Nitrogen → 2-(Chloromethyl)imidazo[1,2-a]pyrimidine

Participants

Reaction Conditions

Reaction Steps

A solution of 2-Aminopyridine (19.02 g, 0.2 mol) in anhydrous DME (70 mL) was added to 1,3-dichloroacetone (25.39 g, 0.2 mol) to form a slurry in a 250-mL 3-necked round bottomed flask outfitted with a reflux condenser and a N2 line. The mixture heated at 65° C. for 18 h, warmed to 80° C. for 3 h and allowed to cool back to room temperature over 2 h. The DME was removed in vacuo and H2O was added to dissolve the resulting solid. Saturated NaHCO3 was added to basify the solution to a pH to 8 and ethyl acetate was used to extract the product (3×300 mL). Both phases were stored in the freezer overnight. The organic phase was dried over Na2SO4, filtered and concentrated to give an orange solid. The aqueous layer was extracted again with ethyl acetate (2×200 mL), then CH2Cl2 (2×200 mL) and these organic layers were dried over Na2SO4, filtered and concentrated to an orange solid. The two solids were combined and dissolved in hot 5-10% MeOH in CH2Cl2, and allowed to cool. The resulting orange crystals were filtered and washed with cold CH2Cl2. A small amount of ether was added to the mother liquor and scratched and put in the freezer. The resulting solid was filtered cold and washed with cold ether. The two batches of solid were combined and dried in the vacuum oven to yield 4.93 g (14%) of the desired product. 1H NMR (CDCl3) d 4.78 (s, 2H) 6.87 (dd, J=6.6 Hz, J=4.3 Hz, 1H) 7.61 (s, 1H) 8.45 (d, J=6.8 Hz 1H) 8.53 (d, J=1.9 Hz, 1H). MS (APCI) calcd for C7H6ClN3: 167.60; found (M+H+) 168.0.

Provenance & Evidence