Uses
4-Hydroxy-1-methyl-2-pyridone is a reactant used in the synthesis of 3-deaza-3-halouracil nucleosides with cytostatic activity in three cancer cell lines.
Synthesis
General Steps:
Example 1 d-R2 group 3 preparation of 4-(benzyloxy)-1-methylpyridin-2(1H)-one: to a round-bottomed flask equipped with a condenser was added 4-(benzyloxy)pyridin-2(1H)-one (2.012 g, 10.0 mmol), K2CO3 (2.76 g, 20.0 mmol), MeI (2.129 g, 15.0 mmol) and MeOH (12.5 mL, 0.8 M) and then heated at 65 °C overnight. At this temperature, LCMS showed complete conversion to product. Post-treatment: the reaction mixture was filtered through diatomaceous earth. The filtrate was concentrated to an oil and left to solidify. The mass recovery was 1.95 g (91%). The substance could be used in the next step without further purification.
Preparation of 4-hydroxy-1-methylpyridin-2(1H)-one: To a round bottom flask was added 4-(benzyloxy)-1-methylpyridin-2(1H)-one (646 mg, 3.0 mmol), 10% Pd/C (160 mg), ammonium formate (568 mg, 9.0 mmol) and methanol (15 mL, 0.2 M). The resulting mixture was heated at 40 °C for 1 h, at which point the LCMS showed complete conversion to product. Post-treatment: the mixture was filtered through diatomaceous earth, concentrated and purified by preparative high performance liquid chromatography (PvPLC) to afford 1-methyl-4-hydroxy-2-pyridone as a colorless oil (215 mg, 57%).
References
[1] Journal of Medicinal Chemistry, 2008, vol. 51, # 17, p. 5243 - 5263
[2] Patent: WO2014/43272, 2014, A1. Location in patent: Paragraph 0260; 0262
[3] Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 7, p. 871 - 874
