Potassium Carbonate → [3-(1-Benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-4-(2-methylsulfanyl-pyrimidin-4-yl)-pyrazol-1-yl]-acetonitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of the 5-{4-[2-(methylthio)pyrimidin-4-yl]-1H-pyrazol-3-yl}-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine (C-1-3) (638 mg, 1.42 mmol) and bromoacetonitrile (0.5 mL, 7 mmol) in DMF was added freshly ground Potassium Carbonate (254 mg, 1.84 mmol). The resulting suspension was stirred at 75° C. for 18 hr. LCMS showed complete consumption of starting material. The mixture was partitioned between ethyl acetate and saturated aqueous NaCl. The aqueous layer was extracted with ethyl acetate twice. The combined organics were washed with water twice, saturated aqueous NaCl, dried over MgSO4 and reduced to minimum volume. The residue was purified on silica gel using a gradient of 25 to 100% methyl tert-butyl ether in hexanes as eluent to give [3-(1-Benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-4-(2-methylsulfanyl-pyrimidin-4-yl)-pyrazol-1-yl]-acetonitrile (C-1-4) (440 mg, 63%) as a crisp foam. 1H NMR (400 MHz, ACETONITRILE-d3) δ ppm 8.46 (d, J=2.02 Hz, 1H), 8.36 (d, J=5.31 Hz, 1H), 8.31 (s, 1H), 8.11-8.16 (m, 2H), 8.09 (d, J=2.02 Hz, 1H), 7.83 (d, J=4.04 Hz, 1H), 7.64-7.71 (m, 1H), 7.57 (t, J=7.71 Hz, 2H), 7.01 (d, J=5.31 Hz, 1H), 6.75 (d, J=4.04 Hz, 1H), 5.26 (s, 2H), 1.88 (s, 3H).

Provenance & Evidence