Diisopropylethylamine → (S)-4-(4-((6-oxo-6,6a,7,8-tetrahydro-5H-azeto[1,2-a]pyrido[3,2-e]pyrazin-3-yl)methyl)piperazin-1-yl)benzonitrile

Participants

Reaction Conditions

Reaction Steps

(S)-3-(hydroxymethyl)-7,8-dihydro-5H-azeto[1,2-a]pyrido[3,2-e]pyrazin-6(6aH)-one (103 mg, 0.5 mmol), 4-(piperazin-1-yl)benzonitrile (108 mg, 0.575 mmol), (cyanomethyl)trimethylphosphonium iodide (207 mg, 0.850 mmol) and N,N-diisopropylethylamine (0.437 ml, 2.500 mmol) were suspended in Propiononitrile (Volume: 1.502 ml) and heated in a closed vial at 90° C. for 23 h. The reaction mixture was cooled, diluted with MeOH (2 mL) and purified using preparative HPLC (basic phase). The fractions containing product were concentrated in vacuo and crystallized from water-methanol (3 mL, ˜5:1) The precipitate was filtered and dried in vacuum to afford (S)-4-(4-((6-oxo-6,6a,7,8-tetrahydro-5H-azeto[1,2-a]pyrido[3,2-e]pyrazin-3-yl)methyl)piperazin-1-yl)benzonitrile (11.7 mg, 0.031 mmol, 6.25% yield) as a light brown solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.37-2.47 (m, 4 H) 2.68-2.80 (m, 1 H) 2.94 (tt, J=10.67, 7.26 Hz, 1 H) 3.30 (d, J=4.80 Hz, 4 H) 3.36 (s, 2 H) 3.87-4.00 (m, 1 H) 4.21 (q, J=7.66 Hz, 1 H) 4.93 (t, 1 H) 6.98 (d, J=1.77 Hz, 1 H) 7.00 (d, J=9.09 Hz, 2 H) 7.57 (d, J=9.09 Hz, 2 H) 7.65 (d, J=1.77 Hz, 1 H) 10.34 (s, 1 H). [M+H] calc'd for C21H22N6O, 374; found, 374.

Provenance & Evidence