2-bromo-N-methylaniline

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

Procedure: 2-Bromo-N-methylaniline (1.00 g, 5.37 mmol) and diisopropylethylamine (2.0 ml, 11.50 mmol) were dissolved in dichloromethane (50 mL) and cooled in an ice bath. Methyl chloroformate (1.0 ml, 12.94 mmol) was added dropwise and the reaction stirred overnight. The reaction mixture was partitioned between water (200 mL) and ethyl acetate (200 mL). The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure. The crude was used without further purification. cooled in an ice bath The reaction mixture was partitioned between water (200 mL) and ethyl acetate (200 mL) The organic was dried with magnesium sulfate evaporated to dryness under reduced pressure The crude was used without further purification

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

Procedure: 2-Bromo-N-methylaniline (1.00 g, 5.37 mmol) and diisopropylethylamine (2.0 ml, 11.50 mmol) were dissolved in dichloromethane (50 mL) and cooled in an ice bath. Methyl chloroformate (1.0 ml, 12.94 mmol) was added dropwise and the reaction stirred overnight. The reaction mixture was partitioned between water (200 mL) and ethyl acetate (200 mL). The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure. The crude was used without further purification. cooled in an ice bath The reaction mixture was partitioned between water (200 mL) and ethyl acetate (200 mL) The organic was dried with magnesium sulfate evaporated to dryness under reduced pressure The crude was used without further purification

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

Procedure: To a reaction vial charged with 8-fluoro-4H-thieno[3,2-c]chromene-2-carbonyl chloride (0.05 g, 0.2 mmol) and 2-bromo-N-methylaniline (0.044 g, 0.24 mmol) was added a catalytic amount of DMAP. Pyridine in methylene chloride (1.2 M, 0.66 mL) was added and the reaction was stirred at room temperature with LC/MS monitor. The reaction was complete in a couple hours. After aqueous work up, the reaction mixture was concentrated in vacuo, taken into DMF at 100 mg/ml and purified by preparative RP-HPLC to give 162bp. Yield=24% of theoretical. MS: (ESI+)=419.5 To a reaction After aqueous work up, the reaction mixture was concentrated in vacuo purified by preparative RP-HPLC to give 162bp

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

Procedure: To a reaction vial charged with 8-fluoro-4H-thieno[3,2-c]chromene-2-carbonyl chloride (0.05 g, 0.2 mmol) and 2-bromo-N-methylaniline (0.044 g, 0.24 mmol) was added a catalytic amount of DMAP. Pyridine in methylene chloride (1.2 M, 0.66 mL) was added and the reaction was stirred at room temperature with LC/MS monitor. The reaction was complete in a couple hours. After aqueous work up, the reaction mixture was concentrated in vacuo, taken into DMF at 100 mg/ml and purified by preparative RP-HPLC to give 162bp. Yield=24% of theoretical. MS: (ESI+)=419.5 To a reaction After aqueous work up, the reaction mixture was concentrated in vacuo purified by preparative RP-HPLC to give 162bp

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

Procedure: To a solution of 2-bromo-N-methylaniline (2.07 g, 11.22 mmol), in dichloroethane (45 mL) was added acetone (1.31 g, 22.5 mmol), AcOH (4.04 g, 67.32 mmol) and Na(OAc)3BH (7.14 g, 33.66 mmol) sequentially at RT. The mixture was stirred for 72 h. The reaction was cooled with ice bath, and 2M NaOH (100 mL) was added slowly, then stirred for 5 min. The organic layer was separated, washed with brine dried and solvent removed. The crude product contained a mixture of 2:1 ratio of Compound 219 and starting material. This mixture was used as is in the next step. The reaction was cooled with ice bath stirred for 5 min The organic layer was separated washed with brine dried solvent removed a mixture of 2:1 ratio of Compound 219

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

Procedure: To a solution of 2-bromo-N-methylaniline (2.07 g, 11.22 mmol), in dichloroethane (45 mL) was added acetone (1.31 g, 22.5 mmol), AcOH (4.04 g, 67.32 mmol) and Na(OAc)3BH (7.14 g, 33.66 mmol) sequentially at RT. The mixture was stirred for 72 h. The reaction was cooled with ice bath, and 2M NaOH (100 mL) was added slowly, then stirred for 5 min. The organic layer was separated, washed with brine dried and solvent removed. The crude product contained a mixture of 2:1 ratio of Compound 219 and starting material. This mixture was used as is in the next step. The reaction was cooled with ice bath stirred for 5 min The organic layer was separated washed with brine dried solvent removed a mixture of 2:1 ratio of Compound 219

