反应详情

A mixture of tert-butyl piperazine-1-carboxylate (6.5 gm, 35.2 mmol), 2-chloro-4-ethylpyrimidine (5 gm, 35.2 mmol), triethylamine (3.55 gm, 35.2 mmol), and absolute ethanol (60 ml) were refluxed for 12 h and then cooled. Ice water was added and the resulting precipitate was filtered, washed with cold water, and finally dried to afford the desired crude intermediate, tert-butyl 4-(5-ethylpyrimidin-2-yl)piperazine-1-carboxylate, as white flakes (9.24 gm, 90% yield); mp: 67-68° C. 1H-NMR (DMSO-d6): δ 1.19 (t, J=7.56 Hz, 3H), 1.46 (s, 9H), 2.47 (q, J=7.56 Hz, 2H), 3.49 (t, J=4.8 Hz, 4H), 3.76 (t, J=4.8 Hz, 4H), 8.19 (s, 2H). 13C-NMR (DMSO-d6): δ 15.59, 22.66, 28.4, 43.76, 43.77, 79.8, 124.95, 154.84, 157.08, 160.05. MS: calcd 292.19 for C15H24N4O2 [M]+. found, 293.19 [M+1]+. b) HCl/MeOH mixture was prepared by adding 10 ml acetyl chloride dropwise to 100 ml methanol at 0° C. The resulting mixture was warmed to room temperature. The intermediate from step a (9 gm, 30.8 mmol) was then added to the HCl/MeOH and stirred for 12 h at room temperature. Methanol was removed using a row; evaporator. The residue was dissolved in water; the solution was neutralized using solid NaHCO3. The mixture was extracted with CHCl3 (3×200 mL). The combined organic layers was washed successively with saturated NaHCO3, and saturated brine and then dried with anhydrous Na2SO4. Concentration of the organic layer afforded the desired crude product 1 as a white solid (4.8 gm, 81% yield); mp: 115-116° C. 1H-NMR (DMSO-d6): δ 1.20 (t, J=7.56 Hz, 3H), 2.48 (q, J=7.56 Hz, 2H), 3.09 (t, J=5.16 Hz, 4H), 3.94 (t, J=5.16 Hz, 4H), 8.19 (s, 2H). 13C-NMR (DMSO-d6): δ 15.53, 22.67, 42.76, 44.30, 125.52, 157.15, 160.09.

1. temperaturewere refluxed for 12 h
2. temperaturecooled
3. filtrationthe resulting precipitate was filtered
4. washwashed with cold water
5. customfinally dried