Pyridine → HCID 178487785, compound

HRID 245634Notes

Reaction equation

HRID 245634 reaction equation
[NH2:1][C:2]1[C:10]([C:11]([OH:13])=[O:12])=[C:9]2[C:5]([C:6]([Br:14])=[N:7][NH:8]2)=[CH:4][C:3]=1[Cl:15].[Cl:16][C:17]1[C:18]([N:23]2[C:27]([C:28](O)=O)=[CH:26][C:25]([O:31][CH3:32])=[N:24]2)=[N:19][CH:20]=[CH:21][CH:22]=1.N1C=CC=CC=1.CS(Cl)(=O)=O>O1CCCC1>[Br:14][C:6]1[C:5]2=[CH:4][C:3]([Cl:15])=[C:2]3[C:10]([C:11](=[O:13])[O:12][C:28]([C:27]4[N:23]([C:18]5[C:17]([Cl:16])=[CH:22][CH:21]=[CH:20][N:19]=5)[N:24]=[C:25]([O:31][CH3:32])[CH:26]=4)=[N:1]3)=[C:9]2[NH:8][N:7]=1

Participants

6

Reactant 4

HCID 1049Pyridine2×HCID 31297Methanesulfonyl chlorideHCID 509892861-(3-chloropyridin-2-yl)-3-methoxy-1H-pyrazole-5-carboxylic acid2×HCID 178507816HCID 178507816, compound

Product 1

HCID 178487785HCID 178487785, compoundYield 34.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 400 mg (1.38 mmol) of 6-amino-3-bromo-5-chloro-1H-indazole-7-carboxylic acid in 16 mL of anhydrous tetrahydrofuran at 10° C., is added 349 mg (1.38 mmol) of 2-(3-chloro-pyridin-2-yl)-5-methoxy-2H-pyrazole-3-carboxylic acid followed by 499 μL (6.20 mmol) of pyridine. Then the suspension is cooled to 0° C. and 376 μL (4.82 mmol) of methanesulfonyl chloride are added dropwise. The mixture is stirred at ambient temperature over the night. The reaction is not complete and therefore 166 μL (2.07 mmol) of pyridine are added followed by 349 mg (1.38 mmol) of 2-(3-chloro-pyridin-2-yl)-5-methoxy-2H-pyrazole-3-carboxylic acid. The reaction is stirred again at ambient temperature for 5 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 is purified by flash chromatography (SiO2, heptane/ethyl acetate 1:1) affords 200 mg (0.47 mmol, 34%) of the product as a solid; LC/MS:509/511 (M+H)+.

Workup

  1. stirringThe reaction is stirred again at ambient temperature for 5 hours
  2. customThen the solvent is evaporated
  3. customthe residue is triturated with a minimum of cold water
  4. customThe precipitate, which is formed
  5. filtrationis filtrated
  6. washwashed with cold water
  7. customThe pale yellowish product obtained
  8. customis purified by flash chromatography (SiO2, heptane/ethyl acetate 1:1)

Sources & evidence

ORD record
ord-7f455bc4834c40ada7f9d76b3d1f84a5
Source dataset
uspto-grants-2014_02
Patent number
US08658801B2

Reaction notes

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