The reaction of 2-dimethylaminomethylene-3-oxo-N-phenylbutyramide with active methylene nitriles

Article abstract of DOI:10.1002/jhet.356

(Chemical Equation Presented) 2-Dimethylaminomethylene-3-oxo-N- phenylbutyramide 1 reacts with malononitrile 2a to afford the pent-2-enedioic acid 1-amide 5-phenylamide derivative 6, which could be cyclized to give the 6-methylpyridone derivative 7. Compo

Full text of DOI:10.1002/jhet.356

528
The Reaction of 2-Dimethylaminomethylene-3-oxo-N-
phenylbutyramide with Active Methylene Nitriles
Vol 47
Fathy M. Abdelrazek,a* Mohey F. Sharaf,a Peter Metz,b and Anna Jaegerb
aChemistry Department, Faculty of Science,Cairo University, Giza, Egypt
bInstitute of Organic Chemistry, TU-Dresden, Dresden 01062, Germany
*E-mail: prof.fmrazek@gmail.com
Received September 9, 2009
DOI 10.1002/jhet.356
Published online 2 April 2010 in Wiley InterScience (www.interscience.wiley.com).
2-Dimethylaminomethylene-3-oxo-N-phenylbutyramide 1 reacts with malononitrile 2a to afford the
pent-2-enedioic acid 1-amide 5-phenylamide derivative 6, which could be cyclized to give the 6-methyl-
pyridone derivative 7. Compound 1 reacts with cyanoacetamide 2b to afford the same pyridone 7 and
with cyanothioacetamide 2c to afford the analogous pyridinethione 12. Compound 12 reacts with
DMAD to afford the pyridine derivative 15 and with N,N-dimethylchloroacetamide 16 to afford the
thieno[2,3-d]pyridine derivative 18. Compound 18 reacts with morpholine-4-carboxaldehyde 19, N,N-
diemthylformamide 20, and 2,5-dimethoxy-tetrahydrofuran 21 to afford the fully aromatic thieno[2,3-
d]pyridine derivatives 22, 23, and 24, respectively.
J. Heterocyclic Chem., 47, 528 (2010).
INTRODUCTION
of acetoacetanilide with DMFDMA according to the lit-
erature method [16]) seemed a suitable synthone for the
synthesis of the required 2-1H–pyridone derivatives
through its reaction with active methylene reagents.
In the past 2 decades, we have been involved in a
program aiming to develop new simple routes for the
synthesis of heterocyclic compounds of biological inter-
est to be evaluated as biodegradable agrochemicals [1–
5]. Some functionally substituted pyridine and pyridone
derivatives posses marked pharmaceutical activities such
as anti HIV-1 reverse transcriptase agents, calcium
channel blockers, anticongestive heart failure agents,
and antagonists of P2 receptors for neurotransmitters [6–
12]. The reaction of enaminones with active methylene
nitriles represents one of the strategies for the prepara-
tion of 2-1H-pyridone [13–15]. Thus, some functionally
substituted 2-1H-pyridone derivatives were required for
biological activity studies. 2-Dimethylaminomethylene-
3-oxo-N-phenylbutyramide (obtained from the reaction
RESULTS AND DISCUSSION
Thus, the enaminone compound 1 was prepared and
allowed to react with the active methylene compounds
2a-c (Scheme 1) according to the method reported ear-
lier by us [17]. The reaction of 1 with malononitrile 2a
afforded a yellow crystalline solid of mp.197ꢀC. The IR
spectrum of this product showed absorption bands at
tmax ¼ 2217, 1665, and 1656 cmꢁ1 corresponding to a
cyano and two amide carbonyl functions. The mass
spectrum of this product showed a molecular ion peak
C
V
2010 HeteroCorporation

May 2010
The Reaction of 2-Dimethylaminomethylene-3-oxo-N-phenylbutyramide
with Active Methylene Nitriles
529
Scheme 1. Preparation of compounds 6, 7, and 12.
at m/z ¼ 298, which corresponds to the molecular for-
The formation of 6 from the reaction of 1 with 2a is
assumed to take place via the sequence shown in
Scheme 1. The active methylene of malononitrile under-
goes addition to the double bond of 1 to afford the inter-
mediate 3, followed by elimination of dimethyl amine to
afford 2-acetyl-4,4-dicyanobut-2-enoic acid phenylamide
4 that directly undergoes ring closure via its enolized
form to afford the iminopyran intermediate 5. This
newly formed iminopyran is attacked by the dimethyl
amine (still present in the reaction medium) and under-
goes ring opening to afford 6. The ring opening of imi-
nopyran under the effect ammonia and amines is well
1
mula C16H18N4O2 (M. Wt. 298.34). The H NMR spec-
trum of this product revealed a singlet (3H) at 1.69 cor-
responding to a methyl group, a singlet (6H) at 2.75
corresponding to the N(CH3)2 groups, a singlet (1H) at
7.15 due to the ¼¼CH proton, a D2O exchangeable sin-
glet at 8.35 (1H) attributable to an NH, beside an aro-
matic multiplet at 7.24–7.55 (7H, PhþNH2). Based on
these data and on the analogy with our previous reported
work [17], the 2-Cyano-4-(1-dimethylamino-ethylidene)-
pent-2-enedioic acid 1-amide 5-phenylamide 6 was
assigned to this product.
Journal of Heterocyclic Chemistry
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F. M. Abdelrazek, M. F. Sharaf, P. Metz, and A. Jaeger
Vol 47
Scheme 2. Preparation of compounds 15, 18, 22, 23, and 24.
established in the literature [14,17]. The 13C NMR data
of this product are in complete agreement with structure
6 (cf. Scheme 1 and Experimental).
sequence) that undergoes directly the cyclization via
elimination of water without passing through the imino-
pyran step, as the amide group is already present. The
identity of the products obtained from the reactions of 1
with either 2a or 2b was deduced from the typical melt-
ing points and spectral data. A similar result has been
previously observed [17].
Compound 6 could be readily cyclized via elimination
of dimethyl amine upon reflux in acetic acid to afford
yellow crystals of mp. 217–219ꢀC.
1
The H NMR spectrum of 7 revealed the disappear-
ance of the NMe2 signal and the presence of a singlet
integrated for 1H at d ¼ 8.65, which is attributed to the
C4-H, beside the other signals as expected (cf. Experi-
mental). The 2-1H-pyridinone derivative structure 7 was
assigned to this product based on the analytical and
spectral data, and compound 7 has been previously
described in the literature from other route, mp. 216–
218ꢀC [18].
The reaction of compound 1 with cyanothioacetamide
2c was reported earlier to afford the pyridinthione 10
(No. 3 in the original article [19]) via the intermediate 9
(Number 2 in the original article). The author of ref. 19
incorrectly assumed that the reaction proceeds via a
Knoevenagel condensation between the carbonyl group
of 1 and the active methylene of 2c to afford 9 (his 2).
On the basis of our aforementioned results, we have
reinvestigated this reaction. This reaction of 1 and 2c
was found to follow the same pathway as that of 1 with
2b to afford the intermediate 11 (analogous to 8;
Scheme 1) via the addition–elimination sequence, which
The reaction of 1 with cyanoacetamide 2b afforded
the same 2-1H-pyridinone 7. It is assumed that 2b fol-
lowed the same addition elimination sequence to afford
the intermediate 8 (analogous to 4 in the above
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The Reaction of 2-Dimethylaminomethylene-3-oxo-N-phenylbutyramide
with Active Methylene Nitriles
531
C13H12N2O4S for this product, which is not applicable to
13 (old 9) or 14 (assuming that the NH adds to the CBC
in DMAD). The IR spectrum of this product showed two
carbonyl absorption at tmax ¼ 1712 and 1710 assignable
to two ester CO, a cyano absorption band at 2220 cmꢁ1
and no bands that could be assigned to the amide CO.
1
The H and 13C NMR showed a pattern that could not be
justified to either of the structures 13 (reported 9 [19]) or
14 (cf. experimental). From the presence of two ester car-
bonyl absorption bands and the presence of two methyl
signals in the 1H and C13 NMR spectra, we got the
impression that a Michael addition took place from either
the NH in the pyridinethione or the SH in the tautomer
mercapto pyridine to the activated CBC of DMAD, and
from the absence of the amide carbonyl absorption band
in the IR spectrum and the presence of two doublets at d
Figure 1. X-ray crystallographic structure of 15. [Color figure can be
viewed in the online issue, which is available at www.interscience.
wiley.com.]
1
¼ 7.36 and 8.22 ppm with j ¼ 8.56 Hz in the H NMR
spectrum, we got the impression that the amide group
was eliminated either in the form of phenyl isocyanate or
via hydrolysis of the amide linkage followed by decar-
boxylation. Thus, structure 15 was suggested to this prod-
uct. This structure actually fulfills all the requirements of
all the available data. However, it was mandatory to have
an X-ray crystallographic picture for this compound. For-
tunately, the X-ray picture [20,21] came exactly in com-
plete agreement with our imagination; (see Fig. 1 and the
experimental). It shows clearly the attachment of S to the
DMAD, the absence of the anilide group, and also shows
the methyl group at the 6-position of the pyridine ring
(the p-position to the cyano group) which is a further
proof to our suggested mechanism (cf. Scheme 1).
then undergoes cyclization via loss of water to afford
the pyridinethione 12. The melting point, analytical, and
spectral data of our product are the same as those
reported in [19]; however, the 13C NMR data reported
in [19] are wrong; the phenyl carbons should appear as
four signals and not six as reported, and the whole spec-
trum showed only 12 signals.(cf. experimental).
The incorrect assignment in [19] leads to the pyridi-
nethione 10 (his 3) with the methyl group in the 4-posi-
tion, whereas the correct structure is 12 carrying the
methyl group in the 6-position. This has serious conse-
quences for some other reactions described in this arti-
cle. For example, all the reactions depicted in his
Scheme 2 are all based on the imaginary presence of the
methyl group in position-4 and are all vagaries.
Compound 12 reacts also with N,N-dimethyl chloroace-
tamide 16 under the same reaction conditions described
in ref. 19 to afford the fully aromatic thieno[2,3-b]pyri-
dine derivative 18 rather than the claimed dihydro-deriva-
The reaction of this pyridinethione 12 with dimethyl
acetylenedicarboxylate was claimed to afford the thiazolo-
pyridine derivative 13 (Scheme 2) (number 9 in the origi-
nal article [19]). The formation of this thiazolopyridine
seemed doubtful as the pyridinethione has only one proton
on its nitrogen, so how the thiazole ring is formed while
still retaining one hydrogen on C-2. Furthermore, the 13C
NMR data given to 13 (his 9) cited only 10 carbons
(excluding the repeated values for the aromatic carbons),
while it should reveal 17 carbons. Based on all these dis-
crepancies, we decided to reinvestigate this reaction.
1
tive 17 (his 11 [19]). It should be stated that the H NMR
data reported for compound 17 (old 11) are completely
applicable to our compound 18 (cf. experimental part).
Compound 18 was allowed to react with morpholine-4-
carboxaldehyde 19, N,N-diemthylformamide 20, and 2,5-
dimethoxy-tetrahydrofuran 21 under the same reaction
conditions described in ref. 19 to afford products very
similar to those described (his numbers 15, 16, and 17 in
his Scheme 4); however, the obtained products were
found to be the fully aromatic thieno[2,3-b]pyridine
derivatives 22, 23, and 24, respectively (cf. Scheme 2). It
Compound 12 was allowed to react with dimethyl ace-
tylenedicarboxylate (DMAD) in chloroform (the same
reaction conditions reported in [19]) to afford after
recrystallization and purification on column with silica
gel using pentane/ethyl acetate (3:1) as eluent a white
crystalline product of mp. 126ꢀC (Lit. mp. of compound
13 in Scheme 2 (his 9); >300ꢀC [19]). The mass spec-
trum of this product showed m/z ¼ 292 [Mþ]. From this
molecular mass and the elemental analysis data (cf. ex-
perimental), we could calculate a molecular formula
1
should be stated also that the H NMR data reported in
reference [19] for compounds 22, 23, and 24 (Scheme 2;
numbers 15, 16, and 17 in his Scheme 4) are completely
not applicable to their assigned structures.
EXPERIMENTAL
Melting points were measured on an Electrothermal (9100)
apparatus and are uncorrected. IR spectra were recorded as
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532
F. M. Abdelrazek, M. F. Sharaf, P. Metz, and A. Jaeger
Vol 47
KBr pellets on a Perkin Elmer 1430 spectrophotometer. The
1H NMR and 13C NMR spectra were taken on a Varian Gem-
ini 300 MHz spectrometer in DMSO-d6 using TMS as internal
standard and chemical shifts are expressed in d ppm values.
