tert-butyl N-[4-(aminomethyl)cyclohexyl]carbamate

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

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

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

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

Procedure: To a stirred solution of 3-(6-bromo-2-pyridyl)-1-trityl-pyrazolo[5,4-b]pyridine (100 mg, 0.1933 mmol) and tert-butyl N-[4-(aminomethyl)cyclohexyl]carbamate (52.97 mg, 0.232 mmol) in DME (1.5 mL) was added Palladium acetate (4.340 mg, 0.01933 mmol) followed by dicyclohexyl-[2-(o-tolyl)phenyl]phosphane (7.046 mg, 0.01933 mmol) and sodium t-butoxide (27.87 mg, 0.2900 mmol). The reaction mixture was allowed to stir at 120 degrees in the microwave for 2 hours at which time consumption of the SM was observed. The mixture was diluted with DCM and filtered through a 2.5 g celite cartridge, combined washings were evaporated down to a smaller volume (5 ml) and the resultant solution was cooled to 0 degrees (with the aid of an ice bath) and treated with triethylsilane (0.4 mL, excess) followed by TFA (0.8 mL, excess). The reaction was allowed to stir at 0 degrees for 3 hours at which time LCMS analysis showed presence of product. The mixture was evaporated to dryness, taken up in DMSO and purified by the Fractionlynx system. Relevant fractions were collated together and filtered through a NaHCO3 cartridge to give the free base. The washings were evaporated to dryness, taken up in a small amount of MeCN/water and freeze-dried to give the required product as a white solid (19.5 mg, 31%). filtered through a 2.5 g celite cartridge were evaporated down to a smaller volume (5 ml) the resultant solution was cooled to 0 degrees (with the aid of an ice bath) and treated with triethylsilane (0.4 mL, excess) to stir at 0 degrees for 3 hours at which time LCMS analysis The mixture was evaporated to dryness purified by the Fractionlynx system filtered through a NaHCO3 cartridge to give the free base The washings were evaporated to dryness freeze-dried

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

Procedure: To a stirred solution of 3-(6-bromo-2-pyridyl)-1-trityl-pyrazolo[5,4-b]pyridine (100 mg, 0.1933 mmol) and tert-butyl N-[4-(aminomethyl)cyclohexyl]carbamate (52.97 mg, 0.232 mmol) in DME (1.5 mL) was added Palladium acetate (4.340 mg, 0.01933 mmol) followed by dicyclohexyl-[2-(o-tolyl)phenyl]phosphane (7.046 mg, 0.01933 mmol) and sodium t-butoxide (27.87 mg, 0.2900 mmol). The reaction mixture was allowed to stir at 120 degrees in the microwave for 2 hours at which time consumption of the SM was observed. The mixture was diluted with DCM and filtered through a 2.5 g celite cartridge, combined washings were evaporated down to a smaller volume (5 ml) and the resultant solution was cooled to 0 degrees (with the aid of an ice bath) and treated with triethylsilane (0.4 mL, excess) followed by TFA (0.8 mL, excess). The reaction was allowed to stir at 0 degrees for 3 hours at which time LCMS analysis showed presence of product. The mixture was evaporated to dryness, taken up in DMSO and purified by the Fractionlynx system. Relevant fractions were collated together and filtered through a NaHCO3 cartridge to give the free base. The washings were evaporated to dryness, taken up in a small amount of MeCN/water and freeze-dried to give the required product as a white solid (19.5 mg, 31%). filtered through a 2.5 g celite cartridge were evaporated down to a smaller volume (5 ml) the resultant solution was cooled to 0 degrees (with the aid of an ice bath) and treated with triethylsilane (0.4 mL, excess) to stir at 0 degrees for 3 hours at which time LCMS analysis The mixture was evaporated to dryness purified by the Fractionlynx system filtered through a NaHCO3 cartridge to give the free base The washings were evaporated to dryness freeze-dried

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

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

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

Procedure: To a stirred solution of 3-(6-bromo-2-pyridyl)-1-trityl-pyrazolo[5,4-b]pyridine (100 mg, 0.1933 mmol) and tert-butyl N-[4-(aminomethyl)cyclohexyl]carbamate (52.97 mg, 0.232 mmol) in DME (1.5 mL) was added Palladium acetate (4.340 mg, 0.01933 mmol) followed by dicyclohexyl-[2-(o-tolyl)phenyl]phosphane (7.046 mg, 0.01933 mmol) and sodium t-butoxide (27.87 mg, 0.2900 mmol). The reaction mixture was allowed to stir at 120 degrees in the microwave for 2 hours at which time consumption of the SM was observed. The mixture was diluted with DCM and filtered through a 2.5 g celite cartridge, combined washings were evaporated down to a smaller volume (5 ml) and the resultant solution was cooled to 0 degrees (with the aid of an ice bath) and treated with triethylsilane (0.4 mL, excess) followed by TFA (0.8 mL, excess). The reaction was allowed to stir at 0 degrees for 3 hours at which time LCMS analysis showed presence of product. The mixture was evaporated to dryness, taken up in DMSO and purified by the Fractionlynx system. Relavant fractions were collated together and filtered through a NaHCO3 cartridge to give the free base. The washings were evaporated to dryness, taken up in a small amount of MeCN/water and freeze-dried to give the required product as a white solid (19.5 mg, 31%). filtered through a 2.5 g celite cartridge were evaporated down to a smaller volume (5 ml) the resultant solution was cooled to 0 degrees (with the aid of an ice bath) and treated with triethylsilane (0.4 mL, excess) to stir at 0 degrees for 3 hours at which time LCMS analysis The mixture was evaporated to dryness purified by the Fractionlynx system filtered through a NaHCO3 cartridge to give the free base The washings were evaporated to dryness freeze-dried

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

Procedure: To a stirred slurry of (4-aminomethyl-cyclohexyl)-carbamic acid tert-butyl ester (500 mg, 2.19 mmol) and N,N-diisopropylethylamine (382 μL, 2.63 mmol) in DCM (8 mL) at 0° C. under N2 was added benzylchloroformate (311 μL, 2.41 mmol) dropwise via syringe. After 30 min the reaction was allowed to warm to room temperature and stirred for a further 2 h before diluting with DCM (50 mL). The solution was washed successively with 1 N HCl, sat. NaHCO3 and brine before drying over Na2SO4. Residual chloroformate was removed by chromatography using a 12 g ISCO combi-flash cartridge (silica gel, 90:10 to 50:50 hexane/EtOAc) to afford the di-protected intermediate which was treated directly with DCM (2 mL) and TFA (2 mL). After 1 h the volatiles were removed in vacuo and the residue partitioned between sat. NaHCO3 and EtOAc. Concentration of the organic layer in vacuo afforded (4-amino-cyclohexylmethyl)-carbamic acid benzyl ester (517 mg, 90%) as a white solid. The solution was washed successively with 1 N HCl, sat. NaHCO3 and brine before drying over Na2SO4 Residual chloroformate was removed by chromatography to afford the di-protected intermediate which After 1 h the volatiles were removed in vacuo the residue partitioned between sat. NaHCO3 and EtOAc

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

Procedure: To a stirred solution of 3-(6-bromo-2-pyridyl)-1-trityl-pyrazolo[5,4-b]pyridine (100 mg, 0.1933 mmol) and tert-butyl N-[4-(aminomethyl)cyclohexyl]carbamate (52.97 mg, 0.232 mmol) in DME (1.5 mL) was added Palladium acetate (4.340 mg, 0.01933 mmol) followed by dicyclohexyl-[2-(o-tolyl)phenyl]phosphane (7.046 mg, 0.01933 mmol) and sodium t-butoxide (27.87 mg, 0.2900 mmol). The reaction mixture was allowed to stir at 120 degrees in the microwave for 2 hours at which time consumption of the SM was observed. The mixture was diluted with DCM and filtered through a 2.5 g celite cartridge, combined washings were evaporated down to a smaller volume (5 ml) and the resultant solution was cooled to 0 degrees (with the aid of an ice bath) and treated with triethylsilane (0.4 mL, excess) followed by TFA (0.8 mL, excess). The reaction was allowed to stir at 0 degrees for 3 hours at which time LCMS analysis showed presence of product. The mixture was evaporated to dryness, taken up in DMSO and purified by the Fractionlynx system. Relevant fractions were collated together and filtered through a NaHCO3 cartridge to give the free base. The washings were evaporated to dryness, taken up in a small amount of MeCN/water and freeze-dried to give the required product as a white solid (19.5 mg, 31%). filtered through a 2.5 g celite cartridge were evaporated down to a smaller volume (5 ml) the resultant solution was cooled to 0 degrees (with the aid of an ice bath) and treated with triethylsilane (0.4 mL, excess) to stir at 0 degrees for 3 hours at which time LCMS analysis The mixture was evaporated to dryness purified by the Fractionlynx system filtered through a NaHCO3 cartridge to give the free base The washings were evaporated to dryness freeze-dried