Reaktion #2302102

Reaktionsgleichung

methyl iodide

lithium diisopropylamide

2-(4-fluorophenyl)-3-(4-pyrimidinyl)-pyrazolo[1,5-a]pyridine

2-(4-Fluorophenyl)-3-(4-pyrimidinyl)-pyrazolo[1,5-a]pyridine

hexane ethyl acetate

→

title compound

2-(4-Fluorophenyl)-7-methyl-3-(4-pyrimidinyl)pyrazolo[1,5-α]pyridine

Lösungsmittel

heptane tetrahydrofuran ethylbenzene

tetrahydrofuran

diethyl ether

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGstirred for a further 1.5 hours
2. 2
   workup.ADDITIONadded
3. 3
   Sonstigethe organic phase separated
4. 4
   ExtraktionThe aqueous phase was further extracted with ether (20 mL)
5. 5
   Trocknenthe combined ether phases were dried over anhydrous magnesium sulfate
6. 6
   Filtrationfiltered
7. 7
   Sonstigethe solvents evaporated
8. 8
   Sonstigeto give a yellow solid

Vorschrift

A solution of 2-(4-fluorophenyl)-3-(4-pyrimidinyl)-pyrazolo[1,5-a]pyridine (Example 1, 0.2 g, 0.69 mmol) in dry tetrahydrofuran (5 mL) was cooled to −78° C. under nitrogen and lithium diisopropylamide (0.45 mL of a 2M solution in heptane/tetrahydrofuran/ethylbenzene, 0.9 mmol) was added dropwise. The reaction mixture was stirred for about 10 minutes and methyl iodide (0.2 mL, 4 mmol) was added. The solution was allowed to warm to room temperature and stirred for a further 1.5 hours. The reaction mixture was diluted with diethyl ether (20 mL), water (20 mL) added, and the organic phase separated. The aqueous phase was further extracted with ether (20 mL) and the combined ether phases were dried over anhydrous magnesium sulfate, filtered and the solvents evaporated to give a yellow solid. Chromatography on silica gel eluting with 9:1 hexane/ethyl acetate gave the title compound, 0.080 g (38%). 1H NMR (DMSO-d6): δ 2.72 (s, 3H), 7.05 (d, J=6.3 Hz, 2H), 7.32 (t, J=8.8 Hz, 2H), 7.46 (dd, J=7.0, 8.6 Hz, 1H), 7.61 (dd, J=5.5, 8.6 Hz, 2H), 8.32 (d, J=9.0 Hz, 1H), 8.52 (d, J=5.5 Hz, 1H), 9.15 (s, 1H); APESI+MS m/z 305 (M+1)−.

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