Acetic Acid → 2-[4-(Biphenyl-4-ylmethyl)piperazin-1-ylmethyl]-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole

HRID 856282Notes

Reaction equation

HRID 856282 reaction equation
[N+:1]([C:4]1[N:5]=[C:6]2[N:10]([CH:11]=1)[CH2:9][CH:8]([CH2:12][N:13]1[CH2:18][CH2:17][N:16]([C:19](OC(C)(C)C)=O)[CH2:15][CH2:14]1)[O:7]2)([O-:3])=[O:2].C(N(CC)CC)C.[C:33]1([C:39]2[CH:46]=[CH:45][C:42](C=O)=[CH:41][CH:40]=2)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[B-]C#N.[Na+].C(O)(=O)C>FC(F)(F)C(O)=O>[C:33]1([C:39]2[CH:40]=[CH:41][CH:42]=[CH:45][CH:46]=2)[CH:38]=[CH:37][C:36]([CH2:19][N:16]2[CH2:15][CH2:14][N:13]([CH2:12][CH:8]3[O:7][C:6]4=[N:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:11][N:10]4[CH2:9]3)[CH2:18][CH2:17]2)=[CH:35][CH:34]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 8471TriethylamineHCID 76689(1,1'-Biphenyl)-4-carboxaldehydeHCID 20587905Sodium cyanoborohydride [MI]HCID 23081438Tert-butyl 4-(6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylate

Product 1

HCID 694790592-[4-(Biphenyl-4-ylmethyl)piperazin-1-ylmethyl]-6-nitro-2,3-dihydroimidazo[2,1-b]oxazoleYield 40%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A mixture of tert-butyl 4-(6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylate prepared in Example 319 (400 mg, 1.13 mmol) and trifluoroacetic acid (10 ml) was stirred at room temperature for 4 hours. The reaction mixture was concentrated. The residue was dissolved in methylene chloride (10 ml) and neutralized with triethylamine (2 ml, 14.35 mmol). The resulting solution was concentrated under reduced pressure, and the residue was dissolved in methanol (10 ml). To the solution, 4-phenylbenzaldehyde (515 mg, 2.83 mmol), sodium cyanotrihydroborate (214 mg, 3.41 mmol) and acetic acid (0.21 mg, 3.67 mmol) were added in this order followed by stirring at room temperature overnight. The reaction mixture was concentrated. To the residue, water was added, and the solution was extracted with methylene chloride twice. The organic phases were combined, washed with a saturated sodium hydrogen-carbonate solution and a saturated saline solution in this order, dried over magnesium sulfate and then filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methylene chloride/methanol=20/1) to afford 2-[4-(biphenyl-4-ylmethyl)piperazin-1-ylmethyl]-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole (188 mg, yield 40%) as a white powder.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionThe residue was dissolved in methylene chloride (10 ml)
  3. concentrationThe resulting solution was concentrated under reduced pressure
  4. dissolutionthe residue was dissolved in methanol (10 ml)
  5. stirringby stirring at room temperature overnight
  6. concentrationThe reaction mixture was concentrated
  7. additionTo the residue, water was added
  8. extractionthe solution was extracted with methylene chloride twice
  9. washwashed with a saturated sodium hydrogen-carbonate solution
  10. dry with materiala saturated saline solution in this order, dried 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=20/1)

Sources & evidence

ORD record
ord-16870aa8d3274573bd1690c03382d75b
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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