20% |
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4-((N-Ethyl-N-Ferrocenylaminocarbonyl)oxymethyl)-2-phenylboronic acid pina- col ester (prodrug A):Aminoferrocene (0.40 g, 1.98 mmol) and acetaldehyde (0.1 mL, 1.98 mmol) were dissolved on methanol (10 mL) and refluxed for 2 h. Then, Na[B(CN)H3] (0.12 g, 1.98 mmol) dissolved in MeOH (10 mL) was slowly added. The mixture obtained was acidified with HCI (2 mL, 1 M in water) and left stirring for 30 min. Afterwards, the solvent was removed in vacuum (0.01 mbar) and the rest was mixed with triphosgene (0.59 g, 1.98 mmol) in toluene (25 mL). The suspension obtained was refluxed for 1 h, cooled down to 22°C and then mixed with solution of 4-(hydroxymethyl)phenylboronic acid pinacol ester (0.46 g, 1.98 mmol) in toluene (10 mL). The resulting solution was heated to 120°C and stirred at these conditions for 6 h. Then, the solvent was removed in vacuum (0.01 mbar) and the crude product was purified by column chromatography on silica gel using hexane containing 5percent of acetone as eluent. Yield 0.20 g (20percent). Rf= 0.5 (silica, eluent - hexane / acetone, 5/1 , v/v). 1H NMR (400 MHz, acetone- d6), delta in ppm: 1.27 (t, 3H), 1.33 (s, 12H), 3.77 (q, 2H), 4.00 (s, 2H), 4.13 (s, 5H), 4.53 (m, 2H), 5.22 (s, 2H), 7.46 (d, 1 H), 7.77 (d, 2H). 13C NMR (100.55 MHz, acetone-d6), delta in ppm: 14.4, 25.3, 45.8, 62.8, 65.1 , 66.9, 67.5, 69.8, 84.6, 127.8, 128.1 , 135.7 (two overlapping peaks), 139.1 , 141.2. FAB MS: calculated for C26H32BN04Fe 489.2, found 489.2 m/z. C, H, N analysis: calculated for C26H32BN04Fe - C 63.8percent; H 6.6percent; N 2.9percent; found - C 63.8percent; H 6.8percent; N 2.9percent. IR spectra (in KBr), wave number in cm'1: 3101 , 2973, 1696, 1623. |