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}-N-tert-butyl-2-chloro-4-ethoxy-benzenesulfonamide → 5-{(4S,5R)-4,5-Bis-(4-chlorophenyl)-1-[4-(2-methanesulfonylaminoethyl)piperazine-1-carbonyl]-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl}-N-tert-butyl-2-chloro-4-ethoxybenzenesulfonamide

HRID 2263930Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]2([CH3:54])[C@:12]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)([CH3:13])[N:11]([C:21]([N:23]3[CH2:28][CH2:27][N:26]([CH2:29][CH2:30]CS(C)(=O)=O)[CH2:25][CH2:24]3)=[O:22])[C:10]([C:36]3[C:37]([O:51][CH2:52][CH3:53])=[CH:38][C:39]([Cl:50])=[C:40]([S:42]([NH:45][C:46]([CH3:49])([CH3:48])[CH3:47])(=[O:44])=[O:43])[CH:41]=3)=[N:9]2)=[CH:4][CH:3]=1.Cl.Cl.N1(CC[NH:65][S:66]([CH3:69])(=[O:68])=[O:67])CCNCC1>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]2([CH3:54])[C@:12]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)([CH3:13])[N:11]([C:21]([N:23]3[CH2:24][CH2:25][N:26]([CH2:29][CH2:30][NH:65][S:66]([CH3:69])(=[O:68])=[O:67])[CH2:27][CH2:28]3)=[O:22])[C:10]([C:36]3[C:37]([O:51][CH2:52][CH3:53])=[CH:38][C:39]([Cl:50])=[C:40]([S:42]([NH:45][C:46]([CH3:47])([CH3:48])[CH3:49])(=[O:43])=[O:44])[CH:41]=3)=[N:9]2)=[CH:4][CH:3]=1

Participants

Reactant 2

HCID 588943015-{(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}-N-tert-butyl-2-chloro-4-ethoxy-benzenesulfonamide

HCID 67071659N-[2-(piperazin-1-yl)ethyl]methanesulfonamide dihydrochloride

Product 1

HCID 177543615-{(4S,5R)-4,5-Bis-(4-chlorophenyl)-1-[4-(2-methanesulfonylaminoethyl)piperazine-1-carbonyl]-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl}-N-tert-butyl-2-chloro-4-ethoxybenzenesulfonamide

Procedure

In a manner analogous to the method described in example 5, rac-(4S*,5R*)-2-(5-tert-butylsulfamoyl-4-chloro-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl chloride (example 45) was reacted with N-(2-piperazin-1-yl-ethyl)-methanesulfonamide dihydrochloride (prepared as described in Fotouhi, N. et al. WO 2005110996) 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 35% methanol in carbon dioxide). HR-MS (ES, m/z) calculated for C37H48N6O6S2Cl3 [(M+H)+] 841.2137, observed 841.2129.

Sources & evidence

ORD record: ord-da7b5875f3c64ed4a2eee9406cc9f2c3
Source dataset: uspto-grants-2010_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07851626B2

Reaction notes

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