Utility of cyanoacetamides as precursors to pyrazolo-[3,4-d]pyrimidin-4-ones, 2-aryl-6-substituted 1,2,3-triazolo-[4,5-d]pyrimidines and pyrazolo[1,5-a]pyrimidine-3-carboxamides

Article abstract of DOI:10.3987/com-07-11083

Cyanoacetamides (7a-c) were prepared via reacting cyanoacetic acid (5) with amines in the presence of acetic anhydride. Compounds (7a-c) coupled with benzenediazonium chloride to yield the phenylhydrazones (8a-c). These reacted with chloroacetonitrile to yield aminopyrazolecarboxamides (11a-c). Reaction of (8a,b) with hydroxylamine hydrochloride in DMF in presence of anhydrous sodium acetate afforded the amino-1,2,3-triazolecarboxamides (36a,b). Also compounds (7a-c) reacted with dimethylformamide dimethylacetal (DMFDMA) to yield the enamines (9a-c) which react with hydrazine hydrate to afford the aminopyrazoles (16a-c). Compounds (16) and (36) reacted with DMFDMA to yield the title heterocyclic derivatives.

Full text of DOI:10.3987/com-07-11083

HETEROCYCLES, Vol. 71, No. 9, 2007
1951
HETEROCYCLES, Vol. 71, No. 9, 2007, pp. 1951 - 1966. © The Japan Institute of Heterocyclic Chemistry
Received, 18th April, 2007, Accepted, 12th June, 2007, Published online, 15th June, 2007. COM-07-11083
UTILITY OF CYANOACETAMIDES AS PRECURSORS TO PYRAZOLO-
[3,4-d]PYRIMIDIN-4-ONES, 2-ARYL-6-SUBSTITUTED 1,2,3-TRIAZOLO-
[4,5-d]PYRIMIDINES AND PYRAZOLO[1,5-a]PYRIMIDINE-3-
CARBOXAMIDES
Hamada Mohamed Ibrahim,a,b Saad Makhseed,*a Ramadan Maawad
Abdel-Motaleb,b Abdel-Moneim Abdel-Salam Makhlouf,b and Mohamed
Hilmy Elnagdia
a) Chemistry Department, Faculty of Science, Kuwait University, Kuwait, P.O.
Box, 5969 Safate 13060, State of Kuwait
b) Chemistry Department, Faculty of Science, Fayoum University, Fayoum, A.
R. Egypt
E-mail: smakhseed@kuc01.kuniv.edu.kw
Abstract - Cyanoacetamides (7a-c) were prepared via reacting cyanoacetic acid
(5) with
amines in the presence of acetic anhydride. Compounds (7a-c) coupled
with benzenediazonium chloride to yield the phenylhydrazones (8a-c). These
reacted with chloroacetonitrile to yield aminopyrazolecarboxamides (11a-c).
Reaction of (8a,b) with hydroxylamine hydrochloride in DMF in presence of
anhydrous sodium acetate afforded the amino-1,2,3-triazolecarboxamides (36a,b).
Also compounds (7a-c) reacted with dimethylformamide dimethylacetal
(DMFDMA) to yield the enamines (9a-c) which react with hydrazine hydrate to
afford the aminopyrazoles (16a-c). Compounds (16) and (36) reacted with
DMFDMA to yield the title heterocyclic derivatives.
INTRODUCTION
Azolopyrimidines are biologically interesting molecules and their chemistry is receiving a considerable
interest.1-4 For example allopurinol (1) is established as a medicament for treatment gouty arthritis5-7
while sildenafil (2) and zaprinsat (3) are known to be potent and selective phosphodiesterase type 5
(PDE-5) inhibitors which are extensively utilized for treatment of male erectile dysfunction.8-11 On the
other hand, zaleplon (4) is well accepted drug for treatment of insomnia.12-14
Derivatives of (1-4) are efficiently obtained utilizing azoleamines as starting materials.15-17 Recently, we
developed several new efficient synthetic procedures for azoleamines utilizing simple, readily obtainable

1952
HETEROCYCLES, Vol. 71, No. 9, 2007
arylhydrazononitriles18-20 as well as enaminonitriles.21
O
Me
N
Me
O
N
HN
O
O
H
N
N
N
Me
N
HN
O
N
CN
N
N
O
NH
NH
O
N
N
H
N
Me
Me
SO2
N
N
N
Me
4
3
2
1
RESULTS AND DISCUSSION
In conjunction of this work, we report here the synthesis of cyanoacetamides (7a-c) and their utility for
the synthesis of the targeted molecules. Thus, treatment of heterocyclic amines (6a-c) with cyanoacetic
acid (5) in acetic anhydride afforded cyanoacetyl derivatives (7a-c) that revealed low field NH proton
typical for secondary amide NH. Compound (5) would be initially converted into a mixed anhydride and
then acylate the heteroaromatic amines.22, 23
O
O
Ac2O
+
COOH
NC
NC
85 oC
CN
O
Me
5
O
R
NH2
RHN
6
7
-
+
DMFDMA
PhN N Cl
O
H
O
CN
CN
RHN
RHN
N
NMe2
NH
Ph
9
8
N
S
6, 7, 8, 9a, R =
b, R =
Me
N
S
N
c, R =
S
Scheme 1
Compounds (7a-c) readily coupled with benzenediazonium chloride to yield the corresponding
phenylhydrazones (8a-c) for which exact stereochemistry seemed difficult to define as we have recently
shown that stereoelectronic factors in several cases overweigh the potential fixation by hydrogen

HETEROCYCLES, Vol. 71, No. 9, 2007
1953
bonding.24, 25 Although (8c) was proved pure by TLC, its 13 C NMR revealed 20 carbons instead of the
expected 10 carbons, the extra carbons which appear in the 13 C NMR of (8c) are attributed to the
presence of two or more isomeric forms at least under the measured conditions. Compounds (7a-c) also
reacted with dimethylformamide dimethylacetal (DMFDMA) to yield the enamines (9a-c) in good yields.
Enaminonitriles (9a-c) can exist either in E or Z configuration or as a mixture of both, the 1H NMR indicated
presence of only one isomer. While it is most likely that E form is preferred as in this form the molecule
would experience least steric interactions, the Z form can not be totally excluded based on the present data and
spectral data seems to be of little help in discriminating both forms (Scheme 1).
Compounds (8) and (9) could be readily utilized as precursors to azolopyrimidines by adopting our
recently reported methodology for the synthesis of 4-aminopyrazoles,18, 21 5-amino-1,2,3-triazoles26 and
5-aminopyrazoles.27 Thus compounds (8a-c) reacted with chloroacetonitrile in equimolar ratio to give the
O
O
CN
ClCH2CN / TEA
RHN
CN
RHN
equimolar ratio
N
NH
Ph
CN
N
N
Ph
8
10
excess ClCH2CN,
TEA
O
O
H
CN
NH2
N
RHN
RHN
N
O
N
CN
N
N
CN
Ph
11
Ph
14
for 11b
Me
O
DMFDMA
N
H
NMe2
N
N
RHN
N
S
N
H
N
CN
N
CN
N
Me
NH2
Ph
N
Ph
12
15
S
N
N
N
O
N
8, 11, 15a, R =
b, R =
S
Me
N
CN
S
N
N
c, R =
Ph
S
13
Scheme 2
Aminopyrazoles (11a-c) via the cyanomethylated hydrazones (10a-c), whose structure is supported by the
absence of methylene proton signal at δ 3-5 ppm. Intermediates (10a-c) are initially formed and then

1954
HETEROCYCLES, Vol. 71, No. 9, 2007
cyclized under the reaction conditions to the corresponding aminopyrazoles.18 This demonstrates the
general nature of this reaction that, enable synthesis of otherwise not readily obtainable
4-amino-1-arylpyrazoles. Compound (11) reacted with DMFDMA to provide (12) which did not cyclize
into the pyrazolopyrimidine (13). When compounds (8a,b) were reacted with an excess of
chloroacetonitile, it afforded (15a,b) presumably via an intermediacy (14) (Scheme 2).
Compounds (9a-c) reacted with hydrazine hydrate to yield pyrazoles (16). Inspection of 1H NMR enabled
establishing structure (16) for these pyrazoles derivatives since the pyrazole H-3 appeared as a singlet at δ
8.0-8.3 ppm, we could not trace in the1H NMR any signals for the tautomeric (17) as this would reveals
pyrazole H-5 as doublt (Scheme 3).
O
O
NH2
O
NH2
NH
NH2NH2
RHN
CN
RHN
RHN
N
N
H
NMe2
N
16
17
9
N
9, 16 a, R =
b, R =
S
Me
N
S
N
c, R =
S
Scheme 3
Compound (16b) reacted with DMFDMA to give the pyrazolo[4,3-d]pyrimidine (18) while (16a) provide
(19) which did not further cyclized to the corresponding pyrazolopyrmidine. Although (19) may be
presented in the 1H-5-amino form the 1H-3-amino form was established based on the 1H NMR that
revealed H-5 as doublet at δ 8.89. The Reaction of (16a,b) with (20) afforded the 7-amino-
pyrazolo[1,5-a]pyrimidine (21), whose C-6 appeared at δ ~ 92 ppm typical to the C-6 in
7-aminopyrazolo[1,5-a]pyrimidine.16 Although some 5-aminopyrazolo[1,5-a]pyrimidines are known28 13
C
NMR for such derivatives has not been reported to enable comparison however C-6 in
5-aminopyrazolo[1,5-a]pyrimidine should resonate at lower fields as it is not affected by amino lone pair
resonance. Compound (16) also reacted with the enaminone (23) and with the enaminal (24) to yield the
pyrazolo[1,5-a]pyrimidinecarboxamide (25) and (26), respectively (Scheme 4).
It has been shown earlier that arylhydazononitriles (27) react with hydroxylamine hydrochloride to yield
the amidoximes (28) which could be cyclized into isoxazoles the (29), 1,2,3-triazoleamines (30),
1,2,4-triazoleamines (31) or imidazoles (32) depending on the applied reaction conditions and the nature
of substituent R.26,29 When R is acetyl or under acidic condition, the isooxazoles (29) are formed while in
basic media cyclization affords either 1,2,3-triazoleamines (30) or 1,2,4-triazoleamines (31) via a rare
Beckman like rearrangement (Tieman rearrangement).30 Formation of imidazoles (32) from (28) (R=
COPh) with thionyl chloride has also been reported in the old literature31 (Scheme 5).

HETEROCYCLES, Vol. 71, No. 9, 2007
1955
H3C
N
N
S
O
NMe2
N
N
O
N
S
N
H
N
N
NH
19
18
H
N
for 16a
for 16b
DMFDMA
NH2
O
N
O
O
RHN
CHO
O
N
RHN
N
NMe2
Ar
RHN
Me2N
N
NH
N
23
N
Ar
24
N
25
16
N
26
CN
25 a, R =
b, R =
Ar =
S
N
Me
N
26 a, R =
b, R =
N
20
S
N
S
S
O
O
S
N
N
N
NH2
RHN
RHN
N
N
N
NH2
N
22
21
21 a, R =
b, R =
S
Me
N
S
Scheme 4
ArHN
N
H
N
O
R
N
32
NH2
ArN
N
NH2
R
CN
R
NH2OH. HCl
N OH
N
AcONa / EtOH
N
R
O
N
NH
Ar
NH
28
Ar
29
27
R
R
NH2
N
N
N
N
N
NH2
N
Ar
30
Ar
31
Scheme 5

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HETEROCYCLES, Vol. 71, No. 9, 2007
Now it has been found that (8a,b) reacts with hydroxylamine hydrochloride in anhydrous DMF in the
presence of anhydrous sodium acetate to provide an amidoxime intermediate (33), which further cyclized
to the 1,2,3-triazoles (36a,b). The condensation of compound (36b) with DMFDMA afforded the
triazolo[4,5-d]pyrimidine (37) (Scheme 6).
O
N
RHN
N
N
NH2
Ph
35
O
O
NH2
N OH
CN
O
PhNH-N
H2N
NH2OH. HCl
RHN
RHN
N
AcONa / DMF
N
NH
Ph
N
NH
Ph
N
R
36
9
34
Me
N
S
N
O
NH2
O
N
N
RHN
DMFDMA
N
N
N
N
N
9, 37a, R =
b, R =
S
N
Me
Ph
N
Ph
37
S
38
Scheme 6
Conclusion
In conclusion cyanoacetic acid reacted with amines in acetic anhydride to yield cyanoacetamides in good
yields. Cyanoacetamides were proved to be excellent precursors to aminopyrazolecarboxamides and
aminotriazolecarboxamides that readily afford azolopyrimidines with biological and medicinal interest.
EXPERIMENTAL
General Remarks
All melting points are uncorrected. IR spectra were recorded in KBr disks using a Perkin-Elmer System
2000 FT-IR spectrophotometer.1H NMR (400 MHz) and 13C NMR (100 MHz) spectra were recorded on a
Bruker DPX 400, 400 MHz super-conducting NMR spectrometer in CDCl3 or DMSO-d6 as a solvent and
TMS as internal standard; chemical shifts are reported in δ scale. Mass spectra were measured on a VG

