新产品编号:475109
Chemical Name: 4-Chloro-N-[2-[3-[1-(4-pyridyl)-4-piperidinylmethyl]ureido]phenyl]benzamide
CAS No. 219491-38-0
项目整合开发状态: Preclinical
项目研究机构: Lilly (Originator)
合成路线:Treatment of 4-(dimethylamino)benzoic acid (I) with thionyl chloride produced the corresponding acid chloride (II).Subsequent coupling of (II) with 4-tert-butyldimethylsilyloxy-N1-(4-methoxybenzoyl)-1,2-benzenediamine (III) yielded the bisamide (IV).Finally,desilylation of (IV) in the presence of HCl in aqueous THF afforded the title phenol compound.
合成路线:Reduction of ethyl ester (I) with LiAlH4 provides primary carbinol (II),which is then converted into amine (III) by Mitsunobu reaction with phthalimide (A) in the presence of PPh3 and DEAD in THF,followed by an hydrazine mediated deprotection in EtOH.Reaction of amine (III) with 2-nitrophenyl isocyanate (IV) in CHCl3/THF or CH2Cl2,followed by reduction of the nitro group by hydrogenation over Pd/C in EtOH,affords aniline (V).Finally,aniline (V) is condensed with acid chloride (VI) in CHCl3 in the presence of pyridine to furnish the target compound.
📌 参考资料/链接：
参考文献标题:Antithrombotic agents
文献作者:Sawyer,J.S.; Tinsley,J.M.; Wiley,M.R.; Hall,S.E.; Milot,G.; Shuman,R.T.; Goodson,T.Jr.; Klimkowski,V.J.; Kyle,J.A.; Masters,J.J.; Weir,L.C.; Mendel,D.; Beight,D.W.; Tebbe,A.L.; Yee,Y.K.; et al.(Eli Lilly and Company)
参考来源:WO 9900121
📄 详细内容
合成路线:Reduction of ethyl ester (I) with LiAlH4 provides primary carbinol (II),which is then converted into amine (III) by Mitsunobu reaction with phthalimide (A) in the presence of PPh3 and DEAD in THF,followed by an hydrazine mediated deprotection in EtOH.Reaction of amine (III) with 2-nitrophenyl isocyanate (IV) in CHCl3/THF or CH2Cl2,followed by reduction of the nitro group by hydrogenation over Pd/C in EtOH,affords aniline (V).Finally,aniline (V) is condensed with acid chloride (VI) in CHCl3 in the presence of pyridine to furnish the target compound.
参考文献标题:Non-amidine-containing 1,2-dibezamidobenzene inhibitors of human factor Xa with potent anticoagulant and antithrombotic activity
文献作者:Masters,J.J.; Franciskoich,J.B.; Tinsley,J.M.; Campbell,C.; Campbell,J.B.; Craft,T.J.; Froelich,L.L.; Gifford-Moore,D.S.; Hay,L.A.; Herron,D.K.; Klimkowski,V.J.; Kurz,K.D.; Metz,J.T.; Ratz,A.M.; Shuman,R.T.; Smith,G.F.; Smith,T.; et al.
参考来源:J Med Chem 2000,43(11),2087