Catalyst-free 1,3-dipolar cycloaddition: An efficient route for the formation of the 1,2,3-triazole-fused diazepinone framework

Article abstract of DOI:10.1055/S-0029-1218610

A catalyst-free, effective method for the synthesis of the hitherto unreported 1,2,3-triazole-fused diazepinone framework in good to excellent yield through 1,3-dipolar cycloaddition is reported. The generality of the reaction is demonstrated by the synthesis of an array of [1,2,3]triazolodiazepinones. The methodology offers a clean reaction and easy isolation of the products in good to excellent yield. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/S-0029-1218610

858
PAPER
Catalyst-Free 1,3-Dipolar Cycloaddition: An Efficient Route for the
Formation of the 1,2,3-Triazole-Fused Diazepinone Framework
Efficient
Route to
.1,2,3-Triazol
C
e-Fuse
d
D
iazepi
.nones Majumdar,* Krishanu Ray, Sintu Ganai, Tapas Ghosh
Department of Chemistry, University of Kalyani, Kalyani 741235, India
Fax +91(33)25828282; E-mail: kcm_ku@yahoo.co.in
Received 2 November 2009; revised 5 November 2009
triazole-fused 1,4-benzodiazepinones are still lacking in
the literature. Considering the utility of both 1,2,3-triaz-
oles and 1,4-benzodiazepinones, we have undertaken a
study to synthesize fused triazolobenzodiazepinones us-
Abstract: A catalyst-free, effective method for the synthesis of the
hitherto unreported 1,2,3-triazole-fused diazepinone framework in
good to excellent yield through 1,3-dipolar cycloaddition is report-
ed. The generality of the reaction is demonstrated by the synthesis
of an array of [1,2,3]triazolodiazepinones. The methodology offers ing the Huisgen 1,3-dipolar cycloaddition reaction. The
a clean reaction and easy isolation of the products in good to excel-
results are reported here.
lent yield.
The precursors 3a–f required for our present investigation
were synthesized from compounds 2a–f, which were in
Key words: triazoles, diazepinones, 1,3-dipolar cycloaddition
turn synthesized in one step by Sonogashira coupling of
the corresponding bromo derivatives 1a–f with phenyl-
Heterocycles containing the 1,2,3-triazole ring system are
reported to possess several biological activities including
anti-HIV,1 antiallergic,2 antifungal,3 antiviral,4 anti-
microbial5 and antihistamine activity.2 1,2,3-Triazoles
have also found industrial application such as their use as
dyes, corrosion inhibitors, photostabilizers, photographic
materials and agrochemicals.6 Therefore, importance has
been given to the development of new and more efficient
synthetic pathways to a diverse array of 1,2,3-triazole
pharmacophores. The most popular method for the con-
struction of the 1,2,3-triazole framework is the Huisgen
1,3-dipolar cycloaddition reaction of azides with alkynes.7
This methodology has been widely used by many research
groups for the synthesis of several bicyclic, as well as
polycyclic, triazole-fused nitrogen-containing heterocy-
cles,8 and also in the synthesis of triazole-fused oxygen-
rich heterocycles.9 There are also some other reports for
the formation of this framework which include the use of
copper(I) systems in the presence of a base10 or in aqueous
poly(ethylene glycol),11 and the redox couple copper(II)/
ascorbic acid12 in organic or organoaqueous systems and
in the solid phase.13
acetylene using PdCl2(PPh3)2 as catalyst and copper(I) io-
dide as cocatalyst in anhydrous N,N-dimethylformamide
containing triethylamine as base, at 120 °C (Scheme 1).
