Study of the reaction of 5-aryl-7-hydrazino-2-phenylpyra-zolo[1,5-c] pyrimidines with 1,3-dicarbonyl compounds

Article abstract of DOI:10.1002/cjoc.201180416

A novel synthetic method for the preparation of 5-aryl-7-(3,5-dimethyl-1H- pyrazol-1-yl)-2-phenylpyrazolo[1,5-c]-pyrimidines and 1-(5-aryl-2- phenylpyrazolo[1,5-c]pyrimidin-7-yl)-3-methyl-1H-pyrazol-5-ols is provided by condensative cyclization of 5-aryl-

Full text of DOI:10.1002/cjoc.201180416

FULL PAPER
Study of the Reaction of 5-Aryl-7-hydrazino-2-phenylpyra-
zolo[1,5-c]pyrimidines with 1,3-Dicarbonyl Compounds
Atta, Kamal F. M.*
Chemistry Department, Faculty of Science, Alexandria University, Ibrahimia P.O. Box 426, Alexandria 21321,
Egypt
A novel synthetic method for the preparation of 5-aryl-7-(3,5-dimethyl-1H-pyrazol-1-yl)-2-phenylpyra-
zolo[1,5-c]-pyrimidines and 1-(5-aryl-2-phenylpyrazolo[1,5-c]pyrimidin-7-yl)-3-methyl-1H-pyrazol-5-ols is
provided by condensative cyclization of 5-aryl-7-hydrazino-2-phenylpyrazolo[1,5-c]pyrimidines with
1,3-dicarbonyl compounds. The study of the more reactive position for electrophilic substitusion reactions on such
ring system was also achieved.
Keywords cyclization, electrophilic substitution, pyrazolylpyrazolopyrimidine, IR, NMR, mass spectrometry
－1
1
Introduction
frequencies are reported in cm . The H NMR spectra
were recorded on a JEOL JNM ECA 500 MHZ and
chemical shifts δ are relative to tetramethylsilane as an
internal standard. Mass spectra were recorded at 70 eV
with GCMS-QP 1000 EX. Reactions were routinely
followed by thin layer chromatography (TLC) Merck
Kiesel gel; 60-F254 precoated plastic plates, and spots
were visualized using an ultraviolet (UV) lamp. All re-
agents of analytical grade were obtained from a com-
mercial source and used without further purification.
Pyrimidines and fused pyrimidines, are an integral
part of DNA and RNA and play an essential role in sev-
eral biological processes. Also, they have considerable
chemical and pharmacological importance; particallarly,
as nucleoside antibiotics, antibacterials, cardio vascular
as well as agro chemical and veterin products.1-9 Vari-
ous pyrimidine derivaties have been reported to possess
wide spread pharmacological properties such as analge-
sic, antiarrhythmic, and anticancer activities,10-12 as well
as, anti-inflammatory, antiparkinosnian, and androgenic
anabolic activities.13-18
5-Aryl-7-hydrazino-2-phenylpyrazolo[1,5-c]pyrimi-
dines (1a— 1d)
Moreover, pyrazole nucleus has pronounced phar-
macological applications as anti-anxiety,19,20 antipyretic,
analgesic, and anti-inflammatory drugs.21-23 Certain al-
kyl pyrazoles show significant bacteriostatic and fungi-
cidal activities.24
The compounds 1 were prepared from the respective
acetylenic β-diketones as described earlier.29,30
5-Aryl-7-(3,5-dimethyl-1H-pyrazol-1-yl)-2-phenylpy-
razolo[1,5-c]pyrimidines (3a— 3d)
Encouraged by the above observations and in con-
tinuation of our work for the syntheses of heterocyclic
compounds from hydrazino heterocycles,25-28 a new se-
ries of 5-aryl-7-(3,5-dimethyl-1H-pyrazol-1-yl)-2-
phenylpyrazolo[1,5-c]pyrimidines and 1-(5-aryl-2-
phenylpyrazolo[1,5-c]pyrimidin-7-yl)-3-methyl-1H-
pyrazol-5-ols were synthesized, with a view to explore
the possibility of achieving better biological activities.
