ピリド[2,3-d]ピリミジン系抗菌剤(第5報)1H, 5H-Imidazo[1,2-a]-pyrido[2,3-d]pyrimidine類の合成と反応

抄録

7-Carboxy-9-ethyl-2, 3, 6, 9-tetrahydro-1-methyl-6-oxo-1H-imidazo[1, 2-a]pyrido[2, 3-d]pyrimidin-4-ium chloride (5), consisting of a new heterocyclic ring system, was produced when 8-ethyl-5, 8-dihydro-2-[N-(2-hydroxyethyl)-N-methylamino]-5-oxopyrido[2, 3-d]pyrimidine-6-carboxylic acid (3) was treated with SOCl₂. The structure of 5 was assigned on the basis of chemical and spectral evidence. The hydroxide (6) derived from 5 was unstable and was readily converted into a pseudo base (7). Oxidation of 7 with KMnO₄ in alkaline medium gave 5-oxo compound (8). Reduction of 6 or 7 with NaBH₄ afforded 5-unsubstituted 1H, 5H-imidazo[1, 2-a]pyrido[2, 3-d]pyrimidine derivative (9). The 5-positions of 6 and 7 reacted with methoxide, ethoxide, and carbanions of acetone and nitromethane to give the corresponding 5-methoxy (11), -ethoxy (12), -(2-oxopropyl) (13), and -nitromethyl derivatives (14), respectively. Antibacterial agents, piromidic acid (1) and pipemidic acid (2), as well as 3 were hydrogenated with Pd-C as a catalyst across the 3, 4 C=N bond, giving the 3, 4-dihydro derivatives 15, 16, and 10, respectively. Structure-activity relationships of these compounds were discussed briefly.