4-溴-1H-吲哚-7-甲酰胺

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of DMF (8.42 mL, 109 mmol) in CH2Cl2(105 mL) stirred on a salt-ice bath was treated dropwise with phosphorus oxychloride (2.57 mL, 27.6 mmol). After 15 min, 4-bromo-1H-indole-7-carboxamide (2 g, 8.37 mmol) was added in one portion while maintaining the temperature below −10° C. After addition, the mixture was stirred at room temperature overnight. After 16 h, ice was added, followed by NaHCO3 and 1 M aqueous NaOH added in portions to make the mixture basic. The mixture was extracted with dichloromethane (3 times), and the combined organic phases were washed with brine, dried and concentrated. The residue was subjected to column chromatography on silica gel (80 g), eluting with a gradient from 100% CH2Cl2 to 15% Methanol-85% CH2Cl2, to provide the desired product as a pale solid (1.36 g, 65% yield). LCMS (M+H)+ m/z 248.9, 250.9. while maintaining the temperature below −10° C After addition After 16 h ice was added added in portions The mixture was extracted with dichloromethane (3 times) the combined organic phases were washed with brine dried concentrated eluting with a gradient from 100% CH2Cl2 to 15% Methanol-85% CH2Cl2

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of DMF (8.42 mL, 109 mmol) in CH2Cl2(105 mL) stirred on a salt-ice bath was treated dropwise with phosphorus oxychloride (2.57 mL, 27.6 mmol). After 15 min, 4-bromo-1H-indole-7-carboxamide (2 g, 8.37 mmol) was added in one portion while maintaining the temperature below −10° C. After addition, the mixture was stirred at room temperature overnight. After 16 h, ice was added, followed by NaHCO3 and 1 M aqueous NaOH added in portions to make the mixture basic. The mixture was extracted with dichloromethane (3 times), and the combined organic phases were washed with brine, dried and concentrated. The residue was subjected to column chromatography on silica gel (80 g), eluting with a gradient from 100% CH2Cl2 to 15% Methanol-85% CH2Cl2, to provide the desired product as a pale solid (1.36 g, 65% yield). LCMS (M+H)+ m/z 248.9, 250.9. while maintaining the temperature below −10° C After addition After 16 h ice was added added in portions The mixture was extracted with dichloromethane (3 times) the combined organic phases were washed with brine dried concentrated eluting with a gradient from 100% CH2Cl2 to 15% Methanol-85% CH2Cl2

