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

Temperature

-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 vocuo. 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 vocuo
9. customThe resulting residue was purified by flash chromatography (1:1 ethyl acetate-hexane)

ORD record

ord-b9817c1ae8f74c4586561c1f95adcd78

Source dataset

uspto-grants-2006_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07030134B2