Linetastine, Linazolast, YM-257, TMK-688

利奈他斯汀Chemical Name: N-[2-[4-(Diphenylmethoxy)piperidin-1-yl]ethyl]-5-[4-(ethoxycarbonyloxy)-3-methoxyphenyl]-2(E),4(E)-pentadienamide
CAS No. 159776-68-8, 110501-66-1 (undefined isomer)
项目整合开发状态: Phase III
项目研究机构: Terumo (Originator)
合成路线:TMK 688 is derived trom the condensation ot 5-(3'-methoxy-4'-hydroxyphenyl)-2,4-pentadienoic acid (IV) and N-aminoethyl 4-diphenylmethoxypiperidine (X) in the presence of ethyl chloroformate in dichloromethane.Synthesis of intermediate (IV):Vanillin (I) is protected with ethyl chloroformate to give (II),which is then treated with triethyl 4-phosphonocrotonate and followed by alkali hydrolysis to produce (IV).

合成路线:Synthesis of intermediate (X):4-Hydroxypiperidine (V) is protected with ethyl chloroformate to give (VI),which is then condensed with bromodiphenylmethane in the presence of sodium carbonate yielding (VII).AIkali hydrolysis of (VII) gives (VIII),which is then treated with N-(2-bromoethyl)phthalimide to yield (IX).(IX) is then deprotected by a treatment of 80% hydrazine hydrate,producing (X).