1-(4-amino-3,5-dichlorophenyl)ethanone

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5 g. of 4-amino-3,5-dichloroacetophenone, 5 ml. of phosgene, and 30 ml. of toluene was heated to 150° C. for 24 hours at a sealed tube. The reaction mixture obtained was cooled and concentrated under a reduced pressure to provide crude 4-acetyl-2,6-dichlorophenyl isocyanate. The crude product was dissolved in 100 ml. of toluene and after adding 10 g. of cyclohexanol to the solution, the mixture was stirred overnight at 100° C. The reaction mixture was cooled and concentrated under reduced pressure. The residue formed was then recrystallized from a mixture of benzene and n-hexane to provide 4.3 g. of 3,5-dichloro-4-cyclohexyloxycarbonylaminoacetophenone having a melting point of 88°-89° C. A mixture of 5 g The reaction mixture obtained was cooled concentrated under a reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5 g. of 4-amino-3,5-dichloroacetophenone, 5 ml. of phosgene, and 30 ml. of toluene was heated to 150° C. for 24 hours in a sealed tube. The reaction mixture was cooled and concentrated under reduced pressure to provide crude 4-acetyl-2,6-dichlorophenyl isocyanate. The crude product was dissolved in 150 ml. of toluene and then 5 ml. of aniline was added to the solution. The crystals thus formed were recovered by filtration and recrystallized from ethanol to provide 4.56 g. of 3,5-dichloro-4-phenylcarbamoylaminoacetophenone having a melting point of 239°-240° C. A mixture of 5 g The reaction mixture was cooled concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5 g. of 4-amino-3,5-dichloroacetophenone, 5 ml. of phosgene, and 30 ml. of toluene was heated to 150° C. for 24 hours in a sealed tube. The reaction mixture was cooled and concentrated under reduced pressure to provide crude 4-acetyl-2,6-dichlorophenyl isocyanate. The crude product was dissolved in 150 ml. of toluene and then 5 ml. of aniline was added to the solution. The crystals thus formed were recovered by filtration and recrystallized from ethanol to provide 4.56 g. of 3,5-dichloro-4-phenylcarbamoylaminoacetophenone having a melting point of 239°-240° C. A mixture of 5 g The reaction mixture was cooled concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5 g. of 4-amino-3,5-dichloroacetophenone, 5 ml. of phosgene, and 30 ml. of toluene was heated to 150° C. for 24 hours in a sealed tube. The reaction mixture was cooled and concentrated under reduced pressure to provide crude 4-acetyl-2,6-dichlorophenyl isocyanate. The crude product was dissolved in 100 ml. of toluene and then dry dimethylamine was passed through the solution for one hour at room temperature. The reaction mixture was concentrated under reduced pressure and the residue formed was recrystallized from a mixture of benzene and n-hexane to provide 2.58 g. of 3,5-dichloro-4-N,N-dimethylcarbamoylaminoacetophenone having a melting point of 138°-140° C. A mixture of 5 g The reaction mixture was cooled concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5 g. of 4-amino-3,5-dichloroacetophenone, 5 ml. of phosgene, and 30 ml. of toluene was heated to 150° C. for 24 hours at a sealed tube. The reaction mixture obtained was cooled and concentrated under a reduced pressure to provide crude 4-acetyl-2,6-dichlorophenyl isocyanate. The crude product was dissolved in 100 ml. of toluene and after adding 10 g. of cyclohexanol to the solution, the mixture was stirred overnight at 100° C. The reaction mixture was cooled and concentrated under reduced pressure. The residue formed was then recrystallized from a mixture of benzene and n-hexane to provide 4.3 g. of 3,5-dichloro-4-cyclohexyloxycarbonylaminoacetophenone having a melting point of 88°-89° C. A mixture of 5 g The reaction mixture obtained was cooled concentrated under a reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5 g. of 4-amino-3,5-dichloroacetophenone, 5 ml. of phosgene, and 30 ml. of toluene was heated to 150° C. for 24 hours in a sealed tube. The reaction mixture was cooled and concentrated under reduced pressure to provide crude 4-acetyl-2,6-dichlorophenyl isocyanate. The crude product was dissolved in 150 ml. of toluene and then 5 ml. of aniline was added to the solution. The crystals thus formed were recovered by filtration and recrystallized from ethanol to provide 4.56 g. of 3,5-dichloro-4-phenylcarbamoylaminoacetophenone having a melting point of 239°-240° C. A mixture of 5 g The reaction mixture was cooled concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5 g. of 4-amino-3,5-dichloroacetophenone, 5 ml. of phosgene, and 30 ml. of toluene was heated to 150° C. for 24 hours in a sealed tube. The reaction mixture was cooled and concentrated under reduced pressure to provide crude 4-acetyl-2,6-dichlorophenyl isocyanate. The crude product was dissolved in 100 ml. of toluene and then dry dimethylamine was passed through the solution for 1 hour at room temperature. The reaction mixture was concentrated under reduced pressure and the residue formed was recrystallized from a mixture of benzene and n-hexane to provide 2.58 g. of 3,5-dichloro-4-N,N-dimethylcarbamoylaminoacetophenone having a melting point of 138°-140° C. A mixture of 5 g The reaction mixture was cooled concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5 g. of 4-amino-3,5-dichloroacetophenone, 5 ml. of phosgene, and 30 ml. of toluene was heated to 150° C. for 24 hours in a sealed tube. The reaction mixture was cooled and concentrated under reduced pressure to provide crude 4-acetyl-2,6-dichlorophenyl isocyanate. The crude product was dissolved in 100 ml. of toluene and then dry dimethylamine was passed through the solution for 1 hour at room temperature. The reaction mixture was concentrated under reduced pressure and the residue formed was recrystallized from a mixture of benzene and n-hexane to provide 2.58 g. of 3,5-dichloro-4-N,N-dimethylcarbamoylaminoacetophenone having a melting point of 138°-140° C. A mixture of 5 g The reaction mixture was cooled concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-(4-Amino-3,5-dichlorophenyl)ethanone (15 g, 73.5 mmol), pyridinium p-toluene sulfonic acid (5.5 g, 22 mmol), and ethylene glycol (6.2 mL, 110 mmol) were heated together in benzene (250 mL) with a Dean Stark trap at 100° C. overnight. The benzene was distilled off until ˜75 mL remained and the reaction mixture was extracted with EtOAc and saturated NaHCO3. The organic layer was separated, dried with MgSO4, filtered, and concentrated under rotary evaporation to afford a oily residue. The crude mixture was purified on silica gel chromatography (100% Hex to 100% EtOAc) to afford the desired product. The benzene was distilled off until ˜75 mL the reaction mixture was extracted with EtOAc and saturated NaHCO3 The organic layer was separated dried with MgSO4 filtered concentrated under rotary evaporation to afford a oily residue The crude mixture was purified on silica gel chromatography (100% Hex to 100% EtOAc)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the procedure and workup for Compound 354, Compound 354e (100 mg, 0.256 mmol) was reacted with 1-(4-amino-3,5-dichloro-phenyl)-ethanone (0.256 mmol) in ethanol (2 mL) using 10% w/v KOH in ethanol (506 μL, 0.64 mmol) to produce the title compound (31 mg, 25% yield).