Cp?CoIII-Catalyzed Synthesis of Pyrido[2′,1′:2,3]pyrimido[1,6-a]indol-5-iums via Tandem C-H Activation and Subsequent Annulation from 1-(Pyridin-2-yl)-1H-indoles and Internal Alkynes

Article abstract of DOI:10.1021/acs.joc.6b02314

A Cp?Co^III-catalyzed C2-selective C-H alkenylation/annulation cascade transformation of 1-(pyridin-2-yl)-1H-indoles with internal alkynes to afford pyrido[2′,1′:2,3]pyrimido[1,6-a]indol-5-iums is presented. Moreover, 6,7-dihydro-4H-pyrido[2′,1′:2,3]pyrimido[1,6-a]indole, a new functionalized N-fused indole core heterocycle, could be constructed effectively via reduction of pyrido[2′,1′:2,3]pyrimido[1,6-a]indol-5-ium by NaBH₄.

Full text of DOI:10.1021/acs.joc.6b02314

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Article
Cp*CoIII-Catalyzed Synthesis of Pyrido[2',1':2,3]pyrimido[1,6-
a]indol-5-iums via Tandem C-H Activation and Subsequent
Annulation from 1-(Pyridin-2-yl)-1H-indoles and Internal Alkynes
Yuhan Yang, Bo Li, Wenmin Liu, Rumeng Zhang, Lintao
Yu, Qin-Ge Ma, Rongrong Lv, Donghua Du, and Ting Li
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02314 • Publication Date (Web): 25 Oct 2016
Downloaded from http://pubs.acs.org on October 27, 2016
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Cp*CoIIIꢀCatalyzed Synthesis of
Pyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀiums via
Tandem C−H Activation and Subsequent Annulation
from 1ꢀ(Pyridinꢀ2ꢀyl)ꢀ1Hꢀindoles and
Internal Alkynes
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Yuhan Yang, Bo Li, Wenmin Liu, Rumeng Zhang,
Lintao Yu, QinꢀGe Ma, Rongrong Lv, Donghua Du, and Ting Li*
College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University,
Nanyang, Henan 473061, P. R. China
Eꢀmail:chemlt2015@nynu.edu.cn
ABSTRACT
A Cp*CoIIIꢀcatalyzed C2ꢀselective C−H alkenylation/ annulation cascade
transformation of 1ꢀ(pyridinꢀ2ꢀyl)ꢀ1
pyrido[2',1':2,3]pyrimido[1,6ꢀ ]indolꢀ5ꢀiums
6,7ꢀdihydroꢀ4 ꢀpyrido[2',1':2,3]pyrimido[1,6ꢀ
ꢀfused indole core heterocycle, could be constructed effectively via reduction of
H
ꢀindoles with internal alkynes to afford
is presented. Moreover,
]indole, a new functionalized
a
H
a
N
pyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium by NaBH4.
INTRODUCTION
Indoles are important structural constituents of numerous pharmaceuticals, natural
products, and biologically active molecules.1 In addition, starting from indoles, a
series of interesting nitrogenꢀcontaining heterocycles could be constructed
effectively.2 Therefore, the development of efficient synthetic methodologies that
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allow the synthesis and modification of indoles is a longꢀstanding task for organic
chemists and there is continuing interest in new synthetic methods that would provide
selective access to substituted indole derivatives.3 Transitionꢀmetalꢀcatalyzed C−H
functionalization was recognized to be a powerful strategy in organic synthesis and
the past decade has witnessed the rapid development of transitionꢀmetalꢀcatalyzed
C−H functionalization transformations.4 Especially, cobalt complexes as an effective
catalyst for C−H activation transformations have attracted much attention by the
synthestic community.5 Recently, considerable progress has been achieved using
highꢀvalent cobalt complexes by Kanai/Matsunaga,6 Ackermann,7 Daugulis,8
Glorius,9 Ellman,10 Chang,11 and many others,12 respectively.
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Scheme
1.
Cp*CoIIIꢀcatalyzed
facile
synthesis
of
pyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀiums.
On the other hand, fused polycyclic aromatic and polycyclic heteroaromatic
compounds are embedded in a large number of compounds due to their potential
utility in organic and polymeric functional materials.13 Therefore, the synthesis of
π
ꢀconjugated systems containing indole skeleton is highly desirable.14 While,
applications of the indole C−H functionalization process to cascade reactions
providing access to more functionalized
ꢀfused indole cores have been rare.2
Thus, methods for efficiently providing a functionalized ꢀfused indole cores unit
N
N
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from readily available starting materials via a C−H activation process are
interesting and in great demand. Several groups have already carried out the
Co−catalyzed research on indoles C−2 selectively C−H bond activation with
heteroatomꢀassisted chelation.6b,6c,15 In 2012, Yoshikai group reported the
stereoꢀselective C2ꢀalkenylation reaction of indoles with alkynes catalyzed by a low
valent Co–pyphos catalyst (Scheme 1a).16 Shortly after, Matsunaga and Kanai
described the C2ꢀselective C−H alkenylation/ annulation cascade of Nꢀcarbamoyl
indoles with alkynes to afford pyrroloindolones in oneꢀpot (Scheme 1b).6c Here, we
present the Coꢀcatalyzed C2ꢀselective C−H alkenylation/ annulation cascade
transformation of 1ꢀ(pyridinꢀ2ꢀyl)ꢀ1Hꢀindoles with internal alkynes to afford
pyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀiums in oneꢀpot (Scheme 1c).17
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RESULTS AND DISCUSSION
Table 1. Optimization of the Reaction Conditionsa.
Entry
1
Reaction Conditions
Yield (%)
4
.
[Cp*RhCl2]2 (2 %), Cu(OAc)2 H2O (2.0),
AgBF4 (5%), 135 oC, PhMe
.
2
3
4
5
CoCp*(CO)I2 (2 %), Cu(OAc)2 H2O (2.0),
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48
48
76
AgBF4 (1.0), 135 oC, PhMe
.
CoCp*(CO)I2 (2 %), Cu(OAc)2 H2O (1.0),
AgBF4 (1.0), 135 oC, PhMe
.
CoCp*(CO)I2 (5 %), Cu(OAc)2 H2O (1.0),
AgBF4 (1.0), 135 oC, PhMe
CoCp*(CO)I2 (2 %), AgOAc (4%),
.
Cu(OAc)2 H2O (1.0), AgBF4 (1.0), 135 oC,
PhMe
6
7
8
9
CoCp*(CO)I2 (2 %), AgOAc (4%),
56
86
0
.
Cu(OAc)2 H2O (1.0), AgBF4 (1.0), 135 oC,
PhCl
CoCp*(CO)I2 (2 %), AgOAc (4%),
.
Cu(OAc)2 H2O (1.0), AgBF4 (1.0), 135 oC,
DCE
CoCp*(CO)I2 (2 %), AgOAc (4%),
.
Cu(OAc)2 H2O (1.0), AgBF4 (1.0), 135 oC,
DMF
CoCp*(CO)I2 (2 %), AgOAc (4%),
<5
.
Cu(OAc)2 H2O (1.0), AgBF4 (1.0), 125 oC,
DCE
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10b
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CoCp*(CO)I2 (2 %), AgOAc (4%),
52
.
Cu(OAc)2 H2O (1.0), AgBF4 (1.0), 135 oC,
DCE
CoCp*(CO)I2 (1 %), AgOAc (4%),
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.
Cu(OAc)2 H2O (1.0), AgBF4 (1.0), 135 oC,
DCE
12
CoCp*(CO)I2 (1 %), KOAc (4%),
trace
.
