3A-苯甲基-2-甲基-4,5,6,7-四氢-2H-吡唑并[4,3-C]吡啶-3(3AH)-酮

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 3-benzyl4-oxo-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester (1935.97 g, 5.36 mol) in toluene (9700 mL) was added methylhydrazine (299.2 mL, 5.63 mol), followed by acetic acid (325 mL, 5.68 mol) slowly at about 8° C. The reaction mixture was heated slowly to about 65° C. and stirred for about 7.5 hours. After cooling to room temperature, the organic layer was washed with 10% sodium bicarbonate, water and saturated NaCl solution and concentrated in vacuo to a low volume. The reaction was repeated at same scale twice. The concentrated product solutions from the three reactions were combined and mixed with IPE (50 L), cooled to about 0° C., HCl gas was introduced repeatedly and stirred at room temperature overnight until the deprotection was complete. The mixture was concentrated in vacuo to about half of the original volume, methylene chloride (24 L) was added, followed by NH4OH (22 L). The mixture was then extracted with methylene chloride and concentrated to a low volume (6 to 7 L). Hexane (20 L) was added and the mixture was cooled to about 15-20° C. The free base product was collected as crystals and dried under vacuum (2985 g total, yield 84.8%). After cooling to room temperature the organic layer was washed with 10% sodium bicarbonate, water and saturated NaCl solution concentrated in vacuo to a low volume mixed with IPE (50 L) cooled to about 0° C. HCl gas was introduced repeatedly stirred at room temperature overnight until the deprotection The mixture was concentrated in vacuo to about half of the original volume, methylene chloride (24 L) was added The mixture was then extracted with methylene chloride concentrated to a low volume (6 to 7 L) Hexane (20 L) was added the mixture was cooled to about 15-20° C The free base product was collected as crystals dried under vacuum (2985 g total, yield 84.8%)

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 3-benzyl4-oxo-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester (1935.97 g, 5.36 mol) in toluene (9700 mL) was added methylhydrazine (299.2 mL, 5.63 mol), followed by acetic acid (325 mL, 5.68 mol) slowly at about 8° C. The reaction mixture was heated slowly to about 65° C. and stirred for about 7.5 hours. After cooling to room temperature, the organic layer was washed with 10% sodium bicarbonate, water and saturated NaCl solution and concentrated in vacuo to a low volume. The reaction was repeated at same scale twice. The concentrated product solutions from the three reactions were combined and mixed with IPE (50 L), cooled to about 0° C., HCl gas was introduced repeatedly and stirred at room temperature overnight until the deprotection was complete. The mixture was concentrated in vacuo to about half of the original volume, methylene chloride (24 L) was added, followed by NH4OH (22 L). The mixture was then extracted with methylene chloride and concentrated to a low volume (6 to 7 L). Hexane (20 L) was added and the mixture was cooled to about 15-20° C. The free base product was collected as crystals and dried under vacuum (2985 g total, yield 84.8%). After cooling to room temperature the organic layer was washed with 10% sodium bicarbonate, water and saturated NaCl solution concentrated in vacuo to a low volume mixed with IPE (50 L) cooled to about 0° C. HCl gas was introduced repeatedly stirred at room temperature overnight until the deprotection The mixture was concentrated in vacuo to about half of the original volume, methylene chloride (24 L) was added The mixture was then extracted with methylene chloride concentrated to a low volume (6 to 7 L) Hexane (20 L) was added the mixture was cooled to about 15-20° C The free base product was collected as crystals dried under vacuum (2985 g total, yield 84.8%)

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 3-benzyl-4-oxo-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3ethyl ester (1935.97 g, 5.36 moo in toluene (9700 mL) was added methylhydrazine (299.2 mL, 5.63 mot), followed by acetic acid (325 mL, 5.68 mol) slowly at about 8° C. The reaction mixture was heated slowly to about 65° C. and stirred for about 7.5 hours. After cooling to room temperature, the organic layer was washed with 10% sodium bicarbonate, water and saturated NaCl solution and concentrated in vacuo to a low volume. The reaction was repeated at same scale, twice. The concentrated product solutions from the three reactions were combined and mixed with IPE (50 L), cooled to about 0° C., HCl gas was introduced repeatedly and stirred at room temperature overnight until the deprotection was complete. The mixture was concentrated in vacuo to about half of the original volume, methylene chloride (24 L) was added, followed by NH4OH (22 L). The mixture was then extracted with methylene chloride and concentrated to a low volume (6 to 7 L). Hexane (20 L) was added and the mixture was cooled to about 1520° C. The free base product was collected as crystals and dried under vacuum (2985 g total, yield 84.8%). After cooling to room temperature the organic layer was washed with 10% sodium bicarbonate, water and saturated NaCl solution concentrated in vacuo to a low volume mixed with IPE (50 L) cooled to about 0° C. HCl gas was introduced repeatedly stirred at room temperature overnight until the deprotection The mixture was concentrated in vacuo to about half of the original volume, methylene chloride (24 L) was added The mixture was then extracted with methylene chloride concentrated to a low volume (6 to 7 L) Hexane (20 L) was added the mixture was cooled to about 1520° C The free base product was collected as crystals dried under vacuum (2985 g total, yield 84.8%)

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 3-benzyl-4-oxo-piperidine1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester (1935.97 g, 5.36 mol) in toluene (9700 mL) was added methylhydrazine (299.2 mL, 5.63 mol), followed by acetic acid (325 mL, 5.68 mol) slowly at about 8° C. The reaction mixture was heated slowly to about 65° C. and stirred for about 7.5 hours. After cooling to room temperature, the organic layer was washed with 10% sodium bicarbonate, water and saturated NaCl solution and concentrated in vacuo to a low volume. The reaction was repeated at same scale twice. The concentrated product solutions from the three reactions were combined and mixed with IPE (50 L), cooled to about 0° C., HCl gas was introduced repeatedly and stirred at room temperature overnight until the deprotection was complete. The mixture was concentrated in vacuo to about half of the original volume, methylene chloride (24 L) was added, followed by NH4OH (22 L). The mixture was then extracted with methylene chloride and concentrated to a low volume (6 to 7 L). Hexane (20 L) was added and the mixture was cooled to about 15-20° C. The free base product was collected as crystals and dried under vacuum (2985 g total, yield 84.8%). After cooling to room temperature the organic layer was washed with 10% sodium bicarbonate, water and saturated NaCl solution concentrated in vacuo to a low volume mixed with IPE (50 L) cooled to about 0° C. HCl gas was introduced repeatedly stirred at room temperature overnight until the deprotection The mixture was concentrated in vacuo to about half of the original volume, methylene chloride (24 L) was added The mixture was then extracted with methylene chloride concentrated to a low volume (6 to 7 L) Hexane (20 L) was added the mixture was cooled to about 15-20° C The free base product was collected as crystals dried under vacuum (2985 g total, yield 84.8%)

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 3-benzyl4-oxo-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester (1935.97 g, 5.36 mol) in toluene (9700 mL) was added methylhydrazine (299.2 mL, 5.63 mol), followed by acetic acid (325 mL, 5.68 mol) slowly at about 8° C. The reaction mixture was heated slowly to about 65° C. and stirred for about 7.5 hours. After cooling to room temperature, the organic layer was washed with 10% sodium bicarbonate, water and saturated NaCl solution and concentrated in vacuo to a low volume. The reaction was repeated at same scale twice. The concentrated product solutions from the three reactions were combined and mixed with IPE (50 L), cooled to about 0° C., HCl gas was introduced repeatedly and stirred at room temperature overnight until the deprotection was complete. The mixture was concentrated in vacuo to about half of the original volume, methylene chloride (24 L) was added, followed by NH4OH (22 L). The mixture was then extracted with methylene chloride and concentrated to a low volume (6 to 7 L). Hexane (20 L) was added and the mixture was cooled to about 15-20° C. The free base product was collected as crystals and dried under vacuum (2985 g total, yield 84.8%). After cooling to room temperature the organic layer was washed with 10% sodium bicarbonate, water and saturated NaCl solution concentrated in vacuo to a low volume mixed with IPE (50 L) cooled to about 0° C. HCl gas was introduced repeatedly stirred at room temperature overnight until the deprotection The mixture was concentrated in vacuo to about half of the original volume, methylene chloride (24 L) was added The mixture was then extracted with methylene chloride concentrated to a low volume (6 to 7 L) Hexane (20 L) was added the mixture was cooled to about 15-20° C The free base product was collected as crystals dried under vacuum (2985 g total, yield 84.8%)

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 3-benzyl-4-oxo-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3ethyl ester (1935.97 g, 5.36 moo in toluene (9700 mL) was added methylhydrazine (299.2 mL, 5.63 mot), followed by acetic acid (325 mL, 5.68 mol) slowly at about 8° C. The reaction mixture was heated slowly to about 65° C. and stirred for about 7.5 hours. After cooling to room temperature, the organic layer was washed with 10% sodium bicarbonate, water and saturated NaCl solution and concentrated in vacuo to a low volume. The reaction was repeated at same scale, twice. The concentrated product solutions from the three reactions were combined and mixed with IPE (50 L), cooled to about 0° C., HCl gas was introduced repeatedly and stirred at room temperature overnight until the deprotection was complete. The mixture was concentrated in vacuo to about half of the original volume, methylene chloride (24 L) was added, followed by NH4OH (22 L). The mixture was then extracted with methylene chloride and concentrated to a low volume (6 to 7 L). Hexane (20 L) was added and the mixture was cooled to about 1520° C. The free base product was collected as crystals and dried under vacuum (2985 g total, yield 84.8%). After cooling to room temperature the organic layer was washed with 10% sodium bicarbonate, water and saturated NaCl solution concentrated in vacuo to a low volume mixed with IPE (50 L) cooled to about 0° C. HCl gas was introduced repeatedly stirred at room temperature overnight until the deprotection The mixture was concentrated in vacuo to about half of the original volume, methylene chloride (24 L) was added The mixture was then extracted with methylene chloride concentrated to a low volume (6 to 7 L) Hexane (20 L) was added the mixture was cooled to about 1520° C The free base product was collected as crystals dried under vacuum (2985 g total, yield 84.8%)