Was dissolved in dichloromethane (10.0 mL) within a one hundred mL round bottom flask and

Was dissolved in dichloromethane (10.0 mL) within a one hundred mL round bottom flask and toluene (18.2 mL) was added. To this solution was slowly added aluminum chloride (1.80 g). The reaction was stirred at reflux in an oil bath for 15 min, then cooled to space temperature and poured into ice. The organics had been extracted with ethyl acetate, and the organic layers were dried over sodium 21-Deoxycortisone-d9 manufacturer sulfate, filtered, and concentrated to provide a crude oil that was purified by column chromatography (silica gel; hexanes) to give 60 (three.024 g, 92) as a colorless oil: 1 H NMR (400 MHz, CDCl3) 7.03.04 (m, 2H), 6.95 (s, 1H), two.37 (s, 3H), 1.93 (s, 2H), 1.32 (s, 6H), 1.31 (s, 6H). six.33. Methyl 2-(1,1,3,3,6-pentamethyl-2,3-dihydro-1H-indene-5-carbonyl)pyrimidine5-carboxylate (65) To a answer of 60 (three.05 g, 16.0 mmols) and methyl 2-(chlorocarbonyl)pyrimidine-5carboxylate 63 (three.19 g, 15.9 mmols) in dichloromethane (35 mL) within a one hundred mL round bottom flask was gradually added aluminum chloride (five.6 g) as well as the resulting mixture was stirred in an oil bath at reflux for 15 min. The reaction solution was cooled to space temperature and quenched by pouring onto 100 mL of an ice water resolution. The resolution was extracted with ethyl acetate, along with the combined organic layers had been dried over sodium sulfate, filtered, and concentrated to offer a crude product that was purified by column chromatography (silica gel; 1:9 ethyl acetate:hexanes to 1:four ethyl acetate:hexane) to offer pure 65 (1.5869 g, 28) as an orange, Benzbromarone-d5 Epigenetic Reader Domain crystalline strong (98.103.2 C): 1 H NMR (400 MHz, CDCl3) 9.42 (s, 2H), 7.17 (s, 1H), 7.03 (s, 1H), four.02 (s, 3H), two.44 (s, 3H), 1.92 (s, 2H), 1.31 (s, 6H), 1.23 (s, 6H); 13 C NMR (one hundred.6 MHz, CDCl3) 193.two, 166.0, 163.five, 158.five, 156.6, 148.six, 138.9, 133.5, 126.1, 126.0, 124.1, 56.five, 52.9, 42.eight, 42.2, 31.three, 31.1, 21.3. ES-MS (M Na) calcd for C21 H24 N2 O3 Na 375.1685, identified 375.1668. 6.34. Methyl 4-(1,1,three,three,6-pentamethyl-2,3-dihydro-1 H-indene-5-carbonyl)benzoate (66) To a resolution of 60 (4.8058 g, 25.five mmols) and methyl 4-(chlorocarbonyl)benzoate 64 (3.214 g, 16.18 mmols) in dichloromethane (35 mL) within a 100 mL round bottom flask was slowly added aluminum chloride (5.54 g) as well as the resulting mixture was stirred in an oil bath at reflux for 15 min. The reaction resolution was cooled to area temperature and quenched by pouring onto 100 mL of an ice water answer. The remedy was extracted with ethyl acetate, along with the combined organic layers had been dried over sodium sulfate, filtered, and concentrated to provide a crude solution that was purified by column chromatography (150 mL silica gel; 2.five ethyl acetate:hexanes) to provide pure 66 (4.4007 g, 77.six) as a white, crystalline solid (120.222.2 C): 1 H NMR (400 MHz, CDCl3) 8.11 (dd, J = 6.eight, two.0, 2H), 7.86 (dd, J = six.8, two.0, 2H), 7.05 (s, 1H), 7.03 (s, 1H), three.95 (s, 3H), two.35 (s, 3H), 1.94 (s, 2H), 1.34 (s, 6H), 1.26 (s, 6H); 13 C NMR (100.6 MHz, CDCl3) 198.1, 166.three, 154.5, 148.four, 141.eight, 136.3, 136.two, 133.four, 129.9, 129.5, 125.three, 123.7, 56.5, 52.4, 42.6, 42.two, 31.3, 31.two, 20.three. ES-MS (M H) calcd for C23 H27 O3 351.1960, found 351.1959.Int. J. Mol. Sci. 2021, 22,28 of6.35. Methyl 4-(1-(1,1,three,three,6-pentamethyl-2,3-dihydro-1 H-inden-5-yl)vinyl)benzoate (67) To a solution of diisopropylamine (0.66 mL, four.71 mmols) in THF (2 mL) within a one hundred mL round bottom flask was added a 1.6 M option of n-butyl lithium in hexanes (2.7 mL, four.32 mmols) at space temperature with stirring. Following 15 min of stirring, methyltriphenylphosphonium bromide (1.15 g, three.22 mmol) was added.