Pyridinium salts - Versatile reagents for the regioselective synthesis of functionalized thiazocino[2,3-b]indoles by tandem dinucleophilic reactions of thiooxindoles

Article abstract of DOI:10.1016/j.tet.2012.09.059

The reaction of thiooxindoles with various 2- and 3-substituted pyridinium salts afforded a variety of functionalized thiazocinoindoles. The products have been prepared in good to excellent yields by regioselective dinucleophilic C/S-cyclocondensation of

Full text of DOI:10.1016/j.tet.2012.09.059

Tetrahedron 68 (2012) 9685e9693
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Pyridinium saltsdversatile reagents for the regioselective synthesis
of functionalized thiazocino[2,3-b]indoles by tandem dinucleophilic
reactions of thiooxindoles
,
,
a
c
Mostafa Kiamehr a b, Firouz Matloubi Moghaddam b , Pavel V. Gormay , Volodymyr Semeniuchenko ,
*
Alexander Villinger a, Peter Langer a d, Viktor O. Iaroshenko a
,
,c,
*
a
€
€
Institut fur Chemie, Universitat Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
b Laboratory of Organic Synthesis and Natural Products, Department of Chemistry, Sharif University of Technology, PO Box 11155-9516, Tehran, Iran
c National Taras Shevchenko University, 62 Volodymyrska st., 01033 Kyiv-33, Ukraine
d
€
€
Leibniz-Institut fur Katalyse e.V. an der Universitat Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 June 2012
Received in revised form 5 September 2012
Accepted 11 September 2012
Available online 18 September 2012
The reaction of thiooxindoles with various 2- and 3-substituted pyridinium salts afforded a variety of
functionalized thiazocinoindoles. The products have been prepared in good to excellent yields by re-
gioselective dinucleophilic C/S-cyclocondensation of thiooxindoles with pyridinium salts.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Condensation
Heterocycles
Nucleophilic addition
Pyridines
Regioselectivity
1. Introduction
various [3þ3] cycloadditions (Scheme 1). Reactions of this type
offer routes to the bridged nitrogen-containing scaffolds, such as
Pyridinium salts are well known for their reactions with nu-
cleophilic species with or without ring opening. They represent
important building blocksl,2 for the synthesis of various pharma-
cologically relevant tetrahydropyridine derivatives.3,4 These sub-
structures occur in various natural products and synthetic
pharmaceuticals.5,6 At the same time, heterocyclic systems con-
taining an annulated pyridinium core, such as quinolinium and
isoquinolinium salts, are of considerable importance as building
blocks for the synthesis of various alkaloid frameworks.7
pyrroles and indoles, which are of pharmacological significance.
Scheme 1.
In recent years, our laboratory studied various cyclization re-
actions of dinucleophiles with pyridinium salts, e.g., the cyclization
of 1,3-bis(silyl enol ethers), masked 1,3-dicarbonyl dianions, with
quinolinium,8 isoquinolinium,9 quinazolinium,10 and quinox-
alinium11 salts. Moghaddam and co-workers studied cyclization
reactions of quinolinium12 and isoquinolinium13 salts with various
other 1,3-dinucleophiles. In these reactions the pyridinium salt
reacts as a 1,3-dielectrophile, which opens up possibilities of
Herein, we report for the first time the formation of a bridged
thiazocinoindole framework by reaction of thiooxindoles with
substituted pyridinium salts (Scheme 2).
2. Results and discussion
At the beginning, we have investigated the optimal conditions
for reactions of 3-acyl-pyridinium iodide and bromide with thio-
oxindoles. The optimization was carried out using the unsub-
stituted thiooxindole 1a (R1¼H) and 3-(ethoxycarbonyl)-1-
methylpyridin-1-ium iodide 2h (R2¼Me, R3¼H, R4¼COOEt, X¼I).
* Corresponding authors. Tel.: þ49 381 4986410; fax: þ49 381 49864112; e-mail
addresses: viktor.iaroshenko@uni-rostock.de, iva108@googlemail.com (V.O.
Iaroshenko).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.09.059

9686
M. Kiamehr et al. / Tetrahedron 68 (2012) 9685e9693
yield was observed for potassium carbonate using acetonitrile as
the solvent (reaction at room temperature) (Table 1).
To generalize this methodology, we investigated the scope and
limitation of the reaction with a series of 3-acyl-pyridinium iodides
and bromides and different thiooxindoles under the optimized
reaction conditions (Scheme 3).
The reactions of thiooxindoles 1 and 3-carbonyl pyridinium salts 2
proceeded cleanly under mild conditions to give the corresponding
polycyclic 2,5,6,11-tetrahydro-2,6-methano[1,5]thiazocino-[2,3-b]in-
doles 3aer in 56e99% yield (Table 2). All reactions proceeded with
highregioselectivity. ItcanbenoticedthatreactionwithN-substituted
thiooxindoles offers higher yields of the desired products. The reason
may be their inability to undergo a competing N-deprotonation.
Table 2
Synthesis of compounds 3
Product
R1
R2
R3
X
Yielda (%)
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
H
H
H
H
H
H
H
Me
Me
Me
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
Me
Allyl
Bn
Me
Allyl
Bn
Me
Me
Bn
Me
Et
Me
Me
Me
Ph
Ph
Ph
OEt
Me
Me
Ph
Ph
Ph
OEt
Me
Me
Me
Ph
I
69
56
64
78
80
56
84
98
84
70
85
76
94
97
94
99
85
98
Br
Br
I
Br
Br
I
I
Br
I
Scheme 2. Reagents and conditions: (i) conditions see Table 1.
In all cases, we observed the formation of only one product of
condensation, i.e., thiazocino[2,3-b]indole 3g (Table 1, Scheme 3).
The effect of solvent, base nature and temperature on the re-
action was studied to optimize the reaction conditions. Our in-
Table 1
Br
Br
I
Optimization of the synthesis of 3ga
Bn
Me
Me
Et
Allyl
Allyl
Me
Entry
Base
Solvent
Temp (ꢀC)
Time (h)
Yield
I
1
2
3
4
5
6
7
8
No base
NaHCO3
NaHCO3
K2CO3
K2CO3
K2CO3
Na2CO3
K2CO3
Cs2CO3
NEt3
Pyridine
NaH
AcOK
K2CO3
K2CO3
K2CO3
No base
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DMF
20e80
20
80
20
20
20
20
80
20
16
24
8
12
24
48
24
8
24
24
24
24
24
24
24
24
16
0
5
Br
Br
Br
I
18
54
84
82
58
25
34
16
0
0
0
8
45
0
OEt
a
Yields of isolated products.
It is worth to mention that no reaction is observed in the case of
pyridinium salts, which do not contain any electron-withdrawing
groups. In case of a 3-nitro-substituted pyridinium salt, no forma-
tion of thiazocinoindoles was detected; we speculate that a ring
opening process occurred instead, however the reason was not
specially investigated.
The reaction of 3-cyano-substituted pyridinium salts with thi-
ooxindole resulted in the formation of mixtures of the regioiso-
meric thiazocinoindoles 4 and 5 (Scheme 4, Table 3). The structures
of the products 4 and 5 were elucidated by 1H NMR and 13C
NMR spectroscopy. The structures of compounds 4e and 5e
were independently confirmed by X-ray crystal structure analysis
(Figs. 3 and 4).14
9
10
11
12
13
14
15
16
17
20
20
ꢁ5 to 20
AcOH
20
CH2Cl2
Acetone
H2O
20
20
20
20e80
CH3CN
0
a
Yields of isolated products. Reaction of 1a (R1¼H) with 2h (R2¼Me, R3¼H,
R4¼COOEt, X¼I), Scheme 3.
The structures of products 3 were established by spectroscopic
methods. The structures of 3g and 3j were independently con-
firmed by X-ray14 crystallography (Figs. 1 and 2).
To demonstrate the scope of this reaction, the reaction of thio-
oxindoles 1 with different 2-, 3-, and 4-substituted pyridinium salts
was investigated. The latter were prepared by simple alkylation of
appropriate pyridines and could be used without additional
purification.
The reaction of thiooxindoles 1 with 2-cyano-substituted pyr-
idiniumsaltsaffordedtheisomericthiazocinoindoles6aee(Scheme5)
ingoodtoexcellentyieldsastheonlyproducts(Table4).
To explain the mechanism of the formation of products 3e6, we
proposed a mechanism as shown in Scheme 6. Pyridinium salts 2
can be attacked by nucleophiles at positions 2, 4 and 6. Due to the
steric effect of the substituent located at carbon C-2, carbons C-4
and C-6 in the pyridinium salts they become more susceptible
to attack by nucleophiles. According to our assumptions, a base-
Scheme 3. Tandem dinucleophilic reaction of thiooxindoles with 3-
carbonylpyridinium salts. Reagents and conditions: (i) CH3CN, K2CO3, 20 ꢀC, 24 h.
vestigation revealed that the base plays an important role. There is
no reaction without base, and the yield is low in case of employ-
ment of a weak base, such as sodium bicarbonate. Organic bases
like tertiary amines or pyridine are also unfavourable. The best
mediated dinucleophilic addition of the thiooxindole
1 and

M. Kiamehr et al. / Tetrahedron 68 (2012) 9685e9693
9687
Scheme 4. Tandem dinucleophilic reaction of thiooxindoles with 3-cyanopyridinium
salts. Reagents and conditions: (i) CH3CN, K2CO3, 20 ꢀC, 24 h.
Fig. 3. ORTEP plot of structure 4e.
