新产品编号:465617
Chemical Name: 1-(4-Methoxyphenyl)-3-methyl-N-(2'-sulfamoylbiphenyl-4-yl)-1H-pyrazole-5-carboxamide
CAS No. 218629-72-2
项目整合开发状态: Preclinical
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:Ethyl 2,4-dioxopentanoate (V) was converted into the O-methyloxime (VI) and subsequently cyclized with 4-methoxyphenylhydrazine (VII) to furnish pyrazole (VIII) (1,2).Optionally,ester (VIII) was hydrolyzed and then converted to acid chloride (IX) by treatment with oxalyl chloride (1).Biphenylamine (IV) was coupled with ester (VIII) in the presence of trimethylaluminium (2) or,alternatively,with acid chloride (IX) (1) to give amide (X).The N-tert-butyl group of (X) was finally removed by refluxing in trifluoroacetic acid.
📌 参考资料/链接：
参考文献标题:Inhibitors of factor Xa with a neutral P1 specificity group
文献作者:Dominguez,C.; Fevig,J.M.; Galemmo,R.A.Jr.; Pinto,D.J.P.; Pruitt,J.R.; lma,P.; Quan,M.L.; Han,Q.(DuPont Pharmaceuticals Co.)
参考来源:US 5998424; WO 9857937
📄 详细内容
合成路线:The intermediate biphenylamine (IV) was prepared by Suzuki coupling of N-Boc-4-bromoaniline (I) with 2-(N-tert-butylaminosulfonyl)phenylboronic acid (II),followed by deprotection of the Boc group.
合成路线:Ethyl 2,4-dioxopentanoate (V) was converted into the O-methyloxime (VI) and subsequently cyclized with 4-methoxyphenylhydrazine (VII) to furnish pyrazole (VIII) (1,2).Optionally,ester (VIII) was hydrolyzed and then converted to acid chloride (IX) by treatment with oxalyl chloride (1).Biphenylamine (IV) was coupled with ester (VIII) in the presence of trimethylaluminium (2) or,alternatively,with acid chloride (IX) (1) to give amide (X).The N-tert-butyl group of (X) was finally removed by refluxing in trifluoroacetic acid.
参考文献标题:New functional groups for interaction with the S1 pocket of factor Xa: The discovery of 1-(4-methoxyphenyl)pyrazole inhibitors
文献作者:Galemmo,R.A.Jr.; Fevig,J.; Lam,P.Y.; et al.
参考来源:220th ACS Natl Meet (Aug 20 2000,Washington DC) 2000,Abst MEDI 290