Sodium hydride → 4-(Cyclopropyl(4-methoxybenzyl)amino)-2-(methylthio)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 921610Notes

Reaction equation

HRID 921610 reaction equation
[H-].[Na+].[CH:3]1([NH:6][C:7]2[C:12]3=[N:13][CH:14]=[C:15]([C:16]#[N:17])[N:11]3[N:10]=[C:9]([S:18][CH3:19])[N:8]=2)[CH2:5][CH2:4]1.Cl[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=1>CN(C=O)C>[CH:3]1([N:6]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)[C:7]2[C:12]3=[N:13][CH:14]=[C:15]([C:16]#[N:17])[N:11]3[N:10]=[C:9]([S:18][CH3:19])[N:8]=2)[CH2:4][CH2:5]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 699934-Methyloxybenzyl chlorideHCID 867084574-(Cyclopropylamino)-2-(methylthio)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Product 1

HCID 867084584-(Cyclopropyl(4-methoxybenzyl)amino)-2-(methylthio)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileYield 91%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

(I2C): Sodium hydride (60% in mineral oil, 0.890 g, 22.02 mmol) was added to a solution of 4-(cyclopropylamino)-2-(methylthio)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (3.39 g, 13.76 mmol) in DMF (110 mL) at room temperature and the resulting mixture was stirred for 30 min. 1-(chloromethyl)-4-methoxybenzene (3.05 mL, 22.02 mmol) was added and the reaction mixture was heated at 80° C. for 2 h. The reaction solution was quenched with ethyl acetate/sodium bicarbonate saturated solution. The organic phase was separated, washed with 10% lithium chloride solution, dried and concentrated. The crude product was purified by flash chromatography on silica gel using an automated ISCO system (220 g column, eluting with 5-20% ethyl acetate/hexanes). 4-(cyclopropyl(4-methoxybenzyl)amino)-2-(methylthio)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (4.59 g) was obtained as an off-white solid.

Workup

  1. customThe reaction solution was quenched with ethyl acetate/sodium bicarbonate saturated solution
  2. customThe organic phase was separated
  3. washwashed with 10% lithium chloride solution
  4. customdried
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography on silica gel using
  7. washan automated ISCO system (220 g column, eluting with 5-20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-ade8e2cc5d1240c184ffcfee8aaac9cd
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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