Dimethylformamide → (3-(1-(2,6-difluorophenyl)-4-methoxy-1H-pyrazolo[4,3-c]pyridin-3-yl)phenyl)acetic acid

HRID 2206214Notes

Reaction equation

HRID 2206214 reaction equation
FC(F)(F)S(O[C:7]1[C:11]2[C:12]([O:16][CH3:17])=[N:13][CH:14]=[CH:15][C:10]=2[N:9]([C:18]2[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:19]=2[F:25])[N:8]=1)(=O)=O.CN(C=O)C.CC1(C)C(C)(C)OB([C:41]2[CH:42]=[C:43]([CH2:47][C:48]([O:50]C)=[O:49])[CH:44]=[CH:45][CH:46]=2)O1.C(=O)([O-])[O-].[K+].[K+]>O>[F:24][C:23]1[CH:22]=[CH:21][CH:20]=[C:19]([F:25])[C:18]=1[N:9]1[C:10]2[CH:15]=[CH:14][N:13]=[C:12]([O:16][CH3:17])[C:11]=2[C:7]([C:41]2[CH:42]=[C:43]([CH2:47][C:48]([OH:50])=[O:49])[CH:44]=[CH:45][CH:46]=2)=[N:8]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 110977913-(2-Methoxy-2-oxoethyl)phenylboronic acid, pinacol esterHCID 1179878991-(2,6-difluorophenyl)-4-methoxy-1H-pyrazolo[4,3-c]pyridin-3-yl trifluoromethanesulfonate

Product 1

HCID 117988351(3-(1-(2,6-difluorophenyl)-4-methoxy-1H-pyrazolo[4,3-c]pyridin-3-yl)phenyl)acetic acidYield 35.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
90 °C

Procedure

To a solution of 1-(2,6-difluorophenyl)-4-methoxy-1H-pyrazolo[4,3-c]pyridin-3-yl trifluoromethanesulfonate (600 mg) obtained in Step C of Example 35 in a mixed solvent of DMF (5 mL)/water (0.5 mL) were added methyl (3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetate (567 mg), (1,1′-bis(diphenylphosphino)ferrocene)dichloropalladium(II) (60 mg) and potassium carbonate (405 mg). The reaction mixture was stirred overnight at 90° C. The reaction mixture was diluted with water, and the aqueous layer was washed with ethyl acetate. The aqueous layer was neutralized with 1M hydrochloric acid at 0° C., and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (205 mg).

Workup

  1. washthe aqueous layer was washed with ethyl acetate
  2. customwas neutralized with 1M hydrochloric acid at 0° C.
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-79f20118c84a416f8ddafec6e5401a0c
Source dataset
uspto-grants-2016_06
Patent number
US09371320B2

Reaction notes

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