反应详情

温度

110 °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 (75 mg, 0.16 mmol) and 1,1′-carbonyldiimidazole (100 mg, 0.62 mmol) in 1,4-dioxane (1 mL) was heated at 110° C. for 3 h. After cooling to ambient temperature, the mixture was loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was then washed with methanol 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 flash chromatography (Si—PPC, DCM: 2 M NH3 in MeOH 100:0 to 99:1 to 98:2) to afford 183 as a cream solid (45 mg, 57%). LCMS (Method G): RT=6.72 min, M+H+=509. 1H NMR (CDCl3, 400 MHz) δ 8.71 (s, 1 H); 7.77 (m, 1 H); 7.15-7.05 (m, 3 H); 4.42 (m, 4 H); 4.01 (s, 2 H); 3.86 (m, 4 H); 3.71 (m, 6 H); 3.15 (s, 3 H) and 2.36 (m, 4 H)

1. temperatureAfter cooling to ambient temperature
2. washThe cartridge was then washed with methanol
3. washthe desired product was subsequently eluted
4. customThe product was collected
5. concentrationconcentrated in vacuo
6. customThe resultant residue was purified by flash chromatography (Si—PPC, DCM: 2 M NH3 in MeOH 100:0 to 99:1 to 98:2)