反应详情

温度

0 °C

To a solution of 4-(2-(6-chloro-2-methyl-1H-indol-1-yl)ethyl)morpholine (48 mg, 0.17 mmol) in 0.5 mL CH2Cl2 at 0° C. was added dropwise ethyl aluminum dichloride (0.14 mL, 0.26 mmol, 1.8 M in toluene). The reaction mixture was stirred at 0° C. for 30 min, then a solution of 4-methyl-1-naphthoyl chloride (43 mg, 0.21 mmol) in 0.5 mL CH2Cl2 was added and stirred at 0° C. for 1 h, then allowed to slowly warm to room temperature overnight. The reaction stirred at room temp for 3 d. The reaction mixture was then poured into ice cold 1M HCl and extracted three times with CH2Cl2. The combined organic extract was washed three times with a saturated solution of sodium bicarbonate, dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified via silica gel chromatography using a gradient from 0 to 5% MeOH in CH2Cl2 to give CBX004 (23 mg, 0.052 mmol). 1H NMR (500 MHz, CDCl3, δ): 2.46 (s, 3H), 2.48-2.59 (m, 4H), 2.71 (t, J=6.9 Hz, 2H), 2.80 (s, 3H), 3.71 (t, J=4.6 Hz, 4H), 4.20 (t, J=6.9 Hz, 2H), 7.02 (dd, J=8.6 Hz, 1.8 Hz, 1H), 7.25 (d, J=8.6 Hz, 1H), 7.33 (d, J=1.7 Hz, 1H), 7.37 (d, J=7.2 Hz, 1H), 7.44-7.53 (m, 2H), 7.58 (td, J=7.6 Hz, 1.1 Hz, 1H), 8.11 (d, J=8.4 Hz, 1H), 8.18 (d, J=8.4 Hz, 1H). 13C NMR (500 MHz, CDCl3, δ): 12.62, 19.93, 41.40, 54.10, 57.36, 66.88, 109.40, 115.34, 122.34, 122.49, 124.40, 125.72, 125.76, 126.03, 126.08, 126.21, 126.66, 128.25, 130.43, 132.91, 136.51, 137.22, 138.35, 146.00, 193.43. MS m/z 447.6 [M+H]+.

1. stirringstirred at 0° C. for 1 h
2. temperatureto slowly warm to room temperature overnight
3. stirringThe reaction stirred at room temp for 3 d
4. extractionextracted three times with CH2Cl2
5. extractionThe combined organic extract
6. washwas washed three times with a saturated solution of sodium bicarbonate
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe crude product was purified via silica gel chromatography
11. customto give CBX004 (23 mg, 0.052 mmol)