Thionyl Chloride → 3,5-dichloro-4-({7-[(cyclopropylcarbonyl)amino]-2-methyl-1H-pyrrolo[2,3-c]pyridin-3-yl}carbonyl)-N-methylbenzamide

HRID 875457노트

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HRID 875457 반응식
[Cl:1][C:2]1[CH:10]=[C:9]([C:11](=[O:14])[NH:12][CH3:13])[CH:8]=[C:7]([Cl:15])[C:3]=1[C:4]([OH:6])=O.S(Cl)(Cl)=O.[CH3:20][C:21]1[NH:35][C:24]2=[C:25]([NH:29][C:30]([CH:32]3[CH2:34][CH2:33]3)=[O:31])[N:26]=[CH:27][CH:28]=[C:23]2[CH:22]=1.[Cl-].[Al+3].[Cl-].[Cl-]>ClCCl.CO>[Cl:15][C:7]1[CH:8]=[C:9]([CH:10]=[C:2]([Cl:1])[C:3]=1[C:4]([C:22]1[C:23]2[C:24](=[C:25]([NH:29][C:30]([CH:32]3[CH2:33][CH2:34]3)=[O:31])[N:26]=[CH:27][CH:28]=2)[NH:35][C:21]=1[CH3:20])=[O:6])[C:11]([NH:12][CH3:13])=[O:14]

참가 물질

7

반응물 4

HCID 24386Thionyl ChlorideHCID 6451240Aluminum(III) ChlorideHCID 71061496N-(2-methyl-1H-pyrrolo[2,3-c]pyridin-7-yl)cyclopropanecarboxamideHCID 710616332,6-Dichloro-4-(methylcarbamoyl)benzoic acid

생성물 1

HCID 867206553,5-dichloro-4-({7-[(cyclopropylcarbonyl)amino]-2-methyl-1H-pyrrolo[2,3-c]pyridin-3-yl}carbonyl)-N-methylbenzamide수율 29%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매

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온도
100 °C

실험 절차

To a solution of 2,6-dichloro-4-(methylcarbamoyl)benzoic acid (276 mg, 1.1 mmol) in dry dichloromethane, was added thionyl chloride (5 mL) and heated at 100° C. for about 3 hours. The mixture was concentrated under vacuum. The residue was dissolved in dry dichloromethane (3 mL) and added to the stirred solution of N-(2-methyl-1H-pyrrolo[2,3-c]pyridin-7-yl)cyclopropanecarboxamide (120 mg, 0.55 mmol) in aluminium chloride (743 mg, 5.57 mmol) drop wise. The resulting reaction mixture was stirred overnight at room temperature. After completion, methanol (10 mL) was added cautiously to quench the reaction mass followed by concentration under vacuum. The reaction mass was diluted with water and extracted with ethyl acetate. The combined organic layer was washed with aq. sodium bicarbonate solution, brine, dried over anhydrous sodium sulfate, and concentrated. Purification by silica gel (100-200) column chromatography using dichloromethane and methanol gradient as eluent afforded 3,5-dichloro-4-({7-[(cyclopropylcarbonyl)amino]-2-methyl-1H-pyrrolo[2,3-c]pyridin-3-yl}carbonyl)-N-methylbenzamide (70 mg, 29%).

후처리

  1. concentrationThe mixture was concentrated under vacuum
  2. dissolutionThe residue was dissolved in dry dichloromethane (3 mL)
  3. customThe resulting reaction mixture
  4. customto quench the reaction mass
  5. concentrationfollowed by concentration under vacuum
  6. additionThe reaction mass was diluted with water
  7. extractionextracted with ethyl acetate
  8. washThe combined organic layer was washed with aq. sodium bicarbonate solution, brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated
  11. customPurification by silica gel (100-200) column chromatography

출처 및 근거

ORD 기록
ord-00cfa3ab2a784c02a6168f3e7358591e
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08980911B2

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