Dmap-catalyzed synthesis of novel pyrrolo[2,3-D]pyrimidine derivatives bearing an aromatic sulfonamide moiety

Article abstract of DOI:10.1080/10426507.2013.858253

(Equation present) 4-(N,N-Dimethylamino)pyridine (DMAP), with a dual role as a basic nucleophilic catalyst, was shown to be a highly efficient catalyst for the synthesis of some new N-(2-aryl-7-benzyl-5,6-diphenyl-7H-pyrrolo[2,3-d] pyrimidin-4-yl)benzenesulfonamides through the reaction of 2-aryl-7-benzyl-5,6- diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-amines (7-deazaadenines) with benzenesulfonyl chlorides. It was also found that the use of DMAP under solvent-free conditions is much more effective than other catalytic systems such as pyridine as both the catalyst and solvent, t-BuOK in t-BuOH, Et₃N in ethanol (EtOH), and even DMAP in dimethylformamide (DMF). The influences of the reaction parameters, temperature, and the catalyst amount, on the catalytic performance have been studied. All synthetic compounds were characterized on the basis of their full spectral data. 2014 Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426507.2013.858253

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Phosphorus, Sulfur, and Silicon and the
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Dmap-Catalyzed Synthesis of Novel
Pyrrolo[2,3-D]Pyrimidine Derivatives
Bearing an Aromatic Sulfonamide Moiety
Maryam Khashia, Abolghasem Davoodniaa & Jamshidkhan Chamanib
a Department of Chemistry, Mashhad Branch, Islamic Azad
University, Mashhad, Iran
b Department of Biology, Mashhad Branch, Islamic Azad University,
Mashhad, Iran
Accepted author version posted online: 26 Feb 2014.Published
online: 12 Jun 2014.
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To cite this article: Maryam Khashi, Abolghasem Davoodnia & Jamshidkhan Chamani (2014)
Dmap-Catalyzed Synthesis of Novel Pyrrolo[2,3-D]Pyrimidine Derivatives Bearing an Aromatic
Sulfonamide Moiety, Phosphorus, Sulfur, and Silicon and the Related Elements, 189:6, 839-848, DOI:
10.1080/10426507.2013.858253
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Phosphorus, Sulfur, and Silicon, 189:839–848, 2014
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2013.858253
DMAP-CATALYZED SYNTHESIS OF NOVEL
PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES
BEARING AN AROMATIC SULFONAMIDE MOIETY
Maryam Khashi,1 Abolghasem Davoodnia,1 and
Jamshidkhan Chamani2
1Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad,
Iran
2Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran
GRAPHICAL ABSTRACT
Abstract 4-(N,N-Dimethylamino)pyridine (DMAP), with a dual role as a basic nucleophilic
catalyst, was shown to be a highly efficient catalyst for the synthesis of some new N-(2-aryl-7-
benzyl-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzenesulfonamides through the reac-
tion of 2-aryl-7-benzyl-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-amines (7-deazaadenines)
with benzenesulfonyl chlorides. It was also found that the use of DMAP under solvent-free
conditions is much more effective than other catalytic systems such as pyridine as both the
catalyst and solvent, t-BuOK in t-BuOH, Et3N in ethanol (EtOH), and even DMAP in dimethyl-
formamide (DMF). The influences of the reaction parameters, temperature, and the catalyst
amount, on the catalytic performance have been studied. All synthetic compounds were char-
acterized on the basis of their full spectral data.
Keywords DMAP; benzenesulfonamides; pyrrolo[2,3-d]pyrimidin-4-amines; solvent-free
conditions
INTRODUCTION
Sulfonamides, specially their aryl derivatives, represent a class of medicinally impor-
tant compounds having interesting pharmacological activities. Many of these compounds
Received 5 August 2013; accepted 12 October 2013.
The authors would like to thank Dr. V. S. Prasada Rao Lingam (Medicinal Chemistry Division, Glenmark
Research Center, Glenmark Pharmaceutical Ltd., MIDC, Mahape, Navi Mumbai 400709, India) for his valuable
advices.
Address correspondence to Abolghasem Davoodnia, Department of Chemistry, Mashhad Branch, Islamic
Azad University, Mashhad, Iran. E-mail: adavoodnia@mshdiau.ac.ir
839

840
M. KHASHI ET AL.
are extensively used for their antibacterial,1 antiinflammatory,2 hypoglycemic,3 antifungal,4
antidiabetic5 activities and as anticonvulsant agents.6,7 Also, some of them are protease,8
and carbonic anhydrase inhibitors.9,10 Recently, a host of structurally novel sulfonamide
derivatives was reported to show substantial antitumor activity in vitro and/or in vivo.11–14
On the other hand, pyrrolo[2,3-d]pyrimidines are widely used as antitumor,15 antimi-
crobial,16 and antiangiogenic17 agents with potential application as enzyme inhibitors.18
Moreover, pyrrolo[2,3-d]pyrimidin-4-amines (i), which may be regarded as an analog of
adenine (ii) in which its N-7 (purine (iii) numbering) has been replaced by a CH group
and therefore can be named as 7-deazaadenines, are known to show antiinflammatory,19
antifungal,20 and antibacterial20 activities. Also, some 4-substituted aminopyrrolo[2,3-
d]pyrimidine derivatives are selective A1-adenosine receptor antagonists.21
These facts prompted us to the synthesis of novel pyrrolo[2,3-d]pyrimidine derivatives
bearing an aromatic sulfonamide moiety that can also be named as substituted amino-7-
deazaadenines. Among the reported methods, the sulfonylation of amines with sulfonyl
chlorides in the presence of a base is still the most commonly employed method for
the synthesis of sulfonamides.22,23 A perusal of the literature revealed that sulfonylation
of amines with sulfonyl chlorides is commonly performed in pyridine as the base and
medium.24–28
4-(N,N-Dimethylamino)pyridine (DMAP) is a very good nucleophilic catalyst and
is more basic than pyridine. DMAP is widely used as a superb nucleophilic catalyst for
many organic reactions such as Baylis–Hillman reaction,29,30 regioselective acylation of
6-O-protected octyl β-D-glucopyranosides,31 synthesis of electrophilic alkenes,32 heroin
synthesis,33 and synthesis of N-sulfonyl monocyclic β-lactams.34
In continuation of our previous works in the synthesis of new heterocyclic compounds
with potential biological activities,35–45 recently, we prepared some new 2-aryl-7-benzyl-
5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-amines (derivatives of 7-deazaadenine) by re-
action of 2-amino-1-benzyl-4,5-diphenyl-1H-pyrrole-3-carbonitriles with aryl nitriles.46 In
this paper, we report the synthesis of new N-(2-aryl-7-benzyl-5,6-diphenyl-7H-pyrrolo[2,3-
d]pyrimidin-4-yl)benzenesulfonamides 3a–3i in synthetically useful yields by sulfonylation
reaction of amino moiety in 2-aryl-7-benzyl-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-
amines 1a–1c with benzenesulfonyl chlorides 2a–2c in the presence of DMAP with a dual
role as a base and also a nucleophilic catalyst under solvent-free conditions (Scheme 1).
RESULTS AND DISCUSSION
The starting materials 2-aryl-7-benzyl-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-
amines 1a–1c were prepared according to the literature method.46 Initially, we started the
condensation of 7-benzyl-5,6-diphenyl-2-m-tolyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine 1b

DMAP-CATALYZED SYNTHESIS OF NOVEL PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES 841
Scheme 1 Synthesis of N-(2-aryl-7-benzyl-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzenesulfonam-
ides catalyzed by DMAP.
(1 mmol) with 4-methylbenzenesulfonyl chloride 2b (1 mmol) as a model in refluxing
ethanol (EtOH) or dimethylformamide (DMF) and also under solvent-free conditions at
high temperature in the absence of catalyst. No product was observed in these conditions
even after prolonged reaction time (Table 1, entries 1–3). To enhance the yield of the
desired product, it was thought worthwhile to carry out the reaction in the presence of a
base as catalyst. Among the various tested catalyst–solvent systems such as pyridine as
both catalyst and solvent, t-BuOK in t-BuOH, Et3N in EtOH, DMAP in DMF, and also
DMAP under solvent-free conditions, the reaction was proceeded to give the high yield
Table 1 Synthesis of compound 3e in the presence of DMAP as catalyst in different reaction conditionsa
Entry
Catalyst (amount)
Solvent
T (◦C)
Time (h:min)
Yield (%)b
1
2
3
4
5
6
7
8
None
None
None
—
EtOH
DMF
—
t-BuOH
EtOH
DMF
—
—
—
—
—
160
78
153
115
83
18:00
18:00
18:00
10:00
10:00
10:00
10:00
4:30
10:00
10:00
8:00
6:00
2:30
—
—
—
Trace
—
—
Trace
65
Trace
27
42
50
Pyridine (2 mL)
t-BuOK (0.2 g)
NEt3 (0.5 mL)
DMAP (0.1 g)
DMAP (0.05 g)
DMAP (0.1 g)
DMAP (0.1 g)
DMAP (0.1 g)
DMAP (0.1 g)
DMAP (0.1 g)
DMAP (0.1 g)
DMAP (0.2 g)
78
153
160
90
110
120
140
160
180
160
9
10
11
12
13
14
15
—
—
—
88
88
88
2:30
3:00
aReaction conditions: 7-benzyl-5,6-diphenyl-2-m-tolyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine 1b (1 mmol), and
4-methylbenzenesulfonyl chloride 2b (1 mmol). bIsolated yields.

842
M. KHASHI ET AL.
Table 2 Synthesis of N-(2-aryl-7-benzyl-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzenesulfonamides
3a–3ia
Entry
Ar
Arꢁ
Productb
Time (h:min)
Yield (%)c
mp (◦C)
1
2
3
4
5
6
7
8
9
C6H5
C6H5
C6H5
3-MeC6H4
3-MeC6H4
3-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
C6H5
3a
3b
3c
3d
3e
3f
3g
3h
3i
1:00
1:30
1:00
2:00
2:30
2:00
1:30
1:00
1:00
90
89
90
85
88
85
93
97
97
275–277
233–235
235–237
197–199
195–197
206–208
264–267
207–209
205–207
4-MeC6H4
4-ClC6H4
C6H5
4-MeC6H4
4-ClC6H4
C6H5
4-MeC6H4
4-ClC6H4
aReaction conditions: 2-aryl-7-benzyl-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-amines 1a–1c (1 mmol),
benzenesulfonyl chlorides 2a–2c (1 mmol), DMAP (0.1 g), 160 ◦C, solvent-free.
bAll the products were characterized according to their IR, 1H NMR, 13C NMR, and MASS spectral data.
cIsolated yields.
of the product 3e, using DMAP under solvent-free conditions. In order to determine the
optimum conditions, we examined the influence of the reaction temperature and the amount
of DMAP as catalyst. The best result was obtained when the reaction was conducted at
160 ◦C in the presence of 0.1 g of the catalyst under solvent-free conditions (Table 1, entry
13). A further increase in temperature and catalyst amount did not improve the product
yield.
With the above result in hand, and in order to show the generality and scope of this
new protocol, a range of N-(2-aryl-7-benzyl-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-
yl)benzenesulfonamides 3a–3i was prepared in the presence of DMAP under optimized
conditions and the results are summarized in Table 2. In all cases, the reactions proceeded
to produce the corresponding products in high yields.
The structures of the new compounds 1c and 3a–3i were deduced from their spectral
data. For example, the 1H NMR spectrum of 3e in CDCl3 did not show the NH2 signal at δ
5.18 ppm belonging to the precursor 1b,46 but instead showed a sharp single (1H) signal at
δ 12.93 ppm for an NH group along with two sharp 3H signals at δ 2.40 and 2.51 ppm for
methyl groups, a signal at δ 5.46 ppm for methylene hydrogens as well as the signals in the
aromatic region due to 23 aromatic protons indicating the formation of the compound 3e.
Also, this product gave satisfactory 13C NMR, mass spectrometry, and elemental analysis
data corresponding to the molecular formula C39H32N4O2S (Experimental section).
According to the proposed catalytic roles for DMAP in some organic reactions,33,47–49
a plausible mechanism for the formation of products 3a–3i using DMAP as catalyst can be
depicted in Scheme 2. As shown, it is proposed that DMAP can play a dual role as a base and
also nucleophilic catalyst and therefore can activate both reactants in this transformation.
Since the nitrogen atom in DMAP is more nucleophilic than the amino group in compounds
1a–1c, andalsotheintermediate I ismorereactivethanthebenzenesulfonylchlorides 2a–2c,
the conditions required for nucleophilic catalysis therefore exist, and the reaction is faster
in the presence of DMAP than in its absence. On the other hand, DMAP can neutralize the
protons generated in the reaction and prevents the development of high acid concentration.
