Dimethylformamide → Methyl (3-chloro-4-((1-methyl-3-indazolylcarbonyl)amino)phenyl)acetate

HRID 1372744

反応式

HRID 1372744 の反応式
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:11]([OH:13])=O)=[N:3]1.CN(C=O)C.C(Cl)(=O)C(Cl)=O.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][C:33]([O:35][CH3:36])=[O:34])=[CH:28][C:27]=1[Cl:37].C(N(CC)CC)C>C(Cl)Cl.O>[Cl:37][C:27]1[CH:28]=[C:29]([CH2:32][C:33]([O:35][CH3:36])=[O:34])[CH:30]=[CH:31][C:26]=1[NH:25][C:11]([C:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[N:2]([CH3:1])[N:3]=1)=[O:13]

参加物

8

反応物 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 6891051H-Indazole-3-carboxylic acid, 1-methyl-HCID 13616273Methyl 2-(4-amino-3-chlorophenyl)acetate

生成物 1

HCID 58778393Methyl (3-chloro-4-((1-methyl-3-indazolylcarbonyl)amino)phenyl)acetate収率 89%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

To 1-methylindazole-3-carboxylic acid (600 mg, 3.41 mmol) and DMF (27.0 μl, 0.34 mmol) was added methylene chloride (20 ml). Under stirring at room temperature, oxalyl chloride (0.36 ml, 4.09 mmol) was added dropwise to the resulting mixture. After completion of the dropwise addition, the reaction mixture was stirred at room temperature for 50 hours and the solvent was distilled off under reduced pressure. The residue was dissolved in methylene chloride (5 ml). The resulting solution was added to a solution of methyl 4-amino-3-chlorophenylacetate (680 mg, 3.41 mmol) and triethylamine (1.42 ml, 10.2 mmol) in methylene chloride (5 ml) under stirring at room temperature. The reaction mixture was heated under reflux at room temperature for 7 hours. After the reaction mixture was cooled to room temperature, water was added thereto, followed by extraction with chloroform. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from n-hexane-ethyl acetate (2:1, v/v) eluate fractions, methyl (3-chloro-4-((1-methyl-3-indazolylcarbonyl)amino)phenyl)acetate (1.08 g, 89%) was obtained as a yellow solid.

後処理

  1. additionAfter completion of the dropwise addition
  2. stirringthe reaction mixture was stirred at room temperature for 50 hours
  3. distillationthe solvent was distilled off under reduced pressure
  4. dissolutionThe residue was dissolved in methylene chloride (5 ml)
  5. stirringunder stirring at room temperature
  6. temperatureThe reaction mixture was heated
  7. temperatureunder reflux at room temperature for 7 hours
  8. temperatureAfter the reaction mixture was cooled to room temperature
  9. extractionfollowed by extraction with chloroform
  10. washThe extract was washed with saturated brine
  11. dry with materialdried over anhydrous sodium sulfate
  12. distillationdistilled under reduced pressure
  13. customto remove the solvent
  14. customThe residue was purified by chromatography on a silica gel column, whereby from n-hexane-ethyl acetate (2:1

出典と根拠

ORDレコード
ord-e74ccd3037b044969bfe2b00997d3b10
出典データセット
uspto-grants-2007_01
特許番号
US07157487B2

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