反应详情

温度

105 °C

Under N2, a solution of 2-{[2-chloro-5-(trifluoromethyl)pyrimidin-4-yl]amino}-N-methylbenzamide (40.0 mg, 0.12 mmol) and diethyl [(4-aminophenyl)(hydroxy)methyl]-phosphonate (37.6 mg, 0.15 mmol) in a mixture of TFA (28 uL, 0.36 mmol) and EtOH (0.5 mL) was stirred at 105° C. for 45 min in a Biotage microwave reactor. The solvents were removed under reduced pressure and to the residue was added sat. NaHCO3 (aq) (2 mL) and DCM (5 mL). Layers were separated and the aqueous layer was extracted with DCM (3×5 mL). The combined organic phases were dried over MgSO4, concentrated, and purified by silica gel chromatography (5% 7 N NH3 in MeOH in DCM) to afford the desired product as a white-colored solid (8.4 mg, yield: 12%). 1H NMR (CD3OD, 400 MHz): δ=1.22 (dt, J=0.8, 7.6 Hz, 6 H), 1.30 (t, J=7.2 Hz, 3 H), 2.90 (s, 3 H), 3.47-3.57 (m, 2 H), 3.95-4.15 (m, 4 H), 4.72 (d, J=16.0 Hz, 1 H), 7.18 (dt, J=1.2, 7.6 Hz, 1 H), 7.35 (dd, J=2.0, 8.4 Hz, 2 H), 7.49 (dd, J=1.6, 8.8 Hz, 1 H), 7.63-7.65 (m, 3 H), 8.34 (s, 1 H), 8.45 (m, 1 H). MS (ES+): m/z 582.17 [MH+]. HPLC: tR=3.44 min (OpenLynx, polar—5 min).

1. customThe solvents were removed under reduced pressure and to the residue
2. additionwas added sat. NaHCO3 (aq) (2 mL) and DCM (5 mL)
3. customLayers were separated
4. extractionthe aqueous layer was extracted with DCM (3×5 mL)
5. dry with materialThe combined organic phases were dried over MgSO4
6. concentrationconcentrated
7. custompurified by silica gel chromatography (5% 7 N NH3 in MeOH in DCM)