反应详情

A mixture of 2-[1-(5-chloro-7-morpholin-4-yl-thiazolo[4,5-d]pyrimidin-2-ylmethyl)piperidin-4-yl]propan-2-ol (100 mg, 0.243 mmol), 2-ethyl-1H-benzoimidazole (39 mg, 0.267 mmol), Pd2(dba)3 (11 mg, 0.0122 mmol), XPhos (23 mg, 0.049 mmol) and cesium carbonate (158 mg, 0.486 mmol) in 1,4-dioxane (1.5 mL) was purged with argon gas for 15 min. The resulting reaction mixture was irradiated with microwaves at 150° C. for 30 min. The crude residue was loaded on an Isolute® SCX-2 cartridge (5 g). The cartridge was washed with DCM/MeOH and the desired product was subsequently eluted using a mixture of 2M NH3 in MeOH and DCM. The resulting residue was further purified by column chromatography (Si—PCC, 2 M NH3 in MeOH:DCM: gradient 0:100 to 5:95) to afford 420 as a brown solid (47 mg, 37%) LCMS (Method I): RT 2.53 min, [M+H]+ 522. 1H NMR (400 MHz, CDCl3): δ 8.11 (1 H, m), 7.77-7.70 (1 H, m), 7.23 (2 H, m), 4.01-3.99 (6 H, m), 3.87 (5 H, m), 3.42-3.39 (2 H, m), 3.10 (2 H, m), 2.27 (2 H, m), 1.79 (2 H, m), 1.50 (2 H, d, m), 1.46-1.40 (3 H, m), 1.32 (1 H, m), 1.20 (6 H, s)

1. customwas purged with argon gas for 15 min
2. customThe resulting reaction mixture
3. customwas irradiated with microwaves at 150° C. for 30 min
4. washThe cartridge was washed with DCM/MeOH
5. washthe desired product was subsequently eluted
6. additiona mixture of 2M NH3 in MeOH and DCM
7. customThe resulting residue was further purified by column chromatography (Si—PCC, 2 M NH3 in MeOH:DCM: gradient 0:100 to 5:95)