Description
6-Chloro-4-methylpyridazin-3-amine is an organic amine compound featuring chlorine and methyl functional groups on its benzene ring structure. This compound can be used in the preparation of risdiplam, a drug indicated for the treatment of spinal muscular atrophy (SMA).
Synthesis
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: [Linholter, S., et al., Acta Chem. Scand. 15:1660-1666 (1961)]. To a solution of 3,6-dichloro-4-methylpyridazine (200 mg) in ethanol (3 mL) was added 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 was used directly in the subsequent reaction 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
