Cu(I)-Catalyzed Ligand-Free Tandem One-Pot or Sequential Annulation via Knoevenagel Intermediates: An Entry into Multifunctional Naphthalenes, Phenanthrenes, Quinolines, and Benzo[ b]carbazoles

Article abstract of DOI:10.1021/acs.joc.9b02991

A simple but efficient one-pot or sequential copper-catalyzed protocol using 2-bromoaldehydes and active methylene group containing substrates that affords multifunctional naphthalenes, phenanthrenes, quinolines, and benzo[b]carbazoles via Knoevenagel con

Full text of DOI:10.1021/acs.joc.9b02991

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Article
Cu(I)-Catalyzed Ligand-free Tandem One Pot or Sequential Annulation
via Knoevenagel Intermediate: An Entry into Multifunctional
Naphthalenes, Phenanthrenes, Quinolines and Benzo[b]carbazoles
K C Kumara Swamy, Rajnikanth Sunke, and ADULA KALYANI
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02991 • Publication Date (Web): 11 Dec 2019
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Cu(I)-Catalyzed Ligand-free Tandem One Pot or Sequential Annulation via
Knoevenagel Intermediate: An Entry into Multifunctional Naphthalenes,
Phenanthrenes, Quinolines and Benzo[b]carbazoles
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Rajnikanth Sunke, Adula Kalyani and K. C. Kumara Swamy*
School of Chemistry, University of Hyderabad, Hyderabad 500 046, Telangana, India
ABSTRACT
A simple but efficient one-pot or sequential copper-catalyzed protocol using 2-bromo-
aldehydes and active methylene group containing substrates that affords multifunctional
naphthalenes, phenanthrenes, quinolines and benzo[b]carbazoles via Knoevenagel
condensation, C-arylation and decarboxylation followed by aromatization, has been
developed. The reaction utilizes the potential of Knoevenagel intermediates and does not
require ancillary ligand. The phenanthrene products thus obtained show moderate
fluorescence activity. Structural elaboration of the products to obtain
dihydrobenzoquinazolines is also highlighted.
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INTRODUCTION
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The development of new and efficient methodologies for the construction of highly
substituted polycyclic arenes and N-heteroarenes with flexible substituent patterns is a
worthwhile exercise as it allows access to the diversity based chemical space useful for
pharmaceuticals and electronic materials.1 Among polycyclic arenes, multifunctional
naphthalenes and phenanthrenes are important classes of organic compounds because
they have not only found widespread applications in pharmaceutical chemistry (cf. Figure
1)2 but also play a significant role in supramolecular chemistry, nanotechnology,
electronic materials and the design of chiral catalysts.3 Therefore, the development of
efficient strategies to access such structural motifs from readily accessible starting
materials has immense impact and value. Consequently, a number of synthetic strategies
toward polysubstituted naphthalenes or phenanthrenes have been developed. The most
important avenues include Diels-Alder reaction,4 annulation reaction,5 metathesis,6
rearrangements of strained rings,7 catalytic cyclization,8 C-H activation,9 cyclo-
isomerization10 and cross-coupling protocol.11 In addition, N-heteroarenes such as
quinolines and benzocarbazoles also feature prominently among many natural products
and drug candidates.12 As a result, a number of synthetic platforms are used for the
construction of such structural systems.13 While significant progress has been achieved
for the construction of naphthalenes, phenanthrenes, quinolines and benzo[b]carbazoles
with diverse substitutions, the number of approaches based on Cu(I)-catalyzed reactions
is rather limited.
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Figure 1. Selected examples of natural products and biologically active molecules
containing substituted naphthalenes, phenanthrenes, quinolines and benzo[b]carbazoles.
Although Cu(I)-catalyzed cross-coupling reactions are well-studied in domino and
multi-component reactions,14 their application for the construction of polysubstituted
naphthalene derivatives is very limited. Panda et al. developed an efficient method for
the synthesis of polysubstituted α-naphthols from simple monocyclic enol esters
(Scheme 1a).15a Jiang and co-workers disclosed a copper-catalyzed tandem reaction of
methyl-3-(2-bromophenyl)-3-oxopropanoate with methyl-3-oxobutanoate for the
synthesis of dimethyl-4-hydroxy-2-methylnaphthalene-1,3-dicarboxylate (Scheme
1b),15b Liu and co-workers described a copper-catalyzed borylative cyclization
strategy to construct 3-boryl-1-naphthylamines from o-(cyano)phenyl propargyl
carbonates (Scheme 1c).15c In the year 2011, Beifuss and coworkers developed an
efficient copper-catalyzed domino method for the synthesis of dialkyl-2-
alkylnaphthalene-1,3-dicarboxylates via the reaction of o-halobenzyl halide with two
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molecules of a β-ketoester (Scheme 1d).15d Later, the same group extended this
protocol to o-halobenzaldehydes as substrates to access same substituted naphthalenes
(Scheme 1e).15e Inspite of these outstanding efforts, it is still challenging to prepare
polysubstituted aromatic compounds (PACs) possessing diverse substituents directly
from readily available building blocks in a single synthetic operation. In this context,
we report herein a convenient and efficient copper-catalyzed tandem or sequential
synthesis of multifunctional naphthalenes, phenanthrenes, quinolines and
benzo[b]carbazoles by using commercially available starting materials such as o-
bromoarylaldehydes, alkyl cyanoacetates, dialkyl malonates and malononitrile
(Scheme 1f). Our reaction works under ligand-free conditions and further elaboration
of the products can be readily achieved, as shown by the isolation of
dihydrobenzoquinazolines. Also, the phenanthrene products are fluorescence active, a
property that may be useful in applications.
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Scheme 1. Selected Related Reports on [Cu]-Mediated Approaches to
Polysubstituted Naphthalenes and Our Present Work
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RESULTS AND DISCUSSION
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Initially, 2-bromobenzaldehyde 1a was treated with ethyl 2-cyanoacetate 2a in the
presence of CuBr (10 mol%) and K2CO3 (3.0 equiv) in DMSO at 120 °C for 3 h. TLC
analysis showed that 1a was consumed completely to give ethyl 3-amino-4-cyano-2-
naphthoate 3aa in 74% yield (Table1, entry1). To identify the best reaction condition, we
have varied the catalysts, bases and solvents as shown in Table 1. First, copper catalysts
CuBr, CuCl, CuI, CuCl2, Cu(OAc)2 and Cu(OTf)2 (0.1equiv) were checked by using 3.0
equiv of K2CO3 as the base and DMSO as the solvent at 120 ºC (Table 1, entries 1-6).
CuI provided the highest yield and the target product 3aa was isolated in 81% yield
(entry 4). In the absence of copper catalyst, product 3aa was not at all observed (entry 7).
