Dimethylformamide → 2-(3{(2-Methoxy-6-methylpyridin-4-yl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl}benzoic acid

HRID 1161454Notes

Reaction equation

HRID 1161454 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.[CH3:20][O:21][C:22]1[CH:27]=[C:26]([C:28](=[N:32][C:33]2[CH:38]=[CH:37][C:36]([C:39]3[N:43]=[C:42]([CH3:44])[O:41][N:40]=3)=[CH:35][CH:34]=2)[C:29]([NH2:31])=S)[CH:25]=[C:24]([CH3:45])[N:23]=1.CN([CH:49]=[O:50])C>>[CH3:20][O:21][C:22]1[CH:27]=[C:26]([CH:28]([NH:32][C:33]2[CH:38]=[CH:37][C:36]([C:39]3[N:43]=[C:42]([CH3:44])[O:41][N:40]=3)=[CH:35][CH:34]=2)[C:29]2[NH:31][C:49](=[O:50])[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:25]=[C:24]([CH3:45])[N:23]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 104169Benzoic acid, 2-hydrazinyl-, hydrochloride (1:1)HCID 86617918HCID 86617918, compound

Product 1

HCID 1363664682-(3{(2-Methoxy-6-methylpyridin-4-yl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl}benzoic acid

Conditions

Temperature
85 °C

Procedure

After adding 39 mg of 2-hydrazinobenzoic acid hydrochloride and 57 μl of triethylamine to a solution of 90 mg of 2-(2-methoxy-6-methylpyridin-4-yl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]thioacetamide (Example (19b)) in 3 ml of DMF, the mixture was stirred at 85° C. for 16 hours under a nitrogen atmosphere. The reaction mixture was concentrated, and the residue was dissolved in 2 ml of a methanol:THF=1:1 mixed solvent. After adding 41 μl of acetic acid and 64 mg of sodium cyanotrihydroborate to the reaction mixture, the mixture was stirred at room temperature for 4 hours. After filtering the reaction mixture, it was purified by reverse-phase high performance liquid chromatography (acetonitrile-water, 0.1% acetic acid) to give 2-(3{(2-methoxy-6-methylpyridin-4-yl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl}benzoic acid (35 mg).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue was dissolved in 2 ml of a methanol
  3. additionAfter adding 41 μl of acetic acid and 64 mg of sodium cyanotrihydroborate to the reaction mixture
  4. stirringthe mixture was stirred at room temperature for 4 hours
  5. filtrationAfter filtering the reaction mixture, it
  6. customwas purified by reverse-phase high performance liquid chromatography (acetonitrile-water, 0.1% acetic acid)

Sources & evidence

ORD record
ord-1aa251dace2d4e67952498efa008f731
Source dataset
uspto-grants-2010_10
Patent number
US07816522B2

Reaction notes

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