6-amino-3-bromo-2-methylbenzonitrile

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

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a dry nitrogen atmosphere, 0.5 gram (0.0004 mole) of tetrakis(triphenylphosphine)palladium(0) was added to a stirred mixture of 2.8 grams (0.0132 mole) of 2-amino-5-bromo-6-methylbenzonitrile (prepared as in Step C of Example 1), 35 mL of aqueous 2M sodium carbonate and 50 mL of toluene. To this was then added dropwise a solution of 3.3 grams (0.0159 mole) of 3-fluoro-5-trifluoromethylphenylboronic acid in 10 mL of ethanol. Upon completion of addition, the reaction mixture was warmed to about 80° C., where it was stirred for seven hours. After this time the reaction mixture was poured into 200 mL of water. The mixture was then extracted with four 100 mL portions of ethyl acetate. The combined extracts were dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue. The residue was subjected to column chromatography on silica gel. Elution was accomplished with methylene chloride. The product-containing fractions were combined and concentrated under reduced pressure, yielding 4.0 grams of 2-amino-6-methyl-5-(3-fluoro-5-trifluoromethylphenyl)benzonitrile, mp 96°-97° C. The NMR spectrum was consistent with the proposed structure. Upon completion of addition The mixture was then extracted with four 100 mL portions of ethyl acetate The combined extracts were dried with magnesium sulfate filtered The filtrate was concentrated under reduced pressure to a residue Elution concentrated under reduced pressure

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

Procedure: A stirred solution of 1.7 grams (0.008 mole) of 2-amino-5-bromo-6-methylbenzonitrile, 3.2 grams (0.012 mole) of 3,5-di(trifluoromethyl)-phenylboronic acid, 4.3 grams (0.031 mole) of potassium carbonate and 0.3 mL of tetrakis(triphenylphosphine)palladium(0) in 150 mL of toluene was heated at 90° C. for about 20 hours. After this time, the reaction mixture was stirred with 100 mL of water, and the organic layer was separated. The organic layer was concentrated under reduced pressure to a residue. The residue was subjected to column chromatography on silica gel, using 30/65/5 and 20/60/20 methylene chloride/petroleum ether/ethyl acetate as eluants. The product-containing fractions were combined and concentrated under reduced pressure, yielding about 1.0 gram of 2-amino-6-methyl-5-[3,5-di(trifluoromethyl)phenyl]benzonitrile. The NMR spectrum was consistent with the proposed structure. the organic layer was separated The organic layer was concentrated under reduced pressure to a residue concentrated under reduced pressure

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

Procedure: A stirred solution of 8.3 grams (0.063 mole) of 2-amino-6-methylbenzonitrile in 125 mL of N,N-dimethylformamide was cooled in an ice bath, and a solution of 11.2 grams (0.063 mole) of N-bromosuccinimide in 125 mL of N,N-dimethylformamide was added dropwise during a 30 minute period, while maintaining the reaction mixture temperature at about 15°-25° C. Upon completion of addition, the reaction mixture was stirred at ambient temperature for about 20 hours. After this time, the reaction mixture was poured into 1 liter of aqueous 3N sodium hydroxide. The mixture was then diluted to a volume of about 1700 mL with distilled water. A solid precipitate was collected by filtration and dried under reduced pressure, yielding 12.3 grams of 2-amino-5-bromo-6-methylbenzonitrile, mp 111°-113° C. The NMR spectrum was consistent with the proposed structure. while maintaining the reaction mixture temperature at about 15°-25° C Upon completion of addition A solid precipitate was collected by filtration dried under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a dry nitrogen atmosphere, 0.5 gram (0.0004 mole) of tetrakis(triphenylphosphine)palladium(0) was added to a stirred mixture of 2.8 grams (0.0132 mole) of 2-amino-5-bromo-6-methylbenzonitrile (prepared as in Step C of Example 1), 35 mL of aqueous 2M sodium carbonate and 50 mL of toluene. To this was then added dropwise a solution of 3.3 grams (0.0159 mole) of 3-fluoro-5-trifluoromethylphenylboronic acid in 10 mL of ethanol. Upon completion of addition, the reaction mixture was warmed to about 80° C., where it was stirred for seven hours. After this time the reaction mixture was poured into 200 mL of water. The mixture was then extracted with four 100 mL portions of ethyl acetate. The combined extracts were dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue. The residue was subjected to column chromatography on silica gel. Elution was accomplished with methylene chloride. The product-containing fractions were combined and concentrated under reduced pressure, yielding 4.0 grams of 2-amino-6-methyl-5-(3-fluoro-5-trifluoromethylphenyl)benzonitrile, mp 96°-97° C. The NMR spectrum was consistent with the proposed structure. Upon completion of addition The mixture was then extracted with four 100 mL portions of ethyl acetate The combined extracts were dried with magnesium sulfate filtered The filtrate was concentrated under reduced pressure to a residue Elution concentrated under reduced pressure

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

Procedure: A stirred solution of 1.7 grams (0.008 mole) of 2-amino-5-bromo-6-methylbenzonitrile, 3.2 grams (0.012 mole) of 3,5-di(trifluoromethyl)-phenylboronic acid, 4.3 grams (0.031 mole) of potassium carbonate and 0.3 mL of tetrakis(triphenylphosphine)palladium(0) in 150 mL of toluene was heated at 90° C. for about 20 hours. After this time, the reaction mixture was stirred with 100 mL of water, and the organic layer was separated. The organic layer was concentrated under reduced pressure to a residue. The residue was subjected to column chromatography on silica gel, using 30/65/5 and 20/60/20 methylene chloride/petroleum ether/ethyl acetate as eluants. The product-containing fractions were combined and concentrated under reduced pressure, yielding about 1.0 gram of 2-amino-6-methyl-5-[3,5-di(trifluoromethyl)phenyl]benzonitrile. The NMR spectrum was consistent with the proposed structure. the organic layer was separated The organic layer was concentrated under reduced pressure to a residue concentrated under reduced pressure

