反应详情

温度

60 °C

A mixture of 3-chloro-5-fluorophenylboronic acid (44 mg, 0.25 mmole) 127.b, powdered 4 Å molecular sieves (0.3 g), cupric acetate (83 mg, 0.45 mmole), triethylamine (69 μL (0.68 mmole), and anhydrous THF (3 mL) was stirred under a N2 atmosphere for 5 min. A solution of (2S,6R,8aR)-2-amino-6-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)hexahydroindolizin-3(5H)-one (0.1 g) 127.5 in anhydrous THF (1.5 mL) was added and the reaction mixture was stirred at room temperature for 24 hr and then heated at 60° C. for 48 hr. The mixture was diluted with EtOAc and filtered through a celite plug. The filtrate was concentrated in vacuo, absorbing onto 3 g silica gel. Purification by flash column chromatography (ISCO 24 g SiO2, 40% EtOAc/hex then gradient to 100% EtOAc) afforded 19.4 mg of (2S,6R,8aR)-2-(3-chloro-5-fluorophenylamino)-6-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)hexahydroindolizin-3(5H)-one 127.6 as a white solid. LCMS (ESI) m/z: 569.2 [M+H]+.

1. stirringthe reaction mixture was stirred at room temperature for 24 hr
2. filtrationfiltered through a celite plug
3. concentrationThe filtrate was concentrated in vacuo
4. customabsorbing onto 3 g silica gel
5. customPurification by flash column chromatography (ISCO 24 g SiO2, 40% EtOAc/hex