General procedure for the synthesis of 2-amino-5-bromo-3-morpholin-4-ylpyrazine from morpholine and 2-amino-3,5-dibromopyrazine: intermediate 1-01 (15 g, 59.3 mmol) was dissolved in morpholine (15 ml, 178 mmol), and the resulting solution was subjected to a Parr reactor and heated for 48 hours at 120 °C. Upon completion of the reaction, a brown solid was observed to be produced. The solid was suspended in dichloromethane (DCM) and washed twice sequentially with aqueous sodium bicarbonate (NaHCO3). The organic phase was separated, dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated to dryness under reduced pressure to afford the target product I-02 as a brown solid in a yield of 14.8 g in 96% yield.
[1] Patent: WO2011/36461, 2011, A1. Location in patent: Page/Page column 77
[2] Tetrahedron Letters, 2012, vol. 53, # 9, p. 1082 - 1084
[3] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 5, p. 1874 - 1878
[4] Patent: US2012/83492, 2012, A1. Location in patent: Page/Page column 91
[5] Molecules, 2017, vol. 22, # 2,
