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【结 构 式】 
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【药物名称】KP-103 【化学名称】(R,R)-2-(2,4-Difluorophenyl)-3-(4-methylenepiperidin-1-yl)-1-(1,2,4-triazol-1-yl)-2-butanol 【CA登记号】164650-44-6 【 分 子 式 】C18H22F2N4O 【 分 子 量 】348.39904 |
【开发单位】Kaken (Originator) 【药理作用】Antifungal Agents, ANTIINFECTIVE THERAPY |
合成路线1
Condensation of ethyl 4-piperidinecarboxylate (I) with benzoyl chloride in pyridine afforded the corresponding benzamide (II). After reduction of the ester group of (II) with NaBH4, the resulting alcohol (III) was converted to chloride (IV) by means of SOCl2. Elimination of the chlorine atom of (IV) with potassium tert-butoxide produced N-benzoyl-4-methylenepiperidine (V), which was hydrolyzed with KOH to yield 4-methylenepiperidine (VI). Finally, condensation of (VI) with the known epoxide (VII) in refluxing EtOH furnished the title compound.
| 【1】 Ogura, H.; et al.; Synthesis and antifungal activities of (2R,3R)-2-aryl-1-azolyl-3-(substituted amino)-2-butanol derivatives as topical antifungal agents. Chem Pharm Bull 1999, 47, 10, 1417. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 10463 | Benzoyl chloride | 98-88-4 | C7H5ClO | 详情 | 详情 | |
| (I) | 17410 | Ethyl isonipecotate; ethyl 4-piperidinecarboxylate | 1126-09-6 | C8H15NO2 | 详情 | 详情 |
| (II) | 31733 | ethyl 1-benzoyl-4-piperidinecarboxylate | C15H19NO3 | 详情 | 详情 | |
| (III) | 31734 | [4-(hydroxymethyl)-1-piperidinyl](phenyl)methanone | C13H17NO2 | 详情 | 详情 | |
| (IV) | 31735 | [4-(chloromethyl)-1-piperidinyl](phenyl)methanone | C13H16ClNO | 详情 | 详情 | |
| (V) | 31736 | (4-methylene-1-piperidinyl)(phenyl)methanone | C13H15NO | 详情 | 详情 | |
| (VI) | 31737 | 4-methylenepiperidine | C6H11N | 详情 | 详情 | |
| (VII) | 31738 | 1-[[(2R,3S)-2-(2,4-difluorophenyl)-3-methyloxiranyl]methyl]-1H-1,2,4-triazole | C12H11F2N3O | 详情 | 详情 |