6- Ethyl-4-methyl-2-quinolone

The reaction of haplophyllidine (11) or its hydration product, perforine (12), with concentrated sulphuric acid results in dehydration, loss of methanol, and cyclization the structure (13) of the product was established by spectroscopy and by conversion, with methyl iodide, into the corresponding N-methyl-4-quinolone. The reaction of the Haplophyllum alkaloid haplatine (14) with methyl iodide also results in formation of an N-methyl-quinolone ( 15), and in this case the methylation of the allylic hydroxy-group gives a second product (16). Reductive cleavage of haplatine furnishes the 3-ethyl-2-quinolones (17) and (18). ... 

Reaction of the silyl derivative of quinoline with 2-acetoxyethyl acetoxy-methyl ether in dichloroethane with stannic chloride gave a cyclonucleoside. Removal of both the acetyl and ethyl ester groups in NaOH afforded the fully deprotected nucleoside 788. Acylation of 788 could be carried out with different esters in the presence of amino Ps lipase [91SC1477 92JCR(S)216]. The 4-quinolones showed no significant antiviral activity (91SC1477). 

Domagala JM, et al. l-Ethyl-7-[3-[(ethyl-amino)methyl]-l-pyrrolidinyl]-6,8-difluoro-l,4-dihydro-4-oxo-3-quinoline-carboxylic acid. New quinolone antibacterial with potent gram-positive activity. J. Med. Chem., 1986, 29, 445-448. 

Hydroxy-l-methyl-3-phenyl-2-quinolone (56) is formed with a yield of 80% as a result of the reaction of the anhydride 2 with ethyl phenylacetate in the presence of potassium bis(trimethylsilyl)amide at -78°C [34],... 

Ethyl l-diloro-2-anilinocrotonate refluxed 3 hrs. with aniline -> 3-anilino-2-methyl-4(lH)-quinolone. Y 87%. F. e., also 3-organothio analogs s. H. Bohme and R. Braun, Ardi. Pharm. 305y 93 (1972). 

It is worth mentioning that the first drug in the series of quinolones, nalidixic acid (1 -ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridin-3-carboxylic acid), bearing no fluorine atoms, was launched into medicinal practice in 1963. 

The first approach has been used to obtain [a]-annelated fluoroquinolones 57 and 58 from the correspondingly substituted ethyl acetates and 2-chlorobenzazoles or iminoesters (Scheme 28). 7-(l-Piperazinyl)- and 7-(4-methyl-l-piperazinyl)-benzothiazolo-[3,2-fl]quinolones 57 have been established to exhibit rather good activity against a number of bacteria [201]. 

The [fl]-annelation in which the starting material is N-methylaminoquinolone has been described [204,205]. Use of the 1,4-addition to the activated multiple bonds followed by the Michael intramolecular reaction leads to tetrahydropyrazolo[l,5-a] quinolones 61, which are oxidized into the corresponding pyrazolo[l,5-a]quino-lones. Hexahydropyrrolo[l,2-a]quinolones 62 can be regarded as [3+2] adducts derived from the reactions of N-(ethoxycarbonyl)methyl substituted ethyl esters of di-, three- and tetrafluoro-4-oxo-l,4-dihydroquinolin-3-carboxylic acids with methylmetacrylate (Scheme 30) [206]. 

Matsuoka M, Segawa J, Makita Y (1997) Studies on pyridonecarboxyUc acids. V. A practical synthesis of ethyl 6,7-difluoro-l-methyl-4-oxo-477-[l,3]thiazEto[3,2-a]quinoUne-3-carboxylate, a key intermediate for the new tricycUc quinolone, pruUfloxacin (NM441) and versatile new syntheses of the 2-thioquinoUne skeleton. J. Heterocycl Chem 34 1773-1779... 

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