Dimethylformamide → HCID 22240125, compound

HRID 891942Notes

Reaction equation

HRID 891942 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:14]=[N:13][CH:12]=[C:11]([CH2:15]O)[CH:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].CN(C=O)C.S(Cl)(Cl)=O.[CH3:26][C:27]1[NH:28][CH:29]=[CH:30][N:31]=1>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:14]=[N:13][CH:12]=[C:11]([CH2:15][N:28]3[CH:29]=[CH:30][N:31]=[C:27]3[CH3:26])[CH:10]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 127492-MethylimidazoleHCID 24386Thionyl ChlorideHCID 22240129[6-(3-Chloro-4-fluoro-phenyl)-pyridazin-4-yl]-methanol

Product 1

HCID 22240125HCID 22240125, compoundYield 24.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

[6-(3-Chloro-4-fluoro-phenyl)-pyridazin-4-yl]-methanol (13 mg, 0.054 mmol) was dissolved in MeCl2 (1 ml) under argon and a drop of DMF was added. The mixture was cooled with an icebath, thionylchloride (0.02 ml, 0.27 mmol) was added dropwise and the reaction mixture was allowed to warm to room temperature. After 30 minutes the reaction mixture was concentrated in vacuo. The residue was dissolved in ethanol and treated with 2-methyl-imidazole (22.3 mg, 0.27 mmol). The reaction mixture was refluxed for 12 hours then cooled to room temperature and concentrated. Ethyl acetate and a saturated NaHCO3 solution were added. The aqueous layer was extracted twice with ethyl acetate. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The residue was chromatographed over silica gel (CH2Cl2—MeOH 19:1) to provide 3-(3-chloro-4-fluoro-phenyl)-5-(2-methyl-imidazol-1-yl-methyl)-pyridazine (4 mg, 24%) as a light brown oil, MS: m/e=303.2 (M+H+).

Workup

  1. additionwas added dropwise
  2. concentrationAfter 30 minutes the reaction mixture was concentrated in vacuo
  3. dissolutionThe residue was dissolved in ethanol
  4. temperatureThe reaction mixture was refluxed for 12 hours
  5. temperaturethen cooled to room temperature
  6. concentrationconcentrated
  7. additionEthyl acetate and a saturated NaHCO3 solution were added
  8. extractionThe aqueous layer was extracted twice with ethyl acetate
  9. dry with materialThe combined organic layers were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was chromatographed over silica gel (CH2Cl2—MeOH 19:1)

Sources & evidence

ORD record
ord-47ecde26c0744d60b5c5b78388bd47f7
Source dataset
uspto-grants-2006_02
Patent number
US07005432B2

Reaction notes

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