Potassium Carbonate → 8-Methylbenzo[f][1,7]naphthyridin-5-amine

HRID 340185ノート

反応式

HRID 340185 の反応式
[CH3:1][C:2]1[CH:3]=[CH:4][C:5](B2OC(C)(C)C(C)(C)O2)=[C:6]([NH:8]C(=O)OC(C)(C)C)[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+]>C1(C)C=CC=CC=1.CO.ClCCl.O>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]2=[C:26]3[C:27](=[C:32]([NH2:33])[N:8]=[C:6]2[CH:7]=1)[N:28]=[CH:29][CH:30]=[CH:31]3

参加物

8

反応物 3

HCID 11430Potassium CarbonateHCID 8176943-Bromopyridine-2-carbonitrileHCID 46737997tert-Butyl (5-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate

生成物 1

HCID 442323988-Methylbenzo[f][1,7]naphthyridin-5-amine

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 962Water溶媒HCID 1140Toluene溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
100 °C

実験手順

A solution of tert-butyl 5-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 pure solid. 1H NMR (acetone d-6): δ 8.98 (d, 1H), 8.87 (d, 1H), 8.32 (d, 1H), 7.79-7.82 (dd, 1H), 7.42 (s, 1H), 7.18 (d, 1H), 6.6 (br, 2H), 2.45 (s, 3H). LRMS [M+H]=210.1

後処理

  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 pure solid

出典と根拠

ORDレコード
ord-5d08c52723334796a2fe8e9e15868c59
出典データセット
uspto-grants-2014_11
特許番号
US08895577B2

反応ノート

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