反应详情

A mixture of the product of Example 43A (342 mg, 1.29 mmol), hexahydro-2,5-methano-pentalene-3a-carboxylic acid (256 mg, 1.54 mmol), HATU (737 mg, 1.24 mmol) and triethylamine (1.08 mL, 7.74 mmol) in 20 mL of DMF was stirred at room temperature for overnight. The mixture was diluted with ethyl acetate and washed with water. The organic extract was dried (MgSO4), filtered and concentrated. The residue was purified by preparative HPLC on a Waters Symmetry C8 column (40 mm×100 mm, 7 μm particle size) using a gradient of 10% to 100% acetonitrile:ammonium acetate (10 mM) over 15 minutes at a flow rate of 70 mL/minutes to afford the title compound: 1H NMR (500 MHz, DMSO-d6l) δ 1.51-1.61 (m, 4 H) 1.64-1.75 (m, 4 H) 2.06 (d, J=9.2 Hz, 2 H) 2.22-2.27 (m, 2 H) 2.51-253 (m, 1 H) 3.25 (s, 3 H) 3.67 (t, J=5.3 Hz, 2 H) 3.95 (s, 2 H) 4.23 (t, J=5.2 Hz, 2 H) 7.15 (t, J=8.8 Hz, 2 H) 7.23 (s, 1 H) 7.29 (dd, J=8.4, 5.6 Hz, 2 H); MS (DCI/NH3) m/z 415 (M+H)+.

1. washwashed with water
2. extractionThe organic extract
3. dry with materialwas dried (MgSO4)
4. filtrationfiltered
5. concentrationconcentrated
6. customThe residue was purified by preparative HPLC on a Waters Symmetry C8 column (40 mm×100 mm, 7 μm particle size)