2-Bromo-6-chloroquinoline → 4-((6-Chloroquinolin-2-yl)(5-ethoxy-2-fluoro-3-isopropoxyphenyl)methylamino)benzonitrile
Reaktionsgleichung
Br[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:12])[CH:8]=2)[N:3]=1.[Li]CCCC.[CH2:18]([O:20][C:21]1[CH:22]=[C:23]([O:38][CH:39]([CH3:41])[CH3:40])[C:24]([F:37])=[C:25]([CH:36]=1)/[CH:26]=[N:27]/[C:28]1[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][CH:29]=1)[CH3:19]>C1COCC1>[Cl:12][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([N:27]([CH2:26][C:25]1[CH:36]=[C:21]([O:20][CH2:18][CH3:19])[CH:22]=[C:23]([O:38][CH:39]([CH3:41])[CH3:40])[C:24]=1[F:37])[C:28]1[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][CH:29]=1)[CH:11]=[CH:10]2Komponenten
5
Edukt 3
Produkt 1
Reagenzien, Katalysatoren, Lösungsmittel 1
Reaktionsbedingungen
- Temperatur
- -78 °C
Versuchsvorschrift
To a solution of Intermediate 90.1 (100 mg, 0.412 mmol) in 2 mL THF at −78° C., was added BuLi (1.4 M in hexanes, 324 μL, 0.454 mmol). The mixture was stirred at −78° C. for 10 min, then a solution of Intermediate 7.3 (134 mg, 0.412 mmol) in 0.7 mL THF was added. The mixture was stirred 15 min at −78° C., allowed to warm to rt over 30 min, then was quenched with sat. NH4Cl and diluted with EtOAc. The organic phase was washed with H2O and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 30% EtOAc/hexanes gradient) to afford 112 mg of Intermediate 90.2 as a pale orange solid.
Aufarbeitung
- stirringThe mixture was stirred 15 min at −78° C.
- temperatureto warm to rt over 30 min
- customwas quenched with sat. NH4Cl
- additiondiluted with EtOAc
- washThe organic phase was washed with H2O and brine
- dry with materialdried (Na2SO4)
- concentrationconcentrated
- customThe crude product was purified by flash chromatography (0 to 30% EtOAc/hexanes gradient)
Quellen und Nachweise
- ORD-Eintrag
- ord-16f243183ca04a0c88f82602f26104ca
- Quelldatensatz
- uspto-grants-2009_08
- Patentnummer
- US07576098B2
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