5-Chloro-2-methylaniline → 2-bromo-5-[(4-chloro-phenyl)-5-chloro-2-methyl-phenylamino]-1-isopropyl-1H-imidazole-4-carboxylic acid ethyl ester

HRID 2410097ノート

反応式

HRID 2410097 の反応式
O(S(C)(=O)=O)S(C)(=O)=O.[CH2:10]([O:12][C:13]([C:15]1[N:16]=[C:17]([Br:32])[N:18]([CH:29]([CH3:31])[CH3:30])[C:19]=1C(C1C=CC(Cl)=CC=1)O)=[O:14])[CH3:11].[Cl:33][C:34]1[CH:35]=[CH:36][C:37]([CH3:41])=[C:38]([CH:40]=1)[NH2:39]>C(Cl)Cl.C(Cl)Cl.O>[CH2:10]([O:12][C:13]([C:15]1[N:16]=[C:17]([Br:32])[N:18]([CH:29]([CH3:30])[CH3:31])[C:19]=1[N:39]([C:37]1[CH:36]=[CH:35][C:34]([Cl:33])=[CH:40][CH:38]=1)[C:38]1[CH:40]=[C:34]([Cl:33])[CH:35]=[CH:36][C:37]=1[CH3:41])=[O:14])[CH3:11]

参加物

6

反応物 3

HCID 72605-Chloro-2-methylanilineHCID 81560Methanesulfonic anhydrideHCID 86707749ethyl 2-bromo-5-((4-chlorophenyl)(hydroxy)methyl)-1-isopropyl-1H-imidazole-4-carboxylate2 回

生成物 1

HCID 867077542-bromo-5-[(4-chloro-phenyl)-5-chloro-2-methyl-phenylamino]-1-isopropyl-1H-imidazole-4-carboxylic acid ethyl ester

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 21908982Water methylene chloride溶媒

反応条件

温度
5 °C

実験手順

Ms2O (3.6 g, 20.9 mmol) was added to a stirred solution of 2-bromo-5-[(4-chlorophenyl)-hydroxy-methyl]-1-isopropyl-1H-imidazole-4-carboxylic acid ethyl ester (intermediate B; 4.2 g, 20.9 mmol) and TEA (5.3 g, 52.0 mmol) in DCM (80 mL) at 5° C. and the reaction mixture was stirred at 5° C. for 15 min. 5-Chloro-2-methyl aniline (2.2 g, 15.7 mmol) was then added. The reaction mixture was allowed to reach rt in 45 min and stirred at rt for 2 h. The reaction mixture was diluted in DCM/water, extracted twice with DCM and the combined organic extracts were washed with brine, dried (Na2SO4) and concentrated. The crude was purified by flash chromatography (silica gel, EtOAc/hexanes 2:8) to afford the title compound as a white foam; ESI-MS: 526.2 [M+H]+ (LC-MS 2); 1H-NMR (DMSO-d6, 400 MHz) δ ppm 1.15 (dd, J=9.97, 4.11 Hz, 2 H) 1.15 (s, 1 H) 1.24 (t, J=7.23 Hz, 3 H) 1.45 (d, J=7.04 Hz, 3 H) 2.17 (s, 3 H) 4.24 (quin, J=6.74 Hz, 2 H) 4.83-5.04 (m, 1 H) 5.92 (d, J=5.47 Hz, 1 H) 6.47 (bs, 1 H) 6.63 (dd, J=7.82, 1.95 Hz, 1H) 6.79 (bs, 1H) 7.04 (d, J=8.21 Hz, 1 H) 7.26 (m, J=8.60 Hz, 2 H) 7.43 (m, J=8.60 Hz, 2 H).

後処理

  1. waitto reach rt in 45 min
  2. stirringstirred at rt for 2 h
  3. extractionextracted twice with DCM
  4. washthe combined organic extracts were washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude was purified by flash chromatography (silica gel, EtOAc/hexanes 2:8)

出典と根拠

ORDレコード
ord-6699b79aca7c4808856f06f42466d273
出典データセット
uspto-grants-2014_08
特許番号
US08815926B2

反応ノート

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