Dimethyl Sulfoxide → 7-(2-Chloro-6-fluorobenzyloxy)-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxylic Acid

HRID 1486303Notes

Reaction equation

HRID 1486303 reaction equation
C([O:3][C:4]([C:6]1[C:7]([CH3:26])=[N:8][N:9]2[C:14]([O:15][CH2:16][C:17]3[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=3[Cl:24])=[CH:13][C:12]([CH3:25])=[CH:11][C:10]=12)=[O:5])C.[OH-].[Na+].CS(C)=O>O1CCOCC1>[Cl:24][C:18]1[CH:19]=[CH:20][CH:21]=[C:22]([F:23])[C:17]=1[CH2:16][O:15][C:14]1[N:9]2[N:8]=[C:7]([CH3:26])[C:6]([C:4]([OH:5])=[O:3])=[C:10]2[CH:11]=[C:12]([CH3:25])[CH:13]=1

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 14798Sodium HydroxideHCID 1178646837-[(2-Chloro-6-fluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxylic Acid ethyl Ester

Product 1

HCID 1178595577-(2-Chloro-6-fluorobenzyloxy)-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxylic AcidYield 27%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 198 mg (0.62 mmol) of 7-(2-chloro-6-fluorobenzyloxy)-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxylic acid ethyl ester (Example 136A) in 6.7 ml of 1,4-dioxane was admixed with 2 M sodium hydroxide solution (2.5 ml). The mixture was stirred at 90° C. for a further 18 hours. The reaction mixture was admixed with 0.8 ml of dimethyl sulphoxide and stirred at 90° C. for a further 6 hours. The reaction mixture was concentrated under reduced pressure. The residue was admixed with acetonitrile (5 ml) and trifluoroacetic acid (0.8 ml), and then with water and dichloromethane. The organic phase was removed and concentrated under reduced pressure. The residue was purified by flash chromatography using a prepacked silica gel cartridge (mobile phase: dichloromethane/methanol, gradient 80% to 100%), which gave 105 mg (27% yield, 56% pure) of the target compound, which was used in the next step without further purification.

Workup

  1. stirringstirred at 90° C. for a further 6 hours
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customThe organic phase was removed
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash chromatography
  6. customgave 105 mg (27% yield, 56% pure) of the target compound, which
  7. customwas used in the next step without further purification

Sources & evidence

ORD record
ord-85e56f15b8f74b3597fc80e4012f2e0c
Source dataset
uspto-grants-2016_08
Patent number
US09422285B2

Reaction notes

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