N-(α-Amidoalkyl)benzotriazole-mediated synthesis of β′-amido β-diketones: a general synthetic protocol for N-[β-(3,5-di and 1,3,5-trisubstituted pyrazol-4-yl)alkyl] amides

Article abstract of DOI:10.1016/j.tet.2008.10.047

Various β′-amido-β-diketones were first synthesized with N-(α-amidoalkyl)benzotriazole-mediated amidoalkylation of 1,3-diketones in moderate yields. These intermediates undergo rapid condensation with hydrazines to give the corresponding N-[β-(3,5-di and

Full text of DOI:10.1016/j.tet.2008.10.047

Tetrahedron 65 (2009) 328–335
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
N-(
a
-Amidoalkyl)benzotriazole-mediated synthesis of
b
0-amido
b-(3,5-di and 1,3,5-trisubstituted
b-diketones:
a general synthetic protocol for N-[
pyrazol-4-yl)alkyl] amides
_
*
Ilhami Çelik , Nevin Kanıs¸kan, S¸ule Ko¨kten
Department of Chemistry, Faculty of Science, Anadolu University, 26470 Eskis¸ehir, Turkey
a r t i c l e i n f o
a b s t r a c t
b b-diketones were first synthesized with N-(a-amidoalkyl)benzotriazole-mediated
0-amido-
Article history:
Received 29 July 2008
Received in revised form 1 October 2008
Accepted 16 October 2008
Available online 1 November 2008
Various
amidoalkylation of 1,3-diketones in moderate yields. These intermediates undergo rapid condensation
with hydrazines to give the corresponding N-[
b
-(3,5-di and 1,3,5-trisubstituted pyrazol-4-yl)alkyl]amides.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Benzotriazole
N-(
Pyrazole
0-Amido
b-diketone
a-Amidoalkyl)benzotriazole
b
1. Introduction
1,3-dicarbonyl compounds or their functional derivatives, although
it gives a mixture of isomers.
Substituted pyrazoles represent an important class of hetero-
cyclic compounds used in the pharmaceutical industry, since they
form the core structures of many commercial drugs such as
Zometapine,1a Sildenafil,1b Celebrex,1c and Rimonabant (Fig. 1).1d
They are also known to show a wide range of biological properties
such as selective Human C1s inhibition,2a antitumor cyclin-de-
pendent kinase (CDK) inhibition,2b monoamine oxidase-B (MOA-B)
inhibition, and anti-inflammation.2c,11d In addition to their bi-
ological activities, pyrazoles are also used for the preparation of
pyrazole dyes,3 couplers for photographic material,4 herbicides,5
and luminescent and fluorescent substances.6 Recently, they have
appeared as intermediates for fused pyrazoles,7 chiral catalysts,8
ligands,9 and moieties to enhance regio- and stereoselectivity.
Many methods for the synthesis of pyrazoles have been de-
veloped.10 The methods developed to synthesize pyrazoles are: (i)
cyclocondensation of hydrazine with 2,3-dibromopropionitriles,11a
propargyl aldehydes, 1,3-dicarbonyl compounds,11b–f or their
Benzotriazole-mediated amidoalkylation was introduced in
1988, and provides advantages over previously reported methods.
It was already demonstrated for the amidoalkylation of (i) Grignards,14a
CH3
N
Cl
O
N
S
O
H3C
H3C
O
N
H3C
N
NH
N
N
CH3
N
N
N
CH3
H
O
Zometapine
Sildenafil
O
N
CF3
N
H3C
N
H
N
functional derivatives such as enol ethers, acetales, enamine, a,b-
N
ethynyl ketones, or esters,11g–k (ii) 1,3-dipolar cycloadditions of
diazoalkanes or nitrile imines with alkynes or alkenes,12 (iii)
elimination of pyrazoline.13 Among the methods reported, the most
common method is the cyclocondensation of hydrazine with
N
H3C
Cl
Cl
SO2NH2
Celebrex
Cl
Rimonabant
* Corresponding author. Tel.: þ90 2223350580/4792; fax: þ90 2223204910.
_
E-mail address: ilcelik@anadolu.edu.tr (I. Çelik).
Figure 1. Some commercial drugs having pyrazole ring.
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.10.047

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I. Çelik et al. / Tetrahedron 65 (2009) 328–335
329
(ii) malonates and acetoacetates,14b (iii) cyanide anion,14c (iv)
(12–90%) (Scheme 2 and Table 1). The formation of the
b-diketones of type 3 is indicated by the loss of benzotriazole sig-
b
0-amido
mercaptans and alcohols,14d,e (v) electron-rich aromatics,14f (vi)
amines,14g and (vii) nitroalkanes, nitriles, and esters14h (Scheme 1).
nals in the 1H and 13C NMR spectra. The doublets at 7.93–6.20 ppm
and at 6.45–6.23 ppm in the 1H NMR spectra of 3a–j were assigned
to the NH proton and double activated methine protons, re-
spectively. The doublets in the 1H NMR spectra of 3a–j were
assigned to the methine proton next to NH. In the 13C NMR spectra
of compounds 3a–j, resonances arising from the diketone and
amide carbonyls are found in the regions 205.6–195.9 ppm, 202.8–
193.7 ppm, and 178.4–169.5 ppm. The 1H and 13C NMR spectra of
3a–j showed that while 3b was a diastereoisomeric mixture, 3a,c–j
were single diastereomers. The ratio of syn/anti diastereomers was
determined by the 1H NMR spectra. The structures of compounds
3a–j were also supported by their elemental analyses and spectral
data.
XR3
O
CN
O
Ar
O
O
X = S,O
R2
R
N
R
R2
N
N
R
R2
R4
R1
R1
R1
R3
R2
CN-
v
N
R3XH
Bt
iii
vi
O
X
Y
ArH
O
O
R
N
R1
R2
R
R
N
ii
R1
R3
R
N
R1
R2
R3
X
O
R3MgBr
i
vii
R3X
R1 = alkyl orH
R2
R
N
R2
N
R1
R1
O
O
NHCOR
R1
X = NO2, CN, COOR4
O
O
R
Bt
R2
t-BuOK, DMSO
rt, 8h
Scheme 1.
R2
N
H
R1
O
R3
R3
We now report that N-(
amidoalkylation extends the amidoalkylation of 1,3-diketones to
give the corresponding novel -diketones and the
0-amido
synthesis of N-[ -(3,5-di and 1,3,5-trisubstituted pyrazol-4-yl)al-
kyl]amides by condensation of hydrazines with the
0-amido
-diketones.
a-amidoalkyl)benzotriazole-mediated
1a-j
3a-j
2
Scheme 2.
b
b
b
During the course of our work, we noticed that when the al-
dehyde contains a nitro group, it gives both byproduct 3f0, which is
the major product, and the expected product 3f. This byproduct 3f0
was fully characterized by 1H and 13C NMR spectroscopy and ele-
mental analyses. Scheme 3 gives a possible explanation for the
formation of the byproduct.
b
b
2. Result and discussion
2.1. Preparation of N-( -amidoalkyl)benzotriazoles
The amidoalkylating reagents employed, N-( -amidoalkyl)-
a
Ph
a
OK
Bt
NHCOMe
NO2
Bt
O
NO2
NHCOMe
NO2
2
benzotriazoles 1a–j, are easily available by the well-established
condensation of benzotriazole, an aldehyde, and an amide in the
presence of a catalytic amount of p-toluenesulfonic acid in toluene
at reflux with azeotropic removal of water.14 Aromatic and hetero-
aromatic aldehydes gave stable products 1 in good yields, which
were fully characterized on the basis of their 1H and 13C NMR
spectra and elemental analyses. The 1H and 13C NMR spectra of
these N-(a-amidoalkyl)benzotriazoles confirmed that the products
1a–j are all benzotriazol-1-yl compounds with no isomerization to
benzotriazol-2-yl isomers.
O
Ph
NHCOMe
Ph
Ph
O
Bt
1f
Bt
Ph
H
+K-O
Ph
NO2
NO2
Ph
H
NHCOMe
O
O
3f'
Scheme 3.
2.2. Synthesis of
b
0-amido
b-diketones
The synthesis of
b
-acetamido carbonyl compounds has attracted
We assumed that it provides the alkene owing to electronic
effects or electron withdrawing nature of the nitro group.
attention in organic synthesis, being used for the synthesis of var-
ious bioactive molecules such as antibiotic nikkomycins or neo-
polyoxines15 and the preparation of 1,3-amino alcohols16 or
b
-amino acids.17
b
0-Amido
b-diketones were previously prepared
2.3. Synthesis of N-[b-(3,5-di and 1,3,5-trisubstituted
pyrazol-4-yl)alkyl]amides
by one-pot multi-component reactions (MCRs) using CoCl2,17
FeCl3,18a and BiOCl18b as catalysts, and by the asymmetric Mannich
reaction of dicarbonyl compounds with
by cinchona.18c Although multi-component reactions (MCRs) have
been used for the preparation of -diketones, they also
0-amido
a
-amido sulfones catalyzed
As mentioned above, many methods for the preparation of
pyrazoles have been developed. In spite of the fact that among
these methods, cyclocondensation of hydrazine with 1,3-dicarbonyl
compounds or their functional derivatives give a mixture of iso-
mers, it is the most common method for the preparation of pyr-
azoles. In this manner, the next step in our synthetic sequence was
b
b
have some disadvantages. Acetoacetone was only used as a starting
material in the methods mentioned above. Therefore, they
obtained limited amounts of
The second step in our synthetic sequence was the preparation
of the -diketones by the reaction of potassium enolates,
0-amido
prepared in situ by treating the corresponding 1,3-diketones with
t-BuOK in DMSO at room temperature, with 1a–j. N-( -Amidoalkyl)-
b b-diketones.
0-amido
to obtain N-[
amides by the cyclocondensation of hydrazine or substituted
hydrazine with -diketones. A solution of hydrazine was
0-amido
slowly added to the corresponding -diketone in absolute
0-amido
b-(3,5-di and 1,3,5-trisubstituted pyrazol-4-yl)alkyl]-
b
b
b
b
a
b
b
benzotriazoles 1a–j reacted efficiently with the appropriate 1,3-
diketones 2 in the presence of 1.2 equiv t-BuOK in DMSO at room
temperature to afford the amidoalkylated product 3 in good yields
EtOH and then the mixture was stirred at reflux for 1 h. The solvent
was evaporated and the residue was placed on a silica gel column
and eluted with hexanes/EtOAc (1:1) to give the corresponding

_
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I. Çelik et al. / Tetrahedron 65 (2009) 328–335
Table 1
Preparation of b b-diketones 3a–j
0-amido
N-(
a
-Amidoalkyl)benzotriazole
Diketone
Product
Yield (%)
89a
O
O
N
O
O
N
Me
Me
N
1a
1b
3a
3b
Me
Ph
Me
Me
MeCOHN
MeCOHN
O
Me
O
O
Me O
N
N
O
O
Ph
Ph
Me
O
Ph
N
69b
EtCOHN
EtCOHN
EtCOHN
Me
Me
Me
O
Ph
N
N
O
O
O
O
N
N
1c
3c
53
t-BuCOHN
Ph
Ph
t-BuCOHN
OMe
OMe
O
Me
O
N
N
1d
3d
79
Me
Me
EtCOHN
EtCOHN
F
F
O
Me
O
N
N
O
O
O
O
Me
O
N
1e
1f
3e
3f
68
12
EtCOHN
Me
Ph
Me
Ph
EtCOHN
Cl
Cl
O
Ph
N
N
Ph
N
MeCOHN
MeCOHN
O2N
O2N
O
O
N
N
Me
MeCOHN
Me
N
O
O
1g
3g
85
MeCOHN
Me
Me
O
O
N
N
O
O
O
O
Me
N
Me
N
1h
1i
3h
3i
90
88
t-BuCOHN
Me
Me
Me
Me
t-BuCOHN
N
O
Me
O
N
N
Me
N
EtCOHN
EtCOHN
O
O
O
O
N
O
O
N
Ph
Ph
N
1j
3j
44
Ph
Ph
MeCOHN
MeCOHN
S
S
a
Lit.18b yield.
b
Diastereomeric ratio was evaluated by 1H NMR analysis.

_
I. Çelik et al. / Tetrahedron 65 (2009) 328–335
331
Table 2
Sythesis of N-[b-(3,5-di and 1,3,5-trisubstituted pyrazol-4-yl)alkyl]amides 4a–k
b
0-Amido
b
-diketone
Hydrazine
Product
Yield (%)a
66
O
O
Me
MeCOHN
Me
Me
N
N
3a
3b
3c
3d
3e
3f
NH2NH2
4a
4b
4c
4d
4e
4f
MeCOHN
H
Me
Me
Ph
O
O
Ph
EtCOHN
N
N
Me
NH2NH2
78
84
80
82
89
95
63
78
EtCOHN
H
Me
Me
Ph
O
O
t-BuCOHN
N
N
Ph
Ph
MeNHNH2
PhNHNH2
PhNHNH2
NH2NH2
t-BuCOHN
Me
Ph
OMe
MeO
Me
O
Me
O
O
EtCOHN
N
Me
Me
N
EtCOHN
Ph
Me
F
F
Me
O
Me
EtCOHN
N
N
EtCOHN
Ph
Me
Cl
Cl
O
Ph
O
Ph
MeCOHN
Ph
N
N
MeCOHN
H
O N
Ph
2
O2N
O
O
Me
MeCOHN
Me
MeCOHN
Me
N
N
3g
3h
3h
NH2NH2
4g
4h
4i
H
Me
O
O
Me
t-BuCOHN
Me
Me
N
NH2NH2
N
t-BuCOHN
H
Me
N
N
O
Me
O
Me
t-BuCOHN
Me
N
N
N
MeNHNH2
t-BuCOHN
Me
Me
N
O
Me
O
Me
EtCOHN
Me
N
N
3i
3j
NH2NH2
NH2NH2
4j
77
59
EtCOHN
H
Me
O
O
O
Ph
O
Ph
MeCOHN
Ph
N
N
4k
MeCOHN
H
Ph
S
S
a
Isolated yields.

_
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I. Çelik et al. / Tetrahedron 65 (2009) 328–335
NHCOR
139.2, 133.5, 132.8, 129.7, 127.9, 126.3, 124.3, 119.9, 109.9, 64.4, 29.2,
21.0, 9.2. Anal. Calcd for C17H18N4O: C, 69.37; H, 6.16; N, 19.03.
Found: C, 69.20; H, 6.31; N, 18.95.
R1
R2
O
O
R3
R4NHNH2/ EtOH
reflux/ 1h
R2
RCOHN
R3
N
R1
N
R4
4a-k
4.2.3. N-[Benzotriazol-1-yl-(4-methoxyphenyl)methyl]-2,2-
dimethyl propionamide 1c
3a-j
White crystals, yield 82%, mp 134–140 ꢀC; IR nmax (KBr): 3401
Scheme 4.
(NH), 1667 (CO) cmꢁ1
;
1H NMR
d
8.08 (d, J¼8.4 Hz, 1H), 7.81 (d,
J¼8.8 Hz, 1H), 7.64 (d, J¼8.4 Hz, 1H), 7.49 (t, J¼7.5 Hz, 1H), 7.39 (t,
J¼7.6 Hz, 1H), 7.26 (d, J¼8.6 Hz, 1H), 7.19 (d, J¼8.8 Hz, 2H), 6.88 (d,
N-[b-(3,5-di and 1,3,5-trisubstituted pyrazol-4-yl) alkyl] amide 4 in
J¼8.8 Hz, 2H), 3.79 (s, 3H), 1.25(s, 9H); 13C NMR
d 178.2, 160.2, 145.7,
good yields (59–95%) (Scheme 4 and Table 2).
The formation of the substituted pyrazole of 4 is indicated by the
loss of the carbonyl signals in 13C NMR spectra. The doublets at
6.97–6.19 ppm and at 6.23–5.96 ppm in the 1H NMR spectra of
4a–k were assigned to the methine proton next to the NH and NH
protons, respectively. The structure of compounds 4a–k was also
supported by their elemental analyses and spectral data.
132.7, 128.8, 127.9, 127.7, 124.3, 119.9, 114.5, 109.7, 64.4, 55.4, 38.9,
27.4. Anal. Calcd for C19H22N4O2: C, 67.44; H, 6.55; N, 16.56. Found:
C, 67.20; H, 6.87; N, 16.41.
4.2.4. N-[Benzotriazol-1-yl-(4-fluorophenyl)methyl]-
propionamide 1d
White crystals, yield 63%, mp 123–125 ꢀC; IR nmax (KBr): 3284
3. Conclusion
(NH), 1652 (CO) cmꢁ1
;
1H NMR
d
8.09 (d, J¼8.4 Hz, 1H), 7.91 (d,
J¼9.3 Hz, 1H), 7.67 (d, J¼8.3 Hz, 1H), 7.53 (t, J¼7.6 Hz, 1H), 7.42 (t,
J¼7.7 Hz, 2H), 7.29 (t, J¼6.8 Hz, 2H), 7.04 (t, J¼8.5 Hz, 2H), 2.39–2.29
In summary, we have developed a novel and convenient route
for the synthesis of a wide range of
method developed is simple and applicable to the preparation of b0
amido -diketones 3a–j. In many cases, -diketones were
0-amido
obtained in high yields. -diketones were treated with
0-Amido
hydrazine and substituted hydrazines to form N-[ -(3,5-di and
b b-diketones 3a–j. The
0-amido
(m, 2H), 1.17 (t, J¼7.5 Hz, 3H); 13C NMR
d 173.5, 145.7, 132.7, 128.5,
-
128.4, 128.2, 124.6, 120.0, 116.2, 116.0, 109.7, 63.7, 29.3, 9.2. Anal.
Calcd for C16H15FN4O: C, 64.42; H, 5.07; N, 18.78. Found: C, 64.37; H,
5.01; N, 18.52.
b
b
b
b
b
b
1,3,5-trisubstituted pyrazol-4-yl)alkyl]amides 4a–k in good to ex-
cellent yields. Our method proved that it is useful for the prepa-
ration of chiral pyrazole amides and allowed us to reach novel
pyrazole amides.
4.2.5. N-[Benzotriazol-1-yl-(4-chlorophenyl)methyl]-
propionamide 1e
White crystals, yield 74%, mp 133–134 ꢀC; IR nmax (KBr): 3298
(NH), 1650 (CO) cmꢁ1
;
1H NMR
d
8.07 (d, J¼8.3 Hz, 1H), 7.91 (d,
J¼9.0 Hz, 1H), 7.72 (d, J¼9.0 Hz, 1H), 7.68 (d, J¼8.3 Hz, 1H), 7.52 (t,
J¼7.5 Hz, 1H), 7.42 (t, J¼7.5 Hz, 1H), 7.30 (d, J¼8.3 Hz, 2H), 7.22 (d,
J¼8.1 Hz, 2H), 2.43–2.28 (m, 2H), 1.15 (t, J¼7.4 Hz, 3H); 13C NMR
4. Experimental section
4.1. General
d
173.8, 145.6, 135.3, 134.9, 132.8, 129.2, 128.2, 128.0, 124.6, 119.9,
109.8, 63.7, 29.2, 9.2. Anal. Calcd for C16H15ClN4O: C, 61.05; H, 4.80;
N, 17.80. Found: C, 61.16; H, 5.01; N, 17.62.
All melting points are uncorrected. The glassware was routinely
oven-dried at 110 ꢀC for a minimum of 4 h. DMSO was dried over
molecular sieves prior to use. Column chromatography was per-
formed on silica gel 70–230 mesh. 1H and 13C NMR spectra were
recorded on a Bruker Advance 500 DPX spectrometer (1H at
500 MHz and 13 C at 125 MHz) in CDCl3 with TMS as the internal
standard. Elemental analyses were carried out on a VarioEL III in-
strument. FTIR spectra were determined on a PerkinElmer 100 FT-
IR spectrometer.
