反应详情

温度

90 °C

A solution of 8-tert-butoxycarbonyl-1,3,8-triaza-spiro[4.5]decane-2,4-dione (75 mg) in DMF (1 mL) was added to a solution of 2-(4-(4-cyano-1-methyl-1H-imidazo[4,5-c]pyridin-6-yl)-2-(trifluoromethyl)phenoxy)ethyl methanesulfonate (90 mg) in DMF (1 mL), K2CO3 (83 mg) and TBAI (48 mg). The mixture was stirred overnight at 90° C. The solvent was removed under reduced pressure. The residue was partitioned between ethyl acetate (50 ml) and a saturated solution of Na2CO3 (20 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure to afford 3-(2-(4-(4-cyano-1-methyl-1H-imidazo[4,5-c]pyridin-6-yl)-2-trifluoromethyl-phenoxy)-ethyl)-2,4-dioxo-1,3,8-triaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester (70 mg). The crude product was dissolved in MeOH (2 mL) and a 5N solution of HCl in iPrOH (0.05 ml) was added. The mixture was stirred 2 hours at 60° C., then the solvent was evaporated under reduced pressure. The crude product was directly purified by preparative HPLC (HPLC:column XBridge MS C18 30×100 mm, 5 μm, Eluent:A:NH4HCO3, 10 mmol, pH=9.5/B:Acetonitrile, Focused gradient/8 minutes/50 mL/min) to afford 6-{4-[2-(2,4-dioxo-1,3,8-triaza-spiro[4.5]dec-3-yl)-ethoxy]-3-(trifluoromethyl)-phenyl}-1-methyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile (23 mg).

1. customThe solvent was removed under reduced pressure
2. customThe residue was partitioned between ethyl acetate (50 ml)
3. dry with materialThe organic layer was dried over sodium sulphate
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure