5.1 General synthetic procedure of DHP and DHP-OH
Ammonium acetate (500 mg, 6.49 mmol) or 2-aminoethan-1-ol (392 µL, 6.49 mmol) were dissolved in 10 mL of H2O:DMSO (1:1, v/v) in an ace pressure tube. Methylpropiolate (1,731 µL, 3.00 equiv), piperazine (111 mg, 0.2 equiv), and TMSCl (165 µL, 0.2 equiv) were added into the reaction solution. The mixture was heated and stirred at 120°C overnight. The reaction mixture was evaporated under reduced pressure, washed with saturated brine solution, and extracted with CH2Cl2. The organic fraction was dried over anhydrous Na2SO4 and evaporated under vacuum pressure. The crude product was purified by column chromatography (Silica gel, Hexane:EtOAc = 1:1, v/v) to obtain DHP or DHP-OH as a yellow solid in the yield of 72% or 83%.
Dimethyl 4-(2-methoxy-2-oxoethyl)-1,4-dihydropyridine-3,5-dicarboxylate (DHP):
1H NMR (500 MHz, acetone-d6) δ (ppm): 8.38 (br s, 1H), 7.38 (s, 1H), 4.16 (t, J = 5.6 Hz, 1H), 3.67 (s, 6H), 3.52 (s, 3H), 2.34 (d, J = 5.6 Hz, 2H); 13C NMR (125 MHz, acetone-d6) δ (ppm): 171.76, 167.56, 137.03, 105.06, 51.26, 51.15, 41.37, 30.50. HRMS (ESI): calcd. for [M + Na]+ 292.0792, found 292.0806.
Dimethyl 1-(2-hydroxyethyl)-4-(2-methoxy-2-oxoethyl)-1,4-dihydropyridine-3,5-dicarboxylate (DHP-OH):
1H NMR (500 MHz, acetone-d6) δ (ppm): 7.30 (s, 2H), 4.11 (t, J = 5.2 Hz, 1H), 3.74 (t, J = 5.4 Hz, 2H), 3.67 (s, 6H), 3.61 (t, J = 5.2 Hz, 2H), 3.54 (s, 3H), 2.37 (d, J = 5.2 Hz, 2H); 13C NMR (125 MHz, acetone-d6) δ (ppm): 172.55, 167.64, 141.32, 105.52, 62.09, 57.67, 51.54, 51.41, 41.31, 30.39. HRMS (ESI): calcd. for [M + Na]+ 336.1059, found 336.1034.