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

HRID 245617Notes

Reaction equation

HRID 245617 reaction equation
[NH2:1][C:2]1[C:10]([C:11]([OH:13])=[O:12])=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][C:3]=1[CH3:14].[Cl:15][C:16]1[C:17]([N:22]2[C:26]([C:27](O)=O)=[CH:25][C:24]([O:30][CH2:31][C:32]([F:35])([F:34])[F:33])=[N:23]2)=[N:18][CH:19]=[CH:20][CH:21]=1.N1C=CC=CC=1.CS(Cl)(=O)=O>O1CCCC1>[Cl:15][C:16]1[C:17]([N:22]2[C:26]([C:27]3[O:12][C:11](=[O:13])[C:10]4[C:2](=[C:3]([CH3:14])[CH:4]=[C:5]5[CH:6]=[N:7][NH:8][C:9]5=4)[N:1]=3)=[CH:25][C:24]([O:30][CH2:31][C:32]([F:35])([F:33])[F:34])=[N:23]2)=[N:18][CH:19]=[CH:20][CH:21]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 211133851-(3-Chloropyridin-2-yl)-3-(2,2,2-trifluoroethoxy)-1H-pyrazole-5-carboxylic acidHCID 468557186-amino-5-methyl-2H-indazole-7-carboxylic acid

Product 1

HCID 579901947-[2-(3-chloro-pyridin-2-yl)-5-(2,2,2-trifluoro-ethoxy)-2H-pyrazol-3-yl]-5-methyl-1H-8-oxa-1,2,6-triaza-cyclopenta[a]naphthalen-9-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 500 mg (2.61 mmol) of 6-amino-5-methyl-1H-indazole-7-carboxylic acid in 20 mL of anhydrous tetrahydrofuran is added 790 mg (2.61 mmol) of 2-(3-chloro-pyridin-2-yl)-5-(2,2,2-trifluoro-ethoxy)-2H-pyrazole-3-carboxylic acid followed by 945 μL (11.7 mmol) of pyridine. The mixture is stirred at ambient temperature during 30 minutes. Then the suspension is cooled to 0° C. and 708 μL (9.1 mmol) of methanesulfonyl chloride are added dropwise. The mixture is stirred at 50° C. for 16 hours. Then the solvent is evaporated and the residue is triturated with a minimum of cold water. The precipitate, which is formed is filtrated and washed with cold water. The pale yellowish product obtained (1.0 g) is engaged in the next step: LC/MS:477/479 (M+H)+.

Workup

  1. temperatureThen the suspension is cooled to 0° C.
  2. stirringThe mixture is stirred at 50° C. for 16 hours
  3. customThen the solvent is evaporated
  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 pale yellowish product obtained (1.0 g)

Sources & evidence

ORD record
ord-49fcc60da7c14ecf992c63590dc7c1ee
Source dataset
uspto-grants-2014_02
Patent number
US08658801B2

Reaction notes

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