2-(2,3-difluorophenyl)acetyl chloride

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

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

Procedure: A solution of 2,3-difluorophenylacetyl chloride (1.0 mmol) in CH2Cl 2(3 ml) was added dropwise to a mixture of [4-(1H-pyrrolo[2,3-]pyridin-5-yl)-cyclohexyl]-carbamic acid tert-butyl ester (280 mg, 0.88 mmol) and AlCl3 (612 mg, 4.6 mmol) in CH2Cl2(15 ml) at 0° C. After the addition, the reaction was stirred for 1.5 hrs at 0° C. Methanol (5 ml) was added to the reaction. After 1 hr. the reaction was evaporated and the resulting residue purified by flash chromatography to afford 1-[5-(4-Amino-cyclohexyl)-1H-pyrrolo[2,3-b]pyridin-3-yl ]-2-(2,3-difluoro-phenyl)-ethanone (229 mg) in 70.5% yield. LC-MS: m/e=370.3 (M+H), 368.4 (M−H). After the treatment of the above cyclohexylamine (220 mg, 0.60 mmol) with 37% formaldehyde (2 ml) and formic acid (4 ml) at 80° C. for 15 h, pure 2-(2,3-Difluoro-phenyl)-1-[5-(4-dimethylamino-cyclohexyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-ethanone was obtained by FC (167 mg) in 70.1% yield. LC-MS: m/e: 398.4 (M+H), 396.4 (M−H). After the addition After 1 hr the reaction was evaporated the resulting residue purified by flash chromatography

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

Procedure: A solution of 2,3-difluorophenylacetyl chloride (1.0 mmol) in CH2Cl 2(3 ml) was added dropwise to a mixture of [4-(1H-pyrrolo[2,3-]pyridin-5-yl)-cyclohexyl]-carbamic acid tert-butyl ester (280 mg, 0.88 mmol) and AlCl3 (612 mg, 4.6 mmol) in CH2Cl2(15 ml) at 0° C. After the addition, the reaction was stirred for 1.5 hrs at 0° C. Methanol (5 ml) was added to the reaction. After 1 hr. the reaction was evaporated and the resulting residue purified by flash chromatography to afford 1-[5-(4-Amino-cyclohexyl)-1H-pyrrolo[2,3-b]pyridin-3-yl ]-2-(2,3-difluoro-phenyl)-ethanone (229 mg) in 70.5% yield. LC-MS: m/e=370.3 (M+H), 368.4 (M−H). After the treatment of the above cyclohexylamine (220 mg, 0.60 mmol) with 37% formaldehyde (2 ml) and formic acid (4 ml) at 80° C. for 15 h, pure 2-(2,3-Difluoro-phenyl)-1-[5-(4-dimethylamino-cyclohexyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-ethanone was obtained by FC (167 mg) in 70.1% yield. LC-MS: m/e: 398.4 (M+H), 396.4 (M−H). After the addition After 1 hr the reaction was evaporated the resulting residue purified by flash chromatography

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

Procedure: 2,3-Difluorophenylacetyl chloride(58.1 mmol) in CH2Cl2 (150 ml)was added to a suspension of 5-bromo-1H-pyrrolo[2,3-b]pyridine (8.0 g, 40.6 mmol) and AlCl3 (46 g, 345 mmol) in CH2Cl2 (100 ml) at 0° C. After the addition, the cooling bath was removed and the reaction mixture was stirred at room temperature for 1.5 hrs. The reaction was cooled with ice-bath and methanol (100 ml) was added to the reaction mixture while maintaining the temperature below 30° C. The reaction mixture was evaporated and the residue was suspended in water. The solid was collected by vacuum filtration, washed with water and hexane to give the title compound (14.03 g) in 98% yield. After the addition the cooling bath was removed The reaction was cooled with ice-bath methanol (100 ml) was added to the reaction mixture while maintaining the temperature below 30° C The reaction mixture was evaporated The solid was collected by vacuum filtration washed with water and hexane

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

Procedure: 2,3-Difluorophenylacetyl chloride(58.1 mmol) in CH2Cl2 (150 ml)was added to a suspension of 5-bromo-1H-pyrrolo[2,3-b]pyridine (8.0 g, 40.6 mmol) and AlCl3 (46 g, 345 mmol) in CH2Cl2 (100 ml) at 0° C. After the addition, the cooling bath was removed and the reaction mixture was stirred at room temperature for 1.5 hrs. The reaction was cooled with ice-bath and methanol (100 ml) was added to the reaction mixture while maintaining the temperature below 30° C. The reaction mixture was evaporated and the residue was suspended in water. The solid was collected by vacuum filtration, washed with water and hexane to give the title compound (14.03 g) in 98% yield. After the addition the cooling bath was removed The reaction was cooled with ice-bath methanol (100 ml) was added to the reaction mixture while maintaining the temperature below 30° C The reaction mixture was evaporated The solid was collected by vacuum filtration washed with water and hexane

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

Procedure: 189 mg of crude Dimethyl-[3-(1H-pyrrolo[2,3-b]pyridin-5-yl)-prop-2-ynyl]-amine was stirred in 5 ml of DCM with AlCl3 (4 equivalents) for 30 minutes. Two equivalents of (2,3-Difluoro-phenyl)-acetyl chloride were added and the reaction was stirred in a sealed tube overnight. The LC/MS showed the reaction to be complete and was worked-up under standard conditions. Normal phase column chromatography yielded 101 mg of 2-(2,3-Difluoro-phenyl)-1-[5-(3-dimethylamino-prop-1-ynyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-ethanone with a yield over two steps of 33%. LC/MS retention time of 1.83 minutes. M+ 354.17, M− 352.1 the reaction

