Cesium carbonate → 5-(6-(2,4-Difluorophenyl)imidazo[2,1-b]oxazol-5-yl)-3-isopropylbenzo[d]isoxazole

HRID 1711791Notes

Reaction equation

HRID 1711791 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:9][N:8]=[C:7]([CH:10]([CH3:12])[CH3:11])[C:6]=2[CH:13]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].C(=O)([O-])[O-].[Cs+].[Cs+].[F:43][C:44]1[CH:49]=[C:48]([F:50])[CH:47]=[CH:46][C:45]=1[C:51]1[N:52]=[C:53]2[N:57]([C:58]=1I)[CH:56]=[CH:55][O:54]2>CN(C=O)C.O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:43][C:44]1[CH:49]=[C:48]([F:50])[CH:47]=[CH:46][C:45]=1[C:51]1[N:52]=[C:53]2[N:57]([C:58]=1[C:2]1[CH:3]=[CH:4][C:5]3[O:9][N:8]=[C:7]([CH:10]([CH3:12])[CH3:11])[C:6]=3[CH:13]=1)[CH:56]=[CH:55][O:54]2

Participants

11

Reactant 5

HCID 10796Cesium carbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 594578066-(2,4-Difluorophenyl)-5-iodoimidazo[2,1-b]oxazoleHCID 594578545-Bromo-3-isopropylbenzo[d]isoxazole

Product 1

HCID 594578075-(6-(2,4-Difluorophenyl)imidazo[2,1-b]oxazol-5-yl)-3-isopropylbenzo[d]isoxazoleYield 6.33%

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

5-Bromo-3-isopropylbenzo[d]isoxazole (0.120 g, 0.500 mmol), bis(pinacolato)diboron (0.130 g, 0.512 mmol), potassium acetate (0.098 g, 0.99 mmol) and PdCl2(dppf) (0.033 g, 0.045 mmol) in DMF (3 mL) was heated to about 90° C. for about 2 h then cooled, evaporated, triturated with DCM then filtered. The filtrate was concentrated under reduced pressure to give a dark oil which was dissolved in 1,4-dioxane (3 mL) and water (0.5 mL). Cesium carbonate (0.405 g, 1.24 mmol), PdCl2(PPh3)2 (0.035 g, 0.050 mmol) and 6-(2,4-difluorophenyl)-5-iodoimidazo[2,1-b]oxazole (0.173 g, 0.500 mmol; Example #2, step A) were added and the mixture was heated to about 90° C. oil bath for about 16 h. The solvents were evaporated and the material was purified by reverse phase chromatography (Table 1, Method c). Evaporation of the fractions with the desired product resulted in a precipitate which was collected by filtration to give the title compound (0.012 g, 6.33% yield) as a tan solid: LC/MS (Table 1, Method a) Rt, =3.08 min; MS m/z: 380.1 (M+H)+.

Workup

  1. temperaturethen cooled
  2. customevaporated
  3. customtriturated with DCM
  4. filtrationthen filtered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customto give a dark oil which
  7. customThe solvents were evaporated
  8. customthe material was purified by reverse phase chromatography (Table 1, Method c)
  9. customEvaporation of the fractions with the desired product
  10. customresulted in a precipitate which
  11. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-fc3ad397889f4a128ea303c822a2f245
Source dataset
uspto-grants-2010_09
Patent number
US07790741B2

Reaction notes

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