反应详情

温度

140 °C

A mixture of 4-(4-bromo-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (400 mg, 0.96 mol, prepared in analogy to 4-(4-chloro-6-(trifluoromethoxy)quinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide in Example 17-1), (4R)-4-hydroxypyrrolidin-2-one (116.3 mg, 1.15 mmol), copper(I) iodide (90 mg, 0.47 mmol), potassium carbonate (265 mg, 1.92 mmol), trans-N,N′-dimethylcyclohexane-1,2-diamine (0.1 mL, 0.63 mmol) and diethylene glycol dimethyl ether (10 mL) was heated with stirring in a 10 mL of microwave process vial for 2 hours at 140° C. The mixture was diluted with dichloromethane, washed with water. The aqueous was back extracted with dichloromethane. The combined organic layer was dried over sodium sulfate, filtered, concentrated in vacuo. The residue was purified by column chromatography on silica gel to give 160 mg of produce as a gray solid. MS obsd. (ESI+) [(M+H)+] 438, 1H NMR (400 MHz, DMSO-d6) δ ppm 7.96 (d, J=7.2 Hz, 1 H), 7.88 (dd, J=1.2, 8.0 Hz, 1 H), 7.64 (td, J=1.2, 7.6 Hz, 1 H), 7.56 (d, J=8.8 Hz, 1 H), 7.48 (dd, J=6.8, 7.6 Hz, 1 H), 7.40 (m, 2 H), 7.24 (s, 1 H), 5.51 (d, J=3.6 Hz, 1 H), 5.13 (s, 2 H), 5.55 (d, J=2.4 Hz, 1 H), 4.41 (brs, 2 H), 4.08 (dd, J=4.8, 10.0 Hz, 1 H), 3.66 (s, 2 H), 3.52 (d, J=9.6 Hz, 1 H), 2.87 (dd, J=6.4, 16.8 Hz, 1 H), 2.36 (dd, J=2.0, 16.8 Hz, 1 H), 2.36 (s, 3 H).

1. temperaturewas heated
2. washwashed with water
3. extractionThe aqueous was back extracted with dichloromethane
4. dry with materialThe combined organic layer was dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by column chromatography on silica gel
8. customto give 160 mg
9. customof produce as a gray solid