Trifluoroacetic acid → HCID 69481769, compound

HRID 856237Notes

Reaction equation

HRID 856237 reaction equation
[CH3:1][N:2]([CH2:18][C@:19]1([CH3:30])[O:23][C:22]2=[N:24][C:25]([N+:27]([O-:29])=[O:28])=[CH:26][N:21]2[CH2:20]1)[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11](OC(C)(C)C)=O)[CH2:7][CH2:6]1.FC(F)(F)C(O)=O.[F:38][C:39]([F:49])([F:48])[C:40]1[CH:47]=[CH:46][C:43](C=O)=[CH:42][CH:41]=1.[B-]C#N.[Na+].C(=O)([O-])O.[Na+]>C(Cl)Cl.C(O)(=O)C>[CH3:1][N:2]([CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:43]2[CH:46]=[CH:47][C:40]([C:39]([F:49])([F:48])[F:38])=[CH:41][CH:42]=2)[CH2:7][CH2:6]1)[CH2:18][C@:19]1([CH3:30])[O:23][C:22]2=[N:24][C:25]([N+:27]([O-:29])=[O:28])=[CH:26][N:21]2[CH2:20]1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 679964-(Trifluoromethyl)benzaldehydeHCID 516892Sodium BicarbonateHCID 20587905Sodium cyanoborohydride [MI]HCID 69635278HCID 69635278, compound

Product 1

HCID 69481769HCID 69481769, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent2×

Procedure

Tert-butyl (S)-4-[2-(N-methyl-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethylamino)-ethyl]piperazine-1-carboxylate prepared in Example 173 (400 mg, 0.94 mmol) was dissolved in methylene chloride (5 ml). To the solution, trifluoroacetic acid (5 ml) was added followed by stirring at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure and added methylene chloride (2 ml) and triethylamine (2 ml). After stirring for 5 minutes at room temperature, the solution was concentrated under reduced pressure. The residue was dissolved in methanol (10 ml). To the solution, 4-(trifluoromethyl)benzaldehyde (0.4 ml, 2.83 mmol), sodium cyanotrihydroborate (178 mg, 2.83 mmol) and acetic acid (0.2 ml) were added followed by stirring at room temperature for 30 minutes. To the solution, a saturated sodium hydrogencarbonate solution and methylene chloride were added followed by stirring, and the mixture was extracted with methylene chloride. The organic phase was dried over magnesium sulfate. After filtration, the resulting filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methylene chloride/methanol=200/1) and crystallized from methylene chloride-isopropyl ether to afford (S)-N-methyl-N-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)-2-[4-(4-trifluoromethylbenzyl)piperazin-1-yl]ethylamine (307 mg, yield 68%) as a white powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionadded methylene chloride (2 ml) and triethylamine (2 ml)
  3. stirringAfter stirring for 5 minutes at room temperature
  4. concentrationthe solution was concentrated under reduced pressure
  5. dissolutionThe residue was dissolved in methanol (10 ml)
  6. stirringby stirring at room temperature for 30 minutes
  7. stirringby stirring
  8. extractionthe mixture was extracted with methylene chloride
  9. dry with materialThe organic phase was dried over magnesium sulfate
  10. filtrationAfter filtration
  11. concentrationthe resulting filtrate was concentrated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (methylene chloride/methanol=200/1)
  13. customcrystallized from methylene chloride-isopropyl ether

Sources & evidence

ORD record
ord-734faf7a9c9d4a18ae126686797c3672
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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