Diisopropylethylamine → (2S,4R)-2-[3-chloro-2-fluoro-5-(2H-tetrazol-5-yl)-benzylcarbamoyl]-4-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester

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Reaction Steps

To a mixture of N-boc-trans-4-fluoro-L-proline (107 mg, 0.46 mmol) and HATU (260 mg, 0.69 mmol) in DMF (2 mL) was added a 1:2 mixture of 5-(1-tert-butyl-1H-tetrazol-5-yl)-3-chloro-2-fluoro-benzylamine and 3-chloro-2-fluoro-5-(2H-tetrazol-5-yl)-benzylamine (preparation described in Part C, 220 mg, 0.46 mmol) and DIPEA (319 μl, 1.8 mmol) and the resulting solution was stirred overnight at ambient temperature. The reaction mixture 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 compounds (2S,4R)-2-[3-chloro-2-fluoro-5-(2H-tetrazol-5-yl)-benzylcarbamoyl]-4-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester: MS (LC-MS): 343.0 [M−100]+; tR (HPLC conditions c): 3.27 min and (2S,4R)-2-[5-(1-tert-butyl-1H-tetrazol-5-yl)-3-chloro-2-fluoro-benzylcarbamoyl]-4-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester: MS (LC-MS): 499.0 [M]+; tR (HPLC conditions c): 4.02 min.

Provenance & Evidence