2-Methyl-[1,8]naphthyridine

Uses

2-Methyl-[1,8]-naphthidine, also known as 2-methyl-1,8-naphthidine, is a pharmaceutical intermediate.

Synthesis

General procedure for the synthesis of 2-methyl-[1,8]-naphthyridine from 2-amino-3-pyridinecarboxaldehyde and acetone: 2-amino-3-pyridinecarboxaldehyde (11.10 g, 91 mmol), acetone (15.83 g, 272.9 mmol), and L-proline (11.40 g, 100.1 mmol) were dissolved in ethanol (120 mL), and the reaction was carried out under refluxing conditions with The reaction was stirred for 16 hours. After completion of the reaction, the reaction solution was cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in dichloromethane (100 mL) and filtered to remove insoluble material. The filtrate was washed with deionized water (3 x 100 mL), the organic phase was dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by fast column chromatography with the eluent ethyl acetate:petroleum ether (1:10, v/v) to afford 2-methyl-[1,8]-naphthyridine as a white solid (13.0 g, 99% yield). Mass spectrum (ESI): m/z 145 [M + H]+.

References

[1] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 10, p. 2679 - 2684
[2] Patent: WO2014/85284, 2014, A1. Location in patent: Paragraph 00227
[3] Organic and Biomolecular Chemistry, 2016, vol. 14, # 28, p. 6683 - 6686
[4] Patent: WO2018/132268, 2018, A1. Location in patent: Page/Page column 57
[5] Patent: WO2004/58761, 2004, A1. Location in patent: Page 32