Carbon Tetrachloride → N-cyclopentyl-4-[5,7-dichloro-2-(4-fluorophenyl)pyrazolo(1,5-a]pyridin-3-yl]-2-pyrimidinamine

Temperatur

-78 °C

To a solution of 4-[5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-2-pyrimidinamine (100 mg, 0.25 mmol) in anhydrous tetrahydrofuran (5 mL) at −78° C. was added n-butyllithium (0.5 mL of 1.6 M solution in hexanes, 0.8 mmol). The resulting reaction mixture was stirred at −78° C. for 10 minutes, followed by addition of carbon tetrachloride (1 mL) and stirring at −78° C. for additional 20 minutes. The reaction was then quenched by the addition of water. The mixture was extracted with ethyl acetate. The ethyl acetate phase was washed with brine, dried (magnesium sulfate), filtered and concentrated in vacuo. The resulting residue was purified by flash chromatography (1:1 ethyl acetate-hexane) to give 50 mg (45%) of N-cyclopentyl-4-[5,7-dichloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinamine as a yellow foam. 1H NMR (CDCl3): δ 8.53 (broad s, 1H), 8.06 (d, 1H), 7.63 (m, 2H), 7.15 (t, 2H), 7.05 (d, 1H), 6.27 (d, 1H), 5.17 (d, 1H), 4.35 (m, 1H), 2.0-2.1 (m, 2H), 1.4-1.9 (m, 6H); 19F NMR (CDCl3): δ−112.2; MS m/z 442 (M+1).

1. customThe resulting reaction mixture
2. stirringstirring at −78° C. for additional 20 minutes
3. customThe reaction was then quenched by the addition of water
4. extractionThe mixture was extracted with ethyl acetate
5. washThe ethyl acetate phase was washed with brine
6. dry with materialdried (magnesium sulfate)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe resulting residue was purified by flash chromatography (1:1 ethyl acetate-hexane)

ORD-Eintrag

ord-032dc276a82d49798f5dcf9a45d6c0ec

Quelldatensatz

uspto-grants-2005_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06962914B2