反应详情

A mixture of 2-(1-((7-morpholino-5-(tributylstannyl)thiazolo[5,4-d]pyrimidin-2-yl)methyl)piperidin-4-yl)propan-2-ol (0.211 g, 0.32 mmol), 3-iodo-1H-indazole (0.116 g, 0.48 mmol), copper(I) 2-thiophene carboxylate (0.012 g, 0.064 mmol) and Pd(PPh3)4 (0.037 g, 0.032 mmol) in dioxane (3 mL) was subjected to microwave irradiation at 150° C. for 90 min. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the desired product was eluted using 2 M NH3 in MeOH. The eluent was concentrated in vacuo and the resultant residue was purified by flash chromatography (Si—PPC, MEOH:DCM, gradient 0:100 to 10:90) to give 209 as a yellow solid (0.043 g, 28%). LCMS (Method G): RT=7.71 min, [M+H]+ 494.3. 1H NMR (400 MHz, DMSO-d): δ 13.45 (s, 1 H); 8.48 (d, J=8.3 Hz, 1 H); 7.61 (d, J=8.3 Hz, 1 H); 7.41 (t, J=7.6 Hz, 1 H); 7.26 (t, J=7.6 Hz, 1 H); 4.37 (m, 4 H); 3.88 (s, 2 H); 3.82 (t, J=4.6 Hz, 4 H); 3.02 (d, J=11.0 Hz, 2 H); 2.12 (t, J=11.0 Hz, 2 H); 1.74-1.69 (m, 2 H); 1.36-1.28 (m, 2 H); 1.26-1.23 (m, 2 H); 1.06 (s, 6 H)

1. customirradiation at 150° C. for 90 min
2. washThe cartridge was washed with MeOH
3. washthe desired product was eluted
4. concentrationThe eluent was concentrated in vacuo
5. customthe resultant residue was purified by flash chromatography (Si—PPC, MEOH:DCM, gradient 0:100 to 10:90)