Dimethoxy-3-isochromanone 1 in 20 mL of formic acid. The mixture was heated to 90 for 2 h after which hydrolyzed by the addition of 10 mL of water. The aqueous layer was extracted 3 instances with ethyl acetate. The organic layer was washed twice with brine, dried more than magnesium sulfate, filtered, and evaporated to dryness to yield four.18 g of crude material. Trituration in a mixture of isopropylic ether/AcOEt resulted in three.2 g (78 ) of compound 2 as an off-white strong. 1 H NMR (CDCl3) 7.07 (s, 1H), six.80 (s, 1H), 6.58 (s, 1H), six.47 (s, 1H), 3.99 (s, 2H), 3.90 (s, 3H), three.88 (s, 3H), 3.79 (s, 3H), 3.68 (s, 3H), 3.61 (s, 2H). 3.six.4. Synthesis of Tert-butyl 2-(2-[(2-bromo-4,5-dimethoxyphenyl)methyl]-4,5-dimethoxy phenyl) Acetate (DIV879, Figure three) A total of 1.six g (7.35 mmol, 3 eq.) O-tert-butyl-N,N-diisopropylisourea was added in portions over a period of 2 h to a answer of 1.04 g (two.45 mmol) of acid 2 in 30 mL of dichloromethane at room temperature. The mixture was stirred overnight and filtered to eliminate insoluble materials. The filtrate was evaporated below vacuum along with the residue purified twice by chromatography on silica gel (1-eluant: CH2Cl2/AcOEt 85/15, 2-eluant: heptane/AcOEt gradient) to receive 749 mg (63 ) of DIV879 as an off-white strong. 1 H NMR (CDCl3) 7.05 (s, 1H), 6.78 (s, 1H), six.55 (s, 1H), 6.43 (s, 1H), 3.96 (s, 2H), three.89 (s, 3H), 3.86 (s, 3H), three.77 (s, 3H), three.67 (s, 3H), three.44 (s, 2H). 13C NMR (CDCl3) 170.9, 148.4, 147.9, 147.3,Int. J. Mol. Sci. 2013,131.eight, 130.2, 125.six, 115.3, 114.Taltobulin intermediate-1 Price 4, 113.886779-69-7 Chemical name six, 113.2, 113.1, 56.1, 55.8, 55.7, 39.five, 38.1, 27.9. LCMS (X-Bridge? Waters, Milford, MA, USA, C18 four.6 ?150 mm, 5 m) rt = 13.475 min (210.0 nm), UV 98.7 ; ESI [M + Na]+ = 503.three, 505.three. three.7. Synthesis of DIV880 three.7.1. Synthesis of 2-(2-[(three,4-dimethoxyphenyl)methyl]-4,5-dimethoxyphenyl) Acetic Acid (Compound 3, Figure 4) A total of 2.2 mL (17.3 mmol, 1.two eq.) of veratrole was added to a remedy of 3.0 g (14.four mmol) of 6,7-dimethoxy-3-isochromanone 1 in 30 mL of formic acid at space temperature. The mixture was maintained at 95 overnight and then hydrolyzed by the addition of 30 mL of water.PMID:23489613 The aqueous layer was extracted 3 instances with ethyl acetate. The organic layer was washed twice with brine, dried over magnesium sulfate, and evaporated to dryness to receive 7.0 g of crude material. Chromatography on silica gel (eluant: heptane/AcOEt 1/1 + 1 AcOH) followed by trituration in isopropylic ether resulted in two.two g (44 ) of compound 3 as an off-white strong after filtration. 1H NMR (CDCl3) 6.75 (m, 2H), six.62 (m, 3H), three.91 (s, 2H), three.86 (s, 3H), 3.83 (s, 3H), three.78 (s, 3H), three.77 (s, 3H), 3.55 (s, 2H). Figure 4. Schematic representation in the synthesis of DIV880.HCOOH 90, r.t.Chloramine T NaI AcOH, r.t. four DIV3.7.two. Synthesis of 2-(2-[(three,4-dimethoxyphenyl)methyl]-4,5-dimethoxy phenyl) Acetate (Compound 4, Figure four) A total of six.1 g (28.six mmol, 4.5 eq.) of O-tert-butyl-N,N’-diisopropylisourea was added drop-wise more than a period of two h to a solution of 2.2 g (six.35 mmol) of compound 2 in 33 mL of dichloromethane at area temperature. The mixture was stirred overnight and filtered to remove insoluble supplies. The filtrate was evaporated under vacuum plus the residue purified by chromatography on silica gel (eluant: heptane/AcOEt 7/3) to receive 1.72 g (67 ) of compound three as a yellow oil. 1H NMR (CDCl3) six.79 (d, 1H, J = 7.35 Hz), six.78 (s, 1H), six.64 (m, 3H), 3.93 (s, 2H), 3.89 (s, 3H), three.87 (s, 3H), 3.83 (s, 3H), three.81 (s, 3H), three.46 (s, 2H).Int. J. Mol.