1-(3-(Methylsulfonyl)propyl)piperazine dihydrochloride → 5-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-1-[4-(3-methanesulfonyl-propyl)-piperazine-1-carbonyl]-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl}-2-tert-butyl-4-ethoxy-N,N-dimethyl-benzenesulfonamide

HRID 2263896

Reaktionsgleichung

Reaktionsgleichung von HRID 2263896
[C:1]([C:5]1[C:10]([S:11](=[O:16])(=[O:15])[N:12]([CH3:14])[CH3:13])=[CH:9][C:8]([C:17]2[N:18]([C:38](Cl)=[O:39])[C:19]([C:31]3[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=3)([CH3:30])[C:20]([C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=3)([CH3:22])[N:21]=2)=[C:7]([O:41][CH2:42][CH3:43])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.Cl.[CH3:46][S:47]([CH2:50][CH2:51][CH2:52][N:53]1[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]1)(=[O:49])=[O:48]>C(N(CC)CC)C>[Cl:29][C:26]1[CH:25]=[CH:24][C:23]([C@@:20]2([CH3:22])[C@:19]([C:31]3[CH:32]=[CH:33][C:34]([Cl:37])=[CH:35][CH:36]=3)([CH3:30])[N:18]([C:38]([N:56]3[CH2:55][CH2:54][N:53]([CH2:52][CH2:51][CH2:50][S:47]([CH3:46])(=[O:48])=[O:49])[CH2:58][CH2:57]3)=[O:39])[C:17]([C:8]3[C:7]([O:41][CH2:42][CH3:43])=[CH:6][C:5]([C:1]([CH3:2])([CH3:4])[CH3:3])=[C:10]([S:11]([N:12]([CH3:14])[CH3:13])(=[O:15])=[O:16])[CH:9]=3)=[N:21]2)=[CH:28][CH:27]=1

Komponenten

4

Edukt 2

HCID 498534791-(3-(Methylsulfonyl)propyl)piperazine dihydrochlorideHCID 86612876rac-(4S*,5R*)-2-(4-tert-butyl-5-dimethylsulfamoyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl chloride

Produkt 1

HCID 177548915-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-1-[4-(3-methanesulfonyl-propyl)-piperazine-1-carbonyl]-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl}-2-tert-butyl-4-ethoxy-N,N-dimethyl-benzenesulfonamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

In a manner analogous to the method described in example 3, rac-5-[(4S*,5R*)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl]-2-tert-butyl-4-ethoxy-N,N-dimethyl-benzenesulfonamide was reacted with phosgene in the presence of triethylamine to give rac-(4S*,5R*)-2-(4-tert-butyl-5-dimethylsulfamoyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl chloride. The carbamoyl chloride was then reacted with 1-(3-methanesulfonyl-propyl)-piperazine dihydrochloride (prepared as described in Fotouhi, N. et al. WO 2005110996) in the presence of triethylamine to give the title compound as a racemic mixture. The enantiomers were then separated by supercritical fluid chromatography (Berger Instrument Multi-Gram II, Daicel ChiralPak OD-H 3×25 cm, 35° C. at 100 bar, eluting with 30% methanol in carbon dioxide). HR-MS (ES, m/z) calculated for C40H53N5O6S2Cl2 [(M+H)+] 834.2887, observed 834.2878.

Quellen und Nachweise

ORD-Eintrag
ord-3dcf6c92391f4c70bee11ade829936ae
Quelldatensatz
uspto-grants-2010_12
Patentnummer
US07851626B2

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