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【结 构 式】 
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【分子编号】45829 【品名】2-(4-bromophenyl)acetonitrile; 4-Bromobenzyl cyanide 【CA登记号】16532-79-9 |
【 分 子 式 】C8H6BrN 【 分 子 量 】196.04638 【元素组成】C 49.01% H 3.08% Br 40.76% N 7.14% |
合成路线1
该中间体在本合成路线中的序号：(I)The intermediate amine (V) was prepared via a Heck reaction between p-bromophenylacetonitrile (I) and tert-butyl acrylate (II) to afford the p-(cyanomethyl)cinnamate (III) . Catalytic double bond hydrogenation in (III) provided the saturated cyano ester (IV), which was then reduced to amine (V) by using NaBH4 in the presence of CoCl2. Alternatively, simultaneous double bond and cyano group reduction was accomplished by hydrogenation of (III) in the presence of Pd/C and HCl.
| 【1】 Hutchison, A.J.; Williams, M.; de Jesus, R.; Yokoyama, R.; Oei, H.H.; Ghai, G.R.; Webb, R.L.; Zoganas, H.C.; Stone, G.A.; Jarvis, M.F.; 2-(Arylalkylamino)adenosin-5'-uronamides: A new class of highly selective adenosine A2 receptor ligands. J Med Chem 1990, 33, 7, 1919. |
| 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) | 12760 | tert-butyl acrylate | 1663-39-4 | C7H12O2 | 详情 | 详情 |
| (III) | 62371 | tert-butyl (E)-3-[4-(2-nitriloethyl)phenyl]-2-propenoate | C15H17NO2 | 详情 | 详情 | |
| (IV) | 62372 | tert-butyl 3-[4-(2-nitriloethyl)phenyl]propanoate | C15H19NO2 | 详情 | 详情 | |
| (V) | 62373 | tert-butyl 3-[4-(2-aminoethyl)phenyl]propanoate | C15H23NO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)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 |