Decarboxylative cascade cyclization of α-keto acids with 2-cyano-3-arylaniline-derived acrylamides

Article abstract of DOI:10.1039/c9ob02023c

An oxidative decarboxylative cascade cyclization of α-keto acids with 2-cyano-3-arylaniline-derived acrylamides was developed. This cascade reaction exhibits a broad substrate scope, and provides an efficient access to carbonyl-containing pyrido[4,3,2-gh]

Full text of DOI:10.1039/c9ob02023c

Organic &
Biomolecular Chemistry
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Decarboxylative cascade cyclization of α-keto
acids with 2-cyano-3-arylaniline-derived
acrylamides†
Cite this: Org. Biomol. Chem., 2019,
17, 9447
Jia-Qi Shang,‡a Xiang-Xiang Wang,‡a Yangchun Xin,b Yi Li,a Bin Zhoua and
a
Ya-Min Li
*
Received 17th September 2019,
Accepted 14th October 2019
An oxidative decarboxylative cascade cyclization of α-keto acids with 2-cyano-3-arylaniline-derived acryl-
amides was developed. This cascade reaction exhibits a broad substrate scope, and provides an efficient
access to carbonyl-containing pyrido[4,3,2-gh]phenanthridines. A possible mechanism is proposed.
DOI: 10.1039/c9ob02023c
rsc.li/obc
useful strategy to access pyrido[4,3,2-gh]phenanthridine deriva-
tives via the cascade cyclization has been established.10 We
Introduction
Decarboxylative coupling is one of the most efficient strategies disclosed a radical cascade cyclization of N-arylacrylamide
for carbon–carbon bond and carbon–heteroatom bond derivatives with alkylnitriles and tert-butyl peroxybenzoate to
formation.1,2 Since Gooßen and co-workers first reported the form cyanomethyl- and methyl-substituted pyrido[4,3,2-gh]phe-
decarboxylative acylation of aryl bromides with α-keto acid nanthridines.10h This process involves an intramolecular
salts using a palladium catalytic system for the synthesis of addition of the cyanomethyl or methyl radical to the C–C
unsymmetrical diaryl ketones,3 the use of α-keto acids as acyl double bond and two radical-mediated cyclizations. We
surrogates in decarboxylation has drawn much attention reasoned that the carbonyl-substituted pyrido[4,3,2-gh]phenan-
because keto acids are stable and convenient to store and thridines might also be constructed if the cyanomethyl or
handle, and decarboxylation of α-keto acids presents many methyl radical were replaced by an acyl radical. As part of our
advantages, such as high efficiency and formation of the non- continuous interest in developing new decarboxylative coup-
toxic byproduct (CO2).4 Although much effort has been made ling reactions,11 herein, we present an oxidative decarboxyla-
to explore new decarboxylative acylations of α-keto acids with tive cascade cyclization of α-keto acids with 2-cyano-3-arylani-
aromatic C–H and C–X (X = I, Br and Cl) bonds,5 and the dec- line-derived acrylamides to give carbonyl-containing pyrido
arboxylative coupling and cascade reactions of α-keto acids [4,3,2-gh]phenanthridines (Scheme 1).
with alkenes and alkynes,6 the development of new decarboxyl-
ation reactions for the efficient and facile synthesis of valuable
carbonyl-substituted molecules is still desired.
N-Polyheterocycles widely exist in many biologically active
compounds and natural products. They also play an important
Results and discussion
Our investigation started with the decarboxylative cascade
cyclization of anthranilonitrile-derived N-(2-cyano-[1,1′-biphe-
nyl]-3-yl)-N-methyl methacrylamide (1a) with phenylglyoxylic
acid (2a). To our delight, the desired pyrido[4,3,2-gh]phenan-
thridine 3aa was isolated in 47% yield when 1a was treated
with 2a in the presence of catalytic Ag2CO3 (5 mol%) and 1.0
role in materials science, supramolecular and polymer chem-
istry, photochemistry and electrochemistry.7 Therefore, devel-
oping new methodologies for the construction of novel
N-polyheterocycles is always an attractive area of organic chem-
istry. In this context, the cascade cyclization which involves
nitrogen-centered radicals8 has been proven to be a powerful
equiv. of (NH4)2S2O8 in 3 mL of acetone/H2O at 120 °C for 12 h
strategy for the synthesis of such compounds.9 Recently, a very
(Table 1, entry 1). In order to improve the reaction efficiency,
aFaculty of Life Science and Technology, Kunming University of Science and
Technology, Kunming 650500, P. R. China. E-mail: liym@kust.edu.cn
bKatzin Diagnostic & Research PET/MR Center, Nemours/Alfred I. DuPont Hospital
for Children, Wilmington, DE 19803, USA
†Electronic supplementary information (ESI) available: Experimental procedures
and copies of NMR spectra. See DOI: 10.1039/c9ob02023c
‡These authors contributed equally.
Scheme 1 Oxidative decarboxylative cascade cyclization.
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Table 1 Screening of reaction conditionsa
entries 20–23). Control experiments showed that pyridophe-
nanthridine 3aa could be isolated in 39% yield in the absence
of Ag2O, whereas no 3aa was obtained in the absence of
(NH4)2S2O8 (Table 1, entries 24 and 25), which suggested that
Ag2O acts as a promoter rather than a catalyst in this reaction.
With the optimal reaction conditions in hand, a variety of
acrylamides were chosen to expand the scope of the decarboxy-
Yieldb (%) lative cascade cyclization, and the results are presented in
Entry
Oxidant (equiv.)
Solvent (mL, v/v)
Table 2. Initially, we investigated the substitution effect on the
nitrogen atom. It was found that the optimal conditions were
compatible with N-methyl- and N-benzyl-substituted acryl-
amides, and the corresponding polyheterocycles 3aa and 3ba
were obtained in 66% and 45% yields, respectively. However,
acrylamide with N-acetyl, N-tosyl or N-H failed to provide the
products 3ca, 3da and 3ea. The acrylamides bearing an elec-
tron-withdrawing group (CF3, CN, F, Cl, and Br) or an electron-
donating group (Me, MeO, and PhO) on the aromatic ring also
reacted well with phenylglyoxylic acid, giving the products 3fa–
3pa in moderate yields. In addition, ortho-substituted sub-
strates could also react with 1a to provide the products 3na–
3pa in moderate yields, which illustrates that the steric hin-
drance effect on the phenyl ring was not obvious in this trans-
formation. Multi-substituted acrylamide was suitable for the
reaction, and the corresponding product 3qa was obtained in
51% yield. By replacing the benzene ring with naphthalene
1c
(NH4)2S2O8 (1)
(NH4)2S2O8 (1)
(NH4)2S2O8 (1)
(NH4)2S2O8 (1)
(NH4)2S2O8 (1)
K2S2O8 (1)
Oxone (1)
BPO (1)
DCP (1)
TBPB (1)
(NH4)2S2O8 (2)
(NH4)2S2O8 (3)
(NH4)2S2O8 (4)
(NH4)2S2O8 (3)
(NH4)2S2O8 (3)
(NH4)2S2O8 (3)
(NH4)2S2O8 (3)
(NH4)2S2O8 (3)
(NH4)2S2O8 (3)
(NH4)2S2O8 (3)
(NH4)2S2O8 (3)
(NH4)2S2O8 (3)
(NH4)2S2O8 (3)
(NH4)2S2O8 (3)
(NH4)2S2O8 (3)
(NH4)2S2O8 (3)
(NH4)2S2O8 (3)
—
Acetone/H2O (3, 1/1)
Acetone/H2O (3, 1/1)
Acetone/H2O (3, 1/1)
Acetone/H2O (3, 1/1)
Acetone/H2O (3, 1/1)
Acetone/H2O (3, 1/1)
Acetone/H2O (3, 1/1)
Acetone/H2O (3, 1/1)
Acetone/H2O (3, 1/1)
Acetone/H2O (3, 1/1)
Acetone/H2O (3, 1/1)
Acetone/H2O (3, 1/1)
Acetone/H2O (3, 1/1)
THF/H2O (3, 1/1)
CH3CN/H2O (3, 1/1)
Dioxane/H2O (3, 1/1)
Toluene/H2O (3, 1/1)
Acetone/H2O (1.5, 1/1)
Acetone/H2O (4.5, 1/1)
Acetone/H2O (3, 1/1)
Acetone/H2O (3, 1/1)
Acetone/H2O (3, 1/1.2)
Acetone/H2O (3, 1/1.3)
Acetone/H2O(3, 1/1.4)
Acetone/H2O (3, 1.5/1)
Acetone/H2O (3, 1/1.3)
Acetone/H2O (3, 1/1.3)
Acetone/H2O (3, 1/1.3)
47
33
28
46
54
43
Trace
11
Trace
Trace
57
61
60
27
35
33
Trace
42
38
61
47
58
66
58
48
46
39
0
2d
3e
4f
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20g
21h
22g
23g
24g
25g
26g,i
27g, j
28g
Table 2 Scope of arylacrylamidesa,b
a Reaction conditions: 1a (0.30 mmol), 2a (3.0 equiv.), Ag2O (5 mol%)
and oxidant in solvent at 120 °C for 12 h under air. b Isolated yield of
3aa. c Ag2CO3 instead of Ag2O. d AgF instead of Ag2O. e AgOAc instead
of Ag2O. f AgOTf instead of Ag2O. g The reaction was carried out at
100 °C. h The reaction was carried out at 130 °C. i AgNO3 instead of
Ag2O. j The reaction was carried out in the absence of Ag2O.
different metal salts such as AgF, AgOAc, AgOTf and Ag2O were
screened, and the results demonstrated that Ag2O was superior
to others (Table 1, entries 2–5). Other oxidants including
K2S2O8, oxone, benzoyl peroxide (BPO), dicumyl peroxide
(DCP), and tert-butyl peroxybenzoate (TBPB) were also tested;
(NH4)2S2O8 was still more effective to produce polyheterocycle
3aa, and the appropriate amount of (NH4)2S2O8 was 3.0 equiv.
(Table 1, entries 6–13). Subsequently, different solvents were
explored, and the results revealed that acetone/H2O was the
most suitable medium for this decarboxylative cascade cycliza-
tion (Table 1, entries 14–17). Different reaction concentrations
were evaluated, and the results demonstrated that 0.1 M (1a)
was still the preferred concentration. We also investigated
different reaction temperatures. It was found that the reaction
proceeded equally well at 100 °C, and increasing the tempera-
ture to 130 °C led to a lower yield of 3aa (Table 1, entries 18
and 19). The ratio of acetone to H2O also had an effect on the
reaction efficiency. When the volume ratio of acetone and H2O
was 1 : 1.3, the best results (66%) were achieved (Table 1,
a Reaction conditions: 1 (0.30 mmol), 2a (3.0 equiv.), Ag2O (5 mol%)
and (NH4)2S2O8 (3.0 equiv.) in 3 mL of acetone/H2O (1/1.3) at 100 °C
for 12 h under air. b Isolated yield.
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and phenanthrene, the substrates also underwent the reaction tion, affording the corresponding pyrido[4,3,2-gh]phenanthri-
smoothly, giving products 3ra and 3sa in moderate yields. dines 3al and 3am in 40% and 33% yields, respectively.
What’s more, the acrylamides bearing other functional groups, However, alkyl-substituted keto acid, 2-oxopropanoic acid, was
including phenyl and benzyl, at the α-position of the carbon– inert under the standard conditions (3an). N-Phenyloxamic
carbon double bond were also compatible with this system, acid was also not compatible with this system (3ao).
and provided polyheterocycles 3ta and 3ua in 37% and 39%
Several experiments were performed to gain some insight
yields, respectively. Moderate yields were observed in most of into this reaction. As shown in Scheme 2, initially, the radical-
the cases because acrylamides were partly consumed under trapping reaction was carried out. When a stoichiometric
the optimized conditions.
amount of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), a
The scope of α-keto acids was next investigated. As shown radical inhibitor, was added, the decarboxylative cascade cycli-
in Table 3, this decarboxylative cascade cyclization was found zation process was almost completely suppressed, and TEMPO
to be compatible with a broad range of α-keto acids. Both elec- captured product 4 was detected by HRMS. This result
tron-deficient (F, Cl, and Br) and -rich (Me) aryl-substituted suggests that free-radical intermediates might be involved in
phenylglyoxylic acids underwent the reaction smoothly, giving this decarboxylative cascade cyclization. Furthermore, inter-
products 3ab–3aj in moderate yields. ortho-F and -Br-substi- and intramolecular competition experiments were carried out.
tuted phenylglyoxylic acids were all suitable substrates, and No kinetic isotope effects (KIE = 1.0) were observed in the reac-
showed a high reactivity in this transformation (3ai and 3aj). tion of phenylglyoxylic acid with 1a/1a-D5 (1/1) or 1a-D1. The
2-(Naphthalen-1-yl)-2-oxoacetic acid provided the desired absence of inter- and intramolecular isotope effects illustrates
product 3ak in 42% yield. For heterocyclic derivatives, 2-oxo-2- that the rate-determining step might not be the C(sp2)–H bond
(thiophen-2-yl)acetic acid and 2-(furan-2-yl)-2-oxoacetic acid cleavage, and C(sp2)–H bond cleavage occurs after C(sp2)–N
are also tolerated well in this decarboxylative cascade cycliza- bond formation.12
A plausible mechanism for the decarboxylative cascade
cyclization is shown in Scheme 3, based on the aforemen-
tioned experimental results and the literature.10,13–15 Initially,
α-keto acids undergo an oxidative radical decarboxylative
Table 3 Scope of α-keto acidsa,b
process to afford the acyl radical in the presence of
(NH4)2S2O8. Subsequently, the acyl radical attacks the carbon–
carbon double bond of acrylamide 1a to generate the alkyl
radical A, which then combines with the nitrile to form an
imine radical B. Finally, imine radical B undergoes intra-
molecular cyclization to generate intermediate C,13 followed by
aryl ring H-abstraction giving the final product 3aa. Ag2O prob-
ably acts as a Lewis acid to coordinate with the O-atom of
a Reaction conditions: 1 (0.30 mmol), 2a (3.0 equiv.), Ag2O (5 mol%)
and (NH4)2S2O8 (3.0 equiv.) in 3 mL of acetone/H2O (1/1.3) at 100 °C
for 12 h under air. b Isolated yield.
Scheme 2 Mechanistic studies.
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mixture was cooled to room temperature. Aqueous Na2CO3
(1.0 M, 5.0 mL) was added and extracted with ethyl acetate (3 ×
15 mL). The combined organic layers were dried over anhy-
drous Na2SO4 and concentrated under vacuum. The residue
was purified by flash chromatography on silica gel with pet-
roleum ether/ethyl acetate as the eluent to afford the desired
product 3.
4,6-Dimethyl-6-(2-oxo-2-phenylethyl)-4H-pyrido[4,3,2-gh]phen-
anthridin-5(6H)-one (3aa). Purified by column chromatography
(petroleum ether/ethyl acetate = 6/1, v/v). Pale yellow solid, mp
228–230 °C. 1H NMR (600 MHz, CDCl3) δ 8.50 (dd, J = 8.1,
0.8 Hz, 1H), 8.27 (d, J = 8.3 Hz, 1H), 7.95 (ddd, J = 7.9, 4.3,
0.9 Hz, 3H), 7.85 (t, J = 8.1 Hz, 1H), 7.67–7.61 (m, 1H), 7.59–7.55
(m, 1H), 7.54–7.49 (m, 1H), 7.41 (t, J = 7.8 Hz, 2H), 7.30 (d, J =
7.9 Hz, 1H), 4.80 (d, J = 17.8 Hz, 1H), 4.28 (d, J = 17.8 Hz, 1H),
3.64 (s, 3H), 1.66 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 198.3,
174.3, 160.2, 144.6, 139.2, 136.3, 133.4, 133.1, 131.7, 129.5,
128.8, 128.4, 128.2, 126.2, 122.9, 122.5, 115.9, 112.1, 110.9, 48.8,
48.4, 29.9, 29.8. IR (film) νmax: 3064, 2910, 1656, 1610, 1590,
1465, 1341, 1219, 1078, 1003, 761, 687 cm−1. HRMS calc. for
C25H20N2O2 (M + H)+, 381.1598; found, 381.1598.
Scheme 3 Proposed mechanism.
α,β-unsaturated carbonyls to increase the activity of the
carbon–carbon double bond or stabilize the radical intermedi-
ates.14 However, the mechanism involving Ag(II)-mediated dec-
arboxylative process cannot be completely ruled out.15
4-Benzyl-6-methyl-6-(2-oxo-2-phenylethyl)-4H-pyrido[4,3,2-gh]
phenanthridin-5(6H)-one (3ba). Purified by column chromato-
graphy (petroleum ether/ethyl acetate = 5/1, v/v). Pale yellow
solid, mp 170–173 °C. 1H NMR (600 MHz, CDCl3) δ 8.47 (d, J =
8.1 Hz, 1H), 8.21 (d, J = 8.3 Hz, 1H), 8.00 (d, J = 7.4 Hz, 2H),
7.95 (d, J = 8.2 Hz, 1H), 7.68 (t, J = 8.1 Hz, 1H), 7.65–7.60 (m,
1H), 7.56 (ddd, J = 12.5, 9.7, 4.2 Hz, 2H), 7.43 (dd, J = 15.5,
7.7 Hz, 4H), 7.35 (t, J = 7.7 Hz, 2H), 7.24 (d, J = 7.3 Hz, 1H),
7.15 (d, J = 8.0 Hz, 1H), 4.87 (d, J = 17.8 Hz, 1H), 4.34 (d, J =
17.8 Hz, 1H), 1.76 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 198.3,
174.6, 160.1, 144.6, 138.1, 136.5, 136.4, 133.6, 133.1, 131.7,
129.5, 128.9, 128.8, 128.4, 128.3, 127.1, 126.4, 126.3, 123.0,
Conclusions
In conclusion, we have demonstrated an oxidative decarboxyla-
tive cascade cyclization of α-keto acids with 2-cyano-3-arylani-
line-derived acrylamides. The present reaction generates one
C–N bond, two C–C bonds, and a quaternary carbon center in
a single step, providing an access to a variety of carbonyl-con-
taining pyrido[4,3,2-gh]phenanthridines.
Experimental
General information
122.5, 116.0, 112.2, 112.1, 48.8, 48.6, 46.2, 29.9. IR (film) νmax
:
.
1H NMR and 13C NMR spectra were recorded using a Bruker
AVANCE III HD instrument (600 MHz for 1H NMR; 151 MHz
for 13C NMR) internally referenced to the tetramethylsilane
(TMS) signal. Chemical shifts (δ) and coupling constants (J)
are expressed in ppm and Hz, respectively. CDCl3 was used as
the NMR solvent in all cases. Mass spectra were measured
using a Thermo LTQ Orbitrap XL spectrometer. IR spectra
were recorded using a Bruker Tensor 27 FT-IR spectrometer
and only major peaks are reported in cm−1. Unless otherwise
noted, materials were obtained from commercial suppliers
and used without further purification. Column chromato-
graphy was carried out on silica gel (particle size
200–300 mesh ASTM). Acrylamides10h and α-keto acids16 were
all prepared following literature procedures.
3059, 2958, 1674, 1588, 1464, 1372, 1220, 766, 732, 687 cm−1
HRMS calc. for C31H24N2O2 (M + H)+, 457.1911; found,
457.1913.
4,6,9-Trimethyl-6-(2-oxo-2-phenylethyl)-4H-pyrido[4,3,2-gh]
phenanthridin-5(6H)-one (3fa). Purified by column chromato-
graphy (petroleum ether/ethyl acetate = 7/1, v/v). Pale yellow
solid, mp 190–192 °C. 1H NMR (600 MHz, CDCl3) δ 8.38 (d, J =
8.4 Hz, 1H), 8.22 (d, J = 8.3 Hz, 1H), 7.95 (d, J = 7.3 Hz, 2H),
7.82 (t, J = 8.1 Hz, 1H), 7.75 (s, 1H), 7.57–7.49 (m, 1H),
7.45–7.37 (m, 3H), 7.26 (d, J = 7.8 Hz, 2H), 4.78 (d, J = 17.8 Hz,
1H), 4.27 (d, J = 17.8 Hz, 1H), 3.64 (s, 3H), 2.51 (s, 3H), 1.65 (s,
3H). 13C NMR (151 MHz, CDCl3) δ 198.3, 174.3, 160.2, 144.7,
139.1, 139.0, 136.3, 133.5, 133.1, 131.7, 129.0, 128.4, 128.2,
128.0, 122.3, 120.6, 115.8, 111.8, 110.5, 48.9, 48.3, 29.9, 29.8,
21.5. IR (film) νmax: 2917, 1658, 1589, 1449, 1341, 1219,
1089, 1004, 805, 756, 689 cm−1. HRMS calc. for C26H22N2O2
(M + H)+, 395.1754; found, 395.1754.
General procedure for the oxidative decarboxylative cascade
cyclization
Acrylamide 1 (0.3 mmol), α-keto acid 2 (0.9 mmol), Ag2O
9-Methoxy-4,6-dimethyl-6-(2-oxo-2-phenylethyl)-4H-pyrido
(0.015 mmol), (NH4)2S2O8 (0.9 mmol) and acetone/H2O [4,3,2-gh]phenanthridin-5(6H)-one (3ga). Purified by column
[3.0 mL, 1/1.3 (v/v)] were added in a sealed tube with a Teflon- chromatography (petroleum ether/ethyl acetate = 8/1, v/v). Pale
lined cap. The mixture was allowed to stir at 100 °C for yellow solid, mp 179–182 °C. 1H NMR (600 MHz, CDCl3) δ 8.37
12 hours. After the substrate was consumed, the reaction (d, J = 9.1 Hz, 1H), 8.15 (d, J = 8.3 Hz, 1H), 7.99–7.93 (m, 2H),
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7.80 (t, J = 8.1 Hz, 1H), 7.53 (t, J = 7.4 Hz, 1H), 7.42 (t, J = graphy (petroleum ether/ethyl acetate = 6/1, v/v). Pale yellow
1
7.8 Hz, 2H), 7.34 (d, J = 2.6 Hz, 1H), 7.23–7.17 (m, 2H), 4.76 (d, solid, mp 221–223 °C. H NMR (600 MHz, CDCl3) δ 8.43 (dd,
J = 17.8 Hz, 1H), 4.28 (d, J = 17.8 Hz, 1H), 3.91 (s, 3H), 3.63 (s, J = 9.1, 5.9 Hz, 1H), 8.15 (d, J = 8.3 Hz, 1H), 7.98–7.92 (m, 2H),
3H), 1.66 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 198.2, 174.2, 7.81 (t, J = 8.1 Hz, 1H), 7.58 (dd, J = 9.9, 2.7 Hz, 1H), 7.52 (t, J =
160.7, 160.2, 146.3, 139.2, 136.3, 133.6, 133.1, 131.8, 128.4, 7.4 Hz, 1H), 7.41 (t, J = 7.8 Hz, 2H), 7.33–7.28 (m, 1H), 7.26 (d,
128.3, 123.7, 117.5, 117.0, 115.5, 111.2, 109.8, 109.1, 55.5, 48.8, J = 7.9 Hz, 1H), 4.76 (d, J = 17.9 Hz, 1H), 4.29 (d, J = 17.8 Hz,
48.4, 29.9, 29.8. IR (film) νmax: 2922, 1668, 1581, 1461, 1341, 1H), 3.63 (s, 3H), 1.65 (s, 3H). 13C NMR (151 MHz, CDCl3)
1230, 1166, 1008, 801, 758, 689 cm−1. HRMS calc. for δ 198.3, 174.0, 162.7 (d, J = 248.2 Hz), 161.7, 145.9 (d, J =
C26H22N2O3 (M + H)+, 411.1703; found, 411.1705.
12.1 Hz), 139.3, 136.2, 133.2, 132.1, 128.4, 128.2, 124.5 (d, J =
4,6-Dimethyl-6-(2-oxo-2-phenylethyl)-9-phenoxy-4H-pyrido 9.7 Hz), 119.6 (d, J = 1.8 Hz), 115.7, 115.3 (d, J = 23.8 Hz), 113.8
[4,3,2-gh]phenanthridin-5(6H)-one (3ha). Purified by column (d, J = 20.4 Hz), 111.6, 110.7, 48.8, 48.5, 29.9, 29.7. IR (film)
chromatography (petroleum ether/ethyl acetate = 7/1, v/v). Pale νmax: 2917, 1683, 1656, 1610, 1578, 1470, 1341, 1221, 802, 757,
yellow solid, mp 194–196 °C. 1H NMR (600 MHz, CDCl3) δ 8.44 688 cm−1. HRMS calc. for C25H19FN2O2 (M + H)+, 399.1503;
(d, J = 9.0 Hz, 1H), 8.17 (d, J = 8.2 Hz, 1H), 7.96–7.88 (m, 2H), found, 399.1503.
7.81 (t, J = 8.1 Hz, 1H), 7.53–7.47 (m, 1H), 7.43–7.33 (m, 5H),
9-Chloro-4,6-dimethyl-6-(2-oxo-2-phenylethyl)-4H-pyrido[4,3,2-gh]
7.32 (dd, J = 8.9, 2.6 Hz, 1H), 7.23 (s, 1H), 7.17–7.12 (m, 1H), phenanthridin-5(6H)-one (3la). Purified by column chromato-
7.09 (dd, J = 8.5, 0.8 Hz, 2H), 4.70 (d, J = 17.9 Hz, 1H), 4.25 (d, graphy (petroleum ether/ethyl acetate = 5/1, v/v). Pale yellow
J = 17.8 Hz, 1H), 3.62 (s, 3H), 1.63 (s, 3H). 13C NMR (151 MHz, solid, mp 218–220 °C. 1H NMR (600 MHz, CDCl3) δ 8.38 (d, J =
CDCl3) δ 198.3, 174.2, 161.1, 158.2, 156.4, 146.0, 139.2, 136.2, 8.8 Hz, 1H), 8.17 (d, J = 8.2 Hz, 1H), 7.95 (dd, J = 7.9, 1.5 Hz,
133.4, 133.1, 131.9, 129.9, 128.4, 128.2, 124.2, 123.9, 119.8, 3H), 7.83 (t, J = 8.1 Hz, 1H), 7.56–7.51 (m, 1H), 7.50 (dd, J =
118.69, 118.67, 115.8, 115.6, 111.5, 110.3, 48.9, 48.4, 29.9, 29.7. 8.8, 2.2 Hz, 1H), 7.42 (dd, J = 10.8, 4.8 Hz, 2H), 7.29 (d, J =
IR (film) νmax: 3061, 2966, 2924, 1674, 1590, 1468, 1341, 1234, 7.9 Hz, 1H), 4.75 (d, J = 17.9 Hz, 1H), 4.28 (d, J = 17.8 Hz, 1H),
800, 757, 689 cm−1. HRMS calc. for C31H24N2O3 (M + H)+, 3.63 (s, 3H), 1.65 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 198.3,
473.1860; found, 473.1862.
174.2, 161.7, 145.3, 139.3, 136.1, 134.5, 133.2, 133.0, 132.2,
4,6-Dimethyl-6-(2-oxo-2-phenylethyl)-9-(trifluoromethyl)-4H- 128.6, 128.6, 128.2, 126.8, 123.9, 121.4, 115.8, 112.0, 111.1,
pyrido[4,3,2-gh]phenanthridin-5(6H)-one (3ia). Purified by 48.9, 48.5, 29.9, 29.7. IR (film) νmax: 3084, 2926, 2921, 1677,
column chromatography (petroleum ether/ethyl acetate = 5/1, 1591, 1466, 1339, 1225, 814, 770, 688 cm−1. HRMS calc. for
v/v). Pale yellow solid, mp 202–204 °C. 1H NMR (600 MHz, C25H19ClN2O2 (M + H)+, 415.1208; found, 415.1211.
CDCl3) δ 8.58 (d, J = 8.6 Hz, 1H), 8.29–8.20 (m, 2H), 7.98–7.92
9-Bromo-4,6-dimethyl-6-(2-oxo-2-phenylethyl)-4H-pyrido[4,3,2-
(m, 2H), 7.89 (td, J = 8.1, 1.3 Hz, 1H), 7.75 (d, J = 8.6 Hz, 1H), gh]phenanthridin-5(6H)-one (3ma). Purified by column chrom-
7.56–7.50 (m, 1H), 7.43 (t, J = 7.8 Hz, 2H), 7.37 (d, J = 8.0 Hz, atography (petroleum ether/ethyl acetate = 4/1, v/v). Pale yellow
1H), 4.78 (dd, J = 17.9, 1.3 Hz, 1H), 4.32 (dd, J = 17.9, 1.2 Hz, solid, mp 240–242 °C. 1H NMR (600 MHz, CDCl3) δ 8.32 (d, J =
1H), 3.65 (s, 3H), 1.67 (s, 3H). 13C NMR (151 MHz, CDCl3) 8.8 Hz, 1H), 8.19 (d, J = 8.3 Hz, 1H), 8.12 (d, J = 2.0 Hz, 1H),
δ 198.3, 173.9, 162.1, 143.9, 139.4, 136.1, 133.3, 132.7, 132.4, 7.98–7.91 (m, 2H), 7.84 (t, J = 8.1 Hz, 1H), 7.64 (dd, J = 8.7,
130.5 (q, J = 32.7 Hz), 128.5, 128.2, 127.0 (q, J = 4.1 Hz), 125.2, 2.1 Hz, 1H), 7.54 (t, J = 7.4 Hz, 1H), 7.42 (t, J = 7.8 Hz, 2H), 7.31
124.0 (q, J = 272.4 Hz), 123.6, 122.0 (q, J = 3.3 Hz), 116.1, 112.6, (d, J = 7.9 Hz, 1H), 4.74 (d, J = 17.8 Hz, 1H), 4.28 (d, J = 17.8
112.0, 49.0, 48.5, 30.0, 29.7. IR (film) νmax: 2962, 2926, 1678, Hz, 1H), 3.63 (s, 3H), 1.64 (s, 3H). 13C NMR (151 MHz, CDCl3)
1594, 1450, 1467, 1341, 1121, 817, 751, 688 cm−1. HRMS calc. δ 198.3, 174.0, 161.7, 145.5, 139.4, 136.1, 133.3, 133.1, 132.2,
for C26H19F3N2O2 (M + H)+, 449.1471; found, 449.1472.
131.8, 129.4, 128.5, 128.2, 124.1, 122.6, 121.8, 115.8, 112.0,
4,6-Dimethyl-5-oxo-6-(2-oxo-2-phenylethyl)-5,6-dihydro-4H- 111.3, 48.9, 48.5, 30.0, 29.7. IR (film) νmax: 3083, 2962, 2920,
pyrido[4,3,2-gh]phenanthridine-9-carbonitrile (3ja). Purified 1676, 1591, 1467, 1338, 1224, 814, 754, 688 cm−1. HRMS calc.
by column chromatography (petroleum ether/ethyl acetate = for C25H19BrN2O2 (M + H)+, 459.0703; found, 459.0706.
3/1, v/v). Pale yellow solid, mp 229–231 °C. 1H NMR (600 MHz,
11-Fluoro-4,6-dimethyl-6-(2-oxo-2-phenylethyl)-4H-pyrido[4,3,2-
CDCl3) δ 8.50 (dd, J = 5.6, 2.9 Hz, 1H), 8.27 (s, 1H), 8.20 (d, J = gh]phenanthridin-5(6H)-one (3na). Purified by column chrom-
8.3 Hz, 1H), 7.95 (d, J = 8.2 Hz, 2H), 7.92–7.86 (m, 1H), atography (petroleum ether/ethyl acetate = 5/1, v/v). Pale yellow
1
7.74–7.66 (m, 1H), 7.58–7.51 (m, 1H), 7.43 (t, J = 7.8 Hz, 2H), solid, mp 207–210 °C. H NMR (600 MHz, CDCl3) δ 8.70 (dd,
7.39 (d, J = 7.9 Hz, 1H), 4.75 (dd, J = 17.9, 0.9 Hz, 1H), 4.34 (d, J = 8.5, 1.3 Hz, 1H), 7.95 (d, J = 7.3 Hz, 2H), 7.88 (t, J = 8.3 Hz,
J = 0.6 Hz, 1H), 3.64 (s, 3H), 1.66 (s, 3H). 13C NMR (151 MHz, 1H), 7.76 (d, J = 8.1 Hz, 1H), 7.58–7.47 (m, 2H), 7.42 (t, J =
CDCl3) δ 198.3, 173.8, 162.8, 143.8, 139.5, 136.0, 134.4, 133.4, 7.8 Hz, 2H), 7.36 (d, J = 8.0 Hz, 1H), 7.30–7.26 (m, 1H), 4.76 (d,
132.7, 132.3, 128.5, 128.2, 127.6, 126.2, 123.9, 118.6, 116.2, J = 17.8 Hz, 1H), 4.29 (d, J = 17.8 Hz, 1H), 3.65 (s, 3H), 1.65 (s,
112.63, 122.55, 112.0, 48.9, 48.6, 30.0, 29.6. IR (film) νmax
:
3H). 13C NMR (151 MHz, CDCl3) δ 198.3, 173.9, 161.4, 160.6 (d,
3062, 2924, 2225, 1672, 1592, 1469, 1342, 1225, 1005, 807, 748, J = 255.2 Hz), 146.5 (d, J = 2.6 Hz), 138.9, 136.2, 133.2, 132.3 (d,
688 cm−1. HRMS calc. for C26H19N3O2 (M + Na)+, 428.1369; J = 1.9 Hz), 131.4 (d, J = 5.0 Hz), 128.4, 128.2 (d, J = 8.2 Hz),
found, 428.1368.
