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【结 构 式】 
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【分子编号】41005 【品名】5-methyl-3,4-diphenyl-4,5-dihydro-5-isoxazolol 【CA登记号】 |
【 分 子 式 】C16H15NO2 【 分 子 量 】253.30064 【元素组成】C 75.87% H 5.97% N 5.53% O 12.63% |
与该中间体有关的原料药合成路线共 2 条
合成路线1
该中间体在本合成路线中的序号：(III)Deoxybenzoin (I) is converted to the corresponding oxime (II) by treatment with NH2OH·HCl 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.
| 【1】 Leeson, P.; Castañer, J.; Castañer, R.M.; Sorbera, L.A.; Valdecoxib and Parecoxib Sodium. Drugs Fut 2001, 26, 2, 133. |
| 【2】 Carter, J.S.; Talley, J.J.; Brown, D.L.; et al.; 4-[5-Methyl-3-phenylisoxazol]4-yl]-benzenesulfonamide, valdecoxib: A potent and selective inhibitor of COX-2. J Med Chem 2000, 43, 5, 775. |
| 【3】 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.); Substd. isoxazoles for the treatment of inflammation. EP 0809636; JP 1999503722; US 5633272; WO 9625405 . |
| 【4】 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.); Substd. sulfonylphenylheterocycles as cyclooxygenase-2 and 5-lipoxygenase inhibitors. EP 0828736; EP 0995747; US 5643933; WO 9638442 . |
| 【5】 Talley, J.J. (Pharmacia Corp.); Isoxazole cpds. as cyclooxygenase inhibitors. US 5859257 . |
合成路线2
该中间体在本合成路线中的序号： (II)
| 【1】 Di Nunno L. Vitale P, Scilimati A, et aL. 2004. Novel synthesis of 3,4-diarylisoxuole analogues of valdecoxib; reversal cyclooxygenase-2 selectivity by sulfonamide group removal. J Med Chem, 47: 4881～4890 |
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