Ammonia → HCID 70818014, compound

HRID 1501334Notes

Reaction equation

HRID 1501334 reaction equation
Cl[C:2]1[CH:3]=[C:4]([O:35][CH3:36])[C:5]2[N:6]([C:8]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([C:17]4([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19][CH2:18]4)=[CH:13][CH:12]=3)[N:10]=2)[N:7]=1.[NH3:37].[CH3:38][OH:39]>>[C:38]([C:2]1[CH:3]=[C:4]([O:35][CH3:36])[C:5]2[N:6]([C:8]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([C:17]4([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:26])([CH3:27])[CH3:25])[CH2:18][CH2:19][CH2:20]4)=[CH:15][CH:16]=3)[N:10]=2)[N:7]=1)(=[O:39])[NH2:37]

Participants

4

Reactant 3

HCID 222AmmoniaHCID 887MethanolHCID 86716508HCID 86716508, compound

Product 1

HCID 70818014HCID 70818014, compoundYield 57%

Procedure

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%):

Workup

  1. additionwas added 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) dichloride DCM complex (0.16 g, 0.20 mmol, 0.20 equiv)
  2. customThe autoclave was flushed with CO (approximately 5 bar) three times
  3. customwas then pressurized with CO (5.9 bar at 20° C.)
  4. temperatureheated to 100° C.
  5. stirringstirred at this temperature for 18 h
  6. filtrationThe resulting material was filtered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-7bfff6463afb462395455e8f714c4aec
Source dataset
uspto-grants-2015_12
Patent number
US09206185B2

Reaction notes

Loading…