Diisopropylethylamine → 1-{2-[(1R,3S,5R)-3-(2-Fluoro-3-trifluoromethoxy-phenylcarbamoyl)-2-aza-bicyclo[3.1.0]hex-2-yl]-2-oxo-ethyl}-1H-indazole-3-carboxylic acid amide

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Reaction Conditions

Reaction Steps

To a solution of (3-carbamoyl-indazol-1-yl)-acetic acid (73.4 mg, 0.335 mmol, prepared as described in Scheme A25) in DMF (2 mL) were successively added (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-3-carboxylic acid (2-fluoro-3-trifluoromethoxy-phenyl)-amide trifluoroacetate (140 mg, 0.335 mmol), DIPEA (0.234 mL, 1.34 mmol) and HBTU (152 mg, 0.402 mmol). The reaction mixture was stirred at 25° C. for 2 h, concentrated and the residue was purified by preparative HPLC (Waters Sunfire C18-OBD, 5 μm, 30×100 mm, flow: 40 mL/min, eluent: 5% to 100% CH3CN in H2O in 20 min, 100% CH3CN 2 min, CH3CN and H2O containing 0.1% TFA). The pure fractions were combined, CH3CN was evaporated under reduced pressure and the resulting aqueous solution was lyophilized. White powder: MS: 506 [M+H]+; tR (HPLC conditions k): 3.40 min.

Provenance & Evidence