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

HRID 1852954Notes

Reaction equation

HRID 1852954 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.[CH3:12][N:13]1[CH:17]=[C:16](B2OC(C)(C)C(C)(C)O2)[CH:15]=[N:14]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(O)(C)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]>[CH3:12][N:13]1[CH:17]=[C:16]([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:15]=[N:14]1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole2×HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 213201027-Chloroimidazo[1,2-c]pyrimidin-5-ol

Product 1

HCID 674519397-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5(6H)-oneYield 76%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 3776IsopropanolSolvent

Procedure

To a mixture of 7-chloroimidazo[1,2-c]pyrimidin-5(6H)-one (Preparation H, 10.0 g, 59.0 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (19.0 g, 88.5 mmol) and XPHOS (2.81 g, 5.90 mmol) in isopropyl alcohol (400 mL) was added 2M K3PO4 (88.5 mL, 177 mmol). The mixture was purged with N2 for 15 minutes with vigorous mixing and Pd2dba3 (2.70 g, 2.95 mmol) was added. The mixture was heated at reflux under a N2 atmosphere for 20 hours. The mixture was charged additional 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (6.00 g) and Pd2dba3 (1.00 g) and heated at reflux for an additional 20 hours. The mixture was cooled to ambient temperature and concentrated to an aqueous syrup. The syrup was partitioned into H2O (500 mL) and 50% EtOAc-hexanes (250 mL) and mixed. The mixture was filtered through filter paper and the orange organic layer was removed. The aqueous layer was washed with 50% EtOAc/hexanes and was cooled on an ice bath. The solution was treated with concentrated HCl to pH 6 with stirring and the resulting fine precipitate was collected, washed with H2O and Et2O and dried under vacuum to provide the title compound (9.65 g, 76% yield) as faint grey solid. MS (apci) m/z=216.2 (M+H).

Workup

  1. customThe mixture was purged with N2 for 15 minutes
  2. additionwith vigorous mixing
  3. temperatureThe mixture was heated
  4. temperatureat reflux under a N2 atmosphere for 20 hours
  5. temperatureheated
  6. temperatureat reflux for an additional 20 hours
  7. concentrationconcentrated to an aqueous syrup
  8. customThe syrup was partitioned into H2O (500 mL) and 50% EtOAc-hexanes (250 mL)
  9. additionmixed
  10. filtrationThe mixture was filtered
  11. filtrationthrough filter paper
  12. customthe orange organic layer was removed
  13. washThe aqueous layer was washed with 50% EtOAc/hexanes
  14. temperaturewas cooled on an ice bath
  15. additionThe solution was treated with concentrated HCl to pH 6
  16. customthe resulting fine precipitate was collected
  17. washwashed with H2O and Et2O
  18. customdried under vacuum

Sources & evidence

ORD record
ord-3b6affd909b54a9fbf3f5c661ef97018
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

Loading…