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

Procedure: To a reaction vial charged with 8-fluoro-4H-thieno[3,2-c]chromene-2-carbonyl chloride (0.05 g, 0.2 mmol) and 2-bromo-N-methylaniline (0.044 g, 0.24 mmol) was added a catalytic amount of DMAP. Pyridine in methylene chloride (1.2 M, 0.66 mL) was added and the reaction was stirred at room temperature with LC/MS monitor. The reaction was complete in a couple hours. After aqueous work up, the reaction mixture was concentrated in vacuo, taken into DMF at 100 mg/ml and purified by preparative RP-HPLC to give 162bp. Yield=24% of theoretical. MS: (ESI+)=419.5 To a reaction After aqueous work up, the reaction mixture was concentrated in vacuo purified by preparative RP-HPLC to give 162bp

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

Procedure: To a reaction vial charged with 8-fluoro-4H-thieno[3,2-c]chromene-2-carbonyl chloride (0.05 g, 0.2 mmol) and 2-bromo-N-methylaniline (0.044 g, 0.24 mmol) was added a catalytic amount of DMAP. Pyridine in methylene chloride (1.2 M, 0.66 mL) was added and the reaction was stirred at room temperature with LC/MS monitor. The reaction was complete in a couple hours. After aqueous work up, the reaction mixture was concentrated in vacuo, taken into DMF at 100 mg/ml and purified by preparative RP-HPLC to give 162bp. Yield=24% of theoretical. MS: (ESI+)=419.5 To a reaction After aqueous work up, the reaction mixture was concentrated in vacuo purified by preparative RP-HPLC to give 162bp

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

Procedure: To a reaction vial charged with 8-fluoro-4H-thieno[3,2-c]chromene-2-carbonyl chloride (0.05 g, 0.2 mmol) and 2-bromo-N-methylaniline (0.044 g, 0.24 mmol) was added a catalytic amount of DMAP. Pyridine in methylene chloride (1.2 M, 0.66 mL) was added and the reaction was stirred at room temperature with LC/MS monitor. The reaction was complete in a couple hours. After aqueous work up, the reaction mixture was concentrated in vacuo, taken into DMF at 100 mg/ml and purified by preparative RP-HPLC to give 162bp. Yield=24% of theoretical. MS: (ESI+)=419.5 To a reaction After aqueous work up, the reaction mixture was concentrated in vacuo purified by preparative RP-HPLC to give 162bp

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

Procedure: 2-Bromo-N-methylaniline (1.00 g, 5.37 mmol) and diisopropylethylamine (2.0 ml, 11.50 mmol) were dissolved in dichloromethane (50 mL) and cooled in an ice bath. Methyl chloroformate (1.0 ml, 12.94 mmol) was added dropwise and the reaction stirred overnight. The reaction mixture was partitioned between water (200 mL) and ethyl acetate (200 mL). The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure. The crude was used without further purification. cooled in an ice bath The reaction mixture was partitioned between water (200 mL) and ethyl acetate (200 mL) The organic was dried with magnesium sulfate evaporated to dryness under reduced pressure The crude was used without further purification

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

Procedure: To a reaction vial charged with 8-fluoro-4H-thieno[3,2-c]chromene-2-carbonyl chloride (0.05 g, 0.2 mmol) and 2-bromo-N-methylaniline (0.044 g, 0.24 mmol) was added a catalytic amount of DMAP. Pyridine in methylene chloride (1.2 M, 0.66 mL) was added and the reaction was stirred at room temperature with LC/MS monitor. The reaction was complete in a couple hours. After aqueous work up, the reaction mixture was concentrated in vacuo, taken into DMF at 100 mg/ml and purified by preparative RP-HPLC to give 162bp. Yield=24% of theoretical. MS: (ESI+)=419.5 To a reaction After aqueous work up, the reaction mixture was concentrated in vacuo purified by preparative RP-HPLC to give 162bp

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

Procedure: To a solution of 2-bromo-N-methylaniline (2.07 g, 11.22 mmol), in dichloroethane (45 mL) was added acetone (1.31 g, 22.5 mmol), AcOH (4.04 g, 67.32 mmol) and Na(OAc)3BH (7.14 g, 33.66 mmol) sequentially at RT. The mixture was stirred for 72 h. The reaction was cooled with ice bath, and 2M NaOH (100 mL) was added slowly, then stirred for 5 min. The organic layer was separated, washed with brine dried and solvent removed. The crude product contained a mixture of 2:1 ratio of Compound 219 and starting material. This mixture was used as is in the next step. The reaction was cooled with ice bath stirred for 5 min The organic layer was separated washed with brine dried solvent removed a mixture of 2:1 ratio of Compound 219