1,2-Dimethoxyethane → 6,8-Dichloro-2-(chloromethyl)imidazo[1,2-a]pyridine

HRID 849485Notes

Reaction equation

HRID 849485 reaction equation
[NH2:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([Cl:9])=[CH:4][N:3]=1.[Cl:10][CH2:11][C:12]([CH2:14]Cl)=O.C(COC)OC>C(O)C>[Cl:9][C:5]1[CH:6]=[C:7]([Cl:8])[C:2]2[N:3]([CH:14]=[C:12]([CH2:11][Cl:10])[N:1]=2)[CH:4]=1

Participants

5

Reactant 3

HCID 80711,2-DimethoxyethaneHCID 107931,3-DichloroacetoneHCID 778863,5-Dichloro-3-pyridylamine

Product 1

HCID 47730446,8-Dichloro-2-(chloromethyl)imidazo[1,2-a]pyridineYield 30%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 2-amino-3,5-dichloropyridine (Aldrich; 5.12 g), 1,3-dichloroacetone (Aldrich; 4.68 g), and dimethoxyethane (28 mL) is stirred overnight at room temperature. Ethanol (28 mL) is then added and the mixture is refluxed for 7.5 h and then stirred overnight at room temperature. The mixture is then refluxed for an additional 24 h and is then concentrated under reduced pressure and partitioned between saturated aq. sodium bicarbonate and dichloromethane. The combined organic layers are washed with brine, dried with MgSO4, and concentrated under reduced pressure. The residue is adsorbed to silica gel and chromatographed on silica gel using ethyl acetate/chloroform (10/90), followed by a second chromatography of the combined product fractions using methanol/dichloromethane (2/98), to give 2.22 g of 6,8-dichloro-2-(chloromethyl)imidazo[1,2-a]pyridine in three crops after crystallization from methanol/dichloromethane; mp 162-163° C.; MS m/z 234, 236, 238; IR (mineral oil) 994, 808, 861, 1522, 3056 cm-1, 1H NMR (CDCl3) δ 4.79, 7.69, 8.10.

Workup

  1. temperaturethe mixture is refluxed for 7.5 h
  2. stirringstirred overnight at room temperature
  3. temperatureThe mixture is then refluxed for an additional 24 h
  4. concentrationis then concentrated under reduced pressure
  5. custompartitioned between saturated aq. sodium bicarbonate and dichloromethane
  6. washThe combined organic layers are washed with brine
  7. dry with materialdried with MgSO4
  8. concentrationconcentrated under reduced pressure
  9. customchromatographed on silica gel

Sources & evidence

ORD record
ord-5db67ea50c694c499ae80ed13071cb54
Source dataset
uspto-grants-2000_01
Patent number
US06013654

Reaction notes

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