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

Procedure: A stirred solution of 8.3 grams (0.063 mole) of 2-amino-6-methylbenzonitrile in 125 mL of N,N-dimethylformamide was cooled in an ice bath, and a solution of 11.2 grams (0.063 mole) of N-bromosuccinimide in 125 mL of N,N-dimethylformamide was added dropwise during a 30 minute period, while maintaining the reaction mixture temperature at about 15°-25° C. Upon completion of addition, the reaction mixture was stirred at ambient temperature for about 20 hours. After this time, the reaction mixture was poured into 1 liter of aqueous 3N sodium hydroxide. The mixture was then diluted to a volume of about 1700 mL with distilled water. A solid precipitate was collected by filtration and dried under reduced pressure, yielding 12.3 grams of 2-amino-5-bromo-6-methylbenzonitrile, mp 111°-113° C. The NMR spectrum was consistent with the proposed structure. while maintaining the reaction mixture temperature at about 15°-25° C Upon completion of addition A solid precipitate was collected by filtration dried under reduced pressure

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

Procedure: A stirred solution of 8.3 grams (0.063 mole) of 2-amino-6-methylbenzonitrile in 125 mL of N,N-dimethylformamide was cooled in an ice bath, and a solution of 11.2 grams (0.063 mole) of N-bromosuccinimide in 125 mL of N,N-dimethylformamide was added dropwise during a 30 minute period, while maintaining the reaction mixture temperature at about 15°-25° C. Upon completion of addition, the reaction mixture was stirred at ambient temperature for about 20 hours. After this time, the reaction mixture was poured into 1 liter of aqueous 3N sodium hydroxide. The mixture was then diluted to a volume of about 1700 mL with distilled water. A solid precipitate was collected by filtration and dried under reduced pressure, yielding 12.3 grams of 2-amino-5-bromo-6-methylbenzonitrile, mp 111°-113° C. The NMR spectrum was consistent with the proposed structure. while maintaining the reaction mixture temperature at about 15°-25° C Upon completion of addition A solid precipitate was collected by filtration dried under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a dry nitrogen atmosphere, 0.5 gram (0.0004 mole) of tetrakis(triphenylphosphine)palladium(0) was added to a stirred mixture of 2.8 grams (0.0132 mole) of 2-amino-5-bromo-6-methylbenzonitrile (prepared as in Step C of Example 1), 35 mL of aqueous 2M sodium carbonate and 50 mL of toluene. To this was then added dropwise a solution of 3.3 grams (0.0159 mole) of 3-fluoro-5-trifluoromethylphenylboronic acid in 10 mL of ethanol. Upon completion of addition, the reaction mixture was warmed to about 80° C., where it was stirred for seven hours. After this time the reaction mixture was poured into 200 mL of water. The mixture was then extracted with four 100 mL portions of ethyl acetate. The combined extracts were dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue. The residue was subjected to column chromatography on silica gel. Elution was accomplished with methylene chloride. The product-containing fractions were combined and concentrated under reduced pressure, yielding 4.0 grams of 2-amino-6-methyl-5-(3-fluoro-5-trifluoromethylphenyl)benzonitrile, mp 96°-97° C. The NMR spectrum was consistent with the proposed structure. Upon completion of addition The mixture was then extracted with four 100 mL portions of ethyl acetate The combined extracts were dried with magnesium sulfate filtered The filtrate was concentrated under reduced pressure to a residue Elution concentrated under reduced pressure

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

Procedure: A stirred solution of 1.7 grams (0.008 mole) of 2-amino-5-bromo-6-methylbenzonitrile, 3.2 grams (0.012 mole) of 3,5-di(trifluoromethyl)phenylboronic acid, 4.3 grams (0.031 mole) of potassium carbonate and 0.3 mL of tetrakis(triphenylphosphine)palladium(0) in 150 mL of toluene was heated at 90° C. for about 20 hours. After this time, the reaction mixture was stirred with 100 mL of water, and the organic layer was separated. The organic layer was concentrated under reduced pressure to a residue. The residue was subjected to column chromatography on silica gel, using 30/65/5 and 20/60/20 methylene chloride/petroleum ether/ethyl acetate as eluants. The product-containing fractions were combined and concentrated under reduced pressure, yielding about 1.0 gram of 2-amino-6-methyl-5-[3,5-di(trifluoromethyl)phenyl]benzonitrile. The NMR spectrum was consistent with the proposed structure. the organic layer was separated The organic layer was concentrated under reduced pressure to a residue concentrated under reduced pressure

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

Procedure: A stirred solution of 8.3 grams (0.063 mole) of 2-amino-6-methylbenzonitrile in 125 mL of N,N-dimethylformamide was cooled in an ice bath, and a solution of 11.2 grams (0.063 mole) of N-bromosuccinimide in 125 mL of N,N-dimethylformamide was added dropwise during a 30 minute period, while maintaining the reaction mixture temperature at about 15°-25° C. Upon completion of addition, the reaction mixture was stirred at ambient temperature for about 20 hours. After this time, the reaction mixture was poured into 1 liter of aqueous 3N sodium hydroxide. The mixture was then diluted to a volume of about 1700 mL with distilled water. A solid precipitate was collected by filtration and dried under reduced pressure, yielding 12.3 grams of 2-amino-5-bromo-6-methylbenzonitrile, mp 111°-113° C. The NMR spectrum was consistent with the proposed structure. while maintaining the reaction mixture temperature at about 15°-25° C Upon completion of addition A solid precipitate was collected by filtration dried under reduced pressure