反应详情

温度

23 °C

trans-N-cyclopropyl-4-(pyridine-3-yl)cyclohexylamine (7.3 g, 34.0 mmol, prepared as described above), (S)-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)benzoic acid (8.7 g, 37.3 mmol), EDCI (9.1 g, 47.6 mmol), HOAt (6.5 g, 47.6 mmol), and NaHCO3 (5.7 g, 68.0 mmol) were combined and dissolved in DMF (125 mL). After being stirred for 16 h at 23° C., the reaction was quenched with 1 M NaOH (150 mL) and diluted with EtOAc (300 mL). The aqueous layer was extracted with EtOAc (100 mL) and 10% MeOH/CH2Cl2 (5×100 mL) and the combined organic layers were washed with H2O (400 mL) and brine (400 mL), dried with MgSO4, filtered, and concentrated in vacuo. The crude material was purified by flash column chromatography (gradient elution, 3%→10% MeOH/CH2Cl2) to afford the product: 1H NMR (CDCl3, 500 MHz) δ 8.49 (s, 1H), 8.46 (d, J=3.6 Hz, 1H), 7.61 (d, J=8.1 Hz, 2H), 7.58 (d, J=7.7 Hz, 1H), 7.50 (d, J=8.3 Hz, 2H), 7.24 (dd, 1H-overlapping with CDCl3), 4.23 (m, 1H), 2.80 (m, 1H), 2.62 (m, 2H), 2.05 (m, 6H), 1.80 (s, 3H), 1.65 (m, 2H), 0.60 (d, J=4.8 Hz, 2H). 0.49 (m, 2H); MS(ESI) 433.3 [M+H]+; Anal. (C24H27 F3N2O2) C, H, N.

1. customthe reaction was quenched with 1 M NaOH (150 mL)
2. additiondiluted with EtOAc (300 mL)
3. extractionThe aqueous layer was extracted with EtOAc (100 mL) and 10% MeOH/CH2Cl2 (5×100 mL)
4. washthe combined organic layers were washed with H2O (400 mL) and brine (400 mL)
5. dry with materialdried with MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe crude material was purified by flash column chromatography (gradient elution, 3%→10% MeOH/CH2Cl2)
9. customto afford the product