Also, DMAP as a base, can promote the reactions by the deprotonation of the amino group,
enhancing the nucleophilicity of this moiety in intermediate II. Two intermediates I and II
subsequently react together to give the final products 3a–3i.

DMAP-CATALYZED SYNTHESIS OF NOVEL PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES 843
Scheme 2 The role of DMAP as a base and nucleophilic catalyst in the synthesis of compounds 3a–3i.
CONCLUSION
In conclusion, DMAP was found to be highly efficient catalyst for the syn-
thesis of some new N-(2-aryl-7-benzyl-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-
yl)benzenesulfonamides 3a–3i in high yields by the reaction of 2-aryl-7-benzyl-5,6-
diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-amines 1a–1c with benzenesulfonyl chlorides
2a–2c. The use of DMAP under solvent-free conditions is much more effective than other
catalytic systems such as pyridine as both the catalyst and solvent, t-BuOK in t-BuOH,
Et3N in EtOH, and even DMAP in DMF. It is proposed that DMAP can play a dual role as
a base and also a nucleophilic catalyst.
EXPERIMENTAL
Melting points were recorded on a Stuart SMP3 melting point apparatus (UK). The
IR spectra were obtained using a Perkin-Elmer Spectrum-1 (USA) spectrophotometer using
KBr disks. The 1H NMR were recorded with a Varian-400 MHz (USA) spectrometer. The

844
M. KHASHI ET AL.
13C NMR were recorded with varian-300 and 400 MHz spectrometers (USA) at 75 and
100 MHz frequencies. Mass spectra were obtained using a Thermo Finnegan LCQ DECA
XP MAX (USA) mass spectrometer. Elemental analysis was performed on a Thermo
Finnigan Flash EA (USA) microanalyzer.
General Procedure for the Synthesis of N-(2-Aryl-7-benzyl-5,6-diphenyl-
7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzenesulfonamides 3a–3i
A mixture of 2-aryl-7-benzyl-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-amines
1a–1c (1 mmol), benzenesulfonyl chlorides 2a–2c (1 mmol), and DMAP (0.1 g) was
◦
heated in an oil bath at 160 C for 1–2.5 h. The reaction was monitored by thin layer
chromatography (TLC). Upon completion, the mixture was cooled to room temperature
and hot EtOH/H2O was added. This resulted in the precipitation of the product that was
collected by filtration. The crude product was washed repeatedly with ethanol and water
to give compounds 3a–3i in 85%–97% yields.
Spectral Data for Compounds 1c and 3a–3i
7-Benzyl-2-(4-methylphenyl)-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidin-
4-amine 1c (Ar = 4-MeC6H4). This new compound was prepared according to the
method reported in ref. [46]. Time 8 h, yield 95%, mp 210–212 ◦C; 1H NMR (400 MHz,
CDCl3): δ 2.43 (s, 3H, CH3), 5.04 (s br, 2H, NH2), 5.49 (s, 2H, CH2), 7.04–7.35 (m, 17H,
arom-H), 8.38 (d, J = 8.2 Hz, 2H, arom-H); 13C NMR (75 MHz, CDCl3): δ 21.4 (CH3),
46.0 (CH2), 100.3, 114.1, 126.7, 127.1, 127.6, 127.8, 128.1, 128.3, 128.4, 128.9, 130.4,
130.8, 131.1, 134.7, 135.1, 136.4, 138.3, 139.2, 152.3, 156.8, 158.3 (aromatics); IR (KBr
disk): ν 3473, 3296, 3152, 3059, 3032, 2922, 1637, 1583, 1559, 1451, 1412, 1358, 1310,
728, 695 cm−1; MS (APCI): m/z 467.43 (MH+, 100%) (466.58 calcd. for C32H26N4); Anal.
Calcd. for C32H26N4: C, 82.38; H, 5.62; N, 12.01; found: C, 82.06; H, 5.85; N, 11.84.
N-(7-Benzyl-2,5,6-triphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzene–
1
sulfonamide 3a (Ar = Ph, Arꢀ = Ph). H NMR (400 MHz, CDCl3): δ 5.47 (s, 2H,
CH2), 6.93–7.65 (m, 21H, arom-H), 7.80 (d, J = 7.4 Hz, 2H, arom-H), 8.14–8.24 (m, 2H,
arom-H), 12.97 (s, 1H, NH); 13C NMR (75 MHz, CDCl3): δ 46.4 (CH2), 104.2, 118.9,
125.9, 126.4, 126.5, 127.0, 127.2, 127.5, 128.2, 128.4, 128.5, 128.6, 129.4, 130.1, 131.1,
131.5, 131.6, 131.8, 132.3, 136.6, 137.1, 143.4, 148.4, 148.5, 150.1 (aromatics); IR (KBr
disk): ν 3434, 2925, 1630, 1445, 1260, 1021, 814 cm−1; MS (APCI): m/z 593.69 (MH+,
100%) (592.71 calcd. for C37H28N4O2S); Anal. Calcd. for C37H28N4O2S: C, 74.98; H,
4.76; N, 9.45; S, 5.41; found: C, 74.69; H, 4.54; N, 9.77; S, 5.16.
N-(7-Benzyl-2,5,6-triphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-methyl–
1
benzenesulfonamide 3b (Ar = Ph, Arꢀ = 4-MeC6H4). H NMR (400 MHz, CDCl3):
δ 2.40 (s, 3H, CH3), 5.46 (s, 2H, CH2), 6.93–7.65 (m, 19H, arom-H), 7.69 (d, 2H, J =
8.1 Hz, arom-H), 8.06–8.21 (m, 3H, arom-H), 13.01 (s, 1H, NH); 13C NMR (100 MHz,
CDCl3): δ 21.4 (CH3), 46.4 (CH2), 104.1, 119.0, 125.9, 126.3, 126.5, 127.0, 127.2, 127.5,
128.3, 128.5, 128.6, 129.0, 129.4, 130.2, 130.2, 131.1, 131.6, 131.7, 132.3, 136.5, 137.9,
140.6, 142.0, 148.4, 148.4, 150.0 (aromatics); IR (KBr disk): ν 3443, 3061, 2924, 1624,
1445, 1434, 1389, 1341, 1259, 1066, 814 cm−1; MS (APCI): m/z 607.26 (MH+, 100%)
(606.74 calcd. for C38H30N4O2S); Anal. Calcd. for C38H30N4O2S: C, 75.22; H, 4.98; N,
9.23; S, 5.28; found: C, 74.89; H, 5.24; N, 9.47; S, 5.56.

DMAP-CATALYZED SYNTHESIS OF NOVEL PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES 845
N-(7-Benzyl-2,5,6-triphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-chloro–
1
benzenesulfonamide 3c (Ar = Ph, Arꢀ = 4-ClC6H4). H NMR (400 MHz, CDCl3): δ
5.45 (s, 2H, CH2), 6.92–7.38 (m, 18H, arom-H), 7.55–7.62 (m, 2H, arom-H), 7.66 (d, J =
8.6 Hz, 2H, arom-H), 8.12–8.17 (m, 2H, arom-H), 12.84 (s, 1H, NH); 13C NMR (75 MHz,
CDCl3): δ 46.5 (CH2), 104.2, 118.9, 126.5, 127.1, 127.2, 127.4, 127.6, 128.4, 128.5, 128.6,
128.7, 129.4, 129.9, 131.1, 131.5, 131.6, 131.9, 132.3, 136.8, 137.1, 137.7, 142.0, 148.4,
148.5, 150.0 (aromatics); IR (KBr disk): ν 3435, 3063, 2928, 1626, 1445, 1393, 1261, 1068,
813 cm−1; MS (APCI): m/z 627.21 (M+, 100%), 628.28 (MH+, 40%) (627.15 calcd. for
C37H27ClN4O2S); Anal. Calcd. for C37H27ClN4O2S: C, 70.86; H, 4.34; N, 8.93; S, 5.11;
found: C, 71.18; H, 4.59; N, 8.66; S, 4.94.
N-(7-Benzyl-5,6-diphenyl-2-m-tolyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)–
1
benzenesulfonamide 3d (Ar = 3-MeC6H4, Arꢀ = Ph). H NMR (400 MHz, CDCl3):
δ 2.51 (s, 3H, CH3), 5.46 (s, 2H, CH2), 6.93–7.01 (m, 2H, arom-H), 7.07 (d, J = 7.5 Hz,
2H, arom-H), 7.11–7.52 (m, 16H, arom-H), 7.79 (d, J = 7.5 Hz, 2H, arom-H), 7.93–7.99
(m, 2H, arom-H), 12.91 (s, 1H, NH); 13C NMR (100 MHz, CDCl3): δ 21.6 (CH3), 46.5
(CH2), 104.2, 119.0, 123.7, 126.0, 126.4, 127.0, 127.2, 127.3, 127.6, 128.4,128.4, 128.5,
128.6, 129.3, 130.2, 131.2, 131.6, 131.7, 132.4, 132.7, 136.6, 137.2, 139.3, 143.5, 148.6,
148.7, 150.2 (aromatics); IR (KBr disk): ν 3436, 3062, 3031, 2924, 1622, 1447, 1435,
1386, 1349, 1258, 1068, 829 cm−1; MS (APCI): m/z 607.34 (MH+, 100%) (606.74 calcd.
for C38H30N4O2S); Anal. Calcd. for C38H30N4O2S: C, 75.22; H, 4.98; N, 9.23; S, 5.28;
found: C, 75.46; H, 5.15; N, 9.01; S, 5.04.
N-(7-Benzyl-5,6-diphenyl-2-m-tolyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-
1
methylbenzenesulfonamide 3e (Ar = 3-MeC6H4, Arꢀ = 4-MeC6H4). H NMR
(400 MHz, CDCl3): δ 2.40 (s, 3H, CH3), 2.51 (s, 3H, CH3), 5.46 (s, 2H, CH2), 6.94–7.51
(m, 19H, arom-H), 7.68 (d, J = 8.3 Hz, 2H, arom-H), 7.93–7.98 (m, 2H, arom-H), 12.93
(s, 1H, NH); 13C NMR (100 MHz, CDCl3): δ 21.4 (CH3), 21.6 (CH3), 46.4 (CH2), 104.1,
118.9, 123.7, 125.9, 126.3, 127.0, 127.1, 127.2, 127.5, 128.3, 128.5, 128.6, 129.0, 129.3,
130.2, 131.1, 131.6, 132.3, 132.6, 136.5, 137.2, 139.3, 140.6, 142.0, 148.5, 148.7, 150.0
(aromatics); IR (KBr disk): ν 3435, 3061, 3028, 2920, 1625, 1434, 1390, 1354, 1301,
1259, 1127, 1069, 863, 699 cm−1; MS (APCI): m/z 621.27 (MH+, 100%) (620.76 calcd.
for C39H32N4O2S); Anal. Calcd. for C39H32N4O2S: C, 75.46; H, 5.20; N, 9.03; S, 5.17;
found: C, 75.84; H, 4.91; N, 8.74; S, 5.38.
N-(7-Benzyl-5,6-diphenyl-2-m-tolyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-
1
chlorobenzenesulfonamide 3f (Ar = 3-MeC6H4, Arꢀ = 4-ClC6H4). H NMR
(400 MHz, CDCl3): δ 2.51 (s, 3H, CH3), 5.47 (s, 2H, CH2), 6.94–7.52 (m, 19H, arom-H),
7.67 (d, J = 8.6 Hz, 2H, arom-H), 7.92–7.97 (m, 2H, arom-H), 12.79 (s, 1H, NH); 13C
NMR (100 MHz, CDCl3): δ 21.6 (CH3), 46.5 (CH2), 104.2, 118.9, 123.7, 126.5, 127.1,
127.1, 127.2, 127.4, 127.6, 128.4, 128.5, 128.6, 128.7, 129.3, 130.0, 131.1, 131.5, 131.6,
132.3, 132.7, 136.8, 137.1, 137.7, 139.4, 142.0, 148.7, 150.1 (aromatics); IR (KBr disk): ν
3436, 3058, 2924, 1625, 1435, 1389, 1350, 1262, 1128, 1072, 865, 701 cm−1; MS (APCI):
m/z 641.37 (M+, 100%), 642.38 (MH+, 39%) (641.18 calcd. for C38H29ClN4O2S); Anal.
Calcd. for C38H29ClN4O2S: C, 71.18; H, 4.56; N, 8.74; S, 5.00; found: C, 70.86; H, 4.37;
N, 8.52; S, 5.19.
N-(7-Benzyl-5,6-diphenyl-2-p-tolyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)
1
benzene sulfonamide 3g (Ar = 4-MeC6H4, Arꢀ = Ph). H NMR (400 MHz, CDCl3):
δ 2.48 (s, 3H, CH3), 5.45 (s, 2H, CH2), 6.94–7.52 (m, 20H, arom-H), 7.80 (d, J = 7.4 Hz,
2H, arom-H), 8.06 (d, J = 8.1 Hz, 2H, arom-H), 12.91 (s, 1H, NH); 13C NMR (75 MHz,
CDCl3): δ 21.5 (CH3), 46.3 (CH2), 103.9, 118.8, 125.9, 126.4, 126.5, 127.0, 127.2, 127.5,

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M. KHASHI ET AL.
