Triethylamine → 5-{(2-Fluoro-4,5-dimethoxyphenyl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-2-pyridazin-3-yl-2,4-dihydro-[1,2,4]triazol-3-one

HRID 2079204Notes

Reaction equation

HRID 2079204 reaction equation
CO[C:3](=[O:33])[N:4]=[C:5](SC)[C:6]([C:20]1[CH:25]=[C:24]([O:26][CH3:27])[C:23]([O:28][CH3:29])=[CH:22][C:21]=1[F:30])=[N:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:18]=[C:17]([CH3:19])[O:16][N:15]=2)=[CH:10][CH:9]=1.Cl.[NH:35]([C:37]1[N:38]=[N:39][CH:40]=[CH:41][CH:42]=1)[NH2:36].C(N(CC)CC)C>CN(C=O)C>[F:30][C:21]1[CH:22]=[C:23]([O:28][CH3:29])[C:24]([O:26][CH3:27])=[CH:25][C:20]=1[CH:6]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:18]=[C:17]([CH3:19])[O:16][N:15]=2)=[CH:10][CH:9]=1)[C:5]1[NH:4][C:3](=[O:33])[N:35]([C:37]2[N:38]=[N:39][CH:40]=[CH:41][CH:42]=2)[N:36]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 214559923-Hydrazinylpyridazine hydrochlorideHCID 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 1363666045-{(2-Fluoro-4,5-dimethoxyphenyl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-2-pyridazin-3-yl-2,4-dihydro-[1,2,4]triazol-3-oneYield 57.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 98 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 (Example (1d)) in 3 ml of DMF there were added 30.5 mg of 3-hydrazinopyridazine hydrochloride [CAS No. 117043-87-5] and 29 μl of triethylamine, and the mixture was stirred at 85° C. for 18 hours under a nitrogen atmosphere. The reaction mixture was concentrated, and the residue was dissolved in 3 ml of a methanol:THF=1:1 mixed solvent. After adding 44 μl of acetic acid and 65 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 5-{(2-fluoro-4,5-dimethoxyphenyl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-2-pyridazin-3-yl-2,4-dihydro-[1,2,4]triazol-3-one (60 mg).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue was dissolved in 3 ml of a methanol
  3. additionAfter adding 44 μl of acetic acid and 65 mg of sodium cyanotrihydroborate to the reaction mixture, it
  4. filtrationAfter filtering the reaction mixture, it
  5. customwas purified by reverse-phase high performance liquid chromatography (acetonitrile-water, 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-7699f4bb217e476691d672be68d77008
Source dataset
uspto-grants-2011_04
Patent number
US07928228B2

Reaction notes

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