反应详情

A mixture of 5-chloro-7-morpholin-4-yl-2-[3-(tetrahydropyran-4-yl)azetidin-1-ylmethyl]thiazolo[5,4-d]pyrimidine (0.1 g, 0.25 mmol), 2-isopropyl-1H-benzoimidazole 0.078 g, 0.49 mmol), Xphos (0.024g, 0.049 mmol), Pd2(dba)3 (0.012 g, 0.012 mmol) and Cs2CO3 (0.159 g, 0.49 mmol) in dioxane (1.5 mL) was subjected to microwave irradiation at 145° C. for 45 min. The reaction mixture was filtered through Celite and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography (Si—PPC, MEOH:DCM, gradient 0:100 to 5:95) to give 470 as a yellow solid (0.044 g, 34%). LCMS (Method I): RT=2.88 min, [M+H]+ 534.2. 1H NMR (400 MHz, DMSO-d): δ 7.89-7.85 (m, 1 H); 7.66-7.61 (m, 1 H); 7.28-7.22 (m, 2 H); 4.36-4.30 (m, 4 H); 4.00 (s, 2 H); 3.97-3.89 (m, 1 H); 3.85 (dd, J=11.2, 4.0 Hz, 2 H); 3.79 (t, J=4.6 Hz, 4 H); 3.49 (t, J=7.3 Hz, 2 H); 3.39-3.35 (m, 2 H); 3.07 (t, J=6.8 Hz, 2 H); 2.27-2.21 (m, 1 H); 1.73-1.64 (m, 1 H); 1.52 (d, J=13.1 Hz, 2 H); 1.33 (dd, J=6.8, 4.0 Hz, 6 H); 1.10 (td, J=12.2, 4.6 Hz, 2 H)

1. customirradiation at 145° C. for 45 min
2. filtrationThe reaction mixture was filtered through Celite
3. concentrationthe filtrate was concentrated in vacuo
4. customThe residue was purified by flash chromatography (Si—PPC, MEOH:DCM, gradient 0:100 to 5:95)