B 40 A / 60 B (ten CV), 40 A / 60 B (four CV); flow rate: 40 mL/min; monitored at 254 and 280 nm] resulted inside the desired 6,7dimethoxy2phenylindole eight (0.50 g, 1.76 mmol, 51 , Rf = 0.35 (80:20 hexanes:EtOAc)) as a tan solid. 1H NMR (CDCl3, 500 MHz): eight.61 (br s, 1H, NH), 7.61 (d, J = 8.7 Hz, 2H, ArH), 7.28 (d, J = eight.five Hz, 1H, ArH), 6.97 (d, J = 8.7 Hz, 2H, ArH), six.87 (d, J = 8.six Hz, 1H, ArH), six.66 (d, J = 2.1 Hz, 1H, ArH), 4.09 (s, 3H, OCH3), three.97 (s, 3H, OCH3), three.85 (s, 3H, OCH3). 13C NMR (CDCl3, 125 MHz): 159.2, 147.1, 138.0, 134.two, 131.3, 126.4, 126.0, 125.3, 115.three, 114.five, 108.5, 98.eight, 61.1, 57.4, 55.4. HPLC: 15.30 min., purity at 254 nm 90.6 . HRMS (ESI): m/z calculated for C17H18NO3 [MH] 284.1281, found 284.1282. four.1.six. 2(4Methoxyphenyl)6methoxy7hydroxyindole (9)Trimethoxyindole 8 (0.61 g, two.16 mmol) was dissolved inside a solution of [Al2Cl7][TMAH] (6.three mL, three.13 mmol, 0.496 M in CH2Cl2).N-Mal-N-bis(PEG4-NH-Boc) site The reaction mixture was sealed and subjected to microwave irradiation at 80 for 1 h.(6-Chloropyridazin-3-yl)methanol uses Upon completion from the reaction, the reaction mixture was diluted with NaHCO3 and extracted with CH2Cl2 (3 20 mL).PMID:33653255 The combined organic extract was dried over Na2SO4 and concentrated below reduced pressure. Purification by flash chromatography utilizing a prepacked 100 g silica column [solvent A: EtOAc; solvent B: hexanes; gradient: 7 A / 93 B (four CV), 7 A / 93 B 60 A / 40 B (ten CV), 60 A / 40 B (two CV); flow rate: 40 mL/min; monitored at 254 and 280 nm] resulted within the preferred 6methoxy7hydroxy2phenylindole 9 (0.42 g, 1.55 mmol, 71 , Rf = 0.36 (70:30 hexanes:EtOAc)) as a tan strong. 1H NMR ((CD3)2CO, 500 MHz): ten.11 (br s, 1H, NH), 7.85 (d, J = eight.7 Hz, 2H, ArH), 7.66 (s, 1H, OH), six.98 (m, 3H, ArH), six.81 (d, J = eight.five Hz, 1H, ArH), 6.66 (d, J = two.two Hz, 1H, ArH), three.83 (s, 3H, OCH3), three.81 (s, 3H, OCH3). 13C NMR ((CD3)2CO, 125 MHz): 159.9, 142.five, 138.eight, 133.1, 128.4, 127.2, 127.1, 126.5, 115.0, 111.three, 108.9, 99.0, 58.three, 55.7. HPLC: 13.47 min., purity at 254 nm 85.eight . HRMS (ESI): m/z calculated for C16H16NO3 [MH] 270.1125, found 270.1129. four.1.7. two(4Methoxyphenyl)6methoxy7tertbutyldimethylsilyloxyindole (10) To a resolution of no cost phenol indole 9 (0.08 g, 0.28 mmol) in CH2Cl2 (5 mL) at 0 was added Et3N (0.04 mL, 0.31 mmol) and DMAP (0.01 g, 0.11 mmol). The reaction mixture was stirred for 10 min, and TBSCl (0.05 g, 0.31 mmol) was added steadily. The solution was allowed to warm to space temperature more than 12 h. Upon completion of your reaction, water (10 mL) was added, and also the reaction mixture was extracted with CH2Cl2 (3 50 mL). The combined organic extract was dried over Na2SO4 and concentrated below decreased stress. Purification by flash chromatography working with a prepacked 25 g silica column [solvent A: EtOAc; solvent B: hexanes; gradient: two A / 98 B (4 CV), two A / 98 B 20 A / 80 B (ten CV), 20 A / 80 B (5.2 CV); flow rate: 35 mL/min; monitored at 254 and 280 nm] resulted within the TBS indole item 10 (0.05 g, 0.02 mmol, 45 , Rf = 0.64 (70:30 hexanes:EtOAc)) as a light tan solid. 1H NMR (CDCl3, 500 MHz): eight.03 (br s, 1H, NH), 7.53 (d, J = 8.7 Hz, 2H, ArH ), 7.13 (d, J = 8.five Hz, 1H, ArH), 6.98 (d, J = 8.7 Hz, 2H, ArH),NIHPA Author Manuscript NIHPA Author Manuscript NIHPA Author ManuscriptBioorg Med Chem. Author manuscript; readily available in PMC 2014 November 01.MacDonough et al.Page6.80 (d, J = eight.5 Hz, 1H, ArH), six.61 (d, J = 2.two Hz, 1H, ArH), three.86 (s, 6H, OCH3), 1.11 (s, 9H, C(CH3)three), 0.24 (s, 6H, Si(CH3)two). 13C NMR (CDCl3, 125 MHz): 159.three, 145.two, 137.five, 131.2, 130.two, 126.2, 125.9, 125.six.
