2-Aminopyridine → 2-Chloromethyl-imidazo(1,2-A)pyridine

HRID 1798691Notes

Reaction equation

HRID 1798691 reaction equation
[Cl:1][CH2:2][C:3]([CH2:5]Cl)=O.[NH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=1>C(#N)C>[Cl:1][CH2:2][C:3]1[N:7]=[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]2[CH:5]=1

Participants

4

Reactant 2

HCID 104392-AminopyridineHCID 107931,3-Dichloroacetone

Product 1

HCID 9576142-Chloromethyl-imidazo(1,2-A)pyridineYield 47.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1,3-Dichloroacetone (22.9 g, 180.3 mmol) was added to a solution of 2-amino pyridine (10 g, 106.3 mmol) in acetonitrile (200 ml). The mixture was heated at reflux for 14 h (the reaction was monitored by TLC). Upon completion of the reaction, the volatiles were removed under reduced pressure. The residue was diluted with water and adjusted the pH to 7.5 with sodium bicarbonate solution which was 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 12% ethyl acetate in n-hexanes and silica gel (230-400 mesh) to afford 2-(chloromethyl) imidazo[1,2-a]pyridine (8.0 g, 47.9%) as pale yellow solid. 1H NMR: 200 MHz, CDCl3: δ 8.15 (d, 1H), 7.6 (dd, 2H), 7.1 (t, 1H), 6.8 (t, 1H), 4.75 (s, 2H). MS: [M+H]+: m/z=167.2.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 14 h (the reaction
  3. customUpon completion of the reaction
  4. customthe volatiles were removed under reduced pressure
  5. additionThe residue was diluted with water
  6. extractionwas extracted with EtOAc
  7. dry with materialThe combined organics were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-b47144836ed24620b7301bb00b26c5cf
Source dataset
uspto-grants-2013_01
Patent number
US08343973B2

Reaction notes

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