Etate/hexane; 20 ethyl acetate/hexane to provide pure 76 (0.4293 g, 57.6) as a colorless, waxy solid, mp 112.1-113.9 C: 1 H NMR (400 MHz, CDCl3) eight.02 (dd, J = eight.4, two.0, 2H), 7.44 (dd, J = eight.4, two.0, 2H), 7.27 (d, J = 8.four, 1H), 7.24 (d, J = two.0, 1H), 7.08 (dd, J = eight.0, two.0, 1H), 5.54 (d, J = 1.two, 1H), 5.48 (d, J = 1.two, 1H), 3.93 (s, 3H), 1.70 (s, 4H), 1.30 (s, 6H), 1.24 (s, 6H); 13C NMR (one hundred.six MHz, CDCl3) 166.9, 149.3, 146.3, 144.8, 144.six, 137.five, 129.three, 129.1, 128.two, 126.four, 126.3, 125.3, 114.9, 52.0, 35.0, 34.9, 34.2, 34.1, 31.7. ES-MS (M H) calcd for C24 H29 O2 349.2168, found 349.2168. six.46. 4-(1-(5,five,eight,8-tetramethyl-5,six,7,8-tetrahydronaphthalen-2-yl)vinyl)benzoic acid (27) Compound 27 was synthesized in accordance with the method of Boehm and co-workers. Compound 76 (1.5597 g, four.476 mmols) was suspended in methanol (28.0 mL) along with a option of potassium hydroxide (0.7420 g, 13.22 mmols) in water (1.08 mL) was added. The reaction was refluxed in an oil bath at 85 C. Immediately after 70 min of reflux, the remedy was cooled to area Caroverine Neuronal Signaling temperature plus the crude item was precipitated with 1 N hydrochloric acid (200 mL) and filtered to offer (1.4655 g, 97.9) of crude 27. It was then purified by column chromatography (150 mL SiO2 , with 2.five ethyl acetate/hexanes; five ethyl acetate/hexane; 20 ethyl acetate/hexane) to provide pure 27 (1.3152 g, 87.9) as tint yellow solid, mp 211.3-215.eight C: 1 H NMR (400 MHz, CDCl3) 10.33 (br s, 1H), 8.ten (dd, J = 6.eight, 2.0, 2H), 7.48 (dd, J = six.eight, two.0, 2H), 7.29 (d, J = eight.four, 1H), 7.25 (d, J = two.0, 1H), 7.08 (dd, J = eight.4, two.0, 1H), 5.57 (d, J = 0.8, 1H), 5.51 (d, J = 1.2, 1H), 1.70 (s, 4H), 1.31 (s, 6H), 1.25 (s, 6H); 13C NMR (one hundred.six MHz, CDCl3) 172.1, 149.3, 147.2, 144.9, 144.7, 137.4, 130.0, 128.four, 128.three, 126.4, 126.3, 125.three, 115.2, 35.1, 35.0, 34.two, 34.1, 31.8. ES-MS- (M-H)- calcd for C23 H25 O2 333.1855, found 333.1872. six.47. Methyl 2-(1-(5,5,eight,8-tetrahydronaphthalen-2-yl)vinyl)pyrimidine-5-carboxylate (77) A solution of 73 (five.2603 g, 14.926 mmols) in toluene (53.0 mL) inside a 250 mL round bottom flask was cooled to -10 C beneath nitrogen with stirring as well as a three.0 M resolution methyl magnesium chloride (six.56 mL, 19.68 mmols) was added dropwise. Just after 15 min of stirring, the reaction solution was warmed to area temperature and stirred for an extra 35 min. The reaction mixture was then quenched by the slow addition of 1.0 N hydrochloric acid (35.0 mL, 35.0 mmols). The mixture was extracted with ethyl acetate, along with the organic layers had been washed with water and saturated sodium chloride, then dried over sodium sulfate, filtered, and concentrated within a 300 mL round bottom flask to offer a crude GW-870086 manufacturer alcohol product that was made use of without the need of further purification. The alcohol item was dissolved in toluene (110.0 mL) and p-TsOH two O (5.7782 g, 33.56 mmol) was added, plus the reaction flask was fitted having a Dean Stark trap and a water condenser. The vessel was evacuatedInt. J. Mol. Sci. 2021, 22,32 ofand back-filled with nitrogen 3 occasions, and then heated to reflux in an oil bath at 130 C and stirred for three h, during which time water collected inside the Dean Stark trap. The reaction was cooled to area temperature, poured into water, and extracted with ethyl acetate. The combined organic layers were dried more than sodium sulfate, filtered, and concentrated to give a crude solution that was purified by column chromatography (silica gel; 2.5 ethyl acetate:hexanes to five ethyl acetate:hexanes) to give pure 77 (0.2936 g, five.6) as a white solid (171.374.1 C): 1 H NMR (.