Tetrahydrofuran → N-({[2-(3,4-dihydro-1H-isoquinolin-2-yl)-2-oxo-ethyl]-isobutyl-carbamoyl}-methyl)-N-cyano-2-phenyl-acetamide

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of N-cyano-2-phenyl-acetamide (0.15 g, 0.9 mmol) (see Example 1) in DMF (5.0 mL), potassium tert-butoxide (0.9 mL of a 1.0 M THF solution, 0.9 mmol) was added dropwise at 0° C., under argon. The resulting mixture was stirred at 0° C. for 20 min, then at ambient temperature for 15 min. After this time, the resulting anion was added dropwise to a stirred solution of the 2-bromo-N-[2-(3,4-dihydro-1H-isoquinolin-2-yl)-2-oxo-ethyl]-N-isobutyl-acetamide (0.34 g, 0.9 mmol) from above in DMF (5.0 mL) at room temperature, under argon. Upon complete addition, the reaction was stirred at room temperature for 1.5 h, then warmed to 40° C. for 6 h. The reaction was cooled to room temperature and stirred for 48 h after which time it was concentrated to dryness. The resulting residue was dissolved in EtOAc and washed with 5% citric acid (aqueous). The layers were separated and the aqueous phase was extracted with EtOAc (2×). The combined organics were dried (MgSO4), filtered and concentrated to give the crude product which was purified via reverse phase HPLC (C18 column, 20-100% CH3CN/H2O over 20 min at a flow rate of 20 mL/min, UV detection was at 220 nm). Retention time of the product was 16 min. Product-containing fractions were concentrated to give 49 mg (12%) of the title compound.

Provenance & Evidence