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Benzo[4,5]imidazo[2,1-b]quinazolin-12-ones and benzo[4,5]imidazo[1,2-a]pyrido[2,3-d]pyrimidin-5-ones by a sequential N-acylation–SNAr reaction
- Gnanasekaran, Krishna Kumar, Muddala, Nagendra Prasad, Bunce, Richard A.
- Tetrahedron letters 2015 v.56 no.52 pp. 7180-7183
- Lewis acids, Lewis bases, acylation, benzimidazole, chemical structure, chlorides, heat, nitrogen, organochlorine compounds
- An efficient synthesis of benzo[4.5]imidazo[2,1-b]quinazolin-12-ones and benzo[4,5]imidazo[1,2-a]pyrido[2,3-d]pyrimidin-5-ones is reported from the reaction of 2-aminobenzimidazole with 2-haloaroyl chlorides. The reaction takes advantage of the 1,3-disposition of nucleophilic centers in 2-aminobenzimidazole and the similar arrangement of electrophilic sites in the acid chloride to assemble the central six-membered ring. Initial treatment of 2-aminobenzimidazole (1.2equiv) with the acid chloride (1equiv) in the presence of NaHCO3 (2equiv) in DMF at −10°C gives acylation at the saturated benzimidazole nitrogen. Subsequent heating to 75°C, in the same reaction vessel, then completes the synthesis via an SNAr ring closure by the C2 amino group. The reaction has broad scope, and gives 76–98% yields for the two-step sequence. The final products exist in a tautomeric equilibrium, which can be blocked by acylation at N6.