JB-99157
Chemical Name: 3-[5-(Adamant-1-yloxymethyl)-2-cyclohexyl-1H-imidazol-4-ylcarboxamido]benzoic acid
CAS No. 269069-71-8, 372489-10-6 (Na salt)
项目整合开发状态: Preclinical
项目研究机构: James Black Foundation (Originator), Janssen (Originator)
合成路线:Saponification of ethyl adamantyloxyacetate (I),followed by treatment of the resultant carboxylic acid (II) with oxalyl chloride gives rise to acid chloride (III).This is then condensed with benzyl (triphenylphosphoranylidene)acetate (IV) to produce the phosphoranylidene keto ester (V).Subsequent oxidative cleavage of phosphorane (V) with oxone under phase transfer conditions leads to diketo ester (VI).Cyclization between diketo ester (VI),cyclohexanecarboxaldehyde (VII) and ammonium acetate in hot AcOH affords imidazole (VIII).The benzyl ester group of (VIII) is removed by catalytic hydrogenolysis,yielding acid (IX),which is further coupled with benzyl 3-aminobenzoate (X) to furnish amide (XI).Finally,benzyl ester hydrogenolysis in the presence of Pd/C provides the target compound (1,2).
📌 参考资料/链接：
参考文献标题:Pharmaceutical compsns.comprising proton pump inhibitors and gastrin/cholecystokinin receptor ligands
文献作者:Kalindjian,S.B.; Mesens,J.L.; Black,J.W.; Hull,R.A.D.; Shankley,N.P.; Andries,L.J.(James Black Foundation Ltd.; Janssen Pharmaceutica NV)
参考来源:WO 0185167
📄 详细内容
合成路线:Saponification of ethyl adamantyloxyacetate (I),followed by treatment of the resultant carboxylic acid (II) with oxalyl chloride gives rise to acid chloride (III).This is then condensed with benzyl (triphenylphosphoranylidene)acetate (IV) to produce the phosphoranylidene keto ester (V).Subsequent oxidative cleavage of phosphorane (V) with oxone under phase transfer conditions leads to diketo ester (VI).Cyclization between diketo ester (VI),cyclohexanecarboxaldehyde (VII) and ammonium acetate in hot AcOH affords imidazole (VIII).The benzyl ester group of (VIII) is removed by catalytic hydrogenolysis,yielding acid (IX),which is further coupled with benzyl 3-aminobenzoate (X) to furnish amide (XI).Finally,benzyl ester hydrogenolysis in the presence of Pd/C provides the target compound (1,2).
参考文献标题:Gastrin and cholecystokinin receptor ligands
文献作者:Kalindjian,S.B.; Black,J.W.; Low,C.M.R.; McDonald,I.M.; Hull,R.A.D.; Shankley,N.P.; Pether,M.J.; Dunstone,D.J.; Steel,K.I.M.; Buck,I.M.; Tozer,M.J.; Harper,E.A.; Watt,G.F.; Linney,I.D.; Wright,P.T.; et al.(James Black Foundation Ltd.)
参考来源:JP 2002529455; US 6479531; WO 0027823