反应详情

Ethanolamine (29 mg, 0.47 mmol) and DIPEA (122 uL, 90 mg, 0.70 mmol) were added to a solution of 1-{[2-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]sulfonyl}-1H-pyrazole-4-carboxylic acid (4.0 mL, 0.23 mmol) (see following step B for preparation). Stirring for 20 min, HATU (117 mg, 0.47 mmol) was added. The reaction mixture was stirred overnight at room temperature, diluted with H2O (100 mL), and extracted with EtOAc (3×50 mL). The combined organic phases were washed with NaCl saturated aqueous solution (2×10 mL) and dried over Na2SO4. The crude product was purified by MPLC using EtOAc/MeOH (20:1-9:1) on silica gel to give 80 mg (71%) of a white solid as the title compound. 1H NMR (400 MHz, METHANOL-D4) δ 1.41-1.57 (m, 4 H), 1.60 (s, 9 H), 2.25-2.36 (m, 1 H), 3.24-3.34 (m, 2 H), 3.40 (t, J=5.66 Hz, 2 H), 3.63 (t, J=5.76 Hz, 2 H), 3.86-3.94 (m, 2 H), 4.43 (d, J=7.42 Hz, 2 H), 7.95 (d, J=8.8 Hz, 1 H), 8.02 (dd, J=8.8, 1.8 Hz, 1H), 8.06 (d, J=0.78 Hz, 1 H), 8.35 (d, J=1.17 Hz, 1 H), 8.78 (s, 1 H); MS (ESI) (M+H)+=490.3.

1. stirringThe reaction mixture was stirred overnight at room temperature
2. extractionextracted with EtOAc (3×50 mL)
3. washThe combined organic phases were washed with NaCl saturated aqueous solution (2×10 mL)
4. dry with materialdried over Na2SO4
5. customThe crude product was purified by MPLC