1,2-dimethyl-1H-imidazole-5-carbaldehyde → (4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)methanol

HRID 926542

Reaktionsgleichung

Reaktionsgleichung von HRID 926542
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH:12]([C:14]3C(C)=NC(C)=C[CH:19]=3)[OH:13])[CH:10]=2)[N:5]=[C:4]([O:22][CH3:23])[C:3]=1[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][CH:26]=1.[Li]CCCC.[CH3:40][N:41]1C(C=O)=C[N:43]=[C:42]1[CH3:48]>C1COCC1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH:12]([C:14]3[N:41]([CH3:40])[C:42]([CH3:48])=[N:43][CH:19]=3)[OH:13])[CH:10]=2)[N:5]=[C:4]([O:22][CH3:23])[C:3]=1[CH2:24][C:25]1[CH:26]=[CH:27][C:28]([C:31]([F:32])([F:34])[F:33])=[CH:29][CH:30]=1

Komponenten

5

Edukt 3

HCID 31596101,2-dimethyl-1H-imidazole-5-carbaldehydeHCID 86715629(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)methanol2×HCID 178418339Butyllithium

Produkt 1

HCID 86715633(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)methanol

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-70 °C

Versuchsvorschrift

To a flask containing 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (2.0 g, 4.64 mmol, Intermediate 12: step d) was added THF (25 mL). The solution was cooled to −70° C. and then n-BuLi (2.5 M in hexanes, 1.8 mL, 4.5 mmol) was added dropwise. After 2 minutes, 1,2-dimethyl-1H-imidazole-5-carbaldehyde (720 mg, 5.8 mmol in 5 mL THF) was introduced. The reaction mixture was allowed to warm to 0° C. over 60 minutes at which time it was quenched with aqueous NH4Cl solution. The aqueous portion was extracted with EtOAc:THF (10:1, 5×50 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated to dryness. The solid was triturated with EtOAc:Et2O (1:1), collected by filtration and rinsed with additional Et2O and dried to afford the title compound. The mother liquors were concentrated and chromatographed on silica gel (3% MeOH-DCM increasing to 10% MeOH) to provide additional title compound.

Aufarbeitung

  1. temperatureto warm to 0° C. over 60 minutes at which time it
  2. customwas quenched with aqueous NH4Cl solution
  3. extractionThe aqueous portion was extracted with EtOAc:THF (10:1, 5×50 mL)
  4. washThe combined organics were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe solid was triturated with EtOAc:Et2O (1:1)
  9. filtrationcollected by filtration
  10. washrinsed with additional Et2O
  11. customdried

Quellen und Nachweise

ORD-Eintrag
ord-343f51654bde4df08bfcf78917fbb2f4
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09284308B2

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