Synthesis of new compounds containing the pyrazolo[3,4-b]pyridine-3-one subunit

Article abstract of DOI:10.1002/jhet.199

(Chemical Equation Presented) A convenient route for the synthesis of pyrazolo[3,4-b]pyridine-3-ones via condensation of 3-amino-1-phenylpyrazolin-5- one with 4-hydroxy-6-methylpyran-2-one is described. The pyrazolo[3,4-b] pyridine-3-one isomers obtained

Full text of DOI:10.1002/jhet.199

November 2009
Synthesis of New Compounds Containing the
Pyrazolo[3,4-b]pyridine-3-one Subunit
1177
S. Fadel,a F. Suzenet,b A. Hafid,a E. M. Rakib,a M. Khouili,a* M. D. Pujol,c
and G. Guillaumetb
a
´
Laboratoire de Chimie Organique et Analytique, FST Beni-Mellal, BP 523,
´
´
23000 Beni-Mellal, Universite Sultan Moulay Slimane, Morocco
bInstitut de Chimie Organique et Analytique (ICOA), UMR-CNRS 6005, BP 6759,
´
´
´
45067 Orleans Cedex 2, Universite d’Orleans, France
cLaboratori Quimica Farmacutica, Facultat de Farmacia, 08028, Barcelona,
Universitat de Barcelona, Spain
*E-mail: mkhouili@yahoo.fr
Received February 26, 2009
DOI 10.1002/jhet.199
Published online 5 November 2009 in Wiley InterScience (www.interscience.wiley.com).
A convenient route for the synthesis of pyrazolo[3,4-b]pyridine-3-ones via condensation of 3-amino-
1-phenylpyrazolin-5-one with 4-hydroxy-6-methylpyran-2-one is described. The pyrazolo[3,4-b]pyridine-
3-one isomers obtained were functionalized at 1-, 4-, or 6- position by different pharmacophore entities
allowing the synthesis of new compounds with promising biological activities.
J. Heterocyclic Chem., 46, 1177 (2009).
INTRODUCTION
butanol at reflux with or without PTSA as catalyst. Pyr-
azolo[3,4-b]pyridine-3-one 4 was isolated in both cases
with moderate yields (36–40%). Depending on the reac-
tion conditions used (presence or not of the catalyst),
the product 4 was accompanied with pyrazolo[3,4-b]pyr-
idine-3-ones 3 or 5 in comparable yields of 42 and 49%,
respectively (Scheme 1) [8].
The pyrazolo[3,4-b]pyridines are important com-
pounds, particularly in pharmaceutical research because
of their significant and versatile biological activities such
as antimicrobial, antimalarial, antiviral, antiproliferative,
anticoagulative, hypotensive, and antiarrythmic [1–5].
Because of the potential of pyrazolo[3,4-b]pyridines,
much work has been done over the years. The most im-
portant synthetic method used to reach these derivatives
the condensation of aminopyrazole with a,b-unsaturated
compounds reported by Quiroga et al. [6,7].
This sequence is of particular interest since it allows
a rapid and easy functionalization of 1-, 4-, and 6-posi-
tions of the pyrazolo[3,4-b]pyridine-3-one scaffold.
Thus, the development of synthesis of new molecules
with potential biological and/or pharmacological proper-
ties appears attractive.
We were interested in the synthesis of pyridine ana-
logues of these systems involving the condensation of
the aminopyrazolone 1 with 2-pyrone 2 [8]. The latter
skeleton was proven to be valuable scaffold to obtain
new heterocyclic compounds [9,10]. The pyrazolo[3,4-
b]pyridines prepared will be functionalized at 1-, 4-, and
6-positions.
Synthesis of pyrazolo[3,4-b]pyridine-3-ones func-
tionalized at 1- position. To widen the substitution of
1-position of pyrazolo[3,4-b]pyridine-3-ones, we decided
to introduce a bromoethane linker in order to incorpo-
rate a bicyclic compound such as a saturated pyridodia-
zepine known to interact with 5-HT7/5-HT1A receptors
[11].
For this purpose, Deprotonation of pyrazolo[3,4-
b]pyridine-3-one 3 with sodium hydride and further
nucleophilic substitution with dibromoethane allows the
alkylation of position 1 and compound 7 was isolated in
60% yield (Scheme 2) [12].
RESULTS AND DISCUSSION
Synthesis of pyrazolo[3,4-b]pyridine-3-ones. The
reaction of 3-amino-1-phenylpyrazolin-5-one 1 with 4-
hydroxy-6-methylpyran-2-one 2 was carried out in
C
V
2009 HeteroCorporation

1178
S. Fadel, F. Suzenet, A. Hafid, E. M. Rakib, M. Khouili, M. D. Pujol, and G. Guillaumet
Vol 46
Scheme 1
We then carried out the preparation of the decahydro-
pyrido[1,2-a][1,4]diazepine 6. This cyclic diamine was
prepared in four steps from the piperidine-2-carboxylic
acid ethyl ester according to the literature [13].
function occurred under these conditions to yield addi-
tional product 11 (29%).
To increase the chemioselectivity of the reduction
reaction, we performed the reaction in diethyl ether at
0ꢀC. These conditions lead only to the reduction of the
function ester making it possible to obtain compound 10
with an average yield (53%). Activation of the alcohol
function with methylsulfonyl chloride in the presence of
pyridine led to the mesylate derivative 12 in good yield.
Substitution of the leaving group with N,N-dibutylamine
and phenylpiperazine provided compounds 13 and 14 in
92 and 93% yields, respectively. The deprotection of the
pyrazolic amine group of 13 and 14 was carried out in
TFA at reflux leading to compounds 15 and 16 in very
good yields (Scheme 4).
The final step of this synthetic route was the substitu-
tion of the bromine of derivative 7 with the saturated
pyridodiazepine 6 in acetonitrile, in the presence of po-
tassium carbonate and a catalytic amount of potassium
iodide. The desired compound 8 was obtained in a good
yield (78%) (Scheme 3).
Synthesis of pyrazolo[3,4-b]pyridine-3-ones func-
tionalized at 4- or 6-position with an amine chain. In
a second approach, we focused on the reactivity of the
alkyl acetate group present at 4- or 6-position on pyra-
zolo[3,4-b]pyridine-3-ones.
Functionalizations
with
amines and notably with aryl piperazines, often present in
serotoninergic ligands, have been especially chosen.
First, the protection of the amine present in compound
5 was necessary. To carry out this step, we choose the
para-methoxybenzyl chloride (PMBCl) like protective
agent. In a basic medium, reaction of pyrazolo[3,4-
b]pyridine-3-one 5 with the PMBCl led to the amino
protected derivative 9 in an excellent yield (97%).
Reduction of the ester group with LiAlH4 in THF at
reflux led to the desired alcohol 10 in 40% yield. It is
worth mentioning that a further reduction of the amide
According to the procedure quoted earlier, we then
prepared 4-aminoethylpyrazolo[3,4-b]pyridin-3-ones 22
and 23 from ester 4 with good yields (Scheme 5). The
protection of the amine group of the pyrazoline ring
with PMBCl was also realized in a quantitative yield.
The ester group of the resulting protected amine 17 was
reduced by LiAlH4 leading to alcohol 18 in 55% yield.
The mesylation of the alcohol was carried out leading to
the pyrazolo[3,4-b]pyridine-3-one 19 in 89% yield. Reac-
tion of N,N-dibutylamine and phenylpiperazine provided
Scheme 3
Scheme 2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009
Synthesis of New Compounds Containing the
Pyrazolo[3,4-b]pyridine-3-one Subunit
1179
Scheme 4. (a) PMBCl, K2CO3, CH2Cl2, rt, 48 h; (b) LiAlH4, THF, reflux, 3 h; (c) LiAlH4, diethyl ether, 0ꢀC, 24 h; (d) CH3SO2Cl, pyridine, 0ꢀC
to rt, 48 h; (e) N,N-dibutylamine or phenylpiperazine, DMF, 70ꢀC, 1 night ; (f) TFA, reflux, 5 h.
amino compounds 20 and 21 in 92 and 93% yields,
respectively.
2-phenyl-4-(2-(4-phenylpiperazin-1-yl)ethyl)-1,2-dihydropyr-
azolo[3,4-b]pyridin-3-one 23 in a 96% yield.
The final deprotection of the pyrazole amine systems
was unrolled, like previously, in TFA at reflux affording
4-(2-(dibutylamino)ethyl)-6-methyl-2-phenyl-1,2-dihydropyr-
azolo[3,4-b]pyridin-3-one 22 in a 94% yield and 6-methyl-
Synthesis of pyrazolo[3,4-b]pyridine-3-ones func-
tionalized at 4- or 6-position with an amide chain. At
last, we showed that the ester function at 4- or 6-posi-
tion could be converted into amide. The preparation of
Scheme 5. (a) PMBCl, K2CO3, CH2Cl2, rt, 48 h; (b) LiAlH4, diethyl ether, 0ꢀC, 24 h; (c) CH3SO2Cl, pyridine, 0ꢀC to rt, 48 h; (d) N,N-
dibutylamine or phenylpiperazine, DMF, 70ꢀC, 1 night ; (e) TFA, reflux, 5 h.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1180
S. Fadel, F. Suzenet, A. Hafid, E. M. Rakib, M. Khouili, M. D. Pujol, and G. Guillaumet
Vol 46
Scheme 6
1-(2-Bromoethyl)-4,6-dimethyl-2-phenyl-1,2-dihydropyra-
zolo[3,4-b]pyridin-3-one.(7). Sixty milligrams (1.51 mmol;
1.8 eq) of sodium hydride 60% were suspended in 8 mL of
THF then 200 mg (0.84 mmol; 1 eq) of 4,6-dimethyl-2-phe-
nyl-1,2-dihydro-pyrazolo[3,4-b]pyridin-3-one 3 were dissolved
in 10 mL of THF and added slowly. The mixture was stirred
for 40 min at room temperature. Then 0.216 mL (2.51 mmol;
5 eq) of dibromoethane in 3 mL of THF were added dropwise.
The resulting mixture was heated at reflux for 30 h. The solu-
tion was hydrolyzed and extracted with CH2Cl2. The organic
extracts were dried over MgSO4 and evaporated under reduced
pressure. The residue was purified by column chromatography
on silica gel (eluent: petroleum ether/ethyl acetate, 6.5:3.5).
Yield 60% (maroon solid); mp 84–86ꢀC; IR (KBr) cmꢂ1: 1656
(CO); 1H NMR (CDCl3): d (ppm) 2.59 (s, 3H), 2.68 (s, 3H),
3.25 (t, 2H, J ¼ 7.3 Hz), 4.25 (t, 2H, J ¼ 7.3 Hz), 6.81 (s,
1H), 7.28–7.35 (m, 1H), 7.45–7.53 (m, 4H); 13C NMR
(CDCl3): d (ppm) 17.3 (CH3), 25.1 (CH3), 25.9 (CH2), 49.2
(NCH2), 107.7 (C), 120.6 (CH), 124.0 (2CH), 126.0 (CH),
129.4 (2CH), 135.0 (C), 149.6 (C), 160.7 (C), 162.3 (C), 163.8
(C); MS (m/z, %): 347 (Mþ1, 65), 348 (Mþ2, 82), 106 (100).
1-(2-(Hexanhydropyrido[1,2-a][1,4]diazepin-2(1H,3H,7H)-yl)
ethyl)-4,6-dimethyl-2-phenyl-1,2-dihydropyrazolo[3,4-b]pyri-
din-3-one (8). Under inert atmosphere, 45 mg (0.29 mmol; 1
eq) of decahydropyrido[1,2-a][1,4]diazepine 6 were put in 8
mL of acetonitrile then 120 mg (0.87 mmol; 3 eq) of potas-
sium carbonate, 7 mg (0.43 mmol; 0.15 eq) of potassium
iodide and 100 mg (0.29 mmol;1 eq) of bromoethylpyra-
zolo[3,4-b]pyridin-3-one 7 were added. The resulting mixture
was stirred overnight at 60ꢀC. The solvent was evaporated and
the residue was taken again with water and extracted with
CH2Cl2. The organic phases were dried over MgSO4 and
evaporated under reduced pressure. The residue was purified
by column chromatography on silica gel (eluent: CH2Cl2/
MeOH/NH4OH, 9:1:0.5). Yield 78% (maroon solid); mp 94–
amido-pyrazolopyridinones 26–29 was accomplished
easily in two-step sequence by saponification of ester 4
and 5 followed by peptidic coupling with N,N-dibutyl-
amine and phenylpiperazine using DCC as coupling
agent (Scheme 6).
