91% |
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(8S,9S)-9-epi-Azido-9-dehydroxy quinine (1.045 g, 3.0 mmol)was dissolved in a mixture of tert-butanol and water (12 mL, 1:1,v/v), and 2-(TMS-ethynyl)-pyrimidine (631 mg, 3.58 mmol,1.2 equiv) was added. Then pyridine (0.25 mL, 3.1 mmol,1.0 equiv), CuSO4.5H2O (290 mg, 1.25 mmol 0.4 equiv), sodiumascorbate (494 mg, 2.49 mmol, 0.8 equiv) and K2CO3 (806 mg,5.83 mmol, 1.9 equiv) were added. The suspension was stirred atroom temperature for 3 days. Then saturated aqueous Na2S solutionwas added and the mixture stirred for an additional 0.5 h,while dark brown precipitate formed. The mixture was filteredthrough Celite and washed with CH2Cl2. The filtrate was washedwith water, dried over Na2SO4 and evaporated. Chromatographyon silica gel (CHCl3/MeOH, 10:1 v/v.) gave white crystalline solid(1.233 g, 91%). M.p.: 248.53-250.7 C, [a]D21 = -182 (c 0.91, CH2Cl2).1H NMR (600 MHz, CDCl3) delta 8.81 (d, J = 4.4 Hz, 1H), 8.69 (d,J = 4.7 Hz, 2H), 8.15 (s, 1H), 7.99 (d, J = 9.1 Hz, 1H), 7.603-7.57(m, 1H), 7.50 (d, J = 4.7 Hz, 1H), 7.34 (dd, J = 9.1, 2.2 Hz, 1H), 7.11(t, J = 4.9 Hz, 1H), 6.51 (d, J = 11.3 Hz, 1H), 5.91 (ddd, J = 17.5,10.7, 6.9 Hz, 1H), 5.08 (d, J = 9.4 Hz, 1H), 5.06 (d, J = 18.2 Hz, 1H),3.94 (s, 3H), 3.933-3.88 (m, 1H), 3.493-3.42 (m, 1H), 3.14 (dd,J = 14.0, 10.1 Hz, 1H), 2.74 (dd, J = 14.3, 4.1 Hz, 1H), 2.713-2.65(m, 1H), 2.343-2.27 (m, 1H), 1.96 (t, J = 11.9 Hz, 1H), 1.793-1.76(m, 1H), 1.653-1.54 (m, 2H), 0.94 (dd, J = 14.1, 7.1 Hz, 1H)(Fig. S8a, SI).13C NMR (151 MHz, CDCl3) delta 159.1, 158.8, 157.4, 147.3, 147.2,145.1, 141.4, 138.8, 132.0, 128.2, 123.4, 122.6, 119.5, 119.2,114.8, 100.8, 61.0, 58.0, 56.1, 55.9, 41.1, 39.1, 27.74, 27.72, 27.70(Fig. S8a, SI).HRMS (ESI) Calc. for [C26H27N7O+H]+: 454.2350, found:454.2353 (Fig. S5, SI). |