Table 3
Synthesis of compounds 4 and 5
Products
R1
R2
X
Ratio 4/5
Overall yielda (%)
4a/5a
4b/5b
4c/5c
4d/5d
4e/5e
4f/5f
H
H
Me
Me
Ph
Ph
Me
Bn
Allyl
Bn
Me
Allyl
I
60:40
86:14
100:0
80:20
65:35
73:27
87
87
64
67
85
88
Br
Br
Br
I
Br
a
Yields of isolated products.
Fig. 4. ORTEP plot of structure 5e.
Fig. 1. ORTEP plot of structure 3g.
Scheme 5. Tandem dinucleophilic reaction of thiooxindoles with 2-cyanopyridinium
salts. Reagents and conditions: (i) CH3CN, K2CO3, 20 ꢀC, 24 h.
pyridinium salts 2 to produce compounds 3 and 5 can proceed via
intermediates A and B (path a). Initially, the thioxindole is depro-
tonated by base to yield a carbanion. Subsequently, its nucleophilic
addition onto carbon C-6 of the pyridinium salt leads to the
Fig. 2. ORTEP plot of structure 3j.

9688
M. Kiamehr et al. / Tetrahedron 68 (2012) 9685e9693
Table 4
Synthesis of compounds 6
formation of intermediate A, which can exist in the thioamide-form
A1 as well as in the thioenol-form A2. Intermolecular proton mi-
gration delivers the zwitterionic structure B; this is followed by
a second nucleophile attack to give compounds 3 and 5. The for-
mation of the other isomer can be explained by attack of the thi-
ooxindole anion to position C-4 of the pyridinium salt (path b). The
subsequent protonation converts C to the next key intermediate D,
which is then transformed to products 4 and 6.
Product
R1
R2
X
Yielda (%)
6a
6b
6c
6d
6e
Me
Me
Ph
Ph
Ph
Me
Bn
Me
Allyl
Bn
I
Br
I
Br
Br
65
80
88
92
78
a
Yields of isolated products.
In the case of the presence of a moderate electron-withdrawing
group (e.g., acetyl) located at position-3 in pyridinium salts, the
difference between the reactivities of carbons C-6 and C-4 seems to
be sufficient resulting in a good selectivity. In contrast, the selec-
tivity is low for pyridinium salts containing a strong electron-
withdrawing group, such as the cyano-group. For 2-substituted
pyridinium salts it seems that the steric effects of the substituent
located at the nitrogen atom plays an important role to direct the
attack of the nucleophile to the sterically less hindered position 4.
R3
R2
R3
R2
N
R4
N
R4
S
N
R1
A1
SH
N
R1
3. Conclusions
A2
In conclusion, we have reported a novel dinucleophilic cyclo-
condensation for the synthesis of various bridged thiazocinoindoles
starting from thiooxindoles and pyridinium salts. The latter must
carry an EWG as substituent, otherwise the reaction cannot pro-
ceed; the base (K2CO3) was found also to be crucial component. The
reaction regioselectivity depends on substituent: 3-acyl group in
pyridinium salt leads no only one regioisomer (attack of 4-C of
pyridine ring, product 3) while 3-CN group results in bad dis-
crimination of 2-C and 4-C thus leading to the regioisomeric mix-
ture of products 4 and 5. 2-CN group directs the nucleophile to 4-C
due to steric effect thus leading regiospecifically to products 6.
R3
R2
N
R4
R1
N
R4
R3
S
S
+
N
R2
X_
N
R1
B
path a
R2
N
4. Experimental part
4.1. General methods
S
N
1
R1
N
S
3, 5
R4
Commercially available materials were purchased from Sigmae
Aldrich and ACROS and were used without any additional purifica-
tion. Analytical thin layer chromatography was performed on
R1
R4
i
R4
+
+
N
R2
2
R3
ꢀ
R3
R2
0.20 mm 60 A silica gel plates. Column chromatography was per-
X
ꢀ
formed using 60 A silica gel (60e200 mesh). Infrared spectra were
N
recorded in an ATR apparatus. Mass spectrometric data (MS) were
obtained by electron ionization (EI, 70 eV), chemical ionization (CI,
isobutane) or electrospray ionization (ESI). Melting points are un-
corrected. 1H and C NMR and DEPT spectra in CDCl3 and DMSO-d6 at
N
R1
S
4, 6
path b
room temperature; d in parts per million relative to Me4Si as internal
standard, J in Hz.
4.2. General procedure for the synthesis of compounds 2
R3
R4
R4
R3
R2
N
Alkyl bromide or iodide (0.2 mol) was added dropwise to the
acetone solution (150e200 mL) of corresponding pyridine de-
rivative (0.1 mol). The mixture was stirred under argon for 2e3 days
(progress of alkylation was controlled by TLC). After completion the
formed precipitate was filtered, washed with acetone and dried in
vacuum at room temperature (heating caused decomposition). The
obtained pyridinium salt was used without further purification or
characterization.
S
N
R2
N
R1
X
S
N
R1
D
R3
R3
R4
R4
R2
N
R2
4.3. General procedure for the synthesis of compounds 3e6
N
In the 25 mL Schlenk flask, under argon flow, 0.75 mmol of
indolin-2-thiones 1, 0.75 mmol of appropriate pyridinium salts 2
and 0.75 mmol (104 mg) of K2CO3 were loaded. The flask was
covered with septum stopper and 7 mL of absolute CH3CN was
added by syringe; reaction mixture stirred at room temperature for
S
N
R1
SH
N
R1
C1
C2
Scheme 6. A plausible mechanism for the formation of compounds 3e6.

M. Kiamehr et al. / Tetrahedron 68 (2012) 9685e9693
9689
24 h. Then the solvent was removed under reduced pressure and
the crude material was subjected to column chromatography.
d
¼2.17e2.42 (m, 2H, CHCH2CH), 4.07e4.24 (m, 2H, NCH2CHCH2),
4.73 (s, 1H, CH), 4.93 (s, 1H, CH), 5.23e5.36 (m, 2H, NCH2CHCH2),
5.84e5.96 (m, 1H, NCH2CHCH2), 7.00e7.07 (m, 2H, HAr), 7.23e7.26
(m, 2H, HAr, CH), 7.32e7.44 (m, 5H, HAr), 7.56e7.58 (m, 1H, HAr),
4.3.1. 1-(5-Methyl-2,5,6,11-tetrahydro-2,6-methano[1,5]thiazocino
[2,3-b]indol-3-yl)ethanone (3a). Pale white solid, mp 234e236 ꢀC,
11.29 (s, 1H, NH). 13C NMR (62.9 MHz, DMSO-d6):
d¼28.4 (CH2), 31.3
yield: 69% (147 mg). 1H NMR (300 MHz, DMSO-d6)
COMe), 2.17e2.35 (m, 2H, CH2), 3.31 (s, 3H, NMe), 4.49 (s,1H, CH), 4.82
(s, 1H, CH), 7.00e7.04 (m, 2H, HAr), 7.21e7.24 (m, 1H, HAr), 7.60e7.63
(m, 1H, HAr), 7.65 (s, 1H, CH), 11.22 (s, 1H, NH). 13C NMR (62.9 MHz,
d
¼2.05 (s, 3H,
(CH), 46.2 (CH), 56.7 (NCH2), 109.6 (C), 110.2 (CH), 110.9 (C), 115.8
(CH), 118.2 (CH2), 119.2, 120.0 (CH), 127.2 (C), 127.9, 128.0, 129.5
(CH), 129.8 (C), 133.9 (CH), 136.0, 140.3 (C), 150.7 (CH), 189.4 (CO). IR
~
(ATR, cmꢁ1):
n
¼3140 (w), 1643 (w), 1600 (w), 1578 (m), 1556 (s),
DMSO-d6):
d
¼23.6 (CH3), 28.1 (CH2), 30.8 (CH), 41.9 (CH), 47.2 (NCH3),
1549 (s), 1435 (m), 1394 (m), 1345 (m), 1216 (m), 1202 (m), 1024
(m), 926 (m), 740 (s), 7001 (s), 643 (m). MS (GC, 70 eV): m/z (%)¼
372 (Mþ, 100), 331 (82), 224 (15), 161 (11), 105 (70), 77 (29). HRMS
(ESI): calcd for C23H20N2OS (Mþ) 372.12909, found 372.128832.
109.6 (C), 110.0 (CH), 111.2 (C), 115.8, 119.1, 119.9 (CH), 127.6, 129.8,
135.9 (C),149.2 (CH),189.6 (CO). IR (ATR, cmꢁ1):
n
¼3167 (w),1614 (w),
~
1557 (s),1488(w),1436 (m),1384 (m),1331 (s),1195(m),1165(s),1093
(m), 1008 (m), 742 (s), 664 (s), 569 (s). MS (GC, 70 eV): m/z (%)¼284
(Mþ, 100), 283 (26), 251 (21), 241 (23), 161 (76), 136 (21). HRMS (ESI):
calcd for C16H17N2OS (MþH) 285.10561, found 285.10614.
4.3.6. (5-Benzyl-2,5,6,11-tetrahydro-2,6-methano[1,5]thiazocino
[2,3-b]indol-3-yl)(phenyl)methanone (3f). Pale yellow solid, mp
211e213 ꢀC, yield: 56% (177 mg). 1H NMR (300 MHz, DMSO-d6)
4.3.2. 1-(5-Allyl-2,5,6,11-tetrahydro-2,6-methano[1,5]thiazocino[2,3-
d
¼2.23e2.35 (m, 2H, CHCH2CH), 4.72e4.74 (m, 3H, NCH2, CH),
4.84 (s, 1H, CH), 7.00e7.25 (m, 2H, HAr), 7.27e7.46 (m, 12H, HAr
CH), 7.53e7.56 (m, 1H, HAr), 11.31 (s, 1H, NH). 13C NMR (62.9 MHz,
DMSO-d6):
b]indol-3-yl)ethanone (3b). Pale yellow solid, mp 189e191 ꢀC, yield:
,
56% (130 mg). 1H NMR (300 MHz, DMSO-d6)
d
¼2.04 (s, 3H, COMe),
2.17e2.31 (m, 2H, CHCH2CH), 4.18e4.20 (m, 2H, NCH2CHCH2), 4.49
(m, 1H, CH), 4.83 (s, 1H, CH), 5.31e5.46 (m, 2H, NCH2CHCH2),
5.94e6.07 (m, 1H, NCH2CHCH2), 6.97e7.06 (m, 2H, HAr), 7.20e7.23
(m,1H, HAr), 7.51e7.54 (m,1H, HAr), 7.66 (s,1H, CH),11.20 (s,1H, NH).
d
¼28.4 (CH2), 31.3 (CH), 46.2 (CH), 57.8 (NCH2), 109.4
(C), 110.2 (CH), 110.9 (C), 115.7, 119.3, 120.1 (CH), 127.3 (C), 127.6,
127.7, 127.8, 127.9, 128.8, 129.5 (CH), 129.9, 136.1, 136.7, 140.2 (C),
151.1 (CH), 189.5 (CO). IR (ATR, cmꢁ1):
n
¼3241 (w), 1602 (w), 1577
~
13C NMR (62.9 MHz, DMSO-d6):
45.8 (CH), 57.0 (NCH2), 109.1 (C), 110.1 (CH), 112.0 (C), 114.8 (CH),
d
¼23.4 (CH3), 28.2 (CH2), 30.7 (CH),
(w), 1538 (s), 1438 (m), 1386 (m), 1350 (m), 1340 (s), 1234 (m), 1197
(s), 1109 (m), 1020 (m), 887 (m), 739 (s), 698 (s), 662 (m). MS (GC,
70 eV): m/z (%)¼422 (Mþ, 44), 331 (61), 183 (23), 149 (23), 105
(84), 91 (100), 77 (40). HRMS (ESI): calcd for C27H23N2OS (MþH)
423.15256, found 423.15244.
118.4 (CH2), 119.0, 119.7 (CH), 127.0, 130.0 (C), 132.8 (CH), 136.0 (C),
147.2 (CH), 190.8 (CO). IR (ATR, cmꢁ1):
n
¼3272 (w), 1644 (w), 1611
~
(w), 1568 (s), 1557 (s), 1428 (m), 1393 (m), 1338 (s), 1192 (m), 1010
(m), 923 (m), 735 (s), 651 (m), 536 (m). MS (GC, 70 eV): m/z (%)¼310
(Mþ,100), 277(20), 269 (85), 267 (17),162 (23),161 (35). HRMS (ESI):
calcd for C18H18N2OS (Mþ) 310.11344, found 310.113214.
4.3.7. Ethyl 5-methyl-2,5,6,11-tetrahydro-2,6-methano[1,5]thiazo-
cino[2,3-b]indole-3-carboxylate (3g). Pale yellow solid, mp
200e202 ꢀC, yield: 84% (198 mg). 1H NMR (300 MHz, DMSO-d6)
4.3.3. 1-(5-Benzyl-2,5,6,11-tetrahydro-2,6-methano[1,5]thiazocino
d
¼1.18 (t, 3H, J¼7.2 Hz, OCH2CH3), 2.23e2.39 (m, 2H, CHCH2CH),
[2,3-b]indol-3-yl)ethanone (3c). White solid, mp 225e227 ꢀC, yield:
3.14 (s, 3H, NMe), 4.04e4.16 (m, 2H, OCH2CH3), 4.43e4.44 (m, 1H,
CH), 4.55 (s, 1H, CH), 6.96e7.03 (m, 2H, HAr), 7.13e7.18 (m, 1H,
64% (173 mg). 1H NMR (300 MHz, DMSO-d6)
d
¼2.11 (s, 3H, COMe),
2.19 (m, 2H, CHCH2CH), 4.52 (s, 1H, CH), 4.73e4.88 (m, 3H, NCH2,
CH), 7.01e7.10 (m, 2H, HAr), 7.24e7.27 (m, 1H, HAr), 7.40e7.57 (m,
6H, HAr), 7.91 (s, 1H, CH), 11.27 (s, 1H, NH). 13C NMR (62.9 MHz,
HAr), 7.32 (s, 1H, CH), 7.40e7.43 (m, 1H, HAr), 8.14 (s, 1H, NH). 13
C
NMR (75.5 MHz, DMSO-d6):
42.6 (CH), 48.1 (NCH3), 59.3 (OCH2), 99.2 (C), 110.3 (CH), 110.5 (C),
d
¼14.7 (CH3), 28.9 (CH2), 33.5 (CH),
DMSO-d6):
d
¼23.8 (CH3), 28.5 (CH2), 30.9 (CH), 45.1 (CH), 57.6
115.7, 120.0, 120.8 (CH), 128.0, 130.4, 136.2 (C), 147.2 (CH), 167.1
(NCH2), 109.5 (C), 110.1 (CH), 111.7 (C), 115.6, 119.3, 120.0 (CH), 127.1
(CO). IR (ATR, cmꢁ1):
n
¼3271 (m), 2929 (w), 1651 (s), 1598 (s),
~
(C), 127.4, 127.7, 128.9 (CH), 129.9, 136.0, 137.2 (C), 148.9 (CH), 190.1
1451 (m), 1318 (m), 1284 (m), 1162 (s), 1070 (s), 1027 (s), 928 (m),
771 (m), 735 (s), 671 (m), 642 (m). MS (GC, 70 eV): m/z (%)¼314
(Mþ, 100), 313 (21), 285 (29), 267 (17), 241 (32), 235 (23), 207 (27),
186 (25), 166 (23), 161 (74). HRMS (ESI): calcd for C17H19N2O2S
(MþH) 315.11618, found 315.11681.
(CO). IR (ATR, cmꢁ1):
n
¼3306 (w), 1614 (w), 1580 (s), 1575 (s), 1428
~
(m), 1343 (s), 1192 (m), 1024 (m), 730 (s), 695 (m), 643 (m). MS (GC,
70 eV): m/z (%)¼360 (Mþ, 80), 327 (15), 270 (17), 269 (100),161 (17),
149 (16), 91 (53), 69 (26), 57 (17), 44 (41), 43 (39), 40 (23). HRMS
(ESI): calcd for C22H20N2OS (Mþ) 360.12909, found 360.128886.
4.3.8. 1-(5,11-Dimethyl-2,5,6,11-tetrahydro-2,6-methano[1,5]thia-
4.3.4. (5-Methyl-2,5,6,11-tetrahydro-2,6-methano[1,5]thiazocino
zocino[2,3-b]indol-3-yl)ethanone (3h). Pale yellow solid, mp
[2,3-b]indol-3-yl)(phenyl)methanone
217e219 ꢀC, yield: 78% (202 mg). 1H NMR (300 MHz, DMSO-d6)
¼2.24e2.45 (m, 2H, CH2), 3.24 (s, 3H, NMe), 4.70 (m,1H, CH), 4.90 (s,
1H, CH), 6.99e7.05(m, 2H, HAr), 7.17(s,1H, CH), 7.23e7.25(m,1H, HAr),
7.33e7.44 (m, 5H, HAr), 7.60e7.63 (m, 1H, HAr), 11.29 (s, 1H, NH). 13
NMR (62.9 MHz, DMSO-d6):
(3d). Yellow solid, mp
174e176 ꢀC, yield: 98% (219 mg). 1H NMR (300 MHz, CDCl3)
d
¼2.14
(s, 3H, COMe), 2.28e2.43 (m, 2H, CH2), 3.30 (s, 3H, NMe), 3.57 (s,
3H, NMe), 4.68e4.70 (m, 2H, 2xCH), 7.08e7.22 (m, 3H, HAr), 7.28
(s, 1H, CH), 7.50e7.53 (m, 1H, HAr). 13C NMR (75.5 MHz, CDCl3):
d
C
d
¼23.8 (CH3), 28.3 (CH2), 30.5 (NCH3), 31.3 (CH), 42.9 (CH), 48.6
d
¼28.0 (CH2), 31.1 (CH), 42.3 (CH), 47.7
(NCH3), 108.5 (CH), 108.6, 112.7 (C), 115.6, 119.8, 120.3 (CH), 127.5,
133.6, 137.1 (C), 148.9 (CH), 191.4 (CO). IR (ATR, cmꢁ1):
n
¼1613 (w),
~
(NCH3), 109.5 (C), 110.1 (CH), 110.5 (C), 115.8, 119.2, 120.0 (CH), 127.5
(C), 127.8, 128.0, 129.3 (CH), 129.7, 136.0, 140.4 (C), 151.7 (CH), 189.1
1564 (s), 1460 (m), 1329 (s), 1170 (m), 1047 (m), 947 (m), 749 (s),
627 (m), 566 (m). MS (GC, 70 eV): m/z (%)¼298 (Mþ, 98), 297 (18),
265 (22), 255 (22), 224 (13), 200 (17), 175 (100), 136 (27). HRMS
(ESI): calcd for C17H18N2OS (Mþ) 298.11344, found 298.113405.
(CO). IR(ATR, cmꢁ1):
n
¼3258(w),1610(w),1578(w),1544(s),1538(s),
~
1440 (m), 1384 (m), 1328 (m), 1201 (m), 1124 (m), 1027 (m), 936 (m),
737 (s), 704 (m), 639 (m). MS (GC, 70 eV): m/z (%)¼346 (Mþ,100), 345
(20), 313 (15), 241 (14), 198 (18), 186 (15), 161 (27), 105 (41), 77 (18).
HRMS (ESI): calcd for C21H18N2OS (Mþ) 346.11344, found 346.113238.
4.3.9. 1-(5-Benzyl-11-methyl-2,5,6,11-tetrahydro-2,6-methano
[1,5]thiazocino[2,3-b]indol-3-yl)ethanone (3i). Yellow solid, mp
4.3.5. (5-Allyl-2,5,6,11-tetrahydro-2,6-methano[1,5]thiazocino[2,3-b]
indol-3-yl)(phenyl)methanone (3e). Pale brown solid, mp
207e209 ꢀC, yield: 80% (223 mg). 1H NMR (300 MHz, DMSO-d6)
97e99 ꢀC, yield: 84% (236 mg). 1H NMR (300 MHz, CDCl3)
(s, 3H, COMe), 2.31e2.34 (m, 2H, CHCH2CH), 3.58 (s, 3H, NMe),
4.52 (d, 1H, J¼15.0 Hz, NCH2), 4.74 (m, 2H, 2xCH), 4.85 (d, 1H,
d
¼2.15

9690
M. Kiamehr et al. / Tetrahedron 68 (2012) 9685e9693
J¼15.0 Hz, NCH2), 7.12e7.23 (m, 3H, HAr), 7.38e7.50 (m, 7H, HAr
,
7.41 (s, 1H, CH), 7.49e7.54 (m, 1H, HAr). 13C NMR (62.9 MHz,
CDCl3):
(CH), 48.2 (NCH3), 59.2 (OCH2), 99.2 (C), 108.3 (CH), 108.9 (C),
CH). 13C NMR (62.9 MHz, CDCl3):
d
¼23.9 (CH3), 28.6 (CH2), 30.4
d
¼14.7 (CH3), 28.7 (CH2), 30.5 (NCH3), 33.4 (CH), 42.4
(NCH3), 31.4 (CH), 46.1 (CH), 59.0 (NCH2), 108.5 (CH), 108.6, 113.0
(C), 115.5, 119.8, 120.3 (CH), 127.4 (C), 127.4, 128.3, 129.1 (CH),
133.7, 136.3, 137.1 (C), 148.6 (CH), 191.7 (CO). IR (ATR, cmꢁ1):
~
115.7, 119.7, 120.2 (CH), 127.6, 133.2, 137.1 (C), 147.1 (CH), 166.9
(CO). IR (ATR, cmꢁ1):
n
¼2916 (w), 1672 (m), 1667 (m), 1599 (s),
~
n
¼1573 (s), 1464 (m), 1333 (s), 1188 (s), 1151 (m), 1046 (m), 1013
1463 (m), 1315 (m), 1281 (m), 1241 (m), 1155 (s), 1068 (s), 1049 (s),
1011 (m), 770 (m), 736 (s), 704 (m), 651 (m). MS (GC, 70 eV): m/z
(%)¼328 (Mþ, 100), 299 (28), 281 (24), 255 (35), 254 (22), 249
(16), 224 (16), 221 (27), 200 (46), 187 (20), 175 (80), 166 (27).
HRMS (ESI): calcd for C18H20N2O2S (Mþ) 328.12400, found
328.123997.
(m), 735 (s), 705 (m), 670 (m). MS (GC, 70 eV): m/z (%)¼374 (Mþ,
57), 284 (16), 283 (100), 175 (25), 91 (37), 43 (16). HRMS (ESI):
calcd for C23H22N2OS (Mþ) 374.14474, found 374.144680.
4.3.10. (5,11-Dimethyl-2,5,6,11-tetrahydro-2,6-methano[1,5]thiazo-
cino[2,3-b]indol-3-yl)(phenyl)methanone (3j). Pale yellow solid, mp
200e202 ꢀC, yield: 70% (190 mg). 1H NMR (300 MHz, CDCl3)
4.3.14. 1-(5-Methyl-11-phenyl-2,5,6,11-tetrahydro-2,6-methano
[1,5]thiazocino[2,3-b]indol-3-yl)ethanone (3n). Grey solid, mp
127e129 ꢀC, yield: 97% (262 mg). 1H NMR (300 MHz, CDCl3)
d
¼2.36e2.53 (m, 2H, CH2), 3.23 (s, 3H, NMe), 3.61 (s, 3H, NMe),
4.73e4.74 (m, 1H, CH), 4.90e4.92 (m, 1H, CH), 7.06 (s, 1H, CH),
7.11e7.16 (m, 2H, HAr), 7.21e7.25 (m, 1H, HAr), 7.31e7.42 (m, 6H,
d
¼2.07 (s, 3H, COMe), 2.27e2.40 (m, 2H, CH2), 3.32 (s, 3H, NMe),
HAr). 13C NMR (62.9 MHz, CDCl3):
d
¼28.2 (CH2), 30.5 (NCH3), 31.4
4.57e4.59 (m, 1H, CH), 4.70e4.71 (m, 1H, CH), 6.99e7.21 (m, 4H,
(CH), 42.9 (CH), 48.9 (NCH3), 108.4 (C), 108.5 (CH), 112.0 (C), 115.5,
HAr), 7.31 (s, 1H, CH), 7.32e7.54 (m, 5H, HAr). 13C NMR (62.9 MHz,
119.8, 120.3 (CH), 127.5 (C), 127.9, 128.3, 129.5 (CH), 133.8, 137.1,
CDCl3):
d
¼23.8 (CH3), 28.2 (CH2), 31.1 (CH), 43.1 (CH), 48.6 (NCH3),
140.4 (C), 152.3 (CH), 191.2 (CO). IR (ATR, cmꢁ1):
n
¼1608 (w), 1599
109.7 (CH), 110.2, 112.8 (C), 115.6 (CH), 117.8 (C), 1120.5, 120.9,
~
(w), 1576 (m), 1548 (s), 1463 (m), 1411 (m), 1379 (m), 1328 (s), 1206
(m), 1121 (m), 1037 (m), 946 (m), 739 (s), 702 (m), 662 (m), 572 (m).
MS (GC, 70 eV): m/z (%)¼360 (Mþ, 98), 327 (16), 255 (16), 198 (26),
175 (100), 105 (41), 77 (26). HRMS (ESI): calcd for C22H20N2OS (Mþ)
360.12909, found 360.128978.
127.1, 128.0, 129.4 (CH), 134.0, 136.9, 137.5 (C), 148.6 (CH), 191.4
(CO). IR (ATR, cmꢁ1): ¼1574 (s), 1568 (s), 1558 (s), 1497 (m), 1446
~
n
(m), 1327 (s), 1320 (s), 1166 (s), 1088 (m), 1024 (m), 739 (s), 695 (s),
670 (m), 595 (m). MS (GC, 70 eV): m/z (%)¼360 (Mþ, 100), 359
(18), 327 (32), 317 (23), 262 (19), 238 (18), 237 (91), 236 (87), 136
(32). HRMS (ESI): calcd for C22H20N2OS (Mþ) 360.12909, found
360.128093.
4.3.11. (5-Athyl-11-methyl-2,5,6,11-tetrahydro-2,6-methano[1,5]
thiazocino[2,3-b]indol-3-yl)(phenyl)methanone (3k). Yellow solid,
mp 167e169 ꢀC, yield: 85% (238 mg). 1H NMR (300 MHz, CDCl3)
4.3.15. 1-(5-Ethyl-11-phenyl-2,5,6,11-tetrahydro-2,6-methano[1,5]
d
¼1.30 (t, 3H, J¼7.1 Hz, NCH2CH3), 2.41 (t, 2H, J¼3.2 Hz, CHCH2CH),
thiazocino[2,3-b]indol-3-yl)ethanone (3o). Pale grey solid, mp
3.23e3.35 (m, 1H, NCH2CH3), 3.61 (s, 3H, NMe), 3.65e3.76 (m, 1H,
NCH2CH3), 4.88 (m, 1H, CH), 4.93e4.95 (m, 1H, CH), 7.11e7.16 (m,
3H, HAr, CH), 7.22e7.25 (m,1H, HAr), 7.31e7.43 (m, 6H, HAr). 13C NMR
(62.9 MHz, CDCl3):
46.8 (CH), 49.8 (NCH2), 108.5 (CH), 108.7, 111.8 (C), 115.4, 119.8,120.3
188e190 ꢀC, yield: 94% (264 mg). 1H NMR (300 MHz, CDCl3)
d¼1.43
(t, 3H, J¼7.5 Hz, CH2CH3), 2.13 (s, 3H, COMe), 2.29e2.42 (m, 2H,
CHCH2CH), 3.40e3.52 (m, 1H, CH2CH3), 3.76e3.88 (m, 1H, CH2CH3),
4.64e4.65 (m, 1H, CH), 4.89 (s, 1H, CH), 7.03e7.18 (m, 3H, HAr),
d¼14.4 (CH3), 28.8 (CH2), 30.5 (NCH3), 31.8 (CH),
7.36e7.54 (m, 7H, HAr, CH). 13C NMR (62.9 MHz, CDCl3):
d¼14.6
(CH), 127.2 (C), 127.9, 128.3, 129.5 (CH), 133.9, 137.1, 140.5 (C), 150.9
(CH3), 23.9 (CH3), 28.7 (CH2), 31.6 (CH), 46.5 (CH), 49.9 (NCH2),
109.8 (CH), 110.6, 112.6 (C), 115.5, 120.5, 120.9, 127.1 (CH), 127.8 (C),
128.0, 129.4 (CH), 134.1, 136.9, 137.5 (C), 147.2 (CH), 191.4 (CO). IR
~
(CH), 191.2 (CO). IR (ATR, cmꢁ1):
n
¼1598 (w), 1575 (w), 1546 (s),
~
1463 (m), 1440 (m), 1381 (m), 1329 (m), 1201 (m), 1123 (s), 1036
(m), 752 (m), 735 (s), 701 (m), 660 (m). MS (GC, 70 eV): m/z (%)¼374
(Mþ, 100), 341 (23), 322 (51), 321 (22), 269 (15), 212 (35), 175 (79),
163 (24), 105 (38), 77 (23). HRMS (ESI): calcd for C23H22N2OS (Mþ)
374.14474, found 374.144616.
(ATR, cmꢁ1):
n
¼1594 (w), 1565 (s), 1498 (m), 1448 (m), 1336 (s),
1318 (m), 1160 (s), 1013 (m), 746 (s), 696 (s), 671 (m), 615 (m). MS
(GC, 70 eV): m/z (%)¼374 (Mþ,100), 345 (25), 341 (36), 331 (23), 262
(18), 237 (87), 236 (72), 150 (33). HRMS (ESI): calcd for C23H22N2OS
(Mþ) 374.14474, found 374.144467.
4.3.12. (5-Benzyl-11-methyl-2,5,6,11-tetrahydro-2,6-methano[1,5]
thiazocino[2,3-b]indol-3-yl)(phenyl)methanone (3l). Light brown
solid, mp 180e182 ꢀC, yield: 76% (249 mg). 1H NMR (300 MHz,
4.3.16. 1-(5-Allyl-11-phenyl-2,5,6,11-tetrahydro-2,6-methano[1,5]
thiazocino[2,3-b]indol-3-yl)ethanone
(3p). Grey solid, mp
CDCl3)
d
¼2.24e2.37 (m, 2H, CHCH2CH), 3.53 (s, 3H, NMe), 4.30 (d,
122e124 ꢀC, yield: 99% (287 mg). 1H NMR (300 MHz, CDCl3)
1H, J¼15.5 Hz, NCH2), 4.68e4.74 (m, 2H, NCH2, CH), 4.87 (m, 1H,
d
¼2.13 (s, 3H, COMe), 2.36e2.39 (m, 2H, CHCH2CH), 3.98e4.05
CH), 7.02e7.35 (m, 15H, HAr, CH). 13C NMR (62.9 MHz, CDCl3):
(m, 1H, NCH2CHCH2), 4.35 (dd, 1H, J¼15, 6 Hz, NCH2CHCH2),
4.64e4.66 (m, 1H, CH), 4.87e4.88 (m, 1H, CH), 5.40e5.50 (m, 2H,
NCH2CHCH2), 5.91e6.00 (m, 1H, NCH2CHCH2), 7.04e7.18 (m, 3H,
HAr), 7.36e7.55 (m, 7H, HAr, CH). 13C NMR (62.9 MHz, CDCl3):
d
¼28.6 (CH2), 30.5 (NCH3), 31.7 (CH), 46.4 (CH), 59.1 (NCH2), 108.5
(C), 108.5 (CH), 112.3 (C), 115.4, 119.8, 120.3, 127.3 (CH), 127.4 (C),
127.9, 128.3, 128.4, 129.2, 129.7 (CH), 133.9, 136.0, 137.1, 140.3 (C),
152.1 (CH), 191.4 (CO). IR (ATR, cmꢁ1):
n
¼1609 (w), 1580 (m), 1563
d
¼23.9 (CH3), 28.5 (CH2), 31.3 (CH), 46.5 (CH), 57.7 (NCH2), 109.7
~
(s), 1556 (s), 1464 (m), 1435 (m), 1352 (m), 1334 (s), 1195 (m), 1106
(m), 1025 (m), 733 (s), 695 (s), 654 (m). MS (GC, 70 eV): m/z (%)¼
436 (Mþ, 64), 346 (20), 345 (100), 322 (65), 321 (28), 290 (16), 275
(19), 274 (17), 183 (18), 175 (17), 163 (28), 105 (49), 91 (35), 77 (27).
HRMS (ESI): calcd for C28H24N2OS (Mþ) 436.16039, found
436.160388.
(CH), 110.4, 113.1 (C), 115.6 (CH), 119.1 (CH2), 120.5, 120.9, 127.1
(CH), 127.7 (C), 128.0, 129.3, 129.4, 133.2 (CH), 134.1, 136.9, 137.5
(C), 147.7 (CH), 191.6 (CO). IR (ATR, cmꢁ1):
n
¼1574 (s), 1568 (s),
~
1557 (s), 1497 (s), 1446 (m), 1338 (m), 1191 (m), 1150 (m), 1015
(m), 912 (m), 738 (s), 695 (s), 670 (m). MS (GC, 70 eV): m/z (%)¼
386 (Mþ, 75), 353 (19), 346 (24), 345 (100), 237 (25), 236 (29), 162
(20). HRMS (ESI): calcd for C24H22N2OS (Mþ) 386.14474, found
386.144703.
4.3.13. Ethyl 5,11-dimethyl-2,5,6,11-tetrahydro-2,6-methano[1,5]
thiazocino[2,3-b]indole-3-carboxylate (3m). Yellow solid, mp
86e88 ꢀC, yield: 94% (231 mg). 1H NMR (300 MHz, CDCl3)
(t, 3H, J¼7.1 Hz, OCH2CH3), 2.30e2.49 (m, 2H, CHCH2CH), 3.23 (s,
3H, NMe), 3.58 (s, 3H, NMe), 4.15e4.26 (m, 2H, OCH2CH3),
4.58e4.60 (m, 1H, CH), 4.65 (s, 1H, CH), 7.08e7.21(m, 3H, HAr),
d
¼1.29
4.3.17. (5-Allyl-11-phenyl-2,5,6,11-tetrahydro-2,6-methano[1,5]thia-
zocino[2,3-b]indol-3-yl)(phenyl)methanone (3q). Yellow solid, mp
93e95 ꢀC, yield: 85% (286 mg). 1H NMR (300 MHz, CDCl3)
d¼2.45e2.47 (m, 2H, CHCH2CH), 3.85e3.92 (m, 1H, NCH2CHCH2),

M. Kiamehr et al. / Tetrahedron 68 (2012) 9685e9693
9691
4.28e4.35 (dd, 1H, J¼15.6, 7.0 Hz, NCH2CHCH2), 4.88e4.93 (m, 2H,
2ꢂCH), 5.36e5.45 (m, 2H, NCH2CHCH2), 5.89e5.91 (m, 1H,
NCH2CHCH2), 7.07e7.22 (m, 4H, HAr, CH), 7.31e7.57 (m, 11H, HAr).
6.98e7.32 (m, 8H, HAr), 7.60 (d, J¼7.8 Hz, 1H, HAr), 7.85 (s, 1H, NH).
13C NMR (62.9 MHz, CDCl3):
(NCH2), 82.9 (C), 110.1 (CH), 115.4 (C), 117.0, 120.4, 121.4 (CH), 121.7,
d
¼25.4 (CH), 28.8 (CH2), 56.4 (CH), 57.1
13C NMR (62.9 MHz, CDCl3):
d¼28.4 (CH2), 31.5 (CH), 46.7 (CH), 57.8
122.9, 126.7 (C), 128.0, 128.5, 129.2 (CH), 135.1, 136.4 (C), 145.1 (CH).
IR (ATR, cmꢁ1):
n
¼3271 (w), 2183 (s), 1613 (s), 1449 (m), 1415 (m),
~
(NCH2), 109.8 (CH), 110.3, 112.5 (C), 115.6 (CH), 119.1 (CH2), 120.6,
121.0, 127.1 (CH), 127.8 (C), 127.9, 128.1, 128.3, 129.5, 129.7, 133.0
(CH), 134.2, 136.9, 137.6, 140.4 (C), 151.4 (CH), 191.4 (CO). IR (ATR,
~
1189 (m), 1108 (m), 1023 (m), 739 (s), 697 (m), 606 (m). MS (GC,
70 eV): m/z (%)¼343 (Mþ, 46), 342 (27), 252 (24), 161 (10), 149 (20),
104 (14), 91 (100). HRMS (ESI): calcd for C21H18N3S (MþH)
344.12159, found 344.12111.
cmꢁ1):
n
¼1595 (w), 1580 (s), 1562 (s), 1556 (s), 1498 (m), 1447 (m),
1340 (m), 1219 (m), 1201 (s), 1020 (m), 735 (s), 697 (s), 648 (m). MS
(GC, 70 eV): m/z (%)¼448 (Mþ, 73), 415 (19), 408 (25), 407 (100),
262 (12), 237 (19), 236 (20), 225 (46), 224 (70), 183 (18),105 (53), 77
(29). HRMS (ESI): calcd for C29H24N2OS (Mþ) 448.16039, found
448.160276.
