Cesium carbonate → HCID 86702814, compound

HRID 1850050Notes

Reaction equation

HRID 1850050 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:8][CH2:9][O:10][C:11]1[CH:16]=[C:15]([F:17])[CH:14]=[C:13]([F:18])[CH:12]=1.[NH:19]1[CH:23]=[C:22](/[CH:24]=[CH:25]/[C:26]([NH:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:27])[CH:21]=[N:20]1>CN(C=O)C.CCOC(C)=O>[F:18][C:13]1[CH:12]=[C:11]([CH:16]=[C:15]([F:17])[CH:14]=1)[O:10][CH2:9][CH2:8][N:19]1[CH:23]=[C:22](/[CH:24]=[CH:25]/[C:26]([NH:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[NH:35][C:36](=[O:42])[O:37][C:38]([CH3:40])([CH3:39])[CH3:41])=[O:27])[CH:21]=[N:20]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 22247028HCID 22247028, compoundHCID 68349180HCID 68349180, compound

Product 1

HCID 86702814HCID 86702814, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

As described for the synthesis of B5 above, cesium carbonate (64 mg, 0.27 mmol) followed by a solution of 1-(2-bromoethoxy)-3,5-difluorobenzene (76 mg, 0.30 mmol) in DMF (1 mL) were added to a solution of (E)-tert-butyl (2-(3-(1H-pyrazol-4-yl)acrylamido)phenyl)carbamate (90 mg, 0.27 mmol) in anhydrous DMF (4 mL). The reaction mixture was stirred overnight at room temperature under a nitrogen atmosphere. It was then diluted with 30 mL EtOAc and washed with water (2×40 mL) and brine (10 mL). The organic layer was dried over anhydrous Na2SO4 and filtered. The concentrated filtrate was purified by silica gel column chromatography using a gradient of 0-100% of EtOAc in hexanes to provide, after evaporation under reduced pressure of pooled fractions, 123 mg of (E)-tert-butyl (2-(3-(1-(2-(3,5-difluorophenoxy)ethyl)-1H-pyrazol-4-yl)acrylamido)phenyl)carbamate as a white solid. MS: ES+(M+Na)+: 507

Workup

  1. washwashed with water (2×40 mL) and brine (10 mL)
  2. dry with materialThe organic layer was dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. customThe concentrated filtrate was purified by silica gel column chromatography
  5. customto provide
  6. customafter evaporation under reduced pressure of pooled fractions, 123 mg of (E)-tert-butyl (2-(3-(1-(2-(3,5-difluorophenoxy)ethyl)-1H-pyrazol-4-yl)acrylamido)phenyl)carbamate as a white solid

Sources & evidence

ORD record
ord-c085b90f4bdc477daea5fcb31dca4fca
Source dataset
uspto-grants-2015_02
Patent number
US08957066B2

Reaction notes

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