Potassium bis(trimethylsilyl)amide → 1-(6-Bromo-pyridin-2-ylmethyl)-3-(3,4-dimethyl-benzoyl)-6-fluoro-1H-quinolin-4-one

HRID 226963

Reaktionsgleichung

Reaktionsgleichung von HRID 226963
[CH3:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[CH3:22])[C:5]([C:7]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([F:18])[CH:14]=2)[NH:9][CH:8]=1)=[O:6].C[Si](C)(C)[N-][Si](C)(C)C.[K+].[Br:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([CH2:40]Br)[N:35]=1>O1CCCC1>[Br:33][C:34]1[N:35]=[C:36]([CH2:40][N:9]2[C:10]3[C:15](=[CH:14][C:13]([F:18])=[CH:12][CH:11]=3)[C:16](=[O:17])[C:7]([C:5](=[O:6])[C:4]3[CH:19]=[CH:20][C:21]([CH3:22])=[C:2]([CH3:1])[CH:3]=3)=[CH:8]2)[CH:37]=[CH:38][CH:39]=1

Komponenten

5

Edukt 3

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 46065703-(3,4-dimethylbenzoyl)-6-fluoroquinolin-4(1H)-oneHCID 129547962-Bromo-6-(bromomethyl)pyridine

Produkt 1

HCID 167312441-(6-Bromo-pyridin-2-ylmethyl)-3-(3,4-dimethyl-benzoyl)-6-fluoro-1H-quinolin-4-oneAusbeute 73,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a solution of 0.050 g (0.169 mmol) of 3-(3,4-dimethyl-benzoyl)-6-fluoro-1H-quinolin-4-one 4tt in 1.0 mL of tetrahydrofuran was added 0.4 mL (0.5 M in toluene, 0.203 mmol) of potassium hexamethyldisilazide and the reaction solution was stirred for 5 min, followed by the addition of 50.9 mg (0.203 mmol) of 2-bromo-6-bromomethyl-pyridine in 0.5 ml of tetrahydrofuran. The resultant solution was stirred at 60° C. for 3 h. The reaction solution was quenched by the addition of water and the aqueous phase was extracted with 3×5 mL of ether. The combined organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to yield 58 mg of 1-(6-Bromo-pyridin-2-ylmethyl)-3-(3,4-dimethyl-benzoyl)-6-fluoro-1H-quinolin-4-one 4tt as a yellow solid: LC-MSD, m/z for C24H18BrFN2O2, [M+H]=465.4, 466.5, 467.4, 468.4; Reverse phase HPLC gradient, 20-95% acetonitrile with 0.1% TFA in 4 minutes, retention time=2.8 min; 1H NMR (400 MHz, CDCl3): δ 8.27 (1H, s), 8.12 (1H, m), 7.64 (1H, s), 7.56 (1H, m), 7.51 (1H, m), 7.47 (1H, m), 7.40-7.34 (2H, m), 7.19 (1H, m), 7.00 (1H, m), 5.46 (2H, s), 2.32 (3H, s), 2.31 (3H, s).

Aufarbeitung

  1. customThe reaction solution was quenched by the addition of water
  2. extractionthe aqueous phase was extracted with 3×5 mL of ether
  3. dry with materialThe combined organic layer was dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-c1cd007b65ac49388038cdf2af29d690
Quelldatensatz
uspto-grants-2009_07
Patentnummer
US07557213B2

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