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(10, 11) Reaction was performed by following procedure B; N- 8.7 Hz, 1H), 1.92 (m, 2H), 1.81 (m, 1H), 1.7 (m, 4H), 1.5 (m, 2H),
methyl isatin (0.5 g, 3.105 mmol), proline (0.357 g, 3.105 mmol), 1.24 (t, J ¼ 7.3 Hz, 3H), 0.58 (t, J ¼ 7.3 Hz, 3H). 13C NMR (100
˚
dry toluene (30 ml), 4 A MS (200 mol%), time ¼ 6 h.
MHz, CDCl3): d 11.6, 12.6, 20.9, 21.1, 27.4, 27.8, 34.1, 34.2, 46.6,
Synthesis of (3R,70S)-1,100-dimethyl-1,100,2,200 tetrahydrodispiro- 46.8, 58.9, 60.9, 67.6, 71.3, 107.3, 107.6, 120.5, 120.9, 125.2,
[indole-3.80-[6,9]diazatricyclo[7.3.0.02,6]dodecane-70,300-indole]- 125.4, 126.1, 128.8, 129.0, 129.3, 143.6, 143.7, 172.3, 173.4. TOF
2,200-dione (10). Yield ¼ 42%, white solid, mp ¼ 183–186 ꢁC, IR MS ES+ 457 (M + H). HRMS calcd. for C28H32N4O2Na (M + Na)
(neat): nmax 2970, 2816, 2313, 1737, 1696, 1608, 1466, 1344 cmꢀ1
.
479.2418 found 479.2439.
1H NMR (400 MHz, CDCl3): d 7.28 (d, J ¼ 7.7 Hz, 2H), 7.08 (t, J ¼
(14, 15) Reaction was performed by following procedure B; N-
7.7 Hz, 2H), 6.89 (t, J ¼ 7.7 Hz, 2H), 6.38 (d, J ¼ 7.7 Hz, 2H), 3.72 benzyl isatin (0.5 g, 2.11 mmol), proline (0.243 g, 2.11 mmol),
˚
(t, J ¼ 4.7 Hz, 2H), 2.9 (s, 6H), 2.62 (td, J ¼ 8.2, 2.4 Hz, 2H), 2.09 dry toluene (30 ml), 4 A MS (200 mol%), time ¼ 13 h.
(q, J ¼ 8.2 Hz, 2H), 1.9 (brs, 2H), 1.79 (q, J ¼ 8.6 Hz, 2H), 1.63
Synthesis of (3R,70S)-1,100-dibenzyl-1,100,2,200-tetrahydrodispiro-
(brm, 4H). 13C NMR (100 MHz, CDCl3): d 21.1, 24.9, 27.6, 47.8, [indole-3.80-[6,9]diazatricyclo[7.3.0.02,6]dodecane-70,300-indole]-
59.3, 69.0, 107.2, 121.6, 125.2, 125.7, 129.1, 143.6, 174.7. TOF 2,200-dione (14). Yield ¼ 37%, white solid, mp ¼ 172–173 ꢁC, IR
MS ES+ 429 (M + H). HRMS calcd. for C26H29N4O2 (M + H) (neat): nmax 2975, 2949, 2878, 2812, 1693, 1604, 1468, 1339, 1180,
429.229 found 429.2301.
1165, 767 cmꢀ1. 1H NMR (400 MHz, CDCl3): d 7.3 (d, J ¼ 7.7 Hz,
Synthesis of (3R,70R)1,100-dimethyl-1,100,2,200
tetrahy- 2H), 7.2–7.25 (m, 6H), 7.11 (t, J ¼ 7.7 Hz, 2H), 6.95 (t, J ¼ 7.7 Hz,
drodispiro[indole-3.80
[6,9]diazatricyclo[7.3.0.02,6]dodecane- 2H), 6.7 (t, J ¼ 7.7 Hz, 2H), 6.31 (d, J ¼ 7.7 Hz, 2H), 4.88 (d, J ¼
70,300-indole]-2,200-dione (11). Yield ¼ 0.265 g, 20%, white solid, 15.7 Hz, 2H), 4.47 (d, J ¼ 15.7 Hz, 2H), 3.7 (t, J ¼ 6.7 Hz, 2H), 2.6
mp ¼ 174–176 ꢁC, IR (neat): nmax 3016, 2971, 2316, 1736, 1368, (t, J ¼ 6.7 Hz, 2H), 2.13 (q, J ¼ 6.7 Hz, 2H), 1.91 (br, 2H), 1.78 (dd,
1222 cmꢀ1. 1H NMR (400 MHz, CDCl3): d 8.05 (d, J ¼ 7.7 Hz, 1H), J ¼ 8.3, 7.8 Hz, 2H), 1.65 (m, 4H), 1.23 (td, J ¼ 7.0, 0.78 Hz, 2H).
