RSC Advances
Page 8 of 12
ARTICLE
Journal Name
0
2
8
.742 mmol) at 60 °C for 50 h to generate 21 (49 mg, 52%) and rotamer) 21.4 (s), 23.4 (s), 24.2 (s), 40.5 (s), 41.4 (d,
J
= 31.6
0b (35 mg, 41%).
Hz), 50.3 (s), 53.0 (s), 60.1 (s), 67.1 (s), 84.1 (d, J = 27.8 Hz),
: colourless needles. Mp 166–167 °C (from hexane/CH
2
Cl
2
). 106.7 (d,
= 24.0 Hz), 127.9 (s), 128.2 (s), 128.5 (s), 131.2 (s), 136.0 (s),
871, 1717, 1687, 1673, 1509, 1477, 1468, 1456, 1419, 1386, 148.3 (d, = 4.8 Hz), 156.2 (s), 171.7 (s), 173.5 (s). F (376
339, 1321, 1285, 1255, 1226, 1212, 1171, 1142, 1128, 1096, MHz, CDCl , a mixture of two rotamers in ca. 1:2 ratio) –131.6
J = 195.1 Hz), 110.5 (s), 119.4 (s), 123.4 (s), 126.5 (d,
DOI: 10.1039/C4RA08741K
2
5
–1
[
]D –113.1 (
c
0.5 in CHCl3). max (KBr)/cm 3374, 2959,
J
2
1
1
J
3
058, 1038, 1021, 960, 919, 842, 805, 782, 762, 700. H (400 (1/3F, q,
= 6.4 Hz), 0.88 (3H, d, = 6.4 Hz), Hz). MS (EI)
.43–1.51 (1H, m), 1.58–1.68 (2H, m), 2.61 (3H, s), 2.98 (1H, HRMS (EI) calcd for C H FN O ([M] ): 483.2169, found
J = 20.7 Hz), –145.0 (2/3F, ddd, J = 32.8, 25.2, 17.5
+
+
+
MHz, CDCl ) 0.76 (3H, d,
1
J
J
m/z 484 ([M+H] ), 483 ([M] ), 463 ([M–HF] ).
3
+
2
6
30
3
5
td,
J
= 12.8, 8.7 Hz), 3.16 (1H, d,
= 12.4 Hz), 5.12 (1H, d,
= 8.7 Hz), 5.48 (1H, br d, = 8.7
= 12.4 Hz), 7.17 (1H, dd, = 7.8, 7.3 Hz),
.31–7.45 (7H, m), 8.06 (1H, br d, = 8.2 Hz). C (100 MHz,
CDCl ) 21.1 (s), 23.3 (s), 23.5 (s), 24.4 (s), 37.7 (d,
J = 12.8 Hz), 3.21 (3H, s), 483.2157.
4
1
.16–4.22 (1H, m), 5.07 (1H, d,
2.4 Hz), 5.28 (1H, br d,
J
J =
(
3S,5aR,10bR,11aR)-6-Acetyl-10b-fluoro-6,10b,11,11a-
J
J
tetrahydro-3-(2-methylpropyl)-2H-
Hz), 6.31 (1H, br d,
7
J
J
pyrazino[1',2':1,5]pyrrolo[2,3-b]indole-1,4(3H,5aH)-dione (3).
J
3
J
= 29.7 To a solution of
= 5.8 Hz), 67.3 (s), was added 10% palladium on carbon (22 mg) at room
= 204.2 Hz), 119.4 (s), 124.5 temperature. After stirring under 3–4 atm of hydrogen for 4 h,
= 6.7 Hz), 124.6 (s), 126.3 (d, = 22.0 Hz), 128.0 (s), the mixture was filtered through a small pad of celite and
28.3 (s), 128.6 (s), 132.2 (d, = 2.9 Hz), 135.8 (s), 145.0 (d, concentrated under reduced pressure. The residue was purified
3.8 Hz), 156.5 (s), 169.7 (s), 171.0 (s), 174.3 (s). F (376 by silica gel column chromatography (eluent: hexane/EtOAc =
MHz, CDCl , a mixture of two rotamers in ca. 1:16 ratio) – 2/3) to give (37 mg, 50%) as a colourless crystalline solid.
8 (109 mg, 0.207 mmol) in MeOH (0.4 mL)
Hz), 40.9 (s), 50.3 (s), 52.5 (s), 59.9 (d,
9.8 (d, = 32.6 Hz), 102.0 (d,
d,
J
7
(
1
=
J
J
J
J
J
J
3
3
2
5
1
m
42.4 (1/17F, br s), –143.9 (16/17F, br t,
/z 526 ([M+H] ), 525 ([M] ). HRMS (EI) calcd for CHCl ).
3
J
= 12.2 Hz). MS (EI) Mp 182–183 °C (from hexane/CH Cl ). [
]D +27.3 (
max (KBr)/cm 3286, 2960, 2931, 2874, 1686, 1480,
1468, 1418, 1385, 1330, 1292, 1185, 1146, 1096, 1061, 1040,
: colourless crystalline solid. Mp 157–158 °C (from 937, 771, 759. (400 MHz, CDCl ) 0.91 (3H, d, = 6.4 Hz),
= 6.4 Hz), 1.63 (2H, dd, = 7.8, 6.4 Hz), 1.71
= 6.4 Hz), 2.55 (3H, s), 2.92 (1H, ddd, = 18.8,
672, 1607, 1539, 1479, 1469, 1415, 1389, 1317, 1294, 1260, 14.2, 10.5 Hz), 3.37 (1H, dt, = 14.2, 4.6 Hz), 3.77 (1H, td,
219, 1179, 1051, 995, 941, 781, 758, 741, 700. H (400 MHz, 7.8, 4.6 Hz), 4.52 (1H, dd, = 10.5, 4.6 Hz), 5.96 (1H, d,
= 4.6 Hz), 7.17 (1H, dd,
= 7.8, 1.8 Hz), 7.47 (1H, dt, = 7.3, 1.8 Hz),
= 7.8 Hz). C (100 MHz, CDCl ) 21.1 (s), 22.9
c 0.50 in
2
2
+
+
–1
+
C H FN O ([M] ): 525.2275, found 525.2271.
2
hexane/CH Cl ). [
2
8
32
3
6
1
H
3
J
2
5
]D
+28.9 (
c
0.25 in CHCl3). max 0.97 (3H, d,
J
J
J
2
1
2
–
(
KBr)/cm 3242, 3033, 2994, 2953, 2868, 1749, 1703, 1685, (1H, septet,
J
1
1
J
J
J
J
=
=
CDCl , a mixture of two rotamers in ca. 1:3 ratio) 0.71–0.97 12.4 Hz), 6.68 (1H, br d,
J
J = 7.8, 7.3
3
(
3H, br m), 0.89 (3H, d,
.49–1.80 (2H, br m), 2.19–2.79 (4H, br m), 2.80–3.29 (1H, br 8.00 (1H, br d,
m), 3.60–4.10 (1H, br m), 3.70 (3/4H, br s), 3.83 (9/4H, br s), (s), 24.3 (s), 24.5 (s), 32.3 (d,
J
= 6.4 Hz), 1.21–1.44 (1H, br m), Hz), 7.39 (1H, tt,
J
J
1
J
3
J
= 30.7 Hz), 41.3 (s), 55.8 (d,
= 33.6 Hz), 100.9 (d, = 201.3 Hz),
.59 (35/4H, br m), 7.97 (1/4H, br s). F (376 MHz, CDCl , a 118.8 (s), 124.9 (s), 125.0 (d, = 2.9 Hz), 127.6 (d, = 22.0
= 2.9 Hz), 142.8 (d, = 3.8 Hz), 167.4 (s),
526 ([M+H] ), 525 ([M] ). 167.8 (s), 170.4 (s). F (376 MHz, CDCl ) –138.4 (1F, br t, J =
J =
4
7
.58–5.33 (4H, br m), 6.08 (3/4H, br s), 6.83 (1/4H, br s), 7.15– 4.8 Hz), 56.0 (s), 81.3 (d,
J
J
3
J
J
mixture of two rotamers in ca. 1:3 ratio) –144.2 (3/4F, br s), – Hz), 132.1 (d,
1
J
J
+
+
44.4 (1/4F, br s). MS (EI)
m
/
z
3
+
+
HRMS (EI) calcd for C H FN O ([M] ): 525.2275, found 15.3 Hz). MS (EI)
m
/
z
359 ([M] ). HRMS (EI) calcd for
2
8
32
3
6
+
5
2
+
25.2281.
C H FN O ([M] ): 359.1645, found 359.1637.
1
9
22
3
3
2
5
0b: colourless crystalline solid. Mp 49–51 °C (dec.). []
D
150.4 (c 0.4 in CHCl3). max (KBr)/cm 3396, 3331, 2956,
–
1
(3S,5aS,10bS,11aR)-6-Acetyl-10b-fluoro-6,10b,11,11a-
tetrahydro-3-(2-methylpropyl)-2H-
pyrazino[1',2':1,5]pyrrolo[2,3-b]indole-1,4(3H,5aH)-dione (22).
2
1
871, 1749, 1714, 1653, 1618, 1523, 1486, 1472, 1437, 1322,
301, 1257, 1219, 1187, 1094, 1058, 922, 753, 698. H (400
MHz, CDCl , a mixture of two rotamers in ca. 1:2 ratio) 0.87 To a solution of 21 (49 mg, 0.0930 mmol) in MeOH (0.4 mL)
3
(
6
(
2H, d,
.4 Hz), 1.00 (1H, d,
2H, m), 2.54–2.70 (1H, m), 2.79 (1/3H, ddd,
Hz), 2.97 (2/3H, dd, = 17.4, 14.2 Hz), 3.72 (1H, s), 3.83 (2H, concentrated under reduced pressure. The residue was purified
s), 4.32 (2/3H, td, = 9.6, 3.7 Hz), 4.64 (1/3H, dd, = 8.7, 4.6 by silica gel column chromatography (eluent: hexane/EtOAc =
Hz), 4.88 (1/3H, ddd, = 10.1, 8.7, 5.5 Hz), 5.02 (2/3H, d, 2/3) to give 22 (26 mg, 78%) as colourless needles. Mp 214–
2.4 Hz), 5.08 (2/3H, d, = 12.4 Hz), 5.12 (1/3H, d, = 11.9 216 °C (from hexane/CH Cl ). [
Hz), 5.16 (1/3H, d, = 11.9 Hz), 5.25–5.41 (8/3H, m), 5.82 max (KBr)/cm 3233, 3161, 2968, 2932, 2871, 1685, 1669,
2/3H, dd, = 25.7, 4.1 Hz), 5.90 (1/3H, dd, = 22.4, 5.5 Hz), 1645, 1483, 1466, 1437, 1392, 1330, 1294, 1200, 1146, 1090,
.63 (2/3H, d, = 7.8 Hz), 6.823 1060, 1037, 820, 793, 757. H (400 MHz, CDCl ) 0.92 (3H, d,
1/3H, d, = 7.3 Hz), 6.96 (1/3H, t,
J
= 6.4 Hz), 0.93 (2H, d,
= 6.4 Hz), 1.53–1.60 (1H, m), 1.65–1.78 temperature. After stirring under 3–4 atm of hydrogen for 2 h,
= 19.2, 14.2, 4.6 the mixture was filtered through a small pad of celite and
J
= 6.4 Hz), 0.97 (1H, d,
J
=
was added 10% palladium on carbon (10 mg) at room
J
J
J
J
J
J
J =
2
5
1
J
J
]D +212.6 (c 0.20 in CHCl3).
2
2
–
1
J
(
6
(
=
J
J
J
= 7.8 Hz), 6.820 (2/3H, t,
J
3
J
J
J
= 7.3 Hz), 7.21 (2/3H, t,
J
= 6.4 Hz), 0.94 (3H, d,
J
= 6.4 Hz), 1.50–1.75 (3H, m), 2.62
= 12.4,
7.8 Hz), 7.26–7.36 (19/3H, m). C (100 MHz, CDCl , major (3H, s), 2.75 (1H, dt,
J
= 13.7, 12.4 Hz), 3.07 (1H, dd, J
3
8
| J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 2012