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

Procedure: 189 mg of crude Dimethyl-[3-(1H-pyrrolo[2,3-b]pyridin-5-yl)-prop-2-ynyl]-amine was stirred in 5 ml of DCM with AlCl3 (4 equivalents) for 30 minutes. Two equivalents of (2,3-Difluoro-phenyl)-acetyl chloride were added and the reaction was stirred in a sealed tube overnight. The LC/MS showed the reaction to be complete and was worked-up under standard conditions. Normal phase column chromatography yielded 101 mg of 2-(2,3-Difluoro-phenyl)-1-[5-(3-dimethylamino-prop-1-ynyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-ethanone with a yield over two steps of 33%. LC/MS retention time of 1.83 minutes. M+ 354.17, M− 352.1 the reaction

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

Procedure: To 7-azaindole (1 g, 8.5 mmol) and AlCl3 (1.2 g, 9.0 mmol) in methlene chloride at 0° C. was added (2,3-difluorophenyl)-acetyl chloride [prepared by treating (2,3-difluoro-phenyl)-acetic acid (1.5 mg, 8.72 mmol) with oxalyl chloride (0.90 mL)] in methlene chloride. After stirring at room temperature for 2 hours, the solution was poured into ice water and extracted with methlene chloride, dried (Na2SO4), and concentrated to give 300 mg (13% yield) of title compound used without purification. LCMS Rt=3.00 minutes, MH+ 273.1, M− 271.1. extracted with methlene chloride dried (Na2SO4) concentrated

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

Procedure: To 7-azaindole (1 g, 8.5 mmol) and AlCl3 (1.2 g, 9.0 mmol) in methlene chloride at 0° C. was added (2,3-difluorophenyl)-acetyl chloride [prepared by treating (2,3-difluoro-phenyl)-acetic acid (1.5 mg, 8.72 mmol) with oxalyl chloride (0.90 mL)] in methlene chloride. After stirring at room temperature for 2 hours, the solution was poured into ice water and extracted with methlene chloride, dried (Na2SO4), and concentrated to give 300 mg (13% yield) of title compound used without purification. LCMS Rt=3.00 minutes, MH+ 273.1, M− 271.1. extracted with methlene chloride dried (Na2SO4) concentrated

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

Procedure: A solution of 2,3-difluorophenylacetyl chloride (1.0 mmol) in CH2Cl 2(3 ml) was added dropwise to a mixture of [4-(1H-pyrrolo[2,3-]pyridin-5-yl)-cyclohexyl]-carbamic acid tert-butyl ester (280 mg, 0.88 mmol) and AlCl3 (612 mg, 4.6 mmol) in CH2Cl2(15 ml) at 0° C. After the addition, the reaction was stirred for 1.5 hrs at 0° C. Methanol (5 ml) was added to the reaction. After 1 hr. the reaction was evaporated and the resulting residue purified by flash chromatography to afford 1-[5-(4-Amino-cyclohexyl)-1H-pyrrolo[2,3-b]pyridin-3-yl ]-2-(2,3-difluoro-phenyl)-ethanone (229 mg) in 70.5% yield. LC-MS: m/e=370.3 (M+H), 368.4 (M−H). After the treatment of the above cyclohexylamine (220 mg, 0.60 mmol) with 37% formaldehyde (2 ml) and formic acid (4 ml) at 80° C. for 15 h, pure 2-(2,3-Difluoro-phenyl)-1-[5-(4-dimethylamino-cyclohexyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-ethanone was obtained by FC (167 mg) in 70.1% yield. LC-MS: m/e: 398.4 (M+H), 396.4 (M−H). After the addition After 1 hr the reaction was evaporated the resulting residue purified by flash chromatography

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

Procedure: 2,3-Difluorophenylacetyl chloride(58.1 mmol) in CH2Cl2 (150 ml)was added to a suspension of 5-bromo-1H-pyrrolo[2,3-b]pyridine (8.0 g, 40.6 mmol) and AlCl3 (46 g, 345 mmol) in CH2Cl2 (100 ml) at 0° C. After the addition, the cooling bath was removed and the reaction mixture was stirred at room temperature for 1.5 hrs. The reaction was cooled with ice-bath and methanol (100 ml) was added to the reaction mixture while maintaining the temperature below 30° C. The reaction mixture was evaporated and the residue was suspended in water. The solid was collected by vacuum filtration, washed with water and hexane to give the title compound (14.03 g) in 98% yield. After the addition the cooling bath was removed The reaction was cooled with ice-bath methanol (100 ml) was added to the reaction mixture while maintaining the temperature below 30° C The reaction mixture was evaporated The solid was collected by vacuum filtration washed with water and hexane

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

Procedure: 2,3-Difluorophenylacetyl chloride(58.1 mmol) in CH2Cl2 (150 ml)was added to a suspension of 5-bromo-1H-pyrrolo[2,3-b]pyridine (8.0 g, 40.6 mmol) and AlCl3 (46 g, 345 mmol) in CH2Cl2 (100 ml) at 0° C. After the addition, the cooling bath was removed and the reaction mixture was stirred at room temperature for 1.5 hrs. The reaction was cooled with ice-bath and methanol (100 ml) was added to the reaction mixture while maintaining the temperature below 30° C. The reaction mixture was evaporated and the residue was suspended in water. The solid was collected by vacuum filtration, washed with water and hexane to give the title compound (14.03 g) in 98% yield. After the addition the cooling bath was removed The reaction was cooled with ice-bath methanol (100 ml) was added to the reaction mixture while maintaining the temperature below 30° C The reaction mixture was evaporated The solid was collected by vacuum filtration washed with water and hexane