反应详情

温度

100 °C

A mixture of 5-bromo-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (510 mg, 2.246 mmol), 1,1-dimethylethyl 4-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole-1-carboxylate (853 mg, 2.246 mmol), Pd2(dba)3 (103 mg, 0.112 mmol) and Potassium Phosphate (K3PO4) (954 mg, 4.49 mmol) and (t-Bu)3PHBF4 (6.52 mg, 0.022 mmol) in 1,4-Dioxane (10 mL) and Water (3.3 mL) in a sealed tube was heated at 100° C. on a stirrer hot plate. At this time, LCMS analysis indicated good conversion, so the reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (3×100 mL), and the combined organics dried over sodium sulfate and concentrated. The residue was dissolved in DCM (ca. 100 mL), concentrated to minimum volume (ca. 40 mL), then purified by flash chromatography (0-100% EtOAc in hexanes, 40-g silica gel column) to afford 1,1-dimethylethyl 5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-chloro-2,3-dihydro-1H-indole-1-carboxylate (0.716 g) as a yellow solid. LC-MS (ES) m/z=400 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.52 (s, 9H), 3.14 (t, J=8.59 Hz, 2H), 3.74 (s, 3H), 3.96-4.07 (m, 2H), 5.73-6.04 (m, 2H), 7.15-7.26 (m, 2H), 7.57-7.80 (m, 1H), 8.13 (s, 1H).

1. extractionextracted with ethyl acetate (3×100 mL)
2. dry with materialthe combined organics dried over sodium sulfate
3. concentrationconcentrated
4. dissolutionThe residue was dissolved in DCM (ca. 100 mL)
5. concentrationconcentrated to minimum volume (ca. 40 mL)
6. custompurified by flash chromatography (0-100% EtOAc in hexanes, 40-g silica gel column)