1,2-Dichloroethane → HCID 178509907, compound

HRID 1875252Notes

Reaction equation

HRID 1875252 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.[Cl:35][C:36]1[N:37]=[CH:38][N:39](COCC[Si](C)(C)C)[C:40]=1[C:41](O)=[O:42].FC(F)(F)C(O)=O>CN(C=O)C.ClCCl>[Br:23][C:20]1[CH:21]=[CH:22][C:17]([CH2:16][NH:15][C:41]([C:40]2[NH:39][CH:38]=[N:37][C:36]=2[Cl:35])=[O:42])=[C:18]([F:34])[C:19]=1[O:24][C:25]1[CH:26]=[C:27]([C:28]#[N:29])[CH:30]=[C:31]([Cl:33])[CH:32]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 6422Trifluoroacetic acidHCID 757711-HydroxybenzotriazoleHCID 671971663-{[3-(Aminomethyl)-6-bromo-2-fluorophenyl]oxy}-5-chlorobenzonitrileHCID 684855334-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acid

Product 1

HCID 178509907HCID 178509907, compoundYield 2.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

EDC (0.028 g, 0.148 mmol) and HOBT (0.020 g, 0.148 mmol) were added to a solution of 3-{[3-(aminomethyl)-6-bromo-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.053 g, 0.148 mmol) and 4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acid (0.041 g, 0.148 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. The organic layer was dried over sodium sulfate and concentrated to give a yellow oil which was dissolved in dichloromethane (1.5 mL). Trifluoroacetic acid (0.5 ml, 6.49 mmol) was added and the mixture was stirred at RT overnight. Purification by reverse phase HPLC (acetonitrile:water with 0.1% formic acid) gave the title compound 0.002 g, 2.5%) as a white solid. 1H NMR (400 MHz, methanol-d4) δ ppm 7.69 (s, 1H), 7.48-7.55 (m, 2H), 7.29 (t, 1H), 7.22 (d, 1H), 7.19 (s, 1H), 4.61 (s, 2H). ES MS m/z 483 (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. customto give a yellow oil which
  5. stirringthe mixture was stirred at RT overnight
  6. customPurification by reverse phase HPLC (acetonitrile:water with 0.1% formic acid)

Sources & evidence

ORD record
ord-fa3e649daf8c463f8b9a2ed5812e1a80
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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