Reaction #1355340

Reaction equation

hydrogen chloride

hydrogen chloride

N-[3-(5-amidino-2-fluorophenyl)-2-(E)-propenyl]-N-[4-(piperidin-4-yloxy)phenyl]ethanesulfonamide dihydrochloride

ethyl acetimidate hydrochloride

triethylamine

→

title compound

Yield 144.3%

N-[4-(1-Acetimidoylpiperidin-4-yloxy)phenyl]-N-[3-(5-amidino-2-fluorophenyl)-2-(E)-propenyl]ethanesulfonamide Dihydrochloride

Yield 144.3%

Solvents

dioxane

methanol

dioxane

ethanol

Conditions

Workup

1. 1
   Concentrationthe resulting mixture was concentrated in vacuo
2. 2
   OtherThe residue was purified by preparative HPLC (YMC-Pack ODS YMC)
3. 3
   Otherto afford an amorphous solid
4. 4
   Concentrationthe mixture was concentrated to dryness in vacuo
5. 5
   workup.DISSOLUTIONThe resulting amorphous solid was dissolved in water (10 ml)

Procedure

To a solution of N-[3-(5-amidino-2-fluorophenyl)-2-(E)-propenyl]-N-[4-(piperidin-4-yloxy)phenyl]ethanesulfonamide dihydrochloride (534 mg) in ethanol (20 ml) were added ethyl acetimidate hydrochloride (371 mg) and triethylamine (0.70 ml) at room temperature. The resulting mixture was stirred at room temperature for 12 hours. After addition of a 4M solution of hydrogen chloride in dioxane (2 ml), the resulting mixture was concentrated in vacuo. The residue was purified by preparative HPLC (YMC-Pack ODS YMC) using 20% aqueous acetonitrile as an eluant to afford an amorphous solid. To a solution of the solid in methanol (10 ml) was added a 4M solution of hydrogen chloride in dioxane (0.5 ml) and the mixture was concentrated to dryness in vacuo. The resulting amorphous solid was dissolved in water (10 ml) and the solution was lyophilized to give the title compound (415 mg, yield 75%) as a colorless amorphous solid.

Source