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【结 构 式】 
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【药物名称】Y-34959 【化学名称】N-[5-[4-(4-Amino-5-chloro-2-methoxybenzamidomethyl)piperidin-1-yl]pentyl]-1-methyl-1H-indole-3-carboxamide hydrochloride 【CA登记号】173339-89-4 (free base) 【 分 子 式 】C29H39Cl2N5O3 【 分 子 量 】576.57188 |
【开发单位】Mitsubishi Pharma (Originator) 【药理作用】Gastric Emptying Disorders,Treatment of of, GASTROINTESTINAL DRUGS, Prokinetic Agents, 5-HT4 Agonists |
合成路线1
1-Benzyl-4-(aminomethyl)piperidine (I) was protected at the primary amino group as the Boc derivative (II) and the N-benzyl group was subsequently removed by transfer hydrogenolysis with hydrazine and Pd/C to give piperidine (III). Alkylation of (III) with N-(5-bromopentyl)phthalimide (IV) afforded (V), which was subjected to hydrazinolysis of the phthalimido group, yielding primary amine (VI). Coupling of (VI) with 1-methylindole-3-carboxylic acid (VII) by means of EDC and HOBt gave rise to amide (VIII). The Boc protecting group of (VIII) was then cleaved by acidic treatment to furnish amine (IX). Finally, coupling of (IX) with 4-amino-5-chloro-2-methoxybenzoic acid (X) provided the title benzamide.
| 【1】 Haga, K.; Tomozane, H.; Sato, N.; Kawakita, T.; Itoh, K.; Sonda, S.; Asano, K.; Fujimura, M.; Hakira, H.; Synthesis and pharmacological properties of novel benzamide derivatives acting as ligands to the 5-hydroxytryptamine 4 (5-HT4) receptor. Eur J Med Chem 1999, 34, 12, 1101. |
| 【2】 Kawakita, T.; Hakira, H.; Haga, K.; Murozono, T.; Kuroita, T. (Welfide Corporation); Benzoic acid cpd. and use thereof as medicine. EP 0774460; WO 9526953 . |
| 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) | 37901 | (1-benzyl-4-piperidinyl)methylamine; (1-benzyl-4-piperidinyl)methanamine | C13H20N2 | 详情 | 详情 | |
| (II) | 37902 | tert-butyl (1-benzyl-4-piperidinyl)methylcarbamate | C18H28N2O2 | 详情 | 详情 | |
| (III) | 37903 | tert-butyl 4-piperidinylmethylcarbamate | C11H22N2O2 | 详情 | 详情 | |
| (IV) | 37904 | 2-(5-bromopentyl)-1H-isoindole-1,3(2H)-dione | 954-81-4 | C13H14BrNO2 | 详情 | 详情 |
| (V) | 37905 | tert-butyl [1-[5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)pentyl]-4-piperidinyl]methylcarbamate | C24H35N3O4 | 详情 | 详情 | |
| (VI) | 37906 | tert-butyl [1-(5-aminopentyl)-4-piperidinyl]methylcarbamate | C16H33N3O2 | 详情 | 详情 | |
| (VII) | 15067 | 1-methyl-1H-indole-3-carboxylic acid; N-Methylindole-3-carboxylic acid | 32387-21-6 | C10H9NO2 | 详情 | 详情 |
| (VIII) | 37907 | tert-butyl [1-(5-[[(1-methyl-1H-indol-3-yl)carbonyl]amino]pentyl)-4-piperidinyl]methylcarbamate | C26H40N4O3 | 详情 | 详情 | |
| (IX) | 37908 | N-[5-[4-(aminomethyl)-1-piperidinyl]pentyl]-1-methyl-1H-indole-3-carboxamide | C21H32N4O | 详情 | 详情 | |
| (X) | 12419 | 4-Amino-5-chloro-2-methoxybenzoic acid | 7206-70-4 | C8H8ClNO3 | 详情 | 详情 |