Novel synthesis of some new pyrimido[1,6-a]pyrimidine and pyrazolo[1,5-a]pyrimidine derivatives

Article abstract of DOI:10.1002/jhet.852

An easy and efficient route for synthesis of some pyrimido[1,6-a]pyrimidine and pyrazolo[1,5-a]pyrimidine derivatives was described through the reaction of sodium salts of formyl ketones with 6-aminothiouracil and 5-aminopyrazole derivatives, respectively. The characterization of the reaction products was confirmed by using elemental analysis and spectral data. Copyright

Full text of DOI:10.1002/jhet.852

446
Novel Synthesis of Some New Pyrimido[1,6-a]pyrimidine and
Pyrazolo[1,5-a]pyrimidine Derivatives
Vol 49
Ahmed M. Hussein*
Chemistry Department (Organic Chemistry Division), Faculty of Science, Beni-Suef University,
Beni-Suef, Egypt
*E-mail: amh_ali69@yahoo.com
Received December 11, 2010
DOI 10.1002/jhet.852
Published online 20 December 2011 in Wiley Online Library (wileyonlinelibrary.com).
An easy and efficient route for synthesis of some pyrimido[1,6-a]pyrimidine and pyrazolo[1,5-a]py-
rimidine derivatives was described through the reaction of sodium salts of formyl ketones with 6-amino-
thiouracil and 5-aminopyrazole derivatives, respectively. The characterization of the reaction products
was confirmed by using elemental analysis and spectral data.
J. Heterocyclic Chem., 49, 446 (2012).
INTRODUCTION
RESULTS AND DISCUSSION
Pyrimidopyrimidines, analogs of folic acid (one of the
B vitamins that is a key factor in the synthesis of
nucleic acids RNA and DNA) and an important class of
annulated uracil and thiouracil, are pharmacologically
useful as powerful inhibitors of aggregation of thrombo-
cytes [1], hepatoprotective [2], bronchodilators, anti-
cancer [3–5], vasodilators [6], antiallergic [7], and anti-
hypertensive [8] agents. It was also reported that pyrimi-
dopyrimidine derivatives inhibited lipid peroxidation in
human and rat liver [9]. Here, an easy construction of
some new and interesting pyrimidopyimidines, the ring
systems that can be found in marine-derived natural
products such as crambescidin [10] and batzelladine
alkaloids has been achieved [11]. On the other hand,
pyrazolopyrimidine systems, as they are structurally
related to purine, are considered as typical examples for
purine analogs that are reported as inhibitors for the syn-
thesis of DNA and RNA in the cells of some kinds of
cancers [12] and viruses [13,14] and many other biologi-
cal activities for these compounds are reported [15–21].
It was also reported that some 3(H)-pyrimidopyrimidine
derivatives exhibited potent antihyperlipidemic and anti-
hyperglycemic activity in alloxan diabetic–hypercholes-
terolemic and streptozotocin diabetic rats, respectively
[22–32].
The construction of pyrimido[1,6-a]pyrimidine ring
systems are mostly multistep synthesis [33,34]. How-
ever, our synthetic strategy commences from the reac-
tion of easily available compounds, 6-aminothiouracil
and the sodium salts of formyl ketones, which led to the
direct construction of the novel pyrimido[1,6-a]pyrimi-
dine nucleus. Thus, fusion of 6-aminothiouracil with the
formyl salts (1) in piperidine acetate and acetic acid
afforded, with considerable yields, the cyclocondensed
pyrimido[1,6-a]pyrimidines 4a–d as outlined in Chart 1.
The reaction mode for the formation of the products
is suggested to proceed through the initial nucleophilic
attack by the exocyclic amino group of 6-aminothioura-
cil at the formyl group of compound (2), that formed in
situ due to the reaction of the formyl salts (1) with
water, followed by cyclization through the elimination
of two water molecules leading to the formation of the
nonplanner products (4) rather than the planner products
(6) [35–37].
The identity of compounds (4a–d) was proven on the
basis of their elemental analyses and spectral data. How-
ever, the fact that the nucleus of pyrimido[1,6-a]pyrimi-
dine has more than one resonating forms must be taken
into consideration while discussing their spectral data.