Cu(OAc)2 H2O (1.0), AgBF4 (1.0), 135 oC,
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DCE
aConditions: 1a (0.20 mmol), 2a (0.22 mmol, 1.1 equiv), [M], and solvent (2 mL)
b
under N2 atmosphere for 24 h. Isolated products based on 1a. Reaction performed
under air atmosphere.
As demonstrated in Table 1, initially, the reaction of 1ꢀ(pyridinꢀ2ꢀyl)ꢀ1Hꢀindole 1a
with 1.1 equiv of diphenylethyne 2a was conducted under N2 atmosphere with 2 %
.
mol [Cp*RhCl2]2 as catalyst and 2.2 equiv of Cu(OAc)2 H2O as oxidant in the
presence of AgBF4 (5 % mol) for 24 h. Serendipitously, the unexpected red
compound 3aa, which contains the pyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium
skeleton, was generated in about 4% isolated yield (Entry 1). The definite structure of
3 was confirmed by Xꢀray crystallographic studies of 3ha, as shown in Figure 1 (vide
infra).18 The formation of the pyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium skeleton is
interesting. To the best of our knowledge, efficient construction of
pyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀiums, a recurring structural motif found in
many pharmaceuticals and functional materials, have rarely been reported.19 However,
further studies to increase the yield of product 3aa by using rhodium catalyst
conditions failed. When CoCp*(CO)I2 was used as the catalyst instead, the reaction
was accelerated and compound 3aa could be isolated in 46% yield (Entry 2). Ongoing
studies revealed that the addition of AgOAc would accelerate the transformation
obviously (Entries 2ꢀ5). We have also examined the solvent effects for this
transformation (Entries 5ꢀ8) and found DCE was found to be the most suitable solvent,
which gave 3aa in about 86% yield (Entry 7). Further investigation demonstrated that
the reaction temperature (135 oC), the N2 atmosphere and the amount of CoCp*(CO)I2
catalyst loading were integrant for this transformation (Entries 9ꢀ11). In addition, the
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use of KOAc as an alternative to the use of AgOAc and Cu(OAc)2 was also tested,
5
6
and only trace amount of product 3aa could be tested (Entry 12).
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Scheme 2. Subsrate scope for 1ꢀ(pyridinꢀ2ꢀyl)ꢀ1Hꢀindolea
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aStandard reaction conditions: A mixture of derivatives 1 (0.20 mmol), 2a (0.22
.
mmol), CoCp*(CO)I2 (2 mol %), AgOAc (4 mol %), Cu(OAc)2 H2O (0.20 mmol),
AgBF4 (0.20 mmol), and DCE (2 mL) was added to a sealed schlenk tube under N2
o
atmosphere. Then the mixture was stirred at 135 C for 24 h. Isolated products based
on 1.
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Under the optimized reaction conditions in Table 1, we sought to further explore
5
6
the scope and limitation of this reaction. Firstly,
a
series of
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1ꢀ(pyridinꢀ2ꢀyl)ꢀ1Hꢀindoles were investigated (Scheme 2). It was found that
installation of a Me substituent on the pyridyl Cꢀ2 or Cꢀ3 position would furnish
products 3ca or 3da in 78% and 83% yields, respectively. In contrast, when the Cꢀ1 or
Cꢀ4 position of the pyridyl directing group was blocked with a Me group, the reaction
was completely suppressed, probably as a result of steric factors (3ba and 3ea). The
generality of the indole ring was next examined. Installation of a Me group at the Cꢀ4,
Cꢀ5, Cꢀ6, or Cꢀ7 position on indole ring had an negative influence on the
transformation (3fa, 3ga, 3ha, and 3ia). While, when the Me group was at the Cꢀ3
position, the reaction was suppressed and 3ja was isolated in about only 20% yield.
The reaction also accommodated Cl, F, Br, I, NO2, and OMe groups, thus affording
products 3ka, 3la, 3ma, 3na, 3oa, 3pa, and 3qa in good yields. Besides, when Cꢀ5
position of the indole ring was fixed with a COOMe substituent, the reaction also
worked well to provide 3ra in 74% yields. Horeover, the transformation was not
tolerative with the CN group, and product 3sa could only be detected in about 10%
yield. To further demonstrate the power of this cobalt catalytic system, other
substrates were also tested. Under similar reaction conditions, substrates 1t and 1u
could react with alkynes smoothly to afford the expected products
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pyrido[1,2ꢀa]pyrido[3',2':4,5]pyrrolo[1,2ꢀc]pyrimidinꢀ5ꢀiums
(3ta)
and
pyrido[1,2ꢀa]pyrrolo[1,2ꢀc]pyrimidinꢀ5ꢀiums in good yields (3ua, 3ug), while
substrate 1v failed.
Figure 1. Xꢀray crystal structure of compound 3ha (drawn at 50% ellipsoids).
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Scheme 3. Subsrate scope for alkynesa
R
AgOAc (4 mol %)
Cu(OAc)2.H2O (1 equiv.)
N
AgBF4 (1 equiv.)
N
+
N
N
DCE, N2, 135 o
C
R
2
3
1a
BF4
R
Cl
Me
3ab, pꢀMe, 81%
N
N
N
3ac
, mꢀMe, 77%
, oꢀMe, <10%
Cl
N
N
N
3ad
Me
BF4
BF4
BF4
3aa, 86%
3ae, 71%
NO2
S
S
N
N
N
N
N
N
NO2
N
N
BF4
3ah, <10%
BF4
BF4
3ag, 86%
BF4
3af, 52%
3ai, (95: 5), 81%
aStandard reaction conditions: A mixture of derivatives 1a (0.20 mmol), 2 (0.22
.
mmol), CoCp*(CO)I2 (2 mol %), AgOAc (4 mol %), Cu(OAc)2 H2O (0.20 mmol),
AgBF4 (0.20 mmol), and DCE (2 mL) was added to a sealed schlenk tube under N2
o
atmosphere. Then the mixture was stirred at 135 C for 24 h. Isolated products based
on 1a.
Consequently, the scope for the internal alkynes was further investigated (Scheme
3). Substrates bearing a Me group at the meta or para position on the phenyl ring
proceeded smoothly (3ab, 3ac), while that with a Me group at the ortho position
failed to yield the desired product 3ad, possibly due to the steric hindrance. Alkynes
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containing substituents including Cl and NO2 at the para position on the phenyl ring
were well tolerated to provide the corresponding products in good yields (3aeꢀ3af). It
is worthy to note that this methodology could be further extended to thiophene
containing substrate 2g to afford the corresponding product 3ag, which was isolated
in about 86% yield. Further studies revealed that aliphatic alkyne 2h was not
compatible with this transformation, and only trace 3ah could be detected in the
reaction mixture. In addition, the unsymmetrical alkyne 2i was also tested and two
regioisomeric salts were isolated with a 95:5 ratio in 81% combined yield (3ai).
Moreover, we have also performed experiments with aryl silyl alkynes and aryl
alkoxycarbonyl alkynes as the coupling alkyne. However, the reactions turned messy
with only traceless desired products detected.
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Scheme 4. Mechanism Studies.
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It is reasonable to believe that the reaction first underwent C−H activation of
substrate 1a, followed by annulation of the alkyne to generate the target product 3aa.
