Paper
Organic & Biomolecular Chemistry
+
7
7
.12 (t, J = 9.0 Hz, 2H), 7.31 (s, 1H), 7.35 (d, J = 9.0 Hz, 2H), 162.75, 162.87. HRMS (EI) for C25
H
24
O
6
N
2
S (M ): calcd,
1
3
.45 (s, 1H), 7.55 (d, J = 16.0 Hz, 1H), 7.63–7.65 (m, 2H).
C
480.1355; found, 480.1353.
5-Bromo-1-(4-methoxyphenylsulfonyl)-7-nitroindoline (21). To
15.16, 119.47, 122.56, 128.45, 128.89, 129.43, 130.03, 130.13, a solution of 20 (2.0 g, 8.23 mmol) in pyridine (10 mL),
31.45, 131.58, 134.01, 134.08, 136.35, 137.53, 139.65, 140.67, 4-methoxybenzenesulfonyl chloride (3.4 g, 16.46 mmol) was
59.81, 162.68, 163.16. MS (EI) m/z: 468 (M , 1.24%), 263 added, and the mixture was stirred at 95 °C overnight. The
NMR (75 MHz, DMSO): 28.37, 51.91, 55.76, 114.40, 114.87,
1
1
1
+
+
(100%). HRMS (EI) for C24
H
21
O
5
N
2
FS (M ): calcd, 468.1155; mixture was quenched with NaHCO3(aq) and extracted with
found, 468.1158.
CH Cl . The organic layer was dried over anhydrous MgSO
2 2 4
(
E)-N-Hydroxy-3-(1-(4-methoxyphenylsulfonyl)-7-(pyridin-4-yl)- and concentrated. The residue was purified by column chrom-
indolin-5-yl)acrylamide (16). The title compound was obtained atography (EtOAc–n-hexane = 1 : 2) to afford 21 (2.96 g, 87%).
1
in 31% overall yield from 28h in a similar manner as that
H NMR (500 MHz, CDCl ): δ 2.70 (t, J = 7.5 Hz, 2H), 3.87 (s,
3
1
described for the preparation of 14; H NMR (500 MHz, 3H), 4.05 (t, J = 7.5 Hz, 2H), 6.95 (d, J = 9.0 Hz, 2H), 7.50 (s,
DMSO-d ): δ 2.27 (t, J = 7.0 Hz, 2H), 3.79 (s, 3H), 4.04 (t, J = 7.0 1H), 7.66 (d, J = 9.0 Hz, 2H), 7.90 (s, 1H).
Hz, 2H), 6.49 (d, J = 16.0 Hz, 1H), 6.98 (d, J = 9.0 Hz, 2H), 7.32 (E)-Methyl 3-(1-(4-methoxyphenylsulfonyl)-7-nitroindolin-5-yl)-
d, J = 9.0 Hz, 2H), 7.40–7.42 (m, 2H), 7.54 (s, 1H), 7.66 (d, J = acrylate (22a). To a suspension of TEA (1.03 mL, 7.40 mmol),
.5 Hz, 2H), 8.60 (d, J = 5.5 Hz, 2H). C (75 MHz, DMSO): PPh (0.26 g, 0.99 mmol), and Pd(OAc) (0.11 g, 0.49 mmol),
8.22, 51.89, 55.81, 114.50, 119.82, 123.02, 123.71, 128.08, compound 21 (2.04 g, 4.94 mmol) in DMF (5 mL), methyl acry-
6
(
1
3
5
2
1
1
3
2
28.85, 129.48, 132.19, 134.34, 137.34, 139.87, 140.75, 147.66, late (0.53 mL, 5.92 mmol) was added, and the mixture was
49.44, 162.68, 163.28. MS (EI) m/z: 451 (M , 0.09%), 236 stirred at 90 °C overnight. The mixture was cooled to room
+
+
(100%). HRMS (EI) for C24
H
22
O
5
N
2
S (M ): calcd, 451.1202; temperature and filtered through a pad of Celite. The filtrate
found, 451.1201.
was extracted with CH Cl and NaHCO3(aq). The organic layer
2
2
(E)-3-(7-Cyano-1-(4-methoxyphenylsulfonyl)indolin-5-yl)-N-hydro- was dried over anhydrous MgSO4 and concentrated. The
xyacrylamide (17). The title compound was obtained in 27%
residue was purified by column chromatography (EtOAc–
n-hexane = 1 : 4) to afford 22a (1.81 g, 88%) as a yellow solid.
overall yield from 22i in a similar manner as that described for
1
1
the preparation of 9; H NMR (500 MHz, CD OD): δ 2.40 (t, J =
3
mp 155.2 °C. H NMR (500 MHz, CDCl ): δ 2.70 (t, J = 7.5 Hz,
3
7
1
7
.5 Hz, 2H), 3.79 (s, 3H), 4.03 (t, J = 7.5 Hz, 2H), 6.44 (d, J =
6.0 Hz, 1H), 6.96 (d, J = 9.0 Hz, 2H), 7.46 (d, J = 16.0 Hz, 1H),
.51 (d, J = 9.0 Hz, 2H), 7.58 (s, 1H), 7.76 (s, 1H). C (75 MHz,
2
H), 3.80 (s, 3H), 3.85 (s, 3H), 4.07 (t, J = 7.5 Hz, 2H), 6.44 (d,
J = 16.0 Hz, 1H), 6.92 (d, J = 9.0 Hz, 2H), 7.50 (s, 1H), 7.60 (d, J
1
3
13
=
(
1
1
16.0 Hz, 1H), 7.62 (d, J = 9.0 Hz, 2H), 7.86 (s, 1H). C NMR
75 MHz, CDCl ): 29.12, 52.08, 55.84, 114.56, 120.21, 123.47,
27.75, 128.83, 129.91, 133.28, 136.74, 140.70, 141.69, 142.45,
DMSO): 28.04, 52.19, 55.85, 104.85, 114.83, 116.63, 121.08,
3
1
1
27.77, 127.83, 129.61, 132.22, 134.02, 135.75, 139.68, 143.92,
62.16, 163.56. MS (EI) m/z: 389 (M , 0.27%), 171 (100%).
