2-Amino-4-methylpyridine → 2-(Chloromethyl)-7-methylimidazo[1,2-a]pyridine

HRID 849483Notes

Reaction equation

HRID 849483 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][N:3]=1.[Cl:9][CH2:10][C:11]([CH2:13]Cl)=O.COCCOC>C(O)C>[Cl:9][CH2:10][C:11]1[N:1]=[C:2]2[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][N:3]2[CH:13]=1

Participants

5

Reactant 3

HCID 15332-Amino-4-methylpyridineHCID 80711,2-DimethoxyethaneHCID 107931,3-Dichloroacetone

Product 1

HCID 140427782-(Chloromethyl)-7-methylimidazo[1,2-a]pyridineYield 1.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 2-amino-4-picoline (Aldrich; 500 g), 1,3-dichloroacetone (Aldrich; 5.89 g), and 1,2-dimethoxyethane (Aldrich; 44 mL) is stirred for 25 min at 53° C., at which time ethanol (47.5 mL) is added. After stirring for 2.5 h at reflux, the mixture is concentrated under reduced pressure and the residue is partitioned between dichloromethane and saturated sodium bicarbonate and brine. The organic layers are dried over MgSO4 and concentrated under reduced pressure. The crude material is chromatographed on silica gel using methanol/dichloromethane (1/99 to 2/98) to give, after crystallization from dichloromethane/hexane, 3.06 g of product. A portion of this material is dissolved in dichloromethane and refluxed with activated charcoal for 30 min. The activated charcoal is removed by filtration through a pad of diatomaceous earth and the filtrate is atmospherically concentrated, at which time hexane is added. The resulting solids are filtered, washed with hexane, and vacuum dried to give 0.15 g of 2-(chloromethyl)-7-methylimidazo[1,2-a]pyridine; mp 250° C. (decomp); ms m/z 180, 182; IR (mineral oil) 774, 1649, 1504, 1252, 701 cm-1 ; 1H NMR (CDCl3) δ 2.39, 4.75, 6.63, 7.32, 7.53, 7.95.

Workup

  1. additionis added
  2. temperatureat reflux
  3. concentrationthe mixture is concentrated under reduced pressure
  4. customthe residue is partitioned between dichloromethane and saturated sodium bicarbonate and brine
  5. dry with materialThe organic layers are dried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material is chromatographed on silica gel
  8. customto give
  9. customafter crystallization from dichloromethane/hexane, 3.06 g of product
  10. dissolutionA portion of this material is dissolved in dichloromethane
  11. temperaturerefluxed with activated charcoal for 30 min
  12. customThe activated charcoal is removed by filtration through a pad of diatomaceous earth
  13. concentrationthe filtrate is atmospherically concentrated, at which time hexane
  14. additionis added
  15. filtrationThe resulting solids are filtered
  16. washwashed with hexane, and vacuum
  17. customdried

Sources & evidence

ORD record
ord-56f151afd68742f89a99f2343fd291a9
Source dataset
uspto-grants-2000_01
Patent number
US06013654

Reaction notes

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