Sodium hydride → 2-{3-[4-(4-Methoxy-benzoyl)-piperidin-1-yl]-2-oxo-pyrrolidin-1-ylmethyl}-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-[4-(4-methoxy-benzoyl)-piperidin-1-yl]-pyrrolidin-2-one (43.7 mmol, 13.2 g) and 2-chloromethyl-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one (48 mmol, 9.6 g) in THF (400 mL) and DMF formula (20 mL) was added sodium hydride (60%, 153 mmol, 6.1 g) and heated to 70° C. for 1 hour. The reaction was allowed to cool to ambient temperature, diluted with 1 L of ether, and the resulting solid in suspension was filtered and dried under vacuum provided the title compound as an off-white solid (22 g, 95.3% yield). HRMS calculated for C25H30N4O5 466.5417. found (ESI, [M+H]+) 467.2305. 1H NMR (400 MHz, MeOD) δ ppm 1.67-1.92 (m, 4H) 2.05-2.24 (m, 2H) 2.47-2.64 (m, 3H) 2.72-2.82 (m, 1H) 2.84-2.93 (m, 1H) 3.06-3.15 (m, 1H) 3.26-3.47 (m, 10H) 3.68 (t, J=8.78 Hz, 1H) 3.83-3.99 (m, 5H) 4.16 (d, J=15.56 Hz, 1H) 4.40-4.58 (m, 3H) 7.01 (d, J=9.03 Hz, 2H) 7.97 (d, J=9.03 Hz, 2H), analytical RP-HPLC (Novapak 150×3.9 mm C18 column: mobile phase: 10-90% acetonitrile/water with 0.1% TFA, at 2 mL/min over 5 min.) retention time=2.455 min.

Provenance & Evidence