E and extracted with EtOAc (three 50 mL). The combined organic extract was

E and extracted with EtOAc (three 50 mL). The combined organic extract was dried over Na2SO4 and concentrated below decreased pressure. Purification by flash chromatography making use of a prepacked 50 g silica column [solvent A: EtOAc; solvent B: hexanes; gradient: 5 A / 95 B (4 CV), five A / 95 B 40 A / 60 B (10 CV), 40 A / 60 B (2 CV); flow rate: 50 mL/min; monitored at 254 and 280 nm] resulted within the desired six,7-dimethoxy-2-phenylindole 11 (1.43 g, three.47 mmol, 43 , Rf = 0.40 (80:20 hexanes:EtOAc)) as a tan strong. 1H NMR (CDCl3, 500 MHz): eight.63 (br s, 1H, NH), 7.33 (d, J = eight.5 Hz, 1H, ArH), 7.28 (d, J = 2.2 Hz, 1H, ArH), 7.26 (dd, J = 8.five Hz, two.2 Hz 1H, ArH), six.92 (dd, J = eight.four Hz, 1.4 Hz, 2H, ArH), six.71 (d, J = 2.2 Hz, 1H, ArH), 4.15 (s, 3H, OCH3), 4.01 (s, 3H, OCH3), three.88 (s, 3H, OCH3), 1.15 (s, 9H, C(CH3)3), 0.31 (s, 6H, Si(CH3)2). 13C NMR (CDCl3, 125 MHz): 150.7, 147.1, 145.4, 137.9, 134.two, 131.two, 126.0, 125.7, 118.four, 118.1, 115.two, 112.3, 108.7, 99.0, 60.9, 57.3, 55.four, 25.eight, 18.5, -4.five. HPLC: 21.28 min., purity at 254 nm 99 . HRMS (ESI+): m/z calculated for C23H32NO4Si [M+H]+ 414.2095, discovered 414.Aliskiren 2095. four.1.9. 2-(3-tert-Butyldimethylsiloxy-4-methoxyphenyl)-3-(3, 5dinitrobenzoyl)-6-methoxyindole (13)–To a answer of compound 5 (0.50 g, 1.30 mmol) in o-dichlorobenzene (20 mL) was added 3,5-dinitrobenzoylchloride (0.45 g, 1.90 mmol). The reaction mixture was heated to reflux at 160 for 12 h. The o-dichlorobenzene was removed by easy distillation, as well as the resulting dark colored strong was subjected to flash chromatography making use of a prepacked 50 g silica column [solvent A: EtOAc; solvent B: hexanes; gradient: 7 A / 93 B (4 CV), 7 A / 93 B 60 A / 40 B (11 CV), 60 A / 40 B (two CV); flow price: 40 mL/min; monitored at 254 and 280 nm] resulting in TBS-indole 13 as a pale yellow powder (0.40 g, 0.69 mmol, 53 , Rf = 0.59 (70:30 hexanes:EtOAc)). 1H NMR (CDCl3, 500 MHz): eight.85 (t, J = two.0 Hz, 1H, ArH), 8.62 (d, J = 2.0 Hz, 2H, ArH), 8.60 (br s, 1H, NH) 8.15 (d, J = 8.5 Hz, 1H, ArH), 7.00 (dd, J = 8.five Hz, two.0 Hz, 1H, ArH), 6.95 (d, two.0 Hz, 1H, ArH), six.87 (dd, J = 8.0 Hz, 2.0 Hz, 1H, ArH), six.61 (d, J = eight.5 Hz, 1H, ArH), six.56 (d, J = 2.5 Hz, 1H, ArH), three.90 (s, 3H, OCH3), 3.70 (s, 3H, OCH3), 0.89 (s, 9H, C(CH3)3), 0.00 (s, 6H, Si(CH3)2). 13C NMR (CDCl3, 125 MHz): 187.3, 158.1, 152.1, 147.eight, 145.3, 145.1, 143.1, 136.5, 129.1, 123.five, 123.4, 122.7, 122.4, 122.3, 120.1, 112.eight, 112.5, 111.Baicalein 8, 95.PMID:24518703 0, 55.9, 55.5, 25.six, 18.four, -4.8. HPLC: 20.28 min., purity at 254 nm 93.1 . HRMS (ESI+): m/z calculated for C29H32N3O8Si [M+H]+ 578.1953, discovered 578.1950. 4.1.10. 2-(3-tert-Butyldimethylsiloxy-4-methoxyphenyl)-3-(4-nitrobenzoyl)-6methoxyindole (14)–To a answer of compound five (0.20 g, 0.52 mmol) in odichlorobenzene (ten mL) was added 3-nitrobenzoylchloride (0.15 g, 0.78 mmol). The reaction mixture was heated to reflux at 160 for 12 h. The o-dichlorobenzene was removed by simple distillation, along with the resulting dark colored solid was subjected to 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 (10 CV), 60 A / 40 B (8.eight CV); flow price: 40 mL/min; monitored at 254 and 280 nm] resulting in TBSindole 14 as a yellow powder (0.14 g, 0.28 mmol, 51 , Rf = 0.36 (70:NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptBioorg Med Chem. Author manuscript; obtainable in PMC 2014 November 01.MacDonough et al.Pagehexanes:EtOAc)). 1H NMR (CDCl3, 500 MHz): eight.37 (br s, 1H, N.