Mass spectra were taken on a Shimadzu GCMS-GB 1000 PX
(70 ev). Elemental analyses were carried out at the Micro-ana-
lytical Center at Cairo University. X-ray data [20] were col-
lected using a Bruker Nonius 5622 diffractometer and were
corrected by SADABS factors and emperical absorption. The
structure was solved by direct methods and expanded using
Fourier technique. SCHAKAL 99 program system was used in
the graphic representation of the structure [21]. The nonhydro-
gen atoms are refined anisotropically and the hydrogen atoms
were refined according to theoretical models. X-ray crystallog-
raphy, elemental and spectral data of compound 15 were made
in the Institute of Organic Chemistry, TU-Dresden, Germany.
2-Cyano-4-(1-dimethylamino-ethylidene)-pent-2-enedioic
acid 1-amide 5-phenylamide 6. To a mixture of 2-dimethyla-
minomethylene-3-oxo-N-phenylbutyramide 1 (2.32 g; 10 mmol)
and malononitrile 2a (0.66 g; 10 mmol) in ethanol (15 mL) was
added few drops of piperidine as catalyst. The reaction mixture
was refluxed for 2 h and then left to cool to room temperature.
The solid product thus precipitated was collected by filtration and
recrystallized from dioxan to give yellow crystals, yield (2.23 g,
75%); mp 197–198ꢀC (Dioxan); tmax ¼ 3435–3284 (NH2 and
NH), 2217 (CN), 1665, and 1656 cmꢁ1 (2 CO); MS: m/z ¼ 298
5-Cyano-2-methyl-6-thioxo-1,6-dihydro-pyridine-3-car-
boxylic acid phenylamide 12. A mixture of compound 1
(2.32 g, 10 mmol) and cyanothioacetamide 2c (1.0 g, 10
mmol) in ethanol (25 mL) with sodium ethoxide catalyst was
refluxed for 30 min. After cooling down, the reaction mixture
was poured onto cold water and acidified with dil. HCl. The
precipitated solid product thus formed was collected by filtra-
tion and recrystallized from ethanol to afford 12 as yellow
crystals, Yield (1.94 g, 72%), mp. 225–227ꢀC (lit. 235ꢀC
[19]), tmax ¼ 3345, 3228 (NH), 2215 (CN), and 1658 cmꢁ1
(CO); MS: m/z ¼ 269 [Mþ]; dH ¼ 1.74 (s, 3H, CH3), 7.05–
7.68 (m, 5H, Ph), 8.15 (s, 1H, H-4), 9.25 (br.s., 1H, NH),
13.92 (br.s., 1H, NH). dC ¼ 185.65 (s), 167.46 (d), 163.85 (s),
143.15 (s), 135.26 (s), 128.66 (d), 124.25 (d), 120.38 (d),
116.24 (s), 116.58 (s), 107.47 (s), 15.42 (q).
Anal. Calcd for C14H11N3OS: (269.32): C, 62.43; H, 4.12;
N, 15.60. Found: C, 62.45; H, 4.18; N, 15.70.
2-(3-Cyano-6-methylpyridin-2-ylsulfanyl)-but-2-enedioic
acid dimethyl ester 15. To a suspension of 12 (2.69 g, 10
mmol) in 15 mL of chloroform was added (2.13 g, 15 mmol)
dimethyl acetylenedicarboxylate (DMAD) and
a catalytic
amount of triethylamine. The reaction mixture was stirred at
room temperature for 3h. The precipitated solid formed after
evaporation of the solvent was collected and recrystallized
from methanol and then purified by flash chromatography
using a column with silica gel (10 cm height with 2 cm2 diam-
eter) using pentane/ethyl acetate (3:1) as eluent to afford com-
pound 15 as yellow crystals, yield (2.29 g, 65%), mp. 125–
126ꢀC (lit. >300ꢀC [19]), tmax ¼ 2220 (CN), 1712 and 1710
(2 ester CO); MS: m/z ¼ 292 [Mþ]; dH ¼ 2.47 (s, 3H, CH3),
3.62 (s, 3H, CH3), 3.78 (s, 3H, CH3), 6.98 (s, 1H, olefin H),
7.36 (d, 1H, j ¼ 8.65 Hz, H-5); 8.22 (d, 1H, j ¼ 8.56 Hz, H-
4). dC ¼ 24.04 (q), 52.00 (q), 52.50 (q), 104.46 (s), 115.57 (s),
121.24 (d), 127.82 (d), 139.63 (s), 142.16 (d), 157.74 (s),
162.85 (s), 163.85 (s), 163.93 (s).
[Mþ]; d ¼ 1.69 (s, 3H, CH3), 2.75 (s, 6H, 2CH3), 7.15 (s, 1H,
H
CH), 7.10–7.65 (m, 7H, PhþNH2), 8.35 (s, 1H, NH). d ¼ 15.4
C
(q), 38.8 (q), 104,7 (s), 104,9 (s), 116,8 (s), 120.6 (d), 124.3 (d),
128.9 (d), 138.4 (s), 154.3 (s), 156.9 (d), 163.1 (s), 167.5 (s).
Anal. Calcd. for C14H18N4O2: (298.34): C, 64.41; H, 6.08;
N, 18.78. Found: C, 64.45; H, 6.10; N, 18.90.
Synthesis of 5-cyano-2-methyl-6-oxo-1,6-dihydro-pyri-
dine-3-carboxylic acid phenyl amide 7. Method A: Cycli-
zation of compound 6. Compounds 6 (2.98 g, 10 mmol) was
refluxed in ethanolic sodium ethoxide (15 mL) for 30 min.
The solvent was reduced to one third of its volume under
reduced pressure and left to cool overnight. The solid precipi-
tate that appeared was collected by filtration and crystallized
from ethanol to afford 7 as yellow crystals, yield (2.15 g,
85%), mp. 219–220ꢀC.
Method B: The reaction of 2-dimethylaminomethylene-3-
oxo-N-phenylbutyramide 1 with cyanoacetamide 2b. To a
mixture of 1 (2.32 g, 10 mmol) and cyanoacetamide 2b (0.84
g, 10 mmol) in ethanol (20 mL) was added a catalytic amount
of piperidine (5 drops). The reaction mixture was refluxed for
6 h and then left to cool to room temperature. The contents of
the flask were poured onto ice-cold water and acidified with
few drops of conc. HCl till just neutral (pH paper). The pre-
cipitated solid product was filtered off, washed thoroughly
with cold water, dried, and recrystallized from ethanol/DMF
(4:1) to give 7 as yellow crystals, yield (1.97 g, 78%); mp.
217–219ꢀC (Lit. mp. 216–218ꢀC [18]); tmax ¼ 3382, 3275
(NH), 2235 (CN), and 1657 and 1638 cmꢁ1 (2CO); MS: m/z
¼ 253 [Mþ]; dH ¼ 2.63 (s, 3H, CH3), 7.12–7.68 (m, 5H, Ph),
7.82 (br.s., 1H, NH), 8.65 (s, 1H, H-4), 10.60 (br.s., 1H, NH).
dC ¼ 16.48 (q), 104.66 (s), 112.65 (s), 116.15 (s), 121.05 (d),
124.57 (d), 128.65 (d), 138.45 (s), 145.6 (s), 153.95 (d),
159.86 (s), 164.55 (s).
X-ray
crystallographic
data:
Colourless
crystals,
C13H12N2O4S (Mr ¼ 292.31 g molꢁ1), monoclinic, space
˚
˚
group P21/c (No. 14), a ¼ 8.950(2) A, b ¼ 21.930(4) A, c ¼
O
O
O
˚
7.337(2) A, a[ ] ¼ 90.00, b[ ] ¼ 104.48 (3), c[ ] ¼ 90.00;
3
V[A ] ¼ 1394.3 (6), Z ¼ 4, Dcalc. ¼ 1.392 g cmꢁ3, F(000) ¼
˚
608e, l(Mo Ka) ¼ 0.246 nmꢁ1; the final difference Fourier q
¼ 0.29 (ꢁ0.21) e Aꢁ3.crystal dimensions ¼ 0.33 ꢂ 0.17 ꢂ
˚
0.08 mm. Max. resolution [sin y/k]max ¼ 0.64 Aꢁ1/ 99.8%.
˚
Data were collected using a Bruker Nonius area detector at
T[ꢀC] ¼ ꢁ75 (2), with graphite monochromator with Mo Ka
˚
radiation (k ¼ 0.71073 A) using the CCD data collection and
SADABS absorption correction method; min 90.5%; max
98.1%. No. of independent reflections are 3043 were counted
with observed reflections 2415. Rav ¼ 0.071. The final R and
2
RW ¼ 0.040 and 0.098, respectively.
Anal. Calcd for C13H12N2O4S: (292.31): C, 53.42; H, 4.14;
N, 9.58; S, 10.97. Found: C, 53.01; H, 3.86; N, 9.73; S, 10.88.
3-Amino-6-methyl-thieno[2,3-b]pyridine-2,5-dicarboxylic
acid 2-dimethylamide 5-phenylamide 18. To a solution of 12
(2.69 g, 10 mmol) in methanol (25 mL) was added N,N-di-
methyl chloroacetamide 16 (1.22 g, 10 mmol) followed by few
drops of sodium methoxide. The reaction mixture was refluxed
for 1 h and then left to cool to room temperature. The mixture
was then poured onto ice-cold water and acidified by few
drops of dil. HCl till just neutral. The precipitated solid prod-
uct was filtered off and recrystallized from methanol to afford
Anal. Calcd. for C14H11N3O2: (253.26): C, 66.40; H, 4.38;
N, 16.59. Found: C, 66.45; H, 4.47; N, 16.70.
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533
REFERENCES AND NOTES
compound 18 as yellow crystals, yield (2.4 g, 68%), mp. 221–
222ꢀC (lit. 220ꢀC [19]), tmax ¼ 3445, 3328 (NH2 and NH),
1680 and 1668 (2CO) cmꢁ1; MS: m/z ¼ 354 [Mþ]; d
¼
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Pharm Chem life Sci (Weinheim) 2006, 339, 305.
H
2.32 (s, 3H, CH3), 3.54 (s, 6H, 2CH3), 7.05–7.80 (m, 7H,
PhþNH2), 8.22 (s, 1H, H-4), 9.35 (br.s., 1H, NH).
[2] Abdelrazek, F. M.; Metz, P.; Kataeva, O.; Jaeger, A.; El-
Mahrouky, S. F. Arch Pharm Chem Life Sci (Weinheim) 2007, 340,
543.
Anal. Calcd for C18H18N4O2S: (354.43): C, 61.00; H, 5.12;
N, 15.81; S, 9.05. Found: C, 60.92; H, 5.15; N, 15.87; S, 9.25.
The reaction of compound 18 with morpholine-4-carbox-
aldehyde 19, N,N-diemthylformamide 20, and 2,5-dime-
thoxy-tetrahydrofuran 21 (general procedure). To a solution
of 18 (3.54 g; 10 mmol) in 20 mL of phosphorus oxychloride
was added each of 19, 20, or 21. The reaction mixture was
refluxed for 2 h in each case, left to cool to room temperature,
and then poured onto ice-cold water and neutralized with am-
monia. The precipitated solids thus formed were filtered off
and recrystallized from the proper solvent to afford 22, 23,
and 24, respectively.
[3] Abdelrazek, F. M.; Ghozlan, S. A.; Michael, F. A. J Hetero-
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[4] Abdelrazek, F. M.; Mohamed, A. M. Afinidad 2008, 65, 56.
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1147.
6-Methyl-3-[(morpholin-4-ylmethylene)-amino]-thieno
[2,3-b]pyridine-2,5-dicarboxylic acid 2-dimethylamide
5-phenylamide 22. Yellow crystals, Yield (3.16 g; 70%),
mp. 279–281ꢀC (EtOH/DMF) (lit. 280ꢀC [19]), tmax ¼ 3385,
3258 (NH), 1675 and 1668 cmꢁ1 (2CO); MS: m/z ¼ 451
[Mþ]; dH ¼ 2.25 (s, 3H, CH3), 3.05 (t, 4H, 2CH2), 3.29 (s,
6H, 2CH3), 3.72 (t, 4H, 2CH2), 7.05–7.60 (m, 6H, Ph þ olefin
H), 8.22 (s, 1H, H-4), 9.34 (br.s., 1H, NH).
[9] Robertson, R. M.; Robertson, D. In The Pharmacological
Basis of Therapeutics, Goodman and Gilman’s, 9th ed.; Gillman, A.
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[10] Farah, A. E.; Alousi, A. A. Life Sci 1978, 22, 543.
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2000, 37, 395.
Anal. Calcd. for C23H25N5O3S: (451.54): C, 61.18; H, 5.58;
N, 15.51; S, 7.10. Found: C, 61.25; H, 5.68; N, 15.57; S, 7.23.
3-(Dimethylamino-methyleneamino)-6-methyl-thieno[2,3-b]
pyridine-2,5-dicarboxylic acid 2-dimethylamide 5-phenyla-
mide 23. Coffee brown crystals, yield (2.66 g; 65%), mp.
272–273ꢀC (dioxan) (lit. 275ꢀC [19]), tmax ¼ 3442, 3328
(NH), 1678, and 1669 cmꢁ1 (2CO); MS: m/z ¼ 409 [Mþ]; dH
¼ 2.23 (s, 3H, CH3), 2.55 (s, 6H, 2CH3), 3.15 (s, 6H, 2CH3),
7.05–7.55 (m, 6H, Ph þ olefin H), 8.28 (s, 1H, H-4), 9.31
(br.s., 1H, NH).
[12] Bremner, D. H.; Dunn, A. D.; Wilson, K. A.; Sturrock, K.
R.; Wishart, G. Synthesis 1997, 494.
[13] Torres, M.; Gil, S.; Parra, M. Curr Org Chem 2005, 9, 1757
(Review).
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[15] Yermolayev, S. A.; Gorobets, N. Y.; Lukinova, E. V.;
Shishkin, O. V.; Shishkina, S. V.; Desenko, S. M. Tetrahedron 2008,
64, 4649.
Anal. Calcd for C21H23N5O2S: (409.50): C, 61.59; H, 5.66;
N, 17.10; S, 7.83. Found: C, 61.72; H, 5.73; N, 17.25; S, 7.98.
6-Methyl-3-pyrrol-1-yl-thieno[2,3-b]pyridine-2,5-dicarboxy-
lic acid 2-dimethylamide 5-phenylamide 24. Yellow crystals,
Yield (2.9 g; 72%), mp. 312–313ꢀC (EtOH/DMF) (lit. >300ꢀC
[19]), tmax ¼ 3435, 3329 (NH), 1676, and 1667 cmꢁ1 (2CO);
MS: m/z ¼ 404 [Mþ]; dH ¼ 2.24 (s, 3H, CH3), 3.05 (s, 6H,
2CH3), 6.12–7.68 (m, 9H, Ph þ pyrrole H), 8.25 (s, 1H, H-4),
9.33 (br.s., 1H, NH).
[16] Abu Elmaati, T. M.; Said, S. B.; Abu Elenein, N. S.; Sofan,
M. A.; Khodeir, M. N. Pol J Chem 2002, 76, 945.
[17] Abdelrazek, F. M.; Elsayed, A. N. J Heterocycl Chem
2009, 46, 949.
[18] Deyanov, A. B.; Konshin, M. E. Chem Heterocycl Compd
2004, 40, 452; (Translated from: Khimiya Geterotsiklicheskikh Soedi-
nenii 2004, No.4, 547 Plenum Publishing Corporation).
[19] Abu Elmaati, T. M. J Heterocycl Chem 2004, 41, 947.
[20] Crystallographic data (excluding structure factors) for the
structure 15 reported in this paper have been deposited with the Cam-
bridge Crystallographic Data Centre as supplementary publication no.
CCDC 746861. Copies of the data can be obtained free of charge on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax.:
(internat.) þ 44 1223/336-033; E-mail: deposit@ccdc.cam.ac.uk].
Anal. Calcd for C22H20N4O2S: (404.48): C, 65.33; H, 4.98;
N, 13.85; S, 7.93. Found: C, 65.37; H, 4.85; N, 13.72; S, 8.13.
Acknowledgment. F. M. Abdelrazek thanks the Alexander von
Humboldt Foundation (Germany) for granting a research fellow-
ship from July to August 2009; during this time, the X-ray crystal-
lographic, elemental and spectral data of compound 15 were
made.
[21] Keller, E. SCHAKAL 99, A Computer Program for the
Graphic Representation of Molecular and Crystallographic Models;
¨
Universitat Freiburg: Freiburg, Germany, 1999.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet