4-bromo-2-fluoro-N,N-dimethylaniline

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

Procedure: 4-Bromo-2-fluoro-N,N-dimethyl aniline (2.83 g, 13 mmols), tetrakis triphenyl palladium (0) (0.508 g, 0.4 mmols), diethyl (4-pyridyl borane) (1.3 g, 9 mmols), potassium hydroxide (2.81 g, 50 mmols) and tetrabutylammonium bromide (1.42 g, 4 mmols) were combined in tetrahydrofuran (50 ml). The resulting mixture was heated at reflux for 18 hrs under nitrogen then cooled to ambient temperature. Ethyl acetate (100 ml) and brine (50 ml) were added and the organic solution was separated. This was dried over magnesium sulfate filtered and evaporated to yield a yellow solid. The product was purified by column chromatography on silica eluted with ethyl acetate:hexanes 50:50 to give 0.9 g of 2-Fluoro-N,N-dimethyl-4-(pyridin-4-yl)aniline (XII) in a 44% yield as a pale yellow solid. The resulting mixture was heated at reflux for 18 hrs under nitrogen the organic solution was separated This was dried over magnesium sulfate filtered evaporated to yield a yellow solid The product was purified by column chromatography on silica eluted with ethyl acetate:hexanes 50:50

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

Procedure: 4-Bromo-2-fluoroaniline was methylated by treating it with dimethylsulphate to give a 26% yield of 4-Bromo-2-fluoro-N,N-dimethylaniline (XI) as a red oil. The resultant 4-Bromo-2-fluoro-N,N-dimethylaniline was coupled to diethyl (4-pyridyl)borane (I) using a tetrakis triphenyl phosphine palladium (0) catalyst to give 2-Fluoro-N,N-dimethyl-4-(pyridin-4-yl)aniline (XII) in a 44% yield. This was methylated by refluxing it in acetonitrile in the presence of methyl iodide and the product 4-(4-(dimethylamino)-3-fluorophenyl)-1-methylpyridinium iodide (XIII) IDT330 was obtained in a 21% yield.

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

Procedure: 4-Bromo-2-fluoro-N,N-dimethyl aniline (2.83 g, 13 mmols), tetrakis triphenyl palladium (0) (0.508 g, 0.4 mmols), diethyl (4-pyridyl borane) (1.3 g, 9 mmols), potassium hydroxide (2.81 g, 50 mmols) and tetrabutylammonium bromide (1.42 g, 4 mmols) were combined in tetrahydrofuran (50 ml). The resulting mixture was heated at reflux for 18 hrs under nitrogen then cooled to ambient temperature. Ethyl acetate (100 ml) and brine (50 ml) were added and the organic solution was separated. This was dried over magnesium sulfate filtered and evaporated to yield a yellow solid. The product was purified by column chromatography on silica eluted with ethyl acetate:hexanes 50:50 to give 0.9 g of 2-Fluoro-N,N-dimethyl-4-(pyridin-4-yl)aniline (XII) in a 44% yield as a pale yellow solid. The resulting mixture was heated at reflux for 18 hrs under nitrogen the organic solution was separated This was dried over magnesium sulfate filtered evaporated to yield a yellow solid The product was purified by column chromatography on silica eluted with ethyl acetate:hexanes 50:50

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

Procedure: IDT330. 4-Bromo-2-fluoroaniline was methylated by treating it with dimethylsulphate to give a 26% yield of 4-Bromo-2-fluoro-N,N-dimethylaniline (XI) as a red oil. The resultant 4-Bromo-2-fluoro-N,N-dimethylaniline was coupled to diethyl (4-pyridyl) borane (I) using a tetrakis triphenyl phosphine palladium (0) catalyst to give 2-Fluoro-N,N-dimethyl-4-(pyridin-4-yl)aniline (XII) in a 44% yield. This was methylated by refluxing it in acetonitrile in the presence of methyl iodide and the product 4-(4-(dimethylamino)-3-fluorophenyl)-1-methylpyridinium iodide (XIII) IDT330 was obtained in a 21% yield.

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

Procedure: IDT330. 4-Bromo-2-fluoroaniline was methylated by treating it with dimethylsulphate to give a 26% yield of 4-Bromo-2-fluoro-N,N-dimethylaniline (XI) as a red oil. The resultant 4-Bromo-2-fluoro-N,N-dimethylaniline was coupled to diethyl (4-pyridyl) borane (I) using a tetrakis triphenyl phosphine palladium (0) catalyst to give 2-Fluoro-N,N-dimethyl-4-(pyridin-4-yl)aniline (XII) in a 44% yield. This was methylated by refluxing it in acetonitrile in the presence of methyl iodide and the product 4-(4-(dimethylamino)-3-fluorophenyl)-1-methylpyridinium iodide (XIII) IDT330 was obtained in a 21% yield.

