T-2585.HCl
Chemical Name: 2-[4-[6,7-Diethoxy-2,3-bis(hydroxymethyl)naphthalen-1-yl]pyridin-2-yl]-4-(3-pyridyl)phthalazin-1(2H)-one hydrochloride
CAS No. 186461-09-6, 186461-26-7 (free base)
项目整合开发状态: Preclinical
项目研究机构: Tanabe Seiyaku (Originator)
合成路线:The reaction of 2-bromo-4,5-diethoxybenzaldehyde dimethylacetal (I) with 2-chloropyridine-4-carbaldehyde (II) by means of BuLi in THF gives the diarylcarbinol (III),which is cyclized with dimethyl fumarate (IV) by means of AcOH in refluxing toluene (or xylene) yielding the naphthalene-2,3-dicabroxylic ester (V).The reduction of (V) with NaBH4 in THF/methanol affords the bis(hydroxymethyl)naphthalene (VI),which is treated with hydrazine in refluxing water to give the 2-pyridylhydrazine derivative (VII).Finally,this compound is cyclized with 2-(3-pyridylcarbonyl)benzoic acid (VIII) by heating at 150 C in ethylene glycol.
📌 参考资料/链接：
参考文献标题:Naphthalene derivs.,process for the preparation thereof,and pharmaceutical compsns.comprising them
文献作者:Ukita,T.; Ikezawa,K.; Yamagata,S.(Tanabe Seiyaku Co.,Ltd.)
参考来源:CA 2178974; EP 0748805; JP 1997059255; US 6005106
📄 详细内容
合成路线:The reaction of 2-bromo-4,5-diethoxybenzaldehyde dimethylacetal (I) with 2-chloropyridine-4-carbaldehyde (II) by means of BuLi in THF gives the diarylcarbinol (III),which is cyclized with dimethyl fumarate (IV) by means of AcOH in refluxing toluene (or xylene) yielding the naphthalene-2,3-dicabroxylic ester (V).The reduction of (V) with NaBH4 in THF/methanol affords the bis(hydroxymethyl)naphthalene (VI),which is treated with hydrazine in refluxing water to give the 2-pyridylhydrazine derivative (VII).Finally,this compound is cyclized with 2-(3-pyridylcarbonyl)benzoic acid (VIII) by heating at 150 C in ethylene glycol.
参考文献标题:Novel,potent,and selective phosphodiesterase-4 inhibitors as antiasthmatic agents: Synthesis and biological activities of a series of 1-pyridylnaphthalene derivatives
文献作者:Ukita,T.; Sugahara,M.; Terakawa,Y.; Kuroda,T.; Wada,K.; Nakata,A.; Ohmachi,Y.; Kikkawa,H.; Ikezawa,K.; Naito,K.
参考来源:J Med Chem 1999,42(6),1088