Preparation and application of 2-hydroxy-4-methoxy-5-nitropyridine_Industrial additives

Preparation and application background and overview of 2-hydroxy-4-methoxy-5-nitropyridine

2-Hydroxy-4-methoxy-5-nitropyridine is a pharmaceutical intermediate that can be prepared from 4-methoxy-3-nitropyridine. There are reports in the literature that 2-hydroxy-4-methoxy-5-nitropyridine can be used to prepare GPR17 modulators.

Preparation and application of 2-hydroxy-4-methoxy-5-nitropyridine

To a solution of anhydrous NH₃ (150 mL) in THF (50 mL) was added potassium tert-butoxide (19.1 g, 170 mmol) at -78°C, and the reaction mixture was warmed to -35℃. A solution of 4-methoxy-3-nitropyridine (10.5 g, 68.2 mmol) in 100 mL THF was cooled to 0 °C, and 15 mL t-BuOOH (5 M in decane, 75 mmol) was added slowly over 5 min. . The resulting solution was then added dropwise to the t-BuOK solution prepared above over 1 h, then stirred at -35°C for 2 h, and then carefully quenched with 50 mL of saturated NH₄Cl aqueous solution. The reaction mixture was vented and allowed to warm to room temperature overnight, then the organics were concentrated and the residue acidified with NH₄Cl solution and filtered. The resulting solid was washed with cold water and dried under vacuum to give 2-hydroxy-4-methoxy-5-nitropyridine (10.6 g, 91%) as a brown solid. ¹H NMR (MHz, CDCl₃)δ8.48(s,1H),5.58(s,1H),3.84(s,3H); MS(ESI) m/z 171[M+H]+.

Preparation and application of 2-hydroxy-4-methoxy-5-nitropyridine

2-Hydroxy-4-methoxy-5-nitropyridine can be used to prepare the following compound, which is a GPR17 modulator. G protein-coupled receptors (GPCRs) constitute the largest family of membrane receptors in cells. They transduce extracellular signals into intracellular effector systems and are involved in a variety of physiological phenomena, thus representing the most common targets of drugs. GPR17 has also been linked to food intake, insulin control and obesity. According to various reports, GPR17’s calcium carbonate modulator may help control food intake and treat obesity.

References

[1] [China invention, China invention authorization] CN201380027654.7 Bicyclic heteroaryl derivatives as MNK1 and MNK2 modulators and their uses

[2] From PCT Int. Calcium Carbonate Appl., 2019243303, 26 Dec 2019