Lowering of catalyst loading to 5 mol % decreased the yield (entry 8) whereas increasing
the catalyst loading to (20 mol %) did not improve yield of the reaction (entry 8). Among
the bases K2CO3, Cs2CO3, Na2CO3, K3PO4, t-BuOK, Et3N and DBU (entries 4, 9-14) that
were checked, K2CO3 provided the highest yield. Among the solvents DMSO, N,N-
dimethylacetamide (DMA), 1,4-dioxane, toluene, and PEG-400 (entries 4, 16-19) that
were tested, DMSO was found to be the solvent of choice, although DMF (entry 15) also
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o
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gave a comparable yield. Conducting the reaction at 70 C/10 h or 150 C/ 3 h afforded
3aa in nearly the same yield (entry 20). It was also noteworthy that this reaction protocol
required neither an inert atmosphere nor any additional ligand to produce alkyl 3-amino-
4-cyano-2-naphthoate 3aa in good yield (entry 22). Eventually, reaction conditions in
entry 4 was determined as optimal [1a (1.0 mmol), 2b (2.0 mmol), CuI (10 mol %), and
K2CO3 (3.0 mmol) in DMSO at 120 °C/ 3 h].
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Table 1. Optimization of the Reaction Conditionsa
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Entry
catalyst
base
solvent
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
yield of 3aa (%)b
1
CuBr
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
Na2CO3
K3PO4
t-BuOK
Et3N
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81c
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CuCl
CuCl2 (anh.)
4
CuI
5
Cu(OAc)2 (anh.)
6
Cu(OTf)2
-
d
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-
8
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
54 (80)e
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71
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42
14
DBU
25
K2CO3
K2CO3
K2CO3
K2CO3
75
DMA
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Dioxane
Toluene
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CuI
CuI
CuI
CuI
K2CO3
K2CO3
-
PEG-400
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DMSO
DMSO
DMSO
77 (80)f
g
-
80(77)h
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K2CO3
aReaction conditions: 1a (0.54 mmol), 2a (1.09 mmol), base (1.62 mmol), catalyst (0.054
o
mmol), solvent (2 mL), 120 C (oil bath) for 3 h in a stoppered Schlenk tube in air.
bIsolated yield of 3aa. cReaction performed under nitrogen gave the same yield but under
oxygen (balloon), the yield was only 45%. dNo catalyst was added. e5 mol % and 20 mol
f
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% of CuI were used. The yields are for the reaction performed at 70 C/10 h (77%) and
o
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150 C/ 3 h (80%). No base was added; only Knoevenagel product (38%) was isolated.
h10 mol % of L-proline (or 1,10-phenanthroline) was used.
As shown in Table 2, 2-bromobenzaldehydes 1a-1f possessing electron-neutral, electron
rich or electron-withdrawing substituents smoothly converted to the corresponding
products 3 in good yields. The nitriles 2a, 2c and 2d containing CO2R4 [R4 = Me, Et, n-
Bu, n-octyl) could also be successfully utilized. We were pleased to find that the tandem
reaction of 1-bromo-2-naphthaldehyde 1g with alkyl-2-cyanoacetates 2a-2d afforded the
fluorescence active (vide infra) alkyl 3-amino-4-cyanophenanthrene-2-carboxylates 3ga
(X-ray in Figure S2, SI), 3gb, and 3gd in good yields. We subsequently examined the
reaction of 2-bromo-3-pyridinecarboxaldehyde 1h with alkyl cyanoacetates 2a, 2b and
2d; satisfyingly, the reaction furnished the desired products 3ha, 3hb and 3hd in
moderate to good yields of 72-52% (Table 3) along with < 17% yield of 3ha' and 3hd'.
We successfully extended this chemistry to the synthesis of alkyl 7-amino-8-cyano-5-
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ethyl-5H-benzo[b]carbazole-9-carboxylate 3ia (X-ray; Figure S5, SI), 3ib and 3id by
using precursor 1i16 (Table 3).
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Table 2. Substrate Scope for [Cu]-Catalyzed Tandem Synthesis of Multifunctional
Naphthalenes and Phenanthrenes 3a,b
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aReaction conditions: 1 (0.5 mmol), 2 (1.0 mmol), K2CO3 (1.6 mmol), CuI (0.05 mmol),
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DMSO (2 mL) in a stoppered Schlenk tube in air at 120 C (oil bath) for 3h. Yield of
product 3.
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Table 3. Cu(I)-Catalyzed Tandem Synthesis of Multifunctional Quinolines and
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Benzo[b]carbazoles 3a,b
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aReaction conditions: 1 (0.5 mmol), 2 (1.0 mmol), K2CO3 (1.6 mmol), CuI (0.05 mmol),
o
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DMSO (2 mL), in a stoppered Schlenk tube in air at 120 C (oil bath) for 3 h. Yield of
product 3.
In order to decipher the reaction pathway, we performed the reaction of 2-
bromobenzaldehyde 1a (1 mmol) with ethyl cyanoacetate 2a (1 mmol) using K2CO3 (1.0
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mmol) in DMSO at rt (25 C) for 1 h that provided the Knoevenagel adduct I in 82%
yield (Scheme 2, eq 1). In the absence of K2CO3, the Knoevenagel adduct I was obtained
in only 38% yield, along with unreacted starting material 1a (Scheme 2, eq 2). When we
treated I (1 mmol) with ethyl cyanoacetate 2a (1 mmol), CuI (0.1 mmol), and K2CO3 (2.0
mmol) at 120 ºC for 2 h, the desired product 3aa was obtained in excellent yield (Scheme
2, eq 3). In the absence of CuI, the reaction did not proceed (Scheme 2, eq 4). These
simple observations clearly showed that copper mediated C-arylation is the key step in
this tandem process.
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Scheme 2. Control Experiments
On the basis of the above control experiments and literature reports,17, 15b, 5i a plausible
pathway for the formation of 3aa is illustrated in Scheme 3. Initially, the reaction of 2-
bromobenzaldehyde 1 and alkyl cyanoacetate 2 generated Knoevenagel adduct I. Copper-
catalyzed coupling of I with 2 leads to C-arylation product II. Then, the base abstracts a
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proton from an active methine carbon of II forming the highly nucleophilic carbanion III
that attacks the nitrile leading to the cyclized intermediate IV which undergoes hydrolysis
to give V. Decarboxylation, followed by aromatization of V affords alkyl 3-amino-4-
cyano-2-naphthoate (3). We wish to emphasize here that (i) the later stages of this
reaction pathway as well as the resulting products differ from the one reported using β-
ketoesters wherein an oxetane intermediate and elimination of carboxylate species is
proposed15e and (ii) the formation of 3ha’ and 3hd’ albeit in very low yields perhaps
offers a different type of mechanism for their formation but currently it is a puzzling
observation.
