新产品编号:1266109

Chemical Name: 1-(3-Chloro-4-fluorobenzoyl)-4-[6-(dimethylamino)pyridin-2-yl-methylaminomethyl]-4-fluoropiperidine fumarate
项目整合开发状态: Preclinical
项目研究机构: Pierre Fabre (Originator)
合成路线:Acylation of 4-piperidone ethylene ketal (I) with 3-chloro-4-fluorobenzoyl chloride (II) in the presence of Et3N gave amide (III).After ketal hydrolysis of (III) using 80% formic acid and CuSO4,treatment of the resulting N-acyl piperidone (IV) with dimethyloxosulfonium methylide provided epoxide (V).Subsequent ring opening of (V) with HF-pyridine complex afforded the fluoro alcohol (VI),which was converted to tosylate (VII).Then,Gabriel synthesis via the corresponding phthalimide (VIII) produced amine (IX).The pyridine-2-carboxaldehyde (XII) was prepared by reduction of ethyl 6-chloro-5-methylpyridine-2-carboxylate (X) with NaBH4,followed by displacement of the chloro group by ethanolic methylamine in a sealed vessel at 100 C yielding pyridinealcohol (XI),which was further oxidized to the desired aldehyde (XII) using MnO2.The title compound was then obtained by condensation of amine (IX) with aldehyde (XII),followed by reduction of the intermediate imine with KBH4 in MeOH.

合成路线:Acylation of 4-piperidone ethylene ketal (I) with 3-chloro-4-fluorobenzoyl chloride (II) in the presence of Et3N gave amide (III).After ketal hydrolysis of (III) using 80% formic acid and CuSO4,treatment of the resulting N-acyl piperidone (IV) with dimethyloxosulfonium methylide provided epoxide (V).Subsequent ring opening of (V) with HF-pyridine complex afforded the fluoro alcohol (VI),which was converted to tosylate (VII).Then,Gabriel synthesis via the corresponding phthalimide (VIII) produced amine (IX).The title compound was then obtained by condensation of 6-(dimethylamino)pyridine-2-carboxaldehyde (X) with amine (IX),followed by reduction of the intermediate imine with KBH4 in MeOH.

合成路线:Acylation of 4-piperidone ethylene ketal (I) with 3-chloro-4-fluorobenzoyl chloride (II) in the presence of Et3N gave amide (III).After ketal hydrolysis of (III) using 80% formic acid and CuSO4,treatment of the resulting N-acyl piperidone (IV) with dimethyloxosulfonium methylide provided epoxide (V).Subsequent ring opening of (V) with HF-pyridine complex afforded the fluoro alcohol (VI),which was converted to tosylate (VII).Then,Gabriel synthesis via the corresponding phthalimide (VIII) produced amine (IX).The title compound was then obtained by condensation of 6-(2-furanyl)pyridine-2-carboxaldehyde (X) with amine (IX),followed by reduction of the intermediate imine with KBH4 in MeOH.