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

HRID 1882143Notes

Reaction equation

HRID 1882143 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([O-])(O)=O.[Na+].Cl[CH:14]([C:20]([CH3:22])=O)[C:15]([O:17][CH2:18][CH3:19])=[O:16]>C(COC)OC>[CH3:22][C:20]1[N:1]=[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]2[C:14]=1[C:15]([O:17][CH2:18][CH3:19])=[O:16]

Participants

5

Reactant 3

HCID 104392-AminopyridineHCID 11858Ethyl 2-chloroacetoacetateHCID 516892Sodium Bicarbonate

Product 1

HCID 743829ethyl 2-methylimidazo[1,2-a]pyridine-3-carboxylateYield 61.6%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

To a stirred solution of 2-aminopyridine (15.0 g. 159.00 mmol) in dimethoxyethane (150 mL) was added NaHCO3 (14.72 g, 175 mmol) followed by ethyl 2-chloroacetoacetate (39.34 g, 239 mmol) at room temperature. After refluxing for 16 h the solvent was removed under reduced pressure. The residue was taken up in water (200 mL) and extracted with dichloromethane (2×200 mL). The combined organic layers were washed with water (100 mL), brine (100 mL), and dried over anhydrous Na2SO4. Evaporation of solvents under reduced pressure afforded crude product which was further purified by column chromatography to give 20 g of the product as an off-white solid; 1H NMR (300 MHz, CDCl3) δ 1.44 (t, J=6.9 Hz, 3H), 2.72 (s, 3H), 4.43 (q, J=7.2 Hz, 2H), 6.98 (t, J=6.6 Hz, 1H), 7.38 (t, J=8.7 Hz, 1H), 7.62 (d, J=8.7 Hz, 1H), 9.31 (d, J=6.9 Hz, 1H); ESI-MS (m/z) 205.13 (MH)+.

Workup

  1. temperatureAfter refluxing for 16 h the solvent
  2. customwas removed under reduced pressure
  3. extractionextracted with dichloromethane (2×200 mL)
  4. washThe combined organic layers were washed with water (100 mL), brine (100 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. customEvaporation of solvents under reduced pressure
  7. customafforded crude product which
  8. customwas further purified by column chromatography

Sources & evidence

ORD record
ord-fd6ef2663edb48ffb30fc8cad31abf8f
Source dataset
uspto-grants-2012_11
Patent number
US08318928B2

Reaction notes

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