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Scheme 3. Plausible Pathway for the Formation of Products 3
For expanding the scope of substrates, we treated 2-bromobenzaldehyde 1a (1.0 mmol)
with methyl cyanoacetate 2b (1.0 mmol) and K2CO3 (1.0 mmol) in DMSO at rt for 1 h to
generate intermediate I; after consumption of all of 1a (TLC), CuI (10 mol%), K2CO3
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(2.0 mmol) and dimethylmalonate (4b, 1.0 mmol) were added and the contents heated at
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120 C for 2 h. The overall reaction proceeded smoothly to afford dimethyl 2-
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aminonaphthalene-1,3-dicarboxylate 5abb (X-ray in Figure S6, SI) in 68% yield (Table
4). The scope of this protocol was examined using diverse 2-bromobenzaldehydes (1a,
1c, 1d and 1g), alkyl 2-cyanoacetates (2a-b) and dialkylmalonates (4a-c; R5 = Et, Me, i-
Pr). The corresponding products 5aaa-5aac, 5abb, 5cbb, and 5dab were isolated in good
yields (Table 4). This new one-pot sequence also allows for the synthesis of
polysubstituted phenanthrene 5gaa in 80% yield (Table 4).
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Table 4. Cu(I)-Catalyzed One-Pot Sequential Synthesis of 5a,b
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aReaction conditions: 1 (~0.5 mmol), 2 (0.5 mmol), K2CO3 (0.5 mmol), DMSO (2 mL),
at rt for 1 h in a stoppered Schlenk tube in air; then CuI (0.05 mmol), 4 (0.5 mmol), and
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K2CO3 (1.0 mmol) were added in air and contents heated at 120 C (oil bath) for 2 h.
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bYield of product 5.
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In order to explore the above one pot sequential method further, malononitrile (6; 1
mmol) was used to replace dialkylmalonate 4 in Table 4. Very interestingly, this reaction
afforded 2-aminonaphthalene-1,3-dicarbonitriles 7aa, 7ca and 7da in 67-82% yield
(Table 5). Mechanistically, the reaction seems to involve an initial C-arylation via
copper-catalyzed coupling of I with 6 to give intermediate VI. Hydrolysis of ester on VI
leads to VII. Decarboxylation followed by cyclization of VII leads to intermediate VIII.
Finally, aromatization of VIII afforded product 7. Thus the later stages of this pathway
appears to be slightly different from that shown in Scheme 3 or the one involving β-
ketoesters.15e
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Table 5. Cu(I)-Catalyzed One-Pot Sequential Synthesis of 2-Aminonaphthalene-1,3-
dicarbonitrile 7a,b
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aReaction conditions: 1 (0.5 mmol), 2 (0.5 mmol), K2CO3 (0.5 mmol), DMSO (2 mL), at
rt for 1h, in a stoppered Schlenk tube in air; then CuI (0.05 mmol), 6 (0.5 mmol), and
K2CO3 (1.0 mmol) were added in air and the contents heated at 120 oC (oil bath) for 2h.b
Yield of product 7.
To demonstrate the utility of the present protocol, further structural elaboration of
compounds 3aa and 3da was performed via the reaction with formamide 8 in the
presence of K2CO3 to give the corresponding benzo[g]quinazoline 9. Later, the compound
9aa was converted to 4-oxo-3-phenyl-3,4-dihydrobenzo[g]quinazoline-10-carbonitrile
11aa by using a reported Cu-mediated C-N bond forming reaction (Scheme 4);18 there
was no perceptible reaction when CuI was used in place of Cu(OAc)2 under the
conditions given in Table 2.
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Scheme 4. Structural Elaboration of 3
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To examine the scalability of the optimized method, the tandem reaction between 2-
bromobenzaldehyde 1a and ethyl cyanoacetate 2a was carried out under standard
conditions on a gram scale. The expected product 3aa could be obtained in 68% isolated
yield (Scheme 5).
Scheme 5. Gram-Scale Transformation
Photophysical Properties of Phenanthrenes 3ga, 3gd and 5gaa.
We expected phenanthrene-2-carboxylates 3ga, 3gd and 5gaa to be photo chemically
active and perhaps could be used later. Hence the UV-visible and fluorescence spectra
were recorded. The emission spectra of compounds 3ga, 3gd, and 5gaa were recorded
upon excitation at 330 nm. As expected, these compounds show moderate fluorescence
emission intensity (cf. Figure 2). The absorption peak wavelengths (λabs), molar
extinction coefficient (Ɛ), emission peak wavelengths (λem) in solution are summarized in
Table 6 and Figure 2.
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Table 6. UV−Visible Absorption and Fluorescence Emission Properties of
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Phenanthrene Carboxylates 3ga, 3gd and 5gaa
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entry
compound
3ga
λabs (nm)a
435
λem (nm)b
461
Ɛ (104 M-1cm-1)
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467
3gd
427
488
5gaa
aUV-visible absorption wavelengths, bEmission wavelengths at rt in toluene at
concentration of 1 × 10-5M.
3.0
3gd
3ga
5gaa
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3ga
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Wavelength (nm)
Wavelength (nm)
Figure 2. (A) Absorbance and (B) Fluorescence emission spectra of compounds 3ga, 3gd
and 5gaa in toluene (10-5 M) at rt (25 oC).
CONCLUSIONS
We have developed a simple and highly efficient ligand-free one pot Cu(I)-mediated
tandem or sequential protocol for the synthesis of multifunctional naphthalenes,
phenanthrenes, quinolines and benzo[b]carbazoles. The protocol entails readily
available substrates such as o-bromoarylaldehydes, alkyl cyanoacetates,
dialkylmalonates and active methylene nitriles. The developed methodology was
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utilized further for the synthesis of 4-oxo-3-phenyl-3,4-dihydrobenzo[g]quinazoline-
10-carbonitrile. The photophysical properties of phenanthrene carboxylates reveal
possible applications for the highly fluorescent materials.