General procedure A mixture of a 5-aryl-7-hy-
drazino-2-phenylpyrazolo[1,5-c]pyrimidines (1a—1d, 1
g) and acetylacetone (10 mL) was heated under reflux
for 1 h. The reaction mixture was evaporated under re-
duced pressure, EtOH was added and the product
separated out was filtered, washed with EtOH and
crystallized from EtOH to give the titled compounds
3a—3d as colorless needles.
7-(3,5-Dimethyl-1H-pyrazol-1-yl)-2,5-diphenyl-
pyrazolo[1,5-c]pyrimidine (3a) 1 g, yield 81%; m.p.
Experimental
1
195—196 ℃; H NMR (CDCl3, 500 MHz) δ: 2.44 (s,
Apparatus and materials
3H, CH3), 2.47 (s, 3H, CH3), 6.18 (s, 1H, 1H-pyrazole-
H), 6.99 (s, 1H, pyrazole-H), 7.87 (s, 1H, pyrimidine-H),
7.41—7.52 (m, 5H, aromatic-H), 7.99—8.11 (m, 5H,
aromatic-H); IR (KBr) υmax: 1624 (pyrazole ring C＝N),
Melting points were determined on a Kofler Block
and are uncorrected. Elemental analyses were carried
out in the micro analytical laboratory of the faculty of
science, Cairo University. The IR spectra of compounds
were recorded on a Fourier Transform infrared 8400
spectrophotometer as potassium bromide pellets and
－1
1535 (pyrimidine＋ring C＝N), 1450 (C＝C) cm ; ＋MS
m/z (%): 367 (M ＋2, 9), 365 (M＋, 100), 351 (M －
CH2, 31), 337 (M＋－C2H4, 4), 323 (M＋－C2H4N, 21),
*
E-mail: prof.kf_atta@yahoo.com; Tel.: 002035917883; Fax: 002035932488
Received April 19, 2011; revised June 1, 2011; accepted June 16, 2011.
Chin. J. Chem. 2011, 29, 2451— 2460
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
2451

Atta
FULL PAPER
297 (M＋－C4H6N, 4), 220 (M＋－C10H11N, 6), 193 (M＋
－C11H12N2, 6). Anal. calcd for C23H19N5 (365.43): C
75.59, H 5.24, N 19.16; found C 75.50, H 5.20, N 19.15.
7-(3,5-Dimethyl-1H-pyrazol-1-yl)-2-phenyl-5-p-
tolylpyrazolo[1,5-c]pyrimidine (3b) 1 g, yield 83%;
m.p. 200—201 ℃; 1H NMR (CDCl3, 500 MHz) δ: 2.41
(s, 3H, CH3), 2.42 (s, 3H, CH3), 2.45 (s, 3H, CH3), 6.16
(s, 1H, 1H-pyrazole-H), 6.94 (s, 1H, pyrazole-H), 7.81
(s, 1H, pyrimidine-H), 7.26—7.45 (m, 5H, aromatic-H),
7.96—7.99 (m, 4H, aromatic-H); IR (KBr) υmax: 1618
(pyrazole ring C＝N), 1535 (pyrimidine ring C＝N),
Ethyl 3-(2-(2,5-diphenylpyrazolo[1,5-c]pyrimidin-
7-yl)hydrazono)butanoate (4a) 1 g, yield 81%; m.p.
1
142—144 ℃; H NMR (DMSO-d6, 500 MHz) δ: 1.22
(t, J＝7.2 Hz, 3H, CH2CH3), 2.37 (s, 3H, CH3), 3.55 (s,
2H, CH2), 4.08 (q, J＝6.9 Hz, 2H, CH2CH3), 7.09 (s, 1H,
pyrazole-H), 7.38—7.67 (m, 6H, aromatic-H), 7.52 (s,
1H, pyrimidine-H), 8.04—8.08 (m, 4H, aromatic-H),
9.81 (s, 1H, exchangeable NH); IR (KBr) υmax: 3344
(NH), 1732 (C＝O), 1628 (pyrazole ring C＝N), 1574
－1
(pyrimidine ring C＝N), 1＋450 (C＝C) cm ; MS m/z
(%): 413 (M＋, 38), 399 (M －CH2, 4), 368 (M＋－OEt,
51), 326 (M＋－C2H2CO2Et, 100), 299 (M＋－C6H10O2,
29), 286 (M＋－C6H9NO2, 42), 272 (M＋－C6H9N2O2,
33). Anal. calcd for C24H23N5O2 (413.47): C 69.72, H
5.61, N 16.94; found C 69.69, H 5.63, N 16.90.
