Regioselective deoxygenative chalcogenation of 7-Azindole: N-oxides promoted by I2/PEG-200

Article abstract of DOI:10.1039/c9ob02044f

We developed a general and sustainable approach for the regioselective deoxygenative chalcogenation of 7-Azindole N-oxides; the combination of an internal oxidant and a green solvent has been used successfully for the synthesis of mono-and dichalcogenyl 7-Azaindoles which are of pharmaceutical interest. The regioselectivity is tunable by the variation of the reaction conditions. I₂/PEG was established as an efficient and reusable catalytic system for C-H chalcogenation. This developed methodology has great potential for practical utility, with a broad substrate scope, green reaction conditions, and operational simplicity.

Full text of DOI:10.1039/c9ob02044f

Organic &
Biomolecular Chemistry
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PAPER
Regioselective deoxygenative chalcogenation of
-azindole N-oxides promoted by I /PEG-200†
7
2
Cite this: Org. Biomol. Chem., 2019,
7, 10073
1
a
a
b
a
a
Shanshan Liu, * Heng Yang, Lin-Yu Jiao,
Jian-Hua Zhang, Chen Zhao,
a
a
Yangmin Ma and Xiufang Yang*
We developed a general and sustainable approach for the regioselective deoxygenative chalcogenation of
-azindole N-oxides; the combination of an internal oxidant and a green solvent has been used success-
7
fully for the synthesis of mono- and dichalcogenyl 7-azaindoles which are of pharmaceutical interest. The
Received 19th September 2019,
Accepted 9th November 2019
regioselectivity is tunable by the variation of the reaction conditions. I /PEG was established as an
2
efficient and reusable catalytic system for C–H chalcogenation. This developed methodology has great
DOI: 10.1039/c9ob02044f
potential for practical utility, with a broad substrate scope, green reaction conditions, and operational
simplicity.
rsc.li/obc
9
g
9h
dimethyl carbonate (DMC), polyethylene glycol (PEG), and
Introduction
9
j
9h
9a
9d
glycerol were carried out by Barman,
-Azaindoles, as bioisosteres for indoles, are privileged Lenardão etc. However, in the presence of an additional nitro-
Tian, Sinha,
9
j
7
scaffolds in drug discovery and exhibit significant biological gen atom in the 7-azaindole ring system, when compared to
1
activities. Indeed, several 7-azaindole-containing drugs such indole, the reactivity reduces in terms of aromatic substitution
as vemurafenib (Zelboraf™), Venetoclax, and GSK1070916 are owing to the fused electron-deficient pyridine ring. On the
2
,3
in various stages of clinical development. In particular, their other hand, the metal catalyzed reaction would be prohibited
corresponding sulfides and selenides have been established as due to the coordination of the substrate to metal catalyst.
4
5
5
-HT6 receptor agonists, MKK4 kinase inhibitors, and BRD4 Therefore the modification of 7-azaindoles remains a chal-
6
inhibitors, respectively (Fig. 1). Accordingly, methods for the
synthesis of chalcogenyl 7-azindoles and their derivatives have
attracted continuous interest over the past decades.
7
The direct chalcogenation of the indole ring has been
widely explored towards the synthesis of mono- or dichalco-
genyl compounds and includes two typical strategies: (a) tran-
sition metal-catalyzed chalcogenylation through C–H metala-
8
tion and (b) aromatic chalcogenylation via SEAr by using
9
–12
in situ generated electrophilic chalcogenyl species
Scheme 1). Molecular iodine has emerged as an ideal catalytic
Fig. 1 Representative examples of biologically active C3 chalcogenyl
-azaindoles.
(
7
oxidant for the chalcogenation of indoles due to its commer-
cial availability, low toxicity, and transition-metal free
9
a,b,d–j,m–o
features.
Pioneering studies using molecular iodine
9
d
9a,m,n
in green reaction media such as water,
ethanol,
a
Shaanxi Key Laboratory of Chemical Additives for Industry, College of Chemistry
and Chemical Engineering, Shaanxi University of Science and Technology, Xi’an,
Shaanxi, 710021, P. R. China. E-mail: shanshanliu@sust.edu.cn,
yangxf@sust.edu.cn
b
School of Chemical Engineering, Northwest University, Xi’an, Shaanxi, 710069,
P. R. China
†
Electronic supplementary information (ESI) available: All chiral HPLC chroma-
togram data and spectra for phospha-Michael addition products and copies of
NMR spectra for new compounds. CCDC 1954603. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/c9ob02044f
2
Scheme 1 Previous strategies for C(sp )–H chalcogenation.
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Results and discussion
Initially, the stable and commercially available thiophenols
and diaryl disulfides were employed as sulfenyl sources for the
screening of reaction conditions. As outlined in Table 1, the
mono-and di-sulfenylated products were observed in most
cases. Thiophenol was outperformed by diaryl disulfides to
deliver the C3 sulfenylation product in 54% yield (entries 1
and 2). Furthermore, the influence of solvents on the reaction
3
system was assessed. The desired product 4aa in CH CN and
DMSO was obtained in small amounts (entries 3 and 4).
Surprisingly, the reaction could proceed in water giving 37%
yield. Various surfactants were subsequently employed to
improve the yield; 59% yield was obtained when DDBAC was
added while other surfactants were ineffective (entries 5–9). It
was found that alcohol could improve the yield dramatically,
when tested using methanol, ethanol, and n-butanol, and the
Scheme 2 General procedures for the C–H functionalization of desired sulfide 4aa was obtained in 68%, 72%, and 78%
7
-azaindoles.
yields, respectively (entries 10–12). Since ethanol had to be
heated above its atmospheric boiling point, we switched to
using PEG-200, which is a solvent with a higher boiling point.
lenge. In the past few years, C–H functionalization of 7-azain- Indeed, this change increased the yield remarkably (entry 13).
doles has been accomplished either by transition metal cataly- A significant effort has been made to further improve the yield
1
3
14
sis
or by
a
modified Reissert–Henze type reaction
by varying other reaction parameters. A detrimental effect was
(Scheme 2a). To date, only sporadic examples associated with observed in the presence of water due to the poor solubility of
the chalcogenation of 7-azaindoles have been documented. The diphenyl disulfide in this solvent (entries 14 and 15). In
2
direct chalcogenation through C(sp )–H bond cleavage involves addition, the temperature screening revealed that the best
15
both the copper catalyzed process and the electrophilic aro- efficiency was obtained at 110 °C (entry 16). To our delight,
matic chalcogenation which can be achieved under mild con- lowering the catalyst loading and sulfide had a much more
1
6
17
18
ditions using base, iodine, bifunctional catalyst, photo- pronounced effect, probably due to the inhibition of the com-
19
11b
20
catalyst, electrochemical process or ionic liquids. Despite petitive 2,3-disubstitution reaction in this case. Gratifyingly,
these achievements, the current methods generally provide a 0.6 equiv. of diphenyl disulfide is sufficient for this transform-
sole example of 7-azaindoles, which required a special reaction ation. The results revealed that 10 mol% iodine was necessary
set-up, a superstoichiometric amount of external oxidant or to obtain high yields (entries 17–19). Hence the optimal result
toxic organic solvents. In terms of the synthetic simplicity as obtained through the variations of the reaction conditions is
well as the environmentally benign and sustainable process, indicated in entry 17 of Table 1.
exploration of a green, efficient and recyclable catalytic system
for selective chalcogenation of 7-indoles is highly desirable.
To probe the scope of the reaction, we applied the optimiz-
ation conditions to a variety of diorgano disulfides as outlined
It has been shown that quinoline N-oxides serve as an oxi- in Scheme 3. It was satisfying to find that sulfides bearing
dizing directing group for the alkenylation and additional oxi- either aromatic or heteroaromatic substitution underwent C3
2
1
dants were avoided. Inspired by this, we assume that 7-azain- sulfenylation smoothly. The reaction tolerated a range of func-
dole N-oxides could also be employed as internal oxidants. tional groups, such as halogen, amino, and nitro groups.
Besides, by using the N-oxides to activate the aromatic system, Notably, the reaction was sensitive to the electronic properties
both electrophilic and nucleophilic attack would be easier due of the substituents on the aryls. The electron-withdrawing sub-
to the σ-electron-withdrawing and π-back-donating character of stituents showed superiority over electron-donating substitu-
2
2
the N-oxide moiety.
Moreover, the N-oxide moiety will ents to furnish the products in higher yields. The observed
increase the solubility of the substrate in nontoxic polar sol- substitution effects on the yields were consistent with the elec-
vents. Recently, polyethylene glycol (PEG) has been shown to trophilic aromatic substitution mechanism. In previous
be a useful solvent due to its non-toxicity, cost effectiveness reports, the sulfenylation of dialkyl disulfides was normally
2
3
and reusability. Herein, we developed a general method for promoted by a higher catalyst loading or a relatively higher
2
4
the regioselective deoxygenative chalcogenation of 7-azaindole reaction temperature, owing to the more difficult formation
N-oxides. The combination of an internal oxidant and a green of electrophilic alkylthiolate counterions compared to arylthio-
solvent has emerged as an eco-friendly and sustainable late counterions. Gratifyingly, good yield was achieved by
alternative protocol for the synthesis of diversely substituted employing the benzyl and alkyl thios under our optimal reac-
mono- and bis-arylchalcogen-7-azaindole derivatives. The tion conditions, which shows the efficiency and broad general-
regioselectivity is tunable in different conditions.
ity of our methodology.
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a
Table 1 Optimization of the reaction conditions
b
Entry
S reagent
PhSH (2a)
I
2
(mol%)
Solvent
Additives
Temperature (°C)
Yield (%)
c
1
2
3
4
5
6
7
8
9
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
10
10
5
Toluene
Toluene
DMSO
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
110
110
110
110
54 (9)
c
(PhS)
(PhS)
(PhS)
(PhS)
(PhS)
(PhS)
(PhS)
(PhS)
(PhS)
(PhS)
(PhS)
(PhS)
(PhS)
(PhS)
(PhS)
(PhS)
(PhS)
(PhS)
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
(3a)
(3a)
(3a)
(3a)
(3a)
(3a)
(3a)
(3a)
(3a)
(3a)
(3a)
(3a)
(3a)
(3a)
(3a)
(3a)
(3a)
(3a)
64 (12)
45
39
37
59
42
45
40
3
CH CN
2
H O
2
H O
2
H O
2
H O
2
H O
DDBAC
SDBS
TBAB
DTAC
c
10
11
12
13
14
15
16
17
18
19
Methanol
Butanol
Ethanol
PEG-200
PEG-800/H
PEG-200/H
PEG-200
PEG-200
PEG-200
PEG-200
68 (8)c
72 (9)c
78 (6)
c
86 (5)c
e
e
2
O
O
79 (6)
81 (6)
89
2
d
d
d
92
58
0
—
a
b
c
Reactions were carried out using 1a (0.4 mmol), 2a (0.4 mmol), and solvent (2 mL) for 20 h under air. Isolated yields. Data in the parenthesis
d
e
2
refer to the yield of 2,3-disulfenylation-7-azaindole product 4aa′. 0.6 equiv. of 2a was used. The volume ratio of PEG : H O = 1 : 1. DDBAC = ben-
zyldodecyldimethyl ammonium chloride; SDBS = sodium dodecylbenzenesulfonate; TBAB = tetrabutylammonium bromide; DTAC = dodecyl tri-
methyl ammonium chloride.
Scheme 3 Variation of disulfides in the C3 sulfenylation.
Subsequently, a broad spectrum of 7-azaindole derivatives
were subjected to chalcogenation (Scheme 4). As expected, all
the reactions proceeded smoothly. Interestingly, the halogen
Scheme 4 Substrate scope of 7-azaindoles and organochalcogenating
moieties were intact under our conditions, providing the reagents.
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desired products in excellent yields, amenable for further
functionalization. The position of the substituents on 7-azain-
dole had a negligible effect on the reactivity, whereas a prefer-
ence for electron-rich substituents was observed for this trans-
formation, which provided the evidence for the SEAr pathway.
To our delight, products 4ba and 4qa were obtained in nearly
complete conversion. In addition, replacement of unsubsti-
tuted 7-azaindole with N-alkyl and N-benzyl 7-azaindoles led to
slightly better results. It was rewarding to find that the present
reaction system was applicable to C–H selenation, and structu-
rally diverse 3-selenyl 7-indoles were formed in moderate to
good yields. Notably, compound 4ga is active on protein
kinases and VPS34, which show potential for treating human
Fig. 2 Recyclability of I
between 7-azaindole N-oxide 1a and diphenyl disulfide 2a.
2
/PEG in the deoxygenative C–H sulfenylation
2
5
diseases. Our protocols allow access to a library of chalcoge-
nated 7-azaindole derived bioactive compounds of pharma-
ceutical interest.
The C3-position is the most nucleophilic site of the 7-azain-
dole nucleus, and the presence of a sulfide group may steri-
cally inhibit further sulfenylation. To test this hypothesis, an
intensive screening was conducted (see the ESI† for details).
The disulfenylation was established by using excess amounts
of sulfenylating reagents in the presence of 30 mol% iodine in
glycerol at 120 °C (Scheme 5). It is worth noting that the elec-
tron rich sulfenylating reagents 4ad′–4ap′ afforded the disulfe-
nylated products in higher yields, whereas a reduced yield was
observed in the case of electron poor sulfenylating reagent
4
ab′ with a concomitant monosubstituted product. The reactiv-
ity pattern is contrary to the trend in terms of monosulfenyla-
tion. The data suggested that the migration was presumably
involved in the second sulfenylation. Sulfide bearing electron
rich substituents were preferred for the migration rather than
electron-deficient substituted sulfide.
To further demonstrate the synthetic utility of this protocol,
we studied the reusability of the catalytic system (Fig. 2) and
gram scale experiments were carried out (Scheme 6). The re-
cycling study of the catalytic system using a model substrate
demonstrated that the catalytic system can be reused for up to
three cycles without any notable loss in catalytic activity. The
Scheme 6 The scale-up reaction and late-stage modification.
catalytic system could be reused due to the formation of a firmed by X-ray diffraction. Next, we were pleased to find that
2
6
complex of iodine in polyethylene glycol. Furthermore, scale- halogen substituted 7-azaindoles were suitable building blocks
up reactions were carried out at 10 mmol and a compatible for further elaboration. Gratifyingly, amino and pyridyl groups
yield was obtained. The configuration of compound 4aa is con- were installed at different positions through the palladium
2
5,28
catalyzed coupling reaction.
To elucidate the effect of N-oxides and air on the reaction,
parallel experiments were carried out under air and argon, and
similar high yields were obtained (Scheme 7a), which
suggested that the N-oxides rather than air played a crucial
role in ensuring the efficiency of the reaction. To gain insights
into the reaction mechanism, control experiments were per-
formed. The desired product was generated with a comparable
yield in the presence of butylated hydroxytoluene (BHT) as a
radical scavenger, which excluded the involvement of a free-
radical pathway (Scheme 7b). I and 3a were heated to generate
2
9
b
the in situ formed PhSI, then 1a was added into the above
solution, and 4aa was delivered in 97% yield, which showed
that the reaction would start from the formation of an electro-
Scheme 5 Deoxygenative 2,3-disulfenylation of 7-azaindole N-oxides.
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Scheme 8 Proposed mechanism.
position followed by rearrangement. It was found that the major
isomer was the sulfide bearing electron-rich group at the C2
position, and the electron rich substituted sulfide was favored in
migration, offering a possible explanation in this regard.
Based on the above results and previous reports, a plausible
pathway was proposed as depicted in Scheme 8. Initially, the
electrophilic sulfur species PhSI was generated in situ from
9
b–d,f–h,j,n
PhSSPh and I
2
,
which facilitated the electrophilic sul-
fenylation of 7-azaindole to form intermediate A. Then the
deoxygenation took place by the attack of another PhSI to give
the desired product 4 and compound D. Fortunately, D was
detected by GC-MS. Subsequently, HI was oxidized by D to
regenerate the catalyst I and PhSOH, which would serve as the
2
Scheme 7 Mechanistic studies.
electrophilic sulfur source and involve in the next cycle. On the
other hand, the second sulfenylation occurred by initial
addition at the C3 position of the 7-azaindole ring, leading to
3
,3′-disubstituted azaindolenine intermediate E, followed by
philic sulfur species (Scheme 7c). In order to investigate the
deoxygenation step, intermediate B was synthesized and sub-
sequently subjected to the HI solution (Scheme 7d) and PhSI
the migration of one of the sulfide groups to the C2 position.
Finally, two molecules of HI were oxidized by one molecule of
intermediate G to deliver the disulfenylated product 4′ and
(Scheme 7e), respectively. The desired product 4aa was formed
2
reproduce the catalyst I .
in both cases, which revealed that the formation of B as the
intermediate is involved in the reaction. When 1 equiv. of HI
was used, a deoxygenative product was obtained in 47% yield
(
Scheme 7d), while 91% yield was observed by employing the
Conclusions
in situ formed PhSI (Scheme 7e). These observations demon-
strated that the deoxygenation step of the mono-sulfenylation In conclusion, we disclosed a novel and general approach for
occurred predominantly via the oxidation of PhSI. When the chalcogenation of 7-azindole from the corresponding
excess HI was used, 96% yield was observed, which indicated N-oxides. I /PEG was established as an efficient and reusable
2
that the HI generation in the disulfenylation step was probably catalytic system for deoxygenative C–H chalcogenation. In this
sufficient to reduce the N-oxide.
transformation, 7-azaindole N-oxides served both as substrates
Considering that migration would occur in the second sul- and as internal oxidants, leading to a wide spectrum of bio-
fenylation, the reaction of 3-phenylthio-7-azaindole N-oxide active 7-azaindole derivatives bearing mono- and dichalcogenyl
and 4-methoxy substituted diphenyl disulfide was performed substituents. Alkyl, aryl, and heteroaryl chalcogenating
(Scheme 7f), and mixtures of mixed 2,3-bissulfides were reagents were compatible in our protocol, providing the corres-
obtained instead of a single isomer bearing the second sulfide ponding products in excellent yields. The regioselectivity was
group at the C2 position. This result indicated that the mecha- modulated by variation of the reaction parameters, a reversed
nism proceeded via an initial second sulfenylation at the C3 reactivity pattern for mono- and disulfenylation was observed,
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and a possible mechanism was proposed to account for the 7.46 (d, J = 3.4 Hz, 1H), 7.10 (d, J = 6.7 Hz, 1H), 6.63 (d, J =
observed results. This protocol represents an eco-friendly, scal- 3.3 Hz, 1H) ppm.
able and sustainable process for the derivatization of 7-azain-
dole and has great potential in modern synthetic chemistry
and the pharmaceutical industry.
4
-Iodine-7-azaindole-nitrogen oxide (1d)
1
Pale solid (456 mg, 88%); m.p. = 214–215 °C; H NMR
(
400 MHz, DMSO-d
6
): δ = 12.88 (s, 1H), 7.95 (d, J = 6.4 Hz, 1H),
7
.56 (d, J = 3.4 Hz, 1H), 7.47 (d, J = 6.5 Hz, 1H), 6.36 (d, J =
1
3
Experimental
General remarks
3.3 Hz, 1H) ppm; C NMR (101 MHz, DMSO-d ): δ = 146.8,
6
1
43.1, 127.2, 125.7, 125.0, 103.0, 99.0 ppm; HRMS (ESI-TOF)
+
exact mass for [M + H] (C H IN O): calcd m/z 260.9519,
found: 260.9518.
7
6
2
All reactions were performed in flame-dried glassware with a
magnetic stirring bar. Liquids and solutions were transferred
with syringes. Solvents were purified and dried following the
standard procedures. Technical grade solvents were used for
2
5
-Cyano-7-azaindole-nitrogen oxide (1i)
1
extraction and chromatography (ethyl acetate, petroleum ether, Red solid (276.8 mg, 87%); m.p. = 116–117 °C; H NMR
and diethyl ether) and were distilled prior to use. Substrates (400 MHz, DMSO-d ): δ = 13.17 (s, 1H), 8.76 (d, J = 1.3 Hz, 1H),
a, 1b, 1e–1h, 1j, 1p, and 1q and chalcogenating reagents 2a 8.25 (d, J = 1.3 Hz, 1H), 7.65 (d, J = 3.3 Hz, 1H), 6.72 (d, J =
6
1
and 3a–3n were purchased and used directly without purifi- 3.3 Hz, 1H) ppm.
cation. Analytical thin-layer chromatography (TLC) was per-
formed on silica gel GF254 glass plates obtained from Qingdao N-Methyl-4-bromine-7-azaindole-nitrogen oxide (1k)
Haiyang Chemical Co., Ltd. Flash column chromatography
was performed on silica gel (300–400 mesh) obtained from
1
Brown solid (330 mg, 77%); m.p. = 94–95 °C; H NMR
400 MHz, DMSO-d ): δ = 7.96 (d, J = 6.5 Hz, 1H), 7.51 (d, J =
(
6
Qingdao Haiyang Chemical Co., Ltd using the indicated sol-
3
4
1
.4 Hz, 1H), 7.26 (d, J = 6.5 Hz, 1H), 6.43 (d, J = 3.4 Hz, 1H),
1
13
vents. H and C NMR spectra were recorded in CDCl3 or
DMSO-d6 on a Bruker Avance III 400 MHz instrument.
Chemical shifts are reported in parts per million (ppm) down-
field from tetramethylsilane (TMS) and are referenced to the
13
.27 (s, 3H) ppm; C NMR (101 MHz, DMSO-d
6
): δ = 136.5,
33.7, 133.1, 124.7, 123.8, 116.4, 99.4, 36.9 ppm; HRMS
ESI-TOF) exact mass for [M + H] (C H BrN O): calcd m/z
8 8 2
+
(
226.9815, found: 226.9813.
residual solvent resonance as the internal standard (CHCl : δ =
3
1
13
7
.26 ppm for H and CDCl
reported as follows: chemical shift, multiplicity (br s = broad
singlet, s = singlet, d = doublet, t = triplet, q = quartet, m = Yellow solid (394 mg, 72%); m.p. = 214–215 °C; H NMR
multiplet), coupling constants (Hz) and integration. High (400 MHz, DMSO-d ): δ = 7.97 (s, 1H), 7.63 (s, 1H), 7.54 (s, 1H),
resolution mass spectrometry (HRMS) analyses were per- 6.30 (s, 1H), 3.85 (s, 3H) ppm; C NMR (101 MHz, DMSO-d
formed on an Agilent 6460 instrument. Melting points were δ = 145.9, 142.9, 131.1, 125.9, 124.9, 101.9, 99.3, 31.8 ppm;
3
: δ = 77.16 ppm for C). Data are
N-Methyl-4-iodo-7-azaindole-nitrogen oxide (1l)
1
6
1
3
6
):
H IN O): calcd m/z
8 2
+
measured on SGW X-4B melting point apparatus and are HRMS (ESI-TOF) exact mass for [M + H] (C
uncorrected.
274.9676, found: 274.9678.
8
2
General procedure for the synthesis of 7-azaindole N-oxides (GP1)
To a solution of 7-azaindole derivatives (2 mmol, 1 equiv.) in White solid (281.5 mg, 79%); m.p. = 102–103 °C; H NMR
EtOAc (2 mL) was added m-CPBA (85 wt%, 1.30 equiv.) in por- (400 MHz, DMSO-d ): δ = 8.15 (dd, J = 5.5, 1.3 Hz, 1H), 7.33
tions below 20 °C. The resulting suspension was stirred at (dd, J = 3.5, 1.3 Hz, 1H), 6.67 (dd, J = 5.5, 1.3 Hz, 1H), 6.45 (dd,
5 °C for 12 h and filtered. The resulting solids were washed J = 3.4, 1.4 Hz, 1H), 3.95 (d, J = 1.4 Hz, 3H), 3.79 (d, J = 1.4 Hz,
N-Methyl-4-methoxy-7-azaindole-nitrogen oxide (1m)
1
6
2
1
3
with EtOAc/petroleum ether (40/60, w/w, ×2) and dried at 3H) ppm; C NMR (101 MHz, DMSO-d
): δ = 159.6, 149.7,
6
below 40 °C under reduced pressure to provide 7-azaindole 144.9, 127.8, 110.2, 98.3, 96.5, 55.8, 31.4 ppm; HRMS
+
3 4
N-oxide m-CPBA salts. Then 2 M aqueous K PO
9 11 2 2
solution and (ESI-TOF) exact mass for [M + H] (C H N O ): calcd m/z
water were added to adjust the pH to 10 at 10–15 °C. The sus- 179.0815, found: 179.0816.
pension was stirred at 0 °C for 1 h and filtered. The solid was
washed with cold water and dried under reduced pressure. N-Methyl-5-bromine-7-azaindole-nitrogen oxide (1n)
Purification by flash column chromatography on silica gel
using mixtures of petroleum ether and ethyl acetate as eluents
afforded the analytically pure product.