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EXPERIMENTAL SECTION
General Methods. All reactions were carried out in air, unless specified otherwise. All
required chemicals were procured and used as purchased without further purification,
unless noted otherwise. Melting points were determined using a SUPERFIT hot stage
apparatus and were uncorrected. H and 13C NMR spectra were recorded using 5 mm
1
tubes on a Bruker 400 and 500 MHz NMR spectrometer [field strengths: 400/100 or
500/125 MHz respectively] in CDCl3/DMSO-d6 solution with shifts referenced to TMS
13
(1H, C: ö = 0). All J values are in Hz. Infrared spectra were recorded neat or by using
KBr pellets on an FT/IR spectrometer. Mass spectra were recorded using HRMS (ESI-
TOF analyzer) equipment. Crystallographic data were collected at 293 K on an X-ray
diffractometer system using Mo-Kα radiation (λ = 0.71073 Å) or Cu-Kα (λ = 1.54184 Å)
radiation. Structures were solved and refined using standard methods.19 Thin-layer
chromatography was performed on silica/alumina plates and components were visualized
by observation under iodine/UV light at 254 nm. Column chromatography was performed
on silica gel (100-200 mesh)/neutral alumina, for column elution process hexane-EtOAc
mixture was used as the eluent unless otherwise stated.
o-Bromoarylaldehydes (1a-1h) were purchased from Aldrich and used without further
purification and 1i was prepared by using a literature report.16
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(i). General procedure for the synthesis of compounds 3aa-3ib. To an oven dried
Schlenk tube, with a magnetic stirrer bar was added o-bromoaryl aldehyde 1 (~0.5 mmol,
1 equiv, individual quantities given below), CuI (0.05 mmol, 10 mol %), K2CO3 (1.6
mmol, 3 equiv), alkyl cyanoacetate 2 (1.0 mmol, 2 equiv) and DMSO (2 mL). The tube
with the contents was stoppered and heated at 120 °C (oil bath) for 3h. After completion
of the reaction as monitored by TLC, the crude reaction mixture was cooled to rt (25 oC),
diluted with ethyl acetate (20 mL) and passed through a short celite column. The
resulting solution was washed with water (2 x 20 mL) and the aqueous part extracted
twice with ethyl acetate (20 mL). The combined organic layer was washed with brine
solution (2 x 20 mL), dried over anhydrous Na2SO4, and concentrated in vacuum. The
residue was then purified by using silica gel column chromatography using hexane-ethyl
acetate (9:1) as eluent to afford the pure desired compounds 3. Compounds 3aa-3ib were
prepared from the appropriate o-bromoaryl aldehyde 1 and alkyl cyanoacetate 2 by using
the same procedure using similar molar quantities/ratio.
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(ii). Procedure for the Scale-up Reaction. To an oven dried Schlenk tube, with a
magnetic stirrer bar was added o-bromoaryl aldehyde 1 (1.000 g, 5.40 mmol), CuI (0.103
g, 0.54 mmol), K2CO3 (2.200 g, 16.20 mmol), ethyl cyanoacetate 2 (1.15 mL, 10.81
mmol) and DMSO (20 mL). The tube with the contents was stoppered and heated at 120
°C (oil bath) for 3h. After completion of the reaction as monitored by TLC, the crude
reaction mixture was cooled to rt (25 oC), diluted with ethyl acetate (100 mL) and passed
through a short celite (ca 10 g) column. The resulting solution was washed with water
and the aqueous part extracted twice with ethyl acetate (2 x 100 mL). The combined
organic layer was washed with brine solution (2 x 100 mL), dried over anhydrous
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Na2SO4, and concentrated in vacuum. The residue was then purified by using silica gel
column chromatography using hexane-ethyl acetate (9:1) as eluent to afford the desired
compound 3aa (0.88 g, 68%) as a yellow solid).
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Ethyl 3-amino-4-cyano-2-naphthoate (3aa). This compound was prepared by using
precursors 1a (100 mg, 0.540 mmol) and 2a. Yellow solid, yield 0.106 g (81%); mp 146-
148 oC; 1H NMR (400 MHz, CDCl3) δ 8.68 (s, 1H), 7.90 (d, J = 8.4 Hz, 1H ), 7.79 (d, J
= 8.0 Hz, 1H ), 7.66-7.63 (m, 1H), 7.34 (t, J = 7.4 Hz, 1H), 6.71 (br s, 2H), 4.46 (q, J =
7.2 Hz, 2H), 1.48 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 166.7, 151.0,
138.8, 136.1, 131.5, 130.1, 124.8, 123.8, 122.9, 116.9, 114.1, 88.9, 61.6, 14.3; IR (neat)
νmax 3427, 3327, 2967, 2926, 2203, 1739, 1613, 1366, 1210, 1072, 1029, 787, 747 cm-1;
HRMS (ESI) calcd for C14H12N2NaO2 [M++Na] m/z 263.0796, found 263.0792.
Methyl 3-amino-4-cyano-2-naphthoate (3ab): This compound was prepared by using
precursors 1a (100 mg, 0.540 mmol) and 2b. Yellow solid, yield 0.095 g (77%); mp 152-
154 oC; 1H NMR (400 MHz, CDCl3) δ 8.69 (s, 1H), 7.91 (d, J = 8.4 Hz, 1H), 7.79 (d, J =
8.0Hz, 1H), 7.68-7.64 (m, 1H), 7.36 (t, J = 8.0 Hz, 1H), 6.70 (br s, 2H), 4.01 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 167.1, 151.0, 138.9, 136.2, 131.6, 130.1, 124.8,
123.9, 123.0, 116.8, 113.8, 89.0, 52.5; IR (neat) νmax 3440, 3337, 3015, 2962, 2218, 1739,
1625, 1366, 1213, 1076, 790, 744 cm-1; HRMS (ESI) calcd for C13H11N2O2 [M++H] m/z
227.0821, found 227.0815.
Butyl 3-amino-4-cyano-2-naphthoate (3ac). This compound was prepared by using
precursors 1a (100 mg, 0.540 mmol) and 2c. Yellow solid, yield 0.105 g (72%); mp 142-
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144 oC; 1H NMR (400 MHz, CDCl3) δ 8.65 (s, 1H), 7.89 (d, J = 7.6 Hz, 1H), 7.79 (d, J =
8.4 Hz, 1H), 7.66-7.62 (m, 1H), 7.35-7.31 (m, 1H), 6.70 (br s, 2H), 4.40 (t, J = 6.4 Hz,
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2H), 1.87-1.80 (m, 2H), 1.58-1.49 (m, 2H), 1.04 (t, J = 7.6Hz, 3H); C{1H} NMR (100
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MHz, CDCl3) δ 166.8, 151.1, 138.7, 136.1, 131.5, 130.1, 124.8, 123.8, 122.9, 116.9,
114.1, 89.0, 65.4, 30.7, 29.7, 19.3, 13.8; IR (neat) νmax 3433, 3330, 2957, 2927, 2864,
2207, 1695, 1613, 1455, 1304, 1210, 1077, 794, 750 cm-1; HRMS (ESI) calcd for
C16H16N2O2 [M++H] m/z 269.1290, found 269.1283.
