Dimethyl Sulfoxide → 7-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-5-methylthiomethoxy-2,3,4,5-tetrahydro-1H-benzo[b]azepine

HRID 1184652

Reaktionsgleichung

Reaktionsgleichung von HRID 1184652
[CH3:1][S:2]([CH3:4])=O.C(OC(=O)C)(=O)C.[CH3:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=1[C:19]([NH:21][C:22]1[CH:23]=[CH:24][C:25]([C:29]([N:31]2[C:37]3[CH:38]=[CH:39][C:40]([Cl:42])=[CH:41][C:36]=3[CH:35]([OH:43])[CH2:34][CH2:33][CH2:32]2)=[O:30])=[C:26]([CH3:28])[CH:27]=1)=[O:20].[OH-].[Na+]>O.C(O)(=O)C>[Cl:42][C:40]1[CH:39]=[CH:38][C:37]2[N:31]([C:29](=[O:30])[C:25]3[CH:24]=[CH:23][C:22]([NH:21][C:19](=[O:20])[C:18]4[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=4[CH3:12])=[CH:27][C:26]=3[CH3:28])[CH2:32][CH2:33][CH2:34][CH:35]([O:43][CH2:1][S:2][CH3:4])[C:36]=2[CH:41]=1

Komponenten

7

Edukt 4

HCID 679Dimethyl SulfoxideHCID 7918Acetic AnhydrideHCID 14798Sodium HydroxideHCID 216237Tolvaptan

Produkt 1

HCID 251342157-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-5-methylthiomethoxy-2,3,4,5-tetrahydro-1H-benzo[b]azepine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

Dimethylsulfoxide (DMSO) (3 ml), acetic anhydride (1.5 ml), and acetic acid (1.5 ml) were added to tolvaptan (1.0 g, 2.2 mmol), and the mixture was stirred at 70° C. for 4 hours. Water and 1N aqueous sodium hydroxide solution were added to the reaction mixture, and the mixture was extracted with ethyl acetate, washed with an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue was purified by silica gel flash chromatography (n-hexane:ethyl acetate=80:20→20:80). The purified product was concentrated under reduced pressure to obtain 0.62 g of 7-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-5-methylthiomethoxy-2,3,4,5-tetrahydro-1H-benzo[b]azepine as white amorphous solid.

Aufarbeitung

  1. extractionthe mixture was extracted with ethyl acetate
  2. washwashed with an aqueous saturated sodium chloride solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationAfter filtration and concentration under reduced pressure
  5. customthe residue was purified by silica gel flash chromatography (n-hexane:ethyl acetate=80:20→20:80)
  6. concentrationThe purified product was concentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-13aec5ad380546a894ea2d1be06e15f3
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08669229B2

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