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

Synthesis

Preparation of Method A Steps for the synthesis of intermediate 4: 5-bromo-2-methyl-1H-pyrrolo[2,3-b]pyridine: Ingredient 3 (88 mg, 0.251 mmol) was dissolved in methanol (4 mL), 2 N sodium hydroxide solution (1 mL) was added, and the reaction mixture was heated and refluxed for 2 hours. After completion of the reaction, ethyl acetate was added for extraction and the organic phase was washed sequentially with 1 N sodium hydroxide solution and water. Purification by silica gel column chromatography (slow gradient elution, volume fraction of methanol in dichloromethane increased from 0% to 2%) afforded the target product 4 (40 mg, 0.19 mmol, 76% yield). Product characterization data were as follows: 1H NMR (CDCl3, 300 MHz): δ 10.26 (br s, 1H), 8.22 (d, J = 2.1 Hz, 1H), 8.92 (d, J = 2.1 Hz, 1H), 6.13 (s, 1H), 2.52 (s, 3H). MS (m/z): 210 (M + H).

References

[1] ACS Medicinal Chemistry Letters, 2017, vol. 8, # 5, p. 582 - 586
[2] Patent: WO2011/149950, 2011, A2. Location in patent: Page/Page column 151-152
[3] Patent: WO2014/85795, 2014, A1. Location in patent: Paragraph 0394
[4] Bioorganic Chemistry, 2016, vol. 65, p. 146 - 158
[5] Patent: WO2009/16460, 2009, A2. Location in patent: Page/Page column 74