反应详情

To a solution of 23 (1.02 g, 5.47 mmol) triethylamine (762 μL, 5.47 mmol) and NaI (23 mg, 0.153 mmol) in DMSO but-3-ynyl mesylate (810 mg, 5.47 mmol) is dropwise added. The mixture is heated at 50° C. overnight, then water is added. The aqueous phase is treated with Et2O, and the organic phase is washed with brine, and dried over sodium sulfate. After solvent evaporation, 4-but-3-ynyl-piperazine-1-carboxylic acid t-butyl ester (24) (1.10 g, 4.62 mmol, 84%) is obtained as a yellow oil. 1H NMR (CDCl3, 200 MHz) δ 3.38 (t, J=4.8 Hz, 4H), 2.55 (m, 2H), 2.41-2.28 (m, 6H), 1.94 (t, J=2.6 Hz, 1H), 1.40 (s, 9H) ppm; 13C NMR (CDCl3, 50 MHz) δ 154.3 (s), 82.3 (s), 79.5 (s), 69.1 (d), 56.9 (t), 52.6 (t), 43.5 (t), 28.4 (q), 16.7 (t) ppm. Compound 24 (1.10 g, 4.62 mmol) is left reacting for 16 h in the presence of a 1:1 mixture of CH2Cl2/TFA (2 mL/mmol). After solvent evaporation, the residue is taken up in MeOH, and eluted through a column containing Amberlyst A-21, thus giving pure 1-but-3-ynyl-piperazine (25) (606 mg, 4.39 mmol) in 95% yield. 1H NMR (CDCl3, 200 MHz) δ 6.98 (br, 1H), 3.06-3.01 (m, 4H), 2.62-2.55 (m, 6H), 2.38-2.29 (m, 2H), 1.96 (t, J=2.6 Hz, 1H) ppm; 13C NMR (CDCl3, 50 MHz) δ 82.1 (s), 69.4 (d), 56.6 (t), 50.6 (t), 44.1 (t), 16.8 (t). MS m/z 138 (M+, 7), 99 (100), 70 (48), 56 (98) ppm. To a solution of N,N′-di-Boc-N″-trifluoromethanesulfonylguanidine (1.52 g, 3.88 mmol) in anhydrous CH2Cl2 (18 mL) triethylamine (595 μL, 4.27 mmol) and 25 (590 mg, 4.27 mmol) are added. The mixture is left reacting for 16 h at room temperature, and then the solvent is evaporated. The residue is taken up in EtOAc and treated with a saturated aqueous NaHCO3 solution and brine. Crude product is purified by flash chromatography (CH2Cl2-MeOH 12:1, Rf=0.50), giving pure 5 as a white solid (1.10 g, 2.25 mmol) in 58% yield. 1H NMR (CDCl3, 200 MHz) δ 3.58 (m, 4H), 2.63-2.51 (m, 6H), 2.39-2.33 (m, 2H), 1.96 (t, J=2.6 Hz, 1H) ppm; 13C NMR (CDCl3, 50 MHz) δ 154.7 (s), 151.2 (s), 115.9 (s), 85.9 (s), 82.3 (s), 69.2 (d), 56.6 (t), 52.3 (t), 46.7 (t), 28.0 (q), 27.8 (q), 16.8 (t); MS m/z 380 (M+, 0.11), 160 (17), 121 (79), 57 (100) ppm.

1. customAfter solvent evaporation
2. washeluted through a column
3. additioncontaining Amberlyst A-21