Dimethyl Sulfoxide → 3,3-dimethyl-1-(1-(5-methylpyridin-2-yl)piperidin-4-yl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one

Participants

Reaction Conditions

Reaction Steps

A mixture of 3,3-dimethyl-1-(piperidin-4-yl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one dihydrochloride (intermediate 57, 0.2000 g, 0.628 mmol), cesium acetate (0.869 g, 4.52 mmol), 2-bromo-5-methylpyridine (0.119 g, 0.691 mmol), and dry dimethylsulfoxide (1.0 mL) was heated at 100° C. for 14 hours. Additional 2-bromo-5-methylpyridine (0.119 g, 0.691 mmol) and copper (7.99 mg, 0.126 mmol) were added to the mixture and the reaction was continued for an additional 14 hours. The mixture was diluted with ethyl acetate and ammonium hydroxide and the phases separated. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The crude product was purified by silica gel chromatography (0-100% ethyl acetate in hexane gradient) to give 3,3-dimethyl-1-(1-(5-methylpyridin-2-yl)piperidin-4-yl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one (0.052 g, 0.155 mmol, 24.6% yield). M+1: 337.0. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.37 (s, 6 H) 1.72-1.84 (m, 2 H) 2.20 (s, 3 H) 2.72-3.01 (m, 4 H) 4.40 (d, J=12.52 Hz, 2 H) 4.54 (tt, J=11.93, 3.91 Hz, 1 H) 6.66 (d, J=8.61 Hz, 1 H) 6.92 (dd, J=7.24, 5.28 Hz, 1 H) 7.31 (dd, J=8.61, 1.76 Hz, 1 H) 7.41 (dd, J=7.24, 1.37 Hz, 1 H) 8.02 (s, 1 H) 8.12 (dd, J=5.18, 1.27 Hz, 1 H).

Provenance & Evidence