Ethyl Acetate → 10-Methylbenzo[f][1,7]naphthyridin-5-amine

HRID 1259055Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1259055
[CH3:1][C:2]1[C:3](B2OC(C)(C)C(C)(C)O2)=[C:4]([NH:8]C(=O)OC(C)(C)C)[CH:5]=[CH:6][CH:7]=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+].C(OCC)(=O)C>C1(C)C=CC=CC=1.CO.ClCCl.O.CCCCCC>[CH3:1][C:2]1[C:3]2=[C:26]3[C:27](=[C:32]([NH2:33])[N:8]=[C:4]2[CH:5]=[CH:6][CH:7]=1)[N:28]=[CH:29][CH:30]=[CH:31]3

Komponenten

10

Edukt 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 8176943-Bromopyridine-2-carbonitrileHCID 67117786Tert-butyl 3-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate

Produkt 1

HCID 5821372010-Methylbenzo[f][1,7]naphthyridin-5-amine

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8058HexaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A solution of tert-butyl 3-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 0-40% ethyl acetate in toluene to give a semipure solid, which was then swirled in hot 10% ethyl acetate in hexane, filtered, and dried to give a pure solid. 1H NMR (acetone d-6): δ 9.22 (d, 1H), 8.90 (d, 1H), 7.82-7.85 (dd, 1H), 7.54 (d, 1H), 7.45 (t, 1H), 7.19 (d, 1H), 6.6 (br, 2H), 2.98 (s, 3H). LRMS [M+H]=210.2.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-8d4fa4ab14a849579e30c6cf4664185b
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08466167B2

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