Methyl iodide → 4-(Cyclohexylmethyl)-2-methyl-5-{2-[4-(3-nitrophenyl)piperazino]ethyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 1514166Notes

Reaction equation

HRID 1514166 reaction equation
[CH:1]1([CH2:7][N:8]2[C:12]([CH2:13][CH2:14][N:15]3[CH2:20][CH2:19][N:18]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([N+:27]([O-:29])=[O:28])[CH:22]=4)[CH2:17][CH2:16]3)=[N:11][NH:10][C:9]2=[O:30])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[CH3:33]I>CN(C=O)C>[CH:1]1([CH2:7][N:8]2[C:12]([CH2:13][CH2:14][N:15]3[CH2:16][CH2:17][N:18]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([N+:27]([O-:29])=[O:28])[CH:22]=4)[CH2:19][CH2:20]3)=[N:11][N:10]([CH3:33])[C:9]2=[O:30])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 595364714-(Cyclohexylmethyl)-5-{2-[4-(3-nitrophenyl)piperazin-1-yl]ethyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

Product 1

HCID 595364674-(Cyclohexylmethyl)-2-methyl-5-{2-[4-(3-nitrophenyl)piperazino]ethyl}-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 94.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 4-(cyclohexylmethyl)-5-{2-[4-(3-nitrophenyl)piperazin-1-yl]ethyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (D9; 500 mg, 1.207 mmol) and NaH (60% in mineral oil, 97 mg, 2.412 mmol), DMF (20 mL) was added and the slurry was stirred at room temperature for 10 min. Methyl iodide (0.226 mL, 3.621 mmol) was added and the reaction mixture was stirred at room temperature for 2.5 hrs. The reaction was quenched with water (3 mL) and the solvents were removed in vacuo. The resulting yellow solid was triturated with 10% MeOH in AcOEt (250 mL) and the solid filtered. The filtrate was evaporated to afford 1.3 g crude yellow solid which was further purified by flash chromatography (Flash Master, Biotage Isolute SI, 5 g column, gradient AcOEt for 3 min, then 0-10% MeOH in AcOEt for 27 min and 10% MeOH in AcOEt for 15 min) to afford 490 mg (94%) of the title compound as an orange solid.

Workup

  1. additionwas added
  2. stirringthe reaction mixture was stirred at room temperature for 2.5 hrs
  3. customThe reaction was quenched with water (3 mL)
  4. customthe solvents were removed in vacuo
  5. customThe resulting yellow solid was triturated with 10% MeOH in AcOEt (250 mL)
  6. filtrationthe solid filtered
  7. customThe filtrate was evaporated
  8. customto afford 1.3 g crude yellow solid which
  9. customwas further purified by flash chromatography (Flash Master, Biotage Isolute SI, 5 g column, gradient AcOEt for 3 min
  10. wait0-10% MeOH in AcOEt for 27 min

Sources & evidence

ORD record
ord-e7f31e7788264449b76ef2a2c5ccad73
Source dataset
uspto-grants-2012_07
Patent number
US08222254B2

Reaction notes

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