Potassium Carbonate → 9-Methylbenzo[f][1,7]naphthyridin-5-amine

HRID 1259054Notes

Reaction equation

HRID 1259054 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8]C(=O)OC(C)(C)C)=[C:4](B2OC(C)(C)C(C)(C)O2)[CH:3]=1.Br[C:26]1[C:27]([C:32]#[N:33])=[N:28][CH:29]=[CH:30][CH:31]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.CO.ClCCl.O.C(OCC)(=O)C>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]([CH:7]=1)=[C:26]1[C:27](=[C:32]([NH2:33])[N:8]=2)[N:28]=[CH:29][CH:30]=[CH:31]1

Participants

9

Reactant 3

HCID 11430Potassium CarbonateHCID 8176943-Bromopyridine-2-carbonitrileHCID 66893267Tert-butyl 4-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate

Product 1

HCID 582137289-Methylbenzo[f][1,7]naphthyridin-5-amine

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A solution of tert-butyl 4-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (from step 2) (1.0 eq.) and 3-bromopicolino-nitrile (1.0 eq.) in toluene (0.44 M) was mixed with tetrakis(triphenyl-phosphine)palladium (5 mol %) and 2N aqueous potassium carbonate solution (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 swirled in hot ethyl acetate, filtered, and dried to give a pure solid. 1H NMR (acetone d-6): δ 9.02 (d, 1H), 8.89 (d, 1H), 8.25 (s, 1H), 8.70-7.84 (dd, 1H), 7.52 (d, 1H), 7.40 (d, 1H), 6.5 (br, 2H), 2.48 (s, 3H). LRMS [M+H]=210.2

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. filtrationfiltered
  10. customdried
  11. customto give a pure solid

Sources & evidence

ORD record
ord-cf301ea5455b4156ae1a3861422bd7ec
Source dataset
uspto-grants-2013_06
Patent number
US08466167B2

Reaction notes

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