This ring system may be found in three resonating forms:
C
V
2011 HeteroCorporation

March 2012
Novel Synthesis of Some New Pyrimido[1,6-a]
pyrimidine and Pyrazolo[1,5-a]pyrimidine Derivatives
447
ꢀ
Thus, the IR spectra of 4c revealed bands at t ¼ 3400
cmꢀ1 (NH); 2927 (paraffinic CH); 1680 (C¼¼O); 1613
(C¼¼N); and 1245 (C¼¼S). The 1H-NMR spectrum
showed signals at d ¼ 1.29–1.67 ppm (m, 4H, 2CH2);
2.42–2.92 (m, 4H, 2CH2); 3.22–3.41 (m, 4H, 2CH2),
7.99 (s, 1H, pyrimidine N¼¼CAH); 8.01 (s, 1H, pyrimi-
dine C¼¼CH); and 11.91 (br s, 1H, SH). The mass spec-
trum of this compound showed a molecular ion peak at
m/z ¼ 261 (100%), coincident with the molecular weigh
of the compound (261.35).
A successful trial for establishment of the phenom-
enon has been carried out by the reaction of 6-amino-
thiouracil with sodium salts of acyclic ketones. Thus,
the reaction of 6-aminothiouracil with sodium formyl
Chart 1
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

448
A. M. Hussein
Vol 49
Chart 2
acetone 7 and sodium formyl acetophenone 9 under the
same reaction conditions and following the same reac-
tion mechanism afforded 4-methyl-6-thioxo-6,7-dihydro-
8H-pyrimido[1,6-a]pyrimidin-8-one (8) and 4-phenyl-6-
thioxo-6,7-dihydro-8H-pyrimido[1,6-a]pyrimidin-8-one
(10), respectively, as shown in Chart 2.
peak at m/z ¼ 193 (37.4%) coincident with its molecular
weight (193.23) and the base peak appeared at m/z ¼
189 (100%). The IR spectra of compound 10 showed
ꢀ
ꢀ1
bands at t ¼ 3325 cm (NH); 1630 (C¼¼O); and 1243
(C¼¼S). The mass spectrum showed the molecular ion
peak at m/z ¼ 255 (2.9%) coincident with its molecular
weight (255.30).
The structure of compound 8 was established by its
elemental analysis andꢀt1he IR spectrum which revealed
In a similar manner, the behavior of aminopyrazoles
toward the sodium formyl salts of aliphatic and aromatic
acyclic ketones was also investigated. Thus,
ꢀ
bands at t ¼ 3368 cm (NH); 1627 (C¼¼O); and 1243
(C¼¼S). The mass spectrum showed a molecular ion
Chart 3
Journal of Heterocyclic Chemistry
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Novel Synthesis of Some New Pyrimido[1,6-a]
pyrimidine and Pyrazolo[1,5-a]pyrimidine Derivatives
449
Synthesis of pyrazolo[1,5-a]-pyrimidine derivatives (12a–
d) and (13a–h). General procedure. Respective mixtures of
5-aminopyrazoles 11a–d or 11a–h (0.01 mole) were refluxed
with a solution of sodium salts 7 or 9 (0.012 mole) and piperi-
dine acetate (1.5 mL) for 3–5 min. The hot reaction mixture
was neutralized with acetic acid (1.5 mL), then cooled and the
solid products were collected by filtration and recrystallized
from the suitable solvent.
condensation of 5-aminopyrazole derivatives 11a–d with
sodium formylacetone 7 afforded the 7-methyl-2-(phe-
nylamino)pyrazolo[1,5-a]pyrimidine-3-(N-aryl)carboxa-
mides 12a–d. On the other hand, 11a–h reacted with so-
dium formyl acetophenone 9 to give the 7-phenyl-2-
(phenylamino)pyrazolo[1,5-a]pyrimidine-3-(N-aryl)car-
boxamides 13a–h as shown in Chart 3.
