3-nitro-7,8-dihydro-5H-pyrano[4,3-b]pyridine -Drug Synthesis Database

【结构式】

【分子编号】59826

【品名】3-nitro-7,8-dihydro-5H-pyrano[4,3-b]pyridine

【CA登记号】

【分子式】C₈H₈N₂O₃

【分子量】180.1632

【元素组成】C 53.33% H 4.48% N 15.55% O 26.64%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(III)

3-Nitro-7,8-dihydro-5H-pyrano[4,3-b]pyridine (III) was prepared by heating tetrahydropyranone (I) with dinitropyridone (II) in methanolic ammonia following a reported procedure. Hydrogenation of the nitro derivative (III) and protection of the resulting amine (IV) with trichloroacetyl chloride afforded the trichloroacetamide (V). Oxidation of the pyridine ring of (V) with 3-chloroperoxybenzoic acid gave the N-oxide (VI). Nitration of the pyridine ring of (VI) with fuming nitric acid, followed by amide hydrolysis with ammonium hydroxide provided the 3-amino-4-nitropyridine N-oxide (VII). Reduction of the N-oxide and 4-nitro groups of (VII) was accomplished in a single step by hydrogenation in the presence of Raney-nickel to furnish the bicyclic diaminopyridine (VIII). Subsequent monoacylation of (VIII) with isoxazole-3-carbonyl chloride (IX) followed by thermal cyclization provided the desired imidazopyranopyridine compound (1,2), which was finally isolated as the title phosphate salt

参考文献中间体

合成目标

【1】 Takada, S.; Sasatani, T.; Chomei, N.; Adachi, M.; Fujishita, T.; Eigyo, M.; Murata, S.; Kawasaki, K.; Matsushita, A.; Synthesis and structure-activity relationships of fused imidazopyridines: A new series of benzodiazepine receptor ligands. J Med Chem 1996, 39, 14, 2844.
【2】 Takada, S.; Sasatani, T.; Chomei, N.; Adachi, M.; Matsushita, A. (Shionogi & Co. Ltd.); Condensed imidazopyridine derivs. with psychotropic activity. EP 0556008; JP 1993286973; US 5378848; US 5461062 .

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)	31563	tetrahydro-4H-pyran-4-one	29943-42-8	C₅H₈O₂	详情	详情
(II)	59825	1-methyl-3,5-dinitro-2(1H)-pyridinone		C₆H₅N₃O₅	详情	详情
(III)	59826	3-nitro-7,8-dihydro-5H-pyrano[4,3-b]pyridine		C₈H₈N₂O₃	详情	详情
(IV)	59827	7,8-dihydro-5H-pyrano[4,3-b]pyridin-3-amine; 7,8-dihydro-5H-pyrano[4,3-b]pyridin-3-ylamine		C₈H₁₀N₂O	详情	详情
(V)	59828	2,2,2-trichloro-N-(7,8-dihydro-5H-pyrano[4,3-b]pyridin-3-yl)acetamide		C₁₀H₉Cl₃N₂O₂	详情	详情
(VI)	59829	3-[(2,2,2-trichloroacetyl)amino]-7,8-dihydro-5H-pyrano[4,3-b]pyridin-1-ium-1-olate		C₁₀H₉Cl₃N₂O₃	详情	详情
(VII)	59830	3-amino-4-nitro-7,8-dihydro-5H-pyrano[4,3-b]pyridin-1-ium-1-olate		C₈H₉N₃O₄	详情	详情
(VIII)	59831	3-amino-7,8-dihydro-5H-pyrano[4,3-b]pyridin-4-ylamine; 7,8-dihydro-5H-pyrano[4,3-b]pyridine-3,4-diamine		C₈H₁₁N₃O	详情	详情
(IX)	59832	3-isoxazolecarbonyl chloride		C₄H₂ClNO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

In a related procedure, the pyranopyridine (III) was oxidized to the corresponding N-oxide (X) with 3-chloroperoxybenzoic acid, and the nitro group of (X) was subsequently reduced to amine (XI) by catalytic hydrogenation over Pd/C. Acylation of (XI) with isoxazole-3-carbonyl chloride (IX) provided amide (XII). After pyridine ring nitration with fuming nitric acid to afford (XIII), its N-oxide function was reduced by treatment with phosphorus tribromide. The resultant nitro amide (XIV) was then hydrogenated to the corresponding amino amide derivative (XV), which was finally cyclized in hot ethyleneglycol to the target imidazopyranopyridine

参考文献中间体

合成目标

【1】 Takada, S.; Sasatani, T.; Chomei, N.; Adachi, M.; Matsushita, A. (Shionogi & Co. Ltd.); Condensed imidazopyridine derivs. with psychotropic activity. EP 0556008; JP 1993286973; US 5378848; US 5461062 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(III)	59826	3-nitro-7,8-dihydro-5H-pyrano[4,3-b]pyridine	C₈H₈N₂O₃	详情	详情
(IX)	59832	3-isoxazolecarbonyl chloride	C₄H₂ClNO₂	详情	详情
(X)	59833	3-nitro-7,8-dihydro-5H-pyrano[4,3-b]pyridin-1-ium-1-olate	C₈H₈N₂O₄	详情	详情
(XI)	59834	3-amino-7,8-dihydro-5H-pyrano[4,3-b]pyridin-1-ium-1-olate	C₈H₁₀N₂O₂	详情	详情
(XII)	59835	3-[(3-isoxazolylcarbonyl)amino]-7,8-dihydro-5H-pyrano[4,3-b]pyridin-1-ium-1-olate	C₁₂H₁₁N₃O₄	详情	详情
(XIII)	59836	3-[(3-isoxazolylcarbonyl)amino]-4-nitro-7,8-dihydro-5H-pyrano[4,3-b]pyridin-1-ium-1-olate	C₁₂H₁₀N₄O₆	详情	详情
(XIV)	59837	N-(4-nitro-7,8-dihydro-5H-pyrano[4,3-b]pyridin-3-yl)-3-isoxazolecarboxamide	C₁₂H₁₀N₄O₅	详情	详情
(XV)	59838	N-(4-amino-7,8-dihydro-5H-pyrano[4,3-b]pyridin-3-yl)-3-isoxazolecarboxamide	C₁₂H₁₂N₄O₃	详情	详情

Extended Information