125.4 (d, J = 3.4 Hz), 121.1, 120.9, 113.0 (d, J = 9.0 Hz), 112.6
9-Fluoro-4,6-dimethyl-6-(2-oxo-2-phenylethyl)-4H-pyrido[4,3,2-gh] (d, J = 24.0 Hz), 112.4, 111.6, 48.8, 48.3, 30.0, 29.7. IR (film)
phenanthridin-5(6H)-one (3ka). Purified by column chromato- νmax: 2966, 2930, 1666, 1583, 1464, 1342, 1222, 765, 734,
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697 cm−1. HRMS calc. for C25H19FN2O2 (M + H)+, 399.1503; 126.5, 126.0, 120.8, 119.3, 113.4, 110.1, 48.8, 48.2, 30.0, 29.8.
found, 399.1504.
IR (film) νmax: 3011, 2962, 2922, 1675, 1581, 1426, 1332, 1221,
11-Chloro-4,6-dimethyl-6-(2-oxo-2-phenylethyl)-4H-pyrido[4,3,2- 837, 755, 688 cm−1. HRMS calc. for C29H22N2O2 (M + H)+,
gh]phenanthridin-5(6H)-one (3oa). Purified by column chrom- 431.1754; found, 431.1757.
atography (petroleum ether/ethyl acetate = 4/1, v/v). Pale yellow
4,6-Dimethyl-6-(2-oxo-2-phenylethyl)-4H-dibenzo[a,c]pyrido
solid, mp 224–226 °C. 1H NMR (600 MHz, CDCl3) δ 8.50 (d, J = [4,3,2-gh]phenanthridin-5(6H)-one (3sa). Purified by column
8.1 Hz, 1H), 8.28 (d, J = 8.3 Hz, 1H), 7.95 (dd, J = 7.3, 5.1 Hz, chromatography (petroleum ether/ethyl acetate = 5/1, v/v). Pale
3H), 7.86 (t, J = 8.1 Hz, 1H), 7.64 (t, J = 7.4 Hz, 1H), 7.58 (t, J = yellow solid, mp 234–236 °C. 1H NMR (600 MHz, CDCl3) δ 9.07
7.4 Hz, 1H), 7.53 (t, J = 7.4 Hz, 1H), 7.42 (t, J = 7.7 Hz, 2H), 7.31 (dd, J = 8.1, 1.1 Hz, 1H), 8.87 (d, J = 7.9 Hz, 1H), 8.68 (d, J =
(d, J = 7.9 Hz, 1H), 4.79 (d, J = 17.8 Hz, 1H), 4.28 (d, J = 7.7 Hz, 1H), 8.58 (dd, J = 13.4, 8.4 Hz, 2H), 8.02–7.94 (m, 2H),
17.8 Hz, 1H), 3.65 (s, 3H), 1.66 (s, 3H). 13C NMR (151 MHz, 7.83–7.77 (m, 1H), 7.70–7.61 (m, 3H), 7.56 (ddd, J = 8.1, 7.0,
CDCl3) δ 198.4, 174.3, 160.2, 144.6, 139.2, 136.3, 133.4, 133.1, 1.0 Hz, 1H), 7.54–7.49 (m, 1H), 7.42 (dd, J = 10.7, 4.9 Hz, 2H),
131.7, 129.5, 128.8, 128.4, 128.2, 126.2, 122.9, 122.5, 116.0, 7.26 (s, 1H), 4.92 (d, J = 17.8 Hz, 1H), 4.36 (d, J = 17.8 Hz, 1H),
112.1, 110.9, 48.9, 48.4, 29.9, 29.8. IR (film) νmax: 2962, 2925, 3.69 (s, 3H), 1.74 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 198.4,
1677, 1590, 1462, 1414, 1377, 1261, 801, 687 cm−1. HRMS calc. 174.2, 158.5, 141.7, 138.9, 136.4, 133.4, 133.2, 131.3, 130.8,
for C25H19ClN2O2 (M + H)+, 415.1208; found, 415.1205.
130.6, 130.6, 128.8, 128.6, 128.5, 128.2, 128.1, 127.1, 126.8,
11-Methoxy-4,6-dimethyl-6-(2-oxo-2-phenylethyl)-4H-pyrido 126.4, 125.3, 123.5, 122.2, 120.9, 118.0, 113.9, 109.7, 48.7, 48.5,
[4,3,2-gh]phenanthridin-5(6H)-one (3pa). Purified by column 30.1, 30.0. IR (film) νmax: 3010, 2910, 1671, 1613, 1581, 1567,
chromatography (petroleum ether/ethyl acetate = 5/1, v/v). Pale 1448, 1338, 1218, 754, 727, 691 cm−1. HRMS calc. for
yellow solid, mp 219–221 °C. 1H NMR (600 MHz, CDCl3) δ 8.50 C33H24N2O2 (M + H)+, 481.1911; found, 481.1913.
(d, J = 8.1 Hz, 1H), 8.27 (d, J = 8.3 Hz, 1H), 7.99–7.88 (m, 3H),
4-Methyl-6-(2-oxo-2-phenylethyl)-6-phenyl-4H-pyrido[4,3,2-gh]
7.85 (t, J = 8.1 Hz, 1H), 7.64 (t, J = 7.5 Hz, 1H), 7.57 (t, J = 7.4 phenanthridin-5(6H)-one (3ta). Purified by column chromato-
Hz, 1H), 7.52 (t, J = 7.3 Hz, 1H), 7.42 (t, J = 7.6 Hz, 2H), 7.30 (d, graphy (petroleum ether/ethyl acetate = 6/1, v/v). Pale yellow
1
J = 7.9 Hz, 1H), 4.80 (d, J = 17.8 Hz, 1H), 4.28 (d, J = 17.8 Hz, solid, mp 203–205 °C. H NMR (600 MHz, CDCl3) δ 8.52 (dd,
1H), 3.64 (s, 3H), 1.66 (s, 3H), 0.07 (s, 3H). 13C NMR (151 MHz, J = 8.1, 1.3 Hz, 1H), 8.28 (d, J = 8.2 Hz, 1H), 8.03–7.94 (m, 3H),
CDCl3) δ 198.3, 174.3, 160.2, 144.6, 139.2, 136.3, 133.4, 133.1, 7.83 (t, J = 8.1 Hz, 1H), 7.65 (ddd, J = 8.2, 7.0, 1.4 Hz, 1H), 7.60
131.7, 129.5, 128.8, 128.4, 128.2, 126.2, 122.9, 122.5, 115.9, (ddd, J = 8.2, 7.0, 1.4 Hz, 1H), 7.57–7.52 (m, 1H), 7.46–7.39 (m,
112.1, 110.9, 48.9, 48.4, 29.9, 29.8, 1.0. IR (film) νmax: 2962, 2H), 7.27 (d, J = 8.0 Hz, 1H), 7.23–7.12 (m, 5H), 5.17 (d, J =
2910, 1656, 1590, 1464, 1416, 1342, 1261, 800, 761 cm−1
HRMS calc. for C26H22N2O3 (M + H)+, 411.1703; found, (151 MHz, CDCl3) δ 198.2, 171.8, 158.3, 144.5, 141.4, 139.1,
411.1703. 136.5, 133.3, 133.1, 131.8, 129.9, 128.8, 128.6, 128.5, 128.3,
.
17.6 Hz, 1H), 4.66 (d, J = 17.6 Hz, 1H), 3.66 (s, 3H). 13C NMR
4,6,8,10-Tetramethyl-6-(2-oxo-2-phenylethyl)-4H-pyrido[4,3,2- 127.4, 127.0, 126.6, 123.0, 122.5, 116.1, 113.1, 111.2, 56.7, 49.1,
gh]phenanthridin-5(6H)-one (3qa). Purified by column chrom- 30.3. IR (film) νmax: 3060, 3027, 2922, 1667, 1590, 1468, 1357,
atography (petroleum ether/ethyl acetate = 6/1, v/v). Pale yellow 1219, 755, 701 cm−1. HRMS calc. for C30H22N2O2 (M + H)+,
solid, mp 214–216 °C. 1H NMR (600 MHz, CDCl3) δ 8.22 (d, J = 433.1754; found, 433.1757.
8.3 Hz, 1H), 8.12 (s, 1H), 7.94 (dd, J = 5.3, 4.1 Hz, 2H), 7.78 (t,
6-Benzyl-4-methyl-6-(2-oxo-2-phenylethyl)-4H-pyrido[4,3,2-gh]
J = 8.1 Hz, 1H), 7.53–7.47 (m, 1H), 7.40 (t, J = 7.8 Hz, 2H), 7.32 phenanthridin-5(6H)-one (3ua). Purified by column chromato-
(s, 1H), 7.24 (d, J = 7.8 Hz, 2H), 4.81 (dd, J = 17.7, 1.3 Hz, 1H), graphy (petroleum ether/ethyl acetate = 5/1, v/v). Pale yellow
1
4.21 (dd, J = 17.7, 1.4 Hz, 1H), 3.64 (s, 3H), 2.61 (s, 3H), 2.51 (s, solid, mp 234–236 °C. H NMR (600 MHz, CDCl3) δ 8.48 (dd,
3H), 1.64 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 198.5, 174.4, J = 8.4, 1.0 Hz, 1H), 8.11 (d, J = 8.2 Hz, 1H), 8.03 (dd, J = 8.2,
157.5, 141.5, 139.1, 136.6, 136.6, 135.5, 133.4, 133.0, 131.2, 1.0 Hz, 1H), 7.97 (dd, J = 8.3, 1.2 Hz, 2H), 7.69 (ddd, J = 8.2,
131.2, 128.4, 128.1, 122.5, 119.8, 116.2, 111.9, 110.5, 48.7, 48.6, 7.0, 1.3 Hz, 1H), 7.64–7.56 (m, 2H), 7.56–7.50 (m, 1H),
30.2, 29.8, 21.8, 18.1. IR (film) νmax: 2959, 2923, 1644, 1612, 7.46–7.36 (m, 2H), 6.88–6.84 (m, 1H), 6.83 (d, J = 7.8 Hz, 1H),
1589, 1464, 1340, 1221, 1143, 767, 690 cm−1. HRMS calc. for 6.75 (t, J = 7.7 Hz, 2H), 6.43–6.36 (m, 2H), 4.95 (d, J = 17.8 Hz,
C27H24N2O2 (M + Na)+, 431.1730; found, 431.1727.
1H), 4.41 (d, J = 17.8 Hz, 1H), 3.45 (d, J = 12.3 Hz, 1H),
4,6-Dimethyl-6-(2-oxo-2-phenylethyl)-4H-benzo[a]pyrido[4,3,2-gh] 3.41–3.32 (m, 4H). 13C NMR (151 MHz, CDCl3) δ 198.1, 172.7,
phenanthridin-5(6H)-one (3ra). Purified by column chromato- 159.0, 144.5, 138.5, 136.4, 135.0, 133.2, 132.2, 131.4, 129.6,
graphy (petroleum ether/ethyl acetate = 6/1, v/v). Pale yellow 129.2, 128.7, 128.5, 128.3, 127.1, 126.6, 126.3, 123.0, 122.6,
solid, mp 217–219 °C. 1H NMR (600 MHz, CDCl3) δ 9.05 (d, J = 115.5, 114.1, 110.3, 54.1, 50.4, 49.4, 29.3. IR (film) νmax: 2960,
8.5 Hz, 1H), 8.77 (d, J = 8.6 Hz, 1H), 7.96 (td, J = 17.8, 9.0 Hz, 2925, 1673, 1590, 1464, 1378, 1261, 1097, 1023, 802, 693 cm−1
.
4H), 7.88 (dd, J = 8.4, 6.7 Hz, 2H), 7.71–7.66 (m, 1H), 7.61 (t, HRMS calc. for C31H24N2O2 (M + H)+, 457.1911; found,
J = 7.4 Hz, 1H), 7.52 (t, J = 7.4 Hz, 1H), 7.42 (t, J = 7.8 Hz, 2H), 457.1908.
7.32 (d, J = 7.9 Hz, 1H), 4.82 (d, J = 17.9 Hz, 1H), 4.29 (d, J =
4,6-Dimethyl-6-(2-oxo-2-(p-tolyl)ethyl)-4H-pyrido[4,3,2-gh]phen-
17.9 Hz, 1H), 3.69 (s, 3H), 1.69 (s, 3H). 13C NMR (151 MHz, anthridin-5(6H)-one (3ab). Purified by column chromatography
CDCl3) δ 198.4, 174.2, 159.4, 144.5, 139.0, 136.3, 133.5, 133.1, (petroleum ether/ethyl acetate = 7/1, v/v). Pale yellow solid, mp
1
132.9, 131.4, 129.9, 129.7, 128.7, 128.4, 128.2, 128.1, 127.4, 248–250 °C. H NMR (600 MHz, CDCl3) δ 8.49 (d, J = 8.2 Hz,
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1H), 8.26 (d, J = 8.3 Hz, 1H), 7.94 (d, J = 8.2 Hz, 1H), 7.85 (dt, yellow solid, mp 197–199 °C. 1H NMR (600 MHz, CDCl3) δ 8.50
J = 8.0, 4.0 Hz, 3H), 7.63 (t, J = 7.5 Hz, 1H), 7.57 (dd, J = 7.9, (d, J = 7.8 Hz, 1H), 8.28 (d, J = 8.3 Hz, 1H), 7.99–7.91 (m, 1H),
7.2 Hz, 1H), 7.30 (d, J = 7.9 Hz, 1H), 7.21 (d, J = 8.1 Hz, 2H), 7.86 (t, J = 8.1 Hz, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.68–7.62 (m,
4.77 (d, J = 17.8 Hz, 1H), 4.25 (d, J = 17.8 Hz, 1H), 3.64 (s, 3H), 1H), 7.62–7.56 (m, 2H), 7.41 (td, J = 8.0, 5.6 Hz, 1H), 7.30 (d,
2.38 (s, 3H), 1.65 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 197.9, J = 7.9 Hz, 1H), 7.23 (td, J = 8.2, 2.3 Hz, 1H), 4.76 (d, J =
174.3, 160.3, 144.6, 143.9, 139.2, 133.9, 133.4, 131.7, 129.5, 17.9 Hz, 1H), 4.24 (d, J = 17.9 Hz, 1H), 3.64 (s, 3H), 1.66 (s,
129.1, 128.7, 128.3, 126.2, 122.9, 122.5, 115.9, 112.1, 110.9, 3H). 13C NMR (151 MHz, CDCl3) δ 197.2, 174.1, 162.7 (d, J =
48.9, 48.4, 29.9, 29.7, 21.7. IR (film) νmax: 2962, 2925, 2870, 247.6 Hz), 160.0, 144.6, 139.1, 138.4 (d, J = 6.2 Hz), 133.4,
1662, 1591, 1463, 1387, 1261, 801, 702, 687 cm−1. HRMS calc. 131.8, 130.1 (d, J = 7.6 Hz), 129.4, 128.8, 126.3, 124.0 (d, J =
for C26H22N2O2 (M + H)+, 395.1754; found, 395.1752.
6-(2-(4-Fluorophenyl)-2-oxoethyl)-4,6-dimethyl-4H-pyrido[4,3,2- 22.3 Hz), 112.0, 111.0, 48.8, 48.4, 29.9, 29.8. IR (film) νmax
2.9 Hz), 122.9, 122.6, 120.1 (d, J = 21.4 Hz), 116.0, 114.9 (d, J =
:
gh]phenanthridin-5(6H)-one (3ac). Purified by column chrom- 3065, 2965, 2929, 1662, 1611, 1587, 1464, 1368, 1244, 1077,
atography (petroleum ether/ethyl acetate = 6/1, v/v). Pale yellow 895, 757 cm−1. HRMS calc. for C25H19FN2O2 (M + H)+,
solid, mp 252–254 °C. 1H NMR (600 MHz, CDCl3) δ 8.50 (d, J = 399.1503; found, 399.1503.
8.2 Hz, 1H), 8.27 (d, J = 8.3 Hz, 1H), 7.99–7.96 (m, 2H), 7.95
6-(2-(3-Chlorophenyl)-2-oxoethyl)-4,6-dimethyl-4H-pyrido
(dd, J = 8.2, 0.4 Hz, 1H), 7.85 (t, J = 8.1 Hz, 1H), 7.69–7.61 (m, [4,3,2-gh]phenanthridin-5(6H)-one (3ag). Purified by column
1H), 7.61–7.53 (m, 1H), 7.30 (d, J = 7.9 Hz, 1H), 7.08 (dd, J = chromatography (petroleum ether/ethyl acetate = 6/1, v/v). Pale
14.4, 5.7 Hz, 2H), 4.76 (d, J = 17.8 Hz, 1H), 4.24 (d, J = 17.7 Hz, yellow solid, mp 218–220 °C. 1H NMR (600 MHz, CDCl3) δ 8.51
1H), 3.64 (s, 3H), 1.65 (s, 3H). 13C NMR (151 MHz, CDCl3) (d, J = 7.9 Hz, 1H), 8.28 (d, J = 8.2 Hz, 1H), 7.95 (dd, J = 8.2, 0.8
δ 196.8, 174.2, 165.7 (d, J = 254.6 Hz), 160.1, 144.6, 139.1, Hz, 1H), 7.93–7.90 (m, 1H), 7.86 (t, J = 8.1 Hz, 1H), 7.83 (d, J =
133.4, 132.8 (d, J = 2.9 Hz), 131.8, 130.8 (d, J = 9.3 Hz), 129.4, 7.9 Hz, 1H), 7.68–7.63 (m, 1H), 7.62–7.56 (m, 1H), 7.52–7.47
128.8, 126.2, 122.9, 122.6, 115.8 (d, J = 61.9 Hz), 115.4, 112.0, (m, 1H), 7.37 (t, J = 7.9 Hz, 1H), 7.31 (d, J = 7.9 Hz, 1H), 4.75
111.0, 48.6, 48.4, 29.9, 29.8. IR (film) νmax: 3442, 3066, 2965, (d, J = 17.9 Hz, 1H), 4.23 (d, J = 17.9 Hz, 1H), 3.64 (s, 3H), 1.66
2917, 1666, 1590, 1495, 1341, 1224, 832, 781, 597 cm−1. HRMS (s, 3H). 13C NMR (151 MHz, CDCl3) δ 197.2, 174.1, 160.0,
calc. for C25H19FN2O2 (M + H)+, 399.1503; found, 399.1502.
144.6, 139.1, 137.8, 134.7, 133.4, 133.0, 131.8, 129.8, 129.5,
6-(2-(4-Chlorophenyl)-2-oxoethyl)-4,6-dimethyl-4H-pyrido 128.9, 128.4, 126.34, 126.30, 122.9, 122.6, 116.0, 112.0, 111.0,
[4,3,2-gh]phenanthridin-5(6H)-one (3ad). Purified by column 48.7, 48.5, 29.9, 29.8. IR (film) νmax: 3091, 3063, 2928, 1663,
chromatography (petroleum ether/ethyl acetate = 5/1, v/v). Pale 1588, 1571, 1465, 1340, 1219, 1078, 807, 753 cm−1. HRMS calc.
yellow solid, mp 268–270 °C. 1H NMR (600 MHz, CDCl3) δ 8.51 for C25H19ClN2O2 (M + H)+, 415.1208; found, 415.1209.
(d, J = 8.1 Hz, 1H), 8.28 (d, J = 8.3 Hz, 1H), 7.94 (d, J = 8.2 Hz,
6-(2-(3-Bromophenyl)-2-oxoethyl)-4,6-dimethyl-4H-pyrido
1H), 7.87 (dd, J = 17.1, 8.4 Hz, 3H), 7.68–7.63 (m, 1H), [4,3,2-gh]phenanthridin-5(6H)-one (3ah). Purified by column
7.61–7.56 (m, 1H), 7.39 (d, J = 8.6 Hz, 2H), 7.31 (d, J = 7.9 Hz, chromatography (petroleum ether/ethyl acetate = 5/1, v/v). Pale
1H), 4.75 (d, J = 17.8 Hz, 1H), 4.23 (d, J = 17.8 Hz, 1H), 3.65 (s, yellow solid, mp 220–222 °C. 1H NMR (600 MHz, CDCl3) δ 8.51
3H), 1.65 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 197.2, 174.1, (d, J = 8.1 Hz, 1H), 8.28 (d, J = 8.3 Hz, 1H), 8.08 (t, J = 1.6 Hz,
160.0, 144.6, 139.5, 139.1, 134.7, 133.5, 131.8, 129.6, 129.5, 1H), 7.95 (d, J = 8.1 Hz, 1H), 7.89–7.82 (m, 2H), 7.68–7.62 (m,
128.8, 128.8, 126.3, 122.9, 122.6, 116.0, 112.0, 111.0, 48.6, 48.4, 2H), 7.61–7.55 (m, 1H), 7.30 (t, J = 7.7 Hz, 2H), 4.74 (d, J = 17.9
29.9, 29.8. IR (film) νmax: 3066, 3026, 2990, 2933, 1657, 1604, Hz, 1H), 4.23 (d, J = 17.9 Hz, 1H), 3.64 (s, 3H), 1.66 (s, 3H). 13C
1499, 1310, 1217, 826, 793, 607 cm−1. HRMS calc. for NMR (151 MHz, CDCl3) δ 197.1, 174.1, 159.9, 144.6, 139.1,
C25H19ClN2O2 (M + H)+, 415.1208; found, 415.1206.
138.0, 135.9, 133.4, 131.8, 131.3, 130.0, 129.5, 128.9, 126.7,
6-(2-(4-Bromophenyl)-2-oxoethyl)-4,6-dimethyl-4H-pyrido 126.3, 122.9, 122.8, 122.6, 116.0, 112.0, 111.0, 48.7, 48.5, 29.9,
[4,3,2-gh]phenanthridin-5(6H)-one (3ae). Purified by column 29.8. IR (film) νmax: 2960, 2925, 2853, 1663, 1589, 1464, 1416,
chromatography (petroleum ether/ethyl acetate = 6/1, v/v). Pale 1340, 1261, 1096, 803, 752 cm−1. HRMS calc. for C25H19BrN2O2
yellow solid, mp 272–274 °C. 1H NMR (600 MHz, CDCl3) δ 8.51 (M + H)+, 459.0703; found, 459.0704.
(d, J = 8.1 Hz, 1H), 8.28 (d, J = 8.3 Hz, 1H), 7.94 (d, J = 8.1 Hz,
6-(2-(2-Fluorophenyl)-2-oxoethyl)-4,6-dimethyl-4H-pyrido
1H), 7.87 (t, J = 8.1 Hz, 1H), 7.81 (d, J = 8.6 Hz, 2H), 7.65 (dd, [4,3,2-gh]phenanthridin-5(6H)-one (3ai). Purified by column
J = 11.1, 4.0 Hz, 1H), 7.62–7.52 (m, 3H), 7.31 (d, J = 7.9 Hz, chromatography (petroleum ether/ethyl acetate = 6/1, v/v). Pale
1H), 4.74 (d, J = 17.8 Hz, 1H), 4.22 (d, J = 17.8 Hz, 1H), 3.64 (s, yellow solid, mp 203–205 °C. 1H NMR (600 MHz, CDCl3) δ 8.51
3H), 1.65 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 197.4, 174.1, (d, J = 8.0 Hz, 1H), 8.28 (d, J = 8.3 Hz, 1H), 7.97 (d, J = 8.1 Hz,
160.0, 144.6, 139.1, 135.1, 133.4, 131.8, 131.7, 129.7, 129.5, 1H), 7.85 (t, J = 8.1 Hz, 1H), 7.73–7.67 (m, 1H), 7.67–7.62 (m,
128.9, 128.3, 126.3, 122.9, 122.6, 116.0, 112.0, 111.0, 110.0, 1H), 7.62–7.55 (m, 1H), 7.48 (tdd, J = 7.1, 5.0, 1.7 Hz, 1H), 7.30
48.6, 48.4, 29.9, 29.8. IR (film) νmax: 3061, 2959, 2923, 2869, (d, J = 7.9 Hz, 1H), 7.16 (dd, J = 11.0, 8.5 Hz, 1H), 7.10 (t, J =
1681, 1658, 1586, 1466, 1072, 819, 761, 649 cm−1. HRMS calc. 7.5 Hz, 1H), 4.77 (dd, J = 18.7, 3.6 Hz, 1H), 4.28 (dd, J = 18.7,
for C25H19BrN2O2 (M + H)+, 459.0703; found, 459.0702.
3.7 Hz, 1H), 3.64 (s, 3H), 1.64 (s, 3H). 13C NMR (151 MHz,
6-(2-(3-Fluorophenyl)-2-oxoethyl)-4,6-dimethyl-4H-pyrido CDCl3) δ 196.13 (d, J = 4.2 Hz), 174.2, 162.5 (d, J = 256.1 Hz),
[4,3,2-gh]phenanthridin-5(6H)-one (3af). Purified by column 160.2, 144.6, 139.2, 134.8 (d, J = 9.1 Hz), 133.4, 131.7, 130.7
chromatography (petroleum ether/ethyl acetate = 7/1, v/v). Pale (d, J = 2.3 Hz), 129.5, 128.8, 126.2, 124.6 (d, J = 12.5 Hz), 124.2
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(d, J = 3.2 Hz), 122.9, 122.5, 116.7 (d, J = 23.9 Hz), 115.9, 112.0, 7.83 (t, J = 8.1 Hz, 1H), 7.68–7.63 (m, 1H), 7.58 (dd, J = 11.1, 4.0
110.9, 53.3 (d, J = 8.8 Hz), 48.6 (d, J = 2.1 Hz), 29.9, 29.7. IR Hz, 1H), 7.55–7.52 (m, 1H), 7.28 (d, J = 7.9 Hz, 1H), 7.11 (d, J =
(film) νmax
1453, 1261, 801, 760, 747 cm−1. HRMS calc. for C25H19FN2O2 1H), 4.15 (d, J = 18.0 Hz, 1H), 3.62 (s, 3H), 1.65 (s, 3H). 13C
(M + H)+, 399.1503; found, 399.1506.
NMR (151 MHz, CDCl3) δ 187.4, 174.1, 156.0, 152.4, 146.1,
: 2962, 2925, 2853, 1676, 1656, 1590, 1573, 3.5 Hz, 1H), 6.48 (dd, J = 3.5, 1.7 Hz, 1H), 4.62 (d, J = 18.0 Hz,
6-(2-(2-Bromophenyl)-2-oxoethyl)-4,6-dimethyl-4H-pyrido 144.6, 139.1, 133.4, 131.7, 129.5, 128.8, 126.3, 122.9, 122.5,
[4,3,2-gh]phenanthridin-5(6H)-one (3aj). Purified by column 116.9, 115.9, 112.09, 112.04, 110.9, 48.5, 48.0, 29.9, 29.7. IR
chromatography (petroleum ether/ethyl acetate = 5/1, v/v). Pale (film) νmax
: 2960, 2924, 2853, 1664, 1611, 1589, 1571,
yellow solid, mp 178–180 °C. 1H NMR (600 MHz, CDCl3) δ 8.52 1466, 1261, 882, 802, 761 cm−1. HRMS calc. for C23H18N2O3
(d, J = 8.2 Hz, 1H), 8.28 (d, J = 8.2 Hz, 1H), 8.02 (d, J = 8.1 Hz, (M + H)+, 371.1390; found, 371.1393.
1H), 7.85 (t, J = 8.1 Hz, 1H), 7.73–7.66 (m, 1H), 7.63–7.59 (m,
1H), 7.58–7.52 (m, 2H), 7.35 (td, J = 7.6, 0.9 Hz, 1H), 7.29 (d,
J = 7.9 Hz, 1H), 7.27–7.23 (m, 2H), 4.67 (d, J = 18.2 Hz, 1H), Conflicts of interest
4.21 (d, J = 18.2 Hz, 1H), 3.65 (s, 3H), 1.61 (s, 3H). 13C NMR
(151 MHz, CDCl3) δ 201.9, 173.8, 159.9, 144.6, 140.7, 139.2,
There are no conflicts to declare.
133.7, 133.5, 131.8, 131.5, 129.4, 128.9, 127.1, 126.3, 123.0,
122.6, 118.7, 116.0, 112.0, 111.0, 51.8, 48.9, 30.0, 29.8. IR
Acknowledgements
: 2959, 2922, 2866, 1666, 1609, 1587, 1465,
(film) νmax
1339, 1209, 821, 764, 749 cm−1. HRMS calc. for C25H19BrN2O2
(M + H)+, 459.0703; found, 459.0706.
We are grateful for financial support from the National Natural
Science Foundation of China (No. 21871114 and 21662021),
the Science and Technology Planning Project of Yunnan
Province (No. 2017FB016) and the Program for Innovative
Research Team (in Science and Technology) in Universities of
Yunnan Province.
4,6-Dimethyl-6-(2-(naphthalen-1-yl)-2-oxoethyl)-4H-pyrido
[4,3,2-gh]phenanthridin-5(6H)-one (3ak). Purified by column
chromatography (petroleum ether/ethyl acetate = 7/1, v/v). Pale
yellow solid, mp 208–210 °C. 1H NMR (600 MHz, CDCl3) δ 8.51
(d, J = 8.2 Hz, 1H), 8.26 (dd, J = 13.7, 8.5 Hz, 2H), 8.13–8.07 (m,
1H), 8.02 (d, J = 8.2 Hz, 1H), 7.93 (d, J = 8.2 Hz, 1H), 7.84 (t, J =
8.1 Hz, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.70–7.64 (m, 1H), 7.59
(dd, J = 11.1, 4.0 Hz, 1H), 7.55–7.49 (m, 1H), 7.42 (dd, J = 10.9,
4.0 Hz, 1H), 7.37 (ddd, J = 8.2, 6.9, 1.3 Hz, 1H), 7.30 (d, J =
7.9 Hz, 1H), 4.85 (d, J = 18.0 Hz, 1H), 4.33 (d, J = 18.0 Hz, 1H),
3.68 (s, 3H), 1.65 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 203.1,
174.2, 160.3, 144.7, 139.3, 135.9, 133.7, 133.5, 132.2, 131.8,
129.9, 129.4, 128.9, 128.1, 127.5, 127.4, 126.3, 126.2, 125.8,
124.4, 123.0, 122.6, 115.9, 112.1, 111.0, 51.9, 48.9, 30.0, 29.8.
IR (film) νmax: 2961, 2923, 2852, 1666, 1609, 1587, 1571,
1464, 1261, 801, 764, 749 cm−1. HRMS calc. for C29H22N2O2
(M + H)+, 431.1754; found, 431.1754.
4,6-Dimethyl-6-(2-oxo-2-(thiophen-2-yl)ethyl)-4H-pyrido[4,3,2-gh]
phenanthridin-5(6H)-one (3al). Purified by column chromato-
graphy (petroleum ether/ethyl acetate = 4/1, v/v). Pale yellow
solid, mp 203–205 °C. 1H NMR (600 MHz, CDCl3) δ 8.49 (d, J =
8.1 Hz, 1H), 8.25 (d, J = 8.3 Hz, 1H), 7.97 (dd, J = 8.2, 1.0 Hz,
1H), 7.86–7.77 (m, 2H), 7.67–7.61 (m, 1H), 7.60–7.52 (m, 2H),
7.27 (d, J = 8.0 Hz, 1H), 7.10 (t, J = 4.2 Hz, 1H), 4.72 (d, J =
17.6 Hz, 1H), 4.24 (d, J = 17.6 Hz, 1H), 3.62 (s, 3H), 1.65 (s,
3H). 13C NMR (151 MHz, CDCl3) δ 191.2, 174.0, 159.9, 144.6,
143.3, 139.1, 133.4, 132.2, 131.7, 129.4, 128.8, 127.9, 126.3,
122.9, 122.5, 115.9, 112.0, 110.9, 49.2, 48.3, 30.0, 29.8. IR
(film) νmax: 2960, 2924, 1658, 1611, 1589, 1572, 1464, 1343,
1261, 801, 729 cm−1. HRMS calc. for C23H18SN2O2 (M + H)+,
387.1162; found, 387.1163.
Notes and references
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