Pyridine → 7-[2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazol-3-yl]-1H-8-oxa-1,6-diaza-cyclopenta[a]naphthalen-9-one

HRID 245605Notes

Reaction equation

HRID 245605 reaction equation
[NH2:1][C:2]1[C:10]([C:11]([OH:13])=[O:12])=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[Cl:14][C:15]1[C:16]([N:21]2[C:25]([C:26](O)=O)=[CH:24][C:23]([C:29]([F:32])([F:31])[F:30])=[N:22]2)=[N:17][CH:18]=[CH:19][CH:20]=1.N1C=CC=CC=1.CS(Cl)(=O)=O>C(#N)C>[Cl:14][C:15]1[C:16]([N:21]2[C:25]([C:26]3[O:12][C:11](=[O:13])[C:10]4[C:2](=[CH:3][CH:4]=[C:5]5[CH:6]=[CH:7][NH:8][C:9]5=4)[N:1]=3)=[CH:24][C:23]([C:29]([F:32])([F:30])[F:31])=[N:22]2)=[N:17][CH:18]=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 113921841-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acidHCID 223138806-amino-1H-indole-7-carboxylic acid

Product 1

HCID 1361760267-[2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazol-3-yl]-1H-8-oxa-1,6-diaza-cyclopenta[a]naphthalen-9-oneYield 25%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a suspension of 79 mg (0.45 mmol) of 6-amino-1H-indole-7-carboxylic acid in 7 mL of acetonitrile, is added 130 mg (0.45 mmol) of 2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid followed by 0.16 mL (2.06 mmol) of pyridine. The mixture is stirred at ambient temperature during 30 minutes. Then the suspension is cooled to 0° C. and 0.12 mL (1.57 mmol) of methanesulfonyl chloride is added dropwise. The mixture is stirred at 0° C. during 30 minutes and 2 hours at ambient temperature. After evaporation of the solvent, the residue is triturated with a minimum of cold water. The precipitate which is formed is filtrated and washed with cold water. The residue is then purified by column chromatography on silica gel with hexanes and ethyl acetate as eluents and 47.1 mg (0.11 mmol, 25%) of a yellowish solid are obtained; LC/MS:432/434 (M+H)+.

Workup

  1. temperatureThen the suspension is cooled to 0° C.
  2. stirringThe mixture is stirred at 0° C. during 30 minutes and 2 hours at ambient temperature
  3. customAfter evaporation of the solvent
  4. customthe residue is triturated with a minimum of cold water
  5. customThe precipitate which is formed
  6. filtrationis filtrated
  7. washwashed with cold water
  8. customThe residue is then purified by column chromatography on silica gel with hexanes and ethyl acetate as eluents

Sources & evidence

ORD record
ord-f7597506273241fd9edd7a5cfb9a3700
Source dataset
uspto-grants-2014_02
Patent number
US08658801B2

Reaction notes

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