Repirinast, MY-5116, Romet, -Drug Synthesis Database

【结构式】

【药物名称】Repirinast, MY-5116, Romet

【化学名称】7,8-Dimethyl-4,5-dioxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-2-carboxylic acid 3-methylbutyl ester

【CA登记号】73080-51-0

【分子式】C₂₀H₂₁NO₅

【分子量】355.39407

【开发单位】Mitsubishi Chemical (Originator), Mitsubishi Pharma (Originator), Nikken Chemicals (Originator)

【药理作用】Antiallergy/Antiasthmatic Drugs, Asthma Therapy, RESPIRATORY DRUGS, Mediator Release Inhibitors

合成路线1 合成路线2

合成路线1

1) The cyclization of 2,3-dimethylaniline (I) with diethyl acetylmalonate (II) in 1-chloronaphthalene at 240 C gives 3-acetyl-4-hydroxy-7,8-dimethylquinolin-2(1H)-one (III), which by reaction with diethyl oxalate (IV) by means of sodium ethoxide in refluxing benzene yields ethyl-4-(4-hydroxy-7,8-dimethyl-2-oxo-1,2-dihydroquinolin-3yl)-2,4-dioxo-butanoate (V). The cyclization of (V) in acetic acid concentrated HCl at 100 C affords 5,6-dihydro-7,8 dimethyl-4,5-dioxo-4H-pyrano[3,2-c]quinoline-2-carboxylic acid (VI), which is converted into the corresponding acyl chloride (VII) by reaction with refluxing SOCl2. Finally, this compound is treated with hot 3-methylbutanol (VIII).

参考文献中间体

【1】 Takahashi, K.; Hata, S.; Morinaka, Y.; Yamada, S.; Antiallergic agents I. Pyranoquinoline derivatives. Eur J Med Chem - Chim Ther 1981, 16, 3, 251.
【2】 Castaner, J.; Prous, J.; Repirinast. Drugs Fut 1987, 12, 1, 37.

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)	23025	2,3-Dimethylphenylamine; 2,3-Dimethylaniline; 2,3-Xylidine	87-59-2	C₈H₁₁N	详情	详情
(II)	23026	diethyl 2-acetylmalonate	570-08-1	C₉H₁₄O₅	详情	详情
(III)	23027	3-acetyl-4-hydroxy-7,8-dimethyl-2(1H)-quinolinone		C₁₃H₁₃NO₃	详情	详情
(IV)	17571	Diethyl oxalate; Ethyl 2-ethoxy-2-oxoacetate	95-92-1	C₆H₁₀O₄	详情	详情
(V)	23029	ethyl 4-(4-hydroxy-7,8-dimethyl-2-oxo-1,2-dihydro-3-quinolinyl)-2,4-dioxobutanoate		C₁₇H₁₇NO₆	详情	详情
(VI)	24014	Phenyllithium	591-51-5	C₆H₅Li	详情	详情
(VII)	23031	7,8-dimethyl-4,5-dioxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-2-carbonyl chloride		C₁₅H₁₀ClNO₄	详情	详情
(VIII)	23032	3-methyl-1-butanol	123-51-3	C₅H₁₂O	详情	详情

合成路线2

2) The condensation of quinolone (III) with 3 methylbutyl oxalate (X) [obtained from 3 methyl butanol (VIII) and oxalic acid (IX)] by means of NaH yields 3-methylbutyl-4-(4 hydroxy-7,8-dimethyl-2-oxo-1,2-dihydroquinolin-3-yl)-2,4-dioxobutanoate (XI), which is then cyclized by means of sulfuric acid. ([*]-labeled compound).

参考文献中间体

【1】 Esumi, A.; Jin, Y.; Uohama, K.; Study in vivo of MY-5116. Absorption, distribution and elimination in rats. Clin Rep 1985, 20, 2, 391.
【2】 Castaner, J.; Prous, J.; Repirinast. Drugs Fut 1987, 12, 1, 37.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(III)	23027	3-acetyl-4-hydroxy-7,8-dimethyl-2(1H)-quinolinone		C₁₃H₁₃NO₃	详情	详情
(VIII)	23032	3-methyl-1-butanol	123-51-3	C₅H₁₂O	详情	详情
(IX)	15713	Oxalic acid	144-62-7	C₂H₂O₄	详情	详情
(IX)	44607	2-hydroxy-2-oxoacetic acid		C₂H₂O₄	详情	详情
(X)	23034	isopentyl 2-(isopentyloxy)-2-oxoacetate		C₁₂H₂₂O₄	详情	详情
(X)	44608	isopentyl 2-(isopentyloxy)-2-oxoacetate		C₁₂H₂₂O₄	详情	详情
(XI)	23035	isopentyl 4-(4-hydroxy-7,8-dimethyl-2-oxo-1,2-dihydro-3-quinolinyl)-2,4-dioxobutanoate		C₂₀H₂₃NO₆	详情	详情
(XI)	44609	isopentyl 4-(4-hydroxy-7,8-dimethyl-2-oxo-1,2-dihydro-3-quinolinyl)-2,4-dioxobutanoate		C₂₀H₂₃NO₆	详情	详情

Extended Information