1
Brown solid (354.1 mg, 78%); m.p. = 97–98 °C; H NMR
400 MHz, DMSO-d ): δ = 8.27 (d, J = 1.4 Hz, 1H), 7.84 (t, J =
.3 Hz, 1H), 7.46 (dd, J = 3.4, 1.0 Hz, 1H), 6.50 (dd, J = 3.3,
(
1
1
6
1
3
.1 Hz, 1H), 4.24 (d, J = 1.3 Hz, 3H) ppm; C NMR (101 MHz,
): δ = 136.2, 133.7, 133.6, 126.1, 122.8, 108.2, 101.1,
2
7
4
-Chloro-7-azaindole-nitrogen oxide (1c)
DMSO-d
Pale solid (302 mg, 90%); m.p. = 222–223 °C; H NMR 36.6 ppm; HRMS (ESI-TOF) exact mass for [M
6
1
+
+
H]
(
400 MHz, CDCl ): δ = 14.03 (s, 1H), 8.19 (d, J = 6.7 Hz, 1H), (C H BrN O): calcd m/z 226.9815, found: 226.9817.
3
8
8
2
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1
N-Methyl-5-cyano-7-azaindole-nitrogen oxide (1o)
6
m.p. = 192–193 °C; H NMR (400 MHz, DMSO-d ): δ = 12.43 (s,
1
1H), 8.33 (dd, J = 4.6 Hz, J = 1.5 Hz, 1H), 8.00 (s, 1H), 7.81 (dd,
J = 7.9 Hz, J = 1.5 Hz, 1H), 7.21–7.08 (m, 3H), 6.96 (t, J = 7.6 Hz,
Red solid (207.6 mg, 60%); m.p. = 116–117 °C; H NMR
400 MHz, DMSO-d ): δ = 8.60 (d, J = 1.3 Hz, 1H), 8.16 (d, J =
.4 Hz, 1H), 7.59 (d, J = 3.4 Hz, 1H), 6.67 (d, J = 3.4 Hz, 1H),
(
6
1
3
1H), 6.68 (td, J = 7.9 Hz, J = 1.6 Hz, 1H) ppm; C NMR
1
4
1
1
3
(101 MHz, DMSO-d ): δ = 158.6 (J = 240 Hz), 149.3, 144.3,
6
.29 (s, 3H) ppm; C NMR (101 MHz, DMSO): δ = 145.3, 138.4,
34.8, 125.2, 116.8, 102.9, 101.4, 37.0 ppm; HRMS (ESI-TOF)
exact mass for [M + H] (C H N O): calcd m/z 174.0662, found:
134.4, 127.9 (J = 2.1 Hz), 127.3 (J = 7.3 Hz), 127.1, 126.2 (J =
+
16.5 Hz), 125.5 (J = 3.2 Hz), 121.5, 117.2, 115.8 (J = 21 Hz),
9
8 3
1
9
9
(
6.5 ppm; F NMR (377 MHz, DMSO-d ): δ = −114.28; HRMS
6
1
74.0661.
+
2
APCI) exact mass for [M + H] (C13H10FN S): calcd m/z
2
45.0543, found: 245.0540.
N-Benzyl-7-azaindole-nitrogen oxide (1r)
Light red solid (336 mg, 75%); m.p. = 104–105 °C; H NMR
400 MHz, CDCl ): δ = 8.11 (d, J = 6.2 Hz, 1H), 7.55 (dd, J = 8.0,
.0 Hz, 1H), 7.38–7.30 (m, 4H), 7.29 (s, 1H), 7.12 (t, J = 2.7 Hz,
H), 6.98 (dd, J = 8.0, 6.2 Hz, 1H), 6.53 (t, J = 2.9 Hz, 1H), 6.17
1
2-[(1H-Pyrrolo[2,3-b]pyridin-3-yl)thio]aniline (4ac)
(
1
1
3
Prepared from 1H-pyrrolo[2,3-b]pyridine 7-oxide (1a, 53.6 mg,
0
5
.4 mmol, 1.00 equiv.) and 2,2′-disulfanediyldianiline (3c,
9.6 mg, 0.24 mmol, 0.60 equiv.) according to GP2; purifi-
1
3
(d, J = 1.7 Hz, 2H) ppm; C NMR (101 MHz, DMSO: δ = 147.7,
1
1
43.0, 138.9, 129.4, 129.0, 128.9, 128.7, 127.7, 120.5, 116.2,
00.1, 47.6 ppm; HRMS (ESI-TOF) exact mass for [M + H]
cation by flash column chromatography on silica gel afforded
+
the analytically pure product (62.7 mg, 65%) as a brown solid;
1
14 13 2
(C H N O): calcd m/z 225.1022, found: 225.1021.
m.p. = 212–213 °C; H NMR (400 MHz, DMSO-d ): δ = 12.38 (s,
6
1
7
1
H), 8.33 (dd, J = 4.6 Hz, J = 1.6 Hz, 1H), 7.98–7.90 (m, 2H),
.74 (dd, J = 7.9 Hz, J = 1.5 Hz, 1H), 7.27 (dd, J = 8.0 Hz, J =
.6 Hz, 1H), 7.21–7.09 (m, 2H), 6.70 (d, J = 8.1 Hz, 1H), 4.37 (q,
General procedure for the deoxygenative C3–H chalcogenation
of 7-azaindole N-oxides (GP2)
1
3
6
A Teflon capped vial equipped with a magnetic stir bar was J = 7.1 Hz, 2H) ppm; C NMR (101 MHz, DMSO-d ): δ = 166.1,
successively charged with 1H-pyrrolo[2,3-b]pyridine 7-oxide 149.6, 144.3, 143.6, 134.2, 133.1, 131.3, 127.2, 126.4, 124.6,
derivative (0.40 mmol, 1.0 equiv.), 1,2-diaryldisulfane or 1,2- 121.4, 117.2, 99.2 ppm; HRMS (ESI-TOF) exact mass for
+
diphenyldiselane (0.24 mmol, 0.6 equiv.), and I
2
(0.04 mmol, [M + H] (C13
H
12
N
3
S): calcd m/z 242.0746, found: 242.0744.
1
0 mol%) in PEG-200 (2.0 mL) at room temperature. The reac-
tion mixture was heated to 110 °C for an indicated time. The
reaction was monitored by TLC. After completion, the reaction
mixture was allowed to cool to room temperature and extracted
3
-(p-Tolylthio)-1H-pyrrolo[2,3-b]pyridine (4ad)
Prepared from 1H-pyrrolo[2,3-b]pyridine 7-oxide (1a, 53.6 mg,
0
0
.4 mmol, 1.00 equiv.) and 1,2-di-p-tolyldisulfane (3d, 59.1 mg,
.24 mmol, 0.60 equiv.) according to GP2; purification by flash
with diethyl ether (Et O) at least three times. The combined
2
mixture was concentrated under reduced pressure. Purification
by flash column chromatography on silica gel using mixtures
of petroleum ether and ethyl acetate as eluents afforded the
analytically pure product.
column chromatography on silica gel afforded the analytically
pure product (68.2 mg, 71%) as a white solid; m.p. =
1
1
8
7
7
72–173 °C; H NMR (400 MHz, DMSO-d ): δ = 12.24 (s, 1H),
.30 (d, J = 4.6 Hz, 1H), 7.91 (d, J = 2.3 Hz, 1H), 7.77 (dd, J =
.8 Hz, J = 1.6 Hz, 1H), 7.12 (dd, J = 7.9 Hz, J = 4.6 Hz, 1H),
.06–6.93 (m, 4H), 2.20 (s, 3H) ppm; C NMR (101 MHz,
): δ = 148.9, 143.6, 134.8, 134.5, 132.8, 129.6, 126.7,
26.0, 120.9, 116.5, 99.3, 20.4 ppm; HRMS (APCI) exact mass
6
3
-(Phenylthio)-1H-pyrrolo[2,3-b]pyridine (4aa)
1
3
Prepared from 1H-pyrrolo[2,3-b]pyridine 7-oxide (1a, 53.6 mg,
DMSO-d
1
6
0
0
.4 mmol, 1.00 equiv.) and 1,2-diphenyldisulfane (3a, 52.3 mg,
.24 mmol, 0.60 equiv.) according to GP2; purification by flash
+
for [M + H] (C H N S): calcd m/z 241.0794, found: 241.0798.
1
4
13 2
column chromatography on silica gel afforded the analytically
pure product (83.3 mg, 92%) as a white solid; m.p. =
1
3
-[(4-Chlorophenyl)thio]-1H-pyrrolo[2,3-b]pyridine (4ae)
Prepared from 1H-pyrrolo[2,3-b]pyridine 7-oxide (1a, 53.6 mg,
.4 mmol, 1.00 equiv.) and 1,2-bis(4-chlorophenyl)disulfane
3e, 68.9 mg, 0.24 mmol, 0.60 equiv.) according to GP2; purifi-
1
8
7
7
88–189 °C; H NMR (400 MHz, DMSO-d ): δ = 12.30 (s, 1H),
6
.31 (dd, J = 4.7 Hz, J = 1.6 Hz, 1H), 7.94 (d, J = 2.3 Hz, 1H),
.79 (dd, J = 7.8 Hz, J = 1.6 Hz, 1H), 7.21 (dd, J = 8.3 Hz, J =
0
(
1
3
.1 Hz, 2H), 7.15–7.01 (m, 4H) ppm; C NMR (101 MHz,
): δ = 148.9, 143.7, 138.6, 133.2, 128.9, 126.7, 125.5,
25.0, 120.9, 116.6, 98.5 ppm; HRMS (APCI) exact mass for
DMSO-d
1
6
cation by flash column chromatography on silica gel afforded
the analytically pure product (98.0 mg, 94%) as a white solid;
m.p. = 203–204 °C; H NMR (400 MHz, DMSO-d ): δ = 12.33 (s,
+
1
[
M + H] (C H N S): calcd m/z 227.0737, found: 227.0635.
13 11 2
6
1
1
H), 8.32 (dd, J = 4.7 Hz, J = 1.6 Hz, 1H), 7.96 (d, J = 2.3 Hz,
H), 7.79 (dd, J = 7.9 Hz, J = 1.6 Hz, 1H), 7.32–7.23 (m, 2H),
3
-[(2-Fluorophenyl)thio]-1H-pyrrolo[2,3-b]pyridine (4ab)
Prepared from 1H-pyrrolo[2,3-b]pyridine 7-oxide (1a, 53.6 mg, 7.15 (dd, J = 7.9 Hz, J = 4.7 Hz, 1H), 7.09–7.00 (m, 2H) ppm;
1
3
0
.4 mmol, 1.00 equiv.) and 1,2-bis(2-fluorophenyl)disulfane
C NMR (101 MHz, DMSO-d ): δ = 149.6, 136.9, 132.0, 130.5,
6
(
3b, 61.0 mg, 0.24 mmol, 0.60 equiv.) according to GP2; purifi- 130.4, 129.8, 129.4, 128.0, 127.7, 117.9, 39.9 ppm; HRMS
+
2
cation by flash column chromatography on silica gel afforded (APCI) exact mass for [M + H] (C13H10ClN S): calcd m/z
the analytically pure product (93.8 mg, 96%) as a pale solid; 261.0248, found: 261.0246.
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+
3
-[(4-Nitrophenyl)thio]-1H-pyrrolo[2,3-b]pyridine (4af)
HRMS (APCI) exact mass for [M + H] (C10
H
13
N
2
S): calcd m/z
193.0794, found: 193.0790.
Prepared from 1H-pyrrolo[2,3-b]pyridine 7-oxide (1a, 53.6 mg,
0
7
.4 mmol, 1.00 equiv.) and 1,2-bis(4-nitrophenyl)disulfane (3f,
4.0 mg, 0.24 mmol, 0.60 equiv.) according to GP2; purifi-
3
-(Butylthio)-1H-pyrrolo[2,3-b]pyridine (4aj)
Prepared from 1H-pyrrolo[2,3-b]pyridine 7-oxide (1a, 53.6 mg,
.4 mmol, 1.00 equiv.) and 1,2-dibutyldisulfane (3j, 42.8 mg,
cation by flash column chromatography on silica gel afforded
the analytically pure product (100.9 mg, 93%) as a yellow solid;
m.p. = 222.4–224.6 °C; H NMR (400 MHz, DMSO-d ): δ = 12.53
0
1
0.24 mmol, 0.60 equiv.) according to GP2; purification by flash
column chromatography on silica gel afforded the analytically
pure product (70.1 mg, 85%) as a white solid; m.p. =
6
(s, 1H), 8.37 (dd, J = 4.7 Hz, J = 1.6 Hz, 1H), 8.07 (td, J = 8.6 Hz,
J = 2.6 Hz, 3H), 7.81 (dd, J = 7.9 Hz, J = 1.6 Hz, 1H), 7.19 (ddd,
1
13
178–180 °C; H NMR (400 MHz, DMSO-d
6
): δ = 11.96 (s, 1H),
J = 11.2 Hz, J = 7.5 Hz, J = 3.3 Hz, 3H) ppm; C NMR
101 MHz, DMSO-d ): δ = 149.7, 149.5, 145.0, 144.5, 134.6,
27.1, 125.5, 124.6, 121.0, 117.4, 96.4 ppm; HRMS (APCI) exact
8
1
.26 (dt, J = 4.6 Hz, J = 1.2 Hz, 1H), 7.97 (dt, J = 7.9 Hz, J =
.1 Hz, 1H), 7.64 (d, J = 1.8 Hz, 1H), 7.13 (ddd, J = 7.8 Hz, J =
(
1
6
+
4.6 Hz, J = 0.8 Hz, 1H), 2.64 (t, J = 7.0 Hz, 2H), 1.43–1.29 (m,
mass for [M + H] (C H N O S): calcd m/z 272.0488, found:
2
1
3
10 3 2
1
3
4
H), 0.79 (td, J = 7.2, 1.1 Hz, 3H) ppm; C NMR (101 MHz,
DMSO-d ): δ = 149.1, 143.6, 131.5, 127.1, 121.9, 116.5, 102.8,
5.9, 31.8, 21.4, 14.0 ppm; HRMS (APCI) exact mass for
72.0485.
6
3
3
-(Methylthio)-1H-pyrrolo[2,3-b]pyridine (4ag)
+
[M + H] (C H N S): calcd m/z 207.0950, found: 207.0948.
11 15 2
Prepared from 1H-pyrrolo[2,3-b]pyridine 7-oxide (1a, 53.6 mg,
0
.4 mmol, 1.00 equiv.) and 1,2-dimethyldisulfane (3g, 21.2 μL, 3-(Pyridin-2-ylthio)-1H-pyrrolo[2,3-b]pyridine (4ak)
0
.24 mmol, 0.60 equiv.) according to GP2; purification by flash
Prepared from 1H-pyrrolo[2,3-b]pyridine 7-oxide (1a, 53.6 mg,
column chromatography on silica gel afforded the analytically
pure product (59.3 mg, 90%) as a yellow solid; m.p. =
0
5
.4 mmol, 1.00 equiv.) and 1,2-di(pyridin-2-yl)disulfane (3k,
2.9 mg, 0.24 mmol, 0.60 equiv.) according to GP2; purifi-
1
1
8
7
2
84–185 °C; H NMR (400 MHz, DMSO-d ): δ = 11.94 (s, 1H),
6
cation by flash column chromatography on silica gel afforded
.27 (dd, J = 4.6 Hz, J = 1.6 Hz, 1H), 7.99 (d, J = 7.8 Hz, 1H),
.64 (s, 1H), 7.13 (ddd, J = 7.4 Hz, J = 4.7 Hz, J = 2.4 Hz, 1H),
the analytically pure product (63.6 mg, 70%) as a white solid;
1
m.p. = 183–185 °C; H NMR (400 MHz, DMSO-d
6
): δ = 12.39 (s,
1
3
.33 (d, J = 1.5 Hz, 3H) ppm; C NMR (101 MHz, DMSO-d6):
1
7
7
H), 8.35 (dd, J = 10.6, J = 4.5 Hz, 2H), 7.98 (d, J = 1.8 Hz, 1H),
δ = 149.0, 143.7, 129.7, 127.2, 121.1, 116.3, 105.1, 20.0 ppm;
HRMS (APCI) exact mass for [M + H] (C
1
.82 (d, J = 7.9 Hz, 1H), 7.51 (dd, J = 7.6, J = 1.9 Hz, 1H),
+
8
H
9
N
2
S): calcd m/z
13
.12–7.09 (m, 2H), 6.68 (d, J = 8.1 Hz, 1H) ppm; C NMR
65.0481, found: 165.0477.
(
101 MHz, DMSO-d ): δ = 162.0, 149.7, 149.5, 144.2, 137.6,
6
1
34.1, 127.2, 121.4, 120.2, 119.6, 117.2, 97.7 ppm; HRMS
3
-(Benzylthio)-1H-pyrrolo[2,3-b]pyridine (4ah)
+
(
10 3
APCI) exact mass for [M + H] (C12H N S): calcd m/z
Prepared from 1H-pyrrolo[2,3-b]pyridine 7-oxide (1a, 53.6 mg,
228.0590, found: 228.0587.
0
.4 mmol, 1.00 equiv.) and 1,2-dibenzyldisulfane (3h, 59.1 mg,
0
.24 mmol, 0.60 equiv.) according to GP2; purification by flash 3-(Thiophen-2-ylthio)-1H-pyrrolo[2,3-b]pyridine (4al)
column chromatography on silica gel afforded the analytically
pure product (68.3 mg, 71%) as a white solid; m.p. =
Prepared from 1H-pyrrolo[2,3-b]pyridine 7-oxide (1a, 53.6 mg,
0
5
.4 mmol, 1.00 equiv.) and 1,2-di(thiophen-2-yl)disulfane (3l,
5.3 mg, 0.24 mmol, 0.60 equiv.) according to GP2; purifi-
1
1
8
1
2
1
4
72–173 °C; H NMR (400 MHz, DMSO-d
6
): δ = 11.89 (s, 1H),
.24 (dd, J = 4.6 Hz, J = 1.5 Hz, 1H), 7.79 (dd, J = 7.8 Hz, J =
.5 Hz, 1H), 7.43 (d, J = 2.2 Hz, 1H), 7.22–7.06 (m, 6H), 3.90 (s,
H) ppm; C NMR (101 MHz, DMSO-d
39.2, 131.8, 129.3, 128.6, 127.2, 127.2, 121.8, 116.5, 102.4,
13 2
6.8 ppm; HRMS (APCI) exact mass for [M + H] (C14H N S):
cation by flash column chromatography on silica gel afforded
the analytically pure product (57.6 mg, 62%) as a pale solid;
1
3
): δ = 148.9, 143.5,
1
6
m.p. = 196–198 °C; H NMR (400 MHz, DMSO-d
): δ = 12.20 (s,
6
1H), 8.29 (dd, J = 4.7 Hz, J = 1.5 Hz, 1H), 8.01 (dd, J = 7.9 Hz,
+
J = 1.5 Hz, 1H), 7.91 (d, J = 1.9 Hz, 1H), 7.44 (dd, J = 5.2 Hz, J =
calcd m/z 241.0794, found: 241.0792.
1
1
1
.1 Hz, 1H), 7.25–7.13 (m, 2H), 6.95 (dd, J = 5.3 Hz, J = 3.6 Hz,
1
3
H) ppm; C NMR (101 MHz, DMSO-d ): δ = 148.9, 144.1,
6
3
-(Propylthio)-1H-pyrrolo[2,3-b]pyridine (4ai)
37.3, 132.1, 130.8, 129.0, 128.2, 127.2, 120.9, 117.0,
+
Prepared from 1H-pyrrolo[2,3-b]pyridine 7-oxide (1a, 53.6 mg, 103.1 ppm; HRMS (APCI) exact mass for [M + H] (C11
H
9
N
2
S
2
):
0
0
.4 mmol, 1.00 equiv.) and 1,2-dipropyldisulfane (3i, 36.1 mg, calcd m/z 233.0202, found: 233.0199.
.24 mmol, 0.60 equiv.) according to GP2; purification by flash
2-[(1H-Pyrrolo[2,3-b]pyridin-3-yl)thio]benzo[d]thiazole (4am)
column chromatography on silica gel afforded the analytically
pure product (67.7 mg, 88%) as a white solid; m.p. = Prepared from 1H-pyrrolo[2,3-b]pyridine 7-oxide (1a, 53.6 mg,
1
1
8
1
2
7
1
6
87–188 °C; H NMR (400 MHz, DMSO-d ): δ = 11.98 (s, 1H), 0.4 mmol, 1.00 equiv.) and 1,2-bis(benzo[d]thiazol-2-yl)disul-
.27 (dt, J = 4.8 Hz, J = 1.3 Hz, 1H), 7.97 (dt, J = 7.8 Hz, J = fane (3n, 79.8 mg, 0.24 mmol, 0.60 equiv.) according to GP2;
.3 Hz, 1H), 7.65 (s, 1H), 7.13 (dd, J = 7.9 Hz, J = 4.7 Hz, 1H), purification by flash column chromatography on silica gel
.60 (t, J = 7.2 Hz, 2H), 1.42 (q, J = 7.3 Hz, 2H), 0.88 (t, J = afforded the analytically pure product (90.7 mg, 80%) as a
.3 Hz, 3H) ppm; C NMR (101 MHz, DMSO-d
43.6, 131.5, 127.1, 121.9, 116.5, 102.7, 38.2, 23.0, 13.3 ppm; δ = 12.68 (s, 1H), 8.39 (d, J = 4.6 Hz, 1H), 8.24 (s, 1H), 7.99 (d,
1
3
1
6 6
): δ = 149.1, yellow solid; m.p. = 202–203 °C; H NMR (400 MHz, DMSO-d ):
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1
6
J = 7.8 Hz, 1H), 7.82 (d, J = 8.1 Hz, 2H), 7.42 (t, J = 7.7 Hz, 1H), m.p. = 212–214 °C; H NMR (400 MHz, DMSO-d ): δ = 12.59 (s,
1
3
7
1
1
.30–7.20 (m, 2H) ppm; C NMR (101 MHz, DMSO-d ): δ = 1H), 8.06 (d, J = 2.1 Hz, 1H), 7.92 (d, J = 4.9 Hz, 1H), 7.63 (d, J =
6
73.0, 154.5, 149.3, 144.7, 135.4, 135.2, 127.2, 126.7, 124.5, 4.9 Hz, 1H), 7.21 (t, J = 7.6 Hz, 2H), 7.07 (t, J = 7.6 Hz, 1H),
22.1, 121.6, 120.9, 117.7, 96.8 ppm; HRMS (APCI) exact mass 7.00–6.94 (m, 2H) ppm; C NMR (101 MHz, DMSO-d ): δ =
6
1
3
+
for [M + H] (C H N S ): calcd m/z 284.0311, found: 148.0, 144.1, 141.1, 136.7, 129.3, 128.3, 125.6, 125.2, 122.0,
1
4
10 3 2
+
2
84.0306.
100.7, 97.8 ppm; HRMS (APCI) exact mass for [M + H]
S): calcd m/z 352.9604, found: 352.9601.
13 2
(C H10IN
3
-[(Furan-2-ylmethyl)thio]-1H-pyrrolo[2,3-b]pyridine (4an)
4
-Bromo-3-(phenylthio)-1H-pyrrolo[2,3-b]pyridine (4ea)
.4 mmol, 1.00 equiv.) and 1,2-bis(furan-2-ylmethyl)disulfane Prepared from 4-bromo-1H-pyrrolo[2,3-b]pyridine 7-oxide (1e,
3n, 54.3 mg, 0.24 mmol, 0.60 equiv.) according to GP2; purifi- 85.2 mg, 0.4 mmol, 1.00 equiv.) and 1,2-diphenyldisulfane (3a,
Prepared from 1H-pyrrolo[2,3-b]pyridine 7-oxide (1a, 53.6 mg,
0
(
cation by flash column chromatography on silica gel afforded 52.3 mg, 0.24 mmol, 0.60 equiv.) according to GP2; purifi-
the analytically pure product (65.4 mg, 71%) as a brown solid; cation by flash column chromatography on silica gel afforded
1
m.p. = 187.1–188.6 °C; H NMR (400 MHz, DMSO-d ): δ = 11.98 the analytically pure product (102.5 mg, 84%) as a light yellow
6
1
(
s, 1H), 8.25 (dd, J = 4.7 Hz, J = 1.6 Hz, 1H), 7.78 (dd, J = 7.9 solid; m.p. = 210–212 °C; H NMR (400 MHz, DMSO-d
6
): δ =
Hz, J = 1.6 Hz, 1H), 7.59–7.47 (m, 2H), 7.10 (dd, J = 7.9 Hz, J = 12.68 (s, 1H), 8.14 (d, J = 5.1 Hz, 1H), 8.05 (d, J = 2.4 Hz, 1H),
4
3
.7 Hz, 1H), 6.28 (dd, J = 3.2 Hz, J = 1.9 Hz, 1H), 5.95 (d, J = 7.37 (d, J = 5.1 Hz, 1H), 7.22 (t, J = 7.6 Hz, 2H), 7.08 (t, J =
1
3
13
.2 Hz, 1H), 3.92 (s, 2H) ppm; C NMR (101 MHz, DMSO-d
6
): 7.4 Hz, 1H), 7.00 (d, J = 7.8 Hz, 2H) ppm; C NMR (101 MHz,
): δ = 149.7, 144.5, 140.8, 136.4, 129.4, 125.7, 125.3,
124.2, 121.4, 119.5, 99.6 ppm; HRMS (APCI) exact mass for [M
δ = 151.9, 148.9, 143.7, 142.8, 132.2, 127.1, 121.8, 116.5, 111.1, DMSO-d
1
6
+
08.3, 101.9, 33.4 ppm; HRMS (APCI) exact mass for [M + H]
OS): calcd m/z 231.0587, found: 231.0585.
+
(C
12
H
11
N
2
+ H] (C13
2
H10BrN S): calcd m/z 304.9743, found: 304.9741.
4
-Methoxy-3-(phenylthio)-1H-pyrrolo[2,3-b]pyridine (4ba)
5-{(4-Bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)thio}phenol (4eo)
Prepared from 4-methoxy-1H-pyrrolo[2,3-b]pyridine 7-oxide Prepared from 4-bromo-1H-pyrrolo[2,3-b]pyridine 7-oxide (1e,
(
(
1b, 65.7 mg, 0.4 mmol, 1.00 equiv.) and 1,2-diphenyldisulfane 85.2 mg, 0.4 mmol, 1.00 equiv.) and 4,4′-dihydroxyl-diphenyl
3a, 56.7 mg, 0.24 mmol, 0.65 equiv.) according to GP2; purifi- disulfide (3o, 60 mg, 0.24 mmol, 0.60 equiv.) according to
cation by flash column chromatography on silica gel afforded GP2; purification by flash column chromatography on silica
the analytically pure product (100.4 mg, 98%) as a yellow solid; gel afforded the analytically pure product (113.5 mg, 89%) as a
1
1
m.p. = 175–176 °C; H NMR (400 MHz, DMSO-d ): δ = 12.16 (s, brown solid; m.p. = 222–224 °C; H NMR (400 MHz, DMSO-d ):
6
6
1
2
3
1
5
H), 8.16 (d, J = 5.5 Hz, 1H), 7.63 (s, 1H), 7.20 (t, J = 7.6 Hz, δ = 12.56–12.46 (m, 1H), 8.09 (d, J = 5.2 Hz, 1H), 7.92 (d, J =
H), 7.04 (d, J = 8.1 Hz, 3H), 6.67 (d, J = 5.5 Hz, 1H), 3.72 (s, 2.2 Hz, 1H), 7.34 (d, J = 5.1 Hz, 1H), 6.99 (d, J = 8.5 Hz, 2H),
1
3
13
H) ppm; C NMR (101 MHz, DMSO-d ): δ = 160.7, 151.2, 6.67 (d, J = 8.4 Hz, 2H) ppm; C NMR (101 MHz, DMSO-d6):
6
46.2, 140.9, 131.4, 129.1, 126.1, 125.1, 110.7, 99.4, 98.5, δ = 156.2, 149.5, 144.3, 135.3, 129.3, 128.2, 124.2, 121.3, 119.3,
+
+
5.9 ppm; HRMS (APCI) exact mass for [M + H] (C14
H
13
N
2
OS): 116.5, 102.5 ppm; HRMS (APCI) exact mass for [M + H]
(C H BrN OS): calcd m/z 320.9697, found: 320.9691.
calcd m/z 257.0743, found: 257.0740.
1
3
10
2
4
-Chloro-3-(phenylthio)-1H-pyrrolo[2,3-b]pyridine (4ca)
4-Bromo-3-[(4-methoxyphenyl)thio]-1H-pyrrolo[2,3-b]pyridine
4ep)
(
Prepared from 4-chloro-1H-pyrrolo[2,3-b]pyridine 7-oxide (1c,
6
5
7.4 mg, 0.4 mmol, 1.00 equiv.) and 1,2-diphenyldisulfane (3a, Prepared from 4-bromo-1H-pyrrolo[2,3-b]pyridine 7-oxide (1e,
6.7 mg, 0.24 mmol, 0.65 equiv.) according to GP2; purifi- 85.2 mg, 0.4 mmol, 1.00 equiv.) and 4,4′-dimethoxyl-diphenyl
cation by flash column chromatography on silica gel afforded disulfide (3p, 66.7 mg, 0.24 mmol, 0.60 equiv.) according to
the analytically pure product (95.9 mg, 92%) as a light brown GP2; purification by flash column chromatography on silica
1
solid; m.p. = 198–199 °C; H NMR (400 MHz, DMSO-d
1
7
6
): δ = gel afforded the analytically pure product (114.9 mg, 86%) as a
1
2.67 (s, 1H), 8.24 (d, J = 5.1 Hz, 1H), 8.02 (d, J = 2.1 Hz, 1H), light yellow solid; m.p. = 196–197 °C; H NMR (400 MHz,
.21 (q, J = 6.2 Hz, J = 4.8 Hz, 3H), 7.08 (t, J = 7.3 Hz, 1H), 7.02 DMSO-d ): δ = 12.60 (s, 1H), 8.11 (d, J = 5.2 Hz, 1H), 8.00 (d, J =
): δ = 2.3 Hz, 1H), 7.39–7.32 (m, 1H), 7.09–7.01 (m, 2H), 6.87–6.78
6
1
3
(
d, J = 7.8 Hz, 2H) ppm; C NMR (101 MHz, DMSO-d
6
1
3
1
1
50.4, 144.7, 140.6, 135.9, 135.4, 129.4, 125.7, 125.3, 118.1, (m, 2H), 3.67 (d, J = 1.5 Hz, 3H) ppm; C NMR (101 MHz,
18.0, 98.8 ppm; HRMS (APCI) exact mass for [M + H]
10ClN S): calcd m/z 261.0248, found: 261.0245.
+
6
DMSO-d ): δ = 157.9, 149.6, 144.4, 135.7, 130.7, 128.5, 124.2,
(C
13
H
2
121.3, 119.4, 115.1, 101.6, 55.5 ppm; HRMS (APCI) exact mass
+
for [M + H] (C H BrN OS): calcd m/z 334.9854, found:
1
4
12
2
4
-Iodo-3-(phenylthio)-1H-pyrrolo[2,3-b]pyridine (4da)
334.9854.
Prepared from 4-iodo-1H-pyrrolo[2,3-b]pyridine 7-oxide (1d,
4
-Nitro-3-(phenylthio)-1H-pyrrolo[2,3-b]pyridine (4fa)
1
5
04 mg, 0.4 mmol, 1.00 equiv.) and 1,2-diphenyldisulfane (3a,
6.7 mg, 0.24 mmol, 0.65 equiv.) according to GP2; purifi- Prepared from 4-nitro-1H-pyrrolo[2,3-b]pyridine 7-oxide (1f,
cation by flash column chromatography on silica gel afforded 71.6 mg, 0.4 mmol, 1.00 equiv.) and 4,4′-dimethoxyl-diphenyl
the analytically pure product (93.8 mg, 93%) as a brown solid; disulfide (3a, 87.2 mg, 0.24 mmol, 1 equiv.) according to GP2;
This journal is © The Royal Society of Chemistry 2019
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purification by flash column chromatography on silica gel 1-Methyl-3-(phenylthio)-1H-pyrrolo[2,3-b]pyridine (4ja)
afforded the analytically pure product (73.7 mg, 68%) as a red
Prepared from 1-methyl-1H-pyrrolo[2,3-b]pyridine 7-oxide (1j,
1
solid; m.p. = 191–192 °C; H NMR (400 MHz, DMSO-d
6
): δ =
5
5
9.3 mg, 0.4 mmol, 1.00 equiv.) and 1,2-diphenyldisulfane (3a,
2.3 mg, 0.24 mmol, 0.60 equiv.) according to GP2; purifi-
1
5
3.15 (s, 1H), 8.57 (d, J = 5.1 Hz, 1H), 8.27 (s, 1H), 7.70 (d, J =
.1 Hz, 1H), 7.23 (t, J = 7.7 Hz, 2H), 7.12 (t, J = 7.3 Hz, 1H), 7.03
cation by flash column chromatography on silica gel afforded
1
3
(d, J = 8.2 Hz, 2H) ppm; C NMR (101 MHz, DMSO-d
6
): δ =
the analytically pure product (89.4 mg, 93%) as a light yellow
1
1
52.3, 148.4, 144.6, 139.3, 139.1, 129.4, 126.2, 125.7, 111.0,
10.6, 98.4 ppm; HRMS (APCI) exact mass for [M + H]
1
solid; m.p. = 187–189 °C; H NMR (400 MHz, CDCl ): δ = 8.42
3
+
(
dt, J = 4.7 Hz, J = 1.3 Hz, 1H), 7.89 (dt, J = 7.9 Hz, J = 1.3 Hz,
13 10 3 2
(C H N O S): calcd m/z 272.0494, found: 272.0496.
1
1
3
1
1
H), 7.45 (d, J = 1.0 Hz, 1H), 7.19–7.14 (m, 2H), 7.12 (d, J =
.3 Hz, 1H), 7.09 (dtd, J = 9.3 Hz, J = 3.2 Hz, J = 1.1 Hz, 3H),
1
3
3
.93 (d, J = 1.2 Hz, 3H) ppm; C NMR (101 MHz, CDCl ): δ =
5
-Bromo-3-(phenylthio)-1H-pyrrolo[2,3-b]pyridine (4ga)
48.4, 143.8, 139.0, 135.3, 128.8, 127.9, 125.9, 125.1, 122.2,
Prepared from 5-bromo-1H-pyrrolo[2,3-b]pyridine 7-oxide (1g,
+
16.7, 99.6, 31.5 ppm; HRMS (APCI) exact mass for [M + H]
8
5
5.2 mg, 0.4 mmol, 1.00 equiv.) and 1,2-diphenyldisulfane (3g,
2.3 mg, 0.24 mmol, 0.60 equiv.) according to GP2; purifi-
(
C
14
H
13
N
2
S): calcd m/z 241.0794, found: 241.0792.
cation by flash column chromatography on silica gel afforded
4
-Bromo-1-methyl-3-(phenylthio)-1H-pyrrolo[2,3-b]pyridine (4ka)
the analytically pure product (101.3 mg, 83%) as a white solid;
1
Prepared from 4-bromo-1-methyl-1H-pyrrolo[2,3-b]pyridine
-oxide (1k, 90.8 mg, 0.4 mmol, 1.00 equiv.) and 1,2-diphenyl-
m.p. = 238–240 °C; H NMR (400 MHz, DMSO-d
6
): δ = 12.59 (s,
7
1
1
H), 8.39 (d, J = 2.2 Hz, 1H), 8.05 (s, 1H), 7.94 (d, J = 2.3 Hz,
1
3
disulfane (3a, 52.3 mg, 0.24 mmol, 0.60 equiv.) according to
GP2; purification by flash column chromatography on silica
gel afforded the analytically pure product (109.8 mg, 86%) as a
light yellow solid; m.p. = 209–210 °C; H NMR (400 MHz,
DMSO-d
H), 7.23 (q, J = 8.1 Hz, 2H), 7.13–7.00 (m, 3H) ppm; C NMR
): δ = 147.8, 144.3, 138.5, 135.7, 129.6,
28.9, 126.1, 125.8, 123.3, 112.4, 99.0 ppm; HRMS (APCI) exact
(101 MHz, DMSO-d
6
1
1
+
mass for [M + H] (C H BrN S): calcd m/z 304.9743, found:
1
3
10
2
6
): 8.20 (d, J = 3.9 Hz, 1H), 8.06 (s, 1H), 7.41 (d, J = 3.8
3
04.9740.
Hz, 1H), 7.24 (d, J = 7.1 Hz, 2H), 7.15–7.03 (m, 3H), 3.92 (s, 3H)
ppm; C NMR (101 MHz, CDCl ): δ = 148.5, 143.7, 140.5,
1
3
3
5
-Phenyl-3-(phenylthio)-1H-pyrrolo[2,3-b]pyridine (4ha)
137.4, 128.8, 125.9, 125.4, 125.0, 121.3, 120.4, 100.5, 31.9 ppm;
+
HRMS (APCI) exact mass for [M + H] (C14
H
12BrN
2
S): calcd m/z
Prepared from 5-phenyl-1H-pyrrolo[2,3-b]pyridine 7-oxide (1h,
318.9899, found: 318.9898.
8
5
4.1 mg, 0.4 mmol, 1.00 equiv.) and 1,2-diphenyldisulfane (3a,
2.3 mg, 0.24 mmol, 0.60 equiv.) according to GP2; purifi-
4-Iodo-1-methyl-3-(phenylthio)-1H-pyrrolo[2,3-b]pyridine (4la)
cation by flash column chromatography on silica gel afforded
the analytically pure product (99.1 mg, 82%) as a white solid;
m.p. = 190–191 °C; H NMR (400 MHz, DMSO-d
Prepared
from 4-iodo-1-methyl-1H-pyrrolo[2,3-b]pyridine
1
7-oxide (1l, 109.6 mg, 0.4 mmol, 1.00 equiv.) and 1,2-diphenyl-
disulfane (3a, 52.3 mg, 0.24 mmol, 0.60 equiv.) according to
GP2; purification by flash column chromatography on silica
6
): δ =
1
2
2.46–12.41 (m, 1H), 8.63 (t, J = 1.6 Hz, 1H), 8.01 (dd, J =
.8 Hz, J = 1.2 Hz, 1H), 7.95 (t, J = 1.6 Hz, 1H), 7.65 (dt, J = 8.1
gel afforded the analytically pure product (132.8 mg, 91%) as a
Hz, J = 1.3 Hz, 2H), 7.46–7.42 (m, 2H), 7.35 (dd, J = 7.3 Hz, J =
1
yellow solid; m.p. = 212–213 °C; H NMR (400 MHz, DMSO-d
6
):
1
.4 Hz, 1H), 7.24–7.19 (m, 2H), 7.10–7.05 (m, 3H) ppm;
1
3
δ = 8.11 (s, 1H), 7.97 (d, J = 5.0 Hz, 1H), 7.67 (d, J = 4.9 Hz, 1H),
.23 (t, J = 7.7 Hz, 2H), 7.12–7.07 (m, 1H), 7.00–6.96 (m, 2H),
C NMR (101 MHz, DMSO-d ): δ = 149.0., 143.2, 139.0, 138.9,
6
7
1
1
34.7, 129.8, 129.5, 129.5, 127.6, 127.5, 126.0, 125.6, 124.8,
21.5, 99.4 ppm; HRMS (APCI) exact mass for [M + H]
1
3
+
6
3.88 (s, 3H) ppm; C NMR (101 MHz, DMSO-d ): δ = 147.0,
1
3
43.9, 140.9, 139.9, 129.3, 128.3, 125.6, 125.2, 122.2, 99.4, 98.1,
1.9 ppm; HRMS (APCI) exact mass for [M + H] (C14H12IN S):
2
(C H N S): calcd m/z 303.0950, found: 303.0947.
19 15 2
+
calcd m/z 366.9760, found: 366.9761.