Octyl 3-amino-4-cyano-2-naphthoate (3ad). This compound was prepared by using
precursors 1a (100 mg, 0.540 mmol) and 2d. Yellow solid, yield 0.120 g (68 %); mp 149-
151 oC; 1H NMR (400 MHz, CDCl3) δ 8.67 (s, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.80 (d, J =
8.0 Hz, 1H), 7.67-7.63 (m, 1H), 7.36-7.32 (m, 1H), 6.71 (br s, 2H), 4.40 (t, J = 6.8 Hz,
2H), 1.88-1.81 (m, 2H), 1.53-1.32 (m, 10H), 0.92 (t, J = 6.4 Hz, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 166.8, 151.1, 138.8, 136.1, 131.6, 130.1, 124.8, 123.9, 123.0, 116.9,
114.2, 88.9, 65.8, 31.8, 29.3, 29.2, 28.6, 26.1, 22.7, 14.1; IR (neat) νmax 3436, 3334, 2924,
2857, 2208, 1737, 1699, 1616, 1573, 1456, 1367, 1303, 1211, 1170, 1083, 794, 755 cm-1;
HRMS (ESI) calcd for C20H25N2O2 [M++H] m/z 325.1916, found 325.1917.
Ethyl 3-amino-4-cyano-6,7-dimethoxy-2-naphthoate(3ba). This compound was prepared
by using precursors 1b (100 mg, 0.408 mmol) and 2a. Yellow solid, yield 0.104 g (85%);
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mp 161-163 C; H NMR (500 MHz, CDCl3) δ 8.01 (s, 1H), 7.96 (s, 1H), 6.96 (s, 1H),
6.28 (s, 2H), 4.53 (q, J = 7.0 Hz, 2H), 4.02 (s, 3H), 3.98 (s, 3H), 1.53 (t, J = 7.0 Hz, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 168.5, 153.2, 147.7, 147.3, 137.8, 131.8, 121.6,
117.3, 107.6, 105.1, 104.9, 98.4, 61.2, 55.9, 55.8, 14.5; IR (neat) νmax 3481, 3352, 2924,
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2854, 2214, 1673, 1614, 1435, 1323, 1295, 1013, 814 cm-1; HRMS (ESI) calcd for
C16H16N2O4 [M++H]: m/z 301.1188, found 301.1189.
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Butyl 3-amino-4-cyano-6,7-dimethoxy-2-naphthoate (3bc). This compound was prepared
by using precursors 1b (100 mg, 0.408 mmol) and 2c. Yellow solid, yield 0.107 g (80%);
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mp 157-159 C; H NMR (500 MHz, CDCl3) δ 8.48 (s, 1H), 7.15 (s, 1H), 7.06 (s, 1H),
6.57 (s, 2H), 4.38 (t, J = 6.5 Hz, 2H), 4.07 (s, 3H), 3.99 (s, 3H), 1.85-1.79 (m, 2H), 1.57-
1.50 (m, 2H), 1.03 (t, J = 7.5 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 167.0, 154.3,
150.3, 147.9, 136.3, 133.3, 119.9, 117.3, 111.5, 108.2, 102.0, 88.4, 65.0, 56.2, 56.0, 30.7,
19.3, 13.8; IR (neat) νmax 3437, 3336, 2959, 2926, 2873, 2203, 1686, 1614, 1461, 1299,
1094, 1039, 974,752 cm-1; HRMS (ESI) calcd for C18H20N2O4 [M++H] m/z 329.1501,
found 329.1502.
Octyl 3-amino-4-cyano-6,7-dimethoxy-2-naphthoate (3bd). This compound was prepared
by using precursors 1b (100 mg, 0.408 mmol) and 2d. Yellow solid, yield 0.129 g (82%);
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mp 149-151 C; H NMR (500 MHz, CDCl3) δ 8.48 (s, 1H), 7.15 (s, 1H), 7.06 (s, 1H),
6.57 (s, 2H), 4.36 (t, J = 6.5 Hz, 2H), 4.07 (s, 3H), 3.99 (s, 3H), 1.85-1.80 (m, 2H), 1.51-
1.32 (m, 10H), 0.91 (t, J = 7.0 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 167.0,
154.3, 150.3, 147.9, 136.4, 133.3, 119.9, 117.3, 111.6, 108.3, 102.1, 88.4, 65.4, 56.3,
56.0, 31.8, 29.3, 29.2, 28.7, 26.1, 22.7, 14.1; IR (neat) νmax 3440, 3343, 2955, 2925, 2855,
2204, 1688, 1611, 1509, 1331, 1298, 1039, 1022, 787, 754 cm-1; HRMS (ESI) calcd for
C22H29N2O4 [M++H] m/z 385.2127, found 385.2128.
Ethyl 3-amino-4-cyano-7-methoxy-2-naphthoate (3ca). This compound was prepared by
using precursors 1c (100 mg, 0.465 mmol) and 2a. Yellow solid, yield 0.100 g (79 %);
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mp 165-167 C; H NMR (400 MHz, CDCl3) δ 8.60 (s, 1H), 7.83 (d, J = 8.8 Hz, 1H),
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2H), 3.91 (s, 3H). 1.49 (t, J = 7.2 Hz, 3H); C{1H} NMR (100 MHz, CDCl3) δ 166.7,
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155.9, 150.1, 137.8, 131.3, 125.5, 124.6, 123.7, 117.2, 114.7, 109.3, 88.0, 61.8, 55.8,
14.5; IR (neat) νmax 3429, 3329, 2979, 2205, 1739, 1614, 1366, 1211, 1074, 1031, 787,
749 cm-1; HRMS (ESI) calcd for C15H15N2O3 [M++H] m/z 271.1083, found 271.1077.
Methyl 3-amino-4-cyano-7-methoxy-2-naphthoate (3cb): This compound was prepared
by using precursors 1c (100 mg, 0.465 mmol) and 2b. Yellow solid, yield 0.085 g (71 %);
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mp 170-172 C; H NMR (500 MHz, CDCl3) δ 8.59 (s, 1H), 7.83 (d, J = 9.0 Hz, 1H),
7.33 (dd, J = 9.0, 2.5 Hz, 1H), 7.10 (d, J = 3.0 Hz, 1H), 6.52 (br s, 2H), 3.99 (s, 3H), 3.91
(s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 167.2, 156.2, 149.5, 137.3, 131.5, 125.7,
124.5, 124.3, 116.9, 114.2, 108.0, 89.5, 55.4, 52.4; IR (neat) νmax 3446, 3345, 2959, 2922,
2209, 1738, 1704, 1617, 1505, 1374, 1289, 1215, 1142, 1089, 1012, 824, 787 cm-1;
HRMS (ESI) calcd for C14H13N2O3 [M++H] m/z 257.0926, found 257.0929.
