반응 단계
A 1 L flask is charged with 1-allyl-1H-indole-2,3-dione (Example 25) (63.6 g, 339 mmol), and pyridine (107.5 g, 1.36 mol). To this, malonic acid (42.4 g, 407 mmol) is added, which leads to a slight exothermic reaction. The obtained slurry is heated at 80° C. until the formation of carbon dioxide ceases and TLC indicates no starting material to be present. To the reddish solution, triethyl amine (51.6 g, 441 mmol) is added, and the mixture is stirred for another 10 minutes when a dark red solution forms. To this solution, dimethyl carbamoyl chloride (47.5 g, 441 mmol) is added during 15 minutes which gives an exothermic reaction with vigorous formation of carbon dioxide. The mixture is stirred for another 15 minutes, and then the solvent is removed on the rotavapor. To the residue, water (about 300 mL) and chloroform (about 300 mL) are added. The pH is adjusted to slightly acidic (6.0) by adding 2 N HCl. The organic layer is separated off, and the aqueous layer extracted once more with chloroform (100 mL). The combined organic layers are dried (sodium sulfate), filtered and, after removal of the solvent, a light brown solid is obtained (107 g). This is triturated with cold water (500 mL, 4° C.), and filtered. After washing and drying the title product is obtained as beige crystals (76.6 g, 82%). 1HNMR (DMSO, 300 MHz) δ 2.63, 2.94 (2 s, 3H each, N(CH3)2); 3.04, 3.30 (AB, 2H, 2J=16.4 Hz, CH2CONMe2); 4.28, 4.35 (ABdtr, 2H, 2J=16.3 Hz, NCH2CH═CH2); 5.15 (ddtr, 1H, 2J=1.5 Hz, 3J=10.3 Hz, 4J=1.5 Hz, CH2CH═CHcis); 5.38 (ddtr, 1H, 3J=17.3 Hz, 4J=1.8 Hz, CH2CH═CHtrans); 5.84 (ddtr, 1H, 3J=4.7 Hz, CH2CH═CH2); 6.82 (d, 1H, J=7.6 Hz, H-7); 6.95 (dtr, 1H, 3J=7.6 Hz, 4J=1.2 Hz, H-5); 7.21 (dtr, 1H, 3J=7.6 Hz, 4J=1.5 Hz, H-6); 7.32 (dd, 1H, 3J=7.3 Hz, 4J=1.2 Hz, H-4). 13C-NMR (DMSO, 75 MHz) δ 35.22, 37.67 (N(CH3)2); 41.23 (CH2CONMe2); 42.27 (NCH2CH═CH2); 73.69 (C-3); 109.36 (C-7); 117.34 (NCH2CH═CH2); 122.22 (C-5); 123.66 (C-4); 129.29 (C-6); 132.39 (C-9); 132.75 (NCH2CH═CH2); 144.30 (C-8); 168.79 (CONMe2); 177.13 (C-2).
