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【结 构 式】 
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【药物名称】SB-568849 【化学名称】N-[4-[2-(Diethylamino)ethoxy]-3-methoxyphenyl]-N-methyl-4'-(trifluoromethyl)biphenyl-4-carboxamide 【CA登记号】395679-53-5 【 分 子 式 】C28H31F3N2O3 【 分 子 量 】500.56607 |
【开发单位】GlaxoSmithKline (Originator) 【药理作用】Antidepressants, Antiobesity Drugs, Anxiolytics, METABOLIC DRUGS, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, Treatment of Nutritional Disorders, Melanin-Concentrating Hormone MCH-R1 (SLC-1) Receptor Antagonists |
合成路线1
Substitution of 1-chloro-2-methoxy-4-nitrobenzene (I) with 2-(diethylamino)ethanol (II) gives rise to ether (III). Subsequent nitro group reduction in (III) by catalytic hydrogenation affords aniline (IV). Condensation of amine (IV) with triethyl orthoformate, followed by reduction of the resultant formimidate (V) with NaBH4 leads to the N-methyl amine (VI). This is acylated by 4-bromobenzoyl chloride (VII) to furnish the bromobenzamide (VIII). Finally, Suzuki coupling of bromide (VIII) with 4-trifluoromethylphenylboronic acid (IX) produces the title biphenyl compound
| 【1】 Stemp, G.; Johnson, C.N.; Jones, M.; O'Toole, C.A.; Thewlis, K.M.; Witty, D. (GlaxoSmithKline plc); Carboxamide cpds. and their use as antagonists of a human 11CBy receptor. EP 1305304; WO 0210146 . |
| 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) | 60896 | 1-chloro-2-methoxy-4-nitrobenzene; 2-chloro-5-nitrophenyl methyl ether | C7H6ClNO3 | 详情 | 详情 | |
| (II) | 16183 | Diethylaminoethanol; 2-(diethylamino)-1-ethanol | 100-37-8 | C6H15NO | 详情 | 详情 |
| (III) | 60897 | N,N-diethyl-2-(2-methoxy-4-nitrophenoxy)-1-ethanamine; N,N-diethyl-N-[2-(2-methoxy-4-nitrophenoxy)ethyl]amine | C13H20N2O4 | 详情 | 详情 | |
| (IV) | 60898 | N-[2-(4-amino-2-methoxyphenoxy)ethyl]-N,N-diethylamine; 4-[2-(diethylamino)ethoxy]-3-methoxyaniline | C13H22N2O2 | 详情 | 详情 | |
| (V) | 60899 | ethyl 4-[2-(diethylamino)ethoxy]-3-methoxyphenyliminoformate | C16H26N2O3 | 详情 | 详情 | |
| (VI) | 60900 | N-{4-[2-(diethylamino)ethoxy]-3-methoxyphenyl}-N-methylamine; 4-[2-(diethylamino)ethoxy]-3-methoxy-N-methylaniline | C14H24N2O2 | 详情 | 详情 | |
| (VII) | 45960 | 4-bromobenzoyl chloride | 586-75-4 | C7H4BrClO | 详情 | 详情 |
| (VIII) | 60901 | 4-bromo-N-{4-[2-(diethylamino)ethoxy]-3-methoxyphenyl}-N-methylbenzamide | C21H27BrN2O3 | 详情 | 详情 | |
| (IX) | 48639 | 4-(Trifluoromethyl)phenylboronic acid | C7H6BF3O2 | 详情 | 详情 |