反应详情

NaH (60% dispersion in mineral oil, 0.039 g, 0.98 mmol) was added to a solution of 5-(4H-1,2,4-triazol-4-ylamino)biphenyl-2-carbonitrile (CAB06022) (0.23 g, 0.88 mmol) in DMF (5 mL). After stirring for 30 minutes a solution of PMW04158 (0.38 g, 0.97 mmol) in DMF (3 mL) was added and stirring was continued for 48 h. TBAF (1M in THF, 1.35 mL) was added and after 30 minutes the reaction mixture was poured onto H2O (15 mL) and acidified with 3M aq. AcOH. The product was extracted with EtOAc (0.3×25 ml) and the combined organics were washed with H2O (4×50 ml) and brine (50 mL) then dried (MgSO4) and the solvent was removed in vacuo. The crude product was purified using the Combiflash system (CHCl3/Acetone) to give the title compound (0.18 g, 50%) as a white solid; 1H NMR (270 MHz, DMSO-d6) 2.81 (2H, t, J=7.5, CH2), 4.01 (2H, t, J=7.5, CH2), 6.41-6.51 m, ArH), 6.61 (1H, d, J=2.2, ArH), 7.45-7.56 (5H, m, ArH), 7.83 (1H, d, J=8.8, ArH), 8.93 (2H, s, NCHN), 10.40 (1H, s, OH); HRMS (ESS) calcd. for C13H18F2N5O1 (M++1) 418.1474. found 418.1466; LC/MS (ES+) tr=1.39 min, m/z 418.0 (M++1, 100%).

1. additionwas added
2. additionwas poured onto H2O (15 mL)
3. extractionThe product was extracted with EtOAc (0.3×25 ml)
4. washthe combined organics were washed with H2O (4×50 ml) and brine (50 mL)
5. dry with materialthen dried (MgSO4)
6. customthe solvent was removed in vacuo
7. customThe crude product was purified