Tetrahydrofuran → HCID 178485943, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of Example 275a (150 mg, 0.311 mmol), isocyanatomethane (21.26 mg, 0.373 mmol) and Hunig's base (0.108 mL, 0.621 mmol) in THF (4 mL) was stirred at room temperature for 16 hours. The resulting mixture was concentrated in vacuo. To the residue was added dioxane (5 mL) and NaOH (20%, 0.6 mL) and heated at 80° 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 (10 mg, 0.025 mmol, 8% yield). MS (ESI) m/e 400 (M+H)+; 1H NMR (400 MHz, DMSO-d6) ppm 1.21-1.49 (m, 4H) 1.89-1.96 (m, 2H) 1.99-2.08 (m, J=10.68 Hz, 2H) 2.57 (d, J=4.58 Hz, 3H) 3.34-3.45 (m, 1H) 3.74-3.84 (m, 1H) 5.41-5.47 (m, J=4.27 Hz, 1H) 5.52 (d, J=7.63 Hz, 1H) 7.02 (d, J=7.63 Hz, 1H) 7.07 (s, 1H) 7.17 (dd, J=7.93, 4.58 Hz, 1H) 8.29 (dd, J=4.58, 1.53 Hz, 1H) 8.34 (s, 1H) 8.79 (d, J=7.32 Hz, 1H).

Provenance & Evidence