Description
1-(3-Pyridyl)-3-(dimethylamino)-2-propen-1-one can be used in the synthesis of imatinib and nilotinib (AMN107), a compound currently in multiple Phase II/III clinical trials for chronic granulocytic leukaemia. Imatinib, on the other hand, is a cancer growth blocker known as a tyrosine kinase inhibitor (TKI), which is used to treat a wide range of leukaemias, myelodysplastic/myeloproliferative disorders, systemic mastocytosis, eosinophilia syndromes, raised dermal fibrosarcoma and gastrointestinal mesenchymal tumours.
Synthesis
Example-2: Preparation of 3-dimethylamino-1-pyridin-3-ylacrylone A: 3-acetylpyridine (25 g, 0.20 mol), N,N-dimethylformamide dimethyl acetal (37 g, 0.31 mol) and acetic acid (2.5 mL) were mixed and heated to react for 2 hrs at 90-95°C while successive removal of methanol generated. Upon completion of the reaction, the excess methanol in the reaction was removed by distillation under reduced pressure. The reaction mixture was diluted with water and extracted with dichloromethane (125 mL). The organic layer was washed with water and subsequently concentrated to dryness under reduced pressure to afford 34 g (92% yield) of 1-(3-pyridinyl)-3-(dimethylamino)-2-propen-1-one with a purity of 99.1% by HPLC analysis.
References
[1] Synlett, 2016, vol. 27, # 15, p. 2233 - 2236
[2] RSC Advances, 2018, vol. 8, # 47, p. 26828 - 26836
[3] Molecules, 2009, vol. 14, # 10, p. 4166 - 4179
[4] Patent: WO2011/39782, 2011, A1. Location in patent: Page/Page column 14
[5] Organic Process Research and Development, 2008, vol. 12, # 3, p. 490 - 495
