Ethyl imidazo[1,2-a]pyrimidine-3-carboxylate

109-12-6

70-23-5

64951-07-1

64951-06-0

2-Aminopyrimidine (5 g, 52.6 mmol) and ethyl 3-bromopyruvate (90% purity, 7.35 mL, 52.6 mmol) were dissolved in ethanol (80 mL) and the reaction mixture was heated to 75°C for 16 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure and diluted with an aqueous solution of dichloromethane (CH2Cl2) and saturated sodium bicarbonate (NaHCO3). The organic layer was washed twice with saturated aqueous NaHCO3 and the aqueous layer was extracted three times with CH2Cl2. The organic layers were combined, dried with anhydrous magnesium sulfate (MgSO4) and concentrated under reduced pressure. The brown oil obtained was suspended in cold CH2Cl2, filtered, and the filter cake was washed with cold CH2Cl2 to give ethyl imidazo[1,2-a]pyrimidine-2-carboxylate (3 g, 30% yield) as a light yellow oil. The mother liquor contained a mixture of ethyl imidazo[1,2-a]pyrimidine-2-carboxylate and ethyl imidazo[1,2-a]pyrimidine-3-carboxylate (6 g, 60% yield) as a viscous black oil. This black oil was first purified by silica gel column chromatography and then recrystallized from ethyl acetate (EtOAc) to give pure ethyl imidazo[1,2-a]pyrimidine-3-carboxylate (2 g, 20% yield). For the 2-isomer: 1H NMR (500 MHz, CDCl3) δ 8.69 (dd, J = 2.2,6.6 Hz, 1H), 8.67 (dd, J = 2.2,4.4 Hz, 1H), 8.22 (s, 1H), 7.01 (dd, J = 3.9,6.6 Hz, 1H), 4.46 (q, J = 7.2 Hz, 2H). 1.43 (t, J = 7.2Hz, 3H).13C NMR (500MHz, CDCl3) δ162.8,152.2,147.8,137.7,134.4,115.3,110.0,61.2,14.2.HPLC-MS Phenomenex LUNA C-18 4.6 x 50 mm, 0 to 100% B, 4 min, 1 min hold time, A = 90% water, 10% methanol, 0.1% TFA, B = 10% water, 90% methanol, 0.1% TFA, RT = 0.99 min, 95% homogeneity index.LCMS: Analysis. Calculated.Measured result for C9H9N3O2 191.07 Measured value: 192.13 (M + H)+. For the 3-isomer: HPLC Phenomenex LUNA C-18 4.6 x 50 mm, 0 to 100% B, 4 min, 1 min retention time, A = 90% water, 10% methanol, 0.1% TFA, B = 10% water, 90% methanol, 0.1% TFA, RT = 1.39 min, 100% homogeneity index. lcms: calc. 191.07 measured value for C9H9N3O2: 192.19 (M + H)+.