YM-264

Chemical Name: 1-(3-Methyl-3-phenylbutyl)-4-[2-(3-pyridyl)thiazolidin-4(R)-ylcarbonyl]piperazine fumarate
CAS No. 126911-71-5 (free base)
项目整合开发状态: Phase II
项目研究机构: Yamanouchi (Originator)
合成路线:The cyclization of pyridine-3-carbaldehyde (I) with L-cysteine (II) gives 2-(3-pyridyl)thiazolidine-4(R)-carboxylic acid (II),which is finally condensed with 1-(3-phenylpropyl)piperazine (IV) by means of DCC and HOBT in DMF.The intermediate 1-(3-phenylpropyl)piperazine (IV) has been obtained as follows: The condensation of piperazine-1-carboxylic acid ethyl ester (V) with 3-phenylpropyl bromide (VI) by means of K2CO3 in 2-butanone gives 4-(3-phenylpropyl)piperazine-1-carboxylic acid ethyl ester (VII),which is decarboxylated with NaOH in refluxing ethanol.

合成路线:The cyclization of pyridine-3-carbaldehyde (I) with L-cysteine (II) gives 2-(3-pyridyl)thiazolidine-4(R)-carboxylic acid (III),which is finally condensed with 1-(3-methyl-3-phenylbutyl)piperazine (IV) by means of DCC and HOBT In DMF.The intermediate 1-(3-methyl-3-phenylbutyl)piperazine (IV) has been obtained as follows: The reduction of 3-methyl-3-phenylbutyric acid (IV) with LiAlH4 in THF gives the corresponding butanol (V),which is treated with refluxing 48% HBr to yield the 3-methyl-3-phenylbutyl bromide (VI).The condensation of (VI) with piperazine-1-carboxylic acid ethyl ester (VII) by means of K2CO3 in 2-butanone gives 4-(3-methyl-3-phenylbutyl)piperazine-1-carboxylic acid ethyl ester (VIII),which is decarboxylated with NaOH in refluxing ethanol.