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

HRID 539057Notes

Reaction equation

HRID 539057 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]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH2:14][O:13][C:12]3=[O:22])=[N:7][C:6]=12.[F:23][C:24]1[CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:27]=[CH:26][C:25]=1[C:39]1[N:43]=[CH:42][N:41]([CH2:44][O:45][CH2:46][CH2:47][Si:48]([CH3:51])([CH3:50])[CH3:49])[N:40]=1.C(=O)([O-])[O-].[Na+].[Na+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>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].CCOC(C)=O>[F:23][C:24]1[CH:29]=[C:28]([C:2]2[CH:3]=[N:4][N:5]3[CH:10]=[CH:9][C:8]([N:11]4[C@@H:15]([C:16]5[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=5)[CH2:14][O:13][C:12]4=[O:22])=[N:7][C:6]=23)[CH:27]=[CH:26][C:25]=1[C:39]1[N:43]=[CH:42][N:41]([CH2:44][O:45][CH2:46][CH2:47][Si:48]([CH3:51])([CH3:50])[CH3:49])[N:40]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67034012HCID 67034012, compoundHCID 67034277(S)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-4-phenyloxazolidin-2-one

Product 1

HCID 67034121(S)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-phenyloxazolidin-2-oneYield 94%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (S)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-4-phenyloxazolidin-2-one (0.20 g, 0.56 mmol), 3-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazole (0.35 g, 0.84 mmol) and sodium carbonate (2.0 M, 1.4 ml, 2.8 mmol) in dioxanes (30 mL) was degassed with nitrogen for 30 minutes. Pd2 dba3 (70 mg) and XPHOS (70 mg) were added and the reaction was heated to 80° C. for 4 hours. The reaction was poured into EtOAc and the layers separated. The organic layer was washed with water, brine, dried over MgSO4 and concentrated in vacuo. The crude material was purified by normal phase chromatography, using 25% EtOAc/DCM as the eluent to give (S)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-phenyloxazolidin-2-one as a solid (0.30 g, 0.52 mmol, 94% yield).

Workup

  1. customthe layers separated
  2. washThe organic layer was washed with water, brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by normal phase chromatography

Sources & evidence

ORD record
ord-76887235ce01476ebe9163d6f3b106e7
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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