1,2-Dichloroethane → 4-bromo-N-({4-bromo-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-imidazole-5-carboxamide

HRID 1875251Notes

Reaction equation

HRID 1875251 reaction equation
C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[NH2:15][CH2:16][C:17]1[C:18]([F:34])=[C:19]([O:24][C:25]2[CH:26]=[C:27]([CH:30]=[C:31]([Cl:33])[CH:32]=2)[C:28]#[N:29])[C:20]([Br:23])=[CH:21][CH:22]=1.[Br:35][C:36]1[N:37]=[CH:38][NH:39][C:40]=1[C:41](O)=[O:42]>CN(C=O)C>[Br:35][C:36]1[N:37]=[CH:38][NH:39][C:40]=1[C:41]([NH:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([Br:23])=[C:19]([O:24][C:25]2[CH:26]=[C:27]([C:28]#[N:29])[CH:30]=[C:31]([Cl:33])[CH:32]=2)[C:18]=1[F:34])=[O:42]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 671971663-{[3-(Aminomethyl)-6-bromo-2-fluorophenyl]oxy}-5-chlorobenzonitrileHCID 1785249144-bromo-1H-imidazole-5-carboxylic acid

Product 1

HCID 1785099064-bromo-N-({4-bromo-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-imidazole-5-carboxamideYield 45.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

EDC (0.059 g, 0.309 mmol) and HOBT (0.042 g, 0.309 mmol) were added to a solution of 3-{[3-(aminomethyl)-6-bromo-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.100 g, 0.281 mmol) and 4-bromo-1H-imidazole-5-carboxylic acid (0.054 g, 0.281 mmol) in DMF (2 ml). The mixture was stirred at RT overnight. The reaction mixture was extracted with ethyl acetate and saturated aqueous sodium bicarbonate and the organic layer was dried over sodium sulfate and concentrated. Purification by reverse phase HPLC (acetonitrile:water with 0.1% formic acid) gave 0.068 g (45%) of the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.34 (br. s., 1H), 7.77 (s, 2H), 7.58 (d, 1H), 7.45 (s, 1H), 7.40 (t, 1H), 7.27 (t, 1H), 4.45 (d, 2H). ES MS: m/z 527 (M+1).

Workup

  1. extractionThe reaction mixture was extracted with ethyl acetate and saturated aqueous sodium bicarbonate
  2. dry with materialthe organic layer was dried over sodium sulfate
  3. concentrationconcentrated
  4. customPurification by reverse phase HPLC (acetonitrile:water with 0.1% formic acid)

Sources & evidence

ORD record
ord-aa4658bbf3914063afc5981facc299f5
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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