Dichloromethane. The organic layer was washed 3 instances with saturated sodium

Dichloromethane. The organic layer was washed 3 instances with saturated sodium bicarbonate resolution, dried more than magnesium sulfate, filtered, and evaporated to dryness to receive 7.39 g of crude material. Trituration in isopropylic ether for 1 h resulted in six.51 g (60 ) of compound 1 as an off-white solid after filtration. 1H NMR (CDCl3) 6.76 (s, 1H), six.73 (s, 1H), 5.28 (s, 2H), three.91 (s, 3H), 3.90 (s, 3H), 3.66 (s, 2H). Figure 3. Schematic representation of your synthesis of DIV879.HCHO AcOH/HCl 90 1 HCOOH 90, r.t.DIV3.six.3. Synthesis of 2-([(2-bromo-4,5-dimethoxyphenyl)methyl]-4,5-dimethoxyphenyl) Acetic Acid (Compound two, Figure 3) A total of 2.three g (ten.8 mmol, 1.13 eq.) of bromoveratrole was added in one portion to a solution of two.0 g (9.six mmol) of 6,7-dimethoxy-3-isochromanone 1 in 20 mL of formic acid. The mixture was heated to 90 for 2 h and after that hydrolyzed by the addition of ten mL of water. The aqueous layer was extracted 3 occasions with ethyl acetate. The organic layer was washed twice with brine, dried over magnesium sulfate, filtered, and evaporated to dryness to yield 4.18 g of crude material. Trituration in a mixture of isopropylic ether/AcOEt resulted in 3.2 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), three.99 (s, 2H), three.90 (s, 3H), 3.88 (s, 3H), 3.79 (s, 3H), 3.68 (s, 3H), 3.61 (s, 2H). 3.Menadione 6.Streptomycin four. Synthesis of Tert-butyl 2-(2-[(2-bromo-4,5-dimethoxyphenyl)methyl]-4,5-dimethoxy phenyl) Acetate (DIV879, Figure 3) A total of 1.6 g (7.35 mmol, 3 eq.) O-tert-butyl-N,N-diisopropylisourea was added in portions more than a period of two h to a remedy of 1.04 g (two.45 mmol) of acid 2 in 30 mL of dichloromethane at space temperature. The mixture was stirred overnight and filtered to take away insoluble supplies. The filtrate was evaporated beneath vacuum and the residue purified twice by chromatography on silica gel (1-eluant: CH2Cl2/AcOEt 85/15, 2-eluant: heptane/AcOEt gradient) to get 749 mg (63 ) of DIV879 as an off-white strong. 1 H NMR (CDCl3) 7.05 (s, 1H), six.78 (s, 1H), six.55 (s, 1H), 6.43 (s, 1H), three.96 (s, 2H), three.89 (s, 3H), three.86 (s, 3H), three.77 (s, 3H), 3.67 (s, 3H), three.44 (s, 2H). 13C NMR (CDCl3) 170.9, 148.4, 147.9, 147.three,Int. J. Mol. Sci. 2013,131.eight, 130.2, 125.6, 115.three, 114.four, 113.6, 113.2, 113.1, 56.1, 55.8, 55.7, 39.5, 38.1, 27.PMID:28440459 9. LCMS (X-Bridge Waters, Milford, MA, USA, C18 4.six 150 mm, five m) rt = 13.475 min (210.0 nm), UV 98.7 ; ESI [M + Na]+ = 503.three, 505.three. three.7. Synthesis of DIV880 3.7.1. Synthesis of 2-(2-[(3,4-dimethoxyphenyl)methyl]-4,5-dimethoxyphenyl) Acetic Acid (Compound three, Figure four) A total of two.two mL (17.three mmol, 1.2 eq.) of veratrole was added to a remedy of three.0 g (14.four mmol) of 6,7-dimethoxy-3-isochromanone 1 in 30 mL of formic acid at room temperature. The mixture was maintained at 95 overnight then hydrolyzed by the addition of 30 mL of water. The aqueous layer was extracted three instances with ethyl acetate. The organic layer was washed twice with brine, dried over magnesium sulfate, and evaporated to dryness to acquire 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 2.two g (44 ) of compound 3 as an off-white solid after filtration. 1H NMR (CDCl3) 6.75 (m, 2H), six.62 (m, 3H), 3.91 (s, 2H), 3.86 (s, 3H), three.83 (s, 3H), 3.78 (s, 3H), 3.77 (s, 3H), 3.55 (s, 2H). Figure four. Schematic representation in the synthesis of DIV880.HCOOH 90, r.t.Chloramine T NaI AcOH,.