3-chloro-N-methylaniline

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

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

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

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

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Oxalyl chloride (89 μL, 1.02 mmol) was added to a solution of pent-4-ynoic acid (50 mg, 0.51 mmol) in DCM (3 mL). The reaction mixture was stirred at 50° C. for 1 hour, was cooled to 0° C. and was added dropwise to a solution of (3-chloro-phenyl)-methyl-amine (62 μL, 0.51 mmol). The reaction mixture was stirred for 2 hours at room temperature. After evaporation of the solvent, the crude residue was purified by flash chromatography (DCM/MeOH 99:1) to yield 100 mg (0.45 mmol, 88%) of pent-4-ynoic acid (3-chloro-phenyl)-methyl-amide. was cooled to 0° C. The reaction mixture was stirred for 2 hours at room temperature After evaporation of the solvent the crude residue was purified by flash chromatography (DCM/MeOH 99:1)

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

Procedure: 5-Chloro-3-(4-chloro-3-(trifluoromethyl)phenylsulfonamido)picolinic acid (50 mg, 0.12 mmol), (3-chloro-phenyl)-methyl-amine (50 mg, 0.36 mmol), BOP (69 mg, 0.36 mmol), DIEA (130 μL, 0.72 mmol) were reacted according to the procedure D to provide the title compound. HPLC purification (20→90% gradient of MeCN-water) provided 5-chloro-3-(4-chloro-3-trifluoromethyl-benzenesulfonylamino)-pyridine-2-carboxylic acid (3-chloro-phenyl)-methyl-amide: MS m/z: (M+H) 537.9.

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Oxayl chloride (89 μL, 1.02 mmol) was added to a solution of pent-4-ynoic acid (50 mg, 0.51 mmol) in DCM (3 mL). The reaction mixture was stirred at 50° C. for 1 hour, was cooled to 0° C. and was added dropwise to a solution of (3-chloro-phenyl)-methyl-amine (62 μL, 0.51 mmol). The reaction mixture was stirred for 2 hours at room temperature. After evaporation of the solvent, the crude residue was purified by flash chromatography (DCM/MeOH 99:1) to yield 100 mg (0.45 mmol, 88%) of pent-4-ynoic acid (3-chloro-phenyl)-methyl-amide. was cooled to 0° C. The reaction mixture was stirred for 2 hours at room temperature After evaporation of the solvent the crude residue was purified by flash chromatography (DCM/MeOH 99:1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of the compound 2,4-dichloro-1,3,5-triazine (2.5 g, 16.7 mmol) and solid K2CO3 (6.9 g, 49.9 mmol) was suspended in AcCN (50 mL) under nitrogen at 0° C. followed by addition of N-methyl-3-chloroaniline (2.5 g, 17.7 mmol). The mixture was stirred at 0° C. for 2 h. The reaction was quenched by pouring onto ice/water. The white solid formed was collected by suction filtration and dried under vacuum to give N-methyl-2-chloro-4-(3-chloroanilino)-1,3,5-triazine. MS m/z=256. Calc'd for C10H8Cl2N4: 254.01. The reaction was quenched by pouring onto ice/water The white solid formed was collected by suction filtration dried under vacuum

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

Procedure: To a solution of 4-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-carboxylic acid methyl ester (0.5 g) in 1,4-dioxane (5 ml) was added 3-chloro-N-methyl aniline (0.629 g) and methanesulfonic acid (0.289 ml). The mixture was irradiated under microwave conditions at 180° C. for 30 min. 1,4-dioxane was removed in vacuo and the residue purified by MDAP to give the title compound (350 mg). The mixture was irradiated under microwave conditions at 180° C. for 30 min 1,4-dioxane was removed in vacuo the residue purified by MDAP

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

Procedure: To a solution of 4-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-carboxylic acid methyl ester (0.5 g) in 1,4-dioxane (5 ml) was added 3-chloro-N-methyl aniline (0.629 g) and methanesulfonic acid (0.289 ml). The mixture was irradiated under microwave conditions at 180° C. for 30 min. 1,4-dioxane was removed in vacuo and the residue purified by MDAP to give the title compound (350 mg). The mixture was irradiated under microwave conditions at 180° C. for 30 min 1,4-dioxane was removed in vacuo the residue purified by MDAP

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Oxalyl chloride (89 μL, 1.02 mmol) was added to a solution of pent-4-ynoic acid (50 mg, 0.51 mmol) in DCM (3 mL). The reaction mixture was stirred at 50° C. for 1 hour, was cooled to 0° C. and was added dropwise to a solution of (3-chloro-phenyl)-methyl-amine (62 μL, 0.51 mmol). The reaction mixture was stirred for 2 hours at room temperature. After evaporation of the solvent, the crude residue was purified by flash chromatography (DCM/MeOH 99:1) to yield 100 mg (0.45 mmol, 88%) of pent-4-ynoic acid (3-chloro-phenyl)-methyl-amide. was cooled to 0° C. The reaction mixture was stirred for 2 hours at room temperature After evaporation of the solvent the crude residue was purified by flash chromatography (DCM/MeOH 99:1)

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

Procedure: 5-Chloro-3-(4-chloro-3-(trifluoromethyl)phenylsulfonamido)picolinic acid (50 mg, 0.12 mmol), (3-chloro-phenyl)-methyl-amine (50 mg, 0.36 mmol), BOP (69 mg, 0.36 mmol), DIEA (130 μL, 0.72 mmol) were reacted according to the procedure D to provide the title compound. HPLC purification (20→90% gradient of MeCN-water) provided 5-chloro-3-(4-chloro-3-trifluoromethyl-benzenesulfonylamino)-pyridine-2-carboxylic acid (3-chloro-phenyl)-methyl-amide: MS m/z: (M+H) 537.9.