新产品编号:596923
Chemical Name: 3-Chloro-N-[4-chloro-2-(5-chloropyridin-2-ylcarbamoyl)-6-methoxyphenyl]-4-[[N-(4,5-dihydro-1,3-oxazol-2-yl)-N-methylamino]methyl]-2-thiophenecarboxamide
CAS No. 229335-75-5
项目整合开发状态: Preclinical
项目研究机构: Berlex (Originator)
合成路线:Treatment of 3-methoxy-2-nitrobenzoic acid (I) with oxalyl chloride gave the corresponding acid chloride (II),which was then coupled with 2-amino-5-chloropyridine (III) to yield amide (IV).The reduction of the nitro group of (IV) using sodium hydrosulfite afforded aniline (V).Further chlorination of (V) with N-chlorosuccinimide furnished the 5-chloro derivative (VI).
合成路线:Benzylic bromination of 2-(methoxycarbonyl)-3-chloro-4-methylthiophene (VII) gave rise to dibromide (VIII),which was further hydrolyzed to aldehyde (IX) using sodium acetate and acetic acid.Reduction of aldehyde (IX) with NaBH4 afforded alcohol (X).After basic hydrolysis of the methyl ester group of (X),the resulting hydroxy acid was treated with thionyl chloride to furnish (XI).Condensation of aniline (VI) with acid chloride (XI) gave amide (XII).Subsequent chloride displacement with methylamine yielded amine (XIII).This was then condensed with 2-bromoethyl isocyanate,producing the N-(2-bromoethyl)urea (XIV).Cyclization of bromo urea (XIV) upon treatment with triethylamine (1,2) or with other amines generated the title oxazoline derivative.
📌 参考资料/链接：
参考文献标题:Ortho-anthranilamide derivs.as anticoagulants
文献作者:Snider,R.M.; Liang,A.M.; Wu,S.C.; Arnaiz,D.O.; Sacchi,K.L.; Kochanny,M.J.; Phillips,G.B.; Ye,B.; Zhao,Z.; Morrissey,M.M.; Griedel,B.D.; Lee,W.; Sakata,S.T.; Karanjawala,R.E.; Chou,Y.-L.; Shaw,K.J.(Schering AG)
参考来源:EP 1040108; JP 2001526283; US 6140351; WO 9932477
📄 详细内容
合成路线:Treatment of 3-methoxy-2-nitrobenzoic acid (I) with oxalyl chloride gave the corresponding acid chloride (II),which was then coupled with 2-amino-5-chloropyridine (III) to yield amide (IV).The reduction of the nitro group of (IV) using sodium hydrosulfite afforded aniline (V).Further chlorination of (V) with N-chlorosuccinimide furnished the 5-chloro derivative (VI).
合成路线:Benzylic bromination of 2-(methoxycarbonyl)-3-chloro-4-methylthiophene (VII) gave rise to dibromide (VIII),which was further hydrolyzed to aldehyde (IX) using sodium acetate and acetic acid.Reduction of aldehyde (IX) with NaBH4 afforded alcohol (X).After basic hydrolysis of the methyl ester group of (X),the resulting hydroxy acid was treated with thionyl chloride to furnish (XI).Condensation of aniline (VI) with acid chloride (XI) gave amide (XII).Subsequent chloride displacement with methylamine yielded amine (XIII).This was then condensed with 2-bromoethyl isocyanate,producing the N-(2-bromoethyl)urea (XIV).Cyclization of bromo urea (XIV) upon treatment with triethylamine (1,2) or with other amines generated the title oxazoline derivative.
参考文献标题:Design,synthesis,and biological activity of novel non-amidine factor Xa inhibitors,4: Optimization of hydrophilic substituents for potency and oral availability
文献作者:Cheeseman,S.; Chou,Y.-L.; Ye,B.; et al.
参考来源:221st ACS Natl Meet (April 1 2001,San Diego) 2001,Abst MEDI 128