H
N
H
N
R1
R1
(i)
R2
Br
R2
Ph
2a R1 = Me, R2 = Me
2b R1 = Et, R2 = Me
2c R1 = Et, R2 = H
2d R1 = Me, R2 = H
1a R1 = Me, R2 = Me
1b R1 = Et, R2 = Me
1c R1 = Et, R2 = H
1d R1 = Me, R2 = H
Ph
Br
H
H
N
N
R1
R1
(i)
O
O
O
O
1e R1 = Me
2e R1 = Me
2f R1 = Et
1f R1 = Et
Scheme 1 Reagents and conditions: (i) PhC≡CH, PdCl2(PPh3)2,
CuI, Et3N, anhyd DMF, 120 °C, 4–6 h.
Apart from this, benzodiazepinones have emerged as a
particularly fascinating class of scaffold in medicinal
chemistry and have been viewed repeatedly as the proto-
type of a ‘privileged structure’ as they hit various classes
of pharmacologically relevant targets such as GPCRs, ion
channels and enzymes.14 Prominent examples include the
GABAA agonists Diazepam15 (sedative) and Zolpidem16
(nonadditive hypnotic), the antitumour antibiotic chica-
mycin A,17 and the cholecystokinin antagonist asperli-
cin,18 respectively. There are some reports19 for the
synthesis of 1,4-benzodiazepinone derivatives but 1,2,3-
Compounds 2a–f were subsequently treated with chloro-
acetyl chloride under phase-transfer catalysis conditions
using tetrabutylammonium hydrogen sulfate (TBAHS) as
catalyst and potassium carbonate as base to give the amide
derivatives 3a–f in good yield (Scheme 2).
Treatment of compound 3a with an excess amount of so-
dium azide (2.5 equiv) in N,N-dimethylformamide at
100 °C for 1 hour gave the azide derivative 4a. Azide 4a
was isolated and heated in N,N-dimethylformamide at
110 °C for four hours to afford the desired product 5a in
90% yield. The same sequence of two steps (iii and iv) has
been conducted in one step without isolating the azide de-
rivative 4a to give the 1,2,3-triazole-fused 1,4-benzodiaz-
SYNTHESIS 2010, No. 5, pp 0858–0862
x
x
.
x
x
.2
0
1
0
Advanced online publication: 16.12.2009
DOI: 10.1055/s-0029-1218610; Art ID: Z23209SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Efficient Route to 1,2,3-Triazole-Fused Diazepinones
859
R1
N
benzodiazepinone heterocycles using 1,3-dipolar cyclo-
addition in good to excellent yield.
H
N
R1
Cl
(ii)
In conclusion, we have achieved a catalyst-free 1,3-dipo-
lar cycloaddition reaction of alkynes with azides for the
synthesis of various complex 1,2,3-triazole-fused diaze-
pinone derivatives of potential utility.
O
R2
R2
Ph
Ph
2a R1 = Me, R2 = Me
2b R1 = Et, R2 = Me
2c R1 = Et, R2 = H
2d R1 = Me, R2 = H
3a R1 = Me, R2 = Me
3b R1 = Et, R2 = Me
3c R1 = Et, R2 = H
3d R1 = Me, R2 = H
Melting points were determined in open capillaries and are uncor-
rected. IR spectra (nmax in cm–1) were recorded on a Perkin-Elmer
Ph
Ph
1
120-000A instrument using KBr disks. H and 13C NMR spectra
Cl
were recorded in CDCl3 with TMS as internal standard (chemical
shifts in d) on either a Bruker DPX 400-MHz or a Bruker DPX 500-
MHz spectrometer. MS data were recorded on a Qtof Micro YA263
mass spectrometer. Silica gel (60–120 mesh; Spectrochem, India)
was used for chromatographic separations. Silica gel G (Spectro-
chem, India) was used for TLC. Petroleum ether refers to the frac-
tion boiling between 60 and 80 °C.
O
H
N
(ii)
N
R1
R1
O
O
O
O
2e R1 = Me
3e R1 = Me
2f R1 = Et
3f R1 = Et
CAUTION: Although we encountered no problems during the
course of our studies, azides can be explosive compounds and
should be handled with great care.21
Scheme 2 Reagents and conditions: (ii) ClCH2COCl, TBAHS,
K2CO3, CH2Cl2–H2O, r.t., 0.5 h.