4.2.6. N-[Benzotriazol-1-yl-(2-nitrophenyl)methyl]acetamide 1f
Yellow powder, yield 70%, mp 157–158 ꢀC; IR nmax (KBr): 3245
(NH), 1691 (CO) cmꢁ1
;
1H NMR
d
8.64 (d, J¼9.3 Hz, 1H), 8.07–8.04
(m, 2H), 7.98 (d, J¼8.4 Hz, 1H), 7.88 (d, J¼8.4 Hz, 1H), 7.77 (d,
J¼8.1 Hz, 1H), 7.62–7.56 (m, 3H), 7.42 (t, J¼7.7 Hz, 1H), 2.10 (s, 3H);
13C NMR
d 169.9, 147.9, 145.4, 133.8, 132.8, 130.7, 130.4, 129.3, 128.5,
125.6, 124.9, 119.5, 110.6, 60.8, 22.9. Anal. Calcd for C15H13N5O3: C,
57.87; H, 4.21; N, 22.20. Found: C, 57.67; H, 4.35; N, 22.10.
4.2. General procedure for the preparation of
N-(a
-amidoalkyl)benzotriazoles (1a–j)
4.2.7. N-(Benzotriazol-1-yl-naphthalen-1-yl-methyl)acetamide 1g
White crystals, yield 82%, mp 154–156 ꢀC; IR nmax (KBr): 3311
N-(
a
-Amidoalkyl)benzotriazoles 1 were prepared according to
(NH), 1663 (CO) cmꢁ1
;
1H NMR
d
8.59 (d, J¼9.3 Hz, 1H), 8.09 (dd,
the literature procedure.14a
J¼11.6, 8.3 Hz, 2H), 7.94 (d, J¼7.7 Hz, 1H), 7.87 (d, J¼7.7 Hz, 1H),
7.64–7.57 (m, 2H), 7.54–7.51 (m, 2H), 7.45–7.35 (m, 3H), 7.31 (t,
4.2.1. N-(Benzotriazol-1-yl-phenylmethyl)acetamide 1a
J¼7.8 Hz, 1H), 2.11 (s, 3H); 13C NMR
d 169.8, 133.9, 132.6, 131.7, 130.3,
White crystals, mp 175–177 ꢀC (lit.14h mp 174–177 ꢀC); IR nmax
(KBr): 3298 (NH), 1654 (CO) cmꢁ1; 1H NMR
d
8.24 (d, J¼9.0 Hz, 1H),
130.2, 129.1, 127.9, 127.6, 126.5, 125.1, 124.5, 124.4, 122.4, 120.0,
118.4, 109.9, 62.4, 23.0. Anal. Calcd for C19H16N4O: C, 72.13; H, 5.10;
N, 17.71. Found: C, 72.01; H, 5.23; N, 17.81.
8.03 (d, J¼8.3 Hz, 1H), 7.93 (d, J¼9.1 Hz, 1H), 7.66 (d, J¼8.33 Hz, 1H),
7.44 (t, J¼7.6 Hz, 1H), 7.36 (t, J¼7.6 Hz, 1H), 7.31–7.29 (m, 5H), 2.06
(s, 3H); 13C NMR
d 170.5, 145.6, 136.1, 132.8, 129.2, 129.0, 128.0,
4.2.8. N-(Benzotriazole-1-yl-pyridin-3-yl-methyl)propionamide 1h
White crystals, yield 85%, mp 73–75 ꢀC; IR nmax (KBr): 3336
126.5, 124.5, 119.8, 110.0, 64.7, 22.9. Anal. Calcd for C15H14N4O: C,
67.65; H, 5.30; N, 21.04. Found: C, 67.52; H, 5.25; N, 21.20.
(NH), 1674 (CO) cmꢁ1
;
1H NMR
d
8.62 (d, J¼2.1 Hz, 1H), 8.58 (d,
J¼3.9 Hz, 1H), 8.06 (d, J¼8.4 Hz, 1H), 8.00 (d, J¼9.0 Hz, 1H), 7.83 (d,
J¼8.2 Hz, 1H), 7.71 (d, J¼8.4 Hz, 1H), 7.52 (t, J¼7.3 Hz, 2H), 7.41 (t,
J¼7.3 Hz, 1H), 7.25 (dd, J¼8.0, 4.9 Hz, 1H), 1.24 (s, 9H); 13C NMR
4.2.2. N-(Benzotriazol-1-yl-p-tolylmethyl)propionamide 1b
White crystals, yield 68%, mp 112–113 ꢀC; IR nmax (KBr): 3314
(NH), 1667 (CO) cmꢁ1
;
1H NMR
d
8.07 (d, J¼8.4 Hz, 1H), 7.88 (d,
d
178.7, 150.2, 147.9, 145.6, 134.4, 132.8, 132.6, 128.4, 124.7, 123.7,
J¼9.1 Hz, 1H), 7.67 (d, J¼8.4 Hz, 1H), 7.49 (t, J¼7.3 Hz, 2H), 7.39 (t,
120.0, 109.6, 62.7, 39.0, 27.2. Anal. Calcd for C17H19N5O: C, 66.00; H,
6.16; N, 22.64. Found: C, 65.71; H, 6.52; N, 22.79.
J¼7.3 Hz, 1H), 7.19–7.13 (m, 4H), 2.39–2.34 (m, 1H), 2.33 (s, 3H),
2.32–2.27 (m, 1H), 1.15 (t, J¼7.6 Hz, 3H); 13C NMR
d 173.6, 145.7,

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333
4.2.9. N-(Benzotriazol-1-yl-furan-3-yl-methyl)propionamide 1i
Yellow powder, yield 56%, mp 175–177 ꢀC; IR nmax (KBr): 3255
(d, J¼8.1 Hz, 2H), 7.93 (d, J¼8.6 Hz, 1H), 7.82 (d, J¼8.2 Hz, 2H), 7.67
(t, J¼7.4 Hz, 1H), 7.58–7.52 (m, 3H), 7.40 (t, J¼7.8 Hz, 2H), 7.33 (d,
J¼8.6 Hz, 2H), 6.84 (d, J¼8.6 Hz, 2H), 6.04 (d, J¼3.5 Hz,1H), 5.86 (dd,
(NH), 1685 (CO) cmꢁ1
;
1H NMR
d
8.07 (d, J¼8.4 Hz, 1H), 7.88 (d,
J¼9.1 Hz, 1H), 7.80 (d, J¼8.3 Hz, 1H), 7.52 (t, J¼7.8 Hz, 1H), 7.48 (s,
J¼8.6, 3.3 Hz, 1H), 3.77 (s, 3H), 1.23 (s, 9H); 13C NMR
d 196.7, 193.8,
1H), 7.45 (d, J¼9.1 Hz,1H), 7.43–7.39 (m, 3H), 2.38–2.21 (m, 2H),1.13
178.0, 158.8, 136.5, 135.2, 134.1, 133.8, 132.3, 129.3, 128.9, 128.6,
128.3, 127.7, 114.1, 59.0, 55.3, 52.2, 38.8, 27.5. Anal. Calcd for
C28H29NO4: C, 75.82; H, 6.59; N, 3.16. Found: C, 75.61; H, 6.81; N,
3.02.
(t, J¼7.5 Hz, 3H); 13C NMR
d 173.6, 145.5, 144.2, 140.9, 132.5, 128.1,
124.5, 122.5, 119.8, 110.0, 109.2, 58.2, 29.1, 9.2. Anal. Calcd for
C14H14N4O2: C, 62.21; H, 5.22; N, 20.73. Found: C, 61.83; H, 5.30; N,
20.63.
4.3.4. N-[2-Acetyl-1-(4-fluorophenyl)-3-oxobutyl]propionamide 3d
White crystals, yield 79%, mp 138–139 ꢀC; IR nmax (KBr): 3291
(NH), 1723 (CO, diketone), 1701 (CO, diketone), 1647 (CO,
4.2.10. N-(Benzotriazol-1-yl-thiophen-2-yl-methyl)acetamide 1j
Brown crystals, yield 67%, mp 141–142 ꢀC; IR nmax (KBr): 3240
(NH), 1684 (CO) cmꢁ1
;
1H NMR
d
8.56 (d, J¼8.9 Hz, 1H), 8.17 (d,
amide) cmꢁ1
;
1H NMR
d
7.28–7.25 (m, 2H), 7.09 (d, J¼9.2 Hz, 1H),
J¼8.9 Hz, 1H), 8.05 (d, J¼8.2 Hz, 1H), 7.76 (d, J¼8.2 Hz, 1H), 7.50 (t,
J¼7.6 Hz, 1H), 7.40 (t, J¼7.6 Hz, 1H), 7.28 (d, J¼4.8 Hz, 1H), 7.03 (d,
J¼3.4 Hz, 1H), 6.92 (AB, JAB¼4.8, 3.8 Hz, 1H), 2.06 (s, 3H); 13C NMR
7.02 (d, J¼8.6 Hz, 2H), 5.84 (dd, J¼9.3, 6.0 Hz, 1H), 4.29 (d,
J¼5.9 Hz, 1H), 2.26 (s, 3H), 2.22 (q, J¼7.6 Hz, 2H), 2.11 (s, 3H),
1.13 (t, J¼7.6 Hz, 3H); 13C NMR
d 205.1, 202.4, 173.5, 128.2, 128.1,
d
170.2, 145.4, 138.8, 132.3, 127.9, 126.9, 126.8, 126.7, 124.4, 119.7,
115.8, 115.6, 70.6, 51.1, 31.0, 30.0, 29.7, 9.7. Anal. Calcd for
C15H18FNO3: C, 64.50; H, 6.50; N, 5.01. Found: C, 64.42; H, 6.67;
N, 4.88.
110.0, 61.0, 22.6. Anal. Calcd for C13H12N4OS: C, 57.34; H, 4.44; N,
20.57. Found: C, 57.16; H, 4.50; N, 20.21.
4.3. General procedure for the preparation of
-diketones (3a–j)
b
0-amido
4.3.5. N-[2-Acetyl-1-(4-chlorophenyl)-3-oxobutyl]propionamide 3e
White crystals, yield 68%, mp 146–147 ꢀC; IR nmax (KBr): 3288
(NH), 1703 (CO, diketone), 1701 (CO, diketone), 1646 (CO,
b
A mixture of 1,3-diketone (2 mmol) and potassium tert-but-
oxide (0.25 g, 2.4 mmol) in DMSO (10 mL) was stirred at room
temperature for 40 min. To the resulting solution, N-( -ami-
doalkyl)benzotriazoles 1 (2 mmol) in DMSO (10 mL) was added
dropwise and the mixture was stirred at room temperature for 8 h.
The mixture was poured into water (40 mL) and then extracted
with ethyl acetate (4ꢂ25 mL). The extracts were washed with
water, dried over MgSO4, and the solvent was removed under re-
duced pressure. The residue was placed in a silica gel column and
eluted with hexanes/EtOAc (1:1) to give the pure product 3.
amide) cmꢁ1
;
1H NMR
d
7.32–7.29 (m, 2H), 7.23 (d, J¼8.5 Hz, 2H),
7.06 (d, J¼9.2 Hz, 1H), 5.84 (dd, J¼9.3, 5.6 Hz, 1H), 4.28 (d, J¼5.6 Hz,
a
1H), 2.29 (s, 3H), 2.25 (q, J¼7.6 Hz, 2H), 2.11 (s, 3H), 1.15 (t, J¼7.6 Hz,
3H); 13C NMR
d 205.1, 202.3, 173.5, 138.0, 133.6, 129.0, 127.8, 70.2,
51.1, 31.2, 29.9, 29.7, 9.7. Anal. Calcd for C15H18ClNO3: C, 60.91; H,
6.13; N, 4.74. Found: C, 60.73; H, 6.34; N, 4.54.
4.3.6. N-[2-Benzoyl-(2-nitrophenyl)-3-oxo-3-
phenylpropyl]acetamide 3f
Yellow crystals, yield 12%, mp 106–107 ꢀC; IR nmax (KBr): 3284
(NH), 1695 (CO, diketone), 1669 (CO, amide) cmꢁ1 1H NMR
; d 8.15
4.3.1. N-(2-Acetyl-3-oxo-1-phenylbutyl)acetamide 3a
(d, J¼7.6 Hz, 2H), 7.97 (d, J¼7.2 Hz, 1H), 7.80 (d, J¼7.5 Hz, 2H), 7.77
(d, J¼7.9 Hz, 1H), 7.65 (t, J¼7.4 Hz, 1H), 7.57–7.52 (m, 5H), 7.39 (t,
J¼7.9 Hz, 3H), 6.45 (d, J¼4.7 Hz, 1H), 6.28 (dd, J¼7.9, 4.4 Hz, 1H),
White crystals, yield 89% mp 133–134 ꢀC (lit.18b mp 132–133 ꢀC);
IR nmax (KBr): 3359 (NH), 1700 (CO, diketone), 1670 (CO, diketone),
1649 (CO, amide), 1586, 1529, 1456, 1366, 1298, 1274, 1201, 1162,
2.00 (s, 3H); 13C NMR
d 195.9, 193.7, 169.6, 148.2, 136.5, 135.3, 134.9,
1104, 953, 891, 758, 706, 617 cmꢁ1
;
1H NMR
d
7.35–7.25 (m, 5H),
7.13 (d, J¼9.5 Hz, 1H), 5.88 (dd, J¼9.4, 5.9 Hz, 1H), 4.32 (d, J¼5.9 Hz,
1H), 2.27 (s, 3H), 2.11 (s, 3H), 2.01 (s, 3H); 13C NMR
205.3, 202.6,
134.3, 134.1, 133.5, 131.0, 129.2, 129.0, 128.9, 128.7, 128.3, 125.1, 56.6,
50.3, 23.2. Anal. Calcd for C24H20N2O5: C, 69.22; H, 4.84; N, 6.73.
Found: C, 68.84; H, 5.05; N, 6.96.
d
169.8, 139.3, 128.9, 127.7, 126.4, 70.5, 51.9, 31.1, 30.0, 23.3. Anal.
