(2-bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)methanol Chemical Properties

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

(2-bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)methanol Usage And Synthesis

Synthesis

Step 2. Synthesis of (2-bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)methanol. An aqueous solution of sodium hydroxide (NaOH, 70.3 g, 1.758 mol) (880 mL) was added slowly and dropwise to an aqueous solution of (2-bromo-5H-pyrrolo[2,3-b]pyrazin-5,7-diyl)dimethanol (150 g, 586 mmol) in tetrahydrofuran (THF, 1.5 L) suspension. After the dropwise addition, the reaction mixture was stirred for 18 h at room temperature. The reaction progress was monitored by hydrogen nuclear magnetic resonance (HNMR), which showed about 18% of the feedstock remaining. The reaction mixture was continued to be stirred at room temperature for 48 hours until HNMR confirmed complete consumption of the feedstock. Three batches of the reaction mixture were combined for post-processing. First, most of the THF was removed by rotary evaporation.Subsequently, the aqueous phase residue was acidified to pH = 3-4 with 2 M hydrochloric acid (HCl) and extracted with ethyl acetate (EtOAc, 3 × 3 L). The organic layers were combined, washed sequentially with water (3 L) and saturated brine (3 L), dried over anhydrous sodium sulfate (Na2SO4), and concentrated to afford (2-bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)methanol (381 g, 96% yield) as a yellow solid, which could be used in the subsequent steps without further purification.

References

[1] Patent: US2015/158864, 2015, A1. Location in patent: Paragraph 0649
[2] Patent: US2011/230462, 2011, A1. Location in patent: Page/Page column 54; 56
[3] Patent: WO2011/144584, 2011, A1. Location in patent: Page/Page column 36
[4] Patent: WO2011/144585, 2011, A1. Location in patent: Page/Page column 98
[5] Journal of Medicinal Chemistry, 2013, vol. 56, # 1, p. 345 - 356