Me
N
Me
N
Amide 3a; Typical Procedure
To a stirred soln of chloroacetyl chloride (383 mg, 3.39 mmol) in
CH2Cl2 (20 mL), a mixture of amine 2a (500 mg, 2.26 mmol) and a
catalytic amount of TBAHS in CH2Cl2 (20 mL) was added. To this
mixture, a soln of K2CO3 (468 mg, 3.39 mmol) in H2O (10 mL) was
added slowly. After the mixture was stirred for 30 min, a TLC check
indicated completion of the reaction. Then, the reaction mixture was
washed with 5% aq HCl (2 × 20 mL) and then with 5% aq NaOH
(2 × 20 mL). Finally, the organic layer was washed with brine (20
mL), dried (anhyd Na2SO4) and filtered. The filtrate was concentrat-
ed and the crude product was purified by column chromatography
over silica gel (60–120 mesh) using petroleum ether–EtOAc (4:1)
as eluant to give 3a in 72% yield. Amides 3b–f were prepared ac-
cordingly.
Cl
N3
(iii)
O
O
Ph
Ph
4a
3a
(iv)
Me
O
N
N
N
5a
N
Ph
Scheme 3 Reagents and conditions: (iii) NaN3, DMF, 100 °C; (iv)
110 °C.
Compound 3a
Yield: 72%; solid; mp 78–80 °C.
IR (KBr): 1673, 2218 cm–1.
epinone 5a without affecting the yield of the
1H NMR (400 MHz, CDCl3): d = 7.46–7.48 (m, 2 H), 7.42 (br s, 1
H), 7.33–7.34 (m, 3 H), 7.17–7.22 (m, 2 H), 3.85 (q, J = 13.1 Hz, 2
H), 3.31 (s, 3 H), 2.38 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 20.9, 37.2, 41.9, 84.5, 95.0,
122.2, 127.9, 128.5, 128.9, 130.7, 131.7, 133.5, 138.9, 141.2, 166.7.
cycloaddition reaction (Scheme 3).
We have also attempted the same reaction in other sol-
vents, such as dimethyl sulfoxide and 1,4-dioxane, but
none of these solvents afforded the desired cyclized prod-
uct. N,N-Dimethylformamide is the best choice, with the
cycloaddition taking place in one pot to give the desired
cyclized products in high yield. The other substrates 3b–f
were treated similarly to give the desired 1,3-dipolar cy-
cloaddition products 5b–f in 86–92% yield (Table 1).
Ko and Lee20 synthesized substituted triazolobenzazepine
derivatives in 72–77% yield from the Baylis–Hillman ad-
ducts of 2-alkynylbenzaldehydes by a 1,3-dipolar cy-
cloaddition reaction. Recently, Chandrasekaran and co-
workers reported the synthesis of [1,2,3]triazolopyrazi-
nones in above 90% yield from amines and amino acids.8g
Therefore, triazole-fused nitrogen heterocycles have at-
tracted much attention from both biological and medicinal
interests. In view of the importance of both the triazole
and the 1,4-benzodiazepinone moiety, we have described
the synthesis of some complex 1,2,3-triazole-fused 1,4-
TOFMS (ES+): m/z = 298.10 [M + H]+.
Anal. Calcd for C18H16ClNO: C, 72.60; H, 5.42; N, 4.70. Found: C,
72.51; H, 5.39; N, 4.83.
Compound 3b
Yield: 74%; solid; mp 82–84 °C.
IR (KBr): 1674, 2213 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.43–7.48 (m, 3 H), 7.32–7.34 (m,
3 H), 7.20 (d, J = 8.0 Hz, 1 H), 7.13 (d, J = 8.2 Hz, 1 H), 3.74–3.94
(m, 4 H), 2.38 (s, 3 H), 1.14 (t, J = 7.4 Hz, 3 H).