128.32, 128.4, 128.4, 128.5, 130.0, 130.1, 131.1, 131.5, 132.3, 136.4, 137.2, 142.4, 143.4,
145.3, 145.7, 148.6, 150.0 (aromatics); IR (KBr disk): ν 3434, 3055, 3028, 2923, 1626,
1446, 1387, 1352, 1259, 1161, 1128, 1066, 703 cm−1; MS (APCI): m/z 607.33 (MH+,
100%) (606.74 calcd. for C38H30N4O2S); Anal. Calcd. for C38H30N4O2S: C, 75.22; H,
4.98; N, 9.23; S, 5.28; found: C, 75.01; H, 4.79; N, 9.48; S, 5.09.
N-(7-Benzyl-5,6-diphenyl-2-p-tolyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-
1
methylbenzenesulfonamide 3h (Ar = 4-MeC6H4, Arꢀ = 4-MeC6H4). H NMR
(400 MHz, CDCl3): δ 2.40 (s, 3H, CH3), 2.48 (s, 3H, CH3), 5.45 (s, 2H, CH2), 6.93–7.01
(m, 2H, arom-H), 7.07 (d, J = 7.0 Hz, 2H, arom-H), 7.12–7.36 (m, 13H, arom-H), 7.40
(d, J = 7.0 Hz, 2H, arom-H), 7.68 (d, J = 8.2 Hz, 2H, arom-H), 8.06 (d, J = 8.2 Hz, 2H,
arom-H), 12.93 (s, 1H, NH); 13C NMR (75 MHz, CDCl3): δ 21.4 (CH3), 21.5 (CH3), 46.4
(CH2), 103.9, 118.9, 125.9, 126.3, 126.5, 127.0, 127.2, 127.5, 128.3, 128.5, 128.5, 128.8,
129.0, 130.1, 130.2, 131.1, 131.6, 132.4, 136.3, 137.2, 140.7, 142.0, 142.4, 148.5, 150.0
(aromatics); IR (KBr disk): ν 3434, 3063, 3032, 2921, 1619, 1430, 1382, 1348, 1263,
1160, 1123, 1096, 1067, 813, 699 cm−1; MS (APCI): m/z 621.24 (MH+, 100%) (620.76
calcd. for C39H32N4O2S); Anal. Calcd. for C39H32N4O2S: C, 75.46; H, 5.20; N, 9.03; S,
5.17; found: C, 75.19; H, 5.41; N, 8.72; S, 5.42.
N-(7-Benzyl-5,6-diphenyl-2-p-tolyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-
1
chlorobenzenesulfonamide 3i (Ar = 4-MeC6H4, Arꢀ = 4-ClC6H4). H NMR
(400 MHz, DMSO-d6): δ 2.08 (s, 3H, CH3), 5.44 (s, 2H, CH2), 6.92–7.42 (m, 19H,
arom-H), 7.65 (d, J = 8.2 Hz, 2H, arom-H), 8.02 (d, J = 8.2 Hz, 2H, arom-H), 12.78 (s,
1H, NH); 13C NMR (75 MHz, CDCl3): δ 21.5 (CH3), 46.4 (CH2), 104.1, 118.8, 126.5,
127.0, 127.2, 127.4, 127.6, 128.4, 128.5, 128.6, 128.7, 128.7, 130.0, 130.1, 131.1, 131.6,
132.4, 136.6, 137.1, 137.7, 142.1, 142.6, 148.6, 148.7, 150.1 (aromatics); IR (KBr disk):
ν 3421, 3062, 3030, 2925, 1624, 1432, 1386, 1347, 1263, 1069, 817, 699 cm−1; MS, m/z
(APCI): 641.29 (M+, 100%), 642.32 (MH+, 39%) (641.18 calcd. for C38H29ClN4O2S);
Anal. Calcd. for C38H29ClN4O2S: C, 71.18; H, 4.56; N, 8.74; S, 5.00; found: C, 71.55; H,
4.81; N, 8.49; S, 4.72.
FUNDING
The authors express their gratitude to the Islamic Azad University, Mashhad Branch
for its financial support.
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