Ethanone, 1-(1H-pyrrolo[2,3-b]pyridin-3-yl)- (9CI)

Chemical Properties

Solid

Uses

1-(1H-Pyrrolo[2,3-b]pyridin-3-yl)ethanone is an intermediate used in the preparation of vemurafenib, a kinase inhibitor for the treatment of BRAF-mutated melanoma and in other clinical studies.

Synthesis

General procedure for the synthesis of 3-acetyl-7(1H)-azaindole from 7-azaindole and acetyl chloride: 7-azaindole (0.59 g, 5 mmol) was dissolved in 80 mL of dichloromethane, aluminum trichloride (3.39 g, 25 mmol) was added, followed by a slow dropwise addition of acetyl chloride (3.4 mL, 47.8 mmol). The reaction mixture was stirred at room temperature for 10 hours. Upon completion of the reaction, the reaction solution was placed in an ice bath and 20 mL of methanol was slowly added to quench the reaction. The reaction mixture was concentrated and 30 mL of water was added to the residue and the pH was adjusted with 1 N aqueous sodium hydroxide to about 4. The reaction solution was extracted with ethyl acetate (15 mL x 3), and the organic phases were combined, washed with saturated brine (20 mL x 2) and dried over anhydrous sodium sulfate. After filtration and concentration, the residue was purified by column chromatography (eluent: petroleum ether/ethyl acetate=1:1, v/v) to give 0.72 g of a pale yellow solid in 90% yield.

References

[1] Journal of Organic Chemistry, 2002, vol. 67, # 17, p. 6226 - 6227
[2] Patent: CN103508930, 2016, B. Location in patent: Paragraph 0296-0299
[3] Patent: CN104817490, 2017, B. Location in patent: Paragraph 0188; 0189
[4] Patent: US2007/112020, 2007, A1. Location in patent: Page/Page column 38
[5] Patent: WO2007/79239, 2007, A2. Location in patent: Page/Page column 83