Cyclobutanone → HCID 50940101, compound

Participants

Reaction Steps

To a solution of Example 270a (350 mg, crude, ˜0.414 mmol) in MeOH (5 mL) was added cyclobutanone (29.0 mg, 0.414 mmol) and the solution was stirred at room temperature for 10 minutes before NaCNBH3 (52.0 mg, 0.828 mmol) and zinc chloride (0.6 mg, 0.004 mmol) were added. The reaction mixture was stirred at room temperature overnight and concentrated in vacuo. To the residue was added dioxone (5 mL) and NaOH (20%, 1 mL) and stirred at 90° C. for 1 hour. The reaction mixture was concentrated and purified by reverse-phase HPLC performed on a Phenomenex Luna C8 AXIA column (30×75 mm, 100 Å) using a gradient of 10% to 95% acetonitrile: 10 mM ammonium acetate in water over 12 minutes at a flow rate of 50 mL/minutes to provide the title compound (26 mg, 0.066 mmol, 16% yield). MS (ESI) m/e 397 (M+H)+; 1H NMR (400 MHz, DMSO-d6) ppm 0.95-2.21 (m, 16H) 2.55-2.65 (m, 1H) 3.26-3.36 (m, 1H) 3.79-3.92 (m, 1H) 7.07 (s, 1H) 7.11 (d, J=7.63 Hz, 1H) 7.17 (dd, J=7.93, 4.58 Hz, 1H) 8.29 (dd, J=4.73, 1.68 Hz, 1H) 8.34 (s, 1H) 8.77 (d, J=7.63 Hz, 1H).

Provenance & Evidence