反应详情

温度

70 °C

Diisopropylethylamine (0.24 mL, 1.38 mmol) was added to a suspension of 12-amino-dodecanoic acid amide hydrochloride (8) (0.068 g, 0.27 mmol) in absolute ethanol (5 mL). The resulting solution was stirred at 70° C. (oil bath) for 5 min, after which time 1-(3,5-diamino-6-chloropyrazine-2-carbonyl)-2-methylisothiourea hydriodide (115 mg, 0.30 mmol) was added in one portion. The reaction mixture was then stirred at this temperature for 3 hours then cooled to room temperature. After removal of the solvent by rotary evaporation the resulting residue was dissolved in small volume of methanol, and the solution passed through an ion exchange resin column (Dowex 550A OH type). The resin was rinsed with methanol and the methanol solution concentrated in vacuo to a yellow residue. This residue was stirred in a minimal volume of methanol and the resulting solid was collected by suction filtration and washed with a small amount of methanol to give 12-[N′-(3,5-diamino-6-chloropyrazine-2-carbonyl)guanidino]-dodecanoic acid amide 9 (0.065 g, 56%) as a yellow solid: 1H NMR (300 MHz, DMSO-d6) 1.23 (m, 14H), 1.49 (m, 4H), 2.01 (t, 2H), 3.11 (m, 2H), 6.65 (m, 4H), 7.21 (br, 1H), 9.06 (br, 1H). m/z (ESI) 427 [C18H31ClN8O2+H]+. mp 192-194° C.

1. stirringThe reaction mixture was then stirred at this temperature for 3 hours
2. temperaturethen cooled to room temperature
3. customAfter removal of the solvent
4. customby rotary evaporation the resulting residue
5. dissolutionwas dissolved in small volume of methanol
6. washThe resin was rinsed with methanol
7. concentrationthe methanol solution concentrated in vacuo to a yellow residue
8. stirringThis residue was stirred in a minimal volume of methanol
9. filtrationthe resulting solid was collected by suction filtration
10. washwashed with a small amount of methanol