1-Methylimidazole → HCID 86716074, compound

HRID 627499Notes

Reaction equation

HRID 627499 reaction equation
[Li]CCCC.[CH3:6][N:7]1[CH:11]=[CH:10][N:9]=[CH:8]1.Cl[Si](CC)(CC)CC.CON(C)[C:23]([C:25]1[CH:30]=[CH:29][N:28]=[N:27][CH:26]=1)=[O:24].CC#N.C(=O)=O>C1COCC1>[CH3:6][N:7]1[CH:11]=[CH:10][N:9]=[C:8]1[C:23]([C:25]1[CH:30]=[CH:29][N:28]=[N:27][CH:26]=1)=[O:24]

Participants

7

Reactant 5

HCID 13901-MethylimidazoleHCID 13819ChlorotriethylsilaneHCID 59574572N-Methoxy-N-methylpyridazine-4-carboxamideHCID 86587134Acetonitrile dry iceHCID 178418339Butyllithium2×

Product 1

HCID 86716074HCID 86716074, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

n-BuLi (1.6 M in hexane, 3.65 mL, 5.84 mmol) was added to a solution of 1-methylimidazole (0.452 mL, 5.7 mmol) in THF (30 mL) at −78° C. The mixture was stirred at −78° C. for 15 min. Chlorotriethylsilane (0.955 mL, 5.7 mmol) was added slowly. The mixture was removed from the dry ice/acetone bath and was stirred for 30 min. The mixture was again cooled in a dry ice/acetone bath before addition of a second portion of n-BuLi (1.6 M in hexane, 3.65 mL, 5.84 mmol). The mixture was stirred at −78° C. for 1 hour, then transferred to an ice bath and stirred 10 min. The mixture was again cooled in a dry ice/acetone bath before addition of a solution of N-methoxy-N-methylpyridazine-4-carboxamide (793 mg, 4.74 mmol, Intermediate 29, step a) in THF (15 mL) via cannula. The reaction mixture was stirred at −78° C. for 30 min, then was transferred to a slurry of CH3CN/dry ice and stirred for 15 min. The reaction was quenched by addition of water (50 mL) and the mixture was extracted with EtOAc three times. The organic phase was dried (Na2SO4), filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, gradient 0-4% MeOH-DCM first column, 75-100% EtOAc-heptanes second column) to afford the title compound.

Workup

  1. customThe mixture was removed from the dry ice/acetone bath
  2. stirringwas stirred for 30 min
  3. stirringThe mixture was stirred at −78° C. for 1 hour
  4. customtransferred to an ice bath
  5. stirringstirred 10 min
  6. stirringThe reaction mixture was stirred at −78° C. for 30 min
  7. stirringstirred for 15 min
  8. customThe reaction was quenched by addition of water (50 mL)
  9. extractionthe mixture was extracted with EtOAc three times
  10. dry with materialThe organic phase was dried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was purified by flash column chromatography (silica gel, gradient 0-4% MeOH-DCM first column, 75-100% EtOAc-heptanes second column)

Sources & evidence

ORD record
ord-3b0eceec6eab432fac706ed4f826ce37
Source dataset
uspto-grants-2016_04
Patent number
US09309222B2

Reaction notes

Loading…