Sodium hydride → 4-((1,5-dimethyl-1H-1,2,4-triazol-3-yl)(4-methoxybenzyl)amino)-2-(methylthio)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 1430933Notes

Reaction equation

HRID 1430933 reaction equation
[CH3:1][N:2]1[C:6]([CH3:7])=[N:5][C:4]([NH:8][C:9]2[C:14]3=[N:15][CH:16]=[C:17]([C:18]#[N:19])[N:13]3[N:12]=[C:11]([S:20][CH3:21])[N:10]=2)=[N:3]1.[H-].[Na+].Cl[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1>CN(C=O)C>[CH3:1][N:2]1[C:6]([CH3:7])=[N:5][C:4]([N:8]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[C:9]2[C:14]3=[N:15][CH:16]=[C:17]([C:18]#[N:19])[N:13]3[N:12]=[C:11]([S:20][CH3:21])[N:10]=2)=[N:3]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 699934-Methyloxybenzyl chlorideHCID 867086354-((1,5-dimethyl-1H-1,2,4-triazol-3-yl)amino)-2-(methylthio)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Product 1

HCID 867086364-((1,5-dimethyl-1H-1,2,4-triazol-3-yl)(4-methoxybenzyl)amino)-2-(methylthio)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileYield 84.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-((1,5-dimethyl-1H-1,2,4-triazol-3-yl)amino)-2-(methylthio)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (157 mg, 0.521 mmol) was taken up in DMF (6 mL) under argon and NaH (22.92 mg, 0.573 mmol) was added. The reaction mixture was stirred at rt for 30 min, then alpha-chloro-4-methoxytoluene (0.074 mL, 0.547 mmol) was added. The reaction mixture was heated at 80° C. for 3 h. The reaction was quenched with sat'd NaHCO3 solution and extracted 3× with EtOAc. The organic layers were combined, dried over Na2SO4, filtered, and concentrated to give 4-((1,5-dimethyl-1H-1,2,4-triazol-3-yl)(4-methoxybenzyl)amino)-2-(methylthio)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (185 mg) as a red solid.

Workup

  1. temperatureThe reaction mixture was heated at 80° C. for 3 h
  2. customThe reaction was quenched with sat'd NaHCO3 solution
  3. extractionextracted 3× with EtOAc
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-8995d874a0ce436c8f434fe81d48fcf2
Source dataset
uspto-grants-2015_01
Patent number
US08940736B2

Reaction notes

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