Triethylamine → 7-methyl-5-[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]-4-(1H-1,2,4-triazol-1-yl)imidazo[5,1-f][1,2,4]triazine

HRID 1907181Notes

Reaction equation

HRID 1907181 reaction equation
[NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.P(Cl)(Cl)(Cl)=O.C(N(CC)CC)C.[CH3:18][C:19]1[N:27]2[C:22]([C:23](=O)[NH:24][CH:25]=[N:26]2)=[C:21]([C:29]2[CH:30]=[N:31][N:32]([CH3:41])[C:33]=2[C:34]2[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][CH:35]=2)[N:20]=1>ClCCl>[CH3:18][C:19]1[N:27]2[C:22]([C:23]([N:1]3[CH:5]=[N:4][CH:3]=[N:2]3)=[N:24][CH:25]=[N:26]2)=[C:21]([C:29]2[CH:30]=[N:31][N:32]([CH3:41])[C:33]=2[C:34]2[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][CH:35]=2)[N:20]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 92571H-1,2,4-TriazoleHCID 24813Phosphorus oxychlorideHCID 1363502817-methyl-5-[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]imidazo[5,1-f][1,2,4]triazin-4(3H)-one

Product 1

HCID 681821117-methyl-5-[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]-4-(1H-1,2,4-triazol-1-yl)imidazo[5,1-f][1,2,4]triazine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

1H-1,2,4-Triazole (162 mg, 2.34 mmol) was pulverized, mixed with dichloromethane (4.0 mL) and cooled to 0° C. Phosphorus oxychloride (58.2 μL, 0.624 mmol) was added, followed after 1 minute by the drop-wise addition of triethylamine (0.349 mL, 2.50 mmol). After 10 minutes at 0° C., the ice bath was removed; 5 minutes later, 7-methyl-5-[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]imidazo[5,1-f][1,2,4]triazin-4(3H)-one (50 mg, 0.16 mmol) was added. The reaction mixture was maintained at room temperature for 4 hours, then cooled to 0° C. and quenched with water, then treated with saturated aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate, and the combined organic layers were washed with water, washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. This crude material was taken directly to the following step. LCMS m/z 372.5 (M+1). 1H NMR (400 MHz, DMSO-d6) δ 2.27 (br s, 3H), 2.70 (s, 3H), 3.73 (s, 3H), 6.86 (br d, J=8.2 Hz, 2H), 7.06 (br d, J=8.0 Hz, 2H), 7.37 (s 1H), 8.14 (s, 1H), 8.53 (s, 1H), 8.84 (s, 1H).

Workup

  1. customthe ice bath was removed
  2. temperatureThe reaction mixture was maintained at room temperature for 4 hours
  3. temperaturecooled to 0° C.
  4. customquenched with water
  5. additiontreated with saturated aqueous sodium bicarbonate solution
  6. extractionThe mixture was extracted with ethyl acetate
  7. washthe combined organic layers were washed with water
  8. washwashed with saturated aqueous sodium chloride solution
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2ef83b1e0ab9443eafecc5ae1fb4d946
Source dataset
uspto-grants-2013_12
Patent number
US08598155B2

Reaction notes

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