3
-(Phenylthio)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile (4ia)
4
(
-Methoxy-1-methyl-3-(phenylthio)-1H-pyrrolo[2,3-b]pyridine
4ma)
2.3 mg, 0.24 mmol, 0.60 equiv.) according to GP2; purifi- Prepared from 4-methoxy-1-methyl-1H-pyrrolo[2,3-b]pyridine
Prepared from 5-cyano-1H-pyrrolo[2,3-b]pyridine 7-oxide (1i,
6
5
3.6 mg, 0.4 mmol, 1.00 equiv.) and 1,2-diphenyldisulfane (3a,
cation by flash column chromatography on silica gel afforded 7-oxide (1m, 71.3 mg, 0.4 mmol, 1.00 equiv.) and 1,2-diphenyl-
the analytically pure product (78.4 mg, 78%) as a pale solid; disulfane (3a, 52.3 mg, 0.24 mmol, 0.60 equiv.) according to
1
m.p. = 234–236 °C; H NMR (400 MHz, DMSO-d ): δ = 12.96 (s, GP2; purification by flash column chromatography on silica
6
1
2
H), 8.71 (d, J = 1.9 Hz, 1H), 8.34 (d, J = 1.9 Hz, 1H), 8.21 (d, J = gel afforded the analytically pure product (102.7 mg, 95%) as a
1
3
.6 Hz, 1H), 7.25 (t, J = 7.6 Hz, 2H), 7.12–7.09 (m, 3H) ppm; yellow solid; m.p. = 201–203 °C; H NMR (400 MHz, CDCl ):
1
3
C NMR (101 MHz, DMSO-d ): δ = 150.1, 146.9, 138.1, 136.6, δ = 8.26 (d, J = 5.6 Hz, 1H), 7.26 (s, 1H), 7.19–7.16 (m, 4H), 7.09
6
1
31.7, 129.6, 126.6, 126.0, 120.9, 118.9, 101.5, 101.2 ppm; (d, J = 7.0 Hz, 1H), 6.54 (d, J = 5.6 Hz, 1H), 3.89 (s, 3H), 3.79 (s,
+
13
HRMS (APCI) exact mass for [M + H] (C14
52.0590, found: 252.0594.
10 3 3
H N S): calcd m/z 3H) ppm; C NMR (101 MHz, CDCl ): δ = 161.0, 150.2, 145.7,
2
140.3, 133.1, 128.5, 126.4, 124.9, 111.4, 99.26, 98.72, 55.5,
10082 | Org. Biomol. Chem., 2019, 17, 10073–10087
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Paper
+
3
1.7 ppm; HRMS (APCI) exact mass for [M + H] (C15
H
15
N
2
OS): Hz, 2H), 7.15–7.06 (m, 2H), 6.99 (d, J = 7.7 Hz, 2H), 3.84 (s,
1
3
calcd m/z 271.0900, found: 271.0897.
3H), 2.54 (s, 3H) ppm; C NMR (101 MHz, DMSO-d ): δ =
6
1
1
48.2, 145.4, 142.8, 138.9, 129.5, 126.3, 125.7, 125.4, 122.0,
5
(
-Bromo-1-methyl-3-(phenylthio)-1H-pyrrolo[2,3-b]pyridine
4na)
Prepared from 5-bromo-1-methyl-1H-pyrrolo[2,3-b]pyridine
-oxide (1n, 90.8 mg, 0.4 mmol, 1.00 equiv.) and 1,2-diphenyl-
17.1, 95.4, 29.0, 11.2 ppm; HRMS (APCI) exact mass for
+
[M + H] (C H N S): calcd m/z 255.0950, found: 255.0945.
1
5
15 2
1
-Benzyl-3-(phenylthio)-1H-pyrrolo[2,3-b]pyridine (4ra)
7
disulfane (3a, 52.3 mg, 0.24 mmol, 0.60 equiv.) according to Prepared from 1-benzyl-1H-pyrrolo[2,3-b]pyridine 7-oxide (1r,
GP2; purification by flash column chromatography on silica 89.7 mg, 0.4 mmol, 1.00 equiv.) and 1,2-diphenyldisulfane (3a,
gel afforded the analytically pure product (93.2 mg, 73%) as a 52.3 mg, 0.24 mmol, 0.60 equiv.) according to GP2; purifi-
1
brown solid; m.p. = 206–208 °C; H NMR (400 MHz, DMSO-d ): cation by flash column chromatography on silica gel afforded
6
δ = 8.42 (d, J = 2.1 Hz, 1H), 8.08 (s, 1H), 7.95 (d, J = 2.1 Hz, 1H), the analytically pure product (121.6 mg, 96%) as a light yellow
1
7
.22 (d, J = 7.5 Hz, 2H), 7.14–7.03 (m, 3H), 3.88 (s, 3H) ppm; solid; m.p. = 193–194 °C; H NMR (400 MHz, DMSO-d
6
): δ =
1
3
C NMR (101 MHz, DMSO-d ): δ = 146.9, 144.2, 139.0, 138.5, 8.38 (dd, J = 4.8 Hz, J = 1.6 Hz, 1H), 8.17 (s, 1H), 7.83 (dd, J =
6
1
29.6, 129.1, 126.2, 125.8, 123.5, 112.6, 97.8, 31.9 ppm; HRMS 7.9 Hz, J = 1.6 Hz, 1H), 7.36–7.15 (m, 8H), 7.07 (t, J = 8.8 Hz,
+
13
(APCI) exact mass for [M + H] (C14
H
12BrN
2
S): calcd m/z 3H), 5.58 (s, 2H) ppm; C NMR (101 MHz, DMSO-d
148.1, 144.3, 138.8, 138.3, 136.3, 129.5, 129.1, 128.0, 127.9,
27.7, 126.0, 125.7, 121.8, 117.5, 99.0, 48.0 ppm; HRMS (APCI)
6
): δ =
3
18.9899, found: 318.9898.
1
1
-Methyl-3-(phenylthio)-1H-pyrrolo[2,3-b]pyridine-5-
+
exact mass for [M + H] (C20
found: 317.1103.
17 2
H N S): calcd m/z 317.1107,
carbonitrile (4oa)
Prepared from 5-cyano-1-methyl-1H-pyrrolo[2,3-b]pyridine
3-(Phenylselanyl)-1H-pyrrolo[2,3-b]pyridine (6aa)
7
-oxide (1o, 69.3 mg, 0.4 mmol, 1.00 equiv.) and 1,2-diphenyl-
disulfane (3a, 87.1 mg, 0.24 mmol, 1 equiv.) according to GP2; Prepared from 1H-pyrrolo[2,3-b]pyridine 7-oxide (1a, 53.6 mg,
purification by flash column chromatography on silica gel 0.4 mmol, 1.00 equiv.) and 1,2-diphenyldiselane (5a, 74.9 mg,
afforded the analytically pure product (68.9 mg, 65%) as a 0.24 mmol, 0.60 equiv.) according to GP2; purification by flash
1
brown solid; m.p. = 237–238 °C; H NMR (400 MHz, DMSO-d ): column chromatography on silica gel afforded the analytically
6
δ = 8.43 (d, J = 2.2 Hz, 1H), 8.09 (s, 1H), 7.96 (d, J = 2.3 Hz, 1H), pure product (83.1 mg, 76%) as a white solid; m.p. =
1
7
.24–7.21 (m, 3H), 7.07 (d, J = 7.8 Hz, 2H), 3.89 (s, 3H) ppm; 173–174 °C; H NMR (400 MHz, DMSO-d
6
): δ = 12.32 (s, 1H),
1
3
C NMR (101 MHz, DMSO-d ): δ = 146.9, 144.2, 139.0, 138.5, 8.30 (d, J = 4.6 Hz, 1H), 7.92 (s, 1H), 7.79 (d, J = 7.8 Hz, 1H),
29.6, 129.1, 126.2, 125.9, 123.5, 112.6, 99.9, 97.8, 31.9 ppm; 7.20–7.10 (m, 6H) ppm; C NMR (101 MHz, DMSO-d
HRMS (APCI) exact mass for [M + H] (C15H N S): calcd m/z 149.4, 144.1, 134.1, 133.7, 129.7, 128.7, 127.8, 126.3, 122.3,
12 3
6
1
3
1
6
): δ =
+
+
2
66.0746, found: 266.0743.
117.1, 94.4 ppm; HRMS (APCI) exact mass for [M + H]
(
C
13
H
11
N
2
Se): calcd m/z 275.0082, found: 275.0080.
2
-Methyl-3-(phenylthio)-1H-pyrrolo[2,3-b]pyridine (4pa)
4-Chloro-3-(phenylselanyl)-1H-pyrrolo[2,3-b]pyridine (6ca)
Prepared from 2-methyl-1H-pyrrolo[2,3-b]pyridine 7-oxide (1p,
5
5
9.3 mg, 0.4 mmol, 1.00 equiv.) and 1,2-diphenyldisulfane (3a, Prepared from 4-chloro-1H-pyrrolo[2,3-b]pyridine 7-oxide (1c,
2.3 mg, 0.24 mmol, 0.60 equiv.) according to GP2; purifi- 67.4 mg, 0.4 mmol, 1.00 equiv.) and 1,2-diphenyldiselane (5a,
cation by flash column chromatography on silica gel afforded 74.9 mg, 0.24 mmol, 0.60 equiv.) according to GP2; purifi-
the analytically pure product (87.5 mg, 91%) as a light yellow cation by flash column chromatography on silica gel afforded
1
solid; m.p. = 172–174 °C; H NMR (400 MHz, DMSO-d
1
6
): δ = the analytically pure product (100.9 mg, 82%) as a light yellow
1
2.26 (s, 1H), 8.22 (dt, J = 4.7, 1.5 Hz, 1H), 7.70 (dt, J = 7.8 Hz, solid; m.p. = 120–121 °C; H NMR (400 MHz, DMSO-d ): δ =
6
J = 1.5 Hz, 1H), 7.19 (td, J = 7.7 Hz, J = 1.5 Hz, 2H), 7.06 (ddt, 12.67 (s, 1H), 8.24 (d, J = 5.1 Hz, 1H), 8.02 (s, 1H), 7.21 (q, J =
J = 7.6 Hz, J = 6.2 Hz, J = 3.0 Hz, 2H), 6.99–6.93 (m, 2H), 2.48 6.2 Hz, J = 4.8 Hz, 3H), 7.05 (dd, J = 25.5 Hz, J = 7.6 Hz, 3H)
1
3
13
(
d, J = 1.3 Hz, 3H) ppm; C NMR (101 MHz, DMSO-d ): δ = ppm; C NMR (101 MHz, DMSO-d ): δ = 150.4, 144.7, 140.5,
6
6
1
1
48.6, 144.0, 142.9, 139.0, 129.5, 126.1, 125.6, 125.3, 122.5, 135.9, 135.4, 129.4, 125.8, 125.4, 118.1, 118.0, 98.8 ppm;
+
+
16.9, 95.9, 12.2 ppm; HRMS (APCI) exact mass for [M + H]
HRMS (APCI) exact mass for [M + H] (C13
H
10ClN
2
Se): calcd
(
C H N S): calcd m/z 241.0794, found: 241.0793.
m/z 308.9692, found: 308.9692.
1
4
13 2
1
,2-Dimethyl-3-(phenylthio)-1H-pyrrolo[2,3-b]pyridine (4qa)
5-Bromo-3-(phenylselanyl)-1H-pyrrolo[2,3-b]pyridine (6ga)
Prepared from 1,2-dimethyl-1H-pyrrolo[2,3-b]pyridine 7-oxide Prepared from 5-bromo-1H-pyrrolo[2,3-b]pyridine 7-oxide (1g,
(
(
1q, 64.9 mg, 0.4 mmol, 1.00 equiv.) and 1,2-diphenyldisulfane 85.2 mg, 0.4 mmol, 1.00 equiv.) and 1,2-diphenyldiselane (5a,
3a, 56.7 mg, 0.24 mmol, 0.65 equiv.) according to GP2; purifi- 74.9 mg, 0.24 mmol, 0.60 equiv.) according to GP2; purifi-
cation by flash column chromatography on silica gel afforded cation by flash column chromatography on silica gel afforded
the analytically pure product (99.7 mg, 98%) as a light yellow the analytically pure product (116.5 mg, 83%) as a light yellow
1
1
solid; m.p. = 191–193 °C; H NMR (400 MHz, DMSO-d
6
): δ = solid; m.p. = 191–192 °C; H NMR (400 MHz, DMSO-d
6
): δ =
8
.28 (d, J = 4.7 Hz, 1H), 7.75 (d, J = 7.8 Hz, 1H), 7.20 (t, J = 7.6 12.61 (s, 1H), 8.41 (d, J = 17.6 Hz, 1H), 8.01 (dd, J = 37.3 Hz, J =
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13
1
6.8 Hz, 2H), 7.24 (d, J = 18.2 Hz, 5H) ppm; C NMR 2,3-Bis(p-tolylthio)-1H-pyrrolo[2,3-b]pyridine (4ad′)
(
1
101 MHz, DMSO-d ): δ = 147.7, 144.1, 135.8, 133.1, 129.7,
6
Prepared from 1H-pyrrolo[2,3-b]pyridine 7-oxide (1a, 33.5 mg,
29.5, 128.9, 126.5, 124.2, 112.3, 94.3 ppm; HRMS (APCI) exact
0
0
.25 mmol, 1.0 equiv.) and 1,2-di-p-tolyldisulfane (3d, 123 mg,
.50 mmol, 2.0 equiv.) according to GP3; purification by flash
+
mass for [M + H] (C13
52.9185.