＋
－1
1441 (C＝C) cm ; ＋MS m/z (%): 381 (M ＋2, 12), 379
(M＋, 100), 365 (M －CH2, 37), 351 (M＋－C2H4, 4),
337 (M＋－C2H4N, 21), 322 (M＋－C3H7N, 3), 296 (M＋
－C5H9N, 4), 167 (M＋－C13H14N3, 13). Anal. calcd for
C24H21N5 (379.50): C 75.97, H 5.58, N 18.46; found C
75.95, H 5.60, N 18.50.
Ethyl 3-(2-(2-phenyl-5-p-tolylpyrazolo[1,5-c]py-
rimidin-7-yl)hydrazono)butanoate (4b) 1 g, yield
78%; m.p. 152—153 ℃; 1H NMR (CDCl3, 500 MHz) δ:
1.28 (t, J＝7.4 Hz, 3H, CH2CH3), 2.25 (s, 3H, CH3),
2.40 (s, 3H, CH3), 3.61 (s, 2H, CH2), 4.22 (q, J＝7.4 Hz,
2H, CH2CH3), 6.76 (s, 1H, pyrazole-H), 7.25—7.50 (m,
5H, aromatic-H), 7.37 (s, 1H, pyrimidine-H), 7.99—
8.01 (m, 4H, aromatic-H), 9.44 (s, 1H, exchangeable
NH); IR (KBr) υmax: 3443 (NH), 1734 (C＝O), 1633
(pyrazole ring C＝N), 1610 (pyrimidine r＋ing C＝N),
5-(4-Methoxyphenyl)-7-(3,5-dimethyl-1H-pyra-
zolo-1-yl)-2-phenylpyrazolo[1,5-c]pyrimidine (3c)
1
g, yield 84%; m.p. 192—193 ℃; 1H NMR (CDCl3, 500
MHz) δ: 2.42 (s, 3H, CH3), 2.45 (s, 3H, CH3), 3.86 (s,
3H, OCH3), 6.16 (s, 1H, 1H-pyrazole-H), 6.92 (s, 1H,
pyrazole-H), 7.74 (s, 1H, pyrimidine-H), 6.98 (d, J＝9.2
Hz, 2H, aromatic-H), 7.37—7.45 (m, 3H, aromatic-H),
7.97 (d, J＝8.4 Hz, 2H, aromatic-H), 8.02 (d, J＝8.5 Hz,
2H, aromatic-H); IR (KBr) υmax: 1618 (pyrazole ring C
－1
1451 (C＝C) cm ; MS m/z (%): 428 (M , 45), 413
－1
＝N), 1529 (pyrimidine ring C＝N), 1450 (C＝C) cm ;
(M＋ －CH3, 4), 382 (M＋ －EtOH, 55), 340 (M＋ －
CH3CO2Et, 100), 313 (M＋－C6H11O2, 20), 300 (M＋－
C6H10NO2, 33), 285 (M＋－C6H11N2O2, 26), 270 (M＋－
C7H14N2O2, 9). Anal. calcd for C25H25N5O2 (427.50): C
70.24, H 5.89, N 16.38; found C 70.20, H 5.91, N 16.41.
Ethyl 3-(2-(5-(4-methoxyphenyl)-2-phenylpyra-
zolo[1,5-c]pyrimidin-7-yl)hydrazono)-butanoate (4c)
MS m/z (%): 380 (M＋－CH3, 100), 354 (M＋－C2H3N,
34), 316 (M＋－C5H5N, 12), 303 (M＋－C7H8, 6), 275
(M＋－C7H8N2, 30), 197 (M＋－C14H16N, 46). Anal.
calcd for C24H21N5O (395.50): C 72.89, H 5.35, N 17.71;
found C 72.90, H 5.33, N 17.68.
