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

HRID 12712

반응식

HRID 12712 반응식
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

참가 물질

9

반응물 4

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

생성물 1

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

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

반응 조건

온도
90 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-c4c1cbbe3d4c4342ab9166f0952850e1
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07727988B2

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