反应详情

温度

85 °C

To a solution of 3-amino-N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-4,4,4-trifluorobutanamide (120 mg, 0.245 mmol) was added a solution of borane-methyl sulfide complex in methyl sulfide (5 M, 1.0 mL). The resulting solution was heated at 85° C. for 2 hours. After being cooled to room temperature, the mixture was acidified by careful addition of an aqueous solution of hydrochloric acid (1 M) to about pH 4, and then stirred at room temperature overnight. The resulting mixture was concentrated in vacuo. The residue was neutralized with a 10% aqueous solution of sodium hydroxide to pH >9, and then extracted with dichloromethane (20 mL×3). The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by flash chromatography to afford 60 mg of the title product as a solid (yield was 65%). MS obsd. (ESI+) [(M+H)+] 479, 1H NMR (400 MHz, CDCl3) δ ppm 8.04 (d, J=7.6 Hz, 1 H), 7.65 (d, J=7.6 Hz, 1 H), 7.50-7.49 (m, 2 H), 7.38 (t, J=7.2 Hz, 1 H), 7.30 (m, 1 H), 6.06 (s, 1 H), 5.93 (s, 1 H), 5.12 (s, 1 H), 3.63 (m, 3 H), 4.62 (brs, 2 H), 3.45 (m, 1 H), 3.33 (m, 1 H), 2.42 (s, 3 H), 2.22 (m, 1 H), 2.03 (s, 1 H), 1.82 (m, 1 H).

1. temperatureAfter being cooled to room temperature
2. concentrationThe resulting mixture was concentrated in vacuo
3. extractionextracted with dichloromethane (20 mL×3)
4. washThe combined organic layers were washed with brine
5. dry with materialdried over sodium sulfate
6. concentrationconcentrated in vacuo
7. customThe residue was purified by flash chromatography