Hydrochloric Acid → 1-Benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridazin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

HRID 1411048ノート

反応式

HRID 1411048 の反応式
[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:30])=[C:7]2[C:12](=[C:13](Br)[N:14]=1)[N:11]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:10](=[O:23])[C:9]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[CH:8]2)=[O:4].C([Sn](CCCC)(CCCC)[C:36]1[N:37]=[N:38][CH:39]=[CH:40][CH:41]=1)CCC.CCOC(C)=O.Cl>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:30])=[C:7]2[C:12](=[C:13]([C:36]3[N:37]=[N:38][CH:39]=[CH:40][CH:41]=3)[N:14]=1)[N:11]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:10](=[O:23])[C:9]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[CH:8]2)=[O:4]

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 27632603-(Tributylstannanyl)pyridazineHCID 867141061-Benzyl-8-bromo-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

生成物 1

HCID 1363772531-Benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridazin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester収率 17.6%

試薬・触媒・溶媒 3

HCID 178418476HCID 178418476、化合物触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
120 °C

実験手順

A mixture of 1-benzyl-8-bromo-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (100 mg, 0.22 mmol), 3-tributylstannanyl-pyridazine (119 mg, 0.32 mmol) and PdCl2(PPh3)2 (30 mg, 0.043 mmol) in 5 mL of DMF was heated at 120° C. for 2 h under nitrogen atmosphere. After the mixture was cooled to r.t., EtOAc and water were added. 1 M HCl was added with stirring until pH was about 3-4. The aqueous layer was extracted with additional EtOAc, and the combined organic layer was washed with water and brine, and dried over MgSO4. After evaporating the solvent in vacuo, the crude product was dissolved in anhydrous MeOH (40 mL). Concentrated H2SO4 (10 drops) was added, and the mixture was refluxed overnight. After cooling to r.t., pH of the mixture was adjusted to about 3-4, and the mixture was extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (5-100% EtOAc/hexanes+1% AcOH) to give 18 mg of the title compound as a light brown solid. MS: (+) m/z 465.35 (M+1).

後処理

  1. temperatureAfter the mixture was cooled to r.t.
  2. extractionThe aqueous layer was extracted with additional EtOAc
  3. washthe combined organic layer was washed with water and brine
  4. dry with materialdried over MgSO4
  5. customAfter evaporating the solvent in vacuo
  6. dissolutionthe crude product was dissolved in anhydrous MeOH (40 mL)
  7. additionConcentrated H2SO4 (10 drops) was added
  8. temperaturethe mixture was refluxed overnight
  9. temperatureAfter cooling to r.t.
  10. extractionthe mixture was extracted with EtOAc
  11. dry with materialThe organic layer was dried over MgSO4
  12. concentrationconcentrated
  13. customThe crude product was purified by silica gel chromatography (5-100% EtOAc/hexanes+1% AcOH)

出典と根拠

ORDレコード
ord-5aee44e23a7e4779b8ac766bd03a96d6
出典データセット
uspto-grants-2014_12
特許番号
US08921389B2

反応ノート

読み込み中…