Trifluoroacetic acid → (S)-2-[4-(2,6-diphenylpyrimidin-4-yl)piperazin-1-ylmethyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole

HRID 856334Notes

Reaction equation

HRID 856334 reaction equation
[CH3:1][C@@:2]1([CH2:13][N:14]2[CH2:19][CH2:18][N:17](C(OC(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.Cl[C:35]1[CH:40]=[C:39]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[N:38]=[C:37]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[N:36]=1.C1CCN2C(=NCCC2)CC1>C(Cl)Cl.O>[C:47]1([C:37]2[N:36]=[C:35]([N:17]3[CH2:16][CH2:15][N:14]([CH2:13][C@:2]4([CH3:1])[O:6][C:5]5=[N:7][C:8]([N+:10]([O-:12])=[O:11])=[CH:9][N:4]5[CH2:3]4)[CH2:19][CH2:18]3)[CH:40]=[C:39]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[N:38]=2)[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 5820414-Chloro-2,6-diphenylpyrimidineHCID 69635111tert-butyl (S)-4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylate

Product 1

HCID 69481071(S)-2-[4-(2,6-diphenylpyrimidin-4-yl)piperazin-1-ylmethyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazoleYield 17%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Tert-butyl (S)-4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylate prepared in Example 393 (500 mg, 1.36 mmol) was dissolved in methylene chloride (2 ml). To the solution, trifluoroacetic acid (10 ml) was added followed by stirring at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, and added methylene chloride (4 ml) and triethylamine (4 ml). The reaction mixture was stirred at room temperature for 5 minutes and then concentrated under reduced pressure, and the residue was dissolved in DMF (5 ml). To the solution, 4-chloro-2,6-diphenylpyrimidine (400 mg, 1.50 mmol) and DBU (0.2 ml, 1.36 mmol) were added followed by stirring at 100° C. for 5 hours. The reaction mixture was allowed to return to room temperature, poured into water, and then the mixture was extracted with ethyl acetate. The organic phase was washed with 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=100/1) and crystallized from methylene chloride-diisopropyl ether to afford (S)-2-[4-(2,6-diphenylpyrimidin-4-yl)piperazin-1-ylmethyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole (113 mg, yield 17%) as a white powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionadded methylene chloride (4 ml) and triethylamine (4 ml)
  3. stirringThe reaction mixture was stirred at room temperature for 5 minutes
  4. concentrationconcentrated under reduced pressure
  5. dissolutionthe residue was dissolved in DMF (5 ml)
  6. stirringby stirring at 100° C. for 5 hours
  7. customto return to room temperature
  8. extractionthe mixture was extracted with ethyl acetate
  9. washThe organic phase was washed with a saturated saline solution
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationThe filtrate was concentrated under reduced pressure
  13. customthe residue was purified by silica gel column chromatography (methylene chloride/methanol=100/1)
  14. customcrystallized from methylene chloride-diisopropyl ether

Sources & evidence

ORD record
ord-0278ecb79627436780fc5d03063ef3d6
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

Loading…