2,6-difluoro-4-iodobenzonitrile

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

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

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

Procedure: 5.6 g of this 1,3-difluoro-2-cyano-5-iodobenzene was dissolved in 35 ml of N,N-dimethylformamide, to which was added 7.3 mg of bis(triphenylphosphine) palladium (II) chloride and 34 m of cuprous iodide. Next, 3 g of the 4-propylphenylacetylene obtained in Step 2 was added and allowed to react at 50° to 60° C. for 0.5 hour. After completion of the reaction, 35 ml of 9% hydrochloric acid was added to the reaction solution. After being extracted with chloroform, the crystals were washed with water three times to distill off the chloroform. The residue was purified by silica gel-chloroform column chromatography, followed by recrystallization with a mixed solvent of acetone and methanol to obtain 1.6 g of 4-propyl-3',5'-difluoro-4'-cyanotolan. The melting (C-I) point of this compound was 83.3° C. to react at 50° to 60° C. for 0.5 hour was added to the reaction solution After being extracted with chloroform the crystals were washed with water three times to distill off the chloroform The residue was purified by silica gel-chloroform column chromatography followed by recrystallization with a mixed solvent of acetone and methanol

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

Procedure: 12 g of sodium nitrite was dissolved in 91 ml of sulfuric acid and cooled to 10° C or less, and then 100 ml of acetic acid was added. At 20 to 25° C, 39 g of the 2,6-difluoro-4-iodoaniline from Step 3 was added to the solution, and then the solution was agitated for one hour. A second solution was made by dissolving 37 g of copper sulfate pentahydrate in 91 ml of water to which was added 62 g of ice, and this solution was added to the first. A third solution containing 39 of potassium cyanide dissolved in 92 ml of water, 221 g of sodium bicarbonate, and 91 ml of benzene was added to the first solution, and a diazonium salt sulfuric acid solution was added therein. After agitation at room temperature for 3 hours, a sodium hydroxide aqueous solution was added to dissolve the crystals. After being extracted with chloroform, the crystals were washed three times alternating with a 10% sodium hydroxide solution and water. After distillation of the chloroform, the residue was extracted with hexane, and the hexane was distilled off. This residue was recrystallized with methanol to obtain 6.7 g of 1,3-difluoro-2-cyano-5-iodobenzene. cooled to 10° C or less this solution was added to the first After agitation at room temperature for 3 hours to dissolve the crystals After being extracted with chloroform the crystals were washed three times After distillation of the chloroform the residue was extracted with hexane the hexane was distilled off This residue was recrystallized with methanol

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

Procedure: 12 g of sodium nitrite was dissolved in 91 ml of sulfuric acid and cooled to 10° C or less, and then 100 ml of acetic acid was added. At 20 to 25° C, 39 g of the 2,6-difluoro-4-iodoaniline from Step 3 was added to the solution, and then the solution was agitated for one hour. A second solution was made by dissolving 37 g of copper sulfate pentahydrate in 91 ml of water to which was added 62 g of ice, and this solution was added to the first. A third solution containing 39 of potassium cyanide dissolved in 92 ml of water, 221 g of sodium bicarbonate, and 91 ml of benzene was added to the first solution, and a diazonium salt sulfuric acid solution was added therein. After agitation at room temperature for 3 hours, a sodium hydroxide aqueous solution was added to dissolve the crystals. After being extracted with chloroform, the crystals were washed three times alternating with a 10% sodium hydroxide solution and water. After distillation of the chloroform, the residue was extracted with hexane, and the hexane was distilled off. This residue was recrystallized with methanol to obtain 6.7 g of 1,3-difluoro-2-cyano-5-iodobenzene. cooled to 10° C or less this solution was added to the first After agitation at room temperature for 3 hours to dissolve the crystals After being extracted with chloroform the crystals were washed three times After distillation of the chloroform the residue was extracted with hexane the hexane was distilled off This residue was recrystallized with methanol

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

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

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

Procedure: starting from 6,7-dihydro-5H-imidazo[1,5-a]pyridinone [426219-51-4] and 2,6-difluoro-4-iodobenzonitrile [141743-50-2]

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

Procedure: 5.6 g of this 1,3-difluoro-2-cyano-5-iodobenzene was dissolved in 35 ml of N,N-dimethylformamide, to which was added 7.3 mg of bis(triphenylphosphine) palladium (II) chloride and 34 m of cuprous iodide. Next, 3 g of the 4-propylphenylacetylene obtained in Step 2 was added and allowed to react at 50° to 60° C. for 0.5 hour. After completion of the reaction, 35 ml of 9% hydrochloric acid was added to the reaction solution. After being extracted with chloroform, the crystals were washed with water three times to distill off the chloroform. The residue was purified by silica gel-chloroform column chromatography, followed by recrystallization with a mixed solvent of acetone and methanol to obtain 1.6 g of 4-propyl-3',5'-difluoro-4'-cyanotolan. The melting (C-I) point of this compound was 83.3° C. to react at 50° to 60° C. for 0.5 hour was added to the reaction solution After being extracted with chloroform the crystals were washed with water three times to distill off the chloroform The residue was purified by silica gel-chloroform column chromatography followed by recrystallization with a mixed solvent of acetone and methanol

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

Procedure: 12 g of sodium nitrite was dissolved in 91 ml of sulfuric acid and cooled to 10° C or less, and then 100 ml of acetic acid was added. At 20 to 25° C, 39 g of the 2,6-difluoro-4-iodoaniline from Step 3 was added to the solution, and then the solution was agitated for one hour. A second solution was made by dissolving 37 g of copper sulfate pentahydrate in 91 ml of water to which was added 62 g of ice, and this solution was added to the first. A third solution containing 39 of potassium cyanide dissolved in 92 ml of water, 221 g of sodium bicarbonate, and 91 ml of benzene was added to the first solution, and a diazonium salt sulfuric acid solution was added therein. After agitation at room temperature for 3 hours, a sodium hydroxide aqueous solution was added to dissolve the crystals. After being extracted with chloroform, the crystals were washed three times alternating with a 10% sodium hydroxide solution and water. After distillation of the chloroform, the residue was extracted with hexane, and the hexane was distilled off. This residue was recrystallized with methanol to obtain 6.7 g of 1,3-difluoro-2-cyano-5-iodobenzene. cooled to 10° C or less this solution was added to the first After agitation at room temperature for 3 hours to dissolve the crystals After being extracted with chloroform the crystals were washed three times After distillation of the chloroform the residue was extracted with hexane the hexane was distilled off This residue was recrystallized with methanol

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