Rearrangement reactions of heterocycles. <b>12</b>. Rearrangement of 6‐substituted pyrido[1,2‐<i>a</i>]pyrimidines to isomeric 1,8‐naphthyridines and some of their further reactions

Abstract

Abstract 2‐Amino‐6‐methylpyridine ( 4 ) reacts with active malonates 2a‐d or 3a‐d either in acetone solution with triethylamine as catalyst at room temperature or with active malonates 2a‐d in acetone solution at reflux temperature to yield the pyrido[1,2‐ a ]pyrimidines 5a‐d . 2,6‐Diaminopyridine ( 8 ) already reacts without triethylamine with 2a‐d at room temperature to afford the pyrido[1,2‐ a ]pyrimidines 9a‐d . At higher temperatures pyrido[1,2‐ a ]pyrimidines 5 and 9 are rearranged via ketene intermediates [1] to yield the 1,8‐naphthyridines 6a‐d , and 10a‐d , respectively. The naphthyridines 6 and 10 can also be synthesized directly from 4 or 8 using either diethyl malonates 1 or — with better results — the active malonates 2 at 240–250°. Further reaction of 10a‐e with 2c,d leads to the pyridonaphthyridines 12a‐f . Nitration of 6c yields the nitro derivative 16 and chlorination of 6c,d gives 15c,d , while the chlorination of 10c affords the di‐chloro derivative 17 .