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Acetic acid (1.15 mL, 20.08 mmol) was added to a suspension of 4-bromo-1H-indole-7-carboxamide (3 g, 12.55 mmol), paraformaldehyde (0.603 g, 20.08 mmol) and dimethylamine (2 M in methanol, 10 mL, 20.08 mmol) in ethanol (50 mL). The mixture was heated to 80° C. After 2 h, the ethanol was removed under vacuum. The residue was partitioned between NaHCO3 (aq) and EtOAc. The organic phase was washed with brine (15 mL), dried and concentrated to afford the crude desired product as a light brown solid (4.08 g). LCMS (M+H)+ m/z 295.8, 297.8. the ethanol was removed under vacuum The residue was partitioned between NaHCO3 (aq) and EtOAc The organic phase was washed with brine (15 mL) dried concentrated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A dark red-brown solution of 4-bromo-1H-indole-7-carboxamide (0.79 g, 3.30 mmol) and (E)-N,N-dimethyl-2-nitroethenamine (0.422 g, 3.63 mmol) in TFA (9.44 mL) was stirred at room temperature overnight. After 16 h, LCMS indicated residual starting materials in addition to desired product. Additional (E)-N,N-dimethyl-2-nitroethenamine (77 mg) was added and the mixture was stirred at room temperature for 6 h. The mixture was partitioned between 1 M NaOH (pH was adjusted to ca. 4) and EtOAc. The organic phase was washed with NaHCO3 (aq) and brine, dried and concentrated to afford a bright orange-red solid. The crude product was suspended in EtOAc and the desired product was collected by filtration, washed with EtOAc and air dried to provide a solid (0.89 g, 87% yield). LCMS (M+H)+ m/z 309.7, 311.7.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 4-bromo-1H-indole-7-carboxylic acid (10.04 g, 75% purity, 31.2 mmol), EDC (8.96 g, 46.7 mmol), and 1-hydroxybenzotriazole hydrate (7.16 g, 46.7 mmol) in THF (198 mL) and CH2Cl2 (247 mL) was stirred at room temperature for 1 h. The mixture was then bubbled with NH3 gas for 15 min and stirred at room temperature for 4 h. LCMS showed residual starting material, so aqueous ammonium hydroxide (4.85 mL, 125 mmol) was added and the mixture was stirred at room temperature overnight. After 20 h, the mixture was concentrated and partitioned between NaHCO3 (aq) and EtOAc. The organic phase was washed with brine, dried and concentrated. The residue was suspended in EtOAc and the solid was collected by filtration and air-dried to provide the desired product. The filtrates were subjected to column chromatography on silica gel (40 g), eluting with EtOAc-hexane (gradient from 20:80 to 50:50) to provide additional desired product for a total of 4.86 g (65% yield) over two steps. LCMS (M−H)−: 237.2, 239.2. The mixture was then bubbled with NH3 gas for 15 min stirred at room temperature for 4 h was added the mixture was stirred at room temperature overnight After 20 h the mixture was concentrated partitioned between NaHCO3 (aq) and EtOAc The organic phase was washed with brine dried concentrated the solid was collected by filtration air-dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 4-bromo-1H-indole-7-carboxylic acid (10.04 g, 75% purity, 31.2 mmol), EDC (8.96 g, 46.7 mmol), and 1-hydroxybenzotriazole hydrate (7.16 g, 46.7 mmol) in THF (198 mL) and CH2Cl2 (247 mL) was stirred at room temperature for 1 h. The mixture was then bubbled with NH3 gas for 15 min and stirred at room temperature for 4 h. LCMS showed residual starting material, so aqueous ammonium hydroxide (4.85 mL, 125 mmol) was added and the mixture was stirred at room temperature overnight. After 20 h, the mixture was concentrated and partitioned between NaHCO3 (aq) and EtOAc. The organic phase was washed with brine, dried and concentrated. The residue was suspended in EtOAc and the solid was collected by filtration and air-dried to provide the desired product. The filtrates were subjected to column chromatography on silica gel (40 g), eluting with EtOAc-hexane (gradient from 20:80 to 50:50) to provide additional desired product for a total of 4.86 g (65% yield) over two steps. LCMS (M−H)−: 237.2, 239.2. The mixture was then bubbled with NH3 gas for 15 min stirred at room temperature for 4 h was added the mixture was stirred at room temperature overnight After 20 h the mixture was concentrated partitioned between NaHCO3 (aq) and EtOAc The organic phase was washed with brine dried concentrated the solid was collected by filtration air-dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 4-bromo-1H-indole-7-carboxylic acid (10.04 g, 75% purity, 31.2 mmol), EDC (8.96 g, 46.7 mmol), and 1-hydroxybenzotriazole hydrate (7.16 g, 46.7 mmol) in THF (198 mL) and CH2Cl2 (247 mL) was stirred at room temperature for 1 h. The mixture was then bubbled with NH3 gas for 15 min and stirred at room temperature for 4 h. LCMS showed residual starting material, so aqueous ammonium hydroxide (4.85 mL, 125 mmol) was added and the mixture was stirred at room temperature overnight. After 20 h, the mixture was concentrated and partitioned between NaHCO3 (aq) and EtOAc. The organic phase was washed with brine, dried and concentrated. The residue was suspended in EtOAc and the solid was collected by filtration and air-dried to provide the desired product. The filtrates were subjected to column chromatography on silica gel (40 g), eluting with EtOAc-hexane (gradient from 20:80 to 50:50) to provide additional desired product for a total of 4.86 g (65% yield) over two steps. LCMS (M−H)−: 237.2, 239.2. The mixture was then bubbled with NH3 gas for 15 min stirred at room temperature for 4 h was added the mixture was stirred at room temperature overnight After 20 h the mixture was concentrated partitioned between NaHCO3 (aq) and EtOAc The organic phase was washed with brine dried concentrated the solid was collected by filtration air-dried