Tandem copper (Cu) catalysed N-arylation-vinylogous nitroaldol condensation of 3,5-disubstituted 4-nitropyrazoles

Article abstract of DOI:10.1039/c5ob01011j

A tandem process involving copper catalysed N-arylation and vinylogous nitroaldol condensation is described. The reaction of 3,5-dialkyl substituted 4-nitropyrazoles and ortho-halo substituted (hetero)aryl aldehydes or ketones furnished 3-nitropyrazolo[1,5-a]quinoline and heteroaryl-fused 3-nitropyrazolo[1,5-a]pyridine derivatives in moderate to high yields.

Full text of DOI:10.1039/c5ob01011j

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Tandem copper (Cu) catalysed N-arylaꢀon―vinylogous nitroaldol
condensation of 3,5-disubstituted 4-nitropyrazoles†‡
Received 00th January 20xx,
Accepted 00th January 20xx
Owk Obulesu,a,b Jagadeesh Babu Nanubolu,c and Surisetti Suresha,b
*
A tandem process involving copper catalysed N-arylation and vinylogous nitroaldol condensation is described. The reaction
of 3,5-dialkylsubstituted 4-nitropyrazoles and ortho-halo substituted (hetero)aryl aldehyes or ketones furnished 3-
nitropyrazolo[1,5-a]quinoline and heteroaryl-fused 3-nitropyrazolo[1,5-a]pyridine derivatives in moderate to high yields.
DOI: 10.1039/x0xx00000x
www.rsc.org/
Introduction
Tandem reactions have attracted greater attention in organic
synthesis in recent years.1 Indeed, Robinson's seminal work, about a
century ago, on the total synthesis of tropinone describes the
power of tandem reaction processes in organic synthesis.2 These
processes offer the construction of complex molecules in an
efficient manner.3 Transition metals and catalysts thereof have
been used extensively to perform tandem reactions.4 Among the
transition metal catalysts, copper catalysts have received a great
deal of attention due to their availability and inexpensiveness.5 N-
arylation reaction catalysed by copper6 has attracted significant
interest due to the reason that N-aryl linkage is an integral part of
several therapeutic molecules.7 Tandem reactions triggered by
copper catalysed N-arylation followed by condensations offer the
synthesis of a variety of N-heterocycles8 which are potential
compounds for applications in biology and medicine. The
condensation reactions in these processes include imine or aldol or
Knoevenagel condensations wherein nucleophile that participates
in the condensation being a primary amine group8a-l or an active α-
methylene group.8a,8m-q
Figure
arylation―vinylogous nitroaldol condensation process.
1
Strategy for tandem copper catalysed N-
O
H
pyrazoloquinoline system
N
indole-fused
pyrazoloquinoline
system
N
pyrazolopyridine
system
O
O
N
N
OH
HOOC
H
N
N
OMe
N
N
N
N
O
H
MeO
D
.
pTsOH
F
OMe
E (E2508)
Figure 2 Biologically active N-fused pyrazoloquinoline and
pyrazolopyridine derivatives.
This process would furnish the corresponding quinoline or
heteroaryl-fused pyridine systems C containing the nitro group that
could be useful for further functional group transformation.
Employment of suitable NH-heterocycles such as pyrazoles in this
process would lead to the synthesis of N-fused pyrazoloquinoline or
heteroaryl- and N-fused pyrazolopyridine derivatives that are
We envisaged to develop a tandem process involving copper valuable compounds in medicinal chemistry.10 For instance, N-fused
catalysed N-arylaꢀon―vinylogous nitroaldol9 condensation9b using pyrazoloquinoline derivative D act as GPR109A agonist agent.10h
Pyrazolo[1,5-a]pyridine E has been proved to possess excellent drug
properties and advanced into clinical trials for the treatment of
stress related disorders.10j Indole-fused pyrazolopyridine derivative
F was shown to be potent anticancer agent (Figure 2).10k
substrates of type
A and ortho-halo (hetero)aryl carbonyl
compounds B (Figure 1). The model substrate A contains the
essential functionalities like NH for N-arylation and an active γ-
methylene group, activated by a nitro group through conjugation,
to participate in the vinylogous nitroaldol condensation reaction.
Results and Discussion
We have identified readily available NH-heterocycle such as 3,5-
dimethyl-4-nitropyrazole 1a as a suitable substrate to test the
proposed tandem copper catalysed N-arylation―vinylogous
nitroaldol condensation (Table 1). The substrate 1a contains the
required NH group for N-arylation and an active 5-methyl group,
activated by 4-nitro group through conjugation, for the vinylogous
nitroaldol condensation.
a.Organic and Biomolecular Chemistry Division, CSIR-Indian Institute of Chemical
Technology (CSIR-IICT), Hyderabad, 500007, India. E-mail: surisetti@iict.res.in
b.Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of
Chemical Technology (CSIR-IICT), Hyderabad, 500007, India.
c. Center for X-ray Crystallography, CSIR-Indian Institute of Chemical Technology
(CSIR-IICT), Hyderabad, 500007, India.
† This work is dedicated to Professor Mariappan Periasamy
‡ Electronic Supplementary Informaꢀon (ESI) available: Experimental procedures,
spectral data, copies of NMR spectra for products, CIF of 3a (CCDC 1052135) and
5a (CCDC 1057420), see DOI: 10.1039/x0xx00000x
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Table 1 Optimization survey for the reaction of 1a and 2a
Scheme 1
Reaction scope for the synthesis of pyrazolo[1,5-
a]quinoline derivativesa
R1
R3
R1
O
O2N
R2
R3
CuI, Neocuproine, K2CO3
DMSO, 120 oC, 48 h
O2N
NH
N
N
R4
Br
N
R5
R2
2a-j
3a-nb
1a-c
Entry
X
Catalyst
Ligand
Base
Yield
3
4
: R , R = H; : R3 = H, R4 = 5-Br;
2a
2b
: R1 = H, R2 = Me
: R1 = Me, R2 = Et
: R1 = H, R2 = iBu
3ab
1a
1b
1c
2c: R3 = H, R4 = 5-F; 2d: R3 = H, R4 = 4,5-di-OMe;
: R3 = H, R4 = 4,5-(OCH2O) : R3 = H, R4 = 5-OMe;
2e
; 2f
1
2
3
4
Br
Br
Br
Br
CuI
CuI
CuI
CuI
Ethylenediamine
K2CO3
K2CO3
K2CO3
K2CO3
40
33
17
: R3 = H, R4 = 4-Me; : R3 = H, R4 = 5,6-(C4H4);
2g
2i
2h
: R3 = Ph, R4 = H; : R3 = Me, R4 = H
2j
(
L
)-Proline
BINOL
O2N
O2N
O2N
Neocuproine
91
N
N
F
N
Br
(84)c
N
N
N
3a
, 91%
3c
, 24%
3b, 71%
5
6
Br
CuBr
Neocuproine
Neocuproine
Neocuproine
Neocuproine
Neocuproine
Neocuproine
K2CO3
K2CO3
NaHCO3
K3PO4
K2CO3
K2CO3
18
29
85
22
17
49
Br Cu(OTf)2
O2N
O2N
O2N
O2N
O2N
N
OMe
OMe
N
N
3e
N
OMe
7
Br
Br
Cl
I
CuI
CuI
CuI
CuI
O
N
N
O
8
, 19%
3d
, 25%
3f
, 18%
9
Ph
O2N
O2N
10
N
N
N
N
N
a. Reaction conditions: 1a (0.5 mmol),
2 (0.5 mmol), Cu
N
Me
catalyst (0.05 mmol), ligand (0.1 mmol), base (1.65 mmol),
DMSO (2 mL); b. Yields are for isolated products; c. Reaction
was run at 10 mmol scale.
