Potassium Carbonate → HCID 178491187, compound

HRID 1620140Notes

Reaction equation

HRID 1620140 reaction equation
[C:1]([O:5][C:6](=[O:49])[NH:7][CH:8]([C:21](=[O:48])[N:22]([CH:34]([C:36]1[NH:37][CH:38]=[C:39]([C:41]2[CH:46]=[CH:45][CH:44]=[C:43](Br)[CH:42]=2)[N:40]=1)[CH3:35])[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[C:26]([O:32][CH3:33])[CH:25]=1)[CH2:9][C:10]1[C:15]([CH3:16])=[CH:14][C:13]([C:17](=[O:19])[NH2:18])=[CH:12][C:11]=1[CH3:20])([CH3:4])([CH3:3])[CH3:2].[C:50]([O-])([O-:52])=[O:51].[K+].[K+]>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].[CH-]1C(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=C1.[CH-]1C(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=C1.[Fe+2]>[C:1]([O:5][C:6]([NH:7][CH:8]([CH2:9][C:10]1[C:15]([CH3:16])=[CH:14][C:13]([C:17](=[O:19])[NH2:18])=[CH:12][C:11]=1[CH3:20])[C:21]([N:22]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[C:26]([O:32][CH3:33])[CH:25]=1)[CH:34]([C:36]1[NH:37][CH:38]=[C:39]([C:41]2[CH:42]=[C:43]([CH:44]=[CH:45][CH:46]=2)[C:50]([OH:52])=[O:51])[N:40]=1)[CH3:35])=[O:48])=[O:49])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 11430Potassium CarbonateHCID 178491183HCID 178491183, compound

Product 1

HCID 178491187HCID 178491187, compoundYield 87%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 152416121,1`-Bis(diphenylphosphino)ferroceneCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of [1-[{1-[4-(3-bromo-phenyl)-1H-imidazol-2-yl]-ethyl}-(3,4-dimethoxy-benzyl)-carbamoyl]-2-(4-carbamoyl-2,6-dimethyl-phenyl)-ethyl]-carbamic acid tert-butyl ester (290 mg; 0.40 mmol) in DMF (5 mL) was added K2CO3 (262 mg; 1.9 mmol) and the resulting mixture was degassed with Argon for 5 min. At this time, Pd(OAc)2 (8.9 mg; 0.04 mmol) and 1,1-bis(diphenylphosphino) ferrocene (46 mg; 0.083 mmol) were added. Carbon monoxide was then bubbled through the resulting mixture for 10 min at rt, the reaction was capped, and warmed to 100° C. for 6 h. After cooling to rt the mixture was partitioned between EtOAc and water, filtered through Celite, and then separated. The aqueous phase was then washed with a second portion of EtOAc. The aqueous phase was then acidified to pH 5 with 2N citric acid and the resulting aqueous solution extracted with EtOAc (4×). These latter EtOAc extracts were combined, dried over Na2SO4, filtered, and concentrated under reduced pressure to give the crude product (HPLC: 87% at 254 nm).

Workup

  1. customthe resulting mixture was degassed with Argon for 5 min
  2. customCarbon monoxide was then bubbled through the resulting mixture for 10 min at rt
  3. customthe reaction was capped
  4. temperatureAfter cooling to rt the mixture
  5. customwas partitioned between EtOAc and water
  6. filtrationfiltered through Celite
  7. customseparated
  8. washThe aqueous phase was then washed with a second portion of EtOAc
  9. extractionthe resulting aqueous solution extracted with EtOAc (4×)
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-89df05254f044da0b94fcd82d57f9d03
Source dataset
uspto-grants-2014_07
Patent number
US08772325B2

Reaction notes

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