5-(4-Chlorophenyl)-7-(3,5-dimethyl-1H-pyrazol-
1-yl)-2-phenylpyrazolo[1,5-c]pyrimidine (3d) 1 g,
1
1 g, yield 75%; m.p. 151—152 ℃; H NMR (CDCl3,
1
yield 84%; m.p. 181—182 ℃; H NMR (CDCl3, 500
500 MHz) δ: 1.24 (t, J＝8.4 Hz, 3H, CH2CH3), 2.36 (s,
3H, CH3), 3.54 (s, 2H, CH2), 3.83 (s, 3H, OCH3), 4.07
(q, J＝6.9 Hz, 2H, CH2CH3), 6.98 (s, 1H, pyrazole-H),
7.43 — 7.62 (m, 5H, aromatic-H), 7.46 (s, 1H,
pyrimidine-H), 8.03—8.12 (m, 4H, aromatic-H), 9.76 (s,
1H, exchangeable NH); IR (KBr) υmax: 3468 (NH), 1742
(C＝O), 1630 (pyrazole ring－C＝N), 1580 (pyrimidine
MHz) δ: 2.41 (s, 3H, CH3), 2.44 (s, 3H, CH3), 6.16 (s,
1H, 1H-pyrazole-H), 6.97 (s, 1H, pyrazole-H), 7.81 (s,
1H, pyrimidine-H), 7.38—7.45 (m, 5H, aromatic-H),
7.97 (d, J＝6.9 Hz, 2H, aromatic-H), 8.01 (d, J＝9.2 Hz,
2H, aromatic-H); IR (KBr) υmax: 1618 (pyrazole ring
C＝N), 1535 (pyrimidine＋ring C＝N), 1440 (C＝C)
＋
＋
－1
1
cm ; MS m/z (%): 401 (M ＋1, 32), 399 (M －1, 100),
386 (M＋－CH2, 9), 371 (M＋－C2H5, 4), 357 (M＋－
C2H5N, 28), 330 (M ＋ － C3H6N2, 4), 227 (M ＋ －
C10H11N3, 9), 192 (M＋－C10H11ClN3, 7). Anal. calcd for
C23H18ClN5 (399.90): C 69.08, H 4.54, N 17.51; found
C 69.00, H 4.50, N 17.61.
ring C＝N), ＋1459 (C＝C) cm ; MS m/z (%): 444 (M ,
36), 398 (M －EtOH, 85), 356 (M＋－CH3CO2Et, 81),
331 (M＋－C6H9O2, 43), 329 (M＋－C6H11O2, 24), 316
(M＋－C6H10NO2, 100), 302 (M＋－C6H10N2O2, 85), 271
(M＋ －C7H13N2O3, 33), 242 (M＋ －C7H14N4O3, 26).
Anal. calcd for C25H25N5O3 (443.50): C 67.70, H 5.68,
N 15.79; found C 67.67, H 5.70, N 15.82.
Ethyl 3-(2-(5-aryl-2-phenylpyrazolo[1,5-c]pyrimidin-
7-yl)hydrazono)butanoates (4a— 4d)
Ethyl 3-(2-(5-(4-chlorophenyl)-2-phenylpyrazolo-
[1,5-c]pyrimidin-7-yl)hydrazono)butanoate (4d) 1 g,
1
General procedure Ethyl acetoacetate (0.4 g, 3
mmol) was added to a suspension of 5-aryl-7-hy-
drazino-2-phenylpyrazolo[1,5-c]pyrimidines (1a—1d, 3
mmol) in ethanol (50 mL) and the reaction mixture was
stirred overnight for 24 h at room temperature. The ob-
tained product was filtered off, washed with EtOH and
crystallized from CHCl3/EtOH to give the titled com-
pounds 4a—4d as colorless needles.
yield 75%; m.p. 157—158 ℃; H NMR (CDCl3, 500
MHz) δ: 1.30 (t, J＝7.4 Hz, 3H, CH2CH3), 2.25 (s, 3H,
CH3), 3.60 (s, 2H, CH2), 4.22 (q, J＝4.2 Hz, 2H,
CH2CH3), 6.78 (s, 1H, pyrazole-H), 7.41—7.50 (m, 5H,
aromatic-H), 7.36 (s, 1H, pyrimidine-H), 8.00 (d, J＝7.3
Hz, 2H, aromatic-H), 8.03 (d, J＝8.6 Hz, 2H, aro-
matic-H), 9.44 (s, 1H, exchangeable NH); IR (KBr) υmax
3435 (NH), 1730 (C＝O), 1627 (pyrazole ring C＝N),
:
2452
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 2451— 2460

Study of the Reaction of 5-Aryl-7-hydrazino-2-phenylpyrazolo[1,5-c]pyrimidines
－1
1578 (pyrimidine＋ring C＝N), 1451＋(C＝C) cm ; ＋MS
m/z (%): 450 (M ＋2, 37), 448 (M ,＋79), 432 (M －
CH4, 8), 404 (M＋－C3H8, 48), 401 (M －C2H7O, 100),
362 (M＋－CHCO2Et, 47), 333 (M＋－C6H11O2, 38), 320
(M＋－C6H10NO2, 39), 305 (M＋－C6H11N2O2, 41). Anal.
calcd for C24H22ClN5O2 (447.90): C 64.35, H 4.95, N
15.64; found C 64.32, H 4.98, N 15.60.
C5H3O, 17), 316 (M＋ －C4H3NO, 52), 287 (M＋ －
C5H4NO2, 16). Anal. calcd for C23H19N5O2 (397.40): C
69.51, H 4.82, N 17.62; found C 69.49, H 4.80, N 17.66.
1-(5-(4-Chlorophenyl)-2-phenylpyrazolo[1,5-c]-
pyrimidin-7-yl)-3-methyl-1H-pyrazol-5-ol (6d) 0.80
1
g, yield 66%; m.p. 242—243 ℃; H NMR (DMSO-d6,
500 MHz) δ: 2.01 (s, 3H, CH3), 7.08 (s, 1H, pyrazole-H),
7.41 (s, 1H, pyrazole-H), 7.42—7.50 (m, 5H, aromatic-
H), 7.66 (s, 1H, pyrimidine-H), 8.09 (d, J＝8.6 Hz, 4H,
aromatic-H), 10.14 (s, 1H, exchangeable aromatic
C-OH); IR (KBr) υmax: 3451 (OH), 1652 (pyrazole ring
C＝N), 1558 (pyrimidine ring C＝N), 1450 (C＝C)
1-(5-Aryl-2-phenylpyrazolo[1,5-c]pyrimidin-7-yl)-3-
methyl-1H-pyrazol-5-ols (6a— 6d)
General procedure Ethyl 3-(2-(5-aryl-2-phenyl-
pyrazolo[1,5-c]pyrimidin-7-yl)hydrazono)butanates (4a
—4d, 1 g) and glacial acetic acid (20 mL) were heated
under reflux for 2 h. Evaporation of the acetic acid un-
der reduced pressure gave a residue which crystallized
from CHCl3/EtOH to give the titled compounds 6a—6d
as colorless needles.
＋
＋
－1
cm ; MS m/z (%): 402 (M , 1), 377 (M －C2H, 13),
366 (M＋－Cl, 1), 337 (M＋－C4HO, 4), 336 (M＋－
C4H2O, 9), 308 (M ＋ － C4H2N2O, 6), 306 (M ＋ －
C4H4N2O, 19). Anal. calcd for C22H16ClN5O (401.80):
C 65.76, H 4.01, N 17.43; found C 65.72, H 3.99, N
17.40.
1-(2,5-Diphenylpyrazolo[1,5-c]pyrimidin-7-yl)-3-
methyl-1H-pyrazol-5-ol (6a) 0.80 g, yield 73%; m.p.
