Diisopropylethylamine → (S)-3-chloro-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)benzonitrile

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-chloro-4-(piperazin-1-yl)benzonitrile hydrochloride (118 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 propionitrile (2 ml) and heated in a closed vial at 90° C. for 2 h. The reaction mixture became a dark brown solution. It was cooled to room temperature, concentrated in vacuo and purified using flash column chromatography on silica gel (80 g SiO2, dichloromethane-methanol 100:0-95:5). The resulting solid was suspended in ether (7 mL), stirred until a fine suspension resulted, filtered and the solid was dried in vacuum to afford (S)-3-chloro-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)benzonitrile (135.4 mg, 0.320 mmol, 70.2% yield) as a light brown solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 1.80-2.03 (m, 3 H) 2.10-2.25 (m, 1 H) 2.39-2.61 (m, 4 H) 2.94-3.19 (m, 4 H) 3.35-3.46 (m, 3 H) 3.51-3.65 (m, 1 H) 3.91-4.05 (m, 1 H) 6.97 (d, J=1.77 Hz, 1 H) 7.22 (d, J=8.59 Hz, 1 H) 7.62 (d, J=1.52 Hz, 1 H) 7.74 (dd, J=8.46, 1.89 Hz, 1 H) 7.93 (d, J=1.77 Hz, 1 H) 10.44 (s, 1 H); [M+H] calc'd for C22H23ClN6O, 423; found, 423; melting point 213-215° C.

Provenance & Evidence