Potassium Carbonate → (S)-4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoic acid

HRID 538998Notes

Reaction equation

HRID 538998 reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([N:11]3[C@@H:15]([CH:16]([CH3:18])[CH3:17])[CH2:14][O:13][C:12]3=[O:19])=[N:7][C:6]=12.CC1(C)C(C)(C)OB([C:28]2[CH:36]=[CH:35][C:31]([C:32]([OH:34])=[O:33])=[CH:30][CH:29]=2)O1.C([O-])([O-])=O.[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:16]([C@H:15]1[CH2:14][O:13][C:12](=[O:19])[N:11]1[C:8]1[CH:9]=[CH:10][N:5]2[N:4]=[CH:3][C:2]([C:28]3[CH:36]=[CH:35][C:31]([C:32]([OH:34])=[O:33])=[CH:30][CH:29]=3)=[C:6]2[N:7]=1)([CH3:18])[CH3:17]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 27346214-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67034128(S)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one

Product 1

HCID 67034480(S)-4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoic acidYield 45%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

In a vial, a mixture of (S)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one (Example 1, Step 4; 1.82 g, 5.58 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid (2.08 g, 8.37 mmol), and 2 M K2CO3 (8.37 mL, 16.7 mmol) in dioxane (20 mL) was degassed by bubbling N2 for 5 minutes. Pd2 dba3 (0.51 g, 0.56 mmol) and XPHOS (0.266 g, 0.558 mmol) were added and the reaction was capped under N2 and heated at 100° C. After 19 hours, the mixture was cooled to ambient temperature, diluted with EtOAc, washed with water and brine, dried over MgSO4, and concentrated under reduced pressure. The crude was purified by silica gel flash column chromatography (0-3% MeOH in dichloromethane) to afford 0.92 g (45%) of (S)-4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoic acid. LCMS (APCI+) m/z 367.4 [M+H]+.

Workup

  1. customwas degassed
  2. customby bubbling N2 for 5 minutes
  3. customthe reaction was capped under N2
  4. temperaturethe mixture was cooled to ambient temperature
  5. washwashed with water and brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customThe crude was purified by silica gel flash column chromatography (0-3% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-4e53a554e7b64723a1967699f8d53026
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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