KF-24345
3-[1-[6,7-二乙氧基-2-(4-吗啉基)喹唑啉-4-基]哌啶-4-基]-1,6-二甲基喹那唑仑-2,4(1H,3H)-二酮Chemical Name: 3-[1-[6,7-Diethoxy-2-(4-morpholinyl)quinazolin-4-yl]piperidin-4-yl]-1,6-dimethylquinazolin-2,4(1H,3H)-dione
CAS No. 178750-21-5, 178750-22-6 (monohydrochloride)
项目整合开发状态: Preclinical
项目研究机构: Kyowa Hakko (Originator)
合成路线:4-Amino-1-benzylpiperidine (II) was acylated with 5-methyl-2-nitrobenzoyl chloride (I) to afford the ortho-nitrobenzamide (III),which was reduced to the amino derivative (IV) by catalytic hydrogenation in the presence of Pd/C.Treatment of (IV) with ethyl chloroformate produced the bis-carbamate (V) with concomitant cleavage of the N-benzyl group.This was cyclized to the dioxoquinazoline (VI) upon treatment with KOH in refluxing EtOH.After N-methylation employing iodomethane and NaH in DMF,hydrolysis of the carbamate group with concentrated HBr yielded the piperidinylquinazoline (VIII).This was then condensed with 2,4-dichloro-6,7-diethoxyquinazoline (IX) to furnish adduct (X).Finally,displacement of the remaining chlorine of (X) with morpholine (XI) in hot NMP gave rise to the title compound.
📌 参考资料/链接：
参考文献标题:Quinazoline deriv.
文献作者:Fujiwara,S.; Okamura,Y.; Takai,H.; Nonaka,H.; Moriyama,T.(Kyowa Hakko Kogyo Co.,Ltd.)
参考来源:EP 0726267; JP 1997165385; US 5948784; WO 9606841
📄 详细内容
合成路线:4-Amino-1-benzylpiperidine (II) was acylated with 5-methyl-2-nitrobenzoyl chloride (I) to afford the ortho-nitrobenzamide (III),which was reduced to the amino derivative (IV) by catalytic hydrogenation in the presence of Pd/C.Treatment of (IV) with ethyl chloroformate produced the bis-carbamate (V) with concomitant cleavage of the N-benzyl group.This was cyclized to the dioxoquinazoline (VI) upon treatment with KOH in refluxing EtOH.After N-methylation employing iodomethane and NaH in DMF,hydrolysis of the carbamate group with concentrated HBr yielded the piperidinylquinazoline (VIII).This was then condensed with 2,4-dichloro-6,7-diethoxyquinazoline (IX) to furnish adduct (X).Finally,displacement of the remaining chlorine of (X) with morpholine (XI) in hot NMP gave rise to the title compound.
参考文献标题:Synthesis and evaluation of adenosine transporter inhibitors
文献作者:Kase,H.; Fujiwara,S.; Okamura,Y.; Karasawa,A.; Nonaka,H.; Yao,K.; Takai,H.
参考来源:16th Int Symp Med Chem (Sept 18 2000,Bologna) 2000,Abst PC-19
产品链接: CAS No. 178750-21-5››