Tandem Michael addition/imino-nitrile cyclization synthesis of 2-amino-6-(1-aryl-5-methyl-1H-1,2,3-triazol-4yl)-4-phenylpyridine-3-carbonitrile

Article abstract of DOI:10.1002/jhet.336

(Chemical Equation Presented) Several 2-amino-6-(1-aryl-5-methyl-1H-1,2,3- triazol-4-yl)-4-phenylpyridine-3-carbonitrile have been synthesized by Tandem Michael addition/imino-nitrile cyclization and the structures of these compounds were established by M

Full text of DOI:10.1002/jhet.336

March 2010
Tandem Michael Addition/Imino-Nitrile Cyclization Synthesis of
2-Amino-6-(1-aryl-5-methyl-1H-1,2,3-triazol-4yl)-4-phenylpyri-
dine-3-carbonitrile
389
Heng-Shan Dong,* Hui-Cheng Wang, Zhong-Lian Gao, Rong-Shan Li,
and Fu-Hong Cui
State Key Laboratory of Applied Organic Chemistry, Institute of Organic Chemistry,
College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000,
People’s Republic of China
*E-mail: donghengshan@lzu.edu.cn
Received April 9, 2009
DOI 10.1002/jhet.336
Published online 4 March 2010 in Wiley InterScience (www.interscience.wiley.com).
Several 2–amino-6-(1-aryl-5-methyl-1H-1,2,3-triazol-4-yl)-4-phenylpyridine-3-carbonitrile have been
synthesized by Tandem Michael addition/imino-nitrile cyclization and the structures of these
compounds were established by MS, IR, CHN, and 1H NMR spectral data. The crystal structure of
2-amino-6-[1-(4-methoxyphenyl)-5-methyl-1H-1,2,3-triazol-4-yl]-4-phenylpyridine-3-carbonitrile was
established by X-ray diffraction.
J. Heterocyclic Chem., 47, 389 (2010).
INTRODUCTION
class of compounds prompted the synthesis, several new
2-amino-6-(1-aryl-5-methyl-1H-1,2,3-triazol-4-yl)-4-phe-
nylpyridine-3-carbonitrile have been synthesized by Tan-
dem Michael addition/amino-nitrile cyclization.
The pyridine ring is one of the most well-known sys-
tems among the naturally occurring heterocycles [1]. Pyr-
idine and fused pyridine moieties was shown in numerous
natural products such as quinoline and isoquinoline alka-
loids [2], and nicotine and its analogs [3], 2-aminopyri-
dines are promising substituted pyridines which have
been shown to be biologically active molecules [4]. Addi-
tionally, because of their chelating abilities, 2-aminopyri-
dines are commonly used as ligands in inorganic and
organometallic chemistry [5]. If substituted with optically
active groups, they could potentially serve for chiral aux-
iliaries or chiral ligands in asymmetric reactions. For this
reaction, 2-aminopyridine derivatives are valuable syn-
thetic target compounds. The synthesis of 2-aminopyri-
dine derivatives has been extensively reviewed [4–10]. In
addition there have been some reports concerning biolog-
ical interest for 1,2,3-triazole nucleus have been reported
as antibacterial [11], antifungal [12], antiviral [13], anti-
inflammatory and analgesic [14] and 1,2,3-triazole deriva-
tives have been synthesized to inhibit tumor proliferation,
invasion, and metastasis [15]. However, there is a little
data describing compounds containing the two heterocy-
clic moieties, thiazoline and 1,2,3-triazole. Interest in this
RESULTS AND DISCUSSION
The some new 2-amino-6-(1-aryl-5-methyl-1H-1,2,3-
triazol-4yl)-4-phenylpyridine-3-carbonitrile (3a–j) have
been synthesized by Tandem Michael addition/imino-
nitrile cyclization [16] with (E)-1-(1-aryl-5-methyl-1H-
1,2,3-triazol-4-yl)-3-phenylprop-2-en-1-one from 1-(1-
aryl-5-methyl-1H-1,2,3-triazol-4-yl)-ethanone derivatives
(Scheme 1).
Our own interest in the development of new 2–amino-6-
(1-aryl-5-methyl-1H-1,2,3-triazol-4-yl)-4-phenylpyridine-
3-carbonitrile derivatives and in extending this type of tan-
dem reaction prompted us to examine potential applications
and generalizations to the synthesis of substituted pyridine.
The reactivity of (E)-1-(1-aryl-5-methyl-1H-1,2,3-triazol-
4-yl)-3-phenylprop-2-en-1-one would be regarded particu-
larly closely during the cyclization step to shed further light
on the course of this short transformation and, also, to gain
further insight into the mechanistic aspects of this tandem
reaction.
C
V
2010 HeteroCorporation

390
H.-S. Dong, H.-C. Wang, Z.-L. Gao, R.-S. Li, and F.-H. Cui
Vol 47
ꢁ
˚
Scheme 1
1.343(4) A, C15AN5AH, HAN5AH angle is 120 , di-
hedral angle of C11AN4AC15AN5 is 179.4ꢁ, dihedral
angle of N5AC15AC14AC13 is 178.2ꢁ, N5 is came
under the action of sp2 hybridized.
On pyridine ring, 2-amino has two NAH bond and two
intermolecular hydrogen bonds as the superamolecular
structure in the crystal. The intermolecular O01ꢂꢂꢂH5A-N5
hydrogen-bond between the O1 atoms of the CH3O group
and N5AH, intermolecular N06ꢂꢂꢂH5AAN5 hydrogen
bond between the N atoms of the CN group and N5AH
was given (Fig. 2; Table 2). The orderly range of the
structure forms stratification polymer in the crystal. The
intermolecular hydrogen bond connects the translated
molecules into an infinite chain on a layer.
Scheme 2
Identified as a cyano compound showing IR absorption at
2207–2213 cmꢀ1 and amino at 3436–3494, 3353–3374
cmꢀ1 of 3a–j, as a carbonyl compound showing strong IR
absorption at 1679–1683 cmꢀ1 of 1a–j and 1659–1666 cmꢀ1
1
of 2a–j. H NMR ACOACH3 peak at 2.694–2.778 ppm of
1a–j and showing
1H NMR dual peak 8.057–8.173
ppm, 7.809–8.076 ppm, J ¼ 15.6–15.9 Hz of 2a–j but it
is disappearance in compounds 3a–j (Scheme 2).
Compound 2-amino-6-[1-(4-methoxyphenyl)-5-
methyl-1H-1,2,3-triazol-4-yl]-4-phenylpyridine-3-car-
bonitrile. This consists of a substituted triazolyl ring
and a phenyl ring is not planar (torsion angles is shown
for dihedral angle of CtriazolylANtriazolylACphenylACphenyl
is 48.6(4)ꢁ by the hindering of triazole ring C9ACH3 and
benzene ring C2AH or C6AH, and so dihedral angle of
CpyridylACpyridylACphenylACphenyl is 38.3(4)ꢁ in stable con-
formation of the crystal). The substituted triazolyl ring and
substituted pyridyl ring is an approximation planar (torsion
angles is shown for dihedral angle of NtriazolylACtriazo-
lylACpyridylANpyridyl is 176.5(3)ꢁ) by the p–p conjugation
of triazole ring p bond and pyridine ring p bond,
˚
C10AC11 bond 1.475 A is shorter than nonconjugation
2
2
˚
Csp -Csp bond C13AC17 1.484 A (Fig. 1; Table 1).
On pyridine ring, the p-p conjugation was indicated
between amino N5 and ring C15, N5AC15 length is
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2010
Tandem Michael Addition/Imino-Nitrile Cyclization Synthesis of 2-Amino-6-
(1-aryl-5-methyl-1H-1,2,3-triazol-4yl)-4-phenylpyridine-3-carbonitrile
391
Figure 1. A PLATON (Spek, 2001) view of the molecular structure of (I), the asymmetric unit showing 50% probability displacement ellipsoids.
[Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
EXPERIMENTAL
concentrated hydrochloric acid. 1-(1-Aryl-5-methyl-1H-1,2,3-
triazol-4-yl)ethanone 1a–j was separated and crystallized from
methanol.
All melting points were determined on an XT4-100ꢃ micro-
scopic melting point apparatus and are uncorrected. Mass spec-
trum was performed on a ESQ6K esquire6000 spectrometer
(3a–j) and HP-5988A (2a–j) spectrometer (EI at 70 eV). IR
spectra were obtained in KBr discus using a Nicolet NEXUS
670 FTIR spectrometer. 1H NMR spectroscopy (CDCl3) was
recorded on Avance Mercury plus-300 with TMS as an inter-
nal standard. Elemental analyses were carried out on a Yanaco
CHN Corder MT-3 analyzer.
General procedure for the preparation of 1-(1-aryl-5-
methyl-1H-1,2,3-triazol-4-yl)-ethanone derivatives (1a–j). 1-
(1-Aryl-5-methyl-1H-1,2,3-triazol-4-yl)-ethanone 1a–j was pre-
pared following condensation methods of 1-azido-4-methylben-
zene [17] with pentane-2,4-dione. A cold solution of sodium
methanolate (0.23 mol, in 120 mL absolute methanol) was
added to the mixture of pentane-2,4-dione (17 mL, 0.165 mol)
and 1-azido-4-methylbenzene (about 0.15 mol) and stirred for
1 h at 0–5ꢁC. Then the mixture was heated under reflux on an
oil-bath for 10 h. Finally the mixture was neutralized with
1-(5-Methyl-1-p-tolyl-1H-1,2,3-triazol-4-yl) ethanone
(1a). Yield: 52.6%; buff crystals; mp: 105–107ꢁC (Lit 106–
107ꢁC); 1H NMR: 7.360–7.384(d, 2H, J ¼ 7.2 Hz, Ar-2,6),
7.306–7.333(d, 2H,
J
¼
8.1 Hz, Ar-3,5), 2.757(s, 3H,
CH3CO), 2.573(s, 3H, TRZ-CH3), 2.468(s, 3H, ArACH3); MS:
215(Mþ,19); CA 194478-14-3 [17].
1-(5-Methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethanone (1b). Yield:
58.5%; buff crystals; mp: 99–100ꢁC (Lit 108ꢁC); 1H NMR:
7.552–7.578(m, 3H, J ¼ 7.8 Hz, Ar-3,4,5), 7.408–7.432(m,
2H, J ¼ 7.2 Hz, Ar-2,6), 2.729(s, 3H, CH3CO), 2,571(s, 3H,
TRZ-CH3); MS: 201(Mþ, 13) CA 51118-32-2 [18].
1-[1-(4-Chlorophenyl)-5-methyl-1H-1,2,3-triazol-4-yl]etha-
none (1c). Yield: 53.2%; white crystals; mp: 108–110ꢁC (Lit
119ꢁC); 1H NMR: 7.546–7.564(d, 2H, J ¼ 5.4 Hz, Ar-2, 6),
7.399–7.429(d, 2H,
J
¼
9.0 Hz, Ar-3,5), 2.757(s, 3H,
CH3CO), 2.599(s, 3H, TRZ-CH3); MS: 235(Mþ, 4). Found: C,
56.47; H, 4.42; N, 17.57 CA 33821-38-4 [18].
Table 1
Selected geometric parameters (A, ꢁ).
˚
ꢁ
ꢁ
)
˚
Bond (A,
˚
Bond (A,
Atom-atom
C10AC11
C13AC17
C15AN5AH5A
)
Atom-atom
1.475 (4)
1.484 (4)
120.0
C15AN5
1.343 (4)
120.0
H5AAN5AH5B
C15AN5AH5B
120.0
N3AC10AC11AN4
C13AC14AC15AN5
C12AC13AC17AC22
ꢀ176.5 (3)
ꢀ178.2 (3)
ꢀ38.3 (4)
C2AC1AN1AC9
N5AC15AN4AC11
ꢀ48.6 (4)
ꢀ179.4 (3)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

392
H.-S. Dong, H.-C. Wang, Z.-L. Gao, R.-S. Li, and F.-H. Cui
Vol 47
Figure 2. A PLATON (Spek, 2001) view of the hydrogen-bonded motif of the superamolecular structure. Hydrogen bonds are shown as dashed
lines (Symmetry codes: (i) ꢀx þ 1, ꢀy þ 1, ꢀz; (ii) ꢀx, ꢀy, ꢀz). [Color figure can be viewed in the online issue, which is available at
www.interscience.wiley.com.]
IR: 3429, 3346, 3057(ACH3), 1927, 1681(C¼¼O), 1598,
1-[1-(2,5-Dichlorophenyl)-5-methyl-1H-1,2,3-triazol-4-yl]
ethanone (1d). Yield: 54.9%; white crystals; mp: 100–102ꢁC;
1557(Ar), 1420, 1363, 1272, 1215, 1079, 951(NAN¼¼N), 865,
826(Ar-H), 755; 1H NMR: 7.896–8.038(m, 4H, Ar-1,4,5,8),
7.501–7.624(m, 3H, Ar-3,6,7), 2.778(s, 3H, CH3CO), 2.642(s,
IR: 3458, 3356, 3098(ACH3), 1895, 1682(C¼¼O), 1557,
1487(Ar), 1395, 1360, 1280, 1231, 1092, 955(NAN¼¼N), 877,
3H, TRZ-CH3); MS: 251(Mþ, 17), 222(3), 208(9), 194(3),
810(ArAH), 680; 1H NMR: 7.534–7.545(d, 2H, J ¼ 3.3 Hz,
180(61), 153(14), 127(63), 101(12), 77(22), 63(10), 51(13),
43(100); Anal. Calcd. for C15H13N2O: C, 71.70; H, 5.21; N,
16.72; Found: C, 71.57; H, 5.45; N, 16.56.
Ar-3,4), 7.448(s, 1H, Ar-6), 2.735(s, 3H, CH3CO), 2.451(s,
3H, TRZ-CH3); MS: 269(Mþ, 3), 241(1), 226(4), 199(11),
186(3), 172(3), 145(9), 109(14), 74(10), 43(100); Anal. Calcd.
for C11H9Cl2N3O: C, 48.91; H, 3.36; N, 15.56; Found: C,
48.67; H, 3.21; N, 15.86 CA 668471-36-1.
1-[1-(3-Bromophenyl)-5-methyl-1H-1,2,3-triazol-4-yl]etha-
none (1i). Yield:59.8%; white crystals; mp: 102–104ꢁC; IR:
3444, 3348, 3073(ACH3), 1683(C¼¼O), 1554, 1494(Ar), 1420,
1365, 1282, 1219, 1066, 1029, 952(NAN¼¼N), 765(Ar-H),
671; 1H NMR: 7.790(s, 1H, Ar-2), 7.505–7.528(m, 3H,Ar-
4,5,6), 2.728(s, 3H, CH3CO), 2.452(s, 3H, TRZ-CH3); MS:
279(Mþ, 5), 251(1), 236(7), 211(13), 196(4), 182(3), 157(18),
144(7), 102(8), 75(25), 63(9), 50(22), 43(100); Anal. Calcd.
for C11H10BrN3O: C, 47.16; H, 3.60; N, 15.00; Found: C,
47.36; H, 3.19; N, 15.13.
1-[1-(4-Menthoxyphenyl)-5-methyl-1H-1,2,3-triazol-4-yl]
ethanone (1j). Yield: 58.4%; buff crystals; mp: 117–119ꢁC
(Lit 120ꢁC); 1H NMR: 7.299–7.329(d, 2H, J ¼ 9.0 Hz, Ar-
2,6), 7.012–7.032(d, 2H, J ¼ 6.0 Hz, Ar-3,5), 3.837(s, 3H,
1-[1-(3-Chlorophenyl)-5-methyl-1H-1,2,3-triazol-4-yl]etha-
none (1e). Yield: 57.5%; white crystals; mp: 78–80ꢁC; IR:
3422, 3334, 3061(ACH3), 1896, 1679(C¼¼O), 1554, 1489(Ar),
1436, 1413, 1370, 1290, 1240, 1084, 955(NAN¼¼N), 869,
792(Ar-H), 683; 1H NMR: 7.503–7.528(m, 3H, J ¼ 7.5 Hz,
Ar-4,5,6), 7.325–7.354(s, 1H, J ¼ 8.7 Hz, Ar-2), 2.733(s, 3H,
CH3CO), 2.598(s, 3H, TRZ-CH3); MS: 235(Mþ,3), 207(1),
192(4), 178(1), 164(16), 130(3), 111(20), 75(33), 65(1),
43(100); Anal. Calcd. for C11H10ClN3O: C, 56.06; H, 4.28; N,
17.83; Found: C, 56.53; H, 4.33; N, 17.67 CA 1017399-61-9.
1-[1-(2-Chlorophenyl)-5-methyl-1H-1,2,3-triazol-4-yl]etha-
none (1f). Yield: 58.5%; buff crystals; mp: 92–94ꢁC; IR:
3441, 3344, 3069(ACH3), 1936, 1681(C¼¼O), 1552, 1489(Ar),
1420, 1365, 1282, 1216, 1080, 951(NAN¼¼N), 764(Ar-H),
654; 1H NMR: 7.374–7.606(m, 4H, Ar-3,4,5,6), 2.753(s, 3H,
CH3CO), 2.428(s, 3H, TRZ-CH3); MS: 235(Mþ,9), 207(2),
192(15), 178(2), 164(35), 130(5), 111(32), 75(49), 65(1),
43(100); Anal. Calcd. for C11H10ClN3O: C, 56.06; H, 4.28; N,
17.83; Found: C, 56.47; H, 4.39; N, 17.57 CA 1017471-30-5.
1-[1-(4-Bromophenyl)-5-methyl-1H-1,2,3-triazol-4-yl]etha-
none (1g). Yield: 64.2%; yellow crystals; mp: 108–110ꢁC (Lit
120ꢁC); 1H NMR: 7,720–7.751(d, 2H, J ¼ 9.3 Hz, Ar-2,6),
Table 2
Hydrogen-bond geometry (A, ꢁ).
˚
DAHꢂꢂꢂA
DAH
HꢂꢂꢂA
DꢂꢂꢂA
DAHꢂꢂꢂA
N50AH50AꢂꢂꢂO1a
0.86
0.86
0.86
0.86
2.25
2.30
2.42
2.22
3.023 (5)
3.119 (5)
3.200 (4)
3.039 (5)
150
159
151
160
N50AH50BꢂꢂꢂN6b
a
N5AH5AꢂꢂꢂO10
7.364–7.396(d, 2H,
J
¼
9.6 Hz, Ar-3,5), 2.739(s, 3H,
b
N5AH5BꢂꢂꢂN60
CH3CO), 2.601(s, 3H, TRZ-CH3); MS: 279(Mþ,3). Found: C,
47.46; H, 3.24; N, 15.31 CA 33722-11-1 [18].
