Potassium Phosphate, Tribasic → 7-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5(6H)-one

HRID 1852988Notes

Reaction equation

HRID 1852988 reaction equation
Cl[C:2]1[NH:7][C:6](=[O:8])[N:5]2[CH:9]=[CH:10][N:11]=[C:4]2[CH:3]=1.CC1(C)C(C)(C)OB([C:20]2[CH:21]=[N:22][N:23]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[CH:24]=2)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>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].CCOCC>[CH3:30][Si:29]([CH3:32])([CH3:31])[CH2:28][CH2:27][O:26][CH2:25][N:23]1[CH:24]=[C:20]([C:2]2[NH:7][C:6](=[O:8])[N:5]3[CH:9]=[CH:10][N:11]=[C:4]3[CH:3]=2)[CH:21]=[N:22]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 213201027-Chloroimidazo[1,2-c]pyrimidin-5-olHCID 574776664-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole

Product 1

HCID 866853107-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5(6H)-oneYield 76%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

A flask was charged with 7-chloroimidazo[1,2-c]pyrimidin-5(6H)-one (Preparation H, 1.02 g, 6.00 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole (Preparation E, 3.24 g, 9.00 mmol), K3PO4 (2.55 g, 12.0 mmol) and XPHOS (0.572 g, 1.20 mmol). Degassed iPrOH (24 mL) and degassed H2O (2 mL) were added and the suspension was sonicated for 1-2 minutes. The mixture was purged with N2 for 10 minutes with vigorous mixing and Pd2dba3 (0.549 g, 0.600 mmol) was added. The mixture was heated at reflux under an N2 atmosphere for 24 hours and was cooled to ambient temperature. The mixture was diluted with EtOAc (20 mL) and was sonicated for 5 minutes. The suspension was filtered through a packed Celite plug (EtOAc elution) and concentrated to give an orange, oily solid. The solid was treated with Et2O and was stirred until a granular suspension formed. The solid was collected, washed with Et2O and H2O and dried in vacuum to give the title compound (1.51 g, 76% yield) as a light tan powder. MS (apci) m/z=332.3 (M+H).

Workup

  1. customDegassed iPrOH (24 mL) and degassed H2O (2 mL)
  2. additionwere added
  3. customthe suspension was sonicated for 1-2 minutes
  4. customThe mixture was purged with N2 for 10 minutes
  5. additionwith vigorous mixing
  6. temperatureThe mixture was heated
  7. temperatureat reflux under an N2 atmosphere for 24 hours
  8. customwas sonicated for 5 minutes
  9. filtrationThe suspension was filtered through a packed Celite plug (EtOAc elution)
  10. concentrationconcentrated
  11. customto give an orange, oily solid
  12. customformed
  13. customThe solid was collected
  14. washwashed with Et2O and H2O
  15. customdried in vacuum

Sources & evidence

ORD record
ord-8be0b7c51ee44b8986e3584f66ed646a
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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