Isopropanol → 4-(1-(4-methoxyphenyl)-1H-imidazol-2-yl)pyridine

HRID 1170383ノート

反応式

HRID 1170383 の反応式
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=O)[C:11]2[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=2)=[CH:5][CH:4]=1.P(Cl)(Cl)(Cl)(Cl)Cl.CO[CH:26](OC)[CH2:27][NH2:28].C(O)(C)C>P(Cl)(Cl)(Cl)=O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH:26]=[CH:27][N:28]=[C:10]2[C:11]2[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=2)=[CH:5][CH:4]=1

参加物

6

反応物 4

HCID 3776IsopropanolHCID 24819Phosphorus pentachlorideHCID 89728Aminoacetaldehyde dimethyl acetalHCID 532207N-(4-methoxyphenyl)pyridine-4-carboxamide

生成物 1

HCID 685789244-(1-(4-methoxyphenyl)-1H-imidazol-2-yl)pyridine収率 74%

試薬・触媒・溶媒 1

HCID 24813Phosphorus oxychloride溶媒2 回

反応条件

温度
120 °C

実験手順

Preparation 87 (N-(4-methoxyphenyl)isonicotinamide, 1 g, 4.39 mmol) was dissolved in phosphorous oxychloride (POCl3) (5 mL) then phosphorous pentachloride (913 mg, 4.39 mmol) was added. The mixture was heated at 120° C. for 4 h. The POCl3 was removed in vacuo, aminoacetaldehyde dimethyl acetal (9.5 mL, 87.8 mmol) and isopropanol (10 mL) were added, and the mixture was stirred at 23° C. for ca. 16 h. The reaction mixture was concentrated in vacuo and concentrated hydrochloric acid (36.5%, 25 mL) in isopropanol (15 mL) was added. The reaction mixture was heated at 90° C. for 24 h. After cooling to 23° C., aqueous sodium hydroxide (1N) and aqueous sodium bicarbonate were added to obtain pH=8. The mixture was extracted with methylene chloride, was dried (MgSO4), and was filtered and concentrated in vacuo. The residue was purified by silica gel chromatography with ethyl acetate/hexanes/methanol (80:20:0 to 76:19:5) to afford 811 mg (74% yield) of the title compound; diagnostic 13C NMR signals (100 MHz, CDCl3) δ 160.069, 149.952, 144.142, 137.853, 131.004, 129.882, 127.414, 124.977, 122.195, 115.114, 55.808; MS (AP/CI) 252.4 (M+H)+.

後処理

  1. additionwere added
  2. concentrationThe reaction mixture was concentrated in vacuo and concentrated hydrochloric acid (36.5%, 25 mL) in isopropanol (15 mL)
  3. additionwas added
  4. temperatureThe reaction mixture was heated at 90° C. for 24 h
  5. temperatureAfter cooling to 23° C.
  6. additionaqueous sodium hydroxide (1N) and aqueous sodium bicarbonate were added
  7. customto obtain pH=8
  8. extractionThe mixture was extracted with methylene chloride
  9. dry with materialwas dried (MgSO4)
  10. filtrationwas filtered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by silica gel chromatography with ethyl acetate/hexanes/methanol (80:20:0 to 76:19:5)

出典と根拠

ORDレコード
ord-6121f360dd3f43819df94f89863b6767
出典データセット
uspto-grants-2010_11
特許番号
US07825254B2

反応ノート

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