Sodium Carbonate → (S)-4-isopropyl-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)oxazolidin-2-one

HRID 538979Notes

Reaction equation

HRID 538979 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:33]=[CH:32][C:31]([C:34]3[N:35]([CH2:39][O:40][CH2:41][CH2:42][Si:43]([CH3:46])([CH3:45])[CH3:44])[CH:36]=[CH:37][N:38]=3)=[CH:30][CH:29]=2)O1.O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>O.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:29]=[CH:30][C:31]([C:34]4[N:35]([CH2:39][O:40][CH2:41][CH2:42][Si:43]([CH3:46])([CH3:45])[CH3:44])[CH:36]=[CH:37][N:38]=4)=[CH:32][CH:33]=3)=[C:6]2[N:7]=1)([CH3:18])[CH3:17]

Participants

9

Reactant 5

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67034128(S)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-oneHCID 670343202-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole

Product 1

HCID 67034475(S)-4-isopropyl-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)oxazolidin-2-one

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a sealed tube was added (S)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one (2.5 g, 7.69 mmol), 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole (4.62 g, 11.5 mmol), dioxane (76.9 mL, 7.69 mmol) and 2.0M Na2CO3 (11.5 mL, 23.1 mmol). The mixture was degassed by bubbling N2 through the solution. Pd2 dba3 (0.704 g, 0.769 mmol) and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.367 g, 0.769 mmol) were added and the vessel was sealed under a N2 atmosphere. The mixture was heated at 90° C. for 72 hours. The reaction mixture was diluted with H2O (150 mL) and EtOAc (150 mL), separated, and the aqueous layer was further extracted with EtOAc. The combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated. Purification of the crude material by normal phase chromatography, eluting with 0-4% (9:1 MeOH:NH4OH)/dichloromethane, provided (S)-4-isopropyl-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)oxazolidin-2-one as a bright yellow-orange foamy solid, 2.09 g (52%). LCMS (APCI+) m/z 519 [M+H]+.

Workup

  1. customThe mixture was degassed
  2. customby bubbling N2 through the solution
  3. customthe vessel was sealed under a N2 atmosphere
  4. customseparated
  5. extractionthe aqueous layer was further extracted with EtOAc
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification of the crude material by normal phase chromatography
  11. washeluting with 0-4% (9:1 MeOH:NH4OH)/dichloromethane

Sources & evidence

ORD record
ord-c510a635badb4da48a83d64d2f5f2c8f
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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