反应详情

温度

100 °C

To a round bottomed flask was added 1-(trans-3-aminocyclobutyl)-3-cyclopropyl-1H-imidazo[4,5-b]pyrazin-2(3H)-one hydrochloride (Intermediate 79, 0.1128 g, 0.400 mmol), 2-bromo-5-chloropyridine (0.092 g, 0.480 mmol, Matrix Scientific), copper (2.035 mg, 0.032 mmol, Fisher Scientific), and cesium acetate (0.476 g, 2.482 mmol, Sigma-Aldrich Chemical Company, Inc.) in DMSO (0.500 ml) to stir at 100° C. for 2 days. The crude product was purified by reverse-phase preparative HPLC using a Phenomenex Gemini column, micron, C18, 110 Å, 100×50 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 900 over 12 min. Fractions containing product peak were concentrated in vacuo. The product was taken up in DCM and loaded onto a Silicyle Si-carbonate cartridge to remove any salts to give the title compound (5.4 mg, 0.015 mmol, 3.8% yield). LCMS showed product peak at 1.448 min (m+1=356.9). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.95-1.03 (m, 2 H) 1.02-1.09 (m, 2 H) 2.26-2.36 (m, 2 H) 2.96 (tt, J=7.09, 3.77 Hz, 1 H) 3.15-3.28 (m, 2 H) 4.42 (d, J=5.67 Hz, 1 H) 5.13 (quin, J=8.26 Hz, 1 H) 6.50 (d, J=9.00 Hz, 1 H) 7.30 (d, J=6.06 Hz, 1 H) 7.47 (dd, J=9.00, 2.54 Hz, 1 H) 7.92-8.03 (m, 3 H)

1. customThe crude product was purified by reverse-phase preparative HPLC
2. customover 12 min
3. additionFractions containing product peak
4. concentrationwere concentrated in vacuo
5. customto remove any salts