8-methyl-1,3,8-triazaspiro[4.5]decane-2,4-dione

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 8-methyl-1,3,8-triaza-spiro[4.5]decane-2,4-dione (40 mg) in DMF (0.6 mL) was added to a solution of 2-(4-(4-cyano-1-methyl-1H-imidazo[4,5-e]pyridin-6-yl)-2-(trifluoromethyl)phenoxy)ethyl methanesulfonate (50 mg) in DMF (0.4 mL), K2CO3 (41 mg) and tetrabutyl ammonium iodide (TBAI, 26 mg). The mixture was stirred at 90° C. for 14 hours. The crude mixture was directly purified by preparative HPLC (HPLC:column XBridge MS C18 30×100 mm, 5 μm, Eluent:A:NH4HCO3, 10 mmol, pH=9.5/B:Acetonitrile, Focused gradient/8 minutes/50 mL/min) to afford 1-methyl-6-{4-[2-(8-methyl-2,4-dioxo-1,3,8-triaza-spiro[4.5]dec-3-yl)-ethoxy]-3-(trifluoromethyl)-phenyl}-1H-imidazo[4,5-c]pyridine-4-carbonitrile (20 mg). The crude mixture was directly purified by preparative HPLC (HPLC gradient/8 minutes/50 mL/min

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

Procedure: 1-methylpiperidine-4-spiro-5'-hydantoin (9.75 g., 0.0533 mole) and barium hydroxide octahydrate (28.8 g., 0.00913 mole) in water (150 ml.) were heated at 160° C. in an autoclave for three hours. The contents of four such batches were combined and the precipitated barium carbonate was filtered off. The liltrate was neutralized with solid carbon dioxide and the precipitate was removed by filtration. The liltrate was concentrated to a small volume to give 4-amino-l-methylpiperidine-4-carboxylic acid (32.0 g., 95% yield), m.p. 275°-280° C. (dec.). the precipitated barium carbonate was filtered off the precipitate was removed by filtration The liltrate was concentrated to a small volume

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

Procedure: 1-Methylpiperidine-4-spiro-5'-hydantoin (9.75 g, 0.0533 mole) and barium hydroxide octahydrate (28.8 g, 0.0913 mole) in water (150 ml) were heated at 160° C. in a bomb for 3 hr. The content of four such batches were combined and the precipitated barium carbonate was filtered off. The filtrate was neutralized with solid CO2 and the precipitate removed by filtration. The filtrate was concentrated to give 4-amino-1-methylpiperidine-4-carboxylic acid (32.0 g., 95%) mp. 275°-280° C. (dec.). the precipitated barium carbonate was filtered off the precipitate removed by filtration The filtrate was concentrated

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

Procedure: 1 -methylpiperidine-4-spiro-5'-hydantoin (9.75 g., 0.0533 mole) and barium hydroxide octahydrate (28.8 g., 0.00913 mole) in water (150 ml.) were heated at 160° C. in an autoclave for three hours. The contents of four such batches were combined and the precipitated barium carbonate was filtered off. The filtrate was neutralized with solid carbon dioxide and the precipitate was removed by filtration. The filtrate was concentrated to a small volume to give 4-amino-1-methylpiperidine-4-carboxylic acid (32.0 g., 95% yield), m.p. 275°-280° C. (dec.). the precipitated barium carbonate was filtered off the precipitate was removed by filtration The filtrate was concentrated to a small volume

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

Procedure: 1-Methylpiperidine-4-spiro-5'-hydantoin (9.75 g. 0.0533 mole) and barium hydroxide octahydrate (28.8 g, 0.9913 mole) in water (150 ml) were heated at 160° C. in a bomb for 3 hr. The content of four such batches were combined and the precipitated barium carbonate was filtered off. The filtrate was neutralized with solid CO2 and the precipitate removed by filtration. Concentration of the filtrate gave 4-amino-1-methyl-piperidine-4-carboxylic acid (32.0 g, 95%) mp. 275°-280° C. (dec.). the precipitated barium carbonate was filtered off the precipitate removed by filtration