Triethylamine → 2-[4-(4-Methoxy-3-methyl-benzoyl)-piperidin-1-yl]-N-(4-oxo-3,5,7,8-tetrahydro-4H-pyrano[4,3-d]pyrimidin-2-ylmethyl)-acetamide

Participants

Reaction Steps

A solution of [4-(4-methoxy-3-methyl-benzoyl)-piperidin-1-yl]-acetic acid (0.10 g, 0.34 mmol), EDCl (0.08 g, 0.41 mmol), HOBT (0.06 g, 0.41 mmol) and triethylamine (0.17 g, 1.7 mmol) in 10 mL of DMF was stirred at ambient temperature for 20 min., then 2-aminomethyl-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one (0.06 g, 0.34 mmol) was added. The reaction mixture was stirred at ambient temperature for 15 hours. The reaction mixture was diluted with 50 mL of water, extracted with DCM (100 mL) and the combined organic layers were washed with saturated aqueous NaHCO3 solution. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo to provide crude product. Purification by flash chromatography gave the title compound (42.8 mg, 0.09 mmol) as a yellow solid. MS (ESI) m/z 454.8 (M+H+); HPLC (Insertsil ODS3 100×3 mm C-18 column: mobile phase: 5-95% acetonitrile/water with 0.1% TFA, at 1 mL/min over 7.75 min.), t=1.21 min. 1H NMR (400 MHz, dichloromethane-d2) δ ppm 1.77-1.97 (m, 4H), 2.28 (br. s., 3H), 2.42-2.55 (m, 2H), 2.64-2.77 (m, 2H), 2.90-3.11 (m, 3H), 3.17-3.24 (m, 2H), 3.25-3.36 (m, 1H), 3.93 (br. s., 3H), 4.31-4.41 (m, 2H), 4.48-4.65 (m, 3H), 6.89-7.02 (m, 1H), 7.78 (br. s., 1H), 7.84 (d, J=8.59 Hz, 1H), 8.20 (br. s., 1H), 10.84 (s, 1H). HRMS calculated for C24H31N4O5: 455.2294 (M+H). found (ESI, [M+H]+): 455.2311.

Provenance & Evidence