Potassium Carbonate → HCID 44232400, compound

HRID 1479478Notes

Reaction equation

HRID 1479478 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6](B2OC(C)(C)C(C)(C)O2)=[C:7]([NH:9]C(=O)OC(C)(C)C)[CH:8]=1.Br[C:27]1[C:28]([C:33]#[N:34])=[N:29][CH:30]=[CH:31][CH:32]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.CO.ClCCl.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2=[C:27]3[C:28](=[C:33]([NH2:34])[N:9]=[C:7]2[CH:8]=1)[N:29]=[CH:30][CH:31]=[CH:32]3

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 8176943-Bromopyridine-2-carbonitrileHCID 66893334HCID 66893334, compound

Product 1

HCID 44232400HCID 44232400, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
100 °C

Procedure

A solution of tert-butyl 5-methoxy-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (from step 3) (1.0 eq.) and 3-bromopicolino-nitrile (1.0 eq.) in toluene/ethanol (10:1, 0.23 M) was mixed with tetrakis(triphenyl-phosphine)palladium (5 mol %) and anhydrous potassium carbonate (2.0 eq.). The reaction was heated to 100° C. and stirred overnight. After cooling to ambient temperature, the reaction content was diluted with 2% methanol in dichloromethane and water. The two phases were separated, and the aqueous layer was extracted twice with 2% methanol in dichloromethane. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo. The crude product was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-5% methanol in dichloromethane to give a semipure solid, which was then recrystallized in ethyl acetate, filtered, and dried to give a pure solid. 1H NMR (acetone d-6): δ 8.91 (d, 1H), 8.82 (d, 1H), 8.33 (d, 1H), 7.76-7.79 (dd, 1H), 7.07 (s, 1H), 6.96 (d, 1H), 6.6 (br, 2H), 3.90 (s, 3H).

Workup

  1. temperatureAfter cooling to ambient temperature
  2. customThe two phases were separated
  3. extractionthe aqueous layer was extracted twice with 2% methanol in dichloromethane
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous MgSO4
  6. concentrationconcentrated en vacuo
  7. customThe crude product was purified by flash chromatography on a COMBIFLASH® system (ISCO)
  8. customto give a semipure solid, which
  9. customwas then recrystallized in ethyl acetate
  10. filtrationfiltered
  11. customdried
  12. customto give a pure solid

Sources & evidence

ORD record
ord-558f6935c07a44039f2dc55acf3b0d34
Source dataset
uspto-grants-2016_08
Patent number
US09408907B2

Reaction notes

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