6,7,8,9-Tetrahydropyrido[1,2-a]indole → (4-Methylnaphthalen-1-yl)(6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl)methanone

HRID 574611

Reaktionsgleichung

Reaktionsgleichung von HRID 574611
[CH3:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12](Cl)=[O:13])=[CH:4][CH:3]=1.[CH:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[CH:17]=[C:18]1[CH2:27][CH2:26][CH2:25][CH2:24][N:19]12.[Cl-].[Cl-].C([Al+2])C>C(Cl)Cl>[CH3:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]([C:17]2[C:16]3[C:20](=[CH:21][CH:22]=[CH:23][CH:15]=3)[N:19]3[CH2:24][CH2:25][CH2:26][CH2:27][C:18]=23)=[O:13])=[CH:4][CH:3]=1

Komponenten

5

Edukt 3

HCID 108559426,7,8,9-Tetrahydropyrido[1,2-a]indoleHCID 16686341Ethyl aluminium dichloride4×HCID 248874124-Methylnaphthalene-1-carbonyl chloride4×

Produkt 1

HCID 66764509(4-Methylnaphthalen-1-yl)(6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl)methanone

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

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]+.

Aufarbeitung

  1. temperaturethen cooled to −70° C.
  2. temperatureto warm to room temperature
  3. stirringstirred 6 h
  4. temperatureThe reaction mixture was again cooled to −70° C.
  5. temperatureto warm to room temperature overnight
  6. temperatureIt was again cooled to −70° C.
  7. temperatureto warm to room temperature overnight
  8. customThe reaction mixture was then partitioned between ethyl acetate and cold H2O
  9. extractionthe aqueous layer extracted twice with ethyl acetate
  10. extractionThe combined organic extract
  11. washwas washed successively with H2O, 10% K2CO3, and brine
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customThe crude product was purified via silica gel chromatography
  16. customto give CBX005 (22 mg, 0.065 mmol)

Quellen und Nachweise

ORD-Eintrag
ord-a05bf03165c947128bab189405a9ef6f
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09034895B2

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