Butyl 3-amino-4-cyano-7-methoxy-2-naphthoate (3cc). This compound was prepared by
using precursors 1c (100 mg, 0.465 mmol) and 2c. Yellow solid, yield 0.095 g (68 %);
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mp 161-163 C; H NMR (400 MHz, CDCl3) δ 8.57 (s, 1H), 7.82 (d, J = 9.2 Hz, 1H),
7.33 (dd, J = 9.2, 2.4 Hz, 1H), 7.11 (d, J = 2.8 Hz, 1H), 6.53 (br s, 2H), 4.40 (t, J = 6.4
Hz, 2H), 3.92 (s, 3H), 1.87-1.80 (m, 2H), 1.57-1.49 (m, 2H), 1.05 (t, J = 7.2 Hz, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 166.8, 156.1, 149.6, 137.1, 131.4, 125.7, 124.4,
124.2, 117.0, 114.5, 107.9, 89.5, 65.3, 55.4, 30.7, 19.3, 13.8; IR (neat) νmax 3437, 3335,
2925, 2858, 2207, 1738, 1691, 1609, 1459, 1375, 1227, 1080, 1024, 799 cm-1; HRMS
(ESI) calcd. for C17H19N2O3 [M++H] m/z 299.1396, found: 299.1390.
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Octyl 3-amino-4-cyano-7-methoxy-2-naphthoate (3cd). This compound was prepared by
using precursors 1c (100 mg, 0.465 mmol) and 2d. Yellow solid, yield 0.121 g (73%); mp
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153-155 C; 1H NMR (400 MHz, CDCl3) δ 8.56 (s, 1H), 7.82 (d, J = 9.2 Hz, 1H), 7.33
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(dd, J = 8.8, 2.4 Hz, 1H), 7.10 (d, J = 2.4 Hz, 1H), 6.53 (br s, 2H), 4.39 (t, J = 6.8 Hz,
2H), 3.92 (s, 3H), 1.88-1.81 (m, 2H), 1.53-1.27 (m, 10H), 0.92 (t, J = 6.8 Hz, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 166.8, 156.1, 149.6, 137.1, 131.4, 125.6, 124.4,
124.2, 117.0, 114.4, 107.9, 89.4, 65.7, 55.4, 31.8, 29.24, 29.18, 28.6, 26.0, 22.6, 14.1; IR
(neat) νmax 3440, 3337, 2924, 2854, 2207, 1694, 1611, 1505, 1463, 1380, 1296, 1233,
1184, 1170, 1086, 1005, 818, 731 cm-1; HRMS (ESI) calcd for C21H26N2O3 [M++H] m/z
355.2022, found 355.2019.
Ethyl 3-amino-4-cyano-7-fluoro-2-naphthoate (3da). This compound was prepared by
using precursors 1d (100 mg, 0.493 mmol) and 2a. Yellow solid, yield 0.089 g (70 %);
mp 161-163 oC; 1H NMR (400 MHz, CDCl3) δ 8.59 (s, 1H), 7.90-7.86 (m, 1H), 7.45-7.40
(m, 2H), 6.65 (br s, 2H), 4.46 (q, J = 7.2 Hz, 2H), 1.49 (t, J = 7.2 Hz, 3H); 13C{1H}
NMR (125 MHz, CDCl3) δ 166.4, 159.0 (J = 243.6 Hz), 150.5, 137.6 (J = 5.0 Hz), 132.9,
125.2 (J = 8.3 Hz), 125.1,121.6 (J = 25.2 Hz), 116.6, 115.2, 113.1 (J = 20.8 Hz), 89.2,
61.7, 14.3; IR (neat) νmax 3429, 3330, 2958, 2922, 2858, 2209, 1739, 1696, 1616, 1506,
1372, 1281, 1220, 1162, 1087, 1025, 823, 794 cm-1; HRMS (ESI) calcd for
C14H11FN2NaO2 [M++Na] m/z 281.0697, found 281.0696.
Butyl 3-amino-4-cyano-7-fluoro-2-naphthoate (3dc). This compound was prepared by
using precursors 1d (100 mg, 0.493 mmol) and 2c. Yellow solid, yield 0.095 g (67 %);
mp 154-156 oC; 1H NMR (400 MHz, CDCl3) δ 8.60 (s, 1H), 7.92-7.88 (m, 1H), 7.46-7.41
(m, 2H), 6.67 (s, 2H), 4.41 (t, J = 6.8 Hz, 2H), 1.87-1.80 (m, 2H), 1.56-1.48 (m, 2H),
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1.04 (t, J = 7.2 Hz, 3H); C{1H} NMR (100 MHz, CDCl3) δ 166.5, 159.0 (J = 243.7
Hz), 150.5, 137.6 (J = 5.1 Hz), 132.9, 125.2 (J = 8.2 Hz), 125.1 (J = 8.8 Hz), 121.6 (J =
25.3 Hz), 116.7, 115.2, 113.2 (J = 20.1 Hz), 89.2, 65.6, 30.6, 19.3, 13.8; IR (neat) νmax
3440, 3338, 2961, 2208, 1738, 1609, 1506, 1373, 1297, 1225, 1082, 1036, 818, 740 cm-1;
HRMS (ESI) calcd for C16H16FN2O2 (M+ + H) m/z 287.1196, found 287.1183.
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Octyl 3-amino-4-cyano-7-fluoro-2-naphthoate (3dd). This compound was prepared by
using precursors 1d (100 mg, 0.493 mmol) and 2d. Yellow solid, yield 0.110 mg (65 %);
mp 149-151 oC; 1H NMR (500 MHz, CDCl3) δ 8.59 (s, 1H), 7.91-7.88 (m, 1H), 7.45-7.41
(m, 2H), 6.66 (s, 2H), 4.40 (t, J = 6.5 Hz, 2H), 1.87-1.81 (m, 2H), 1.51-1.45 (m, 2H),
1.43-1.31 (m, 8H), 0.92 (t, J = 7.0 Hz, 3H); C{1H} NMR (100 MHz, CDCl3) δ 166.5,
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159.0 (J = 243.6 Hz), 150.5, 137.6 (J = 5.0 Hz), 132.9, 125.2 (J = 8.4 Hz), 125.1 (J = 8.8
Hz), 121.6 (J = 25.1 Hz), 116.7, 115.2, 113.2 (J = 20.1 Hz), 89.2, 65.9, 31.8, 29.24, 29.20,
28.6, 26.0, 22.7, 14.1; IR (neat) νmax 3483, 3363, 2958, 2927, 2856, 2204, 1796, 1693,
1609, 1572, 1376, 1279, 1216, 1157, 1077, 1024, 831, 732 cm-1 ; HRMS (ESI) calcd for
C20H24FN2O2 [M++H] m/z 343.1822, found 343.1814.
