Ethyl bromoacetate → ethyl 4-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-3-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]-4-oxo-butanoate

HRID 710665Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 710665
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[CH2:15][CH2:14][CH2:13][N:12]([C:17](=[O:29])[CH2:18][N:19]4[C:23]([CH3:24])=[CH:22][C:21]([C:25]([F:28])([F:27])[F:26])=[N:20]4)[C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[Li+].CC([N-]C(C)C)C.Br[CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41]>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[CH2:15][CH2:14][CH2:13][N:12]([C:17](=[O:29])[CH:18]([N:19]4[C:23]([CH3:24])=[CH:22][C:21]([C:25]([F:27])([F:26])[F:28])=[N:20]4)[CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])[C:11]=3[CH:10]=[N:9]2)=[CH:6][CH:7]=1

Komponenten

5

Edukt 3

HCID 7748Ethyl bromoacetateHCID 2724682Lithium diisopropylamideHCID 733351261-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]ethanone

Produkt 1

HCID 86711682ethyl 4-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-3-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]-4-oxo-butanoateAusbeute 83 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a mixture of 1-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]ethanone (0.150 g, 0.37 mmol) in THF (4 ml) at −78° C. was added LDA (0.247 mL, 0.50 mmol, 2 M in THF). After stirring for 10 min at −78° C., ethyl bromoacetate (0.061 mL, 0.55 mmol) was added. The mixture was then warmed to rt for 10 min and quenched with sat. NH4Cl. The mixture was partitioned between EtOAc (50 mL) and brine (30 mL). The organic layer was separated, dried over Na2SO4, concentrated in vacuo and purified by flash chromatography (SiO2 with a gradient elution of 0-60% EtOAc/hexanes) to afford ethyl 4-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-3-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]-4-oxo-butanoate (0.120 g, 83%).

Aufarbeitung

  1. temperatureThe mixture was then warmed to rt for 10 min
  2. customquenched with sat. NH4Cl
  3. customThe mixture was partitioned between EtOAc (50 mL) and brine (30 mL)
  4. customThe organic layer was separated
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. custompurified by flash chromatography (SiO2
  8. washwith a gradient elution of 0-60% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-d601f55e2ae0405f82dd74b0477944f6
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09181241B2

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