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【结 构 式】 
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【药物名称】Labetalol hydrochloride, AH-5158A, Sch-15719W, Amipress, Trandate, Normodyne 【化学名称】2-Hydroxy-5-[1-hydroxy-2-(1-methyl-3-phenylpropylamino)ethyl]benzamide monohydrochloride 【CA登记号】32780-64-6, 36894-69-6 (free base) 【 分 子 式 】C19H25ClN2O3 【 分 子 量 】364.8757 |
【开发单位】Schering-Plough (Originator), Celltech (Not Determined), GlaxoSmithKline (Not Determined), Salus (Not Determined), Takeda (Not Determined) 【药理作用】Angina pectoris, Treatment of, CARDIOVASCULAR DRUGS, Hypertension, Treatment of, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, alpha-Adrenoceptor Antagonists, beta-Adrenoceptor Antagonists |
合成路线1
Condensation of 5-bromoacetylsalicylamide (I) with N-benzyl-N-(1-methyl-3-phenylpropyl)amine (II) in refluxing butanone to 5-(N-benzyl-N-(1-methyl-3-phenylpropyl) glycyl)salicylamide hydrochloride (III), m.p. 139-141 C, which is reduced with H2 over Pt-Pd/C in ethanol.
| 【1】 Castaner, J.; Blancafort, P.; Labetalol. Drugs Fut 1976, 1, 3, 125. |
| 【2】 Lunts, L.H.; et al.; 1-Phenyl-2-aminoethanol derivatives bronchodilators. DE 1643224; FR 1557677; FR 8010M; GB 1200886; US 3642896; US 3644353; US 3705233 . |
| 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) | 30353 | N-benzyl-N-(1-methyl-3-phenylpropyl)amine; N-(4-phenyl-2-butyl)benzylamine; N-benzyl-4-phenyl-2-butanamine | C17H21N | 详情 | 详情 | |
| (II) | 40347 | 5-(2-bromoacetyl)-2-hydroxybenzamide; 5-Bromoacetylsalicylamide | 73866-23-6 | C9H8BrNO3 | 详情 | 详情 |
| (III) | 40348 | 5-[2-[benzyl(1-methyl-3-phenylpropyl)amino]acetyl]-2-hydroxybenzamide | C26H28N2O3 | 详情 | 详情 |
合成路线2
Reductocondensation of 5-(N,N-dibenzylglycyl)salicylamide (IV) and benzylace-tone (V) with H2 over Pd-Pt/C in methanol - acetic acid.
| 【1】 Lunts, L.H.; et al.; 1-Phenyl-2-aminoethanol derivatives bronchodilators. DE 1643224; FR 1557677; FR 8010M; GB 1200886; US 3642896; US 3644353; US 3705233 . |
| 【2】 Castaner, J.; Blancafort, P.; Labetalol. Drugs Fut 1976, 1, 3, 125. |
合成路线3
Reaction of methyl 5-(2-amino-1-hydroxyethyl)salicylate hydrochloride (VI) with NH3 to 5-(2-amino-1-hydroxyethyl)salicylamide hydrochloride (VII), m.p. >360 C, which is finally condensed with benzylacetone (V) and reduced with H2 over Pd-Pt/C in methanol.
| 【1】 Lunts, L.H.; et al.; 1-Phenyl-2-aminoethanol derivatives bronchodilators. DE 1643224; FR 1557677; FR 8010M; GB 1200886; US 3642896; US 3644353; US 3705233 . |
| 【2】 Castaner, J.; Blancafort, P.; Labetalol. Drugs Fut 1976, 1, 3, 125. |