7-BENZYL-5,6,7,8-TETRAHYDROPYRIDO[3,4-D]PYRIMIDINE-2,4(1H,3H)-DIONE

To a 0 °C solution of ethyl l-benzyl-3-oxopiperidine-4-carboxylate 1 (12.0 g, 40.4mmol) in MeOH (200 ml) were added urea (5.1g, 84.8 mmol) and NaOMe (12.3 g, 228 mmol) under nitrogen atmosphere, The resulting solution was stirred at 60 °C for 96 hours. The reaction mixture was cooled down to the room temperature and concentrated, the residue was purified by column chromatography (silica gel, dichloromethane/methanol= 10: 1) to provide the desire compound 2 (6.3 g, 61percent). LRMS (M + HCommercially available ethyl 1-benzyl-3-oxo-4-piperidinecarboxylate hydrochloride (25.0 g, 84.0 mmol) was dissolved in ethanol (350 mL), and the solution was mixed with urea (25.0 g, 416 mmol) and sodium methoxide (56.7 g), followed by a reaction under reflux for seventeen hours. After checking the completion of the reaction by thin layer chromatography, the reaction mixture was cooled to yield a suspension, and the pH of the suspension was adjusted to 6.0 by the addition of diluted hydrochloric acid (4 mol/L) . The mixture was stirred at room temperature for one hour, and the precipitated crystals were collected by filtration. The crystals were reslurried with ethanol, were collected by filtration, were dried under reduced pressure and thereby yielded 7-benzyl-5, 6, 7, 8-tetrahydropyrido[3, 4-d]pyrimidine-2, 4(1H, 3H)-dione (17.2 g, in a yield of 80percent).To a solution of sodium methoxide (25 wt-percent in methanol) (90 mL, 392 mmol) and MeOH(50 mL) at room temperature was added urea (7.34 mL, 163 mmol) and then ethyl N-benzyl-3-oxo-4-piperidine-carboxylatehydrochloride (9.72 g, 32.6 mmol). The resulting mixture was stirred at reflux for 18h. After cooling to room temperature the mixture, which included a heavy precipitate, was diluted with ~300 mL of water. The resulting solution was filtered to remove a small quantity of brown solid. The filtrate was adjusted to pH 6 by the dropwise addition of ~40 g of conc. hydrochloric acid. The precipitate was recovered by fitration, washed with aqueous methanol, and dried under vacuum to provide7-benzyl-5, 6, 7, 8-tetrahydropyrido[3, 4-d]pyrimidine-2, 4(1H, 3H)-dione (4.90 g, 19.04 mmol, 58.3 percent yield) as a beige powder. LC/MS: m/z 258.11 (M + 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