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【结 构 式】

【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%

与该中间体有关的原料药合成路线共 1 条

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
Extended Information