1-(3-bromo-4-fluorophenyl)-N-methylmethanamine

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

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

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the solution of [(3-bromo-4-fluorophenyl)methyl]methylamine (0.52 g, 2.39 mmol) in p-dioxane/H2O (15/5 mL) was added {3-[(4-{[(1,1-dimethylethyl)oxy]carbonyl}-1-piperazinyl)methyl]phenyl}boronic acid (1.15 g, 3.60 mmol), Pd(PPh3)4 (139 mg, 0.12 mmol), and K2CO3 (1.33 g, 9.6 mmol). The result mixture was heated in a microwave machine at 150° C. for 15 mins. The organic layer was separated and concentrated. The residue was redissolved in EtOAc (˜70 mL), washed with H2O (20 mL), brine (20 mL), dried over Na2SO4, filtered, concentrated and purified by CombiFlash chomatograph to afford 0.65 g (66%) of the title compound. LC-MS m/z 414 (M+H)+. The organic layer was separated concentrated The residue was redissolved in EtOAc (˜70 mL) washed with H2O (20 mL), brine (20 mL) dried over Na2SO4 filtered concentrated purified by CombiFlash chomatograph

Conditions: temp:8.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the solution of 1,1-dimethylethyl [(3-bromo-4-fluorophenyl)methyl]carbamate (0.755 g, 2.48 mmol) in THF (1 mL) was added BH3.THF (12.5 mL, 1.0 M in THF). The mixture was heated in a microwave machine at about 8° C. for about 30 mins twice. The reaction was then quenched with HCl (10 mL, 1 N) slowly, stirred for 2 h at room temperature, basified with NaHCO3 to pH ˜9, and extracted with EtOAc (50+20 mL). The organic layer was washed with brine, dried over Na2SO4, filtered, concentrated to afford 0.52 g (96%) of the title compound. LC-MS m/z 218 (M+H)+. The reaction was then quenched with HCl (10 mL, 1 N) slowly extracted with EtOAc (50+20 mL) The organic layer was washed with brine dried over Na2SO4 filtered concentrated

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the solution of [(3-bromo-4-fluorophenyl)methyl]methylamine (0.52 g, 2.39 mmol) in p-dioxane/H2O (15/5 mL) was added {3-[(4-{[(1,1-dimethylethyl)oxy]carbonyl}-1-piperazinyl)methyl]phenyl}boronic acid (1.15 g, 3.60 mmol), Pd(PPh3)4 (139 mg, 0.12 mmol), and K2CO3 (1.33 g, 9.6 mmol). The result mixture was heated in a microwave machine at 150° C. for 15 mins. The organic layer was separated and concentrated. The residue was redissolved in EtOAc (˜70 mL), washed with H2O (20 mL), brine (20 mL), dried over Na2SO4, filtered, concentrated and purified by CombiFlash chomatograph to afford 0.65 g (66%) of the title compound. LC-MS m/z 414 (M+H)+. The organic layer was separated concentrated The residue was redissolved in EtOAc (˜70 mL) washed with H2O (20 mL), brine (20 mL) dried over Na2SO4 filtered concentrated purified by CombiFlash chomatograph

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the solution of 1,1-dimethylethyl[(3-bromo-4-fluorophenyl)methyl]carbamate (0.755 g, 2.48 mmol) in THF (1 mL) was added BH3.THF (12.5 mL, 1.0 M in THF). The mixture was heated in a microwave machine at about 80° C. for about 30 mins twice. The reaction was then quenched with HCl (10 mL, 1 N) slowly, stirred for 2 h at room temperature, basified with NaHCO3 to pH ˜9, and extracted with EtOAc (50+20 mL). The organic layer was washed with brine, dried over Na2SO4, filtered, concentrated to afford 0.52 g (96%) of the title compound. LC-MS m/z 218 (M+H)+. The reaction was then quenched with HCl (10 mL, 1 N) slowly extracted with EtOAc (50+20 mL) The organic layer was washed with brine dried over Na2SO4 filtered concentrated

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the solution of 1,1-dimethylethyl[(3-bromo-4-fluorophenyl)methyl]carbamate (0.755 g, 2.48 mmol) in THF (1 mL) was added BH3.THF (12.5 mL, 1.0 M in THF). The mixture was heated in a microwave machine at about 80° C. for about 30 mins twice. The reaction was then quenched with HCl (10 mL, 1 N) slowly, stirred for 2 h at room temperature, basified with NaHCO3 to pH ˜9, and extracted with EtOAc (50+20 mL). The organic layer was washed with brine, dried over Na2SO4, filtered, concentrated to afford 0.52 g (96%) of the title compound. LC-MS m/z 218 (M+H)+. The reaction was then quenched with HCl (10 mL, 1 N) slowly extracted with EtOAc (50+20 mL) The organic layer was washed with brine dried over Na2SO4 filtered concentrated

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

Procedure: To a solution of [(3-bromo-4-fluorophenyl)methyl]methylamine (0.355 g, 1.63 mmol) in THF (16 mL) was added 3-[(methyloxy)carbonyl]benzoic acid (0.294 g, 1.63 mmol), HBTU (0.929 g, 2.45 mmol), Et3N (0.458 mL, 3.26 mmol) and stirred at room temperature for 65 h, and then quenched with H2O. The organic layer was loaded onto silica gel cartridge and purified by CombiFlash chromatograph to afford the title compound 0.419 g (68%). LC-MS m/z 380 (M+H)+. quenched with H2O purified by CombiFlash chromatograph

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

Procedure: To a solution of 3-(chloromethyl)-N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}benzamide (0.284 g, 0.623 mmol) in DMF (2.5 mL) was added [(3-bromo-4-fluorophenyl)methyl]methylamine (0.436 g, 2.0 mmol). This mixture was stirred at room temperature for 66 h. Then EtOAc (50 mL) was added and that solution washed with H2O (7.5+2×5 mL), brine (5 mL), dried over Na2SO4. The dried organic solution was filtered, concentrated and purified by CombiFlash chromatograph to afford the title compound 0.371 g (93%). LC-MS m/z 637 (M+H)+. washed with H2O (7.5+2×5 mL), brine (5 mL) dried over Na2SO4 The dried organic solution was filtered concentrated purified by CombiFlash chromatograph

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of [(3-bromo-4-fluorophenyl)methyl]methylamine (0.52 g, 2.39 mmol) in p-dioxane/H2O (15/5 mL) was added {3-[(4-{[(1,1-dimethylethyl)oxy]carbonyl}-1-piperazinyl)methyl]phenyl}boronic acid (1.15 g, 3.60 mmol), Pd(PPh3)4 (139 mg, 0.12 mmol), and K2CO3 (1.33 g, 9.6 mmol). The mixture was heated with a microwave at 150° C. for 15 min. The organic layer was separated, concentrated. The residue was redissolved in EtOAc (˜70 mL), which was washed with H2O (20 mL), brine (20 mL), dried over Na2SO4, filtered, concentrated and purified by CombiFlash chromatograph to afford the title compound 0.65 g (66%). LC-MS m/z 414 (M+H)+. The organic layer was separated concentrated The residue was redissolved in EtOAc (˜70 mL) which was washed with H2O (20 mL), brine (20 mL) dried over Na2SO4 filtered concentrated purified by CombiFlash chromatograph

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1,1-dimethylethyl [(3-bromo-4-fluorophenyl)methyl]carbamate (0.755 g, 2.48 mmol) in THF (1 mL) was added BH3.THF (12.5 mL, 1.0 M in THF). The mixture was heated with a microwave at 80° C. for 30 min twice. The reaction was then quenched with HCl (10 mL, 1 N) slowly, after which the mixture was stirred for 2 h at room temperature, basified with NaHCO3 to pH ˜9, and extracted with EtOAc (50+20 mL). The combined organic phases were washed with brine, dried over Na2SO4, filtered, concentrated to afford the title compound 0.52 g (96%). LC-MS m/z 218 (M+H)+. The reaction was then quenched with HCl (10 mL, 1 N) slowly extracted with EtOAc (50+20 mL) The combined organic phases were washed with brine dried over Na2SO4 filtered concentrated

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1,1-dimethylethyl [(3-bromo-4-fluorophenyl)methyl]carbamate (0.755 g, 2.48 mmol) in THF (1 mL) was added BH3.THF (12.5 mL, 1.0 M in THF). The mixture was heated with a microwave at 80° C. for 30 min twice. The reaction was then quenched with HCl (10 mL, 1 N) slowly, after which the mixture was stirred for 2 h at room temperature, basified with NaHCO3 to pH ˜9, and extracted with EtOAc (50+20 mL). The combined organic phases were washed with brine, dried over Na2SO4, filtered, concentrated to afford the title compound 0.52 g (96%). LC-MS m/z 218 (M+H)+. The reaction was then quenched with HCl (10 mL, 1 N) slowly extracted with EtOAc (50+20 mL) The combined organic phases were washed with brine dried over Na2SO4 filtered concentrated