Benzimidazole condensed ring systems. 2. New synthesis of substituted 1‐oxo‐1 H ,5 H ‐pyrido[1,2‐ a ]benzimidazole‐4‐carbonitriles and related derivatives

The synthesis of some 3‐substituted and 2,3‐disubstituted‐1‐oxo‐1 H ,5 H ‐pyrido[1,2‐ a ]benzimidazole‐4‐carbo‐nitriles 5,6 by fusing 1 H ‐benzimidazole‐2‐acetonitrile 1 with some β‐keto esters 2,4 in the presence of ammonium acetate or with ethyl β‐aminocrotonate 3 is described. The tricyclic compounds were converted to their N‐5 methyl of N‐5 ethyl derivatives 8,9. Vilsmeir‐Haack formylation of 3‐methyl‐1‐oxo‐1 H ,5 H ‐pyrido[1,2‐ a ]‐benzimidazole‐4‐carbonitrile 5a afforded its 2‐formyl derivative 10. Chlorination of 5 and 6 with phosphorus oxychloride yielded the respective 1‐chloropyrido[1,2‐ a ]benzimidazole‐4‐carbonitriles 11,12 which were utilized to prepare the 1‐azido, 1‐amino, 1‐piperidino and 1‐methoxy derivatives of the ring system. Compound 11a exhibited strong in vitro activity against S. aureus. Four compounds were screened against P‐388 lymphocytic leukemia in mice but were inactive.