5,8-dihydroxy-3,4-dihydro-2(1H)-quinolinone -Drug Synthesis Database

【结构式】

【分子编号】39066

【品名】5,8-dihydroxy-3,4-dihydro-2(1H)-quinolinone

【CA登记号】

【分子式】C₉H₉NO₃

【分子量】179.1754

【元素组成】C 60.33% H 5.06% N 7.82% O 26.79%

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：(V)

The nitration of 8-hydroxy-3,4-dihydrocarbostyril (I) with HNO3 in acetic acid-acetic anhydride gives 5-nitro-8-hydroxy-3,4-dihydrocarbostyril (II), which is reduced with SnCl2 in concentrated HCl yielding 5-amino-8-hydroxy-3,4-dihydrocarbostyril (III). The oxidation of (III) with FeCl3 in aqueous HCl affords 5,8-dioxo-3,4,5,8-tetrahydrocarbostyril (IV), which by treatment with SO2 in water is converted into 5,8-dihydroxy-3,4-dihydrocarbostyril (V). The treatment of (V) with benzyl chloride (A) and potassium carbonate in acetone gives 5-hydroxy-8-benzyloxy-3,4-dihydrocarbostyril (VII), which by reaction with epichlorohydrin (B) by means of piperidine affords 8-benzyloxy-5-(2,3-epoxypropoxy)-3,4-dihydrocarbostyril (VII). The opening of the epoxide ring of (VII) with tert-butylamine (C) in methanol yields 8-benzyloxy-5-(3-tert-butylamino-2-hydroxypropoxy)-3,4-dihydrocarbostyril (VIII) (1,2), which is finally hydrogenated with H2 over Pd/C.

参考文献中间体

合成目标

【1】 Castaner, J.; Blancafort, P.; Serradell, M.N.; 8-Hydroxycarteolol. Drugs Fut 1980, 5, 2, 78.
【2】 Uchida, M.; et al.; Synthesis of 5-(3-tert-butylamino-2-hydroxypropxy)-8-3,4-dihydrocarbostyril hydochloride and its beta-adrenergic blocking agent. Yakugaku Zasshi 1976, 96, 5, 571-577.
【3】 Nakagawa, K.; et al.; US 4072683 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(A)	19171	1-(Chloromethyl)benzene; Benzyl chloride	100-44-7	C₇H₇Cl	详情	详情
(I)	39062	8-hydroxy-3,4-dihydro-2(1H)-quinolinone	22246-18-0	C₉H₉NO₂	详情	详情
(II)	39063	8-hydroxy-5-nitro-3,4-dihydro-2(1H)-quinolinone		C₉H₈N₂O₄	详情	详情
(III)	39064	5-amino-8-hydroxy-3,4-dihydro-2(1H)-quinolinone		C₉H₁₀N₂O₂	详情	详情
(IV)	39065	3,4,4a,8a-tetrahydro-2,5,8(1H)-quinolinetrione		C₉H₉NO₃	详情	详情
(V)	39066	5,8-dihydroxy-3,4-dihydro-2(1H)-quinolinone		C₉H₉NO₃	详情	详情
(VI)	39067	8-(benzyloxy)-5-hydroxy-3,4-dihydro-2(1H)-quinolinone		C₁₆H₁₅NO₃	详情	详情
(VII)	39068	8-(benzyloxy)-5-(2-oxiranylmethoxy)-3,4-dihydro-2(1H)-quinolinone		C₁₉H₁₉NO₄	详情	详情
(VIII)	39069	8-(benzyloxy)-5-[3-(tert-butylamino)-2-hydroxypropoxy]-3,4-dihydro-2(1H)-quinolinone		C₂₃H₃₀N₂O₄	详情	详情
(C)	17895	2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine	75-64-9	C₄H₁₁N	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The dihydroxy compound (V) can also be obtained as follows: the nitration of 8-hydroxycarbostyril (XII) with HNO3 in acetic acid-acetic anhydride gives 5-nitro-8-hydroxycarbostyril (XIII), which is reduced with SnCl2 yielding 5-amino-8-hydroxycarbostyril (XIV). The oxidation of (XIV) with FeCl3 affords 5,8-dioxo-5,8-dihydrocarbostyril (XV), which is reduced with SO2 giving 5,8-dihydroxycarbostyril (XVI). Finally, this compound is reduced with H2 over Pd/C. The 5-amino-8-hydroxy compound (XIV) can also be obtained by nitrosation of (XII) with NaNO2 in acetic acid acetic anhydride to give 5-nitroso-8-acetoxycarbostyril (XVII), which is then reduced with SnCl2 in concentrated HCl.

参考文献中间体

合成目标

【1】 Castaner, J.; Blancafort, P.; Serradell, M.N.; 8-Hydroxycarteolol. Drugs Fut 1980, 5, 2, 78.
【2】 Uchida, M.; et al.; Synthesis of 5-(3-tert-butylamino-2-hydroxypropxy)-8-3,4-dihydrocarbostyril hydochloride and its beta-adrenergic blocking agent. Yakugaku Zasshi 1976, 96, 5, 571-577.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	39066	5,8-dihydroxy-3,4-dihydro-2(1H)-quinolinone		C₉H₉NO₃	详情	详情
(XII)	39072	8-hydroxy-2(1H)-quinolinone	15450-76-7	C₉H₇NO₂	详情	详情
(XIII)	39073	8-hydroxy-5-nitro-2(1H)-quinolinone		C₉H₆N₂O₄	详情	详情
(XIV)	39074	5-amino-8-hydroxy-4a,5,8,8a-tetrahydro-2(1H)-quinolinone		C₉H₁₂N₂O₂	详情	详情
(XV)	39075	4a,8a-dihydro-2,5,8(1H)-quinolinetrione		C₉H₇NO₃	详情	详情
(XVI)	39076	5,8-dihydroxy-2(1H)-quinolinone		C₉H₇NO₃	详情	详情
(XVII)	39077	5-nitroso-2-oxo-1,2,4a,5,8,8a-hexahydro-8-quinolinyl acetate		C₁₁H₁₂N₂O₄	详情	详情

Extended Information