cyclopentylhydrazine;dihydrochloride

反応条件: temp:88.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: treating said 3-methoxy-pyridinone compound of Formula (7.0.0) with cyclopentylhydrazine dihydrochloride; wherein a reaction mixture is established with tetrahydrofuran (THF) solvent and heating of said reaction mixture to 88° C., for 12 hours, while said reaction mixture is being swept by nitrogen in order to remove methanol, THF, and HCl; whereby there is produced a pyrazolopyridinone compound N-protected by p-methoxybenzyl, of Formula (8.0.0): treating reaction mixture to remove methanol, THF, and HCl

反応条件: temp:88.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Methoxy-1-(4-methoxybenzyl)-4-propionyl-5,6-dihydro-1H-pyridin-2-one (14.471 kg, 47.76 moles) was dissolved in tetrahydrofuran (10.5 gal, 39.7 L) in a clean and dry 100 gallon tank. Cyclopentylhydrazine dihydrochloride (7.664 kg, 44.3 moles) was added and the reaction mixture warmed slowly to 88° C. while nitrogen was swept over the reaction to remove methanol, THF, and HCl. The reaction was monitored by HPLC until the conversion was complete which required heating overnight in most cases. The pot reaction product was a thick dark oil. A sample of 1-cyclopentyl-3-ethyl-6-(4-methoxybenzyl)-1,4,5,6-tetrahydropyrazolo[3,4-c]pyridin-7-one was isolated for characterization. dry 100 gallon tank was swept over the reaction to remove methanol, THF, and HCl required heating overnight in most cases

反応条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Cyclopentanol (6.127 kg, 71.1 moles) and triphenylphosphine (18.667 kg, 71.25 moles) were dissolved in tetrahydrofuran (40 gal) in a clean and dry, nitrogen purged 100 gallon tank and the reaction mixture was cooled to 5° C. A solution of di-t-butyl azodicarboxylate (14.9 kg, 64.7 moles) in tetrahydrofuran (36 L) was added over about 2 hours keeping the temperature <6° C. The reaction was allowed to stir for 5 hours as the temperature was allowed to slowly increase to 20-25° C. 6N HCl (26.5 L) was added to the reaction which was at 20° C. The reaction was allowed to stir 24 hours at 20-25° C. at which point the starting material had reacted. Water (10 gal, 37.85 L) was added and the tetrahydrofuran was removed by vacuum distillation. During the concentration, triphenylphosphine oxide precipitated and an additional 20 gal (75.7 L) of water was added. The reaction was cooled and methylene chloride (30 gal, 113.6 L) was added. The layers were separated and the aqueous was extracted twice more with methylene chloride (10 gal, 37.85 L) The aqueous was distilled to remove water. As the volume was reduced, isopropanol (3×20 gal (75.7 L)) was added to azeotrope the residual water. The resulting slurry was filtered and the solids were vacuum oven dried to give 7.682 kg (68.6% of theoretical) over multiple crops. This material was characterized to be the dihydrochloride salt; mp 189-194° C. dry nitrogen purged 100 gallon tank the temperature <6° C to slowly increase to 20-25° C was at 20° C to stir 24 hours at 20-25° C. at which point the starting material had reacted the tetrahydrofuran was removed by vacuum distillation During the concentration, triphenylphosphine oxide precipitated an additional 20 gal (75.7 L) of water was added The reaction was cooled methylene chloride (30 gal, 113.6 L) was added The layers were separated the aqueous was extracted twice more with methylene chloride (10 gal, 37.85 L) The aqueous was distilled to remove water isopropanol (3×20 gal (75.7 L)) was added The resulting slurry was filtered dried to give 7.682 kg (68.6% of theoretical) over multiple crops

反応条件: temp:88.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: treating said 3-methoxy-pyridinone compound of Formula (7.0.0) with cyclopentylhydrazine dihydrochioride; wherein a reaction mixture is established with tetrahydrofuran (THF) solvent and heating of said reaction mixture to 88° C., for 12 hours, while said reaction mixture is being swept by nitrogen in order to remove methanol, THF, and HCl; whereby there is produced a pyrazolopyridinone compound N-protected by p-methoxybenzyl, of Formula (8.0.0): treating reaction mixture to remove methanol, THF, and HCl