Phosgene → 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

HRID 2263895ノート

反応式

HRID 2263895 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]2([CH3:40])[C@:12]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)([CH3:13])[NH:11][C:10]([C:21]3[C:22]([O:37][CH2:38][CH3:39])=[CH:23][C:24]([C:33]([CH3:36])([CH3:35])[CH3:34])=[C:25]([S:27]([N:30]([CH3:32])[CH3:31])(=[O:29])=[O:28])[CH:26]=3)=[N:9]2)=[CH:4][CH:3]=1.[C:41](Cl)([Cl:43])=[O:42]>C(N(CC)CC)C>[C:33]([C:24]1[C:25]([S:27](=[O:28])(=[O:29])[N:30]([CH3:31])[CH3:32])=[CH:26][C:21]([C:10]2[N:9]([C:41]([Cl:43])=[O:42])[C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)([CH3:40])[C:12]([C:14]3[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=3)([CH3:13])[N:11]=2)=[C:22]([O:37][CH2:38][CH3:39])[CH:23]=1)([CH3:34])([CH3:36])[CH3:35]

参加物

4

反応物 2

HCID 6371PhosgeneHCID 686842965-[(4S,5R)-4,5-bis(4-chlorophenyl)-4,5-dimethyl-1H-imidazol-2-yl]-2-tert-butyl-4-ethoxy-N,N-dimethylbenzenesulfonamide

生成物 1

HCID 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

試薬・触媒・溶媒 1

HCID 8471Triethylamine溶媒

実験手順

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.

出典と根拠

ORDレコード
ord-30da8b388d304c56a133177b4605f06a
出典データセット
uspto-grants-2010_12
特許番号
US07851626B2

反応ノート

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