Uses
Ethyl [4-Chloro-2-(methylsulfanyl)pyrimidin-5-yl]acetate is used in preparation of the dihydropyrrolopyrimidine-selective JAK2 inhibitors.
Synthesis
Step 3: General procedure for the synthesis of ethyl 4-chloro-2-methylthio-5-pyrimidineacetate from ethyl 2-(2-(methylthio)-6-oxo-1,6-dihydropyrimidin-5-yl)acetate: ethyl 2-(2-(methylthio)-6-oxo-1,6-dihydropyrimidin-5-yl)acetate (28.8 g, 0.128 mol) was dissolved in phosphorous triclosan (240 mL ) in the reaction and refluxed for 4 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure. The concentrated residue was co-evaporated twice with benzene to completely remove the residual phosphorous trichloride. Finally, it was purified by silica gel column chromatography (eluent: ethyl acetate-hexane, 1:3) to afford ethyl 4-chloro-2-(methylthio)pyrimidin-5-yl acetate (29.72 g, 95.5% yield). The product was characterized by 1H NMR (400 MHz, CDCl3): δ 8.32 (s, 1H), 4.13 (q, J=5.7 Hz, 2H), 3.62 (s, 2H), 2.52 (s, 3H), 1.21 (t, J=5.7 Hz, 3H).
References
[1] Patent: WO2009/152027, 2009, A1. Location in patent: Page/Page column 22; 25
[2] Patent: WO2017/176812, 2017, A1. Location in patent: Paragraph 0374
[3] Monatshefte fur Chemie, 2016, vol. 147, # 4, p. 767 - 773
[4] Patent: WO2016/22644, 2016, A1. Location in patent: Page/Page column 73
