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

HRID 1852992Notes

Reaction equation

HRID 1852992 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[CH:12]=2)[N:5]2[CH:21]=[CH:22][N:23]=[C:4]2[CH:3]=1.[CH:24]([N:27]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[N:28]1)([CH3:26])[CH3:25].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>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:24]([N:27]1[CH:31]=[C:30]([C:2]2[N:7]=[C:6]([C:8]3[CH:9]=[N:10][N:11]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[CH:12]=3)[N:5]3[CH:21]=[CH:22][N:23]=[C:4]3[CH:3]=2)[CH:29]=[N:28]1)([CH3:26])[CH3:25]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 467380211-(Propan-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 866852957-chloro-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine

Product 1

HCID 674589287-(1-isopropyl-1H-pyrazol-4-yl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidineYield 78.1%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
65 °C

Procedure

To a flask charged with 7-chloro-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine (Preparation G; 0.200 g, 0.572 mmol), 1-isopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.202 g, 0.857 mmol) (Table 2, compound a), and potassium phosphate (0.857 mL, 1.71 mmol) was added 5 mL of Dioxane and argon was bubbled through for 10 minutes before dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.0545 g, 0.114 mmol) and tris(dibenzylideneacetone)dipalladium (0.0523 g, 0.0572 mmol) were added quickly and argon was bubbled through the reaction for 10 minutes before it was sealed and heated to 65° C. overnight. The reaction was diluted with ethyl acetate (100 mL) and washed with aqueous saturated sodium bicarbonate (40 mL) and brine (40 mL). The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. The crude was purified by silica gel column chromatography, eluting with a mixture of ethyl acetate and 0.5% ammonium hydroxide to afford 7-(1-isopropyl-1H-pyrazol-4-yl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine (0.191 g, 0.446 mmol, 78.1% yield). MS (apci) m/z=424.2 (M+H).

Workup

  1. additionwere added quickly
  2. customargon was bubbled through the reaction for 10 minutes before it
  3. customwas sealed
  4. additionThe reaction was diluted with ethyl acetate (100 mL)
  5. washwashed with aqueous saturated sodium bicarbonate (40 mL) and brine (40 mL)
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude was purified by silica gel column chromatography
  10. washeluting with a mixture of ethyl acetate and 0.5% ammonium hydroxide

Sources & evidence

ORD record
ord-1d604afcab024e57b1558cdd17d59abe
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

Loading…