Copper(I) iodide catalyzed synthesis of 1,4-disubstituted 1,2,3-triazoles from anti-3-aryl-2,3-dibromopropanoic acids and organic azides

Article abstract of DOI:10.1055/s-0030-1261030

A series of 1,4-disubstituted 1,2,3-triazoles were synthesized in a one-pot process from anti-3-aryl-2,3-dibromopropanoic acids and organic azides in dimethyl sulfoxide with inexpensive copper (I) iodide as the catalyst. Georg Thieme Verlag Stuttgart - Ne

Full text of DOI:10.1055/s-0030-1261030

PAPER
2907
Copper(I) Iodide Catalyzed Synthesis of 1,4-Disubstituted 1,2,3-Triazoles
from anti-3-Aryl-2,3-dibromopropanoic Acids and Organic Azides
1
, 4-Disubstituted 1
u
, 2,3-Triazoles zhi Cheng,a Yiwen Yang,a Chunxiang Kuang,*a Qing Yang*b
a
Department of Chemistry, Tongji University, Siping Road 1239, Shanghai 200092, P. R. of China
Fax +86(21)65983191; E-mail: kuangcx@tongji.edu.cn
b
Department of Biochemistry, School of Life Sciences, Fudan University, Handan Road 220, Shanghai 200433, P. R. of China
E-mail: yangqing68@fudan.edu.cn
Received 30 May 2011; revised 4 July 2011
series of substituted anti-3-aryl-2,3-dibromopropanoic
acids and organic azides. In the current study, we exam-
ined the synthesis of 1,4-disubstituted 1,2,3-triazoles from
easily available anti-3-aryl-2,3-dibromopropanoic acids
with copper(I) iodide as the catalyst (Scheme 1). In this
reaction, the anti-3-aryl-2,3-dibromopropanoic acids
served as precursors of terminal alkynes and underwent
direct reaction with organic azides in a one-pot process.
Abstract: A series of 1,4-disubstituted 1,2,3-triazoles were synthe-
sized in a one-pot process from anti-3-aryl-2,3-dibromopropanoic
acids and organic azides in dimethyl sulfoxide with inexpensive
copper (I) iodide as the catalyst.
Key words: cyclizations, heterocycles, azides, triazoles
Click chemistry was developed at the beginning of the
21st century from the Huisgen 1,3-dipolar cycloaddition
of azides to alkynes.1 Since then, the synthesis of 1,2,3-tri-
azoles has become important in medical,2 materials,3 and
biological4 research. Further interest in this reaction stems
from the interesting biological activities of 1,2,3-triazoles,
including their antibacterial,5 herbicidal, fungicidal,6 anti-
allergic,7 and anti-HIV8 properties. Recently, the use of
1,2,3-triazoles as catalysts and ligands in transition-metal
catalysis systems has also been reported.9 The rapidly in-
creasing number of requirements for the synthesis of these
heterocycles has led to a need to develop effective meth-
ods for the preparation of diverse 1,2,3-triazole deriva-
tives.
Br
N
N
CuI, Na ascorbate
R2
CO2H
N3 R2
N
+
R1
base, DMSO
R1
Br
R1, R2 = alkyl, aryl
Scheme 1 One-pot synthesis of 1,4-disubstituted 1,2,3-triazoles
To determine the optimal reaction conditions, we used
anti-2,3-dibromo-3-(4-tolyl)propanoic acid (1a) and 4-
tolyl azide (2a) as model substrates. We initially chose the
inorganic compounds potassium carbonate and cesium
carbonate as bases, and dimethyl sulfoxide and N,N-di-
methylformamide as solvents. When the reaction was per-
formed at 110 °C for twelve hours, the products were
isolated in moderate yields (Table 1, entries 1–3). We also
examined several organic bases. No product was obtained
when triethylamine was used (entry 4) but, interestingly,
an excellent yield of 85% was obtained when 1,8-diaza-
bicyclo[5.4.0]undec-7-ene (DBU) was used at 80 °C for
three hours (entry 5). When the solvent used was changed
to N,N-dimethylformamide instead of dimethyl sulfoxide,
the yield fell markedly to 70% (entry 6). At room temper-
ature, a surprisingly moderate yield of product 3a (70%)
was obtained (entry 7).The reaction proceeded most effi-
ciently and was completed within three hours when it was
promoted by copper(I) iodide (20 mol%) and sodium
ascorbate (40 mol%) and when DBU (3 equivalents) was
used as the base, and dimethyl sulfoxide was used as the
solvent at 80 °C (entry 5).
