Condensed isoquinolines 32. Synthesis of 4H-thieno-[3′,2′:5,6]-and-[2′,3′: 5,6]pyrimido-[1,2-b]isoquinolines and 6,12-dihydro-5H-isoquino-[2,3-a]quinazoline-5,12-dione derivatives

Abstract

dione respectively. NMR spectroscopy showed that an intramolecular acylation of the above acids occurs at the atom N-1 of the pyrimidinone part of the bicycle.We have previously reported 2-(4-oxo-3,4-dihydrothieno[2,3-d]-and -[3,2-d]pyrimidin-2-ylmethyl)-benzoic acids 1 and 2 [2] and 2-(4-oxo-3,4-dihydro-2-quinazolinylmethyl)benzoic acid 3 [3]. This work continues our investigation of thienopyrimidines and quinazolones.The attempted esterification of acids 1-3 by a classical method [4] (heating an alcohol suspension in the presence of concentrated sulfuric acid) gave yellow crystalline materials whose properties differed from the starting materials although not being the esters. Hence like the starting acid they dissolve in a 2N solution of base but, in contrast, are completely insoluble in 2N hydrochloric acid. According to TLC data their chromatographic mobility is markedly greater than the starting acids and esters. The elemental analytical data and chromato-mass spectra of the products obtained point to the loss of a molecule of water from the starting acids, i.e. that an intramolecular acylation had occurred under these reaction conditions. It was found that the sulfuric acid dehydrating agent originally used by us was not a totally suitable reagent since cyclization is accompanied by a vigorous tarring of the reaction product and this significantly lowers the yields. A smoother dehydration occurs upon refluxing a suspension of the acids 1-3 in acetic anhydride.