Phosphorus oxychloride → 4-[2-cyclopentyl-1-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-ethyl]-benzonitrile

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of N-tert-butyl-4-[2-cyclopentyl-1-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-ethyl]-benzamide (250 mg, 0.61 mmol) in chloroform (6 mL) at room temperature was added phosphorus oxychloride (0.32 mL, 3.15 mmol). The mixture was heated at 80° C. and stirred for 3 h. The resulting mixture was concentrated in vacuo and the residue was extracted with ethyl acetate, washed with a saturated aqueous sodium bicarbonate solution (2×50 mL), brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification using a Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded 4-[2-cyclopentyl-1-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-ethyl]-benzonitrile (120 mg, 58.8%) as a white solid: LC/MS m/e calcd for C21H20FN3 [M+H]+ 334.41, observed 334.1; 1H NMR (400 MHz, CD3OD) δ ppm 8.01 (s, 1H), 7.63-7.70 (m, 3H), 7.53 (d, J=8.3 Hz, 2H), 6.39 (s, 1H), 4.28 (t, J=7.8 Hz, 1H), 2.23-2.31 (m, 1H), 2.03-2.13 (m, 1H), 1.61-1.87 (m, 5H), 1.51 (dd, J=7.3, 4.0 Hz, 2H), 1.17-1.35 (m, 2H).

Provenance & Evidence