HOFQ

Chemical Name: 4-Hydroxymethyl-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one
项目整合开发状态: Preclinical
项目研究机构: Universit?degli Studi di Padova (Originator)
合成路线: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).

合成路线: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.