Studies on quinazolines. VII. Reactions of anthranilamide with β- diketones; new approaches toward the synthesis of tetrahydropyrido[2,1- b]quinazolin-11-one derivatives

Condensation of anthranilamide and its derivatives with various 1,3- cyclohexanediones 5a,b or 2,4-pentanediones under acidic conditions produced a variety of heterocycles, leading to the synthesis of tetrahydropyridol[2,1- b]-quinazolin-11-one derivatives. Condensation of anthranilamide with 5a or 5b in the presence of p-toluenesulfonic acid at the reflux temperature of tetrahydrofuran (THF) afforded compound 6a (40%) and compound 7a (22%) or compound 6b (47%) and compound 7b (39%), respectively. However, reflux of anthranilamide with 5a or 5b in 6% ethanolic hydrogen chloride provided compounds 6a and 6b in 77% and 73% yields, respectively. Heating 7a with 5a in 6% ethanolic hydrogen chloride furnished 6a in 82.4% yield. Reaction of anthranilamide with 5c under the same conditions resulted in the formation of 11 (57%). Treatment of compounds 6a and 6b with NaBH₄ furnished 8a,b (89, 87% yields), which were subsequently subjected to the Mitsunobu reaction to produce 6,7,8,9-tetrahydro-9-methyl-11H-pyrido[2,1-b]quinazolin-11-one (9a) and 6,7,8,9-tetrahydro-7,7,9-trimethyl-11H-pyrido[2,1-b]quinazolin-11-one (9b) in 56 and 72% yields, respectively. However, heating 14 with 15a in CH₃CN in the presence of p-toluenesulfonic acid furnished 19 in 31% yield. Under similar conditions, treatment of 21 with 15a provided 23a (42.4% yield), a key intermediate for the synthesis of rutaecarpine. Analogous reaction of 21 with 15b, 15c and 5a provided 22b-d in 63-99.3% yield, respectively.