MS: m/z = 311 [M+].
Anal. Calcd for C19H18ClNO: C, 73.19; H, 5.82; N, 4.49. Found: C,
73.31; H, 5.89; N, 4.31.
Compound 3c
Yield: 78%; solid; mp 92–94 °C.
IR (KBr): 1680, 2215 cm–1.
Synthesis 2010, No. 5, 858–862 © Thieme Stuttgart · New York

860
K. C. Majumdar et al.
PAPER
Table 1 Summarized Results of the 1,3-Dipolar Cycloaddition Reactions
Starting material
Time (h)
Product
Yield (%)
Me
Me
N
O
N
Cl
Cl
3a
5
5a
90
88
86
92
O
N
N
O
Ph
N
Ph
Et
Et
N
N
3b
3c
3d
5.1
5b
5c
5d
O
N
N
Ph
Cl
N
Ph
Et
Et
N
O
N
5
O
N
N
O
Ph
N
Ph
Me
Me
N
N
Cl
5
O
N
N
N
Ph
Ph
Ph
N
N
Cl
N
O
O
Ph
3e
3f
5.3
5.3
5e
5f
87
89
N
N
Me
Me
O
O
O
O
Ph
N
N
Cl
Et
N
O
O
Ph
N
N
Et
O
O
O
O
1H NMR (400 MHz, CDCl3): d = 7.37–7.42 (m, 3 H), 7.26–7.29 (m,
IR (KBr): 1673, 1716, 2212 cm–1.
3 H), 7.07–7.16 (m, 3 H), 3.64–3.89 (m, 4 H), 1.08 (t, J = 7.0 Hz, 3
1H NMR (400 MHz, CDCl3): d = 8.19 (d, J = 9.7 Hz, 1 H), 7.54 (d,
J = 7.3 Hz, 2 H), 7.48 (d, J = 8.7 Hz, 1 H), 7.36–7.41 (m, 4 H), 6.57
(d, J = 9.7 Hz, 1 H), 3.85 (q, J = 13.2 Hz, 2 H), 3.35 (s, 3 H).
H).
MS: m/z = 297 [M+].
Anal. Calcd for C18H16ClNO: C, 72.60; H, 5.42; N, 4.70. Found: C,
72.42; H, 5.32; N, 4.89.
MS: m/z = 351 [M+].
Anal. Calcd for C20H14ClNO3: C, 68.28; H, 4.01; N, 3.98. Found: C,
68.11; H, 4.08; N, 4.11.
Compound 3d
Yield: 72%; solid; mp 80–82 °C.
IR (KBr): 1676, 2218 cm–1.
Compound 3f
Yield: 70%; solid; mp 156–158 °C.
1H NMR (400 MHz, CDCl3): d = 7.60–7.63 (m, 1 H), 7.48–7.50 (m,
2 H), 7.39–7.42 (m, 2 H), 7.31–7.37 (m, 4 H), 3.85 (q, J = 13.1 Hz,
2 H), 3.34 (s, 3 H).
IR (KBr): 1676, 1737, 2213 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.19 (d, J = 9.76 Hz, 1 H), 7.53 (d,
J = 7.36 Hz, 2 H), 7.36–7.46 (m, 5 H), 6.57 (d, J = 9.72 Hz, 1 H),
3.79–3.94 (m, 4 H), 1.17 (t, J = 6.96 Hz, 3 H).
MS: m/z = 283 [M+].
Anal. Calcd for C17H14ClNO: C, 71.96; H, 4.97; N, 4.94. Found: C,
71.77; H, 4.88; N, 4.75.
MS: m/z = 365 [M+].
Anal. Calcd for C21H16ClNO3: C, 68.95; H, 4.41; N, 3.83. Found: C,
69.11; H, 4.33; N, 3.77.
Compound 3e
Yield: 68%; solid; mp 204–206 °C.
