p-Toluenesulfonic acid → (S)-8-chloro-12,12a-dihydro-1-[5-(pyrrolidin-1-ylmethyl)-1,2,4-oxadiazol-3-yl]-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one

HRID 1377977

Reaktionsgleichung

Reaktionsgleichung von HRID 1377977
[N:1]1([CH2:6][C:7]([OH:9])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N1C=CN=C1)(N1C=CN=C1)=O.[Cl:22][C:23]1[C:28]2[C:29](=[O:43])[N:30]3[CH2:42][CH2:41][C@H:31]3[C:32]3[N:33]([CH:34]=[N:35][C:36]=3[C:37](=[N:39]O)[NH2:38])[C:27]=2[CH:26]=[CH:25][CH:24]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C)C=O>[Cl:22][C:23]1[C:28]2[C:29](=[O:43])[N:30]3[CH2:42][CH2:41][C@H:31]3[C:32]3[N:33]([CH:34]=[N:35][C:36]=3[C:37]3[N:39]=[C:7]([CH2:6][N:1]4[CH2:2][CH2:3][CH2:4][CH2:5]4)[O:9][N:38]=3)[C:27]=2[CH:26]=[CH:25][CH:24]=1

Komponenten

6

Edukt 4

HCID 6101p-Toluenesulfonic acidHCID 682631,1'-CarbonyldiimidazoleHCID 414564Pyrrolidin-1-ylacetic acidHCID 54137540HCID 54137540, Verbindung

Produkt 1

HCID 53845854(S)-8-chloro-12,12a-dihydro-1-[5-(pyrrolidin-1-ylmethyl)-1,2,4-oxadiazol-3-yl]-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-oneAusbeute 32 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

2.55 g (13.5 mmol) of 1-pyrrolidine-acetic acid were dissolved in 20 ml of N,N-dimethylformamide and treated portionwise with 2.6 g (15.9 mmol) of 1,1'-carbonyldiimidazole. After stirring for 45 minutes 3.9 g (12.3 mmol) of (S)-8-chloro-12,12a-dihydro-9-oxo-9H,11H- azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxamidoxime were added and the mixture was stirred at 90° overnight. 0.2 g of p-toluenesulphonic acid was added and the mixture was stirred at 90° for a further 4 hours. The reaction mixture was concentrated. By chromatography of the residue on silica gel while eluting with methylene chloride/methanol 19/1 and recrystallization from ethyl acetate and hexane there were obtained 1.6 g (32%) of (S)-8-chloro-12,12a-dihydro-1-[5-(pyrrolidin-1-ylmethyl)-1,2,4-oxadiazol-3-yl]-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one of m.p. 117°-120°, which was converted into the hydrochloride.

Aufarbeitung

  1. additionwere added
  2. stirringthe mixture was stirred at 90° for a further 4 hours
  3. concentrationThe reaction mixture was concentrated
  4. washBy chromatography of the residue on silica gel while eluting with methylene chloride/methanol 19/1 and recrystallization from ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-c6799e52443444a1a28cf3624a5122d6
Quelldatensatz
uspto-grants-1997_09
Patentnummer
US05665718

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