反应详情

To a mixture of N-boc-trans-4-fluoro-L-proline (143 mg, 0.61 mmol), 3-aminomethyl-5-chloro-4-fluoro-benzoic acid methyl ester (prepared as described in Part C, 275 mg, 0.61 mmol) and HATU (0.35 g, 0.92 mmol) in DMF (4 mL) was added DIPEA (430 μl, 2.45 mmol) and the resulting solution was stirred overnight at ambient temperature. The reaction mixture was splitted in two batches and the crude product was purified without aqueous workup by RP-preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 40 ml/min) to give the title compound. MS (LC-MS): 333.0 [M−100]+; tR (HPLC conditions c): 5.05 min.

1. customThe reaction mixture was splitted in two batches
2. customthe crude product was purified without aqueous workup by RP-preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 40 ml/min)