Acetic Acid → 10-bromo-3-((dimethylamino)methyl)-9-fluoro-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamide

HRID 575314Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 575314
[Br:1][C:2]1[C:3]([F:22])=[CH:4][C:5]2[CH:11]3[CH2:12][CH:9]([CH2:10]3)[N:8]3[C:13]([CH:19]=O)=[C:14]([C:16]([NH2:18])=[O:17])[N:15]=[C:7]3[C:6]=2[CH:21]=1.C(O)(=O)C.Cl.[CH3:28][NH:29][CH3:30].C([BH3-])#N.[Na+]>CN(C)C=O>[Br:1][C:2]1[C:3]([F:22])=[CH:4][C:5]2[CH:11]3[CH2:12][CH:9]([CH2:10]3)[N:8]3[C:13]([CH2:19][N:29]([CH3:30])[CH3:28])=[C:14]([C:16]([NH2:18])=[O:17])[N:15]=[C:7]3[C:6]=2[CH:21]=1

Komponenten

6

Edukt 4

HCID 176Acetic AcidHCID 10473Dimethylamine, hydrochlorideHCID 5003444Sodium cyanoborohydrideHCID 8669316110-bromo-9-fluoro-3-formyl-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamide

Produkt 1

HCID 8669334910-bromo-3-((dimethylamino)methyl)-9-fluoro-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a suspension of 10-bromo-9-fluoro-3-formyl-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamide (75 mg) in anhydrous N,N-Dimethylformamide was added acetic acid, dimethylamine hydrochloride and 200 mg powdered 4 angstrom molecular sieves. The reaction was stirred for 30 minutes before the addition of sodium cyanoborohydride then continued to stir at room temperature for 18 hours. The reaction mixture was then extracted with dichloromethane and saturated ammonium chloride. The organic layer was dried, filtered and concentrated to afford crude 10-bromo-3-((dimethylamino)methyl)-9-fluoro-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamide. This crude intermediate was directly reacted with 2-Methyl-3-butyne-ol via General Procedure E to afford 34 mg (41%) of 3-[(dimethylamino)methyl]-9-fluoro-10-(3-hydroxy-3-methyl-but-1-ynyl)-5,6,7,12-tetrahydro-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamide.

Aufarbeitung

  1. extractionThe reaction mixture was then extracted with dichloromethane and saturated ammonium chloride
  2. customThe organic layer was dried
  3. filtrationfiltered
  4. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-44b0f740cbbb4488b2f199751e9491ce
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09034866B2

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