Tandem synthesis of pyrroloacridones via [3 + 2] alkyne annulation/ring-opening with concomitant intramolecular aldol condensation

Article abstract of DOI:10.1021/jo400539x

An efficient cascade strategy for the direct synthesis of pyrrolo[3,2,1-de]acridones 4a-v, 5a-h from iodo-pyranoquinolines 2a-i by the palladium-catalyzed regioselective [3 + 2] alkyne annulation/ring-opening followed by intramolecular aldol condensation under microwave irradiation is described. The chemistry involves the in situ formation of pyrroloquinolines Y, via palladium-catalyzed selective [3 + 2] annulation of iodopyranoquinolines and internal akynes with ring-opening and successive intramolecular cross-aldol condensation. Both the symmetrical and unsymmetrical internal alkynes were reacted smoothly to provide the desired pyrroloacridones in good yields. This methodology provides the facile conversion of easily accessble iodopyranoquinoline into highly functionalized biologically important pyrroloacridones in a single process.

Full text of DOI:10.1021/jo400539x

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Article
Tandem Synthesis of Pyrroloacridones via [3 + 2] Alkyne Annulation/
Ring Opening with Concomitant Intramolecular Aldol Condensation
Akhilesh K. Verma, Siva K.Reddy Kotla, Trapti Aggarwal,
Sonu Kumar, Rakesh Kumar Tiwari, and Hemlata Nimesh
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo400539x • Publication Date (Web): 03 May 2013
Downloaded from http://pubs.acs.org on May 6, 2013
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Tandem Synthesis of Pyrroloacridones via [3 + 2]
Alkyne Annulation/Ring Opening with Concomitant
Intramolecular Aldol Condensation
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Akhilesh K. Verma,†,* Siva K. Reddy Kotla,† Trapti Aggarwal, † Sonu Kumar,† Hemlata Nimesh¥
and Rakesh K. Tiwari‡
† Synthetic Organic Chemistry Laboratory, Department of Chemistry, University of Delhi,
Delhi, 110007, India
‡ Department of Biomedical & Pharmaceutical Sciences, College of Pharmacy,
University of Rhode Island, Kingston-02881, Rhode Island, USA
¥ Chemical Biology Laboratory, Department of Chemistry, University of Delhi,
Delhi, 110007, India
E-mail: averma@acbr.du.ac.in
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ABSTRACT: An efficient cascade strategy for the direct synthesis of pyrrolo[3,2,1-de]acridones
4a–v, 5a–h from iodo-pyranoquinolines 2a–i by the palladium-catalyzed regioselective [3 + 2]
alkyne annulation/ring opening followed by intramolecular aldol condensation under microwave
irradiation is described. The chemistry involves the insitu formation of pyrroloquinolines Y, via
palladium-catalyzed selective [3 + 2] annulation of iodopyranoquinolines and internal akynes
with ring opening and successive intramolecular cross-aldol condensation. Both the symmetrical
and unsymmetrical internal alkynes were reacted smoothly to provide the desired
pyrroloacridones in good yields. This methodology provides the facile conversion of easily
accessble iodopyranoquinoline into highly functionalized biologically important
pyrroloacridones in a single process.
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INTRODUCTION
The substituted acridines represent an important class of compounds which exhibit a wide
spectrum of biological activities.l Some of their derivatives inhibit the growth of cancerous cells
via binding to DNA.2 Amsacrine3 is one of acridine based drug which is in clinical use to cure
acute lymphoblastic leukemia (Figure 1, I). Significantly, the nucleus of pyrroloacridones and
pyrroloacridines family are associated with wide range of biological activities including
antihelmintic,4 antitumor5 and antifungal activity.6 The tetracyclic core of these compounds
enhances their DNA intercalation7 and topoisomerase I and II inhibition8 properties, where upon
provided the potential lead frameworks for the development of novel anticancer drugs. The
majority of these compounds were found in metabolites from marine sources such as
plakinidines (Figure 1, II and III) and alpkinidine (Figure 1, IV).9 Plakinidine A exhibited in
vitro activity against Nippostrongylus brastiliensis.4 In recent years, marine sponges have
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received considerable attention due to the production of secondary metabolites, with numerous
studies focusing on culturing these micro-organisms and screening them for the production of
bioactive compounds.10 Despite their significant biological activities, less attention has been paid
for the synthesis of pyrroloacridones,11–12 therefore the development of efficient and concise
protocol for the synthesis of these heterocyclic cores represents a major challenge for the organic
chemist.
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Me
O S O
Me
O
MeO
HN
N
Me
HN
N
N
HO
H2N
O
O
O
N
N
N
N
NH
NH
Me
N
Alpkinidine (IV)
Plakinidine A (II)
Plakinidine D (III)
Amsacrine (I)
Synthetic drug
Marine natural products
Figure 1. Biologically and medicinally important substituted acridines.
In the past decade, palladium-catalyzed reactions13 become known for the synthesis of
fused carbocyclic compounds and natural-product-like scaffolds14 because of its high reactivity,
tolerance towards many functional groups15 and excellent ability to trigger the π-systems, toward
C−C and C−N bond formations. Among various reactions, tandem cyclization16 have received a
considerable interest as these reactions can quickly synthesized the complex molecules from
simple starting material in an iterative manner.
In 2012, Shi and co-workers17 reported an interesting domino approach for the synthesis
of pyrrolo[2,3,4-kl]acridin-1-one from isatin using L-proline. In continuation of our ongoing
work on the synthesis of heterocyclic scaffolds from alkynes,18 recently we have reported the
first silver-catalyzed/iodine-mediated tandem synthesis of pyrrolo[1,2-a]quinolines (Q) from
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iodopyranoquinolines (P) via site-selective electrophilic cyclization (preferential attack of the
pyridyl nitrogen over aryl ring) and subsequent opening of pyran ring under mild reaction
conditions (Scheme 1, i). The formation of 5-endo-dig cyclized products Q over 6-endo-dig
cyclized products R, was supported by the quantum chemical calculations.19 Encouraged by the
above finding, we have extended this interesting chemistry for the direct synthesis of
pyrrolo[1,2-a]quinolines via palladium-catalyzed regioselective [3 + 2] alkyne annulation with
concomitant ring opening (Scheme 1, ii).20 During the course of our study, we have also
observed that the pyrrolo[1,2-a]quinolines having α-H (R2= alkyl) were insitu converted in to
pyrroloacridones via successive intramolecular aldol condensation. Herein, we wish to report the
full details of our study on the palladium-catalyzed tandem synthesis of highly functionalized
pyrrolo[3,2,1-de]acridones 4a–v, 5a–h from iodo-pyranoquinolines 2a–i by the [3 + 2] alkyne
annulations/ring opening with concomitant intramolecular cross aldol condensation. We have
explored various iodo-pyranoquinolines with variety of symmetrical and unsymmetrical internal
alkynes for the designed reaction.
