反应详情

A mixture of 5-(1,2-dioxo-4-methyl-3-cyclobuten-3-yl)aminomethyl-3-(3-methanesulfonyloxypropyl)indole (21) (0.500 g, 1.33 mmol), 1-(5-methoxy-4-pyrimidyl)-piperazine (0.285 g, 1.47 mmol), finely pulverized KI (0.244 g, 1.47 mmol) and diisopropylethylamine (1.20 mL, 6.9 mmol) in 10 mL of acetonitrile was heated to reflux under Ar for 4 h. The resulting mixture was diluted with ethyl acetate, washed (H2O, brine), dried (Na2SO4) and evaporated to give a beige foam. Flash chromatography (SiO2 /CH2Cl2 --MeOH--NH4OH, 90:9:1) afforded the title compound (0.570 g, 90%) as a foam. This material was taken up in excess methanolic HCl, the resulting solution was evaporated and the residue was triturated with acetone to give a solid. Recrystallization from methanol-acetone gave the hydrochloride (0.220 g, 27%) as an off-white solid, mp 95° C. (foams): IR (KBr) 3420 (br), 3230 (br), 1785, 1720, 1605 cm-1 ; 1H NMR (DMSO-d6, 200 MHz) δ 11.1 (br s, 1H), 10.92 (s, 1H), 9.49 (m, 0.3H), 9.32 (m, 0.7H), 8.60 (s, 1H), 8.20 (s, 1H), 7.49 (m, 1H), 7.35 (d, J=8.3 Hz, 1H), 7.22 (s, 1H), 7.05 (d, J=8.3 Hz, 1H), 4.89-4.77 (m, 3H), 4.64 (d, J=6.0 Hz, 1H), 3.90 (s, 3H), 3.61 (br m, 6H), 3.13 (m, 4H), 2.75 (m, 2H), 2.14 (s, 1H), 2.07 (s, 2H). Anal. Calcd for C26H30N6O3.3 HCl.2.2 H2O: C, 50.08; H, 6.05; N, 13.48. Found: C, 49.84; H, 5.80; N, 13.71.

1. temperaturewas heated
2. temperatureto reflux under Ar for 4 h
3. washwashed (H2O, brine)
4. dry with materialdried (Na2SO4)
5. customevaporated
6. customto give a beige foam