反应详情

A mixture of [(9H-fluoren-9-ylmethoxy)carbonyl]-L-proline (3.23 g, 9.59 mmol), 1-[5-chloro-2-(1H-1,2,4-triazol-1-yl)phenyl]methanamine (Example 4, 2.00 g, 9.59 mmol, 1.0 equiv), EDC (2.76 g, 14.38 mmol, 1.5 equiv) and HOAt (652 mg, 4.79 mmol, 0.5 equiv) in DMF (5 mL) was brought to pH 6 by dropwise addition of Hünig's Base and stirred at room temperature for 18 h. The reaction was diluted with water and extracted into EtOAc three times. The combined organic layers were dried (anhydrous Na2SO4) and concentrated. The resulting oil was suspended and rigorously stirred in water to afford the title compound as white solid upon filtration. 1H NMR (400 MHz, CD3OD): δ 8.77 (m, 1 H), 8.24–8.22 (m, 1 H), 7.81–7.75 (m, 2 H), 7.66–7.62 (m, 2 H), 7.54–7.50 (m, 1 H), 7.45–7.31 (m, 5 H), 7.25–7.19 (m, 1 H), 4.43–4.36 (m, 2 H), 4.30–4.20 (m, 3 H), 4.05–4.02 (m, 1 H), 3.55–3.40 (m, 2 H), 2.28–2.18 (m, 1 H), 1.91–1.88 (m, 3 H). LCMS (M+H): 528.0.

1. extractionextracted into EtOAc three times
2. dry with materialThe combined organic layers were dried (anhydrous Na2SO4)
3. concentrationconcentrated
4. stirringrigorously stirred in water