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ChemicalBook CAS DataBase List 7-BENZYL-5,6,7,8-TETRAHYDROPYRIDO[3,4-D]PYRIMIDINE-2,4(1H,3H)-DIONE
62459-02-3

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

2synthesis methods
-

Yield: 83.2%

Reaction Conditions:

with sodium in ethanol at 75; for 36 h;

Steps:

A Step A: 7-benzyl-6.8-dihydro-5H-pyrido[3.4-dlpyrimidine-2.4-diol:
To EtOH (600 mL) was added Na (5.56 g, 241 mmol, 5.73 mL, 2.40 eq) in portions. The reaction mixture was stirred for 1 hour. To the mixture was added ethyl l-benzyl-3-oxo-piperidine-4-carboxylate (30.0 g, 100 mmol, 1.00 eq, HC1) and urea (14.5 g, 242 mmol, 13.0 mL, 2.40 eq). The reaction mixture was stirred at 75 °C for 36 hours, and then the solvent was removed under vacuum. The residue was dissolved in water (50 mL) and acidified with HC1 (120 mL, 2M). A white solid precipitated from the solution and was collected by filtration. The filter cake was dried under vacuum to provide 7-benzyl-6,8-dihydro-5H-pyrido[3,4-d]pyrimidine-2,4-diol (22.0 g, 83.8 mmol, 83.2 % yield, 98 % purity) as a white solid.1HNMR (400 MHz, DMSO-de) δ = 10.97 (br s, 1H), 10.66 (br s, 1H), 7.55 - 6.95 (m, 5H), 3.81 - 3.50 (m, 2H), 3.26 - 2.91 (m, 2H), 2.77 - 2.58 (m, 2H), 2.34 - 2.09 (m, 2H).

References:

MIRATI THERAPEUTICS, INC.;ARRAY BIOPHARMA, INC.;FISCHER, John, P.;FELL, Jay, Bradford;BLAKE, James, F.;HINKLIN, Ronald, Jay;MEJIA, Macedonio, J.;HICKEN, Erik, James;CHICARELLI, Mark, Joseph;GAUDINO, John, J.;VIGERS, Guy, P.A.;BURGESS, Laurence, E.;MARX, Matthew, Arnold;CHRISTENSEN, James, Gail;LEE, Matthew, Randolf;SAVECHENKOV, Pavel;ZECCA, Henry, J. WO2017/201161, 2017, A1 Location in patent:Paragraph 0221; 0267

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