反应详情

温度

100 °C

To the DME solution of 4,4,5,5-tetramethyl-2-(3-methylbenzo[b]thiophen-2-yl)-[1,3,2]dioxaborolane (2.3 mL, 0.50 mmol, 2 eq.) from the previous step were added 4-[4-(6-amino-5-bromopyridin-3-yl)-pyrazol-1-yl]piperidine-1-carboxylic acid tert-butyl ester (BB3) (120 mg, 0.29 mmol, 1 eq.), potassium carbonate (104 mg, 0.75 mmol, 3 eq.), water (0.5 mL), and 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium DCM (10 mg, 0.01 mmol, 0.05 eq.). The mixture was evacuated and filled with nitrogen (3×) and heated in a microwave reactor to 100° C. for 30 min. The crude was passed through Thiol-SPE to remove Pd. The clear solution was purified with the MDPS. 1H NMR (400 MHz, CD3OD): δ=1.47 (s, 9H), 1.87-2.00 (m, 2H), 2.09 (d, J=10.4 Hz, 2H). 2.31 (s, 3H), 2.95 (br. s., 2H), 3.35 (s, 2H), 4.22 (d, J=13.4 Hz, 2H), 4.37 (tt, J=11.6, 4.1 Hz, 1H), 7.36-7.47 (m, 2H), 7.75-7.82 (m, 3H), 7.87 (d, J=7.6 Hz, 1H), 8.05 (s, 1H), 8.25 (d, J=1.8 Hz, 1H). MS (ES+): m/z=490.37 (100) [MH+]. HPLC: tR=0.93 min (UPLC-ACQUITY, Analytical).

1. customThe mixture was evacuated
2. additionfilled with nitrogen (3×)
3. customto remove Pd
4. customThe clear solution was purified with the MDPS