1,2-Dichloroethane → HCID 178509915, compound

HRID 1875105Notes

Reaction equation

HRID 1875105 reaction equation
[NH2:1][CH2:2][C:3]1[C:4]([F:22])=[C:5]([O:12][C:13]2[CH:14]=[C:15]([CH:18]=[C:19]([Cl:21])[CH:20]=2)[C:16]#[N:17])[C:6]([CH:9]([F:11])[F:10])=[CH:7][CH:8]=1.[Cl:23][C:24]1[N:25]=[CH:26][N:27](COCC[Si](C)(C)C)[C:28]=1[C:29](O)=[O:30].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C([O-])(O)=O.[Na+].C(O)(C(F)(F)F)=O>CN(C=O)C.ClCCl.C(OCC)(=O)C>[Cl:23][C:24]1[N:25]=[CH:26][NH:27][C:28]=1[C:29]([NH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]([F:11])[F:10])=[C:5]([O:12][C:13]2[CH:14]=[C:15]([C:16]#[N:17])[CH:18]=[C:19]([Cl:21])[CH:20]=2)[C:4]=1[F:22])=[O:30]

Participants

10

Reactant 6

HCID 111,2-DichloroethaneHCID 6422Trifluoroacetic acidHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 684803913-{[3-(Aminomethyl)-6-(difluoromethyl)-2-fluorophenyl]oxy}-5-chlorobenzonitrileHCID 684855334-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acid

Product 1

HCID 178509915HCID 178509915, compoundYield 30.5%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-{[3-(aminomethyl)-6-(difluoromethyl)-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.08 g, 0.245 mmol), 4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acid (0.068 g, 0.245 mmol), EDC (0.047 g, 0.245 mmol) and HOBT (0.037 g, 0.245 mmol) in DMF (4 ml) was stirred at RT under an atmosphere of nitrogen for 16 h then ethyl acetate (30 mL) and saturated aqueous NaHCO3 solution (30 mL) were added. The organic layer was separated, washed with saturated aqueous NaHCO3 solution (30 mL), water (30 mL), brine (30 mL), dried over MgSO4, filtered and concentrated. A solution of this residue and TFA (0.019 ml, 0.246 mmol) in dichloromethane (10 ml) was stirred at RT under an atmosphere of nitrogen for 16 h. The solvent was removed under vacuum and the resulting oil was purified by Reverse Phase HPLC (MeCN/water+0.1% TFA). The desired compound was washed with saturated aqueous NaHCO3 solution (25 mL) and extracted with ethyl acetate (25 mL). The organic layer was separated, washed with water (25 mL), brine (25 mL), dried over MgSO4, filtered and concentrated to give the title compound (0.034 g, 30%) as a white powder. 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.73 (s, 1H), 7.44-7.63 (m, 3H), 7.27 (d, 2H), 6.92 (t, 1H), 4.70 (s, 2H). LC/MS m/z 453.2 (M−H).

Workup

  1. customThe organic layer was separated
  2. washwashed with saturated aqueous NaHCO3 solution (30 mL), water (30 mL), brine (30 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe solvent was removed under vacuum
  7. customthe resulting oil was purified by Reverse Phase HPLC (MeCN/water+0.1% TFA)
  8. washThe desired compound was washed with saturated aqueous NaHCO3 solution (25 mL)
  9. extractionextracted with ethyl acetate (25 mL)
  10. customThe organic layer was separated
  11. washwashed with water (25 mL), brine (25 mL)
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-d5aaa45e075346249a8b06225adec923
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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