反应详情

温度

105 °C

(S)-3-(hydroxymethyl)-6a,7,8,9-tetrahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-6(5H)-one (100 mg, 0.456 mmol), 3-chloro-N-methyl-4-(piperazin-1-yl)benzamide hydrochloride (132 mg, 0.456 mmol), (cyanomethyl)trimethylphosphonium iodide (166 mg, 0.684 mmol) and N,N-diisopropylethylamine (0.398 ml, 2.281 mmol) were suspended in propiononitrile (Volume: 1.370 ml) and heated in a closed vial at 90-120° C. for 4 h. The reaction mixture became a dark brown solution. It was cooled to room temperature, concentrated in vacuo, dissolved in DMSO (2 mL) and purified using HPLC (basic, 45-95% ACN in water, basic). The fractions were concentrated in vacuo and the resulting solid was recrystallized from water-MeOH (2:1, 6 mL) and dried in vacuum to afford (S)-3-chloro-N-methyl-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzamide (53.1 mg, 0.117 mmol, 25.6% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.83-2.02 (m, 3 H) 2.10-2.24 (m, 1 H) 2.51 (br. s., 4 H) 2.75 (d, J=4.55 Hz, 3 H) 3.03 (br. s., 4 H) 3.36-3.45 (m, 3 H) 3.52-3.65 (m, 1 H) 3.93-4.03 (m, 1 H) 6.98 (d, J=1.77 Hz, 1 H) 7.17 (d, J=8.34 Hz, 1 H) 7.63 (d, J=1.77 Hz, 1 H) 7.75 (dd, J=8.34, 2.02 Hz, 1 H) 7.86 (d, J=2.02 Hz, 1 H) 8.41 (q, J=4.13 Hz, 1 H) 10.45 (s, 1 H). [M+H] calc'd for C23H27ClN6O2, 455; found, 455.

1. temperatureIt was cooled to room temperature
2. concentrationconcentrated in vacuo
3. dissolutiondissolved in DMSO (2 mL)
4. custompurified
5. concentrationThe fractions were concentrated in vacuo
6. customthe resulting solid was recrystallized from water-MeOH (2:1, 6 mL)
7. customdried in vacuum