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【结 构 式】 
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【分子编号】63452 【品名】7-chlorothieno[3,2-b]pyridine 【CA登记号】 |
【 分 子 式 】C7H4ClNS 【 分 子 量 】169.6342 【元素组成】C 49.56% H 2.38% Cl 20.9% N 8.26% S 18.9% |
合成路线1
该中间体在本合成路线中的序号：(VII)Decarboxylation of methyl 3-aminothiophene-2-carboxylate (I) in 2 N NaOH leads to 3-aminothiophene (II). Meldrum's acid (III) is condensed with triethyl orthoformate to produce the ethoxymethylene derivative (IV). Subsequent reaction of enol ether (IV) with 3-aminothiophene (II) gives rise to enamine (V), which is further cyclized to thienopyridinone (VI) upon heating in dowtherm A at 260 C. This is then chlorinated by means of oxalyl chloride to furnish 4-chlorothieno[3,2-b]pyridine (VII). Metalation of (VII) with butyllithium in cold THF, followed by treatment with I2 affords the aryl iodide (VIII). Palladium-catalyzed coupling of (VIII) with the lithiated derivative of 1-methylimidazole (IX) yields (X). Finally, displacement of the chloride group of (X) with 5-amino-2-methylindole (XI) provides the title compound.
| 【1】 Munchhof, M.J.; Adams, M.A.; Atherton, J.A.; et al.; Development of thienopyridines as VEGFR-2 kinase inhibitors. 225th ACS Natl Meet (March 23 2003, New Orleans) 2003, Abst MEDI 129. |
| 【2】 Sobolov-Jaynes, S.B.; Munchhof, M.J. (Pfizer Products Inc.); Thienopyrimidine and thienopyridine derivs. useful as anticancer agents. EP 1028964; JP 2001522853; WO 9924440 . |
| 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) | 27686 | 3-amino-2-thiophenecarboxylic acid methyl ester; methyl 3-amino-2-thiophenecarboxylate | 22288-78-4 | C6H7NO2S | 详情 | 详情 |
| (II) | 63448 | 3-thiophenylamine; 3-thiophenamine | C4H5NS | 详情 | 详情 | |
| (III) | 14738 | Meldrum's acid; 2,2-dimethyl-1,3-dioxane-4,6-dione；Malonic acid cyclic isopropylidene ester | 2033-24-1 | C6H8O4 | 详情 | 详情 |
| (IV) | 63449 | 5-[(ethyloxy)methylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione | C9H12O5 | 详情 | 详情 | |
| (V) | 63450 | 2,2-dimethyl-5-[(3-thiophenylamino)methylidene]-1,3-dioxane-4,6-dione | C11H11NO4S | 详情 | 详情 | |
| (VI) | 63451 | thieno[3,2-b]pyridin-7(4H)-one | C7H5NOS | 详情 | 详情 | |
| (VII) | 63452 | 7-chlorothieno[3,2-b]pyridine | C7H4ClNS | 详情 | 详情 | |
| (VIII) | 63453 | 7-chloro-2-iodothieno[3,2-b]pyridine | C7H3ClINS | 详情 | 详情 | |
| (IX) | 38630 | 1-methyl-1H-imidazole | 616-47-7 | C4H6N2 | 详情 | 详情 |
| (X) | 63454 | 7-chloro-2-(1-methyl-1H-imidazol-2-yl)thieno[3,2-b]pyridine | C11H8ClN3S | 详情 | 详情 | |
| (XI) | 63455 | 2-methyl-1H-indol-5-ylamine; 2-methyl-1H-indol-5-amine | C9H10N2 | 详情 | 详情 |