Diisopropylethylamine → (S)-3-fluoro-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

Participants

Reaction Conditions

Reaction Steps

(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-fluoro-N-methyl-4-(piperazin-1-yl)benzamide hydrochloride (125 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-fluoro-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 (128.5 mg, 0.293 mmol, 64.2% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.83-2.03 (m, 3 H) 2.09-2.25 (m, 1 H) 2.50 (m, 4 H) 2.75 (d, J=4.29 Hz, 3 H) 2.96-3.14 (m, 4 H) 3.35-3.45 (m, 3 H) 3.53-3.65 (m, 1 H) 3.93-4.05 (m, 1 H) 6.98 (d, J=1.77 Hz, 1 H) 7.04 (t, J=8.59 Hz, 1 H) 7.51-7.67 (m, 3 H) 8.27-8.38 (m, 1 H) 10.44 (s, 1 H). [M+H] calc'd for C23H27FN6O2, 439; found, 439.

Provenance & Evidence