3g, 49%
3h
, 45%
3i, 41%
O2N
O2N
N
N
N
N
Initially, we have performed the reaction of 1a and 2-
N
N
3k
, 57%
Me
bromobenzaldehyde 2a in DMSO using CuI as
a catalyst,
3j
, 36%
3l
, 51%
ethylenediamine as a ligand and K2CO3 as a base. Gratifyingly, this
reaction has resulted in the formation of the expected 2-methyl-3-
nitropyrazolo[1,5-a]quinoline 3a in 40% isolated yield (Table 1,
entry 1). The X-ray crystallographic analysis of the product 3a
confirmed its structure (for an ORTEP diagram, see Table 1).11 We
have then screened several copper catalysts, ligands, bases and
solvents (Table 1, entries 1-8) for this reacꢀon―it turned out that
the combination of CuI-neocuproine-K2CO3 in DMSO proved the
best to provide the compound 3a in excellent yield (Table 1, entry
4). It is noteworthy that this combination enabled to scale up the
O2N
O2N
N
N
N
N
3n
, 48%
3m
, 42%
a. Reaction conditions: 1 (0.5 mmol), 2 (0.5 mmol), CuI (0.05
mmol), neocuproine (0.1 mmol), K2CO3 (1.65 mmol), DMSO (2
mL); b. Yields are for isolated products.
reaction to a gram scale (1.9 g, 84%, Table 1, entry 4). It was also The reaction of 1a and 2-bromo-1-naphtaldehyde 2h furnished
observed that either copper catalyst-base combination or base benzo-fused pyrazolo[1,5-a]quinoline product 3h in moderate yield.
alone did give the product 3a albeit in significantly lower yields. In Use of sterically hindered ortho-bromo carbonyl compounds 2i-j
the presence of CuI-ligand and in the absence of base the formation afforded the corresponding pyrazoloquinolines 3i-j in reasonable
of the product 3a was not observed (see supporting information for yields. 3,5-Dialkyl substituted 4-nitropyrazoles 1b-c were employed
a
detailed optimization survey). Among the ortho- in this copper catalyzed tandem N-arylation-vinylogous nitroaldol
halobenzaldehydes, 2-bromobenzaldehyde gave the best isolated condensation process to give the corresponding pyrazolo[1,5-
yield of product 3a (Table 1, entries 4, 9 and 10).
a]quinoline products 3k-3n.
Having the set of optimized conditions in hand, we next turned
We then turned our focus to subject ortho-halo heteroaryl
to extend the scope of this tandem process with respect to 3,5- carbonyl compounds and 3,5-dialkyl substituted 4-nitropyrazoles in
disubstituted 4-nitropyrazoles and ortho-bromo substituted aryl the tandem copper catalysed N-arylation―vinylogous nitroaldol
aldehydes or ketones. The results are summarized in Scheme 1.
condensation process that would deliver heteroaryl-fused 3-
The reaction of 1a and 2,5-dibromobenzaldehyde 2b gave good nitropyrazolo[1,5-a]pyridine derivatives. The results
yield of the corresponding pyrazolo[1,5-a]quinoline product 3b. summarized in Table 2.
are
Whereas the reaction of 1a and 2-bromo-5-fluorobenzaldehyde 2c
The reactions of 1a-c with 2-chloro-1-methyl-1H-indole-3-
gave low yield of the corresponding pyrazolo[1,5-a]quinoline carbaldehyde 4a afforded the corresponding tetracyclic indole-
product 3c. The reaction of 1a and 2-bromobenzaldehydes 2d-g, fused pyrazolo[1,5-a]pyridine systems 5a-c in high yields (Table 2,
bearing electron donating substituents, gave low to moderate yields entries 1-3). The structure of the product 5a was revealed by X-ray
of the corresponding pyrazolo[1,5-a]quinoline products 3d-3g.
crystallographic analysis (for an ORTEP diagram, see Table 2).12
2 | J. Name., 2012, 00, 1-3
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Table 2 Reaction of 3,5-dialkyl substituted 4-nitropyrazoles 1a-c
and ortho-halo heteroaryl aldehydes 4a-ea
Scheme 2 Control experiments
Entry
1
Substrate 1
Substrate 4
Product 5, yieldb
Scheme 3 Attempted individual N-arylation and vinylogous
nitroaldol condensation of 1a
It is important to note that the reaction of 1a and 4a in the
absence of copper catalyst provided the corresponding adduct 5a in
39% yield only. This reaction may be explained by a nucleophilic
aromatic substitution (SNAr) reaction via an addition-elimination
process.6q,r However, the reaction of 1a and 4b did not give the
desired product by using the combination of CuI-neocuproine-
K2CO3. The N-arylaꢀon―vinylogous nitroaldol condensaꢀon of 1a-c
with benzyl substituted 2-chloro-1H-indole-3-carbaldehyde 4c
furnished the corresponding indole-fused pyrazolo[1,5-a]pyridine
derivatives 5d-f in moderate yields (Table 2, entries 5-7). The
reactions of 1a-c and 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-
carbaldehyde 4d provided the corresponding dipyrazole-fused
pyridine derivatives 5g-i in good yields (Table 2, entries 8-10). The
reactions of 2-bromo-3-pyridinecarbaldehyde 4e and 1a-1b
afforded the corresponding pyridine-fused pyrazolo[1,5-a]pyridine
derivatives 5j-5k in good yields (Table 2, entries 11-12).
