3-Chloro-5H-pyrrolo[2,3-b]pyrazine

Uses

3-Chloro-5H-pyrrolo[2,3-b]pyrazine is used in the preparation of pyrazole compounds as Raf inhibitors.

Synthesis

Step 3: A solution of 6-chloro-3-((trimethylsilyl)ethynyl)pyrazin-2-amine (6.0 g, 26.57 mmol) in anhydrous THF (130 mL) was cooled to 0°C. In another vessel, potassium tert-butanolate (tBuOK, 5.96 g, 53.15 mmol) was suspended in THF (30 mL). This suspension was slowly added to the previously cooled solution. The reaction mixture was stirred at 0 °C for 30 min and then warmed up to reflux state for 2.5 h of reaction. The progress of the reaction was monitored by thin layer chromatography (TLC, 30% ethyl acetate/hexane) to confirm complete consumption of the feedstock. Upon completion of the reaction, the mixture was cooled to 25 °C and filtered through a bed of diatomaceous earth to remove insoluble impurities. The filtrate was concentrated under reduced pressure to give the crude product. The crude product was further purified by column chromatography on silica gel (100-200 mesh) using ethyl acetate/hexane (25:60) as eluent to afford the final brown solid product 3-chloro-5H-pyrrolo[2,3-b]pyrazine (2.51 g, 61% yield). Mass spectrometry (MS) analysis showed m/z(ES): 154(M+H)+.

References

[1] Patent: US2011/59118, 2011, A1. Location in patent: Page/Page column 88-89
[2] Patent: WO2016/203404, 2016, A1. Location in patent: Paragraph 00336