HETEROCYCLES, Vol. 71, No. 9, 2007
1957
Autospec-Q spectrometer and shimadzu GCMS-QP 1000 EX spectrometer at 70 eV. Microanalyses were
performed on a LECO CHNS-932 Elemental Analyzer.
General procedure for the preparation of compounds (7a-c).
A solution of cyanoacetic acid (5) (10 mmol) in Ac2O (10 mL) was heated on a water bath for 10 min.
Then, the appropriate heteroaromatic amines (6a-c) were added to the reaction mixture and the heating
continued under reflux for further 15 min. The reaction mixture was left to cool and poured onto cooled
water. The solid product so formed was collected by filtration, recrystallized from the appropriate solvent
and identified as (7a-c).
N-(Benzothiazol-2-yl)-2-cyanoacetamide (7a).
o
Recrystallized from EtOH/dioxane as creamy white crystals, yield: 2.1 g (97%), mp 220 C; IR (KBr):
1
3288 (NH), 2261 (CN), 1688 cm-1 (CO); H NMR (DMSO-d6): δ 4.14 (s, 2H, CH2), 7.29-8.01 (m, 4H,
13
Ar-H) and 12.74 (br, 1H, NH); C NMR (DMSO-d6): δ 27.3 (CH2), 116.0 (CN), 121.5, 122.6, 124.7,
127.1, 132.3, 149.1, 158.4 (Ar-C) and 163.8 (CO); ms (EI): m/z (%) 217 (M+, 31.93), 218 (M++1, 4.6).
Anal. Calcd for C10H7N3OS (217.25): C, 55.29; H, 3.25; N, 19.34; S, 14.76. Found: C, 55.48; H, 3.32; N,
19.20; S, 14.74.
N-(4-Methylthiazol-2-yl)-2-cyanoacetamide (7b).
Recrystallized from EtOH as creamy white crystals, yield: 1.6 g (88%), mp 160-162 oC; IR (KBr): 3291
(NH), 2261 (CN), 1676 cm-1 (CO); 1H NMR (DMSO-d6): δ 2.26 (s, 3H, CH3), 4.02 (s, 2H, CH2), 6.82 (s,
13
1H, thiazolyl H) and 12.38 (br, 1H, NH); C NMR (DMSO-d6): δ 17.9 (CH3), 27.0 (CH2), 116.3 (CN),
109.3, 147.8, 157.8 (thiazole carbons) and 162.7 (CO); ms (EI): m/z (%) 181 (M+, 21.3), 182 (M++1, 3.9).
Anal. Calcd for C7H7N3OS (181.22): C, 46.40; H, 3.89; N, 23.19; S, 17.69. Found: C, 46.37; H, 3.94; N,
23.28; S, 17.60.
N-(Thiazol-2-yl)-2-cyanoacetamide (7c).
o
Recrystallized from EtOH/dioxane as creamy white crystals, yield: 1.4 g (84%), mp 223 C; IR (KBr):
3436 (NH), 2259 (CN), 1693 cm-1 (CO); 1H NMR (DMSO-d6): δ 4.04 (s, 2H, CH2), 7.29 (d, J = 3.57 Hz,
1H, thiazolyl H), 7.50 (d, J = 3.57 Hz, 1H, thiazolyl H) and 12.47 (br, 1H, NH). ms (EI): m/z (%) 167
(M+, 34.9), 168 (M++1, 9.43). Anal. Calcd for C6H5N3OS (167.19): C, 43.10; H, 3.01; N, 25.13; S, 19.18.
Found: C, 43.26; H, 3.13; N, 25.19; S, 19.28.
General method for the preparation of compounds (8a-c).
To a stirred solution of (7a-c) (10 mmol) in EtOH/dioxane (1:1, 30 mL each) containing NaOAc (10 g)
was added the benzenediazonium chloride (prepared from 10 mmol of aniline and the appropriate
quantities of sodium nitrite and hydrochloric acid). The solid product separated on standing was filtered
off and recrystallized from the appropriate solvent.

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HETEROCYCLES, Vol. 71, No. 9, 2007
N-(Benzothiazol-2-yl)(phenylhydrazono)-2-cyanoacetamide (8a).
Recrystallized from EtOH/dioxane mixture as yellow crystals, yield: 2.8 g (87 %), mp 238 oC; IR (KBr):
1
3391, 3201 (2 NH), 2216 (CN), 1678 cm-1 (CO); H NMR (CDCl3): δ 7.28-7.90 (m, 9H, Ar-H), 9.50 (br,
1H, NH) and 13.97 (br, 1H, NH); 13C NMR (CDCl3): δ 107.0 (C2), 116.3 (CN), 111.9, 117.8, 121.1,
122.6, 124.6, 125.8, 127.2, 129.9, 130.4, 132.3, 142.7 (Ar-C) and 161.9 (CO); ms (EI): m/z (%) 321 (M+,
75.8), 322 (M++1, 15.5). Anal. Calcd for C16H11N5OS (321.36): C, 59.80; H, 3.45; N, 21.79; S, 9.98.
Found: C, 59.71; H, 3.48; N, 21.75; S, 9.89.
N-(4-Methylthiazol-2-yl)(phenylhydrazono)-2-cyanoacetamide (8b).
o
Recrystallized from EtOH as orange crystals, yield: 2.4 g (85 %), mp 190-192 C; IR (KBr): 3230, 3192
1
(2 NH), 2218 (CN), 1697 cm-1 (CO); H NMR (CDCl3): δ 2.40 (s, 3H, CH3), 6.60 (s, 1H, thiazolyl H),
7.19-7.58 (m, 5H, Ar-H), 9.44 (br, 1H, NH) and 13.95 (br, 1H, NH); 13C NMR (CDCl3): δ 17.8 (CH3),
108.1 (thiazole C-5), 109.1 (C2), 116.1 (CN), 117.7, 125.4, 125.7, 130.1, 130.6, 143.0 (Ar-C and thiazole
carbons) and 161.9 (CO); ms (EI): m/z (%) 285 (M+, 52.5), 286 (M++1, 13.1). Anal. Calcd for
C13H11N5OS (285.33): C, 54.72; H, 3.89; N, 24.54; S, 11.24. Found: C, 54.60; H, 3.82; N, 24.35; S,
11.30.
(Phenylhydrazono)-N-(thiazol-2-yl)-2-cyanoacetamide (8c).
o
Recrystallized from EtOH/dioxane as orange crystals, yield: 2.2 g (81 %), mp 259 C; IR (KBr): 3435,
3371 (2 NH), 2218 (CN), 1667 cm-1 (CO); 1H NMR (DMSO-d6): δ 7.16 (t, J = 7.9 Hz, 1H, Ar-H), 7.29
(d, J = 3.6 Hz, 1H, thiazolyl H), 7.40 (t, J = 7.9 Hz, 2H, Ar-H), 7.56 (d, J = 3.6 Hz, 1H, thiazolyl H), 7.85
13
(d, J = 8.0 Hz, 2H, Ar-H), 12.37 (br, 1H, NH) and 14.08 (br, 1H, NH); C NMR (DMSO-d6): δ 107.3,
112.1, 113.5, 113.6, 114.9, 116.1, 117.8, 118.5, 125.3, 125.7, 126.1, 130.0, 130.5, 138.4, 142.6, 142.9,
159.3, 161.2, 168.0 and 169.7 (Ar-C, thiazole carbons and CO); ms (EI): m/z (%) 271 (M+, 100), 272
(M++1, 21.76). Anal. Calcd for C12H9N5OS (271.30): C, 53.13; H, 3.34; N, 25.81; S, 11.82. Found: C,
53.19; H, 3.42; N, 25.63; S, 11.64.
General procedure for the preparation of compounds (9a-c).
A mixture of (7a-c) (10 mmol) and DMFDMA (1.2 g, 10 mmol) in dioxane (30 mL) was refluxed for 4 h.
Then the solvent was reduced to one third of its volume under reduced pressure, and the reaction mixture
was allowed to cool down to rt. The solid product obtained on standing was collected by filtration and
crystallized from the appropriate solvent.
(E)-N-(Benzothiazol-2-yl)-2-cyano-3-(dimethylamino)acrylamide (9a).
o
Recrystallized from dioxane as creamy white crystals. yield: 2.3 g (84 %), mp 232-234 C; IR (KBr):
3405 (NH), 2189 (CN), 1679 cm-1 (CO). 1H NMR (DMSO-d6): δ 3.24 (s, 3H, CH3), 3.32 (s, 3H, CH3),
7.23-7.91 (m, 4H, Ar-H), 8.05 (s, 1H, olefinic CH) and 11.72 (br, 1H, NH); 13C NMR (DMSO-d6): δ 39.6
(CH3), 48.2 (CH3), 72.5 (C2), 119.5 (CN), 120.1, 122.7, 123.9, 124.2, 127.1, 131.8, 148.4, 157.7 (Ar-C

HETEROCYCLES, Vol. 71, No. 9, 2007
1959
and olefinic C) and 161.07 (CO) ms (EI): m/z (%) 272 (M+, 35.3), 273 (M++1, 11.24). Anal. Calcd for
C13H12N4OS (272.33): C, 57.34; H, 4.44; N, 20.57; S, 11.77. Found: C, 57.37; H, 4.51; N, 20.53; S,
11.75.
(E)-2-Cyano-3-(dimethylamino)-N-(4-methylthiazol-2-yl)acrylamide (9b).
o
Recrystallized from EtOH as buff crystals. yield: 2.1 g (89 %), mp 228 C; IR (KBr): 3104, (NH), 2190
(CN), 1672 cm-1 (CO). 1H NMR (CDCl3): δ 2.36 (s, 3H, thiazolyl CH3), 3.28 (s, 3H, CH3), 3.42 (s, 3H,
13
CH3), 6.51 (s, 1H, thiazolyl H), 7.91 (s, 1H, olefinic CH) and 9.07 (br, 1H, NH); C NMR (CDCl3): δ
17.7 (thiazolyl CH3), 39.3 (CH3), 48.5 (CH3), 71.9 (C-2), 108.6 (thiazole C-5), 118.9 (CN), 147.9
(thiazole C-4), 157.7 (olefinic C), 158.0 (thiazole C-2) and 163.1 (CO); ms (EI): m/z (%) 236 (M+, 13.2),
237 (M++1, 4.1). Anal. Calcd for C10H12N4OS (236.30): C, 50.83; H, 5.12; N, 23.71; S, 13.57. Found: C,
50.91; H, 5.06; N, 23.82; S, 13.56.
(E)-2-Cyano-3-(dimethylamino)-N-(thiazol-2-yl)acrylamide (9c).
o
Recrystallized from EtOH/dioxane as pale yellow crystals. yield: 1.6 g (72 %), mp 215 C; IR (KBr):
3435 (NH), 2187 (CN), 1656 cm-1 (CO). 1H NMR (DMSO-d6): δ 3.19 (s, 3H, CH3), 3.29 (s, 3H, CH3),
7.11 (d, 1H, J = 3.65 Hz, thiazolyl H), 7.43 (d, J = 3.65 Hz, 1H, thiazolyl H), 8.0 (s, 1H, olefinic CH) and
11.41 (br, 1H, NH); ms (EI): m/z (%) 222 (M+, 35.5), 223 (M++1, 8.3). Anal. Calcd for C9H10N4OS
(222.27): C, 48.63; H, 4.53; N, 25.21; S, 14.43. Found: 48.54; H, 4.60; N, 25.36; S, 14.39.
General method for the preparation of compounds (11a-c).
Equimolar amounts of chloroacetonitrile and (8a-c) (5 mmol) in Et3N (15 mL) were refluxed for 30 min.
Then, the reaction mixture was allowed to cool to rt. The obtained residual product was triturated with
methanol to give a solid product which collected by filtration, washed with water and recrystallized from
the appropriate solvent.
4-Amino-N-(benzothiazol-2-yl)-5-cyano-1-phenyl-1H-pyrazole-3-carboxamide (11a).
Recrystallized from EtOH as yellow crystals, yield: 1.3 g (72 %), m.p. 272-274 oC; IR (KBr): 3441, 3357,
3170 (NH2 and NH), 2216 (CN), 1645 (CO), 1539 cm-1 (C=N); 1H NMR (DMSO-d6): δ 5.71 (s, 2H, NH2),
7.19-8.10 (m, 9H, Ar-H) and 13.77 (br, 1H, NH); 13C NMR (DMSO- d6): δ 116.9 (CN) 113.3, 113.8,
117.1, 124.8, 124.9, 125.5, 126.3, 126.5, 129.2, 130.4, 130.6, 136.0, 142.3, 168.4, (Ar-C) and 169.4 (CO);
ms (EI): m/z (%) 360 (M+, 38.9), 361 (M++1, 10.9). Anal. Calcd for C18H12N6OS (360.40): C, 59.99; H,
3.36; N, 23.32; S, 8.90. Found: C, 59.89; H, 3.50; N, 23.27; S, 8.79.
4-Amino-5-cyano-N-(4-methylthiazol-2-yl)-1-phenyl-1H-pyrazole-3-carboxamide (11b).
Recrystallized from EtOH as yellow crystals, yield: 1.25 g (77 %), mp 242 oC; IR (KBr): 3457, 3356,
3136 (NH2 and NH), 2218 (CN), 1595 cm-1 (CO); 1H NMR (DMSO-d6): δ 2.42 (s, 3H, CH3), 5.43 (s, 2H,
NH2), 6.34 (s, 1H, thiazolyl H), 7.15-7.73 (m, 5H, Ar-H) and 13.78 (br, 1H, NH); 13C NMR (DMSO-d6):
δ 14.3 (CH3), 106.7 (thiazole C-5), 116.1 (CN), 116.5 (pyrazole C-5), 123.5, 125.8, 129.8, 130.6, 130.7,

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135.2, 144.8, 168.4 (Ar-C) and 169.1 (CO); ms (EI): m/z (%) 324 (M+, 23.3), 325 (M++1, 6.4). Anal.
Calcd for C15H12N6OS (324.37): C, 55.54; H, 3.73; N, 25.91; S, 9.89. Found: C, 55.67; H, 3.75; N, 25.84;
S, 9.81.
4-Amino-5-cyano-1-phenyl-N-(thiazol-2-yl)-1H-pyrazole-3-carboxamide (11c).
Recrystallized from dioxane as yellow crystals, yield: 1.15 g (74 %), mp 270 oC; IR (KBr): 3457, 3422,
3149 (NH2 and NH), 2216 (CN), 1597 cm-1 ( CO); 1H NMR (DMSO- d6): δ 5.46 (s, 2H, NH2), 7.17 (t, J =
8.0 Hz, 1H, Ar-H), 7.34 (d, J = 3.7 Hz, 1H, thiazolyl H), 7.42 (t, J = 8.0 Hz, 2H, Ar-H), 7.47 (d, J = 8.0
Hz, 2H, Ar-H), 7.82 (d, J = 3.7 Hz, 1H, thiazolyl H) and 13.74 (br, 1H, NH); ms (EI): m/z (%) 309 (M+,
48.65), 325 (M++1, 13.7). Anal. Calcd for C14H10N6OS (310.34): C, 54.18; H, 3.25; N, 27.08; S, 10.33.
Found: C, 54.03; H, 3.32; N, 26.88; S, 10.13.
5-Cyano-4-(dimethylaminomethyleneamino)-N-(4-methylthiazol-2-yl)-1-phenyl-1H-pyrazole-3-carbox-
amide (12).
A mixture of (11b) (5 mmol) and DMFDMA (0.6 g, 5 mmol) in dioxane (15 mL) was refluxed for 4h.
Then, the reaction mixture was poured into ice cold water and the formed solid product was collected by
o
filtration and recrystallized from EtOH as orange crystals; yield: 1.2 g (63 %), mp 124 C; IR (KBr):
3137, (NH), 2218 (CN), 1646 cm-1 (CO). 1H NMR (DMSO- d6): δ 1.30 (s, 3H, CH3), 2.40 (s, 3H, CH3),
3.81 (s, 3H, CH3), 6.48 (s, 1H, thiazolyl H), 7.12-7.34 (m, 5H, Ar-H), 7.46 (s, 1H, imino CH) and 14.14
(br, 1H, NH); m/z (%) 379 (M+, 39.3), 380 (M++1, 18.1). Anal. Calcd for C18H17N7OS (379.45): C, 56.98;
H, 4.52; N, 25.84; S, 8.45. Found: C, 57.09; H, 4.38; N, 25.73; S, 8.40.
General method for the preparation of compounds (15a, b).
A mixture of (8a,b) (5 mmol) and chloroacetonitrile (1.2 g, 15 mmol) in Et3N (15 mL) were refluxed for
30 min. Then, the reaction mixture was allowed to cool down to rt. The obtained residual product was
triturated with ethanol to give a solid product, which collected by filtration, washed with water and
recrystallized from the appropriate solvent.
6-Amino-N-(benzothiazol-2-yl)-5-cyano-1,4-dihydro-1-phenylpyrrolo[3,2-c]pyrazole-3-carboxamide
(15a).
o
Recrystallized from EtOH/dioxane as yellow crystals, yield: 1.35 g (68 %), mp 268 C; IR (KBr): 3462,
3351, 3238, 3180 (NH2 and 2NH), 2219 (CN), 1631 (CO), 1587 cm-1 (C=N); 1H NMR (CDCl3): δ 5.52 (s,
2H, NH2), 7.15-7.83 (m, 10H, Ar-H and NH) and 14.11 (br, 1H, NH); 13C NMR (DMSO-d6): δ 112.2
(CN), 111.6, 116.4, 122.9, 124.0, 124.1, 125.9, 126.2, 126.3, 128.5, 129.0, 129.5, 130.2, 130.2, 135.1,
141.8, 167.8, (Ar-C) and 170.7 (CO); ms (EI): m/z (%) 399 (M+, 100), 400 (M++1, 24.1). Anal. Calcd for
C20H13N7OS (399.44): C, 60.14; H, 3.28; N, 24.55; S, 8.03. Found: C, 60.22; H, 3.41; N, 24.52; S, 7.92.
6-Amino-5-cyano-1,4-dihydro-N-(4-methylthiazol-2-yl)-1-phenylpyrrolo[3,2-c]pyrazole-3-carboxamide
(15b).

HETEROCYCLES, Vol. 71, No. 9, 2007
1961
o
Recrystallized from EtOH/dioxane as yellow crystals, yield: 1.1 g (60 %), m.p. 257 C; IR (KBr): 3456,
3354, 3285, 3104 (NH2 and 2NH), 2217 (CN), 1670 (CO), 1595 cm-1 (C=N); 1H NMR (DMSO-d6):
δ 2.46 (s, 3H, CH3), 5.43 (s, 2H, NH2), 6.85 (s, 1H, thiazolyl H), 7.42-7.74 (m, 6H, Ar-H and NH) and
13.79 br, 1H, NH); ms (EI): m/z (%) 399 (M+, 100), 400 (M++1, 24.1). Anal. Calcd for C17H13N7OS
(363.40): C, 56.19; H, 3.61; N, 26.98; S, 8.82. Found: C, 55.99; H, 3.72; N, 27.08; S, 8.75.
General procedure for the preparation of compounds (16a-c).
A mixture of the enamine (9a-c) (10 mmol), and hydrazine hydrate (0.5 ml, 10 mmol) in dioxane (20 mL)
was refluxed for 3 h. The reaction mixture was allowed to cool down to rt and then poured into ice cold
water. The crude product was then collected by filtration washed with water and crystallized from the
appropriate solvent.
5-Amino-N-(benzothiazol-2-yl)1H-pyrazole-4-carboxamide (16a).
o
Recrystallized from dioxane as buff crystals. yield: 2.0 g (77 %), mp 286-88 C; IR (KBr): 3443, 3348,
3262, 3166 (NH2 and 2NH), 1662 (CO), 1600 cm-1 (C=N); 1H NMR (DMSO-d6): δ 6.24 (s, 2H, NH2),
7.28 (t, J = 8.0 Hz, 1H, Ar-H), 7.43 (t, J = 8.0 Hz, 1H, Ar-H), 7.72 (d, J = 7.9 Hz, 1H, Ar-H ), 7.95 (d, J =
7.9 Hz, 1H, Ar-H ), 8.21(s, 1H, pyrazole H-3), 11.96 (br, 1H, NH) and 12.14 (br, 1H, NH); 13C NMR
(DMSO-d6): δ 96.5 (pyrazole C-4), 121.0, 122.5, 122.9, 124.2, 124.8, 127.0, 132.6, 138.7, 149.7, 154.5,
159.7 (Ar-C), 163.3 (CO) (EI): m/z (%) 259 (M+, 25.5), 260 (M++1, 8.1). Anal. Calcd for C11H9N5OS
(259.29): C, 50.96; H, 3.50; N, 27.01; S, 12.37. Found: C, 60.08; H, 3.55; N, 26.98; S, 12.25.
5-Amino-N-(4-methylthiazol-2-yl)-1H-pyrazole-4-carboxamide (16b).
o
Recrystallized from EtOH/dioxane as creamy white crystals. yield: 1.9 g (85 %), mp 276 C; IR (KBr):
3440, 3349, 3238, 3187 (NH2 and 2 NH), 1665 (CO), 1618 cm-1 (C=N); 1H NMR (DMSO-d6): δ 2.28 (s,
3H, CH3), 6.08 (s, 2H, NH2), 6.68 (s, 1H, thiazolyl H), 8.15 (s, 1H, pyrazole H-3) and 11.84 (br, 2H,
2NH); 13C NMR (DMSO-d6): δ 17.9 (CH3), 96.8 (pyrazole C-4), 108.0 (thiazole C-5), 138.4, 147.3, 153.6,
158.9 (Ar-C), 162.8 (CO); ms (EI): m/z (%) 223 (M+, 22.1), 224 (M++1, 6.8). Anal. Calcd for C8H9N5OS
(223.26): C, 43.04; H, 4.06; N, 31.37; S, 14.36. Found: C, 42.89; H, 4.12; N, 31.46; S, 14.42.
5-Amino-1H-pyrazole-N-(thiazol-2-yl)-4-carboxamide (16c).
o
Recrystallized from EtOH/dioxane as creamy white crystals. yield: 1.6 g (77 %), mp 212 C; IR (KBr):
3448, 3353, 3183, 3126 (NH2 and 2NH), 1653 (CO), 1621 cm-1 (C=N); 1H NMR (DMSO-d6): δ 6.15 (s,
2H, NH2), 7.15 (d, J = 3.6 Hz, 1H, thiazolyl H), 7.47 (d, J = 3.6 Hz, 1H, thiazolyl H), 8.15 (s, 1H,
13
pyrazole H-3) and 11.90 (br, 2H, 2NH); C NMR (DMSO-d6): δ 97.0 (pyrazole C-4), 113.8 (thiazole
C-5), 137.1 (pyrazole C-3), 138.4 (thiazole C-4), 154.5 (pyrazole C-5), 159.6 (thiazole C-2), 162.8 (CO);
ms (EI): m/z (%) 209 (M+, 28.4), 210 (M++1, 12.8). Anal. Calcd for C7H7N5OS (209.23): C, 40.18; H,
3.37; N, 33.47; S, 15.32. Found: 40.07; H, 3.50; N, 33.39; S, 15.21.
General procedure for the preparation of compounds (18, 19).

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HETEROCYCLES, Vol. 71, No. 9, 2007
A mixture of (16a,b) (5 mmol) and DMFDMA (0.6 mL, 5 mmol) in anhydrous DMF (15 mL) was
refluxed for 5 h. Then, the reaction mixture was allowed to cool to rt then poured into ice cold water
containing few drops from hydrochloric acid then the crude product was collected by filtration washed
with water and crystallized from the appropriate solvent.
5-(4-Methylthiazol-2-yl)-1,5-dihydropyrazolo[3,4-d]pyrimidine-4-one (18).
Recrystallized from EtOH as orange crystals, yield: 0.9 g (77 %), mp 177 oC; IR (KBr): 3183 (NH), 1701
cm-1(CO); 1H NMR (DMSO-d6):δ 2.26 (s, 3H, CH3), 5.56 (s, 1H, thiazolyl H), 6.72 (s, 1H, H-6), 8.26 (s,
1H, H-3) and 12.05 (br, H, NH); ms (EI): m/z (%) 233 (M+, 43.1 % ), 234 (M++1, 12.5%). Anal. Calcd
for C9H7N5OS (233.25): C, 46.34; H, 3.02; N, 30.02; S, 13.75. Found: C, 46.45; H, 2.98; N, 29.89; S,
13.66.
(E)-N-(benzothiazol-2-yl)-3-[(Dimethylamino)methyleneamino]-1H-pyrazole-4-carboxamide (19).
o
Recrystallized from EtOH/dioxane as creamy white crystals, yield: 1.0 g (63 %), mp 297 C; IR (KBr):
3432, 3202 (2NH), 1687 (CO), 1599 cm-1 (C=N); 1H NMR (DMSO-d6): δ 3.82 (s, 3H, CH3), 3.91 (s, 3H,
CH3), 7.36 (t, J = 8.0 Hz, 1H, Ar-H), 7.54 (t, J = 8.0 Hz, 1H, Ar-H), 7.69 (d, J = 8.0 Hz, 1H, Ar-H ), 7.91
(d, J = 8.0 Hz, 1H, Ar-H ), 8.33 (s, 1H, imino CH), 8.89 (d, J = 11.0 Hz, 1H, pyrazolyl H), 9.75 (br, 1H,
NH) and 11.12 (br, 1H, NH); ms (EI): m/z (%) 314 (M+, 12.5 % ). Anal. Calcd for C14H14N6OS (314.37):
C, 53.49; H, 4.49; N, 26.73; S, 10.20. Found: C, 53.40; H, 4.38; N, 26.84; S, 10.06.
General procedure for the preparation of compounds (21).
A mixture of (16a,b) (10 mmol), and (20) (1.36 g, 10 mmol) in pyridine (20 mL) was refluxed for 7 h.
The reaction mixture was allowed to cool to rt and poured into ice cold water, then acidified with
hydrochloric acid. The formed crude solid product was collected by filtration, washed with water and
recrystallized from the appropriate solvent.
7-Amino-N-(benzothiazol-2-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (21a).
Recrystallized from dioxane as pale brown crystals, yield: 2.5 g (81%), mp above 300 oC; IR (KBr): 3465,
3314, 3176 (NH2 and NH), 1648 (CO), 1600 cm-1 (C=N); 1H NMR (DMSO-d6): δ 6.43 (d, J = 5.5 Hz, 1H,
H-6), 7.33 (t, J = 8.0 Hz, 1H, Ar-H), 7.46 (t, J = 8.0 Hz, 1H, Ar-H), 7.78 (d, J = 8.0 Hz, 1H, Ar-H ), 8.01
(d, J = 8.0 Hz, 1H, Ar-H ), 8.42 (d, 1H, J = 5.5 Hz, H-5), 8.55 (br, 2H, NH2), 8.71 (s, 1H, H-2) and 11.89
(br, 1H, NH); 13C NMR (DMSO-d6): δ 92.5 (C-6), 101.4, 121.4, 122.8, 124.5, 127.2, 132.7, 146.2, 148.9,
149.6, 150.4, 152.6, 158.4 (Ar-C) and 160.6 (CO); ms (EI): m/z 310 (M+, 34.35 % ), 311 (M++1, 9.81 %).
Anal. Calcd for C14H10N6OS (310.34): C, 54.18; H, 3.25; N, 27.08; S, 10.33. Found: C, 54.06; H, 3.32; N,
26.96; S, 10.22.
7-Amino-N-(4-methylthiazol-2-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (21b).
Recrystallized from EtOH/dioxane as pale brown crystals, yield: 2.0 g (73 %), mp 228 oC; IR (KBr): 3424,
3313, 3120 (NH2 and NH), 1659 (CO), 1599 cm-1 (C=N);1H NMR (DMSO-d6): δ 2.29 (s, 3H, CH3), 6.48 (d,

HETEROCYCLES, Vol. 71, No. 9, 2007
1963
J = 6.0 Hz, 1H, H-6), 6.82 (s, 1H, thiazolyl H), 8.31 (d, J = 6.0 Hz, 1H, H-5), 8.82 (s, 1H, H-2), 9.35 (br, 2H,
NH2), and 12.13 (br, 1H, NH); 13C NMR (DMSO-d6): δ 16.7 (CH3), 92.1 (C-6), 100.9, 107.6, 144.6, 145.6,
147.0, 150.6, 157.7, 159.5 (Ar-C) and 161.6 (CO); ms (EI): m/z 274 (M+, 17.7 % ), 275 (M++1, 6.5 %).
Anal. Calcd for C11H10N6OS (274.31): C, 48.17; H, 3.67; N, 30.64; S, 11.69. Found: C, 48.06 H, 3.82; N,
30.78; S, 11.71.
General procedure for the preparation of compounds (25).
A mixture of (16a,b) (10 mmol) and enaminone (23) (1.81 g, 10 mmol) in pyridine (20 mL) was refluxed
for 6 h. The reaction mixture was allowed to cool to rt and poured onto ice cold water, then acidified with
hydrochloric acid. The formed crude solid product was collected by filtration, washed with water and
crystallized from the appropriate solvent.
N-(Benzothiazol-2-yl)-7-(thiophen-2-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (25a).
o
Recrystallized from dioxane/DMF as yellow crystals, yield: 2.9 g (78 %), mp above 300 C; IR (KBr):
3289 (NH), 1684 (CO), 1599 cm-1 (C=N); 1H NMR (DMSO-d6): δ 7.34 (t, J = 8.0 Hz, 1H, Ar-H), 7.46-
7.50 (m, 2H, Ar-H and thiophene H), 7.81 (d, J = 8.0 Hz, 1H, Ar-H), 8.04 (d, J = 8.0 Hz, 1H, Ar-H ), 8.13
(d, J = 3.7 Hz, 1H, thiophene H), 8.26 (d, J = 5.0 Hz, 1H, H-6), 8.67 (d, J = 3.7 Hz, 1H, thiophene H ),
9.01 (d, J = 5.0 Hz, 1H, H-5), 9.05 (s, 1H, H-2) and 11.80 (br, 1H, NH); ms (EI): m/z 377 (M+, 28.9 % ),
378 (M++1, 9.5 %). Anal. Calcd for C18H11N5OS2 (377.45): C, 57.28; H, 2.94; N, 18.55; S, 16.99. Found:
C, 57.33; H, 3.04; N, 18.64; S, 17.11.
N-(4-Methylthiazol-2-yl)-7-(thiophen-2-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (25b).
Crystallized from dioxane/DMF as pale yellow crystals, yield: 2.7 g (79 %), mp 273 oC; ; IR (KBr): 3241
(NH), 1660 (CO), 1598 cm-1 (C=N); 1H NMR (DMSO-d6): δ 2.9 (s, 3H, CH3), 6.82 (s, 1H, thiazolyl H),
7.44 (t, J = 4.0 Hz, 1H, thiophene H), 8.08 (d, J = 5.0 Hz, 1H, H-6), 8.23 (d, J = 4.0 Hz, 1H, thiophene
H ), 8.64 (d, J = 4.0 Hz, 1H, thiophene H ), 8.94 (d, J = 5.0 Hz, 1H, H-5), 9.00 (s, 1H, H-2) and 11.50 (br,
1H, NH); 13C NMR (DMSO-d6): δ 17.9 (CH3), 103.8 (thiazole C-5), 107.2 (C-3), 109.2 (C-6), 129.3,
130.2, 134.8, 137.5, 142.4, 146.7, 147.9, 148.1, 153.0, 157.6 (Ar-C) and 159.5 (CO) ; ms (EI): m/z 341
(M+, 22.8 % ), 342 (M++1, 4.5 %). Anal. Calcd for C15H11N5OS2 (341.42): C, 52.77; H, 3.25; N, 20.51; S,
18.78. Found: C, 52.83; H, 3.31; N, 20.65; S, 18.82.
General procedure for the preparation of compounds (26).
A mixture of (16a,c) (10 mmol) and enaminal (24) (1.0 g, 10 mmol) in pyridine (20 mL) was refluxed for
6 h. Then, the solvent was evaporated under reduced pressure, and the remaining residue was triturated
with MeOH to afford crystals, which were then collected by filtration and recrystallized from the
appropriate solvent.

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HETEROCYCLES, Vol. 71, No. 9, 2007
N-(Benzothiazol-2-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (26a).
Recrystallized from dioxane/DMF as pale brown crystals, yield: 2.2 g (75 %), mp 298 oC; IR (KBr): 3251
(NH), 1677 (CO), 1618 cm-1 (C=N); 1H NMR (DMSO-d6): δ 7.33 (t, J = 8.0 Hz, 1H, Ar-H), 7.42-7.48 (m,
2H, Ar-H and H-6), 7.78 (d, J = 8.0 Hz, 1H, Ar-H), 8.02 (d, J = 8.0 Hz, 1H, Ar-H), 8.90 (s, 1H, H-2),
9.00 (d, J = 5.7 Hz, 1H, H-5), 9.44 (d, J = 5.7 Hz, 1H, H-7) and 11.64 (br, 1H, NH);13C NMR
(DMSO-d6): δ 103.8 (C-3), 112.0 (C-6), 121.5, 122.9, 124.7, 127.3, 132.7, 139.3, 147.2, 147.4, 149.5,
154.7, 158.4 (Ar-C) and 160.2 (CO) ms (EI): m/z 295 (M+, 37.8 % ), 296 (M++1, 7.9 %). Anal. Calcd
for C14H9N5OS (295.32): C, 56.94; H, 3.07; N, 23.71; S, 10.86. Found: C, 57.08; H, 2.92; N, 23.80; S,
10.89.
N-(Thiazol-2-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (26b).
Recrystallized from dioxane/DMF as pale brown crystals, yield: 1.9 g (78 %), mp 248 oC; IR (KBr): 3268
(NH), 1675 (CO), 1617 cm-1 (C=N); 1H NMR (DMSO-d6): δ 7.28 (d, J = 3.6 Hz, 1H, thiazolyl H), 7.41
(t, J = 6.0 Hz, 1H, H-6), 7.52 (d, J = 3.6 Hz, 1H, thiazolyl H), 8.84 (s, 1H, H-2), 8.97 (d, J = 6.0 Hz, 1H,
H-5), 9.42 (d, J = 6.0 Hz, 1H, H-7) and 11.41 (br, 1H, NH); 13C NMR (DMSO-d6): δ 103.5 (C-3), 111.7
(C-6), 114.8 (thiazole C-5), 138.6, 139.0, 146.8, 147.0, 154.3, 158.2 (Ar-C) and 159.4 (CO); ms (EI): m/z
245 (M+, 24.2 % ), 246 (M++1, 7.3 %). Anal. Calcd for C10H7N5OS (245.26): C, 48.97; H, 2.88; N,
28.55; S, 13.07. Found: 49.10; H, 2.96; N, 28.65; S, 12.98.
General procedures for Preparation of compounds (36a,b).
A mixture of the phenylhydrazones (8a,b) (10 mmol), hydroxylamine (10 mmol), and anhydrous NaOAc
(3 g ) in anhydrous DMF (20 ml) was refluxed for 3 h. The reaction mixture was allowed to cool to rt and
poured into ice cold water, and the crude product was collected by filtration, washed with water and
recrystallized from the appropriate solvent.
5-Amino-N-(benzothiazol-2-yl)-2-phenyl-2H-1,2,3-triazole-4-carboxamide (36a).
o
Recrystallized from dioxane as pale brown crystals yield: 1.9 g (57 %), mp 182-84 C; IR (KBr): 3451,
1
3390, 3250 (NH2 and NH), 1661(CO), 1617 cm-1 (C=N); H NMR (DMSO-d6): δ 6.31 (s, 2H, NH2),
7.33-8.08 (m, 5H, Ar-H) and 12.73 (br, 1H, NH); ms (EI): m/z (%) 336 (M+, 14.8), 337 (M++1, 3.26).
Anal. Calcd for C16H12N6OS (336.38): C, 57.13; H, 3.60; N, 24.98; S, 9.53. Found: C, 57.21; H, 3.56; N,
24.88; S, 9.46.
5-Amino-N-(4-methyl-thiazol-2-yl)-2-phenyl-2H-1,2,3-triazole-4-carboxamide (36b).
Recrystallized from EtOH/dioxane as pale brown crystals yield: 2.0 g (66 %), mp 139 oC; IR (KBr): 3454,
1
3439, 3232 (NH2 and NH), 1661 (CO), 1618 cm-1 (C=N); H NMR (DMSO-d6): δ 2.29 (s, 3H, CH3),
6.22 (s, 2H, NH2), 6.82 (s, 1H, thiazolyl H), 7.38-8.04 (m, 5H, Ar-H) and 12.41 (br, 1H, NH); 13C NMR
(DMSO-d6): δ 17.6 (CH3), 108.8 (thiazole C-5), 117.1, 124.4, 128.5, 130.0, 130.3, 130.6, 139.9, 156.0,
(Ar-C) and 161.1 ppm (CO); ms (EI): m/z (%) 300 (M+, 35.8), 301 (M++1, 8.8). Anal. Calcd for

HETEROCYCLES, Vol. 71, No. 9, 2007
1965
C13H12N6OS (300.34): C, 51.99; H, 4.03; N, 27.98; S, 10.68. Found: C, 51.85; H, 4.11; N, 28.07; S,
10.72.
2,5-Dihydro-5-(4-Methylthiazol-2-yl)-2-phenyl-1,2,3-triazolo[4,5-d]pyrimidine-4-one (37).
A mixture of (36b) (1.5 g, 5 mmol) and DMFDMA (0.6 g, 5 mmol) in anhydrous DMF (15 mL) was
refluxed for 5 h. Then, the reaction mixture was allowed to cool to rt and poured over ice cold water the
formed solid product was collected by filtration and recrystallized from dioxane as pale brown crystals,
yield: 1.6 g (53 %), mp 151 oC; IR (KBr): 1690 (CO), 1628 cm-1 (C=N); 1H NMR (DMSO-d6): δ 2.31 (s,
3H, CH3), 6.90 (s, 1H, thiazolyl H), 7.29-8.17 (m, 5H, Ar-H) and 8.57 (s, 1H, H-6); 13C NMR
(DMSO-d6): δ 17.9 (CH3), 109.5 (thiazole C-5), 119.0, 123.2, 129.9. 130.6, 132.4, 139.9, 148.2, 156.0,
157.3 (Ar-C) and 159.9 (CO); ms (EI): m/z (%) 310 (M+, 18.5), 311 (M++1, 5.8). Anal. Calcd for
C14H10N6OS (310.34): C, 54.18; H, 3.25; N, 27.08; S, 10.33. Found: C, 53.99; H, 3.14; N, 26.92; S,
10.21.
ACKNOWLEDGEMENTS
The authors are grateful to university of Kuwait AR for support through project Sc 06/03 and to Analab at
Kuwait university for spectral measurements. H. M. Ibrahim is grateful for Egyptian ministry of
education for covering the travel expenses.
REFERENCES
1. V. J. Ram, P. Srivastava, and A. Goel, Tetrahedron, 2003, 59, 7141.
2. L. D. S. Yadav, V. K. Rai, and S. Yadav, Tetrahedron, 2006, 62, 5464.
3. B. S. Holla, M. Mahalinga, M. S. Karthikeyan, P. M. Akberali, and N. S. Shetty, Bioorg. Med.
Chem., 2006, 14, 2040.
4. A. F. Burchat, D. J. Calderwood, M. M. Friedman, G. C. Hirst, B. Li, P. Rafferty, K. Ritter, and B.
S. Skinner, Bioorg. Med. Chem. Lett., 2002, 12, 1687.
5. F. Lioté and T. Bardin, Revue du Rhumatisme, 2007, 74, 160.
6. G. F. Falasca, Clinics in Dermatology, 2006, 24, 498.
7. G. Nuki, Medicine, 2006, 34, 417.
8. I. Wawer, M. Pisklata, and Z. Chilmoczyk, J. Pharm. Biochem. Anal., 2005, 38, 865.
9. Y. Wang, J. Wang, Y. Cui, J. P. Fawcett, and J. Gu, J. Chromatogr. B., 2005, 828, 118.
10. C. G. Wermuth, "The Practice of Medicinal Chemistry 2nd Ed" Academic Press, Oxford (2003).
11. K. C. Lai, Y. C. Liu, M. C. Tseng, and J. Hueilin, J. Food Drug Anal., 2006, 14, 19.
12. C. F. P. George, Lancet, 2001, 358, 1623.
13. D. Drover, H. Lemmens, S. Naidu, W. Cevallos, M. Darwish, and D. Stanski, Clinical
Therapeutics, 2000, 22, 1443.

1966
HETEROCYCLES, Vol. 71, No. 9, 2007
14. K. W. Weitzel, J. M. Wickman, S. G. Augustin, and J. G. Strom, Clinical Therapeutics, 2000, 22,
1254.
15. M. H. Elnagdi, N, Al. Awadi, and I. A. Abdelshafi, Comprehensive Heterocyclic Chem. III, 2007,
Volume 9 in press.
16. H. F. Anwar, D. H. Fleita, H. Kolshorn, H. Meier, and M. H. Elnagdi, Arkivoc, 2006, xv, 133.
17. M. H. Elnagdi, M. R. H. Elmoghayar, and G. E. H. Elgomei, Advances in Heterocyclic Chem.,
1987, 41, 319.
18. R. M. Abdel-Motaleb, A.-M. A.-S. Makhloof, H. M. Ibrahim, and M. H. Elnagdi., J. Heterocycl.
Chem., 2006, 43, 931.
19. O. M. E. El-Dusouqui, M. A. Abdelkhalik, N. Al. Awadi, H. H. Dib, B. J. George, and M. H.
Elnagdi, J. Chem. Res., 2006, 291.
20. S. Aziz, H. F. Anwar, and M. H. Elnagdi, J. Heterocycl.Chem., 2007, 44, 931.
21. R. M. Abdel-Motaleb, A.-M. A.-S. Makhloof, H. M. Ibrahim, and M. H. Elnagdi., J. Heterocycl.
Chem., 2007, 44, 109.
22. J. Slatt, I. Romero, and J. Bergman, Synthesis, 2004, 2760.
23. J. Slatt, T. Janosik, N. Wahlstrom, and J. Bergman, J. Heterocycl.Chem., 2005, 42, 141.
24. S. A. S. Ghozlan, I. A. Abdelshafi, H. M. Hassaneen, and M. H. Elnagdi, J. Heterocycl. Chem.,
2007, 44, 104.
25. I. M. Kenawi and M. H. Elnagdi, Spectrochemica Acta., Part A, 2006, 65, 805.
26. S. A. S. Ghozlana, I. A. Abdelhamida, H. M. Ibrahim, and M. H. Elnagdia, Arkivoc, 2006, XV,
53.
27. S. O. Abdallah, N. H. Metwally, H. F. Anwar, and M. H. Elnagdi, J. Heterocycl. Chem., 2005, 42,
781.
28. O. B. Smolii, S. Ya. Panchishin, L. V. Meerwelt, N. I. Mishchenko, E. A. Romanenko, and B. S.
Drach, Russ. J. Gen. Chem., 1998, 68, 458.
29. S. M. Almousawi and M. S. H. Moustafa, Beilstein J. Org. Chem., 2007, 3, 12.
30. H. Almater, S. Riad, and M. H. Elnagdi, Arkivoc, 2007, XIII, 53.
31. M. H. Elnagdi, M. R. H. Elmoghayar, E. A. A. Hafez, and H. H. Alnima, J. Org. Chem., 1975, 40,
2604.