One-Pot regioselective synthesis of 2,6,9-trisubstituted adenines

Article abstract of DOI:10.1055/s-0030-1259289

A series of 2,6,9-substituted adenines were obtained from the easily accessible 5-amino-4-cyanoformimidoyl imidazoles, acetic and benzoic anhydrides, and primary alkyl amines in a three-step sequence. Acylation of 5-amino-4-cyanoformimidoyl imidazoles fol

Full text of DOI:10.1055/s-0030-1259289

LETTER
181
One-Pot Regioselective Synthesis of 2,6,9-Trisubstituted Adenines
S
ynthesis of 2,6,9-
á
T
risubstitut
d
ed Adeninesia Senhorães, Alice M. Dias,* L. Miguel Conde, M. Fernanda Proença
Departamento de Química, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal
Fax +351(253)678983; E-mail: ad@quimica.uminho.pt
Received 18 October 2010
route is amination of the 5-amino-4,6-dihalopyrimidine,
followed by a ring-closing reaction with triethyl orthofor-
mate or acid derivatives.2,4b,9c
Abstract: A series of 2,6,9-substituted adenines were obtained
from the easily accessible 5-amino-4-cyanoformimidoyl imida-
zoles, acetic and benzoic anhydrides, and primary alkyl amines in a
three-step sequence. Acylation of 5-amino-4-cyanoformimidoyl
imidazoles followed by addition of the amine led to the intermedi-
ates 5-amino-4-(N-acyl)formamidino imidazoles under mild condi-
tions. Cyclization of 5-amino-4-(N-acyl)formamidino imidazoles
under reflux in ethanol led to the desired substituted adenine. A pre-
liminary stepwise study led to the development of three general and
efficient one-pot methods for the synthesis of adenine derivatives.
The one-pot, three-step reaction in the presence of DMAP was the
most convenient synthetic approach.
To the best of our knowledge, there are few reports on the
synthesis of adenines from 5-amino-4-carboxamidino im-
idazoles, prepared from ring opening of N1-alkoxy-
adenines or from 5-amino-4-cyano imidazoles, mostly
involving multistep, low-yield processes.10
In our research group, 5-amino-4-cyanoformimidoyl imi-
dazoles 1 have been used as versatile precursors for sub-
stituted purines.11 In previous work, imidazoles 1 were
easily reacted with ethyl chloroformate at the imine car-
bon atom. The obtained ethoxycarbonyl derivatives
promptly reacted with methyl and benzylamine under
mild conditions to give mixtures of N1- and N6-substitut-
ed isoguanines.12a The acylation of imidazoles 1 with ace-
tic and benzoic anhydrides also occurred under mild
experimental conditions, and the corresponding acetyl
and benzoyl imidazoles 2 and 3 were obtained in good
yield (Table 1). The reaction of 2 and 3 with hydrazine led
to imidazolyl 1,2,4-triazoles.12b
Key words: heterocycles, cyclization, ring closure, ring opening,
imidazole, purine
Adenine is one of the most important naturally occurring
nitrogen heterocycles. This purine nucleobase plays a fun-
damental role in the nucleic acid chemistry and cellular
biochemistry.1 In fact, the function of a remarkable num-
ber of proteins is governed by adenine nucleotides as co-
factors or co-substrates.1,2 Moreover, the increasing num-
ber of reports describing new biological activities of syn-
thetic adenine derivatives reveals the great potential of
these compounds as new chemical-biological tools and
therapeutic target as enzyme inhibitors or receptor ago-
nists/antagonists.2,3 For instance, adenines, adenine nucle-
In the present work, an efficient synthetic method was de-
veloped for the preparation of 2,6,9-substituted adenines
6/7 from imidazoles 2/3 and primary aliphatic amines
(Table 1).
osides, and their analogues have found potential When benzylamine was added to a suspension of 2 in eth-
therapeutic application against cancer,4 autoimmune dis- anol, the resulting solution was concentrated in the rotary
ease,5 viral infections,6 and microbial infections.7 The nat- evaporator using a hot bath to accelerate the process. Ad-
ural catalytic role and supramolecular assembly capacity dition of acetone to the residue gave a first crop of a white
of adenine inspired intense research on the field of orga- solid identified as adenine 6a. The second crop, isolated
nocatalysis and other applications ranging from coordina- by the same method, proved to be a mixture of two com-
tion chemistry to the synthesis of new materials.1,8
ponents in a 2:1 ratio. The major component was identi-
fied as the desired product 4a and, according to 1H NMR
data, imidazole 8a was the most plausible structure for the
second component (Scheme 1). Attempts to reproduce
this procedure evidenced that this is an instantaneous re-
action even at 0 °C, nevertheless the product 4a always re-
mained in solution. Maintaining the reaction mixture for
ca. 24 hours, at room temperature, led to a mixture of 8a
and adenine 6a as a minor contaminant. Heating the reac-
tion mixture for several hours, at 40–80 °C, selectively led
to adenine 6a.