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

Procedure: 4-Bromo-2-fluoro-N,N-dimethyl aniline (2.83 g, 13 mmols), tetrakis triphenyl palladium (0) (0.508 g, 0.4 mmols), diethyl (4-pyridyl borane) (1.3 g, 9 mmols), potassium hydroxide (2.81 g, 50 mmols) and tetrabutylammonium bromide (1.42 g, 4 mmols) were combined in tetrahydrofuran (50 ml). The resulting mixture was heated at reflux for 18 hrs under nitrogen then cooled to ambient temperature. Ethyl acetate (100 ml) and brine (50 ml) were added and the organic solution was separated. This was dried over magnesium sulfate filtered and evaporated to yield a yellow solid. The product was purified by column chromatography on silica eluted with ethyl acetate:hexanes 50:50 to give 0.9 g of 2-Fluoro-N,N-dimethyl-4-(pyridin-4-yl)aniline (XII) in a 44% yield as a pale yellow solid. The resulting mixture was heated at reflux for 18 hrs under nitrogen the organic solution was separated This was dried over magnesium sulfate filtered evaporated to yield a yellow solid The product was purified by column chromatography on silica eluted with ethyl acetate:hexanes 50:50

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

Procedure: 4-Bromo-2-fluoroaniline was methylated by treating it with dimethylsulphate to give a 26% yield of 4-Bromo-2-fluoro-N,N-dimethylaniline (XI) as a red oil. The resultant 4-Bromo-2-fluoro-N,N-dimethylaniline was coupled to diethyl (4-pyridyl)borane (I) using a tetrakis triphenyl phosphine palladium (0) catalyst to give 2-Fluoro-N,N-dimethyl-4-(pyridin-4-yl)aniline (XII) in a 44% yield. This was methylated by refluxing it in acetonitrile in the presence of methyl iodide and the product 4-(4-(dimethylamino)-3-fluorophenyl)-1-methylpyridinium iodide (XIII) IDT330 was obtained in a 21% yield.

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

Procedure: To a solution of 2-fluoro-4-bromoaniline (1.0 g, 5.26 mmol) in AcOH (20 mL) at rt was added NaCNBH3 (1.654 g, 26.3 mmol). The mixture was stirred at rt overnight (˜17 h). The reaction was cooled in an ice bath. Water (10 mL) was added, followed by solid KOH until pH>11. The mixture was extracted with DCM. The combined extracts were dried (MgSO4) and concentrated to afford the title compound, which was used without further purification. LC-MS: calculated for C8H9BrFN 218.07, observed m/e 219.99 (M+H)+ (Rt 0.96 min). The reaction was cooled in an ice bath The mixture was extracted with DCM The combined extracts were dried (MgSO4) concentrated

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

Procedure: To a solution of 2-fluoro-4-bromoaniline (1.0 g, 5.26 mmol) in AcOH (20 mL) at rt was added NaCNBH3 (1.654 g, 26.3 mmol). The mixture was stirred at rt overnight (˜17 h). The reaction was cooled in an ice bath. Water (10 mL) was added, followed by solid KOH until pH >11. The mixture was extracted with DCM. The combined extracts were dried (MgSO4) and concentrated to afford the title compound, which was used without further purification. LC-MS: calculated for C8H9BrFN 218.07, observed m/e 219.99 (M+H)+ (Rt 0.96 min). The reaction was cooled in an ice bath The mixture was extracted with DCM The combined extracts were dried (MgSO4) concentrated

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

Procedure: To a solution of 2-fluoro-4-bromoaniline (1.0 g, 5.26 mmol) in AcOH (20 mL) at rt was added NaCNBH3 (1.654 g, 26.3 mmol). The mixture was stirred at rt overnight (˜17 h). The reaction was cooled in an ice bath. Water (10 mL) was added, followed by solid KOH until pH>11. The mixture was extracted with DCM. The combined extracts were dried (MgSO4) and concentrated to afford the title compound, which was used without further purification. LC-MS: calculated for C8H9BrFN 218.07, observed m/e 219.99 (M+H)+ (Rt 0.96 min). The reaction was cooled in an ice bath The mixture was extracted with DCM The combined extracts were dried (MgSO4) concentrated

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

Procedure: 4-Bromo-2-fluoro-N,N-dimethyl aniline (2.83 g, 13 mmols), tetrakis triphenyl palladium (0) (0.508 g, 0.4 mmols), diethyl (4-pyridyl borane) (1.3 g, 9 mmols), potassium hydroxide (2.81 g, 50 mmols) and tetrabutylammonium bromide (1.42 g, 4 mmols) were combined in tetrahydrofuran (50 ml). The resulting mixture was heated at reflux for 18 hrs under nitrogen then cooled to ambient temperature. Ethyl acetate (100 ml) and brine (50 ml) were added and the organic solution was separated. This was dried over magnesium sulfate filtered and evaporated to yield a yellow solid. The product was purified by column chromatography on silica eluted with ethyl acetate:hexanes 50:50 to give 0.9 g of 2-Fluoro-N,N-dimethyl-4-(pyridin-4-yl)aniline (XII) in a 44% yield as a pale yellow solid. The resulting mixture was heated at reflux for 18 hrs under nitrogen the organic solution was separated This was dried over magnesium sulfate filtered evaporated to yield a yellow solid The product was purified by column chromatography on silica eluted with ethyl acetate:hexanes 50:50

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

Procedure: IDT330. 4-Bromo-2-fluoroaniline was methylated by treating it with dimethylsulphate to give a 26% yield of 4-Bromo-2-fluoro-N,N-dimethylaniline (XI) as a red oil. The resultant 4-Bromo-2-fluoro-N,N-dimethylaniline was coupled to diethyl (4-pyridyl) borane (I) using a tetrakis triphenyl phosphine palladium (0) catalyst to give 2-Fluoro-N,N-dimethyl-4-(pyridin-4-yl)aniline (XII) in a 44% yield. This was methylated by refluxing it in acetonitrile in the presence of methyl iodide and the product 4-(4-(dimethylamino)-3-fluorophenyl)-1-methylpyridinium iodide (XIII) IDT330 was obtained in a 21% yield.