5-Methoxy-1H-pyrrolo[2,3-b]pyridine

Chemical Properties

Tan solid

Uses

5-Methoxy-7-azaindole can be used as a pharmaceutical intermediate, mainly used in laboratory research and development processes and chemical production processes, especially in the synthesis of drug molecules with specific biological activities.

Synthesis

General procedure for the synthesis of 5-methoxy-1H-pyrrolo[2,3-b]pyridine (30) from sodium methanol and 5-bromo-7-azaindole: to a solution of 5-bromo-7-azaindole (0.98 g, 5.0 mmol) in DMF (32 mL) was added a 25% (w/w) solution of sodium methanol (48 mL, 210 mmol), followed by addition of copper(I) bromide (1.43 g, 10.0 mmol). The reaction mixture was heated at 140 °C for 2.5 hours. After completion of the reaction, the reaction mixture was cooled and concentrated under reduced pressure to remove DMF. water (100 mL) and saturated aqueous sodium bicarbonate (20 mL) were added to the residue. The aqueous phase was extracted with ethyl acetate (3 x 100 mL), the organic phases were combined and dried over anhydrous magnesium sulfate. After filtration, the organic phase was concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (ethyl acetate:hexane, gradient elution to 30:70) to afford the target compound 30 as a green solid (0.58 g, 78% yield).1H NMR (400 MHz, CDCl3) δ 3.90 (s, 3H), 6.45 (d, J = 2.3 Hz, 1H), 7.33 (d, J = 2.8 Hz, 1H ), 7.48 (d, J = 2.2 Hz, 1H), 8.00-8.20 (bs, 1H), 10.60-10.80 (bs, NH).

References

[1] Journal of the American Chemical Society, 2006, vol. 128, # 45, p. 14426 - 14427
[2] Patent: EP1749829, 2007, A1. Location in patent: Page/Page column 52
[3] Patent: US2007/72896, 2007, A1. Location in patent: Page/Page column 51
[4] Patent: WO2012/88469, 2012, A1. Location in patent: Page/Page column 175-177
[5] Patent: WO2007/2325, 2007, A1. Location in patent: Page/Page column 122