Triethylamine → 1-(3-Imino-2-oxopropyl)-3-pyridin-2-yl-1,3-dihydro-2H-benzimidazol-2-one

HRID 656418ノート

反応式

HRID 656418 の反応式
[O:1]=[C:2]1[N:6]([CH2:7][C:8]([OH:10])=O)[C:5]2[CH:11]=[CH:12][CH:13]=[CH:14][C:4]=2[N:3]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=1.[CH2:21]([N:23](CC)CC)C.ClC(OCC(C)C)=O.[N+](=C)=[N-]>C1COCC1.CCOCC>[NH:23]=[CH:21][C:8](=[O:10])[CH2:7][N:6]1[C:5]2[CH:11]=[CH:12][CH:13]=[CH:14][C:4]=2[N:3]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)[C:2]1=[O:1]

参加物

7

反応物 4

HCID 8471TriethylamineHCID 9550Diazomethane2 回HCID 62365Isobutyl chloroformateHCID 18449368(2-Oxo-3-pyridin-2-yl-2,3-dihydro-1H-benzimidazol-1-yl)acetic acid2 回

生成物 1

HCID 866322931-(3-Imino-2-oxopropyl)-3-pyridin-2-yl-1,3-dihydro-2H-benzimidazol-2-one

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒2 回HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-10 °C

実験手順

To a stirred solution of (2-oxo-3-pyridin-2-yl-2,3-dihydro-1H-benzimidazol-1-yl)acetic acid (144 mg, 0.535 mmol, described in Intermediate 16) in THF (5 mL) at −10° C. was added triethylamine (0.097 mL, 0.695 mmol), followed by isobutyl chloroformate (0.090 mL, 0.695 mmol) and the resulting mixture was stirred at −10° C. for 3 h. A cold solution of diazomethane (ca. 1.0 mmol) in Et2O (3 mL) was added, and stirring was continued for 16 h, allowing the mixture to warm slowly to ambient temperature. The mixture was cooled to −10° C. and a cold solution of diazomethane (ca. 1.5 mmol) in Et2O (5 mL) was added, and the resulting mixture was allowed to warm to ambient temperature and stirred for 3 h. The solvent was removed in vacuo and the residue was partitioned between Et2O (20 mL) and saturated aqueous NaHCO3 (10 mL). The aqueous layer was extracted further with Et2O (2×10 mL) and the combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was triturated with MeOH to give a pale solid. This solid was further purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc—100:0 to 50:50, to give the title compound. MS: m/z=266 (M−N).

後処理

  1. stirringstirring
  2. waitwas continued for 16 h
  3. temperatureto warm slowly to ambient temperature
  4. temperatureThe mixture was cooled to −10° C.
  5. temperatureto warm to ambient temperature
  6. stirringstirred for 3 h
  7. customThe solvent was removed in vacuo
  8. customthe residue was partitioned between Et2O (20 mL) and saturated aqueous NaHCO3 (10 mL)
  9. extractionThe aqueous layer was extracted further with Et2O (2×10 mL)
  10. dry with materialthe combined organic layers were dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was triturated with MeOH
  14. customto give a pale solid
  15. customThis solid was further purified by silica gel chromatography
  16. washeluting with a gradient of hexane

出典と根拠

ORDレコード
ord-1fef5a14d3824de8b95df5df709d7c17
出典データセット
uspto-grants-2011_12
特許番号
US08071771B2

反応ノート

読み込み中…