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Nicotinoyl chloride → N-{3-[2,6-difluoro-3-(propane-1-sulfonylamino)-benzoyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-nicotinamide

HRID 60110
ノート
印刷プレビュー

反応式

HRID 60110 の反応式
[NH:1]1[C:5]2=[N:6][CH:7]=[C:8]([NH:10][C:11](=[O:18])[C:12]3[CH:17]=[CH:16][CH:15]=[N:14][CH:13]=3)[CH:9]=[C:4]2[CH:3]=[CH:2]1.[Cl-].[Cl-].[Cl-].[Al+3].[F:23][C:24]1[C:32]([NH:33][S:34]([CH2:37][CH2:38][CH3:39])(=[O:36])=[O:35])=[CH:31][CH:30]=[C:29]([F:40])[C:25]=1[C:26](Cl)=[O:27].C(Cl)(=O)C1C=CC=NC=1>ClCCl.O.O1CCCC1.C(N(CC)CC)C>[F:23][C:24]1[C:32]([NH:33][S:34]([CH2:37][CH2:38][CH3:39])(=[O:35])=[O:36])=[CH:31][CH:30]=[C:29]([F:40])[C:25]=1[C:26]([C:3]1[C:4]2[C:5](=[N:6][CH:7]=[C:8]([NH:10][C:11](=[O:18])[C:12]3[CH:17]=[CH:16][CH:15]=[N:14][CH:13]=3)[CH:9]=2)[NH:1][CH:2]=1)=[O:27]
参加物実験手順後処理出典と根拠反応ノート

参加物

9

反応物 4

HCID 82604Nicotinoyl chlorideHCID 6451240Aluminum(III) ChlorideHCID 580868612,6-Difluoro-3-(propane-1-sulfonylamino)-benzoyl chlorideHCID 58368850N-(1H-pyrrolo[2,3-b]pyridin-5-yl)-nicotinamide

生成物 1

HCID 53261721N-{3-[2,6-difluoro-3-(propane-1-sulfonylamino)-benzoyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-nicotinamide

試薬・触媒・溶媒 4

HCID 962Water溶媒2 回
HCID 6344Dichloromethane溶媒
HCID 8028Tetrahydrofuran溶媒
HCID 8471Triethylamine溶媒

実験手順

In a reaction vial, N-(1H-pyrrolo[2,3-b]pyridin-5-yl)-nicotinamide (37, 0.050 g, 0.21 mmol) is dissolved in 2 mL of dichloromethane. Aluminum trichloride (0.1 g, 1 mmol) and 2,6-difluoro-3-(propane-1-sulfonylamino)-benzoyl chloride (38, 0.075 g, 0.25 mmol) are added in one portion, and the reaction is stirred at room temperature for 36 hours, then diluted with water and extracted 3× with ethyl acetate. The organic layers are combined and washed 2× with brine, dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The amide linked at the 5-position is lost, so half the material is mixed with 3 mL of triethylamine in 2 mL of tetrahydrofuran and nicotinoyl chloride (36, 0.036 g, 0.25 mmol) is added and stirred at room temperature overnight. The reaction is diluted with water and extracted 3× with ethyl acetate. The organic layers are combined and washed 2× with brine, dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is further purified by reverse phase chromatography and the resulting material confirmed by LC-MS.

後処理

  1. extractionextracted 3× with ethyl acetate
  2. washwashed 2× with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated under vacuum
  6. additionis added
  7. stirringstirred at room temperature overnight
  8. extractionextracted 3× with ethyl acetate
  9. washwashed 2× with brine
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationthe filtrate concentrated under vacuum
  13. customThe resulting material is further purified by reverse phase chromatography

出典と根拠

ORDレコード
ord-85fa2634a78c4b4f9fce70bf9e55d550
出典データセット
uspto-grants-2016_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09440969B2

反応ノート

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