1H-Pyrrolo[2,3-b]pyridine-3-acetonitrile

General procedure: A gramine derivative (1.0 equiv) was dissolved in ethanol (5.5mL for 1.34mmol of starting material) and water (0.55mL for 1.34mmol of starting material). The gramine solution was added to potassium cyanide (2.0 equiv) prepared in a separate flask. Iodomethane (2.6 equiv) was added and the reaction was stirred vigorously at room temperature for 16h. Saturated sodium bicarbonate was added to quench the reaction, followed by extraction with ethyl acetate thrice. The combined organic layer was washed with brine, dried over anhydrous sodium sulphate and concentrated in vacuo. Purification by flash silica gel column chromatography afforded the indole-3-acetonitrile derivative product.To a solution of N, N-dimethyl-1-(1H-pyrrolo[2, 3-b]pyridin-3-yl)methanamine 30 (5.60 g, 32.0 mmol) in DMF (20 mL) was added a solution of sodium cyanide (2.35 g, 48.2 mmol) in water (16 mL). Acetic acid (5 mL) was then added to the mixture in a dropwise manner, and the resulting solution was heated to 110 °C for 8 h. After cooling to room temperature, the solution was diluted with saturated aq KTo a solution of compound N, N-dimethyl- l-(lH-pyrrolo[2, 3-b]pyridin-3-yl)methanamine (35 g, 199.74 mmol) in THF (180 mL) and MeOH (180 mL) was added Me1) To a solution of 1H-pyrrolo[2, 3-b]pyridine (1.5 g, 12.7 mmol, 1.0 eq.)and paraformaldehyde (0.46 g, 15.2 mmol, 1.2 eq.) in isopropanol (20 mL) was addeddimethylamine hydrochloride (1.24 g, 15.2 mmol, 1.2 eq). The reaction mixturewas refluxing for 20 minutes and after cooling to room temperature basified topH 12 with 5M aqueous NaOH solution. The reaction mixture was extracted with EtOAc. The organiclayer was washed with HTo a mixture of N, N, N-trimethyl-1 -(1 H-pyrrolo[2, 3-b]pyridin-3-yl)methanaminium iodide (5.20 g, 27.33 mmcl) in THE (160 mL) was added TMSCN (4.07 g, 41.0 mmol, 5.15 mL) followed by TBAF (1 M, 81 .99 mL). The solution was stirred at 20°C for 4 hours. The reaction solution was concentrated and thethe residue was dissolved in ethyl acetate (200 mL). The organic layer was washed with saturated aqueous Na2003 (200 mL), dried over Na2SO4, filtered and concentrated. The crude product was washed with water (250 mL) and dried in vacuum to give 2-(1H-pyrrolo[2, 3-b]pyridin-3-yl)acetonitrile (3.90 g) as a white solid.Ms: (M÷H)1581H NMR (400 MHz, MeOD) 6=3.99 (s, 2H), 7.18-7.14 (m, 1H), 7.41 (s, 1H), 8.08 (d, J= 8.0 Hz, 1H), 8.23 (d, J4.8 Hz, 1H).