Potassium Carbonate → HCID 76900026, compound

HRID 1484169Notes

Reaction equation

HRID 1484169 reaction equation
F[C:2]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[C:17]([C:25]([F:28])([F:27])[F:26])[C:3]=1[C:4]([NH:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]([O:15]C)=[O:14])=[N:11][CH:12]=1)=[O:5].[CH3:29][O:30][C:31]1[CH:36]=[C:35]([O:37][CH3:38])[CH:34]=[CH:33][C:32]=1[OH:39].C([O-])([O-])=O.[K+].[K+].[OH-].[Na+]>CN(C=O)C>[CH3:29][O:30][C:31]1[CH:36]=[C:35]([O:37][CH3:38])[CH:34]=[CH:33][C:32]=1[O:39][C:2]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[C:17]([C:25]([F:27])([F:26])[F:28])[C:3]=1[C:4]([NH:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]([OH:15])=[O:14])=[N:11][CH:12]=1)=[O:5]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 5930062,4-DimethoxyphenolHCID 90314496HCID 90314496, compound

Product 1

HCID 76900026HCID 76900026, compoundYield 22.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

Methyl 5-[[2-fluoro-4,6-bis(trifluoromethyl)benzoyl]amino]pyridine-2-carboxylate (60 mg, 0.15 mmol), 2,4-dimethoxyphenol (24.80 mg, 0.16 mmol) and K2CO3 (60.66 mg, 0.44 mmol) were combined in DMF (0.4 mL) and heated at 70° C. Once the reaction was completed (by HPLC), aqueous 5 M NaOH (87.8 μL, 0.44 mmol) was added and the reaction was heated to 50° C. and monitored by HPLC until the reaction was complete. The reaction was cooled to 25° C., filtered and purified by reverse phase HPLC using a gradient of 1-99% ACN in Water and HCl as a modifier to yield 5-(2-(2,4-dimethoxyphenoxy)-4,6-bis(trifluoromethyl)benzamido)picolinic acid (49) (18 mg, 22%). ESI-MS m/z calc. 530.09. found 531.3 (M+1)+; Retention time: 1.54 minutes (3 minutes run). 1H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 8.89 (d, J=2.5 Hz, 1H), 8.32 (dd, J=8.6, 2.5 Hz, 1H), 8.10 (d, J=8.5 Hz, 1H), 7.90 (s, 1H), 7.17 (d, J=8.8 Hz, 1H), 7.07 (s, 1H), 6.79 (d, J=2.8 Hz, 1H), 6.61 (dd, J=8.9, 2.8 Hz, 1H), 3.78 (d, J=14.3 Hz, 6H) ppm.

Workup

  1. additionwas added
  2. temperaturethe reaction was heated to 50° C.
  3. temperatureThe reaction was cooled to 25° C.
  4. filtrationfiltered
  5. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-cccf9b281968404ebae8f152bc085027
Source dataset
uspto-grants-2016_08
Patent number
US09421196B2

Reaction notes

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