The crude products was Title Loaded From File purified by flash Title Loaded From File column chromatography (gradient: 250 EtOAc in hexanes) to yield 47.6 mg (73 ) of 8 as a yellow amorphous strong. 1H NMR (400 MHz, chloroform-d) seven.83 (s, 1H), 7.50.33 (m, 6H), 7.30 (d, J = eight.0 Hz, 1H), seven.15 (t, J = seven.seven Hz, 1H), six.98 (d, J = seven.two Hz, 1H), 3.74 (s, 3H), 3.71 (s, 3H), 3.17 (d, J = eleven.three Hz, 1H), 3.04 (dt, J = 13.one, 3.seven Hz, 1H), 2.97 (dd, J = eleven.seven, 2.2 Hz, 1H), 2.78.73 (m, 1H), two.71.64 (m, 1H), two.fifty five (q, J = twelve.six Hz, 1H), 2.41 (dd, J = 11.3, three.one Hz, 1H), 2.33 (td, J = ten.seven, ten.two, four.one Hz, 1H), 2.01.94 (m, 1H), one.85 (d, J = twelve.9 Hz, 1H), one.81.71 (m, 2H), one.22 (d, J = eight.0 Hz, 1H), 0.85 (t, J = seven.three Hz, 3H).Educed strain along with the residue was extracted with DCM (3 20 mL). The combined extracts were washed with brine (3 1/3 vol.), dried (Na2SO4), and concentrated to provide the crude products. The crude product was purified by flash column chromatography (gradient: 250 EtOAc in hexanes) to yield 47.six mg (73 ) of eight being a yellow amorphous solid. 1H NMR (400 MHz, chloroform-d) 7.81 (s, 1H), 7.55.50 (m, 1H), seven.47 (d, J = one.0 Hz, 1H), seven.44 (d, J = 0.9 Hz, 1H), seven.30.27 (m, 1H), 7.eleven (dd, J = 8.1, seven.two Hz, 1H), 7.00.96 (m, 1H), 6.62.58 (m, 1H), 3.74 (s, 3H), three.71, (s, 3H), 3.17 (d, J = eleven.three Hz, 1H), 3.02 (ddd, J = twenty.5, 11.0, 2.9 Hz, 2H), two.91.80 (m, 2H), 2.55 (q, J = 12.five Hz, 1H), two.46.36 (m, 3H), one.84 (d, J = 13.4 Hz, 1H), one.78 (dt, J = 13.three, five.eight Hz, 1H), 1.63 (d, J = 11.four Hz, 1H), one.25.19 (m, 1H), 0.86 (t, J = seven.3 Hz, 3H). 13C NMR (125 MHz, chloroform-d) 169.40, 160.75, 142.twelve, 140.18, 136.49, 136.thirty, 125.82, 125.76, 125.38, 121.33, 121.17, 113.22, 111.70, 110.25, 108.36, 61.77, 61.72, 58.00, 53.94, 51.57, 40.84,J Med Chem. Writer manuscript; out there in PMC 2021 October 21.Chakraborty et al.Page40.17, 30.21, 24.92, 19.36, 13.03. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C26H31N2O4 435.2278; uncovered 435.2273. Methyl(E)-2-((2S,3S,12bS)-3-ethyl-8-phenyl-1,2,three,four,six,seven,12,12b-octahydroindolo[2,3 a]quinolizin-2-yl)-3-methoxyacrylate (9). 7 (77.5 mg, 0.15 mmol) was dissolved in dry toluene (0.5 mL), and also the solvent was eliminated beneath lowered stress to guarantee azeotropic removal of water residues. Dry methanol (1 mL) and dry toluene (one.5 mL) had been extra. For the resulting resolution have been extra phenylboronic acid (19.5 mg, 0.sixteen mmol, 1.1 equiv), K2CO3 (41.five mg, two equiv), and Pd(PPh3)4 (eight.7 mg, 0.05 equiv). The mixture was stirred at 80 for eight h. The solvent was evaporated under decreased strain, as well as the residue was extracted with DCM (three twenty mL). The mixed extracts had been washed with brine (3 1/3 vol), dried (Na2SO4), and concentrated to supply the crude products. The crude product was purified by flash column chromatography (gradient: 250 EtOAc in hexanes) to yield 43.three mg (65 ) of 9 as a light yellow amorphous strong.