新产品编号:484601
Chemical Name: 3-Chloro-4-hydroxy-N2-(4-hydroxynaphthalen-1-ylmethylidene)benzohydrazide
CAS No. 219680-33-8
项目整合开发状态: Preclinical
项目研究机构: 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: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.
参考文献标题:Identification of alkylidene hydrazides as glucagon receptor antagonists
文献作者:Ling,A.; Hong,Y.; Gonzalez,J.; Gregor,V.; Polinsky,A.; Kuki,A.; Shi,S.; Teston,K.; Murphy,D.; Porter,J.B.; Kiel,D.; Lakis,J.; Anderes,K.; May,J.M.; Knudsen,L.B.; Lau,J.
参考来源:J Med Chem 2001,44(19),3141