Chloroacetaldehyde → Methyl imidazo(1,2-a)pyridine-7-carboxylate

HRID 985513Notes

Reaction equation

HRID 985513 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][N:8]=[C:7]([NH2:11])[CH:6]=1)=[O:4].C(=O)([O-])O.[Na+].Cl[CH2:18][CH:19]=O>CO.O>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][N:8]2[CH:18]=[CH:19][N:11]=[C:7]2[CH:6]=1)=[O:4]

Participants

6

Reactant 3

HCID 33ChloroacetaldehydeHCID 236984Methyl 2-aminopyridine-4-carboxylateHCID 516892Sodium Bicarbonate

Product 1

HCID 15096964Methyl imidazo(1,2-a)pyridine-7-carboxylateYield 38%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A solution of crude 2-aminopyridin-4-ylcarboxylic acid methyl ester (13.0 g) in methanol (150 ml) was treated with sodium hydrogencarbonate (14.3 g, 0.171 mol) and chloroacetaldehyde (8 ml of a 45 wt % solution in water) then heated at reflux for 16 h. The reaction was cooled and pre-adsorbed directly on to silica gel. Purification by flash chromatography eluting with dichloromethane (+1% conc. ammonia) on a gradient of methanol (1%-4%) gave a solid which was triturated with 5% ether in isohexane to afford imidazo[1,2-α]pyridine-7-carboxylic acid methyl ester (8.0 g, 38% from pyridine N-oxide) as a tan solid. 1H NMR (400 MHz, CDCl3) δH 3.97 (3H, s), 7.37-7.43 (2H, m), 7.70 (1H, s), 7.80 (1H, s), 8.18 (1H, dd, J 1 and 7), 8.38 (1H, s).

Workup

  1. temperaturethen heated
  2. temperatureat reflux for 16 h
  3. temperatureThe reaction was cooled and pre-adsorbed directly on to silica gel
  4. customPurification by flash chromatography
  5. washeluting with dichloromethane (+1% conc. ammonia) on a gradient of methanol (1%-4%)
  6. customgave a solid which
  7. customwas triturated with 5% ether in isohexane

Sources & evidence

ORD record
ord-12c4cbd3ea074da09cda86b88ea647c4
Source dataset
uspto-grants-2005_03
Patent number
US06872731B2

Reaction notes

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