D SiO2, 3 g, one hundred CH2Cl2, 1 MeOH/ CH2Cl2) to afford 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 = 7.8, 1.7 Hz, 1H), 7.05 (d, J = 1.7 Hz, 1H), five.24 (s, 2H), 4.98 (s, 2H), 4.45 (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, 164.5, 160.eight, 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.eight, 55.6, 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, (Macrophage migration inhibitory factor (MIF) Inhibitor Purity & Documentation calculated for C24H24N5O, 398.1981). HPLC (a) tR = 19.2 min, 99.six ; (b) tR = 17.5 min, 99.five . Carbamic Acid 4-[3-(two,4-Diamino-6-ethyl-pyrimidin-5-yl)-1methyl-prop-2-ynyl]-3-methoxy-biphenyl-4-yl Ester (33). In line with the basic Sonogahisra MMP-3 Formulation 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 and every) at 60 for 12 h. Immediately after the mixture was cooled, the dark reddish brown option was concentrated, plus the item was purified by flash chromatography (SiO2, 5 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, three 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 = 7.8 Hz, 1H), 7.46 (d, J = 8.6 Hz, 2H), 7.13 (dd, J = 7.eight,1.60, 1H), 7.11 (d, J = 1.three Hz, 1H), six.85 (d, J = eight.six Hz, 2H), 4.41 (q, J = 6.9 Hz, 1H), three.93 (s, 3H), two.67 (q, J = 7.6 Hz, 2H), 1.52 (d, J = 7.0 Hz, 3H), 1.22 (t, J = 7.6 Hz, 3H); 13C NMR (125 MHz, MeOD) 173.five, 166.1, 162.two, 158.three, 157.9, 142.7, 133.8, 130.9, 129.1, 128.9, 119.9, 116.7, 110.1, 103.two, 91.4, 74.9, 56.2, 30.4, 27.9, 23.four, 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.eight min, 98 ; (b) tR = 8.two 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 common Sonogahisra coupling procedure, ethyliodopyrimidine (0.061g, 0.23 mmol), CuI (0.009 g, 0.05 mmol, 21 mol ), Pd(PPh3)2Cl2 (0.016 g, 0.023 mmol, 10 mol ), and alkyne 24 (0.one hundred g, 0.34 mmol) were reacted in DMF/Et3N (1 mL every) at 60 for 12 h. Immediately after the mixture was cooled, the dark reddish brown answer was concentrated, plus the product 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, three g, one hundred CH2Cl2, 1 MeOH/CH2Cl2): TLC Rf = 0.1 (five MeOH/CH2Cl2); mp 168.2-170.8 ; 1H NMR (500 MHz, CDCl3) eight.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), 4.84 (s, 2H), 4.43 (q, J = 7.0 Hz, 1H), three.93 (s, 3H), three.92 (s, 3H), 2.70 (q, J = 7.6 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, 167.2, 164.five, 160.8, 156.7, 145.7, 140.two, 131.9, 130.3, 129.2, 128.three, 127.2, 120.0, 109.7, 102.1, 90.9, 74.7, 55.eight, 52.four, 29.9, 26.9, 2.