6-BENZYL-5,6,7,8-TETRAHYDRO-1H-PYRIDO[4,3-D]PYRIMIDINE-2,4-DIONE

A commercially available compound 51 (10.0 g, 33.5 mmol) was dissolved in ethanol (150.0 mL), then urea (10.0 g, 167.0 mmol) and sodium methoxide (22.7 g, 118.0 mmol) were added thereto and the mixture was made to react for 24 h under the condition of heating to reflux. After cooled to 0 °C, crystals separated out therefrom were filtered. The crystals were suspended in water, hydrochloric acid (6.0 mol/L) was added thereto and pH was adjusted to 6.0. Stirring was further conducted at room temperature for 1 h and the crystals separated out therefrom were filtered and dried in vacuo to prepare compound 52 (6.5 g, 75percent), which was used without further purification. RA commercially available compound (A) (100 g, 0.335 mol) was dissolved in ethanol (1, 500 mL), then urea (100 g, 1.67 mol) and sodium methoxide (227 g, 1.18 mol) were added thereto and the mixture was made to react for 24 hours under the condition of heating to reflux. Progress of the reaction was confirmed by a thin-layer chromatography and, after cooled, crystals separated out therefrom were filtered. The crystals were suspended in water, hydrochloric acid (6 mol/L) was added thereto and pH was adjusted to 6.0. Stirring was further conducted at room temperature for 1 hour and the crystals separated out therefrom were filtered and dried in vacuo to prepare compound (B) (60 g, yield: 70percent).A commercially available compound (A) (100 g, 0.335 mol) was dissolved in ethanol (1, 500 mL), then urea (100 g, 1.67 mol) and sodium methoxide (227 g, 1.18 mol) were added thereto and the mixture was made to react for 24 hours under the condition of heating to reflux. Progress of the reaction was confirmed by a thin-layer chromatography and, after cooled, crystals separated out therefrom were filtered. The crystals were suspended in water, hydrochloric acid (6 mol/L) was added thereto and pH was adjusted to 6.0. Stirring was further conducted at room temperature for 1 hour and the crystals separated out therefrom were filtered and dried in vacuo to prepare compound (B) (60 g, yield: 70percent).Commercially available ethyl 1-benzyl-4-oxo-3-piperidinecarboxylate hydrochloride (100 g, 0.335 mol) was dissolved in ethanol (1, 500 mL), and the solution was mixed with urea (100 g, 1.67 mol) and sodium methoxide (227 g, 1.18 mol), followed by a reaction under reflux for twenty-four hours. After checking the completion of the reaction by thin layer chromatography, the reaction mixture was cooled, and the precipitated crystals were collected by filtration. The crystals were suspended in water, and the pH of the suspension was adjusted to 6.0 by the addition of diluted hydrochloric acid (6 mol/L). The mixture was stirred at room temperature for one hour, and the precipitated crystals were collected by filtration. The crystals were dried under reduced pressure and thereby yielded 6-benzyl-5, 6, 7, 8-tetrahydropyrido[4, 3-d]pyrimidine-2, 4(1H, 3H)-dione (60 g, in a yield of 70percent).A stirred solution of ethyl-1-benzyl-4-oxo-3-piperidine carboxylate, hydrochloride (15 g, 50.4 mmol, combi blocks) and urea (6.36 g, 105 mmol) in dry MeOH (1 10 mL), sodium methoxide (16.4 mL, 75.14 mmol, and 25percent wt. in methanol) was added drop wise at rt and the mixture was refluxed for 40 h. It was cooled to 0°C and filtered. The residue was stirred with water (40 mL) for 30 min at rt and again cooled to 0 °C and filtered. The residue was washed with diethyl ether (2 x 20 mL) and dried, affording the title compound. Yield: 60percent (7.2 g, Off white solid). To a 0 °C solution of ethyl l-benzyl-4-oxopiperidine-3-carboxylate hydrochloride 1 (6.0 g, 20.2 mmol), urea (2.54 g, 42.42 mmol) in MeOH (100 ml) was added NaOMe (6.14 g, 113.7 mmol) under nitrogen atmosphere. The resulting mixture was stirred at 60 °C for 20 hours. The reaction mixture was cooled down to the room temperature and concentrated under reduced pressure, the residue was purified by column chromatography (silica gel, dichloromethane/methanol= 10: 1) to provide the desired compound 2 (2.2 g, 42percent). LRMS (M + HA stirred solution of ethyl-1-benzyl-4-oxo-3-piperidine carboxylate, hydrochloride (15 g, 50.4 mmol, combi blocks) and urea (6.36 g, 105 mmol) in dry MeOH (110 mL), sodiummethoxide (16.4 mL, 75.14 mmol, and 25percent wt. in methanol) was added drop wise at rt and the mixture was refluxed for 40 h. It was cooled to 0°C and filtered. The residue was stirred with water (40 mL) for 30 mm at rt and again cooled to 0 °C and filtered. The residue was washed with diethyl ether (2 x 20 mL) and dried, affording the title compound. Yield: 60percent (7.2 g, Off white solid). 1H NMR (400 MHz, DMSO-d6): 6 9.03 (5, 2H), 7.33-7.32 (m, 4H), 7.26-7.25 (m, IH), 3.56 (5, 2H), 2.68 (5, 2H), 2.55 (t, J = 5.2 Hz, 2H), 2.26 (t, J = 5.2 Hz, 2H). LCMS: (Method A) 258.2 (M +2), Rt. 1.31mm, 99.60percent (Max).A mixture of l-benzyl-3-carbethoxy-4-piperidone hydrochloride (100.0 g, 0.34 mol, vendor : Acros Organics, CAS registry number: 1454-53-1), NaOMe (181.4 g, 3.36 mol) and urea (100.8 g, 1.68 mol) in EtOH (1.5 L) was heated at 80°C with stirring for 16 hrs under nitrogen. The resulting mixture was cooled to rt and filtered. The collected solid was suspended in H

Molecular Weight:257.29
XLogP3:0.4
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:257.116426730
Monoisotopic Mass:257.116426730
Topological Polar Surface Area:61.4
Heavy Atom Count:19
Complexity:424
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes