5-BROMO-3-METHOXYPYRAZIN-2-YLAMINE

Chemical Properties

Off-White Solid

Uses

5-Bromo-3-methoxy-2-pyrazinamine is an intermediate in the preparation of N-pyrazinylbenzenesulfonamides used in treatment of chemokine mediated diseases such as asthma.

Synthesis

1. A 30% w/w methanolic solution of sodium methanolate (8.4 mL, 44.8 mmol) was slowly added to a stirring suspension of 3,5-dibromo-2-aminopyrazine (10 g, 39.5 mmol) in anhydrous methanol (40 mL). 2. The reaction mixture was heated to reflux and the reaction was maintained for 3 h. 3. Upon completion of the reaction, the reaction was cooled to room temperature and concentrated to 1/3 of the original volume by rotary evaporation. 4. The concentrated reaction mixture was partitioned between dichloromethane (DCM) and saturated aqueous sodium bicarbonate (NaHCO3).5 The organic and aqueous layers were separated and the organic phase was washed three times with saturated aqueous NaHCO3.6 The aqueous phases were combined and back-extracted three times with DCM.7 All the organic phases were combined, washed with saturated saline, dried with anhydrous sodium sulfate, filtered, and concentrated to give 5 mL of the reaction mixture.8 The reaction mixture was then dried. dried, filtered and concentrated to give 5-bromo-3-methoxypyrazin-2-amine (8.1 g). The product was characterized by 1H NMR (300 MHz, CDCl3): δ 7.64 (s, 1H), 4.79 (br s, 2H), 4.01 (s, 3H).

References

[1] ACS Medicinal Chemistry Letters, 2017, vol. 8, # 9, p. 981 - 986
[2] Bioorganic and Medicinal Chemistry, 2001, vol. 9, # 5, p. 1149 - 1154
[3] Patent: US2013/210818, 2013, A1. Location in patent: Paragraph 0384
[4] Patent: WO2014/68171, 2014, A1. Location in patent: Page/Page column 27
[5] Patent: WO2009/115572, 2009, A2. Location in patent: Page/Page column 116