Methoxyphenyl)-3-(3trifluoromethoxybenzoyl)-6-methoxyindole (19)–To a answer of compound five (1.14 g, two.97 mmol) in o-dichlorobenzene (15 mL) was added 3-trifluoromethoxybenzoyl chloride (0.70 mL, four.45 mmol). The reaction mixture was heated to reflux at 170 for 12 h. The o-dichlorobenzene was removed by simple distillation, along with the resulting dark green colored solid was subjected to flash chromatography applying a prepacked 50 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 (two CV); flow rate: 40 mL/min; monitored at 254 and 280 nm] resulting in TBS-indole 19 as a yellow powder (1.21 g, two.11 mmol, 71 , Rf = 0.43 (70:30 hexanes:EtOAc)). 1H NMR (CDCl3, 500 MHz): 8.31 (br s, 1H, NH), 7.96 (d, J = 8.four Hz, 1H, ArH), 7.52 (dt, J = 7.5 Hz, 1.3 Hz, 1H, ArH) 7.Bestatin 48 (s, 1H, ArH), 7.17 (t, J = 7.8 Hz, 1H, ArH), 7.13 (d, J = 8.2 Hz, 1H, ArH), six.93 (m, 2H, ArH), six.81 (m, 2H, ArH), six.62 (d, J = 9.0 Hz, 1H, ArH), three.88 (s, 3H, OCH3), three.73 (s, 3H, OCH3), 0.97 (s, 9H, C(CH3)three), 0.08 (s, 6H, Si(CH3)2). 13C NMR (CDCl3, 125 MHz): 191.eight, 157.4, 151.6, 148.8, 144.9, 144.1, 142.1, 136.6, 129.2, 128.0, 124.three, 123.6, 123.five, 122.9, 122.2, 122.0, 121.four, 120.4 (q, JC-F = 256 Hz), 112.six, 112.0, 111.six, 94.eight, 55.7, 55.3, 25.7, 18.four, -4.7. 19F NMR (CDCl3,NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptBioorg Med Chem. Author manuscript; accessible in PMC 2014 November 01.MacDonough et al.Page470 MHz): -57.eight (s, 3F, OCF3). HPLC: 21.53 min.Donanemab , purity at 254 nm 99 . HRMS (ESI+): m/z calculated for C30H33F3NO5Si [M+H]+ 572.2075, discovered 572.2071.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript4.1.16. (2-(3-tert-Butyldimethylsilyloxy-4-methoxyphenyl)-3-(4trifluoromethoxybenzoyl)-6-methoxyindole (20)–To a option of compound five (1.14 g, two.97 mmol) in o-dichlorobenzene (15 mL) was added 4-trifluoromethoxybenzoyl chloride (0.70 mL, four.45 mmol). The reaction mixture was heated to reflux at 170 for 12 h. The o-dichlorobenzene was removed by easy distillation, as well as the resulting dark green colored solid was subjected to flash chromatography applying a prepacked 50 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 (1.1 CV); flow price: 40 mL/min; monitored at 254 and 280 nm] resulting in TBS-indole 20 as a yellow powder (0.92 g, 1.61 mmol, 54 , Rf = 0.43 (70:30 hexanes:EtOAc)). 1H NMR (CDCl3, 500 MHz): 8.29 (br s, 1H, NH), 8.00 (d, J = 8.6 Hz, 1H, ArH), 7.64 (d, J = eight.PMID:23543429 7 Hz, 2H, ArH) six.97 (d, J = eight.0 Hz, 2H, ArH), 6.93 (m, 2H, ArH), 6.83 (d, J = 2.two Hz, 1H, ArH), six.73 (dd, J = eight.3 Hz, 2.two Hz, 1H, ArH), six.58 (d, J = eight.4 Hz, 1H, ArH), 3.88 (s, 3H, OCH3), 3.73 (s, 3H, OCH3), 0.98 (s, 9H, C(CH3)three), 0.ten (s, 6H, Si(CH3)2). 13C NMR (CDCl3, 125 MHz): 191.9, 157.three, 151.six, 151.0, 144.8, 144.1, 138.4, 136.six, 131.three, 124.2, 123.eight, 122.eight, 122.two, 121.4, 120.3 (q, JC-F = 256 Hz), 119.7, 112.six, 111.9, 111.three, 94.8, 55.six, 55.1, 25.six, 18.four, -4.8. 19F NMR (CDCl3, 470 MHz): -57.7 (s, 3F, OCF3). HPLC: 21.61 min., purity at 254 nm 99 . HRMS (ESI+): m/z calculated for C30H33F3NO5Si [M+H]+ 572.2075, discovered 572.2075. 4.1.17. 2-(3-tert-Butyldimethylsiloxy-4-methoxyphenyl)-3-(3,4,5trimethoxybenzoyl)-6-tert-butyldimethylsiloxyindole (21)–To a resolution of compound 6 (0.19 g, 0.39 mmol) in o-dichlorobenzene (20 mL) was added three,four,5trimethoxybenzoyl chloride (0.13 g, 0.58 mmol). The reaction mixture was heate.
