反应详情

温度

70 °C

Diisopropylethylamine (0.23 mL, 1.31 mmol) was added to a suspension of 12-amino-dodecanoic acid (3-dimethylaminopropyl)amide dihydrochloride (5) (0.081 g, 0.22 mmol) in absolute ethanol (5 mL). The mixture became homogeneous. It was stirred at 70° C. (oil bath) for 5 min and then 1-(3,5-diamino-6-chloropyrazine-2-carbonyl)-2-methylisothiourea hydriodide (0.093 g, 0.24 mmol) was added in one portion. The reaction mixture was stirred at this temperature for 3 hours and cooled to room temperature. The solvent was then removed by rotary evaporation, the residue dissolved in small volume of methanol, and this solution passed through an ion exchange resin column (Dowex 550A OH type). The resin was rinsed with methanol and the methanol solution was concentrated in vacuo. The resulting residue was purified by Biotage silica gel column chromatography, eluting with a gradient of 1% to 10% of 9:1 methanol/ammonium hydroxide in dichloromethane, to give 12-[N′-(3,5-diamino-6-chloropyrazine-2-carbonyl)guanidino]dodecanoic acid (3-dimethylaminopropyl)amide 6 (0.070 g, 63%) as a yellow solid: 1H NMR (300 MHz, DMSO-d6) δ 1.25 (m, 14H), 1.50 (m, 6H), 2.01 (t, 2H), 2.11 (s, 6H), 2.20 (t, 2H), 3.02 (m, 2H), 3.12 (t, 2H), 6.80 (br, 3H), 7.75 (m, 1H). m/z (ESI) 512 [C23H42ClN9O2+H]+. mp 82-84° C.

1. stirringThe reaction mixture was stirred at this temperature for 3 hours
2. temperaturecooled to room temperature
3. customThe solvent was then removed by rotary evaporation
4. dissolutionthe residue dissolved in small volume of methanol
5. washThe resin was rinsed with methanol
6. concentrationthe methanol solution was concentrated in vacuo
7. customThe resulting residue was purified by Biotage silica gel column chromatography
8. washeluting with a gradient of 1% to 10% of 9:1 methanol/ammonium hydroxide in dichloromethane