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Dimethylformamide → Ethyl (5-chloro-2-fluoro-4-((2-methyl-3-indazolylcarbonyl)amino)phenyl)acetate

HRID 1372742
Notes
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Reaction equation

HRID 1372742 reaction equation
[CH3:1][N:2]1[C:10]([C:11]([OH:13])=O)=[C:9]2[C:4]([CH:5]=[CH:6][CH:7]=[CH:8]2)=[N:3]1.CN(C=O)C.C(Cl)(=O)C(Cl)=O.[NH2:25][C:26]1[C:31]([Cl:32])=[CH:30][C:29]([CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])=[C:28]([F:39])[CH:27]=1.C(N(CC)CC)C>C1C=CC=CC=1>[Cl:32][C:31]1[C:26]([NH:25][C:11]([C:10]2[N:2]([CH3:1])[N:3]=[C:4]3[C:9]=2[CH:8]=[CH:7][CH:6]=[CH:5]3)=[O:13])=[CH:27][C:28]([F:39])=[C:29]([CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH:30]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 70605372-Methyl-2H-indazole-3-carboxylic acidHCID 17858807Ethyl 4-amino-5-chloro-2-fluorophenylacetate

Product 1

HCID 58778670Ethyl (5-chloro-2-fluoro-4-((2-methyl-3-indazolylcarbonyl)amino)phenyl)acetate
Yield 27.1%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Procedure

To 2-methylindazole-3-carboxylic acid (650 mg, 3.69 mmol) and DMF (29.0 μl, 0.37 mmol) was added benzene (20 ml). Under stirring at room temperature, oxalyl chloride (0.39 ml, 4.43 mmol) was added dropwise to the resulting mixture. After completion of the dropwise addition, the reaction mixture was stirred for further 1 hour at room temperature. A solution of ethyl (4-amino-5-chloro-2-fluorophenyl)acetate (855 mg, 3.69 mmol) and triethylamine (3.09 ml, 22.1 mmol) in benzene (3.0 ml), which had been prepared in advance, was added dropwise to the reaction mixture, and the mixture was heated under reflux for 16 hours. The reaction mixture was then cooled to room temperature, followed by extraction with ethyl acetate. 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 (5:1, v/v) eluate fractions, ethyl (5-chloro-2-fluoro-4-((2-methyl-3-indazolylcarbonyl)amino)phenyl)acetate (390 mg, 27%) was obtained as a pale yellow solid.

Workup

  1. additionAfter completion of the dropwise addition
  2. stirringthe reaction mixture was stirred for further 1 hour at room temperature
  3. additionwas added dropwise to the reaction mixture
  4. temperaturethe mixture was heated
  5. temperatureunder reflux for 16 hours
  6. temperatureThe reaction mixture was then cooled to room temperature
  7. extractionfollowed by extraction with ethyl acetate
  8. washThe extract was washed with saturated brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. distillationdistilled under reduced pressure
  11. customto remove the solvent
  12. customThe residue was purified by chromatography on a silica gel column, whereby from n-hexane-ethyl acetate (5:1

Sources & evidence

ORD record
ord-0870bf82d9e24a0cb22dfac5df9e4d52
Source dataset
uspto-grants-2007_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07157487B2

Reaction notes

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