反应详情

A mixture of 4-methyl-5-(1,2-dioxo-4-methyl-3-cyclobuten-3-yl)amino-3-(3-methanesulfonyloxypropyl)indole (0.154 g, 0.41 mmol), 1-(5-methoxy-4-pyrimidyl)piperazine (0.087 g, 0.45 mmol), finely pulverized KI (0.075 g, 0.45 mmol) and diisopropylethylamine (0.365 mL, 2.1 mmol) in 5 mL of acetonitrile was heated to reflux under Ar for 13 h. The resulting slurry was diluted with ethyl acetate, washed (H2O×2; brine), dried (Na2SO4) and evaporated to give a light brown gum. Flash chromatography of this gum (SiO2 /MeCN--MeOH--NH4OH, 90:9:1) afforded the title compound (0.151 g, 78%) as a pale yellow foam. A 142 mg sample of this material was taken up in methanol (ca. 3 mL) and 1N HCl (ca. 3 mL) was added. The resulting solution was concentrated and then stored at -20° C. to give a solid. This material was filtered, washed (1N HCl, acetone, ether) and then dried in vacuo to give the hydrochloride (0.140 g, 77%) as an off-white solid, mp >240° C. (dec): IR (KBr) 3400, 3200, 1784, 1722, 1595 cm-1 ; 1H NMR (DMSO-d6, 200 MHz) δ11.46 (br s, 1H), 11.09 (s, 0.7H), 11.01 (s, 0.3H), 10.62 (s, 0.7H), 10.46 (s, 0.3H), 8.62 (s, 1H), 8.21 (s, 1H), 7.24 (s, 1H), 7.22 (d, J=8.5 Hz, 0.7H), 7.16 (d, J=8.4 Hz, 0.3H), 6.95 (d, J=8.5 Hz, 0.7H), 6.88 (d, J=8.6 Hz, 0.3H), 4.88 (m, 2H), 3.91 (s, 3H), 3.66 (m, 4H), 3.17 (br s, 4H), 2.94 (m, 2H), 2.5-2.6 (m, 2H), 2.52 (s, 3H), 2.26 (s, 0.9H), 2.10 (m, 2H), 1.57 (s, 2.1H). Anal. Calcd for C26H30N6O3. 2 HCl. 1.7 H2O. 0.2 C2H3N. 0.25 C4H10O: C, 54.41; H, 6.42; N, 14.36. Found: C, 54.47; H, 6.80; N, 14.32.

1. temperaturewas heated
2. temperatureto reflux under Ar for 13 h
3. washwashed (H2O×2; brine)
4. dry with materialdried (Na2SO4)
5. customevaporated
6. customto give a light brown gum