反应详情

A mixture of 4-{4-[6-Amino-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (BB4) (170 mg, 0.358 mmol), 5-fluoro-1,2,3,4-tetrahydroisoquinoline (114 mg, 0.716 mmol), cupric acetate (65.7 mg, 0.358 mmol), pyridine (59 μL, 0.72 mmol), 4 Å molecular sieves (95 mg, 264 mg/mmol SM), and DCM (9 mL, 100 mmol) was stirred at rt under an atmosphere of air for 5 d. The mixture was diluted with DCM (50 ml), washed with EDTA solution (2%, 3×50 ml), water (3×50 ml) and brine (50 ml), dried over MgSO4, filtered, and concentrated in vacuo to give a dark black oil that was purified by MDPS to give the title compound as a brown oil. 1H NMR (400 MHz, CDCl3): δ=1.48 (s, 9H), 1.87-1.99 (m, 2H), 2.12-2.19 (m, 2H), 2.84-2.98 (m, 2H), 3.00 (t, J=5.6 Hz, 2H), 3.34 (t, J=6.0 Hz, 2H), 4.17 (s, 2H), 4.22-4.36 (m, 3H), 6.90 (d, J=7.2 Hz, 1H), 6.98 (t, J=8.4 Hz, 1H), 7.18-7.24 (m, 1H), 7.50 (d, J=2.0 Hz, 1H), 7.59 (s, 1H), 7.65 (s, 1H), 7.67 (d, J=1.6 Hz, 1H). MS(ES+): m/z=494.38 (100) [MH+]. HPLC: tR=2.84 min (ZQ2, polar—5 min).

1. washwashed with EDTA solution (2%, 3×50 ml), water (3×50 ml) and brine (50 ml)
2. dry with materialdried over MgSO4
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. customto give a dark black oil that
6. customwas purified by MDPS