E-4010
Chemical Name: 4-(3-Chloro-4-methoxybenzylamino)-1-(4-hydroxypiperidin-1-yl)phthalazine-6-carbonitrile hydrochloride
CAS No. 178308-66-2, 178308-65-1 (free base)
项目整合开发状态: Preclinical
项目研究机构: Eisai (Originator)
合成路线:The reaction of 4-aminophthalimide (I) with NaNO2/HCl and then with CuCl/KCN gives 4-cyanophthalimide (II),which is treated with hydrazone in ethanol,yielding 6-cyanophthalazine-2,3(1H,4H)-dione (III).The reaction of (III) with refluxing POCl3 affords 1,4-dichlorophthalazine-6-carbonitrile (IV),which is condensed with 3-chloro-4-methoxybenzylamine (V) by means of TEA in THF to provide the secondary amine (VI).Finally,this compound is condensed with 4-hydroxypiperidine (VII) by means of DIEA in N-methyl-2-pyrrolidone to furnish the target phthalazine.
📌 参考资料/链接：
参考文献标题:Fused pyridazine cpd.
文献作者:Watanabe,N.; Kabasawa,Y.; Takase,Y.; Ozaki,F.; Ishibashi,K.; Miyazaki,K.; Matsukura,M.; Souda,S.; Miyake,K.; Ishihara,H.; Kodama,K.; Adachi,H.(Eisai Co.,Ltd.)
参考来源:EP 0722936; JP 1996225541; US 6218392; WO 9605176
📄 详细内容
合成路线:The reaction of 4-aminophthalimide (I) with NaNO2/HCl and then with CuCl/KCN gives 4-cyanophthalimide (II),which is treated with hydrazone in ethanol,yielding 6-cyanophthalazine-2,3(1H,4H)-dione (III).The reaction of (III) with refluxing POCl3 affords 1,4-dichlorophthalazine-6-carbonitrile (IV),which is condensed with 3-chloro-4-methoxybenzylamine (V) by means of TEA in THF to provide the secondary amine (VI).Finally,this compound is condensed with 4-hydroxypiperidine (VII) by means of DIEA in N-methyl-2-pyrrolidone to furnish the target phthalazine.
参考文献标题:4-(3-Chloro-4-methoxybenzyl)aminophthalazines: Synthesis and inhibitory activity toward phosphodiesterase 5
文献作者:Watanabe,N.; Adachi,H.; Takase,Y.; Ozaki,H.; Matsukura,M.; Miyazaki,K.; Ishibashi,K.; Ishihara,H.; Kodama,K.; Nishino,M.; Kakiki,M.; Kabasawa,Y.
参考来源:J Med Chem 2000,43(13),2523
合成路线:The condensation of the commercially available (Amersham) 14C-labeled 1-chloro-4-(3-chloro-4-methoxybenzylamino)phthalazine-6-carbonitrile (I) with 4-hydroxypiperidine (II) by means of K2CO3 and N-methyl-2-pyrrolidinone at 170 C yields the target phthalazine derivative.
参考文献标题:Synthesis of 14C-labeled E4010
文献作者:Watanabe,N.; et al.
参考来源:J Label Compd Radiopharm 2001,44(12),843
产品链接: CAS No. 178308-66-2›› 产品链接: CAS No.178308-65-1››