ethyl 4-bromo-1H-pyrrolo[2,3-b]pyridine-2-carboxylate

Uses

Ethyl 4-bromo-1H-pyrrolo[2,3-b]pyridine-2-carboxylate is used in pharmaceutical synthesis and experiments.

Synthesis

Step A: Synthesis of ethyl 4-bromo-1H-pyrrolo[2,3-b]pyridine-2-carboxylate Ethyl 1H-pyrrolo[2,3-b]pyridine-2-carboxylate-7-oxide (1 g, 5 mmol) (prepared according to the method disclosed in WO 2000/044753, see Example 6, Step C) was added to a suspension of tetramethylammonium bromide (1.2 g, 7.5 mmol) in N,N-dimethylformamide (50 mL). The reaction mixture was cooled to 0 °C, followed by batchwise addition of methylsulfonic anhydride (1.7 g, 10 mmol). The mixture was warmed to room temperature and stirring was continued for 6 hours. Upon completion of the reaction, the mixture was poured into water (100 mL) and neutralized with 50% aqueous sodium hydroxide solution. The aqueous phase was extracted with ethyl acetate and the organic layer was washed sequentially with brine and deionized water. The organic phase was concentrated under reduced pressure to give the crude product. Purification by SCX column chromatography afforded ethyl 4-bromo-1H-pyrrolo[2,3-b]pyridine-2-carboxylate as a light yellow solid (1 g, 77% yield). 1H NMR (400MHz, DMSO-d6) δ ppm: 1.35 (t, 3H, J=7.1Hz), 4.36 (q, 2H, J=7.1Hz), 7.05 (d, 1H, J=2.0Hz), 7.48 (d, 1H, J=5.1Hz), 8.28 (d, 1H, J=5.1Hz), 12.95 (brs , 1H).

References

[1] Journal of Medicinal Chemistry, 2010, vol. 53, # 10, p. 3973 - 4001
[2] Patent: WO2008/49855, 2008, A2. Location in patent: Page/Page column 54
[3] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 16, p. 4610 - 4614
[4] Patent: US2009/18156, 2009, A1. Location in patent: Page/Page column 18-19
[5] Patent: WO2007/76423, 2007, A2. Location in patent: Page/Page column 96