Trifluoroacetic acid → (s)-4-(2-Methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylic acid[3-(4-trifluoromethylphenyl)-2-propenyl]amide

HRID 856328Notes

Reaction equation

HRID 856328 reaction equation
[CH3:1][C@@:2]1([CH2:13][N:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22]C(C)(C)C)=O)[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.[F:41][C:42]([F:54])([F:53])[C:43]1[CH:48]=[CH:47][C:46]([CH:49]=[CH:50][CH2:51][NH2:52])=[CH:45][CH:44]=1.C(N1C=CN=C1)(N1C=CN=C1)=O>O.CN(C=O)C.C(Cl)Cl>[F:41][C:42]([F:53])([F:54])[C:43]1[CH:44]=[CH:45][C:46]([CH:49]=[CH:50][CH2:51][NH:52][C:20]([N:17]2[CH2:18][CH2:19][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)[CH2:15][CH2:16]2)=[O:22])=[CH:47][CH:48]=1

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 694813093-(4-Trifluoromethylphenyl)-2-propenylamineHCID 69635111tert-butyl (S)-4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylate

Product 1

HCID 69479568(s)-4-(2-Methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylic acid[3-(4-trifluoromethylphenyl)-2-propenyl]amideYield 96.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of tert-butyl (S)-4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylate prepared in Example 393 (926 mg, 2.52 mmol), trifluoroacetic acid (10 ml) and methylene chloride (3 ml) was stirred at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in DMF (3 ml) and neutralized with triethylamine (2 ml, 14.35 mmol). To the solution, a mixture of 3-(4-trifluoromethylphenyl)-2-propenylamine (761 mg, 3.78 mmol), 1,1′-carbonyldiimidazole (613 mg, 3.78 mmol) and DMF (3 ml) stirred at room temperature overnight was added followed by stirring at room temperature overnight. To the reaction mixture, water was added followed by extraction with ethyl acetate. The extract was washed with water three times and a saturated saline solution, dried over magnesium sulfate and then filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (methylene chloride/methanol=20/1) to afford (S)-4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylic acid[3-(4-trifluoromethylphenyl)-2-propenyl]amide (1.2 g, yield 96%) as a light yellow powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in DMF (3 ml)
  3. stirringstirred at room temperature overnight
  4. additionwas added
  5. stirringby stirring at room temperature overnight
  6. extractionfollowed by extraction with ethyl acetate
  7. washThe extract was washed with water three times
  8. dry with materiala saturated saline solution, dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customthe residue was purified by silica gel column chromatography (methylene chloride/methanol=20/1)

Sources & evidence

ORD record
ord-fad85264a1d9402c8969d5e7524a81ba
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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