ER-129517

Chemical Name: 3-[4-[2-[3-(Methylsulfonyl)thien-2-yl]ethyl]piperidin-1-ylmethyl]pyridin-2(1H)-one
CAS No. 351407-14-2
项目整合开发状态: Preclinical
项目研究机构: Eisai (Originator)
合成路线:The reaction of 3-bromothiophene-2-carbaldehyde (I) with CH3-SNa in DMF gives 3-(methylsulfanyl)thiophene-2-carbaldehyde (II),which is reduced with NaBH4 in methanol to yield the corresponding methanol derivative (III).The reaction of (III) with SOCl2 in dichloromethane affords the chloromethyl derivative (IV),which is treated with triphenylphosphine in refluxing toluene to provide the phosphonium salt (V).The reaction of (V) with 1-(tert-butoxycarbonyl)piperidine-4-carbaldehyde (VI) by means of tBu-OK in DMF gives the vinyl adduct (VII),which is oxidized with MCPBA in chloroform to yield the methylsulfonyl derivative (VIII).The reduction of the vinyl group of (VIII) with H2 over Pd/C in ethanol affords the saturated compound (IX),which is treated with HCl in ethyl acetate to deprotect the piperidine NH providing piperidine (X).The condensation of (X) with 3-(chloromethyl)-2-methoxypyridine (XI) by means of K2CO3 in DMF gives the adduct (XII),which is finally treated with SOCl2 in refluxing ethanol to yield the target pyridinone derivative.