Triethylamine → 2-(3-{(5-ethoxy-2-fluoro-4-methoxyphenyl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-1H-[1,2,4]triazol-1-yl)benzoic acid

HRID 1161482Notes

Reaction equation

HRID 1161482 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][CH2:46][CH3:47])[C:42]([O:48][CH3:49])=[CH:41][C:40]=1[F:50])=[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>CN(C=O)C>[CH2:46]([O:45][C:43]1[C:42]([O:48][CH3:49])=[CH:41][C:40]([F:50])=[C:39]([CH:25]([NH:26][C:27]2[CH:28]=[CH:29][C:30]([C:33]3[N:37]=[C:36]([CH3:38])[O:35][N:34]=3)=[CH:31][CH:32]=2)[C:24]2[NH:23][C:22](=[O:21])[N:2]([C:4]3[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=3[C:6]([OH:8])=[O:7])[N:3]=2)[CH:44]=1)[CH3:47]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 104169Benzoic acid, 2-hydrazinyl-, hydrochloride (1:1)HCID 86617920HCID 86617920, compound

Product 1

HCID 1363661532-(3-{(5-ethoxy-2-fluoro-4-methoxyphenyl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-1H-[1,2,4]triazol-1-yl)benzoic acidYield 63.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

After adding 16 mg of 2-hydrazinobenzoic acid hydrochloride and 25 μl of triethylamine to a solution of 85 mg of {2-(5-ethoxy-2-fluoro-4-methoxyphenyl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanyl-ethylidene}carbamic acid methyl ester (see Example (115b)) in 3 ml of DMF, the mixture was stirred at 90° C. for 14 hours under a nitrogen atmosphere. The reaction mixture was concentrated, and the residue was dissolved in 3 ml of a methanol:THF=2:1 mixed solvent. After adding 35 μl of acetic acid and 55 mg of sodium cyanotrihydroborate to the reaction mixture, it was stirred at room temperature for 6 hours. After filtering the reaction mixture, it was purified by reverse-phase high performance liquid chromatography (acetonitrile-water, 0.1% trifluoroacetic acid) to give 2-(3-{(5-ethoxy-2-fluoro-4-methoxyphenyl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-1H-[1,2,4]triazol-1-yl)benzoic acid (30 mg).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue was dissolved in 3 ml of a methanol
  3. additionAfter adding 35 μl of acetic acid and 55 mg of sodium cyanotrihydroborate to the reaction mixture, it
  4. stirringwas stirred at room temperature for 6 hours
  5. filtrationAfter filtering the reaction mixture, it
  6. customwas purified by reverse-phase high performance liquid chromatography (acetonitrile-water, 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-1311a9e839414c09a1990bce734ca33d
Source dataset
uspto-grants-2010_10
Patent number
US07816522B2

Reaction notes

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