Uses
3-Chloro-6-methoxypyridazine was used in the preparation of number of α-aryl-α-(pyridazin-3-yl)-acetonitriles.
Synthesis Reference(s)
The Journal of Organic Chemistry, 60, p. 1466, 1995
DOI: 10.1021/jo00110a059
General Description
3-Chloro-6-methoxypyridazine undergoes regioselective metallation using various lithium alkylamides, temperatures and solvents (THF and ether). It was lithiated using lithium 2,2,6,6-tetramethylpiperidide during the synthesis of minaprine.
Synthesis
A methanolic solution of 0.5 M sodium methanolate (NaOMe/MeOH, 7.4 mL, 3.69 mmol) was slowly added dropwise to a solution of anhydrous tetrahydrofuran (12 mL) containing 3,6-dichloropyridazine (500 mg, 3.36 mmol), and the reaction mixture was stirred for 1 h at room temperature. Subsequently, the reaction was quenched by the addition of water. The reaction mixture was extracted with ethyl acetate and the organic phases were combined. The organic phase was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography to afford 6-methoxy-3-chloropyridazine (436 mg, 90% yield) as a white solid.1H NMR (400 MHz, CDCl3) δ 4.12 (s, 3H), 6.98 (d, J = 9.2 Hz, 1H), 7.38 (d, J = 9.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 55.5 (d, J = 9.2 Hz, 1H). CDCl3) δ 55.2, 119.9, 130.6, 150.9, 164.2.
References
[1] Journal of Heterocyclic Chemistry, 2005, vol. 42, # 4, p. 509 - 513
[2] Patent: US2010/261727, 2010, A1. Location in patent: Page/Page column 31
[3] ACS Chemical Neuroscience, 2017, vol. 8, # 11, p. 2374 - 2380
[4] Journal of Heterocyclic Chemistry, 2013, vol. 50, # 5, p. 1165 - 1173
[5] Journal of the American Chemical Society, 1959, vol. 81, p. 6511,6512
