Synthesis of apixaban was written by He, Chao;Hou, Yunlei;Zhu, Yan;Ma, Longsheng;Zhao, Yanfang. And the article was included in Zhongguo Yiyao Gongye Zazhi in 2014.Quality Control of 1-(4-Nitrophenyl)piperidin-2-one This article mentions the following:
The key intermediate 3-(4-morpholinyl)-1-(4-nitrophenyl)-5,6-dihydropyridin-2(1H)-one (5) was obtained via amidation, cyclization, dichlorination and elimination with 4-nitroaniline as the starting material. While another intermediate Et 2-chloro-2-[2-(4-methoxyphenyl)hydrazono]acetate (6) was prepared from 4-anisidine by diazotization and Japp-Klingemann reaction with Et 2-chloro-3-oxobutanoate. Apixaban, a factor Xa direct inhibitor, was synthesized from 5 and 6 by 1,3-dipolar cycloaddition, olefination, reduction, amidation, cyclization and aminolysis with an overall yield of 25% (based on 4-nitroaniline) and a HPLC purity of 99%. The improved process had several advantages over those reported procedures, such as mild conditions and simple operations, which is more suitable for industrial production In the experiment, the researchers used many compounds, for example, 1-(4-Nitrophenyl)piperidin-2-one (cas: 38560-30-4Quality Control of 1-(4-Nitrophenyl)piperidin-2-one).
1-(4-Nitrophenyl)piperidin-2-one (cas: 38560-30-4) belongs to piperidine derivatives.Piperidine is a key saturated heterocyclic scaffold found in several of the top-selling small molecule pharmaceuticals and natural alkaloids, with a diverse range of biological activities. Piperidine prefers a chair conformation, similar to cyclohexane. Unlike cyclohexane, piperidine has two distinguishable chair conformations: one with the N鈥揌 bond in an axial position, and the other in an equatorial position.Quality Control of 1-(4-Nitrophenyl)piperidin-2-one
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem