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【结 构 式】 
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【药物名称】LY-404187 【化学名称】N-[2-(4'-Cyanobiphenyl-4-yl)propyl]propane-2-sulfonamide 【CA登记号】211311-95-4 【 分 子 式 】C19H22N2O2S 【 分 子 量 】342.46339 |
【开发单位】Lilly (Originator) 【药理作用】Antidepressants, Cognition Disorders, Treatment of, Mood Disorders, Treatment of, NEUROLOGIC DRUGS, PSYCHOPHARMACOLOGIC DRUGS, AMPA Receptor Modulators |
合成路线1
Methylation of (4-bromophenyl)acetonitrile (I) to afford 2-(4-bromophenyl)propionitrile (III) was carried out by heating with K2CO3 and dimethyl carbonate at 180 C in a sealed vessel. Alternatively, nitrile (III) was obtained by treatment of 4'-bromoacetophenone (II) with tosylmethyl isocyanide and potassium tert-butoxide. Nitrile (III) was reduced to amine (IV) using borane-dimethyl sulfide complex. Condensation of this amine with isopropylsulfonyl chloride furnished the corresponding sulfonamide (V). 4-Cyanophenylboronic acid (VII) was obtained by lithiation of 4-bromobenzonitrile (VI), followed by treatment with triisopropyl borate. Then, Suzuki coupling of boronic acid (VII) with bromide (V) furnished the title compound.
| 【1】 Nakamura, J.; Kuwana, Y.; Kitamura, S.; Ichikawa, S.; Yamada, K.; Ornstein, P.L.; Biarylpropylsulfonamides as novel, potent potentiators of 2-amino-3-(5-methyl-3-hydroxyisoxazol-4-yl)-propanoic acid (AMPA) receptors. J Med Chem 2000, 43, 23, 4354. |
| 【3】 Ornstein, P.L.; Jones, W.D.; Zarrinmayeh, H.; Zimmerman, D.M.; Arnold, M.B. (Eli Lilly and Company); N-Substd. sulfonamide derivs.. WO 0006537 . |
| 【2】 Arnold, M.B.; Bleakman, D.; Simon, R.L.; Cantrell, B.E.; Ornstein, P.L.; McKennon, T.E.; Tizzano, J.P.; Bleisch, T.J.; Zimmerman, D.M.; Baker, S.R.; Smith, E.; Zarrinmayeh, H.; Matsumoto, K.; Escribano, A.M. (Eli Lilly and Company); Sulphonamide derivs.. EP 0860428; WO 9833496 . |
| 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) | 45829 | 2-(4-bromophenyl)acetonitrile; 4-Bromobenzyl cyanide | 16532-79-9 | C8H6BrN | 详情 | 详情 |
| (II) | 25421 | 1-(4-bromophenyl)-1-ethanone | 99-90-1 | C8H7BrO | 详情 | 详情 |
| (III) | 45830 | 2-(4-bromophenyl)propanenitrile | C9H8BrN | 详情 | 详情 | |
| (IV) | 45831 | 2-(4-bromophenyl)propylamine; 2-(4-bromophenyl)-1-propanamine | C9H12BrN | 详情 | 详情 | |
| (V) | 45832 | N-[2-(4-bromophenyl)propyl]-2-propanesulfonamide | C12H18BrNO2S | 详情 | 详情 | |
| (VI) | 45833 | 4-Bromobenzonitrile | 623-00-7 | C7H4BrN | 详情 | 详情 |
| (VII) | 38835 | 4-cyanophenylboronic acid | 126747-14-6 | C7H6BNO2 | 详情 | 详情 |