Phosgene → 4-{4-[4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazine-1-carbonyl}-piperazin-2-one

HRID 31519

反応式

HRID 31519 の反応式
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C:21]([N:23]3[CH2:28][CH2:27][N:26]([CH2:29]CC#N)[CH2:25][CH2:24]3)=[O:22])[C:11]([C:33]3[CH:38]=[CH:37][C:36]([C:39]([F:42])([F:41])[F:40])=[CH:35][C:34]=3[O:43][CH2:44][CH3:45])=[N:10]2)=[CH:5][CH:4]=1.C(Cl)(Cl)=[O:47].[NH:50]1[CH2:55][CH2:54][NH:53][CH2:52][C:51]1=[O:56].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH:13]([C:14]3[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=3)[N:12]([C:21]([N:23]3[CH2:28][CH2:27][N:26]([C:29]([N:53]4[CH2:54][CH2:55][NH:50][C:51](=[O:56])[CH2:52]4)=[O:47])[CH2:25][CH2:24]3)=[O:22])[C:11]([C:33]3[CH:38]=[CH:37][C:36]([C:39]([F:42])([F:40])[F:41])=[CH:35][C:34]=3[O:43][CH2:44][CH3:45])=[N:10]2)=[CH:5][CH:4]=1

参加物

6

反応物 4

HCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 231360Piperazin-2-oneHCID 111814993-{4-[4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-propionitrile hydrochloride

生成物 1

HCID 117640044-{4-[4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazine-1-carbonyl}-piperazin-2-one

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

[4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazol-1-yl]-piperazin-1-yl-methanone (50 mg, 0.085 mmol, example 8A) was dissolved in methylene chloride (1 mL) and cooled in an ice bath. Phosgene (250 uL, 20% solution in toluene)) was added, and the mixture was stirred for 30 min. The solvent was evaporated and the residue was taken in methylene chloride. One third of this solution (0.028 mmol) was treated with 2-piperazinone (8.5 mg) and diisopropylethylamine (15 ul). The mixture was sonicated to aid in dissolving the amine and allowed to stand at ambient temperature overnight. It was diluted with methylene chloride and washed with water. The organic portion was separated and evaporated to give the crude urea. Purification of the crude urea by flash chromatography (silica gel) using ethyl acetate and hexanes gave 4-{4-[4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazine-1-carbonyl}-piperazin-2-one (9.0 mg). LR-MS: 718.4 [(M+H)+].

後処理

  1. temperaturecooled in an ice bath
  2. customThe solvent was evaporated
  3. customThe mixture was sonicated
  4. waitto stand at ambient temperature overnight
  5. washwashed with water
  6. customThe organic portion was separated
  7. customevaporated
  8. customto give the crude urea
  9. customPurification of the crude urea by flash chromatography (silica gel)

出典と根拠

ORDレコード
ord-c028a1774c4c45dd938a698fb5c8d8e4
出典データセット
uspto-grants-2008_09
特許番号
US07425638B2

関連ノート

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