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Scheme 1. Previous Work of our Laboratory
i. Synthesis of pyrrolo[1,2-a]quinolines via site-selective electrophilic cyclization and
subsequent ring opening.
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ii. Synthesis of pyrrolo[1,2-a]quinolines via palladium-catalyzed regioselective [3 + 2] alkyne
5
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annulation with concomitant ring opening.
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The designed tandem process for the direct sythesis of pyrroloacridones is advantageous
in improving the efficiency, atom economy, and modularity of the synthesis (Scheme 2).
Scheme 2. Designed Retrosynthetic Approach for the Tandem Synthesis of Pyrrolo[3,2,1-
de]acridones
RESULTS AND DISCUSSION
Preparation of 4-Iodopyrano[4,3-b]quinolines. The substrates 4-iodopyranoquinolines 2a–i,
required for designed approach, were prepared in good yields by the electrophilic iodocyclization
of 2-(alkynyl)quinoline-3-carbaldehydes 1a–i using standard procedure developed in our
laboratory (Scheme 3).21
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Scheme 3. Synthesis of 4-Iodopyrano[4,3-b]quinolines 2a–i
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To identify the optimal reaction conditions for the synthesis of pyrroloacridones, we
examined the reaction of 4-iodo-1-methoxy-3-(phenoxymethyl)-1H-pyrano[4,3-b]quinoline (2a)
with 1,2-di-p-tolylethyne (3a) using 3.0 equiv of LiCl and 2.0 equiv of NaOAc with 5 mol % of
Pd(OAc)2 in DMF at 120 °C for 10 min under microwave irradiation, the desired product 4a was
obtained in only 45% (Table 1, entry 1). When reaction was allowed to run for 15 and 20 min,
the desired product 4a was obtained in 60 and 78% yields, respectively (entries 2 and 3). When
the reaction was further allowed to run for 30 min, no significant improvement in the yield was
observed (entry 4). The efficiency of this organic transformation was affected when the catalyst
loading was decreased from 5 to 3 mol % (entry 5). When 5 mol % of PdCl2 was used, the
desired product 4a was obtained in 72% yield (entry 6). The Pd-complexes such as PdCl2(PPh3)2,
Pd(PPh3)4 and Pd2(dba)3 were also found to be effective and afforded the desired products in 74,
70 and 65% yields, respectively (entries 7–9). From entries 10 to 12, it is noticeable that other
solvents like DMSO, DMA and toulene afforded the desired product 4a in lower yields. Use of
KOAc as a base provided the product 4a in 70% yield (entry 13), while, significant decrease in
the yield was observed with K2CO3 and Na2CO3 (entries 14 and 15). Lowering the reaction
temperature, leads to incomplete conversion of the substrates (entries 16 and 17).
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Table 1. Optimization of the Reaction Conditionsa
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base
entry
1
solvent
DMF
catalyst
mol % t (min) yieldb
NaOAc
Pd(OAc)2
5
5
5
5
3
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65c
50d
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3
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
DMA
Toulene
DMF
DMF
DMF
DMF
DMF
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
KOAc
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
4
5
6
7
Pd(PPh3)2Cl2
Pd(PPh3)4
Pd2(dba)3
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
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K2CO3
Na2CO3
NaOAc
NaOAc
a Reactions were performed using 0.25 mmol of 2a, 2.0 equiv of NaOAc, 3.0 equiv
of LiCl, catalyst in 3.0 mL solvent at 120 °C under microwave irradiation. b Isolated
yield. c at 110 °C. d at 100 °C.
Synthesis of pyrrolo[3,2,1-de]acridones (4a–v) using symmetrical internal alkynes. With
this standard protocol in hand, we examined the scope and generality of the reaction by
employing a vide variety of iodopyranoquinolines 2a–i and alkynes 3a–e. Reaction of phenoxy
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substituted iodopyranoquinolines 2a–b, 2e, 2h with internal alkynes 3a–e afforded the desired
pyrrolo[3,2,1-de]acridones 4a–d, 4k–l and 4o–s in good yields (entries 1–5, 12–13 and 16–20).
However, reaction of benzyl substituted iodopyranoquinolines 2c, 2g and 2i with alkynes 3a–e
afforded the desired products 4e–i, 4n, 4t–v comparatively in lower yields (entries 6–10, 15, 21–
23 vs 1–5, 12–13, 16–20). The reaction of alkynes 3e and 3a with substrates 2d and 2f bearing
aliphatic substitutents at R2 provided the desired products 4j and 4m in 68 and 72% yields
respectivly (entries 11 and 14). A marginal improvement in the yields of the products was
observed with substrates bearing methyl and methoxy substituents at R1 (entries12–23 vs 1–11).
Substrates 2b and 2d bearing an ethyl group at R3 afforded the desired products 4b and 4j
comparatively in lower yields, and required 50 min for completion of the reaction (entries 5 and
11). Electron-rich heterocyclic internal alkyne 1,2-di(thiophen-3-yl)ethyne (3c), afforded the
desired products 4c, 4g, 4l and 4q in good yields (entries 3, 8, 13 and 18). The products of the
reaction were fully characterized by 1H and 13C NMR and mass spectroscopic data.
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Table 2. Synthesis of Pyrrolo[3,2,1-de]acridones using Developed Tandem Strategya
3a
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yieldb
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OMe
O
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4b
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O
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4c
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a Reactions were performed using 0.25 mmol of 2, 1.2 equiv of 3, 5 mol % of Pd(OAc)2,
3.0 equiv of LiCl and 2.0 equiv of NaOAc in 3.0 mL DMF at 120 °C under microwave
irradiation for 20 min unless otherwise noted. b Isolated yield. c For 50 min.d For 25 min.
It is evident from Table 2 that products were obtained in good yields with the presence of
phenoxy and benzyl group at R2. The presence of phenoxy and benzyl group (-I effect) at R2
increases the acidity of α-hydrogen of the pyrroloquinoline intermediate Y (generated in situ by
the [3 + 2] alyne annulations followed by the ring opening), and generates stable enolate Y'
(Scheme 4, a); however presence of an alkyl group (+ I effect) decreases the acidity and
generates the less stable enolate (Scheme 4, b). Thus, the attack of more stable enolate
(nucleophile) to the carbonyl carbon of the adjacent aldehydic group is faster and leads to the
higher yield of the product.
Scheme 4. Effect of Substituent R2 on the Reaction
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Synthesis of pyrrolo[3,2,1-de]acridones (5a–h) using unsymmetrical internal alkynes.
With our successful results on the symmetrical internal alkynes, next we employed the
unsymmetrical alkynes for this tandem transformation. A variety of unsymmetrical internal
alkynes 3f–i exhibiting different electronic properties at aryl substituents was evaluated (Table 3,
entries 1-8). The reaction of alkynes bearing a phenyl, 4-methoxyphenyl and thienyl moiety at
one end of the alkyne and electron-withdrawing p-substituted nitro aryl group at other end,
afforded the mixture of regioisomers in 60–72% yield (entries 2–8). This study proved that the
regioselectivity of the reaction was independent of electronic effects as most of the alkynes gave
mixtures of regioisomers of pyrroloacridones. The ratio of regioisomers was obtained on the
basis of their 1H NMR data analysis. The formation of major product was analyzed on the basis
of steric effect of substituents attached on the alkyne as previously reported by the Larock.22
Table 3. Synthesis of Pyrrolo[3,2,1-de]acridones 5a–h using Unsymmetrical Alkynes a
3f
3g
3h
3i
entry substrate alkyne
product (major)
ratio 5/6
yieldb
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a
All reactions were performed using pyranoquinolines 2 (0.25 mmol), 1.2 equiv of
internal alkynes 3, 5 mol % of Pd(OAc)2, 3.0 equiv of LiCl and 2.0 equiv of NaOAc
in 3.0 mL of DMF at 120 °C under microwave irradiation. Isolated yields.
Seperated by HPLC.
b
c
After obtaining a mixture of regioisomers with unsymmetrical alkynes, we have separated
1
the regioisomers 5c–d, 5f and 6c–d, 6f by HPLC to confirmed their structures. We analyzed H
and NOESY NMR data of product 5f and 6f to uncover the major isomer. However, due to the
spatial arrangement of bulky aryl group, no interaction between Ha and Hb was observed in
NOESY (Figure 2). Therefore, we have performed the 1D-NOE experiment by irradiating
various protons. The weak enhancement of Hb by the irradiation of Ha supported our concept that
the bulky group is adjacent to nitrogen at R4 (See supporting Information).
Figure 2. Spatial rearrangement of compound 5f and 6f
To validate our hypothesis, we next employed the TMS substituted unymmetrical alkynes.
Due to basic conditions employed in the reaction TMS group was removed during the course of
reaction and we obtained selectively single isomer 7a–b (Scheme 5). The reaction underwent
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smoothly with substrates 2a and 2e and afforded the desired single isomers 7a–b in good yields.
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The structure of the product 7a–b was confirmed by their spectral data H, 13C and NOESY
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analysis. The NOESY spectrum of 7a shows the interaction of H present on the pyrrole ring with
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proton present on the adjacent aryl ring as shown in Scheme 5. (see supporting information).
Scheme 5. Regioselective Synthesis of Pyrrolo[3,2,1-de]acridones 5a–h using TMS
Substituted Unsymmetrical Alkynes
1
A detailed study of H NMR revealed a significant shift of the Ha peak of the acridone ring
(from ׽8.09 to ׽7.27 ppm) (Figure 3), which could be attributed due to the anisotropic effect of
the aryl ring, which is believed to be perpendicular to this proton (For details see supporting
information).
7.85 (d, J = 8.0 Hz, 1H)
Hb; 7.71 (d, J = 8.0 Hz, 1H)
Due to the anisotropic effect the protons
Ha moves up field in the product 5f and
merged with other aromatic protons
appeared as multiplet.
OMe
Ph
O
3h
N
O
N
Ph
7.27-7.21(m)
O2N
I
H
a; 8.09 (d, J = 8.0 Hz, 1H)
5f
2c
OMe
Figure 3. Study of the anisotropic effect in 1H NMR
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To further validate the anisotropic effect, the reaction of pyranopyridine 2j with alkyne 3e
under optimized condition was carried out to obtained pyrroloquinoline 8 (Scheme 6). The
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structure of compound 8 was confirmed by its H and C NMR. The thorough study of NMR
data indicates that no anisotropic effect was observed in pyrroloquinoline which might be due to
the absence of one ring in the starting substrate 2j (Scheme 6).
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Scheme 6. Synthesis of Pyrrolo[3,2,1-ij]quinolin-9-one 8 from 2-(phenoxyethynyl)
nicotinaldehyde 2j
A plausible mechanism was proposed on the basis of our previously reported mechanism20
(Scheme 7). The substrate 2 forms an vinyl palladium intermediate X with internal alkyne 3 in
the presence of Pd(OAc)2. The attack of nitrogen lone pair on the vinyl palladium followed
reductive elimination and subsequent opening of the pyran ring forms the [3 + 2] annulated
product Y. The base CH3COONa present in the reaction abstract the α-hydrogen and generates
enolate Y', which on successive intramolecular aldol condensation leads to the generation of
unstable β-hydroxy carbonyl intermediate Z. The instability of the intermediate Z subsequently
leads to the loss of water molecule and provided the stable aromatic product 4.
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Scheme 7. Plausible Mechanism
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CONCLUSIONS
In summary, we have demonstrated a direct one-pot approach for the tandem synthesis of
pharmaceutically important pyrrolo[3,2,1-de]acridones by [3 + 2] alkyne annulation with
successive opening of the pyran ring followed by intramolecular cross-aldol condensation under
microwave irradiation. This developed chemistry accomodates variety of functional groups
present on the alkynes as well on the substrates. From a synthetic point of view, this organic
transformation involves a one-step conversion of easily acessble iodo-pyranoquinolines into an
interesting class of natural-product like heterocyclic compounds. Further investigation of the
scope and synthetic applications of the developed strategy are currently underway and will be
reported in due course.
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EXPERIMENTAL SECTION
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General Method: H NMR (400 MHz) and 13C NMR (100 MHz) spectra were recorded in
CDCl3. Chemical shifts for carbons are reported in ppm from tetramethylsilane and are
referenced to the carbon resonance of the solvent. Data are reported as follows: chemical shift,
multiplicity (s=singlet, d=doublet, t=triplet, q=quartet, m=multiplet, dd = doublet of doublet),
coupling constants in Hertz, and integration. High-resolution mass spectra were recorded on
(QqTOF) LC/MS/MS System with electrospray mass spectrometer. TLC analysis was performed
on commercially prepared 60 F254 silica gel plates and visualized by either UV irradiation or by
staining with I2. All purchased chemicals were used as received. A CEM Discover microwave
synthesizer (Model No: 908010) operating at 180/264 V and 50/60 Hz with microwave power
maximum level of 300 W and frequency of 2455 MHz was employed for the microwave-assisted
experiments .
