Pharmaceutical Applications
6-Chloro-5-methylpyridazin-3-amine is used as an intermediate in
pharmaceutical manufacturing, particularly in the synthesis of complex
organic molecules. It is a crystalline solid and features prominently in
the formation of novel drug compounds.
Synthesis
The general procedure for the synthesis of 3-amino-5-methyl-6-chloropyridazine and 3-amino-4-methyl-6-chloropyridazine from 3,6-dichloro-4-methylpyridazine is as follows [Linholter, S., et al., Acta Chem. Scand. 15:1660-1666 (1961)]: to a 3,6-dichloro-4-methylpyridazine (200 mg) solution in ethanol (3 mL) was added to liquid ammonia (3 mL). The reaction mixture was placed in a sealed tube and heated at 120 °C for 12 hours. After completion of the reaction, it was cooled to room temperature and the methanol and ammonia were removed by evaporation. The residue was purified by fast chromatography (eluent: ethyl acetate) to give 153 mg of a mixture of 3-amino-5-methyl-6-chloropyridazine and 3-amino-4-methyl-6-chloropyridazine (1:1 ratio) in 87% yield. The mixture could be used directly for subsequent experiments without further separation.
References
[1] Patent: WO2007/33080, 2007, A2. Location in patent: Page/Page column 26; 37
[2] Patent: WO2014/72261, 2014, A1. Location in patent: Page/Page column 48
[3] Pharmaceutical Bulletin, 1957, vol. 5, p. 229,233
[4] Australian Journal of Chemistry, 1986, vol. 39, # 11, p. 1803 - 1809
[5] Pharmaceutical Bulletin, 1957, vol. 5, p. 229,233
