Cesium carbonate → 6-(2,4-Difluorophenyl)-5-(6-hydrazinylpyridin-3-yl)imidazo[2,1-b]oxazole

HRID 1711785Notes

Reaction equation

HRID 1711785 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]=1I)[CH:14]=[CH:13][O:12]2.F[C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][N:20]=1.C([O-])([O-])=O.[Cs+].[Cs+].O.[NH2:35][NH2:36]>O1CCOCC1.C(O)CC.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:22]1[CH:23]=[CH:24][C:19]([NH:35][NH2:36])=[N:20][CH:21]=1)[CH:14]=[CH:13][O:12]2

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 24654Hydrazine hydrate (1:1)HCID 2783397(6-Fluoropyridin-3-yl)boronic acidHCID 594578066-(2,4-Difluorophenyl)-5-iodoimidazo[2,1-b]oxazole

Product 1

HCID 594578146-(2,4-Difluorophenyl)-5-(6-hydrazinylpyridin-3-yl)imidazo[2,1-b]oxazoleYield 63%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 10311-PropanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 6-(2,4-difluorophenyl)-5-iodo-imidazo[2,1-b]oxazole (5 g, 14.5 mmol), 2-fluoropyridine-5-boronic acid (3.1 g, 22 mmol; Asymchem), Cs2CO3 (12 g, 36 mmol), and trans-dichloro[bis(triphenylphosphine)]palladium (II) (1.1 g, 1.5 mmol) was dissolved in 1,4-dioxane (100 mL) and water (10 mL) at ambient temperature. The reaction was vacuum purged with N2 three times followed by heating to about 80° C. for about 2 h. The reaction was allowed to cool to ambient temperature upon which time it was concentrated under reduced pressure. The resulting oil was dissolved in DCM, filtered through a pad of silica gel and the silica gel was washed DCM (3×10 mL). The filtrate was concentrated under reduced pressure to provide a yellow solid. This solid was dissolved in n-PrOH (50 mL) followed by the addition of hydrazine hydrate (5.0 mL, 160 mmol) and the reaction was heated at about 100° C. for about 16 h. After this time the reaction was concentrated, and the resulting solid was triturated with Et2O and filtered. The filter cake was washed with water and dried in a vacuum oven for about 16 h to provide the title compound (2.98 g, 63% for 2 steps) as an off-white solid: LC/MS (Table 1, Method a) Rt=1.62 min; MS m/z: 342.1 (M+H)+.

Workup

  1. customat ambient temperature
  2. custompurged with N2 three times
  3. temperatureto cool to ambient temperature upon which time it
  4. concentrationwas concentrated under reduced pressure
  5. dissolutionThe resulting oil was dissolved in DCM
  6. filtrationfiltered through a pad of silica gel
  7. washthe silica gel was washed DCM (3×10 mL)
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customto provide a yellow solid
  10. temperaturethe reaction was heated at about 100° C. for about 16 h
  11. concentrationAfter this time the reaction was concentrated
  12. customthe resulting solid was triturated with Et2O
  13. filtrationfiltered
  14. washThe filter cake was washed with water
  15. customdried in a vacuum oven for about 16 h

Sources & evidence

ORD record
ord-cbb5a77a44ee4a9aa7cccd6f9a8abc29
Source dataset
uspto-grants-2010_09
Patent number
US07790741B2

Reaction notes

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