Acrivastine, BW-825C, Semprex

阿伐斯汀Chemical Name: (E,E)-3-[6-[1-(4-Methylphenyl)-3-(1-pyrroldidinyl)-1-propenyl]-2-pyridinyl]-2-propenoic acid; (E)-6-[(E)-3-(1-Pyrrolidinyl)-1-p-tolylpropenyl]-2-pyridineacrylic acid
CAS No. 87848-99-5
项目整合开发状态: Launched-1988
项目研究机构: GlaxoSmithKline (Originator)
合成路线:A synthesis of deuterium-labeled acrivastine has been published.The reaction of 2,6-dibromopyridine (I) with butyllithium in ethyl ether gives the monolithium salt (II),which is condensed with perdeuterated 4-methylbenzaldehyde (III) in the same solvent to yield the methanol (IV).The oxidation of (IV) with pyridinium chlorochromate in dichloromethane affords the corresponding ketone (V),which is condensed with ethyl acrylate (VI) by means of palladium acetate,triphenylphosphine and tributylamine at 130 C to give 3-[6-([2H]-4-methylbenzoyl)pyridin-2-yl]acrylic acid ethyl ester (VII).The Wittig condensation of (VII) with triphenyl[2-(1-pyrrolidinyl)ethyl]phosphonium bromide (VIII) by means of butyllithium in THF affords a cis:trans mixture that is submitted to chromatography yielding the (E,E)-isomer (IX),which is finally hydrolyzed with NaOH in ethanol,at room temperature.