To gain insight into the C−H cleavage step, substrate 1a was allowed to react with
excess CD3OD (10 equiv.) for 2 h under standard reaction conditions, and 84%
deuterium incorporation at C−2 position as well as 78% (C−3 position of indole) and
84% (C−6 position of pyridine) deuterium incorporation was observed (Scheme 4, eq
1). This result clearly indicated that a reversible deprotonative C−H bond activation
step might exist in the transformation. Subsequently, the kinetic isotope effect
experiment on 1a and D-1a (95% D) with alkyne 2a was carried out under the
standard conditions, resulting in a KIE value of 1.3 (see the Supporting Information),
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which indicated that the C−H cleavage of
Nꢀ(2ꢀpyridyl)indole is not likely to be the
rateꢀlimiting step for this transformation (Scheme 4, eq 2). As shown in eq 3, 3aa was
not obtained when treating 5a under standard reaction conditions. The result
suggested that the 2ꢀalkenylꢀsubstituted Nꢀ(2ꢀpyridyl)indole 5a was not the key
intermediate of this Coꢀcatalyzed cascade cyclization for the formation of 3aa.
Besides, the competition experiments with substrates bearing varied electronic
properties were also investigated. As shown in Scheme 3, it was found that the
formation of products derived from electronꢀdeficient 1ꢀ(pyridinꢀ2ꢀyl)ꢀ1Hꢀindole 1p
and electronꢀrich alkyne 2b was favored in the transformation (Scheme 4, eq 4).
Based on these experiment results and the previous reports,17 a tentative mechanism
for the formation of compound pyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium is
proposed as shown in Scheme 5. Initially, reaction of CoCp*(CO)I2 with AgOAc
generates the catalytic active species [Cp*Co]2+ (I), which is followed by the
nitrogenꢀdirected reversible ortho cyclometalation to provide intermediate II. Then,
coordination of the alkyne to intermediate II form intermediate III and the subsequent
insertion reaction would provide the sevenꢀmembered cobaltacyclic intermediate IV.
Reductive elimination of intermediate IV with the aid of AgBF4 and Cu(OAc)2 give
the desired product 3aa and regenerate the cobaltIII catalyst species to finish the
catalystic cycle. The role of AgBF4 is probably twoꢀfold. It not only offers a BF4
ligand but also acts as an oxidant for the transformation.
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Scheme 5. A tentative reaction mechanism for the transformation
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Scheme 6. Gramꢀscale synthesis of C−H activation compounds 3aa, 3la, and
3pa
.
Besides, to demonstrate the synthetic potential of this transformation, 10 mmol
scale reactions were conducted using 1a, 1l, and 1p as substrates, and the reaction
proceeded smoothly to provide products 3aa, 3la, and 3pa in 75%, 81%, and 84%
yields, respectively (Scheme 6). In addition, it was found that the C−H activation
products could be readily reduced by NaBH4 to give the addition products
6,7ꢀdihydroꢀ4Hꢀpyrido[2',1':2,3]pyrimido[1,6ꢀa]indoles 4 in to good yields (66% to
86% yields), and this transformation tolerate function groups including F, Cl, OMe, as
well as Me groups (Scheme 7). These transformations thus further strengthen the
synthetic impact of this protocol for the preparation of new nitrogenꢀcontaining
heterocycles starting from indoles. Moreover, we also characterized the UV−vis
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absorption of several representative products and found that the synthesized
polycyclic compounds showed strong UV−vis absorption in the range of 440−480 nm
as shown in Figure 2.
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Scheme 7. Application of the C−H activation products for the construction of
6,7ꢀdihydroꢀ4Hꢀpyrido[2',1':2,3]pyrimido[1,6ꢀa]indoles 4.
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aStandard reaction conditions: To a stirred solution of
3 (0.20 mmol) in dry MeOH (5
mL) at 0 °C was added NaBH4 (0.80 mmol). Then the mixture was allowed to stir at
0 °C for 2 h. Isolated products based on 1a.
Figure
2.
UVꢀvis
absorption
spectra
of
selected
pyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀiums compounds in CH2Cl2 at 1×10ꢀ6
M
concentration.
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CONCLUSIONS
In conclusion, we have successfully developed a Cp*CoIIIꢀcatalyzed C−H
annulation reaction of 1ꢀ(pyridinꢀ2ꢀyl)ꢀ1Hꢀindole with interal alkynes towards the
syntheses of pyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀiums in moderate to good yields.
In
addition,
a
new
Nꢀcontaining
could
heterocycle,
constructed
6,7ꢀdihydroꢀ4Hꢀpyrido[2',1':2,3]pyrimido[1,6ꢀa]indole,
be
effectively via reduction of pyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium by NaBH4.
The evaluation of the biological activity of these products is underway in our
laboratories. Given the simplicity of this reaction and the importance of heterocyclic
quaternary ammonium salts as functional molecules in organic chemistry, we
anticipate this transformation may find applications.
EXPERIMENTAL SECTION
General Remarks: All reactions were carried out in flameꢀdried sealed tubes with
magnetic stirring. Unless otherwise noted, all experiments were performed under N2
atmosphere. Commercially available reagents and solvents were used without further
purification except as noted. Products were purified by column chromatography on
1
200ꢀ300 mesh silica gels. All melting points were determined without correction. H
NMR and 13C NMR spectra were recorded at 400 and 100 MHz, respectively, in
DMSOꢀd6 or CDCl3. Splitting patterns are designated as singlet (s), doublet (d), triplet
(t), or quartet (q). All chemical shifts are given as δ values (in ppm) with reference to
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tetramethylsilane (TMS) as an internal standard. Splitting patterns that could not be
interpreted or easily visualized are designated as multiplet (m). HRMS was performed
on an FTꢀMS instrument using electrospray ionization (APCI or ESI).
9
Crystallographic
data
were
recorded
on
a
diffractometer
using
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graphiteꢀmonochromated Mo Kα radiation (λ = 0.71073 Å). Structures were solved by
1
direct methods in SHELXSꢀ97. Copies of the H NMR and 13C NMR spectra and
crystallographic data in CIF are provided in the Supporting Information. Substrates
including 1ꢀ(pyrimidinꢀ2ꢀyl)ꢀ1Hꢀindole21 and 2ꢀ(1Hꢀpyrrolꢀ1ꢀyl)pyridine22 were
prepared by previously reported procedures.
General procedure the preparation of substrates 1 21
A mixture of indoles (5.0
:
mmol), 2ꢀbromopyridine (6.0 mmol), KOH (0.70 g, 12.5 mmol) in DMSO (5 mL)
was vigorously stirred at 130 °C under nitrogen atmosphere for 36 h. After cooling the
mixture to ambient temperature, the reaction mixture was diluted with EtOAc (20 mL)
and washed with H2O (2×20 mL). The aqueous phase was extracted with EtOAc
(2×20 mL), and the combined organic phase was dried over Na2SO4. After filtration
and evaporation of the solvents in vacuo, the crude product was purified by column
chromatography on silica gel (petroleum ether/EtOAc = 100:1ꢀ30:1) to afford the
desired products.
General procedure for the preparation of alkynes 2 23
Pd(PPh3)2Cl2 (105 mg, 0.15
:
mmol, 5 mol%), 1,4ꢀ bis(diphenylꢀphosphino)butane (128 mg, 0.30 mmol, 10 mol%),
aryl halides (6.00 mmol, 2.00 equiv.), and propiolic acid (212 mg, 3.00 mmol, 1.00
equiv.) were combined with DBU (913 mg, 6.0 mmol, 2.00 equiv.) in a small round
bottomed flask. DMSO (15.0 mL) was added, and the flask was sealed with a septum.
The resulting mixture was placed in an oil bath at 80 °C for 16 h. After that, the
reaction was poured into 25 mL of saturated aqueous ammonium chloride solution
and extracted with EtOAc (4×20 mL). The combined organic layers were washed with
brine (60 mL), dried over Na2SO4, and filtered. The solvent was removed under
vacuum and the resulting crude product was adsorbed on silica and purified by
column chromatography (Pentane/EtOAc).
General procedure for the synthesis of 3: Synthesis of compound 3aa is
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representative. A mixture of 1ꢀ(pyridinꢀ2ꢀyl)ꢀ1Hꢀindole 1a (0.20 mmol),
1,2ꢀdiphenylethyne 2a (0.22 mmol), [CoCp*(CO)I2] (2 mol %), AgOAc (4 mol %),
.
Cu(OAc)2 H2O (0.20 mmol), AgBF4 (0.20 mmol), and DCE (2 mL) was added to a
o
sealed schlenk tube under N2 atmosphere. Then the mixture was stirred at 135 C
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(bath temperature, preꢀheated) for desired time (usually 24 h) until complete
consumption of starting materials judged by TLC. Then the reaction mixture was
filtered through a short plug of silica gel, washed with CH2Cl2 and concentrated, the
residue was purified by chromatography with petroleum ether/EtOAc (v/v, 1/1) and
then CH2Cl2/MeOH (v/v, 20/1) to afford pyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium
3aa in 86% yield.
6,7ꢀdiphenylpyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3aa): red solid (78.8 mg,
1
86%), mp. 177ꢀ179 °C. H NMR (400 MHz, DMSOꢀd6) δ 9.26 (d, J = 8.7 Hz, 1H),
8.80 (d, J = 8.4 Hz, 1H), 8.70 (t, J = 7.7 Hz, 1H), 8.45 (d, J = 6.4 Hz, 1H), 8.01 (d, J =
7.6 Hz, 1H), 7.86ꢀ7.68 (m, 2H), 7.64 (t, J = 7.2 Hz, 1H), 7.50 (s, 5H), 7.37 (d, J =
12.2 Hz, 5H), 6.78 (s, 1H). 13C NMR (101 MHz, DMSOꢀd6) δ 145.81, 143.72, 137.80,
133.26, 133.06, 133.04, 132.95, 131.98, 131.42, 130.91, 129.86, 129.76, 129.63,
129.33, 129.08, 128.53, 126.06, 126.02, 123.11, 120.67, 116.40, 116.04, 104.11.
HRMS m/z (ESI) [MꢀBF4] calculated for C27H19N2: 371.1548, found 371.1548.
3ꢀmethylꢀ6,7ꢀdiphenylpyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3ca): red solid
1
(73.7 mg, 78%), mp. 181ꢀ183 °C. H NMR (400 MHz, DMSOꢀd6) δ 9.19 (d, J = 9.0
Hz, 1H), 8.78 (d, J = 8.4 Hz, 1H), 8.58 (d, J = 8.8 Hz, 1H), 8.15 (s, 1H), 7.99 (d, J =
7.5 Hz, 1H), 7.70 (t, J = 7.4 Hz, 1H), 7.62 (t, J = 7.2 Hz, 1H), 7.50 (s, 5H), 7.36 (d, J
= 14.8 Hz, 5H), 6.75 (s, 1H), 2.40 (s, 3H). 13C NMR (101 MHz, DMSOꢀd6) δ 147.21,
142.20, 135.23, 133.35, 132.96, 132.85, 132.81, 132.02, 131.31, 130.94, 130.59,
129.82, 129.67, 129.64, 129.28, 129.05, 128.61, 125.89, 123.03, 116.01, 115.95,
103.82, 17.92. HRMS m/z (ESI) [MꢀBF4] calculated for C28H21N2: 385.1705, found
385.1704.
2ꢀmethylꢀ6,7ꢀdiphenylpyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3da): red solid
(78.4 mg, 83%), mp. 186ꢀ188 °C. 1H NMR (400 MHz, DMSOꢀd6) δ 8.97 (s, 1H), 8.93
(d, J = 8.6 Hz, 1H), 8.32 (d, J = 7.1 Hz, 1H), 8.00 (d, J = 7.8 Hz, 1H), 7.72 (t, J = 7.8
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Hz, 1H), 7.64 (dd, J = 13.3, 7.0 Hz, 2H), 7.50 (s, 5H), 7.38 (t, J = 6.9 Hz, 3H), 7.34 (d,
J = 7.6 Hz, 2H), 6.76 (s, 1H), 2.86 (s, 3H). 13C NMR (101 MHz, DMSOꢀd6) δ 159.68,
143.15, 136.86, 133.32, 133.20, 132.97, 132.80, 131.96, 131.34, 130.86, 129.84,
129.82, 129.72, 129.25, 129.05, 127.59, 125.93, 125.84, 122.90, 122.02, 116.39,
115.02, 104.02, 22.34. HRMS m/z (ESI) [MꢀBF4] calculated for C28H21N2: 385.1705,
found 385.1704.
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9ꢀmethylꢀ6,7ꢀdiphenylpyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3fa): red solid
1
(71.8 mg, 76%), mp. 179ꢀ181 °C. H NMR (400 MHz, DMSOꢀd6) δ 9.26 (d, J = 8.7
Hz, 1H), 8.70 (t, J = 7.7 Hz, 1H), 8.64 (d, J = 8.5 Hz, 1H), 8.46 (d, J = 6.5 Hz, 1H),
7.77 (t, J = 6.7 Hz, 1H), 7.64 (t, J = 7.8 Hz, 1H), 7.50 (s, 6H), 7.38 (d, J = 12.0 Hz,
5H), 6.74 (s, 1H), 2.59 (s, 3H). 13C NMR (101 MHz, DMSOꢀd6) δ 145.75, 143.70,
137.79, 133.23, 132.99, 132.85, 132.71, 132.33, 131.99, 131.03, 130.87, 129.84,
129.67, 129.35, 129.11, 128.61, 126.20, 126.14, 120.69, 116.40, 113.54, 102.24,
18.91. HRMS m/z (ESI) [MꢀBF4] calculated for C28H21N2: 385.1705, found 385.1704.
10ꢀmethylꢀ6,7ꢀdiphenylpyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3ga): red solid
1
(77.4 mg, 82%), mp. 180ꢀ182 °C. H NMR (400 MHz, DMSOꢀd6) δ 9.22 (d, J = 8.9
Hz, 1H), 8.70 (d, J = 8.5 Hz, 2H), 8.42 (d, J = 6.8 Hz, 1H), 7.79 (s, 1H), 7.74 (s, 1H),
7.55 (d, J = 8.7 Hz, 1H), 7.50 (s, 5H), 7.38 (t, J = 6.8 Hz, 3H), 7.33 (d, J = 7.2 Hz,
2H), 6.71 (s, 1H), 2.54 (s, 3H). 13C NMR (101 MHz, DMSOꢀd6) δ 145.64, 143.55,
137.68, 135.70, 133.30, 133.15, 132.93, 131.98, 131.76, 131.23, 130.88, 129.84,
129.62, 129.31, 129.08, 128.44, 127.54, 122.56, 120.44, 116.25, 115.73, 103.72,
21.49. HRMS m/z (ESI) [MꢀBF4] calculated for C28H21N2: 385.1705, found 385.1704.
11ꢀmethylꢀ6,7ꢀdiphenylpyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3ha): red solid
1
(82.2 mg, 87%), mp. 183ꢀ185 °C. H NMR (400 MHz, DMSOꢀd6) δ 9.28 (d, J = 8.7
Hz, 1H), 8.68 (t, J = 7.6 Hz, 1H), 8.63 (s, 1H), 8.42 (d, J = 6.2 Hz, 1H), 7.89 (d, J =
7.9 Hz, 1H), 7.75 (t, J = 6.4 Hz, 1H), 7.50 (s, 6H), 7.35 (d, J = 13.6 Hz, 5H), 6.73 (s,
1H), 2.68 (s, 3H). 13C NMR (101 MHz, DMSOꢀd6) δ 145.64, 143.72, 137.71, 136.24,
133.37, 133.32, 132.53, 132.02, 130.85, 129.84, 129.61, 129.28, 129.25, 129.05,
128.62, 127.69, 122.65, 120.55, 116.44, 115.78, 104.05, 22.31. HRMS m/z (ESI)
[MꢀBF4] calculated for C28H21N2: 385.1705, found 385.1704.
