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【结 构 式】 
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【分子编号】54580 【品名】5-methyl-N-[4-(trifluoromethyl)phenyl]-4-isoxazolecarboxamide 【CA登记号】 |
【 分 子 式 】C12H9F3N2O2 【 分 子 量 】270.2109496 【元素组成】C 53.34% H 3.36% F 21.09% N 10.37% O 11.84% |
合成路线1
该中间体在本合成路线中的序号：(IV)5-Methylisoxazole-4-carboxylic acid (I) was converted to the corresponding acid chloride (II) upon refluxing with SOCl2. Coupling of acid chloride (II) with 4-(trifluoromethyl)aniline (III) produced anilide (IV). Finally, isoxazole ring opening in the presence of NaOH gave rise to the title cyano amide.
| 【1】 Bartlett, R.R.; Kämmerer, F.-J. (Aventis SA); Isoxazole-4-carboxamides and hydroxyalkylidene-cyanoacetamides, drugs containing these cpds. and use of such drugs. EP 0527736; JP 1993506425; JP 1999322700; JP 1999343285; US 5494911; US 5532259; WO 9117748 . |
| 【2】 Coghlan, M.J.; Luly, J.R.; Wiedeman, P.E. (Abbott Laboratories Inc.); Immunosuppressive agents. WO 9424095 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 17340 | 5-methyl-4-isoxazolecarboxylic acid | 42831-50-5 | C5H5NO3 | 详情 | 详情 |
| (II) | 17341 | 5-methyl-4-isoxazolecarbonyl chloride | 67305-24-2 | C5H4ClNO2 | 详情 | 详情 |
| (III) | 17333 | 4-(trifluoromethyl)aniline; p-Trifluoromethylaniline; 4-(trifluoromethyl)phenylamine; 4-aminobenzotrifluoride | 455-14-1 | C7H6F3N | 详情 | 详情 |
| (IV) | 54580 | 5-methyl-N-[4-(trifluoromethyl)phenyl]-4-isoxazolecarboxamide | C12H9F3N2O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)FK-778 is obtained by selective alkylation of leflunomide (I) at the methyl group with propargyl iodide (II) by means of butyl lithium in THF at 78 C to give N-(4-trifluoromethylphenyl)-5-(3-butynyl)isoxazole-4-carboxamide (III), which is finally treated with water at 0 C.
| 【3】 Bartlett, R.R.; Kay, D.P.; Kuo, E.A.; Schleyerbach, R.; Schwab, W. (Aventis Pharma SA); Cyano-2-hydroxy-3-enamide derivs., process for their preparation, their use as drugs, pharmaceutical compsns. containing them and intermediates obtained. EP 0551230; JP 1993310672; US 5308865 . |
| 【1】 Cullell-Young, M.; Castaner, R.M.; Leeson, P.A.; FK-778. Drugs Fut 2002, 27, 8, 733. |
| 【2】 Graul, A.; Castaner, J.; Leflunomide < Rec INN >. Drugs Fut 1998, 23, 8, 827. |