反应详情

温度

100 °C

To 5-bromo-7-[2-(dimethylamino)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (100 mg, 0.352 mmol), 1-[(2,5-difluorophenyl)acetyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole (183 mg, 0.457 mmol) in a 5 ml sealable vial was added 1,4-Dioxane (2 mL) and saturated NaHCO3 (1 mL). The mixture was then bubbled N2 gas for 10 minutes then Pd(Ph3P)4 (40.7 mg, 0.035 mmol) was added. The mixture was again bubbled N2 gas for 5 minutes then capped and the reaction was heated at 100° C. overnight. The reaction was diluted with water (3 ml) then extracted with EtOAc (3×mL). The organics were combined and washed with brine, dried over Mg2SO4, filtered and concentrated. The resulting amber color oil was dissolved in 3 mL of DMSO and purified by HPLC: (HPLC condition: Gilson using Trilution software with a Sunfire 5u C18(2) 100A. 50×30.00 mm 5 micron. 7.3-minute run (47 ml/min, 7% ACN/H2O, 0.1% TFA to 37% ACN/H2O, 0.1% TFA) with UV detection at 254 nm). Product fractions were combined and the volume was reduced to remove most of the MeCN. The water left behind was added to saturated NaHCO3 and then extracted with EtOAc (3×15 mL). The organic was combined wash with saturated NaCl solution, dried over MgSO4, filtered and concentrated. Then it was transferred into a 40 mL vial with MeCN then added water and freeze-dried to give 5-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-[2-(dimethylamino)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (35 mg). LC/MS (ES) m/z=477.5 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 8.14 (s, 1H), 8.09 (d, J=8.08 Hz, 1H), 7.33 (s, 2H), 7.15-7.30 (m, 4H), 6.06 (br. s., 2H), 4.24-4.33 (m, 4H), 3.95 (s, 2H), 3.24-3.30 (m, 2H), 2.72 (br. s., 2H), 2.24 (br. s., 6H).

1. customfor 5 minutes
2. customthen capped
3. extractionthen extracted with EtOAc (3×mL)
4. washwashed with brine
5. dry with materialdried over Mg2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. dissolutionThe resulting amber color oil was dissolved in 3 mL of DMSO
9. custompurified by HPLC
10. custom7.3-minute
11. customto remove most of the MeCN
12. waitThe water left behind
13. additionwas added to saturated NaHCO3
14. extractionextracted with EtOAc (3×15 mL)
15. washThe organic was combined wash with saturated NaCl solution
16. dry with materialdried over MgSO4
17. filtrationfiltered
18. concentrationconcentrated
19. dry with materialadded water and freeze-dried