D SiO2, three g, 100 CH2Cl2, 1 MeOH/ CH2Cl2) to afford Proteasome Source 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), 4.98 (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.four, 164.five, 160.8, 156.8, 145.7, 139.3, 132.eight, 132.5, 128.5, 127.9, 119.9, 119.1, 111.1, 109.6, 101.9, 90.eight, 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 = 19.2 min, 99.six ; (b) tR = 17.five 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). In accordance with the basic Sonogahisra coupling procedure, 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, ten mol ), and alkyne 23 (0.092 g, 0.31 mmol) had been reacted in DMF/Et3N (1 mL every) at 60 for 12 h. Just 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 33 as a pale white powder (0.076 g, 84 ) followed by reverse phase flash chromatography (NH2 NPY Y5 receptor Species 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.eight Hz, 1H), 7.46 (d, J = eight.6 Hz, 2H), 7.13 (dd, J = 7.8,1.60, 1H), 7.11 (d, J = 1.3 Hz, 1H), six.85 (d, J = 8.six Hz, 2H), four.41 (q, J = 6.9 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) 173.5, 166.1, 162.2, 158.three, 157.9, 142.7, 133.eight, 130.9, 129.1, 128.9, 119.9, 116.7, 110.1, 103.2, 91.four, 74.9, 56.two, 30.4, 27.9, 23.four, 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.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 accordance with the basic 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 (0.100 g, 0.34 mmol) were reacted in DMF/Et3N (1 mL every single) at 60 for 12 h. Following the mixture was cooled, the dark reddish brown resolution was concentrated, as well as the item 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, 100 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 = 8.55 Hz, 2H), 7.64-7.60 (m, 3H), 7.21 (dd, J = 7.eight, 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), 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) 173.5, 167.2, 164.five, 160.8, 156.7, 145.7, 140.2, 131.9, 130.three, 129.2, 128.3, 127.2, 120.0, 109.7, 102.1, 90.9, 74.7, 55.8, 52.4, 29.9, 26.9, 2.
