D SiO2, three g, 100 CH2Cl2, 1 MeOH/ CH2Cl2) to afford Akt Molecular

D SiO2, three g, 100 CH2Cl2, 1 MeOH/ CH2Cl2) to afford Akt Molecular Weight coupled pyrimidine 32 as a pale white powder (0.065 g, 78 ); TLC Rf = 0.two (5 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), five.24 (s, 2H), four.98 (s, 2H), four.45 (q, J = 7.0 Hz, 1H), three.94 (s, 3H), two.71 (q, J = 7.6 Hz, 2H), 1.55 (d, J = 7.0 Hz, 3H), 1.24 (t, J = 7.six Hz, 3H); 13C NMR (125 MHz, CDCl3) 173.4, 164.five, 160.8, 156.eight, 145.7, 139.three, 132.eight, 132.five, 128.5, 127.9, 119.9, 119.1, 111.1, 109.six, 101.9, 90.8, 74.8, 55.six, 29.eight, 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 = 19.2 min, 99.six ; (b) tR = 17.five min, 99.5 . Carbamic Acid 4-[3-(2,4-Diamino-6-ethyl-pyrimidin-5-yl)-1methyl-prop-2-ynyl]-3-methoxy-biphenyl-4-yl Ester (33). As outlined by the basic 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) have been CDK11 Species reacted in DMF/Et3N (1 mL every) at 60 for 12 h. Soon after the mixture was cooled, the dark reddish brown option was concentrated, as well as the solution 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 reverse phase flash chromatography (NH2 capped SiO2, 3 g, one hundred CH2Cl2, 1 MeOH/ CH2Cl2) for biological evaluation: TLC Rf = 0.07 (five MeOH/ CH2Cl2); 1H NMR (500 MHz, MeOD) 7.53 (d, J = 7.eight Hz, 1H), 7.46 (d, J = 8.6 Hz, 2H), 7.13 (dd, J = 7.8,1.60, 1H), 7.11 (d, J = 1.three Hz, 1H), 6.85 (d, J = 8.6 Hz, 2H), four.41 (q, J = six.9 Hz, 1H), three.93 (s, 3H), 2.67 (q, J = 7.6 Hz, 2H), 1.52 (d, J = 7.0 Hz, 3H), 1.22 (t, J = 7.six Hz, 3H); 13C NMR (125 MHz, MeOD) 173.five, 166.1, 162.two, 158.3, 157.9, 142.7, 133.eight, 130.9, 129.1, 128.9, 119.9, 116.7, 110.1, 103.two, 91.4, 74.9, 56.two, 30.four, 27.9, 23.4, 13.three; 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 = 6.8 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). In line with 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.one hundred g, 0.34 mmol) were reacted in DMF/Et3N (1 mL each) at 60 for 12 h. Following the mixture was cooled, the dark reddish brown solution was concentrated, as well as the solution was purified by flash chromatography (SiO2, 5g, two 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, one hundred CH2Cl2, 1 MeOH/CH2Cl2): TLC Rf = 0.1 (5 MeOH/CH2Cl2); mp 168.2-170.8 ; 1H NMR (500 MHz, CDCl3) eight.08 (d, J = 8.55 Hz, 2H), 7.64-7.60 (m, 3H), 7.21 (dd, J = 7.8, 1.six Hz, 1H), 7.08 (d, J = 1.five Hz, 1H), 5.15 (s, 2H), four.84 (s, 2H), four.43 (q, J = 7.0 Hz, 1H), 3.93 (s, 3H), three.92 (s, 3H), two.70 (q, J = 7.6 Hz, 2H), 1.54 (d, J = 7.0 Hz, 3H), 1.23 (t, J = 7.six Hz, 3H); 13C NMR (126 MHz, CDCl3) 173.5, 167.two, 164.five, 160.8, 156.7, 145.7, 140.two, 131.9, 130.3, 129.2, 128.3, 127.2, 120.0, 109.7, 102.1, 90.9, 74.7, 55.eight, 52.4, 29.9, 26.9, 2.