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【结 构 式】 
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【分子编号】10846 【品名】2-(4-Pyridinyl)butanenitrile 【CA登记号】 |
【 分 子 式 】C9H10N2 【 分 子 量 】146.19188 【元素组成】C 73.94% H 6.89% N 19.16% |
合成路线1
该中间体在本合成路线中的序号：(III)1) The reaction of 4-(chloromethyl)pyridine (I) with KCN in refluxing methanol gives 2-(4-pyridyl)acetonitrile (II), which is alkylated with ethyl iodide and sodium hydride in DMF, yielding 2-(4-pyridyl)butyronitrile (III). The condensation of (III) with acrylonitrile (IV) by means of Triton B in tert-butanol affords 2-cyano-2-(4-pyridyl)hexanenitrile (V), which is finally cyclized with concentrated H2SO4 in refluxing acetic acid. 2) The alkylation of 2-(4-pyridyl)acetic acid ethyl ester (VI) with ethyl iodide and potassium tert-butoxide gives 2-(4-pyridyl)butanoic acid ethyl ester (VII), which is condensed with acrylamide (VIII) by means of potassium tert-butoxide, yielding 4-carbamoyl-2-ethyl-2-(4-pyridyl)butanoic acid ethyl ester (IX). Finally, this compound is cyclized in the presence of potassium tert-butoxide. 3) The condensation of ester (VI) with acrylonitrile (IV) in the presence of Triton B gives 4-cyano-2-(4-pyridyl)butanoic acid ethyl ester (X), which is alkylated with ethyl iodide and lithium diisopropylamide yielding 4-cyano-2-ethyl-2-(4-pyridyl)butanoic acid ethyl ester (XI). Finally, this compound is cyclized with concentrated H2SO4 in refluxing acetic acid.
| 【1】 Foster, A.B.; Jarman, M.; Taylor, G.N.; Kwan, C.-S. (Institute of Cancer Research); 2,6-Dioxopiperidine derivs., their preparation and pharmaceutical compsns. containing them. EP 0147121; GB 2151226; JP 1986500613; US 5071857; WO 8502618 . |
| 【2】 Markson, A.J.; Boss, A.M.; Clissold, D.W.; Thickitt, C.P.; Mann, J.; A concise synthesis of racemic pyridoglutethimide and its resolution using chiral stationary phase HPLC. Tetrahedron 1989, 45, 18, 6011. |
| 【3】 Jarman, M.; Griggs, L.J.; Wilman, D.E.V.; Rowlands, M.G.; Foster, A.B.; Leung, C.-S.; Analogues of 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione as selective inhibitors of aromatase: Derivatives with variable 1-alkyl and 3-alkyl substituents. J Med Chem 1987, 30, 9, 1550. |
| 【4】 Sampson, P.; Taylor, G.N.; Leung, C.-S.; Rowlands, M.G.; Plevey, R.G.; Jarman, M.; Foster, A.B.; Analogues of animoglutethimide: Selective inhibition of aromatase. J Med Chem 1989, 28, 2, 200. |
| 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) | 10844 | 4-(Chloromethyl)pyridine | 10445-91-7 | C6H6ClN | 详情 | 详情 |
| (II) | 10845 | 2-(4-Pyridinyl)acetonitrile | C7H6N2 | 详情 | 详情 | |
| (III) | 10846 | 2-(4-Pyridinyl)butanenitrile | C9H10N2 | 详情 | 详情 | |
| (IV) | 10847 | Acrylonitrile | 107-13-1 | C3H3N | 详情 | 详情 |
| (V) | 10848 | 2-Ethyl-2-(4-pyridinyl)pentanedinitrile | C12H13N3 | 详情 | 详情 | |
| (VI) | 10849 | ethyl 2-(4-pyridinyl)acetate; Ethyl 4-pyridylacetate | 54401-85-3 | C9H11NO2 | 详情 | 详情 |
| (VII) | 10850 | ethyl 2-(4-pyridinyl)butanoate | C11H15NO2 | 详情 | 详情 | |
| (VIII) | 10851 | Acrylamide | 79-06-1 | C3H5NO | 详情 | 详情 |
| (IX) | 10852 | ethyl 5-amino-2-ethyl-5-oxo-2-(4-pyridinyl)pentanoate | C14H20N2O3 | 详情 | 详情 | |
| (X) | 10853 | ethyl 4-cyano-2-(4-pyridinyl)butanoate | C12H14N2O2 | 详情 | 详情 | |
| (XI) | 10854 | ethyl 4-cyano-2-ethyl-2-(4-pyridinyl)butanoate | C14H18N2O2 | 详情 | 详情 |