Synthesis of fully-substituted pyridines and dihydropyridines in a highly chemoselective manner utilizing a multicomponent reaction (MCR) strategy

Article abstract of DOI:10.1039/c4ra08237k

An efficient protocol has been developed for the synthesis of pyridines and 1,4-dihydropyridines based on chemoselective multicomponent reactions. Using readily available aldehydes, malononitrile and primary aliphatic amines, this procedure provides a divergent but straightforward access to a wide range of fully substituted pyridines and dihydropyridines via a primary amine based chemoselective strategy. Simple reaction procedure, good yields, mild reaction conditions, applicabilility to a wide range of substrates with the aid of chemoselectivity make this present protocol more innovative than existing ones. This journal is

Full text of DOI:10.1039/c4ra08237k

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Synthesis of fully-substituted pyridines and
dihydropyridines in a highly chemoselective
manner utilizing a multicomponent reaction (MCR)
strategy†
Cite this: RSC Adv., 2014, 4, 53752
*
Satavisha Sarkar, Deb K. Das and Abu T. Khan‡
An efficient protocol has been developed for the synthesis of pyridines and 1,4-dihydropyridines based on
chemoselective multicomponent reactions. Using readily available aldehydes, malononitrile and primary
aliphatic amines, this procedure provides a divergent but straightforward access to a wide range of fully
substituted pyridines and dihydropyridines via a primary amine based chemoselective strategy. Simple
reaction procedure, good yields, mild reaction conditions, applicabilility to a wide range of substrates
with the aid of chemoselectivity make this present protocol more innovative than existing ones.
Received 6th August 2014
Accepted 3rd October 2014
DOI: 10.1039/c4ra08237k
www.rsc.org/advances
natural products, pharmaceuticals, and synthetic organic
moieties.2,3 These pyridine skeletons are the most predominant
Introduction
due to their broad spectrum of potential biological activities
as antimitotic agents,4a anti-inammatory agents4b,c and
anticonvulsants.5
Multicomponent reactions (MCRs) have attracted much atten-
tion recently due to their wide applicability in combinatorial,
medicinal and heterocyclic chemistry. Formations of complex
molecular architectures with multiple bond-making and/or
bond-breaking in a single step along with high atom economy
are the key features of MCRs. Chemoselectivity in such reac-
tions is of obvious importance to devise strategies for different
target molecules with suitable chemical modications. In the
past decades, many investigators have reported the chemo-
selectively controlled MCRs with various metal catalysts,1a–d
solvents1e–g and substrate patterns.1h In a true sense such che-
moselective MCRs represent a unique processes by combining
several readily available starting materials to construct different
molecular frameworks via ne tuning of the reaction
conditions.
Construction of functionalized N-heterocycles utilizing MCR
strategy has evolved as a new synthetic tool. Nitrogen contain-
ing heterocycles show a vast abundance in numerous natural
products and several biologically active pharmaceuticals.
Among the all heteroaromatic compounds, highly substituted
pyridines are unrivaled and also considered as “privileged
medicinal scaffolds” because they are partial structures of many
They display signicant pharmacological properties for
regulation of arterial pressure6 and cholesterol levels in blood.7
Some polysubstituted pyridines are used as non-linear optical
materials,8 electrical materials,9 chelating agents in metal
ligand chemistry10 and as uorescent liquid crystals.11 More-
over, 2-amino-3-cyanopyridine derivatives have raised signi-
cant response as potent inhibitors of HIV-1.12 Dihydropyridines
and their derivatives are key intermediates for the synthesis of
several biological active compounds as those for the treatment
of cardiovascular disease and hypertension,13 potent calcium
channel antagonist, and agonist.14 They also have prospective
application in other pharmacological activities.15 Some of these
biologically active scaffolds are shown in Fig. 1.
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781
039, India. E-mail: atk@iitg.ernet.in; Fax: +91 361 2582349; Tel: +91 361 2582305
† Electronic supplementary information (ESI) available: 1H and 13C NMR spectra
and HRMS spectra, X-ray crystallographic data (CIF les) of 4a and 6d, spectral
data of all compounds and copies of 1H and 13C NMR spectra of products.
CCDC 1006358 and 913525. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c4ra08237k
‡ Present address: Vice-Chancellor, Aliah University, DN 18, 8th Floor, Sector V,
Kolkata-700 091, India.
Fig. 1 Some biologically active pyridine and dihydropyridine moieties.
53752 | RSC Adv., 2014, 4, 53752–53760
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The classical recipes for the construction of pyridine deriv-
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Results and discussion
atives such as the Hantzsch,16 Knoevenagel17 and Chichibabin18
reactions generally involve condensation of amines and
carbonyl compounds. From the 19th century several efficient
synthetic procedures have been developed for the synthesis of
pyridine derivatives, mostly based on cycloaddition reactions,
or cross-coupling chemistry, which initiates the search for new
approaches that offer concise and regiospecic strategies,
making it topic of considerable interest.19 Recently several
scientists have used the MCR strategy to synthesize highly
dense 6-thio-pyridine skeletons from aldehydes, malononitrile
and aromatic thiols under basic environments20 or in presence
of ionic liquids.21 Now-a-days Lewis acid catalysts are also used
to produce aryl thiol substituted pyridine moieties.22 We found
during literature survey that the 2-amino-6-alkylamino-3,5-
dicyano pyridine derivatives can be synthesized directly from
2-chloro-pyridine moieties23 or from thio-pyran derivatives.24
Ramakrishnan et al. synthesized25a these pyridine skeletons
utilizing pyrrolidine from chalcones as well as aromatic alde-
hydes under reux conditions for several hours. Use of such
secondary amines was also mentioned by Choudhury et al.
during their synthesis and photo-physical studies of 6-thio-
pyridine derivatives.25b The fully substituted pyridine skele-
tons can also be synthesized using aqueous solution of methyl
amine or dimethyl amine in excess amounts.25c The use of
amino triazole compounds with malononitrile and carbonyl
groups for the synthesis of 1,2,4-triazolo[4,3-a]pyrimidines have
also been observed earlier.25d The demerits of the above
mentioned procedures are longer reaction time, reux condi-
tions and/or use of excess reagents.23–25 Over the past several
years, various nucleophiles mainly the thiophenols have been
used in these reactions.20–22 However, the use of aliphatic
amines as nucleophiles in these reactions were rarely explored.
In this paper, we report a novel one-pot primary aliphatic amine
based multicomponent domino reaction for the synthesis of
polysubstituted pyridine and dihydropyridine derivatives in a
highly chemoselective manner from simple and readily avail-
able aliphatic amines, aromatic aldehydes and malononitrile
with good yields under mild reaction conditions (Scheme 1).
