Hydrochloric Acid → 3-Iodo-8-(4-methyl-piperazin-1-yl)-quinoline

Temperatur

150 °C

A mixture of 3-bromo-8-(4-methyl-piperazin-1-yl)-quinoline (D1)(1.75 g, 5.7 mmol), copper (I) iodide (5.4 g, 28.5 mmol) and potassium iodide (9.6 g, 57.8 mmol) in hexamethylphosphoramide (20 ml) was heated in an oil bath at 150° C. for 21 h under argon. To the cooled reaction mixture was added toluene (120 ml) and 1M hydrochloric acid (120 ml) and the whole was shaken vigorously for 5 minutes. The insoluble brown solid was then collected by filtration, washed with methanol (3×40 ml) and resuspended in a mixture of dichloromethane (150 ml) and 2M sodium hydroxide (150 ml). After shaking the mixture vigorously, the insoluble material was filtered, washed with dichloromethane (2×50 ml) and discarded. The filtrate and washings were transferred to a separating funnel and the layers were separated. The aqueous phase was extracted with dichloromethane (2×100 ml) and the combined organic extracts were dried (MgSO4) and concentrated to a brown oil (1.5 g) which was identified by NMR spectroscopy as a mixture of the title compound (D2) and 3-bromo-8-(4-methyl-piperazin-1-yl)-quinoline (D1) in a ratio of 4:1. This mixture was used directly in the next stage (see Example 1).

1. customTo the cooled reaction mixture
2. filtrationThe insoluble brown solid was then collected by filtration
3. washwashed with methanol (3×40 ml)
4. additionresuspended in a mixture of dichloromethane (150 ml) and 2M sodium hydroxide (150 ml)
5. stirringAfter shaking the mixture vigorously
6. filtrationthe insoluble material was filtered
7. washwashed with dichloromethane (2×50 ml)
8. customThe filtrate and washings were transferred to a separating funnel
9. customthe layers were separated
10. extractionThe aqueous phase was extracted with dichloromethane (2×100 ml)
11. dry with materialthe combined organic extracts were dried (MgSO4)
12. concentrationconcentrated to a brown oil (1.5 g) which
13. additionwas identified by NMR spectroscopy as a mixture of the title compound (D2) and 3-bromo-8-(4-methyl-piperazin-1-yl)-quinoline (D1) in a ratio of 4:1

ORD-Eintrag

ord-075e9c41cf6d43dca990ccf147925871

Quelldatensatz

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07452888B2