Ethyl aluminium dichloride → (2-methyl-1-(2-morpholino ethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)(4-methylnaphthalen-1-yl)methanone

HRID 574605Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 574605
[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.[CH3:15][C:16]1[N:24]([CH2:25][CH2:26][N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)[C:19]2=[N:20][CH:21]=[CH:22][CH:23]=[C:18]2[CH:17]=1.[Cl-].[Cl-].C([Al+2])C>C(Cl)Cl>[CH3:15][C:16]1[N:24]([CH2:25][CH2:26][N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)[C:19]2=[N:20][CH:21]=[CH:22][CH:23]=[C:18]2[C:17]=1[C:12]([C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]([CH3:1])=[CH:3][CH:4]=1)=[O:13]

Komponenten

5

Edukt 3

HCID 16686341Ethyl aluminium dichlorideHCID 248874124-Methylnaphthalene-1-carbonyl chlorideHCID 667647374-(2-(2-methyl-1H-pyrrolo[2,3-b]pyridin-1-yl)ethyl)morpholine

Produkt 1

HCID 66764751(2-methyl-1-(2-morpholino ethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)(4-methylnaphthalen-1-yl)methanone

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of 4-methyl-1-naphthoyl chloride (112 mg, 0.55 mmol) and 4-(2-(2-methyl-1H-pyrrolo[2,3-b]pyridin-1-yl)ethyl)morpholine (143 mg, 0.59 mmol) in 2.5 mL CH2Cl2 at −70° C. was added dropwise ethyl aluminum dichloride (0.67 mL, 1.21 mmol, 1.8 M in toluene). The reaction mixture was allowed to slowly 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 5% MeOH in CH2Cl2, then taken up in CHCl3 and washed with a saturated solution of Na2CO3, dried over Na2SO4, filtered, and concentrated in vacuo to give CBX003(32 mg, 0.077 mmol). 1H NMR (500 MHz, CDCl3, δ): 2.46-2.58 (m, 4H), 2.60 (s, 3H), 2.78 (t, J=6.8 Hz, 2H), 2.81 (s, 3H), 3.69 (t, J=4.5 Hz, 4H), 4.47 (t, J=6.8 Hz, 2H), 6.91-7.02 (m, 1H), 7.38 (d, J=7.2 Hz, 1H), 7.43 (dd, J=7.9 Hz, 1.4 Hz, 1H), 7.45-7.52 (m, 2H), 7.58 (td, J=7.6 Hz, 1.1 Hz, 1H), 8.11 (d, J=8.4 Hz, 1H), 8.16 (d, J=8.4 Hz, 1H), 8.26 (dd, J=4.7 Hz, 1.5 Hz, 1H). 13C NMR (500 MHz, CDCl3, δ): 12.83, 19.93, 39.55, 53.99, 57.68, 66.93, 113.29, 118.10, 119.85, 124.42, 125.76, 125.78, 126.06, 126.24, 126.66, 129.10, 130.36, 132.90, 137.15, 138.40, 143.02, 146.42, 147.59, 193.21. MS m/z 415.5 [M+H]+.

Aufarbeitung

  1. customThe reaction mixture was then partitioned between ethyl acetate and cold H2O
  2. extractionthe aqueous layer extracted twice with ethyl acetate
  3. extractionThe combined organic extract
  4. washwas washed successively with H2O, 10% K2CO3, and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified via silica gel chromatography
  9. washwashed with a saturated solution of Na2CO3
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customto give CBX003(32 mg, 0.077 mmol)

Quellen und Nachweise

ORD-Eintrag
ord-643fab67627c455fbf5850b1f2bf00f1
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09034895B2

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