Tilmacoxib, JTE-522

4-(4-环己基-2-甲基-1,3-恶唑-5-基)-2-氟苯磺酰胺Chemical Name: 4-(4-Cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide
CAS No. 180200-68-4
项目整合开发状态: Discontinued
项目研究机构: Japan Tobacco (Originator), R.W. Johnson (Licensee)
合成路线:The condensation of cyclohexanecarbonyl chloride (I) with 3-fluorobenzyl bromide (II) by means of tetrakis(triphenylphosphine)palladium and Zn in dimethoxyethane gives the ethanone (III),which is treated with lead tetraacetate in acetic acid,yielding the alpha-acetoxyethanone (IV).The cyclization of (IV) with ammonium acetate in refluxing acetic acid affords the oxazole derivative (V),which is treated with chlorosulfonic acid at 100 C,yielding the 4-chlorosulfonyl derivative (VI).Finally,this compound is amidated with ammonia in THF/water.
📌 参考资料/链接:
参考文献标题:Heteroaromatic oxazole cpds.and use thereof
文献作者:Haruta,J.; Hashimoto,H.; Matsushita,M.(Japan Tobacco Inc.)
参考来源:EP 0745596; EP 0826676; JP 1996325249; JP 1997052882; US 5994381; WO 9619462; WO 9619463

📄 详细内容


合成路线:The condensation of cyclohexanecarbonyl chloride (I) with 3-fluorobenzyl bromide (II) by means of tetrakis(triphenylphosphine)palladium and Zn in dimethoxyethane gives the ethanone (III),which is treated with lead tetraacetate in acetic acid,yielding the alpha-acetoxyethanone (IV).The cyclization of (IV) with ammonium acetate in refluxing acetic acid affords the oxazole derivative (V),which is treated with chlorosulfonic acid at 100 C,yielding the 4-chlorosulfonyl derivative (VI).Finally,this compound is amidated with ammonia in THF/water.

参考文献标题:JTE-522
文献作者:Silvestre,J.S.; Leeson,P.A.; Castar,J.
参考来源:Drugs Fut 1998,23(6),598


合成路线:The condensation of cyclohexanecarbonyl chloride (I) with 3-fluorobenzyl bromide (II) by means of tetrakis(triphenylphosphine)palladium and Zn in dimethoxyethane gives the ethanone (III),which is treated with lead tetraacetate in acetic acid,yielding the alpha-acetoxyethanone (IV).The cyclization of (IV) with ammonium acetate in refluxing acetic acid affords the oxazole derivative (V),which is treated with chlorosulfonic acid at 100 C,yielding the 4-chlorosulfonyl derivative (VI).Finally,this compound is amidated with ammonia in THF/water.
参考文献标题:4-(4-Cycloalkyl/aryl-oxazol-5-yl)benzenesulfonamides as selective cyclooxygenase-2 inhibitors: Enhancement of the selectivity by introduction of a fluorine atom and identification of a potent,highly selective,and orally active COX-2 inhibitor JTE-522
文献作者:Hashimoto,H.; Imamura,K.; Haruta,J.; Wakitani,K.
参考来源:J Med Chem 2002,45(7),1511


产品链接: CAS No. 180200-68-4››