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The starting material 1 was prepared by the sonogashira coupling21a–b and the substrates 2
were synthesized by the electrophilic iodocyclization using reported procedure.21 All the
symmetrical and unsymmetrical internal alkynes 3 were either commercially available or
synthesized by using reported methodology.23
HPLC conditions
A high-performance liquid chromatography (HPLC) system consisted of Dionex instruments
equipped with a quaternary pump and a PDA detector. The analytical column used was C18
reversed-phase column (4.6 mm X 250 mm) packed with 5 µm particles. The column
temperature was maintained at the room temperature (25°C). The mobile phase consisted of
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acetonitrile and water in gradient manner. The solution was filtered and degassed by vacuum
filtration through a 0.22µm membrane filter before use. The flow rate of the mobile phase was
adjusted to 1.3 ml/min.
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2-(4-Phenylbut-1-yn-1-yl)quinoline-3-carbaldehyde (1b). The product was obtained as off-
white crystals (1.18 g, 80%): mp 66–68 °C; 1H NMR (400 MHz, CDCl3) δ 10.36 (s, 1H), 8.65 (s,
1H), 8.10 (d, J = 8.8 Hz, 1H), 7.90 (d, J = 8.8 Hz, 1H), 7.83–7.79 (m, 1H), 7.59–7.55 (m, 1H),
7.33–7.30 (m, 2H), 7.27–7.24 (m, 3H), 3.01 (t, J = 7.3 Hz, 2H), 2.88 (t, J = 7.3 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ 191.1, 149.8, 144.0, 139.9, 136.8, 132.9, 129.6, 129.0, 128.7, 128.6,
128.4, 128.0, 126.6, 126.3, 97.1, 78.0, 34.3, 21.8; HRMS (ESI) calcd for [C20H15NO] requires
[M]+ 285.1154, found [M]+ 285.1153.
6-Methyl-2-(3-phenoxyprop-1-yn-1-yl)quinoline-3-carbaldehyde (1d). The product was
1
obtained as white crystals (1.09 g, 75%): mp 116–118 °C; H NMR (400 MHz, CDCl3) δ 10.39
(s, 1H), 8.52 (s, 1H), 7.94 (d, J = 9.2 Hz, 1H), 7.61–7.58 (m, 2H), 7.28–7.24 (m, 2H), 7.00–6.93
13
(m, 3H), 4.98 (s, 2H), 2.48 (s, 3H); C NMR (100 MHz, CDCl3) δ 190.6, 157.4, 148.6, 142.0,
138.9, 136.2, 135.5, 129.6, 129.0, 128.2, 126.6, 121.9, 115.0, 89.8, 83.3, 56.3, 21.6; HRMS
(ESI) calcd for [C20H15NO2] requires [M]+ 301.1103, found [M]+ 301.1102.
6-Methyl-2-(4-phenylbut-1-yn-1-yl)quinoline-3-carbaldehyde (1f). The product obtained as
1
off-white crystals (1.12 g, 77% ): mp 98–100 °C; H NMR (400 MHz, CDCl3) δ 10.36 (s, 1H),
8.55 (s, 1H), 7.99 (d, J = 8.8 Hz, 1H), 7.65–7.63 (m, 2H), 7.33–7.30 (m, 2H), 7.27–7.22 (m, 3H),
3.01 (t, J = 7.3 Hz, 2H), 2.87 (t, J = 7.3 Hz, 2H), 2.52 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
191.1, 148.2, 143.0, 139.9, 138.4, 136.3, 135.5, 128.7, 128.6, 128.4, 128.2, 126.6, 126.4, 97.2,
34.3, 21.8, 21.6; HRMS (ESI) calcd for [C21H17NO] requires [M]+ 299.1310, found [M]+
299.1311.
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6-Methoxy-2-(3-phenoxyprop-1-yn-1-yl)quinoline-3-carbaldehyde (1g). The product was
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1
obtained as white crystals (1.18 g, 83%): mp 120–122 °C; H NMR (400 MHz, CDCl3) δ 10.44
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(s, 1H), 8.55 (s, 1H), 8.00 (d, J = 8.8 Hz, 1H), 7.49–7.46 (m, 1H), 7.33–7.29 (m, 2H), 7.13–7.12
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(m, 1H), 7.04–6.98 (m, 3H), 5.03 (s, 2H), 3.92 (s, 3H); C NMR (100 MHz, CDCl3) δ 190.6,
159.2, 157.4, 146.2, 140.3, 135.3, 130.7, 129.6, 129.1, 128.0, 126.4, 121.9, 115.0, 106.1, 89.6,
83.1, 56.3, 55.8; HRMS (ESI) calcd for [C20H15NO3] requires [M]+ 317.1052, found [M]+
317.1053.
6-Methoxy-2-(4-phenylbut-1-yn-1-yl)quinoline-3-carbaldehyde (1h). The product was
1
obtained as off-white crystals (1.14 g, 80%): mp 112–114 °C; H NMR (400 MHz, CDCl3) δ
10.36 (s, 1H), 8.52 (s, 1H), 7.98 (d, J = 9.5 Hz, 1H), 7.45 (dd, J = 2.9, 9.5 Hz, 1H), 7.34–7.30
(m, 2H), 7.27–7.24 (m, 3H), 7.10 (d, J = 2.9 Hz, 1H), 3.92 (s, 3H), 3.00 (t, J = 8.0 Hz, 2H), 2.87
13
(t, J = 6.5 Hz, 2H); C NMR (100 MHz, CDCl3) δ 191.5, 158.7, 146.4, 141.8, 140.0, 135.0,
130.6, 129.0, 128.5, 128.4, 127.5, 126.6, 126.1, 106.1, 95.8, 78.0, 55.7, 34.4, 21.7; HRMS (ESI)
calcd for [C21H17NO2] requires [M]+ 315.1259, found [M]+ 315.1260.
2-(3-Phenoxyprop-1-yn-1-yl)nicotinaldehyde (1i) The product was obtained as a white solid
1
(500 mg, 82%): mp 100–102 °C; H NMR (400 MHz, CDCl3) δ 10.35 (s, 1H), 8.78–8.76 (m,
1H), 8.17–8.15 (m, 1H), 7.42–7.39 (m, 1H), 7.35–7.31 (m, 2H), 7.05–7.02 (m, 3H), 5.02 (s, 2H).
