反应详情

Cs2CO3 (11.58 g, 35.5 mmol) was added to a solution of 1-[3-(4-bromo-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone (7.59 g, 23.7 mmol) and epichlorohydrin (20 mL, 234 mmol) in DMF (100 mL). The mixture was stirred for 18 h then diluted with EtOAc (800 mL) and washed with saturated aqueous NaHCO3 (2×100 mL), H2O (2×100 mL), and brine (100 mL). The NaHCO3 layer was extracted with EtOAc (2×150 mL). The combined washes were extracted with EtOAc (2×100 mL). The combined extracts were dried over Na2SO4 and concentrated. Column chromatography (silica, 10-20% acetone/CH2Cl2) afforded 4.98 g (56%) of the title compound. HPLC, tR=4.90 min. (Reverse phase conditions: HP 1100 LCMS, Phenomenex luna 2.1×150 mm column, 60% MeOH/H2O (0.5% AcOH) to 90% MeOH/H2O (0.5% AcOH), held at initial conditions for 2 min then ramped to final conditions over 5 min.) MS (electrospray): m/z calculated for C17H1979BrN3O2, [M+H]+, 376.07. found 376.0. 1H NMR (CDCl3, 400 MHz, a mixture of amide rotamers): 7.47 (d with fine splittings, J=8.5, Hz, 2H), 7.44 (m, 4H), 7.38 (d with fine splittings, J=8.5, Hz, 2H), 4.71 and 4.64 (A and B of AB quartet, Jab=15.7 Hz, 2H), 4.51 (s, 2H), 4.39 (dd, J=15.1, 2.5 Hz, 1H), 4.34 (dd, J=15.0, 2.9 Hz, 1H), 4.02 (dd, J=5.2, 3.9 Hz, 1H), 3.98 (dd, J=5.3, 3.7 Hz, 1H), 3.83 (m, 2H), 3.64 (m, 2H), 3.25 (br m, 2H), 2.80-2.60 (m, 6H), 2.46 (dd, J=4.6, 2.6 Hz, 1H), 2.38 (dd, J=4.6, 2.6 Hz, 1H), 2.10 (s, 3H), 2.06 (s, 3H).

1. washwashed with saturated aqueous NaHCO3 (2×100 mL), H2O (2×100 mL), and brine (100 mL)
2. extractionThe NaHCO3 layer was extracted with EtOAc (2×150 mL)
3. extractionThe combined washes were extracted with EtOAc (2×100 mL)
4. dry with materialThe combined extracts were dried over Na2SO4
5. concentrationconcentrated