As initial endeavor, a trial reaction was performed with 1 mmol
of 4-chlorobenzaldehyde (1d), 2 mmol of malononitrile (2) and 1
mmol of cyclohexylamine (3a) in methanol as solvent in the
presence of 15 mol% 4-dimethylaminopyridine (DMAP) as the
catalyst. Aer 5 h, a solid precipitate (4d) was separated out
which was characterized from spectroscopic techniques and
was found to be the desired fully substituted pyridine derivative
(Table 1, entry 1). It was observed that the yield increased upto
81% in presence of 20 mol% of DMAP. However, increasing the
amount of catalyst up to 30 mol% did not affect the reaction any
longer (Table 1, entries 2 & 3). To verify the effect of solvents the
similar reaction was executed with different solvents such as
EtOH, CH3CN, CH2Cl2 and H2O (Table 1, entries 4 to 7). Cata-
lysts with basic nature such as DBU, Et3N, PPh3, N,N-dimethyl
aniline (DMA) provided either lower yields or required longer
reaction time (Table 1, entries 8 to 11). The reaction prolonged
with very poor yield in absence of the catalyst (Table 1, entry 12).
It has been observed the 20 mol% DMAP in presence of
MeOH is the best reaction conditions for this particular
reaction.
With the condition optimized, we next wanted to verify the
scope and generality of this reaction with various aromatic
aldehydes using malononitrile and cyclohexylamine to generate
our desired pyridine moiety (Table 2). Aromatic aldehydes with
electron donating functionalities as –Me, –OMe (4b & 4c)
procured better yields as compared to electron withdrawing
groups as –Cl, –Br (4d & 4e). Unfortunately, no desired product
Table 1 Optimization of reaction conditions for the synthesis of
functionalized pyridine (4d)a
Sl. no.
Catalyst (mol%)
Solvent
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
DMAP (15)
DMAP (20)
DMAP (30)
DMAP (20)
DMAP (20)
DMAP (20)
DMAP (20)
DBU (20)
Et3N (20)
PPh3 (20)
DMA (20)
—
MeOH
MeOH
MeOH
EtOH
CH3CN
CH2Cl2
H2O
MeOH
MeOH
MeOH
MeOH
MeOH
5
4.5
4.5
9
10
8
12
7
6
74
81
82
35
26
57
<10
65
68
62
57
14
9
10
11
12
6.5
8
17
a
All the reactions were performed with 4-chlorobenzaldehyde (1.0
mmol), malononitrile (2.0 mmol) and cyclohexylamine (1.0 mmol) at
rt. b Isolated yields.
Scheme 1 Differential selectivity during synthesis of fully substituted
pyridines and dihydropyridines.
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Table 2 Scope of various substituted pyridine derivativesa
(4f) was obtained when the similar reaction was performed with
highly electron decient 4-nitrobenzaldehyde. Still satisfactory
results were gained for 4-formylbenzonitrile, 3-uo-
robenzaldehyde and 3-nitrobenzaldehyde (4g to 4i) under
identical reaction conditions. Even cyclohexane-carboxaldehyde
gave the desired pyridine moiety (4j). Apart from cyclohexane-
carboxaldehyde, other aliphatic aldehydes such as long chain
butyraldehyde or 3-methylbutyraldehyde produced the expected
pyridine skeletons (4k & 4l) in moderate yields.
We further extended the scope of the reaction with a series of
different primary aliphatic amines utilizing benzaldehyde and
malononitrile under similar reaction conditions. From strained
cyclopropylamine to acyclic butyl-1-amine upto long chain
hexadecan-1-amine led to our desired 6-alkyl amino pyridine
derivatives (4m to 4o) in good to moderate yields. Even cyclo-
hexylmethanamine gave corresponding pyridine derivative 4p
in good yields. With chiral primary amines such as (R/S)-1-
phenylethanamine we observed the corresponding pyridine
moieties (4q & 4r) bearing chiral centre in the product. Next, we
carried out the reactions of malononitrile and benzaldehyde or
4-methylbenzaldehyde with secondary amines such as piperi-
dine or pyrrolidine under similar reaction conditions to
generate the anticipated pyridine moieties (4s to 4v) in good to
moderate yields.
Encouraged by the above results, we extended the substrate
variety utilizing benzylamine with benzaldehyde and malononi-
trile under similar reaction conditions. Aer the usual spectro-
scopic analysis, it was found that the product was 2,6-diamino-1-
benzyl-4-phenyl-1,4-dihydropyridine-3,5-dicarbonitrile instead of
our expected substituted pyridine derivatives i.e. 2-amino-6-
1
(benzylamino)-4-phenylpyridine-3,5-dicarbonitrile. The H NMR
spectrum of 6a showed one broad singlet at d ¼ 6.26 due to the
four NH2 protons, a singlet at d ¼ 3.96 ppm due to the –CH
proton of the dihydropyridine ring and in 13C NMR two peaks at
the region of d ¼ 75–80 ppm, for the carbon atoms attached with
the –CN groups in the pyridine rings, were found to be missing.
From these observations, it was quite obvious that instead of fully
substituted pyridine ring totally substituted dihydropyridine
skeleton was formed (Table 3).
To examine the generality of this protocol, we performed the
reactions of malononitrile and benzyl amine with different
aromatic aldehydes under the optimised condition. The
aromatic aldehydes with electron donating substituents as
–OMe (6b) provided better yield than the electron decient
substituents as –F, –Cl, –Br (6c to 6e). When the reaction was
extended for aliphatic aldehydes, the desired dihydropyridine
moiety (6f) was obtained as product. Replacing the aromatic
moiety of the benzyl amine skeleton with heteroaromatic one
such as furan-3-ylmethanamine gave the expected highly
substituted dihydropyridine ring. These reactions were also
repeated successfully even with aromatic aldehydes having
different substituents such as –OMe, –Cl, –Br (6h to 6j) in the
ring.
a
Isolated yields.
However, the reaction did not proceed in presence of
aromatic amines. When the reaction was carried with 4-chlor-
obenzaldehyde, malononitrile and aniline under similar reac-
tion conditions, we isolated only the Knoevenagel product may
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Table 3 Scope of various substituted 1,4-dihydropyridine derivativesa
The formation of these fully substituted pyridines and
dihydropridines were further established by X-ray crystallo-
graphic structure analysis of the compound 4a and 6d Fig. 2.
Based on literature reports,20,25 a plausible mechanism for
the formation of these fully substituted pyridine 4 and dihy-
dropyridine 6 rings is shown in Scheme 2. The mechanistic
approach involves the Knoevenagel condensation of aromatic
aldehyde and malonitrile forming adduct A in the rst step,
followed by Michael addition with malononitrile to form a tet-
racyano intermediate II & VI by amine. In the next step, the
intermediates III & VI forms dihydropyridine moieties through
cyclization as shown in intermediates IV & VII which is further
followed by aromatization for cyclohexylamines and 1,3 H shi
for benzyl amines and to form 2-amino-6-alkylamino-3,5-
dicyanopyridines 4 and 2,6-diamino-3,5-dicyano dihydropyr-
idines 6, respectively.
