Tolvaptan → HCID 66733251, Verbindung

HRID 1184645

Reaktionsgleichung

Reaktionsgleichung von HRID 1184645
[CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][C:7]=1[C:8]([NH:10][C:11]1[CH:12]=[CH:13][C:14]([C:18]([N:20]2[C:26]3[CH:27]=[CH:28][C:29]([Cl:31])=[CH:30][C:25]=3[CH:24]([OH:32])[CH2:23][CH2:22][CH2:21]2)=[O:19])=[C:15]([CH3:17])[CH:16]=1)=[O:9].Cl.[CH3:34][N:35]([CH3:42])[CH2:36][CH2:37][CH2:38][C:39](O)=[O:40].Cl.CN(C)CCCN=C=NCC.C(=O)([O-])O.[Na+]>CN(C)C1C=CN=CC=1.ClCCl.C(N(CC)CC)C>[ClH:31].[CH3:34][N:35]([CH3:42])[CH2:36][CH2:37][CH2:38][C:39]([O:32][CH:24]1[CH2:23][CH2:22][CH2:21][N:20]([C:18](=[O:19])[C:14]2[CH:13]=[CH:12][C:11]([NH:10][C:8](=[O:9])[C:7]3[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=3[CH3:1])=[CH:16][C:15]=2[CH3:17])[C:26]2[CH:27]=[CH:28][C:29]([Cl:31])=[CH:30][C:25]1=2)=[O:40]

Komponenten

8

Edukt 4

HCID 216237TolvaptanHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 126916404-(Dimethylamino)butyric acid hydrochloride

Produkt 1

HCID 66733251HCID 66733251, VerbindungAusbeute 138,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

Tolvaptan (1.0 g, 2.2 mmol), 4-dimethylamino-butyric acid hydrochloride (0.48 g, 2.9 mmol), and 4-dimethylaminopyridine (27 mg, 0.22 mmol) were suspended in dichloromethane (5 ml). Triethylamine (0.4 ml) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (WSC) (0.55 g, 2.9 mmol) were added thereto, and the mixture was stirred at room temperature for 12 hours. An aqueous saturated sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was 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=50:50→0:100). The purified product was concentrated under reduced pressure. The residue was then dissolved in ethyl acetate, a 4N hydrogen chloride ethyl acetate solution was added thereto, and the resultant mixture was concentrated under reduced pressure. To the residue was added water (10 ml). After filteration, the filtrate was freeze-dried to obtain 0.91 g of 7-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl 4-dimethylaminobutyrate hydrochloride as white amorphous solid.

Aufarbeitung

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed 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=50:50→0:100)
  6. concentrationThe purified product was concentrated under reduced pressure
  7. dissolutionThe residue was then dissolved in ethyl acetate
  8. additiona 4N hydrogen chloride ethyl acetate solution was added
  9. concentrationthe resultant mixture was concentrated under reduced pressure
  10. additionTo the residue was added water (10 ml)
  11. customAfter filteration, the filtrate was freeze-dried

Quellen und Nachweise

ORD-Eintrag
ord-a321a6aa93664227ac09a582f8845467
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08669229B2

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