Sodium hydride → 3-{6-[2-(2-Methoxyethoxy)ethoxy]isoquinolin-1-yl}-2-oxo-2,3-dihydro-1H-indole-5-carbonitrile Trifluoroacetate

HRID 1271231Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1271231
[H-].[Na+].[O:3]=[C:4]1[CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:13]#[N:14])[CH:10]=2)[NH:5]1.Cl[C:16]1[C:25]2[C:20](=[CH:21][C:22]([O:26][CH2:27][CH2:28][O:29][CH2:30][CH2:31][O:32][CH3:33])=[CH:23][CH:24]=2)[CH:19]=[CH:18][N:17]=1.[F:34][C:35]([F:40])([F:39])[C:36]([O-:38])=[O:37]>O1CCCC1.O1CCCC1.CN1CCCC1=O>[F:34][C:35]([F:40])([F:39])[C:36]([OH:38])=[O:37].[CH3:33][O:32][CH2:31][CH2:30][O:29][CH2:28][CH2:27][O:26][C:22]1[CH:21]=[C:20]2[C:25](=[CH:24][CH:23]=1)[C:16]([CH:12]1[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([C:13]#[N:14])[CH:10]=3)[NH:5][C:4]1=[O:3])=[N:17][CH:18]=[CH:19]2

Komponenten

7

Edukt 4

HCID 24758Sodium hydrideHCID 84468TrifluoroacetateHCID 27733462-Oxo-2,3-dihydro-1H-indole-5-carbonitrileHCID 18452920Chloro-6-[2-(2-methoxyethoxy)ethoxy]isoquinoline

Produkt 1

HCID 98494573-{6-[2-(2-Methoxyethoxy)ethoxy]isoquinolin-1-yl}-2-oxo-2,3-dihydro-1H-indole-5-carbonitrile TrifluoroacetateAusbeute 27 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel2×HCID 22156051tetrahydrofuran N-methylpyrrolidinoneLösungsmittel

Versuchsvorschrift

A suspension of sodium hydride (92 mg, 3.55 mmol, 95% powder) in tetrahydrofuran (10 mL) was slowly added via a cannula to a solution of 2-oxo-5-indolinecarbonitrile (292 mg, 1.85 mmol) in tetrahydrofuran/N-methylpyrrolidinone (15 mL, 2:1) under nitrogen atmosphere. The reaction mixture was stirred at room temperature for 25 min. A solution of chloro-6-[2-(2-methoxyethoxy)ethoxy]isoquinoline (400 mg, 1.42 mmol) in tetrahydrofuran (10 mL) was added and the reaction solution was stirred at room temperature over night. The reaction was quenched by slow addition of hydrochloric acid (1 M) and concentrated in vacuo to a slurry. The slurry was diluted with acetonitrile (5 mL) and purified by prep RP-HPLC (C18 2″ column, gradient:acetonitril/water, 20:80→0:100+0.1% TFA). The appropriate fractions were pooled and lyophilized giving 193 mg (27% yield) of the title compound as an orange trifluoroacetate salt. MS (AP+) m/z 404 (M+1).

Aufarbeitung

  1. stirringthe reaction solution was stirred at room temperature over night
  2. customThe reaction was quenched by slow addition of hydrochloric acid (1 M)
  3. concentrationconcentrated in vacuo to a slurry
  4. additionThe slurry was diluted with acetonitrile (5 mL)
  5. custompurified by prep RP-HPLC (C18 2″ column

Quellen und Nachweise

ORD-Eintrag
ord-6ff0d6fcb50f406c8800b8630bed7c77
Quelldatensatz
uspto-grants-2007_04
Patentnummer
US07205314B2

Notizen zur Reaktion

Wird geladen…