反应详情

温度

120 °C

A glass microwave reaction vessel was charged with (4R)-tert-butyl 4-(6-(5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)-6-azaspiro[2.5]octane-6-carboxylate (115 mg, 0.20 mmol), 3-(cyclopropylcarbamoyl)phenylboronic acid (81 mg, 0.39 mmol), PdCl2(PPh3)2 (11 mg, 0.016 mmol) and Na2CO3 (104 mg, 0.98 mmol) in dioxane (0.8 mL) and water (0.2 mL). The reaction was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 120° C. for 20 min. The layers were separated and the organic phase was dried over anhydrous Na2SO4, filtered and concentrated. The crude was purified by silica gel chromatography, eluting with a gradient of 0-75% EtOAc in hexanes, to provide (4R)-tert-butyl 4-(6-(5-(3-(cyclopropylcarbamoyl)phenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)-6-azaspiro[2.5]octane-6-carboxylate (107 mg, 0.16 mmol, 82% yield) as a clear, colorless oil. MS (ESI, pos. ion) m/z: 665.3 (M+1).

1. customA glass microwave reaction vessel
2. customThe layers were separated
3. dry with materialthe organic phase was dried over anhydrous Na2SO4
4. filtrationfiltered
5. concentrationconcentrated
6. customThe crude was purified by silica gel chromatography
7. washeluting with a gradient of 0-75% EtOAc in hexanes