Thionyl Chloride → 6-(Chloromethyl)imidazo[1,2-b]pyridazine

HRID 1798696Notes

Reaction equation

HRID 1798696 reaction equation
[N:1]1[CH:2]=[CH:3][N:4]2[C:9]=1[CH:8]=[CH:7][C:6]([CH2:10]O)=[N:5]2.S(Cl)([Cl:14])=O>>[Cl:14][CH2:10][C:6]1[CH:7]=[CH:8][C:9]2[N:4]([CH:3]=[CH:2][N:1]=2)[N:5]=1

Participants

3

Reactant 2

HCID 24386Thionyl ChlorideHCID 59580099Imidazo[1,2-b]pyridazin-6-ylmethanol

Product 1

HCID 595801656-(Chloromethyl)imidazo[1,2-b]pyridazineYield 69%

Procedure

Thionyl chloride (10 ml) was added to imidazo[1,2-b]pyridazin-6-ylmethanol (1.5 g, 9.0 mmol) at 20° C. under an atmosphere of nitrogen at RT. The reaction mixture was stirred at reflux for 3 h (the reaction was monitored by TLC) upon which the volatiles were removed under reduced pressure. The reaction mixture was diluted with water and extracted with EtOAc. The combined organics were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography using 15% ethyl acetate in n-hexane and silica gel (230-400 mesh) to afford 6-(chloromethyl) imidazo[1,2-b]pyridazine (1.2 g, 69%) as an off-white solid. 1H NMR, 200 MHz, DMSO-d6: δ 8.35 (s, 1H), 8.3 (d, 1H), 7.85 (s, 1H), 7.35 (d, 1H), 4.95 (s, 2H). MS: [M+H]+: m/z=149.9.

Workup

  1. temperatureat reflux for 3 h (the reaction
  2. customwere removed under reduced pressure
  3. additionThe reaction mixture was diluted with water
  4. extractionextracted with EtOAc
  5. dry with materialThe combined organics were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-c48cf72a4dcd491b9241998dadf82698
Source dataset
uspto-grants-2013_01
Patent number
US08343973B2

Reaction notes

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