tert-butyl N-[(3S)-2-oxopiperidin-3-yl]carbamate

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution containing 1-(6-bromo-2-pyridyl)-6-chloro-pyrazolo[4,3-c]pyridine (200 mg, 0.646 mmol), tert-butyl N-[(3S)-2-oxo-3-piperidyl]carbamate (166 mg, 0.775 mmol), Copper(I) iodide (123 mg, 0.646 mmol), Potassium carbonate (107 mg, 0.775 mmol) and N,N′-Dimethylethylenediamine (114 mg, 1.29 mmol) was stirred at 110° C. 4 h. The reaction was filtered through celite and concentrated. The crude product purified by isco column (EtOAc/Hep eluted at 70% EtOAc) to give the desired product 135 mg 47% yield. MS (ESI) m/z: 443.1. 4 h The reaction was filtered through celite concentrated The crude product purified by isco column (EtOAc/Hep eluted at 70% EtOAc)

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

Procedure: (S)-tert-butyl 1-(2-(tert-butyldimethylsilyloxy)ethyl)-2-oxopiperidin-3-ylcarbamate was prepared from (S)-tert-butyl 2-oxopiperidin-3-ylcarbamate (Example 7) and (2-bromoethoxy)(tert-butyl)dimethylsilane according to the general procedure of Example 9. The crude product was purified by column chromatography, eluting with 50% ethyl acetate/hexanes, to provide compound (2d) in 26% yield. The crude product was purified by column chromatography eluting with 50% ethyl acetate/hexanes

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

Procedure: (S)-tert-butyl 1-methyl-2-oxopiperidin-3-ylcarbamate was prepared from (S)-tert-butyl 2-oxopiperidin-3-ylcarbamate (Example 7) and methyl iodide according to the general procedure of Example 9. The crude product was purified by column chromatography, eluting with 100% ethyl acetate, to provide compound (2c) in 31% yield. The crude product was purified by column chromatography eluting with 100% ethyl acetate

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

Procedure: (S)-tert-butyl 1-methyl-2-oxopiperidin-3-ylcarbamate was prepared from (S)-tert-butyl 2-oxopiperidin-3-ylcarbamate (Example 7) and methyl iodide according to the general procedure of Example 9. The crude product was purified by column chromatography, eluting with 100% ethyl acetate, to provide compound (2c) in 31% yield. The crude product was purified by column chromatography eluting with 100% ethyl acetate

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a sealed-vial was added (S)-tert-butyl 2-oxopiperidin-3-ylcarbamate (162 mg, 0.756 mmol), potassium phosphate (321 mg, 1.51 mmol), iodobenzene (0.101 mL, 0.907 mmol), ethylenediamine (0.020 mL, 0.30 mmol), dioxane (3 mL) and molecular sieves followed by copper(I) iodide (57.6 mg, 0.302 mmol). The vial was purged with nitrogen gas and sealed. Then the reaction was stirred at 110° C. for 40 hr. The reaction was diluted with EtOAc (30 mL) and washed with water (20 mL) and saturated aqueous NaCl (20 mL). The organic layer was separated, dried over MgSO4, filtered and concentrated. The residue was purified by RP prep-HPLC (Method A) to give (S)-tert-butyl 2-oxo-1-phenylpiperidin-3-ylcarbamate (100 mg, 0.344 mmol, 45.6% yield) as a white solid. Anal. Calcd. for C16H22N2O3 m/z 290.3. found: 291.2 (M+H)+; 1H NMR (500 MHz, CDCl3) δ ppm 7.40 (t, J=7.70 Hz, 2H), 7.33-7.20 (m, 3H), 5.56 (br. s., 1H), 4.37-4.20 (m, 1H), 3.78-3.66 (m, 2H), 2.63 (dd, J=12.37, 5.77 Hz, 1H), 2.16-1.97 (m, 2H), 1.81-1.661 (m, 1H), 1.47 (s, 9H). The vial was purged with nitrogen gas sealed The reaction was diluted with EtOAc (30 mL) washed with water (20 mL) and saturated aqueous NaCl (20 mL) The organic layer was separated dried over MgSO4 filtered concentrated The residue was purified by RP prep-HPLC (Method A)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a sealed-vial was added (S)-tert-butyl 2-oxopiperidin-3-ylcarbamate (162 mg, 0.756 mmol), potassium phosphate (321 mg, 1.51 mmol), iodobenzene (0.101 mL, 0.907 mmol), ethylenediamine (0.020 mL, 0.30 mmol), dioxane (3 mL) and molecular sieves followed by copper(I) iodide (57.6 mg, 0.302 mmol). The vial was purged with nitrogen gas and sealed. Then the reaction was stirred at 110° C. for 40 hr. The reaction was diluted with EtOAc (30 mL) and washed with water (20 mL) and saturated aqueous NaCl (20 mL). The organic layer was separated, dried over MgSO4, filtered and concentrated. The residue was purified by RP prep-HPLC (Method A) to give (S)-tert-butyl 2-oxo-1-phenylpiperidin-3-ylcarbamate (100 mg, 0.344 mmol, 45.6% yield) as a white solid. Anal. Calcd. for C16H22N2O3 m/z 290.3. found: 291.2 (M+H)+; 1H NMR (500 MHz, CDCl3) δ ppm 7.40 (t, J=7.70 Hz, 2H), 7.33-7.20 (m, 3H), 5.56 (br. s., 1H), 4.37-4.20 (m, 1H), 3.78-3.66 (m, 2H), 2.63 (dd, J=12.37, 5.77 Hz, 1H), 2.16-1.97 (m, 2H), 1.81-1.661 (m, 1H), 1.47 (s, 9H). The vial was purged with nitrogen gas sealed The reaction was diluted with EtOAc (30 mL) washed with water (20 mL) and saturated aqueous NaCl (20 mL) The organic layer was separated dried over MgSO4 filtered concentrated The residue was purified by RP prep-HPLC (Method A)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution containing 1-(6-bromo-2-pyridyl)-6-chloro-pyrazolo[4,3-c]pyridine (200 mg, 0.646 mmol), tert-butyl N-[(3S)-2-oxo-3-piperidyl]carbamate (166 mg, 0.775 mmol), Copper(I) iodide (123 mg, 0.646 mmol), Potassium carbonate (107 mg, 0.775 mmol) and N,N′-Dimethylethylenediamine (114 mg, 1.29 mmol) was stirred at 110° C. 4 h. The reaction was filtered through celite and concentrated. The crude product purified by isco column (EtOAc/Hep eluted at 70% EtOAc) to give the desired product 135 mg 47% yield. MS (ESI) m/z: 443.1. 4 h The reaction was filtered through celite concentrated The crude product purified by isco column (EtOAc/Hep eluted at 70% EtOAc)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution containing 1-(6-bromo-2-pyridyl)-6-chloro-pyrazolo[4,3-c]pyridine (200 mg, 0.646 mmol), tert-butyl N-[(3S)-2-oxo-3-piperidyl]carbamate (166 mg, 0.775 mmol), Copper(I) iodide (123 mg, 0.646 mmol), Potassium carbonate (107 mg, 0.775 mmol) and N,N′-Dimethylethylenediamine (114 mg, 1.29 mmol) was stirred at 110° C. 4 h. The reaction was filtered through celite and concentrated. The crude product purified by isco column (EtOAc/Hep eluted at 70% EtOAc) to give the desired product 135 mg 47% yield. MS (ESI) m/z: 443.1. 4 h The reaction was filtered through celite concentrated The crude product purified by isco column (EtOAc/Hep eluted at 70% EtOAc)

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

Procedure: (S)-tert-butyl 1-(2-(tert-butyldimethylsilyloxy)ethyl)-2-oxopiperidin-3-ylcarbamate was prepared from (S)-tert-butyl 2-oxopiperidin-3-ylcarbamate (Example 7) and (2-bromoethoxy)(tert-butyl)dimethylsilane according to the general procedure of Example 9. The crude product was purified by column chromatography, eluting with 50% ethyl acetate/hexanes, to provide compound (2d) in 26% yield. The crude product was purified by column chromatography eluting with 50% ethyl acetate/hexanes

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

Procedure: (S)-tert-butyl 1-methyl-2-oxopiperidin-3-ylcarbamate was prepared from (S)-tert-butyl 2-oxopiperidin-3-ylcarbamate (Example 7) and methyl iodide according to the general procedure of Example 9. The crude product was purified by column chromatography, eluting with 100% ethyl acetate, to provide compound (2c) in 31% yield. The crude product was purified by column chromatography eluting with 100% ethyl acetate

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a sealed-vial was added (S)-tert-butyl 2-oxopiperidin-3-ylcarbamate (162 mg, 0.756 mmol), potassium phosphate (321 mg, 1.51 mmol), iodobenzene (0.101 mL, 0.907 mmol), ethylenediamine (0.020 mL, 0.30 mmol), dioxane (3 mL) and molecular sieves followed by copper(I) iodide (57.6 mg, 0.302 mmol). The vial was purged with nitrogen gas and sealed. Then the reaction was stirred at 110° C. for 40 hr. The reaction was diluted with EtOAc (30 mL) and washed with water (20 mL) and saturated aqueous NaCl (20 mL). The organic layer was separated, dried over MgSO4, filtered and concentrated. The residue was purified by RP prep-HPLC (Method A) to give (S)-tert-butyl 2-oxo-1-phenylpiperidin-3-ylcarbamate (100 mg, 0.344 mmol, 45.6% yield) as a white solid. Anal. Calcd. for C16H22N2O3 m/z 290.3. found: 291.2 (M+H)+; 1H NMR (500 MHz, CDCl3) δ ppm 7.40 (t, J=7.70 Hz, 2H), 7.33-7.20 (m, 3H), 5.56 (br. s., 1H), 4.37-4.20 (m, 1H), 3.78-3.66 (m, 2H), 2.63 (dd, J=12.37, 5.77 Hz, 1H), 2.16-1.97 (m, 2H), 1.81-1.661 (m, 1H), 1.47 (s, 9H). The vial was purged with nitrogen gas sealed The reaction was diluted with EtOAc (30 mL) washed with water (20 mL) and saturated aqueous NaCl (20 mL) The organic layer was separated dried over MgSO4 filtered concentrated The residue was purified by RP prep-HPLC (Method A)