Although there are numerous methods for the preparation
of 1,4-disubstituted 1,2,3-triazoles,10 the starting materi-
als are mainly terminal alkynes that need to be prepared
and isolated separately.11 Hence, a method that eliminates
the need to isolate the terminal alkynes is desirable.12 The
generation of terminal alkynes in situ from suitable pre-
cursors, followed by the reaction with azides in a one-pot
process to form the corresponding 1,2,3-triazoles would
avoid the difficulties associated with the volatile nature of
terminal alkynes.
Our group recently reported13 an interesting one-pot syn-
thesis of 4-aryl-1H-1,2,3-triazoles from easily available
anti-3-aryl-2,3-dibromopropanoic acids and sodium azide
by using a catalyst system consisting of tris(benzylidene-
acetone)dipalladium and (9,9-dimethyl-9H-xanthene-4,5-
diyl)bis(diphenylphosphine) (Xantphos).13 Later, the re-
action conditions were simplified by using inexpensive
copper(I) iodide as the catalyst, and the reaction times
were reduced to four hours.14 Inspired by these results, we
attempted to expand the scope of the reaction by using a
Having identified the optimal conditions, we examined
the substrate scope of the copper(I) catalyzed-catalyzed
synthesis of 1,4-disubstituted-1,2,3-triazoles (Table 2).
The necessary anti-3-aryl-2,3-dibromopropanoic acids
were easily prepared by bromination of the corresponding
trans-a,b-unsaturated carboxylic acids,15 and the organic
azides were obtained from the corresponding organic
amine or organic halide.16 The results summarized in
Table 2 show that the method can be used for the synthe-
SYNTHESIS 2011, No. 18, pp 2907–2912
x
x.
x
x
.
2
0
1
1
Advanced online publication: 05.08.2011
DOI: 10.1055/s-0030-1261030; Art ID: H55911SS
© Georg Thieme Verlag Stuttgart · New York

2908
X. Cheng et al.
PAPER
Table 1 Screening for Optimal Reaction Conditions
N
N
Br
N
CuI, Na ascorbate
CO2H
+
N3
base, solvent, N2
Br
1a
2a
3a
Entrya
Base
Solvent
DMSO
DMSO
DMF
Temp (°C)
Time (h)
Yield (%)b
1
2
3
4
5
6
7
K2CO3
Cs2CO3
Cs2CO3
Et3N
110
110
110
80
12
12
12
3
54
60
56
0
DMSO
DMSO
DMF
DBU
80
3
85
70
70
DBU
80
3
DBU
DMSO
25
3
a 1a (0.5 mmol), 2a (1.5 equiv), base (3 equiv), CuI (20 mol%), Na ascorbate (40 mol%), solvent (4 mL), under N2.
b Isolated yield based on 1a.
sis of 1,4-disubstituted 1,2,3-triazoles carrying either an bromide ions, to generate the intermediate (Z)-b-arylvinyl
electron-donating substituent (such as methyl, isopropyl, bromide. A subsequent E2 trans-elimination gives the ter-
tert-butyl, or methoxy; entries 1–3 and 9) or an electron- minal alkyne. A copper-catalyzed [3+2] cycloaddition of
withdrawing group (entries 4–8) as the R1 or R2 group. the aralkyne with azide 2 then gives the 1,4-disubstituted
Notably, pyridyl- and alkyl-substituted products were also 1,2,3-triazole 3.
smoothly obtained in moderate-to-excellent yields (en-
tries 10–12). Moreover, the yield was not significantly de-
creased by steric congestion. Substrates bearing an
electron-donating or an electron-withdrawing group at the
para-, meta-, or ortho- position all gave the corresponding
1,4-disubstituted 1,2,3-triazoles in good-to-excellent
yields (entries 1–9).
