新产品编号:799419
Chemical Name: 3(R)-[1-(3,5-Dichlorophenylsulfonyl)azetidin-2(S)-ylcarboxamido]-3-(4-methoxyphenyl)propionic acid
CAS No. 309976-72-5
项目整合开发状态: Preclinical
项目研究机构: Merck & Co. (Originator)
合成路线:Condensation of 3,5-dichlorobenzenesulfonyl chloride (VIII) with (S)-azetidine-2-carboxylic acid (IX) under Schotten-Baumann conditions gives sulfonamide (X).This is subsequently coupled with aminoester (VII) by means of PyBOP to afford amide (XI).The methyl ester group of (XI) is finally hydrolyzed to the target carboxylic acid employing LiOH.
📌 参考资料/链接：
参考文献标题:Substd.beta-alanine derivs.as cell adhesion inhibitors
文献作者:Hagmann,W.K.; Durette,P.L.; Mumford,R.A.; Kopka,I.E.; Mills,S.G.; MacCoss,M.; Magriotis,P.A.(Merck & Co.,Inc.)
参考来源:WO 0071572
📄 详细内容
合成路线:The Michael addition of the chiral amine (II) to methyl 4-(benzyloxy)cinnamate (I) in the presence of butyllithium produces diastereoselectively the amino ester (III) as the major isomer.After catalytic hydrogenolysis of the benzyl groups of (III),the resultant amino ester (IV) is converted to the N-Boc derivative (V) upon treatment with Boc2O.O-alkylation of phenol (V) with iodomethane in the presence of Cs2CO3 yields methyl ether (VI).The N-Boc group of (VI) is subsequently removed under acidic conditions to furnish (VII).
合成路线:Condensation of 3,5-dichlorobenzenesulfonyl chloride (VIII) with (S)-azetidine-2-carboxylic acid (IX) under Schotten-Baumann conditions gives sulfonamide (X).This is subsequently coupled with aminoester (VII) by means of PyBOP to afford amide (XI).The methyl ester group of (XI) is finally hydrolyzed to the target carboxylic acid employing LiOH.
参考文献标题:The discovery of acylated beta-amino acids as potent and orally bioavailable VLA-4 antagonists
文献作者:Lin,L.S.; Kopka,I.E.; Mumford,R.A.; Magriotis,P.A.; Lanza,T.Jr.; Durette,P.L.; Kamenecka,T.; Young,D.N.; de Laszlo,S.E.; McCauley,E.; Riper,G.V.; Kidambi,U.; Egger,L.A.; Tong,X.; Lyons,K.A.; Vincent,S.H.; Stearns,R.A.; et al.
参考来源:Bioorg Med Chem Lett 2002,12(4),611