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 2410097Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2410097
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]

Komponenten

6

Edukt 3

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 21908982Water methylene chlorideLösungsmittel

Reaktionsbedingungen

Temperatur
5 °C

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-6699b79aca7c4808856f06f42466d273
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08815926B2

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