反应详情

温度

150 °C

A mixture of 2-[4-(4-morpholin-4-yl-2-(tributylstannanyl)thieno[3,2-d]pyrimidin-6-ylmethyl)piperazin-1-yl]isobutyramide (150 mg, 0.22 mmol), 5-bromo-[1,2,4]triazolo[4,3-a]pyridine (51 mg, 0.26 mmol), bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium (II) (15 mg, 0.02 mmol) and copper(I) iodide (41 mg, 0.22 mmol) in dioxane (2.5 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 appropriate fractions were combined and evaporated. The resulting residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 10:90) followed by reverse phase HPLC (Phenomenex Gemini 5u C18, 20 mM triethylamine in water on a gradient of acetonitrile 95:5 to 2:98) to give 690 as a white solid (14 mg, 12%). LCMS (Method F) RT 5.50 min; [M+H]+ 522. 1H NMR (400 MHz, CHCl3-d): δ 10.53 (d, J=0.9 Hz, 1 H); 8.08 (dd, J=7.0, 0.9 Hz, 1 H); 7.93 (d, J=9.1 Hz, 1 H); 7.41 (dd, J=9.1, 7.0 Hz, 1 H); 7.38 (s, 1 H); 7.08 (d, J=5.3 Hz, 1 H); 5.20 (d, J=5.3 Hz, 1 H); 4.07 (t, J=4.8 Hz, 4 H); 3.92 (t, J=4.8 Hz, 4 H); 3.88 (s, 2 H); 2.62 (m, 8 H);1.25 (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. customevaporated
5. customThe resulting residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 10:90)