CONCLUSION
In summary, we have developed an efficient method
for the synthesis of novel pyrazolo[3,4-b]pyridine-3-one
derivatives. Thereafter, we have shown that 1-, 4-, and
6-positions of the pyrazolopyridine skeleton can be eas-
ily and rapidly functionalized in order to introduce new
pharmacophore entities allowing the synthesis of poten-
tial biological molecules. One of the new molecules
tested, is compound 26, has shown pharmacological
activities toward the serotoninergic receptors 5-HT1A
(Ki ¼ 220 nM) and 5-HT7 (Ki ¼ 870 nM).
1
96ꢀC; IR (KBr) cmꢂ1: 1683 (CO); H NMR (CDCl3): d (ppm)
1.02–1.32 (m, 4H), 1.48–1.68 (m, 5H), 1.81–1.94 (m, 2H),
2.04–2.10 (m, 1H), 2.23–2.32 (m, 1H), 2.35–2.40 (m, 4H),
2.57 (s, 3H), 2.60–2.71 (m, 5H), 4.02 (t, 2H, J ¼ 6.0 Hz,),
6.75 (s, 1H), 7.24–7.30 (m, 1H), 7.44–7.58 (m, 4H); 13C NMR
(CDCl3): d (ppm) 17.3 (CH3), 24.3 (CH2), 25.1 (CH3), 26.0
(CH2), 27.4 (CH2), 31.2 (CH2), 46.0 (CH2), 54.0 (CH2), 55.6
(CH2), 55.7 (CH2), 57.3 (CH2), 61.1 (CH2), 65.6 (CH), 107.3
(C), 119.5 (CH), 123.4 (2CH), 126.2 (CH), 129.2 (2CH), 135.5
(C), 149.1 (C), 161.9 (C), 162.2 (C), 162.8 (C); MS (m/z, %):
420 (Mþ1, 100), 119 (25).
EXPERIMENTAL
Butyl.2-(1-(4-methoxybenzyl)-4-methyl-3-oxo-2-phenyl-2,3-
dihydro-1H-pyrazolo[3,4-b]pyridin-6-yl)acetate (9). Ninety
milligrams (0.65 mmol; 1.1 eq) of potassium carbonate were put
in 8 mL of CH2Cl2 and 200 mg (0.59 mmol; 1 eq) of pyra-
zolo[3,4-b]pyridine-3-one 5 were added. After 20 min of
stirring, 0.09 mL (0.65 mmol; 1.1 eq) of para-methoxybenzyl
chloride in 4 mL of CH2Cl2 were added. The mixture was stirred
for three days at room temperature. The solution was hydrolyzed
and extracted with CH2Cl2. The organic extracts were dried over
MgSO4 then evaporated in vacuo. The residue was purified by
column chromatography on silica gel (eluent: petroleum ether/
ethyl acetate, 7.5:2.5). Yield 97% (maroon clearly oil); IR
(NaCl) cmꢂ1: 1650, 1723 (CO); 1H NMR (CDCl3): d (ppm)
0.86 (t, 3H, J ¼ 7.2 Hz), 1.19–1.36 (m, 2H), 1.48–1.59 (m, 2H),
2.67 (s, 3H), 3.68 (s, 3H), 4.04–4.12 (m, 4H), 5.01 (s, 2H), 6.62
All reagents were purchased either from Acros Organics or
Aldrich. Thin layer chromatography was performed on 0.5 mm
ꢁ 20 cm ꢁ 20 cm E. Merck silica gel plates (60 F-254). Infrared
(IR) spectra were obtained on Perkin–Elmer Paragon 1000 PC
FTIR. Infrared spectra were recorded using NaCl films or KBr
pellets. 13C and 1H NMR spectra were recorded at room temper-
ature using a Bruker Advance DXP250 at 62.9 and 250 MHz,
respectively. Chemical shifts (d) are given in parts per million
downfield from tetramethylsilane as internal standard. Mass
spectra were determined with a Perkin-Elmer SCIEX AOI 300
spectrometer. All chemicals were of reagent grade and used
without further purification. THF was freshly distilled from Na/
benzophenone, while CH2Cl2 was distilled over CaH2. The bio-
logical characterization of the compounds was based on the
screening protocol described by Zajdel et al. [14,15].
Journal of Heterocyclic Chemistry
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Synthesis of New Compounds Containing the
Pyrazolo[3,4-b]pyridine-3-one Subunit
1181
(AB, 4H, JAB ¼ 8.8 Hz, Dm ¼ 24.1 Hz), 6.90 (s, 1H), 7.25–7.33
(m, 1H), 7.53 (d, 4H, J ¼ 3.1 Hz); 13C NMR (CDCl3): d (ppm)
13.6 (CH3), 19.0 (CH2), 25.1 (CH3), 30.4 (CH2), 35.4 (CH2),
51.3 (NCH2), 55.0 (OCH3), 65.0 (OCH2), 108.1 (C), 113.4
(2CH), 119.7 (CH), 123.9 (2CH), 125.5 (C), 126.3 (CH), 129.1
(2CH), 130.3 (2CH), 135.0 (C), 143.9 (C), 159.3 (C), 160.7 (C),
161.2 (C), 163.6 (C), 169.9 (C); MS (m/z, %): 460 (Mþ1, 90),
119 (100).
107.7 (C), 113.4 (2CH), 120.1 (CH), 124.0 (2CH), 125.3 (C),
126.6 (CH), 129.2 (2CH), 130.3 (2CH), 134.7 (C), 146.5 (C),
159.3 (C), 160.8 (C), 161.0 (C), 163.9 (C); MS (m/z, %):
468 (Mþ1, 70), 119 (100).