The most common synthetic method to prepare 2- and 6-
substitued adenines involves nucleophilic substitution of
a suitable leaving group from commercially available 2-
halo and 6-chloro, 6-amino or 6-sulfonyl purines with
amines or carbon nucleophiles and metal-catalyzed cou-
plings.2–7 To introduce functionality at the 9-position,
N-alkylation(arylation) of adenine or 6-chloropurine has
been accessed by treatment with alkyl halides, by a
Mitsunobu reaction with an appropriate alcohol, or the
coupling of purine bases with aryl boronic acids.2,9 These
methods suffer from several drawbacks including the use The same reaction was carried out in dichloromethane at
of toxic, expensive, and explosive reagents. An alternative room temperature, and the bright yellow solid disappeared
instantly also leading to a homogeneous solution. The
pure imidazole 4a could be isolated as an off-white solid,
in 71% yield, but a careful workup was required to avoid
evolution of this compound in solution.
SYNLETT 2011, No. 2, pp 0181–0186
Advanced online publication: 04.01.2011
DOI: 10.1055/s-0030-1259289; Art ID: G29010ST
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x.
2
0
1
1

182
N. Senhorães et al.
LETTER
In a final attempt, the same synthesis was performed using Attempts to prepare imidazoles 4/5 with other primary
acetonitrile at 0 °C. The imidazole 4a precipitated from amines demonstrated that, in general, these products are
solution after 20 minutes and was isolated in 63% yield. not easy to isolate.
Evolution to side products was never detected. Thus, ace-
tonitrile was selected for the preparation of 4b–d and the
products were isolated in 44–63% yield (Table 1).13
Table 1 Synthesis of Compounds 4–7
R1
R1
R1
R1
NH2
NH
NH2
NH2
N
R2
N
N
N
(R2CO)2O
NH2R3
N
R2
R2
N
N
N
N
N
N
N
NHR3
O
3 O
NHR
CN
CN
2 R2 = Me
4 R2 = Me
6 R2 = Me
7 R2 = Ph
1
3 R2 = Ph
5 R2 = Ph
Compd
4a
R1
R3
Methoda
Reaction conditionsa
MeCN, 20 min, 0 °C
MeCN, 10 min, 0 °C
MeCN, 5 min, 0 °C
MeCN, 10 min, r.t.
MeCN, 90 min, r.t.
Yield (%)
Ph
Bn
Bn
Me
i-Pr
Bn
Bn
63
47
44
56
59
76
4b
Me
Me
Me
Me
Ph
4c
4d
5b
6a
D
C
A
1. MeCN, DMAP, 5 min, r.t.
2. EtOH, 1 h, reflux
6b
Me
Bn
1. MeCN, 1 h, r.t.
2. EtOH, 6.5 h, reflux
80
90
6c
Me
Me
Me
EtOH, 2.5 h, reflux
6d
i-Pr
A
A
EtOH, 35 min, reflux
MeCN, 2.5 h, reflux
96
94
6e
6f
Ph
Me
Bn
A
C
EtOH, 5 min, reflux
92
55
4-MeC6H4
4-FC6H4
4-FC6H4
(CH2)2OH
4-FC6H5
1. MeCN, 3 h, r.t.
2. EtOH, 6 h, reflux
6g
6h
6i
Bn
C
B
D
D
1. MeCN, 3 h, r.t.
2. EtOH, 7 h, reflux
67
36
52
88
(CH2)2OMe
(CH2)2OMe
Me
1. EtOH, 5 min, r.t.
2. MeCN, 3 h, reflux
1. MeCN, DMAP, 5 min, r.t.
2. EtOH, 2 h, reflux
6j
1. MeCN, DMAP, 5 min, r.t.
2. EtOH, 1 h, reflux
7b
7f
Me
Bn
Bn
A
B
EtOH, 1.5 h, reflux
75
50
4-MeC6H4
1. MeCN, 2 h, r.t.
2. MeCN,7 h, reflux
C
C
1. MeCN, 5 h, r.t.
2. EtOH, 5 h, reflux
63
67
7g
4-FC6H4
Bn
1. MeCN, 3 h, r.t.
2. EtOH, 7.5 h, reflux
Synlett 2011, No. 2, 181–186 © Thieme Stuttgart · New York

LETTER
Synthesis of 2,6,9-Trisubstituted Adenines
183
Table 1 Synthesis of Compounds 4–7 (continued)
R1
R1
R1
R1
NH2
NH
NH2
NH2
N
R2
N
N
N
(R2CO)2O
NH2R3
N
R2
R2
N
N
N
N
N
N
N
NHR3
O
3 O
CN
CN
NHR
2 R2 = Me
4 R2 = Me
6 R2 = Me
7 R2 = Ph
1
3 R2 = Ph
5 R2 = Ph
Compd
R1
R3
Methoda
Reaction conditionsa
Yield (%)
7j
4-FC6H4
Me
C
1. MeCN, 5 h, r.t.
2. EtOH, 9 h, reflux
40
D
C
B
1. MeCN, 5 h, r.t.
2. EtOH, 5 h, reflux
53
62
49
7l
(CH2)2OH
Bn
Bn
1. MeCN, 6 h, r.t.
2. EtOH, 9 h, reflux
7m
(CH2)2OMe
1. MeCN, 30 min, r.t.
2. EtOH, 7 h, reflux
a Method A (from 4 or 5): MeCN or EtOH, reflux. Method B (from 2 or 3): 1. RNH2 (1.2 equiv), MeCN, r.t. or 0 °C; 2. MeCN or EtOH, reflux.
Method C (from 1): 1. (a) Ac2O or Bz2O (2 equiv), MeCN, r.t. or 0 °C; (b) RNH2 (1.2 equiv), r.t. or 0 °C; 2. EtOH, reflux. Method D (from 1):
1. (a) Ac2O or Bz2O (1.2 equiv), DMAP (1.5 equiv), MeCN, 0 °C; (b) RNH2 (1.2 equiv); 2. EtOH, reflux.
To generate adenines 6/7,14 different experimental meth-
ods were investigated.
R1
R1
R1
NH2
NH2
NH
N
R2
N
N
N
(R2CO)2O
In method A, imidazoles 4/5 were isolated after a stepwise
process and refluxed as a suspension in ethanol. Intramo-
lecular cyclization led to adenines 6c–e and 7b, isolated in
very good to excellent yield (75–96%) after 5 minutes to
2.5 hours reflux. Two parallel experiments were carried
out to generate purine 6d in ethanol and in acetonitrile.
This product was isolated in a similar yield (96% and 94%
yield, respectively) although a slower reaction was ob-
served in acetonitrile. A 52% global yield was achieved
from 2/3 and a further reduction to 30–40% yield could be
estimated if the first step of the sequence (synthesis of 2/
3) was included.
R2
N
N
N
N
N
2 R2 = Me
9
1
CN
N
O
CN
3 R2 = Ph
CN
NH2R3
R2
O
R1
N
R1
R1
H
R2
NH2
N
N
N
R2
N
N
NH
N
N
N
4 R2 = Me
6 R2 = Me
7 R2 = Ph
NHR3
8
5 R2 = Ph
3 O
NHR3
NHR
Scheme 1
To prevent synthesis and manipulation of 2/3, the one-pot,
three-step sequence, starting from imidazoles 1, was ex-
amined (method C). Treatment of 1 with anhydrides was
carried out in acetonitrile at 0 °C or room temperature.
When imidazole 1 was consumed, addition of an excess of
amine was followed by dilution with ethanol and heating
under reflux. Most of the adenines 6/7 were isolated in
50–67% yield, an improved global yield for the one-pot
reaction. Methods B and C were compared for the synthe-
sis of 7f and demonstrated the higher global yield of the
last method (50% vs. 63%).
Method B involves the reaction of imidazoles 2/3 with the
amine, at room temperature, followed by reflux. This
method would allow to overcome the experimental prob-
lems associated with the isolation of imidazoles 4/5. Ace-
tonitrile was also the solvent selected. Alternatively,
ethanol was added in the second step. The two procedures
exhibited good and consistent yields (49–52%), with a
global efficiency similar to that of method A.
The synthesis of precursors 2/3 from imidazoles 1 suffers
from experimental problems associated with the manipu-
lation of these compounds. In fact, these yellow-orange
solids are highly soluble and unstable, undergoing rapid
intramolecular cyclization to give 6-cyanopurines 9 after
ca. 4–6 hours in solution (Scheme 1). A fast acyl migra-
tion also occurs leading to imidazoles 10 (Scheme 2). Fi-
nally, degradation with formation of dark polymeric
materials was often observed, a problem particularly im-
portant in the scale-up process.
A final approach to optimize the three-step sequence in-
volved the activation of the anhydride by the use of
DMAP in acetonitrile. An instantaneous acylation oc-
curred, with precipitation of the ammonium salt, removed
from solution by filtration. Addition of the appropriate
amine followed by reflux in ethanol provided adenines
6a,i,j and 7j (method D). A much faster first step was ob-
served, and cleaner reaction mixtures were obtained, fa-
cilitating the workup process in a highly efficient reaction
(52–88%).
Synlett 2011, No. 2, 181–186 © Thieme Stuttgart · New York

184
N. Senhorães et al.
LETTER
The structures 6/7 were confirmed by their spectral data. ate 11. At room temperature, intermediate 11 mainly
1
In the H NMR spectra, a broad NH band was always evolves to the kinetic product 8. Above 40–80 °C, dehy-
present, and the chemical shift depends on the amine sub- dratation of 11 leads to the thermodynamic product 6/7. A
stituent. For example, the spectrum of 6b showed the NH dynamic equilibrium, between imidazole 8 and intermedi-
signal as a broad triplet (J = 5.4 Hz) at d = 8.06 ppm, and ate 11, results in the complete evolution to the adenine de-
the corresponding signal for the methylene protons ap- rivative. The formation of a single isomer, the N6-
peared as a broad duplet. This confirmed the presence of subtituted adenine 6/7 can be rationalized by a selective
the NHCH2Ph group and supported the structure assigned nucleophilic attack by the unsubstituted nitrogen atom of
to the N6-substituted isomer. This was reinforced by the the amidine group (a, Scheme 3), governed by the thermo-
solitary HMBC three-bond correlation of the methylene dynamic stability of the final product.
protons with the C6 signal of the purine ring.
R1
Inspired in previous work,11g a different synthetic se-
quence was designed (Scheme 2 – pathway b) to generate
compound 8a.15 Migration of the acetyl group was in-
duced by stirring an ethanolic solution of imidazole 2a at
room temperature. The product 10a was allowed to react
with benzylamine in situ leading selectively to structure
8a. This compound was fully characterized, confirming
the structure previously assigned.
H
OH
N
R2
N
N
N
R1
R2
a
R1
H
N
NHR3
NH2
N
N
11
O
NH
R2
N
b
N
N
R1
NHR3
3 O
NHR
4, 5
N
N
R2
N
8
To examine the involvement of product 8 in the synthesis
of adenines 6/7, two parallel experiments were conducted:
(a) cyclization of imidazole 4a under reflux in ethanol; (b)
cyclization of imidazole 8a under the same conditions
(Scheme 2). Both reactions were complete after five min-
utes and adenine 6a16 was isolated in 92% and 87% from
both experiments.
N
NHR3
6, 7
Scheme 3 Proposed mechanism for the formation of adenines 6/7
In conclusion, a general, regioselective, and efficient
three-step method was developed to prepare a series of
different 2,6,9-substituted adenines 6 and 7 from the eas-
ily accessible imidazoles 1, acetic and benzoic anhy-
drides, and various alkyl amines. These products could be
obtained by multistep synthesis involving N-acylamidino
imidazoles 4 and 5 as intermediates, in a moderate yield.
The one-pot, two-step, and three-step synthetic approach-
es offered superior results. A particularly easy and effi-
cient one-pot method was devised through a three-step
sequence in the presence of DMAP. A wide range of N9-
substituents, including alkyl, aryl, and hydroxyalkyl
groups, was incorporated in the purine ring.
a) EtOH,
5 min,
reflux,
92%
Ph
Ph
NH2
NH2
N
N
a) NH2Bn
N
N
N
N
Ph
O
O
N
CN
2a
NHBn
4a
N
N
N
b) EtOH
NHBn
Ph
6a
Ph
H
N
H
N
N
N
b) NH2Bn
O
O
b) EtOH,
5 min,
reflux,
87%
NH
NH
N
N
Acknowledgment
NHBn
CN
10a
8a
The authors gratefully acknowledge the financial support by the
University of Minho and Fundação para a Ciência e Tecnologia.
Scheme 2 Two alternative pathways for the synthesis of adenine 6a
In order to establish the reaction mechanism, a solution of
imidazole 4a in DMSO-d6 was maintained at room tem-
perature and followed by 1H NMR. After ca. 24 hours, the
starting imidazole 4a was totally consumed leading to the
formation of 8a and traces of the corresponding adenine
6a. Conversion of imidazole 8a into purine 6a could also
be demonstrated upon heating the sample tube at a tem-
perature close to the boiling point of the solvent (ca. 5–15
min).
References and Notes
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These results prompted us to postulate the mechanism for
the conversion of imidazoles 4/5 into adenines 6/7
(Scheme 3). The reaction is initiated by nucleophilic at-
tack of the 5-amino group to the carbonyl carbon atom of
the acyl group, providing the cyclic tetrahedral intermedi-
Synlett 2011, No. 2, 181–186 © Thieme Stuttgart · New York

LETTER
Synthesis of 2,6,9-Trisubstituted Adenines
185
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Method C
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was stirred at r.t. for 5 h, when the mixture turned into an
orange suspension. Benzylamine (1.2 equiv) and EtOH (4
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was filtered and washed with MeCN, EtOH, and Et2O to
give compound 7c (63%).
Characterization of N-Benzyl-2-phenyl-9-(p-tolyl)-9H-
purin-6-amine (7c)
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Mp 199.8–200.7 °C. 1H NMR (300 MHz, DMSO-d6):
d = 8.57 (s, 1 H), 8.56 (br s, 1 H), 8.34 (d, J = 7.2 Hz, 2 H),
7.93 (d, J = 8.4 Hz, 2 H), 7.83 (d, J = 8.4 Hz, 2 H), 7.47–7.41
(m, 3 H), 7.38 (d, J = 7.6 Hz, 2 H), 7.30 (t, J = 7.6 Hz, 2 H),
7.20 (t, J = 7.6 Hz, 1 H), 4.85 (br s, 2 H), 2.39 (s, 3 H). 13
NMR (75 MHz, DMSO-d6): d = 158.00, 154.29, 149.49,
140.35, 139.96, 138.38, 136.85, 132.73, 129.66, 129.14,
128.19, 128.12, 127.64, 127.39, 126.62, 122.84, 118.73,
C
43.17, 20.57. Anal. Calcd for C25H21N5: C, 76.70; H, 5.41;
N, 17.89. Found: C, 76.70; H, 5.24; N, 17.64. IR (mull):
3270, 3084, 1623, 1571, 1529, 1519, 1496 cm–1.
(15) General Procedure for the Synthesis of 8a
A yellow suspension of imidazole 2 (1.82 mmol) in EtOH
(50 mL) was stirred at r.t. for 50 min. Benzylamine (1.1
equiv) was added to this solution and 10 min later, the
mixture was evaporated in vacuum (30 °C). The residual oil
was cooled and a solid precipitated by addition of acetone.
The solid was filtered and washed with EtOH and Et2O to
give compound 8a (91%).
Characterization of N-{4-[(benzylamino)(imino)methyl]-
1-phenyl-1H-imidazol-5-yl}acetamide (8a)
(12) (a) Dias, A. M.; Cabral, I. M.; Vila-Chã, A. S.; Proença, M.
F. Synlett 2007, 1231. (b) Dias, A. M.; Cabral, I. M.; Vila-
Chã, A. S.; Cunha, D.; Senhorães, N.; Nobre, S.; Sousa, C.;
Proença, M. F. Synlett 2010, 2792.
Mp 160.6–161.5 °C. 1H NMR (300 MHz, DMSO-d6):
d = 7.81 (s, 1 H), 7.46–7.43 (m, 5 H), 7.43–7.34 (m, 5 H),
4.50 (s, 2 H), 1.72 (s, 3 H). 13C NMR (75 MHz, DMSO-d6):
d = 171.83, 155.80, 148.66, 138.73, 136.01, 134.17, 129.08,
128.32, 127.44, 126.92, 124.09, 115.21, 45.52, 24.78. Anal.
Calcd for C19H19N5O: C, 68.45; H, 5.74; N, 21.01. Found: C,
68.41; H, 5.75; N, 20.86. IR (mull) 3370, 3251, 1631, 1551
cm–1.
(13) General Procedure for the Synthesis of 4a–d
Benzylamine (1.1 equiv for 4a,b), methylamine (for 4c), or
isopropylamine (for 4d) was added to a suspension of the
acylated imidazole 2 (0.59–2.82 mmol) in MeCN (0.5 mL),
and the mixture turned immediately into a beige solution.
The mixture was stirred at 0 °C (20 min for 4a, 10 min for
4b, and 5 min for 4c) or at r.t. (10 min for 4d). Bright white
solids precipitated and were filtered and washed with MeCN
and Et2O to give compounds 4a–d (44–63%). The structure
of the products was confirmed by elemental analysis, 1H
NMR, and 13C NMR spectroscopy.
(16) General Procedure for the Synthesis of 6a
(a) Method A
A white suspension of 4a (1.75 mmol) in EtOH (2 mL) was
heated at reflux for 5 min. The solution was evaporated in
vacuum and after cooling, a white solid precipitated out of
solution. The bright white solid was filtered and washed with
EtOH and Et2O to give compound 6a (92%).
Characterization of N-[(5-Amino-1-phenyl-1H-imidazol-
4-yl)benzylaminomethylene]acetamide (4a)
(b) A suspension of imidazole 8a in EtOH (2 mL) was
heated under reflux for 5 min. After that, the solution was
evaporated in vacuum and, after cooling, a solid precipitated
out of solution. The bright white solid was filtered and
washed with EtOH and Et2O to give compound 6a (87%
yield). The structure of the product obtained was confirmed
by elemental analysis, 1H NMR and 13C NMR spectroscopy.
Mp 159.1–160.2 °C. 1H NMR (300 MHz, DMSO-d6):
d = 11.69 (br s, 1 H), 7.58 (m, 2 H), 7.52–7.47 (m, 3 H), 7.49
(s, 1 H), 7.40–7.30 (m, 5 H), 7.30 (br s, 2 H), 5.32 (br s, 2 H),
1.98 (s, 3 H). 13C NMR (75 MHz, DMSO-d6): d = 182.93,
161.94, 147.19, 139.09, 131.30, 129.91, 129.05, 128.51,
Synlett 2011, No. 2, 181–186 © Thieme Stuttgart · New York

186
N. Senhorães et al.
Method D
LETTER
Characterization of N-Benzyl-2-methyl-9-phenyl-9H-
Acetic anhydride (1.2 equiv) and DMAP (1.5 equiv) were
added to a beige suspension of 1 (1.80 mmol) in MeCN (1
mL) at 0 °C. The mixture immediately turned in an orange
solution and 3 min later, a white solid precipitated out of
solution. The solid was filtered and benzylamine (1.2 equiv)
and EtOH (2 mL) were added, and the mixture was heated
under reflux for 1 h. After cooling, a white solid precipitated
out of solution and it was filtered and washed with EtOH and
Et2O to give compound 6a (76% yield).
purin-6-amine (6a)
Mp 175.6–176.7 °C. 1H NMR (300 MHz, DMSO-d6):
d = 8.48 (s, 1 H), 8.30 (br s, 1 H), 7.85 (d, J = 7.8 Hz, 2 H),
7.57 (t, J = 7.8 Hz, 2 H), 7.43 (t, J = 7.8 Hz, 1 H), 7.38 (d,
J = 6.9 Hz, 2 H), 7.30 (t, J = 6.9 Hz, 2 H), 7.20 (t, J = 6.9 Hz,
1 H), 4.80 (br s, 2 H)), 2.42 (s, 3 H). 13C NMR (75 MHz,
DMSO-d6): d = 161.84, 154.32, 149.39, 140.21, 139.11,
135.15, 129.46, 128.19, 127.61, 127.60, 126.19, 123.15,
117.95, 42.60, 26.11. Anal. Calcd for C19H17N5: C, 72.36; H,
5.43; N, 22.21. Found: C, 72.21; H, 5.28; N, 22.06. IR
(mull): 3270, 3223, 3063, 1617, 1598, 1581, 1530 cm–1.
Synlett 2011, No. 2, 181–186 © Thieme Stuttgart · New York

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