Tetrahydrofuran → 2,4-dimethoxy-7-(4-methoxy-3,5-dimethylphenyl)-1,6-naphthyridin-5(6H)-one

HRID 336716

反応式

HRID 336716 の反応式
[CH3:1][O:2][C:3]1[C:8]([C:9]([NH2:11])=[O:10])=[C:7]([CH3:12])[N:6]=[C:5]([O:13][CH3:14])[CH:4]=1.C([Li])CCC.CO[C:22]1C=[CH:28][C:25]([C:26]#N)=[CH:24][CH:23]=1.[CH2:30]1[CH2:34][O:33][CH2:32][CH2:31]1>>[CH3:14][O:13][C:5]1[CH:4]=[C:3]([O:2][CH3:1])[C:8]2[C:9](=[O:10])[NH:11][C:28]([C:25]3[CH:24]=[C:23]([CH3:22])[C:34]([O:33][CH3:32])=[C:30]([CH3:31])[CH:26]=3)=[CH:12][C:7]=2[N:6]=1

参加物

5

反応物 4

HCID 8028Tetrahydrofuran2 回HCID 701294-MethoxybenzonitrileHCID 666614724,6-Dimethoxy-2-methyl-nicotinamideHCID 178418339Butyllithium

生成物 1

HCID 249597052,4-dimethoxy-7-(4-methoxy-3,5-dimethylphenyl)-1,6-naphthyridin-5(6H)-one収率 12%

反応条件

温度
0 °C

実験手順

To a solution of 4,6-dimethoxy-2-methyl nicotinamide (2.0 g, 10.2 mmol) in THF (80 mL), n-butyl lithium (19.12 mL, 30.6 mmol, 1.6 M solution in hexane) was added slowly under nitrogen at −78° C. After completion of addition the mixture was stirred for 1 h at 0° C. Then cooled to −78° C. and a solution of 4-methoxy benzonitrile (1.65 g, 10.2 mmol) in THF (10 mL) was added quickly. The cooling bath was removed and the reaction mixture was allowed to warm to room temperature and stirred for 16 h at room temperature. Saturated NH4Cl solution was added with cooling. The organic layer was washed with water, brine, dried over Na2SO4 and concentrated to give crude product. The crude product was purified by chromatography using 50% ethyl acetate in hexane and then 2% methanol in ethyl acetate to give 2,4-dimethoxy-7-(4-methoxy-3,5-dimethylphenyl)-1,6-naphthyridin-5(6H)-one (410 mg, 12%), as a yellow solid. Selected data: MS (ES) m/z: 341.1; mp 262-263° C. (at decomposition).

後処理

  1. additionAfter completion of addition the mixture
  2. temperatureThen cooled to −78° C.
  3. customThe cooling bath was removed
  4. temperatureto warm to room temperature
  5. stirringstirred for 16 h at room temperature
  6. additionSaturated NH4Cl solution was added
  7. temperaturewith cooling
  8. washThe organic layer was washed with water, brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated
  11. customto give crude product
  12. customThe crude product was purified by chromatography

出典と根拠

ORDレコード
ord-6339288a487b4e269ea689d2a861adb5
出典データセット
uspto-grants-2014_11
特許番号
US08889698B2

関連ノート

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