4-Methylmorpholine → 5-(2-(2-chloro-4-fluorophenoxy)-6-(trifluoromethyl)benzamido)picolinic Acid

HRID 515081Notes

Reaction equation

HRID 515081 reaction equation
[Cl:1][C:2]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:3]=1[O:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[C:6]=1[C:7](O)=[O:8].[NH2:23][C:24]1[CH:25]=[CH:26][C:27]([C:30]([O:32]CC)=[O:31])=[N:28][CH:29]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[H-].[Na+]>>[Cl:1][C:2]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:3]=1[O:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:15])([F:17])[F:16])[C:6]=1[C:7]([NH:23][C:24]1[CH:25]=[CH:26][C:27]([C:30]([OH:32])=[O:31])=[N:28][CH:29]=1)=[O:8]

Participants

6

Reactant 5

HCID 79724-MethylmorpholineHCID 24758Sodium hydrideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 13816714Ethyl 5-aminopyridine-2-carboxylateHCID 903153352-(2-Chloro-4-fluoro-phenoxy)-6-(trifluoromethyl)benzoic acid

Product 1

HCID 778456145-(2-(2-chloro-4-fluorophenoxy)-6-(trifluoromethyl)benzamido)picolinic AcidYield 5.5%

Conditions

Temperature
100 °C

Procedure

A solution of 2-(2-chloro-4-fluoro-phenoxy)-6-(trifluoromethyl)benzoic acid (33.46 mg, 0.10 mmol), ethyl 5-aminopyridine-2-carboxylate (19.94 mg, 0.12 mmol), HATU (41.83 mg, 0.11 mmol) and N-methylmorpholine (21.99 μL, 0.20 mmol) was stirred at 100° C. for 8 hours. NaH (16.00 mg, 0.40 mmol) was added and the mixture was stirred at 100° C. for 10 min. The mixture was filtered and purified by reverse phase HPLC using a gradient of acetonitrile in Water (1-99%) and HCl as a modifier, to give 5-[[2-(2-chloro-4-fluoro-phenoxy)-6-(trifluoromethyl)benzoyl]amino]pyridine-2-carboxylic acid (74) (2.52 mg, 5%) as a white solid. ESI-MS m/z calc. 454.03, found 455.3 (M+1)+; Retention time: 1.42 minutes (3 minutes run).

Workup

  1. filtrationThe mixture was filtered
  2. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-74980e14a5f54648a41fe038f44899bb
Source dataset
uspto-grants-2015_08
Patent number
US09108903B2

Reaction notes

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