Reaktion #661793

Reaktionsgleichung

4-methyl-1-naphthoyl chloride

ethyl aluminum dichloride

4-methyl-1-naphthoyl chloride

6,7,8,9-tetrahydropyrido[1,2-a]indole

ethyl aluminum dichloride

4-methyl-1-naphthoyl chloride

ethyl aluminum dichloride

4-methyl-1-naphthoyl chloride

ethyl aluminum dichloride

→

(4-methylnaphthalen-1-yl)(6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl)methanone

Lösungsmittel

CH2Cl2

CH2Cl2

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthen cooled to −70° C.
2. 2
   Temperaturto warm to room temperature
3. 3
   workup.STIRRINGstirred 6 h
4. 4
   TemperaturThe reaction mixture was again cooled to −70° C.
5. 5
   Temperaturto warm to room temperature overnight
6. 6
   TemperaturIt was again cooled to −70° C.
7. 7
   Temperaturto warm to room temperature overnight
8. 8
   SonstigeThe reaction mixture was then partitioned between ethyl acetate and cold H2O
9. 9
   Extraktionthe aqueous layer extracted twice with ethyl acetate
10. 10
    ExtraktionThe combined organic extract
11. 11
    Waschenwas washed successively with H2O, 10% K2CO3, and brine
12. 12
    Trocknendried over MgSO4
13. 13
    Filtrationfiltered
14. 14
    Einengenconcentrated in vacuo
15. 15
    SonstigeThe crude product was purified via silica gel chromatography
16. 16
    Sonstigeto give CBX005 (22 mg, 0.065 mmol)

Vorschrift

To a solution of 4-methyl-1-naphthoyl chloride (37 mg, 0.18 mmol) and 6,7,8,9-tetrahydropyrido[1,2-a]indole (30 mg, 0.18 mmol) in 1 mL CH2Cl2 at −70° C. was added dropwise ethyl aluminum dichloride (0.22 mL, 0.40 mmol, 1.8 M in toluene). The reaction mixture was allowed to slowly warm to room temperature and stirred for 3 d then cooled to −70° C. and 4-methyl-1-naphthoyl chloride (4 mg, 0.020 mmol) and ethyl aluminum dichloride (20 μL, 0.036 mmol) added and allowed to warm to room temperature and stirred 6 h. The reaction mixture was again cooled to −70° C. and 4-methyl-1-naphthoyl chloride (4 mg, 0.020 mmol) and ethyl aluminum dichloride (20 μL, 0.036 mmol) added and allowed to warm to room temperature overnight. It was again cooled to −70° C. and 4-methyl-1-naphthoyl chloride (8 mg, 0.040 mmol), ethyl aluminum dichloride (40 μL, 0.072 mmol), and 1 mL CH2Cl2 added and allowed to warm to room temperature overnight. The reaction mixture was then partitioned between ethyl acetate and cold H2O, and the aqueous layer extracted twice with ethyl acetate. The combined organic extract was washed successively with H2O, 10% K2CO3, and brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified via silica gel chromatography using a gradient from 0 to 25% ethyl acetate in hexanes to give CBX005 (22 mg, 0.065 mmol). 1H NMR (500 MHz, CDCl3, δ): 1.80-1.95 (m, 2H), 2.05-2.33 (m, 2H), 2.82 (s, 3H), 2.97 (t, J=6.3 Hz, 2H), 4.13 (t, J=6.2 Hz, 2H), 7.09 (t, J=7.6 Hz, 1H), 7.22 (t, J=7.6 Hz, 1H), 7.30-7.37 (m, 2H), 7.40 (d, J=7.1 Hz, 1H), 7.43-7.52 (m, 2H), 7.58 (t, J=7.6 Hz, 1H), 8.08-8.19 (m, 2H). 13C NMR (500 MHz, CDCl3, δ): 19.87, 20.03, 22.31, 25.20, 42.65, 108.94, 113.75, 121.25, 122.03, 122.44, 124.31, 124.99, 125.93, 126.05, 126.24, 126.41, 126.97, 130.34, 132.89, 136.27, 139.26, 147.09, 193.08. MS m/z 340.4 [M+H]+.

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