2-Chloroethyl isocyanate → {7-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl} (2-chloroethyl)carbamate

HRID 1184654

Reaktionsgleichung

Reaktionsgleichung von HRID 1184654
[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:33][CH2:34][CH2:35][N:36]=[C:37]=[O:38]>C1(C)C=CC=CC=1.CN(C)C1C=CN=CC=1>[Cl:31][C:29]1[CH:28]=[CH:27][C:26]2[N:20]([C:18](=[O:19])[C:14]3[CH:13]=[CH:12][C:11]([NH:10][C:8](=[O:9])[C:7]4[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=4[CH3:1])=[CH:16][C:15]=3[CH3:17])[CH2:21][CH2:22][CH2:23][CH:24]([O:32][C:37](=[O:38])[NH:36][CH2:35][CH2:34][Cl:33])[C:25]=2[CH:30]=1

Komponenten

5

Edukt 2

HCID 160352-Chloroethyl isocyanateHCID 216237Tolvaptan

Produkt 1

HCID 86708937{7-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl} (2-chloroethyl)carbamateAusbeute 82 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

Tolvaptan (1.0 g, 2.2 mmol) was suspended in toluene (7 ml). 2-Chloroethyl isocyanate (0.28 ml, 3.3 mmol) and 4-dimethylaminopyridine (DMAP) (27 mg, 0.22 mmol) were added thereto, and the mixture was stirred at 80° C. for 24 hours. After cooling to room temperature, the insoluble materials were filtered off and washed with ethyl acetate. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (n-hexane:ethyl acetate=54:46→33:67). The purified product was concentrated under reduced pressure to obtain 1.0 g of {7-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl}(2-chloroethyl)carbamate as white amorphous solid.

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. filtrationthe insoluble materials were filtered off
  3. washwashed with ethyl acetate
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by silica gel flash chromatography (n-hexane:ethyl acetate=54:46→33:67)
  6. concentrationThe purified product was concentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-9557162d57b747b49db1b568ee972bde
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08669229B2

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