1-(4-Methoxybenzyl)-6-(2-(dibutylamino)ethyl)-4-methyl-2-
phenyl-1,2-dihydropyrazolo[3,4-b]pyridin-3-one
(13). Two
hundred milligrams (0.43 mmol; 1 eq) of sulphonate 12 were
introduced into a sealed tube containing 2 mL of DMF then 1
mL (5.95 mmol; 13.9 eq) of N,N-dibutylamine. The mixture
was heated with stirring at 70ꢀC overnight. The solvent was
evaporated under reduced pressure and the crude product was
purified by column chromatography on silica gel (eluent: pe-
troleum ether/ethyl acetate, 5:5). Yield 92% (yellow oil); IR
1-(4-Methoxybenzyl)-6-(2-hydroxyethyl)-4-methyl-2-phe-
nyl-1,2-dihydropyrazolo[3,4-b]pyridin-3-one
(10). Under
inert atmosphere, 440 mg (0.96 mmol; 1 eq) of compound 9
weredissolved in 8 mL of Et2O and this mixture was added at
0ꢀC to suspension of 36 mg (0.96 mmol; 1 eq) of LiAlH4 in
10 mL of Et2O. The resulting mixture was maintained at 0ꢀC
for 24 h. The medium was hydrolyzed and the salt was filtered
off. The solution was extracted with CH2Cl2 and the organic
phases were dried over MgSO4 and evaporated in vacuo. The
residue was purified by column chromatography on silica gel
(eluent: petroleum ether/ethyl acetate, 4.5:6.5). Yield 53%
(white foam); IR (KBr) cmꢂ1: 1681 (CO), 3419 (OH); 1H
NMR (CDCl3): d (ppm) 2.67 (s, 3H), 3.21 (t, 2H, J ¼ 6.0 Hz),
3.70 (s, 3H), 3.91 (t, 2H, J ¼ 6.0 Hz), 5.03 (s, 2H), 6.62 (AB,
4H, JAB ¼ 8.8 Hz, Dm ¼ 19.6 Hz), 6.83 (s, 1H), 7.29–7.35 (m,
1H), 7.44–7.49 (m, 4H); 13C NMR (CDCl3): d (ppm) 25.3
(CH3), 35.2 (CH2), 51.4 (NCH2), 55.2 (OCH3), 63.0 (CH2),
108.6 (C), 113.6 (2CH), 120.1 (CH), 124.4 (2CH), 125.6 (C),
126.8 (CH), 129.3 (2CH), 130.4 (2CH), 134.9 (C), 150.2 (C),
159.5 (C), 160.6 (C), 162.3 (C), 163.8 (C); MS (m/z, %): 390
(Mþ1, 60), 119 (100).
1
(NaCl) cmꢂ1: 1672 (CO); H NMR (CDCl3): d (ppm) 0.86 (t,
6H, J ¼ 7.2 Hz), 1.19–1.30 (m, 4H), 1.33–1.40 (m, 4H), 2.44
(t, 4H, J ¼ 7.5 Hz), 2.65 (s, 3H), 2.75 (t, 2H, J ¼ 7.5 Hz),
3.11 (t, 2H, J ¼ 7.5 Hz), 3.68 (s, 3H), 4.99 (s, 2H), 6.62 (AB,
4H, JAB ¼ 8.8 Hz, Dm ¼ 23.7 Hz), 6.81 (s, 1H), 7.28–7.34 (m,
1H), 7.50 (d, 4H, J ¼ 4.1 Hz); 13C NMR (CDCl3): d (ppm)
14.2 (2CH3), 20.7 (2CH2), 25.2 (CH3), 28.5 (CH2), 29.7
(2CH2), 51.6 (CH2), 53.7 (2CH2), 54.3 (CH2), 55.2 (CH3),
108.3 (C), 113.5 (2CH), 119.7 (CH), 124.1 (2CH), 125.8 (C),
126.3 (CH), 129.3 (2CH), 130.5 (2CH), 135.4 (C), 152.3 (C),
159.4 (C); 161.1 (C); 161.6 (C), 163.1 (C); MS (m/z, %): 501
(Mþ1, 100), 102 (10).
1-(4-Methoxybenzyl)-4-methyl-2-phenyl-6-(2-(4-phenylpi-
perazin-1-yl)ethyl)-1,2-dihydropyrazolo[3,4-b]pyridin-3-one
(14). This product was obtained using same procedure as for
13 (eluent: petroleum ether/ethyl acetate, 6:4). Yield 93% (yel-
low oil); IR (NaCl) cmꢂ1: 1686 (CO); 1H NMR (CDCl3): d
(ppm) 2.66–2.76 (m, 9H), 3.14–3.25 (m, 6H), 3.68 (s, 3H),
5.00 (s, 2H), 6.63 (AB, 4H, JAB ¼ 8.8 Hz, Dm ¼ 24.8 Hz),
6.80–6.86 (m, 2H), 6.90 (d, 2H, J ¼ 7.8 Hz), 7.21–7.33 (m,
3H), 7.51 (d, 4H, J ¼ 4.4 Hz); 13C NMR (CDCl3): d (ppm)
25.3 (CH3), 28.5 (CH2), 49.2 (2CH2), 51.6 (CH2), 52.9
(2CH2), 55.2 (CH3), 58.4 (CH2), 108.3 (C), 113.5 (2CH),
116.1 (2CH), 119.6 (CH), 119.7 (CH), 124.2 (2CH), 125.7 (C),
126.5 (CH), 129.2 (2CH), 129.3 (2CH), 130.5 (2CH), 135.3
(C), 151.5 (2C), 159.5 (C), 161.1 (C), 161.5 (C), 163.4 (C);
MS (m/z, %): 534 (Mþ1, 80), 102 (100).
2-(1-(4-Methoxybenzyl)-4-methyl-2-phenyl-2,3-dihydro-1H-
pyrazolo[3,4-b]pyridin-6yl)ethanol (11). This compound was
obtained from 10 (eluent: petroleum ether/ethyl acetate, 6:4).
Yield 29% (white foam); IR (KBr) cmꢂ1: 3416 (OH); 1H
NMR (CDCl3): d (ppm) 2.46 (s, 3H), 2.56 (t, 2H, J ¼ 6.6
Hz), 3.68–3.77 (m, 5H), 4.48 (s, 2H), 4.56 (s, 2H), 6.47 (s,
1H), 6.66 (d, 2H, J ¼ 8.7 Hz), 6.90 (t, 1H, J ¼ 7.3 Hz),
6.99 (d, 2H, J ¼ 8.7 Hz), 7.07 (d, 2H, J ¼ 8.5 Hz), 7.25–
7.34 (m, 2H); 13C NMR (CDCl3): d (ppm) 24.1 (CH3), 36.3
(CH2), 55.3 (OCH3), 57.4 (CH2), 57.5 (CH2), 62.1 (CH2),
115.2 (2CH), 118.9 (C), 120.1 (CH), 127.2 (CH), 127.8
(2CH), 129.2 (2CH), 129.3 (C), 130.1 (2CH), 136.7 (C),
143.1 (C), 152.2 (C), 157.2 (C), 162.2 (C); 376 (Mþ1, 100),
119 (23).