The synthesis of pyridine and dihydropyridine moiety
depends mainly on two major characters of the amine groups,
the strength of the amine and its steric effect. In a polar protic
solvent like MeOH, nucleophilicity as well as basicity of amines
together regulate the chemoselectivity issue. According to the
literature survey26 benzylamine is less basic (having lower pKa
values < 10) compared to other amines viz. cyclohexylamine,
cyclohexylmethylamine, heptylamine, piperidine, pyrrolidine,
a
Isolated yields.
Fig. 2 X-ray crystal structure of 4a (CCDC 1006358) and 6d (CCDC
913525).
be due to lower basicity of the aromatic amines. As these pyri-
dine scaffolds are utilized in several step reactions or in natural
product synthesis, we wanted to examine its efficiency in large
scale. During the synthesis of 4d in multigram quantities we
carried out the reaction with 4-chlorobenzaldehyde, malono-
nitrile and cyclohexylamine under identical reaction condition
in 10 mmol scale which afforded the desired product in 2.25 g
with a yield of 64%.
Scheme 2 Plausible mechanism for the formation of pyridine and
dihydropyridine.
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etc. (pKa values > 10). On the other hand for the amines the was concentrated in vacuo and puried through column
effect of delocalization (free bases and its conjugate acids) chromatography.
increases with increasing the basic strength. Thus delocaliza-
2-Amino-6-(cyclohexylamino)-4-phenylpyridine-3,5-dicarbo-
tion is preferred for amines having higher pKa values (>10) i.e. nitrile. White solid (0.247 g, 78%); Mp 250–254 ꢁC;1H NMR
having higher basicity which is followed by further attack of (DMSO-D6, 400 MHz): d 1.08–1.15 (m, 1H), 1.22–1.31 (m, 2H),
other –NH2 functionality of the amidine group to generate cyclic 1.38–1.46 (m, 2H), 1.58–1.61 (m, 1H), 1.71–1.80 (m, 4H), 3.96–
intermediate IV from III. However amines containing lower pKa 4.18 (m, 1H), 6.95 (d, J ¼ 8.4 Hz, 1H), 6.95 (bs, 2H), 7.4–7.51 (m,
values (<10) viz. benzylamine and furfurylamine, both prefer to 5H); 13C NMR (DMSO-D6, 150 MHz): d 25.10, 25.14, 31.79, 49.50,
behave as nucleophile rather than base. Thus for both these two 78.97, 80.43, 116.43, 116.57, 128.26, 128.59, 129.85, 135.22,
amines the nitrogen atom directly attacks to form the cyclized 158.14, 159.72, 161.00; IR (KBr, cmꢂ1): 1559, 1630, 2205, 2925,
moiety VII from VI. The other regulating factor could be 3333, 3363, 3484; Anal. calcd for C19H19N5: C, 71.90; H, 6.03; N,
attributed to the steric effect caused by the cyclic ring present 22.07; found: C, 71.98; H, 6.12; N, 21.96. HRMS (ESI) calcd for
next to the amine group, forcing the amine to take the 6th
position in the ring instead of initiating the amine group to
C
19H19N5 (M + H+) 318.1719, found 318.1725.
2-Amino-6-(cyclohexylamino)-4-(p-tolyl)pyridine-3,5-dicarbo-
involve in the ring formation directly. As for the benzylic nitrile. White solid (0.278 g, 84%); Mp 213–216 ꢁC;1H NMR
amines, the carbon atom adjacent to the amine group is (CDCl3, 400 MHz): d 1.15–1.31 (m, 3H), 1.32–1.48 (m, 2H), 1.59–
substituted by planar aromatic ring, whereas in case of C- 1.7 (m, 1H), 1.71–1.88 (m, 2H), 1.95–2.09 (m, 2H), 2.40 (s, 3H),
methyl-substituent in benzylamines the presence of both 3.95–4.05 (m, 1H), 5.44 (s, 1H), 5.47 (s, 2H), 7.3 (d, J ¼ 7.6 Hz,
methyl and phenyl group in carbon atom adjacent to the amine 2H), 7.4 (d, J ¼ 8 Hz, 2H)13C NMR (CDCl3, 100 MHz): d 21.58,
creates strong steric hindrance to form pyridine ring and not 24.99, 25.57, 32.92, 50.21, 80.04, 82.53, 116.91, 117.07, 128.33,
the dihydropyridine moiety.
129.21, 129.53, 129.63, 131.59, 140.85, 158.86, 159.47, 161.22; IR
(KBr, cmꢂ1): 1508, 1567, 1596, 2209, 2935, 3311, 3383, 3502.;
Anal. calcd for C20H21N5: C, 72.48; H, 6.39; N, 21.13; found: C,
72.57; H, 6.46; N, 21.04. HRMS (ESI) calcd for C20H21N5 (M + H+)
332.1875, found 332.1867.
Conclusions
In summary, we have disclosed a convenient one-pot synthesis
of multisubstituted pyridine and dihydropyridine molecule of
potent synthetic and pharmacological importance via base
catalyzed multicomponent reaction utilizing readily available
primary aliphatic amines in a highly chemoselective manner.
In case of pyridine rings, the nitrogen atom from the malo-
nonitrile is solely responsible for forming the ring where as in
dihydropyridines the nitrogen atom of the ring comes from
benzyl amines or methyl-furfural amines. Besides simple and
mild reaction conditions, chemoselective switch in reaction
procedure are the remarkable features of this present protocol.
It should be noted that the richness of the functionality in the
fully substituted pyridine and dihydropyridine moieties, for
example amino and cyano groups, may render these
compounds as useful synthons for further synthetic organic
transformations.
2-Amino-6-(cyclohexylamino)-4-(4-methoxyphenyl)pyridine-
3,5-dicarbonitrile. White solid (0.297 g, 86%); Mp 208–211 C;
ꢁ
1H NMR (DMSO-D6, 400 MHz): d 1.05–1.19 (m, 1H), 1.2–1.34 (m,
2H), 1.35–1.5 (m, 2H), 1.55–1.65 (m, 1H), 1.67–1.85 (m, 4H), 3.83
(s, 3H), 3.95–4.19 (m, 1H), 6.87 (d, J ¼ 8 Hz, 1H), 7.07 (d, J ¼ 8.8
Hz, 2H), 7.28 (bs, 2H), 7.41 (d, J ¼ 8.8 Hz, 2H);13C NMR (DMSO-
D6, 150 MHz): d 25.40, 25.46, 32.14, 49.78, 55.63, 79.28, 80.72,
114.27, 117.00, 117.12, 127.50, 130.28, 158.60, 159.68, 160.77,
161.43; IR (KBr, cmꢂ1):1482, 1559, 1626, 2208, 2927, 3307, 3341,
3447; Anal. calcd for C20H21N5O: C, 69.14; H, 6.09; N, 20.16;
found: C, 69.26; H, 6.18; N, 20.03. HRMS (ESI) calcd for
C
20H21N5O (M + H+) 348.1824, found 348.1826.
2-Amino-4-(4-chlorophenyl)-6-(cyclohexylamino)pyridine-3,5-
dicarbonitrile. White solid (0.285 g, 81%); Mp 227–230 ꢁC;1H
NMR (DMSO-D6, 600 MHz): d 1.02–1.2 (m, 1H), 1.21–1.32 (m,
2H), 1.38–1.49 (m, 2H), 1.56–1.65 (m, 1H), 1.68–1.72 (m, 4H),
4.0–4.09 (m, 1H), 6.99 (d, J ¼ 7.8 Hz, 1H), 7.36 (bs, 2H), 7.49 (d, J
¼ 8.4 Hz, 2H), 7.60 (d, J ¼ 8.4 Hz, 2H), 13C NMR (CDCl3, 150
MHz): d 25.06, 25.09, 31.73, 49.47, 78.87, 80.33, 116.24, 116.37,
128.69, 128.82, 130.24, 130.34, 134.04, 134.70, 158.00, 158.52,
Experimental section
General procedure
In a dried 25 mL round-bottomed ask was taken a mixture of 160.86; IR (KBr, cmꢂ1): 1480, 1539, 1629, 2208, 2936, 3311, 3328,
aldehyde (1.0 mmol), malononitrile (2.0 mmol) and 20 mol% 4- 3471; Anal. calcd for C19H18ClN5: C, 64.86; H, 5.16; N, 19.91;
dimethylaminopyridine (DMAP). It was kept for stirring for 1 h found: C, 64.97; H, 5.27; N, 19.78. HRMS (ESI) calcd for
at room temperature. Aer adding the requisite amine (1.0 C19H18ClN5 (M + H+) 352.1329, found 352.1336.
mmol) into it, the reaction mixture was le for stirring. A thick
2-Amino-4-(4-bromophenyl)-6-(cyclohexylamino)pyridine-3,5-
1
precipitate separated out aer some time, which was then dicarbonitrile. White solid (0.301 g, 76%); Mp 239–242 ꢁC; H
¨
ltered off through a Buchner funnel and the precipitate was NMR (DMSO-D6, 600 MHz): d 1.06–1.15 (m, 1H), 1.21–1.31 (m,
washed with 30 mL of hexane–ethyl acetate (7 : 3) to remove 2H), 1.38–1.47 (m, 2H), 1.57–1.63 (m, 1H), 1.69–1.82 (m, 4H),
unreacted starting material, if any. In case of aliphatic alde- 3.85–4.10 (m, 1H), 7.01 (d, J ¼ 8.4 Hz, 1H), 7.36(bs, 2H), 7.42 (d, J
hydes, aer completion of the reaction the solvent was removed ¼ 8.4 Hz, 2H), 7.74 (d, J ¼ 8.4 Hz, 2H), 13C NMR (DMSO-D6, 150
in rotary evaporator. It was extracted with dichloromethane (2 ꢀ MHz): d 25.08, 25.11, 31.75, 49.51, 78.80, 80.28, 116.27, 116.40,
10 mL), washed with water and dried over anhydrous Na2SO4. It 123.46, 130.47, 130.55, 131.66, 131.79, 134.44, 158.01, 158.60,
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160.88; IR (KBr, cmꢂ1):1479, 1551, 1628, 2208, 2937, 3225, 3309, 5.28 (d, J ¼ 7.8 Hz, 1H), 5.34 (s, 2H); 13C NMR (CDCl3, 150 MHz):
3472; Anal. calcd for C19H18BrN5: C, 57.59; H, 4.58; N, 17.67; d 14.04, 23.28, 25.03, 25.66, 33.06, 36.01, 50.18, 80.41, 82.87,
found: C, 57.68; H, 4.67; N, 17.56. HRMS (ESI) calcd for 116.37, 116.55, 158.84, 161.07, 162.05; IR (KBr, cmꢂ1): 1465,
C19H18BrN5 (M + H+) 396.0824, found 396.0828.
1582, 1628, 2206, 2220, 2854, 3307, 3353, 3495; Anal. calcd for
C16H21N5: C, 67.82; H, 7.47; N, 24.71; found: C, 67.94; H, 7.61; N,
2-Amino-4-(4-cyanophenyl)-6-(cyclohexylamino)pyridine-3,5-
dicarbonitrile. Yellow solid (0.229 g, 67%); Mp 221–223 C; H 24.58. MS (ESI) calcd for C16H21N5 (M + H+) 284.1875, found
1
ꢁ
NMR (CDCl3, 600 MHz): d 0.79–0.91 (m, 2H), 1.35–1.46 (m, 2H), 284.2983.
1.58–1.61 (m, 2H), 1.77–1.82 (m, 2H), 1.96–2.08 (m, 2H), 3.85–
2-Amino-6-(cyclohexylamino)-4-isobutylpyridine-3,5-dicar-
4.10 (m, 1H), 5.48 (d, J ¼ 7.8 Hz, 1H), 5.53 (s, 2H), 7.61 (d, J ¼ 7.8 bonitrile. Solid (0.198 g, 67%); Mp 174–177 ꢁC; 1H NMR (CDCl3,
Hz, 2H), 7.42 (d, J ¼ 7.8 Hz, 2H); 13C NMR (CDCl3, 150 MHz): d 600 MHz): d 1.01 (d, J ¼ 6.6 Hz, 6H), 1.16–1.27 (m, 2H), 1.32–1.41
25.01, 25.61, 32.95, 50.52, 79.85, 80.53, 114.62, 116.05, 116.24, (m, 2H), 1.61–1.69 (m, 2H), 1.78–1.80 (m, 2H), 1.94–2.0 (m, 2H),
118.12, 129.43, 132.90, 138.92, 157.20, 158.70, 161.08; IR (KBr, 2.08–2.16 (m, 1H), 2.63 (d, J ¼ 7.8 Hz, 2H), 3.89–3.98 (m, 1H),
cmꢂ1): 1498, 1577, 1625, 2208, 2932, 3222, 3327; Anal. calcd for 5.28 (d, J ¼ 7.8 Hz, 1H) 5.33 (s, 2H); 13C NMR (CDCl3, 150 MHz):
C
20H18N6: C, 70.16; H, 5.30; N, 24.54; found: C, 70.24; H, 3.43; N, d 22.56, 25.04, 25.67, 29.88, 33.07, 42.83, 50.20, 80.93, 83.43,
24.41. MS (ESI) calcd for C20H18N6 (M + H+) 343.1671, found 116.57, 116.76, 158.81, 161.02, 161.17; IR (KBr, cmꢂ1): 1484,
343.2391. 1581, 1629, 2202, 2218, 2927, 3216, 3372, 3499; Anal. calcd for
2-Amino-6-(cyclohexylamino)-4-(3-uorophenyl)pyridine-3,5- 17H23N5: C, 68.66; H, 7.80; N, 23.55; found: C, 68.78; H, 7.92; N,
C
1
ꢁ
dicarbonitrile. White solid (0.241 g, 72%); Mp 264–268 C; H 23.67.
