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Valdecoxib, YM-974, SC-65872, Kudeq, Valdyn, Bextra

伐地考昔Chemical Name: 4-(5-Methyl-3-phenylisoxazol-4-yl)benzenesulfonamide
CAS No. 181695-72-7
项目整合开发状态: Launched-2002
项目研究机构: Pfizer (Originator), Yamanouchi (Licensee), Pfizer (Codevelopment)
合成路线:Deoxybenzoin (I) is converted to the corresponding oxime (II) by treatment with NH2OH稨Cl under basic conditions either with sodium acetate in aqueous ethanol or in toluene in presence of potassium hydroxide in absolute ethanol.Deprotonation of the oxime under nitrogen with 2eq of butyllithium in THF followed by cyclization in ethyl acetate or acetic anhydride affords isoxazoline (III).Finally,treatment of (III) with cold chlorosulfonic acid followed by reaction of the intermediate sulfonyl chloride with aqueous ammonia affords the desired product.
📌 参考资料/链接:
参考文献标题:Substd.isoxazoles for the treatment of inflammation
文献作者:Talley,J.J.; Brown,D.L.; Nagarajan,S.; Carter,J.S.; Weier,R.M.; Stealey,M.A.; Collins,P.W.; Seibert,K.; Graneto,M.J.; Xu,X.; Partis,R.(Pharmacia Corp.)
参考来源:EP 0809636; JP 1999503722; US 5633272; WO 9625405

📄 详细内容


合成路线:Deoxybenzoin (I) is converted to the corresponding oxime (II) by treatment with NH2OH稨Cl under basic conditions either with sodium acetate in aqueous ethanol or in toluene in presence of potassium hydroxide in absolute ethanol.Deprotonation of the oxime under nitrogen with 2eq of butyllithium in THF followed by cyclization in ethyl acetate or acetic anhydride affords isoxazoline (III).Finally,treatment of (III) with cold chlorosulfonic acid followed by reaction of the intermediate sulfonyl chloride with aqueous ammonia affords the desired product.

参考文献标题:Substd.sulfonylphenylheterocycles as cyclooxygenase-2 and 5-lipoxygenase inhibitors
文献作者:Talley,J.J.; Sikorski,J.A.; Devadas,B.; Graneto,M.J.; Carter,J.S.; Norman,B.H.; Lu,H.-F.; Brown,D.L.(Pharmacia Corp.)
参考来源:EP 0828736; EP 0995747; US 5643933; WO 9638442


合成路线:Deoxybenzoin (I) is converted to the corresponding oxime (II) by treatment with NH2OH稨Cl under basic conditions either with sodium acetate in aqueous ethanol or in toluene in presence of potassium hydroxide in absolute ethanol.Deprotonation of the oxime under nitrogen with 2eq of butyllithium in THF followed by cyclization in ethyl acetate or acetic anhydride affords isoxazoline (III).Finally,treatment of (III) with cold chlorosulfonic acid followed by reaction of the intermediate sulfonyl chloride with aqueous ammonia affords the desired product.

参考文献标题:Isoxazole cpds.as cyclooxygenase inhibitors
文献作者:Talley,J.J.(Pharmacia Corp.)
参考来源:US 5859257


合成路线:Deoxybenzoin (I) is converted to the corresponding oxime (II) by treatment with NH2OH稨Cl under basic conditions either with sodium acetate in aqueous ethanol or in toluene in presence of potassium hydroxide in absolute ethanol.Deprotonation of the oxime under nitrogen with 2eq of butyllithium in THF followed by cyclization in ethyl acetate or acetic anhydride affords isoxazoline (III).Finally,treatment of (III) with cold chlorosulfonic acid followed by reaction of the intermediate sulfonyl chloride with aqueous ammonia affords the desired product.

参考文献标题:4-[5-Methyl-3-phenylisoxazol]4-yl]-benzenesulfonamide,valdecoxib: A potent and selective inhibitor of COX-2
文献作者:Talley,J.J.; Brown,D.L.; Carter,J.S.; Graneto,M.J.; Koboldt,C.M.; Masferrer,J.L.; Perkins,W.E.; Rogers,R.S.; Shaffer,A.F.; Zhang,Y.Y.; Zweifel,B.S.; Seibert,K.
参考来源:J Med Chem 2000,43(5),775


合成路线:Deoxybenzoin (I) is converted to the corresponding oxime (II) by treatment with NH2OH稨Cl under basic conditions either with sodium acetate in aqueous ethanol or in toluene in presence of potassium hydroxide in absolute ethanol.Deprotonation of the oxime under nitrogen with 2eq of butyllithium in THF followed by cyclization in ethyl acetate or acetic anhydride affords isoxazoline (III).Finally,treatment of (III) with cold chlorosulfonic acid followed by reaction of the intermediate sulfonyl chloride with aqueous ammonia affords the desired product.

合成路线:The acylation of 4-(5-methyl-3-phenylisoxazol-4-yl)benzenesulfonamide,valdecoxib (I),with propionic anhydride (II) by means of TEA and DMAP in THF gives N-[4-(5-methyl-3-phenylisoxazol-4-yl)phenylsulfonyl]propionamide (III),which is then treated with NaOH in ethanol.
参考文献标题:Valdecoxib and Parecoxib Sodium
文献作者:Leeson,P.; Castar,J.; Castar,R.M.; Sorbera,L.A.
参考来源:Drugs Fut 2001,26(2),133


产品链接: CAS No. 181695-72-7››