4-(Piperazin-1-yl)-1lambda6-thiane-1,1-dione dihydrochloride → {(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(1-hydroxy-1-methyl-ethyl)-phenyl]-4,5-dimethyl-4,5-dihydro-imidazol-1-yl}-[4-(1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-piperazin-1-yl]-methanone

HRID 2263971Notes

Reaction equation

HRID 2263971 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH3:37])[C:12]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)([CH3:13])[N:11]([C:21](Cl)=[O:22])[C:10]([C:24]3[CH:29]=[CH:28][C:27]([C:30]([OH:33])([CH3:32])[CH3:31])=[CH:26][C:25]=3[O:34][CH2:35][CH3:36])=[N:9]2)=[CH:4][CH:3]=1.Cl.Cl.[O:40]=[S:41]1(=[O:53])[CH2:46][CH2:45][CH:44]([N:47]2[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]2)[CH2:43][CH2:42]1>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]2([CH3:37])[C@:12]([C:14]3[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=3)([CH3:13])[N:11]([C:21]([N:50]3[CH2:51][CH2:52][N:47]([CH:44]4[CH2:43][CH2:42][S:41](=[O:40])(=[O:53])[CH2:46][CH2:45]4)[CH2:48][CH2:49]3)=[O:22])[C:10]([C:24]3[CH:29]=[CH:28][C:27]([C:30]([OH:33])([CH3:31])[CH3:32])=[CH:26][C:25]=3[O:34][CH2:35][CH3:36])=[N:9]2)=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 567734904-(Piperazin-1-yl)-1lambda6-thiane-1,1-dione dihydrochlorideHCID 73408763rac-(4S*,5R*)-4,5-bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(1-hydroxy-1-methyl-ethyl)-phenyl]-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl chloride

Product 1

HCID 17754728{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(1-hydroxy-1-methyl-ethyl)-phenyl]-4,5-dimethyl-4,5-dihydro-imidazol-1-yl}-[4-(1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-piperazin-1-yl]-methanone

Procedure

In a manner analogous to the method described in example 5, rac-(4S*,5R*)-4,5-bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(1-hydroxy-1-methyl-ethyl)-phenyl]-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl chloride was reacted with 1-(1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-piperazine dihydrochloride (example 22) 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% of 1:1 ethanol/acetonitrile in carbon dioxide). HR-MS (ES, m/z) calculated for C38H47N4O5SCl2 [(M+H)+] 741.2639, observed 741.2637.

Sources & evidence

ORD record
ord-bba2f12032bb4981851ddf506e64552e
Source dataset
uspto-grants-2010_12
Patent number
US07851626B2

Reaction notes

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