2
H10BrN Se): calcd m/z 352.9187, found:
3
column chromatography on silica gel afforded the analytically
pure product (70.5 mg, 78%) as a white solid; m.p. = 82–83 °C;
1
H NMR (400 MHz, DMSO-d ): δ = 12.78 (s, 1H), 8.34 (d, J = 4.3
6
General procedure for the deoxygenative C2–H/C3–H
dichalcogenation of 7-azaindole N-oxides (GP3)
Hz, 1H), 7.76 (d, J = 7.8 Hz, 1H), 7.18–7.07 (m, 5H), 7.01 (d, J =
8
.1 Hz, 2H), 6.93 (d, J = 8.1 Hz, 2H), 2.25 (s, 3H), 2.20 (s, 3H)
A Teflon capped vial equipped with a magnetic stir bar was
successively charged with 1H-pyrrolo[2,3-b]pyridine 7-oxide
derivative (0.25 mmol, 1.0 equiv.), 1,2-diaryldisulfane or 1,2-
13
ppm; C NMR (101 MHz, DMSO-d ): δ = 149.6, 145.4, 137.0,
6
1
1
35.3, 135.0, 134.2, 131.6, 130.5, 130.1, 129.4, 127.6, 127.0,
22.0, 117.6, 107.6, 21.0, 20.9 ppm; HRMS (APCI) exact mass
diphenyldiselane (0.50 mmol, 2.0 equiv.), and I
2
(0.075 mmol,
+
for [M + H] (C H N S ): calcd m/z 363.0984, found:
2
1
19 2 2
3
0 mol%) in glycerol (2.0 mL) at room temperature. The reac-
363.0980.
tion mixture was heated to 120 °C. After 36 h, the reaction
mixture was allowed to cool to room temperature, diluted with
water and ethyl acetate, and extracted with diethyl ether (Et O)
4,4′-{(1H-Pyrrolo[2,3-b]pyridine-2,3-diyl}bis(sulfanediyl))
2
diphenol (4ao′)
at least three times. The combined extract was concentrated
under reduced pressure. Purification by flash column chrom-
atography on silica gel using mixtures of petroleum ether and
ethyl acetate as eluents afforded the analytically pure product.
Prepared from 1H-pyrrolo[2,3-b]pyridine 7-oxide (1a, 33.5 mg,
0
1
.25 mmol, 1.0 equiv.) and 4,4′-disulfanediyldiphenol (3o,
25 mg, 0.50 mmol, 2.0 equiv.) according to GP3; purification
by flash column chromatography on silica gel afforded the
analytically pure product (80.6 mg, 88%) as a light yellow
1
2
,3-Bis(phenylthio)-1H-pyrrolo[2,3-b]pyridine (4aa′)
solid; m.p. = 246–248 °C; H NMR (400 MHz, DMSO-d
6
): δ =
1
7
1
6
2.48 (s, 1H), 9.71 (s, 1H), 9.47 (s, 1H), 8.27 (d, J = 4.7 Hz, 1H),
Prepared from 1H-pyrrolo[2,3-b]pyridine 7-oxide (1a, 33.5 mg,
.76 (d, J = 9.4 Hz, 1H), 7.22 (d, J = 8.6 Hz, 2H), 7.11 (d, J =
2.6 Hz, 1H), 7.01 (d, J = 8.7 Hz, 2H), 6.73 (d, J = 8.6 Hz, 2H),
0
1
.25 mmol, 1.0 equiv.) and 1,2-diphenyldisulfane (3a,
09.2 mg, 0.50 mmol, 2.0 equiv.) according to GP3; purifi-
1
3
6
.64 (d, J = 8.6 Hz, 2H) ppm; C NMR (101 MHz, DMSO-d ):
cation by flash column chromatography on silica gel afforded
δ = 158.6, 156.7, 149.4, 144.9, 136.4, 133.4, 130.6, 129.9, 127.4,
125.8, 122.5, 122.1, 116.9, 116.6, 108.2 ppm; HRMS (APCI)
exact mass for [M + H] (C19
found: 367.0571.
the analytically pure product (55.2 mg, 66%) as a white solid;
1
m.p. = 126–127 °C; H NMR (400 MHz, DMSO-d
6
): δ = 12.88 (s,
+
15 2 2 2
H N O S ): calcd m/z 367.0569,
1
H), 8.37 (dd, J = 4.7 Hz, J = 1.6 Hz, 1H), 7.80 (dd, J = 7.9 Hz,
J = 1.6 Hz, 1H), 7.30 (dd, J = 8.0 Hz, J = 6.8 Hz, 2H), 7.24–7.16
1
3
(m, 6H), 7.11 (d, J = 7.3 Hz, 1H), 7.06–7.00 (m, 2H) ppm;
C
2,3-Bis[(4-methoxyphenyl)thio]-1H-pyrrolo[2,3-b]pyridine (4ap′)
NMR (101 MHz, DMSO-d
6
): δ = 149.7, 145.7, 137.9, 135.4,
Prepared from 1H-pyrrolo[2,3-b]pyridine 7-oxide (1a, 33.5 mg,
0.25 mmol, 1.0 equiv.) and 1,2-bis(4-methoxyphenyl)disulfane
1
1
34.4, 129.9, 129.5, 128.6, 127.7, 127.2, 126.5, 125.9, 122.1,
17.7, 107.5 ppm; HRMS (APCI) exact mass for [M + H]
+
(
3p, 139 mg, 0.50 mmol, 2.0 equiv.) according to GP3; purifi-
19 15 2 2
(C H N S ): calcd m/z 335.0671, found: 335.0668.
cation by flash column chromatography on silica gel afforded
the analytically pure product (82.8 mg, 84%) as an orange
1
2
,3-Bis[(2-fluorophenyl)thio]-1H-pyrrolo[2,3-b]pyridine (4ab′)
solid; m.p. = 187.1–188.6 °C; H NMR (400 MHz, CDCl ): δ =
3
1
7
7
2.57 (s, 1H), 8.16 (dd, J = 4.9 Hz, J = 1.6 Hz, 1H), 7.89 (dd, J =
.9 Hz, J = 1.6 Hz, 1H), 7.41 (dd, J = 5.7 Hz, J = 3.5 Hz, 2H),
.17–7.05 (m, 3H), 6.81–6.68 (m, 4H), 3.73 (d, J = 6.5 Hz, 6H)
Prepared from 1H-pyrrolo[2,3-b]pyridine 7-oxide (1a, 33.5 mg,
.25 mmol, 1.0 equiv.) and 1,2-bis(2-fluorophenyl)disulfane
3b, 127 mg, 0.50 mmol, 2.0 equiv.) according to GP3; purifi-
0
(
1
3
ppm; C NMR (101 MHz, CDCl ): δ = 159.8, 158.1, 148.7,
1
115.1, 114.5, 106.5, 55.6, 55.4 ppm; HRMS (APCI) exact mass
for [M + H] (C H N O S ): calcd m/z 395.0882, found:
cation by flash column chromatography on silica gel afforded
3
42.6, 137.8, 133.5, 132.7, 129.5, 129.0, 128.2, 123.3, 116.9,
the analytically pure product (55.6 mg, 60%) as a white solid;
1
m.p. = 197–199 °C; H NMR (400 MHz, DMSO-d
6
): δ = 13.03 (s,
+
1
H), 8.38 (d, J = 4.7 Hz, 1H), 7.82 (d, J = 7.9 Hz, 1H), 7.32–7.12
21 19 2 2 2
3
95.0880.
(
1
m, 5H), 7.06 (dt, J = 19.7 Hz, J = 7.8 Hz, 2H), 6.94 (t, J = 6.9 Hz,
H), 6.65 (t, J = 7.9 Hz, 1H) ppm; C NMR (101 MHz, DMSO-
1
3
2
,3-Bis(thiophen-2-ylthio)-1H-pyrrolo[2,3-b]pyridine (4am′)
d6): δ = 159.6 (J = 243 Hz), 158.9 (J = 241 Hz), 149.7, 145.8,
1
1
1
1
−
(
33.7, 131.1, 129.7 (J = 7.1 Hz), 128.4, 127.9 (J = 7.5 Hz), 127.6, Prepared from 1H-pyrrolo[2,3-b]pyridine 7-oxide (1a, 33.5 mg,
25.9 (J = 3.3 Hz), 125.5 (J = 3.2 Hz), 124.6 (J = 16.7 Hz), 122.2, 0.25 mmol, 1.0 equiv.) and 1,2-di(thiophen-2-yl)disulfane (3m,
21.6 (J = 16.8 Hz), 117.9, 116.4 (J = 2.1 Hz), 115.9 (J = 2.1 Hz), 116 mg, 0.50 mmol, 2.0 equiv.) according to GP3; purification
1
9
04.8 ppm; F NMR (377 MHz, DMSO-d
113.63 ppm; HRMS (APCI) exact mass for [M + H]
C H F N S ): calcd m/z 371.0483, found: 371.0480.
6
): δ = −111.49, by flash column chromatography on silica gel afforded the
+
analytically pure product (69.3 mg, 80%) as a pale solid; m.p. =
1
200–202 °C; H NMR (400 MHz, CDCl ): δ = 12.75 (s, 1H), 8.31
1
9
13
2
2
2
3
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(d, J = 4.7 Hz, 1H), 8.04 (dd, J = 7.9 Hz, J = 1.4 Hz, 1H), Reuse of catalytic system study
7
4
5
1
1
.42–7.34 (m, 2H), 7.25–7.18 (m, 2H), 7.16 (dd, J = 7.9 Hz, J =
The feasibility of recycling the catalyst system was studied
under the optimized reaction conditions according to GP2. To
a Teflon capped vial were added 1H-pyrrolo[2,3-b]pyridine
.7 Hz, 1H), 7.00 (dd, J = 5.3 Hz, J = 3.6 Hz, 1H), 6.93 (dd, J =
1
3
3
.3 Hz, J = 3.6 Hz, 1H) ppm; C NMR (101 MHz, CDCl ): δ =
48.4, 143.5, 136.5, 136.0, 135.3, 131.2, 131.1, 129.4, 128.1,
7
-oxide (1a, 53.6 mg, 0.4 mmol, 1.00 equiv.), 1,2-diphenyldisul-
fane (3a, 52.3 mg, 0.24 mmol, 0.60 equiv.), and I (10 mg,
.04 mmol, 10 mol%) in PEG-200 (2.0 mL). The resulting
28.0, 127.9, 127.3, 122.8, 117.2, 107.5 ppm; HRMS (APCI)
2
+
exact mass for [M + H] (C15
found: 346.9797.
11 2 4
H N S ): calcd m/z 346.9800,
0
mixture was heated to 110 °C for 20 hours. After completion of
the reaction, the product was separated by extraction with
diethyl ether. The upper layer of diethyl ether contained a
4
-Methoxy-2,3-bis(phenylthio)-1H-pyrrolo[2,3-b]pyridine (4ba′)
Prepared from 4-methoxy-1H-pyrrolo[2,3-b]pyridine 7-oxide product mixture that was directly used for purification. The
(
(
1b, 41.1 mg, 0.25 mmol, 1.0 equiv.) and 1,2-diphenyldisulfane remaining mixture was subsequently subjected to vacuum to
3a, 109.2 mg, 0.50 mmol, 2.0 equiv.) according to GP3; purifi- remove the rest of the solvents before it was reused in the next
cation by flash column chromatography on silica gel afforded catalytic run. Purification by flash column chromatography
the analytically pure product (63.9 mg, 70%) as a light yellow afforded the pure product (83.3 mg, 92%), (83.1 mg, 92%), and
1
solid; m.p. = 183–185 °C; H NMR (400 MHz, CDCl ): δ = 7.88 (81.4 mg, 90%) in three cycles, respectively.
3
(d, J = 5.6 Hz, 1H), 7.34 (d, J = 8.0 Hz, 2H), 7.24 (t, J = 7.5 Hz,
2
1
H), 7.17 (dd, J = 13.3 Hz, J = 5.7 Hz, 5H), 7.08 (d, J = 7.0 Hz, Preparation and characterization data of the C4-amination
H), 6.48 (d, J = 5.7 Hz, 1H), 3.82 (s, 3H) ppm; C NMR product 8 from 4ka under palladium catalysis: 1-methyl-N-
13
2
8
3
(101 MHz, CDCl ): δ = 160.8, 150.7, 145.3, 139.4, 135.1, 132.9, phenyl-3-(phenylthio)-1H-pyrrolo[2,3-b]pyridin-4-amine (8)
1
5
29.3, 128.9, 128.5, 126.8, 126.7, 124.9, 112.5, 107.1, 98.9,
A flame-dried Schlenk tube equipped with a magnetic stir bar
was successively charged with 4ka (0.30 mmol, 1.0 equiv.),
aniline (7, 0.36 mmol, 1.2 equiv.), Pd (dba) (0.015 mmol,
+
5.5 ppm; HRMS (APCI) exact mass for [M
OS ): calcd m/z 365.0777, found: 365.0775.
+
H]
(C
20
H
17
N
2
2
2
3
5
mol%), Xantphos (0.030 mmol, 10 mol%), and Cs CO
2 3
4
-Bromo-1-methyl-2,3-bis(phenylthio)-1H-pyrrolo[2,3-b]
(
0.6 mmol, 2.0 equiv.) in dioxane (2 mL) at room temperature.
