Sodium hydride → tert-butyl 8-[(2,6-difluorophenyl)sulfonyl]-6-methoxy-1-methyl-1,3,4,8-tetrahydro-2H-[1,4]oxazepino[6,7-e]indole-2-carboxylate

HRID 2423190Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2423190
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[CH:8][NH:9]2)=[C:5]2[CH:12]([CH3:24])[N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:14][CH2:15][O:16][C:4]=12.[H-].[Na+].[F:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[C:29]=1[S:35](Cl)(=[O:37])=[O:36]>CN(C=O)C.O>[F:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[C:29]=1[S:35]([N:9]1[C:10]2[C:6](=[C:5]3[CH:12]([CH3:24])[N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:14][CH2:15][O:16][C:4]3=[C:3]([O:2][CH3:1])[CH:11]=2)[CH:7]=[CH:8]1)(=[O:37])=[O:36]

Komponenten

6

Edukt 3

HCID 24758Sodium hydrideHCID 27342712,6-Difluorobenzenesulfonyl chlorideHCID 69096461tert-Butyl 6-methoxy-1-methyl-1,3,4,8-tetrahydro-2H-[1,4]oxazepino[6,7-e]indole-2-carboxylate2×

Produkt 1

HCID 67241521tert-butyl 8-[(2,6-difluorophenyl)sulfonyl]-6-methoxy-1-methyl-1,3,4,8-tetrahydro-2H-[1,4]oxazepino[6,7-e]indole-2-carboxylateAusbeute 22 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

tert-Butyl 6-methoxy-1-methyl-1,3,4,8-tetrahydro-2H-[1,4]oxazepino[6,7-e]indole-2-carboxylate (Intermediate 36, 25 mg, 0.059 mmol) was dissolved in DMF (1 mL) and sodium hydride (60% in mineral oil, 4.0 mg, 0.15 mmol) was added. The reaction mixture was stirred at room temperature for 15 minutes before 2,6-difluorobenzenesulfonyl chloride (24.0 mg, 0.113 mmol) was added. The reaction mixture was allowed to stir at room temperature overnight and a few drops of water were added. The crude product was purified by preparative HPLC (XTerra C18, 50 mM NH4HCO3 pH 10-CH3CN) to give tert-butyl 8-[(2,6-difluorophenyl)sulfonyl]-6-methoxy-1-methyl-1,3,4,8-tetrahydro-2H-[1,4]oxazepino[6,7-e]indole-2-carboxylate (6.6 mg, 0.013 mmol ) which was dissolved in DCM (1 mL) and TFA (1 mL) was added. The reaction mixture was stirred at room temperature for 3 hours and evaporated to give the title compound (6.8 mg). MS m/z 409 [M+H]+.

Aufarbeitung

  1. additionwas added
  2. customThe crude product was purified by preparative HPLC (XTerra C18, 50 mM NH4HCO3 pH 10-CH3CN)

Quellen und Nachweise

ORD-Eintrag
ord-bbec9980cdee46b1a26d53228adb4a61
Quelldatensatz
uspto-grants-2011_06
Patentnummer
US07960374B2

Notizen zur Reaktion

Wird geladen…