2
3
4
5
6
―
It was thought that the present tandem copper catalysed N-
arylation―vinylogous nitroaldol condensation reaction would
involve the intermediates 6 or 7 that could result from the sole N-
arylation or sole vinylogous nitroaldol condensation, respectively
(Scheme 2). We have monitored the reaction of 3,5-dimethyl-4-
nitropyrazole 1a and 2-bromobenzaldehyde 2a by TLC and ESI-MS
at different intervals under the reaction conditions to find out
whether the formation of intermediates 6 or 7 takes place or not. It
was observed that the formation of product 3a only occurred in this
reaction. But no mass peaks (ESI-MS) were observed that
correspond to either of the products 6 or 7.
7
8
9
We have also conducted few experiments to perform N-
arylation and vinylogous nitroaldol condensation separately using
1a with suitable substrates. It is important to note that simple N-
aylation of 1a using bromobenzene did not give the corresponding
N-arylated product 8 under the reaction conditions (Scheme 3).6j,k
The unsuccessful N-arylation may be due to the reasons that (i) 3,5-
10
11
12
dimethyl-4-nitropyrazole is
a weak N-nucleophile due to the
conjugation of NH with 4-nitro group, and or (ii) lack of ortho-
coordinating group in the bromobenzene. The reaction of 1a and
benzaldehyde did not give the expected condensation product 9
(Scheme 3). In this case 5-methyl group of 1a may not be enough
acidic, due to the presence of NH group, to undergo vinylogous
nitroaldol condensation with benzaldehyde. Hence it may be noted
that the present tandem process is triggered by copper-catalysed N-
arylation of 1 with the assistance of carbonyl group of 2 (or 4) and
the carbonyl group would participate in the vinylogous nitroaldol
condensation to culminate the process.
a. Reaction conditions:
1
(0.5 mmol),
4
(0.5 mmol), CuI (0.05
mmol), neocuproine (0.1 mmol), K2CO3 (1.65 mmol), DMSO (2
mL); b. Yields are for isolated products; c. The reaction was
performed using only K2CO3.
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Experimental
General
Reactions were carried out in oven dried reaction flasks or screw-
cap vials. Solvents and reagents were transferred by oven-dried
syringes at ambient temperature. Analytical thin layer
chromatography (TLC) was performed on Merck glass or aluminium
sheets pre-coated with silica gel 60 F254 by using UV as a visualizing
agent (or) a 0.5% aqueous potassium permanganate soluꢀon―heat
(or) iodine as developing agents. Solvents were removed under
reduced pressure. Column chromatography was performed using
silica gel (60-120 or 100-200 or 230-400 mesh). The elution was
assisted by applying pressure with an air pump. Melting points
reported in this work are uncorrected and were determined using a
Superfit capillary point apparatus. The IR spectra were recorded on
a Bruker FT-IR spectrophotometer by dissolving the sample in
chloroform. IR (KBr) spectra were recorded on a Thermo Nicolet
NEXUS 670 FT-IR instrument. 1HNMR spectra were recorded on 300
and 500 MHz spectrometers in appropriate solvents and chemical
shifts are referenced to TMS via residual solvent signals. The
following abbreviations were used to explain multiplicities: s =
singlet, d = doublet, dd = double doublet, t = triplet, m = multiplet.
13C NMR spectra were recorded on 75 and 125 MHz spectrometers.
The mass spectral analyses were carried out using Electrospray
Ionization (ESI) techniques. Mass spectra were obtained on a
Shimadzu LCMS-2020 mass spectrometer and high resolution mass
spectra (HRMS) were recorded on a Thermo Scientific Exactive™
Orbitrap Mass Spectrometer or QSTAR XL Hybrid MS/MS mass
spectrometer. X-ray data for compounds 3a and 5a were collected
at room temperature using the Bruker Smart Apex CCD
diffractometer with graphite monochromated MoKα radiation
(λ=0.71073Å) with ω-scan method. All reactions were performed
using freshly distilled and dried solvents wherever it was necessary.
All solvents were distilled using standard procedures. Unless
otherwise noted, starting materials, catalysts, ligands and reagents
were obtained from commercial suppliers (Aldrich, Alfa Aesar, and
TCI) and those were used without further purification.
Scheme 4 Plausible mechanism
Scheme 5 Reduction of nitro group of 3a
Considering the above control experiments and literature
reports, a plausible mechanism can be proposed for the formation
of
3 or 5 in the present tandem copper catalysed N-
arylation―vinylogous nitroaldol condensation. It has been reported
that suitable ortho-substituents promote copper-catalysed N-
arylations.8h,l,n Initially, coordination of ortho-halo (hetero)aryl
carbonyl compound (2 or 4) with copper catalyst would give
intermediate I. Oxidative addition of the intermediate I lead to the
formation of intermediate II. Complexation of II with 1 may provide
intermediate III, in the presence of base. The ensuing intermediate
III on reductive elimination would give the products 3 or 5 via
tandem N-arylation―vinylogous nitroaldol condensation (Scheme
4).
Synthesis of pyrazoles 1a-c
Pyrazoles 1a-c were prepared by following literature reports.13
The reduction of nitro group of 3a using SnCl2 afforded the
corresponding 2-methylpyrazolo[1,5-a]quinolin-3-amine10 in 67%
yield (Scheme 5).
ortho-Halo heteroaryl aldehydes 4a-d
5-Chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde 4d was
prepared according to the reported procedure.14 2-Chloro-1H-
indole-3-carbaldehyde 4b was prepared following the same
procedure as for 4d by using indolin-2-one. The compound 4b was
subjected to alkylation using methyl iodide and benzyl bromide in
the presence of sodium hydride in DMF to obtain 2-chloro-1-
methyl-1H-indole-3-carbaldehyde 4a and 1-benzyl-2-chloro-1H-
indole-3-carbaldehyde 4c, respectively.
Conclusions
In summary, we have developed and demonstrated a new
tandem reaction process involving copper catalysed N-
arylaꢀon―vinylogous nitroaldol condensaꢀon between 3,5-
dialkylsubstituted 4-nitropyrazoles and ortho-halo substituted
(hetero)aryl aldehydes or ketones. This process furnished 3-
nitropyrazolo[1,5-a]quinoline
and
heteroaryl-fused
3-
nitropyrazolo[1,5-a]pyridine derivatives in moderate to high
yields. Further studies on the exploration and exploitation of
tandem processes involving arylaꢀon/addiꢀon―cyclisaꢀon is
an ongoing research work in our laboratory.
General procedure for the synthesis of 3a-n
3,5-Dialkyl-4-nitro-1H-pyrazole 1a-c (0.5 mmol), CuI (9.5 mg, 0.05
mmol), K2CO3 (227 mg, 1.65 mmol), neocuprione (21 mg, 0.1 mmol)
and dimethyl sulfoxide (2 mL) were added into a 10 mL screw cap
vial. The reaction mixture was stirred at room temperature for 30
min, followed by the addition of o-halo aryl aldehyde or ketone 2a-j
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(0.5 mmol). The reaction mixture was stirred at 120 oC for 48 h. The 151.6; MS (ESI) m/z 272 [M+H]+; HRMS (ESI, m/z): calcd for
reaction mixture was cooled to room temperature, diluted with C13H10O4N3 [M+H]+ 272.05931, found 272.06648.
water, extracted with ethyl acetate (2 x 20 mL), dried over
anhydrous Na2SO4 and filtered. The solvent was removed in vacuo 7-Methoxy-2-methyl-3-nitropyrazolo[1,5-a]quinoline 3f:- yellow
to afford a crude residue. The residue was purified by flash column solid 23 mg, 18%, Rf
= 0.3 (EtOAc/hexane, 1:9) Column
chromatography (hexane/EtOAc) on silica gel to obtain Chromatography (EtOAc/hexane, 5:95); MP 198-200 oC; IR (CHCl3)
pyrazolo[1,5-a]quinoline derivatives 3a-n.
741, 1215, 1420, 1516, 3019 cm-1; 1H-NMR (500 MHz, CDCl3) δ =
2.82 (s, 3H), 3.96 (s, 3H), 7.23 (d, J = 2.5 Hz, 1H), 7.42 (dd, J1 = 2.5
2-Methyl-3-nitropyrazolo[1,5-a]quinoline 3a:- yellow solid, 103 Hz, J2 = 9.5 Hz, 1H), 7.84 (d, J = 9.5 Hz, 1H), 8.22 (d, J = 9.5 Hz, 1H),
mg, 91%, Rf = 0.6 (EtOAc/hexane, 1:9) Column Chromatography 8.52 (d, J = 9.0 Hz, 1H); 13C-NMR (125 MHz, CDCl3) δ = 14.6, 55.8,
(EtOAc/hexane, 5:95); MP 192-194 oC; IR (CHCl3) 742, 1214, 1431, 108.5, 116.1, 117.6, 121.5, 125.2, 128.3, 130.7, 134.7, 149.7, 157.9;
1515, 3019 cm-1; 1H-NMR (500 MHz, CDCl3) δ = 2.85 (s, 3H), 7.60- MS (ESI) m/z 258 [M+H]+ HRMS (ESI, m/z): calcd for C13H12O3N3
7.63 (m, 1H), 7.81-7.84 (m, 1H), 7.90-7.94 (m, 2H), 8.26 (d, J = 9.5 [M+H]+ 258.08732, found 258.08783.
Hz, 1H), 8.64 (d, J = 8.5 Hz, 1H); 13C-NMR (125 MHz, CDCl3) δ = 14.7,
115.6, 116.1, 123.9, 126.4, 128.7, 131.2, 131.3, 133.2, 133.4, 135.7, 2,8-Dimethyl-3-nitropyrazolo[1,5-a]quinoline 3g:- yellow solid, 59
149.9; MS (ESI) m/z 228 [M+H]+ 250 [M+Na]+; HRMS (ESI, m/z): mg, 49%, Rf = 0.6 (EtOAc/hexane, 1:9) Column Chromatography
calcd for C12H10N3O2 [M+H]+ 228.07635, found 228.07675.
(EtOAc/hexane, 5:95); MP 198-200 oC; IR (CHCl3) 772, 1219, 1499,
1
1510, 2852, 2922 cm-1; H-NMR (500 MHz, CDCl3) δ = 2.63 (s, 3H),
7-Bromo-2-methyl-3-nitropyrazolo[1,5-a]quinoline 3b:- light green 2.83 (s, 3H), 7.42 (d, J =8.0 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.88 (d, J
solid, 109 mg, 71%, Rf
0.6 (EtOAc/hexane, 1:9) Column = 9.0 Hz, 1H), 8.17 (d, J =9.5 Hz, 1H), 8.42 (s, 1H); 13C-NMR (125
=
Chromatography (EtOAc/hexane, 3:97); MP 220-222 oC; IR (CHCl3) MHz, CDCl3) δ = 14.7, 22.2, 114.5, 115.6, 121.8, 128.1, 128.4, 131.2,
668, 771, 1463, 1514, 2921, 3015 cm-1; 1H-NMR (500 MHz, CDCl3) δ 133.3, 135.8, 142.5, 149.8; MS (ESI) m/z 242 [M+H]+; HRMS (ESI,
= 2.84 (s, 3H), 7.83 (d, J = 9.0 Hz, 1H), 7.89-7.90 (dd,J1 = 2.0 Hz, J2 = 9 m/z): calcd for C13H12O2N3 [M+H]+ 242.08513 found 242.09259.
0 Hz, 1H), 8.06 (d, J = 2.0 Hz, 1H), 8.29 (d, J = 9.5 Hz, 1H), 8.52 (d, J =
9.0 Hz, 1H); 13C-NMR (125 MHz, CDCl3) δ = 14.6, 116.9, 117.9, 119.9, 2-Methyl-3-nitrobenzo[h]pyrazolo[1,5-a]quinoline 3h:- yellow
125.2, 125.8, 129.9, 130.8, 132.2, 134.3, 135.5, 150.2; MS (ESI) m/z solid, 62 mg, 45%, Rf
= 0.5 (EtOAc/hexane, 1:9) Column
305 [M+H]+; HRMS (ESI, m/z): calcd for C12H9O2N3Br [M+H]+ Chromatography (EtOAc/hexane, 5:95); MP 222-224 oC; IR (CHCl3)
305.9799, found 305.98784.
772, 1218, 1511, 2852, 2921 cm-1; 1H-NMR (500 MHz, CDCl3) δ =
2.98 (s, 3H), 7.80-7.90 (m, 3H), 7.98 (d, J = 9.0 Hz, 1H), 8.06 (d, J =
7-Fluoro-2-methyl-3-nitropyrazolo[1,5-a]quinoline 3c:- yellow solid 8.0 Hz, 1H), 8.09 (d, J = 9.0 Hz, 1H), 8.53 (d, J = 9.0 Hz, 1H), 10.71 (d,
29 mg, 24%, Rf = 0.6 (EtOAc/hexane, 1:9) Column Chromatography J = 8.5 Hz, 1H); 13C-NMR (125 MHz, CDCl3) δ = 14.9, 115.7, 123.1,
(EtOAc/hexane, 5:95); MP 180-182 oC; IR (CHCl3) 742, 1214, 1531, 124.0, 125.4, 127.7, 128.1, 128.3, 128.5, 128.6, 130.2, 131.8, 134.9,
1693, 3019 cm-1; 1H-NMR (300 MHz, CDCl3) δ = 2.84 (s, 3H), 7.54- 137.7, 149.6; MS (ESI) m/z 278 [M+H]+; HRMS (ESI, m/z): calcd for
7.61 (m, 2H), 7.86 (d, J = 9.0 Hz, 1H), 8.30 (d, J =9.0 Hz, 1H), 8.62- C16H12O2N3 [M+H]+ 278.09240, found 278.09254.
8.67 (m, 1H); 13C-NMR (125 MHz, CDCl3) δ = 14.6, 113.1, 113.2,
116.9, 118.4 (9.0 Hz), 120.0 (25.2 Hz), 125.0, 130.0, 130.3, 149.9; 2-Methyl-3-nitro-5-phenylpyrazolo[1,5-a]quinoline 3i:- white solid,
MS (ESI) m/z 246 [M+H]+; HRMS (ESI, m/z): calcd for C12H9O2N3F 62 mg, 41%, Rf = 0.6 (EtOAc/hexane, 1:9) Column Chromatography
[M+H]+ 246.06757, found 246.06005.
(EtOAc/hexane, 5:95); MP 220-222 oC; IR (CHCl3) 772, 1219, 1498,
1
1677 cm-1; H-NMR (500 MHz, CDCl3) δ = 2.87(s, 3H), 7.53-7.58 (m,
7,8-Dimethoxy-2-methyl-3-nitropyrazolo[1,5-a]quinoline
3d:- 6H), 7.81-7.85 (m, IH), 7.91 (d, J = 8.5 Hz, 1H), 8.22 (s, 1H), 8.73 (d, J
yellow solid, 36 mg, 25%, Rf = 0.3 (EtOAc/hexane, 50:50) Column = 8.5 Hz, 1H); 13C-NMR (125 MHz, CDCl3) δ = 14.8, 115.5, 116.3,
o
Chromatography (EtOAc/hexane, 25:75); MP 232-234 C; IR (CHCl3) 123.3, 126.2, 127.7, 128.8, 128.9, 129.6, 131.1, 133.5, 135.2, 137.4,
772, 1218, 1514, 2852, 2922 cm-1; 1H-NMR (300 MHz, CDCl3) δ = 144.2, 150.1; MS (ESI) m/z 304 [M+H]+; HRMS (ESI, m/z): calcd for
2.84 (s, 3H), 4.04 (s, 3H), 4.15 (s, 3H), 7.21 (s, 1H), 7.84 (d, J = 9.0 Hz, C18H14O2N3 [M+H]+ 304.10078, found 304.10847.
1H), 8.02 (s, 1H), 8.16 (d, J = 9.3 Hz, 1H); 13C-NMR (125 MHz, CDCl3)
δ = 14.7, 56.3, 56.7, 97.2, 107.6, 113.6, 118.4, 129.1, 130.3, 131.6, 2,5-Dimethyl-3-nitropyrazolo[1,5-a]quinoline 3j:- white solid, 43
135.2, 149.0, 150.0, 153.3; MS (ESI) m/z 288 [M+H]+; HRMS (ESI, mg, 36%, Rf = 0.7 (EtOAc/hexane, 0.5:9.5) Column Chromatography
m/z): calcd for C14H14O4N3 [M+H]+ 288.09061, found 288.09722.
(EtOAc/hexane, 2:98); MP 208-210 oC; IR (CHCl3) 772, 1219, 1515,
1709, 3019 cm-1; 1H-NMR (300 MHz, CDCl3) δ = 2.77 (s, 3H), 2.82 (s,
2-Methyl-3-nitro-[1,3]dioxolo[4,5-g]pyrazolo[1,5-a]quinoline 3e:- 3H), 7.61-7.64 (m, 1H), 7.79-7.85 (m, 1H), 8.01 (d, J = 8.1 Hz, 1H),
yellow solid, 26 mg, 19%, Rf = 0.5 (EtOAc/hexane, 1:9) Column 8.12 (s, 1H), 8.65 (d, J = 8.4 Hz, 1H); 13C-NMR (125 MHz, CDCl3) δ =
Chromatography (EtOAc/hexane, 5:95); MP 212-214 oC; IR (CHCl3) 14.7, 19.6, 115.0, 116.3, 124.1, 124.8, 125.3, 126.2, 130.9, 132.9,
1
752, 1215, 1467, 1514, 2852, 2921 cm-1; H-NMR (300 MHz, CDCl3) 135.4, 139.8, 149.8; MS (ESI) m/z 242 [M+H]+ HRMS (ESI, m/z): calcd
δ = 2.82 (s, 3H), 6.19 (s, 2H), 7.19 (s, 1H), 7.79 (d, J = 9.3 Hz, 1H), for C13H12O2N3 [M+H]+ 242.09240, found 242.09266.
8.03 (s, 1H), 8.14 (d, J = 9.0 Hz, 1H); 13C-NMR (125 MHz, CDCl3) δ =
14.7, 95.9, 102.5, 105.2, 113.6, 119.8, 130.6, 135.4, 147.4, 150.1, 2-Ethyl-4-methyl-3-nitropyrazolo[1,5-a]quinoline 3k:- yellow solid,
73 mg, 57%, Rf = 0.6 (EtOAc/hexane, 1:9) Column Chromatography
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(EtOAc/hexane, 5:95); MP 196-198 oC; IR (CHCl3) 743, 1214, 1420, 281 [M+H]+; HRMS (ESI, m/z): calcd for C15H13O2N4 [M+H]+
1
1531, 3019 cm-1; H-NMR (500 MHz, CDCl3) δ = 1.44 (t, J = 7.5 Hz, 281.10330, found 281.10323.
3H), 2.76 (s, 3H), 3.17 (q, J = 7.5 Hz, 2H), 7.53-7.56 (m, 1H), 7.59 (s,
1H), 7.71.7.74 (m, 1H), 7.77 (d, J =8.0 Hz, 1H), 8.62 (d, J =8.5 Hz, 1H); 2-Ethyl-4,10-dimethyl-3-nitro-10H-pyrazolo[1',5':1,6]pyrido[2,3-
13C-NMR (125 MHz, CDCl3) δ = 12.4, 21.5, 21.9, 116.2, 123.6, 125.8, b]indole 5b:- yellow solid, 119 mg 77%, Rf = 0.5 (EtOAc/Hexane, 1:9)
126.2, 127.1, 127.5, 130.0, 130.5, 132.5, 134.9, 154.4; MS (ESI) m/z Column Chromatography (EtOAc/hexane, 5:95); MP 186-188 oC; IR
256 [M+H]+; HRMS (ESI, m/z): calcd for C14H14O2N3 [M+H]+ (CHCl3) 771, 1215, 1514, 3019 cm-1; 1H-NMR (500 MHz, CDCl3) δ =
256.10805 found, 256.10807.
1.46 (t, J = 7.5 Hz, 3H), 2.79 (s, 3H), 3.19 (q, J = 7.5 Hz, 2H), 4.57 (s,
3H), 7.36-7.39 (m, 1H), 7.52-7.54 (m, 2H), 7.96 (s, 1H), 8.02 (d, J =
2-Ethyl-4,8-dimethyl-3-nitropyrazolo[1,5-a]quinoline 3l:- yellow 7.5 Hz, 1H); 13C-NMR (125 MHz, CDCl3) δ = 12.1, 21.2, 22.2, 32.6,
solid, 69 mg, 51%, Rf
= 0.6 (EtOAc/hexane, 1:9) Column 109.2, 109.8, 117.7, 119.8, 121.1, 121.5, 125.5, 126.2, 133.6, 136.5,
Chromatography (EtOAc/hexane, 5:95); MP 176-178 oC; IR (CHCl3) 138.4, 155.9; MS (ESI) m/z 309 [M+H]+; HRMS (ESI, m/z): calcd for
743, 1214, 1420, 1531, 3019 cm-1; 1H-NMR (500 MHz, CDCl3) δ = C17H17O2N4 [M+H]+309.13460, found 309.13350.
1.45 (t, J = 7.5 Hz 3H), 2.60 (s, 3H), 2.73 (s, 3H), 3.17 (q, J = 7.5 Hz,
2H), 7.35-7.37 (m, 1H), 7.54 (s, 1H), 7.65 (d, J =8.0 Hz, 1H), 8.42 (s, 2-Isobutyl-10-methyl-3-nitro-10H-pyrazolo[1',5':1,6]pyrido[2,3-
1H); 13C-NMR (125 MHz, CDCl3) δ = 12.6, 21.4, 21.9, 22.1, 115.7, b]indole 5c:- yellow solid, 118 mg, 73%, Rf = 0.5 (EtOAc/Hexane,
121.5, 124.6, 127.3, 127.9, 130.5, 132.5, 135.1, 141.0, 154.4; MS 1:9) Column Chromatography (EtOAc/hexane, 5:95); MP 182-184
(ESI) m/z 270 [M+H]+; HRMS (ESI, m/z): calcd for C15H16O2N3 [M+H]+ oC; IR (CHCl3) 771, 1216, 1530, 2853, 2925, 3019 cm-1; 1H-NMR (500
270.12374, found 270.12370.
MHz, CDCl3) δ = 1.08 (d, J = 6.5 Hz, 6H), 2.31-2.39 (m, 1H), 3.16 (d, J
= 7.0 Hz, 2H), 4.60 (s, 3H), 7.40-7.43 (m, 1H), 7.56 (d, J = 4.0 Hz, 2H),
3m:- 8.06-8.08 (m, 1H), 8.13 (d, J = 8.5 Hz, 1H), 8.28 (d, J = 9.0 Hz, 1H);
2-Ethyl-4-methyl-3-nitrobenzo[h]pyrazolo[1,5-a]quinoline
yellow solid, 64 mg, 42%, Rf = 0.6 (EtOAc/hexane, 1:9) Column 13C-NMR (125 MHz, CDCl3) δ = 22.7, 27.5, 32.6, 37.1, 107.9, 109.9,
Chromatography (EtOAc/hexane, 5:95); MP 228-230 oC; IR (CHCl3) 110.1, 120.0, 121.1, 121.4, 121.9, 125.5, 125.8, 134.8, 137.9, 138.3,
753, 1411, 1645, 2824, 2946, 3329 cm-1; H-NMR (500 MHz, CDCl3) 154.2; MS (ESI) m/z 323 [M+H]+; HRMS (ESI, m/z): calcd for
1
δ = 1.58-1.60 (m, 3H), 2.83 (s, 3H), 3.31 (q, J = 7.5 Hz, 2H), 7.74-7.78 C18H19O2N4 [M+H]+ 323.15025, found 323.15094.
(m, 3H), 7.85 (t, J = 7.5 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 8.03 (d, J =
8.5 Hz, 1H), 10.69 (d, J = 8.5 Hz, 1H); 13C-NMR (75 MHz, CDCl3) δ = 10-Benzyl-2-methyl-3-nitro-10H-pyrazolo[1',5':1,6]pyrido[2,3-
12.2, 21.2, 22.0, 122.6, 124.0, 124.7, 125.8, 127.5, 127.8, 127.9, b]indole 5d:- yellow solid, 94 mg, 53%, Rf = 0.5 (EtOAc/Hexane, 1:9)
128.1, 128.6, 131.7, 134.5, 136.6, 153.7; MS (ESI) m/z 306 [M+H]+ Column Chromatography (EtOAc/hexane, 5:95); MP 210-212 oC; IR
HRMS (ESI, m/z): calcd for C18H16O2N3 [M+H]+ 306.12370, found (CHCl3) 742, 1213, 1408, 1519, 1626, 3019 cm-1; 1H-NMR (500 MHz,
306.12278.
CDCl3) δ = 2.81 (s, 3H), 6.40 (s, 2H), 7.21-7.25 (m, 3H), 7.27-7.29 (m,
2H), 7.38-7.42 (m, 1H) 7.46-7.49 (m, 1H), 7.50-7.52 (m, 1H), 8.07 (d,
2-Isobutyl-3-nitropyrazolo[1,5-a]quinoline 3n:- light yellow solid, J = 7.5 Hz, 1H), 8.15 (d, J = 9.0 Hz, 1H), 8.30 (d, J = 9.0 Hz, 1H); 13C-
65 mg, 48%, Rf = 0.6 (EtOAc/hexane, 1:9) Column Chromatography NMR (75 MHz, CDCl3) δ = 15.0, 48.8, 108.1, 110.3, 110.9, 112.0,
(EtOAc/hexane, 5:95); MP 178-180 oC; IR (CHCl3) 770, 1214, 2853, 120.0, 121.6, 122.3, 125.4, 126.0, 126.9, 127.7, 128.8, 134.2, 136.8,
1
2922, 3019 cm-1; H-NMR (300 MHz, CDCl3) δ = 1.05 (d, J = 6.0 Hz, 137.8, 151.5; MS (ESI) m/z 357 [M+H]+; HRMS (ESI, m/z): calcd for
6H), 2.25-2.34 (m, 1H), 3.13 (d, J = 7.5 Hz, 2H), 7.60 (t, J = 7.5 Hz, C21H17O2N4 [M+H]+ 357.13460, found 357.13426.
1H), 7.82 (t, J = 7.5 Hz, 1H), 7.89-7.94 (m, 2H), 8.28 (d, J = 9.3 Hz,
1H), 8.67 (d, J = 8.4 Hz, 1H); 13C-NMR (125 MHz, CDCl3) δ =22.6, 10-Benzyl-2-ethyl-4-methyl-3-nitro-10H-pyrazolo[1',5':1,6]pyrido-
27.7, 36.8, 115.8, 116.2, 124.0, 126.4, 128.6, 131.2, 133.3, 152.8; [2,3-b]indole 5e:- yellow solid, 88 mg, 46%, Rf = 0.5 (EtOAc/Hexane,
MS (ESI) m/z 270 [M+H]+; HRMS (ESI, m/z): calcd for C15H16O2N3 1:9) Column Chromatography (EtOAc/hexane, 5:95); MP 208-210
[M+H]+ 270.12370, found 270.12320.
oC; IR (CHCl3) 742, 1214, 1517, 3019 cm-1; 1H-NMR (400 MHz, CDCl3)
δ = 1.37 (t, J = 7.2 Hz, 3H), 2.81 (s, 3H), 3.16 (q, J = 7.6 Hz, 2H), 6.36
(s, 2H), 7.18-7.22 (m, 2H), 7.22-7.24 (m, 2H), 7.24-7.26 (m, 1H),
General procedure for the synthesis of 5a-k
General procedure for the synthesis of 3a-n was followed by using 7.35-7.39 (m, 1H), 7.44-7.48 (m, 1H), 7.51-7.54 (m, 1H), 7.99 (s, 1H),
3,5-dialkyl-4-nitro-1H-pyrazole 1a-c and o-halo heteroaryl aldehyde 8.03 (d, J = 8.0 Hz, 1H); 13C-NMR (125 MHz, CDCl3) δ = 12.0, 21.2,
4a-d.
22.2, 48.8, 109.5, 110.7, 118.2, 119.9, 121.4, 121.7, 125.7, 126.1,
126.9, 127.6, 128.7, 133.2, 136.5, 137.4, 138.1, 155.9; MS (ESI) m/z
385 [M+H]+; HRMS (ESI, m/z): calcd for C23H21O2N4 [M+H]+
2,10-Dimethyl-3-nitro-10H-pyrazolo[1',5':1,6]pyrido[2,3-b]indole
5a:- yellow solid, 116 mg 83%, Rf = 0.5 (EtOAc/Hexane, 1:9) Column 385.16590, found 385.16571.
Chromatography (EtOAc/hexane, 5:95); MP 258-260 oC; IR (CHCl3)
1
772, 1219, 1507, 1626, 1644, 2920 cm-1; H-NMR (500 MHz, CDCl3) 10-Benzyl-2-isobutyl-3-nitro-10H-pyrazolo[1',5':1,6]pyrido[2,3-
δ = 2.85 (s, 3H), 4.59 (s, 3H), 7.43-7.40 (m, 1H), 7.54-7.58 (m, 2H), b]indole 5f:- yellow solid, 87 mg 44%, Rf = 0.5 (EtOAc/Hexane, 1:9)
8.05 (d, J = 7.5 Hz, 1H), 8.09 (d, J = 9.0 Hz, 1H), 8.26 (d, J = 9.0 Hz, Column Chromatography (EtOAc/hexane, 5:95); MP 206-208 oC; IR
1H); 13C-NMR (125 MHz, CDCl3) δ =15.0, 32.6, 107.7, 109.9, 119.9, (CHCl3) 771, 1216, 1464, 1713, 2912, 3019 cm-1; 1H-NMR (500 MHz,
121.3, 122.0, 125.5, 125.9, 134.7, 137.6, 138.4, 151.4; MS (ESI) m/z CDCl3) δ = 0.97 (d, J = 6.5 Hz, 6H), 2.22-2.30 (m, 1H), 3.10 (d, J = 7.0
Hz, 2H), 6.38 (s, 2H), 7.20-7.25 (m, 5H), 7.39-7.42 (m, 1H), 7.47-7.51
6 | J. Name., 2012, 00, 1-3
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(m, 1H), 7.56 (d, J = 8.0 Hz, 1H), 8.08 (d, J = 8.0 Hz, 1H), 8.18 (d, J = HRMS (ESI, m/z): calcd for C13H13O2N4 [M+H]+ 257.10330, found
9.0 Hz, 1H), 8.32 (d, J = 9.0 Hz, 1H); 13C-NMR (125 MHz, CDCl3) δ = 257.10302.
22.6, 27.3, 37.1, 48.9, 108.6, 110.4, 110.7, 199.9, 121.9, 122.0,
125.4, 126.0, 126.9, 127.7, 128.7, 137.0, 137.9, 154.3; MS (ESI) m/z Synthesis of 2-Methylpyrazolo[1,5-a]quinolin-3-amine 10
399 [M+H]+; HRMS (ESI, m/z): calcd for C24H23O2N4 [M+H]+ Reduction of nitro group15 of 2-methyl-3-nitropyrazolo[1,5-
399.18155, found 399.18233.