Calcd for C14H17NO3: C, 68.00; H, 6.93; N, 5.66. Found: C, 67.85; H,
6.82; N, 5.60.
4.3.7. N-(2-Acetyl-1-naphthalen-1-yl-3-oxobutyl)acetamide 3g
White crystals, yield 85%, mp 181–182 ꢀC; IR nmax (KBr): 3258
(NH), 1722 (CO, diketone), 1703 (CO, diketone), 1648 (CO,
4.3.2. N-(2-Benzoyl-3-oxo-1-p-tolylbutyl)propionamide 3b
White crystals, yield 69%, mp 59–60 ꢀC; diastereoisomeric
mixture (syn/anti: 50:50); IR nmax (KBr): 3285 (NH), 1723 (CO,
amide) cmꢁ1
;
1H NMR
d
8.22 (d, J¼8.5 Hz, 1H), 7.89 (d, J¼8.1 Hz,
1H), 7.79 (t, J¼4.7 Hz, 1H), 7.63 (t, J¼7.7 Hz, 1H), 7.54 (t,
J¼7.5 Hz, 1H), 7.40 (d, J¼4.0 Hz, 2H), 7.34 (br s, 1H), 6.67 (dd, J¼9.2,
5.8 Hz, 1H), 4.49 (d, J¼5.7 Hz, 1H), 2.34 (s, 3H), 2.00 (s, 3H), 1.98 (s,
diketone), 1676 (CO, diketone), 1647 (CO, amide) cmꢁ1 1H NMR
;
d
7.95 (d, J¼8.2 Hz, 1H), 7.80 (d, J¼8.2 Hz, 1H), 7.63–7.57 (m, 1H),
3H); 13C NMR
d 205.6, 202.3, 169.5, 134.7, 134.0, 130.2, 129.3, 128.7,
7.50 (t, J¼7.7 Hz, 1H), 7.45 (t, J¼7.8 Hz, 1.5H), 7.24 (d, J¼8.0 Hz,
1H), 7.20 (d, J¼8.1 Hz, 1H), 7.11 (d, J¼8.0 Hz, 1H), 7.08 (d, J¼8.0 Hz,
1H), 6.57 (d, J¼9.3 Hz, 0.5H), 6.01 (dd, J¼9.2, 4.2 Hz, 0.5H), 5.95 (t,
J¼8.5 Hz, 0.5H), 5.19 (d, J¼4.3 Hz, 0.5H), 5.14 (d, J¼7.6 Hz, 0.5H),
2.41 (s, 1.5H), 2.32–2.29 (m, 1H), 2.31 (s, 1.5H), 2.28 (s, 1.5H), 2.23–
2.21 (m, 1H), 2.19 (s, 1.5H), 1.18 (t, J¼7.6 Hz, 1.5H), 1.13 (t, J¼7.6 Hz,
127.1, 126.0, 125.2, 124.1, 122.4, 69.5, 48.2, 31.5, 29.8, 23.2. Anal.
Calcd for C18H19NO3: C, 72.71; H, 6.44; N, 4.71. Found: C, 72.36; H,
6.41; N, 4.81.
4.3.8. N-(2-Acetyl-3-oxo-1-pyridin-3-yl-butyl)-2,2-dimethyl
propionamide 3h
White crystals, yield 90%, mp 164–165 ꢀC; IR nmax (KBr): 3329
(NH), 1726 (CO, diketone), 1704 (CO, diketone), 1635 (CO,
1.5H); 13C NMR
d 204.2, 202.5, 197.4, 193.9, 173.5, 173.1, 137.5, 137.2,
136.9, 136.4, 136.0, 134.0, 133.9, 129.5, 129.4, 129.0, 128.9, 128.6,
128.3, 126.7, 126.3, 67.0, 64.3, 52.2, 51.8, 29.8, 29.4, 29.0, 21.0, 9.7.
Anal. Calcd for C21H23NO3: C, 74.75; H, 6.87; N, 4.15. Found: C,
75.64; H, 7.20; N, 4.11.
amide) cmꢁ1
;
1H NMR
d
8.57 (d, J¼2.2 Hz, 1H), 8.53 (dd, J¼4.8,
3.4 Hz, 1H), 7.59 (d, J¼8.1 Hz, 1H), 7.45 (d, J¼9.1 Hz, 1H), 7.29–7.28
(m, 1H), 5.89 (dd, J¼9.1, 4.7 Hz, 1H), 4.35 (d, J¼4.7 Hz, 1H), 2.36 (s,
3H), 2.11 (s, 3H), 1.22 (s, 9H); 13C NMR 205.3, 202.2, 178.4, 149.0,
147.9, 135.3, 134.2, 123.5, 69.4, 49.4, 38.9, 31.5, 29.7, 27.3. Anal.
Calcd. for C16H22N2O3: C, 66.18; H, 7.64; N, 9.65. Found: C, 65.97; H,
7.61; N, 9.93.
4.3.3. N-[2-Benzoyl-1-(4-methoxyphenyl)-3-oxo-3-phenylpropyl]-
2,2-dimethyl propionamide 3c
White crystals, yield 53%, mp 180–181 ꢀC; IR nmax (KBr): 3386
(NH), 1690 (CO, diketone), 1655 (CO, amide) cmꢁ1 1H NMR
; d 8.07

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334
4.3.9. N-(2-Acetyl-1-furan-3-yl-3-oxobutyl)propionamide 3i
White crystals, yield 88%, mp 128–130 ꢀC; IR nmax (KBr): 3304
(NH), 1721 (CO, diketone), 1699 (CO, diketone), 1647 (CO,
(m, 3H), 7.24 (dd, J¼8.4, 5.4 Hz, 2H), 7.04 (t, J¼8.6 Hz, 2H), 6.33 (d,
J¼7.7 Hz, 1H), 6.03(d, J¼7.6 Hz, 1H), 2.39–2.34 (m, 2H), 2.21 (s, 3H),
2.10 (s, 3H), 1.25 (t, J¼7.6 Hz, 3H); 13C NMR
d 173.0, 147.2, 137.8,
amide) cmꢁ1
;
1H NMR
d
7.33 (d, J¼13.1 Hz, 2H), 6.96 (d, J¼9.3 Hz,
129.1,128.1,128.0,127.8,125.1,117.8,115.5,115.3, 47.6, 29.7,13.0,11.1,
9.9. Anal. Calcd for C21H22FN3O: C, 71.77; H, 6.31; N, 11.96. Found: C,
71.68; H, 6.51; N, 11.86.
