Tetrahydrofuran → HCID 10409547, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of N-cyano-2-phenyl-acetamide (35 mg, 0.2 mmol) (see Example 1) in DMF (1.25 mL), potassium tert-butoxide (0.22 mL of a 1.0 M THF solution, 0.22 mmol) was added, dropwise at 0° C., under nitrogen. Upon complete addition, the cooling bath was removed and the reaction was stirred for 0.5 h. After this time, the resulting anion was added dropwise to a stirred solution of the above 2-bromo-N-(2,2-dimethyl-propyl)-N-(2-morpholin-4-yl-2-oxo-ethyl)-acetamide (88 mg, 0.24 mmol) in DMF (1.25 mL) at room temperature, under nitrogen. Upon complete addition, the reaction was stirred at room temperature for 0.5 h, then warmed to 45° C. for 15 h. The reaction was cooled to room temperature and concentrated to dryness. The remaining 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/minute, UV detection was at 220 nm). Retention time of the product was 14.7 min. Product-containing fractions were concentrated to give 14 mg (15%) of the title compound.

Provenance & Evidence