반응 #1798969

ord-3a5fe81c8d12404ca796bc8ef8502798

용매

반응 조건

온도
-78°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타prepared
  2. 2
    온도the mixture was warmed to ambient temperature
  3. 3
    workup.STIRRINGthe mixture was stirred overnight
  4. 4
    기타the layers were separated
  5. 5
    건조The organic solution was dried over MgSO4
  6. 6
    여과filtered
  7. 7
    기타The filtrate was evaporated
  8. 8
    기타then purified by flash chromatography on 10 g silica gel with 95:5 DCM/MeOH as an eluent
  9. 9
    기타to give a residue that
  10. 10
    기타was triturated with Et2O/heptane

실험 절차

The ethyl 6-(6-(4-fluorophenyl)imidazo[2,1-b]oxazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-carboxylate (0.250 g, 0.639 mmol; prepared using A from 6-(4-fluorophenyl)-imidazo[2,1-b]oxazole [prepared according to WO2004110990A2, Example 1, Steps 1-3] with NIS, C with 2-fluoropyridine-5-boronic acid [Asymchem], D with hydrazine, K.1 with ethyl 2-oxoacetate) was suspended in THF (2.5 mL) then cooled to about −78° C. Methylmagnesium bromide (1.4 M in THF, 1.0 mL, 1.40 mmol) was added and then the mixture was warmed to ambient temperature. Additional methylmagnesium bromide (0.20 mL; 0.28 mmol) was added and then the mixture was stirred for about 15 min. Saturated aqueous ammonium chloride solution (1-2 mL) was added and then the mixture was stirred overnight. The reaction was diluted with DCM and then the layers were separated. The organic solution was dried over MgSO4 and then filtered. The filtrate was evaporated then purified by flash chromatography on 10 g silica gel with 95:5 DCM/MeOH as an eluent to give a residue that was triturated with Et2O/heptane to give the title compound (0.010 g, 4.1% yield): LC/MS (Table 1, Method a) Rt=1.89 min; MS m/z: 378.1 (M+H)+.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US07790741B2uspto-grants-2010_09