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 2410097노트

반응식

HRID 2410097 반응식
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]

참가 물질

6

반응물 3

HCID 72605-Chloro-2-methylanilineHCID 81560Methanesulfonic anhydrideHCID 86707749ethyl 2-bromo-5-((4-chlorophenyl)(hydroxy)methyl)-1-isopropyl-1H-imidazole-4-carboxylate2회

생성물 1

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

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 21908982Water methylene chloride용매

반응 조건

온도
5 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-6699b79aca7c4808856f06f42466d273
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08815926B2

반응 노트

불러오는 중…