反应详情

A 4 ml vial was loaded with methyl ((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-hydroxypiperidin-4-yl)carbamate (Example 328) (31 mg, 0.061 mmol) and Dess-Martin Periodinane (52 mg, 0.123 mmol). DMSO (1 ml) was added (complete dissolution of starting material). The reaction mixture was stirred at room temperature for 1.5 hours. The reaction was quenched by addition of 2-Propanol (0.10 ml, 1.298 mmol). The reaction mixture was poured into a dilute solution of NaHCO3 and NH4Cl in water. The product precipitated as an off-white solid, which was collected by filtration, washed with water and dried in an air-stream. An analytically pure sample was obtained via purification by prep HPLC with the following conditions: Column: XBridge C18, 19×mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile: water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile: water with 10-mM ammonium acetate; Gradient: 20-80% B over 20 minutes, then a 0-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation. The material was further purified via preparative LC/MS with the following conditions: Column: XBridge C18, 19×mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile: water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile: water with 10-mM ammonium acetate; Gradient: 25-65% B over 20 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to give (R)-methyl (1-(2-chloro-5-cyano-3-((7-cyano-4-(ethylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-oxopiperidin-4-yl)carbamate (4.2 mg). The product exists as a mixture of ketone and hydrate (and if analyzed in MeOH solution also mono- and dimethyl-acetal)

1. dissolution(complete dissolution of starting material)
2. customThe product precipitated as an off-white solid, which
3. filtrationwas collected by filtration
4. washwashed with water
5. customdried in an air-stream
6. customAn analytically pure sample was obtained via purification by prep HPLC with the following conditions
7. waitGradient: 20-80% B over 20 minutes
8. customa 0-minute hold