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【结 构 式】 
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【药物名称】Pifatidine, Roxatidine acetate hydrochloride, Hoe-760, TZU-0460, Gastralgin, Roxit, Altat, Xarcin 【化学名称】N-[3-[3-(1-Piperidinylmethyl)phenoxy]propyl]acetoxyacetamide hydrochloride 【CA登记号】93793-83-0, 78628-28-1 (free base) 【 分 子 式 】C19H29ClN2O4 【 分 子 量 】384.90698 |
【开发单位】Teikoku Hormone (Originator), Sumitomo Pharmaceuticals (Not Determined), Takeda (Not Determined), Aventis Pharma (Licensee), Wassermann (Licensee) 【药理作用】Antiulcer Drugs, Gastric Antisecretory Drugs, GASTROINTESTINAL DRUGS, Histamine H2 Receptor Antagonists |
合成路线1
The reductocondensation of piperidine (I) with 3-hydroxybenzaldehyde (II) by means of sodium borohydride in ethanol gives 3-(1-piperidylmethyl)phenol (III), which is then condensed with N-(3-bromopropyl)phthalimide (IV) by means of NaH in DMF yielding N-[3-[3-(1-piperidylmethyl)phenoxy]propyl]phthalimide (V). The hydrolysis of (V) with hydrazine in ethanol affords 3-[3-(1-piperidylmethyl)phenoxy]propylamine (VI), which is acylated with hydroxyacetic acid (VII) at 200 C giving N-[3-[3-(1-piperidylmethyl)phenoxy]propyl]hydroxyacetamide (VIII). Finally, this compound is acetylated with acetic anhydride at 100 C.
| 【1】 Shibata, K.; et al. (Teikoku Hormone Manufacturing Co., Ltd.); Antiulcer phenoxypropylamine derivatives. EP 0024510; JP 81115750; US 4293557 . |
| 【2】 Castaner, J.; Serradell, M.N.; TZU-0460. Drugs Fut 1985, 10, 12, 995. |
| 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) | 10158 | Piperidine | 110-89-4 | C5H11N | 详情 | 详情 |
| (II) | 28537 | 3-hydroxybenzaldehyde | 100-83-4 | C7H6O2 | 详情 | 详情 |
| (III) | 29854 | 3-(1-piperidinylmethyl)phenol | C12H17NO | 详情 | 详情 | |
| (IV) | 15216 | N-(3-Bromopropyl)phthalimide; 2-(3-bromopropyl)-1H-isoindole-1,3(2H)-dione | 5460-29-7 | C11H10BrNO2 | 详情 | 详情 |
| (V) | 29855 | 2-[2-[3-(1-piperidinylmethyl)phenoxy]ethyl]-1H-isoindole-1,3(2H)-dione | C22H24N2O3 | 详情 | 详情 | |
| (VI) | 16105 | 3-[3-(piperidinomethyl)phenoxy]-1-propanamine; 3-[3-(piperidinomethyl)phenoxy]propylamine | C15H24N2O | 详情 | 详情 | |
| (VII) | 29856 | 2-hydroxyacetic acid;glycolic acid | 79-14-1 | C2H4O3 | 详情 | 详情 |
| (VIII) | 29857 | 2-hydroxy-N-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]acetamide | C17H26N2O3 | 详情 | 详情 |