NMR (DMSO-D6, 600 MHz): d 1.06–1.15 (m, 1H), 1.20–1.31 (m,
2-Amino-6-(cyclopropylamino)-4-phenylpyridine-3,5-dicar-
1
ꢁ
2H), 1.38–1.49 (m, 2H), 1.57–1.62 (m, 1H), 1.69–1.85 (m, 4H), bonitrile. White solid (0.185 g, 67%); Mp 245–248 C; H NMR
3.98–4.09 (m, 1H), 6.98 (d, J ¼ 8.4 Hz, 1H), 7.29 (d, J ¼ 7.8 Hz, (DMSO-D6, 400 MHz): d 0.64–0.79 (m, 4H), 2.88–3.00 (m, 1H),
1H), 7.34–7.40 (m, 2H), 7.55–7.61 (m, 1H); 13C NMR (DMSO-D6, 7.3–7.46 (m, 2H), 7.46–7.5 (m, 1H), 7.51–7.6 (m, 3H); 13C NMR
150 MHz): d 25.06, 25.09, 31.71, 49.47, 78.89, 80.36, 115.35, (DMSO-D6, 100 MHz): d 6.41, 24.67, 79.50, 80.53, 116.22, 116.47,
115.51, 116.14, 116.28, 116.59, 116.72, 124.56, 130.80, 130.86, 128.27, 128.53, 129.79, 135.12, 159.55, 160.22, 160.87; IR (KBr,
137.31, 137.37, 157.96, 158.28, 160.83, 160.89, 165.52; IR (KBr, cmꢂ1): 1481, 1510, 1628, 2203, 3327, 3371, 3488; Anal. calcd for
cmꢂ1):1479, 1559, 1630, 2203, 2926, 3375, 3416, 3490; Anal.
C16H13N5: C, 69.80; H, 4.76; N, 25.44; found: C, 69.91; H, 4.83. N,
calcd for C19H18FN5: C, 68.04; H, 5.41; N, 20.88; found: C, 68.13; 25.36 HRMS (ESI) calcd for C16H13N5 (M + H+) 276.1249, found
H, 5.48; N, 20.79. HRMS (ESI) calcd for C19H18FN5 (M + H+) 276.1247.
336.1624, found 336.1631.
2-Amino-6-(butylamino)-4-phenylpyridine-3,5-dicarbonitrile.
2-Amino-6-(cyclohexylamino)-4-(3-nitrophenyl)pyridine-3,5- White solid (0.217 g, 74%); Mp 175–177 ꢁC; 1H NMR (DMSO-D6,
1
ꢁ
dicarbonitrile. White solid (0.235 g, 65%); Mp 210–213 C; H 400 MHz): d 0.81–0.95 (m, 3H), 1.25–1.41 (m, 2H), 1.45–1.62 (m,
NMR (DMSO-D6, 400 MHz): d 1.04–1.18 (m, 1H), 1.19–1.36 (m, 2H), 3.38–3.45 (m, 2H), 5.40 (s, 2H), 5.53 (s, 1H), 7.4–7.52 (m,
2H), 1.38–1.5 (m, 2H), 1.55–1.68 (m, 1H), 1.69–1.84 (m, 4H), 5H); 13C NMR (DMSO-D6, 150 MHz): d 13.93, 20.18, 31.09, 41.43,
3.98–4.11 (m, 1H), 7.09 (d, J ¼ 8.4 Hz, 1H), 7.43 (s, 2H), 7.85 (t, J 80.26, 82.69, 116.72, 116.88, 128.46, 129.00, 130.20, 130.65,
¼ 7.8 Hz, 1H), 7.97 (d, J ¼ 8 Hz, 1H), 7.34–7.42 (m, 1H); 13C NMR 134.52, 159.35, 159.77, 161.24; IR (KBr, cmꢂ1):1484, 1559, 1653,
(DMSO-D6, 150 MHz): d 25.09, 31.75, 49.59, 78.97, 80.48, 116.16, 2202, 2925, 3337, 3350, 3460; Anal. calcd for C17H17N5: C, C,
116.28, 123.37, 124.70, 130.56, 135.18, 136.72, 147.67, 157.42, 70.08; H, 5.88; N, 24.04; found: C, 70.17; H, 5.97; N, 24.16.
157.97, 160.85; IR (KBr, cmꢂ1):1347, 1559, 1653, 2207, 2925,
2-Amino-6-(hexadecylamino)-4-phenylpyridine-3,5-dicarbo-
3331, 3465, 3496; Anal. calcd for C19H18N6O2: C, 62.97; H, 5.01; nitrile. White solid (0.285 g, 62%); Mp 90–94 ꢁC; 1H NMR
N, 23.19; found: C, 63.11; H, 5.18; N, 23.28. HRMS (ESI) calcd for (CDCl3, 400 MHz): d 0.75–0.88 (m, 3H), 1.09–1.38 (m, 26H),
C
19H18N6O2 (M + H+) 363.1569, found 363.8621.
1.42–1.59 (m, 2H), 3.3–3.42 (m, 2H), 5.46 (s, 2H), 5.62 (s, 1H),
2-Amino-4-cyclohexyl-6-(cyclohexylamino)pyridine-3,5-dicar- 7.38–7.46 (m, 5H); 13C NMR (CDCl3, 150 MHz): d 14.25, 22.81,
bonitrile. Semi solid (0.223 g, 69%); 1H NMR (CDCl3, 400 MHz): 25.10, 27.00, 29.37, 29.44, 29.49, 29.67, 29.74, 29.82, 32.05,
d 1.07–1.24 (m, 3H), 1.25–1.42 (m, 4H), 1.59–1.64 (m, 2H), 1.65– 36.74, 41.71, 80.19, 82.62, 116.68, 116.84, 128.43, 128.84,
1.80 (m, 5H), 1.82–1.86 (m, 2H), 1.87–2.1 (m, 4H), 2.83–2.96 (m, 128.94, 129.28, 129.34, 134.52, 159.29, 159.72, 161.22; IR (KBr,
1H), 3.85–3.98 (m, 1H), 5.29 (s, 1H), 5.35 (s, 2H); 13C NMR cmꢂ1): 1485, 1558, 1628, 2208, 2918, 3228, 3332, 3500; Anal.
(CDCl3, 100 MHz): d 24.98, 25.43, 25.63, 26.52, 30.09, 32.97, calcd for C29H41N5: C, 75.77; H, 8.99; N, 15.24; found: C, 75.86;
44.94, 50.11, 79.08, 81.64, 116.96, 117.27, 159.27, 161.68, H, 9.12; N, 15.15. HRMS (ESI) calcd for C29H41N5 (M + H+)
165.45; IR (KBr, cmꢂ1): 1483, 1572, 1631, 2215, 2199, 2926, 3218, 460.3440, found 460.3442.
3317, 3403; Anal. calcd for C19H25N5: C, 70.56; H, 7.79; N, 21.65;
2-Amino-6-((cyclohexylmethyl)amino)-4-phenylpyridine-3,5-
1
ꢁ
found: C, 70.65; H, 7.86; N, 21.52. HRMS (ESI) calcd for dicarbonitrile. Yellow solid (0.242 g, 73%); Mp 187–191 C; H
C
19H25N5 (M + H+) 324.2188, found 324.2194.
NMR (CDCl3, 600 MHz): d 0.94–1.03 (m, 2H), 1.12–1.31 (m, 2H),
2-Amino-6-(cyclohexylamino)-4-propylpyridine-3,5-dicarbo- 1.55–1.66 (m, 2H), 1.66–1.72 (m, 1H), 1.72–1.84 (m, 4H), 3.33 (t, J
1
nitrile. Solid (0.175 g, 62%); Mp 180–183 C; H NMR (CDCl3, ¼ 6.6 Hz, 2H), 5.47 (s, 1H), 5.68 (s, 2H), 7.48–7.57 (m, 5H) 13C
600 MHz): d 0.89–0.97 (m, 1H), 1.02 (t, J ¼ 7.8 Hz, 3H), 1.06–1.25 NMR (CDCl3, 100 MHz): d 25.92, 26.50, 31.00, 37.79, 47.80,
(m, 3H), 1.32–1.42 (m, 2H), 1.61–1.67 (m, 1H), 1.68–1.79 (m, 80.27, 82.70, 116.71, 116.86, 128.44, 128.99, 130.64, 134.51,
3H), 1.93–2.0 (m, 2H), 2.72 (t, J ¼ 7.2 Hz, 2H), 3.88–3.98 (m, 1H), 159.32, 159.91, 161.17; IR (KBr, cmꢂ1): 1482, 1558, 1627, 2203,
ꢁ
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2925, 3353, 3369, 3488; Anal. calcd for C20H21N5: C, 72.48; H, (DMSO-D6, 600 MHz): d 1.85–1.93 (m, 4H), 2.38 (s, 3H), 3.65–
6.39; N, 21.13; found: C, 72.53; H, 6.48; N, 21.27. HRMS (ESI) 3.72 (m, 4H), 7.24 (bs, 2H), 7.3–7.36 (m, 4H); 13C NMR (DMSO-
calcd for C20H21N5 (M + H+) 332.1875, found 332.1871.
D6, 150 MHz): d 20.92, 24.89, 49.12, 79.16, 80.13, 116.54, 118.23,
(S)-2-Amino-4-phenyl-6-((1-phenylethyl)amino)pyridine-3,5- 128.41, 129.02, 132.62, 139.41, 157.27, 159.62, 161.56; IR (KBr,
1
dicarbonitrile. Yellow solid (0.251 g, 74%); Mp 220–223 C; H cmꢂ1): 1487, 1565, 1624, 2195, 2209, 3217, 3319, 3475; Anal.
ꢁ
NMR (DMSO-D6, 600 MHz): d 1.53 (d, J ¼ 6.6 Hz, 3H), 5.39–5.45 calcd for C18H17N5: C, 71.27; H, 5.65; N, 23.09; found: C, 71.36;
(m, 1H), 7.22 (t, J ¼ 7.2 Hz, 1H), 7.32 (t, J ¼ 7.8 Hz, 2H), 7.42–7.47 H, 5.79; N, 22.94. HRMS (ESI) calcd for C18H17N5 (M + H+)
(m, 2H), 7.48 (d, J ¼ 7.2 Hz, 2H), 7.5–7.54 (m, 3H), 7.66 (d, J ¼ 8.4 304.1562, found 304.1565.
Hz, 1H); 13C NMR (DMSO-D6, 100 MHz): d 21.29, 49.45, 79.32,
2,6-Diamino-1-benzyl-4-phenyl-1,4-dihydropyridine-3,5-dicar-
1
ꢁ
80.40, 116.32, 116.48, 126.75, 126.78, 128.18, 128.19, 128.28, bonitrile. White solid (0.310 g, 57%); Mp 221–223 C; H NMR
128.59, 129.87, 135.16, 144.20, 158.07, 159.92, 160.76; IR (KBr, (DMSO-D6, 400 MHz): d 3.96 (s, 1H), 4.94 (s, 2H), 6.26 (s, 4H),
cmꢂ1): 1553, 1622, 2209, 3217, 3339, 3475; Anal. calcd for 6.82–6.88 (m, 2H), 7.11–7.16 (m, 3H), 7.17–7.22 (m, 2H), 7.27–
C
21H17N5: C, 74.32; H, 5.05; N, 20.63; found: C, 74.44; H, 5.12; N, 7.33 (m, 3H); 13C NMR (DMSO-D6, 150 MHz): d 46.75, 61.30,
20.57. HRMS (ESI) calcd for C21H17N5 (M + H+) 340.1562, found 121.44, 126.50, 126.63, 127.63, 127.70, 128.16, 128.40, 136.61,
340.1573.
145.17, 152.36; IR (KBr, cmꢂ1): 1435, 1651, 2170, 3358, 3379,
(R)-2-Amino-4-phenyl-6-((1-phenylethyl)amino)pyridine-3,5- 3450; Anal. calcd for C20H17N5: C, 73.37; H, 5.23; N, 21.39; found:
1
ꢁ
dicarbonitrile. Yellow solid (0.262 g, 77%); Mp 217–219 C; H C, 73.42; H, 5.31; N, 21.27. HRMS (ESI) calcd for C20H17N5 (M +
NMR (DMSO-D6, 400 MHz): d 1.53 (d, J ¼ 6.8 Hz, 3H), 5.37–5.5 H+) 328.1562, found 328.1573.
(m, 1H), 7.2–7.26 (m, 1H), 7.32 (t, J ¼ 7.6 Hz, 2H), 7.42–7.48 (m,
2,6-Diamino-1-benzyl-4-(4-methoxyphenyl)-1,4-dihydropyr-
2H), 7.48 (d, J ¼ 7.6 Hz, 2H), 7.5–7.63 (m, 3H), 7.72 (d, J ¼ 8 Hz, idine-3,5-dicarbonitrile. White solid (0.310 g, 64%); Mp 204–206
1H); 13C NMR (DMSO-D6, 150 MHz): d 21.22, 49.41, 79.31, 80.40, ꢁC; H NMR (DMSO-D6, 400 MHz): d 3.70 (s, 3H), 3.93 (s, 1H),
1
116.24, 116.39, 126.69, 128.12, 128.22, 128.51, 129.78, 135.13, 4.95 (s, 2H), 6.24 (s, 4H), 6.71 (d, J ¼ 8.4 Hz, 2H), 6.78 (d, J ¼ 8.8
144.13, 158.03, 159.83, 160.71; IR (KBr, cmꢂ1): 1487, 1553, 1622, Hz, 2H), 7.17–7.22 (m, 2H), 7.30–7.38 (m, 3H); 13C NMR (DMSO-
2209, 3217, 3339, 3475; Anal. calcd for C21H17N5: C, 74.32; H, D6, 150 MHz): d 46.80, 55.06, 61.78, 113.58, 113.92, 121.53,
5.05; N, 20.63; found: C, 74.41; H, 5.15; N, 20.51. HRMS (ESI) 126.30, 127.67, 127.75, 128.42, 128.47, 129.80, 136.69, 137.35,
calcd for C26H26N4O3 (M + H+) 340.1562, found 340.1565.
152.22, 158.00; IR (KBr, cmꢂ1): 1430, 1667, 2186, 3214, 3311,
2-Amino-4-phenyl-6-(piperidin-1-yl)pyridine-3,5-dicarbonitrile. 3430; Anal. calcd for C21H19N5O: C, 70.57; H, 5.36; N, 19.59;
Yellow solid (0.252 g, 83%); Mp 199–203 ꢁC; 1H NMR (DMSO-D6, found: C, 70.64; H, 5.45; N, 19.68. HRMS (ESI) calcd for
400 MHz): d 1.45–1.76 (m, 6H), 3.61–3.78 (m, 4H), 7.36–7.6 (m,
5H), 13C NMR (DMSO-D6, 100 MHz): d 23.87, 25.54, 48.41, 80.85,
C
21H19N5O (M + H+) 358.1668, found 358.1659.
2,6-Diamino-1-benzyl-4-(4-uorophenyl)-1,4-dihydropyridine-
81.50, 116.16, 117.72, 128.50, 128.61, 129.91, 135.35, 159.70, 3,5-dicarbonitrile. White solid (0.310 g, 53%); Mp 198–201 ꢁC; 1H
160.66, 161.76; IR (KBr, cmꢂ1): 1025, 1489, 1568, 1625, 2202, 3414; NMR (DMSO-D6, 600 MHz): d 4.01 (s, 1H), 4.95 (s, 2H), 6.29 (s,
Anal. calcd for C18H17N5: C, 71.27; H, 5.65; N, 23.09; found: C, 4H), 6.84–6.91 (m, 2H), 6.97 (t, J ¼ 8.4 Hz, 2H), 7.16–7.24 (m, 2H),
71.34; H, 5.57; N, 23.16. HRMS (ESI) calcd for C18H17N5 (M + H+) 7.3–7.38 (m, 3H); 13C NMR (DMSO-D6, 100 MHz): d 47.07, 61.47,
304.1562, found 304.1571.
114.88, 115.10, 121.48, 127.82, 127.91, 128.63, 136.63, 141.50,
2-Amino-6-(piperidin-1-yl)-4-(p-tolyl)pyridine-3,5-dicarboni- 152.57; IR (KBr, cmꢂ1): 1429, 1568, 1656, 2161, 2192, 3236, 3340,
trile. White solid (0.273 g, 86%); Mp 208–210 ꢁC; 1H NMR 3420; Anal. calcd for C20H16FN5: C, 69.55; H, 4.67; N, 20.28;
(DMSO-D6, 600 MHz): d 1.67–1.78 (m, 6H), 2.49 (s, 3H), 3.78– found: C, 69.67; H, 4.76; N, 20.16. HRMS (ESI) calcd for
3.83 (m, 4H), 7.44 (d, J ¼ 7.8 Hz, 2H), 7.49 (d, J ¼ 7.8 Hz, 2H), 13
C
C20H16FN5 (M + H+) 346.1468, found 346.1470.
NMR (DMSO-D6, 150 MHz): d 20.95, 23.93, 25.60, 48.49, 80.80,
2,6-Diamino-1-benzyl-4-(4-chlorophenyl)-1,4-dihydropyridine-
81.52, 116.36, 117.90, 128.68, 129.12, 132.44, 139.76, 159.83, 3,5-dicarbonitrile. White solid (0.310 g, 59%); Mp 254–256 ꢁC; 1H
160.85, 161.78; IR (KBr, cmꢂ1): 1497, 1579, 1623, 2201, 2936, NMR (DMSO-D6, 400 MHz): d 4.03 (s, 1H), 4.97 (s, 2H), 6.31 (s,
3221, 3327, 3478; Anal. calcd for C19H19N5: C, 71.90; H, 6.03; N, 4H), 6.88 (d, J ¼ 8.4 Hz, 2H), 7.15–7.26 (m, 4H), 7.29–7.38 (m, 3H);
22.07; found: C, 72.04; H, 6.14; N, 22.21. HRMS (ESI) calcd for 13C NMR (DMSO-D6, 100 MHz): d 47.05, 61.09, 121.38, 127.82,
C
19H19N5 (M + H+) 318.1719, found 318.1718.
127.88, 128.24, 128.60, 131.23, 136.61, 144.28, 152.63; IR (KBr,
2-Amino-4-phenyl-6-(pyrrolidin-1-yl)pyridine-3,5-dicarboni- cmꢂ1): 1431, 1560, 1665, 2188, 3224, 3270, 3324, 3440; Anal. calcd
trile. White solid (0.228 g, 79%); Mp 213–215 ꢁC; 1H NMR for C20H16ClN5: C, 66.39; H, 4.46; N, 19.36; found: C, 66.47; H,
(DMSO-D6, 600 MHz): d 1.85–1.94 (m, 4H), 3.65–3.76 (m, 4H), 4.55; N, 19.21. HRMS (ESI) calcd for C20H16ClN5 (M + H+)
7.26 (bs, 2H), 7.42–7.47 (m, 2H), 7.5–7.56 (m, 3H), 13C NMR 362.1172, found 362.1175.
(DMSO-D6, 150 MHz): d 24.92, 49.15, 80.01, 80.17, 116.47,
2,6-Diamino-1-benzyl-4-(4-bromophenyl)-1,4-dihydropyridine-
118.18, 128.45, 128.50, 129.74, 135.57, 157.19, 159.59, 161.59; IR 3,5-dicarbonitrile. White solid (0.310 g, 59%); Mp 254–256 ꢁC; 1H
(KBr, cmꢂ1):1487, 1531, 1624, 2209, 3217, 3319, 3475; Anal. NMR (DMSO-D6, 400 MHz): d 4.00 (s, 1H), 4.95 (s, 2H), 6.33 (s,
calcd for C17H15N5: C, 70.57; H, 5.23; N, 24.21; found: C, 70.68; 4H), 6.80 (d, J ¼ 8.4 Hz, 2H), 7.15–7.22 (m, 2H), 7.23–7.27 (m, 2H),
H, 5.31; N, 24.13. HRMS (ESI) calcd for C17H15N5 (M + H+) 7.3–7.38 (m, 5H); 13C NMR (DMSO-D6, 150 MHz): d 46.99, 60.95,
290.1406, found 290.1414.
119.68, 121.36, 127.79, 127.86, 128.59, 128.97, 131.13, 136.58,
2-Amino-6-(pyrrolidin-1-yl)-4-(p-tolyl)pyridine-3,5-dicarboni- 144.70, 152.61; IR (KBr, cmꢂ1): 1435, 1575, 1652, 2178, 3213,
trile. White solid (0.248 g, 82%); Mp 280–283 ꢁC; 1H NMR 3257, 3322, 3449; Anal. calcd for C20H16BrN5: C, 59.13; H, 3.97; N,
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17.24; found: C, 59.21; H, 4.08; N, 17.11. HRMS (ESI) calcd for
C20H16BrN5 (M + H+) 406.0667, found 406.0672.
Acknowledgements
2,6-Diamino-1-benzyl-4-cyclohexyl-1,4-dihydropyridine-3,5-
dicarbonitrile. Pale yellow solid (0.170 g, 51%); Mp 213–215 ꢁC;
1H NMR (DMSO-D6, 600 MHz): d 0.51–0.6 (m, 1H), 0.62–0.73 (m,
2H), 0.7–0.99 (m, 2H), 1.39–1.44 (m, 2H), 1.45–1.57 (m, 3H), 2.29
(d, J ¼ 6.6 Hz, 1H), 4.86 (s, 2H), 6.12 (s, 4H), 7.21–7.24 (m, 2H),
7.25–7.34 (m, 3H); 13C NMR (DMSO-D6, 150 MHz): d 25.73,
26.11, 29.27, 46.55, 47.47, 60.04, 122.55, 127.84, 128.38, 128.40,
136.71, 153.14; IR (KBr, cmꢂ1): 1437, 1568, 1654, 2186, 2930,
3329, 3434, 3463; Anal. calcd for C20H23N5: C, 72.04; H, 6.95; N,
21.00; found: C, 72.17; H, 7.08; N, 21.11.
2,6-Diamino-1-(furan-3-ylmethyl)-4-phenyl-1,4-dihydropyr-
idine-3,5-dicarbonitrile. White solid (0.310 g, 62%); Mp 207–210
ꢁC;1H NMR (DMSO-D6, 400 MHz): d 3.87 (s, 1H), 4.98 (s, 2H),
6.29 (s, 4H), 6.25–6.27 (m, 1H), 6.42–6.47 (m, 1H), 7.46–7.6 (m,
5H), 7.64 (s, 1H); 13C NMR (DMSO-D6, 100 MHz): d 40.83, 62.02,
109.33, 110.45, 121.26, 126.44, 128.25, 142.88, 145.20, 149.61,
152.37; IR (KBr, cmꢂ1): 1433, 1649, 2178, 3216, 3322, 3449; Anal.
calcd for C18H15N5O: C, 68.13; H, 4.76; N, 22.07; found: C, 68.26;
H, 4.84; N, 22.16. HRMS (ESI) calcd for C18H15N5O (M + H+)
318.1355, found 318.1358.
SS and DKD are thankful to CSIR, New Delhi, India for their
research fellowships. The authors are also grateful to the
Director, IIT Guwahati for providing general facilities to carry
out the research work. We are thankful to DST for providing
XRD facility under the FIST programme.
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2,6-Diamino-1-(furan-3-ylmethyl)-4-(4-methoxyphenyl)-1,4-
dihydropyridine-3,5-dicarbonitrile. White solid (0.310 g, 65%);
1
ꢁ
Mp 209–214 C; H NMR (DMSO-D6, 600 MHz): d 3.70 (s, 3H),
3.82 (s, 1H), 4.97 (s, 2H), 6.22 (s, 4H), 6.29–6.35 (m, 1H), 6.41–
6.49 (m, 1H), 6.67–6.81 (m, 4H), 7.67 (s, 1H); 13C NMR (DMSO-
D6, 150 MHz): d 40.87, 55.03, 62.45, 109.31, 110.50, 113.66,
121.35, 127.52, 137.43, 149.33, 152.20, 157.93; IR (KBr, cmꢂ1):
1435, 1508, 1649, 2170, 2187, 3219, 3321, 3448; Anal. calcd for
˙
C
19H17N5O2: C, 65.69; H, 4.93; N, 20.16; found: C, 65.77; H, 5.14;
S. Chodorowski-Kimmes, J.-P. Collin, P. Laine, J.-P. Launay
N, 20.02. HRMS (ESI) calcd for C19H17N5O2 (M + H+) 348.1460,
found 348.1470.
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2,6-Diamino-4-(4-chlorophenyl)-1-(furan-3-ylmethyl)-1,4-dihy-
dropyridine-3,5-dicarbonitrile. White solid (0.310 g, 61%); Mp >
300 ꢁC; 1H NMR (DMSO-D6, 400 MHz): d 3.86 (s, 1H), 4.98 (s, 2H),
6.23–6.26 (m, 1H), 6.35 (s, 4H), 6.41–6.45 (m, 1H), 6.81 (d, J ¼ 7.6
Hz, 2H), 7.25 (d, J ¼ 7.6 Hz, 2H), 7.70 (s, 1H);13C NMR (DMSO-D6,
100 MHz): d 40.98, 61.65, 109.43, 110.57, 121.08, 128.26, 131.05,
143.03, 144.25, 149.54, 152.54; IR (KBr, cmꢂ1): 1432, 1562, 1663,
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61.46; H, 4.01; N, 19.91; found: C, 61.54; H, 4.12; N, 20.02. HRMS
(ESI) calcd for C18H14ClN5O (M + H+) 352.0965, found 352.0973.
2,6-Diamino-4-(4-bromophenyl)-1-(furan-3-ylmethyl)-1,4-dihy-
dropyridine-3,5-dicarbonitrile. White solid (0.310 g, 59%); Mp >
300 ꢁC;1H NMR (DMSO-D6, 600 MHz): d 3.90 (s, 1H), 4.97 (s, 2H),
6.28–6.32 (m, 1H), 6.33 (s, 4H), 6.43–6.49 (m, 1H), 6.76 (d, J ¼ 7.8
Hz, 2H), 7.39 (d, J ¼ 8.4 Hz, 2H), 7.69 (s, 1H); 13C NMR (DMSO-D6,
150 MHz): d 40.96, 61.54, 109.45, 110.59, 119.55, 121.09, 128.68,
131.16, 143.07, 144.69, 149.53, 152.55; IR (KBr, cmꢂ1): 1431, 1559,
1665, 2186, 3224, 3271, 3324, 3440; Anal. calcd for C18H14BrN5O:
C, 54.56; H, 3.56; N, 17.67; found: C, 54.64; H, 3.67; N, 17.55;
HRMS (ESI) calcd for C18H14BrN5O (M + H+) 396.0460 found
396.0469.
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