反应详情

温度

80 °C

A mixture of tert-butyl 4-(4-(1-cyanocyclobutylamino)phenyl)piperazine-1-carboxylate (Intermediate 86, 0.25 g, 0.70 mmol) and 5-isothiocyanato-3-(trifluoromethyl)picolinonitrile (Intermediate 10, 241 mg, 1.05 mmol) in DMA (5 mL) was heated to 80° C. for 12 h. 2M HCl/MeOH=1/1 (10 mL) was added then and the resulting mixture was heated at 100° C. for 2 h. The reaction mixture was cooled to room temperature and diluted with EtOAc. The organic layer was washed with water (3×), dried over sodium sulfate, and concentrated in vacuo. The residue was purified by Prep-HPLC (20% acetonitrile in water) to afford 75 mg of 5-(8-oxo-5-(4-(piperazin-1-yl)phenyl)-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-3-(trifluoromethyl)picolinonitrile. 1H NMR (DMSO-d6, 300 MHz) δ 9.26 (s, 1H), 9.19 (m, 1H), 8.74 (m, 1H), 7.25 (d, 2H), 7.15 (d, 2H), 3.48 (m, 4H), 3.22 (m, 4H), 2.60-2.49 (m, 2H), 2.48-2.40 (m, 2H), 1.95 (m, 1H), 1.63 (m, 1H). LCMS [M+H]+ 487.1.

1. temperaturethe resulting mixture was heated at 100° C. for 2 h
2. temperatureThe reaction mixture was cooled to room temperature
3. washThe organic layer was washed with water (3×)
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated in vacuo
6. customThe residue was purified by Prep-HPLC (20% acetonitrile in water)