Sodium Hydroxide → 8-chloro-6-(2-fluoro-phenyl)-1-methyl-4H-imidazo[1,2-a][1,4]benzodiazepine-2-methanol

HRID 566283Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 566283
[Al].[Li].[H-].[Cl:4][C:5]1[CH:6]=[CH:7][C:8]2[N:14]3[C:15]([CH3:22])=[C:16]([C:18](OC)=[O:19])[N:17]=[C:13]3[CH2:12][N:11]=[C:10]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[F:29])[C:9]=2[CH:30]=1.[OH-].[Na+]>O1CCCC1.O>[Cl:4][C:5]1[CH:6]=[CH:7][C:8]2[N:14]3[C:15]([CH3:22])=[C:16]([CH2:18][OH:19])[N:17]=[C:13]3[CH2:12][N:11]=[C:10]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[F:29])[C:9]=2[CH:30]=1

Komponenten

7

Edukt 4

HCID 14798Sodium HydroxideHCID 166653HydrideHCID 16211445Aluminum;lithiumHCID 21266007methyl 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,2-a][1,4]benzodiazepine-2-carboxylate

Produkt 1

HCID 212660038-chloro-6-(2-fluoro-phenyl)-1-methyl-4H-imidazo[1,2-a][1,4]benzodiazepine-2-methanolAusbeute 20 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittel2×HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

3.3 ml of a 1M lithium aluminium, hydride solution in tetrahydrofuran was cooled to −75° C. and a solution of 1.26 g of methyl 8-chloro -6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,2-a][1,4]benzodiazepine-2-carboxylate in 15 ml of tetrahydrofuran was added dropwise. After 1 h. in a dry ice/acetone bath the mixture was brought to 0° C. and left for a further h. For the working up, 0.1 ml of water was added dropwise at 0° C. while stirring intensively, 0.1 ml of 15% sodium hydroxide solution was added after 5 min., finally 0.3 ml of water was added after a further 10 min. After 12 h. the mixture was filtered, the residue was suspended in 100 ml of methanol, stirred well for 1 h. and filtered. The combined filtrates were concentrated in a vacuum and purified by chromatography on 80 g of silica gel with dichloromethane containing 5% methanol. There were obtained 234 mg (20%) of 8-chloro-6-(2-fluoro-phenyl)-1-methyl-4H-imidazo[1,2-a][1,4]benzodiazepine-2-methanol. For the preparation of the methanesulphonic acid salt, 230 mg of this product were dissolved in 10 ml of dichloromethane and 6.0 ml of a 0.1M methanesulphonic acid solution in diethyl ether were slowly added dropwise. After removal of the solvent in a vacuum the residue was taken up in 10 ml of water, filtered and lyophilized. There were isolated 183 mg of hygroscopic 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo-[1,2-a][1,4]benzodiazepine-2-methanol methanesulphonate (1:2) of m.p. 116° C.

Aufarbeitung

  1. waitleft for a further h
  2. filtrationAfter 12 h. the mixture was filtered
  3. stirringstirred well for 1 h.
  4. filtrationfiltered
  5. concentrationThe combined filtrates were concentrated in a vacuum
  6. custompurified by chromatography on 80 g of silica gel with dichloromethane containing 5% methanol

Quellen und Nachweise

ORD-Eintrag
ord-f8273a0ca74c4fb585a3e50df5834d4b
Quelldatensatz
uspto-grants-2001_01
Patentnummer
US06174881B1

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