Sodium Carbonate → HCID 89488372, compound

HRID 570143Notes

Reaction equation

HRID 570143 reaction equation
Br[C:2]1[C:3]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[N:4][N:5]2[CH:10]=[CH:9][CH:8]=[N:7][C:6]=12.CC1(C)C(C)(C)OB([C:25]2[CH:30]=[CH:29][N:28]=[C:27]([NH:31]C(=O)OC(C)(C)C)[CH:26]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.[Cl-].[Cl-].[Pd+2]>[C:11]1([C:3]2[C:2]([C:25]3[CH:30]=[CH:29][N:28]=[C:27]([NH2:31])[CH:26]=3)=[C:6]3[N:7]=[CH:8][CH:9]=[CH:10][N:5]3[N:4]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 49760449tert-butyl N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)carbamate2×HCID 83744419HCID 83744419, compound

Product 1

HCID 89488372HCID 89488372, compoundYield 45.8%

Reagents, catalysts & solvents 3

HCID 11556747Bis(tricyclohexylphosphine)palladium(II) DichlorideCatalyst2×HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

3-Bromo-2-phenylpyrazolo[1,5-a]pyrimidine (1.0 g, 3.65 mmol) and tert-butyl [4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]carbamate (1.29 g, 4.01 mmol, 1.1 eq) are dissolved in 10 mL 1,4-dioxan. To this mixture bis(tricyclohexylphosphine)palladium(II)-dichloride (269 mg, 0.37 mmol, 0.1 eq) and 9.1 mL sodium carbonate solution (2 molar) are added. The reaction mixture is flushed with argon for 5 mins and then sealed. Next the mixture is heated for 90 min at 120° C. in the microwave (Biotage). Tert-butyl [4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]carbamate (214 mg, 1.4 mmol, 0.37 eq) and bis(tricyclohexylphosphine)palladium(II)-dichloride (269 mg, 0.37 mmol, 0.1 eq) are then added and the mixture is heated for 2 h at 120° C. The reaction mixture is then poured in water and extracted with ethyl acetate (3×50 mL). The organic layer is dried over anhydrous magnesium sulphate, filtered and concentrated under reduced pressure. The crude material is purified by column chromatography using silica gel in heptane and ethyl acetate (1:0 to 1:1) as eluent and 0.48 g (44%) of 4-(2-phenylpyrazolo[1,5-a]pyrimidin-3-yl)pyridin-2-amine are obtained as a white solid.

Workup

  1. customThe reaction mixture is flushed with argon for 5 mins
  2. customsealed
  3. temperaturethe mixture is heated for 2 h at 120° C
  4. extractionextracted with ethyl acetate (3×50 mL)
  5. dry with materialThe organic layer is dried over anhydrous magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material is purified by column chromatography

Sources & evidence

ORD record
ord-69c649098ac94325996a832ab2d007a6
Source dataset
uspto-grants-2015_05
Patent number
US09023844B2

Reaction notes

Loading…