反应详情

A degassed mixture of 2-bromo-5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one (Intermediate B) (0.314 mmol), 4-methoxy-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine (Intermediate U) (0.627 mmol), PdCl2(dppf).CH2Cl2 adduct (0.047 mmol) and K3PO4 (1.255 mmol) in 3:1 dioxane/H2O (4 mL) was heated at 100° C. for 30 min. After cooling to rt, the reaction mixture was diluted with H2O and extracted with EtOAc (2×). The combined organic phases were washed successively with H2O and brine, dried (Na2SO4) and concentrated. The residue was purified by preparative HPLC (prep-HPLC 1) and then triturated in Et2O to afford the title compound as a white solid. ESI-MS: tR=1.21 min, [M+H]+ 522/524/526 (LC-MS 1); 1H-NMR (d6-DMSO, 600 MHz): 7.93 (s, 1H), 7.76 (s, 1H), 7.37 (m, 2H), 7.24 (m, 2H), 7.14 (m, 1H), 7.10 (m, 1H), 6.89 (s, 2H), 6.47 (s, 1H), 6.22 (s, 1H), 3.94 (m, 1H), 3.80 (s, 3H), 1.92 (s, 3H), 1.29 (m, 3H), 0.49 (m, 3H).

1. extractionextracted with EtOAc (2×)
2. washThe combined organic phases were washed successively with H2O and brine
3. dry with materialdried (Na2SO4)
4. concentrationconcentrated
5. customThe residue was purified by preparative HPLC (prep-HPLC 1)
6. customtriturated in Et2O