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

Synthesis

N,N-dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine (5.60 g, 32.0 mmol) was used as a raw material and dissolved in N,N-dimethylformamide (20 mL). Subsequently, a solution of sodium cyanide (2.35 g, 48.2 mmol) in water (16 mL) was added to this solution. Acetic acid (5 mL) was added slowly and dropwise to the reaction mixture with stirring. The reaction system was heated to 110 °C and maintained at this temperature for 8 hours. Upon completion of the reaction, the mixture was cooled to room temperature, diluted with saturated aqueous potassium carbonate solution (30 mL) and extracted with ethyl acetate (3 x 40 mL). The organic phases were combined, dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give the crude product. Purification by fast column chromatography (eluent: ethyl acetate/hexane=50:50) afforded the target product 1H-pyrrolo[2,3-b]pyridine-3-acetonitrile (2.59 g, 52% yield) as a white crystalline solid. The product characterization data were as follows: melting point 135-137 °C (literature value 136-138 °C); thin-layer chromatography Rf value (50% ethyl acetate/hexane) 0.19; IR spectra (KBr, cm-1) 3089, 2888, 2248, 1611, 1585, 1538, 1420, 1337; 1H NMR (300 MHz, CDCl3) δ 3.85 (2H, s, CH2), 7.14-7.18 (1H, q, J=7.9,4.8 Hz, Ar-H), 7.40 (1H, s, Ar-H), 7.97-8.01 (1H, dd, J=7.9,1.5 Hz, Ar-H), 8.37-8.39 (1H, dd, J=4.8,1.5 Hz, Ar H), 11.92 (1H, br s, NH); 13C NMR (75 MHz, CDCl3) δ 14.6 (CH2), 102.8 (C), 116.0 (CH), 117.8 (C), 119.0 (C), 124.0 (CH), 127.1 (CH), 143.1 (CH), 148.9 (C); mass spectra ( ES+) m/z 158.0 [M+H]+ (100%).

References

[1] Tetrahedron, 2011, vol. 67, # 25, p. 4601 - 4611
[2] Journal of Medicinal Chemistry, 2011, vol. 54, # 13, p. 4752 - 4772
[3] Patent: WO2017/143134, 2017, A1. Location in patent: Page/Page column 20-21