Imidazole → HCID 57417712, compound

HRID 222255Notes

Reaction equation

HRID 222255 reaction equation
N1C=CN=C1.C1CCN2C(=NCCC2)CC1.[C:17]1([CH2:23][C:24](Cl)=[O:25])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[NH2:27][C:28]1[O:32][N:31]=[C:30]([C:33]2[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[C:34]=2[F:40])[C:29]=1[C:41]1[CH:46]=[CH:45][N:44]=[CH:43][CH:42]=1>C1COCC1.O>[F:40][C:34]1[C:35]([F:39])=[CH:36][CH:37]=[CH:38][C:33]=1[C:30]1[C:29]([C:41]2[CH:46]=[CH:45][N:44]=[CH:43][CH:42]=2)=[C:28]([NH:27][C:24](=[O:25])[CH2:23][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:32][N:31]=1

Participants

7

Reactant 4

HCID 795ImidazoleHCID 7679Phenylacetyl chlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2×HCID 57417713HCID 57417713, compound

Product 1

HCID 57417712HCID 57417712, compoundYield 45%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

In 3 mL of THF, 68 mg of imidazole and 152 mg of DBU were dissolved, into which 155 mg of phenylacetyl chloride was dropped under cooling with ice and stirring, followed by 1.5 hours' stirring at room temperature. Then a solution of 137 mg of 5-amino-3-(2,3-difluorophenyl)-4-(4-pyridyl)isoxazole and 152 mg of DBU in 3 mL of THF was added dropwise, followed by 26 hours' stirring at room temperature. After addition of water, the reaction solution was extracted with ethyl acetate. The ethyl acetate extract was washed first with saturated aqueous NaHCO3 solution and then with brine, dried over anhydrous magnesium sulfate, and removed of the solvent by reduced pressure distillation. The resultant residue was purified by thin-layer silica gel chromatography (developer, hexane:ethyl acetate=1:1) to provide 88 mg (yield: 45%) of the title compound as colorless crystal.

Workup

  1. additionwas dropped
  2. temperatureunder cooling with ice
  3. stirring' stirring at room temperature
  4. waitfollowed by 26 hours
  5. stirring' stirring at room temperature
  6. extractionthe reaction solution was extracted with ethyl acetate
  7. extractionThe ethyl acetate extract
  8. washwas washed first with saturated aqueous NaHCO3 solution
  9. dry with materialwith brine, dried over anhydrous magnesium sulfate
  10. customremoved of the solvent by reduced pressure distillation
  11. customThe resultant residue was purified by thin-layer silica gel chromatography (developer, hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-f71f985a88724cb2aa8704667fc536e0
Source dataset
uspto-grants-2012_06
Patent number
US08207203B2

Reaction notes

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