Methyl iodide → HCID 67067674, compound

HRID 1037309Notes

Reaction equation

HRID 1037309 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][N:5]2[C:8](=[O:19])[N:9]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[N:10]=[C:4]2[C:3]=1[O:20][CH2:21]OCC[Si](C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].IC.CCOC(C)=O>O>[Br:1][C:2]1[CH:7]=[CH:6][N:5]2[C:8](=[O:19])[N:9]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:16])([CH3:17])[CH3:18])[N:10]=[C:4]2[C:3]=1[O:20][CH3:21]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 67067921HCID 67067921, compound

Product 1

HCID 67067674HCID 67067674, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred suspension of the mixture of 7-bromo-8-methoxy-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one and 7-bromo-8-hydroxy-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one (from step 4) in DCM (120 mL) at 0° C. was added DIPEA (35 mL, 0.2 mol). After 5 min, (2-chloromethoxy-ethyl)-trimethylsilane (11.9 mL, 67.2 mmol) was added. The mixture was stirred at 0° C. for 1 hour and at RT for a further 2 hours. The resulting mixture was diluted with DCM (200 mL) and washed successively with 0.5 M HCl (aq) (400 mL) and water, dried (Na2SO4), filtered, and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 15 to 30% ethyl acetate in cyclohexane) to afford the title compound (1.30 g, 20%) as a yellow solid. Fractions containing 7-bromo-8-(2-trimethylsilanyl-ethoxymethoxy)-2-(2-trimethylsilanyl-ethoxymethyl)-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one were evaporated and the resultant residue was dissolved in MeOH (120 mL). The solution was stirred for 8 days at RT before evaporating to dryness. The resultant residue was dissolved in DMF (25 mL), cooled to 0° C., and cesium carbonate (13 g, 40 mmol) and iodomethane (3.11 mL, 50 mmol) were added. The reaction mixture was stirred at RT for 16 hours. EtOAc and water were added, the aqueous phase was isolated and extracted twice with EtOAc. The combined organic extracts were washed with water and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 15 to 30% EtOAc in cyclohexane) to afford a further quantity of the title compound (3.26 g, 51%) as a yellow solid. LCMS (Method A): RT=4.70 min, [M+H]+=396/398.

Workup

  1. customwere evaporated
  2. dissolutionthe resultant residue was dissolved in MeOH (120 mL)
  3. custombefore evaporating to dryness
  4. dissolutionThe resultant residue was dissolved in DMF (25 mL)
  5. temperaturecooled to 0° C.
  6. stirringThe reaction mixture was stirred at RT for 16 hours
  7. customthe aqueous phase was isolated
  8. extractionextracted twice with EtOAc
  9. washThe combined organic extracts were washed with water and brine
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b61e3c156eba453bbbd2fffabd7e398b
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Reaction notes

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