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

Participants

Reaction Conditions

Reaction Steps

A mixture of 1-methyl-4-prop-2-ynyl-piperazine (0.122 mL, 0.79 mmol), 5-bromo-7-chloro-2-(4-trifluoromethyl-benzyl)-2,3-dihydro-isoindol-1-one (0.240 g, 0.6 mmol), PdCl2(PPh3)2 (0.023 g, 0.03 mmol), and CuI (0.006 g, 0.03 mmol) in diisopropyl amine (4 mL) was stirred at 100° C. for 2 h. Workup and silica gel column chromatography using 10:1 CHCl3-MeOH afforded 7-chloro-5-[3-(4-methyl-piperazin-1-yl)-prop-1 ynyl)-2-(4-trifluoromethyl-benzyl)-2,3-dihydro-isoindol-1-one (0.250 g, 90%). 1H NMR (300 MHz, CDCl3): δ (ppm) 2.34 (s, 3H), 2.32-2.54 (m, 8H), 3.57 (s, 2H), 4.20 (s, 2H), 4.81 (s, 2H), 7.34 (s, 1H), 7.41-7.63 (m, 5H).

Provenance & Evidence