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

HRID 539061Notes

Reaction equation

HRID 539061 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]([CH2:16][CH2:17][CH3:18])[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:38]=[CH:37][N:36]([CH2:39][O:40][CH2:41][CH2:42][Si:43]([CH3:46])([CH3:45])[CH3:44])[N:35]=3)=[CH:30][CH:29]=2)O1.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>O1CCOCC1.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]>[CH2:16]([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:38]=[CH:37][N:36]([CH2:39][O:40][CH2:41][CH2:42][Si:43]([CH3:46])([CH3:45])[CH3:44])[N:35]=4)=[CH:32][CH:33]=3)=[C:6]2[N:7]=1)[CH2:17][CH3:18]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 595255703-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazoleHCID 67034378(S)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-4-propyloxazolidin-2-one

Product 1

HCID 67035120(S)-4-propyl-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)oxazolidin-2-oneYield 72%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
90 °C

Procedure

To a sealed tube were added (S)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-4-propyloxazolidin-2-one (0.100 g, 0.308 mmol), 3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazole (0.160 g, 0.400 mmol), in dioxane (1.6 mL) and 2.0 M Na2CO3 (0.461 ml, 0.923 mmol). The mixture was degassed by bubbling N2 through the solution. Pd2 dba3 (0.0141 g, 0.0154 mmol) and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.0147 g, 0.0308 mmol) were added and the vessel was sealed under a N2 atmosphere. The mixture was heated at 90° C. for 18 hours. The reaction mixture was cooled to ambient temperature, filtered through GF/F paper, diluted with H2O and separated, and the aqueous layer was further extracted with EtOAc. The combined organic extracts were washed with brine, dried and concentrated. Purification of the crude material by normal phase chromatography, eluting with 1-25% EtOAc/dichloromethane, provided (S)-4-propyl-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)oxazolidin-2-one as a bright yellow-orange foamy solid (0.115 g, 72%). LCMS (APCI+) m/z 520 [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. temperatureThe reaction mixture was cooled to ambient temperature
  5. filtrationfiltered through GF/F paper
  6. additiondiluted with H2O
  7. customseparated
  8. extractionthe aqueous layer was further extracted with EtOAc
  9. washThe combined organic extracts were washed with brine
  10. customdried
  11. concentrationconcentrated
  12. customPurification of the crude material by normal phase chromatography
  13. washeluting with 1-25% EtOAc/dichloromethane

Sources & evidence

ORD record
ord-7def8551e23d46f096e8a7e9329c3ca1
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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