1-Boc-4-Methylaminopiperidine

Colorless liquid

To a suspension of N-(tert-butoxycarbonyl)-4-piperidone (10.00 g, 50.19 mmol) in EtOH (75 mL) was added 10percent Pd/C (1.00 g, 10percent wt.), NHN- (tert-Butoxycarbonyl) -4-Piperidone (10.00 g, 50.19 mmol)Was added to anhydrous ethanol, and 10percent Pd / C (1.00 g, 10percent wt.) Was added thereto, Methylamine in ethanol (33percent, 27 mL, 0.20 mol)And formic acid (46 mg, 1.00 mmol) were added and the mixture sealed in a 4 MPa hydrogen autoclave and stirred overnight at 50 ° C. The system was returned to room temperature and filtered. The filtrate was concentrated under reduced pressure to give the title compound as a pale yellow liquid (10.70 g 99percent).Preparation 52: tert-Butyl 4-(methylamino)piperidine-1-carboxylate 10percent Pd/C (2 g) was added to a solution of tert-butyl 4-oxopiperidine-1-carboxylate (20 g, 100 mmol) in methylamine (33percent in ethanol, 10 mL) and the mixture was stirred at room temperature, under 60 psi of hydrogen, for 18 hours. The reaction mixture was then filtered through Arbocel.(R). and the filtrate was concentrated in vacuo. The residue was azeotroped with dichloromethane (.x.3) and the dried under vacuum for 72 hours to afford the title compound as a solid in 98percent yield, 21.1 g. LRMS APCI m/z 215 [M+H]To a solution of 1-Boc-4-piperidone (500 mg, 2.51 mmol) in methanol (20 mL), were sequentially added 40percent solution of methylamine in methanol (0.90 mL, 8.78 mmol), and 10percent palladium on carbon (50 mg). The reaction mixture placed under an atmosphere of hydrogen for 24 h. The reaction mixture was then purged with nitrogen and filtered through a pad of Celite, which was then washed with methanol. The filtrate was concentrated in vacuo to afford tert butyl4-(methylamino)piperidine-1-carboxylate (4) (520 mg, 97percent).1-TERT-BUTOXYCARBONYLPIPERID-4-ONE (6.18 g, 31 mmol) was dissolved in a 2.0 M solution of methylamine in methanol (56 mL, 112 mmol). This solution was added to 10percent palladium on carbon (wet, 1.3 g) and the mixture placed under an atmosphere of hydrogen for 72 h. The reaction mixture was then purged with nitrogen and filtered through a pad of Celite, which was then washed with methanol. The resulting hazy filtrate was filtered through a 0. 2, UM filter and then concentrated in vacuo to afford the title intermediate (6.16 g, 29 mmol, 93.5percent yield).tert-Butyl 4-(methylamino)piperidine-1-carboxylate A solution of methanamine (38.0 mL, 442 mmol, 40percent aqueous solution) in methanol(100 mL) was added to wet palladium (1.602 g, 1.506 mmol, 10percent on activatedcharcoal) at room temperature under an atmosphere of argon. To this mixture wasadded tert-butyl 4-oxopiperidine-l-carboxylate (20 g, 100 mmol) portionwise and themixture was allowed to stir at 50 °C, 20 bar over lh. The suspension was flushed with argon and was filtered through celite and the celite was washed with DCM. The filtrate was evaporated in vacuum to give the product as a clear oil. The oil was- dissolved in EtOAc and was washed with water. The organic layer was dried (MgSO4)and evaporated in vacuum to give a clear oil. Used without further purification. tertl3utyl 4-(methylamino)piperidine- 1 -carboxylate (20 g, 93 percent yield).To a well purged solution of tert-butyl 4-oxopiperidine-l -carboxylate (20 g, 100 mmol) in methanol (100 mL) and methanamine (40percent in water) (38.0 mL, 442 mmol) was added palladium (10 wtpercent on activated charcoal) (1.602 g, 1.506 mmol) and placed in Parr reactor. The reaction mixture was allowed to stir under HTo a solution of 1 , 1-dimethylethyl 4-oxo-1 -piperidinecarboxylate (5.25 g, 0.026 mol) in MeOH (50 mL) at OIn a 250 mL flask was placed tert-butyl 4-oxopiperidine-l-carboxylate (20 g, 100 mmol) in methanol (100 mL), at room temperature under inert atmosphere, to give a colorless solution. Methanamine (40percent in water) (38 mL, 441 mmol) was added, followed by palladium (10percent on charcoal, 1.709 g, 1.606 mmol). The reaction flask was placed in an autoclave and was charged with 20 bar of hydrogen. The autoclave was heated at 50°C and stirred for 2 h. The reaction mixture was cooled slowly, filtered through celite, and the solvent was evaporated. The crude product was dissolved in water and the aqueous mixture was extracted with ethyl acetate. The organics were dried over MgS03.8 mL (13 mmol) of titanium isopropoxide and 2 g (10 mmol) of 1-tert-butoxycarbonyl-piperidin-4-one are added to 3.7 mL (30 mmol) of a 33percent solution of methylamine in ethanol. ll.2.b4-Methylamino-piperidine-1-carboxylic acid te/f-butyl esterA mixture of 4.5 g (14.78 mmol) 4-(benzyl-methyl-amino)-piperidine-1-carboxylic acid te/f- butyl ester and 1 g of Pd/C (10percent) in 100 ml of methanol is hydrogenated at 501-(6-Methoxypyridin-3-yl)-N-methylpiperidin-4-amine (AMN-51)Reference Example 46

Molecular Weight:214.30
XLogP3:1.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:214.168127949
Monoisotopic Mass:214.168127949
Topological Polar Surface Area:41.6
Heavy Atom Count:15
Complexity:215
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes