Organic & Biomolecular Chemistry
Paper
and 15 were obtained as yellow solids (20 mg, 22%; 33 mg, CH), 68.6 (CH2), 61.9 (CH2), 56.7 (Me), 51.6 (CH2); m/z (ESI)
36% respectively); 16: mp 198–200 °C; (Found: M + Na+, 404 (M + Na+, 100%); HPLC: purity (AUC) 97.6%.
296.0745. C12H11N5O3Na requires 296.0754); νmax (CHCl3)/
6-Methoxy-1-(3-(4-methoxyphenoxy)propyl)-3-(2,4,6-trifluoro-
cm−1 2959, 2931, 2872, 2337, 1710, 1673, 1646, 1602, 1515, phenoxy)methyl-1H-indole-4,7-dione. Prepared by general
1195, 1036; δH (400 MHz; CDCl3) 8.51 (1H, s, NvCHN), 6.78 procedure 3 from 3-hydroxymethyl-6-methoxy-1-(3-(4-methoxy-
(1H, s, CH), 6.05 (2H, s, CH2), 5.74 (1H, s, CH), 3.94 (3H, s, phenoxy)propyl)-1H-indole-4,7-dione 29d (0.266 g, 0.72 mmol)
Me), 3.82 (3H, s, Me); δC (100 MHz; CDCl3) 183.4, 172.1, 159.8, and 2,4,6-trifluorophenol (0.531 g, 3.58 mmol). Column
152.9 (CH), 130.9 (CH), 128.2, 123.6, 116.1, 107.3 (CH), 56.7 chromatography eluting with ethyl acetate and dichloro-
(Me), 47.7 (CH2), 36.6 (Me); HPLC: purity (AUC) 90.0%. 15: mp methane (1 : 49) gave the title compound as a yellow solid
230–232 °C; (Found: M + Na+, 296.0748. C12H11N5O3Na (0.316 g, 88%), mp 138–140 °C; (Found: M + Na+, 524.1280.
requires 296.0754); νmax (CHCl3)/cm−1 2960, 2929, 2873, 2361, C26H22F3NO6Na requires 524.1291); νmax (CHCl3)/cm−1 3009,
2342, 1733, 1675, 1643, 1602, 1459, 1036; δH (400 MHz; CDCl3) 2938, 1668, 1644, 1602, 1509; δH (400 MHz; CDCl3) 7.15 (1H, s,
8.93 (1H, s, NCHvN), 7.03 (1H, s, CH), 5.75 (1H, s, CH), 5.72 CH), 6.84 (4H, s, ArH), 6.67 (2H, t, J 8.4, ArH), 5.71 (1H, s, CH),
(2H, s, CH2), 3.98 (3H, s, Me), 3.85 (3H, s, Me); δC (100 MHz; 5.32 (2H, s, CH2), 4.56 (2H, t, J 6.7, CH2), 3.93 (2H, t, J 5.9,
CDCl3) 183.9, 172.0, 160.1, 143.0 (CH), 131.6 (CH), 126.2, CH2), 3.84 (3H, s, Me), 3.79 (3H, s, Me), 2.28 (2H, tt, J 6.7, 5.9,
123.5, 116.2, 107.2 (CH), 56.8 (Me), 42.4 (CH2), 36.7 (Me); CH2); δC (75 MHz; CDCl3) 183.6, 171.8, 159.9, 157.4 (dt, J 245,
HPLC: purity (AUC) 98.8%.
14), 156.6 (ddd, J 250, 15, 8), 154.1, 152.6, 132.0 (dt, J 15, 5)
6-Methoxy-1-(2-(4-methoxyphenoxy)ethyl)-3-(2,4,6-trifluoro- 130.7 (CH), 127.5, 124.2, 120.6, 115.5 (CH), 114.7 (CH),
phenoxy)methyl-1H-indole-4,7-dione 17. Prepared by general 107.1 (CH), 100.7 (ddd, J 27, 26, 8, CH), 68.5 (CH2), 64.8 (CH2),
procedure 3 from 3-hydroxymethyl-6-methoxy-1-(2-(4-methoxy- 56.6 (Me), 55.7 (Me), 46.6 (CH2), 30.2 (CH2); m/z (ESI) 524
phenoxy)ethyl)-1H-indole-4,7-dione 29c (0.801 g, 2.24 mmol) (M + Na+, 100%).
and 2,4,6-trifluorophenol (1.658 g, 11.20 mmol). Column
1-(3-Hydroxypropyl)-6-methoxy-3-(2,4,6-trifluorophenoxy)-
chromatography eluting with ethyl acetate and dichloro- methyl-1H-indole-4,7-dione 19. A solution of cerium(IV)
methane (1 : 24) gave the title compound as a yellow solid ammonium nitrate (0.785 g, 1.43 mmol) in water (15 mL) was
(0.966 g, 93%), mp 134–136 °C; (Found: M + Na+, 510.1128. added to a stirred solution of 6-methoxy-1-(3-(4-methoxy-
C25H20NO5F3Na requires 510.1135); νmax (CHCl3)/cm−1 3011, phenoxy)propyl)-3-((2,4,6-trifluorophenoxy)methyl)-1H-indole-
1645, 1602, 1509; δH (400 MHz; CDCl3) 7.29 (1H, s, CH), 6.84 4,7-dione (0.287 g, 0.57 mmol) in DMF (15 mL), and the result-
(2H, d, J 9.1, ArH), 6.80 (2H, d, J 9.1, ArH), 6.66 (2H, t, J 8.4, ing mixture was stirred at room temperature for 1.5 h. Water
ArH), 5.71 (1H, s, CH), 5.35 (2H, s, CH2), 4.72 (2H, t, J 5.0, (100 mL) was added and the mixture was extracted with ethyl
CH2), 4.26 (2H, t, J 5.0, CH2), 3.84 (3H, s, Me), 3.78 (3H, s, Me); acetate (3 × 25 mL). The combined organic phases were
δC (75 MHz; CDCl3) 183.5, 172.1, 159.8, 157.3 (dt, J 245, 14, washed with water (25 mL), dried (MgSO4), filtered and con-
CF), 156.3 (ddd, J 250, 15, 8, CF) 154.3, 152.1, 132.2 (dt, J 15, 5, centrated. Column chromatography eluting with ethyl acetate
C) 131.6 (CH), 127.2, 124.3, 120.6, 115.6 (CH), 114.7 (CH), and dichloromethane (1 : 6) gave the title compound as a yellow
107.2 (CH), 100.7 (ddd, J 27, 26, 8, CH), 68.6 (CH2), 67.2 (CH2), solid (0.206 g, 92%), mp 129–131 °C; (Found: M + Na+,
56.7 (Me), 55.7 (Me), 48.9 (CH2); m/z (ESI) 510 (M + Na+, 418.088. C19H16F3NO5Na requires 418.0873); νmax (CHCl3)/
100%); HPLC: purity (AUC) 100%.
cm−1 3690, 3011, 1644, 1602, 1510; δH (400 MHz; CDCl3) 7.19
1-(2-Hydroxyethyl)-6-methoxy-3-(2,4,6-trifluorophenoxy)methyl- (1H, s, CH), 6.70 (2H, t, J 8.6, ArH), 5.72 (1H, s, CH), 5.34 (2H,
1H-indole-4,7-dione 18. A solution of cerium(IV) ammonium s, CH2), 4.50 (2H, t, J 6.6, NCH2), 3.84 (3H, s, OMe), 3.65 (2H, t,
nitrate (2.74 g, 5.0 mmol) in water (10 mL) was added as a J 5.6, CH2OH), 2.07 (2H, m, CH2), 1.90 (1H, br s, OH); δC
single portion to a stirred solution of 6-methoxy-1-(2-(4-meth- (75 MHz; CDCl3) 183.5, 172.1, 159.9, 157.4 (dt, J 246, 14), 156.3
oxyphenoxy)ethyl)-3-((2,4,6-trifluorophenoxy)methyl)-1H-indole- (ddd, J 250, 15, 8), 132.2 (dt, J 15, 5), 131.7 (CH), 127.6, 124.1,
4,7-dione 17 (0.924 g, 2.0 mmol) in DMF (20 mL), and the 121.0, 107.1 (CH), 100.7 (ddd, J 27, 26, 8, CH), 68.6 (CH2), 58.7
resulting mixture was stirred at room temperature for 15 h. (CH2), 56.7 (Me), 45.9 (CH2), 33.4 (CH2); m/z (ESI) 418 (M +
Water (150 mL) was added, and the mixture was extracted with Na+, 100%); HPLC: purity (AUC) 99.2%.
ethyl acetate (3 × 40 mL). The combined organic phases were
1-(2-(Dimethylamino)ethyl)-6-methoxy-3-(2,4,6-trifluoro-
washed with water (50 mL), dried (MgSO4), filtered and con- phenoxy)methyl-1H-indole-4,7-dione 20. Prepared by general
centrated. Column chromatography eluting with ethyl acetate procedure 3 from 1-(2-(dimethylamino)ethyl)-3-hydroxymethyl-
and dichloromethane (1 : 3) gave the title compound as a 6-methoxy-1H-indole-4,7-dione 29e (0.182 g, 0.65 mmol) and
yellow-orange solid (0.732 g, 96%), mp 143–145 °C; (Found: 2,4,6-trifluorophenol (0.484 g, 3.27 mmol). Column chromato-
M + Na+, 404.0717. C18H14F3NO5Na requires 404.0716); νmax graphy eluting with methanol and ethyl acetate (19 : 1) gave the
(CHCl3)/cm−1 3011, 1644, 1602, 1510; δH (400 MHz; CDCl3) title compound as an orange solid (0.142 g, 54%), mp 76–78 °C;
7.24 (1H, s, CH), 6.69 (2H, t, J 8.3, ArH), 5.68 (1H, s, CH), 5.31 (Found:
M +
Na+, 409.1369. C20H20F3N2O4Na requires
(2H, s, CH2), 4.51 (2H, t, J 5.1, CH2), 4.00 (2H, t, J 5.1, CH2), 409.1370); νmax (CHCl3)/cm−1 3011, 2957, 1644, 1602, 1510; δH
3.83 (3H, s, Me); δC (75 MHz; CDCl3) 183.5, 172.2, 159.9, 157.4 (400 MHz; CDCl3) 7.19 (1H, s, CH), 6.69 (2H, t, J 8.4, ArH), 5.71
(dt, J 246, 14), 156.2 (ddd, J 250, 15, 7), 132.3 (dt, J 15, 5), 131.3 (1H, s, CH), 5.34 (2H, s, CH2O), 4.46 (2H, t, J 6.8, CH2), 3.84
(CH), 127.5, 124.2, 120.7, 107.2 (CH), 100.7 (ddd, J 27, 26, 8, (3H, s, OMe), 2.71 (2H, t, J 6.8, CH2), 2.33 (6H, s, Me); δC
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 4848–4861 | 4859