Cyanogen Bromide → HCID 11545345, compound

HRID 229372Notes

Reaction equation

HRID 229372 reaction equation
[NH:1]1[CH2:5][CH2:4][N:3]=[C:2]1[C:6]([NH2:26])([C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[C:19]([CH3:25])[CH:18]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH2:14][CH2:15][CH3:16])[CH:8]=1.[N:27]#[C:28]Br>C(Cl)(Cl)Cl>[CH3:24][O:23][C:20]1[CH:21]=[CH:22][C:17]([C:6]2([C:7]3[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH2:14][CH2:15][CH3:16])[CH:8]=3)[C:2]3=[N:1][CH2:5][CH2:4][N:3]3[C:28]([NH2:27])=[N:26]2)=[CH:18][C:19]=1[CH3:25]

Participants

4

Reactant 2

HCID 10476Cyanogen BromideHCID 68649417HCID 68649417, compound

Product 1

HCID 11545345HCID 11545345, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
60 °C

Procedure

A solution of [4,5-dihydro-1H-imidazol-2-yl(4-methoxy-3-methylphenyl)(3-propoxyphenyl)methyl]amine (0.6 g) in chloroform is treated with cyanogen bromide (0.581 g), heated at 60° C. for 5 days and filtered through a pad of silica. The silica pad was eluted with ethyl acetate, followed by elution with (40:5:5) ethyl acetate: methanol: ammonium hydroxide. The eluents were combined and concentrated in vacuo to give a thick yellow oil, which was purified by Gilson preparative reverse phase HPLC system YMC Pro C18, 20 mm×50 mm ID, 5 uM column; 2 mL injection; Solvent A: 0.02% NH4OH/water; Solvent B:0.02% NH4OH/acetonitrile; Gradient: Time O: 95% A; 2 min: 95% A; 14 min: 10% A, 15 min: 10% A, 16 min: 95% A; Flow rate 22.5 mL/min; Detection: 254 nm DAD to afford the title compound was as an off-white, amphorous solid (0.131 g), characterized by LCMS analysis. LCMS Conditions: HP 1100 HPLC system; Waters Xterra MS C18, 2 mm (i.d.)×50 mm (length), 3.5 um column, set at 50° C.; Flow rate 1.0 mL/min; Solvent A: 0.02% NH4OH in water; Solvent B 0.02% NH4OH in ACN; Gradient: Time O: 10% B; 2.5 min 90% B; 3 min 90% B; Sample concentration: ˜2.0 mM; Injection volume: 5 uL; Detection: 220 nm, 254 nm DAD; retention time: 2.34 min, [M−H] 377, [M+H] 379.

Workup

  1. filtrationfiltered through a pad of silica
  2. washThe silica pad was eluted with ethyl acetate
  3. washfollowed by elution with (40:5:5) ethyl acetate
  4. concentrationconcentrated in vacuo
  5. customto give a thick yellow oil, which
  6. customwas purified by Gilson preparative reverse phase HPLC system YMC Pro C18, 20 mm×50 mm ID, 5 uM column
  7. custom2 min
  8. custom14 min
  9. custom10% A, 15 min
  10. custom10% A, 16 min

Sources & evidence

ORD record
ord-ac1362dcbf374b65a6afc708b57cf6f4
Source dataset
uspto-grants-2009_07
Patent number
US07563796B2

Reaction notes

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