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

HRID 2201851ノート

反応式

HRID 2201851 の反応式
[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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
100 °C

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-609cf58181dd415d82ec439299a55f7a
出典データセット
uspto-grants-2016_06
特許番号
US09364466B2

反応ノート

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