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【结 构 式】 
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【药物名称】YM-53389 【化学名称】(+)-2-Chloro-5-methoxy-4-[5-[piperidin-2(S)-ylmethyl]-1,2,4-oxadiazol-3-yl]phenylamine monohydrochloride 【CA登记号】220850-98-6, 220850-99-7 ((R)-isomer), 174822-16-3 (free base, undefined isomer) 【 分 子 式 】C15H20Cl2N4O2 【 分 子 量 】359.25825 |
【开发单位】Yamanouchi (Originator) 【药理作用】Constipation, Agents for, Gastric Emptying Disorders,Treatment of of, GASTROINTESTINAL DRUGS, Prokinetic Agents, 5-HT4 Agonists |
合成路线1
Benzamide (II) was prepared by treatment of the benzotriazolyl ester (I) with ammonium hydroxide in DMF. Dehydration of amide (II) with phosphorus oxychloride gave rise to nitrile (III), and subsequent addition of hydroxylamine to the cyano group of (III) furnished the N-hydroxybenzamidine (IV). Cyclization of (IV) with methyl 2-piperidineacetate (V) in the presence of NaH produced the oxadiazole compound (VI). Racemic (VI) was resolved employing L-ditoluoyltartaric acid, and the desired (S)-enantiomer was finally converted to the corresponding hydrochloride salt.
| 【1】 Suzuki, T.; Iwaoka, K.; Imanishi, N.; Nagakura, Y.; Miyata, K.; Nakahara, H.; Ohta, M.; Mase, T.; Synthesis of the selective 5-hydroxytryptamine 4 (5-HT4) receptor agonist (+)-(S)-2-chloro-5-methoxy-4-[5-(2-piperidylmethyl)-1,2,4-oxadiazol-3-yl]aniline. Chem Pharm Bull 1999, 47, 1, 120. |
| 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) | 18543 | 4-[(1H-1,2,3-benzotriazol-1-yloxy)carbonyl]-2-chloro-5-methoxyphenylamine; 4-[(1H-1,2,3-benzotriazol-1-yloxy)carbonyl]-2-chloro-5-methoxyaniline | C14H11ClN4O3 | 详情 | 详情 | |
| (II) | 51327 | 4-amino-5-chloro-2-methoxybenzamide | C8H9ClN2O2 | 详情 | 详情 | |
| (III) | 51328 | 4-amino-5-chloro-2-methoxybenzonitrile | C8H7ClN2O | 详情 | 详情 | |
| (IV) | 51329 | 4-amino-5-chloro-N'-hydroxy-2-methoxybenzenecarboximidamide | C8H10ClN3O2 | 详情 | 详情 | |
| (V) | 40753 | methyl 2-(2-piperidinyl)acetate | C8H15NO2 | 详情 | 详情 | |
| (VI) | 51330 | 2-chloro-5-methoxy-4-[5-(2-piperidinylmethyl)-1,2,4-oxadiazol-3-yl]aniline; 2-chloro-5-methoxy-4-[5-(2-piperidinylmethyl)-1,2,4-oxadiazol-3-yl]phenylamine | C15H19ClN4O2 | 详情 | 详情 |