4'-CHLORO-BIPHENYL-2-YLAMINE

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: A solution of 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid (0.68 g) and oxalyl chloride (0.49 g) in methylene chloride (30 ml) is stirred for 2 hours at room temperature in the presence of a catalytic amount of DMF. The resulting acid chloride solution is then added to a solution of 4′-chlorobiphenyl-2-ylamine (0.71 g) and triethylamine (0.36 g) in 15 ml of methylene chloride at 0° C. The reaction mixture is then stirred for 4 hours at room temperature. After distilling off the solvent in a water-jet-vacuum, the residue is taken up in ethylacetate/water. The ethylacetate phase is extracted twice with water. After drying of the organic phase with Na2SO4, the solvent is distilled off in a water-jet-vacuum and the residue purified by column chromatography (silica gel; eluant: ethylacetate/hexane=1:1). 0.8 g of 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid (4′-chlorobiphenyl-2-yl) amide are obtained in the form of slightly brownish crystals having a melting point of 144–146° C. After distilling off the solvent in a water-jet-vacuum The ethylacetate phase is extracted twice with water After drying of the organic phase with Na2SO4 the solvent is distilled off in a water-jet-vacuum the residue purified by column chromatography (silica gel; eluant: ethylacetate/hexane=1:1)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 20 ml autoclave were placed 1 g of xylene, 6 mg of a Pt/C catalyst (containing 1% by weight of Pt with respect to the weight of carbon) and 0.25 g (1 mmol) of 4′-chloro-2-nitrobiphenyl obtained in example 1.4. The mixture was stirred under hydrogen pressure (7-8 bar) at 100° C. until the starting material had disappeared (monitoring via HPLC). After completion of the reaction the mixture was cooled to ambient temperature and diluted with 15 ml of acetone. The catalyst was filtered off and the filtrate was evaporated in vacuo yielding 0.2 g (91% of theory) of the title compound in a purity of 93% (HPLC % by weight). After completion of the reaction the mixture was cooled to ambient temperature The catalyst was filtered off the filtrate was evaporated in vacuo

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 20 ml autoclave were placed 1 g of xylene, 6 mg of a Pt/C catalyst (containing 1% by weight of Pt with respect to the weight of carbon) and 0.25 g (1 mmol) of 4′-chloro-2-nitrobiphenyl obtained in example 1.4. The mixture was stirred under hydrogen pressure (7-8 bar) at 100° C. until the starting material had disappeared (monitoring via HPLC). After completion of the reaction the mixture was cooled to ambient temperature and diluted with 15 ml of acetone. The catalyst was filtered off and the filtrate was evaporated in vacuo yielding 0.2 g (91% of theory) of the title compound in a purity of 93% (HPLC % by weight). After completion of the reaction the mixture was cooled to ambient temperature The catalyst was filtered off the filtrate was evaporated in vacuo

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

Procedure: A solution of 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid (0.68 g) and oxalyl chloride (0.49 g) in methylene chloride (30 ml) is stirred for 2 hours at room temperature in the presence of a catalytic amount of DMF. The resulting acid chloride solution is then added to a solution of 4′-chlorobiphenyl-2-ylamine (0.71 g) and triethylamine (0.36 g) in 15 ml of methylene chloride at 0° C. The reaction mixture is then stirred for 4 hours at room temperature. After distilling off the solvent in a water-jet-vacuum, the residue is taken up in ethylacetate/water. The ethylacetate phase is extracted twice with water. After drying of the organic phase with Na2SO4, the solvent is distilled off in a water-jet-vacuum and the residue purified by column chromatography (silica gel; eluant: ethylacetate/hexane=1:1). 0.8 g of 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid (4′-chlorobiphenyl-2-yl) amide are obtained in the form of slightly brownish crystals having a melting point of 144–146° C. After distilling off the solvent in a water-jet-vacuum The ethylacetate phase is extracted twice with water After drying of the organic phase with Na2SO4 the solvent is distilled off in a water-jet-vacuum the residue purified by column chromatography (silica gel; eluant: ethylacetate/hexane=1:1)

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

Procedure: A solution of 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid (0.68 g) and oxalyl chloride (0.49 g) in methylene chloride (30 ml) is stirred for 2 hours at room temperature in the presence of a catalytic amount of DMF. The resulting acid chloride solution is then added to a solution of 4′-chlorobiphenyl-2-ylamine (0.71 g) and triethylamine (0.36 g) in 15 ml of methylene chloride at 0° C. The reaction mixture is then stirred for 4 hours at room temperature. After distilling off the solvent in a water-jet-vacuum, the residue is taken up in ethylacetate/water. The ethylacetate phase is extracted twice with water. After drying of the organic phase with Na2SO4, the solvent is distilled off in a water-jet-vacuum and the residue purified by column chromatography (silica gel; eluant: ethylacetate/hexane=1:1). 0.8 g of 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid (4′-chlorobiphenyl-2-yl) amide are obtained in the form of slightly brownish crystals having a melting point of 144–146° C. After distilling off the solvent in a water-jet-vacuum The ethylacetate phase is extracted twice with water After drying of the organic phase with Na2SO4 the solvent is distilled off in a water-jet-vacuum the residue purified by column chromatography (silica gel; eluant: ethylacetate/hexane=1:1)

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: The title compound was prepared from 4′-chloro-1,1′-biphenyl-2-amine (3.5 g, 17.19 mmol), acetic anhydride (1.79 mL, 18.9 mmol), pyridine (3.2 mL, 39.5 mmol), and 4-(N,N-dimethylamino)pyridine (0.06 g, 0.52 mmol) according to the procedure and in the same manner as described in Example 60, step b. The crude product was purified by re-crystallization from a mixture of ethyl acetate-hexane to yield N-(4′-chloro-1,1′-biphenyl-2-yl)acetamide (2.16 g, 8.78 mmol, 51%) as a white solid; The crude product was purified by re-crystallization from a mixture of ethyl acetate-hexane

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

Procedure: The title compound was prepared from 2-iodoaniline (5.0 g, 22.83 mmol), 4-chlorophenylboronic acid (3.57 g, 22.8 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) complex with dichloromethane (0.373 g, 0.46 mmol), and a 5.0 M sodium hydroxide solution (9.1 mL, 45.65 mmol) according to the procedure and in the same manner as described in Example 60, step a. The crude product was purified by flash column chromatography on silica gel, eluting with a mixture of ethyl acetate-hexane (1:12) to yield 4′-chloro-1,1′-biphenyl-2-amine (3.67 g, 18.0 mmol, 79%) as an orange oil; The crude product was purified by flash column chromatography on silica gel eluting with a mixture of ethyl acetate-hexane (1:12)

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

Procedure: Triethylamine (0.32 g: 1.5 mmole) was added to a solution of 4′-chlorobiphenyl-2-ylamine (0.3 g: 1.5 mmole) and 3-trifluoromethylpyrazine-2-carboxylic acid chloride (0.32 g: 1.5 mmole) in THF (10 mL), followed by stirring at room temperature for 2 hours. Water was added to the reaction mixture to suspend the reaction, followed by extraction with ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated in vacuo, and the residue was purified by silica gel column chromatography to give the subject compound (0.47 g). the reaction followed by extraction with ethyl acetate The ethyl acetate layer was dried over anhydrous sodium sulfate concentrated in vacuo the residue was purified by silica gel column chromatography