• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【药物名称】A-62824

【化学名称】9-Cyclopropyl-6-fluoro-7-(1-piperazinyl)-2,3,4,9-tetrahydroisothiazolo[5,4-b]quinoline-3,4-dione

【CA登记号】111279-87-9

【 分 子 式 】C17H17FN4O2S

【 分 子 量 】360.41304

【开发单位】Abbott (Originator)

【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY, Quinolones

合成路线1

The cyclization of 2-(2,4-dichloro-5-fluorobenzoyl)acetic acid ethyl ester (I) with S-phenyl(cyclopropylimino)chlorothioformate (II) by means of NaH in DMF gives 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-2-(phenylsulfanyl)-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (III), which is oxidized with MCPBA in dichloromethane, yielding the sulfinyl derivative (IV). The cyclization of (IV) with NaSH and hydroxylamine-O-sulfonic acid in THF affords the isothiazoloquinoline (V), which is finally condensed with piperazine in pyridine to furnish the target compound.

1 Mohamadi, F.; Spees, M.M.; Grindey, G.B.; Antineoplastic bicyclic sulfonylureas. Bioorg Med Chem Lett 1992, 3, 987-992.
2 Chu, D.T.W.; Isothiazoloquinolones: Antibacterial and antineoplastic agents. Drugs Fut 1992, 17, 12, 1101.
3 Ehlhardt, W.J.; Woodland, J.M.; Worzalla, J.F.; Bewley, J.R.; Grindey, G.B.; Todd, G.C.; Toth, J.E.; Howbert, J.J.; Comparison of metabolism and toxicity to the structure of the anticancer agent sulofenur and related sulfonylureas. Chem Res Toxicol 1992, 5, 5, 667.
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) 22096 ethyl 3-(2,4-dichloro-5-fluorophenyl)-3-oxopropanoate C11H9Cl2FO3 详情 详情
(II) 43201 1-[[chloro(cyclopropylimino)methyl]sulfanyl]benzene C10H10ClNS 详情 详情
(III) 43208 ethyl 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-2-(phenylsulfanyl)-1,4-dihydro-3-quinolinecarboxylate C21H17ClFNO3S 详情 详情
(IV) 43209 ethyl 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-2-(phenylsulfinyl)-1,4-dihydro-3-quinolinecarboxylate C21H17ClFNO4S 详情 详情
(V) 43210 7-chloro-9-cyclopropyl-6-fluoroisothiazolo[5,4-b]quinoline-3,4(2H,9H)-dione C13H8ClFN2O2S 详情 详情
(VI) 10355 Diethylenediamine; Piperazine 110-85-0 C4H10N2 详情 详情

合成路线2

The condensation of 2-(2,4,5-trifluorobenzoyl)acetic acid ethyl ester (I) with cyclopropyl isothiocyanate (II) by means of NaH in DMF gives the sodium salt (IIIa-b), which is methylated with methyl iodide to afford the methylsulfanyl derivative (IVa-b). The cyclization of (IVa-b) by means of NaH in THF provides the methylsulfanyl quinolone (V), which is oxidized with MCPBA to the corresponding methylsulfinyl compound (VI). The reaction of (VI) with NaSH in THF furnishes 1-cyclopropyl-6,7-difluoro-4-oxo-2-sulfanyl-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (VII), which is cyclized with hydroxylamine-O-sulfonic acid and NaHCO3 through the intermediate (VIII), affording the isothiazoloquinoline (IX). Finally, this compound is condensed with piperazine (X) in pyridine to give the target compound.

1 Chu, D.T.W.; Isothiazoloquinolones: Antibacterial and antineoplastic agents. Drugs Fut 1992, 17, 12, 1101.
2 Aquilar-Bryan, L.; Bryan, J.; Boyd, A.E. III; et al.; Sulfonylurea signal transduction. Recent Prog Horm Res 1991, 47, 299-317.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(IIIa) 43212 sodium (Z)-1-(cyclopropylamino)-3-ethoxy-3-oxo-2-(2,4,5-trifluorobenzoyl)-1-propene-1-thiolate C15H13F3NNaO3S 详情 详情
(IIIb) 43213 sodium (E)-1-(cyclopropylamino)-3-ethoxy-3-oxo-2-(2,4,5-trifluorobenzoyl)-1-propene-1-thiolate C15H13F3NNaO3S 详情 详情
(IVa) 43214 ethyl (Z)-3-(cyclopropylamino)-3-(methylsulfanyl)-2-(2,4,5-trifluorobenzoyl)-2-propenoate C16H16F3NO3S 详情 详情
(IVb) 43215 ethyl (E)-3-(cyclopropylamino)-3-(methylsulfanyl)-2-(2,4,5-trifluorobenzoyl)-2-propenoate C16H16F3NO3S 详情 详情
(I) 22096 ethyl 3-(2,4-dichloro-5-fluorophenyl)-3-oxopropanoate C11H9Cl2FO3 详情 详情
(II) 43211 1-isothiocyanatocyclopropane; cyclopropyl isothiocyanate 56601-42-4 C4H5NS 详情 详情
(V) 43216 ethyl 1-cyclopropyl-6,7-difluoro-2-(methylsulfanyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylate C16H15F2NO3S 详情 详情
(VI) 43217 ethyl 1-cyclopropyl-6,7-difluoro-2-(methylsulfinyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylate C16H15F2NO4S 详情 详情
(VII) 43218 ethyl 1-cyclopropyl-6,7-difluoro-4-oxo-2-sulfanyl-1,4-dihydro-3-quinolinecarboxylate C15H13F2NO3S 详情 详情
(VIII) 43219 ethyl 2-(aminosulfanyl)-1-cyclopropyl-6,7-difluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate C15H14F2N2O3S 详情 详情
(IX) 43220 9-cyclopropyl-6,7-difluoroisothiazolo[5,4-b]quinoline-3,4(2H,9H)-dione C13H8F2N2O2S 详情 详情
(X) 10355 Diethylenediamine; Piperazine 110-85-0 C4H10N2 详情 详情
Extended Information