Trifluoroacetic acid → (s)-n-[1-(4-Chlorophenyl)ethylidene]-n-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazin-1-yl]amine

HRID 856343Notes

Reaction equation

HRID 856343 reaction equation
[CH3:1][C@@:2]1([CH2:13][N:14]2[CH2:19][CH2:18][N:17]([NH:20]C(=O)OC(C)(C)C)[CH2:16][CH2:15]2)[O:6][C:5]2=[N:7][C:8]([N+:10]([O-:12])=[O:11])=[CH:9][N:4]2[CH2:3]1.FC(F)(F)C(O)=O.C(N(CC)CC)C.[CH3:42][C:43]([C:45]1[CH:50]=[CH:49][C:48]([Cl:51])=[CH:47][CH:46]=1)=O>C(O)C.C(Cl)Cl>[Cl:51][C:48]1[CH:49]=[CH:50][C:45]([C:43](=[N:20][N:17]2[CH2:16][CH2:15][N:14]([CH2:13][C@:2]3([CH3:1])[O:6][C:5]4=[N:7][C:8]([N+:10]([O-:12])=[O:11])=[CH:9][N:4]4[CH2:3]3)[CH2:19][CH2:18]2)[CH3:42])=[CH:46][CH:47]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7467P-ChloroacetophenoneHCID 8471TriethylamineHCID 86760538tert-butyl(S)-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazin-1-yl]carbamate

Product 1

HCID 131726575(s)-n-[1-(4-Chlorophenyl)ethylidene]-n-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazin-1-yl]amineYield 18%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of tert-butyl (S)-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)-piperazin-1-yl]carbamate prepared in Example 503 (200 mg, 0.52 mmol), trifluoroacetic acid (2 ml) and methylene chloride (4 ml) was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in methylene chloride (4 ml) and then neutralized with triethylamine (4 ml, 28.7 mmol). To the neutralized solution, a solution of 4-chloroacetophenone (97 mg, 0.63 mmol) in ethanol (4 ml) was added followed by stirring under reflux for 4 hours. The reaction mixture was allowed to return to room temperature and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/acetone=3/1) to afford (S)-N-[1-(4-chlorophenyl)ethylidene]-N-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazin-1-yl]amine (39 mg, yield 18%) as a light yellow powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in methylene chloride (4 ml)
  3. stirringby stirring
  4. temperatureunder reflux for 4 hours
  5. customto return to room temperature
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (n-hexane/acetone=3/1)

Sources & evidence

ORD record
ord-97d36ffccc094f6089545e2d2d966b14
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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