5-Bromo-7-chloro-2-(4-chloro-benzyl)-2,3-dihydro-isoindol-1-one → 7-Chloro-2-(4-chloro-benzyl)-5-[3-(4-methyl-piperazin-1-yl)-prop-1-ynyl)-2,3-dihydro-isoindol-1-one

Participants

Reaction Conditions

Reaction Steps

A mixture of 1-methyl-4-prop-2-ynyl-piperazine (0.061 mL, 0.4 mmol), 5-bromo-7-chloro-2-(4-chloro-benzyl)-2,3-dihydro-isoindol-1-one (0.11 g, 0.3 mmol), PdCl2(PPh3)2 (0.011 g, 0.015 mmol), and CuI (0.0028 g, 0.015 mmol) in diisopropylamine (4 mL) was stirred at 100° C. for 2 h. Workup and silica gel column chromatography using 10:1 CHCl3-MeOH afforded 7-chloro-2-(4-chloro-benzyl)-5-[3-(4-methyl-piperazin-1-yl)-prop-1-ynyl)-2,3-dihydro-isoindol-1-one (0.090 g, 70%). 1H NMR (300 MHz, CDCl3): δ (ppm) 2.31 (s, 3H), 2.32-2.74 (m, 8H), 3.54 (s, 2H), 4.18 (s, 2H), 4.74 (s, 2H), 7.22-7.36 (m, 5H), 7.44 (s, 1H).

Provenance & Evidence