合成路线:The reaction of 7-fluoro-1-methyl-3,1-benzoxazine-2,4-dione (I) with trimethylsulfoxonium iodide and NaH in DMSO gives the corresponding ylide (II),which is cyclized with methyl orthoformate (III) in refluxing ethanol-acetic acid.
参考文献标题:Pivopril
文献作者:Castar,J.; Prous,J.
参考来源:Drugs Fut 1986,11(3),177
合成路线:Flosequinan has been synthesized by two new related ways:1) The reaction of 2-chloro-4-fluorobenzoic acid (I) with refluxing aqueous methylamine Cu powder and CuCl2 gives 4-fluoro-2-(methylamino)benzoic acid (II),which is cyclized with phosgene to yield 7-fluoro-1-methyl-1,2-dihydro-4H-3,1-benzoxazine-2,4-dione (III).The reaction of (III) with dimethyl sulfoxide and NaH in toluene affords 4-fluoro-2-(methylamino)-alpha-(methylsulfinyl)acetophenone (IV),which is finally cyclized with refluxing triethyl orthoformate.2) The reaction of 2-amino-4-fluorobenzoic acid (V) with phosgene as before gives the corresponding benzoxazine (VI),which is treated with dimethyl sulfoxide and NaH in refluxing toluene to afford 2-amino-4-fluoro-alpha-(methylsulfinyl)acetophenone (VII).The cyclization of (VII) with refluxing trimethyl orthoformate gives 7-fluoro-3-(methylsulfinyl)quinolin-4(1H)-one (VIII),which is finally methylated with dimethyl sulfate and KOH in water.
参考文献标题:Syntheses of flosequinan: A novel 4-quinolone shown to be useful in congestive heart failureSyntheses of flosequinan: A novel 4-quinolone shown to be useful in congestive heart failure
文献作者:Birch,A.M.; Maclean,L.; Robinson,K.; Davies,R.V.
参考来源:J Chem Soc - Perkins Trans I 1994,4387
合成路线:The synthesis of the two enantiomers of flosequinan has been described:The reaction of 7-fluoro-3-(methylsulfanyl)quinolin-4(1H)-one (I) with POCl3 in refluxing CHCl3 gives the corresponding chloroquinoline (II),which by oxidation with m-chloroperbenzoic acid (m-CPBA) in CHCl3/water yields 4-chloro-7-fluoro-3-(methylsulfinyl)quinoline (III).The condensation of (III) with (R)-1-phenylethylamine (IV) affords the secondary amine (V) as a diastereomeric mixture that is separated by fractional crystallization to afford the two diastereomers (VI)-(S) and (VI)-(R).Both compounds are treated with hot 1N HCl to afford (S)-4-amino-7-fluoro-3-(methylsulfinyl)quinoline (VII)-(S) and (R)-4-amino-7-fluoro-3-(methylsulfinyl)quinoline (VII)-(R),respectively.Finally,(VII)-(S) and (VII)-(R) are treated with methyl iodide in hot butanone to afford (S)-flosequinan and (R)-flosequinan,respectively.
参考文献标题:Synthesis and absolute configuration of the enantiomers of 7-fluoro-1-methyl-3-(methylsulfinyl)-4(1H)-quinolinone (flosequinan)
文献作者:Ohtani,T.; Kido,M.; Shimizu,T.; Matsubara,J.; Morita,S.; Ohtsubo,K.; Uchida,M.
参考来源:Chem Pharm Bull 1994,42(10),2157
产品链接: CAS No. 76568-02-0››