-药物合成数据库

【药物名称】

化学结构式(Chemical Structure):

参考文献No.	37876
标题:	Heterocyclic amide cpds. as cell adhesion inhibitors
作者:	Hagmann, W.K.; Durette, P.L.; Mumford, R.A.; Mills, S.G.; Kevin, N.J.; Schmidt, J.A.; MacCoss, M.; Van Riper, G.M. (Merck & Co., Inc.)
来源:	EP 1001764; WO 9853814

合成路线图解说明: N-Boc-L-Phenylalanine (I) is converted into the tert-butyl ester (II) upon treatment with tert-butyl trichloroacetimidate and boron trifluoride. Then, selective removal of the N-Boc group of (II) with HCl in EtOAc provides L-phenylalanine ester (III). Coupling of (III) with N-Cbz-2-methylproline (IV) furnishes dipeptide (V). After hydrogenolysis of the N-Cbz group of (V), the resultant amine (VI) is acylated by means of 3,5-dichlorobenzenesulfonyl chloride (VII), yielding sulfonamide (VIII). The tert-butyl ester group of (VIII) is finally cleaved by treatment with trifluoroacetic acid in CH2Cl2

参考文献No.	666174
标题:	Substituted N-(3,5-dichlorobenzenesulfonyl)-L-prolyl-phenylalanine analogues as potent VLA-4 antagonists
作者:	Kopka, I.E.; Young, D.N.; Lin, L.S.; Mumford, R.A.; Magriotis, P.A.; MacCoss, M.; Mills, S.G.; Van Riper, G.; McCauley, E.; Egger, L.E.; Kidambi, U.; Schmidt, J.A.; Lyons, K.A.; Stearns, R.A.; Vincent, S.H.; Colletti, A.; Wang, Z.; Tong, S.; et al.
来源:	Bioorg Med Chem Lett 2002,12(4),637

合成路线图解说明: In an alternative method, L-phenylalanine (I) is esterified employing SOCl2 in MeOH. The resultant phenylalanine methyl ester (II) is then acylated with the sulfonyl proline derivative (III) by means of PyBOP to furnish the sulfonyl dipeptide (IV). Finally, saponification of the methyl ester group of (IV) with LiOH leads to the title compound