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

반응식

HRID 31519 반응식
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

참가 물질

6

반응물 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

생성물 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

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

[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)+].

후처리

  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)

출처 및 근거

ORD 기록
ord-c028a1774c4c45dd938a698fb5c8d8e4
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07425638B2

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