1-[5-Menthyl-1-(naphthalene-2-yl)-1H-1,2,3-triazol-4-yl]
ethanone (1h). Yield: 73.8%; buff crystals; mp: 146–148ꢁC;
Symmetry codes:
a
ꢀx þ 1, ꢀy þ 1, ꢀz.
b
ꢀx, ꢀy, ꢀz.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2010
Tandem Michael Addition/Imino-Nitrile Cyclization Synthesis of 2-Amino-6-
(1-aryl-5-methyl-1H-1,2,3-triazol-4yl)-4-phenylpyridine-3-carbonitrile
393
CH3O), 2.694(s, 3H, CH3CO), 2.501(s, 3H, TRZ-CH3); MS:
231(Mþ, 13) CA 1017399-41-5 [18].
(E)-1-[1-(3-Chlorophenyl)-5-methyl-1H-1,2,3-triazol-4-yl]-
3-phenylprop-2-en-1-one (2e). Yield: 91.1%; white crystals;
mp: 128–130ꢁC; IR: 1663(C¼¼O), 1612(C¼¼C), 1555, 1489,
1447, 1404, 1306, 1281, 1079, 987(NAN¼¼N), 839(Ar-H),
General procedure for the preparation of (E)-1-(1-aryl-5-
methyl-1H-1,2,3-triazol-4-yl)-3-phenylprop-2-en-1-one
derivatives (2a–j) [19]. A mixture of the aromatic aldehyde
(12 mmol) and compound 1a–j (10mmol) dissolved in ethanol
(70 mL) was added slowly to an aqueous solution of potassium
hydroxide (12.8 mmol) in water (10 mL). The reaction mixture
was stirred in crushed-ice bath for 2 h, stirred at 20–25ꢁC for
4 h. The mixture was filtrated and the solid was washed with
cold water and cold alcohol. The product was crystallized
from ethanol to give 2a–j. All products were new compounds.
(E)-1-(5-Methyl-1-p-tolyl-1H-1,2,3-triazol-4-yl)-3-phenylprop-
2-en-1-one (2a). Yield: 92.5%; white crystals; mp: 178–180ꢁC;
IR:1664(C¼¼O), 1611(C¼¼C), 1034, 1074, 1110, 997,
680; 1H NMR: 8.078–8.131 (d, 1H,
J
¼
15.9 Hz,
CH¼¼CACO), 7.910–7.963 (d, 1H, J ¼ 15.9 Hz, C¼¼CHACO),
7.725–7.757 (m, 2H, Ph-2,6), 7.538–7.566 (m, 3H, Ar-4,5,6),
7.414–7.446 (m, 4H, Ar-2 and Ph-3,4,5), 2.716(s, 3H, TRZ-
CH3); MS: 323(Mþ, 9), 294(3), 267(18), 214(34), 152(100),
131(57), 111(83), 103(67), 77(55), 51(29), 39(14); Anal.
Calcd. for C18H14ClN3O: C, 66.77; H, 4.36; N, 12.98; Found:
C, 66.29; H, 4.39; N, 12.76.
(E)-1-[1-(2-Chlorophenyl)-5-methyl-1H-1,2,3-triazol-4-yl]-
3-phenylprop-2-en-1-one (2f). Yield: 91.2%; white crystals;
mp: 116–118ꢁC; IR: 1669(C¼¼O), 1608(C¼¼C), 1553, 1493,
1447, 1393, 1360, 1278, 1200, 1070, 1033, 988(NAN¼¼N),
1
979(NAN¼¼N), 899, 855, 838(Ar-H), 815, 789, 684(Ar-H); H
1
NMR: 8.080–8.132 (d, 1H, J ¼ 15.6 Hz, CH¼¼CACO), 7.809–
7.862(d, 1H, J ¼ 15.6 Hz, C¼¼CHACO), 7.721–7.434(m, 2H,
Ph-3,5), 7.417–7.434(m, 3H, Ph-2,4,6), 7.376–7.405(d, 2H, J
¼ 8.7 Hz, Ar-2,6), 7.339–7.368(d, 2H, J ¼ 8.7 Hz, Ar-3,5),
2.666(s, 3H, TRZ-CH3), 2.479(s, 3H, CH3); MS: 303(Mþ, 5),
274(3), 260(3), 247(31), 194(36), 144(13), 132(98), 115(34),
103(65), 91(100), 77(63.3), 65(78.6), 51(35.3), 39(31.5); Anal.
Calcd. for C19H17N3O: C, 75.23; H, 5.65; N, 13.85; Found: C,
75.53; H, 5.43; N, 13.76.
770; H NMR: 8.103–8.156(d, 1H, J ¼ 15.9 Hz, CH¼¼C-CO),
7.925–7.978 (d, 1H, J ¼ 15.9 Hz, C¼¼CHACO), 7.735–7.751
(m, 2H, Ph-2,6), 7.429–7.640 (m, 7H, Ar-3,4,5,6 and Ph-
3,4,5), 2.554(s, 3H, TRZ-CH3); MS: 323(Mþ,1), 294(3),
267(20), 214(33), 152(100), 131(34), 111(73), 103(65), 77(71),
51(49), 39(24); Anal. Calcd. for C18H14ClN3O: C, 66.77; H,
4.36; N, 12.98; Found: C, 66.47; H, 4.56; N, 12.81.
(E)-1-[1-(4-Bromophenyl)-5-methyl-1H-1,2,3-triazol-4-yl]-
3-phenylprop-2-en-1-one (2g). Yield: 185–187%; white crys-
tals; mp: 185–187ꢁC; IR: 1662(C¼¼O), 1599(C¼¼C), 1551, 1494,
1443, 1402, 1361, 1275, 1196, 1066, 1031, 987(NAN¼¼N),
838(Ar-H), 687; 1H NMR: 8.057–8.110(d, 1H, J ¼ 15.9 Hz,
CH¼¼CACO) 7.890–7.943 (d, 1H, J ¼ 15.9 Hz, C¼¼CHACO),
7.708–7.735 (m, 4H, Ar-2,3,5,6), 7.388–7.415 (m, 5H, Ph-
2,3,4,5,6), 2.667(s, 3H, TRZ-CH3); MS: 367(Mþ,3), 311(16),
260(24), 217(8), 196(68), 155(56), 131(94), 115(43), 103(100),
77(89), 51(50), 39(25); Anal. Calcd. for C18H14BrN3O: C,
58.71; H, 3.83; N, 11.41; Found: C, 58.47; H, 3.77; N, 11.71.
(E)-1-[5-Methyl-1-(naphthalene-2-yl)-1H-1,2,3-triazol-4-yl]-
3-phenylprop-2-en-1-one (2h). Yield: 97.7%; white crystals;
mp: 178–180ꢁC; IR: 1664(C¼¼O), 1600(C¼¼C), 1556, 1488,
1446, 1421, 1302, 1269, 1206, 1074, 1033, 989(NAN¼¼N),
826(Ar-H), 689; 1H NMR: 8.120–8.173 (d, 1H, J ¼ 15.9 Hz,
CH¼¼CACO), 8.023–8.076 d, 1H, J ¼ 15.9 Hz, C¼¼CHACO),
7.919–7.972 (m, 4H, Ar-1,4,5,8), 7.718–7.747 (m, 2H, Ph-2,6),
7.544–7.632 (m, 3H, Ar-3,6,7), 7.409–7.438 (m, 3H, Ph-3,4,5),
2.732(s, 3H, TRZ-CH3); MS: 339(Mþ,1), 310(3), 283(23),
268(3), 251(7), 230(22), 180(27), 168(42), 127(100), 115(20),
103(51), 77(61), 51(24), 39(11); Anal. Calcd. for C22H17N3O:
C, 77.86; H, 5.05; N, 12.38; Found: C, 77.65; H, 5.27; N, 12.46.
(E)-1-[1-(3-Bromophenyl)-5-methyl-1H-1,2,3-triazol-4-yl]-
3-phenylprop-2-en-1-one (2i). Yield: 89.8%; white crystals;
mp: 168–170ꢁC; IR: 1662(C¼¼O), 1599(C¼¼C), 1551, 1494,
1443, 1402, 1361, 1275, 1196, 1066, 1031, 987(NAN¼¼N),
838(Ar-H), 687; 1H NMR: 8.078–8.131 (d, 1H, J ¼ 15.9 Hz,
CH¼¼CACO), 7.910–7.963 (d, 1H, J ¼ 15.9 Hz, C¼¼CHACO),
7.725–7.757 (m, 2H, Ph-2,6), 7.538–7.566 (m, 3H, Ar-4,5,6),
7.414–7.446 (m, 4H, Ar-2 and Ph-3,4,5), 2.667(s, 3H, TRZ-
CH3); MS: 367(Mþ,2), 311(16), 260(24), 217(8), 196(68),
155(56), 131(94), 115(43), 103(100), 77(89), 51(50), 39(25);
Anal. Calcd. for C18H14BrN3O: C, 58.71; H, 3.83; N, 11.41;
Found: C, 58.57; H, 3.67; N, 11.86.
(E)-1-(5-Methyl-1-phenyl-1H-1,2,3-triazol-4-yl)-3-phenyl-
prop-2-en-1-one (2b). Yield: 95.2%; white crystals; mp: 123–
125ꢁC; IR: 1664(C¼¼O), 1602(C¼¼C), 1554, 1499, 1420, 1276,
1
1113, 1035, 980 (NAN¼¼N), 765(Ar-H), 687; H NMR: 8.101–
8.154(d, 1H, J ¼ 15.9 Hz, CH¼¼CACO), 7.907–7.960(d, 1H, J
¼ 15.9 Hz, C¼¼CHACO), 7.726–7.757(m, 2H, Ph-2,6), 7.575–
7.610(m, 3H, Ar-3,4,5), 7.476–7.509(m, 2H, Ar-2,6), 7.421–
7.438(m, 3H, Ph-3,4,5), 2.691(s, 3H, TRZ-CH3); MS: 289(Mþ,
12), 260(4), 233(24), 180(24), 131(31), 118(59), 103(36),
77(100), 65(5), 51(44), 39(9); Anal. Calcd. for C18H15N3O: C,
74.72; H, 5.23; N, 14.52; Found: C, 74.89; H, 5.34; N, 14.15.
(E)-1-[1-(4-Chlorophenyl)-5-methyl-1H-1,2,3-triazol-4-yl]-
3-phenylprop-2-en-1-one (2c). Yield: 91.1%; white crystals;
mp: 171–173ꢁC; IR: 1665(C¼¼O), 1601(C¼¼C), 1552, 1498,
1427, 1276, 1092, 1032, 990(NAN¼¼N), 844, 776(Ar-H), 733,
690; 1H NMR: 8.074–8.126 (d, 1H,
J
¼
15.6 Hz,
CH¼¼CACO), 7.904–7.956 (d, 1H, J ¼ 15.6 Hz, C¼¼CHACO),
7.718–7.749 (m, 2H, Ph-2,6), 7.565–7.595 (d, 2H, J ¼ 9.0 Hz,
Ar-2,6), 7.456–7.474 (m, 2H, Ar-3,5), 7.419–7.442 (m, 3H,
Ph-3,4,5), 2.687(s, 3H, TRZ-CH3); MS: 323(Mþ, 21), 294(3),
267(70), 214(47), 152(66), 131(100), 111(62), 103(59), 77(58),
51(28), 39(9); Anal. Calcd. for C18H14ClN3O: C, 66.77; H,
4.36; N, 12.98; Found: C, 66.34; H, 4.65; N, 12.79.
(E)-1-[1-(2,5-Dichlorophenyl)-5-methyl-1H-1,2,3-triazol-4-yl]-
3-phenylprop-2-en-1-one (2d). Yield: 92.9%; white crystals;
mp: 163–165ꢁC; IR: 1659(C¼¼O), 1600(C¼¼C), 1552, 1486,
1448, 1396, 1357, 1282, 1201, 1096, 1032, 984(NAN¼¼N),
815(Ar-H), 682; 1H NMR: 8.075–8.128 (d, 1H, J ¼ 15.9 Hz,
CH¼¼CACO), 7.921–7.974 (d, 1H, J ¼ 15.9 Hz, C¼¼CHACO),
7.718–7.749 (m, 2H, Ph-2,6), 7.595(s, 1H, Ar-6), 7.554–7.567
(m, 2H, Ph-3,5), 7.493–7.497 (m, 1H, Ph-4), 7.417–7.446 (m,
2H, Ar-3,4), 2.562(s, 3H, TRZ-CH3); MS: 357(Mþ, 6), 328(2),
301(11), 248(28), 186(100), 145(45), 131(58), 115(40),
103(82), 77(79), 51(36), 39(20); Anal. Calcd. for
C18H13Cl2N3O: C, 60.35; H, 3.66; N, 11.73; Found: C, 60.54;
H, 3.54; N, 11.63.
(E)-1-[1-(4-Methoxyphenyl)-5-methyl-1H-1,2,3-triazol-4-yl]-
3-phenylprop-2-en-1-one (2j). Yield: 92.2%; white crystals; mp:
153–155ꢁC; IR: 1666(C¼¼O), 1604(C¼¼C), 1549, 1511, 1445,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

394
H.-S. Dong, H.-C. Wang, Z.-L. Gao, R.-S. Li, and F.-H. Cui
Vol 47
1412, 1363, 1283, 1256, 1036, 987(NAN¼¼N), 837(Ar-H), 627;
1H NMR: 8.087–8.140 (d, 1H, J ¼ 15.9 Hz, CH¼¼CACO), 7.890–
7.947 (d, 1H, J ¼ 15.9 Hz, C¼¼CHACO), 7.696–7.741 (m, 2H,
Ph-2,6), 7.370–7.425 (m, 5H, Ar-2,6 and Ph-3,4,5), 7.050–7.091
(m, 2H, Ar-3,5), 2.638(s, 3H, TRZ-CH3); MS: 319(Mþ,1), 290(2),
263(25), 210(19), 188(8), 161(20), 148(58), 131(77), 115(21),
103(69), 77(100), 51(30), 39(18); Anal. Calcd. for C19H17N3O2:
C, 71.46; H, 5.37; N, 13.16; Found: C, 71.76; H, 5.54; N, 13.02.
General procedure for the preparation of 2-amino-6-(1-
aryl-5-methyl-1H-1,2,3-triazol-4yl)-4-phenylpyridine-3-car-
bonitrile derivatives (3a–j) [20]. Chalcone 2a–j (10 mmol),
malononitrile (10 mmol, 0.66 g, 1 equiv.), and ammonium ace-
tate (80 mmol, 0.62 g, 8 equiv.) were dissolved in EtOH (10 mL)
and refluxed for 15 h, whereupon no starting material was evident
by TLC. The reaction mixture was allowed to cool to RT and the
solvent was evaporated to leave a yellow solide, dried, and puri-
fied by column chromatography using a mixture of EtOAc /petro-
leum ether 60–90ꢁC 1:4 as eluent to give the corresponding 3a–j.
2-Amino-6-(5-methyl-1-p-tolyl-1H-1,2,3-triazol-4yl)-4-phe-
nylpyridine-3-carbonitrile (3a). Yield: 63.5%; yellow crys-
tals; mp: 168–170ꢁC; IR: 3487, 3368(NH2), 2922(ACH3),
2212(-CN), 1731, 1619, 1581, 1562, 1516, 1420, 1258(CAN),
2,3,4,5,6), 5.434(s, 2H, ANH2), 2.716(s, 3H, TRZ-CH3); MS:
387(Mþþ1). Anal. Calcd. for C21H15ClN6: C, 65.20; H, 3.91;
N, 21.72; Found: C, 65.55; H, 3.65; N, 21.59.
2-Amino-6-[1-(2-chlorophenyl)-5-methyl-1H-1,2,3-triazol-4yl]-
4-phenylpyridine-3-carbonitrile (3f). Yield: 65.0%; yellow crys-
tals; mp: 98–100ꢁC; IR: 3469, 3354(NH2), 2926(ACH3),
2211(ACN), 1710, 1681, 1589, 1544, 1497, 1420, 1262(C-N),
1
1078, 979(NAN¼¼N), 766(Ar-H), 701; H NMR: 7.630(s, 1H,
Py-), 7.489–7.560(m, 9H, Ar-3,4,5,6 and Ph-2,3,4,5,6),
5.420(s, 2H, ANH2), 2.595(s, 3H, TRZ-CH3); MS:
387(Mþþ1). Anal. Calcd. for C21H15ClN6: C, 65.20; H, 3.91;
N, 21.72; Found: C, 65.61; H, 3.55; N, 21.55.
2-Amino-6-[1-(4-bromophenyl)-5-methyl-1H-1,2,3-triazol-
4yl]-4-phenylpyridine-3-carbonitrile (3g). Yield: 54.7%; yel-
low crystals; mp: 215–217ꢁC; IR: 3494, 3370(NH2),
2923(ACH3), 2211(-CN), 1730, 1616, 1580, 1542, 1494, 1418,
1
1258(CAN), 1070, 977(NAN¼¼N), 837(Ar-H), 699; H NMR:
7.794(s, 1H, Py-), 7.673–7.751 (m, 4H, Ar-3,5 and Ph-2,6),
7.507–7.524 (m, 3H, Ph-3,4,5), 7.378–7.407 (m, 2H, Ar-2,6),
5.426(s, 2H, ANH2), 2.685(s, 3H, TRZ-CH3); MS:
431(Mþþ1). Anal. Calcd. for C21H15BrN6: C, 58.48; H, 3.51;
N, 19.49; Found: C, 58.84; H, 3.32; N, 19.28.
1
1111, 977(NAN¼¼N), 839(Ar-H), 702; H NMR: 7.795(s, 1H,
2-Amino-6-[5-methyl-1-(naphthalene-2-yl)-1H-1,2,3-triazol-
4yl]-4-phenylpyridine-3-carbonitrile (3h). Yield: 56.6%; yellow
crystals; mp: 104–106ꢁC; IR: 3464, 3374(NH2), 2923(ACH3),
2208(ACN), 1732, 1610, 1587, 1542, 1481, 1418, 1263(CAN),
1113, 976(NAN¼¼N), 859(Ar-H), 701; 1H NMR: 7.945–8.040 (m,
6H, Ar-1,4,5,8 and Ph-2,6), 7.685(s, 1H, Py-), 7.517–7.616 (m, 6H,
Ar-3,6,7 and Ph-3,4,5), 5.423(s, 2H, ANH2), 2.712(s, 3H, TRZ-
CH3). MS: 415(Mþþ1). Anal. Calcd. for C25H18N6: C, 74.61; H,
4.51; N, 20.88; Found: C, 74.86; H, 4.26; N, 20.88.
