2,4-Dimethoxypyridine

Uses

2,4-Dimethoxypyridine is mainly used as an organic synthesis intermediate for the synthesis of drug compounds such as PI3K inhibitors and has potential applications in anti-tumor therapy.

Synthesis

General procedure for the synthesis of 2,4-dimethoxypyridine from 2,4-dichloropyridine and sodium methanol: Freshly prepared sodium methanol (24 g, 0.44 mol) was added to an anhydrous N-methyl-2-pyrrolidinone (80 mL) solution of 2,4-dichloropyridine (15 g, 0.10 mol). The reaction mixture was stirred at 120 °C for 6 hours. After completion of the reaction, the mixture was cooled to room temperature, diluted with ethyl acetate (800 mL) and washed with water. The organic layer was separated, dried over anhydrous sodium sulfate, filtered and concentrated to give 2,4-dimethoxypyridine (4) as a colorless oil which was pure enough to be used in the next step. Yield: 11.2 g (80%).1H NMR (400 MHz, DMSO-d6): δ 3.80 (s, 3H), 3.84 (s, 3H), 6.33 (d, J = 2.0 Hz, 1H), 6.60 (dd, J = 2.0 Hz, J = 5.6 Hz, 1H), 7.97 (d, J = 5.6 Hz, 1H); 13C NMR (100 MHz, DMSO-d6): δ 167.5, 165.4, 147.4, 106.1, 93.8, 55.3, 53.1; HRMS (ESI) m/z calcd for C7H10NO2 [M+H]+: 140.0706; found: 140.0707.

References

[1] Xiaolin Li. “A Convenient Synthesis of Gimeracil.” Journal of Chemical Research-s 384 1 (2018): 33–34.
[2] Lucas Robke . “Discovery of 2,4-dimethoxypyridines as novel autophagy inhibitors.” Tetrahedron 74 35 (2018): Pages 4531-4537.