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【结 构 式】 
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【分子编号】25421 【品名】1-(4-bromophenyl)-1-ethanone 【CA登记号】99-90-1 |
【 分 子 式 】C8H7BrO 【 分 子 量 】199.04698 【元素组成】C 48.27% H 3.54% Br 40.14% O 8.04% |
合成路线1
该中间体在本合成路线中的序号：(I)Title pyrone was prepared by cyclization of p-bromoacetophenone (I) with methyl 2-cyano-3,3-bis(methylthio)propenoate (II) in the presence of KOH in DMF at r.t.
| 【1】 Ram, V.J.; et al.; Ring transformation reaction: Part II - Reaction specificity of hydrazines towards 6-aryl-4-(methylthio)-2-oxo-2H-pyran-3-carbonitriles and corresponding 3-ethyl carboxylate. Indian J Chem 1993, 32B, 9, 924. |
| 【2】 Tominaga, Y.; et al.; Synthesis and reactions of 6-aryl- and 6-styryl-3-cyano-4-methylthio-2H-pyran-2-ones. Chem Pharm Bull 1984, 32, 9, 3384. |
| 【3】 Tominaga, Y.; et al.; Syntheses of 2-pyrone derivatives. Heterocycles 1976, 4, 9, 1493. |
| 【4】 Parmar, V.S.; et al.; Synthetic and mass spectral fragmentation studies on trisubstituted 2H-pyran-2-ones and comparative EIMS behaviour of biologically active 3,5-disubstituted pyrazoles and isoxazoles. Indian J Chem 1997, 36B, 10, 872. |
合成路线2
该中间体在本合成路线中的序号：(II)The title quinoline derivative was prepared by a Pfitzinger synthesis employing 5-chloro-7-methylisatin (I) and 4'-bromoacetophenone (II) in ethanolic KOH.
| 【1】 Hill, J.M.; Kluge, A.F.; Silverman, J.; Yang, Y.; Yu, G.; Finn, J.; Keith, D.; Yu, X.Y.; Gallant, P.; Structure-activity relationship of quinoline analogs as inhibitors of C. albicans prolyl t-RNA synthetase. 218th ACS Natl Meet (Aug 22 1999, New Orleans) 1999, Abst MEDI 289. |
合成路线3
该中间体在本合成路线中的序号：(II)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 |
合成路线4
该中间体在本合成路线中的序号：(I)Claisen condensation of 4-bromoacetophenone (I) with ethyl acetate provides diketone (II). Subsequent reaction of (II) with carbon disulfide in the presence of LDA leads to thiopyranone thiol (III). Alkylation of thiol (III) with iodoethane and K2CO3 affords sulfide (IV), which is further oxidized to sulfoxide (V) by means of mCPBA. Displacement of either sulfide (IV) or sulfoxide (V) with morpholine gives rise to the morpholinyl thiopyranone (VI). Finally, Suzuki coupling between aryl bromide (VI) and 2-naphthaleneboronic acid (VII) produces the target compound
| 【1】 Griffin, R.J.; Combinatorial methods for identifying antitumour kinase inhibitors. Eur J Cancer 2002, 38, Suppl. 7. |
| 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) | 25421 | 1-(4-bromophenyl)-1-ethanone | 99-90-1 | C8H7BrO | 详情 | 详情 |
| (II) | 61315 | 1-(4-bromophenyl)-1,3-butanedione | C10H9BrO2 | 详情 | 详情 | |
| (III) | 61316 | 2-(4-bromophenyl)-6-sulfanyl-4H-thiopyran-4-one | C11H7BrOS2 | 详情 | 详情 | |
| (IV) | 61317 | 2-(4-bromophenyl)-6-(ethylsulfanyl)-4H-thiopyran-4-one | C13H11BrOS2 | 详情 | 详情 | |
| (V) | 61318 | 2-(4-bromophenyl)-6-(ethylsulfinyl)-4H-thiopyran-4-one | C13H11BrO2S2 | 详情 | 详情 | |
| (VI) | 61319 | 2-(4-bromophenyl)-6-(4-morpholinyl)-4H-thiopyran-4-one | C15H14BrNO2S | 详情 | 详情 | |
| (VII) | 27703 | 1-naphthylboronic acid | 13922-41-3 | C10H9BO2 | 详情 | 详情 |