Water → 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-7-[(1,1,1-trifluoropropan-2-yl)oxy]-3,4-dihydroisoquinolin-1(2H)-one

HRID 577484Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 577484
[Cl:1][C:2]1[C:3]([O:13][CH:14]([CH3:19])[C:15]([F:18])([F:17])[F:16])=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[NH:9][CH2:8][CH2:7]2.[H-].[Na+].[CH2:22]([O:29][C:30]1[C:35]([CH2:36]Cl)=[C:34]([CH3:38])[CH:33]=[C:32]([CH3:39])[N:31]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.O>CN(C=O)C>[CH2:22]([O:29][C:30]1[C:35]([CH2:36][N:9]2[CH2:8][CH2:7][C:6]3[C:11](=[C:2]([Cl:1])[C:3]([O:13][CH:14]([CH3:19])[C:15]([F:18])([F:16])[F:17])=[CH:4][CH:5]=3)[C:10]2=[O:12])=[C:34]([CH3:38])[CH:33]=[C:32]([CH3:39])[N:31]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Komponenten

6

Edukt 4

HCID 962WaterHCID 24758Sodium hydrideHCID 612578682-(Benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridineHCID 867237098-chloro-7-[(1,1,1-trifluoropropan-2-yl)oxy]-3,4-dihydroisoquinolin-1(2H)-one

Produkt 1

HCID 867237102-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-7-[(1,1,1-trifluoropropan-2-yl)oxy]-3,4-dihydroisoquinolin-1(2H)-oneAusbeute 80 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 8-chloro-7-[(1,1,1-trifluoropropan-2-yl)oxy]-3,4-dihydroisoquinolin-1(2H)-one (58a, 50 mg, 0.17 mmol) in dry DMF (6 mL) was added portionwise NaH (60% in oil, 21 mg, 0.51 mmol) at 0° C. under N2 atmosphere. The resulting mixture was stirred at 0° C. for 10 minutes and then 2-(benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridine (Cpd Z, 76 mg, 0.29 mmol) was added. The resulting mixture was stirred at room temperature overnight. To the reaction mixture was added H2O (20 mL). The mixture was extracted with EtOAc (2×10 mL). The combined organic layers were washed with brine (4×15 mL), dried over Na2SO4 and concentrated under vacuum. The residue was purified by column chromatography (petroleum ether/EtOAc=6:1) to give 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-7-[(1,1,1-trifluoropropan-2-yl)oxy]-3,4-dihydroisoquinolin-1(2H)-one (58b, 70 mg, 80%) as a colorless oil.

Aufarbeitung

  1. stirringThe resulting mixture was stirred at room temperature overnight
  2. extractionThe mixture was extracted with EtOAc (2×10 mL)
  3. washThe combined organic layers were washed with brine (4×15 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by column chromatography (petroleum ether/EtOAc=6:1)

Quellen und Nachweise

ORD-Eintrag
ord-bc6c127bc5bf4e6ba806434e63dbc524
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09040515B2

Notizen zur Reaktion

Wird geladen…