1,2-Dimethoxyethane → 7-(Trifluoromethyl)imidazo[1,2-c]pyrimidine

A stirred mixture of bromoacetaldehyde diethyl acetal (2.09 ml, 13.5 mmol) in concentrated hydrobromic acid (0.68 ml) and water (0.68 ml) was heated at reflux under nitrogen for 20 min. The solution was allowed to cool to room temperature, ethylene glycol dimethyl ether (5 ml) was added and the solution was neutralised to pH 7 with solid sodium hydrogen carbonate. The mixture was filtered and the solid was washed with more ethylene glycol dimethyl ether (7 ml). To the combined filtrates was added 4-amino-6-trifluoromethylpyrimidine (2.00 g, 12.3 mmol) and the mixture was stirred at 65° C. for 18 h. After allowing to cool, the solvent was removed in vacuo and the residue was purified by flash chromatography (silica gel, 5% MeOH/CH2Cl2) to give 2.426 g of 7-trifluoromethylimidazo[1,2-c]pyrimidine: 1H NMR (360 MHz, CDCl3) δ 7.81 (1H, s), 7.86 (1H, s), 7.96 (1H, s), 9.13 (1H, s).

1. temperaturewas heated
2. temperatureat reflux under nitrogen for 20 min
3. filtrationThe mixture was filtered
4. washthe solid was washed with more ethylene glycol dimethyl ether (7 ml)
5. temperatureto cool
6. customthe solvent was removed in vacuo
7. customthe residue was purified by flash chromatography (silica gel, 5% MeOH/CH2Cl2)

ORD record

ord-82b5b1cebd134ecea91e22a96cf1c0a5

Source dataset

uspto-grants-2005_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06914065B2