2-Aminopyridine → Methyl 3-methylimidazo[1,2-a]pyridine-2-carboxylate

HRID 1842428Notes

Reaction equation

HRID 1842428 reaction equation
Br[CH:2]([CH3:9])[C:3](=O)[C:4]([O:6][CH3:7])=[O:5].[NH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=1>C(#N)C>[CH3:9][C:2]1[N:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]2=[N:10][C:3]=1[C:4]([O:6][CH3:7])=[O:5]

Participants

4

Reactant 2

HCID 104392-AminopyridineHCID 11183175Methyl 3-bromo-2-oxobutanoate

Product 1

HCID 57690029Methyl 3-methylimidazo[1,2-a]pyridine-2-carboxylateYield 30.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Methyl 3-bromo-2-oxobutanoate (6.5 g, 34.3 mmol) was added to a stirred solution of 2-aminopyridine (4.0 g, 42.5 mmol) in acetonitrile (100 ml). The mixture was heated at reflux for 14 h (the reaction was monitored by TLC). The mixture was concentrated in vacuo and the residue was diluted with water and the pH was to 7.5 using sodium bicarbonate solution. The mixture 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 8% ethyl acetate in n-hexane and silica gel (230-400 mesh) to afford methyl 3-methylimidazo[1,2-a]pyridine-2-carboxylate (2.0 g, 25.1%,) as a pale yellow solid. 1H NMR: 200 MHz, CDCl3: δ 7.95 (d, 1H), 7.7 (d, 1H), 7.25 (t, 1H), 6.8 (t, 1H), 4.0 (s, 3H), 2.8 (s, 3H). MS: [M+H]+: m/z=191.1.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 14 h (the reaction
  3. concentrationThe mixture was concentrated in vacuo
  4. additionthe residue was diluted with water
  5. extractionThe mixture was extracted with EtOAc
  6. dry with materialthe combined organics were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-396131211e2a4de5bd645b406f969916
Source dataset
uspto-grants-2015_02
Patent number
US08946222B2

Reaction notes

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