6-(2-(Dibutylamino)ethyl)-4-methyl-2-phenyl-1,2-dihydro-
pyrazolo[3,4-b]pyridin-3-one (15). One hundred and sixty
milligrams (0.32 mmol; 1 eq) of compound 13 were dissolved
in 5 mL of TFA then the solution was heated at reflux during
5 h. The solvent was evaporated under reduced pressure and
the crude product was purified by column chromatography on
silica gel (eluent: methanol/ethyl acetate, 1:9). Yield 96% (red
solid); mp 114–116ꢀC; IR (KBr) cmꢂ1: 1667 (CO), 3445
(NH); 1H NMR (CDCl3): d (ppm) 0.85 (t, 6H, J ¼ 7.2 Hz),
1.24–1.34 (m, 4H), 1.38–1.46 (m, 4H), 2.47 (s, 3H), 2.91–3.00
(m, 6H), 3.19 (t, 2H, J ¼ 6.8 Hz), 6.61 (s, 1H), 7.16–7.23 (m,
1H), 7.41 (t, 2H, J ¼ 7.8 Hz), 7.88 (d, 2H, J ¼ 7.8 Hz); 13C
NMR (CDCl3): d (ppm) 14.2 (2CH3), 20.5 (2CH2), 25.2
(CH3), 29.2 (CH2), 29.9 (2CH2), 53.6 (2CH2), 54.2 (CH2),
108.9 (C), 118.5 (CH), 119.7 (2CH), 125.3 (CH), 129.2 (2CH),
137.3 (C), 151.8 (C), 156.4 (C), 159.6 (C), 159.9 (C); MS (m/
z, %): 381 (Mþ1, 100), 102 (40).
2-(1-(4-Methoxybenzyl)-4-methyl-3-oxo-2-phenyl-2,3-dihy-
dro-1H-pyrazolo[3,4-b]pyridin-6-yl)ethyl methanesulfonate
(12). 0.63 mL (7.71 mmol; 5 eq) of pyridine were added to
600 mg (1.54 mmol; 1 eq) of alcohol 10 in 15 mL of
CH2Cl2 at 0ꢀC. The solution was stirred 45 min at 0ꢀC then
0.30 mL (3.86 mmol; 2.5 eq) of mesyl chloride in 2 mL of
CH2Cl2 are run. The mixture was stirred for 48 h at room
temperature. The medium was hydrolyzed then the solution
was extracted with CH2Cl2. The organic phases were dried
over MgSO4 and evaporated in vacuo. The residue was puri-
fied by column chromatography on silica gel (eluent: petro-
leum ether/ethyl acetate, 5:5). Yield 89% (yellow oil); IR
(NaCl) cmꢂ1: (1678 (CO); 1H NMR (CDCl3): d (ppm) 2.67
(s, 3H), 2.80 (s, 3H), 3.36 (t, 2H, J ¼ 6.6 Hz), 3.68 (s, 3H),
4-Methyl-2-phenyl-6-(2-(4-phenylpiperazin-1-yl)ethyl)-1,2-
dihydropyrazolo[3,4-b]pyridin-3-one (16). This product was
obtained in 94% yield from the pyrazolopyridine 14 (130 mg,
0.24 mmol) following the procedure described earlier for
4.54 (t, 2H, J ¼ 6.6 Hz), 5.01 (s, 2H), 6.62 (AB, 4H, JAB
¼
8.8 Hz, Dm ¼ 23.1 Hz), 6.85 (s, 1H), 7.30–7.36 (m, 1H),
7.46–7.54 (m, 4H); 13C NMR (CDCl3): d (ppm) 25.1 (CH3),
31.4 (CH2), 36.8 (CH3), 51.3 (CH2), 55.0 (CH3), 68.9 (CH2),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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S. Fadel, F. Suzenet, A. Hafid, E. M. Rakib, M. Khouili, M. D. Pujol, and G. Guillaumet
Vol 46
1
compound 15 as a red solid; mp 116–118ꢀC; IR (KBr) cmꢂ1
:
compound 13 as a yellow oil; IR (NaCl) cmꢂ1: 1697 (CO); H
1674 (CO), 3419 (NH); 1H NMR (CDCl3): d (ppm) 2.35 (s,
3H), 3.03–3.18 (m, 6H), 3.32–3.45 (m, 6H), 6.70 (s, 1H), 6.92
(d, 3H, J ¼ 8.2 Hz), 7.20–7.30 (m, 3H), 7.45 (t, 2H, J ¼ 7.8
Hz), 7.87 (d, 2H, J ¼ 7.8 Hz); 13C NMR (CDCl3): d (ppm)
23.0 (CH3), 27.9 (CH2), 48.5 (2CH2), 52.6 (2CH2), 57.5
(CH2), 108.7 (C), 116.4 (C), 116.5 (2CH), 120.5 (CH), 120.6
(2CH), 125.8 (CH), 129.3 (4CH), 137.8 (C), 150.8 (C), 154.9
(C), 159.2 (C), 159.3 (C); MS (m/z, %): 414 (Mþ1, 100), 102
(30).
NMR (CDCl3): d (ppm) 0.92 (t, 6H, J ¼ 7.2 Hz), 1.24–1.42
(m, 4H), 1.44–1.54 (m, 4H), 2.53 (t, 4H, J ¼ 7.5 Hz), 2.59 (s,
3H), 2.97 (s, 4H), 3.67 (s, 3H), 4.99 (s, 2H), 6.63 (AB, 4H,
JAB ¼ 8.8 Hz, Dm ¼ 32.9 Hz), 6.76 (s, 1H), 7.28–7.32 (m,
1H), 7.47–7.53 (m, 4H); 13C NMR (CDCl3): d (ppm) 14.2
(2CH3), 17.2 (CH3), 20.8 (2CH2), 29.5 (2CH2), 35.9 (CH2),
51.5 (CH2), 53.8 (2CH2), 53.9 (CH2), 55.1 (CH3), 108.8 (C),
113.4 (2CH), 120.2 (CH), 123.9 (2CH), 125.7 (C), 126.2 (CH),
129.2 (2CH), 130.5 (2CH), 135.3 (C), 149.0 (C), 159.4 (C),
161.1 (C), 162.0 (C), 165.7 (C); MS (m/z, %): 501 (Mþ1, 41),
119 (100).
Butyl.2-(1-(4-methoybenzyl)-6-methyl-3-oxo-2-phenyl-2,3-
dihydro-1H-pyrazolo[3,4-b]pyridin-4-yl)acetate (17). This
product was obtained in 98% yield from the pyrazolopyridine
4 (300 mg, 0.89 mmol) following the procedure described ear-
1-(4-Methoxybenzyl)-6-methyl-2-phenyl-4-(2-(4-phenylpi-
perazin-1-yl)ethyl)-1,2-dihydropyrazolo[3,4-b]pyridin-3-one
(21). This product was obtained in 93% yield from the pyrazo-
lopyridine 19 (150 mg, 0.24 mmol) and phenylpiperazine (0.53
mL, 4.50 mmol) following the procedure described earlier for
lier for compound 9 as a maroon clearly oil; IR (NaCl) cmꢂ1
:
1
1683, 1724 (CO); H NMR (CDCl3): d (ppm) 0.93 (t, 3H, J ¼
7.2 Hz), 1.35–1.45 (m, 2H), 1.65–1.70 (m, 2H), 2.63 (s, 3H),
3.69 (s, 3H), 3.91 (s, 2H), 4.20 (t, 2H, J ¼ 6.6 Hz), 4.99 (s,
2H), 6.63 (AB, 4H, JAB ¼ 8.8 Hz, Dm ¼ 26.9 Hz), 6.68 (s,
1H), 7.32 (t, 1H, J ¼ 4.4 Hz), 7.50 (d, 4H, J ¼ 4.4 Hz); 13C
NMR (CDCl3): d (ppm) 13.8 (CH3), 17.3 (CH3), 19.2 (CH2),
30.8 (CH2), 44.4 (CH2), 51.6 (CH2), 55.2 (CH3), 65.2 (CH2),
109.8 (C), 113.5 (2CH), 120.5 (CH), 124.1 (2CH), 125.5 (C),
126.5 (CH), 129.3 (2CH), 130.6 (2CH), 135.2 (C), 150.0 (C),
158.5 (C), 159.5 (C), 160.8 (C), 161.7 (C), 170.3 (C); MS (m/
z, %): 460 (Mþ1, 100), 106 (26).
1
compound 14 as a yellow oil; IR (NaCl) cmꢂ1: 1683 (CO); H
NMR (CDCl3): d (ppm) 2.62 (s, 3H), 2.77 (t, 4H, J ¼ 5.0 Hz),
2.97 (dd, 2H, J ¼ 8.1 Hz, J0 ¼ 6.3 Hz), 3.12 (dd, 2H, J ¼ 8.1
Hz, J0 ¼ 6.3 Hz), 3.27 (t, 4H, J ¼ 5.0 Hz), 3.68 (s, 3H), 5.02
(s, 2H), 6.65 (AB, 4H, JAB ¼ 8.8 Hz, Dm ¼ 32.0 Hz), 6.80 (s,
1H), 6.87 (t, 1H, J ¼ 7.8 Hz), 6.96 (d, 2H, J ¼ 7.8 Hz), 7.25–
7.32 (m, 3H), 7.50–7.54 (m, 4H); 13C NMR (CDCl3): d (ppm)
17.2 (CH3), 36.1 (CH2), 49.3 (2CH2), 51.6 (CH2), 53.3
(2CH2), 55.2 (CH3), 60.5 (CH2), 109.1 (C), 113.5 (2CH),
116.2 (2CH), 119.8 (CH), 120.1 (CH), 124.0 (2CH), 125.7 (C),
126.3 (CH), 129.2 (4CH), 130.5 (2CH), 135.3 (C), 149.3 (C),
151.4 (C), 159.4 (C), 161.0 (C), 162.0 (C), 164.9 (C); MS (m/
z, %): 534 (Mþ1, 42), 102 (100).
1-(4-Methoxybenzyl)-4-(2-hydroxyethyl)-6-methyl-2-phenyl-
1,2-dihydropyrazolo[3,4-b]pyridin-3-one (18). This product
was obtained in 55% yield from the pyrazolopyridine 17 (440
mg, 0.87 mmol) following the procedure described earlier for
compound 10 as a white foam; IR (KBr) cmꢂ1: 1660 (CO), 3412
(OH); 1H NMR (CDCl3): d (ppm) 2.61 (s, 3H), 3.10 (t, 2H, J ¼
5.7 Hz), 3.69 (s, 3H), 4.12 (dd, 2H, J ¼ 11.3 Hz, J0 ¼ 5.3 Hz),
4.96 (s, 2H), 6.66 (AB, 4H, JAB ¼ 8.8 Hz, Dm ¼ 31.4 Hz), 6.76
(s, 1H), 7.29–7.35 (m, 1H), 7.52 (d, 4H, J ¼ 4.1 Hz); 13C NMR
(CDCl3): d (ppm) 17.3 (CH3), 39.8 (CH2), 51.6 (CH2), 55.2
(CH3), 61.7 (CH2), 109.3 (C), 113.6 (2CH), 120.2 (CH), 124.1
(2CH), 125.5 (C), 126.6 (CH), 129.3 (2CH), 130.4 (2CH), 135.1
(C), 149.7 (C), 159.5 (C), 160.4 (C), 161.8 (C), 164.7 (C); MS
(m/z, %): 390 (Mþ1, 17), 102 (100).
4-(2-(Dibutylamino)ethyl)-6-methyl-2-phenyl-1,2-dihydropyra-
zolo[3,4-b]pyridin-3-one (22). This product was obtained in
94% yield from the pyrazolopyridine 20 (150 mg, 0.30 mmol)
following the procedure described earlier for compound 15 as
a red solid; mp 118–120ꢀC; IR (KBr) cmꢂ1: 1697 (CO), 3440
(NH); 1H NMR (CDCl3): d (ppm) 0.94 (t, 6H, J ¼ 7.2 Hz),
1.30–1.40 (m, 4H), 1.61–1.68 (m, 4H), 2.66 (s, 3H), 3.03–3.08
(m, 6H), 3.40 (t, 2H, J ¼ 6.6 Hz), 6.60 (s, 1H), 7.14–7.21 (m,
1H), 7.40 (t, 2H, J ¼ 7.8 Hz), 7.91 (d, 2H, J ¼ 7.8 Hz); 13C
NMR (CDCl3): d (ppm) 13.7 (2CH3), 17.3 (CH3), 20.1
(2CH2), 25.1 (2CH2), 30.6 (CH2), 50.5 (CH2), 52.7 (2CH2),
109.1 (C), 118.3 (CH), 119.7 (2CH), 125.4 (CH), 129.1 (2CH),
137.4 (C), 150.8 (C), 156.8 (C), 159.5 (C), 159.8 (C); MS (m/
z, %): 381 (Mþ1, 100), 102 (44).
2-(1-(4-Methoxybenzyl)-6-methyl-3-oxo-2-phenyl-2,3-dihy-
dro-1H-pyrazolo[3,4-b]pyridin-4-yl)ethyl methanesulfonate
(19). This product was obtained in 89% yield from the pyra-
zolopyridine 18 (500 mg, 1.29 mmol) and mesyl chloride
(0.25 mL, 3.21mmol) following the procedure described ear-
lier for compound 12 as a yellow oil; IR (NaCl) cmꢂ1: 1692
(CO); 1H NMR (CDCl3): d (ppm) 2.61 (s, 3H), 2.94 (s, 3H),
3.29 (t, 2H, J ¼ 6.6 Hz), 3.68 (s, 3H), 4.77 (t, 2H, J ¼ 6.6
Hz), 4.99 (s, 2H), 6.64 (AB, 4H, JAB ¼ 8.8 Hz, Dm ¼ 23.9),
6.79 (s, 1H), 7.29–7.35 (m, 1H), 7.50 (d, 4H, J ¼ 4.1 Hz);
13C NMR (CDCl3): d (ppm) 17.2 (CH3), 37.5 (CH3), 37.7
(CH2), 51.5 (CH2), 55.2 (CH3), 68.3 (CH2), 109.7 (C), 113.6
(2CH), 120.4 (CH), 124.1 (2CH), 125.5 (C), 126.6 (CH),
129.3 (2CH), 130.4 (2CH), 135.1 (C), 149.9 (C), 159.5 (C),
160.7 (C), 160.8 (C), 161.6 (C); MS (m/z, %): 468 (Mþ1,
15), 97 (100).
6-Methyl-2-phenyl-4-(2-(4-phenylpiperazin-1-yl)ethyl)-1,2-
dihydropyrazolo[3,4-b]pyridin-3-one (23). This product was
obtained in 96% yield from the pyrazolopyridine 21 (120 mg,
0.23 mmol) following the procedure described earlier for com-
pound 15 as a red solid; mp 122–124ꢀC; IR (KBr) cmꢂ1: 1669
(CO), 3422 (NH); 1H NMR (CDCl3): d (ppm) 2.63 (s, 3H),
3.10–3.42 (m, 12H), 6.59 (s, 1H), 6.86–6.98 (m, 3H), 7.17
(t, 1H, J ¼ 7.6 Hz), 7.25–7.32 (m, 2H), 7.39 (t, 2H, J ¼ 7.8
Hz), 7.90 (d, 2H, J ¼ 7.8 Hz); 13C NMR (CDCl3): d (ppm)
17.1 (CH3), 31.1 (CH2), 47.0 (2CH2), 52.0 (2CH2), 55.3
(CH2), 109.7 (C), 117.0 (2CH), 119.5 (2CH), 121.6 (CH),
125.4 (CH), 129.1 (2CH), 129.4 (2CH), 137.4 (C), 149.4 (C),
151.0 (C), 159.2 (C), 159.8 (C); MS (m/z, %): 414 (Mþ1,
100), 102 (32).
1-(4-Methoxybenzyl)-4-(2-(dibutylamino)ethyl)-6-methyl-2-
phenyl-1,2-dihydropyrazolo[3,4-b]pyridin-3-one
(20). This
product was obtained in 92% yield from the pyrazolopyridine
19 (200 mg, 0.43 mmol) and N,N-dibutylamine 1 mL (0.53
mL, 5.95 mmol) following the procedure described earlier for
2-(6-Methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazolo[3,4-
b]pyridin-4-yl) acetic acid (24). Three hundred milligrams
(0.88 mmol;
1 eq) of pyrazolo[3,4-b]pyridine 4 were
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009
Synthesis of New Compounds Containing the
Pyrazolo[3,4-b]pyridine-3-one Subunit
1183
introduced under magnetic agitation into 15 mL of NaOH so-
lution 10%. The solution was heated at reflux during 90 min.
After cooling, the solution was neutralized until pH ¼ 2 with
concentrated HCl. The precipitate thus formed was filtered and
washed with water and then with diethyl ether (no purification
was necessary). Yield 98% (yellow solid); mp 122–124ꢀC; IR
(KBr) cmꢂ1: 1706 (CO), 3070 (OH); 1H NMR (CD3OD): d
(ppm) 2.73 (s, 3H), 3.85 (s, 2H), 6.83 (s, 1H), 7.29 (m, 1H),
7.49 (t, 2H, J ¼ 7.9 Hz), 7.91 (d, 2H, J ¼ 7.9 Hz); 13C NMR
(CD3OD): d (ppm) 17.2 (CH3), 42.3 (CH2), 111.9 (C), 119.8
(2CH), 122.6 (CH), 125.2 (CH), 129.9 (2CH), 140.5 (C), 151.9
(C), 155.5 (C), 157.2 (C), 160.5 (C), 178.0 (C); MS (m/z, %):
284 (Mþ1, 100), 181 (65).
(t, 1H, J ¼ 7.7 Hz), 7.41 (t, 2H, J ¼ 7.7 Hz), 7.89 (d, 2H, J ¼
7.7 Hz); 13C NMR (CDCl3): d (ppm) 13.9 (2CH3), 20.0 (CH2),
20.1 (CH2), 23.2 (CH3), 29.7 (CH2), 29.8 (CH2), 42.1 (CH2),
46.2 (CH2), 48.0 (CH2), 109.1 (C), 118.1 (CH), 119.0 (2CH),
125.4 (CH), 129.1 (2CH), 137.5 (C), 148.8 (C), 155.6 (C),
158.7 (C), 159.8 (C), 168.7 (C); MS (m/z, %): 395 (Mþ1, 44),
119 (100).
6-Methyl-4-(2-oxo-2-(4-phenylpiperazin-1-yl)ethyl)-2-phenyl-
1,2-dihydropyrazolo[3,4-b]pyridine-3-one (28). This product
was obtained in 56% yield from acid 24 (100 mg, 0.35 mmol)
and phenylpiperazine (46 lL, 0.39 mmol) following the proce-
dure described earlier for compound 26 as a yellow clearly solid;
mp 142–144ꢀC; IR (KBr) cmꢂ1: 1591, 1651 (CO), 3440 (NH);
1H NMR (CDCl3): d (ppm) 2.69 (s, 3H), 3.03–3.12 (m, 4H),
3.53 (t, 2H, J ¼ 4.9 Hz), 3.69–3.74 (m, 4H), 6.78 (s, 1H), 6.86–
6.93 (m, 3H), 7.19–7.30 (m, 3H), 7.41 (t, 2H, J ¼ 8.0 Hz), 7.90
(d, 2H, J ¼ 8.0 Hz); 13C NMR (CDCl3): d (ppm) 17.4 (CH3),
41.9 (CH2), 42.6 (CH2), 45.9 (CH2), 49.2 (CH2), 49.6 (CH2),
109.5 (C), 116.7 (2CH), 119.4 (2CH), 119.7(CH), 120.7 (CH),
125.3 (CH), 129.2 (2CH), 129.3 (2CH), 137.5 (C), 150.7 (C),
150.8 (C), 157.4 (C), 158.4 (C), 160.0 (C), 167.8 (C); MS (m/z,
%): 428 (Mþ1, 60), 119 (100).
2-(4-Methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazolo[3,4-b]
pyridin-6-yl)-acetic acid (25). Three hundred milligrams (0.88
mmol; 1 eq) of pyrazolo[3,4-b]pyridine 5 were introduced
under magnetic agitation into 15 mL of NaOH solution 10%.
The solution was heated at reflux during 90 min. After cool-
ing, the solution was neutralized until pH ¼ 2 with concen-
trated HCl. The precipitate thus formed was filtered and
washed with water and then with diethyl ether (no purification
was necessary). Yield 97% (yellow solid); mp 172–174ꢀC; IR
(KBr) cmꢂ1: 1700 (CO), 3061 (OH); 1H NMR (CD3OD): d
(ppm) 2.50 (s, 3H), 4.04 (s, 2H), 6.93 (s, 1H), 7.26 (m, 1H),
7.46 (t, 2H, J ¼ 7.9 Hz), 7.85 (d, 2H, J ¼ 7.9 Hz); 13C NMR
(CD3OD): d (ppm) 15.7 (CH3), 48.4 (CH2), 111.3 (C), 120.1
(2CH), 122.5 (CH), 126.2 (CH), 130.8 (2CH), 141.2 (C), 151.5
(C), 155.3 (C), 157.1 (C), 160.9 (C), 178.3 (C); MS (m/z, %):
284 (Mþ1, 53), 181 (100).
4-Methyl-6-(2-oxo-2-(4-phenylpiperazin-1-yl)ethyl)-2-phenyl-
1,2-dihydropyrazolo[3,4-b]pyridin-3-one (29). This product was
obtained in 52% yield from acid 25 (130 mg, 0.46 mmol) and
phenylpiperazine (60 lL, 0.51 mmol) following the procedure
described earlier for compound 26 as a orange solid; mp 136–
1
138ꢀC; IR (KBr) cmꢂ1: 1618, 1690 (CO), 3454 (NH); H NMR
(CDCl3): d (ppm) 2.35 (s, 3H), 3.01–3.11 (m, 4H), 3.51 (t, 2H,
J ¼ 4.9 Hz), 3.64–3.70 (m, 2H), 4.19 (s, 2H), 6.75 (s, 1H), 6.84–
6.92 (m, 3H), 7.18–7.28 (m, 3H), 7.40 (t, 2H, J ¼ 8.2 Hz), 7.88
(d, 2H, J ¼ 8.2 Hz); 13C NMR (CDCl3): d (ppm) 19.4 (CH3),
40.7 (CH2), 43.6 (CH2), 46.0 (CH2), 49.2 (CH2), 49.7 (CH2),
110.5 (C), 115.9 (2CH), 118.8 (2CH), 119.0 (CH), 120.1 (CH),
125.1 (CH), 129.2 (2CH), 129.5 (2CH), 137.7 (C), 149.4 (C),
150.1 (C), 156.8 (C), 159.1 (C), 160.1 (C), 168.8 (C); MS (m/z,
%): 428 (Mþ1, 65), 119 (100).
N,N-Dibutyl-2-(6-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-
pyrazolo[3,4-b]pyridin-4-yl)acetamide (26). One hundred
and nine milligrams (0.53 mmol; 1.5 eq) of DCC were put in
10 mL of THF then 100 mg (0.35 mmol; 1 eq) of acid 24
were added. After stirring at room temperature for 20 min, 65
lL (0.39 mmol; 1.1 eq) of N,N-dibutylamine in 2 ml of THF
were cast. The mixture was stirred for 7 h at room tempera-
ture. The solution was hydrolyzed with a saturated solution of
NH4Cl and extracted with AcOEt. The organic phases were
dried over MgSO4 and evaporated in vacuo. The crude reac-
tion was purified by column chromatography on silica gel (elu-
ent: petroleum ether/ethyl acetate, 5:5). Yield 40% (yellow
clearly solid); mp 134–136ꢀC; IR (KBr) cmꢂ1: 1591, 1637
(CO), 3414 (NH); 1H NMR (CDCl3): d (ppm) 0.87–0.94 (m,
6H), 1.25–1.32 (m, 4H), 1.43–1.49 (m, 4H), 2.69 (s, 3H), 3.16
(t, 2H, J ¼ 7.6 Hz), 3.29 (t, 2H, J ¼ 7.6 Hz), 3.70 (s, 2H),
6.67 (s, 1H), 7.18 (t, 1H, J ¼ 7.9 Hz), 7.41 (t, 2H, J ¼ 7.9
Hz), 7.93 (d, 2H, J ¼ 7.9 Hz); 13C NMR (CDCl3): d (ppm)
13.6 (2CH3), 17.2 (CH3), 19.9 (CH2), 20.0 (CH2), 29.5 (CH2),
29.6 (CH2), 41.9 (CH2), 45.9 (CH2), 47.9 (CH2), 109.6 (C),
118.6 (CH), 118.7 (2CH), 125.1 (CH), 129.0 (2CH), 137.6 (C),
150.8 (C), 156.2 (C), 157.7 (C), 159.9 (C), 168.6 (C); MS (m/
z, %): 395 (Mþ1, 26), 119 (100).
Acknowledgments. The authors acknowledge Prof. A. J. Bojar-
ski of Department of Medicinal Chemistry, Institute of Pharma-
cology, Polish Academy of Sciences in Krakow (Poland) for the
pharmacological tests on serotoninergic receptors.
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4H), 1.40–1.48 (m, 4H), 2.36 (s, 3H), 3.04 (t, 2H, J ¼ 7.6
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S. Fadel, F. Suzenet, A. Hafid, E. M. Rakib, M. Khouili, M. D. Pujol, and G. Guillaumet
Vol 46
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet