1-tert-butylpiperidin-4-amine

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

Procedure: A solution of LHMDS (1.0M in THF, 0.2 mL) was added to methyl 1-tert-butylpiperidine-4-carboxylate (31 mg, 0.16 mmol) in 2 mL THF at −78° C. After 20 minutes the solution was warmed to 0° C. and stirred for an additional 10 minutes. 7-Chloro-5-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-1,8-naphthyridin-2(1H)-one (COMPOUND BBB2) (28.5 mg, 0.063 mmol) was added and the reaction mixture stirred at 45° C. for 30 min. The solution was cooled to rt and quenched with saturated NH4Cl. The mixture was then partitioned between water and ethyl acetate. The organic phase was washed with water, brine and dried over magnesium sulfate. The filtered solution was concentrated and the residue purified by preparative silica gel thin layer chromatography using CHCl3/MeOH/NH4OH (87/12/1) as eluent to give the title compound. Mass spectrum (ESI) 616 (M+1). (Methyl 1-tert-butylpiperidine-4-carboxylate was prepared from 1-tert-butylpiperidin-4-one (COMPOUND PPA-1) by a procedure analogous to that described by Street, L. J.; et al J. Med. Chem. 1990, 33, 2690.) the reaction mixture stirred at 45° C. for 30 min The solution was cooled to rt quenched with saturated NH4Cl The mixture was then partitioned between water and ethyl acetate The organic phase was washed with water, brine dried over magnesium sulfate The filtered solution was concentrated the residue purified by preparative silica gel thin layer chromatography

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

Procedure: A solution of N-benzyl-1-tert-butylpiperidin-4-amine (150 mg) and 10% palladium on carbon (200 mg) in 30 mL of MeOH was hydrogenated in a Parr shaker at 50 psi for 16 h. The solution was filtered and concentrated to give 1-tert-butylpiperidin-4-amine which was used without further purification. Mass spectrum (ESI) 157 (M+1). The solution was filtered concentrated

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

Procedure: To a solution of 1-tert-butylpiperidin-4-one (5.0 g) in methanol (100 mL) and water (10 mL) was added ammonium formate (20.3 g) and 0.5 g of Pd/C (10%). The mixture was stirred overnight. The mixture was filtered and the filtrate was concentrated under vacuum and the residue was diluted with ethyl acetate (500 mL) and washed with water and brine. After drying over Na2SO4 and filtration, the solvent was evaporated under vacuum to provide the title compound. The mixture was filtered the filtrate was concentrated under vacuum the residue was diluted with ethyl acetate (500 mL) washed with water and brine After drying over Na2SO4 and filtration the solvent was evaporated under vacuum

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

Procedure: To a solution of 1-tert-butylpiperidin-4-one (5.0 g) in methanol (100 mL) and water (10 mL) was added ammonium formate (20.3 g) and 0.5 g of Pd/C (10%). The mixture was stirred overnight. The mixture was filtered and the filtrate was concentrated under vacuum and the residue was diluted with ethyl acetate (500 mL) and washed with water and brine. After drying over Na2SO4 and filtration, the solvent was evaporated under vacuum to provide the title compound. The mixture was filtered the filtrate was concentrated under vacuum the residue was diluted with ethyl acetate (500 mL) washed with water and brine After drying over Na2SO4 and filtration the solvent was evaporated under vacuum

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

Procedure: To a solution of 1-tert-butylpiperidin-4-one (5.0 g) in methanol (100 mL) and water (10 mL) was added ammonium formate (20.3 g) and 0.5 g of Pd/C (10%). The mixture was stirred overnight. The mixture was filtered and the filtrate was concentrated under vacuum and the residue was diluted with ethyl acetate (500 mL) and washed with water and brine. After drying over Na2SO4 and filtration, the solvent was evaporated under vacuum to provide the title compound. The mixture was filtered the filtrate was concentrated under vacuum the residue was diluted with ethyl acetate (500 mL) washed with water and brine After drying over Na2SO4 and filtration the solvent was evaporated under vacuum

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

Procedure: A solution of N-benzyl-1-tert-butylpiperidin-4-amine (1.56 g) and 10% palladium on carbon (2 g) in MeOH (250 ml) was hydrogenated in a Parr shaker at 50 psi for 16 hours. The solution was filtered and the reaction mixture reduced in vacuo, to yield 1-tert-butylpiperidin-4-amine (0.64 g) (LC/MS: Rt 02.31, no [M+H]+). The solution was filtered

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

Procedure: A solution of N-benzyl-1-tert-butylpiperidin-4-amine (1.56 g) and 10% palladium on carbon (2 g) in MeOH (250 ml) was hydrogenated in a Parr shaker at 50 psi for 16 hours. The solution was filtered and the reaction mixture reduced in vacuo, to yield 1-tert-butylpiperidin-4-amine (0.64 g) (LC/MS: Rt 02.31, no [M+H]+). The solution was filtered

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

Procedure: To a solution of 1-tert-butylpiperidin-4-one (5.0 g) in methanol (100 mL) and water (10 mL) was added ammonium formate (20.3 g) and 0.5 g of Pd/C (10%). The mixture was stirred overnight. The mixture was filtered and the filtrate was concentrated under vacuum and the residue was diluted with ethyl acetate (500 mL) and washed with water and brine. After drying over Na2SO4 and filtration, the solvent was evaporated under vacuum to provide the title compound. The mixture was filtered the filtrate was concentrated under vacuum the residue was diluted with ethyl acetate (500 mL) washed with water and brine After drying over Na2SO4 and filtration the solvent was evaporated under vacuum

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

Procedure: A solution of LHMDS (1.0M in THF, 0.2 mL) was added to methyl 1-tert-butylpiperidine-4-carboxylate (31 mg, 0.16 mmol) in 2 mL THF at −78° C. After 20 minutes the solution was warmed to 0° C. and stirred for an additional 10 minutes. 7-Chloro-5-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-1,8-naphthyridin-2(1H)-one (COMPOUND BBB2) (28.5 mg, 0.063 mmol) was added and the reaction mixture stirred at 45° C. for 30 min. The solution was cooled to rt and quenched with saturated NH4Cl. The mixture was then partitioned between water and ethyl acetate. The organic phase was washed with water, brine and dried over magnesium sulfate. The filtered solution was concentrated and the residue purified by preparative silica gel thin layer chromatography using CHCl3/MeOH/NH4OH (87/12/1) as eluent to give the title compound. Mass spectrum (ESI) 616 (M+1). (Methyl 1-tert-butylpiperidine-4-carboxylate was prepared from 1-tert-butylpiperidin-4-one (COMPOUND PPA-1) by a procedure analogous to that described by Street, L. J.; et al J. Med. Chem. 1990, 33, 2690.) the reaction mixture stirred at 45° C. for 30 min The solution was cooled to rt quenched with saturated NH4Cl The mixture was then partitioned between water and ethyl acetate The organic phase was washed with water, brine dried over magnesium sulfate The filtered solution was concentrated the residue purified by preparative silica gel thin layer chromatography

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

Procedure: A solution of LHMDS (1.0M in THF, 0.2 mL) was added to methyl 1-tert-butylpiperidine-4-carboxylate (31 mg, 0.16 mmol) in 2 mL THF at −78° C. After 20 minutes the solution was warmed to 0° C. and stirred for an additional 10 minutes. 7-Chloro-5-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-1,8-naphthyridin-2(1H)-one (COMPOUND BBB2) (28.5 mg, 0.063 mmol) was added and the reaction mixture stirred at 45° C. for 30 min. The solution was cooled to rt and quenched with saturated NH4Cl. The mixture was then partitioned between water and ethyl acetate. The organic phase was washed with water, brine and dried over magnesium sulfate. The filtered solution was concentrated and the residue purified by preparative silica gel thin layer chromatography using CHCl3/MeOH/NH4OH (87/12/1) as eluent to give the title compound. Mass spectrum (ESI) 616 (M+1). (Methyl 1-tert-butylpiperidine-4-carboxylate was prepared from 1-tert-butylpiperidin-4-one (COMPOUND PPA-1) by a procedure analogous to that described by Street, L. J.; et al J. Med. Chem. 1990, 33, 2690.) the reaction mixture stirred at 45° C. for 30 min The solution was cooled to rt quenched with saturated NH4Cl The mixture was then partitioned between water and ethyl acetate The organic phase was washed with water, brine dried over magnesium sulfate The filtered solution was concentrated the residue purified by preparative silica gel thin layer chromatography

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

Procedure: A solution of N-benzyl-1-tert-butylpiperidin-4-amine (150 mg) and 10% palladium on carbon (200 mg) in 30 mL of MeOH was hydrogenated in a Parr shaker at 50 psi for 16 h. The solution was filtered and concentrated to give 1-tert-butylpiperidin-4-amine which was used without further purification. Mass spectrum (ESI) 157 (M+1). The solution was filtered concentrated

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

Procedure: A solution of N-benzyl-1-tert-butylpiperidin-4-amine (1.56 g) and 10% palladium on carbon (2 g) in MeOH (250 ml) was hydrogenated in a Parr shaker at 50 psi for 16 hours. The solution was filtered and the reaction mixture reduced in vacuo, to yield 1-tert-butylpiperidin-4-amine (0.64 g) (LC/MS: Rt 02.31, no [M+H]+). The solution was filtered