反応 #1588516

反応方程式

tert-butyl {1-[4-(6-chloro-8-methoxy-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]cyclobutyl}carbamate

ammonia

MeOH

→

tert-butyl {1-[4-(6-carbamoyl-8-methoxy-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]cyclobutyl}carbamate

収率 57.0%

反応条件

後処理

1. 1
   workup.ADDITIONwas added 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) dichloride DCM complex (0.16 g, 0.20 mmol, 0.20 equiv)
2. 2
   その他The autoclave was flushed with CO (approximately 5 bar) three times
3. 3
   その他was then pressurized with CO (5.9 bar at 20° C.)
4. 4
   温度heated to 100° C.
5. 5
   workup.STIRRINGstirred at this temperature for 18 h
6. 6
   ろ過The resulting material was filtered
7. 7
   濃縮concentrated under reduced pressure

実験手順

To a solution of tert-butyl {1-[4-(6-chloro-8-methoxy-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]cyclobutyl}carbamate that was prepared in a manner analgous to that described for Intermediate Example Int-7.3 (0.54 g, 1.00 mmol) in a solution of ammonia in MeOH (7 N; 5.7 mL, 40 mmol, 40 equiv.) in an autoclave was added 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) dichloride DCM complex (0.16 g, 0.20 mmol, 0.20 equiv). The autoclave was flushed with CO (approximately 5 bar) three times, then was pressurized with CO (5.2 bar), stirred at room temperature 30 min., and briefly placed under reduced atmosphere (0.06 bar). The autoclave was then pressurized with CO (5.9 bar at 20° C.), heated to 100° C., and stirred at this temperature for 18 h. The resulting material was filtered and concentrated under reduced pressure to give tert-butyl {1-[4-(6-carbamoyl-8-methoxy-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]cyclobutyl}carbamate (0.29 g, 57%):

出典