新产品编号:740885
Chemical Name: N-[4-Chloro-2-[N-(5-chloropyridin-2-yl)carbamoyl]phenyl]-1-isopropylpiperidine-4-carboxamide
CAS No. 280771-57-5, 280769-08-6 (HCl)
项目整合开发状态: Preclinical
项目研究机构: Lilly (Originator)
合成路线:The condensation between 5-chloro-2-nitrobenzoyl chloride (I) and 2-amino-5-chloropyridine (II) produced the corresponding amide (III).Subsequent catalytic hydrogenation of the nitro group of (III) gave aniline (IV).Acid chloride (VI),prepared from N-Boc-isonipecotic acid (V) and oxalyl chloride,was then coupled to aniline (IV) to furnish amide (VII).Further trifluoroacetic acid-promoted cleavage of the Boc protecting group of (VII) yielded piperidine (VIII).Finally,reductive alkylation with acetone in the presence of sodium triacetoxyborohydride gave rise to the target N-isopropyl piperidine.
合成路线:An alternative preparation for the title compound consisted in the reductive alkylation of ethyl isonipecotate (IX) with acetone to afford the N-isopropyl isonipecotate (X).After basic hydrolysis of the ethyl ester group of (X),the resulting carboxylic acid (XI) was activated as the mixed anhydride (XII) with isobutyl chloroformate.Anhydride (XII) was finally coupled to aniline (IV) to generate the required amide.
📌 参考资料/链接：
参考文献标题:Aromatic amides
文献作者:Wikel,J.H.; Yee,Y.K.; Weir,L.C.; Joseph,S.P.; Tebbe,A.L.; Sawyer,J.S.; Goodson,T.J.; Franciscovich,J.B.; Tinsley,J.M.; Wiley,M.R.; Milot,G.; Pineiro-Nunez,M.M.; Masters,J.J.; Hall,S.E.; (Eli Lilly and Company)
参考来源:WO 0039118
📄 详细内容
合成路线:The condensation between 5-chloro-2-nitrobenzoyl chloride (I) and 2-amino-5-chloropyridine (II) produced the corresponding amide (III).Subsequent catalytic hydrogenation of the nitro group of (III) gave aniline (IV).Acid chloride (VI),prepared from N-Boc-isonipecotic acid (V) and oxalyl chloride,was then coupled to aniline (IV) to furnish amide (VII).Further trifluoroacetic acid-promoted cleavage of the Boc protecting group of (VII) yielded piperidine (VIII).Finally,reductive alkylation with acetone in the presence of sodium triacetoxyborohydride gave rise to the target N-isopropyl piperidine.
参考文献标题:SAR investigations of N-aryl-2-[(piperidin-4-ylcarbonyl)amino]benzamide factor Xa inhibitors
文献作者:Kyle,J.A.; et al.
参考来源:220th ACS Natl Meet (Aug 20 2000,Washington DC) 2000,Abst MEDI 288