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

HRID 340187노트

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HRID 340187 반응식
[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

참가 물질

10

반응물 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

생성물 1

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

시약·촉매·용매 5

HCID 887Methanol용매HCID 962Water용매HCID 1140Toluene용매HCID 6344Dichloromethane용매HCID 8058Hexane용매

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온도
100 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-4d8dd193987a4c829f2e16c6e57707bc
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08895577B2

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