1H), 6.31 (s, 1H), 5.81 (dd, J¼9.4, 5.4 Hz, 1H), 4.23 (d, J¼5.6 Hz, 1H),
2.28 (s, 3H), 2.19 (q, J¼7.6 Hz, 2H), 2.17 (s, 3H), 1.11 (t, J¼7.6 Hz, 3H);
13C NMR
d 205.1, 202.8, 173.5, 143.5, 139.7, 124.5, 109.1, 69.8, 44.5,
31.0, 30.0, 29.6, 9.7. Anal. Calcd for C13H17NO4: C, 62.14; H, 6.82; N,
5.57. Found: C, 62.34; H, 6.83; N, 5.75.
4.4.5. N-[(4-Chlorophenyl)-(3,5-dimethyl-1-phenyl-1H-pyrazol-4-
yl)methyl]propionamide 4e
White crystals, yield 82%, mp 179–180 ꢀC; IR nmax (KBr): 3247
4.3.10. N-(2-Benzoyl-3-oxo-3-phenyl-1-thiophen-2-yl-
propyl)acetamide 3j
(NH),1670 (CO) cmꢁ1; 1H NMR
d
7.49 (t, J¼7.6 Hz, 2H), 7.43–7.38 (m,
3H), 7.32 (d, J¼8.4 Hz, 2H), 7.20 (d, J¼8.4 Hz, 2H), 6.31 (d, J¼7.7 Hz,
White crystals, yield 44%, mp 148–149 ꢀC; IR nmax (KBr): 3346
1H), 6.09 (d, J¼7.5 Hz, 1H), 2.40–2.32 (m, 2H), 2.20 (s, 3H), 2.08 (s,
(NH), 1690 (CO, diketone), 1658 (CO, amide) cmꢁ1
;
1H NMR
d
8.05
3H), 1.24 (t, J¼7.6 Hz, 3H); 13C NMR
d 173.0, 147.2, 139.3, 139.2, 137.8,
(d, J¼8.5 Hz, 2H), 7.90 (d, J¼8.4 Hz, 2H), 7.65 (t, J¼7.4 Hz, 1H), 7.60–
7.55 (m, 4H), 7.44 (t, J¼7.8 Hz, 2H), 7.18 (dd, J¼5.1, 1.1 Hz, 1H), 6.98
(d, J¼3.5 Hz, 1H), 6.90 (dd, J¼5.1, 3.6 Hz, 1H), 6.20 (dd, J¼9.1, 3.9 Hz,
133.0, 129.2, 128.7, 127.8, 125.1, 117.6, 47.6, 29.6, 13.0, 11.1, 9.9. Anal.
Calcd for C21H22ClN3O: C, 68.56; H, 6.03; N, 11.42. Found: C, 68.37;
H, 6.24; N, 11.23.
1H), 6.13 (d, J¼3.9 Hz,1H), 2.00 (s, 3H); 13C NMR
d 196.1,193.7,169.7,
143.2, 136.1, 134.2, 134.0, 129.3, 129.0, 128.6, 128.4, 126.8, 125.3,
125.1,120.0, 59.1, 49.4, 23.2. Anal. Calcd for C22H19NO3S: C, 70.00; H,
5.07; N, 3.71. Found: C, 69.91; H, 5.17; N, 3.57.
4.4.6. N-[(3,5-Diphenyl-1H-pyrazol-4-yl)-(2-nitrophenyl)-
methyl]acetamide 4f
White crystals, yield 89%, mp 255–256 ꢀC; nmax (KBr): 3412
(NH), 3340–3122 (NH, br), 1655 (CO) cmꢁ1 1H NMR
; d 7.59 (dd,
4.4. General procedure for the preparation of N-[
1,3,5-trisubstituted pyrazol-4-yl)alkyl] amides (4a–j)
b
-(3,5-di and
J¼7.9, 1.3 Hz, 1H), 7.30 (d, J¼4.5 Hz, 2H), 7.26 (d, J¼4.4 Hz, 8H), 7.22
(dt, J¼6.9, 1.4 Hz, 2H), 7.16 (dt, J¼7.0, 1.3 Hz, 1H), 6.97 (d, J¼7.8 Hz,
1H), 6.23 (d, J¼7.8 Hz, 1H), 1.78 (s, 3H); 13C NMR
d 169.0, 148.5,
A solution of hydrazine (3 mmol) was slowly added to the cor-
135.0, 132.2, 129.7, 128.7, 128.5, 128.4, 128.1, 124.8, 113.9, 47.1, 22.7.
Anal. Calcd for C24H20N4O3: C, 69.89; H, 4.89; N, 13.58. Found: C,
69.66; H, 5.01; N, 13.37.
responding
b b-diketone (2 mmol) in absolute EtOH
0-amido
(10 mL) and the mixture was stirred at reflux for 1 h. The residue
was placed on a silica gel column and eluted with hexanes/EtOAc
(1:1) to give the pure product 4.
4.4.7. N-[(3,5-Dimethyl-1H-pyrazol-4-yl)naphthalen-1-yl-
methyl]acetamide 4g
4.4.1. N-[(3,5-Dimethyl-1H-pyrazol-4-yl)phenylmethyl]-
acetamide 4a
White crystals, yield 95%, mp 245–246 ꢀC; IR nmax (KBr): 3410–
3155 (NH, br), 1649 (CO) cmꢁ1; 1H NMR
d
7.89 (t, J¼8.3 Hz, 2H), 7.83
White crystals. Yield 66%, mp 208–209 ꢀC; IR nmax (KBr): 3405–
(d, J¼7.8 Hz, 1H), 7.50–7.46 (m, 2H), 7.44 (d, J¼7.7 Hz, 1H), 7.41 (d,
J¼6.7 Hz, 1H), 6.87 (d, J¼7.7 Hz, 1H), 5.96 (d, J¼7.7 Hz, 1H), 2.11 (s,
3150 (NH, br) 1646 (CO) cmꢁ1; 1H NMR
d
7.33 (t, J¼7.5 Hz, 2H), 7.28
(t, J¼7.2 Hz, 1H), 7.22 (d, J¼7.6 Hz, 2H), 6.28 (d, J¼8.0 Hz, 1H), 6.10
3H), 2.04 (s, 6H); 13C NMR
d 168.6, 135.6, 134.1, 130.9, 128.8, 128.5,
(d, J¼7.8 Hz, 1H), 2.10 (s, 3H), 2.08 (s, 6H); 13C NMR
d
169.4, 142.8,
126.4, 125.9, 125.0, 123.9, 123.5, 115.1, 65.9, 46.4, 23.2, 11.6. Anal.
Calcd for C18H19N3O: C, 73.69; H, 6.53; N, 14.32. Found: C, 73.79; H,
6.69; N, 14.28.
140.5, 128.5, 127.1, 126.4, 115.7, 48.0, 23.2, 11.5. Anal. Calcd for
C14H17N3O: C, 69.11; H, 7.04; N, 17.27. Found: C, 69.02; H, 6.93; N,
17.04.
