A Facile and Practical Synthesis of 9-Methyl-3-(1H-tetrazol-5-yl)-4H-pyrido[1, 2-α]pyrimidin-4-one

A facile and practical synthesis of 9-methyl-3-(1H-tetrazol-5-yl)-4H-pyrido[1, 2-α]pyrimidin-4-one (4), the potassium salt of which is used clinically as an anti-asthma agent, is described. Treatment of a key intermediate (6b), prepared from 2-amino-3-methylpyridine (1) and 2-ethoxymethylene-1, 3-propanedinitrile, with sodium azide in N, N-dimethylformamide gave predominantly the cyanotetrazole (7a), while in acetic acid it gave exclusively the iminotetrazole (7b), which was easily converted into 4 by acid hydrolysis. A one-pot process starting from 6b to give 4, avoiding the use of explosive aluminum azide, was established.