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

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Reaction Conditions

Reaction Steps

A mixture of 3k (370 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. To this 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 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 9, 200 mg, 23% yield). 1H NMR (CDCl3, 500 MHz): δ 8.39 (1H, t, J=9.0 Hz), 8.00 (1H, d, J=2.0 Hz), 7.90 (2H, m.br), 7.26 (1H, m.br), 7.18 (1H, dd, J=11.5, 2.0 Hz), 6.71 (1H, br s), 3.00 (3H, d, J=5 Hz), 2.70 (2H, m), 2.52 (2H, m), 2.26 (1H, m), 1.62 (1H, m, br). MS (ES-API positive): 434 (M+H)+.

Provenance & Evidence