HOFQ, -Drug Synthesis Database

【结构式】

【药物名称】HOFQ

【化学名称】4-Hydroxymethyl-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one

【CA登记号】

【分子式】C₁₅H₁₅NO₃

【分子量】257.2917

【开发单位】Università degli Studi di Padova (Originator)

【药理作用】ONCOLYTIC DRUGS, Photosensitizers, Radiation Therapy

合成路线1 合成路线2

合成路线1

Condensation of 2,4-diaminotoluene (I) with methyl 4-methoxyacetoacetate (II) produces quinolinone (III). Conversion of the 7-aminoquinolinone (III) into the 7-hydroxy analogue (IV) is achieved by diazotization, followed by hydrolysis in hot sulfuric acid. Alkylation of phenol (IV) with allyl bromide (V) gives allyl ether (VI). Subsequent methylation of (VI) by means of dimethyl sulfate leads to a mixture of the desired N-methyl quinoline (VII) along with minor amounts of the O-methyl isomer (VIII), which are separated by column chromatography. Claisen rearrangement of the allyl ether (VII) in refluxing N,N-dimethylaniline affords the 7-hydroxy-8-allyl quinolone (IX), which is further acetylated to (X) by means of acetic anhydride and sodium acetate. Bromination of the allyl group of (X) in HOAc yields the dibromo compound (XI).

参考文献中间体

【1】 Chilin, A.; et al.; Synthesis and biological evaluation of a new furo(2,3-h)quinolin-2(1H)-one. J Med Chem 2002, 45, 5, 1146.

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)	57682	4-methyl-1,3-benzenediamine; 3-amino-4-methylphenylamine		C₇H₁₀N₂	详情	详情
(II)	57683	ethyl 4-methoxy-3-oxobutanoate		C₇H₁₂O₄	详情	详情
(III)	57684	7-amino-4-(methoxymethyl)-6-methyl-2(1H)-quinolinone		C₁₂H₁₄N₂O₂	详情	详情
(IV)	57685	7-hydroxy-4-(methoxymethyl)-6-methyl-2(1H)-quinolinone		C₁₂H₁₃NO₃	详情	详情
(V)	11463	3-Bromo-1-propene; 3-Bromopropene；allyl bromide	106-95-6	C₃H₅Br	详情	详情
(VI)	57686	7-(allyloxy)-4-(methoxymethyl)-6-methyl-2(1H)-quinolinone		C₁₅H₁₇NO₃	详情	详情
(VII)	57687	7-(allyloxy)-4-(methoxymethyl)-1,6-dimethyl-2(1H)-quinolinone		C₁₆H₁₉NO₃	详情	详情
(VIII)	57688	7-(allyloxy)-2-methoxy-4-(methoxymethyl)-6-methylquinoline; allyl 2-methoxy-4-(methoxymethyl)-6-methyl-7-quinolinyl ether		C₁₆H₁₉NO₃	详情	详情
(IX)	57689	8-allyl-7-hydroxy-4-(methoxymethyl)-1,6-dimethyl-2(1H)-quinolinone		C₁₆H₁₉NO₃	详情	详情
(X)	57690	8-allyl-4-(methoxymethyl)-1,6-dimethyl-2-oxo-1,2-dihydro-7-quinolinyl acetate		C₁₈H₂₁NO₄	详情	详情
(XI)	57691	8-(2,3-dibromopropyl)-4-(methoxymethyl)-1,6-dimethyl-2-oxo-1,2-dihydro-7-quinolinyl acetate		C₁₈H₂₁Br₂NO₄	详情	详情

合成路线2

Hydrolysis and cyclization of the dibromo acetate (XI) under basic conditions provides the furoquinoline (XII). Cleavage of the methyl ether group of (XII) using HBr in boiling HOAc gives bromide (XIII). Subsequent bromide displacement in (XIII) by sodium acetate yields acetate ester (XIV), which is finally hydrolyzed to the desired alcohol with methanolic KOH.

参考文献中间体

【1】 Chilin, A.; et al.; Synthesis and biological evaluation of a new furo(2,3-h)quinolin-2(1H)-one. J Med Chem 2002, 45, 5, 1146.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XI)	57691	8-(2,3-dibromopropyl)-4-(methoxymethyl)-1,6-dimethyl-2-oxo-1,2-dihydro-7-quinolinyl acetate		C₁₈H₂₁Br₂NO₄	详情	详情
(XII)	57692	4-(methoxymethyl)-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one		C₁₆H₁₇NO₃	详情	详情
(XIII)	57693	5-Hydroxyindole; 5-Indolol	1953-54-4	C₈H₇NO	详情	详情
(XIV)	57694	tert-butyl(dimethyl)silyl 1H-indol-5-yl ether; 5-{[tert-butyl(dimethyl)silyl]oxy}-1H-indole		C₁₄H₂₁NOSi	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)