Table 2 Copper(I) Iodide Catalyzed Synthesis of 1,4-Disubstituted
1,2,3-Triazoles from anti-3-Aryl-2,3-dibromopropanoic Acids and
Organic Azides
Br
N
N
CuI, Na ascorbate, DBU
DMSO, N2, 80 °C
N3 R2
CO2H
N
R2
R1
+
R1
Br
1
2
3
To study the mechanism of the reaction, we carried out a
control experiment with 1a in the absence of the azide
partner and we obtained the corresponding terminal
alkyne in 93% yield. This suggests that an aralkyne is gen-
erated in situ in the one-pot reaction. The proposed reac-
tion pathway is shown in Scheme 2. The reaction
probably proceeds by the initial trans-elimination reac-
tion of the anti-3-aryl-2,3-dibromopropanoic acid 1, in-
volving a simultaneous loss of carbon dioxide and
Entrya
Product
Yield (%)b
N
N
N
1
85
3a
N
N
N
N
N
2
85
DBU
Br
H
R1
DBU
DBU
CO2H
3b
3c
R1
H
R1
N
DMSO
Br
Br
Br
1
3
4
86
73
E2 trans-elimination
R2 N3
CuI, Na ascorbate
N
N
N
R2
R1
N
N
N
R1
3
Cl
Cl
Scheme 2 Mechanism of the one-pot reaction
3d
Synthesis 2011, No. 18, 2907–2912 © Thieme Stuttgart · New York

PAPER
1,4-Disubstituted 1,2,3-Triazoles
2909
Table 2 Copper(I) Iodide Catalyzed Synthesis of 1,4-Disubstituted
1,2,3-Triazoles from anti-3-Aryl-2,3-dibromopropanoic Acids and
Organic Azides (continued)
tuted 1,2,3-triazoles 3 from anti-3-aryl-2,3-dibromo-
propanoic acids 1 and organic azides 2. The catalyst is in-
expensive copper(I) iodide and moderate-to-excellent
yields are obtained. The process has considerable advan-
tages in terms of its use of easily available substrates, its
product diversity, and its mild reaction conditions. The
simplicity of the reaction procedure and the moderate-to-
excellent yields are also advantageous. The method pro-
vides access to various 1,4-disubstituted 1,2,3-triazoles,
important in medical, materials, and biological research.
Br
N
N
CuI, Na ascorbate, DBU
DMSO, N2, 80 °C
N3 R2
CO2H
N
R2
R1
+
R1
Br
1
2
3
Entrya
Product
Yield (%)b
N
N
N
1H and 13C NMR spectra were recorded on a Bruker AM-400 spec-
trometer in CDCl3 with TMS as the internal standard. Melting
points were recorded on a WRS-2A micro melting-point apparatus
and are uncorrected. A Nicolet AVATAR 360 FT-IR spectropho-
tometer was used to record the IR spectra. Commercially sourced
reagents were used without additional purification. All reactions
were conducted under N2 and were monitored by TLC on Huang-
haiGF 254 silica gel coated plates. Column chromatography was
carried out by using 300–400 mesh silica gel at medium pressure.
The anti-3-aryl-2,3-dibromopropanic acids 1 and organic azides 2
were synthesized by the procedures reported in the literature.15,16
(CAUTION! Aryl azides are poisonous and potentially explosive if
subjected to heat, light, or pressure. Any azides synthesized should
be stored in darkness at below 0 °C.)
5
76
Cl
3e
N
N
N
6
80
Br
3f
N
N
N
7
8
75
71
Br
1,4-Disubstituted 1,2,3-Triazoles (3a–3l); General Procedure
A soln of acid 1 (0.5 mmol), azide 2 (0.75 mmol), DBU (228 mg,
1.5 mmol), CuI (19 mg, 0.1 mmol), and Na ascorbate (39.6 mg, 0.2
mmol) in DMSO (4 mL) was placed in a sealed tube and stirred un-
der N2 for 5 min, then heated to 80 °C for 3 h. The mixture then was
allowed to cool to r.t. and the reaction was quenched with H2O (25
mL). The mixture was extracted with EtOAc (3 × 30 mL) and the
combined organic layers were washed with brine (3 × 10 mL). The
extracts were dried (Na2SO4) and concentrated under reduced pres-
sure to afford a crude product that was purified by column chroma-
tography (silica gel; EtOAc–PE).
3g
N
N
N
Br
Br
3h
N
N
N
OMe
9
70
1,4-Bis(4-tolyl)-1H-1,2,3-triazole (3a)17
Yield: 105 mg (85%); yellow solid; mp 197.5–198.5 °C (Lit.17 196–
199 °C).
3i
N
N
IR (KBr): 3108, 3023, 2917, 2858, 1520, 1497, 1226, 1040, 815
cm–1.