Synthesis 2010, No. 5, 858–862 © Thieme Stuttgart · New York

PAPER
Efficient Route to 1,2,3-Triazole-Fused Diazepinones
861
1,2,3-Triazole-Fused 1,4-Benzodiazepinone 5a; Typical Proce-
dure
1H NMR (400 MHz, CDCl3): d = 7.71–7.74 (m, 2 H), 7.55–7.59 (m,
2 H), 7.48 (d, J = 8.0 Hz, 1 H), 7.36–7.44 (m, 3 H), 7.26–7.30 (m, 1
H), 5.44 (d, J = 14.0 Hz, 1 H), 4.54 (d, J = 14.0 Hz, 1 H), 4.28–4.37
(m, 1 H), 3.72–4.28 (m, 1 H), 1.12 (t, J = 6.8 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 13.2, 44.4, 52.4, 122.4, 124.5,
126.6, 127.4, 128.5, 128.8, 129.7, 129.8, 130.3, 130.9, 139.1, 143.9,
164.8.
To a soln of amide 3a (200 mg, 0.67 mmol) in DMF (5 mL) was
added NaN3 (110 mg, 1.68 mmol). The mixture was then heated to
100 °C for 1 h, and then at 110 °C for a further 4 h. After completion
of the reaction (monitored by TLC), the mixture was cooled and
H2O (5 mL) was added. The mixture was then extracted with
CH2Cl2 (3 × 30 mL). The combined organic layer was dried (anhyd
Na2SO4), filtered and concentrated. The crude product was purified
by column chromatography over silica gel (60–120 mesh) using
PE–EtOAc (3:1) as eluant to obtain the pure product 5a in 90%
yield. Similarly, the other amides 3b–f were subjected to the same
reaction conditions to give the products 5b–f in good to excellent
yield.
MS: m/z = 304 [M+].
Anal. Calcd for C18H16N4O: C, 71.04; H, 5.30; N, 18.41. Found: C,
71.16; H, 5.37; N, 18.65.
Compound 5d
Yield: 92%; solid; mp 210–212 °C.
IR (KBr): 1382, 1682 cm–1.
Compound 4a
1H NMR (400 MHz, CDCl3): d = 7.73–7.76 (m, 2 H), 7.54–7.59 (m,
1 H), 7.47–7.52 (m, 2 H), 7.36–7.44 (m, 3 H), 7.25–7.29 (m, 1 H),
5.50 (d, J = 14.4 Hz, 1 H), 4.57 (d, J = 14.8 Hz, 1 H), 3.48 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 37.2, 52.1, 120.7, 123.7, 126.3,
127.4, 127.6, 128.5, 128.7, 129.8, 130.3, 130.9, 140.4, 143.9, 165.9.
Yield: 83%; solid; mp 150–152 °C.
IR (KBr): 1671, 2106, 2211 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.49–7.53 (m, 2 H), 7.45 (d,
J = 1.2 Hz, 1 H), 7.36–7.39 (m, 3 H), 7.22 (dd, J = 2.0, 8.4 Hz, 1 H),
7.14 (d, J = 8.0 Hz, 1 H), 3.73 (d, J = 16.0 Hz, 1 H), 3.58 (d,
J = 16.0 Hz, 1 H), 3.34 (s, 3 H), 2.41 (s, 3 H).
MS: m/z = 290 [M+].
13C NMR (100 MHz, CDCl3): d = 20.9, 36.7, 50.8, 84.4, 95.0,
122.2, 122.3, 127.7, 128.5, 129.0, 130.8, 131.7, 133.6, 139.0, 140.8,
167.7.
Anal. Calcd for C17H14N4O: C, 70.33; H, 4.86; N, 19.30. Found: C,
70.11; H, 4.79; N, 19.19.
Compound 5e
Yield: 87%; solid; mp 310–312 °C.
