Triethylamine → 5-{(8-Methoxychroman-6-yl)-[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 1161418Notes

Reaction equation

HRID 1161418 reaction equation
C[O:2][C:3](=O)[N:4]=[C:5](SC)[C:6]([C:20]1[CH:21]=[C:22]2[C:27](=[C:28]([O:30][CH3:31])[CH:29]=1)[O:26][CH2:25][CH2:24][CH2:23]2)=[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.[NH:35]([C:37]1[N:42]=[CH:41][CH:40]=[CH:39][N:38]=1)[NH2:36].C(N(CC)CC)C>CN(C=O)C>[CH3:31][O:30][C:28]1[CH:29]=[C:20]([CH:6]([NH:7][C:8]2[CH:9]=[CH:10][C:11]([C:14]3[N:18]=[C:17]([CH3:19])[O:16][N:15]=3)=[CH:12][CH:13]=2)[C:5]2[NH:4][C:3](=[O:2])[N:35]([C:37]3[N:42]=[CH:41][CH:40]=[CH:39][N:38]=3)[N:36]=2)[CH:21]=[C:22]2[C:27]=1[O:26][CH2:25][CH2:24][CH2:23]2

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 3465582-HydrazinylpyrimidineHCID 72312814{2-(8-Methoxychroman-6-yl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene}carbamic acid methyl ester

Product 1

HCID 1363664005-{(8-Methoxychroman-6-yl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-2-pyrimidin-2-yl-2,4-dihydro-[1,2,4]triazol-3-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 281 mg of {2-(8-methoxychroman-6-yl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanyl-ethylidene}carbamic acid methyl ester in 2 ml of DMF there were added 58 mg of 2-hydrazinopyrimidine and 130 μl of triethylamine, and the mixture was stirred overnight at 85° C. under a nitrogen atmosphere. The reaction mixture was concentrated, and the residue was dissolved in 8.75 ml of a methanol:acetic acid=10:1 mixed solvent. After adding 265 mg of sodium cyanotrihydroborate to the reaction mixture, the mixture was stirred at room temperature for 1 hour. Water was added to the reaction mixture and extraction was performed with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The desiccating agent was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by NAM silica gel column chromatography (methanol-ethyl acetate) to give 5-{(8-methoxychroman-6-yl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-2-pyrimidin-2-yl-2,4-dihydro-[1,2,4]triazol-3-one.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue was dissolved in 8.75 ml of a methanol
  3. additionAfter adding 265 mg of sodium cyanotrihydroborate to the reaction mixture
  4. stirringthe mixture was stirred at room temperature for 1 hour
  5. additionWater was added to the reaction mixture and extraction
  6. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  7. filtrationThe desiccating agent was filtered off
  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-099d863f852f470cb3125bd90d812212
Source dataset
uspto-grants-2010_10
Patent number
US07816522B2

Reaction notes

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