Sodium hydride → 2-[4-(4-Methoxy-benzoyl)-2'-oxo-[1,3']bipiperidinyl-1'-ylmethyl]-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of NaH (23.8 mg, 0.942 mmol, 2.1 eq) in THF (10 mL) were added 4-(4-methoxy-benzoyl)-[1,3′]bipiperidinyl-2′-one (142 mg, 0.449 mmol, 1.0 eq) and 2-chloromethyl-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one (90 mg, 0.449 mmol, 1.0 eq). The reaction was let to stir at 70° C. for 3 h. The solid precipitate was filtered off and washed with CH2Cl2. The solvent of the mother liquor was evaporated and the residue purified by flash chromatography on silica gel (0-15% MeOH/CH2Cl2) to afford the title compound as an off-white powder (60 mg, 0.139 mmol, 31.1% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.34 (br s, 1H) 7.94 (d, J=8.59 Hz, 2H) 7.03 (d, J=8.59 Hz, 2H) 4.14-4.54 (m, 5H) 4.06-4.10 (m, 1H) 3.45 (br s, 1H) 3.18 (d, J=5.05 Hz, 3H) 3.03 (br s, 1H) 2.85 (br s, 2H) 2.30-2.65 (m, 5H) 1.30-2.05 (m, 9H). HR-MS (m/z, MH+): 481.2461, 482.2471. HPLC retention time: 2.78 min (Agilent column 3.0×100 mm 3 um C18 column; flow rate of 1.0 mL/min with gradient from 5% to 95% acetonitrile in 10 min, 0.1% FA)

Provenance & Evidence