7.3 (t, J ¼ 7.7 Hz, 1H), 7.09 (t, J ¼ 7.7 Hz, 1H), 7.03 (t, J ¼ 7.7 Hz, 13C NMR (100 MHz, CDCl3): d 21.0, 27.5, 43.3, 47.7, 59.4, 68.6,
1H), 6.6 (dd, J ¼ 4.6, 3.1 Hz, 2H), 6.43 (t, J ¼ 7.7 Hz, 1H), 6.04 (d, J 108.5, 122.1, 125.8, 126.0, 127.45, 127.6, 128.7, 128.9, 135.8,
¼ 7.7 Hz, 1H), 3.97 (td, J ¼ 5.8, 4.3 Hz, 1H), 3.16 (s, 3H), 2.87 (m, 143.1, 174.6. TOF MS ES+ 581 (M + H). HRMS calcd. for
1H), 2.87 (m, 1H), 2.83 (s, 3H), 2.73 (brd, J ¼ 7.4 Hz, 1H), 2.53
(td, J ¼ 7.3, 2.7 Hz, 1H), 2.08 (q, J ¼ 8.6 Hz, 1H), 1.92 (m, 2H),
C
38H37N4O2 (M + H) 581.2916 found 581.2933.
Synthesis of (3R,70R)-1,100-dibenzyl-1,100,2,200-tetrahydrodispiro-
1.82 (m, 1H), 1.71 (dd, J ¼ 7.8, 2.75 Hz, 1H), 1.65 (m, 2H), 1.5 (td, [indole-3.80-[6,9]diazatricyclo[7.3.0.02,6]dodecane-70,300-indole]-
J ¼ 7.7, 2.7 Hz, 2H). 13C NMR (100 MHz, CDCl3): d 20.9, 21.1, 2,200-dione (15). Yield ¼ 11%, white solid, mp ¼ 175–176 ꢁC, IR
25.6, 26.1, 27.4, 27.8, 46.6, 46.9, 58.9, 60.9, 67.8, 71.5, 107.3, (neat): nmax 2984, 2949, 2828, 2352, 2312, 1708, 1606, 1485, 1464,
107.6, 120.7, 121.2, 124.8, 125.2, 125.8, 128.9, 129.0, 129.1, 1365, 1349, 1166, 745, 741, 696 cmꢀ1 1H NMR (400 MHz,
.
144.6, 173.0, 174.0. TOF MS ES+ 429 (M + H). HRMS calcd. for CDCl3): d 8.1 (d, J ¼ 7.7 Hz, 1H), 7.34 (d, J ¼ 7.7, 2H), 7.23–7.16
C
26H28N4O2Na (M + Na) 451.21045 found 451.2120. (brm, 4H), 7.1–7.04 (m, 2H), 7.03–6.95 (m, 3H), 6.49–6.43 (dd, J
(12, 13) Reaction was performed by following procedure B; N- ¼ 7.7, 1.8 Hz, 3H), 6.42–6.38 (d, J ¼ 7.7 Hz, 2H), 6.15 (d, J ¼ 7.7
ethyl isatin (0.5 g, 2.857 mmol), proline (0.328 g, 2.857 mmol), Hz, 1H), 5.1 (d, J ¼ 15.9 Hz, 2H), 4.8 (d, J ¼ 15.9 Hz, 1H), 4.34 (d,
˚
dry toluene (30 ml), 4 A MS (200 mol%), time ¼ 8 h.
J ¼ 15.9 Hz, 1H), 4.04 (td, J ¼ 9.9, 5.8 Hz, 1H), 2.95 (td, J ¼ 9.9,
Synthesis of (3R,70S)-1,100-diethyl-1,100,2,200-tetrahydrodispiro- 5.8 Hz, 1H), 2.85 (td, J ¼ 8.4, 2.4 Hz, 1H), 2.61 (td, J ¼ 8.4, 2.4 Hz,
[indole-3.80-[6,9]diazatricyclo[7.3.0.02,6]dodecane-70,300-indole]- 1H), 2.21 (q, J ¼ 8.7 Hz, 1H), 1.98 (m, 2H), 1.86 (m, 1H), 1.74 (m,
2,200-dione (12). Yield ¼ 44%, white solid, mp ¼ 180–181 C, IR 4H), 1.54 (m, 2H). 13C NMR (100 MHz, CDCl3): d 20.9, 21.1, 27.5,
ꢁ
(neat): nmax 2969, 2810, 1696, 1606, 1465, 1347, 1205, 1133, 1094 27.8, 43.4, 43.9, 46.6, 47.0, 59.1, 60.9, 67.7, 71.3, 108.9, 109.0,
cmꢀ1. 1H NMR (400 MHz, CDCl3): d 7.34 (d, J ¼ 7.7 Hz, 2H), 7.05 (t, 121.1, 121.3, 124.7, 125.3, 126.2, 126.4, 126.9, 127.2, 127.5,
J ¼ 7.7 Hz, 2H), 6.83 (t, J ¼ 7.7 Hz, 2H), 6.42 (d, J ¼ 7.7 Hz, 2H), 3.66 128.6, 128.7, 128.9, 129.1, 129.2, 135.1, 136.5, 143.6, 144.1,
(brt, J ¼ 5.5, 4.9 Hz, 2H), 3.4 (q, J ¼ 7.1 Hz, 2H), 3.5 (q, J ¼ 7.2 Hz, 173.1, 173.9. TOF MS ES+ 581 (M + H). HRMS calcd. for
2H), 2.58 (td, J ¼ 8.6, 2.2 Hz, 2H), 2.05 (q, J ¼ 8.4 Hz, 2H), 1.87
C
38H37N4O2 (M + H) 581.2916 found 581.2933.
