Sodium Carbonate → HCID 89488325, compound

HRID 570134Notes

Reaction equation

HRID 570134 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[CH2:10][CH2:9][CH2:8][O: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.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[O:7][CH2:8][CH2:9][CH2:10][N:5]3[N:4]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 49760449tert-butyl N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)carbamateHCID 89488351HCID 89488351, compound

Product 1

HCID 89488325HCID 89488325, compound

Reagents, catalysts & solvents 2

HCID 11556747Bis(tricyclohexylphosphine)palladium(II) DichlorideCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

3-bromo-2-phenyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine (700 mg, 2.25 mmol) and tert-butyl [4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]carbamate (792 mg, 2.47 mmol, 1.1 eq) are dissolved in 10 mL 1,4-dioxan. To this mixture Bis(tricyclohexylphosphine)palladium(II)-dichloride (166 mg, 0.22 mmol, 0.1 eq) and 5.4 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 12 mins at 150° C. in the microwave (Biotage). The procedure is repeated 7× using the same scale and all crude reaction mixtures are combined thereafter. After cooling, insoluble components are filtered off over Celite and the residue washed with 1,4-dioxan. The organic phase is evaporated and the crude product purified by column chromatography over silica gel using dichloromethane/methanole as eluent. After evaporation of the solvents 2.10 g (41%) of 4-(2-phenyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)pyridin-2-amine are obtained as a colourless solid.

Workup

  1. customThe reaction mixture is flushed with argon for 5 mins
  2. customsealed
  3. customall crude reaction mixtures
  4. temperatureAfter cooling
  5. filtrationinsoluble components are filtered off over Celite
  6. washthe residue washed with 1,4-dioxan
  7. customThe organic phase is evaporated
  8. customthe crude product purified by column chromatography over silica gel
  9. customAfter evaporation of the solvents 2.10 g (41%) of 4-(2-phenyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)pyridin-2-amine
  10. customare obtained as a colourless solid

Sources & evidence

ORD record
ord-aebb6ad8c982489ba5f1b5cc6e4075ef
Source dataset
uspto-grants-2015_05
Patent number
US09023844B2

Reaction notes

Loading…