反应详情

温度

100 °C

A mixture of N-[7-morpholin-4-yl-2-(3-morpholin-4-ylazetidin-1-ylmethyl)thiazolo[5,4-d]pyrimidin-5-yl]benzene-1,2-diamine (65 mg, 0.14 mmol) and ethyl difluoroacetate (0.3 mL, 2.8 mmol) in 1,4-dioxane (0.5 mL) was heated at 100° C. for 3 days. The reaction mixture was cooled to ambient temperature and loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was then washed with MeOH and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated in vacuo. The resultant residue was purified by reversed phase HPLC (Phenomenex Luna C-18, 20 mM Et3N in water on a gradient of 20 mM Et3N in acetonitrile 30:70 to 2:98) to afford 184 as a white solid (26 mg, 35%). LCMS (Method G): RT=8.03 min, M+H+=543. 1H NMR (CDCl3, 400 MHz) δ 8.29 (d, J=8.1 Hz, 1 H); 7.91 (d, J=7.8 Hz, 1 H); 7.60 (t, J=53.8 Hz, 1 H); 7.45-7.37 (m, 2 H); 4.43 (m, 4 H); 4.02 (s, 2 H); 3.89 (t, J=4.7 Hz, 4 H); 3.74 (t, J=4.5 Hz, 4 H); 3.69 (t, J=6.2 Hz, 2 H); 3.21-3.07 (m, 3 H) and 2.37 (m, 4 H)

1. temperatureThe reaction mixture was cooled to ambient temperature
2. washThe cartridge was then washed with MeOH
3. washthe desired product was subsequently eluted
4. customThe product was collected
5. concentrationconcentrated in vacuo
6. customThe resultant residue was purified by reversed phase HPLC (Phenomenex Luna C-18, 20 mM Et3N in water on a gradient of 20 mM Et3N in acetonitrile 30:70 to 2:98)