Pyrimido[5,4‐b]quinolines. I. Synthesis of substituted tricyclic systems related to riboflavin

Abstract

Two alternative synthetic routes were investigated for the synthesis of 2,4,10‐substituted‐7,8‐dimethylpyrimido[5,4‐b]quinolines: (1) cyclization of 5‐(3,4‐xylidino)‐2,4‐disubstituted‐pyrimidine‐6‐carboxylic acids, and (2) cyclization of N‐5‐(2,4‐disuhstituted‐pyrimidinyl)‐4,5‐dimethylanthranilic acids. Route (1) invariably led to isomeric mixtures of the corresponding 7,8‐ and 8,9‐dimethylpyrimido[5,4‐b]quinolines which were difficult to separate, while route (2) yielded only the desired 7,8‐dimelhyl derivatives. The required intermediates were synthesized by Ullman‐type condensation of the appropriate pyrimidine and benzene derivatives. Cyclization with polyphosphoric acid, or phosphorus oxychloride (under various conditions) led to a number of new pyrimido[5,4‐b]quinoline derivatives, with oxo, methoxy and/or chloro substituents in the 2,4 and 10 positions. A mild, but effective chlorination procedure was developed for the chlorination of the 10‐(oxo) position without the cleavage of methoxyl groups at positions 2 and 4.

Pyrimido[5,4‐c]quinolines: Synthesis from 3,4‐Di‐functionallized Quinoline, Reactivity and Biological Activities

“…The synthesis of pyrimidoquinolines (Pqs) involves the fusion of pyrimidine 5 and quinoline 6 ring systems, resulting in diverse ring isomers. Notable among these isomers are Pyrimido[4,5-c] quinolines 7, [4] Pyrimido [5,4-c] quinolines 8, [5] Pyrimido [4,5-b] quinolines 9, [6,7] and Pyrimido [5,4-b] quinolines 10, [8] constituting the distinct structural variants within the Pqs family (Figure 2).…”