+
+
18 2 7
63.98, 166.75. HRMS (ESI) for C19H N NaO S (M + Na ):
+
HRMS (EI) for C19
99.0887.
E)-N-Hydroxy-3-(7-(3-hydroxy-3-methylbut-1-ynyl)-1-(4-methoxy-
H
17
O
5
N
3
S (M ): calcd, 399.0889; found,
calcd, 441.0732; found, 441.0711.
E)-Methyl 3-(7-amino-1-(4-methoxyphenylsulfonyl)indolin-5-yl)-
acrylate (22b). A suspension of 21a (0.4 g, 0.96 mmol), iron
powder (0.16 g, 2.87 mmol), and NH Cl (0.1 g, 1.91 mmol) in
IPA (9.5 mL) and water (1.9 mL) was heated to reflux for 4 h.
The mixture was cooled to room temperature and filtered
through a pad of Celite. The filtrate was evaporated under
reduced pressure and extracted with EtOAc. The organic layer
was dried over anhydrous MgSO4 and concentrated. The
residue was purified by column chromatography (EtOAc–
3
(
(
phenylsulfonyl)indolin-5-yl)acrylamide (18). The title compound
was obtained in 7% overall yield from 22j in a similar manner
as that described for the preparation of 9; H NMR (500 MHz,
4
1
CD
.98 (t, J = 7.5 Hz, 2H), 6.40 (d, J = 15.5 Hz, 1H), 6.97 (d, J = 9.0
Hz, 2H), 7.29 (s, 1H), 7.44–7.48 (m, 2H), 7.54 (d, J = 9.0 Hz,
3
OD): δ 1.59 (s, 6H), 2.30 (t, J = 7.5 Hz, 2H), 3.83 (s, 3H),
3
1
3
2
6
1
H). C NMR (75 MHz, DMSO): 28.27, 31.50, 52.39, 55.79,
3.89, 78.34, 99.36, 114.54, 116.67, 123.52, 128.72, 128.88, n-hexane = 1 : 3) to afford 22b (0.3 g, 80%) as a yellow solid.
1
29.55, 131.24, 131.46, 131.59, 132.11, 133.35, 138.97, 163.19. mp 70.4 °C. H NMR (500 MHz, CDCl ): δ 2.20 (t, J = 7.5 Hz,
3
+
MS (EI) m/z: 456 (M , 0.71%), 57 (100%). HRMS (EI) for 2H), 3.79 (s, 3H), 3.83 (s, 3H), 3.99 (t, J = 7.5 Hz, 2H), 6.30 (d,
C
+
23
H
24
O
6
N
2
S (M ): calcd, 456.1355; found, 456.1354.
J = 16.0 Hz, 1H), 6.62 (s, 1H), 6.74 (d, J = 1.0 Hz, 1H), 6.85 (d,
(
E)-3-(7-(Benzyloxy)-1-(4-methoxyphenylsulfonyl)indolin-5-yl)- J = 8.5 Hz, 2H), 7.52 (d, J = 16.0 Hz, 1H), 7.57 (d, J = 9.0 Hz,
1
3
N-hydroxyacrylamide (19). The title compound was obtained 2H). C NMR (75 MHz, CDCl ): 28.98, 51.75, 53.35, 55.68,
3
in 31% overall yield from 22k in a similar manner as that 113.77, 114.25, 115.95, 117.45, 128.28, 129.65, 129.88, 133.98,
1
described for the preparation of 9; mp 151 °C. H NMR 139.38, 140.54, 144.56, 163.64, 167.53. HRMS (ESI) for
+
(
500 MHz, DMSO-d ): δ 2.51 (t, J = 7.5 Hz, 2H), 3.80 (s, 3H), C H N2O S (M + H ): calcd, 389.1171; found, 389.1155.
6
19 21
5
4
6
1
9
6
1
.00 (t, J = 7.5 Hz, 2H), 5.18 (s, 2H), 6.40 (d, J = 16.0 Hz, 1H),
(E)-Methyl 3-(7-chloro-1-(4-methoxyphenylsulfonyl)indolin-5-yl)-
.94 (s, 1H), 6.97 (d, J = 9.0 Hz, 2H), 7.12 (s, 1H), 7.13–7.34 (m, acrylate (22c). The title compound was obtained in 91% overall
H), 7.39 (t, J = 7.5 Hz, 2H), 7.51 (d, J = 7.5 Hz, 2H), 7.55 (d, J = yield from 27c in a similar manner as that described for the
1
3
1
3
.0 Hz, 2H). C NMR (75 MHz, DMSO): 28.74, 52.78, 55.71, preparation of 22d; H NMR (500 MHz, CDCl ): δ 2.49 (t, J =
9.81, 113.01, 114.27, 116.23, 118.96, 127.61, 127.75, 128.35, 7.5 Hz, 2H), 3.80 (s, 3H), 3.85 (s, 3H), 4.03 (t, J = 7.5 Hz, 2H),
29.32, 129.93, 131.79, 134.21, 136.94, 137.96, 139.31, 150.41, 6.37 (d, J = 16.0 Hz, 1H), 6.90 (d, J = 9.0 Hz, 2H), 7.17 (s, 1H),
8972 | Org. Biomol. Chem., 2014, 12, 8966–8976
This journal is © The Royal Society of Chemistry 2014