1-Acetylpiperidin-4-amine

1 -(4-Amino-piperidin-1 -vl)-ethanone:; 1-Acetyl-piperidin-4-one (10 gm (70 mmol)) was dissolved in 200 ml ethanol and treated with 10 gm (143 mmol) hydroxylamine hydrochloride and 10 ml pyridine. The reaction mixture was heated to 70 °Cfor 1.5 hr. The solvent was removed and the residue was treated with water and cooled to 0 °C. The resulting slurry was filtered and dried under vacuum to afford 6.5 gm 1-Acetyl-piperidin-4-one oxime as a white solid (59 percent). The oxime (2.0 gm (12 mmol)) in a Parr bottle was dissolved in 50 ml of ethanol and treated with 0.2 gm of Raney nickel which had been washed several times with water. The reaction was placed in to Parr apparatus and hydrogenated under 50 psi hydrogen pressure for 16 hours. The mixture was carefully filtered and the filtrate was evaporated in vacuo to afford 1.7 gm (100 percent) of the desired amine as a green solid. GC Mass spectrum m/z =142To a stirred suspension of ie f-butyl (1 -acetylpiperidin-4-yl) carbamate (6.61 g, 27.310 mmol) in dioxane (10 ml) was added 2.5 N HCI in dioxane (20 ml) at room temperature and the resulting reaction mixture was stirred at room temperature for 5 h. The resulting reaction mixture was concentrated under reduced pressure yielding 1 -(4-aminopiperidin-1 -yl) ethanone (2.20 g, 15.490 mmol) which was used in the next step without further purification. LCMS: Method B, 0.624 min, MS: ES+ 143.4 (M+1 ).Example 307; 1 -(4-Amino-piperidin-1 -vl)-ethanone:; 1-Acetyl-piperidin-4-one (10 gm (70 mmol)) was dissolved in 200 ml ethanol and treated with 10 gm (143 mmol) hydroxylamine hydrochloride and 10 ml pyridine. The reaction mixture was heated to 70 °Cfor 1.5 hr. The solvent was removed and the residue was treated with water and cooled to 0 °C. The resulting slurry was filtered and dried under vacuum to afford 6.5 gm 1-Acetyl-piperidin-4-one oxime as a white solid (59 percent). The oxime (2.0 gm (12 mmol)) in a Parr bottle was dissolved in 50 ml of ethanol and treated with 0.2 gm of Raney nickel which had been washed several times with water. The reaction was placed in to Parr apparatus and hydrogenated under 50 psi hydrogen pressure for 16 hours. The mixture was carefully filtered and the filtrate was evaporated in vacuo to afford 1.7 gm (100 percent) of the desired amine as a green solid. GC Mass spectrum m/z =142To a solution of 5, 8, 9, 10-tetrahydro-5, 8:7, 10-dimethanobenzo[8]annulen-7(6H)-amine hydrochloride (57 mg, 0.24 mmol) in DCM (1 mL) saturated aqueous NaHCO3 solution (1 mL) and triphosgene (27 mg, 0.09 mmol) were added. The biphasic mixture was stirred at room temperature for 30 minutes and then the two phases were separated and the organic layer was washed with brine (1 mL), dried over anh. Na2SO4, filtered and evaporated under vacuum to obtain 1-2 mL of a solution of the isocyanate in DCM. To this solution was added To a solution of 2, 3-dimethoxy-9-methyl-5, 6, 8, 9, 10, 11-hexahydro-7H-5, 9:7, 11-dimethanobenzo[9]annulen-7-amine hydrochloride (150 mg, 0.46 mmol) in DCM (3 mL) saturated aqueous NaHCO3 solution (3 mL) and triphosgene (51 mg, 0.17 mmol) were added. The biphasic mixture was stirred at room temperature for 30 minutes and then the two phases were separated and the organic layer was washed with brine (3 mL), dried over anh. Na2SO4, filtered and evaporated under vacuum to obtain 1-2 mL of a solution of the isocyanate in DCM. To this solution was added To a solution of 1-fluoro-9-methyl-5, 6, 8, 9, 10, 11-hexahydro-7H-5, 9:7, 11-dimethanobenzo[9]annulen-7-amine hydrochloride (150 mg, 0.53 mmol) in DCM (3 mL) saturated aqueous NaHCO3 solution (3 mL) and triphosgene (58 mg, 0.20 mmol) were added. The biphasic mixture was stirred at room temperature for 30 minutes and then the two phases were separated and the organic layer was washed with brine (3 mL), dried over anh. Na2SO4, filtered and evaporated under vacuum to obtain 1-2 mL of a solution of the isocyanate in DCM. To this solution was added To a solution of 2-methoxy-9-methyl-5, 6, 8, 9, 10, 11-hexahydro-7H-5, 9:7, 11-dimethanobenzo[9]annulen-7-aminehydrochloride (150 mg, 0.51 mmol) in DCM (3 mL) saturated aqueous NaHCO3 solution (3 mL) and triphosgene (56 mg, 0.19 mmol) were added. The biphasic mixture was stirred at room temperature for 30 minutes and then the two phases were separated and the organic layer was washed with brine (3 mL), dried over anh. Na2SO4, filtered and evaporated under vacuum to obtain 1-2 mL of a solution of the isocyanate in DCM. To this solution was added To a solution of 2-fluoro-9-methyl-5, 6, 8, 9, 10, 11-hexahydro-7H-5, 9:7, 11-dimethanobenzo[9]annulen-7-amine hydrochloride (150 mg, 0.53 mmol) in DCM (3 mL) saturated aqueous NaHCO3 solution (3 mL) and triphosgene (59 mg, 0.20 mmol) were added. The biphasic mixture was stirred at room temperature for 30 minutes and then the two phases were separated and the organic layer was washed with brine (3 mL), dried over anh. Na2SO4, filtered and evaporated under vacuum to obtain 1-2 mL of a solution of the isocyanate in DCM. To this solution was added To a solution of 9-methyl-2-nitro-5, 6, 8, 9, 10, 11-hexahydro-7H-5, 9:7, 11-dimethano-benzo[9]annulen-7-amine hydrochloride (600 mg, 1.94 mmol) in DCM (10 mL) saturated aqueous NaHCO3 solution (10 mL) and triphosgene (213 mg, 0.718 mmol) were added. The biphasic mixture was stirred at room temperature for 30 minutes and then the two phases were separated and the organic layer was washed with brine (5 mL), dried over anh. Na2SO4 filtered and evaporated under vacuum to obtain 1-2 mL of a solution of the isocyanate in DCM. To this solution was added To a solution of 1-(7-amino-9-methyl-6, 7, 8, 9, 10, 11-hexahydro-5H-5, 9:7, 11-dimethanobenzo[9]annulen-2-yl)ethan-1-one hydrochloride (300 mg, 0.98 mmol) in DCM (5 mL) and saturated aqueous NaHCO3 solution (3.52 mL) was added triphosgene (145 mg, 0.49 mmol). The biphasic mixture was stirred at room temperature for 30 minutes and then the two phases were separated and the organic layer was washed with brine (5 mL), dried over anh. Na2SO4 filtered and evaporated under vacuum to obtain 1-2 mL of a solution of the isocyanate in DCM. To this solution was added

Molecular Weight:142.20
XLogP3:-0.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:142.110613074
Monoisotopic Mass:142.110613074
Topological Polar Surface Area:46.3
Heavy Atom Count:10
Complexity:128
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes