Sodium Iodide → 2-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazin-1-yl]-N-(4-trifluoromethylphenyl)acetamide

HRID 856283Notes

Reaction equation

HRID 856283 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2([CH3:26])[O:19][C:18]3=[N:20][C:21]([N+:23]([O-:25])=[O:24])=[CH:22][N:17]3[CH2:16]2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.C(N(CC)CC)C.BrC[C:43]([NH:45][C:46]1[CH:51]=[CH:50][C:49]([C:52]([F:55])([F:54])[F:53])=[CH:48][CH:47]=1)=[O:44].C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>O>[CH3:26][C:15]1([CH2:14][N:11]2[CH2:10][CH2:9][N:8]([CH2:6][C:43]([NH:45][C:46]3[CH:47]=[CH:48][C:49]([C:52]([F:53])([F:54])[F:55])=[CH:50][CH:51]=3)=[O:44])[CH2:13][CH2:12]2)[O:19][C:18]2=[N:20][C:21]([N+:23]([O-:25])=[O:24])=[CH:22][N:17]2[CH2:16]1

Participants

8

Reactant 6

HCID 5238Sodium IodideHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 27732524-(Trifluoromethyl)-alpha-bromo-acetanilideHCID 230810802-(4-Tert-butoxycarbonylpiperazin-1-yl)methyl-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole

Product 1

HCID 694814442-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazin-1-yl]-N-(4-trifluoromethylphenyl)acetamideYield 61.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 2-(4-tert-butoxycarbonylpiperazin-1-yl)methyl-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole prepared in Example 306 (500 mg, 1.36 mmol) and trifluoroacetic acid (15 ml) was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in methylene chloride (10 ml) and added triethylamine (2 ml, 14.35 mmol). The solution was concentrated under reduced pressure, and the residue was dissolved in DMF (10 ml). To the solution, 2-bromo-N-(4-trifluoromethylphenyl)acetamide (423 mg, 1.5 mmol), potassium carbonate (207 mg, 1.5 mmol), and sodium iodide (204 mg, 1.36 mmol) were added followed by stirring at room temperature for 5 hours. To the reaction mixture, water was added, and the solution was extracted with ethyl acetate twice. The organic phases were combined, washed with water three times and a saturated saline solution, dried over sodium sulfate and then filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (methylene chloride/methanol=100/1) to afford 2-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazin-1-yl]-N-(4-trifluoromethylphenyl)acetamide (389 mg, yield 61%) as a white powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in methylene chloride (10 ml)
  3. concentrationThe solution was concentrated under reduced pressure
  4. dissolutionthe residue was dissolved in DMF (10 ml)
  5. stirringby stirring at room temperature for 5 hours
  6. extractionthe solution was extracted with ethyl acetate twice
  7. washwashed with water three times
  8. dry with materiala saturated saline solution, dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customthe residue was purified by silica gel column chromatography (methylene chloride/methanol=100/1)

Sources & evidence

ORD record
ord-49e630d4b9d4450f8040a32545b5d4d3
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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