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12ꢀmethylꢀ6,7ꢀdiphenylpyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3ia): red solid
(67.1 mg, 71%), mp. 184ꢀ185 °C. 1H NMR (400 MHz, DMSO) δ 9.31 (d, J = 8.9 Hz, 1H),
8.88 (d, J = 8.7 Hz, 1H), 8.77 (t, J = 8.0 Hz, 1H), 8.54 (d, J = 6.7 Hz, 1H), 7.93 (d, J =
7.7 Hz, 1H), 7.85 (t, J = 6.9 Hz, 1H), 7.68 (t, J = 8.1 Hz, 1H), 7.52 (s, 5H), 7.48ꢀ7.15
(m, 5H), 6.54 (s, 1H), 2.09 (s, 3H). 13C NMR (101 MHz, DMSO) δ 146.29, 143.58,
138.16, 134.17, 134.04, 133.22, 132.86, 131.85, 131.39, 131.06, 129.92, 129.61,
129.57, 129.49, 129.25, 128.86, 128.28, 127.03, 121.46, 116.67, 115.64, 115.40,
102.55, 31.15. HRMS m/z (ESI) [MꢀBF4] calculated for C28H21N2: 385.1705, found
385.1704.
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8ꢀmethylꢀ6,7ꢀdiphenylpyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3ja): red solid
1
(18.9 mg, 20%), mp. 178ꢀ180 °C. H NMR (400 MHz, DMSOꢀd6) δ 9.18 (d, J = 8.9
Hz, 1H), 8.77 (d, J = 8.5 Hz, 1H), 8.65 (t, J = 7.9 Hz, 1H), 8.30 (d, J = 6.5 Hz, 1H),
8.00 (d, J = 7.7 Hz, 1H), 7.76 (t, J = 7.5 Hz, 1H), 7.70 (d, J = 4.9 Hz, 2H), 7.59ꢀ7.44
13
(m, 5H), 7.34 (m, 6H), 1.68 (s, 3H). C NMR (101 MHz, DMSOꢀd6) δ 145.68,
143.95, 137.54, 133.75, 132.92, 132.79, 132.00, 131.69, 130.65, 130.12, 129.83,
129.67, 129.20, 128.88, 127.28, 126.44, 125.82, 120.94, 120.27, 116.27, 115.88,
112.50, 103.53, 9.25. HRMS m/z (ESI) [MꢀBF4] calculated for C28H21N2: 385.1705,
found 385.1704.
11ꢀchloroꢀ6,7ꢀdiphenylpyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3ka): red solid
1
(89.7 mg, 91%), mp. 188ꢀ191 °C. H NMR (400 MHz, DMSOꢀd6) δ 9.28 (d, J = 8.8
Hz, 1H), 8.92 (s, 1H), 8.71 (t, J = 7.2 Hz, 1H), 8.48 (d, J = 6.2 Hz, 1H), 8.04 (d, J =
8.3 Hz, 1H), 7.81 (d, J = 6.2 Hz, 1H), 7.71 (d, J = 8.1 Hz, 1H), 7.50 (s, 5H), 7.36 (d, J
= 17.4 Hz, 5H), 6.82 (s, 1H). 13C NMR (101 MHz, DMSOꢀd6) δ 146.21, 143.43,
137.99, 133.79, 133.37, 133.12, 133.10, 131.94, 130.98, 130.66, 130.12, 129.89,
129.62, 129.40, 129.11, 128.51, 126.52, 124.28, 121.20, 116.78, 115.82, 103.96.
HRMS m/z (ESI) [MꢀBF4] calculated for C27H18ClN2: 405.1159, found 405.1158.
10ꢀchloroꢀ6,7ꢀdiphenylpyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3la): red solid
1
(83.8 mg, 85%), mp. 186ꢀ188 °C. H NMR (400 MHz, DMSOꢀd6) δ 9.24 (d, J = 8.7
Hz, 1H), 8.84 (d, J = 9.0 Hz, 1H), 8.73 (t, J = 7.7 Hz, 1H), 8.49 (d, J = 6.4 Hz, 1H),
8.11 (s, 1H), 7.81 (t, J = 6.6 Hz, 1H), 7.73 (d, J = 8.7 Hz, 1H), 7.51 (s, 5H), 7.38 (d, J
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= 16.3 Hz, 5H), 6.77 (s, 1H). 13C NMR (101 MHz, DMSOꢀd6) δ 146.07, 143.46,
137.97, 134.37, 133.80, 133.05, 132.82, 131.89, 131.47, 131.00, 130.54, 129.89,
129.61, 129.58, 129.42, 129.14, 128.33, 125.63, 122.19, 121.07, 117.68, 116.44,
103.39. HRMS m/z (ESI) [MꢀBF4] calculated for C27H18ClN2: 405.1159, found
405.1158.
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10ꢀbromoꢀ6,7ꢀdiphenylpyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3ma): red solid
(70.9 mg, 66%), mp. 188ꢀ189 °C. 1H NMR (400 MHz, DMSO) δ 9.24 (d, J = 8.8 Hz,
1H), 8.86ꢀ8.65 (m, 2H), 8.49 (d, J = 6.5 Hz, 1H), 8.26 (s, 1H), 7.82 (t, J = 9.9 Hz, 1H),
7.81 (t, J = 6.5 Hz, 1H), 7.51 (s, 5H), 7.38 (dd, J = 25.0, 6.3 Hz, 5H), 6.78 (s, 1H). 13C
NMR (101 MHz, DMSO) δ 146.09, 143.47, 138.00, 134.19, 133.83, 133.25, 133.05,
131.89, 131.78, 131.00, 129.89, 129.61, 129.43, 129.15, 128.33, 128.25, 125.31,
121.10, 118.79, 117.93, 116.50, 103.27. HRMS m/z (ESI) [MꢀBF4] calculated for
C27H18BrN2: 449.0648, found 449.0651.
10ꢀiodoꢀ6,7ꢀdiphenylpyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3na): red solid
(83.0 mg, 71%), mp. 190ꢀ191 °C. 1H NMR (400 MHz, DMSO) δ 9.22 (d, J = 9.0 Hz,
1H), 8.72 (t, J = 8.0 Hz, 1H), 8.64 (d, J = 9.0 Hz, 1H), 8.48 (d, J = 6.7 Hz, 1H), 8.43
(s, 1H), 7.98 (d, J = 8.9 Hz, 1H), 7.79 (t, J = 6.9 Hz, 1H), 7.50 (s, 5H), 7.46ꢀ7.13 (m,
5H), 6.75 (s, 1H). 13C NMR (101 MHz, DMSO) δ 146.02, 143.49, 137.97, 133.79,
133.74, 133.71, 133.60, 133.07, 132.23, 131.90, 131.48, 130.98, 129.88, 129.60,
129.42, 129.14, 128.34, 121.03, 117.96, 116.55, 103.00, 91.47, 40.66, 40.45, 40.24,
40.04, 39.83, 39.62, 39.41. HRMS m/z (ESI) [MꢀBF4] calculated for C27H18IN2:
497.0509, found 497.0516.
10ꢀnitroꢀ6,7ꢀdiphenylpyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3oa): red solid
(65.4 mg, 65%), mp. 190ꢀ191 °C. 1H NMR (400 MHz, DMSO) δ 9.36 (d, J = 8.9 Hz,
1H), 9.05 (d, J = 9.4 Hz, 1H), 8.98 (s, 1H), 8.81 (t, J = 7.9 Hz, 1H), 8.56 (d, J = 6.7
Hz, 1H), 8.49 (d, J = 9.0 Hz, 1H), 7.89 (t, J = 6.9 Hz, 1H), 7.52 (s, 5H), 7.39 (m, 5H),
7.05 (s, 1H). 13C NMR (101 MHz, DMSO) δ 146.66, 145.02, 143.53, 138.45, 135.60,
134.36, 132.84, 131.85, 131.41, 131.11, 129.95, 129.61, 129.38, 129.21, 128.35,
122.01, 119.95, 119.02, 117.00, 116.84, 104.99. RMS m/z (ESI) [MꢀBF4] calculated
for C27H18O2N3: 416.1394, found 416.1399.
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10ꢀmethoxyꢀ6,7ꢀdiphenylpyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3pa): red solid
1
(85.0 mg, 87%), mp. 192ꢀ194 °C. H NMR (400 MHz, DMSOꢀd6) δ 9.19 (d, J = 9.0
7
8
9
Hz, 1H), 8.71 (d, J = 9.3 Hz, 1H), 8.66 (t, J = 8.0 Hz, 1H), 8.42 (d, J = 6.8 Hz, 1H),
7.72 (t, J = 6.9 Hz, 1H), 7.50 (s, 6H), 7.39 (d, J = 6.8 Hz, 3H), 7.36ꢀ7.25 (m, 2H),
6.71 (s, 1H), 3.88 (s, 3H). 13C NMR (101 MHz, DMSOꢀd6) δ 157.74, 145.45, 143.18,
137.54, 133.66, 133.28, 133.08, 132.93, 131.96, 130.88, 129.84, 129.82, 129.63,
129.32, 129.07, 128.12, 127.53, 120.28, 117.11, 116.05, 115.52, 104.30, 103.84, 56.08.
HRMS m/z (ESI) [MꢀBF4] calculated for C28H21ON2: 401.1654, found 401.1661.
10ꢀfluoroꢀ6,7ꢀdiphenylpyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3qa): red solid
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(83.8 mg, 88%), mp. 182ꢀ184 °C. H NMR (400 MHz, DMSOꢀd6) δ 9.25 (d, J = 8.9
Hz, 1H), 8.86 (d, J = 5.4 Hz, 1H), 8.71 (s, 1H), 8.47 (d, J = 6.2 Hz, 1H), 7.90ꢀ7.71 (m,
2H), 7.59 (s, 1H), 7.50 (s, 5H), 7.36 (d, J = 18.7 Hz, 5H), 6.78 (s, 1H). 13C NMR (101
MHz, DMSOꢀd6) δ 160.08 (d, JCꢀF = 242.4 Hz), 145.98, 143.43, 137.87, 134.62,
133.65, 132.92 (d, JCꢀF = 11.1 Hz), 131.90, 130.98, 129.89, 129.62, 129.40, 129.13,
128.21, 120.89, 117.92 (d, JCꢀF = 9.8 Hz), 114.02 (d, JCꢀF = 25.8 Hz), 107.99 (d, JCꢀF
=
24.0 Hz), 103.83 (d, JCꢀF = 4.4 Hz). HRMS m/z (ESI) [MꢀBF4] calculated for
C27H18FN2: 389.1449, found 389.1449.
10ꢀmethoxycarbonylꢀ6,7ꢀdiphenylpyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3ra):
red solid (76.4 mg, 74%), mp. 195ꢀ197 °C. 1H NMR (400 MHz, DMSOꢀd6) δ 9.30 (d,
J = 8.9 Hz, 1H), 8.93 (d, J = 9.1 Hz, 1H), 8.76 (t, J = 8.0 Hz, 1H), 8.66 (s, 1H), 8.50
(d, J = 6.8 Hz, 1H), 8.23 (d, J = 8.8 Hz, 1H), 7.83 (t, J = 7.0 Hz, 1H), 7.51 (s, 5H),
7.47ꢀ7.27 (m, 5H), 6.96 (s, 1H), 3.94 (s, 3H). 13C NMR (101 MHz, DMSOꢀd6) δ
166.40, 146.28, 143.58, 138.16, 135.12, 134.25, 133.68, 133.02, 131.92, 131.28,
131.02, 129.91, 129.64, 129.54, 129.46, 129.14, 128.52, 126.95, 125.89, 124.73,
121.44, 116.64, 116.22, 104.69, 52.92. HRMS m/z (ESI) [MꢀBF4] calculated for
C29H21O2N2: 429.1603, found 429.1602.
6,7ꢀdiphenylpyrimido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3ta): red solid (58.8 mg,
1
64%), mp. 176ꢀ178 °C. H NMR (400 MHz, DMSOꢀd6) δ 9.60 (s, 1H), 9.21 (d, J =
8.2 Hz, 1H), 8.79 (d, J = 6.2 Hz, 1H), 8.02 (d, J = 7.6 Hz, 1H), 7.85 (s, 1H), 7.78ꢀ7.72
(m, 1H), 7.72 ꢀ7.61 (m, 1H), 7.44 (m, 10H), 6.89 (s, 1H). 13C NMR (101 MHz,
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DMSOꢀd6) δ 165.18, 146.02, 145.73, 133.23, 133.09, 132.73, 132.62, 131.95, 131.19,
130.93, 129.98, 129.56, 129.22, 128.69, 128.59, 126.67, 126.44, 122.68, 118.41,
117.28, 105.19, 103.52. HRMS m/z (ESI) [MꢀBF4] calculated for C26H18N3: 372.1495,
found 372.1501.
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6,7ꢀdiphenylpyrido[1,2ꢀa]pyrrolo[1,2ꢀc]pyrimidinꢀ5ꢀium (3ua): red solid (66.9 mg,
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82%), mp. 131ꢀ133 °C. H NMR (400 MHz, DMSOꢀd6) δ 9.04 (d, J = 8.7 Hz, 1H),
8.86 (s, 1H), 8.66 (t, J = 7.8 Hz, 1H), 8.39 (d, J = 6.6 Hz, 1H), 7.78 (t, J = 6.7 Hz, 1H),
7.48 (s, 5H), 7.39ꢀ7.21 (m, 6H), 6.48 (s, 1H). 13C NMR (101 MHz, DMSOꢀd6) δ
144.05, 141.15, 136.58, 133.37, 132.29, 130.78, 130.36, 129.85, 129.82, 129.62,
129.23, 129.00, 128.93, 128.31, 121.57, 119.28, 118.36, 116.05, 108.70. HRMS m/z
(ESI) [MꢀBF4] calculated for C23H17N2: 321.1392, found 321.1383.
6,7ꢀdi(thiophenꢀ2ꢀyl)pyrido[1,2ꢀa]pyrrolo[1,2ꢀc]pyrimidinꢀ5ꢀium (3uq): red solid
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(70.6 mg, 84%), mp. 136ꢀ138 °C. H NMR (400 MHz, DMSOꢀd6) δ 8.99 (d, J = 8.8
Hz, 1H), 8.86 (s, 1H), 8.65 (t, J = 8.0 Hz, 1H), 8.59 (d, J = 6.8 Hz, 1H), 7.99 (d, J =
4.9 Hz, 1H), 7.81 (t, J = 7.0 Hz, 1H), 7.75 (d, J = 4.8 Hz, 1H), 7.46 (d, J = 2.3 Hz,
1H), 7.35 (d, J = 2.5 Hz, 1H), 7.31 (d, J = 3.5 Hz, 2H), 7.19ꢀ7.07 (m, 1H), 6.95 (d, J =
3.0 Hz, 1H). 13C NMR (101 MHz, DMSOꢀd6) δ 144.32, 141.27, 136.52, 135.66,
133.26, 132.99, 131.00, 130.14, 128.98, 128.77, 128.03, 127.66, 124.79, 123.63,
121.69, 119.35, 119.33, 115.90, 110.34. HRMS m/z (ESI) [MꢀBF4] calculated for
C19H13N2S2: 333.0520, found 333.0515.
6,7ꢀdiꢀpꢀtolylpyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3ab): red solid (64.7 mg,
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81%), mp. 184ꢀ186 °C. H NMR (400 MHz, DMSOꢀd6) δ 9.24 (d, J = 8.9 Hz, 1H),
8.79 (d, J = 8.5 Hz, 1H), 8.68 (t, J = 7.8 Hz, 1H), 8.42 (d, J = 6.6 Hz, 1H), 8.00 (d, J =
7.6 Hz, 1H), 7.36 (dd, J = 23.2, 7.5 Hz, 4H), 7.23 (s, 4H), 6.78 (s, 1H), 2.34 (s, 3H),
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2.31 (s, 3H). C NMR (101 MHz, DMSOꢀd6) δ 145.67, 143.72, 140.51, 138.74,
137.72, 133.25, 133.04, 132.93, 131.82, 131.43, 130.54, 130.46, 129.70, 129.54,
128.48, 126.94, 126.01, 125.93, 123.08, 120.60, 116.37, 116.04, 104.07, 21.48, 21.31.
HRMS m/z (ESI) [MꢀBF4] calculated for C29H23N2: 399.1861, found 399.1864.
6,7ꢀdiꢀmꢀtolylpyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3ac): red solid (61.5 mg,
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77%), mp. 181ꢀ183 °C. H NMR (400 MHz, DMSOꢀd6) δ 9.25 (d, J = 8.9 Hz, 1H),
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8.80 (d, J = 8.6 Hz, 1H), 8.69 (t, J = 8.0 Hz, 1H), 8.44 (d, J = 6.8 Hz, 1H), 8.02 (d, J =
7.8 Hz, 1H), 7.84ꢀ7.68 (m, 2H), 7.64 (t, J = 7.4 Hz, 1H), 7.40 (t, J = 7.4 Hz, 1H), 7.30
(dd, J = 17.7, 10.0 Hz, 4H), 7.19 (d, J = 8.1 Hz, 2H), 7.14 (d, J = 7.5 Hz, 1H), 6.79 (s,
1H), 2.30 (s, 3H), 2.27 (s, 3H). 13C NMR (101 MHz, DMSOꢀd6) δ 145.71, 143.70,
139.15, 138.22, 137.81, 133.20, 133.08, 133.00, 132.93, 132.23, 131.55, 131.42,
130.06, 129.98, 129.73, 129.71, 129.06, 128.94, 128.43, 126.77, 126.03, 125.96,
123.09, 120.66, 116.39, 116.05, 104.12, 21.41, 21.40. HRMS m/z (ESI) [MꢀBF4]
calculated for C29H23N2: 399.1861, found 399.1864.
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6,7ꢀbis(4ꢀchlorophenyl)pyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3ae): red solid
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(74.9 mg, 71%), mp. 201ꢀ203 °C. H NMR (400 MHz, DMSOꢀd6) δ 9.29 (d, J = 8.9
Hz, 1H), 8.82 (d, J = 8.5 Hz, 1H), 8.72 (t, J = 7.8 Hz, 1H), 8.53 (d, J = 6.5 Hz, 1H),
8.03 (d, J = 7.7 Hz, 1H), 7.75 (t, J = 7.1 Hz, 2H), 7.69ꢀ7.59 (m, 3H), 7.56ꢀ7.46 (m,
4H), 7.37 (d, J = 8.2 Hz, 2H), 6.87 (s, 1H). 13C NMR (101 MHz, DMSOꢀd6) δ 146.14,
143.66, 138.26, 135.96, 134.30, 133.90, 132.98, 132.63, 132.13, 131.94, 131.59,
131.41, 130.19, 129.44, 128.50, 127.77, 126.24, 123.21, 120.78, 116.34, 116.04,
104.38. HRMS m/z (ESI) [MꢀBF4] calculated for C27H17Cl2N2: 439.0763, found
439.0766.
6,7ꢀbis(4ꢀnitrophenyl)pyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3af): red solid
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(57.0 mg, 52%), mp. 208ꢀ210 °C. H NMR (400 MHz, DMSOꢀd6) δ 9.28 (d, J = 8.9
Hz, 1H), 8.82 (d, J = 8.4 Hz, 1H), 8.72 (t, J = 7.8 Hz, 1H), 8.53 (d, J = 6.6 Hz, 1H),
8.02 (d, J = 7.7 Hz, 1H), 7.75 (t, J = 7.1 Hz, 2H), 7.66 (dd, J = 16.8, 7.8 Hz, 3H),
7.57ꢀ7.46 (m, 4H), 7.38 (d, J = 7.7 Hz, 2H), 6.87 (s, 1H). 13C NMR (101 MHz,
DMSOꢀd6) δ 146.13, 143.66, 138.25, 135.97, 134.30, 133.91, 132.98, 132.64, 132.12,
131.95, 131.60, 131.40, 130.18, 129.44, 128.50, 127.78, 126.23, 126.18, 123.19,
120.78, 116.34, 116.03, 104.38. HRMS m/z (ESI) [MꢀBF4] calculated for C27H17O4N4:
461.1250, found 461.1248.
6,7ꢀdi(thiophenꢀ2ꢀyl)pyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3ag): red solid
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(80.9 mg, 86%), mp. 173ꢀ175°C. H NMR (400 MHz, DMSOꢀd6) δ 9.20 (d, J = 8.8
Hz, 1H), 8.77 (d, J = 8.5 Hz, 1H), 8.68 (dd, J = 13.1, 7.1 Hz, 2H), 8.07 (d, J = 7.7 Hz,
1H), 7.99 (d, J = 4.8 Hz, 1H), 7.80 (dd, J = 12.0, 5.6 Hz, 2H), 7.73 (d, J = 8.0 Hz, 1H),
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7.66 (t, J = 7.4 Hz, 1H), 7.50 (s, 1H), 7.39 (s, 1H), 7.31 (s, 1H), 7.26 (s, 1H), 7.17 (s,
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1H). C NMR (101 MHz, DMSOꢀd6) δ 146.06, 143.73, 137.65, 135.60, 133.29,
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133.22, 132.71, 132.18, 131.27, 131.09, 130.10, 128.75, 128.71, 127.71, 126.92,
126.48, 126.15, 125.19, 123.35, 120.75, 116.27, 116.07, 105.57. HRMS m/z (ESI)
[MꢀBF4] calculated for C23H15S2N2: 383.0677, found 383.0679.
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7ꢀethylꢀ6ꢀphenylpyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium (3ai) (two isomers in a
ratio of 1:19 as determined by NMR analysis): red solid (66.4 mg, 81%), mp.
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143ꢀ145°C. H NMR (400 MHz, DMSOꢀd6) δ 9.09 (d, J = 9.0 Hz, 1H), 8.65 (d, J =
9.3 Hz, 1H), 8.58 (t, J = 7.9 Hz, 1H), 8.25 (d, J = 6.5 Hz, 1H), 7.77 (d, J = 6.4 Hz,
3H), 7.72ꢀ7.60 (m, 4H), 7.52 (s, 1H), 7.47 (s, 1H), 2.58 (q, J = 7.0 Hz, 2H), 1.17 (t, J
= 7.4 Hz, 3H). 13C NMR (101 MHz, DMSOꢀd6) δ 157.69, 144.63, 142.73, 137.30,
133.15, 132.28, 132.11, 131.42, 131.16, 130.67, 129.97, 129.89, 129.41, 128.51,
127.58, 127.36, 120.08, 117.13, 115.86, 115.28, 103.97, 102.10, 23.42, 13.37. HRMS
m/z (ESI) [MꢀBF4] calculated for C23H19N2: 323.1543, found 323.1546.
General procedure for the synthesis of 4: Synthesis of compound 4ca is
representative. To a stirred solution of pyrido[2',1':2,3]pyrimido[1,6ꢀa]indolꢀ5ꢀium
3ca (0.20 mmol) in dry MeOH (5 mL) at 0 °C was added NaBH4 (30 mg, 0.80 mmol).
The mixture was allowed to stir at 0 °C for 2 h. After the completion of reaction, the
reaction mixture was diluted with water and extracted with CH2Cl2 (2×10 mL). The
combined organic layer was washed with brine (2×10 mL) and dried over MgSO4 and
concentrated and purified by ilica gel column chromatography using hexane/ethyl
acetate (v/v = 50:1) as eluent to afford the product 4ca as a colorless solid.
2ꢀmethylꢀ6,7ꢀdiphenylꢀ6,7ꢀdihydroꢀ4Hꢀpyrido[2',1':2,3]pyrimido[1,6ꢀa]indole (4ca):
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colorless solid (55.2 mg, 71%), mp. 91ꢀ93 °C. H NMR (400 MHz, CDCl3) δ 7.26ꢀ
6.79 (m, 13H), 5.85 (dd, J = 16.7, 13.9 Hz, 3H), 5.58 (d, J = 9.7 Hz, 1H), 3.68 (q, J =
18.5 Hz, 2H), 2.93ꢀ2.67 (m, 1H), 2.48ꢀ2.01 (m, 4H). 13C NMR (101 MHz, CDCl3) δ
141.34, 137.59, 136.30, 135.15, 132.69, 132.07, 131.41, 130.29, 130.11, 129.04,
128.71, 127.88, 127.72, 127.49, 127.45, 125.82, 125.73, 122.25, 119.67, 107.67,
107.01, 95.92, 67.02, 49.05, 26.28, 21.49. HRMS m/z (ESI) Calcd for C28H25N2
[M+H+], 389.2012, found 389.2017.
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10ꢀchloroꢀ6,7ꢀdiphenylꢀ6,7ꢀdihydroꢀ4Hꢀpyrido[2',1':2,3]pyrimido[1,6ꢀa]indole (4la):
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colorless solid (63.0 mg, 77%), mp. 100ꢀ102 °C. H NMR (400 MHz, CDCl3) δ 7.37
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(s, 1H), 7.25 (s, 1H), 7.23ꢀ6.90 (m, 11H), 6.01ꢀ5.82 (m, 3H), 5.68 (d, J = 10.0 Hz, 1H),
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3.77 (q, J = 18.7 Hz, 2H), 3.31ꢀ2.72 (m, 1H), 2.32 (d, J = 16.7 Hz, 1H). C NMR
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(101 MHz, CDCl3) δ 142.23, 137.43, 137.16, 134.78, 132.63, 131.33, 130.88, 130.12,
127.95, 127.89, 127.59, 127.46, 126.00, 125.53, 125.44, 120.74, 119.05, 108.70,
106.42, 95.66, 66.99, 49.05, 26.28. HRMS m/z (ESI) Calcd for C27H22N2Cl [M+H+],
409.1472, found 409.1477.
10ꢀmethoxyꢀ6,7ꢀdiphenylꢀ6,7ꢀdihydroꢀ4Hꢀpyrido[2',1':2,3]pyrimido[1,6ꢀa]indole
(
4pa): colorless solid (69.6 mg, 86%), mp. 99ꢀ101 °C. 1H (400 MHz, CDCl3) δ 7.25 (s,
1H), 7.23ꢀ7.00 (m, 10H), 6.92 (s, 1H), 6.78 (d, J = 8.6 Hz, 1H), 6.34ꢀ5.80 (m, 3H),
5.67 (d, J = 9.7 Hz, 1H), 4.08ꢀ3.50 (m, 5H), 2.90 (t, J = 16.3 Hz, 1H), 2.33 (d, J =
16.3 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 154.38, 141.38, 137.49, 136.91, 135.06,
131.38, 130.31, 130.25, 129.57, 127.88, 127.74, 127.49, 127.42, 125.83, 125.68,
110.37, 108.55, 106.90, 102.22, 96.14, 67.12, 55.88, 49.03, 26.28. HRMS m/z (ESI)
Calcd for C28H25N2O [M+H+], 405.1961, found 405.1966.
10ꢀfluoroꢀ6,7ꢀdiphenylꢀ6,7ꢀdihydroꢀ4Hꢀpyrido[2',1':2,3]pyrimido[1,6ꢀa]indole (4qa):
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colorless solid (63.6 mg, 81%), mp. 99ꢀ101 °C. H NMR (400 MHz, CDCl3) δ
7.18ꢀ6.99 (m, 12H), 6.77 (td, J = 9.1, 2.0 Hz, 1H), 5.88ꢀ5.78 (m, 2H), 5.60 (d, J =
10.0 Hz, 1H), 3.69 (q, J = 18.7 Hz, 2H), 2.90ꢀ2.77 (m, 1H), 2.25 (d, J = 16.8 Hz, 1H).
13C NMR (101 MHz, CDCl3) δ 158.19 (d, J = 233.9 Hz), 137.24, 134.84, 131.36,
130.15, 127.95, 127.91, 127.87, 127.57, 127.46, 125.97, 125.59, 108.55 (d, J = 26.3
Hz), 108.20 (d, J = 9.9 Hz), 104.84, 104.72 (d, J = 23.7 Hz), 67.08, 48.96, 26.18.
HRMS m/z (ESI) Calcd for C27H22FN2 [M+H+], 393.1762, found 393.1767.
6,7ꢀdiꢀpꢀtolylꢀ6,7ꢀdihydroꢀ4Hꢀpyrido[2',1':2,3]pyrimido[1,6ꢀa]indole (4ab): colorless
solid (53.1 mg, 66%), mp. 99ꢀ101 °C. 1H NMR (400 MHz, CDCl3) δ 7.34 (t, J = 7.8
Hz, 1H), 7.15 (d, J = 6.0 Hz, 1H), 7.02 (dd, J = 16.1, 7.7 Hz, 2H), 6.98ꢀ6.89 (m, 6H),
6.85 (d, J = 7.6 Hz, 2H), 6.03ꢀ5.73 (m, 2H), 5.59 (d, J = 9.9 Hz, 1H), 3.67 (q, J = 18.8
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Hz, 2H), 2.99ꢀ2.68 (m, 1H), 2.33ꢀ2.30 (m, 1H), 2.19 (s, 6H). C NMR (101 MHz,
CDCl3) δ 141.20, 137.41, 135.00, 134.63, 134.11, 132.05, 131.17, 129.90, 129.60,
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128.62, 128.50, 128.17, 127.44, 125.64, 120.54, 119.76, 119.63, 108.03, 106.63,
95.86, 66.86, 49.05, 26.29, 21.27, 21.15. HRMS m/z (ESI) Calcd for C29H27N2
[M+H+], 403.2169, found 403.2166.
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ASSOCIATED CONTENT
Supporting Information
1
13
Copies of H and C NMR spectra for all new products, Xꢀray data in CIF of 3ha
(CCDC 1498398) and UVꢀvis absorption spectra of selected compounds.
The Supporting Information is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: chemlt2015@nynu.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We are grateful for financial support from the Education Department Fund of Henan
Province (14A150054, 17A150043) and Special Fund of Nanyang Normal University
(ZX2016016).
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