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【结 构 式】 
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【分子编号】17294 【品名】4-(methylsulfonyl)benzaldehyde; 4-Methylsulfonyl benzaldehyde 【CA登记号】5398-77-6 |
【 分 子 式 】C8H8O3S 【 分 子 量 】184.21572 【元素组成】C 52.16% H 4.38% O 26.06% S 17.41% |
合成路线1
该中间体在本合成路线中的序号：(I)By condensation of 4-(methylsulfonyl)benzaldehyde (I) with pentane-2,4-dione (II) by means of SOCl2 in isopropanol.
| 【1】 Graul, A.; Wrobleski, T.; Castañer, J.; Orazipone. Drugs Fut 1998, 23, 1, 28. |
| 【2】 Backstrom, R.J.; Honkanen, E.J.; Pystynen, J.J.; Luiro, A.M.; Aho, P.A.; Linden, I.-B.Y.; Nissinen, E.A.O.; Pohto, P. (Orion Corporation); Substd. beta-diketones and their use. EP 0440324; JP 1992253933; US 5185370 . |
合成路线2
该中间体在本合成路线中的序号：(XXII)2) Synthesis of etoricoxib via ketosulfone (XXIV): a) The reaction of 6-methylpyridine-3-carboxylic acid methyl ester (XVIII) with N,O-dimethylhydroxylamine and isopropylmagnesium chloride in toluene gives the N-methoxyamide (XIX), which is reduced with DIBAL to afford 6-methylpyridine-3-carbaldehyde (XX). Reaction of aldehyde (XX) with aniline and diphenyl phosphite provides the diphenyl phosphonate (XXI), which is condensed with 4-(methylsulfonyl)benzaldehyde (XXII) by means of potassium tert-butoxide in HF to yield the enimine (XXIII). Finally, this compound is hydrolyzed with HCl to give ketosulfone (XXIV). b) Condensation of N-methoxyamide (XIX) with 4-(methylsulfanyl)benzylmagnesium bromide (XXV) in toluene/THF gives 1-(6-methylpyridin-3-yl)-2-[4-(methylsulfanyl)phenyl]ethanone (XXVI), which is finally oxidized with Na2WO4 to yield ketosulfone (XXIV). c) Oxidation of 4'-(methylsulfonyl)acetophenone (XXVII) with S8 and morpholine, followed by esterification with ethanol, affords 2-[4-(methylsulfonyl)phenyl]acetic acid ethyl ester (XXVIII); which is condensed with 6-methylpyridine-3-carboxylic acid methyl ester (XVIII) by means of t-BuMgCl in hot THF to furnish ketosulfone (XXIV).
| 【1】 Castañer, R.M.; Silvestre, J.S.; Sorbera, L.A.; Castañer, J.; Etoricoxib. Drugs Fut 2001, 26, 4, 346. |
| 【2】 Davies, I.W.; Marcoux, J.-F.; Corley, E.G.; et al.; A practical synthesis of a COX-2-specific inhibitor. J Org Chem 2000, 65, 25, 8415. |
| 【3】 Corley, E.G.; Davies, I.W.; Larsen, R.D.; Rossen, K.; Pye, P.J. (Merck & Co., Inc.); Process for synthesizing COX-2 inhibitors. US 6040319; WO 9955830 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVIII) | 14160 | methyl 6-methylnicotinate | 5470-70-2 | C8H9NO2 | 详情 | 详情 |
| (XIX) | 45705 | N-methoxy-N,6-dimethylnicotinamide | C9H12N2O2 | 详情 | 详情 | |
| (XX) | 22949 | 6-methylnicotinaldehyde | C7H7NO | 详情 | 详情 | |
| (XXI) | 45706 | diphenyl anilino(6-methyl-3-pyridinyl)methylphosphonate | C25H23N2O3P | 详情 | 详情 | |
| (XXII) | 17294 | 4-(methylsulfonyl)benzaldehyde; 4-Methylsulfonyl benzaldehyde | 5398-77-6 | C8H8O3S | 详情 | 详情 |
| (XXIII) | 45710 | N-[(E)-1-(6-methyl-3-pyridinyl)-2-[4-(methylsulfonyl)phenyl]ethenyl]-N-phenylamine; N-[(E)-1-(6-methyl-3-pyridinyl)-2-[4-(methylsulfonyl)phenyl]ethenyl]aniline | C21H20N2O2S | 详情 | 详情 | |
| (XXIV) | 45711 | 1-(6-methyl-3-pyridinyl)-2-[4-(methylsulfonyl)phenyl]-1-ethanone | C15H15NO3S | 详情 | 详情 | |
| (XXV) | 45707 | chloro[4-(methylsulfanyl)benzyl]magnesium | C8H9ClMgS | 详情 | 详情 | |
| (XXVI) | 45708 | 1-(6-methyl-3-pyridinyl)-2-[4-(methylsulfanyl)phenyl]-1-ethanone | C15H15NOS | 详情 | 详情 | |
| (XXVII) | 19263 | 1-[4-(methylsulfonyl)phenyl]-1-ethanone; 4-methylsulfonylacetophenone | 10297-73-1 | C9H10O3S | 详情 | 详情 |
| (XXVIII) | 45709 | ethyl 2-[4-(methylsulfonyl)phenyl]acetate | C11H14O4S | 详情 | 详情 |