Hydrochloric Acid → 4-[7-(4-Cyano-3-methoxy-phenyl)-8-oxo-6-thioxo-5,7-diaza-spiro[3.4]oct-5-yl]-2-fluoro-N-methyl-benzamide

Participants

Reaction Conditions

Reaction Steps

A mixture of 3e (380 mg, 2 mmol, prepared by a method similar to the synthesis of 3d) and 6a (494 mg, 2 mmol) in DMF (10 mL) was heated under microwave irradiation at 110° C. for 12 h. After cooled to room temperature, to the reaction mixture was added ethanol (10 mL) and aqueous HCl solution (2N, 5 mL). The resulting mixture was heated at reflux for 1 h. The solution was poured into ice-cold water and the mixture was extracted with ethyl acetate (3×30 mL). The organic layers were combined, dried over MgSO4, and concentrated in vacuo. The residue was purified with silica gel column chromatography using Petroleum ether:Ethyl acetate (1:1), affording the title compound (Example 2, 180 mg, 20% yield). 1H NMR (CDCl3, 500 MHz): δ 8.39 (1H, t, J=9.0 Hz), 7.62 (1H, d, J=8.0 Hz), 7.26 (1H, m.br), 7.18 (1H, d, J=10.0 Hz), 7.10 (2H, m), 6.71 (1H, br s), 3.97 (3H, s), 3.00 (3H, d, J=5 Hz), 2.70 (2H, m), 2.52 (2H, m), 2.26 (1H, m), 1.69 (1H, m, br). MS (ES-API positive): 439 (M+H)+.

Provenance & Evidence