新产品编号:582685
Chemical Name: 2-[4-(3'-Ethoxy-2-methylbiphenyl-4-yl)-1,2,3,6-tetrahydropyridin-1-ylsulfonyl]acetohydroxamic acid; 2-[4-(3'-Ethoxy-2-methylbiphenyl-4-yl)-1,2,3,6-tetrahydropyridin-1-ylsulfonyl]-N-hydroxyacetamide
CAS No. 227304-15-6
项目整合开发状态: Biological Testing
项目研究机构: Pfizer (Originator)
合成路线:Lithiation of 2,5-dibromotoluene (I) with n-butyllithium at -75 C produced a mixture of 5-lithio (II) and 2-lithio (III) toluenes.Addition of this mixture to N-Boc-4-piperidone (IV) at low temperature provided the desired carbinol (V) and the corresponding 2-tolyl regioisomer,which were separated by flash chromatography (1).Alternatively,carbinol (V) was obtained by regioselective metallation of 2-bromo-5-iodotoluene (VI) and then addition to N-Boc-4-piperidone (IV).Dehydration of carbinol (V) with concomitant N-Boc group cleavage under acidic conditions furnished the tetrahydropyridine (VII).This was sulfonylated with methyl chlorosulfonylacetate (VIII) in the presence of either N,O-bis(trimethylsilyl)acetamide or diazabicycloundecene,producing sulfonamide (IX).Suzuki coupling of aryl bromide (IX) with 3-ethoxyphenylboronic acid (X) gave biphenyl (XI).The methyl ester group of (XI) was then condensed with hydroxylamine to afford the title hydroxamic acid.
📌 参考资料/链接：
参考文献标题:Hydroxamic acid derivs.as matrix metalloprotease (MMP) inhibitors
文献作者:Whitlock,G.A.; Dack,K.N.(Pfizer Inc.)
参考来源:EP 1036062; JP 2001525396; WO 9929667
📄 详细内容
合成路线:Lithiation of 2,5-dibromotoluene (I) with n-butyllithium at -75 C produced a mixture of 5-lithio (II) and 2-lithio (III) toluenes.Addition of this mixture to N-Boc-4-piperidone (IV) at low temperature provided the desired carbinol (V) and the corresponding 2-tolyl regioisomer,which were separated by flash chromatography (1).Alternatively,carbinol (V) was obtained by regioselective metallation of 2-bromo-5-iodotoluene (VI) and then addition to N-Boc-4-piperidone (IV).Dehydration of carbinol (V) with concomitant N-Boc group cleavage under acidic conditions furnished the tetrahydropyridine (VII).This was sulfonylated with methyl chlorosulfonylacetate (VIII) in the presence of either N,O-bis(trimethylsilyl)acetamide or diazabicycloundecene,producing sulfonamide (IX).Suzuki coupling of aryl bromide (IX) with 3-ethoxyphenylboronic acid (X) gave biphenyl (XI).The methyl ester group of (XI) was then condensed with hydroxylamine to afford the title hydroxamic acid.
参考文献标题:Design and synthesis of a novel series of matrix metalloproteinase inhibitors with high selectivity for MMP-3
文献作者:Dack,K.N.; et al.
参考来源:222nd ACS Natl Meet (Aug 26 2001,Chicago) 2001,Abst MEDI 260
产品链接: CAS No. 227304-15-6››