Potassium Carbonate → 5-(2-Fluoro-3-pyridinyl)-2,4-bis(methyloxy)pyrimidine

HRID 12712

Reaction equation

HRID 12712 reaction equation
Br[C:2]1[C:3]([O:10][CH3:11])=[N:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[F:12][C:13]1[C:18](B(O)O)=[CH:17][CH:16]=[CH:15][N:14]=1.C(=O)([O-])[O-].[K+].[K+].B(O)O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(C)=O.O.O1CCOCC1>[F:12][C:13]1[C:18]([C:2]2[C:3]([O:10][CH3:11])=[N:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=2)=[CH:17][CH:16]=[CH:15][N:14]=1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 61668Boronic AcidHCID 2557195-Bromo-2,4-dimethoxypyrimidineHCID 27832702-Fluoropyridine-3-boronic acid

Product 1

HCID 589941555-(2-Fluoro-3-pyridinyl)-2,4-bis(methyloxy)pyrimidineYield 93.1%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of 5-bromo-2,4-bis(methyloxy)pyrimidine (Prep86, 3 g, 13.70 mmol), 2-fluoropyridine-3-boronic acid (1.930 g, 13.70 mmol) and Pd(PPh3)4 (0.791 g, 0.685 mmol), dry 1,4-Dioxane (45 ml) was added followed by potassium carbonate 1M solution (27.4 ml, 27.4 mmol). The mixture was degassed with Argon and then heated at 100° C. for 1 h (internal T˜90° C.). Then the mixture was cooled down to ambient, further 1 eq of boronic acid (1.930 g, 13.70 mmol) followed by 5 mol % of PdTetrakis (0.791 g, 0.685 mmol) were added and the mixture heated at 100° C. for two 2 h. The reaction mixture was cooled down to room temperature, taken up with water and AcOEt. The aqueous layer was back extracted with AcOEt. The combined organics were dried over Na2SO4 and evaporated to dryness. The crude material was purified by SiO2 flash chromatography eluting with Cy/EA 8/2 to get the title compound as white solid (3 g).

Workup

  1. additionwas added
  2. customThe mixture was degassed with Argon
  3. temperatureThen the mixture was cooled down
  4. additionwere added
  5. temperaturethe mixture heated at 100° C. for two 2 h
  6. temperatureThe reaction mixture was cooled down to room temperature
  7. extractionThe aqueous layer was back extracted with AcOEt
  8. dry with materialThe combined organics were dried over Na2SO4
  9. customevaporated to dryness
  10. customThe crude material was purified by SiO2 flash chromatography
  11. washeluting with Cy/EA 8/2

Sources & evidence

ORD record
ord-c4c1cbbe3d4c4342ab9166f0952850e1
Source dataset
uspto-grants-2010_06
Patent number
US07727988B2

Linked notes

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