1H NMR (400 MHz, CDCl3): d = 8.12 (s, 1 H), 7.80 (d, J = 8.1 Hz,
2 H), 7.66 (d, J = 8.4 Hz, 2 H), 7.34 (d, J = 8.1 Hz, 2 H), 7.27 (d,
J = 8.4 Hz, 2 H), 2.44 (s, 3 H), 2.40 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 148.3, 138.8, 138.3, 134.9, 130.3,
129.6, 127.5, 125.8, 120.4, 117.3, 21.3, 21.1.
N
10
11
12
72
90
62
N
3j
N
N
N
ESI-MS: m/z (%) = 249 [M+].
3k
3l
4-(4-Isopropylphenyl)-1-(4-tolyl)-1H-1,2,3-triazole (3b)
Yield: 118 mg (85%); yellow solid; mp 174.6–175.6 °C.
N
N
N
IR (KBr): 3124, 3108, 2962, 2924, 2871, 1517, 1493,1226, 1040,
841, 818 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.12 (s, 1 H), 7.83 (d, J = 8.2 Hz,
2 H), 7.67 (d, J = 8.4Hz, 2 H), 7.35–7.31 (m, 4 H), 2.99–2.92 (m, 1
H), 2.44 (s, 3 H), 1.29 (d, J = 6.9 Hz, 6 H).
13C NMR (125 MHz, CDCl3): d = 149.3, 148.3, 138.9, 134.9, 130.3,
127.8, 127.0, 125.9, 120.4, 117.3, 34.0, 23.9, 21.1.
a 1 (0.5 mmol), 2 (0.75 mmol), DBU (1.5 mmol), CuI (0.1 mmol), Na
ascorbate (0.2 mmol), DMSO (4 mL), under N2, 80 °C, 3 h.
b Isolated yield based on substrate 1.
ESI-MS: m/z (%) = 277 [M+].
HRMS (ESI): m/z [M + H]+ calcd for C18H20N3: 278.1657; found:
278.1658.
In conclusion, we have demonstrated a simple and effi-
cient one-pot method for the preparation of 1,4-disubsti-
Synthesis 2011, No. 18, 2907–2912 © Thieme Stuttgart · New York

2910
X. Cheng et al.
PAPER
4-(4-tert-Butylphenyl)-1-(4-tolyl)-1H-1,2,3-triazole (3c)
Yield: 125 mg (86%); yellow solid; mp 187.7–188.4 °C.
13C NMR (125 MHz, CDCl3): d = 145.8, 139.1, 134.7, 133.6, 131.0,
130.7, 130.3, 129.6, 127.8, 121.2, 121.1, 120.6, 21.2.
IR (KBr): 3127, 2965, 2865, 1517, 1495, 1226, 1037, 840, 817
cm–1.
1H NMR (400 MHz, CDCl3): d = 8.12 (s, 1 H), 7.84 (d, J = 8.4 Hz,
2 H), 7.67 (d, J = 8.4 Hz, 2 H), 7.49 (d, J = 8.4 Hz, 2 H), 7.34 (d,
J = 8.2 Hz, 2 H), 2.44 (s, 3 H), 1.36 (s, 9 H).
ESI-MS: m/z (%) = 315 [M + 2]+, 313 [M+].
HRMS (ESI): m/z [M + H]+ calcd for C15H1379BrN3: 314.0294;
found: 314.0292.
1,4-Bis(4-bromophenyl)-1H-1,2,3-triazole (3h)
Yield: 135 mg (71%); yellow solid; mp 164.7–164.5 °C.
13C NMR (125 MHz, CDCl3): d = 151.5, 148.3, 138.8, 134.9, 130.3,
127.5, 125.8, 125.6, 120.4, 117.3, 34.7, 31.3, 21.1.
IR (KBr): 3121, 2922, 2851, 1592, 1471, 1224, 1074, 1040, 1012,
815 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.20 (s, 1 H), 7.98 (s, 1 H), 7.80–
7.75 (m, 3 H), 7.61–7.59 (m, 3 H), 7.45–7.41 (m, 1 H).
13C NMR (125 MHz, CDCl3): d = 137.9, 132.2, 131.9, 131.2, 128.9,
127.4, 123.6, 123.4, 122.6, 119.0, 117.6.
ESI-MS: m/z (%) = 291 [M+].
