Uses
5,6-Diphenylpyrazinol is a diphenylpyrazine derivative which belongs to a class of prostacyclin receptor agonists. It is impurity of Selexipag (S253150) that is a potential drug for the treatment of various vascular disorders such as pulmonary arterial hypertension and arteriosclerosis obliterans.
Synthesis
General procedure for the synthesis of 5,6-diphenyl-2-hydroxypyrazine from glycinamide hydrochloride and biphenylformamide: Biphenylformamide (62.0 g, 0.29 mol), glycinamide hydrochloride (35.37 g, 0.32 mol), and NaOH (23.2 g, 0.58 mol) were added sequentially to 500 mL of methanol, and heated at reflux under nitrogen protection for 3 to 4 hours. The reaction progress was monitored by LC-MS until the ingredients were fully reacted. The reaction solution was cooled to 0-5 °C, and 12N HCl (38 mL) was added slowly and dropwise, followed by stirring for 30 min at room temperature. To the reaction solution was added 30 g of sodium bicarbonate and 350 mL of water, followed by washing with water (20 mL) and methanol (20 mL). The solid product was collected and dried under vacuum to give 65.5 g of 5,6-diphenyl-2-hydroxypyrazine as a white solid in 91.1% yield.
References
[1] Patent: CN108623541, 2018, A. Location in patent: Paragraph 0049-0051; 0069-0072; 0089-0091; 0108-0110; 0127
[2] Patent: US2015/147840, 2015, A1. Location in patent: Page/Page column
[3] Patent: WO2017/60827, 2017, A1. Location in patent: Page/Page column 11
[4] Patent: US2016/108006, 2016, A1. Location in patent: Paragraph 0173-0175