4.4.8. N-[(3,5-Dimethyl-1H-pyrazol-4-yl)-(pyridin-3-yl)methyl]-
2,2-dimethyl propionamide 4h
4.4.2. N-[(3-Methyl-5-phenyl-1H-pyrazol-4-yl)-(p-tolyl)-
methyl]propionamide 4b
White crystals, yield 63%, mp 127–128 ꢀC; IR nmax (KBr): 3461–
White crystals, yield 78%, mp 143–144 ꢀC; IR nmax (KBr): 3428–
3158 (NH, br), 1645 (CO) cmꢁ1
;
1H NMR
d
8.54 (d, J¼15.0 Hz, 2H),
3124 (NH, br), 1647 (CO) cmꢁ1
;
1H NMR
d
7.43–7.40 (m, 2H), 7.36
7.57 (br s, 1H), 7.49 (d, J¼8.3 Hz, 1H), 7.31 (s, 1H), 6.26 (d, J¼7.2 Hz,
1H), 6.18 (d, J¼7.2 Hz, 1H), 2.12 (s, 6H), 1.29 (s, 9H); 13C NMR 177.9,
148.1, 147.7, 142.8, 136.7, 134.4, 123.6, 115.0, 46.2, 38.9, 31.6, 27.6,
11.5. Anal. Calcd for C16H22N4O: C, 67.11; H, 7.74; N, 19.56. Found: C,
67.28; H, 7.93; N, 19.38.
(dd, J¼5.0, 1.6 Hz, 3H), 7.13 (d, J¼8.2 Hz, 2H), 7.09 (d, J¼8.0 Hz, 2H),
6.39 (d, J¼8.4 Hz, 1H), 5.96 (d, J¼8.4 Hz, 1H), 2.35 (s, 3H), 2.16–2.09
(m, 2H), 2.08 (s, 3H), 1.04 (t, J¼7.6 Hz, 3H); 13C NMR
d 172.6, 138.4,
136.9, 129.3, 128.8, 128.4, 126.7, 115.6, 47.7, 29.6, 25.1, 21.0, 9.5. Anal.
Calcd for C21H23N3O: C, 75.65; H, 6.95; N, 12.60. Found: C, 75.47; H,
7.16; N, 12.56.
4.4.9. 2,2-Dimethyl-N-[pyridin-3-yl-(1,3,5-trimethyl-1H-pyrazol-
4-yl)methyl]propionamide 4i
4.4.3. N-[(4-Methoxyphenyl)-(1-methyl-3,5-diphenyl-1H-pyrazol-
4-yl)methyl]-2,2-dimethyl propionamide 4c
White crystals, yield 78%, mp 142–143 ꢀC; IR nmax (KBr): 3309
(NH), 1629 (CO) cmꢁ1 1H NMR
; d 8.51–8.46 (m, 2H), 7.47 (d,
White crystals, yield 84%, mp 111–112 ꢀC; IR nmax (KBr): 3448
J¼7.9 Hz, 1H), 7.27–7.24 (m, 1H), 6.19 (d, J¼7.3 Hz, 1H), 6.08 (d,
(NH), 1660 (CO) cmꢁ1 1H NMR
; d 7.43–7.38 (m, 5H), 7.35–7.32 (m,
J¼7.2 Hz, 1H), 3.70 (s, 3H), 2.12 (s, 3H), 2.02 (s, 3H), 1.26 (s, 9H); 13C
5H), 7.13 (d, J¼8.2 Hz, 2H), 6.87 (d, J¼8.8 Hz, 2H), 6.34 (d, J¼9.1 Hz,
NMR d 177.7, 148.3, 148.1, 145.1, 136.6, 134.1, 123.3, 115.4, 46.5, 36.0,
1H), 6.09 (d, J¼9.0 Hz, 1H), 3.84 (s, 3H), 3.83 (s, 3H), 0.87 (s, 9H); 13C
27.6, 27.3, 12.9, 9.9. Anal. Calcd for C17H24N4O: C, 67.97; H, 8.05; N,
18.65. Found: C, 67.74; H, 8.14; N, 18.46.
NMR
d 176.9, 158.6, 149.2, 142.4, 135.3, 129.9, 129.0, 128.7, 128.5,
128.0, 113.9, 55.3, 47.3, 38.4, 37.3, 27.1. Anal. Calcd for C29H31N3O2:
C, 76.79; H, 6.89; N, 9.26. Found: C, 76.55; H, 7.05; N, 9.04.
4.4.10. N-[(3,5-Dimethyl-1H-pyrazol-4-yl)-furan-3-yl-
methyl]propionamide 4j
4.4.4. N-[(3,5-Dimethyl-1-phenyl-1H-pyrazol-4-yl)-(4-fluoro-
phenyl)methyl]propionamide 4d
Yellow crystals, yield 77%, mp 177–178 ꢀC; IR nmax (KBr): 3464–
3125 (NH, br), 1651(CO) cmꢁ1; 1H NMR
d 9.35 (br s, 1H), 7.37 (s, 1H),
Yellow crystals, yield 80%, mp 178–179 ꢀC; IR nmax (KBr): 3255
7.13 (s, 1H), 6.26 (d, J¼7.9 Hz, 1H), 6.22 (s, 1H), 6.10 (d, J¼7.3 Hz, 1H),
(NH), 1669 (CO) cmꢁ1
;
1H NMR
d
7.49 (t, J¼7.7 Hz, 2H), 7.44–7.39
2.30–2.22 (m, 2H), 2.17 (s, 6H), 1.16 (t, J¼7.6 Hz, 3H); 13C NMR

_
I. Çelik et al. / Tetrahedron 65 (2009) 328–335
335
9. (a) Mukherjee, A.; Sarkar, A. ARKIVOC 2003, ix, 87–95; (b) Sanz, D.; Jimenez,
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A. N.; Grandberg, I. I. Adv. Heterocycl. Chem. 1966, 6, 347–429.
d
173.0, 143.6, 142.4, 139.9, 126.5, 115.0, 109.8, 41.5, 29.6, 11.4, 9.9.
Anal. Calcd for C13H17N3O2: C, 63.14; H, 6.93; N, 16.99. Found: C,
63.07; H, 7.08; N, 16.72.
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4.4.11. N-[(3,5-Diphenyl-1H-pyrazol-4-yl)-thiophen-2-yl-
methyl]acetamide 4k
White crystals, yield 59%, mp 167–169 ꢀC; IR nmax (KBr): 3426
(NH), 3352–3131 (NH, br) cmꢁ1; 1H NMR
d 7.52–7.48 (m, 4H), 7.40–
7.39 (m, 6H), 7.29 (d, J¼4.3 Hz, 1H), 6.95 (t, J¼4.3 Hz, 1H), 6.87 (dd,
J¼3.4, 1.1 Hz, 1H), 6.66 (d, J¼8.9 Hz, 1H), 5.98 (d, J¼8.9 Hz, 1H), 1.68
(s, 3H); 13C NMR
d 168.7, 147.7, 129.0, 128.8, 128.5, 127.2, 125.4, 115.9,
45.1, 22.9. Anal. Calcd for C22H19N3OS: C, 70.75; H, 5.13; N, 11.25.
Found: C, 70.55; H, 5.37; N, 10.98.
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