新产品编号:486183
Chemical Name: 3-Cyano-4-hydroxy-N'-[4-(4-isopropylbenzyloxy)-3,5-dimethoxybenzylidene]benzohydrazide
CAS No. 219681-70-6
项目整合开发状态: Preclinical
项目研究机构: Anadys (Originator), Novo Nordisk (Originator), Pfizer (Originator)
合成路线:Hydrazide (II) was prepared by treatment of methyl 3-chloro-4-hydroxybenzoate (I) with hydrazine in refluxing EtOH.Condensation of hydrazide (II) with 4-hydroxynaphthaldehyde (III) in the presence of a catalytic amount of glacial HOAc in DMSO produced the target acyl hydrazone.
合成路线:Methyl 4-hydroxybenzoate (I) is iodinated by means of iodine monochloride in hot AcOH,producing (II).Displacement of the aryl iodide (II) with CuCN gives nitrile (III).Then,ester group saponification in (III) leads to 3-cyano-4-hydroxybenzoic acid (IV).Coupling of (IV) with tert-butyl carbazate produces the N-Boc hydrazide (V),which is further deprotected to (VI) by treatment with trifluoroacetic acid
合成路线:Alkylation of 4-hydroxy-3,5-dimethoxybenzaldehyde (VII) with 4-isopropylbenzyl chloride (VIII) affords the benzyloxy benzaldehyde (IX).Then,condensation of aldehyde (IX) with hydrazide (VI) furnishes the target N-acyl hydrazone
📌 参考资料/链接：
参考文献标题:Glucagon antagonists/inverse agonists
文献作者:Gonzales,J.; Sams,C.; Teng,M.(Alanex Corp.; Novo Nordisk A/S)
参考来源:EP 0994848; WO 9901423
📄 详细内容
合成路线:Methyl 4-hydroxybenzoate (I) is iodinated by means of iodine monochloride in hot AcOH,producing (II).Displacement of the aryl iodide (II) with CuCN gives nitrile (III).Then,ester group saponification in (III) leads to 3-cyano-4-hydroxybenzoic acid (IV).Coupling of (IV) with tert-butyl carbazate produces the N-Boc hydrazide (V),which is further deprotected to (VI) by treatment with trifluoroacetic acid
合成路线:Alkylation of 4-hydroxy-3,5-dimethoxybenzaldehyde (VII) with 4-isopropylbenzyl chloride (VIII) affords the benzyloxy benzaldehyde (IX).Then,condensation of aldehyde (IX) with hydrazide (VI) furnishes the target N-acyl hydrazone
参考文献标题:Human glucagon receptor antagonists based on alkylidene hydrazides
文献作者:Ling,A.; Plewe,M.; Gonzalez,J.; Madsen,P.; Sams,C.K.; Lau,J.; Gregor,V.; Murphy,D.; Teston,K.; Kuki,A.; Shi,S.; Truesdale,L.K.; Kiel,D.; May,J.M.; Lakis,J.; Anderes,K.; Iatsimirskaia,E.; Sidelmann,U.G.; Knudsen,L.B.; et al.
参考来源:Bioorg Med Chem Lett 2002,12(4),663