Tetrahydrofuran → 3-[4-(1-benzyl-2-methyl-1H-benzimidazol-4-yl)phenyl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

HRID 82525Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 82525
[CH2:1]([N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[C:16](Br)[C:11]=2[N:10]=[C:9]1[CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:27]2[CH:32]=[CH:31][C:30]([N:33]3[C:37]4=[N:38][CH:39]=[CH:40][CH:41]=[C:36]4[N:35]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[C:34]3=[O:50])=[CH:29][CH:28]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].C1COCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH2:1]([N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[C:16]([C:27]3[CH:32]=[CH:31][C:30]([N:33]4[C:37]5=[N:38][CH:39]=[CH:40][CH:41]=[C:36]5[N:35]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:48])([CH3:47])[CH3:49])[C:34]4=[O:50])=[CH:29][CH:28]=3)[C:11]=2[N:10]=[C:9]1[CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

7

Edukt 4

HCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 585773473-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-oneHCID 671269161-benzyl-4-bromo-2-methyl-1H-benzo[d]imidazole

Produkt 1

HCID 585773783-[4-(1-benzyl-2-methyl-1H-benzimidazol-4-yl)phenyl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-oneAusbeute 53,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittel2×

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

Benzyl chloride (1.527 mL) was added to a solution of 4-bromo-2-methyl-1H-benzimidazole (1.40 g) and sodium hydride (0.531 g) in DMF (10 mL) at 0° C. The mixture was stirred at room temperature under a dry atmosphere for 1 h. The reaction mixture was diluted with MeOH and concentrated in vacuo. The residue was purified by column chromatography (NH silica gel, eluted with 5%-50% EtOAc in hexane) to give 1-benzyl-4-bromo-2-methyl-1H-benzo[d]imidazole (1.88 g) as tan oil. The mixture of 1-benzyl-4-bromo-2-methyl-1H-benzo[d]imidazole (496 mg), 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (700 mg), Pd(Ph3P)4 (87 mg), sodium carbonate (476 mg) and THF (18 mL)-water (0.90 mL) was heated at 100° C. for 1 h under microwave irradiation. The mixture was poured into water at room temperature and extracted with EtOAc. The organic layer was separated, washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by column chromatography (silica gel, eluted with 10%-50% EtOAc in hexane) to give 3-[4-(1-benzyl-2-methyl-1H-benzimidazol-4-yl)phenyl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (450 mg) as white crystals.

Aufarbeitung

  1. extractionextracted with EtOAc
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (silica gel, eluted with 10%-50% EtOAc in hexane)

Quellen und Nachweise

ORD-Eintrag
ord-58635b16ce3e4bd2aacf4b4717da7b4a
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846713B2

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