Triethylamine → 5-{(3-Ethoxy-4-methoxyphenyl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-2-pyrimidin-2-yl-2,4-dihydro-[1,2,4]triazol-3-one

HRID 1698640Notes

Reaction equation

HRID 1698640 reaction equation
[NH:1]([C:3]1[N:8]=[CH:7][CH:6]=[CH:5][N:4]=1)[NH2:2].C(N(CC)CC)C.C[O:17][C:18](=O)[N:19]=[C:20](SC)[C:21]([C:35]1[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[C:37]([O:43][CH2:44][CH3:45])[CH:36]=1)=[N:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[N:33]=[C:32]([CH3:34])[O:31][N:30]=2)=[CH:25][CH:24]=1>CN(C=O)C>[CH2:44]([O:43][C:37]1[CH:36]=[C:35]([CH:21]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([C:29]3[N:33]=[C:32]([CH3:34])[O:31][N:30]=3)=[CH:25][CH:24]=2)[C:20]2[NH:19][C:18](=[O:17])[N:1]([C:3]3[N:8]=[CH:7][CH:6]=[CH:5][N:4]=3)[N:2]=2)[CH:40]=[CH:39][C:38]=1[O:41][CH3:42])[CH3:45]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 3465582-HydrazinylpyrimidineHCID 72312787{2-(3-Ethoxy-4-methoxyphenyl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene}carbamic acid methyl ester

Product 1

HCID 1361737645-{(3-Ethoxy-4-methoxyphenyl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-2-pyrimidin-2-yl-2,4-dihydro-[1,2,4]triazol-3-oneYield 38.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

After adding 230 mg of 2-hydrazinopyrimidine and 293 μl of triethylamine to a 50 ml DMF solution containing 983 mg of {2-(3-ethoxy-4-methoxyphenyl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene}carbamic acid methyl ester, the mixture was stirred at 85° C. for 10 hours under a nitrogen atmosphere. The reaction mixture was concentrated, and the residue was dissolved in 30 ml of a methanol:THF=1:1 mixed solvent. After adding 420 μl of acetic acid and 657 mg of sodium cyanotrihydroborate to the reaction mixture, it was stirred at room temperature for 5 hours. Ethyl acetate was added to the reaction mixture which was then filtered through a small amount of NAM silica gel, and the silica gel was washed with ethyl acetate-methanol. The filtrate was concentrated under reduced pressure, and the residue was purified by NAM silica gel column chromatography (methanol-ethyl acetate) to give the title compound (400 mg) as a light yellow solid.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue was dissolved in 30 ml of a methanol
  3. additionAfter adding 420 μl of acetic acid and 657 mg of sodium cyanotrihydroborate to the reaction mixture, it
  4. stirringwas stirred at room temperature for 5 hours
  5. additionEthyl acetate was added to the reaction mixture which
  6. filtrationwas then filtered through a small amount of NAM silica gel
  7. washthe silica gel was washed with ethyl acetate-methanol
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customthe residue was purified by NAM silica gel column chromatography (methanol-ethyl acetate)

Sources & evidence

ORD record
ord-3d2149e0a99a4d3a8ce0f532f8c229b2
Source dataset
uspto-grants-2012_04
Patent number
US08163787B2

Reaction notes

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