Reaktion #168428
ord-0f7cca8580434949b9e293f95f895afa
Reaktionsgleichung
Edukte
Reagenzien
Lösungsmittel
Reaktionsbedingungen
Aufarbeitung
- 1Temperaturto warm slowly to 0° C. over 90 minutes
- 2Sonstigequenched with saturated NH4Cl (10 mL)
- 3workup.ADDITIONEtOAc (75 ml) was added
- 4Waschenthe organic layer was washed with water and brine (25 mL each)
- 5TrocknenThe organic layer was dried over Na2SO4
- 6Filtrationfiltered
- 7Einengenconcentrated
- 8SonstigePurification of the residue on a silica gel column
- 9Wascheneluting with 0 to 50% EtOAc/DCM
Vorschrift
To a −78° C. solution of 4-(5-chloropyridin-3-yl)-2-[(4aR,7aR)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Example 3.2, Step 3; 300 mg, 0.611 mmol) in THF (8 mL) was added 2,2,6,6-tetramethylpiperidinylmagnesium chloride lithium chloride complex (Aldrich, 1M in THF/toluene) (1.22 mL, 1.22 mmol). The resulting yellow solution was stirred at −78° C. for 45 minutes, and then 1,3-dibromo-5,5-dimethylhydantoin (437 mg, 1.527 mmol) was added as a solid in one portion. The reaction was allowed to warm slowly to 0° C. over 90 minutes and then quenched with saturated NH4Cl (10 mL). EtOAc (75 ml) was added, and the organic layer was washed with water and brine (25 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue on a silica gel column eluting with 0 to 50% EtOAc/DCM afforded 7-bromo-4-(5-chloropyridin-3-yl)-2-[(4aR,7aR)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd for C27H30BrClN6O [M+H]+=571. found=571.