GW-3965
3-[3-[[[2-氯-3-(三氟甲基)苯基]甲基](2,2-联苯基乙基)氨基]丙氧基]苯乙酸盐酸盐 GW3965盐酸盐 Chemical Name: 2-[3-[3-[N-[2-Chloro-3-(trifluoromethyl)benzyl]-N-(2,2-diphenylethyl)amino]propoxy]phenyl]acetic acid
CAS No. 405911-09-3, 405911-17-3 (hydrochloride)
项目整合开发状态: Preclinical
项目研究机构: GlaxoSmithKline (Originator)
合成路线:The title compound was prepared by solid-phase synthesis on a Sasrin resin.The silylated m-hydroxyphenylacetic acid (I) was attached to the resin using DCC and DMAP to yield the acid-bound resin (II).The silyl group of (II) was then removed by treatment of resin (II) with tetrabutylammonium fluoride in THF.The resultant phenol (III) was coupled to 3-bromo-1-propanol (IV) under Mitsunobu conditions to afford the bromide functionalized resin (V).Displacement of the bromide ion of (V) with 2,2-diphenylethylamine (VI) furnished the secondary amine (VII),which was subjected to reductive alkylation with aldehyde (VIII) in the presence of NaBH(OAc)3 to produce the resin-bound product (IX).Cleavage from the solid support employing trifluoroacetic acid in CH2Cl2 provided the target carboxylic acid.
合成路线:In a solution-phase synthesis,2,2-diphenylethylamine (VI) was reductively condensed with 2-chloro-3-(trifluoromethyl)benzaldehyde (VIII) using a polymer-supported borohydride resin to give the secondary amine (X).Mitsunobu coupling of methyl 3-hydroxyphenylacetate (XI) with 3-bromo-1-propanol (IV) afforded the bromopropyl ether (XII).Condensation of bromide (XII) with amine (X) in refluxing acetonitrile furnished amino ester (XIII).This was finally hydrolyzed with LiOH to the title carboxylic acid.
📌 参考资料/链接：
参考文献标题:Chemical cpds.
文献作者:Willson,T.M.; Collins,J.L.; Maloney,P.R.; Fivush,A.M.; Stewart,E.L.(GlaxoSmithKline plc)
参考来源:WO 0224632
📄 详细内容
合成路线:The title compound was prepared by solid-phase synthesis on a Sasrin resin.The silylated m-hydroxyphenylacetic acid (I) was attached to the resin using DCC and DMAP to yield the acid-bound resin (II).The silyl group of (II) was then removed by treatment of resin (II) with tetrabutylammonium fluoride in THF.The resultant phenol (III) was coupled to 3-bromo-1-propanol (IV) under Mitsunobu conditions to afford the bromide functionalized resin (V).Displacement of the bromide ion of (V) with 2,2-diphenylethylamine (VI) furnished the secondary amine (VII),which was subjected to reductive alkylation with aldehyde (VIII) in the presence of NaBH(OAc)3 to produce the resin-bound product (IX).Cleavage from the solid support employing trifluoroacetic acid in CH2Cl2 provided the target carboxylic acid.
参考文献标题:Identification of a nonsteroidal liver X receptor agonist through parallel array synthesis of tertiary amines
文献作者:Collins,J.L.; Fivush,A.M.; Watson,M.A.; Galardi,C.M.; Lewis,M.C.; Moore,L.B.; Parks,D.J.; Wilson,J.G.; Tippin,T.K.; Binz,J.G.; Plunket,K.D.; Morgan,D.G.; Beaudet,E.J.; Whitney,K.D.; Kliewer,S.A.; Willson,T.M.
参考来源:J Med Chem 2002,45(10),1963
产品链接: CAS No. 405911-09-3›› 产品链接: CAS No.405911-17-3››