The reaction mixture was heated to 100 °C and monitored by
Prepared from 4-bromo-1-methyl-1H-pyrrolo[2,3-b]pyridine TLC. After 23 h, the reaction mixture was allowed to cool to
-oxide (1k, 56.8 0.25 mmol, 1.0 equiv.) and 1,2-diphenyldisul- room temperature and diluted with ethyl acetate (15 mL). The
pyridine (4ka′)
7
fane (3a, 109.2 mg, 0.50 mmol, 2.0 equiv.) according to GP3; crude reaction mixture was washed with 1% aq. HCl (5 mL)
purification by flash column chromatography on silica gel and H O (5 mL). The organic phase was dried over anhydrous
2
2 4
afforded the analytically pure product (69.5 mg, 65%) as a Na SO and concentrated under reduced pressure. Purification
1
light yellow solid; m.p. = 213–214 °C; H NMR (400 MHz, by flash column chromatography on silica gel using mixtures
CDCl ): δ = 8.19 (dd, J = 5.1 Hz, J = 1.3 Hz, 1H), 7.35 (dd, J = of petroleum ether and ethyl acetate as eluents afforded the
3
5
.2 Hz, J = 1.3 Hz, 1H), 7.23–7.08 (m, 10H), 3.89 (s, 3H) ppm; analytically pure product (85.4 mg, 86%) as a light yellow oil;
1
3
1
C NMR (101 MHz, CDCl ): δ = 149.2, 144.7, 139.8, 139.4,
H NMR (400 MHz, DMSO-d ): δ = 8.12–8.00 (m, 2H), 7.77 (s,
6
3
1
1
34.3, 129.5, 128.8, 128.4, 126.9, 126.3, 125.9, 125.1, 122.3, 1H), 7.28 (dt, J = 15.8 Hz, J = 7.7 Hz, 4H), 7.15 (dd, J = 12.0 Hz,
+
20.5, 109.6, 30.5 ppm; HRMS (APCI) exact mass for [M + H]
J = 7.6 Hz, 3H), 7.05 (dd, J = 15.9 Hz, J = 7.7 Hz, 3H), 6.78 (d,
J = 5.5 Hz, 1H), 3.83 (s, 3H) ppm; C NMR (101 MHz, DMSO-
): δ = 149.7, 145.6, 145.3, 140.1, 139.4, 135.1, 129.9, 129.8,
1
3
(C H BrN S ): calcd m/z 426.9933, found: 426.9929.
2
0
16
2 2
d
6
4
-Bromo-2,3-bis[(4-methoxyphenyl)thio]-1H-pyrrolo[2,3-b]
126.2, 126.1, 123.8, 121.2, 108.2, 99.5, 95.9, 31.8 ppm; HRMS
+
pyridine (4ep′)
(APCI) exact mass for [M + H] (C H N S): calcd m/z
2
0
18 3
332.1216, found: 332.1214.
Prepared from 4-bromo-1H-pyrrolo[2,3-b]pyridine 7-oxide (1e,
5
3.2 mg, 0.25 mmol, 1.0 equiv.) and 1,2-bis(4-methoxyphenyl)
Preparation and characterization data of the C5-
disulfane (3q, 69.5 mg, 0.50 mmol, 2.0 equiv.) according to
GP3; purification by flash column chromatography on silica
gel afforded the analytically pure product (79.3 mg, 67%) as a
heteroarylation product 10 from 4ga under palladium
catalysis: 3-(phenylthio)-5-(pyridin-3-yl)-1H-pyrrolo[2,3-b]
2
5
1
pyridine (10)
light yellow solid; m.p. = 214–215 °C; H NMR (400 MHz,
DMSO-d
6
): δ = 12.95 (s, 1H), 8.11 (d, J = 5.0 Hz, 1H), 7.37 (d, J = A flame-dried Schlenk tube equipped with a magnetic stir bar
5
.0 Hz, 1H), 7.35–7.30 (m, 2H), 6.98–6.94 (m, 2H), 6.92–6.87 was successively charged with 4ga (0.30 mmol, 1.0 equiv.),
1
3
(m, 2H), 6.84–6.78 (m, 2H), 3.71 (s, 3H), 3.70 (s, 3H) ppm;
C
pyridin-3-ylboronic acid (9, 0.30 mmol, 1.0 equiv.), Pd(PPh
3 4
)
NMR (101 MHz, DMSO-d
6
): δ = 159.8, 157.9, 149.8, 144.9, (0.015 mmol, 5 mol%), and K CO (0.78 mmol, 2.6 equiv.) in
2
3
1
1
40.9, 133.6, 130.2, 128.3, 123.9, 123.5, 121.9, 120.2, 115.6, H O/MeCN mixed solvent (2.0 mL, v/v = 1/3) at room tempera-
2
15.2, 106.1, 55.7, 55.6 ppm; HRMS (APCI) exact mass for ture. The reaction mixture was heated to 170 °C and monitored
+
[M + H] (C21
H
18BrN
2
O
2
S
2
): calcd m/z 472.9988, found: by TLC. After 20 h, the reaction mixture was allowed to cool to
4
72.9983.
room temperature and diluted with ethyl acetate (15 mL). The
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crude reaction mixture was washed with 1% aq. HCl (5 mL) 127.4, 126.4, 125.8, 124.4, 122.2, 117.9, 115.5, 105.4, 55.8 ppm;
+
and H O (5 mL). The organic phase was dried over anhydrous HRMS (APCI) exact mass for [M + H] (C H BrN OS ): calcd
2
20 17
2
2
2 4
Na SO and concentrated under reduced pressure. Purification m/z 365.0777, found: 365.0775.
by flash column chromatography on silica gel using mixtures
of petroleum ether and ethyl acetate as eluents afforded the
1
analytically pure product (71.1 mg, 78%) as a yellow oil;
NMR (400 MHz, DMSO-d
H
Conflicts of interest
6
): δ = 12.50 (s, 1H), 8.90 (s, 1H), 8.67
s, 1H), 8.58 (s, 1H), 8.08 (dd, J = 25.6 Hz, J = 3.3 Hz, 3H), 7.47
There are no conflicts of interest to declare.
(
(
1
3
s, 1H), 7.28–7.19 (m, 2H), 7.09 (d, J = 8.2 Hz, 3H) ppm;
C
NMR (101 MHz, DMSO-d
6
): δ = 149.1, 148.6, 148.0, 143.1,
Acknowledgements
1
1
38.7, 135.1, 134.9, 134.5, 129.5, 126.7, 126.2, 125.8, 125.3,
24.6, 121.6, 99.8 ppm; HRMS (APCI) exact mass for [M + H]
+
We are grateful to the National Natural Science Foundation of
China (NSFC: 21606182, 21901150) and the China Postdoctoral
Science Foundation (2018M643806XB) for financial support.
18 15 3
(C H N S): calcd m/z 305.0981, found: 305.0978.
Synthesis of compound B: Prepared from 3-(phenylthio)-
H-pyrrolo[2,3-b]pyridine (4aa, 56.5 mg, 0.25 mmol,) and
1
m-CPBA (56 mg, 1.3 equiv.) according to GP1; purification by
flash column chromatography on silica gel afforded the ana-
lytically pure product (61.2 mg, 42%) as a white solid (54.4 mg,
Notes and references
1
9
1
8
7
0%); m.p. = 197–198 °C; H NMR (400 MHz, DMSO-d
6
): δ =
1 (a) F. Popowycz, S. Routier, B. Josepha and J.-Y. Mérour,
Tetrahedron, 2007, 63, 1031–1064; (b) J.-Y. Mérour,
S. Routier, F. Suzenet and B. Joseph, Tetrahedron, 2013, 69,
4767–4834.
2 C. Han, K. Green, E. Pfeifer and F. Gosselin, Process Res.
Dev., 2017, 21, 664–668.
2.60 (s, 1H), 8.36 (s, 1H), 8.28 (d, J = 4.6 Hz, 1H), 7.68 (d, J =
.2 Hz, 2H), 7.59 (d, J = 8.0 Hz, 1H), 7.51 (t, J = 7.6 Hz, 2H),
.45 (d, J = 7.1 Hz, 1H), 7.02 (dd, J = 7.9 Hz, J = 4.7 Hz, 1H)
1
3
ppm; C NMR (101 MHz, DMSO-d ): δ = 149.5, 145.1, 144.8,
6
1
31.7, 130.6, 129.5, 127.9, 124.7, 117.4, 116.1, 115.9 ppm;
+
HRMS (ESI-TOF) exact mass for [M + H] (C13
m/z 243.0587, found: 243.0585.
H
11
N
2
OS): calcd
3 P. Kannaboina, G. Raina, K. A. Kumar and P. Das, Chem.
Commun., 2017, 53, 9446–9449.
4
X.-F. Chen, Z.-L. Jin, Y. Gong, N. Zhao, X.-Y. Wang,
Y.-H. Ran, Y.-Z. Zhang, L.-M. Zhang and Y.-F. Li,
Neuropharmacology, 2018, 138, 1–9.
2
-[(4-Methoxyphenyl)thio]-3-(phenylthio)-1H-pyrrolo[2,3-b]
pyridine (11′)
Prepared from 3-(phenylthio)-1H-pyrrolo[2,3-b]pyridine 7-oxide
11, 24.2 mg, 0.1 mmol, 1.0 equiv.) and 1,2-bis(4-methoxyphe-
5 W. Albrecht, S. Laufer, R. Selig, P. Kloevekorn and
B. Praefke, PCT Int. Appl, WO2018134254A120180726, 2018.
6 J. Zhang, J. Buell, K. Chan, P. N. Ibrahim, J. Lin, P. Pham,
S. Shi, W. Spevak, G. Wu and J. Wu, PCT Int. Appl,
WO2014145051A120140918, 2014.
7 J. J. Song, J. T. Reeves, F. Gallou, Z. Tan, N. K. Yee and
C. H. Senanayake, Chem. Soc. Rev., 2007, 36, 1120–1132.
8 (a) T. K. Vats, A. Mishra and I. Deb, Adv. Synth. Catal., 2018,
360, 2291–2296; (b) K. Nishino, S. Tsukahara, Y. Ogiwara
and N. Sakai, Eur. J. Org. Chem., 2019, 1588–1593; (c) J. Li,
C. Li, S. Yang, Y. An, W. Wu and H. Jiang, J. Org. Chem.,
2016, 81, 7771–7783; (d) Z. Wu, Y.-C. Li, W.-Z. Ding, T. Zhu,
S.-Z. Liu, X. Ren and L.-H. Zou, Asian J. Org. Chem., 2016, 5,
(
nyl)disulfane (3q, 27.8 mg, 0.20 mmol, 2.0 equiv.) according to
GP3; purification by flash column chromatography on silica
gel afforded the analytically pure product (15 mg, 42%) as a
1
light yellow solid; m.p. = 167–168 °C; H NMR (400 MHz,
DMSO-d
.5 Hz, 1H), 7.34–7.28 (m, 2H), 7.23–7.11 (m, 4H), 7.01–6.95
6
): δ = 12.75 (s, 1H), 8.33 (d, J = 4.5 Hz, 1H), 7.75 (d, J =
6
13
(m, 2H), 6.91–6.84 (m, 2H), 3.72 (s, 3H) ppm; C NMR
(101 MHz, DMSO-d
6
): δ = 159.6, 149.6, 145.2, 138.1, 137.3,
1
1
33.1, 129.5, 127.4, 126.4, 125.8, 124.4, 122.2, 117.6, 115.5,
+
05.4, 55.8 ppm; HRMS (APCI) exact mass for [M + H]
(C
20
H
17BrN
2 2
OS ): calcd m/z 365.0777, found: 365.0776.
6
25–628; (e) X. Ge, F. Sun, X. Liu, X. Chen, C. Qian and
3
-[(4-Methoxyphenyl)thio]-2-(phenylthio)-1H-pyrrolo[2,3-b]
S. Zhou, New J. Chem., 2017, 41, 13175–13180.
pyridine (12′)
9
For examples of chalcogenation of indoles by using iodine,
and its salts, see: (a) F.-L. Yang and S.-K. Tian, Angew. Chem.,
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Prepared
from
3-(phenylthio)-1H-pyrrolo[2,3-b]pyridine
7
-oxidde (11, 24.2 mg, 0.1 mmol, 1.0 equiv.) and 1,2-bis(4-
methoxyphenyl)disulfane (3q, 27.8 mg, 0.2 mmol, 2.0 equiv.)
according to GP3; purification by flash column chromato-
graphy on silica gel afforded the analytically pure product
1
(7.2 mg, 20%) as a light yellow solid; m.p. = 170–171 °C; H
NMR (400 MHz, DMSO-d
6
): δ = 12.79 (s, 1H), 8.35 (d, J =
.4 Hz, 1H), 7.83 (d, J = 7.9 Hz, 1H), 7.31 (t, J = 7.5 Hz, 2H),
.24 (d, J = 6.8 Hz, 1H), 7.18 (d, J = 7.8 Hz, 3H), 7.10 (d, J =
4
7
8
1
3
.7 Hz, 2H), 6.81 (s, 2H), 3.68 (s, 3H) ppm; C NMR (101 MHz,
DMSO-d ): δ = 159.6, 149.5, 145.2, 138.1, 137.3, 133.1, 129.5,
6
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