a]quinoline 3a: Compound 3a (113 mg, 0.5 mmol) was suspended in
water (10 mL) and added a 3.5 M KOH (10 mL) solution. To this
3,7-Dimethyl-6-nitro-1-phenyl-1H-dipyrazolo[1,5-a:4',3'-e]pyridine mixture, solid SnCl2⋅2H2O (0.5 g, 2 mmol) was then added portion-
5g:- white solid, 100 mg 65%, Rf = 0.6 (EtOAc/Hexane, 1:9) Column wise. The reaction mixture was stirred at 100 oC and monitored by
Chromatography (EtOAc/hexane, 5:95); MP 240-242 oC; IR (CHCl3) TLC. After 0.5 h, the compound 3a disappeared (by TLC). The
1
771, 1596, 1622, 2921, cm-1; H-NMR (300 MHz, CDCl3) δ = 2.67 (s, reaction mixture was cooled to room temperature and insoluble
6H), 7.48-7.57 (m, 3H), 7.60-7.67 (m, 2H), 7.90 (d, J = 8.7 Hz, 1H), material was filtered. The filtrate was extracted with chloroform (2
8.11 (d, J = 9.6 Hz, 1H); 13C-NMR (125 MHz, CDCl3) δ = 12.3, 14.9, x 20 mL) and the organic phase was washed with brine (5 mL). The
110.5, 113.1, 125.0, 126.7, 128.4, 128.6, 134.3, 138.0, 138.3, 145.4, organic phase was dried over anhydrous Na2SO4, filtered and
150.7; MS (ESI) m/z 308 [M+H]+; HRMS (ESI, m/z): calcd for concentrated to get the product, 2-methylpyrazolo[1,5-a]quinolin-
C16H14O2N5 [M+H]+ 308.11420, found 308.11421.
3-amine 10 without any further purification.
7-Ethyl-3,5-dimethyl-6-nitro-1-phenyl-1H-dipyrazolo[1,5-a:4',3'-
2-Methylpyrazolo[1,5-a]quinolin-3-amine 10:- yellow solid, 66 mg,
e]pyridine 5h:- yellow solid, 105 mg 63%, Rf = 0.6 (EtOAc/Hexane, 67%, Rf = 0.3 (EtOAc/hexane, 50:50) Column Chromatography
1:9) Column Chromatography (EtOAc/hexane, 5:95); MP 178-180 (EtOAc/hexane, 40:60); MP 164-166 oC; IR (KBr) 764, 1218, 2853,
1
oC; IR (CHCl3) 772, 1219, 1484, 1743, 2923 cm-1; H-NMR (300 MHz, 2923, 3423 cm-1; 1H-NMR (500 MHz, CDCl3) δ = 2.47 (s, 3H), 7.18-
CDCl3) δ = 1.19 (t, J = 7.5 Hz, 3H), 2.63 (s, 3H), 2.72 (s, 3H), 3.00 (q, J 7.22 (m, 1H), 7.23-7.25 (m, 1H), 7.31-7.35 (m, 1H), 7.55-7.60 (m,
= 7.5 Hz, 2H), 7.46-7.53 (m, 3H), 7.56 (s, 1H), 7.60-7.63 (m, 2H); 13C- 1H), 7.64-7.67 (m, 1H), 8.40 (d, J1 = 8.0 Hz, 1H); 13C-NMR (125 MHz,
NMR (125 MHz, CDCl3) δ = 11.3, 12.2, 21.1, 21.7, 112.2, 120.5, CDCl3) δ = 14.7, 115.7, 116.0, 123.9, 126.4, 128.7, 131.2, 131.3,
124.5, 126.9, 128.1, 128.3, 133.5, 136.6, 138.6, 144.4, 154.9; MS 133.4, 135.8, 149.9; MS (ESI) m/z 198 [M+H]+; HRMS (ESI, m/z):
(ESI) m/z 336 [M+H]+; HRMS (ESI, m/z): calcd for C18H18O2N5 [M+H]+ calcd for C12H12N3 [M+H]+ 198.10257, found 198.10239.
336.14550, found 336.14562.
Acknowledgements
7-Isobutyl-3-methyl-6-nitro-1-phenyl-1H-dipyrazolo[1,5-a:4',3'-
e]pyridine 5i:- yellow solid, 89 mg, 51%, Rf = 0.5 (EtOAc/Hexane,
We thank CSIR-IICT for providing start-up grant, Department of
1:9) Column Chromatography (EtOAc/hexane, 5:95); MP 180-182
Science and Technology (DST), India for Fast track grant
1
oC; IR (CHCl3) 771, 1215, 1505, 2852, 2955 cm-1; H-NMR (500 MHz,
(SB/FT/CS-055/2012), and CSIR, New Delhi for financial
CDCl3) δ = 0.95 (d, J = 6.6 Hz, 6H), 2.04-2.16 (m, 1H), 2.68 (s, 3H),
support as part of XII Five Year plan under title ORIGIN (CSC-
2.96 (d, J = 6.9 Hz, 2H), 7.47-7.54 (m, 3H), 7.60-7.66 (m, 2H), 7.90 (d,
J = 9.3 Hz, 1H), 8.11 (d, J = 9.3 Hz, 1H); 13C-NMR (125 MHz, CDCl3) δ
0108). OO thanks CSIR for a fellowship.
= 12.2, 22.5, 26.9, 36.8, 110.6, 112.9, 124.9, 126.8, 128.3, 128.6,
138.0, 138.3, 145.3, 153.3; MS (ESI) m/z 350 [M+H]+; HRMS (ESI,
Notes and references
m/z): calcd for C19H20O2N5 [M+H]+ 350.16115, found 350.16241.
1
For reviews and taxonomy see (a) R. A. Bunce, Tetrahedron,
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2-Methyl-3-nitropyrazolo[1,5-a][1,8]naphthyridine 5j:- light yellow
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=
Chromatography (EtOAc/hexane, 5:95); MP 240-242 oC; IR (CHCl3)
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1H), 7.55-7.59 (m, 1H), 8.16 (d, J1 =8.0 Hz, 1H), 8.92 (m, 1H); 13C-
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DOI: 10.1039/C5OB01011J
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8 | J. Name., 2012, 00, 1-3
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