Hydrochloric Acid → 2-(3-{(2-Fluoro-4,5-dimethoxyphenyl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)benzoic acid

HRID 1698613Notes

Reaction equation

HRID 1698613 reaction equation
Cl.[NH:2]([C:4]1[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=1[C:6]([OH:8])=[O:7])[NH2:3].C(N(CC)CC)C.C[O:21][C:22](=O)[N:23]=[C:24](SC)[C:25]([C:39]1[CH:44]=[C:43]([O:45][CH3:46])[C:42]([O:47][CH3:48])=[CH:41][C:40]=1[F:49])=[N:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]2[N:37]=[C:36]([CH3:38])[O:35][N:34]=2)=[CH:29][CH:28]=1.Cl>CN(C)C=O>[F:49][C:40]1[CH:41]=[C:42]([O:47][CH3:48])[C:43]([O:45][CH3:46])=[CH:44][C:39]=1[C:25](=[N:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]2[N:37]=[C:36]([CH3:38])[O:35][N:34]=2)=[CH:29][CH:28]=1)[C:24]1[NH:23][C:22](=[O:21])[N:2]([C:4]2[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=2[C:6]([OH:8])=[O:7])[N:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 104169Benzoic acid, 2-hydrazinyl-, hydrochloride (1:1)HCID 72312823[2-(2-Fluoro-4,5-dimethoxyphenyl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene]carbamic acid methyl ester

Product 1

HCID 1361736382-(3-{(2-Fluoro-4,5-dimethoxyphenyl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)benzoic acidYield 95.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
85 °C

Procedure

After adding 240 mg of 2-hydrazinobenzoic acid hydrochloride and 0.295 ml of triethylamine to a solution of 500 mg of [2-(2-fluoro-4,5-dimethoxyphenyl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene]carbamic acid methyl ester in 10 ml of N,N-dimethylformamide (hereinafter, “DMF”), the mixture was stirred at 85° C. for 21 hours under a nitrogen atmosphere. After cooling the reaction mixture to room temperature, dilute hydrochloric acid (pH 3-4) was added and extraction was performed with ethyl acetate. The organic layer was then washed with dilute hydrochloric acid (pH 3-4) and saturated brine, and dried over anhydrous sodium sulfate. The desiccating agent was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by NAM silica gel column chromatography (methanol-ethyl acetate) to give the title compound (548 mg) as a light yellow solid.

Workup

  1. temperatureAfter cooling the reaction mixture to room temperature
  2. extractionextraction
  3. washThe organic layer was then washed with dilute hydrochloric acid (pH 3-4) and saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationThe desiccating agent was filtered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe residue was purified by NAM silica gel column chromatography (methanol-ethyl acetate)

Sources & evidence

ORD record
ord-f8f964adff444e07875543df1cd33850
Source dataset
uspto-grants-2012_04
Patent number
US08163787B2

Reaction notes

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