反应详情

温度

80 °C

5-Bromo-N-cyclopropylpyrimidin-2-amine (1.06 g, 5 mmol), trimethylsilylacetylene (2.5 g, 25 mmol), Pd(PPh3)4 (289 mg, 0.25 mmol) and CuI (71 mg, 0.375 mmol) were placed in a two neck flask with a rubber plug. The mixture underwent 3 cycles of vacuum and filling with Ar2, a solution of DIPEA (968 mg, 0.45 mmol) and DMF (10 mL) was injected to the flask. The mixture was stirred at 80° C. for 15 hrs, and then was poured into 50 mL water, extracted with EtOAc (30 mL×3), organic layer was washed with brine, dried with Na2SO4, filtered, and the filtrate was evaporated in vacuo. The residue was purified by chromatography on silica gel (PE/EtOAc 82:18 to 64:36) to give 1.1 g N-cyclopropyl-5-(2-(trimethylsilyl)ethynyl)pyrimidin-2-amine. This compound was dissolved in 20 mL CH2Cl2, a solution of TBAF (1.3 g, 5 mmol) in 10 mL CH2Cl2 was added into the above solution. The mixture was stirred at rt for 1 h, evaporated in vacuo. The residue was purified by chromatography on silica gel (PE/EtOAc 82:18 to 64:36) to give 0.55 g product as a pale yellow solid (72.8%). 1H NMR (300 MHz, CDCl3) δ: 8.43 (2H, s), 5.77 (1H, brs), 3.18 (1H, s), 2.76-2.81 (1H, m), 0.82-0.87 (2H, m), 0.54-0.59 (2H, m). LCMS: m/z [M+H]+ 160.0863.

1. extractionextracted with EtOAc (30 mL×3), organic layer
2. washwas washed with brine
3. dry with materialdried with Na2SO4
4. filtrationfiltered
5. customthe filtrate was evaporated in vacuo
6. customThe residue was purified by chromatography on silica gel (PE/EtOAc 82:18 to 64:36)