1-Thioxo-1,2,8,9-tetrahydrocyclopenta[e]pyrimido[1,6-a]
pyrimidin-3(7H)-one (4a). Pale brown crystals (from EtOH);
yield, 66.3%; mp 276–278ꢁC. IR (KBr) cmꢀ1: 3325 (NH);
2967 (ACH); 1671 (C¼¼O); 1609 (C¼¼N); and 1243 (C¼¼S).
1H-NMR (CDCl3) dH (ppm): 1.89–1.96 (quin, 2H, CH2); 2.64–
2.88 (m, 4H, 2CH2); 7.97 (s, 1H, pyrimidine HC¼¼N); 8.11 (s,
1H, pyrimidine HC¼¼CO) and 8.92 (s, 1H, NH). Mass (m/z):
221 (M þ 2, 6.6%); 219 (Mþ, 100.0%); 161 (34.8%); 131
(14.5%); 104 (19.6%); and 77 (18.8%). Anal. Calcd. for
C10H9N3OS (219): C, 54.78; H, 4.14; N, 19.16; S, 14.62.
Found: C, 54.88; H, 4.21; N, 19.0; S, 14.60.
1-Thioxo-1,2,7,8,9,10-hexahydro-3H-pyrimido[1,6-a]quina-
zolin-3-one (4b). Yellow crystals (from EtOH); yield, 58.8%;
mp 230–232ꢁC. IR (KBr) cmꢀ1: 3390 (NH); 2936 (ACH);
1658 (C¼¼O); 1624 (C¼¼N); and 1255 (C¼¼S). 1H-NMR
(CDCl3) dH (ppm): 1.24–1.72 (m, 4H, 2CH2); 2.60–2.81 (m,
4H, 2CH2); 7.97 (s, 1H, pyrimidine HC¼¼N); 8.14 (s, 1H, py-
rimidine HC¼¼CO) and 11.10 (s, 1H, SH). 13C-NMR (DMSO)
dC (ppm): 19.8, 21.7, 24.6, 27.1 (4CH2); 125.5, 144.2, 156
(pyrimidine Cs); 162.3 (NACANA); 94.9 (¼¼CHACO); 199.8
(C¼¼O); 211.0 (C¼¼S). Mass (m/z): 235 (M þ 2, 6.7%); 233
(Mþ, 100.0%); 175 (18.1%); 143 (31.7%); 119 (15.8%), and
68 (25.2%). Anal. Calcd for C11H11N3OS (233): C, 56.63; H,
4.75; N, 18.01; S, 13.74. Found: C, 56.66; H, 4.66; N, 18.22;
S, 13.71.
1-Thioxo-1,2,7,8,9,10,11,12-octahydro-3H-cycloocta[e]pyr-
imido[1,6-a]pyrimidin-3-one (4c). Pale yellow crystals (from
EtOH); yield, 69.8%; mp 249–251ꢁC. IR (KBr) cmꢀ1: 3400
(NH); 2927 (ACH); 1680 (C¼¼O); 1613 (C¼¼N); and 1245
(C¼¼S). 1H-NMR (CDCl3) dH (ppm): 1.29–1.67 (m, 4H,
2CH2); 2.42–2.92 (m, 4H, 2CH2); 3.22–3.41 (m, 4H, 2CH2),
7.99 (s, 1H, pyrimidine N¼¼CAH); 11.91 (s, 1H, pyrimidine
O¼¼C¼¼CH); and 12.91 (br s, 1H, SH). Mass (m/z): 261 (Mþ,
100.0%); 323 (15.0%); 173 (7.4%); 103 (3.6%), and 77
(11.8%). Anal. Calcd. for C13H15N3OS (261): C, 59.72; H,
5.79; N, 16.08; S, 12.27. Found: C, 59.59; H, 5.89; N, 15.99;
S, 12.26.
The structures of compounds 12 and 13 were con-
firmed on the basis of their elemental analysis and spec-
tral data. Thus, 12a showed a correct elemental analysis
that was compatible with the molecular formula
C20H17N5O. The IR spectrum showed that the absence
of the peaks was related to NH2 of ꢀth1e starting pyrazole
ꢀ
and revealed bands at t ¼ 3304 cm (NH) and at 1653
1
cmꢀ1 (enolic C¼¼O). Its H-NMR spectra revealed a sin-
glet at d ¼ 2.77 ppm related to the CH3 group; 6.68–
7.76 ppm (m, 10H, aromatic protons); 8.32 (s, 1H, py-
rimidine C¼¼CH); 8.34 (s, 1H, pyrimidine N¼¼CH); 9.54
(s, 1H, NH); and 9.88 (s, 1H, NH). The mass spectrum
of this compound revealed a molecular ion peak at m/z
¼ 343 (38.7%) coincident with its molecular weight
(343.39) and showed the base peak at m/z ¼ 251.
CONCLUSIONS
In this work, an easy construction for interesting pyri-
mido[1,6-a]pyrimidine and pyrazolo[1,5-a]pyrimidine
derivatives has been described. In a separate work, some
derivatives of these newly synthesized compounds are
under investigation for their biological activities such as
antihyperglycemic, antihyperlipidemic, and antioxidant.
EXPERIMENTAL
All melting points were determined on an electrothermal ap-
paratus and are uncorrected. IR spectra were recorded (KBr
discs) on a Bruker IFS-25 FTIR spectrophotometer at the
.
region of 400–4000 cmꢀ1 1H-NMR and 13C-NMR spectra
were recorded in CDCl3 and (CD3)2SO solutions on a Varian
Gemini 300 MHz spectrometer, and chemical shifts are
expressed in d units using TMS as an internal reference. Mass
spectra were recorded on a GC-MS QP 1000 EX Shimadzu.
Elemental analyses were carried out at the Microanalytical
Center of the Cairo University, Giza, Egypt. Piperidine acetate
was prepared by addition of 5 mL of piperidine to a mixture
of 4 mL of acetic acid and 10 mL of water [38].
Synthesis of pyrimido[1,6-a]pyrimidine derivatives (4a–
d), (8), and (10). General procedure. A mixture of equiva-
lent amounts of sodium salts (1), (7) or (9) (0.012 moles) and
6-aminothiouracil was refluxed with a solution of piperidine
acetate (1.5 mL) for 15–20 min. The reaction mixture is then
diluted with 20 mL of ethanol and refluxed for another 1 h.
The reaction was quenched by the addition of 1.5 mL of acetic
acid, then the mixture was cooled and solid product was col-
lected by filtration and recrystallized from the appropriate
solvent.
1-Thioxo-1,2,7,8,9,10,11,12,13,14,15,16-dodecahydro-3H-
cyclo-dodeca[e]pyrimido[1,6-a]pyrimidin-3-one (4d). Yellow
ꢁ
crystals (from EtOH); yield, 60.3%; mp 228–230 C. IR (KBr)
cmꢀ1: 3352 (NH); 2923 (ACH); 1679 (C¼¼O); 1621 (C¼¼N);
and 1246 (C¼¼S). Mass (m/z): 319 (Mþ þ 2, 19.8%); 317
(Mþ, 94.0%); 246 (25.5 %); 207 (100.0%); 147 (21.2%); and
91 (19.0%). Anal. Calcd for C17H23N3OS (317): C, 64.32; H,
7.30; N, 13.24; S, 10.10. Found: C, 64.34; H, 7.45; N, 13.33;
S, 9.88.
4-Methyl-6-thioxo-6,7-dihydro-8H-pyrimido[1,6-a]pyrimi-
din-8-one (8). Pale yellow crystals (from EtOH); yield 61.1%;
mp 266–268ꢁC. IR (KBr) cmꢀ1: 3368 (NH); 2970 (ACH);
1627 (C¼¼O); 1591 (C¼¼N); and 1243 (C¼¼S). 1H-NMR
(DMSO) dH (ppm): 1.44 (s, 3H, CH3); 8.00 (s, 1H, pyrimidine
N¼¼CAH); 8.16 (s, 1H, pyrimidine C¼¼CH); 8.26 (s, 1H, py-
rimidine HC¼¼C¼¼O); and 11.87 (s, 1H, SH). Mass (m/z): 193
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A. M. Hussein
Vol 49
(Mþ, 37.4%); 189 (100.0%); 161 (25.2%); 91 (20.3%); and 75
(42.3%). Anal. Calcd for C8H7N3OS (193): C, 49.73; H, 3.65;
N, 21.75; S, 16.59. Found: C, 49.63; H, 3.61; N, 21.65; S,
16.65.
(4.0%); 193 (1.70%); 90 (1.60%); and 64 (30.0%). Anal. Calcd
for C25H19N5O (405): C, 74.06; H, 4.72; N, 17.27. Found: C,
74.21; H, 4.66; N, 17.54.
2-Anilino-N-(4-methylphenyl)-7-phenylpyrazolo[1,5-a]py-
rimidine-3-carboxamide (13b). Orange crystals (from
Dioxan); yield, 62.9%; mp 255–257ꢁC. IR (KBr) cmꢀ1: 3314
(NH); 1649 (C¼¼O) and 1612 (C¼¼N). 1H-NMR (DMSO) dH
(ppm): 2.11 (s, 3H, CH3); 6.99–8.00 (m, 14H, Ar); 8.46 (s,
1H, pyrimidine C¼¼CH); 8.56 (d, 1H, pyrimidine N¼¼CH); and
9.71–9.99 (broad, 2H, 2NH). Mass (m/z): 420 (Mþ þ 1,
8.9%), 313 (100.0%); 302 (65.0%); 189 (3.25%); and 90
(2.96%). Anal. Calcd for C26H21N5O (419): C, 74.44; H, 5.05;
N, 16.70. Found: C, 74.33; H, 5.11; N, 16.59.
2-Anilino-N-(4-chlorophenyl)-7-phenylpyrazolo[1,5-a]pyrim-
idine-3-carboxamide (13c). Yellow crystals (from Dioxan);
yield, 66.0%; mp 261–263ꢁC. IR (KBr) cmꢀ1: 3316, 3259
(NH); 1652 (C¼¼O); and 1603 (C¼¼N). 1H-NMR (DMSO) dH
(ppm): 6.85–7.89 (m, 14H, Ar); 8.44 (s, 1H, pyrimidine
C¼¼CH); 8.60 (d, 1H, pyrimidine N¼¼CH); 9.25 (broad, H,
NH); and 9.36 (broad, H, NH). Anal. Calcd for C25H18N5OCl
(439.5): C, 68.26; H, 4.12; N, 15.92. Found: C, 68.00; H,
4.11; N, 15.99.
2-Anilino-N-(4-methoxyphenyl)-7-phenylpyrazolo[1,5-a]
pyrimidine-3-carboxamide (13d). Orange crystals (from
Dioxan); yield, 68.8%; mp 233–234ꢁC. IR (KBr) cmꢀ1: 3302,
3260 (NH); 1651 (C¼¼O); and 1600 (C¼¼N). 1H-NMR
(DMSO) dH (ppm): 2.89 (s, 3H, OCH3); 7.00–8.12 (m, 14H,
Ar); 8.25 (s, 1H, pyrimidine C¼¼CH); 8.33 (d, 1H, pyrimidine
N¼¼CH); 9.65 (broad s, 1H, NH); and 9.69 (s, 1H, NH). Mass
(m/z): 436 (Mþ þ 1, 65.2%), 329 (100.0%). Anal. Calcd for
C26H21N5 O2 (435): C, 71.71; H, 4.86; N, 16.08. Found: C,
71.51; H, 4.85; N, 15.88.
2-Anilino-N-(4-bromophenyl)-7-phenylpyrazolo[1,5-a]pyrim-
idine-3-carboxamide (13e). Yellow crystals (from Dioxan);
yield, 62.9%; mp 242–244ꢁC. IR (KBr) cmꢀ1: 3304 (NH);
1655 (C¼¼O); and 1597 (C¼¼N). Mass (m/z): 485 (Mþ þ 1,
19.1%), 313 (100.0%); 103 (11.5%); and 77 (21.4%). Anal.
Calcd for C25H18N5OBr (484): C, 61.99; H, 3.75; N, 14.46.
Found: C, 61.90; H, 3.44; N, 14.99.
4-Phenyl-6-thioxo-6,7-dihydro-8H-pyrimido[1,6-a]pyrimi-
din-8-one (10). Yellowish green needles (from EtOH/DMF);
yield, 63%; mp 288–291ꢁC. IR (KBr) cmꢀ1: 3325 (NH); 2970
(ACH); 1630 (C¼¼O); 1592 (C¼¼N); and 1243 (C¼¼S). 1H-
NMR (DMSO) dH (ppm): 6.89–7.89 (m, 5H, Ar); 8.10 (s, 1H,
pyrimidine N¼¼CAH); 8.21 (s, 1H, pyrimidine C¼¼CH); 8.26
(s, 1H, pyrimidine HC¼¼C¼¼O); and 9.21 (s, broad, 1H, NH).
Mass (m/z): 255 (Mþ, 2.9%); 151 (65.5); 95 (81.5%); 80
(17.3%); and 67 (100.0). Anal. Calcd for C13H9N3OS (255):
C, 61.16; H, 3.55; N, 16.46; S, 12.56. Found: C, 61.24; H,
3.42; N, 16.45; S, 12.71.
2-Anilino-7-methyl-N-phenylpyrazolo[1,5-a]pyrimidine-3-
carboxamide (12a). Yellow crystals (from EtOH); yield,
89.2%; mp 188–190ꢁC. IR (KBr) cmꢀ1: 3304 (NH); 1653
(enolic C¼¼O); 1597 (C¼¼N). 1H-NMR (CDCl3) dH (ppm):
2.77 (s, 3H, CH3); 6.68–7.76 (m, 10H, Ar); 8.32 (s, 1H, pyrim-
idine C¼¼CH); 8.34 (s, 1H, pyrimidine N¼¼CH); 9.54 (s, 1H,
NH); and 9.88 (s, broad, 1H, NH). 13C-NMR (DMSO) dC
(ppm): 21.2 (CH3), 111.3–143.6 (Ar Cs); 98.8, 101.6, 114.2
(3C, pyrimidine ring); 92.9, 122.3, 100.4 (3C, pyrazole ring);
188.9 (C¼¼O). Mass (m/z): 343 (Mþ, 38.7%); 251 (100.0%);
223 (3.6%); 132 (1.40%); 105 (2.0%); 78 (4.1%); and 64
(13.9%). Anal. Calcd for C20H17N5O (343): C, 69.96; H, 4.99;
N, 20.39. Found: C, 69.84; H, 4.69; N, 20.44.
2-Anilino-7-methyl-N-(4-methylphenyl)pyrazolo[1,5-a]py-
rimidine-3-carboxamide (12b). Yellow powder (from EtOH);
yield, 72.8%; mp 187–188ꢁC. IR (KBr) cmꢀ1: 3308 (NH);
1659 (enolic C¼¼O); and 1600 (C¼¼N). Mass (m/z): 358 (M þ
1, 14.2%); 251 (46.8%); 121 (12.0%); 111 (4.2%); and 64
(9.0%). Anal. Calcd for C21H19N5O (357): C, 70.57; H, 5.36;
N, 19.59. Found: C, 70.52; H, 5.29; N, 19.50.
2-Anilino-N-(4-chlorophenyl)-7-methylpyrazolo[1,5-a]py-
rimidine-3-carboxamide (12c). Orange crystals (from EtOH);
yield, 69.5%; mp 199–200ꢁC. IR (KBr) cmꢀ1: 3304 (NH);
1661 (enolic C¼¼O); and 1596 (C¼¼N). 1H-NMR (DMSO) dH
(ppm): 2.71 (s, 3H, CH3); 6.66–7.98 (m, 9H, Ar); 8.41 (s, 1H,
pyrimidine C¼¼CH); 8.43 (s, 1H, pyrimidine N¼¼CH); 9.55–
958 (broad s, 1H, NH); and 9.85 (s, 1H, NH). Mass (m/z): 379
(Mþ þ2, 12.2%); 286 (63.5%); 210 (12.3%); 198 (3.4%); 106
(4.2%); and 76 (11.3%). Anal. Calcd for C20H16N5OCl
(377.5): C, 63.58; H, 4.27; N, 18.54. Found: C, 63.88; H,
4.25; N, 18.22.
2-[(4-Chlorophenyl)amino]-N-(4-methylphenyl)-7-phenyl-
pyrazolo-[1,5-a]pyrimidine-3-carboxamide
(13f). Orange
crystals (from Dioxan); yield, 70.0%; mp 270–272ꢁC. IR
1
(KBr) cmꢀ1: 3308 (NH); 1662 (C¼¼O); and 1611 (C¼¼N). H-
NMR (DMSO) dH (ppm): 1.42 (s, 3H, CH3); 6.95–8.00 (m,
13H, Ar); 8.11 (s, 1H, pyrimidine C¼¼CH); 8.28 (d, 1H, pyrim-
idine N¼¼CH); and 9.67–9.69 (broad s, 2H, 2NH). Anal. Calcd
for C26H20N5OCl (453.5): C, 68.80; H, 4.44; N, 15.43. Found:
C, 68.99; H, 4.85; N, 15.00.
2-Anilino-N-(4-methoxyphenyl)-7-methylpyrazolo[1,5-a]
pyrimidine-3-carboxamide (12d). Pale yellow needles (from
EtOH); yield, 60.7%; mp 180–182ꢁC. IR (KBr) cmꢀ1: 3300
(NH); 1664 (enolic C¼¼O); and 1601 (C¼¼N). Mass (m/z): 373
(Mþ, 10.5%); 266 (53.4%); 210 (11.9%); 169 (11.4%); 111
(8.9%); and 76 (13.8%). Anal. Calcd for C21H19N5O2 (373):
C, 67.55; H, 5.13; N, 18.76. Found: C, 67.29; H, 5.30; N,
18.56.
N-(4-Chlorophenyl)-2-[(4-chlorophenyl)amino]-7-phenyl-
pyrazolo-[1,5-a]pyrimidine-3-carboxamide
(13g). Brown
crystals (from Dioxan); yield, 63.8%; mp 259–261ꢁC. IR
(KBr) cmꢀ1: 3335 (NH); 1655 (C¼¼O); and 1601 (C¼¼N).
Mass (m/z): 476 (Mþ þ 2, 63.3%), 405 (100.0%); 364
(11.2%); 298 (2.3%); 182 (11.6%); and 106 (31.6%). Anal.
Calcd for C25H17N5OCl2 (474): C, 63.30; H, 3.61; N, 14.76.
Found: C, 63.46; H, 3.60; N, 14.65.
2-Anilino-N,7-diphenylpyrazolo[1,5-a]pyrimidine-3-carbox-
amide (13a). Reddish yellow crystals (from Dioxan); yield,
65.5%; mp 205–207ꢁC. IR (KBr) cmꢀ1: 3311 (NH); 1648
2-(Benzoylamino)-7-phenyl-N-phenylpyrazolo[1,5-a]pyrimi-
dine-3-carboxamide (13h). Yellow crystals (from Dioxan);
yield, 69.2%; mp 171–173ꢁC. IR (KBr) cmꢀ1: 3377, 3273
1
(enolic C¼¼O); and 1597 (C¼¼N). H-NMR (CDCl3) dH (ppm):
6.98–8.22 (m, 15H, Ar); 8.53 (s, 1H, pyrimidine C¼¼CH); 8.55
(d, 1H, pyrimidine N¼¼CH); 9.65 (s, 1H, NH); and 10.14 (s,
1H, NH). Mass (m/z): 405 (Mþ, 59.7%), 313 (100.0%); 285
1
(NH); 1665 (C¼¼O); 1650 (C¼¼O); and 1659 (C¼¼N). H-NMR
(CDCl3) dH (ppm): 6.98–8.25 (m, 15H, Ar); 8.21–8.31 (broad
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2012
Novel Synthesis of Some New Pyrimido[1,6-a]
pyrimidine and Pyrazolo[1,5-a]pyrimidine Derivatives
451
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398 (100.0%); 356 (10.1%); 298 (8.2%); and 105 (22.3%).
Anal. Calcd for C26H19N5 O2 (433): C, 72.04; H, 4.42; N,
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Acknowledgment. The work was partially funded by the Fac-
ulty of Science, Beni-Suef University, Egypt.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet