Hydrochloric Acid → 4-[7-(2-Chloro-4-cyano-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 6a (388 mg, 2 mmol) and 3d (494 mg, 2 mmol) in DMF (10 mL) was heated under microwave irradiation at 110° C. for 12 h. To this mixture is added ethanol (10 mL) and HCl (2N, 5 mL). The resulting mixture was refluxed for 1 h. After being cooled to room temperature, the reaction mixture was poured into cold water and extracted with ethyl acetate (3×100 mL). Combined organic layers were dried over MgSO4, concentrated. The residue was purified by silica gel column chromatography using petroleum ether:ethyl acetate (1:1), to give the title compound (Example 1, 200 mg, 23% yield). 1H NMR (CDCl3, 500 MHz): δ 8.39 (1H, t, J=9.0 Hz), 7.89 (1H, s), 7.72 (1H, dd, m), 7.54 (1H, d, J=8.0 Hz), 7.26 (1H, m.br), 7.20 (1H, d, J=11 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), 1.69 (1H, m, br). MS (ES-API positive): 443 (M+H)+.

Provenance & Evidence