Ethyl 3-amino-4-cyano-8-fluoro-2-naphthoate (3ea). This compound was prepared by
using precursors 1e (100 mg, 0.493 mmol) and 2a. Yellow solid, yield 0.078 g (61%); mp
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160-162 C; H NMR (400 MHz, CDCl3) δ 8.95 (s, 1H), 7.68 (d, J = 8.4 Hz, 1H),7.61-
7.55 (m, 1H), 7.01-6.97 (m, 1H), 6.83 (s, 2H), 4.48 (q, J = 7.2 Hz, 2H), 1.50 (t, J = 7.2
Hz, 3H); C{1H} NMR (125 MHz, CDCl3) δ 166.5, 160.0 (J = 254.2 Hz), 151.6, 137.3
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(J = 3.4 Hz), 132.0 (J = 9.3 Hz), 131.5 (J = 5.6 Hz), 118.8 (J = 4.1 Hz),116.5, 115.1,
114.3, 107.5 (J = 19.6 Hz), 88.9, 61.8, 14.3; IR (neat) νmax 3429, 3327, 2984, 2926, 2207,
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1735, 1696, 1616, 1574, 1438, 1376, 1273, 1181, 1122, 1048, 866, 796, 747 cm-1; HRMS
(ESI) calcd for C14H11FNaN2O2 [M++Na] m/z 281.0702, found 281.0700.
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Methyl 3-amino-4-cyano-8-fluoro-2-naphthoate (3eb). This compound was prepared by
using precursors 1e (100 mg, 0.493 mmol) and 2b. Yellow solid, yield 0.082 g (68 %);
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mp 165-167 C; 1H NMR (400 MHz, CDCl3) δ 8.95 (s, 1H), 7.68 (d, J = 8.4 Hz, 1H),
7.61-7.55 (m, 1H), 7.01-6.97 (m, 1H ), 6.81 (s, 2H), 4.02 (s, 3H); 13C{1H} NMR (125
MHz, CDCl3) δ 166.9, 160.0 (J = 254.5 Hz), 151.5, 137.3, 132.1 (J = 9.3 Hz), 131.7 (J =
5.8 Hz), 118.8 (J = 4.2 Hz),116.5, 115.2 (J = 17.2 Hz), 114.0, 107.1 (J = 19.6 Hz), 88.9,
52.6; IR (neat) νmax 3440, 3335, 2960, 2922, 2846, 2215, 1710, 1624, 1571, 1443, 1365,
1306, 1208, 1077, 791 cm-1; HRMS (ESI) calcd for C13H10FN2O2 [M++H] m/z 245.0726,
found 245.0726.
Ethyl 3-amino-4-cyano-7-methyl-2-naphthoate (3fa). This compound was prepared by
using precursors 1f (100 mg, 0.502 mmol) and 2a. Yellow solid, yield 0.103 g (80 %);
mp 140-142 oC; 1H NMR (400 MHz, CDCl3) δ 8.63 (s, 1H), 7.69-7.67 (m, 2H), 7.17(dd,
J = 8.4, 1.6 Hz, 1H), 6.68 (s, 2H), 4.44 (q, J = 7.2 Hz, 2H), 2.54 (s, 3H), 1.48 (t, J = 7.2
Hz, 3H); C{1H} NMR (100 MHz, CDCl3) δ 166.8, 151.2, 142.4, 138.5, 136.4, 129.9,
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126.2, 123.1, 122.2, 117.1, 113.1, 88.4, 61.4, 22.2, 14.3; IR (neat) νmax 3427, 3328, 2974,
2931, 2203, 1739, 1705, 1612, 1572, 1366, 1209, 1151, 1071, 1030, 786, 749 cm-1;
HRMS (ESI) calcd for C15H15N2O2 [M++H] m/z 255.1134, found 255.1137.
Ethyl 2-amino-3-cyanophenanthrene-1-carboxylate (3ga). This compound was prepared
by using precursors 1g (100 mg, 0.425 mmol) and 2a. Yellow solid, yield 0.089 g (72%);
mp 176-180 oC; 1H NMR (400 MHz, CDCl3) δ 9.74-9.71 (m, 1H), 8.61 (s, 1H), 7.87-7.85
(m, 1H), 7.70-7.66(m, 2H), 7.59-7.54 (m, 2H), 7.00 (br s, 2H), 4.47 (q, J = 7.2 Hz, 2H),
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1.49 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 166.8, 153.1, 138.5, 134.9,
134.3, 128.9, 127.5, 127.3, 126.6, 125.3, 123.2, 119.9, 112.3, 88.7, 61.5, 14.3; IR (neat):
νmax 3464, 3316, 2922, 2190, 1731, 1601, 1370, 1215, 1093, 1064, 804, 747 cm-1; HRMS
(ESI) calcd for C18H14N2NaO2 [M++Na] m/z 313.0953, found: 313.0945.
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Methyl 2-amino-3-cyanophenanthrene-1-carboxylate (3gb). This compound was
prepared by using precursors 1g (100 mg, 0.425 mmol) and 2b. Yellow solid, yield 0.073
g (62%); mp 178-182 oC; 1H NMR (400 MHz, CDCl3) δ 9.74-9.72 (m, 1H), 8.61 (s, 1H),
7.88-7.86 (m, 1H), 7.71-7.68 (m, 2H), 7.56 (s, 2H), 6.99 (br s, 2H), 4.01 (s, 3H); 13C{1H}
NMR(100 MHz, CDCl3) δ 167.2, 153.0, 138.5, 134.9, 134.3, 128.94, 128.91, 127.4,
127.2, 126.6, 125.34, 125.28, 123.2, 120.0, 111.9, 88.7, 52.4; IR (neat) νmax 3447, 3339,
2958, 2921, 2010, 1702, 1610, 1459, 1609, 1459, 1316, 1279, 1260, 1219, 1092, 1026,
909, 803, 748, 563 cm-1; HRMS (ESI) calcd for C17H13N2O2 [M++H] m/z 277.0977,
found 277.0979.
Octyl 3-amino-4-cyanophenanthrene-2-carboxylate (3gd). This compound was prepared
by using precursors 1g (100 mg, 0.425 mmol) and 2d. Yellow solid, yield 0.104 g (65%);
mp 120-124 oC;1H NMR (500 MHz, CDCl3) δ 9.75-9.74 (m, 1H), 8.61 (s, 1H), 7.89-7.87
(m, 1H), 7.71-7.69 (m, 2H), 7.61-7.57 (m, 2H), 7.02 (br s, 2H), 4.41 (t, J = 6.5 Hz, 2H),
1.89-1.83 (m, 2H), 1.54-1.48 (m, 2H), 1.44-1.32 (m, 8H), 0.93 (t, J = 7.0 Hz, 3H);
13C{1H} NMR(125 MHz, CDCl3) δ 166.8, 153.1, 138.4, 134.9, 134.3, 128.9, 127.4,
127.3, 126.6, 125.3, 123.2, 120.0, 112.3, 88.6, 65.7, 31.8, 29.3, 29.2, 28.7, 26.1, 22.7,
14.1; IR (neat) νmax 3453, 3335, 2923, 2851, 2193, 1737, 1692, 1608, 1581, 1517, 1313,
1282, 1217, 1199, 1122, 1094, 1024, 971, 807, 752, 729, 682, 659 cm-1; HRMS (ESI)
calcd for C24H27N2O2 [M++H] m/z 375.2073, found: 375.2091.
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Ethyl 7-amino-8-cyanoquinoline-6-carboxylate (3ha). This compound (along with 3ha’;
see below) was prepared by using precursors 1h (100 mg, 0.537 mmol) and 2a. Rf 0.3
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(ethyl acetate:hexane 1:9).Yellow solid, yield 0.086 g (66%); mp 151-153 C; H NMR
(500 MHz, CDCl3) δ 8.98 (dd, J = 4.0, 1.5 Hz, 1H), 8.65 (s, 1H), 8.08 (dd, J = 8.0, 1.5
Hz, 1H), 7.29-7.26 (m, 1H), 6.95 (v br, 2H), 4.48 (q, J = 7.0 Hz, 2H), 1.48 (t, J = 7.0 Hz,
3H); 13C{1H} NMR (125 MHz, CDCl3) δ 166.2, 155.0, 153.2, 151.3, 138.1, 137.6, 119.5,
119.4, 116.2, 114.8, 92.0, 61.8, 14.2; IR (neat) νmax 3416, 3325, 3301, 2215, 1738, 1628,
1581, 1565, 1370, 1310, 1206, 1083, 1033, 924, 794, 727, 510 cm-1; HRMS (ESI) calcd
for C13H12N3O2 [M++H] m/z 242.0930, found 242.0930.
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Ethyl 7-amino-6-cyanoquinoline-8-carboxylate (3ha'): Rf 0.5 (ethyl acetate:hexane 1:9).
This compound was prepared by using precursors 1h and 2a along with 3ha as described
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above. Yield 0.015 g (12%) as yellow solid; mp: 142-145 C; H NMR (500 MHz,
CDCl3) δ: 8.74 (s, 1H), 8.01 (dd, J = 7.0, 1.0 Hz, 1H), 7.90 (dd, J = 8.0, 1.5 Hz, 1H ),
7.28 (t, J = 6.0 Hz, 1H), 5.88 (s, 2H), 4.46 (q, J = 7.0 Hz, 2H), 1.48 (t, J = 7.0 Hz, 3H);
13C{1H} NMR (125 MHz, CDCl3): 165.9, 157.6, 150.2, 142.5, 137.9, 133.8, 122.4,
121.6, 117.6, 111.8, 109.0, 61.8, 14.2; IR (neat): νmax 3416, 3294, 3183, 2906, 2221,
1696, 1607, 1564, 1478, 1305, 1281, 1203, 1100, 1020, 795, 755 cm-1; HRMS (ESI):
Calcd. for C13H12N3O2 [M++H]: m/z 242.0930. Found: 242.0930.
Methyl 7-amino-8-cyanoquinoline-6-carboxylate (3hb). This compound was prepared by
using precursors 1h (100 mg, 0.537 mmol) and 2b. Yellow solid, yield 0.088 g (72%);
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mp 134-141 C; H NMR (500 MHz, CDCl3) δ 8.97 (dd, J = 4.5, 1.5 Hz, 1H), 8.65 (s,
1H), 8.07 (dd, J = 8.0, 1.5 Hz, 1H), 7.29-7.26 (m, 1H), 6.94 (v br, 2H), 4.01 (s, 3H);
13C{1H} NMR (125 MHz, CDCl3) δ 166.7, 155.0, 153.2, 151.2, 138.3, 137.7, 119.5,
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116.2, 114.5, 91.8, 52.7; IR (neat) νmax 3479, 3410, 3299, 2949, 2210, 1701, 1619, 1581,
1562, 1488, 1428, 1310, 1197, 1071, 1020, 918, 794, 698, 605 cm-1; HRMS (ESI) calcd
for C12H10N3O2 [M++H] m/z 228.0773, found 228.0774.
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Octyl 7-amino-8-cyanoquinoline-6-carboxylate (3hd). This compound (along with 3hd’;
see below) was prepared by using precursors 1h (100 mg, 0.537 mmol) and 2d. Rf 0.3
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(ethyl acetate:hexane 1:9). Yellow solid, yield 0.107 g (61%); mp 162-164 C; H NMR
(400 MHz, CDCl3) δ 8.99-8.98 (m, 1H), 8.63 (s, 1H), 8.10-8.08 (m, 1H), 7.30-7.27 (m,
1H), 6.92 (v br, 2H), 4.41 (t, J = 6.8 Hz, 2H), 1.88-1.81 (m, 2H), 1.49-1.32 (m, 10H),
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138.1, 137.7, 119.5, 119.4, 116.3, 114.8, 91.9, 66.0, 31.8, 29.23, 29.19, 28.6, 26.0, 22.7,
14.1; IR (neat) νmax 3425, 3310, 3059, 2961, 2227, 1702, 1628, 1566, 1488, 1463, 1439,
1278, 1198, 1015, 966, 755, 691 cm-1; HRMS (ESI), calcd for C19H24N3O2 [M++H] m/z
326.1869, found 326.1869.
Octyl 7-amino-8-cyanoquinoline-6-carboxylate (3hd'): This compound was prepared by
using precursors 1h and 2d along with 3hd as described above. Rf 0.5 (ethyl
acetate:hexane 1:9). Yield 0.030 g (17%) as yellow solid; mp: 169-171 oC; 1H NMR (500
MHz, CDCl3) δ: 8.71 (s, 1H), 8.00 (dd, J = 7.5, 1.5 Hz, 1H), 7.93 (dd, J = 8.0, 1.5 Hz,
1H), 7.29-7.26 (m, 1H), 5.95 (s, 2H), 4.38 (t, J = 6.5 Hz, 2H), 1.86-1.80 (m, 2H), 1.50-
1.45 (m, 2H), 1.40-1.31 (m, 8H), 0.91 (t, J = 6.5 Hz, 3H); 13C{1H} NMR (125 MHz,
CDCl3): 166.0, 157.6, 150.2, 142.5, 138.0, 133.9, 122.3, 121.6, 117.7, 111.8, 108.9, 66.0,
31.8, 29.24, 29.19, 28.6, 26.0, 22.7, 14.1; IR (neat): νmax 3426, 3311, 2954, 2919, 2868,
2226, 1701, 1628, 1565, 1458, 1377, 1305, 1278, 1197, 1081, 966, 892, 799, 758, 590
cm-1; HRMS (ESI): Calcd. for C19H24N3O2 [M++H]: m/z 326.1869. Found: 326.1869.
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