Dichloromethane → 1-(6-(6-(2,4-Difluorophenyl)imidazo[2,1-b]oxazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethanone

HRID 1930011Notes

Reaction equation

HRID 1930011 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[N:15]([C:16]=1[C:17]1[CH:18]=[CH:19][C:20]3[N:21]([C:23]([C:26](OCC)=[O:27])=[N:24][N:25]=3)[N:22]=1)[CH:14]=[CH:13][O:12]2.[CH3:31][Mg]Cl.[Cl-].[NH4+].C(Cl)Cl>C1COCC1.O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[N:15]([C:16]=1[C:17]1[CH:18]=[CH:19][C:20]3[N:21]([C:23]([C:26](=[O:27])[CH3:31])=[N:24][N:25]=3)[N:22]=1)[CH:14]=[CH:13][O:12]2

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 25517Ammonium ChlorideHCID 57929910Ethyl 6-(6-(2,4-difluorophenyl)imidazo[2,1-b]oxazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazine-3-carboxylateHCID 178418332HCID 178418332, compound

Product 1

HCID 579298721-(6-(6-(2,4-Difluorophenyl)imidazo[2,1-b]oxazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethanone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-30 °C

Procedure

In a 100 mL round-bottomed flask, ethyl 6-(6-(2,4-difluorophenyl)imidazo[2,1-b]oxazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazine-3-carboxylate (2.00 g, 4.87 mmol, Example #37, Step D) was suspended in THF (30 mL) and cooled to about −30° C. Methylmagnesium chloride (3.0 M in THF, 6.50 mL, 19.5 mmol) was added over about 10 min to the suspension. The mixture was stirred for about 25 min at about −30° C., followed by slow addition of a saturated solution of ammonium chloride (15 mL). The suspension was diluted with the addition of water (20 mL) and then DCM (20 mL). The layers were separated and the aqueous layer was extracted DCM (2×50 mL). The combined organic extracts were washed with water and brine, dried over MgSO4, filtered, and the solvents were removed under reduced pressure to give a solid that was triturated with Et2O (15 mL) and collected by vacuum filtration as a powder (1.50 g, 81%): LC/MS (Table 1, Method g) Rt=2.06 min; MS m/z: 380.9 (M+H)+.

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted DCM (2×50 mL)
  3. washThe combined organic extracts were washed with water and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customthe solvents were removed under reduced pressure
  7. customto give a solid
  8. customthat was triturated with Et2O (15 mL)
  9. filtrationcollected by vacuum filtration as a powder (1.50 g, 81%)

Sources & evidence

ORD record
ord-f4656d8618f14ca38e56ea0ab5ad05a6
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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