Sodium hydride → 7-methyl-5-[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]imidazo[5,1-f][1,2,4]triazin-4(3H)-one

HRID 1498011Notes

Reaction equation

HRID 1498011 reaction equation
[H-].[Na+].[CH3:3][C:4]1[N:5]([NH:22][CH:23]=[NH:24])[CH:6]=[C:7]([C:9]2[CH:10]=[N:11][N:12]([CH3:21])[C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)[N:8]=1.[C:25](N1C=CN=C1)(N1C=CN=C1)=[O:26]>O1CCOCC1>[CH3:3][C:4]1[N:5]2[C:6]([C:25](=[O:26])[NH:24][CH:23]=[N:22]2)=[C:7]([C:9]2[CH:10]=[N:11][N:12]([CH3:21])[C:13]=2[C:14]2[CH:15]=[CH:16][C:17]([CH3:20])=[CH:18][CH:19]=2)[N:8]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 178423647HCID 178423647, compound

Product 1

HCID 1363502817-methyl-5-[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]imidazo[5,1-f][1,2,4]triazin-4(3H)-one

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

Sodium hydride (60% dispersion in mineral oil, 24 mg, 0.60 mmol) was added to a solution of N-{2-methyl-4-[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]-1H-imidazol-1-yl}imidoformamide (70 mg, 0.24 mmol) in 1,4-dioxane (4.0 mL), and the mixture was heated at 75° C. for 10 minutes. The reaction was cooled, treated with 1,1′-carbonyldiimidazole (135 mg, 0.833 mmol), allowed to stir at room temperature for 30 minutes, and then heated to 100° C. for 18 hours. After the reaction cooled to room temperature, it was quenched with water and diluted with ethyl acetate. The organic layer was washed with water, then with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Silica gel chromatography (Gradient: 0% to 10% methanol in ethyl acetate) afforded the product as a white solid. Yield: 55 mg, 0.17 mmol, 71%. LCMS m/z 321.5 (M+1). 1H NMR (400 MHz, DMSO-d6) δ 2.34 (br s, 3H), 2.36 (s, 3H), 3.71 (s, 3H), 7.22 (br d, J=8 Hz, 2H), 7.30 (d, J=8.2 Hz, 2H), 7.79 (s, 1H), 7.95 (s, 1H).

Workup

  1. temperatureThe reaction was cooled
  2. temperatureheated to 100° C. for 18 hours
  3. temperatureAfter the reaction cooled to room temperature
  4. customit was quenched with water
  5. additiondiluted with ethyl acetate
  6. washThe organic layer was washed with water
  7. dry with materialwith saturated aqueous sodium chloride solution, dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-48d25f6b51de49e4b88f592fbac58a0c
Source dataset
uspto-grants-2015_12
Patent number
US09200000B2

Reaction notes

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