Acetic Acid → 6-(3-{[2-Fluoro-3-(2-fluoroethoxy)-5-methoxyphenyl]-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)pyridine-2-carboxylic acid

HRID 1161528Notes

Reaction equation

HRID 1161528 reaction equation
C[O:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([N:11]2[C:15](=[O:16])[NH:14][C:13]([CH:17]([C:31]3[CH:36]=[C:35]([O:37][CH3:38])[CH:34]=[C:33]([O:39][CH2:40][CH2:41][F:42])[C:32]=3[F:43])[NH:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]4[N:29]=[C:28]([CH3:30])[O:27][N:26]=4)=[CH:21][CH:20]=3)=[N:12]2)[N:6]=1)=[O:4].C1COCC1.[OH-].[Na+].C(O)(=O)C>CO>[F:43][C:32]1[C:33]([O:39][CH2:40][CH2:41][F:42])=[CH:34][C:35]([O:37][CH3:38])=[CH:36][C:31]=1[CH:17]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[N:29]=[C:28]([CH3:30])[O:27][N:26]=2)=[CH:21][CH:20]=1)[C:13]1[NH:14][C:15](=[O:16])[N:11]([C:7]2[N:6]=[C:5]([C:3]([OH:4])=[O:2])[CH:10]=[CH:9][CH:8]=2)[N:12]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 1361736316-(3-{[2-Fluoro-3-(2-fluoroethoxy)-5-methoxyphenyl]-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)pyridine-2-carboxylic acid methyl ester

Product 1

HCID 1361738316-(3-{[2-Fluoro-3-(2-fluoroethoxy)-5-methoxyphenyl]-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)pyridine-2-carboxylic acidYield 49.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

After dissolving 167 mg of 6-(3-{[2-fluoro-3-(2-fluoroethoxy)-5-methoxyphenyl]-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)pyridine-2-carboxylic acid methyl ester in 6 ml of a methanol:THF=2:1 mixed solvent, there was added 562 μl of a 5N aqueous sodium hydroxide solution and the mixture was stirred at room temperature for 15 hours. The mixture was adjusted to acidic with acetic acid and then concentrated under reduced pressure. The residue was dissolved in methanol, and the solution was filtered through celite and then purified by reverse-phase high performance liquid chromatography (acetonitrile-water, 0.1% trifluoroacetic acid) to give the title compound (81 mg) as a light yellow solid.

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residue was dissolved in methanol
  3. filtrationthe solution was filtered through celite
  4. custompurified by reverse-phase high performance liquid chromatography (acetonitrile-water, 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-76c14ea702e4435cb24fdc3bd87a5de3
Source dataset
uspto-grants-2010_10
Patent number
US07816522B2

Reaction notes

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