Diisopropylethylamine → 3-[3-[4-(5-Methoxy-4-pyrimidyl)-1-piperazinyl]propyl]-5-(1,2-dioxo-4-methylamino-3-cyclobuten-3-yl)-1-triisopropylsilyl-1H-indole

Participants

Reaction Steps

A mixture of 5-(1,2-dioxo-4-methylamino-3-cyclobuten-3-yl)-3-[3-(p-toluenesulfonyl)oxypropyl]-1-triisopropylsilylindole (14) 0.247 g, 0.42 mmol), 1-(5-methoxy-4-pyrimidyl)piperazine (1) (0.081 g, 0.42 mmol), finely pulverized KI (0.070 g, 0.42 mmol) and diisopropylethylamine (0.37 mL, 2.1 mmol) in 10 mL of acetonitrile was heated to reflux under Ar for 18 h. The cooled reaction mixture was diluted with ethyl acetate and washed with water. The aqueous phase was back-extracted with dichloromethane (2×) and the combined organic phase was dried (Na2SO4) and evaporated to give a yellow foam. The foam was chromatographed (SiO2 /ethyl acetate--MeOH--NH4OH, 90:9:1 then MeCN--MeOH--NH4OH, 90:9:1) to give the title compound (0.207 g, 80%) as a yellow foam: IR (neat) 3280 (br), 1770, 1720, 1595 (br), 1140 cm-1 ; 1H NMR (CDCl3, 200 MHz) δ 8.34 (s, 1H), 8.08 (d, J=1.5 Hz, 1H), 7.92 (s, 1H), 7.75 (m, 1H), 7.54 (d, J=8.7 Hz, 1H), 7.06 (s, 1H), 6.8 (br s, 1H), 3.90 (br s, 2H), 3.86 (s, 3H), 3.51 (d, J=4.9 Hz, 2H), 3.41 (d, J=4.9 Hz, 1H), 3.2-2.8 (m, 4H), 2.8-2.6 (m, 4H), 2.4-2.0 (m, 4H), 1.67 (hept, J=7.5 Hz, 3H), 1.13 (d, J=7.5 Hz, 18H).

Provenance & Evidence