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【结 构 式】 
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【药物名称】 【化学名称】4'-Amidino-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-2'-methylbiphenyl-4-carboxamide 【CA登记号】256227-71-1 【 分 子 式 】C27H31N5O2 【 分 子 量 】457.58042 |
【开发单位】Merck KGaA (Originator) 【药理作用】Antidepressants, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, 5-HT1B Antagonists, 5-HT1D Antagonists |
合成路线1
Coupling of 4-bromobenzoyl chloride (I) with amine (II) by means of Et3N in CH2Cl2 or THF yields bromo derivative (III), which is then converted into boronic acid derivative (IV) by treatment with triisopropyloxyboron and n-BuLi in THF/hexane. Suzuki reaction between (IV) and oxadiazole (V) by means of Pd(PPd3)4 and Na2CO3 in dimethoxyethane (DME)/H2O affords compound (VI), which is finally hydrogenated over Raney-Ni in H2O/MeOH/AcOH to furnish the desired product.
| 【1】 März, J.; Cremers, T.; Harting, J.; Liao, Y.; Wikstrom, H.; Rautenberg, W.; Greiner, H.; Sundell, S.; Böttcher, H.; van Amsterdam, C.; New selective and potent 5-HT1B/1D antagonists: Chemistry and pharmacological evaluation of N-piperazinylphenyl biphenylcarboxamides and biphenylsulfonamides. J Med Chem 2000, 43, 3, 517. |
| 【2】 Van Amsterdam, C.; Harting, J.; Wikstrom, H.V.; Liao, Y.; Bottcher, H. (Merck Patent GmbH); Biphenyl derivs.. WO 0005225 . |
| 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) | 45960 | 4-bromobenzoyl chloride | 586-75-4 | C7H4BrClO | 详情 | 详情 |
| (II) | 25915 | 4-methoxy-3-(4-methyl-1-piperazinyl)phenylamine; 4-methoxy-3-(4-methyl-1-piperazinyl)aniline | C12H19N3O | 详情 | 详情 | |
| (III) | 45961 | 4-bromo-N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]benzamide | C19H22BrN3O2 | 详情 | 详情 | |
| (IV) | 45964 | 4-[[4-methoxy-3-(4-methyl-1-piperazinyl)anilino]carbonyl]phenylboronic acid | C19H24BN3O4 | 详情 | 详情 | |
| (V) | 45962 | 3-(4-bromo-3-methylphenyl)-5-methyl-1,2,4-oxadiazole | C10H9BrN2O | 详情 | 详情 | |
| (VI) | 45963 | C28H32BrN5O3 | 详情 | 详情 |