Ite powder (0.040 g, 77 ) followed by reverse phase flash chromatography (NH2 Gentamicin, Sterile custom synthesis capped SiO2, three g, 100 CH2Cl2) for biological CDCP1 Protein Species evaluation: TLC Rf = 0.1 (5 MeOH/ CH2Cl2); mp 129.3-131.1 ; 1H NMR (500 MHz, CDCl3) 7.59- 7.55 (m, 4H), 7.48 (d, J = 8. Hz, 2H), 7.42 (dd, J = 7.six, 7.6 Hz, 2H), 7.42 (dd, J = 7.6, 7.6 Hz, 1H), 7.36-7.30 (m, 1H), 5.13 (s, 2H), four.87 (s, 2H), four.07 (q, J = 7.1 Hz, 1H), 2.69 (q, J = 7.6 Hz, 2H), 1.61 (d, J = 7.1 Hz, 3H), 1.23 (t, J = 7.6 Hz, 3H); 13C NMR (125 MHz, CDCl3) 173.7, 164.five, 160.9, 142.six, 140.9, 140.0, 128.9, 127.6, 127.5, 127.four, 127.3, 101.8, 90.eight, 75.6, 32.9, 29.9, 24.9, 12.eight; IR (neat cm-1) 3415, 3304, 3162, 2973, 2927, 2871, 1618, 1547, 1436, 1281, 761, 692, 479; HRMS (ESI, M+ + H) m/z 343.1907 (calculated for C22H23N4, 343.1917). HPLC (a) tR = 19.1 min, 98.9 ; (b) tR = 17.3 min, 98.5 . 6-Ethyl-5-[3-(6-phenyl-pyridin-3-yl)-but-1-ynyl]-pyrimidine-2,4diamine (46). According to the general Sonogahisra coupling process, ethyl-iodopyrimidine (0.071 g, 0.27 mmol), CuI (0.dx.doi.org/10.1021/jm401916j | J. Med. Chem. 2014, 57, 2643-Journal of Medicinal Chemistryg, 0.06 mmol, 21 mol ), Pd(PPh3)2Cl2 (0.019 g, 0.03 mmol, ten mol ), and alkyne 43 (0.061 g, 0.three mmol) had been reacted in DMF/Et3N (1 mL every single) at 60 for 12 h. Immediately after the mixture was cooled, the dark reddish brown solution was concentrated, and the product was purified by flash chromatography (SiO2, 5 g, two MeOH/CHCl3) to afford coupled pyrimidine 46 as a pale white hygroscopic strong (0.070 g, 75 ), followed by reverse phase flash chromatography (NH2 capped SiO2, three g, 100 CH2Cl2, 1 MeOH/CH2Cl2) for biological evaluation: TLC Rf = 0.1 (5 MeOH/CH2Cl2); 1H NMR (500 MHz, CDCl3) 8.72 (d, J = 2.1 Hz, 1H), 7.96 (d, J = 7.two Hz, 2H), 7.81 (dd, J = 8.2, 2.three Hz, 1H), 7.70 (d, J = 8.1 Hz, 1H), 7.46 (dd, J = 7.five, 7.five Hz, 1H), 7.46 (dd, J = 7.5, 7.5 Hz, 1H), 7.41-7.38 (m, 1H), five.09 (s, 2H), 4.84 (s, 2H), four.11 (q, J = 7.1 Hz, 1H), 2.68 (q, J = 7.six Hz, 2H), 1.63 (d, J = 7.1 Hz, 3H), 1.22 (t, J = 7.six Hz, 3H); 13C NMR (125 MHz, CDCl3) 173.9, 164.4, 160.9, 156.four, 148.6, 139.3, 137.3, 135.3, 129.1, 128.9, 127.1, 120.six, 100.6, 90.four, 76.2, 30.six, 29.9, 24.7, 12.7; IR (neat cm-1) 3469, 3308, 3166, 2972, 2931,1730, 1542, 1435, 1238, 1018, 739, 692; HRMS (ESI, M+ + H) m/z 344.1865 (calculated for C21H21N5, 344.1875). HPLC (a) tR = 6.9 min, 99.5 ; (b) tR = 7.1 min, 99.2 . 6-Ethyl-5-[3-(6-p-tolyl-pyridin-3-yl)-but-1-ynyl]-pyrimidine-2,4-diamine (47). In accordance with the common Sonogahisra coupling procedure, ethyl-iodopyrimidine (0.059 g, 0.23 mmol), CuI (0.009 g, 0.05 mmol, 21 mol ), Pd(PPh3)2Cl2 (0.016 g, 0.022 mmol, 10 mol ), and alkyne 44 (0.06 g, 0.27 mmol) had been reacted in DMF/Et3N (1 mL each and every) at 60 for 12 h. Following the mixture was cooled, the dark reddish brown answer was concentrated, along with the solution was purified by flash chromatography (SiO2, 5g, two MeOH/CHCl3) to afford coupled pyrimidine 47 as a pale white powder (0.063 g, 76 ) followed by reverse phase flash chromatography (NH2 capped SiO2, 3g, 100 CH2Cl2, 1 MeOH/CH2Cl2) for biological evaluation: TLC Rf = 0.1 (5 MeOH/CH2Cl2); mp 144-146.1 ; 1H NMR (500 MHz, CDCl3) 8.74 (d, J = 2.2 Hz, 1H), 7.91 (d, J = eight.1 Hz, 2H), 7.82 (dd, J = 8.2, two.3 Hz, 1H), 7.71 (d, J = 8.2 Hz, 1H), 7.30 (d, J = 8.6 Hz, 2H), 5.25 (s, 2H), five.07 (s, 2H), 4.13 (q, J = 7.1 Hz, 1H), two.72 (q, J = 7.six Hz, 2H), 2.42 (s, 3H), 1.66 (d, J = 7.1 Hz, 3H), 1.26 (t, J = 7.6 Hz, 3H); 13C NMR (125 MHz, CDCl3) 173.9, 164.5, 161.1, 156.4, 148.5, 139.1.