反应详情

温度

150 °C

A mixture of 2-[1-(7-morpholin-4-yl-5-(tributylstannanyl)thiazolo[5,4-d]pyrimidin-2-ylmethyl)piperidin-4-yl]propan-2-ol (118 mg, 0.18 mmol), 5-bromo-8-methylimidazo[1,2-a]pyridine (45 mg, 0.21 mmol), Pd(PPh3)4 (20 mg, 0.02 mmol) and copper(I) thiophene-2-carboxylate (7 mg, 0.035 mmol) in dioxane (2 mL) was purged with argon gas then heated at 150° C., for 20 min, in a microwave reactor. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was washed with MeOH then the desired product was eluted with 2 M NH3 in MeOH. The resulting residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 10:90) to give 244 as an off-white solid (80 mg, 89%). LCMS (Method G) RT 5.09 min; [M+H]+ 508. 1H NMR (400 MHz, CHCl3-d): δ 9.22 (s, 1 H); 7.93 (d, J=7.4 Hz, 1 H); 7.75 (d, J=1.3 Hz, 1 H); 7.14 (d, J=7.4 Hz, 1 H); 4.43 (m, 4 H); 3.90 (m, 4 H); 3.87 (s, 2 H); 3.10 (d, J=11.5 Hz, 2 H); 2.73 (s, 3 H); 2.23 (t, J=11.5 Hz, 2 H); 1.78 (m, 2 H); 1.55-1.41 (m, 2 H); 1.35 (m, 2 H); 1.22 (s, 6 H)

1. customwas purged with argon gas
2. washThe cartridge was washed with MeOH
3. washthe desired product was eluted with 2 M NH3 in MeOH
4. customThe resulting residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 10:90)