Eaction, the reaction mixture was cooled to space temperature and extracted with EtOAc (3 50 mL). The combined organic extract was dried over Na2SO4 and concentrated below lowered stress. Purification by flash chromatography making use of a prepacked 100 g silica column [solvent A: EtOAc; solvent B: hexanes; gradient: 2 A / 98 B (4 CV), 2 A / 98 B 20 A / 80 B (10 CV), 20 A / 80 B (2 CV); flow rate: 40 mL/min; monitored at 254 and 280 nm] resulted in the desired 2phenylindole 6 (0.59 g, 1.23 mmol, 44 , Rf = 0.39 (90:ten hexanes:EtOAc)) as a brown strong. 1H NMR (CDCl3, 500 MHz): eight.09 (br s, 1H, NH), 7.37 (d, J = 8.5 Hz, 1H, ArH), 7.10 (d, J = 1.5 Hz, 1H, ArH), 7.01 (dd, J = eight.five Hz, 1.five Hz, 1H, ArH), 6.82 (s, 1H, ArH), six.72 (d, J = 8.five Hz, 1H, ArH), six.67 (dd, J = 8.five Hz, 1.five Hz, 1H, ArH), 6.54 (s, 1H, ArH), three.70 (s, 3H, OCH3), 1.02 (s, 9H, C(CH3)three), 1.01 (s, 9H, C(CH3)three), 0.20 (s, 6H, Si(CH3)two), 0.18 (s, 6H, Si(CH3)2). 13C NMR (CDCl3, 125 MHz): 150.7, 150.6, 145.4, 137.7, 137.3, 126.0, 124.5, 120.six, 118.5, 118.0, 114.6, 112.4, 101.8, 98.7, 55.four, 25.93, 25.89, 18.6, 18.four, four.3, 4.5. HPLC: 25.45 min., purity at 254 nm 99 . HRMS (ESI): m/z calculated for C27H42NO3Si2 [MH] 484.2698, found 484.2698. four.1.4. two(3tertButyldimethylsilyloxy4methoxyphenyl)four,five,6trimethoxyindole (7)To a resolution of 3,four,5trimethoxyaniline (0.336 g, 1.84 mmol) in N,Ndimethylaniline (20 mL) at 170 was added compound three (0.20 g, 0.56 mmol) dropwise in EtOAc (5 mL). The reaction mixture was stirred at 170 for 12 h. Upon completion with the reaction, the reaction mixture was cooled to space temperature and extracted with EtOAc (three 50 mL). The combined organic extract was dried more than Na2SO4 and concentrated beneath decreased stress. Purification by flash chromatography applying 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 (10 CV), 60 A / 40 B (two CV); flow price: 40 mL/min; monitored at 254 and 280 nm] resulted in the desired 2phenylindole 7 (0.14 g, 0.32 mmol, 58 , Rf = 0.31 (70:30 hexanes:EtOAc)) as colorless crystals. 1H NMR (CDCl3, 500 MHz): eight.06 (br s, 1H, NH), 7.15 (dd, J = eight.5 Hz, 2.0 Hz, 1H, ArH), 7.ten (d, J = two.0 Hz, 1H, ArH), six.90 (d, J = 8.5 Hz, 1H, ArH), 6.70 (dd, J = two.0 Hz, 1.0 Hz, 1H, ArH), six.66 (d, J = 0.5 Hz, 1H, ArH), four.13 (s, 3H, OCH3), 3.90 (s, 3H, OCH3), three.88 (s, 3H, OCH3), three.84 (s, 3H, OCH3), 1.03 (s, 9H, C(CH3)3), 0.19 (s, 6H, Si(CH3)2). 13C NMR (CDCl3, 125 MHz): 151.0, 150.6, 145.six, 145.five, 136.4, 135.8, 133.9, 125.8, 118.3, 117.9, 116.6, 112.five,NIHPA Author Manuscript NIHPA Author Manuscript NIHPA Author ManuscriptBioorg Med Chem. Author manuscript; obtainable in PMC 2014 November 01.1551176-24-9 web MacDonough et al.BuySpiro[3.3]heptan-2-amine hydrochloride Page96.PMID:33483741 3, 89.8, 61.six, 60.9, 56.two, 55.2, 25.9, 18.5, four.six. HPLC: 20.17 min., purity at 254 nm 94.2 . HRMS (ESI): m/z calculated for C24H34NO5Si [MH] 444.2201, located 444.2200. 4.1.five. 2(4Methoxyphenyl)6,7dimethoxyindole (8)To a resolution of 2,3dimethoxyaniline (0.92 mL, 6.85 mmol) dissolved in N,Ndimethylaniline (10 mL) was added 4methoxybromoacetophenone 4 (0.79 g, three.43 mmol). The solution was heated to reflux and stirred at 150 for 12 h. Upon completion in the reaction, the reaction mixture was cooled to space temperature and extracted with EtOAc (three 50 mL). The combined organic extract was dried over Na2SO4 and concentrated beneath lowered pressure. Purification by flash chromatography making use of a prepacked 100 g silica column [solvent A: EtOAc; solvent B: hexanes; gradient: 5 A / 95 B (four CV), five A / 95.