反应详情

温度

-15 °C

To a solution of 2-((2-chloro-5-cyano-3-(piperidin-4-yl)phenyl)amino)-4-(cyclopropyl (4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (375D) (50 mg, 0.090 mmol) in dry THF (0.3 mL) was added 1,8-Diazabicyclo[5.4.0]undec-7-ene (diluted with THF, 10V %) (0.013 mL, 9.02 μmol) at RT. The mixture was cooled in an ice/NaCl bath (−15° C.). To this was added 2-(oxetan-3-ylidene)acetaldehyde (36 mg, 0.367 mmol), and left stirring at −15° C. to 0° C. for 2.5 h, then the mixture was put in the freezer for 7 days. To the reaction mixture was added MeOH (1 mL), then sodium borohydride (10.30 mg, 0.271 mmol) at RT and stirred for 2 hrs. Diluted with EtOAc, washed with NaHCO3, water, brine, and dried over Na2SO4. Removal of the solvent. The crude material was purified by radial chromatography, eluting with DCM containing 0 to 1% MeOH to give 2-((2-chloro-5-cyano-3-(1-(3-(2-hydroxyethyl)oxetan-3-yl)piperidin-4-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (29 mg).

1. waitleft
2. waitthe mixture was put in the freezer for 7 days
3. washwashed with NaHCO3, water, brine
4. dry with materialdried over Na2SO4
5. customRemoval of the solvent
6. customThe crude material was purified by radial chromatography
7. washeluting with DCM containing 0 to 1% MeOH