(brm, 2H), 1.76 (m, 2H), 1.6 (m, 4H), 1.07 (t, J ¼ 7.2 Hz, 6H). 13
C
(16, 17) Reaction was performed by following procedure B; N-
NMR (100 MHz, CDCl3): d 12.7, 20.9, 27.5, 33.9, 47.5, 59.2, 68.2, acetyl isatin (0.1 g, 0.5291 mmol), proline (0.06 g, 0.5291 mmol),
˚
107.4, 121.7, 126.0, 126.2, 129.0, 142.9, 174.1. TOF MS ES+ 457 (M + dry toluene (4 ml), 4 A MS (200 mol%), time ¼ 30 min.
H). HRMS calcd. for C28H33N4O2 (M + H) 457.2603 found 457.2614.
Synthesis of (3R,70S)-1,100-diacetyl-1,100,2,200-tetrahydrodispiro-
Synthesis of (3R,70R)-1,100-diethyl-1,100,2,200-tetrahydrodispiro- [indole-3.80-[6,9]diazatricyclo[7.3.0.02,6]dodecane-70,300-indole]-
[indole-3.80 [6,9]diazatricyclo[7.3.0.02,6]dodecane-70,300-indole]- 2,200-dione (16). Yield ¼ 30%, white solid, mp ¼ 170 ꢁC (decom-
2,200-dione (13). Yield ¼ 15%, white solid, mp ¼ 180–181 ꢁC, IR posed) melted at 240–250 ꢁC. IR (neat): nmax 2961, 2917, 2866,
(neat): nmax 2968, 2931, 2874, 2809, 1714, 1605, 1462, 1153, and 2815, 1750, 1708, 1461, 1331, 1268, 1152, 1011, 761 cmꢀ1. 1H NMR
1221. 1H NMR (400 MHz, CDCl3): d 8.04 (d, J ¼ 7.7 Hz, 1H), 7.29 (400 MHz, CDCl3): d 7.84 (d, J ¼ 7.8 Hz, 2H), 7.37 (d, J ¼ 7.8 Hz,
(td, J ¼ 7.7, 1.1 Hz, 1H), 7.6 (td, J ¼ 7.7, 1.1 Hz, 1H), 7.01 (td, J ¼ 2H), 7.18 (td, J ¼ 7.8, 1.4 Hz, 2H), 7.07 (td, J ¼ 7.8, 1.4 Hz, 2H), 3.64
7.7, 1.1 Hz, 1H), 6.6 (d, J ¼ 7.7 Hz, 2H), 6.41 (td, J ¼ 7.7, 1.1 Hz, (m, 2H), 2.28 (m, 2H), 2.62 (s, 6H), 2.10 (q, J ¼ 8.3 Hz, 2H), 1.98 (m,
1H), 5.98 (d, J ¼ 7.7 Hz, 1H), 3.98 (td, J ¼ 10.2, 5.8, 4.2 Hz, 1H), 2H), 1.82 (m, 2H), 1.69 (m, 2H), 1.61 (m, 2H). 13C NMR (100 MHz,
3.78 (q, J ¼ 7.5 Hz, 1H), 3.69 (q, J ¼ 7.5 Hz, 1H), 3.58 (q, J ¼ 7.2 CDCl3): d 21.1, 26.9, 27.8, 48.1, 59.6, 69.3, 116.4, 124.4, 124.6,
Hz, 1H), 3.24 (q, J ¼ 7.2 Hz, 1H), 2.91 (td, J ¼ 9.9, 5.9, 1H), 2.76 124.6, 130.4, 140.0, 169.9, 175.5. TOF MS ES+ 485 (M + H). HRMS
(td, J ¼ 8.3, 2.2 Hz, 1H), 2.54 (td, J ¼ 8.7, 2.7 Hz, 1H), 2.1 (q, J ¼ calcd. for C28H28N4O4Na (M + Na) 507.2008 found 507.2004.
33242 | RSC Adv., 2014, 4, 33236–33244
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