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【结 构 式】 
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【分子编号】12130 【品名】N-(3-Methoxypropyl)-N-pentylamine; N-(3-Methoxypropyl)-1-pentanamine 【CA登记号】 |
【 分 子 式 】C9H21NO 【 分 子 量 】159.27188 【元素组成】C 67.87% H 13.29% N 8.79% O 10.05% |
合成路线1
该中间体在本合成路线中的序号：(II)By condensation of N-(3,4-dichlorobenzoyl)-glutamic acid anhydride (I) with N-(3-methoxypropyl)-N-pentylamine (II) in water at 5 C.
| 【1】 Makovec, F.; Chistè, R.; Rovati, C.L.; Rovati, A.L. (Rotta Research Laboratorium SpA); Pharmaceutically active derivatives of glutamic and aspartic acids. WO 8703869 . |
| 【2】 Patoia, L.; Prous, J.; Castaner, J.; LOXIGLUMIDE. Drugs Fut 1990, 15, 1, 32. |
合成路线2
该中间体在本合成路线中的序号：(V)The reaction of 2-naphthalenethiol (I) with 2-methyleneglutaronitrile (II) followed by treatment first with concentrated hydrochloric acid and then with p-toluenesulfonic acid in methanol gives racemic acid, which is resolved into optically pure (R)-4-methoxycarbonyl-2-(2-naphthylthiomethyl)butyric acid (IV) by use of (R)-(+)-alpha-methylbenzylamine (III). The treatment of compound (IV), first with thionyl chloride and then with N-(3-methoxypropyl)-N-pentylamine (V), affords (R)-methyl 4-[N-(3-methoxypropyl)-N-pentylcarbamoyl]-5-(2-naphthylthio)pentanoate (VI). Oxidation of compound (VI) with m-chloroperbenzoic acid followed by treatment with 1N sodium hydroxide gives (R)-4-[N-(3-methoxypropyl)-N-pentylcarbamoyl]-5-(2-naphthylsulfonyl) pentanoic acid (VII), which is finally converted into KSG-504 by treatment with L-arginine.
| 【1】 Kitazawa, M.; Akahane, M.; Yamazaki, Y.; Kobayashi, M.; KSG-504. Drugs Fut 1995, 20, 5, 472. |
| 【2】 Kitazawa, M.; Akahane, M.; Nakano, Y.; Tsubaki, A.; Sato, K.; Ban, M.; Kobayashi, M. (Kissei Pharmaceutical Co., Ltd.); Napthylsulfonylalkanoic acid cpds. EP 0433064; JP 1991193756; JP 1991197453; JP 1992210956; US 5177069 . |
| 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) | 15234 | 2-Naphthalenethiol; 2-Naphthylhydrosulfide | 91-60-1 | C10H8S | 详情 | 详情 |
| (II) | 63962 | 2-methylenepentanedinitrile | C6H6N2 | 详情 | 详情 | |
| (III) | 10039 | (1R)-1-Phenylethylamine; (1R)-1-Phenyl-1-ethanamine.; L-alpha-Phenylethylamine | 3886-69-9 | C8H11N | 详情 | 详情 |
| (IV) | 15235 | (2R)-5-methoxy-2-[(2-naphthylsulfanyl)methyl]-5-oxopentanoic acid | C17H18O4S | 详情 | 详情 | |
| (V) | 12130 | N-(3-Methoxypropyl)-N-pentylamine; N-(3-Methoxypropyl)-1-pentanamine | C9H21NO | 详情 | 详情 | |
| (VI) | 15236 | methyl (4R)-5-[(3-methoxypropyl)(pentyl)amino]-4-[(2-naphthylsulfanyl)methyl]-5-oxopentanoate | C26H37NO4S | 详情 | 详情 | |
| (VII) | 15237 | (4R)-5-[(3-methoxypropyl)(pentyl)amino]-4-[(2-naphthylsulfonyl)methyl]-5-oxopentanoic acid | C25H35NO6S | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)The condensation of the N-(benzyloxycarbonyl)-D-glutamic acid 5-benzyl ester (I) with N-(3-methoxypropyl)-N-pentylamine (II) by means of ethyl chloroformate and triethylamine in THF gives the corresponding amide (III), which is debenzylated by hydrogenation over Pd/C in methanol, yielding compound (IV). Finally, the free amino group of (IV) is acylated with 3,4-dichlorobenzoyl chloride (V) by means of NaOH in water to give dexloxiglumide.
| 【1】 Castaner, J.; Revel, L.; Makovec, F.; Dexloxiglumide. Drugs Fut 1999, 24, 7, 725. |
| 【2】 Makovec, F.; Chiste, R.; Peris, W.; Rovati, L. (Rotta Research Laboratorium SpA); Derivs. of (R)-5-pentylamino-5-oxopentanoic acid with anticholecystokinin activity. EP 0344184; JP 1988201156; US 5130474; US 5391574; WO 8805774 . |
| 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) | 26353 | (2R)-5-(benzyloxy)-2-[[(benzyloxy)carbonyl]amino]-5-oxopentanoic acid | 5680-86-4 | C20H21NO6 | 详情 | 详情 |
| (II) | 12130 | N-(3-Methoxypropyl)-N-pentylamine; N-(3-Methoxypropyl)-1-pentanamine | C9H21NO | 详情 | 详情 | |
| (III) | 26354 | benzyl (4R)-4-[[(benzyloxy)carbonyl]amino]-5-[(3-methoxypropyl)(pentyl)amino]-5-oxopentanoate | C29H40N2O6 | 详情 | 详情 | |
| (IV) | 26355 | benzyl (4R)-4-amino-5-[(3-methoxypropyl)(pentyl)amino]-5-oxopentanoate | C21H34N2O4 | 详情 | 详情 | |
| (V) | 26356 | 3,4-dichlorobenzoyl chloride | 3024-72-4 | C7H3Cl3O | 详情 | 详情 |