Diisopropylethylamine → 1-{2-[(1R,3S,5R)-3-(2-Fluoro-3-trifluoromethoxy-phenylcarbamoyl)-2-aza-bicyclo[3.1.0]hex-2-yl]-2-oxo-ethyl}-5-methyl-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid amide

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Reaction Conditions

Reaction Steps

To a solution of (3-carbamoyl-5-methyl-pyrazolo[3,4-c]pyridin-1-yl)acetic acid trifluoroacetate salt (3.87 g, 11.1 mmol; prepared as described in Scheme A27) in DMF (45 mL) were successively added (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-3-carboxylic acid (2-fluoro-3-trifluoro methoxy-phenyl)-amide trifluoroacetate salt (5.00 g, 11.1 mmol), DIPEA (7.77 mL, 44.5 mmol) and HBTU (5.06 g, 13.3 mmol). The reaction mixture was stirred at 25° C. for 2 h and was then concentrated in vacuo. The residue was purified by preparative HPLC (Waters Sunfire C18-OBD, 5 μm, 30×100 mm, flow: 50 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 and volatiles were evaporated under reduced pressure. The resulting aqueous solution was adjusted to pH 8 to 9 by addition of an aqueous saturated solution of NaHCO3, and then was extracted with CH2Cl2 (×3). The combined organic extracts were dried (phase separator) and concentrated under vacuum to afford the title compound as a white solid. MS: 521 [M+H]+; tR (HPLC conditions c): 3.81 min.

Provenance & Evidence