HRMS (ESI): m/z [M + H]+ calcd for C19H22N3: 292.1814; found:
292.1813.
4-(2,4-Dichlorophenyl)-1-(4-tolyl)-1H-1,2,3-triazole (3d)
Yield: 110 mg (73%); white solid; mp 140.7–141.7 °C.
ESI-MS: m/z (%) = 379 [M + 2]+, 377 [M+].
IR (KBr): 3182, 3093, 2921, 2854, 1548, 1518, 1467, 1375, 1221,
1103, 1043, 819, 803 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.57 (s, 1 H), 8.29 (d, J = 8.5 Hz,
1 H), 7.68 (d, J = 8.3 Hz, 2 H), 7.51 (d, J = 2.0 Hz, 1 H), 7.40 (dd,
J = 8.5, 2.0 Hz, 1 H), 7.35 (d, J = 8.3 Hz, 2 H), 2.45 (s, 3 H).
HRMS (ESI): m/z [M + H]+ calcd for C14H1079Br2N3: 377.9242;
found: 377.9241.
4-(4-tert-Butylphenyl)-1-(4-methoxyphenyl)-1H-1,2,3-triazole
(3i)
Yield: 107 mg (70%); yellow solid; mp 183.6–184.5 °C.
13C NMR (125 MHz, CDCl3): d = 143.6, 139.2, 134.6, 134.4, 131.7,
130.7, 130.3, 130.0, 127.7, 121.2, 120.6, 21.2.
IR (KBr): 3140, 2959, 2863, 1523, 1493, 1452, 1260, 1233, 1047,
1034, 836 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.08 (s, 1 H), 7.83 (d, J = 7.5 Hz,
2 H), 7.69 (d, J = 7.8 Hz, 2 H), 7.49 (d, J = 7.6 Hz, 2 H), 7.04 (d,
J = 7.9 Hz, 2 H), 3.88 (s, 3 H), 1.36 (s, 9 H).
ESI-MS: m/z (%) = 303 [M+].
HRMS (ESI): m/z [M + H]+ calcd for C15H1235Cl2N3: 304.0410;
found: 304.0409.
4-(2-Chlorophenyl)-1-(4-tolyl)-1H-1,2,3-triazole (3e)
Yield: 102 mg (76%); white solid; mp 104.5–105.2 °C.
13C NMR (125 MHz, CDCl3): d = 159.8, 151.5, 148.2, 130.6, 127.6,
125.8, 125.6, 122.2, 117.5, 114.8, 55.7, 34.7, 31.3.
IR (KBr): 3187, 2924, 1548, 1518, 1470, 1403, 1218, 1120, 1041,
811, 756 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.59 (s, 1 H), 8.32 (d, J = 7.4 Hz,
1 H), 7.69 (d, J = 7.2 Hz, 2 H), 7.49 (d, J = 7.7 Hz, 1 H), 7.43–7.29
(m, 4 H), 2.45 (s, 3 H).
ESI-MS: m/z (%) = 307 [M+].
HRMS (ESI): m/z [M + H]+ calcd for C19H22N3O: 308.1763; found:
308.1764.
3-[1-(4-Tolyl)-1H-1,2,3-triazol-4-yl]pyridine (3j)
Yield: 85 mg (72%); white solid; mp 175.9–176.2 °C.
13C NMR (125 MHz, CDCl3): d = 144.5, 139.0, 134.8, 131.3, 130.3,
130.0, 129.2, 129.0, 127.2, 121.3, 120.6, 21.1.
IR (KBr): 3140, 3051, 2959, 1523, 1493, 1260, 1233, 1047, 1034,
836 cm–1.
1H NMR (400 MHz, CDCl3): d = 9.08 (s, 1 H), 8.62 (s, 1 H), 8.31–
8.25 (m, 2 H), 7.68 (d, J = 7.5 Hz, 2 H), 7.42–7.35 (m, 3 H), 2.45(s,
3 H).
ESI-MS: m/z (%) = 269 [M+].
HRMS (ESI): m/z [M + H]+ calcd for C15H1335ClN3: 270.0799;
found: 270.0798.
4-(3-Bromophenyl)-1-(4-tolyl)-1H-1,2,3-triazole (3f)
Yield: 125 mg (80%); yellow solid; mp 153.9–154.8 °C.
13C NMR (125 MHz, CDCl3): d = 149.9, 147.1, 145.2, 139.3, 134.6,
133.2, 130.4, 126.6, 123.9, 120.5, 118.0, 21.1.
