GW-4064, GW-4064X

3-(2,6-二氯苯基)-4-(3'-羧基-2-氯二苯乙烯-4-基)氧甲基-5-异丙基异恶唑Chemical Name: 3-[2-[2-Chloro-4-[3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-ylmethoxy]phenyl]vinyl]benzoic acid
CAS No. 278779-30-9
项目整合开发状态: Preclinical
项目研究机构: GlaxoSmithKline (Originator)
合成路线:2,6-Dichlorobenzaldehyde (I) was converted to oxime (II) and then chlorinated with N-chlorosuccinimide to afford the oximidoyl chloride (III).The cycloaddition reaction between ketoester (IV) and the nitrile oxide resulting from (III) in the presence of NaOMe gave rise to the isoxazole system (V).The ester group of (V) was then reduced to alcohol (VI) employing diisobutylaluminium hydride.Subsequent coupling of alcohol (VI) with 2-chloro-4-hydroxybenzaldehyde (VII) under Mitsunobu conditions provided ether (VIII).Phosphonate (X) was prepared by heating methyl 3-(bromomethyl)benzoate (IX) with triethyl phosphite at 185 C.Horner-Emmons condensation of aldehyde (VIII) with phosphonate (X) in the presence of NaH in THF furnished the stilbene derivative (XI).The methyl ester group of (XI) was finally hydrolyzed by means of LiOH in aqueous THF.