反应详情

温度

100 °C

A mixture of 5-bromo-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (413 mg, 1.817 mmol), 1,1-dimethylethyl 4-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole-1-carboxylate (660 mg, 1.817 mmol), Pd2(dba)3 (83 mg, 0.091 mmol) and Potassium Phosphate (K3PO4) (771 mg, 3.63 mmol) and (t-Bu)3PHBF4 (52.7 mg, 0.182 mmol) in 1,4-Dioxane (7.5 mL) and Water (2.5 mL) was stirred at 100° C. overnight on a stirrer hot-plate. The reaction mixture was allowed to cool to room temperature, at which point a yellow crystalline precipitate was observed. The organic layer removed, the aqueous was diluted with water (10 mL) and extracted with one portion of ethyl acetate (1×30 mL) and two portions of DCM-MeOH (9:1, x x 30 mL) to solubilize the solids. The combined organics were dried over sodium sulfate, filtered and concentrated. The residue was adsorbed onto silica and purified by flash chromatography (0-100% EtOAc in hexanes→0-10% MeOH in DCM, 40-g silica gel column) to afford 1,1-dimethylethyl 5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoro-2,3-dihydro-1H-indole-1-carboxylate (441 mg, 63.3% yield) as an off-white solid. LC-MS (ES) m/z=384 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.53 (s, 9H), 3.15 (t, J=8.46 Hz, 2H), 3.75 (s, 3H), 4.03 (t, J=8.59 Hz, 2H), 5.88-6.12 (m, 2H), 7.12-7.22 (m, 1H), 7.25 (s, 1H), 7.44-7.72 (m, 1H), 8.15 (s, 1H).

1. temperatureto cool to room temperature, at which point a yellow crystalline precipitate
2. customThe organic layer removed
3. additionthe aqueous was diluted with water (10 mL)
4. extractionextracted with one portion of ethyl acetate (1×30 mL) and two portions of DCM-MeOH (9:1, x x 30 mL)
5. dry with materialThe combined organics were dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. custompurified by flash chromatography (0-100% EtOAc in hexanes→0-10% MeOH in DCM, 40-g silica gel column)