Benzophenone imine → 3-[2-(cyclopentylamino)-4-pyrimidinyl]-N-(diphenylmethylene)-2-(4-fluorophenyl)pyrazolo[1,5-alpha]pyridin-5-amine

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-[5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-3-yl]-N-cyclopentyl-2-pyrimidinamine (0.1 g, 0.25 mmol) in toluene (5 mL) was added benzophenone imine (0.13 g, 0.75 mmol), tris(dibenzylideneacetone)dipalladium (0.02 g, 0.03 mmol), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.05 g, 0.09 mmol) and sodium tert-butoxide (0.07 g, 0.75 mmol). The reaction was heated at 100° C. for 3 hours, then allowed to cool to room temperature. Aqueous sodium bicarbonate and ethyl acetate were added to the reaction mixture. The phases were separated and the organic phase was washed with brine and dried (magnesium sulfate). Filtration and concentration, followed by purification by flash chromatography (1:4 ethyl acetate-hexanes to 1:1 ethyl acetate-hexanes) gave 3-[2-(cyclopentylamino)-4-pyrimidinyl]-N-(diphenylmethylene)-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-5-amine as a solid. This solid was dissolved in tetrahydrofuran (10 mL). To this solution at 0° C. was added 4N hydrochloric acid (2 mL) dropwise. Subsequently, the reaction mixture was stirred for 30 minutes. The reaction mixture was diluted with ethyl acetate, then saturated aquous bicarbonate was added slowly until the ethyl acetate layer turned clear. The resulting mixture was stirred for 30 minutes. The organic phase was washed with water, brine and dried (magnesium sulfate). Filtration and concentration, followed by flash chromatography (ethyl acetate) gave 3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-5-amine (54 mg, 57%) as a yellow foam. 1H-NMR (CDCl3): δ 8.22 (d, 1H), 7.97 (d, 1H), 7.58 (q, 2H), 7.11 (t, 2H), 6.34 (dd, 1H), 6.20 (d, 1H), 5.14 (d, 1H), 4.31 (m, 1H), 4.10 (m, 3H), 1.5–2.2 (m, 8H); 19F-NMR (CDCl3): δ −113.4; MS m/z 389 (M+1).

Provenance & Evidence