D SiO2, three g, 100 CH2Cl2, 1 MeOH/ CH2Cl2) to afford coupled pyrimidine

D SiO2, three g, 100 CH2Cl2, 1 MeOH/ CH2Cl2) to afford coupled pyrimidine 32 as a pale white powder (0.065 g, 78 ); TLC Rf = 0.two (five MeOH/CH2Cl2); mp 130.9-133.1 ; 1H NMR (500 MHz, CDCl3) 7.73-7.70 (m, 2H), 7.69-7.63 (m, 3H), 7.19 (dd, J = 7.eight, 1.7 Hz, 1H), 7.05 (d, J = 1.7 Hz, 1H), 5.24 (s, 2H), 4.98 (s, 2H), 4.45 (q, J = 7.0 Hz, 1H), 3.94 (s, 3H), two.71 (q, J = 7.six Hz, 2H), 1.55 (d, J = 7.0 Hz, 3H), 1.24 (t, J = 7.six Hz, 3H); 13C NMR (125 MHz, CDCl3) 173.four, 164.5, 160.8, 156.eight, 145.7, 139.3, 132.8, 132.five, 128.5, 127.9, 119.9, 119.1, 111.1, 109.6, 101.9, 90.8, 74.eight, 55.six, 29.8, 26.9, 23.0, 12.7; IR (neat cm-1) 3464, 3428, 3332, 3188, 3029, 2925, 2775, 2546, 1651, 1548, 1445, 1286, 1008, 735, 557; HRMS (DART, M+ + H) m/z 398.1983, (calculated for C24H24N5O, 398.1981). HPLC (a) tR = 19.two min, 99.six ; (b) tR = 17.5 min, 99.five . Carbamic Acid 4-[3-(2,4-Diamino-6-ethyl-pyrimidin-5-yl)-1methyl-prop-2-ynyl]-3-methoxy-biphenyl-4-yl Ester (33). As PI3K drug outlined by the general Sonogahisra coupling process, ethyl-iodopyrimidine (0.055 g, 0.21 mmol), CuI (0.008 g, 0.04 mmol, 21 mol ), Pd(PPh3)2Cl2 (0.015 g, 0.021 mmol, 10 mol ), and alkyne 23 (0.092 g, 0.31 mmol) had been reacted in DMF/Et3N (1 mL each) at 60 for 12 h. Soon after the mixture was cooled, the dark reddish brown answer was concentrated, along with the item was purified by flash chromatography (SiO2, five g, two MeOH/CHCl3) to afford coupled pyrimidine 33 as a pale white powder (0.076 g, 84 ) followed by Opioid Receptor Storage & Stability reverse phase flash chromatography (NH2 capped SiO2, three g, one hundred CH2Cl2, 1 MeOH/ CH2Cl2) for biological evaluation: TLC Rf = 0.07 (5 MeOH/ CH2Cl2); 1H NMR (500 MHz, MeOD) 7.53 (d, J = 7.8 Hz, 1H), 7.46 (d, J = eight.six Hz, 2H), 7.13 (dd, J = 7.eight,1.60, 1H), 7.11 (d, J = 1.3 Hz, 1H), 6.85 (d, J = eight.six Hz, 2H), 4.41 (q, J = six.9 Hz, 1H), three.93 (s, 3H), 2.67 (q, J = 7.six Hz, 2H), 1.52 (d, J = 7.0 Hz, 3H), 1.22 (t, J = 7.6 Hz, 3H); 13C NMR (125 MHz, MeOD) 173.5, 166.1, 162.2, 158.3, 157.9, 142.7, 133.8, 130.9, 129.1, 128.9, 119.9, 116.7, 110.1, 103.2, 91.4, 74.9, 56.2, 30.four, 27.9, 23.4, 13.3; IR (neat cm-1) 3477, 3386, 3336, 3195, 2970, 2929, 2873, 2361, 2023, 1603, 1437, 1217, 1027, 813. HRMS (ESI, M+ + Na) m/z 455.1947 (calculated for C24H26N5NaO3, 455.1928). HPLC (a) tR = six.8 min, 98 ; (b) tR = 8.2 min, 98.7 . 4-[3-(two,4-Diamino-6-ethyl-pyrimidin-5-yl)-1-methyl-prop-2ynyl]-3-methoxy-biphenyl-4-carboxylic Acid Methyl Ester (34). Based on the basic Sonogahisra coupling process, ethyliodopyrimidine (0.061g, 0.23 mmol), CuI (0.009 g, 0.05 mmol, 21 mol ), Pd(PPh3)2Cl2 (0.016 g, 0.023 mmol, ten mol ), and alkyne 24 (0.100 g, 0.34 mmol) have been reacted in DMF/Et3N (1 mL every) at 60 for 12 h. Following the mixture was cooled, the dark reddish brown remedy was concentrated, along with the item was purified by flash chromatography (SiO2, 5g, 2 MeOH/CHCl3) to afford coupled pyrimidine 34 as a pale white powder (0.077 g, 77 ) followed by reverse phase flash chromatography (NH2 capped SiO2, 3 g, 100 CH2Cl2, 1 MeOH/CH2Cl2): TLC Rf = 0.1 (five MeOH/CH2Cl2); mp 168.2-170.eight ; 1H NMR (500 MHz, CDCl3) 8.08 (d, J = eight.55 Hz, 2H), 7.64-7.60 (m, 3H), 7.21 (dd, J = 7.8, 1.six Hz, 1H), 7.08 (d, J = 1.5 Hz, 1H), 5.15 (s, 2H), four.84 (s, 2H), 4.43 (q, J = 7.0 Hz, 1H), 3.93 (s, 3H), 3.92 (s, 3H), two.70 (q, J = 7.six Hz, 2H), 1.54 (d, J = 7.0 Hz, 3H), 1.23 (t, J = 7.6 Hz, 3H); 13C NMR (126 MHz, CDCl3) 173.five, 167.two, 164.5, 160.eight, 156.7, 145.7, 140.2, 131.9, 130.three, 129.two, 128.three, 127.two, 120.0, 109.7, 102.1, 90.9, 74.7, 55.8, 52.four, 29.9, 26.9, 2.