95274-54-7

Upstream product

• 118-48-9 isatoic anhydride 
• 61-54-1 tryptamine 
• 33284-02-5 2-amino-N-[2-(1H-indol-3-yl)ethyl]benzamide 
• 120-46-7 1,3-diphenylpropanedione 
• 1022-46-4 2-phenyl-4H-3,1-benzoxazin-4-one 

Relevant academic research and scientific papers

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.

Studies of Rutaecarpine and Related Quinazolinocarboline Alkaloids

Quinazolinocarboline alkaloids, e.g., rutaecarpine (1), can readily be synthesized by treating tryptamine with 2-(trifluoromethyl)-4H-3,1-benzoxazin-4-one (quickly generated in situ from trifluoroacetic anhydride (TFAA) and 2H-3,1-benzoxazine-2,4(1H)-dione.The product formed, 3--2-(trifluoromethyl)-4-(3H)-quinazolinone (5), is then cyclized (HCl/HOAc) to 13b-(trifluoromethyl)-13b,14-dihydrorutaecarpine (6), whereupon CF3H is eliminated by treatment with base.The sequence can conveniently be performed as a three-reaction one-pot procedure giving rutaecarpine (1) in 99percent yield within 3h.The approach can readily be extended to the synthesis of evodiamine (2), 13,13b-dehydroevodiamine (38a), and 13b,14-dihydrorutaecarpine (21).Thus treatment of 3--4(3H)-quinazolinone (19) with TFAA affected cyclization to 13b-(trifluoroacetyl)-13b,14-dihydrorutaecarpine (20), which can be readily hydrolyzed to 13b,14-dihydrorutaecarpine (21).