CAfter cooling, the orange remedy was diluted with EtOAc and washed twice that has a water/saturated NaHCO3 soAn analytical sample was obtained by crystallization from MeCN. TLC Rf 0.61, mp, decomposed above 180, 1H NMR ? seven.06, six.91, 6.79, six.18, 3.77 3.76, three.70, 2.54, one.12, 13C NMR ? 171.5, 164.five, 161.two, 153.1, 150.six, 126.three, 115.0, 111.eight, 111.four, 95.2, 87.9, 76.2, 55.8, 55.3, 28.9, twenty.6, 12.6, HRFAB 319.1736, HPLC LDE225 Smoothened Inhibitors tR six.13 min, 96.0%, tR 8.85 min, 97.0%. 2,4 Diamino 5 iodo six n propylpyrimidine To a flame dried 200 mL flask was additional two,4 diamino 6 n propylpyrimidine in MeOH followed by dropwise addition of one.0 M ICl remedy in CH2Cl2. The remedy was stirred at 25 for 18 h then the solvent removed below lowered stress. The resulting viscous oil was stirred in Et2O for 2 h. The resulting sound was filtered off and washed with Et2O to afford the HCl salt as a yellow solid. The crude salt was suspended in one.0 N NaOH and stirred at 25 for two h. The reliable was filtered, washed with cold water followed by cold Et2O, and dried beneath vacuum to afford the products like a brown powder. An analytical sample was ready by recrystallization from MeCN to provide title compound as colorless crystals. Rf 0.63, mp, 187.0 188.five, 1H NMR ? 6.32, six.03, 2.53, one.58, 0.93, 13C NMR ? 170.1, 163.six, 163.0, 64.five, 42.seven, 21.
6, 14.four, HRMS m/z 279.0106. two,4 Diamino 5 six npropylpyrimidine To an oven dried eight mL vial was extra two,4 diamino 5 iodo six n propylpyrimidine, Pd2Cl2, CuI. Degassed anhydrous DMF and triethylamine have been additional, followed by acetylene 14 in DMF.
The vial was sealed plus the mixture degassed by one cycle of freeze pump thaw. The mixture was stirred at 60 for 17 h. The reaction mixture was then added to a kinase inhibitors separatory funnel containing EtOAc. The natural and organic layer was washed twice by using a water/saturated NaHCO3 resolution and after that brine. The natural and organic layer was then dried more than MgSO4 and concentrated below lowered strain. The residue was preloaded onto silica gel and purified by flash chromatography, eluting with straight EtOAc to afford the coupled pyrimidine 18 like a pale yellow powder. An analytical sample was obtained by crystallization from MeCN. TLC Rf 0.63, mp, decomposed above 158.five, 1H NMR ? seven.twelve, 6.82, six.80, 5.16, 4.76, three.85, 3.80, two.68, one.73, 0.99, 13C NMR ? 172.1, 164.four, 160.five, 153.seven, 151.one, 126.5, 115.4, 112.0, 111.one, 96.2, 91.4, 75.four, 55.9, 55.7, 38.three, 21.88, 21.0, 14.1, HRMS m/z 327.1826, HPLC tR seven.19 min, 98.2%, tR 9.93 min, 99.0%. two,four Diamino five 6 ethylpyrimidine To an oven dried eight mL screw cap vial was extra alkyne 19, 2,four diamino 6 ethyl 5 iodopyrimidine, CuI, and Pd2Cl2. Degassed anhydrous DMF and degassed anhydrous triethylamine were additional, plus the mixture was degassed after using the freeze pump thaw method.