Gantofiban, YM-028, EMD-122-347
Chemical Name: 2-[4-[3-[4-[N1-(Methoxycarbonyl)amidino]phenyl]-2-oxooxazolidin-5(R)-ylmethyl]piperazin-1-yl]acetic acid ethyl ester
CAS No. 183547-57-1
项目整合开发状态: Discontinued
项目研究机构: Merck KGaA (Originator), Yamanouchi (Licensee)
合成路线:The condensation of 4-aminobenzonitrile (I) with the chiral 2,3-epoxypropanol (II) in refluxing methanol gives 4-(2,3-dihydroxypropylamino)benzonitrile (III),which is cyclized with diethyl carbonate (IV) by means of tBu-OK at 100 C to yield the oxazolidinone (V).The reaction of the cyano group of (V) with hydroxylamine in methanol affords the N-hydroxyamidine (VI),which is cyclized with Ac2O at 120 C to provide the 1,2,4-oxadiazole (VII).The hydrolysis of the acetoxy group of (VII) with K2CO3 in refluxing methanol gives the primary alcohol (VIII),which is treated with Ms-Cl and pyridine to yield the corresponding mesylate (IX).The condensation of (IX) with 2-(1-piperazinyl)acetic acid ethyl ester (X) in refluxing acetonitrile affords the adduct (XI),which is hydrogenated with H2 over Pd/C and hydrolyzed with HOAc to obtain the benzamidine derivative (XII).Finally,this compound is acylated with methyl chloroformate (XIII) and NaOH in dichloromethane/water.
📌 参考资料/链接：
参考文献标题:Adhesion receptor antagonists
文献作者:Gante,J.; Juraszyk,H.; Raddatz,P.; Wurziger,H.; Bernotat-Danielowski,S.; Melzer,G.(Merck Patent GmbH)
参考来源:CA 2175767; DE 19516483; EP 0741133; JP 1996301857; US 6455529
📄 详细内容
合成路线:The condensation of 4-aminobenzonitrile (I) with the chiral 2,3-epoxypropanol (II) in refluxing methanol gives 4-(2,3-dihydroxypropylamino)benzonitrile (III),which is cyclized with diethyl carbonate (IV) by means of tBu-OK at 100 C to yield the oxazolidinone (V).The reaction of the cyano group of (V) with hydroxylamine in methanol affords the N-hydroxyamidine (VI),which is cyclized with Ac2O at 120 C to provide the 1,2,4-oxadiazole (VII).The hydrolysis of the acetoxy group of (VII) with K2CO3 in refluxing methanol gives the primary alcohol (VIII),which is treated with Ms-Cl and pyridine to yield the corresponding mesylate (IX).The condensation of (IX) with 2-(1-piperazinyl)acetic acid ethyl ester (X) in refluxing acetonitrile affords the adduct (XI),which is hydrogenated with H2 over Pd/C and hydrolyzed with HOAc to obtain the benzamidine derivative (XII).Finally,this compound is acylated with methyl chloroformate (XIII) and NaOH in dichloromethane/water.
参考文献标题:New antithrombotic RGD-mimetics with bioavailability
文献作者:Gante,J.; et al.
参考来源:Bioorg Med Chem Lett 1996,6(20),2425
产品链接: CAS No. 183547-57-1››