A mixture of 4-(4-(1-Cyanocyclobutylamino)-2-fluorophenyl)-N-methylbutanamide (79) (7 mg, 0.02 mmol) and 4-isothiocyanato-2-trifluoromethylbenzonitrile (96) (12 mg, 0.05 mmol) in DMF (1 mL) was heated to 80° C. using microwave for 16 h. To this mixture was added methanol (3 mL) and aq. 1 N HCl (3 mL). The second mixture was refluxed for 1.5 h. After being cooled to room temperature, the reaction mixture was poured into cold water (30 mL) and extracted with ethyl acetate (30 mL). The organic layer was dried over MgSO4, concentrated and the residue was purified with silica gel column chromatography (dichloromethane:acetone, 95:5) to give 4-(4-(7-(4-Cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-an-5-yl)-2-fluorophenyl)-N-methylbutanamide (78) [ND-7] (8 mg, 62%) as a pale yellowish solid: 1H NMR δ 7.98 (d, 1H, J=8.2 Hz) 7.97 (d, 1H, J=2.0 Hz) 7.84 (dd, 1H, J=8.2, 2.0 Hz), 7.43 (dd, 1H, J=8.0, 8.0 Hz), 7.06 (dd, 1H, J=8.0, 2.0 Hz), 7.02 (dd, 1H, J=9.7, 2.0 Hz), 2.83 (d, 3H, J=4.8 Hz) 2.78 (t, 2H, J=7.7 Hz) 2.63-2.71 (m, 2H), 2.51-2.62 (m, 2H), 2.27 (t, 2H, J=7.3 Hz) 2.18-2.27 (m, 1H), 2.00-2.09 (m, 2H), 1.66-1.76 (m, 1H); 13C NMR δ 179.9, 174.7, 172.8, 161.2 (d, J=247 Hz), 137.0, 135.2, 134.1 (d, J=9.6 Hz), 133.6 (q, J=33.7 Hz), 132.1, 131.9 (d, J=5.6 Hz), 130.8 (d, J=15.2 Hz), 127.1, 125.7 (d, J=3.9 Hz), 121.9 (q, J=272 Hz), 117.3 (d, J=22.3 Hz), 114.8, 110.0, 67.4, 35.8, 31.5, 28.3, 26.4, 25.6, 13.7.
