Tio–TLC separates these isomers after 4 elutions in 1 ethyl acetate:hexanes (41 Rf 0.five and 40 Rf 0.45). This crude oil was purified by column chromatography (0.7 to 1 to five ethyl acetate in hexanes) to give 40 (9.6225 g, 45.three) as a pale yellow oil: 1 H NMR (400 MHz, CDCl3) 8.09 (d, J = two.4, 1H), 8.06 (dd, J = 8.8, two.eight, 1H), 6.84 (d, J = 9.2, 1H), 3.83 (d, J = six.four, 2H), 3.35 (hept, J = 6.eight, 1H), 2.16 (nonet, J = 6.eight, 1H), 1.25 (d, J = 6.eight, 6H), 1.07 (d, J = six.eight, 6H); 13 C NMR (one hundred.six MHz, CDCl3) 161.five, 141.two, 138.0, 123.three, 121.9, 110.2, 28.three, 27.0, 22.1, 19.two; IR (neat) 2962, 1588, 1512, 1336, 1251 cm- 1 ; ES-MS (M Na) calcd for C13 H19 NO3 Na 260.1263, found 260.1256.Int. J. Mol. Sci. 2021, 22,22 of6.16. Methyl 6-((4-isobutoxy-3-isopropylphenyl)amino)nicotinate (45) A option of 1-isobutoxy-2-isopropyl-4-nitrobenzene (40) (two.0064 g, eight.455 mmols) in ethyl acetate (183 mL) was passed through a ten Pd/C cartridge at 1.0 mL/min within the ThalesNano H-cubeat 65 C and 2 bar pressure. The resulting resolution was concentrated in vacuo to give 4-isobutoxy-3-isopropylaniline (42) (1.7057 g, 97) as a yellow oil that was made use of devoid of further purification: 1 H NMR (400 MHz, CDCl3) 6.66 (d, J = eight.four, 1H), six.63 (d, J = two.8, 1H), 6.50 (dd, J = eight.4, two.8, 1H), three.64 (d, J = six.4, 2H), three.63 (br s, 1H), three.31 (hept, J = six.8, 1H), 2.09 (nonet, J = six.8, 1H), 1.20 (d, J = 6.eight, 6H), 1.03 (d, J = 6.eight, 6H); 13 C NMR (100.6 MHz, CDCl) 149.8, 138.9, 138.2, 114.three, 113.1, 112.6, 75.two, 28.5, 26.eight, 22.6, 3 19.four. To a option of 42 (1.783 g, eight.60 mmols) and methyl 6-chloronicotinate (1.6567 g, 9.655 mmols) in dioxane (15.0 mL) was added para-toluenesulfonic acid monohydrate (1.7977 g, 9.45 mmols) and also the reaction was refluxed overnight in an oil bath at 111 C. The reaction was cooled to room temperature, and then the mixture was poured into water, TFC 007 web extracted with ethyl acetate, and the JH-XVII-10 Autophagy organic layers were washed with brine, dried more than sodium sulfate and concentrated to offer a crude oil that was purified by column chromatography (150 mL SiO2 , six ethyl acetate:hexanes) to provide 45 (1.9259 g, 65.4) as a white crystalline strong, m.p. 12324 C: 1 H NMR (400 MHz, CDCl3) 8.76 (dd, J = 2.4, 0.8, 1H), eight.00 (dd, J = 8.eight, 2.4, 1H), 7.77 (br s, 1H), 7.11 (s, 1H), 7.09 (dd, J = 7.6, 2.8, 1H), 6.82 (dd, J = 7.6, 0.eight, 1H), 6.65 (dd, J = 8.8, 0.eight, 1H), 3.86 (s, 3H), three.74 (d, J = six.0, 2H), 3.36 (hept, J = six.8, 1H), two.13 (nonet, J = 6.eight, 1H), 1.22 (d, J = 6.8, 6H), 1.06 (d, J = 6.8, 6H); 13 C NMR (100.six MHz, CDCl3) 166.1, 160.1, 154.1, 151.1, 138.9, 138.4, 131.0, 122.two, 121.9, 115.9, 111.six, 105.five, 51.6, 28.4, 26.9, 22.5, 19.three; IR (neat) 3235, 2953, 1721, 1612, 1598, 1496, 1277, 1115 cm- 1 ; ES-MS (M H) calcd for C20 H27 N2 O3 343.2022, located 343.2024. six.17. Methyl 2-((4-isobutoxy-3-isopropylphenyl)amino)pyrimidine-5-carboxylate(46) To a solution of 42 (1.7057 g, 8.23 mmols) and methyl 2-chloropyrimidine-5-carboxylate (1.5852 g, 9.1859 mmols) in dioxane (15.0 mL) was added para-toluenesulfonic acid monohydrate (1.7197 g, 9.04 mmols) along with the reaction was refluxed overnight in an oil bath at 111 C. The reaction was cooled to area temperature, and after that the mixture was poured into water, extracted with ethyl acetate, along with the organic layers were washed with brine, dried more than sodium sulfate, and concentrated to offer a crude oil that was purified by column chromatography (150 mL SiO2 , 10 ethyl acetate:hexanes) to provide 46 (two.1821 g, 71.3) as a white crystalline strong, m.p. 12224.2 C: 1 H NMR (400 M.