2-methyl-2,8-diazaspiro[4.5]decan-1-one

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate (349 mg, 1.052 mmol), 2-methyl-2,8-diazaspiro[4.5]decan-1-one (177 mg, 1.052 mmol), Pd2dba3 (96 mg, 0.105 mmol), BINAP (197 mg, 0.316 mmol), and Cs2CO3 (1028 mg, 3.16 mmol) in Dioxane (15 mL) was evacuated and filled with nitrogen 3× and heated at 105° C. overnight. The reaction mixture was filtered through a plug of celite and the filtrate was concentrated. The crude product was purified by flash chromatography on silica gel using an automated ISCO system (40 g column, eluting with 10% to 100% EtOAc in Hexane) to give tert-butyl (2-chloro-5-cyano-3-(2-methyl-1-oxo-2,8-diazaspiro[4.5]decan-8-yl)phenyl)carbamate (197 mg) was evacuated filled with nitrogen 3× The reaction mixture was filtered through a plug of celite the filtrate was concentrated The crude product was purified by flash chromatography on silica gel using an automated ISCO system (40 g column, eluting with 10% to 100% EtOAc in Hexane)

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate (349 mg, 1.052 mmol), 2-methyl-2,8-diazaspiro[4.5]decan-1-one (177 mg, 1.052 mmol), Pd2dba3 (96 mg, 0.105 mmol), BINAP (197 mg, 0.316 mmol), and Cs2CO3 (1028 mg, 3.16 mmol) in Dioxane (15 mL) was evacuated and filled with nitrogen 3× and heated at 105° C. overnight. The reaction mixture was filtered through a plug of celite and the filtrate was concentrated. The crude product was purified by flash chromatography on silica gel using an automated ISCO system (40 g column, eluting with 10% to 100% EtOAc in Hexane) to give tert-butyl (2-chloro-5-cyano-3-(2-methyl-1-oxo-2,8-diazaspiro[4.5]decan-8-yl)phenyl)carbamate (197 mg) was evacuated filled with nitrogen 3× The reaction mixture was filtered through a plug of celite the filtrate was concentrated The crude product was purified by flash chromatography on silica gel using an automated ISCO system (40 g column, eluting with 10% to 100% EtOAc in Hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of tert-butyl 2-methyl-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate (315 mg, 1.174 mmol) in DCM (5 mL) was added TFA (1.718 mL, 22.30 mmol) and the mixture was stirred at room temperature for 2 h. The reaction was concentrated under reduced pressure to obtain crude and purified by SCX cartridge, loading with MeOH, washed with additional MeOH. Product was recovered eluting with 2M NH3 in MeOH. Solvent evaporation gave 2-methyl-2,8-diazaspiro[4.5]decan-1-one (177 mg). The reaction was concentrated under reduced pressure to obtain crude purified by SCX cartridge washed with additional MeOH Product was recovered eluting with 2M NH3 in MeOH Solvent evaporation

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate (349 mg, 1.052 mmol), 2-methyl-2,8-diazaspiro[4.5]decan-1-one (177 mg, 1.052 mmol), Pd2dba3 (96 mg, 0.105 mmol), BINAP (197 mg, 0.316 mmol), and Cs2CO3 (1028 mg, 3.16 mmol) in Dioxane (15 mL) was evacuated and filled with nitrogen 3× and heated at 105° C. overnight. The reaction mixture was filtered through a plug of celite and the filtrate was concentrated. The crude product was purified by flash chromatography on silica gel using an automated ISCO system (40 g column, eluting with 10% to 100% EtOAc in Hexane) to give tert-butyl (2-chloro-5-cyano-3-(2-methyl-1-oxo-2,8-diazaspiro[4.5]decan-8-yl)phenyl)carbamate (197 mg) was evacuated filled with nitrogen 3× The reaction mixture was filtered through a plug of celite the filtrate was concentrated The crude product was purified by flash chromatography on silica gel using an automated ISCO system (40 g column, eluting with 10% to 100% EtOAc in Hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of tert-butyl 2-methyl-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate (315 mg, 1.174 mmol) in DCM (5 mL) was added TFA (1.718 mL, 22.30 mmol) and the mixture was stirred at room temperature for 2 h. The reaction was concentrated under reduced pressure to obtain crude and purified by SCX cartridge, loading with MeOH, washed with additional MeOH. Product was recovered eluting with 2M NH3 in MeOH. Solvent evaporation gave 2-methyl-2,8-diazaspiro[4.5]decan-1-one (177 mg). The reaction was concentrated under reduced pressure to obtain crude purified by SCX cartridge washed with additional MeOH Product was recovered eluting with 2M NH3 in MeOH Solvent evaporation