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

【结构式】

【分子编号】31477

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

【CA登记号】

【分子式】C₉H₉NO₂

【分子量】163.176

【元素组成】C 66.25% H 5.56% N 8.58% O 19.61%

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 reaction of cyclohexane-1,3-dione (I) with ammonia gives 3-amino-2-cyclohexen-1-one (II), which is cyclized with acrylic acid (III) by heating at 140 C yielding 1,2,3,4,5,6,7,8-octahydroquinoline-2,5-dione (IV). The dehydrogenation of (IV) by means of Pd/C in refluxing decaline affords 5-hydroxy-1,2,3,4-tetrahydroquinolin-2-one (V), which is condensed with epichlorohydrin (VI) by means of NaOMe or NaOH in methanol giving 5-(2,3-epoxypropoxy)-1,2,3,4-tetrahydroquinolin-2-one (VII). Finally, this compound is treated with tert-butylamine in methanol.

参考文献中间体

合成目标

【1】 Castaner, J.; Sungurbey, K.; Carteolol. Drugs Fut 1977, 2, 5, 288.
【2】 Shono, T.; et al.; A new practical synthesis of 5-hydroxy-3,4-dihydrocarbostyril and 5-hydroxycarbostyril. J Org Chem 1981, 46, 3719.
【3】 Von Winkler, W.; Chemical and analytical data for the pharmaceutically active substance carteolol hydrochloride. Arzneim-Forsch Drug Res 1983, 33, 2a, 279.
【4】 Mori, H.; Tamura, Y,.; Tominaga, M.; Yoshiaki, S.; Nakagawa, K.; Murakami, N. (Otsuka Pharmaceutical Co., Ltd.); 3,4-Dihydrocarbostyril derivs., their preparation, and pharmaceutical compsns. thereof. DE 2302027; GB 1424571 .

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)	11244	1,3-Cyclohexanedione	504-02-9	C₆H₈O₂	详情	详情
(II)	31475	3-amino-2-cyclohexen-1-one	5220-49-5	C₆H₉NO	详情	详情
(III)	19139	acrylic acid	79-10-7	C₃H₄O₂	详情	详情
(IV)	31476	4,6,7,8-tetrahydro-2,5(1H,3H)-quinolinedione		C₉H₁₁NO₂	详情	详情
(V)	31477	5-hydroxy-3,4-dihydro-2(1H)-quinolinone		C₉H₉NO₂	详情	详情
(VI)	29648	2-oxiranylmethanol	556-52-5	C₃H₆O₂	详情	详情
(VII)	31478	5-(2-oxiranylmethoxy)-3,4-dihydro-2(1H)-quinolinone		C₁₂H₁₃NO₃	详情	详情
(VIII)	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：(IX)

The diketone (IV) can also be obtained as follows: the nitration of 5-hydroxy-3,4-dihydrocarbostyril (IX) with HNO3 in acetic acid - acetic anhydride gives 5-hydroxy-8-nitro-3,4-dihydrocarbostyril (X), which is reduced with H2 over Pd/C affording 5-hydroxy-8-amino-3,4-dihydrocarbostyril (Xl). Finally, this compound is oxidized with FeCl3 in aqueous HCl.

参考文献中间体

合成目标

【1】 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.
【2】 Castaner, J.; Blancafort, P.; Serradell, M.N.; 8-Hydroxycarteolol. Drugs Fut 1980, 5, 2, 78.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(IV)	39065	3,4,4a,8a-tetrahydro-2,5,8(1H)-quinolinetrione	C₉H₉NO₃	详情	详情
(IX)	31477	5-hydroxy-3,4-dihydro-2(1H)-quinolinone	C₉H₉NO₂	详情	详情
(X)	39070	5-hydroxy-8-nitro-3,4-dihydro-2(1H)-quinolinone	C₉H₈N₂O₄	详情	详情
(XI)	39071	8-amino-5-hydroxy-3,4-dihydro-2(1H)-quinolinone	C₉H₁₀N₂O₂	详情	详情

Extended Information