7-Bromo-3-(4-fluorophenyl)imidazo[1,5-a]pyridine → 1-[1-(2,2-Dimethyl-1,3-dioxolan-4-ylmethyl)-1H-indol-3-yl]-2,2,2-trifluoro-1-[3-(4-fluorophenyl)imidazo[1,5-a]pyridin-7-yl]ethanol

HRID 244476Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 244476
Br[C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)=[N:9][CH:10]=[C:4]2[CH:3]=1.C([Li])CCC.[CH3:23][C:24]1([CH3:45])[O:28][CH:27]([CH2:29][N:30]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:32]([C:39](=[O:44])[C:40]([F:43])([F:42])[F:41])=[CH:31]2)[CH2:26][O:25]1>C1COCC1>[CH3:23][C:24]1([CH3:45])[O:28][CH:27]([CH2:29][N:30]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:32]([C:39]([C:2]3[CH:7]=[CH:6][N:5]4[C:8]([C:11]5[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=5)=[N:9][CH:10]=[C:4]4[CH:3]=3)([OH:44])[C:40]([F:43])([F:42])[F:41])=[CH:31]2)[CH2:26][O:25]1

Komponenten

5

Edukt 3

HCID 594372397-Bromo-3-(4-fluorophenyl)imidazo[1,5-a]pyridineHCID 594372891-[1-(2,2-dimethyl-1,3-dioxolan-4-ylmethyl)-1H-indol-3-yl]-2,2,2-trifluoroethanoneHCID 178418339Butyllithium

Produkt 1

HCID 249598181-[1-(2,2-Dimethyl-1,3-dioxolan-4-ylmethyl)-1H-indol-3-yl]-2,2,2-trifluoro-1-[3-(4-fluorophenyl)imidazo[1,5-a]pyridin-7-yl]ethanolAusbeute 33,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a chilled (−78° C.) solution of 7-bromo-3-(4-fluorophenyl)imidazo[1,5-a]pyridine (160 mg, 0.55 mmol) in anhydrous THF (3 mL) was added n-butyllithium (275 μL of a 2.5 M solution in hexanes, 0.69 mmol). After 2 minutes, a chilled (−78° C.) solution of 1-[1-(2,2-dimethyl-1,3-dioxolan-4-ylmethyl)-1H-indol-3-yl]-2,2,2-trifluoroethanone (240 mg, 0.73 mmol) in 1 mL of THF was added. After 60 minutes, the mixture was quenched with brine (50 mL) and extracted with ethyl acetate. The combined organic layers were washed with water, dried over anhydrous sodium sulfate, and concentrated in vacuo to afford a yellow oil. The residue was purified by column chromatography over silica gel eluting with 0-75% ethyl acetate in hexanes and fractions corresponding to a MS m/z 540 (MH+) peak were pooled and concentrated in vacuo to afford 100 mg of the title compound as a light yellow solid.

Aufarbeitung

  1. additionwas added
  2. waitAfter 60 minutes
  3. customthe mixture was quenched with brine (50 mL)
  4. extractionextracted with ethyl acetate
  5. washThe combined organic layers were washed with water
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customto afford a yellow oil
  9. customThe residue was purified by column chromatography over silica gel eluting with 0-75% ethyl acetate in hexanes and fractions corresponding to a MS m/z 540 (MH+) peak
  10. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-4e0b77b5eae8429e8be3ff552f1b29a8
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658637B2

Notizen zur Reaktion

Wird geladen…