Py-), 7.682–7.698 (m, 2H, Ph-2,6), 7.513–7.528 (m, 3H, Ph-
3,4,5), 7.392–7.404 (m, 4H, Ar-2,3,5,6), 5.415 (s, 2H, ANH2),
2.712(s, 3H, TRZ-CH3), 2.443(s, 3H, Ar-CH3); MS:
367(Mþþ1). Anal. Calcd. for C22H18N6: C, 72.11; H, 4.95; N,
22.94; Found: C, 72.43; H, 4.83; N, 22.74.
2-Amino-6-(5-methyl-1-phenyl-1H-1,2,3-triazol-4yl)-4-phen-
ylpyridine-3-carbonitrile (3b). Yield: 60.0%; yellow crystals;
mp: 80–82ꢁC; IR: 3471, 3355(NH2), 2924(ACH3), 2210(-CN),
1709, 1614, 1589, 1558, 1501, 1419, 1264(CAN), 1114,
977(NAN¼¼N), 765(Ar-H), 696; 1H NMR: 7.827(s, 1H, Py-),
7.480–7.569(m, 10H, Ar-2,3,4,5,6 and Ph-2,3,4,5,6), 5.299(s,
2H, ANH2), 2.786(s, 3H, TRZ-CH3); MS: 353(Mþþ1). Anal.
Calcd. for C21H16N6: C, 71.58; H, 4.58; N, 23.85; Found: C,
71.79; H, 4.69; N, 23.53.
2-Amino-6-[1-(3-bromophenyl)-5-methyl-1H-1,2,3-triazol-
4yl]-4-phenylpyridine-3-carbonitrile (3i). Yield: 61.3%; yel-
low crystals; mp: 105–107ꢁC; IR: 3466, 3354(NH2),
2925(ACH3), 2212(-CN), 1710, 1618, 1590, 1561, 1494, 1422,
1
1264(CAN), 1119, 976(NAN¼¼N), 767(Ar-H), 701; H NMR:
7.825(s, 1H, Py-), 7.487–7.528 (m, 9H, Ar-2,4,5,6 and Ph-
2,3,4,5,6), 5.430(s, 2H, ANH2), 2.642(s, 3H, TRZ-CH3); MS:
431(Mþþ1). Anal. Calcd. for C21H15BrN6: C, 58.48; H, 3.51;
N, 19.49; Found: C, 58.74; H, 3.52; N, 19.38.
2-Amino-6-[1-(4-chlorophenyl)-5-methyl-1H-1,2,3-triazol-4yl]-
4-phenylpyridine-3-carbonitrile (3c). Yield: 59.7%; yellow
crystals; mp: 192–194ꢁC; IR: 3495, 3369(NH2), 2923(ACH3),
2212(-CN), 1730, 1617, 1581, 1560, 1498, 1420, 1259(C-N),
2-Amino-6-[1-(4-methoxyphenyl)-5-methyl-1H-1,2,3-triazol-
4yl]-4-phenylpyridine-3-carbonitrile (3j). Yield: 57.2%; yellow
crystals; mp: 181–183ꢁC; IR: 3449, 3354(NH2), 2928(ACH3),
2210(-CN), 1731, 1633, 1584, 1559, 1516, 1423, 1250(CAN),
1
1090, 977(NAN¼¼N), 839(Ar-H), 700; H NMR: 7.689(s, 1H,
Py-), 7.442–7.591 (m, 9H, Ar-2,3,5,6 and Ph-2,3,4,5,6),
5.420(s, 2H, ANH2), 2.726(s, 3H, TRZ-CH3); MS: 387
(Mþþ1). Anal. Calcd. for C21H15ClN6: C, 65.20; H, 3.91; N,
21.72; Found: C, 65.65; H, 3.75; N, 21.65.
1
1112, 979(NAN¼¼N), 839(Ar-H), 697; H NMR: 7.755(s, 1H,
Py-), 7.669–7.700 (m, 2H, Ph-2,6), 7.493–7.513 (m, 3H, Ar-2,6
and Ph-4), 7.370–7.384 (m, 2H, Ph-3,5), 7.057–7.085 (d, 2H, J
¼ 8.4 Hz, Ar-3,5), 5.412(s, 2H, ANH2), 2.565(s, 3H, TRZ-CH3).
MS: 383(Mþþ1). Anal. Calcd. for C22H18N6O: C, 69.10; H,
4.74; N, 21.98; Found: C, 69.45; H, 4.56; N, 21.87.
2-Amino-6-[1-(2,5-dichlorophenyl)-5-methyl-1H-1,2,3-tria-
zol-4yl]-4-phenylpyridine-3-carbonitrile (3d). Yield: 52.3%;
yellow crystals; mp: 94–96ꢁC; IR: 3464, 3353(NH2),
2926(ACH3), 2213(ACN), 1710, 1681, 1588, 1562, 1490,
1426, 1264(CAN), 1097, 979(NAN¼¼N), 770(Ar-H), 700; 1H
NMR: 7.663(s, 1H, Py-), 7.528–7.575 (m, 8H, Ar-3,4 and Ph-
2,3,4,5,6), 5.422(s, 2H, ANH2), 2.599(s, 3H, TRZ-CH3); MS:
421(Mþþ1). Anal. Calcd. for C21H14Cl2N6: C, 59.87; H, 3.35;
N, 19.35; Found: C, 59.54; H, 3.54; N, 19.19.
X-ray structure determination of 3j. Colourless Block,
C22H18N6O, Mr ¼ 852.95, Triclinic, space group P-1, a ¼ 10.398
˚
(7), b ¼ 14.925 (10), c ¼ 15.475 (10) A, a ¼ 115.975 (10), b ¼
3
ꢁ
˚
94.707 (12), c ¼ 91.049 (11) , V ¼ 2148 (3) A , Z ¼ 2, Dx ¼
1.319 Mg mꢀ3, F000 ¼ 896, l ¼ 0.09 mmꢀ1. Intensity data were
collected using a Siemens SMART diffractometer at 293(2) K,
graphite monochromator MoKa radiation (k ¼ 0.071073 nm),
using the x-2y scan technique to a maximum 1.5–26.5ꢁ. A total
of 11,896 reflections were collected with 8563 unique ones (R ¼
0.0732), of which 4049 reflections were observed with I > 2r (I).