IR (KBr): 3122, 2917, 1602, 1565, 1518, 1472, 1399, 1225, 1072,
1043, 816, 790, 685 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.17 (s, 1 H), 8.06 (s, 1 H), 7.85
(d, J = 7.7 Hz, 1 H), 7.66 (d, J = 8.3 Hz, 2 H), 7.49 (d, J = 8.0 Hz,
1 H), 7.36–7.31 (m, 3 H), 2.45(s, 3 H).
ESI-MS: m/z (%) = 236 [M+].
HRMS (ESI): m/z [M + H]+ calcd for C14H13N4: 237.1140; found:
237.1141.
1-Benzyl-4-(4-tolyl)-1,2,3-1H-triazole (3k)18
Yield: 112 mg (90%); white solid; mp 154.2–155.0 °C.
IR (KBr): 3143, 3018, 2975, 1496, 1457, 1348, 1223, 1047, 828 cm–1.
13C NMR (125 MHz, CDCl3): d = 146.9, 139.1, 134.6, 132.4, 131.3,
130.5, 130.3, 128.8, 124.4, 123.0, 120.5, 118.0, 21.1.
ESI-MS: m/z (%) = 315 [M + 2]+, 313 [M+].
HRMS (ESI): m/z [M + H]+ calcd for C15H1379BrN3: 314.0294;
1H NMR (400 MHz, CDCl3): d = 7.68 (d, J = 7.5 Hz, 2 H), 7.62 (s,
1 H), 7.38–7.32 (m, 5 H), 7.21 (d, J = 7.1 Hz, 2 H), 5.57 (s, 2 H),
2.36 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 148.3, 138.0, 134.8, 129.5, 129.2,
128.8, 128.1, 127.7, 125.6, 119.2, 54.2, 21.3.
found: 314.0292.
4-(2-Bromophenyl)-1-(4-tolyl)-1H-1,2,3-triazole (3g)
Yield: 117 mg (75%); yellow solid; mp 95.9–96.8 °C.
ESI-MS: m/z (%) = 249 [M+].
IR (KBr): 3157, 3061, 2919, 1517, 1465, 1403, 1222, 1048, 1022,
814, 764 cm–1.
1-(4-Methoxyphenyl)-4-(2-phenylethyl)-1H-1,2,3-triazole (3l)
Yield: 82 mg (62%); yellow solid; mp 112.8–113.7 °C.
1H NMR (400 MHz, CDCl3): d = 8.63 (s, 1 H), 8.19 (d, J = 7.9 Hz,
1 H), 7.69 (d, J = 8.3 Hz, 3 H), 7.47–7.43 (m, 1 H), 7.35 (d, J = 8.1
Hz, 2 H), 7.24–7.22 (m, 1 H), 2.45(s, 3 H).
IR (KBr): 3116, 3073, 3031, 2922, 2856, 1518, 1496, 1453, 1384,
1222, 1049, 821, 725, 697 cm–1.
Synthesis 2011, No. 18, 2907–2912 © Thieme Stuttgart · New York

PAPER
1,4-Disubstituted 1,2,3-Triazoles
2911
1H NMR (400 MHz, CDCl3): d = 7.49–7.46 (m, 3 H), 7.25–7.13 (m,
7 H), 3.09 (t, J = 7.1 Hz, 2 H), 2.99 (t, J = 7.1 Hz, 2 H), 2.34 (s, 3
Chem. 2010, 49, 4278. (h) Mamidyala, S. K.; Finn, M. G.
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13C NMR (125 MHz, CDCl3): d = 147.7, 141.0, 138.7, 134.9, 130.2,
128.5, 128.4, 126.2, 120.4, 119.3, 35.5, 27.4, 21.1.
ESI-MS: m/z (%) = 263 [M+].
HRMS (ESI): m/z [M + H]+ calcd for C17H18N3: 264.1500; found:
264.1501.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
Acknowledgment
The present work was supported by the Natural Science Foundation
of China (No. 30873153), the Key Projects of Shanghai in Biome-
dicine (No. 08431902700), and the Scientific Research Foundation
of the State Education Ministry for Returned Overseas Chinese
Scholars. We would also like to thank the Center for Instrumental
Analysis, Tongji University, China.
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J. Med. Chem. 1986, 29, 2262.
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