Water → (3-(4-(1H-Pyrazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)methanol

HRID 926479

Reaktionsgleichung

Reaktionsgleichung von HRID 926479
C([Li])CCC.[N:6]1([C:11]2[CH:31]=[CH:30][C:14]([CH2:15][C:16]3[C:17]([O:28][CH3:29])=[N:18][C:19]4[C:24]([C:25]=3[Cl:26])=[CH:23][C:22](Br)=[CH:21][CH:20]=4)=[CH:13][CH:12]=2)[CH:10]=[CH:9][CH:8]=[N:7]1.[CH3:32][N:33]1[C:37]([CH:38]=[O:39])=[CH:36][N:35]=[C:34]1[CH3:40].O>O1CCCC1>[N:6]1([C:11]2[CH:31]=[CH:30][C:14]([CH2:15][C:16]3[C:17]([O:28][CH3:29])=[N:18][C:19]4[C:24]([C:25]=3[Cl:26])=[CH:23][C:22]([CH:38]([C:37]3[N:33]([CH3:32])[C:34]([CH3:40])=[N:35][CH:36]=3)[OH:39])=[CH:21][CH:20]=4)=[CH:13][CH:12]=2)[CH:10]=[CH:9][CH:8]=[N:7]1

Komponenten

6

Edukt 4

HCID 962WaterHCID 31596101,2-dimethyl-1H-imidazole-5-carbaldehydeHCID 867155963-(4-(1H-Pyrazol-1-yl)benzyl)-6-bromo-4-chloro-2-methoxyquinoline2×HCID 178418339Butyllithium

Produkt 1

HCID 118005895(3-(4-(1H-Pyrazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)methanol

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
23 °C

Versuchsvorschrift

A solution of n-butyllithium in hexanes (1.6 M, 1.5 mL, 2.3 mmol) was added dropwise to a stirring solution of 3-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-4-chloro-2-methoxyquinoline (1 g, 2.3 mmol, Intermediate 10) in tetrahydrofuran (18 mL) at −78° C. After 3 minutes, a solution of 1,2-dimethyl-1H-imidazole-5-carbaldehyde (347 mg, 2.8 mmol) in tetrahydrofuran (5 mL) was added dropwise. After 5 minutes, the flask was placed into an ice-water bath. After 30 minutes, water (10 mL) was added and the biphasic mixture was allowed to warm to 23° C. The mixture was partitioned between half-saturated sodium chloride solution (50 mL) and ethyl acetate (100 mL). The layers were separated. The organic layer was dried with sodium sulfate and the dried solution was filtered. Silica gel (3 g) was added to the filtrate and the solvent was removed by rotary evaporation to afford a free-flowing powder. The powder was loaded onto a column of silica gel for purification. Elution with ethyl acetate initially, grading to 7% methanol-ethyl acetate provided the title compound as an off-white solid.

Aufarbeitung

  1. waitAfter 5 minutes
  2. customthe flask was placed into an ice-water bath
  3. waitAfter 30 minutes
  4. customThe mixture was partitioned between half-saturated sodium chloride solution (50 mL) and ethyl acetate (100 mL)
  5. customThe layers were separated
  6. dry with materialThe organic layer was dried with sodium sulfate
  7. filtrationthe dried solution was filtered
  8. additionSilica gel (3 g) was added to the filtrate
  9. customthe solvent was removed by rotary evaporation
  10. customto afford a free-flowing powder
  11. customThe powder was loaded onto a column of silica gel for purification
  12. washElution with ethyl acetate initially

Quellen und Nachweise

ORD-Eintrag
ord-ff25b25dc64e4608bc549df76fff9c91
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09284308B2

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