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

HRID 539028Notes

Reaction equation

HRID 539028 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][NH: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.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[Na+].[Na+]>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].O1CCOCC1>[CH:16]([C@@H:15]1[N:11]([C:8]2[CH:9]=[CH:10][N:5]3[N:4]=[CH:3][C:2]([C:28]4[CH:29]=[CH:30][C:31]([C:34]5[N:38]=[CH:37][N:36]([CH2:39][O:40][CH2:41][CH2:42][Si:43]([CH3:46])([CH3:45])[CH3:44])[N:35]=5)=[CH:32][CH:33]=4)=[C:6]3[N:7]=2)[C:12](=[O:19])[NH:13][CH2:14]1)([CH3:18])[CH3:17]

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 67033394HCID 67033394, compound

Product 1

HCID 67033259(S)-5-isopropyl-1-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)imidazolidin-2-oneYield 56.2%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

To a sealed tube was added (S)-1-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-5-isopropylimidazolidin-2-one (1.50 g, 4.63 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 (2.51 g, 6.25 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (XPHOS) (0.221 g, 0.463 mmol) and Pd2 dba3 (0.212 g, 0.231 mmol), dioxane (39 mL) and sodium carbonate (2.0 M solution in water) (6.9 mL, 14 mmol) were added. The reaction mixture was heated to 80° C. overnight under nitrogen. After cooling, the reaction mixture was partitioned between EtOAc and water, and the aqueous layer was extracted once with EtOAc. The combined organic layers were washed with saturated aqueous sodium bicarbonate, brine, dried and concentrated in vacuo. The residue was purified by chromatography using EtOAc as eluent to give (S)-5-isopropyl-1-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)imidazolidin-2-one (1.35 g, 56%) as a yellow solid.

Workup

  1. additionwere added
  2. temperatureAfter cooling
  3. customthe reaction mixture was partitioned between EtOAc and water
  4. extractionthe aqueous layer was extracted once with EtOAc
  5. washThe combined organic layers were washed with saturated aqueous sodium bicarbonate, brine
  6. customdried
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by chromatography

Sources & evidence

ORD record
ord-d62b6e057adb4d19a4532e66b4964ebe
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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