【药物名称】RPR-120844
化学结构式(Chemical Structure):
参考文献No.548631
标题:Design and structure-activity relationships of potent and selective inhibitors of blood coagulation factor Xa
作者:Ewing, W.R.; Becker, M.R.; Manetta, V.E.; Davis, R.S.; Pauls, H.W.; Mason, H.; Choi-Sledeski, Y.M.; Green, D.; Cha, D.; Spada, A.P.; Cheney, D.L.; Mason, J.S.; Maignan, S.; Guilloteau, J.P.; Brown, K.; Colussi, D.; Bentley, R.; Bostwick, J.; et al.
来源:J Med Chem 1999,42(18),3557
合成路线图解说明:

The reduction of 5-bromothiophene-3-carbaldehyde (I) with NaBH4 in THF gives the corresponding carbinol (II), which is treated with Zn(CN)2 and palladium tetrakis(triphenylphosphine) in DMF to yield 4-(hydroxymethyl)thiophene-2-carbonitrile (III). The reaction of (III) with tetrabromomethane and triphenylphosphine affords the corresponding bromomethyl derivative (IV), which is condensed with 3(S)-(tert-butoxycarbonylamino)pyrrolidin-2-one (V) by means of NaH in THF/DMF to give the expected addition product (VI). The deprotection of the amino group of (VI) with HCl in ethyl acetate yields the primary amine (VII), which is acylated with 7-methoxynaphthalene-2-sulfonyl chloride (VIII) and triethylamine in dichloromethane providing the sulfonamide (IX). The methylation of (IX) with methyl iodide and K2CO3 in DMF affords the N-methylsulfonamide (X), which is finally treated first with HCl in ethanol, and then with NH3 in methanol to convert the cyano group of (X) into the amidino group of the target compound.

Drug Information Express,Drug R&D,Chemical Database,Patent Search.
Copyright © 2006-2024 Drug Future. All rights reserved.Contact Us