The Journal of Organic Chemistry
Page 28 of 52
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Hex/EtOAc (98:2) to afford the desired product (8) as pale brown wax (774 mg, 80%). R = 0.21 (silica
f
-1
1
gel, Hex/EtOAc 95:5). IR (NaCl): νmax = 2970, 2928, 1615, 1503, 1373, 1197, 1173, 730 cm . H NMR
CDCl , 200 MHz): δ = 1.21 (t, 6H, CH , J = 7.0 Hz), 3.43 (q, 4H, CH , J = 7.0 Hz), 6.64 (dd, 1H, CH,
J = 8.8, 2.2 Hz), 6.82 (s, 1H, C indole-H), 7.18 (d, 1H, CH, J = 8.8 Hz), 7.36–7.54 (m, 3H, CH), 7.58 (d,
H, J = 2.2 Hz), 7.86 (d, 2H, CH, J = 7.0 Hz). C NMR (CDCl ),
(
3
3
2
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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0
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3
1
3
, 50.3 MHz): δ = 175.5 (C
q
), 146.7 (C
), 120.2 (CH), 110.9
S:
q
141.0 (C
q
), 138.8 (C
q
), 133.9 (CH), 129.2 (CH), 127.3 (CH), 125.0 (CH), 122.4 (C
q
+
(CH), 99.1 (CH), 45.3 (CH
2
), 12.8 (CH
3
). ESI-MS m/z (%): 455 [M + 1] (100). Calcd for C18
H
19IN
2
O
2
C, 47.59; H, 4.22; N, 6.17; found: C, 47.93; H, 4.41; N, 6.30.
Synthesis of 6-morpholino-1-(phenylsulfonyl)-1H-indole (9). Under a nitrogen atmosphere, to a
solution of 1-(phenylsulfonyl)-1H-indol-6-amine (6) (800 mg, 2.94 mmol) in dry DMF (12 mL), N,N-
diisopropyl-ethylamine (1.02 mL, 759 mg, 5.88 mmol) and bis-(2-bromoethyl)ether (0.55 mL, 1.02 g,
4
.41 mmol) were added. The reaction mixture was stirred overnight at 90 °C until no more starting
product was detectable by TLC analysis. The residue was poured into sat. aqueous NaHCO (200 mL)
and extracted with EtOAc (3 × 150 mL), washed with brine and dried over Na SO . The solvent was
3
2
4
removed at reduced pressure and then the crude product was purified by flash chromatography over a
silica gel column using Hex/EtOAc (80:20) to afford the desired product (9) as pale yellow solid (650
mg, 65%). Mp 161–163 °C. R
853, 1615, 1488, 1448, 1367, 1176, 1128, 724 cm . H NMR (CDCl
J = 4.8 Hz), 3.91 (t, 4H, CH , J = 4.8 Hz), 6.56 (dd, 1H, C indole-H, J = 3.7, 0.7 Hz), 6.92 (dd, 1H, CH,
J = 8.8, 2.2 Hz), 7.37–7.55 (m, 6H, CH), 7.82–7.88 (m, 2H, CH). C NMR (CDCl
f
= 0.42 (silica gel, Hex/EtOAc 60:40). IR (KBr): νmax = 3436, 3140, 2967,
-1
1
2
3
, 200 MHz): δ = 3.20 (t, 4H, CH ,
2
2
3
1
3
3
, 50.3 MHz): δ =
1
49.7 (C
q
), 138.6 (C
q
), 136.5 (C
q
), 133.9 (CH), 129.4 (CH), 126.9 (CH), 125.2 (CH), 124.5 (C
q
), 121.9
(CH), 114.3 (CH), 109.4 (CH), 100.8 (CH), 67.1 (CH
2
), 50.6 (CH
2
). ESI-MS m/z (%): 343 [M + 1]+
(100). Calcd for C18
H
18
N
2
3
O S: C, 63.14; H, 5.30; N, 8.18; found: C, 62.88; H, 5.19; N, 8.00.
Synthesis of 2-Iodo-6-morpholino-1-(phenylsulfonyl)-1H-indole (10). The iodination reaction at the
position 2 was performed under the previously optimized reaction conditions (see the synthesis of
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