IR (KBr): 1685, 1735 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.67 (d, J = 9.3 Hz, 1 H), 7.56–
7.61 (m, 3 H), 7.29–7.36 (m, 4 H), 6.14 (d, J = 9.9 Hz, 1 H), 5.56
(d, J = 14.6 Hz, 1 H), 4.66 (d, J = 14.5 Hz, 1 H), 3.46 (s, 3 H).
TOFMS (ES+): m/z = 327.0 [M + Na]+.
Anal. Calcd for C18H16N4O: C, 71.04; H, 5.30; N, 18.41. Found: C,
71.11; H, 5.22; N, 18.60.
Compound 5a
Yield: 90%; solid; mp 182–184 °C.
13C NMR (100 MHz, CDCl3): d = 37.2, 52.1, 116.0, 117.8, 118.5,
120.1, 125.7, 125.8, 126.7, 126.9, 129.2, 129.5, 137.8, 140.6, 145.5,
152.5, 158.9, 166.0.
IR (KBr): 1385, 1684 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.73–7.74 (m, 2 H), 7.34–7.42 (m,
5 H), 7.28 (s, 1 H), 5.45 (d, J = 14.4 Hz, 1 H), 4.53 (d, J = 14.4 Hz,
1 H), 3.43 (s, 3 H), 2.28 (s, 3 H).
MS: m/z = 358 [M+].
13C NMR (125 MHz, CDCl3): d = 20.6, 37.1, 52.1, 120.6, 123.5,
127.3, 128.4, 128.8, 129.8, 129.9, 130.4, 131.7, 136.3, 138.1, 143.7,
165.9.
Anal. Calcd for C20H14N4O3: C, 67.03; H, 3.94; N, 15.63. Found: C,
67.21; H, 4.01; N, 15.88.
Compound 5f
Yield: 89%; solid; mp 298–300 °C.
IR (KBr): 1686, 1732 cm–1.
HRMS: m/z [M + H]+ calcd for C18H17N4O: 305.1397; found:
305.1406.
Compound 5b
Yield: 88%; solid; mp 172–174 °C.
IR (KBr): 1383, 1678 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.74 (d, J = 14.0 Hz, 2 H), 7.34–
7.42 (m, 6 H), 5.41 (d, J = 14.0 Hz, 1 H), 4.52 (d, J = 14.0 Hz, 1 H),
4.27–4.36 (m, 1 H), 3.67–3.75 (m, 1 H), 2.30 (s, 3 H), 1.09 (t,
J = 7.2 Hz, 3 H).
1H NMR (400 MHz, CDCl3): d = 7.67 (d, J = 9.1 Hz, 1 H), 7.51–
7.58 (m, 3 H), 7.28–7.34 (m, 4 H), 6.10 (d, J = 9.9 Hz, 1 H), 5.45
(d, J = 14.3 Hz, 1 H), 4.58 (d, J = 14.2 Hz, 1 H), 4.33–4.42 (m, 1 H),
3.62–3.69 (m, 1 H), 1.06 (t, J = 7.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 13.0, 43.9, 52.4, 116.1, 117.8,
120.1, 120.5, 125.6, 126.8, 127.8, 129.2, 129.3, 129.6, 136.2, 140.5,
145.6, 152.7, 158.9, 165.0.
MS: m/z = 372 [M+].
13C NMR (100 MHz, CDCl3): d = 13.1, 20.6, 44.2, 52.4, 122.2,
124.3, 127.2, 128.4, 128.7, 129.7, 129.8, 130.9, 131.8, 136.6, 136.8,
143.7, 164.9.
Anal. Calcd for C21H16N4O3: C, 67.73; H, 4.33; N, 15.05. Found: C,
67.98; H, 4.41; N, 15.26.
TOFMS (ES+): m/z = 319.08 [M + H]+.
Anal. Calcd for C19H18N4O: C, 71.68; H, 5.70; N, 17.60. Found: C,
71.77; H, 5.66; N, 17.87.
Acknowledgment
We thank the CSIR (New Delhi) and the DST (New Delhi) for fi-
nancial assistance. Three of us (K.R., S.G. and T.G.) are grateful to
the CSIR (New Delhi) for fellowships.
Compound 5c
Yield: 86%; solid; mp 176–178 °C.
IR (KBr): 1393, 1682 cm–1.
Synthesis 2010, No. 5, 858–862 © Thieme Stuttgart · New York

862
K. C. Majumdar et al.
PAPER
(9) (a) Hotha, S.; Anegundi, R. I.; Natu, A. A. Tetrahedron Lett.
2005, 46, 4585. (b) Chandrasekhar, S.; Rao, C. L.; Nagesh,
C.; Reddy, C. R.; Sridhar, B. Tetrahedron Lett. 2007, 48,
5869.
(10) (a) Zhang, X.; Hsung, R. P.; Li, H. Chem. Commun. 2007,
2420. (b) Bertrand, P.; Gesson, J.-P. J. Org. Chem. 2007, 72,
3596. (c) Majumdar, K. C.; Mondal, S. Lett. Org. Chem.
2009, 6, 82.
References
(1) (a) Alvarez, R.; Velázquez, S.; San-Félix, A.; Aquaro, S.;
De Clercq, E.; Perno, C.-F.; Karlsson, A.; Balzarini, J.;
Camarasa, M. J. J. Med. Chem. 1994, 37, 4185.
(b) Velázquez, S.; Alvarez, R.; Pérez, C.; Gago, F.;
De Clercq, E.; Balzarini, J.; Camarasa, M. J. Antiviral Chem.
Chemother. 1998, 9, 481.
(2) Buckle, D. R.; Rockell, C. J. M.; Smith, H.; Spicer, B. A.
J. Med. Chem. 1986, 29, 2262.
(3) (a) Vicentini, C. B.; Brandolini, V.; Guarneri, M.; Giori, P.
Farmaco 1992, 47, 1021. (b) Fung-Tomc, J. C.; Huczko, E.;
Minassian, B.; Bonner, D. P. Antimicrob. Agents
Chemother. 1998, 42, 313.
(11) Kumar, D.; Reddy, V. B.; Varma, R. S. Tetrahedron Lett.
2009, 50, 2065.
(12) (a) Beckmann, H. S. G.; Wittmann, V. Org. Lett. 2007, 9, 1.
(b) Tao, C.-Z.; Cui, X.; Li, J.; Liu, A.-X.; Liu, L.; Guo, Q.-
X. Tetrahedron Lett. 2007, 48, 3525.
(13) Harju, K.; Vahermo, M.; Mutikainen, I.; Kauhaluoma, J. Y.
J. Comb. Chem. 2003, 5, 826.
(14) (a) Evans, B. E.; Rittle, K. E.; Bock, M. G.; DiPardo, R. M.;
Freidinger, R. M.; Whitter, W. L.; Lundell, G. F.; Veber, D.
F.; Anderson, P. S.; Chang, R. S. L.; Lotti, V. J.; Cerino, D.
J.; Chen, T. B.; Kling, P. J.; Kunkel, K. A.; Springer, J. P.;
Hirshfield, J. J. Med. Chem. 1988, 31, 2235. (b) Patchett,
A. A.; Nargund, R. P. Annu. Rep. Med. Chem. 2000, 35, 289.
(15) Sternbach, L. H. J. Med. Chem. 1979, 22, 1.
(16) Pritchett, D. B.; Seeburg, P. H. J. Neurochem. 1990, 54,
1802.
(17) Konishi, M.; Hatori, M.; Tomita, K.; Sugawara, M.; Ikeda,
C.; Nishiyama, Y.; Imanishi, H.; Miyaki, T.; Kawaguchi, H.
J. Antibiot. 1984, 37, 191.
(18) (a) Goetz, M. A.; Lopez, M.; Monaghan, R. L.; Chang, R. S.
L.; Lotti, V. J.; Chen, T. B. J. Antibiot. 1985, 38, 1633.
(b) Chang, R. S. L.; Lotti, V. J.; Monaghan, R. L.; Birnbaum,
J.; Stapley, E. O.; Goetz, M. A.; Albers-Schönberg, G.;
Patchett, A. A.; Liesch, J. M.; Hensens, O. D.; Springer, J. P.
Science (Washington, D.C.) 1985, 230, 177.
(19) (a) Kim, K.; Volkman, S. K.; Ellman, J. A. J. Braz. Chem.
Soc. 1998, 9, 375. (b) Correa, A.; Herrero, M. T.; Tellitu, I.;
Domínguez, E.; Moreno, I.; SanMartin, R. Tetrahedron
2003, 59, 7103.
(20) Ko, S. H.; Lee, K.-J. J. Heterocycl. Chem. 2004, 41, 613.
(21) (a) For a discussion of the hazards associated with azides,
see: Prudent Practice for Handling Hazardous Chemicals in
Laboratories; National Academic Press: Washington DC,
1983, 87–88. (b) For human toxicity, see: The Merck Index,
12th ed.; Merck & Co.: Rahway NJ, 1996, 4818, 8726.
(4) Palhagen, S.; Canger, R.; Henriksen, O.; van Parys, J. A.;
Riviere, M.-E.; Karolchyk, M. A. Epilepsy Res. 2001, 43,
115.
(5) Genin, M. J.; Allwine, D. A.; Anderson, D. J.; Barbachyn,
M. R.; Emmert, D. E.; Garmon, S. A.; Graber, D. R.; Grege,
K. C.; Hester, J. B.; Hutchinson, D. K.; Morris, J.; Reischer,
R. J.; Ford, C. W.; Zurenko, G. E.; Hamel, J. C.; Schaadt, R.
D.; Stapert, D.; Yagi, B. H. J. Med. Chem. 2000, 43, 953.
(6) Fan, W.-Q.; Katritzky, A. R. In Comprehensive
Heterocyclic Chemistry II, Vol. 4; Katritzky, A. R.; Rees, C.
W.; Scriven, E. F. V., Eds.; Elsevier Science: Oxford, 1996,
1–26.
(7) (a) Huisgen, R.; Szeimies, G.; Moebius, L. Chem. Ber. 1967,
100, 2494. (b) Huisgen, R. 1,3-Dipolar Cycloaddition
Chemistry; Wiley & Sons: New York, 1984, 1–176.
(c) Huisgen, R. Pure Appl. Chem. 1989, 61, 613.
(8) (a) Arkitopoulou-Zane, I.; Gracias, V.; Djuric, S. W.
Tetrahedron Lett. 2004, 45, 8439. (b) Couty, F.; Durrat, F.;
Prim, D. Tetrahedron Lett. 2004, 45, 3725. (c) Mahapatra,
D. K.; Maity, P. K.; Gonnade, R. G.; Chorgade, M. S.;
Gurgar, M. K. Synlett 2007, 1893. (d) Rohr, W.; Fischer,
A.; Bad, A.; Sodafabr, A.-G. In Pesticide Chemistry:
Proceedings of the Second International IUPAC Congress,
Vol. 5; Tahori, A. S., Ed.; Gordon & Breach: New York,
1972, 177. (e) Pokorski, J. K.; Millers Jenkins, L. M.; Feng,
H.; Durell, S. R.; Bai, Y.; Appella, D. H. Org. Lett. 2007, 9,
2381. (f) Kumar, I.; Rode, C. V. Chem. Lett. 2007, 36, 592.
(g) Sudhir, V. S.; Nasir Bag, R. B.; Chandrasekaran, S. Eur.
J. Org. Chem. 2008, 2423.
Synthesis 2010, No. 5, 858–862 © Thieme Stuttgart · New York