13C NMR (100 MHz, CDCl3) δ 190.4, 157.3, 154.3, 144.9, 134.7, 132.2, 129.6, 123.7, 121.9,
114.9, 90.9, 82.3, 56.1; HRMS (ESI) calcd for [C15H11NO2] requires [M]+ 237.0790, found [M]+
237.0790.
4-Iodo-1-methoxy-3-(phenoxymethyl)-1H-pyrano[4,3-b]quinoline (2a). The product was
obtained as a brown solid (1.39 g, 90%): mp 116–118 °C; 1H NMR (400 MHz, CDCl3) δ 8.12 (d,
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J = 8.7 Hz, 1H), 7.82 (s, 1H), 7.71 (d, J = 8.0 Hz, 1H), 7.65 (t, J = 7.3 Hz, 1H), 7.42 (t, J = 7.3
Hz, 1H), 7.27–7.24 (m, 2H), 6.98 (d, J = 8.8 Hz, 2H ), 6.95–6.91 (m, 1H), 6.03 (s, 1H), 5.24 (d, J
= 13.2 Hz, 1H), 5.03 (d, J = 12.4 Hz, 1H), 3.38 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.2,
154.6, 148.6, 146.2, 133.2, 130.3, 129.5, 129.4, 127.5, 126.5, 122.0, 121.4, 114.8, 99.7, 80.3,
70.5, 56.0; HRMS (ESI) calcd for [C20H16INO3] requires [M]+ 445.0175, found [M]+ 445.0176.
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1-Ethoxy-4-iodo-3-(phenoxymethyl)-1H-pyrano[4,3-b]quinoline (2b). The product was
obtained as a brown solid (1.18 g, 77%): mp 114–116 °C; 1H NMR (400 MHz, CDCl3) δ 8.11 (d,
J = 8.0 Hz, 1H), 7.83 (s, 1H), 7.72 (d, J = 8.0 Hz, 1H), 7.66–7.62 (m, 1H), 7.43–7.40 (m, 1H),
7.25–7.21 (m, 2H), 6.96–6.88 (m, 3H), 6.13 (s, 1H), 5.22 (d, J = 13.1 Hz, 1H), 5.01 (d, J = 13.2
Hz, 1H), 3.78–3.70 (m, 1H), 3.62–3.55 (m, 1H), 1.00 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 158.2, 155.1, 148.4, 146.4, 133.2, 130.4, 129.6, 129.4, 127.6, 127.5, 126.5, 122.4,
121.4, 114.8, 98.6, 79.9, 70.5, 64.5, 14.7; HRMS (ESI) calcd for [C21H18INO3] requires [M]+
459.0331, found [M]+ 459.0330.
4-Iodo-1-methoxy-3-phenethyl-1H-pyrano[4,3-b]quinoline (2c). The product was obtained as
a brown solid (1.36 g, 88%): mp 118–120 °C; 1H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 8.0 Hz,
1H), 7.83 (s, 1H), 7.71 (d, J = 8.4 Hz, 1H), 7.65–7.60 (m, 1H), 7.42–7.38 (m, 1H), 7.25–7.24 (m,
4H), 7.17–7.14 (m, 1H), 6.00 (s, 1H), 3.51 (s, 3H), 3.08–3.03 (m, 2H), 2.98–2.93 (m, 2H); 13C
NMR (100 MHz, CDCl3) δ 160.4, 148.7, 147.2, 140.6, 133.0, 130.2, 129.5, 129.4, 128.5, 128.4,
127.4, 126.3, 126.1, 121.5, 99.8, 78.1, 56.1, 40.1, 33.2; HRMS (ESI) calcd for [C21H18INO2]
requires [M]+ 443.0382, found [M]+ 443.0381.
3-Butyl-1-ethoxy-4-iodo-1H-pyrano[4,3-b]quinoline (2d). The product was obtained as a
brown semi-solid (1.29 g, 75%); 1H NMR (400 MHz, CDCl3) δ 8.13 (d, J = 8.0 Hz, 1H), 7.86 (s,
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1H), 7.76 (d, J = 8.0 Hz, 1H), 7.69–7.64 (m, 1H), 7.46–7.42 (m, 1H), 6.16 (s, 1H), 4.03–3.97 (m,
1H), 3.83–3.75 (m, 1H), 2.90–2.72 (m, 2H), 1.73–1.61 (m, 2H), 1.48–1.39 (m, 2H), 1.25 (t, J =
6.6 Hz, 3H), 0.95 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 162.1, 148.4, 147.5, 133.0,
130.1, 129.1, 127.4, 127.2, 126.0, 121.8, 98.5, 64.4, 37.8, 29.3, 22.2, 15.0, 14.0; HRMS (ESI)
calcd for [C18H20INO2] requires [M]+ 409.0539, found [M]+ 409.0540.
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4-Iodo-1-methoxy-8-methyl-3-(phenoxymethyl)-1H-pyrano[4,3-b]quinoline
(2e).
The
1
product was obtained as a brown solid (1.29 g, 85%): mp 134–136 °C; H NMR (400 MHz,
CDCl3) δ 8.07 (d, J = 8.7 Hz, 1H), 7.81 (s, 1H), 7.55–7.53 (m, 2H), 7.31–7.27 (m, 2H), 7.03–
6.95 (m, 3H), 6.09 (s, 1H), 5.28 (d, J = 12.0 Hz, 1H), 5.07 (d, J = 12.0 Hz, 1H), 3.43 (s, 3H),
2.50 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.3, 154.1, 147.3, 145.5, 136.6, 132.7, 132.6,
129.6, 129.2, 127.6, 126.4, 122.1, 121.4, 114.9, 99.9, 80.5, 70.6, 56.0, 21.6; HRMS (ESI) calcd
for [C21H18INO3] requires [M]+ 459.0331, found [M]+ 459.0330.
4-Iodo-1-methoxy-8-methyl-3-phenethyl-1H-pyrano[4,3-b]quinoline (2g). The product was
obtained as brown solid (1.24 g, 82%): mp 108–110 °C; 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J
= 8.8 Hz 1H), 7.73 (s, 1H), 7.47–7.45 (m, 2H), 7.26–7.23 (m, 4H), 7.17–7.13 (m, 1H), 5.94 (s,
13
1H), 3.51 (s, 3H), 3.04–3.03 (m, 2H), 2.97–2.95 (m, 2H), 2.44 (s, 3H); C NMR (100 MHz,
CDCl3) δ 160.0, 147.2, 146.4, 140.6, 136.1, 132.5, 132.4, 129.0, 128.5, 128.4, 127.3, 126.4,
126.3, 121.5, 100.0, 78.1, 56.0, 40.1, 33.2, 21.6; HRMS (ESI) calcd for[C22H20INO2] requires
[M+H]+ 458.0617, found [M+H]+ 458.0617.
4-Iodo-1,8-dimethoxy-3-(phenoxymethyl)-1H-pyrano[4,3-b]quinoline (2h). The product was
obtained as a brown solid (1.37 g, 92%): mp 112–114 °C; 1H NMR (400 MHz, CDCl3) δ 8.07 (d,
J = 9.5 Hz, 1H), 7.79 (s, 1H), 7.36 (dd, J = 2.9, 9.5 Hz, 1H) 7.31–7.27 (m, 2H), 7.04–7.01 (m,
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3H), 6.99–6.95 (m, 1H), 6.08 (s, 1H), 5.27 (d, J = 13.2 Hz, 1H), 5.06 (d, J = 13.2 Hz, 1H), 3.89
(s, 3H), 3.43 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.3, 157.9, 153.6, 144.6, 144.1, 132.1,
130.8, 129.5, 128.6, 123.1, 122.4, 121.4, 114.9, 105.1, 99.8, 80.2, 70.6, 55.9, 55.5; HRMS (ESI)
calcd for[C21H18INO4] requires [M]+ 475.0281, found [M]+ 475.0281.
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4-Iodo-1,8-dimethoxy-3-phenethyl-1H-pyrano[4,3-b]quinoline (2i). The product was obtained
as a brown solid (1.35 g, 90%): mp 110–112 °C; 1H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 9.6
Hz, 1H), 7.78 (s, 1H), 7.35 (dd, J = 2.2, 8.8 Hz, 1H), 7.32–7.30 (m, 4H), 7.25–7.20 (m, 1H ),
7.03 (d, J = 2.2 Hz, 1H), 6.05 (s, 1H), 3.90 (s, 3H), 3.58 (s, 3H), 3.15–3.09 (m, 2H), 3.05–3.01
(m, 2H); 13C NMR (100 MHz, CDCl3) δ 159.6, 157.5, 145.0, 144.4, 140.6, 132.0, 130.5, 128.5,
128.4, 128.2, 126.2, 122.8, 121.7, 105.2, 99.9, 77.6, 56.1, 55.5, 40.0, 33.2; HRMS (ESI) calcd
for[C22H20INO3] requires [M]+ 473.0488, found [M]+ 473.0490.
8-Iodo-5-methoxy-7-(phenoxymethyl)-5H-pyrano[4,3-b]pyridine
(2j) The product was
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obtained as a white solid (700 mg, 85%), mp 120–122 °C, H NMR (400 MHz, CDCl3) δ 8.60
(dd, J = 1.4, 5.1 Hz, 1H), 7.38 (dd, J = 1.4, 7.3 Hz, 1H), 7.27–7.23 (m, 2H), 7.16–7.13 (m, 1H),
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6.98–6.91 (m, 3H), 5.93 (s, 1H), 5.23–5.19 (m, 1H), 4.99–4.95 (m, 1H), 3.33 (s, 3H); C NMR
(100 MHz, CDCl3) δ 157.9, 152.8, 150.4, 146.2, 133.3, 129.3, 122.5, 121.1, 114.5, 99.0, 78.7,
69.9, 60.0, 55.5. HRMS (ESI) calcd for [C16H14INO3] requires [M]+ 395.0018, found [M]+
395.0019.
General Procedure for the Synthesis of substituted substituted pyrrolo[3,2,1-de]acridones
(4a–v, 5a–h, 7 and 8) using microwave reactor. In a oven-dried, 10-mL reaction vial
containing a stirring bar, pyranoquinoline/pyridine 2 (0.25 mmol), 1.2 equiv of internal alkyne 3,
2.0 equiv of NaOAc, 3.0 equiv of LiCl , and 5 mol % of Pd (OAc)2 , was added in 3 ml of
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DMF. The vial was sealed tightly with a Teflon cap. The reaction mixture was irradiated for 20
min at 120 °C, with an irradiation power of 100 W in microwave. After completion of the
reaction monitored by the TLC, the reaction mixture was cooled and diluted with H2O and then
extracted with EtOAc. The combined organic layers were dried over Na2SO4, concentrated, and
purified by column chromatography using ethyl acetate/hexane as elutent to afford the
corresponding products.
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4-Phenoxy-1,2-di-p-tolyl-3H-pyrrolo[3,2,1-de]acridin-3-one (4a). The product was obtained
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as a brown crystals (95 mg, 78%): mp 160–162 °C; H NMR (400 MHz, CDCl3) δ 7.83 (d, J =
8.0 Hz, 1H), 7.76 (s, 1H), 7.37–7.34 (m, 4H), 7.31–7.27 (m, 5H), 7.25–7.24 (m, 2H), 7.15–7.12
(m, 3H), 7.00 (d, J = 8.0 Hz, 2H), 6.84 (s, 1H), 2.44 (s, 3H), 2.26 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 174.3, 156.4, 156.0, 139.3, 139.0, 136.5, 133.8, 131.7, 131.5, 130.7, 130.1, 129.8,
129.3, 128.8, 128.0, 127.0, 125.7, 124.3, 124.0, 123.9, 121.2, 119.5, 117.4, 114.0, 112.8, 111.5,
21.5, 21.3; HRMS (ESI) calcd for [C35H25NO2] requires [M]+ 491.1885, found [M]+ 491.1886.
1,2-Bis(4-methoxyphenyl)-4-phenoxy-3H-pyrrolo[3,2,1-de]acridin-3-one (4b). The product
was obtained as a brown crystals (104 mg, 80%): mp 180–182 °C; 1H NMR (400 MHz, CDCl3) δ
7.79–7.74 (m, 1H), 7.70 (s, 1H), 7.35–7.19 (m, 5H), 7.08–7.06 (m, 3H), 6.95–6.85 (m, 4H),
6.79–6.85 (m, 1H), 6.68 (d, J = 8.8 Hz, 2H), 6.57–6.54 (m, 1H), 6.41 (d, J = 8.8 Hz, 1H), 3.81 (s,
3H), 3.67 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 174.3, 160.0, 158.4, 156.3, 156.0, 133.7,
133.2, 132.0, 131.5, 130.4, 130.1, 129.8, 129.6, 129.4, 127.0, 125.7, 124.8, 124.6, 124.4, 124.0,
121.0, 119.5, 117.3, 114.5, 113.2, 112.8, 111.4, 55.3, 55.0; HRMS (ESI) calcd for [C35H25NO4]
requires [M]+ 523.1784, found [M]+ 523.1781
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4-Phenoxy-1,2-di(thiophen-3-yl)-3H-pyrrolo[3,2,1-de]acridin-3-one (4c). The product was
obtained as a brown crystals (88 mg, 74%): mp 184–186 °C; 1H NMR (400 MHz, CDCl3) δ 7.85
(d, J = 7.3 Hz, 1H), 7.79 (s, 1H), 7.71 (s, 1H), 7.60 (t, J = 3.6 Hz, 1H ), 7.42–7.40 (m, 2H), 7.38–
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7.36 (m, 4H), 7.26–7.22 (m, 2H), 7.18–7.14 (m, 2H), 7.11 (s, 2H), 6.84 (s, 1H); C NMR (100
MHz, CDCl3) δ 174.2, 156.2, 156.0, 139.3, 133.6, 133.0, 132.1, 130.2, 129.9, 129.8, 129.3,
128.1, 127.5, 127.2, 126.0, 125.7, 124.9, 124.6, 124.2, 124.0, 123.4, 123.3, 121.0, 119.6, 116.9,
114.05, 111.3; HRMS (ESI) calcd for [C29H17NO2S2] requires [M]+ 475.0701, found [M]+
475.0701.
4-Phenoxy-1,2-di-m-tolyl-3H-pyrrolo[3,2,1-de]acridin-3-one (4d). The product was obtained
as a brown crystals (86 mg, 70%): mp 144–146 °C; 1H NMR (400 MHz, CDCl3) δ 7.98–7.95 (m,
1H), 7.77 (d, J = 7.3 Hz, 1H), 7.73–7.69 (m, 1H), 7.33–7.27 (m, 4H), 7.25–7.21 (m, 3H), 7.23–
7.17 (m, 2H), 7.10–7.08 (m, 3H), 7.02–6.98 (m, 2H), 6.93–6.91 (m, 1H), 6.74–6.70 (m, 1H),
2.28 (s, 3H), 2.19 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 174.1, 156.3, 156.2, 138.6, 136.5,
133.7, 132.7, 132.4, 132.1, 131.7, 131.1, 130.0, 129.9, 129.8, 129.7, 129.3, 129.0, 128.8, 127.8,
127.7, 127.1, 126.9, 125.8, 124.4, 124.1, 121.3, 119.9, 117.5, 116.9, 116.8, 112.8, 110.9, 21.4;
HRMS (ESI) calcd for [C35H25NO2] requires [M]+ 491.1885, found [M]+ 491.1886
4-Benzyl-1,2-di-p-tolyl-3H-pyrrolo[3,2,1-de]acridin-3-one (4e). The product was obtained as a
dark-brown crystals (93 mg, 76%): mp 168–170 °C; 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J =
7.3 Hz, 1H), 7.69 (s, 1H), 7.30–7.28 (m, 1H), 7.26–7.25 (m, 4H), 7.23–7.21 (m, 5H), 7.17–7.15
(m, 4H), 7.06 (s, 1H), 6.98 (d, J = 8.0 Hz, 2H), 3.95 (s, 2H), 2.37 (s, 3H), 2.22 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 179.9, 145.7, 140.1, 138.8, 136.4, 134.1, 132.6, 131.7, 130.6, 130.4, 130.3,
129.8, 129.7, 129.6, 129.5, 128.9, 128.5, 128.4, 128.1, 127.2, 126.1, 125.7, 124.2, 121.9, 117.4,
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114.1, 112.3, 36.0, 21.5, 21.3; HRMS (ESI) calcd for[ C36H27NO] requires [M]+ 489.2093, found
[M]+ 489.2093.
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obtained as a orange crystals (101 mg, 78%): mp 182–184 °C; H NMR (400 MHz, CDCl3) δ
7.84 (d, J = 7.3 Hz, 1H), 7.76 (s, 1H), 7.40–7.35 (m, 2H), 7.32–7.30 (m, 5H), 7.29–7.26 (m, 1H),
7.24–7.19 (m, 4H), 7.14 (s, 1H), 6.97–6.95 (m, 2H), 6.79–6.77 (m, 2H), 4.02 (s, 2H), 3.87 (s,
3H), 3.76 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 180.0, 159.9, 158.4, 145.6, 140.1, 139.3,
134.1, 133.2, 132.5, 131.9, 130.5, 129.6, 128.6, 128.5, 128.3, 127.3, 126.1, 125.8, 125.1, 124.9,
124.2, 121.8, 117.3, 115.9, 114.4, 112.9, 112.1, 55.3, 55.0, 36.0; HRMS (ESI) calcd for
[C36H27NO3] requires [M]+ 521.1991, found [M]+ 521.1992.
4-Benzyl-1,2-di(thiophen-3-yl)-3H-pyrrolo[3,2,1-de]acridin-3-one (4g). The product was
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obtained as a brown crystals (85 mg, 72%): mp 180–182 °C; H NMR (400 MHz, CDCl3) δ
7.82–7.79 (m, 1H), 7.73 (s, 1H), 7.53–7.51 (m, 2H), 7.33–7.30 (m, 4H), 7.28–7.26 (m, 3H),
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7.20–7.18 (m, 2H), 7.16–7.14 (m, 1H), 7.12–7.08 (m, 3H), 3.99 (s, 2H); C NMR (100 MHz,
CDCl3) δ 179.9, 145.5, 140.0, 134.0, 133.0, 132.6, 130.5, 130.2, 129.9, 129.6, 129.2, 128.7,
128.5, 127.9, 127.4, 127.2, 126.1, 125.6, 125.5, 124.8, 124.5, 123.3, 121.7, 116.9, 36.2; HRMS
(ESI) calcd for [C30H19NOS2] requires [M]+ 473.0908, found [M]+ 473.0909.
4-Benzyl-1,2-diphenyl-3H-pyrrolo[3,2,1-de]acridin-3-one (4h). The product was obtained as a
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orange crystals (86 mg, 75%): mp 166–168 °C; H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.0
Hz, 1H), 7.71 (s, 1H), 7.40–7.34 (m, 4H), 7.33–7.30 (m, 3H), 7.28–7.21 (m, 6H), 7.19–7.12 (m,
5H), 7.08 (s, 1H), 3.96 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 180.0, 145.7, 140.0, 134.0, 132.7,
131.9, 130.8, 130.5, 129.6, 129.2, 129.0, 128.9, 128.6, 128.5, 127.4, 127.3, 126.9, 126.1, 125.8,
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124.3, 121.9, 117.4, 112.2, 36.0; HRMS (ESI) calcd for [C34H23NO] requires [M]+ 461.1780,
found [M]+ 461.1781.
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brown crystals (83 mg, 68%): mp 100–102 °C; H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 7.3
Hz, 1H), 7.69 (s, 1H), 7.31–7.29 (m, 1H), 7.26–7.23 (m, 7H), 7.22–7.20 (m, 2H), 7.17–7.12 (m,
4H), 7.09–7.06 (m, 2H), 6.93 (d, J = 7.3 Hz, 1H), 3.96 (s, 2H), 2.22 (s, 3H), 2.18 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 179.9, 145.7, 140.1, 138.5, 136.5, 134.1, 132.7, 132.6, 132.4, 131.5,
130.9, 130.7, 130.4, 129.7, 129.5, 129.2, 129.0, 128.7, 128.5, 128.3, 128.1, 127.9, 127.7, 127.2,
126.5, 126.1, 125.8, 124.2, 121.9, 117.4, 116.3, 112.3, 36.0, 21.5, 21.4; HRMS (ESI) calcd for
[C36H27NO] requires [M]+ 489.2093, found [M]+ 489.2091.
1,2-Diphenyl-4-propyl-3H-pyrrolo[3,2,1-de]acridin-3-one (4j). The product was obtained as a
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orange crystals (70 mg, 68%): mp 160–162 °C; H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 8.0
Hz, 1H), 7.84 (s, 1H), 7.45–7.40 (m, 5H), 7.39–7.36 (m, 3H), 7.31–7.28 (m, 1H), 7.25–7.22 (m,
2H), 7.20–7.18 (m, 2H), 7.09 (s, 1H), 2.66 (t, J = 8.0 Hz, 2H), 1.73–1.63 (m, 2H), 1.00 (t, J = 7.3
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Hz, 3H); C NMR (100 MHz, CDCl3) δ 180.5, 146.2, 133.9, 132.9, 132.8, 132.7, 131.9, 130.8,
130.4, 130.23, 130.18, 129.4, 129.1, 128.9, 128.8, 127.7, 127.5, 127.3, 126.8, 126.6, 125.8,
124.2, 122.2, 117.3, 112.3, 32.6, 22.3, 14.1; HRMS (ESI) calcd for [C30H23NO] requires [M]+
413.1780, found [M]+ 413.1780.
1,2-Bis(4-methoxyphenyl)-8-methyl-4-phenoxy-3H-pyrrolo[3,2,1-de]acridin-3-one (4k). The
product was obtained as a brown crystals (107 mg, 80%): mp 180–182 °C; 1H NMR (400 MHz,
CDCl3) δ 7.64 (s, 1H), 7.55 (s, 1H), 7.31–7.24 (m, 6H), 7.19–7.18 (m, 1H), 7.09–7.06 (m, 4H),
6.91 (d, J = 8.7 Hz, 2H), 6.78 (s, 1H), 6.68 (d, J = 8.8 Hz, 2H), 3.81 (s, 3H), 3.68 (s, 3H), 2.35 (s,
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3H); 13C NMR (100 MHz, CDCl3) δ 174.2, 160.0, 158.4, 156.5, 155.9, 134.0, 133.2, 132.0,
131.9, 131.2, 131.0, 130.2, 129.7, 129.5, 128.4, 126.9, 125.8, 124.8, 124.7, 123.8, 121.0, 119.4,
117.1, 114.4, 112.8, 112.6, 111.7, 55.3, 55.0, 20.8; HRMS (ESI) calcd for [C36H27NO4] requires
[M]+ 537.1940, found [M]+ 537.1941.
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8-Methyl-4-phenoxy-1,2-di(thiophen-3-yl)-3H-pyrrolo[3,2,1-de]acridin-3-one
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The
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CDCl3) δ 7.73–7.71 (m, 2H), 7.62–7.58 (m, 2H), 7.40–7.36 (m, 3H), 7.26–7.21 (m, 3H), 7.18–
7.14 (m, 3H), 7.12–7.09 (m, 2H), 6.84 (s, 1H), 2.43 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
174.1, 156.3, 155.9, 134.4, 133.0, 132.2, 131.8, 131.6, 131.3, 130.2, 129.8, 129.6, 129.3, 128.0,
127.3, 127.0, 125.9, 125.7, 124.7, 124.0, 123.2, 120.9, 119.5, 116.6, 112.4, 111.6, 20.8; HRMS
(ESI) calcd for [C30H19NO2S2] requires [M]+ 489.0857, found [M]+ 489.0858.
8-Methyl-4-propyl-1,2-di-p-tolyl-3H-pyrrolo[3,2,1-de]acridin-3-one (4m). The product was
obtained as a brown crystals (82 mg, 72%): mp 152–154 °C; 1H NMR (400 MHz, CDCl3) δ 7.70
(s, 1H), 7.61 (s, 1H), 7.32 (s, 1H), 7.23–7.21 (m, 4H), 7.18–7.14 (m, 3H), 7.06 (dd, J = 2.2, 9.5
Hz, 1H), 6.97 (d, J = 8.0 Hz, 2H), 2.58 (t, J = 8.0 Hz, 2H), 2.37 (s, 6H), 2.22 (s, 3H), 1.63–1.57
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(m, 2H), 0.93 (t, J = 8.0 Hz, 3H); C NMR (100 MHz, CDCl3) δ 180.4, 146.2, 139.3, 138.7,
136.2, 133.8, 132.2, 131.8, 130.9, 130.7, 130.0, 129.9, 129.60, 129.59, 128.7, 128.1, 127.4,
126.3, 126.1, 126.0, 122.1, 117.3, 114.0, 31.9, 22.7, 22.4, 21.5, 21.3, 14.1; HRMS (ESI) calcd
for [C33H29NO] requires [M]+ 455.2249, found [M]+ 455.2250.
4-Benzyl-1,2-bis(4-methoxyphenyl)-8-methyl-3H-pyrrolo[3,2,1-de]acridin-3-one (4n). The
product was obtained as a orange crystals (105 mg, 78%): mp 188–190 °C; 1H NMR (400 MHz,
CDCl3) δ 7.69 (s, 1H), 7.61 (s, 1H), 7.34 (s, 1H), 7.32–7.30 (m, 5H), 7.29–7.26 (m, 2H), 7.24–
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