4.3.22. 5-Benzyl-2,5,6,11-tetrahydro-2,6-methano[1,5]thiazocino
[2,3-b]indole-3-carbonitrile (minor) (5b). 1H NMR (300 MHz, CDCl3)
d
¼2.18e2.32 (m, 2H, CHCH2CH), 4.09 (s, 1H, CH), 4.18e4.33 (m, 2H,
NCH2), 4.58 (s, 1H, SCHN), 6.82 (s, 1H, CH), 6.98e7.32 (m, 9H, HAr),
4.3.18. Ethyl 5,11-dimethyl-2,5,6,11-tetrahydro-2,6-methano[1,5]thia
8.07 (s, 1H, NH).
zocino[2,3-b]indole-3-carboxylate (3r). Pale white solid, mp
178e180 ꢀC, yield: 98% (287 mg). 1H NMR (300 MHz, CDCl3)
d
¼1.25
4.3.23. 3-Allyl-11-methyl-2,3,6,11-tetrahydro-2,6-methano[1,3]thia-
zocino[8,7-b]indole-5-carbonitrile (4c). Pale yellow solid, mp
169e171 ꢀC, yield: 64% (148 mg). 1H NMR (300 MHz, CDCl3)
(t, 3H, J¼7.1 Hz, OCH2CH3), 2.35e2.50 (m, 2H, CHCH2CH), 3.30 (s,
3H, NMe), 4.16 (q, 2H, J¼7.1 Hz, OCH2CH3), 4.52e4.53 (m, 1H, CH),
4.72 (m, 1H, CH), 7.04e7.17 (m, 3H, HAr), 7.38e7.59 (m, 7H, HAr, CH).
d
¼2.31e2.47 (m, 2H, CHCH2CH), 3.59 (s, 3H, NMe), 3.77e3.92 (m,
13C NMR (62.9 MHz, CDCl3):
42.6 (CH), 48.3 (NCH3), 59.2 (OCH2), 99.5 (C), 109.6 (CH), 110.7 (C),
d
¼14.6 (CH3), 28.6 (CH2), 33.2 (CH),
2H, NCH2CHCH2), 4.01e4.04 (m, 1H, CH), 5.13e5.15 (m, 1H,
SCHN), 5.28e5.36 (m, 2H, NCH2CHCH2), 5.79e5.85 (m, 1H,
NCH2CHCH2), 6.75 (s, 1H, CH), 7.12e7.21 (m, 3H, HAr), 7.67e7.70
115.8, 120.5, 120.9, 127.2, 128.0 (CH), 128.1 (C), 129.4 (CH), 133.7,
137.1, 137.6 (C), 147.0 (CH), 166.9 (CO). IR (ATR, cmꢁ1):
n
¼1664 (s),
(m, 1H, HAr). 13C NMR (62.9 MHz, CDCl3):
d
¼25.5 (CH), 28.7
~
1604 (s), 1497 (m), 1449 (m), 1379 (m), 1315 (m), 1284 (m), 1163 (s),
1124 (m), 1073 (s), 1022 (m), 754 (m), 743 (s), 698 (s), 659 (m). MS
(GC, 70 eV): m/z (%)¼390 (Mþ, 100), 361 (21), 343 (17), 317 (23), 316
(17), 302 (13), 283 (23), 262 (38), 249 (16), 237 (37), 236 (48), 166
(31). HRMS (ESI): calcd for C23H22N2O2S (Mþ) 390.13965, found
390.139663.
(CH2), 30.5 (NCH3), 55.8 (NCH2), 56.5 (CH), 83.2 (C), 108.1 (CH),
113.8 (C), 117.0 (CH), 119.8 (CH2), 119.9, 120.8 (CH), 121.6, 125.8,
126.2 (C), 132.2 (CH), 137.2 (C), 144.6 (CH). IR (ATR, cmꢁ1):
~
n
¼2910 (w), 2184 (s), 1644 (w), 1613 (s), 1462 (m), 1416 (m), 1326
(m), 1195 (m), 1027 (m), 914 (m), 728 (s), 646 (m), 600 (m). MS
(GC, 70 eV): m/z (%)¼307 (Mþ, 100), 306 (74), 274 (16), 266 (44),
265 (26), 233 (29), 232 (23), 225 (19), 200 (42), 175 (15), 163 (24),
145 (34), 41 (25). HRMS (ESI): calcd for C18H18N3S (MþH)
308.12159, found 308.12197.
4.3.19. 3-Methyl-2,3,6,11-tetrahydro-2,6-methano[1,3]thiazocino
[8,7-b]indole-5-carbonitrile
202e204 ꢀC, yield: 52% (105 mg). 1H NMR (300 MHz, DMSO-d6)
¼2.17e2.44 (m, 2H, CHCH2CH), 3.02 (s, 3H, NMe), 3.91e3.93 (m,
1H, CH), 5.35 (m, 1H, SCHN), 7.00e7.05 (m, 2H, HAr), 7.16 (s, 1H, CH),
7.22e7.27 (m, 1H, HAr), 7.49e7.52 (m, 1H, HAr), 11.19 (s, 1H, NH). 13
NMR (62.9 MHz, DMSO-d6):
(4a). Light
brown
solid,
mp
d
4.3.24. 3-Benzyl-11-methyl-2,3,6,11-tetrahydro-2,6-methano[1,3]
thiazocino[8,7-b]indole-5-carbonitrile (major) (4d). Grey solid, mp
176e178 ꢀC, overall ield: 67% (201 mg) (4d/5d; 80:20). 1H NMR
C
d
¼24.1 (CH), 28.2 (CH2), 40.0 (NCH3),
(300 MHz, CDCl3)
d
¼2.19e2.38 (m, 2H, CHCH2CH), 3.53 (s, 3H,
58.0 (CH), 80.2 (C), 110.1 (CH), 114.6 (C), 116.1, 118.9, 120.1 (CH),
NMe), 3.95e3.97 (m, 1H, CH), 4.24e4.39 (m, 2H, NCH2), 4.90 (m, 1H,
SCHN), 6.78 (s, 1H, CH), 7.04e7.39 (m, 8H, HAr), 7.60e7.63 (m, 1H,
122.1, 123.9, 126.3, 136.1 (C), 146.0 (CH). IR (ATR, cmꢁ1):
¼3239
~
n
(m), 2911 (w), 2184 (s), 1731 (w), 1614 (s), 1451 (m), 1396 (m), 1338
(m), 1317 (m), 1229 (m), 1117 (m), 1085 (m), 1029 (m), 756 (m), 734
(s), 680 (m), 596 (m). MS (GC, 70 eV): m/z (%)¼267 (Mþ, 99), 266
(100), 234 (44), 211 (13), 186 (21), 161 (13), 119 (37), 117 (14). HRMS
(ESI): calcd for C15H14N3S (MþH) 268.09029, found 268.09068.
HAr). 13C NMR (75.5 MHz, CDCl3):
d¼25.6 (CH), 28.7 (CH2), 30.5
(NCH3), 56.1 (CH), 57.1 (NCH2), 83.4 (C), 108.2 (CH), 113.8 (C), 117.1,
120.0, 120.9 (CH), 121.6, 126.2, 127.7 (C), 128.1, 128.6, 129.2 (CH),
135.2, 137.3 (C), 145.1 (CH). IR (ATR, cmꢁ1):
n
¼2928 (w), 2188 (s),
~
1617 (s), 1463 (m), 1416 (m), 1327 (m), 1194 (m), 1113 (m), 1037 (m),
734 (s), 723 (m), 697 (m), 601 (m). MS (GC, 70 eV): m/z (%)¼357
(Mþ, 97), 356 (47), 266 (52), 233 (15), 200 (26), 175 (14), 91 (100).
HRMS (ESI): calcd for C22H20N3S (MþH), 358.13724 found
358.13652.
4.3.20. 5-Methyl-2,5,6,11-tetrahydro-2,6-methano[1,5]thiazocino
[2,3-b]indole-3-carbonitrile (5a). Pale green solid, mp 198e200 ꢀC,
yield: 35% (70 mg). 1H NMR (300 MHz, DMSO-d6)
2H, CHCH2CH), 3.18 (s, 3H, NMe), 4.35e4.36 (m, 1H, CH), 4.81 (m,
1H, CH), 7.00e7.06 (m, 2H, HAr), 7.21 (s, 1H, CH), 7.23e7.26 (m, 1H,
HAr), 7.58e7.61 (m, 1H, HAr), 11.33 (s, 1H, NH). 13C NMR (75.5 MHz,
d
¼2.20e2.44 (m,
4.3.25. 5-Benzyl-11-methyl-2,5,6,11-tetrahydro-2,6-methano[1,5]
thiazocino[2,3-b]indole-3-carbonitrile (minor) (5d). 1H NMR
DMSO-d6):
d
¼28.6 (CH2), 34.8 (CH), 41.5 (NCH3), 46.5 (CH), 77.5,
(300 MHz, CDCl3)
d
¼2.19e2.38 (m, 2H, CHCH2CH), 3.55 (s, 3H,
109.6 (C), 110.2, 116.2, 119.3, 120.3 (CH), 122.1, 127.5, 128.2, 136.1 (C),
NMe), 4.17 (m, 1H, CH), 4.24e4.67 (m, 2H, NCH2), 4.67 (m, 1H,
SCHN), 6.86 (s, 1H, CH), 7.04e7.39 (m, 9H, HAr). 13C NMR (75.5 MHz,
CDCl3): 29.1 (CH2), 30.6 (NCH3), 35.7 (CH), 45.8 (CH), 58.6 (NCH2),
80.3 (C), 108.6 (CH), 113.2 (C), 115.9, 120.0, 120.8 (CH), 121.6, 126.2,
127.7 (C), 128.4, 128.6, 129.2 (CH), 136.0, 137.3 (C), 148.2 (CH).
148.9 (CH). IR (ATR, cmꢁ1):
n
¼3272 (m), 2931 (w), 2185 (s), 1731
~
(w), 1609 (s), 1446 (s), 1427 (m), 1337 (m), 1310 (m), 1233 (m), 1118
(m), 1023 (m), 935 (m), 741 (s), 675 (m), 529 (m). MS (GC, 70 eV): m/
z (%)¼267 (Mþ, 100), 266 (28), 252 (13), 234 (14), 186 (58), 161 (55),
117 (17). HRMS (ESI): calcd for C15H14N3S (MþH) 268.09029, found
268.0899.
4.3.26. 5-Methyl-11-phenyl-2,5,6,11-tetrahydro-2,6-methano[1,5]
thiazocino[2,3-b]indole-3-carbonitrile (4e). Pale white solid, mp
186e188 ꢀC, yield: 55% (142 mg). 1H NMR (300 MHz, CDCl3)
4.3.21. 3-Benzyl-2,3,6,11-tetrahydro-2,6-methano[1,3]thiazocino
[8,7-b]indole-5-carbonitrile (major) (4b). Pale yellow solid, mp
181e183 ꢀC, overall yield: 87% (224 mg) (4b/5b; 86:14). 1H NMR
(300 MHz, CDCl3)
4.18e4.33 (m, 2H, NCH2), 4.83 (s, 1H, SCHN), 6.75 (s, 1H, CH),
d
¼2.26e2.44 (m, 2H, CHCH2CH), 2.86 (s, 3H, NMe), 3.96e3.98 (m,
1H, CCHC), 4.81e4.83 (m, 1H, SCHN), 6.63 (s, 1H, CH), 6.97e7.12 (m,
d¼2.18e2.32 (m, 2H, CHCH2CH), 3.91 (s, 1H, CH),
3H, HAr), 7.32e7.46 (m, 5H, HAr), 7.64e7.65 (m, 1H, HAr). 13C NMR
(62.9 MHz, CDCl3):
d¼25.2 (CH), 28.4 (CH2), 41.0 (NCH3), 58.9 (CH),

9692
M. Kiamehr et al. / Tetrahedron 68 (2012) 9685e9693
82.1 (C), 109.4 (CH), 115.7 (C), 117.1, 120.8, 121.6 (CH), 121.7, 125.9,
126.7 (C), 126.9, 127.9, 129.4 (CH), 137.3, 137.6 (C), 145.5 (CH). IR
254 (43), 248 (36), 233 (17), 225 (19), 200 (34), 175 (20), 163 (35),
130 (20), 124 (23), 119 (47), 104 (19), 77 (18), 43 (16). HRMS (ESI):
calcd for C16H15N3S (Mþ) 281.09812, found 281.097720.
(ATR, cmꢁ1):
n
¼2901 (w), 2174 (s), 1615 (s), 1595 (m), 1499 (m),
~
1445 (m), 1368 (m), 1323 (m), 1227 (m), 1094 (m), 1027 (m), 940
(m), 752 (s), 738 (s), 699 (m), 658 (m), 598 (m). MS (GC, 70 eV): m/z
(%)¼343 (Mþ, 100), 342 (88), 310 (26), 308 (13), 262 (47), 236 (16),
119 (26). HRMS (ESI): calcd for C21H17N3S (Mþ), 343.11377 found
343.112945.
4.3.31. 3-Benzyl-11-methyl-2,3,6,11-tetrahydro-2,6-methano[1,3]
thiazocino[8,7-b]indole-4-carbonitrile
(6b). Grey solid, mp
90e92 ꢀC, yield: 80% (215 mg). 1H NMR (300 MHz, CDCl3)
d
¼2.00e2.38 (m, 2H, CHCH2CH), 3.56 (s, 3H, NMe), 3.81e3.89 (m,
1H, CH), 4.18 (d, 1H, J¼14.8 Hz, NCH2), 4.74 (d, 1H, J¼14.8 Hz,
NCH2), 4.92e4.95 (m, 1H, SCHN), 5.78 (dd, 1H, J¼6.6, 1.6 Hz,
CHCCN), 7.00e7.15 (m, 3H, HAr), 7.27e7.39 (m, 6H, HAr). 13C NMR
4.3.27. 5-Methyl-11-phenyl-2,5,6,11-tetrahydro-2,6-methano[1,5]
thiazocino[2,3-b]indole-3-carbonitrile (5e). Pale white solid, mp
191e192 ꢀC, yield: 30% (77 mg). 1H NMR (300 MHz, CDCl3)
(62.9 MHz, CDCl3):
(NCH2), 57.8 (CH), 108.5 (CH), 112.6, 115.6 (C), 115.9, 117.7 (CH),
d
¼24.6 (CH), 28.4 (CH2), 30.6 (NCH3), 54.5
d
¼2.29e2.48 (m, 2H, CHCH2CH), 3.18 (s, 3H, NMe), 4.05e4.06 (m,1H,
CH), 4.65e4.67 (m, 1H, CH), 6.75 (s, 1H, CH), 6.98e7.11 (m, 3H, HAr),
7.34e7.49 (m, 6H, HAr). 13C NMR (62.9 MHz, CDCl3):
119.2 (C), 119.6, 120.6 (CH), 125.6 (C), 128.2 (CH), 128.3 (C), 128.6,
129.0 (CH), 135.9, 137.3 (C). IR (ATR, cmꢁ1):
n
¼2916 (w), 2221 (m),
~
d
¼28.6 (CH2),
35.3 (CH), 42.6 (NCH3), 47.9 (CH), 79.5 (C),109.8 (CH),110.2 (C),115.9,
1606 (s), 1494 (w), 1463 (m), 1455 (m), 1363 (m), 1326 (s), 1145
(m), 1097 (s), 964 (m), 777 (m), 735 (s), 721 (s), 695 (s), 551 (m).
MS (GC, 70 eV): m/z (%)¼357 (Mþ, 57), 356 (12), 330 (26), 266 (51),
233 (32), 163 (41), 130 (17), 104 (25), 91 (100), 77 (14), 65 (12).
HRMS (ESI): calcd for C22H20N3S (MþH) 358.13724, found
358.1366.
120.7, 121.3 (CH), 121.8 (C), 127.2 (CH), 127.8 (C), 128.3, 129.5 (CH),
132.2, 136.8, 137.7 (C), 148.5 (CH). IR (ATR, cmꢁ1):
n
¼2927 (m), 2183
~
(s), 1612 (s), 1596 (m), 1498 (m), 1447 (m), 1313 (s), 1228 (m), 1123
(m),1020 (m), 941 (m), 760 (m), 737 (s), 699 (s), 662 (m), 590 (m). MS
(GC, 70 eV): m/z (%)¼343 (Mþ,100), 342 (32), 328 (14), 310 (11), 263
(23), 262 (99), 249 (13), 237 (21), 236 (47),119 (8). HRMS (ESI): calcd
for C21H17N3S (Mþ), 343.11377 found 343.113502.
4.3.32. 3-Methyl-11-phenyl-2,3,6,11-tetrahydro-2,6-methano[1,3]
thiazocino[8,7-b]indole-4-carbonitrile
(6c). Grey solid, mp
4.3.28. 3-Allyl-11-phenyl-2,3,6,11-tetrahydro-2,6-methano[1,3]thia-
zocino[8,7-b]indole-5-carbonitrile (major) (4f). Pale yellow solid,
mp 167e168 ꢀC, overall yield: 88% (244 mg) (4f/5f; 73:27). 1H NMR
166e168 ꢀC, yield: 88% (226 mg). 1H NMR (300 MHz, CDCl3)
d
¼2.09e2.50 (m, 2H, CHCH2CH), 2.86 (s, 3H, NCH3), 3.85e3.89 (m,
1H, CH), 4.97e5.00 (m, 1H, SCHN), 5.76 (dd, 1H, J¼6.5, 1.7 Hz,
(300 MHz, CDCl3)
d
¼2.38e2.51 (m, 2H, CHCH2CH), 3.69e3.78 (m,
CHCCN), 6.97e7.11 (m, 3H, HAr), 7.34e7.46 (m, 6H, HAr). 13C NMR
2H, NCH2CHCH2), 4.08e4.10 (m, 1H, CH), 5.06 (m, 1H, SCHN),
5.22e5.32 (m, 2H, NCH2CHCH2), 5.72e5.80 (m, 1H, NCH2CHCH2),
6.79 (s, 1H, CH), 7.07e7.21 (m, 3H, HAr), 7.41e7.53 (m, 5H, HAr), 7.76
(62.9 MHz, CDCl3):
(CH), 109.7 (CH), 114.8, 115.4 (C), 116.0, 117.1 (CH), 119.3 (C), 120.4,
d
¼24.4 (CH), 28.4 (CH2), 39.0 (NCH3), 61.9
121.2 (CH), 126.1 (C), 126.9, 127.9 (CH), 128.7 (C), 129.4 (CH), 137.4,
(d, J¼7.8 Hz, HAr). 13C NMR (62.9 MHz, CDCl3):
d
¼25.6 (CH), 28.6
137.7 (C). IR (ATR, cmꢁ1):
n
¼2926 (w), 2223 (m), 1608 (m), 1595
~
(CH2), 55.8 (NCH2), 56.4 (CH), 82.7 (C), 109.4 (CH), 115.6 (C), 117.1
(CH), 119.9 (CH2), 120.8, 121.6 (CH), 121.7, 126.0, 126.7 (C), 126.9,
127.9, 129.4, 132.1 (CH), 137.3, 137.6 (C), 144.8 (CH).
(m), 1501 (s), 1446 (s), 1363 (m), 1277 (m), 1216 (m), 1242 (m),
1088 (m), 1057 (m), 968 (m), 750 (m), 740 (s), 699 (s), 680 (m), 570
(m). MS (GC, 70 eV): m/z (%)¼343 (Mþ, 100), 342 (56), 316 (27),
310 (29), 308 (10), 287 (10), 262 (19), 236 (22), 119 (20). HRMS
(ESI): calcd for C21H17N3S (Mþ) 343.11377, found 343.113021.
4.3.29. 5-Allyl-11-phenyl-2,5,6,11-tetrahydro-2,6-methano[1,5]thia-
zocino[2,3-b]indole-3-carbonitrile (minor) (5f). 1H NMR (300 MHz,
CDCl3)
d
¼2.38e2.51 (m, 2H, CHCH2CH), 3.81e3.95 (m, 1H,
4.3.33. 3-Allyl-11-phenyl-2,3,6,11-tetrahydro-2,6-methano[1,3]thia-
zocino[8,7-b]indole-4-carbonitrile (6d). Light brown solid, mp
78e80 ꢀC, yield: 92% (255 mg). 1H NMR (300 MHz, CDCl3)
NCH2CHCH2), 4.14e4.16 (m, 1H, CH), 4.20e4.25 (m, 1H,
NCH2CHCH2), 4.85 (m, 1H, SCHN), 5.35e5.45 (m, 2H,
NCH2CHCH2), 5.80e5.89 (m, 1H, NCH2CHCH2), 6.91 (s, 1H, CH),
7.07e7.21 (m, 3H, HAr), 7.41e7.53 (m, 6H, HAr). 13C NMR
d
¼2.15e2.45 (m, 2H, CHCH2CH), 3.63 (dd, 1H, J¼15.5, 7.9 Hz,
NCH2CHCH2), 3.88e3.91 (m, 1H, CH), 4.02e4.09 (m, 1H,
NCH2CHCH2), 5.12e5.14 (m, 1H, SCHN), 5.18e5.25 (m, 2H,
NCH2CHCH2), 5.71e5.75 (m, 1H, NCH2CHCH2), 5.79 (dd, 1H, J¼6.8,
(62.9 MHz, CDCl3):
d
¼29.0 (CH2), 35.5 (CH), 46.2 (CH), 57.4
(NCH2), 79.9 (C), 109.9 (CH), 110.4 (C), 115.9 (CH), 119.5 (CH2),
120.7, 121.4 (CH), 121.8 (C), 127.2 (CH), 127.5 (C), 128.3, 129.5 (CH),
132.2 (C), 133.0 (CH), 136.8, 137.7 (C), 147.5 (CH). IR (ATR, cmꢁ1):
~
1.6 Hz, CHCCN), 6.97e7.11 (m, 3H, HAr), 7.33e7.47 (m, 6H, HAr). 13
C
NMR (62.9 MHz, CDCl3):
(CH), 109.7 (CH), 114.6, 115.4 (C), 116.0, 117.1 (CH), 119.0 (C), 119.6
d
¼24.6 (CH), 28.4 (CH2), 53.4 (NCH2), 58.1
n
¼2922 (w), 2180 (s), 1644 (w), 1614 (s), 1592 (m), 1495 (s), 1446
(s), 1413 (m), 1341 (m), 1317 (m), 1222 (m), 1195 (m), 1024 (m),
907 (m), 757 (m), 744 (s), 697 (s), 621 (m). MS (GC, 70 eV): m/z
(%)¼369 (Mþ, 100), 368 (48), 336 (11), 328 (42), 327 (12), 295
(12), 262 (36), 236 (13). HRMS (ESI): calcd for C23H20N3S (MþH)
370.13724, found 370.13758.
(CH2), 120.4, 121.2 (CH), 126.2 (C), 126.9, 127.9 (CH), 128.6 (C), 129.4,
132.8 (CH), 137.3, 137.7 (C). IR (ATR, cmꢁ1):
n
¼2916 (w), 2222 (m),
~
1605 (m), 1595 (m), 1497 (s), 1446 (s), 1366 (m), 1278 (m), 1153 (m),
1100 (m), 966 (m), 737 (s), 696 (s), 682 (m), 571 (m). MS (GC, 70 eV):
m/z (%)¼369 (Mþ, 100), 368 (30), 342 (29), 336 (12), 329 (15), 328
(78), 327 (23), 295 (33), 294 (10), 262 (14), 249 (12), 236 (19), 225
(16), 224 (14),145 (9), 41 (10). HRMS (ESI): calcd for C23H19N3S (Mþ)
369.12942, found 369.129104.
4.3.30. 3,11-Dimethyl-2,3,6,11-tetrahydro-2,6-methano[1,3]thiazo-
cino[8,7-b]indole-4-carbonitrile (6a). Grey solid, mp 88e90 ꢀC,
yield: 65% (136 mg). 1H NMR (300 MHz, CDCl3)
d¼2.02e2.49 (m,
2H, CHCH2CH), 2.92 (s, 3H, NCH3), 3.55 (s, 3H, NCH3), 3.79e3.84 (m,
1H, CH), 5.06e5.09 (m, 1H, SCHN), 5.71 (dd, 1H, J¼6.6, 1.8 Hz,
CHCCN), 7.01e7.14 (m, 3H, HAr), 7.34e7.38 (m, 1H, HAr). 13C NMR
4.3.34. 3-Benzyl-11-phenyl-2,3,6,11-tetrahydro-2,6-methano[1,3]
thiazocino[8,7-b]indole-4-carbonitrile (6e). Pale yellow solid, mp
172e174 ꢀC, yield: 78% (245 mg). 1H NMR (300 MHz, CDCl3)
(62.9 MHz, CDCl3):
d
¼24.4 (CH), 28.5 (CH2), 30.6 (NCH3), 39.1
d
¼2.06e2.39 (m, 2H, CHCH2CH), 3.87e3.92 (m, 1H, CH), 4.12 (d, 1H,
(NCH3), 62.0 (CH), 108.5 (CH), 112.9, 115.4 (C), 115.9, 117.5 (CH), 118.9
J¼14.9 Hz, NCH2), 4.69 (d, 1H, J¼14.9 Hz, NCH2), 4.84e4.87 (m, 1H,
SCHN), 5.83 (dd, 1H, J¼6.6, 1.6 Hz, CHCCN), 6.97e7.48 (m, 14H, HAr).
(C),119.6,120.5 (CH),125.5,128.5,137.3. IR (ATR, cmꢁ1):
n
¼2917 (w),
~
2221 (m), 1608 (m), 1518 (w), 1463 (s), 1387 (m), 1327 (s), 1232 (m),
1141 (m), 1069 (m), 1061 (m), 966 (m), 906 (m), 728 (s), 624 (m),
572 (m), 551 (m). MS (GC, 70 eV): m/z (%)¼281 (Mþ, 100), 280 (64),
13C NMR (75.5 MHz, CDCl3):
d¼24.7 (CH), 28.4 (CH2), 54.4 (NCH2),
57.7 (CH), 109.8 (CH), 114.5, 115.6 (C), 116.0, 117.3 (CH), 119.5 (C),
120.5, 121.3 (CH), 126.2 (C), 127.0, 128.0, 128.1 (CH), 128.4 (C), 128.6,

M. Kiamehr et al. / Tetrahedron 68 (2012) 9685e9693
9693
129.0,129.5 (CH),136.0,137.4,137.8 (C). IR (ATR, cmꢁ1):
n
¼2925 (w),
B. E.; Heck, S. D.; Bryce, D. K.; Schmidt, A. W.; Vanase-Frawley, M.; Callegari, E.;
McLean, S. Bioorg. Med. Chem. Lett. 2010, 20, 503e507; (d) Chowdhury, M. A.;
Abdellatif, K. R. A.; Dong, Y.; Knaus, E. E. Bioorg. Med. Chem. 2008, 16,
8882e8888; (e) Misra, M.; Pandey, S. K.; Pandey, V. P.; Pandey, J.; Tripathi, R.;
Tripathi, R. P. Bioorg. Med. Chem. 2009, 17, 625e633; (f) Krishna, P. R.; Reddy, P.
S. J. Comb. Chem. 2008, 10, 426e435; (g) Scott, J. D.; Li, S. W.; Wang, H. W.; Xia,
Y.; Jayne, C. L.; Miller, M. W.; Duffy, R. A.; Boykow, G. C.; Kowalski, T. J.; Spar, B.
D.; Stamford, A. W.; Chackalamannil, S.; Lachowicz, J. E.; Greenlee, W. J. Bioorg.
Med. Chem. Lett. 2010, 20, 1278e1283.
~
2221 (m), 1738 (w), 1610 (m), 1595 (m), 1498 (s), 1448 (s), 1388 (m),
1372 (m), 1317 (m), 1136 (s), 1104 (m), 968 (m), 781 (m), 752 (m),
742 (s), 736 (s), 694 (s), 573 (s). MS (GC, 70 eV): m/z (%)¼419 (Mþ,
56), 392 (21), 328 (65), 295 (35), 236 (15), 225 (73), 224 (67), 223
(36), 193 (15), 104 (42), 91 (100), 77 (34), 65 (18), 51 (18), 44 (15).
HRMS (ESI): calcd for C27H21N3S (Mþ) 419.14507, found 419.144996.
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Supplementary data
These data include NMR spectra of compounds 3e6. Supple-
mentary data associated with this article can be found in the online
version, at http://dx.doi.org/10.1016/j.tet.2012.09.059.
ꢁ
Bennasar, M. L.; Jimenez, J. M.; Sufi, B. A.; Bosch, J. Tetrahedron Lett. 1996, 37,
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