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【结 构 式】 
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【药物名称】 【化学名称】N-[1-(3,5-Dibromo-4-hydroxybenzyl)-2-oxo-2-(4-phenylpiperazin-1-yl)ethyl]-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1-carboxamide 【CA登记号】204695-47-6 (R-isomer) 【 分 子 式 】C32H34Br2N6O4 【 分 子 量 】726.47358 |
【开发单位】Boehringer Ingelheim (Originator), Merck & Co. (Not Determined) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Antimigraine Drugs, Calcitonin Gene-Related Peptides (CGRP) Antagonists |
合成路线1
Condensation between 3,5-dibromotyrosine methyl ester (I) and 4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine (II) in the presence of carbonyl ditriazole (CDT) furnished the asymmetric urea (III). Subsequent hydrolysis of the ester group using LiOH provided carboxylic acid (IV). This was finally coupled with N-phenylpiperazine (V) employing O-benzotriazolyl-N,N,N',N'-tetramethyluronium tetrafluoroborate and 1-hydroxybenzotriazole to yield the corresponding amide.
| 【1】 Eberlein, W.; Wienen, W.; Doods, H.; Rudolf, K.; Entzeroth, M.; Pieper, H.; Engel, W.; Hallermayer, G. (Dr. Karl Thomae GmbH); Modified aminoacids, pharmaceuticals containing these cpds. and methods for their production. JP 2000505100; WO 9811128 . |
| 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) | 44314 | methyl 2-amino-3-(3,5-dibromo-4-hydroxyphenyl)propanoate | C10H11Br2NO3 | 详情 | 详情 | |
| (II) | 12138 | 1-(4-Piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one; 4-(2-Keto-1-benzimidazolinyl)piperidine | 20662-53-7 | C12H15N3O | 详情 | 详情 |
| (III) | 44315 | methyl 3-(3,5-dibromo-4-hydroxyphenyl)-2-([[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-piperidinyl]carbonyl]amino)propanoate | C23H24Br2N4O5 | 详情 | 详情 | |
| (IV) | 44316 | 3,5-dibromo-4-hydroxy-N-[[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-piperidinyl]carbonyl]phenylalanine | C22H22Br2N4O5 | 详情 | 详情 | |
| (V) | 10756 | N-Phenylpiperazine; 1-Phenylpiperazine; Phenyl piperazine | 92-54-6 | C10H14N2 | 详情 | 详情 |