4-(4-Aminophenyl)piperidine-1-carboxyl...

A solution of 4-(4-amino-phenyl)-3, 6-dihydro-2H-pyridine-l-carboxylic acid tert- butyl ester (0.35 g, 1.2 mmol) (as prepared in the previous step) in methanol was hydrogenated over 10 percent Pd/C at 20 psi for 1 h. The solution was filtered and concentrated to give 0.35 g (100 percent) of the title compound as a yellow solid: Mass spectrum (ESI, m/z): Calcd. for CiA solution of 4-(4-amino-phenyl)-3, 6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (0.35 g, 1.2 mmol) (as prepared in the previous step) in methanol was hydrogenated over 10percent Pd/C at 20 psi for 1 h. The solution was filtered and concentrated to give 0.35 g (100percent) of the title compound as a yellow solid: Mass spectrum (ESI, m/z): Calcd. for Cb) B. B. A solution of 4-(4-amino-phenyl)-3, 6-dihydro-2H-pyridine-l-carboxylic acid tert- butyl ester (0.35 g, 1.2 mmol) (as prepared in the previous step) in methanol was hydrogenated over 10 percent Pd/C at 20 psi for I h. The solution was filtered and concentrated to give 0.35 g (100 percent) of the title compound as a yellow solid: Mass spectrum (ESI, m/z): Calcd. for CiTo a solution of 4-(4-amino-phenyl)-3, 6-dihydro-2H-pyridine-l -carboxylic acid tert- butyl ester (33 g, 0.12 mol) in MeOH (1 L) was added Pd/C (5 g) under Ar. The mixture was stirred at r.t.. under an atmosphere of ¾ (40 psi) for 3 hr. The mixture was filtered and concentrated to afford the desired compound 159 (32.3 g, 97percent). LCMS m/z 221 (M-55)A stirred suspension of tert—butyl 4—(4—aminophenyl)—5, 6— dihydropyridine—1(2H)—carboxylate (79mg, 0.253 mmol) and10percent Pd/C (33.7 mg, 0.032 mmol) in ethanol (2 mL) wassealed then placed under vacuum and backfilled withnitrogen. This was repeated twice further before placingunder vacuum and backfilling with hydrogen (from balloon) . The suspension was stirred for 5 h. Remaining hydrogen was removed under vacuum. The mixture was filtered through Celite® washing with ethanol (5 mL) andthe filtrate was concentrated to dryness under reduced pressure. The residue was purified by flash chromatography (0—10percent Methanol in Dichloromethane) to give the title compound (51.3 mg, 73.3 percent) . LCMS (MethodC): RT = 0.92 mm, m/z = 221 [M—Butene].A mixture of tert-butyl 4- (4-nitrophenyl) -5, 6-dihydropyridine-1 (2H) -carboxylate (495 mg, 1.626 mmol) and 20Pd (OH) A solution of /erf-butyl 4-(4-nitrophenyl)-5, 6-dihydropyridine-1 (2H)-carboxylate (143) (0.570 g, 1.87 mmol) in EtOH (5 mL) and DMF (5 mL) was added to a solution of 10percent Pd/C (200 mg) in DMF (10 mL). The reaction was stirred at room temperature for 24 hours under an atmosphere of hydrogen. The reaction was filtered through a pad of celite and washed through with EtOAc (130 mL). The solvent was removed in vacuo to yield a brown oil which was purified by column chromatography on silica gel (0-50percent EtOAc in petroleum benzine 40-60 °C) to afford the title compound (144) (0.46 g, 89percent) as a crystalline solid, H NMR (400 MHz, CDC1A solution of ferf -butyl 4-(4-nitrophenyl)-5, 6-dihydropyridine-1 (2H)-carboxylate (143) (0.570 g, 1.87 mmol) in EtOH (5 mL) and DMF (5 mL) was added to a solution of 10percent Pd/C (200 mg) in DMF (10 mL). The reaction was stirred at room temperature for 24 hours under an atmosphere of hydrogen. The reaction was filtered through a pad of celite and washed through with EtOAc (130 mL). The solvent was removed in vacuo to yield a brown oil which was purified by column chromatography on silica gel (0-50percent EtOAc in petroleum benzine 40-60 °C) to afford the title compound {144) (0.46 g, 89percent) as a crystalline solid; To a stirred solution of 36 (8.00 g, 26.2 mmol) in EtOH (10 mL) was charged with Pd/C (1.60 g, 10percent wt) under argon atmosphere at room temperature. Hydrogen atmosphere was introduced using a balloon and the reaction mixture was stirred for 12h at the same temperature. The reaction mixture was filtered through celite® bed, washed with CH3OH (50 mL) and was concentrated under reduced pressure to afford 37 (1.50 g, 20percent) as a solid. MS (MM) m/z 277.1 [M + Hj.In an ice-water bath, 15.9 g (48 mmo 1) of intermediate 125C was dissolved in 75 mL of N 'N-dimethylformamide, 30 minA mixture of 54. lg (240 mmol) of stannous chloride dihydrate was added portionwise and stirred at room temperature for 3 hours. TLC detection, after the end of the reaction10percent aqueous sodium hydroxide solution was added dropwise to the reaction solution to a pH of 8-9, filtered, and the filtrate was extracted with methylene chloride. The filter cake was washed with dichloromethaneHexane, combined with organic phase, washed with water, washed with salt, dried, Rotate to obtain 12.4 g of product as a yellow oil in 93.9percentA solution of 4-(4-benzyloxycarbonylaminophenyl)-3, 6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (100 mg) obtained in Example (228b) and palladium-carbon (15 mg) in methanol (30 ml) was stirred at room temperature under a hydrogen atmosphere for one hour. The reaction solution was filtered through Celite and concentrated. The residue was purified by chromatography (hexane: ethyl acetate 5:2) and 57 mg (84percent) of the title compound was obtained as a yellow oil. MS(ESA mixture of 4-pyridyl-nitrobenzene (1.0 g, 5.0 mmol), PtOIn a 250-mL round-bottom flask a solution of 18.3 (1.433 g, 3.53 mmol, 1.00 equiv) and NH00292] Synthesis of compound 4.4. In a 250-mL round-bottom flask a solution of 4.3 (1.433 g, 3.53 mmol, 1.00 equiv) and ΝΗIn a 250-mL round-bottom flask a solution of 4.3 (1.433 g, 3.53 mmol, 1.00 equiv) and ΝΗ

Molecular Weight:276.37
XLogP3:2.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:276.183778013
Monoisotopic Mass:276.183778013
Topological Polar Surface Area:55.6
Heavy Atom Count:20
Complexity:322
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes