6-BENZYL-2,4-DICHLORO-5,6,7,8-TETRAHYDROPYRIDO[4,3-D]PYRIMIDINE

52 (8.5 g, 32.9 mmol) was added to phosphoryl chloride (50.0 mL, 535 mmol) in a 250 mL round-bottom flask equipped with a stir bar, and the solution was refluxed for 3 h under NPhosphorus oxychloride (300 mL) was added to compound (B) (30.0 g, 0.116 mol) prepared in the step 1 and the mixture was stirred under a heating condition for 5 hours. After confirming the progress of the reaction by a thin-layer chromatography, an excessive phosphorus oxychloride was evaporated in vacuo. After that, 2-propanol (300 mL) was added to the residue and a suspension containing the crystals separated out therefrom was stirred under the condition of heating to reflux for 1 hour and further stirred at room temperature for 1 hour. The crystals separated out were filtered and driedin vacuo to prepare compound (C) (33 g, yield: 85percent).Phosphorus oxychloride (300 mL) was added to compound (B) (30.0 g, 0.116 mol) prepared in the step 1 and the mixture was stirred under a heating condition for 5 hours. After confirming the progress of the reaction by a thin-layer chromatography, an excessive phosphorus oxychloride was evaporated in vacuo. After that, 2-propanol (300 mL) was added to the residue and a suspension containing the crystals separated out therefrom was stirred under the condition of heating to reflux for 1 hour and further stirred at room temperature for 1 hour. The crystals separated out were filtered and dried in vacuo to prepare compound (C) (33 g, yield: 85percent).To 6-benzyl-5, 6, 7, 8-tetrahydropyrido [4, 3-d] pyrimidine-2, 4(1 H, 3H)-dione (7.2 g, 27.9 mmol), POCI3 (45mL, 6V) was added slowly at 0°C and refluxed for 4h. The reactionmixture was evaporated under vacuum. EtOAc (200 mL) was added and the solution was poured over cold 3M NaOH solution. The resulting organic layer was separated and washed with brine (30 mL), dried over anhydrous Na2SO4 and evaporated, affording the title compound. Yield: 79percent (6.5 g, brown solid). 1H NMR (400 MHz, DMSO-d6): 6 7.33- 7.32 (m, 5H), 3.77 (s, 2H), 3.56 (s, 2H), 2.94 (t, J = 7.2 Hz, 2H), 2.80 (t, J = 6.8 Hz, 2H).LCMS: (Method A) 296.3 (M +2), Rt. 2.50mm, 97.94percent (Max).To 6-benzyl-5, 6, 7, 8-tetrahydropyrido[4, 3-d] pyrimidine-2, 4(1H, 3H)-dione (7.2 g, 27.9 mmol), POCIA solution of the intermediate 2 (2.2 g, 8.56 mmol) in POCIGeneral procedure: To the solution of compound 8 (0.23g, 1.2mmol) in THF (5mL) was added DIPEA (1.8mmol) and bicyclic amine or piperidin amine (1.44mmol). The reaction was stirred at r.t. for overnight. Then the mixture was diluted with ethyl acetate, washed with brine, dried over MgSO4, and evaporated. The residue was purified by column chromatography to give the product. 4.1.4 40 tert-butyl 4-((2-chloro-6, 7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)amino)piperidine-1-carboxylate (9) (0018) Yellow solid, 87% yield. 1H NMR (600MHz, CDCl3) delta (pmm): 4.35 (d, J=7.6Hz, 1H), 4.27-4.01 (m, 3H), 3.02-2.83 (m, 4H), 2.60 (t, J=7.4Hz, 2H), 2.20-2.09 (m, 2H), 2.08-1.98 (m, 2H), 1.46 (s, 9H), 1.33(m, 2H). MS-ESI: [M-H]-:351.2.

Molecular Weight:294.2
XLogP3:3.5
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:293.0486528
Monoisotopic Mass:293.0486528
Topological Polar Surface Area:29
Heavy Atom Count:19
Complexity:296
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes