tert-butyl (2S)-2-butylpiperazine-1-carboxylate

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

Procedure: The product from Step B (3.75 g, 11.3 mmol) was dissolved in methanol (75 mL) in a Parr bottle, and the vessel purged with argon. To this was added 10% palladium on carbon (0.80 g) and the reaction hydrogenated under 60 psi hydrogen for 24 h. The catalyst as removed by filtration through Celite, and the filtrate evaporated in acuo to give the title compound as an oil. 1HNMR (300 MHz, CDCl3) δ 4.08 (1H, br s), 3.90 (1H, d, J=12 Hz), 2.5-3.8 (6H, m), 1.80 (1H, m), 1.60 (1H, m), 1.46 (9H, s), 1.30 (4H, m),0.90 (3H, t, J=7 Hz). the vessel purged with argon To this was added 10% palladium on carbon (0.80 g) the reaction hydrogenated under 60 psi hydrogen for 24 h The catalyst as removed by filtration through Celite the filtrate evaporated in acuo

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

Procedure: The product from Step B (3.75 g, 11.3 mmol) was dissolved in methanol (75 mL) in a Parr bottle, and the vessel purged with argon. To this was added 10% palladium on carbon (0.80 g) and the reaction hydrogenated under 60 psi hydrogen for 24 h. The catalyst as removed by filtration through Celite, and the filtrate evaporated in acuo to give the title compound as an oil. 1HNMR (300 MHz, CDCl3) δ 4.08 (1H, br s), 3.90 (1H, d, J=12 Hz), 2.5-3.8 (6H, m), 1.80 (1H, m), 1.60 (1H, m), 1.46 (9H, s), 1.30 (4H, m),0.90 (3H, t, J=7 Hz). the vessel purged with argon To this was added 10% palladium on carbon (0.80 g) the reaction hydrogenated under 60 psi hydrogen for 24 h The catalyst as removed by filtration through Celite the filtrate evaporated in acuo

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

Procedure: The product from Step B (3.75 g, 11.3 mmol) was dissolved in methanol (75 mL) in a Parr bottle, and the vessel purged with argon. To this was added 10% palladium on carbon (0.80 g) and the reaction hydrogenated under 60 psi hydrogen for 24 h. The catalyst as removed by filtration through Celite, and the filtrate evaporated in acuo to give the title compound as an oil. 1HNMR (300 MHz, CDCl3) δ 4.08 (1H, br s), 3.90 (1H, d, J=12 Hz), 2.5-3.8 (6H, m), 1.80 (1H, m), 1.60 (1H, m), 1.46 (9H, s), 1.30 (4H, m),0.90 (3H, t, J=7 Hz). the vessel purged with argon To this was added 10% palladium on carbon (0.80 g) the reaction hydrogenated under 60 psi hydrogen for 24 h The catalyst as removed by filtration through Celite the filtrate evaporated in acuo

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

Procedure: The title compound was prepared according to the procedure described in Example 1, Step A, except using 1-tert-butoxycarbonyl-2(S)-n-butyl-piperazine (0.261 g, 1.078 mmol), 8-quinoline carboxylic acid (0.187 g, 1.078 mmol), EDC.HCl (0.217 g, 1.13 mmol), HOBT (0.157g, 1.02 mmol) in DMF at pH 7 (adjusted with triethylamine). The crude product was chromatographed on silica gel with 5% methanol in chloroform. The title compound was obtained as an oil (0.253 g). The title compound was prepared The crude product was chromatographed on silica gel with 5% methanol in chloroform

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

Procedure: The title compound was prepared according to the procedure described in Example 1, Step A except using 1-tert-butoxycarbonyl-2(S)-n-butylpiperazine (0.325 g, 1.34 mmol), 1-naphthalene carboxylic acid (0.230 g, 1.34 mmol), HOBT (0.203 g, 1.34 mmol), EDC.HCl (0.254 g, 1.34 mmol) and triethylamine to adjust the pH to 7. The title compound was obtained as a thick oil (0.490 g). The title compound was prepared

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

Procedure: The title compound was prepared according to the procedure described for Example 1, Step A except using 1-tert-butoxycarbonyl-2(S)-n-butylpiperazine (1.26 g, 5.20 mmol), 2,3-dimethylbenzoic acid (0.820 g, 5.46 mmol), HOBT (0.70 g, 5.20 mmol), EDC.HCl (1.09 g, 5.72 mmol) and triethylamine to adjust the pH to 7. The crude product was chromatographed on silica gel with 20% ethyl acetate in hexane. The title compound was obtained as a thick oil (1.76 g). NMR (300 MHz, DMSO-d6) δ 7.15 (2H, m), 6.06 (1H,m), 4.42 (1H,m), 3.6-4.2 (2H, m), 2.7-3.24 (4H, m), 2.24 (3H, s), 2.03-2.20 (3H, 4s), 1.10-1.6 (15H, m), 0.72-1.00 (3H, m). The title compound was prepared The crude product was chromatographed on silica gel with 20% ethyl acetate in hexane

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

Procedure: The title compound was prepared according to the procedure described in Example 2, Step C, except using 4-benzyl-1-tert-butoxycarbonyl-2(S)-n-butylpiperazine (3.75 g, 11.3 mmol) and 10% palladium on carbon (0.80 g). The title compound was obtained as an oil (2.68 g). NMR (300 MHz, CDCl3) δ 4.08 (1H, br s), 3.90 (1H, d, J=12 Hz), 2.5-3.8 (6H, m), 1.80 (1H, m), 1.60 (1H, m), 1.46 (9H, s), 1.30 (4H, m),0.90 (3H, t, J=7 Hz). The title compound was prepared

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

Procedure: The product from Step B (3.75 g, 11.3 mmol) was dissolved in methanol (75 mL) in a Parr bottle, and the vessel purged with argon. To this was added 10% palladium on carbon (0.80 g) and the reaction hydrogenated under 60 psi hydrogen for 24 h. The catalyst as removed by filtration through Celite, and the filtrate evaporated in acuo to give the title compound as an oil. 1HNMR (300 MHz, CDCl3) δ 4.08 (1H, br s), 3.90 (1H, d, J=12 Hz), 2.5-3.8 (6H, m), 1.80 (1H, m), 1.60 (1H, m), 1.46 (9H, s), 1.30 (4H, m),0.90 (3H, t, J=7 Hz). the vessel purged with argon To this was added 10% palladium on carbon (0.80 g) the reaction hydrogenated under 60 psi hydrogen for 24 h The catalyst as removed by filtration through Celite the filtrate evaporated in acuo