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,C11H11NO2,189.2158,6-methoxy-4-methyl-2(1H)-quinolinone

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摘 要:,C11H11NO2,189.2158,6-methoxy-4-methyl-2(1H)-quinolinone
  • 【化学名】6-methoxy-4-methyl-2(1H)-quinolinone
  • 【CAS登记号】
  • 【结构式】,C11H11NO2,189.2158,6-methoxy-4-methyl-2(1H)-quinolinone--药物合成数据库
  • 【分子式】C11H11NO2
  • 【分子量】189.2158
  • 【来源】
  • 【合成情况】 
  • 〖目标产物〗Tafenoquine succinate, Etaquine, SB-252263, WR-238605
  • 〖合成路线〗
  • 〖合成方法〗Chlorination of 6-methoxy-4-methylquinolin-2(1H)-one (I) with SO2Cl2 in hot acetic acid gives the 5-chloro derivative (II), which is nitrated with HNO3 in H2SO4 to yield the 8-nitroquinolinone (III). Condensation of compound (III) with 3-(trifluoromethyl)phenol (IV) by means of KOH in NMP provides the diaryl ether (V), which is treated with refluxing POCl3 to afford the 2-chloroquinoline (VI). Reaction of compound (VI) with MeONa in refluxing methanol results in the 2,6-dimethoxyquinoline derivative (VII), which is reduced with hydrazine over Pd/C to give the 8-aminoquinoline derivative (VIII). Condensation of aminoquinoline (VIII) with N-(4-iodopentyl)phthalimide (IX) by means of diisopropylamine in hot NMP yields the phthalimido precursor (X), which is finally cleaved with hydrazine in refluxing ethanol.
  • 〖参考〗LaMontagne, M.P.; et al.; Tricyclic compounds as selective muscarinic receptor antagonists. 3. Structure-selectivity relationships in a series of cardioselective (M2) antimuscarinics. J Med Chem 1989, 32, 8, 1728-32
  • 〖目标产物〗Tafenoquine succinate, Etaquine, SB-252263, WR-238605
  • 〖合成路线〗
  • 〖合成方法〗Chlorination of 6-methoxy-4-methylquinolin-2(1H)-one (I) with SO2Cl2 in hot acetic acid gives the 5-chloro derivative (II), which is nitrated with HNO3 in H2SO4 to yield the 8-nitroquinolinone (III). Condensation of compound (III) with 3-(trifluoromethyl)phenol (IV) by means of KOH in NMP provides the diaryl ether (V), which is treated with refluxing POCl3 to afford the 2-chloroquinoline (VI). Reaction of compound (VI) with MeONa in refluxing methanol results in the 2,6-dimethoxyquinoline derivative (VII), which is reduced with hydrazine over Pd/C to give the 8-aminoquinoline derivative (VIII). Condensation of aminoquinoline (VIII) with N-(4-iodopentyl)phthalimide (IX) by means of diisopropylamine in hot NMP yields the phthalimido precursor (X), which is finally cleaved with hydrazine in refluxing ethanol.
  • 〖参考〗McIntyre, J.A.; Castaer, J.; Bays, M.; Tafenoquine Succinate. Drugs Fut 2003, 28, 9, 859
  • 〖目标产物〗Tafenoquine succinate, Etaquine, SB-252263, WR-238605
  • 〖合成路线〗
  • 〖合成方法〗Chlorination of 6-methoxy-4-methylquinolin-2(1H)-one (I) with SO2Cl2 in hot acetic acid gives the 5-chloro derivative (II), which is nitrated with HNO3 in H2SO4 to yield the 8-nitroquinolinone (III). Condensation of compound (III) with 3-(trifluoromethyl)phenol (IV) by means of KOH in NMP provides the diaryl ether (V), which is treated with refluxing POCl3 to afford the 2-chloroquinoline (VI). Reaction of compound (VI) with MeONa in refluxing methanol results in the 2,6-dimethoxyquinoline derivative (VII), which is reduced with hydrazine over Pd/C to give the 8-aminoquinoline derivative (VIII). Condensation of aminoquinoline (VIII) with N-(4-iodopentyl)phthalimide (IX) by means of diisopropylamine in hot NMP yields the phthalimido precursor (X), which is finally cleaved with hydrazine in refluxing ethanol.
  • 〖参考〗Ugwuegbulam, C.O.; Foy, J.E. (GlaxoSmithKline Inc.; GlaxoSmithKline plc); Process for the preparation of anti-malarial drugs. US 6479660; WO 9713753
 
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