Diisopropylethylamine → (S)-2-(2,6-dimethylphenyl)-6-(5-isopropyl-2-methylphenyl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-7,8-dihydro-1,6-naphthyridin-5(6H)-one

Participants

Reaction Steps

A 10-mL reaction flask containing an orange solution of 4-chloro-2-(2,6-dimethylphenyl)-6-(5-isopropyl-2-methylphenyl)-7,8-dihydro-1,6-naphthyridin-5(6H)-one (100 mg, 0.239 mmol), (S)-4-methoxy-3,3-dimethylpiperidine HCl salt (129 mg, 0.716 mmol), and DIEA (208 μL, 1.193 mmol) in DMA (1.2 mL) was placed in a sand bath preheated to 110° C. and stirred at that temperature. After 4 h the reaction mixture was allowed to cool to room temperature, then diluted with DCM and poured into mixture of saturated aqueous sodium bicarbonate solution and brine. The aqueous layer was extracted with DCM (3×), and the combined organic layers were washed with brine, then dried over sodium sulfate, filtered, and concentrated. The residue was purified by FCC (0-100% EtOAc/heptane) to provide (S)-2-(2,6-dimethylphenyl)-6-(5-isopropyl-2-methylphenyl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-7,8-dihydro-1,6-naphthyridin-5(6H)-one. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.07-7.25 (m, 6 H) 6.73 (s, 1 H) 3.80-3.96 (m, 1 H) 3.63-3.79 (m, 1 H) 3.27 (s, 3 H) 3.09-3.24 (m, 2 H) 2.93-3.07 (m, 3 H) 2.79-2.92 (m, 2 H) 2.18-2.22 (m, 3 H) 2.06 (s, 6 H) 1.79-1.94 (m, 1 H) 1.48-1.65 (m, 1 H) 1.21 (d, J=6.8 Hz, 6 H) 1.14-1.19 (m, 1 H) 0.90 (s, 3 H) 0.83 (s, 1 H)* 0.78 (s, 2 H)*; MS (ESI+) m/z 526.3 (M+H)+. (*indicates one methyl group appearing as two peaks due to restricted rotation).

Provenance & Evidence