The final int R and wR values were 0.0732 and 0.1717, s ¼ 0.988,
2-Amino-6-[1-(3-chlorophenyl)-5-methyl-1H-1,2,3-triazol-
4yl]-4-phenylpyridine-3-carbonitrile (3e). Yield: 58.7%; yel-
low crystals; mp: 164–166ꢁC; IR: 3436, 3354(NH2),
2923(ACH3), 2207(-CN), 1733, 1685, 1586, 1544, 1489, 1427,
1
1261(CAN), 1082, 982(NAN¼¼N), 782(Ar-H), 699; H NMR:
7.669(s, 1H, Py-), 7.509–7.591 (m, 9H, Ar-2,4,5,6 and Ph-
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2010
Tandem Michael Addition/Imino-Nitrile Cyclization Synthesis of 2-Amino-6-
(1-aryl-5-methyl-1H-1,2,3-triazol-4yl)-4-phenylpyridine-3-carbonitrile
395
Verkade, J. G. Org Lett 2003, 5, 815; (d) Viciu, M. S.; Kelly, R. A.;
Stevens, E. D.; Naud, F.; Studer, M.; Nolan, S. P. Org Lett 2003, 5,
1479; (e) Basu, B.; Mridha, N. K.; Bhuiyan, Md. M. H. Tetrahedron
Lett 2002, 43, 7967; (f) Brenner, E.; Schneider, R.; Fort, Y. Tetrahe-
dron 1999, 55, 12829.
(D/r) max ¼ 0.000. The maximum peak anꢀd3minimum peak in
˚
the final difference map is 0.20 and -0.32 e A
.
Acknowledgments. The authors wish to acknowledge the sup-
port by Lanzhou University SKLAOC.
[9] Thomas, S.; Roberts, S.; Pasumansky, L.; Gamsey, S.; Sin-
garam, B. Org Lett 2003, 5, 3867.
REFERENCES AND NOTES
[10] (a) Leer, M. T. In Organic Reactions; Adams, R. Ed.;
Wiley: New York, 1942; Vol. 1, p 91; (b) Tomcufcik, A. S.; Starker,
L. N. In the Chemistry of Heterocyclic Compouds, Pyridine and Its
Derivatives, Part III; Klingsberg, E., Ed.; Interscience: NY, 1962; p 1;
(c) Scriven, E. F. V. In Comprehensive Heterocyclic Chemistry, Part
IIA; Boulton, A. J., Mckilop, A., Eds.; Pergamon: Oxford, 1984; Vol.
2, p 165.
[1] Yates, F.; Courts, R. T.; Casy, A. F. In Pyridine and Its
Derivatives; Suppl IV, ed.; Abramovith, 5R. A., Ed.; Wiley: New
York, 1975; p 455.
[2] Yates, F. S. In Comprehensive Heterocyclic Chemistry;
Katritzki, A. R., Rees, C. W., Eds.; Pergamon: Oxford, 1984; Vol. 2, p
511.
[11] Zhang, Z. Y.; Liu, Y.; Yang, S. Y. Pharm Sim 1991, 26,
809 (Chem Abstr 1992, 116, 128807).
[3] (a) Forlano, E. A.; Deferrari, J. O.; Dukat, M. Med Chem
Res 1996, 465; (b) McDonlad, I. A.; Cosford, N.; Vemier, J. M. Annu
Rep Med Chem 1995, 30, 41.
[12] Abdou, N. A.; Soliman, I. N.; Sier Abou, A. H. Bull
Facpharm (Cair Univ) 1990, 28, 29 (Chem Abstr 1992, 117,
69793).
[4] (a) Schwid, S. R.; Petrie, M. D.; McDermontt, M. P.; Tier-
ney, D. S.; Mason, D. H.; Goodman, A. D. Neurology 1997, 48, 817;
(b) Sellin, L. C. Med Biol 1981, 59, 11; (c) Davidson, M.; Zemish-
lany, J. H.; Brunnemann, R. C.; Bunten, D. C. Am J Ther 2002, 9, 29;
(d) Manna, F.; Chimenti, F.; Bolasco, A.; Bizzarri, B.; Filippelli, W.;
Gagliardi, L. Eur J Med Chem 1999, 34, 245.
[13] Srivatava, A. J.; Swarup, S.; Saxena, V. K. J Indian Chem
Soc 1991, 68, 103.
[14] Cooper, K.; Steele, J. EP 329,357 (Chem Abstr 1990, 112,
76957).
[15] Raymond, E.; Raymond, S.; Alan, G. S. GB 2,175,301
(Chem Abstr 1987, 107, 134310).
[5] (a) Kempte, R.; Brenner, S.; Arndt, P. Orgamometallics
1996, 15, 1071; (b) Fuhrmann, H.; Brenner, S.; Arndt, P.; Kempe, R.
Inorg Chem 1996, 35, 6742.
ˇ
[16] Marchalin, S.; Baumlova, B.; Baran, P.; Oulyadi, H.; Daich,
´
A. J Org Chem 2006, 71, 9114.
[6] (a) Henke, B. R.; Drewry, D. H.; Jones, S. A.; Weaver, S.
L.; Wiethe, R. W. Bioorg Med Chem Lett 2001, 11, 1939; (b)
Hashimoto, S.; Otani, S.; Okamoto, T.; Matsumoto, K. Heterocycles
1988, 27, 319; (c) Kotsuki, H.; Sakai, H.; Shinohara, T. Synlett 2000,
116.
[17] Dong, H.-S.; Cao, Z.-P. Indian J Heterocycl Chem 2008,
17, 295.
[18] Kamalraj, V. R.; Senthil, S.; Kannan, P. J Mol Struct 2008,
892, 210.
[19] Dong, H.-S.; Wang, D.-D.; Jin, C.-Q. J Chin Chem Soc
(Taipei) 2005, 52, 1011.
[7] Perron-Sierra, F.; Dizier, S. D.; Bertrand, M.; Genton, A.;
Tucker, G. C.; Casasra, P. Bioorg Med Chem Lett 2002, 12, 3291.
[8] (a) Wagaw, S.; Buchwald, S. L. J Org Chem 1996, 61,
7240; (b) Stauffer, S. R.; Lee, S.; Stambuli, J. P.; Hauck, S. I.; Ver-
kade, J. G. Org Lett 2000, 2, 1423; (c) Urgaonkar, S.; Nagarajan, M.;
[20] Chang, L. C. W.; von Frijtag Drabbe Kunzel, J. K.;
Mulder-Krieger, T.; Westerhout, J.; Brussee, J.; IJzerman, A. P. J Med
Chem 2007, 50, 828.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet