atom from sp2 to sp3. Crystal structure of this compound (Figure 1) confirmed the proposed structure.