1
5-Aryl-3-nitro-2-phenylpyrazolo[1,5-c]pyrimidin-
7(6H)-ones (7a— 7d)
270—272 ℃; H NMR (DMSO-d6, 500 MHz) δ: 2.47
(s, 3H, CH3), 7.14 (s, 1H, pyrazole-H), 7.21—7.54 (m,
6H, aromatic-H), 7.43 (s, 1H, pyrazole-H), 7.64 (s, 1H,
pyrimidine-H), 7.79 (d, J＝5.1 Hz, 2H, aromatic-H),
8.17 (d, J＝4.5 Hz, 2H, aromatic-H), 10.31 (s, 1H, ex-
changeable aromatic C-OH); IR (KBr) υmax: 3356 (OH),
1612 (pyrazole ring C＝N), 1554 (pyrimidine＋ring C＝
General procedure A mixture of nitric acid (d
1.41, 1 mL) and sulfuric acid (d 1.84, 1 mL) in glacial
acetic acid (10 mL) was gradually added to a suspension
of 5-aryl-7-(3,5-dimethyl-1H-pyrazol-1-yl)-2-phenyl-
pyrazolo[1,5-c]-pyrimidines (3a—3d, 1 mmol) in gla-
cial acetic acid (10 mL) with stirring for 3 h at room
temperature. The reaction mixture was then poured onto
cold water with stirring and the yellow precipitated sol-
ids were filtered, washed with cold water, dried and
crystallized from EtOH to give the titled compounds
7a—7d as yellow needles.
－1
N),＋1442 (C＝C) cm ; MS m/z (%): 367 (M , 2), 366
(M＋－1, 9), 350 (M＋－OH, ＋2), 339 (M＋－CO, 21), ＋298
(M －C4H5O, 6), 290 (M －C6H5, 6), 271 (M －
C4H4N2O, 2). Anal. calcd for C22H17N5O (367.40): C
71.92, H 4.66, N 19.06; found C 71.90, H 4.70, N 19.02.
1-(2-Phenyl-5-p-tolylpyrazolo[1,5-c]pyrimidin-7-
yl)-3-methyl-1H-pyrazol-5-ol (6b) 0.80 g, yield 70%;
3-Nitro-2,5-diphenylpyrazolo[1,5-c]pyrimidin-
7(6H)-one (7a) 0.25 g, yield 76%; m.p. 301—302 ℃;
1H NMR (DMSO-d6, 500 MHz) δ: 7.26 (s, 1H,
pyrimidine-H), 7.50—7.57 (m, 6H, aromatic-H), 7.70 (d,
J＝6.9 Hz, 2H, aromatic-H), 7.84 (d, J＝7.7 Hz, 2H,
aromatic-H), 12.72 (s, 1H, exchangeable NH); IR (KBr)
υmax: 3221 (NH), 1717 (C＝O), 1620 (pyrazole ring C＝
1
m.p. 227—228 ℃; H NMR (DMSO-d6, 500 MHz) δ:
2.01 (s, 3H, CH3), 2.32 (s, 3H, CH3), 7.02 (s, 1H, pyra-
zole-H), 7.26—7.57 (m, 5H, aromatic-H), 7.41 (s, 1H,
pyrazole-H), 7.57 (s, 1H, pyrimidine-H), 7.97 (d, J＝7.7
Hz, 2H, aromatic-H), 8.07 (d, J＝8.2 Hz, 2H, aro-
matic-H), 10.13 (s, 1H, exchangeable aromatic C-OH);
IR (KBr) υmax: 3451 (OH), 1625 (pyrazole ring C＝N),
－1
N), 1562 (pyrimidine＋ring C＝N), 1485 (C＝C) cm ;
－1
1585 (pyrimidine ＋ring C＝N), 1440＋(C＝C) cm ; MS
MS m/z (%): 332 (M , 99), 302 (M＋－CH2O, 7), 275
(M＋－CHN2O, 4), 261 (M＋－CHN3O, 11), 257 (M＋－
CHNO3, 5), 212 (M＋ －C7H6NO, 13), 196 (M＋ －
C7H6NO2, 28). Anal. calcd for C18H12N4O3 (332.31): C
65.06, H 3.64, N 16.86; found C 65.08, H 3.66, N 16.86.
3-Nitro-2-phenyl-5-p-tolylpyrazolo[1,5-c]pyri-
midin-7(6H)-one (7b) 0.25 g, yield 71%; m.p. 179—
m/z (%): 380 (M －1, 1), 316 (M －C4HO, 8), 315
(M＋－C4H2O, 8), 301 (M＋－C4H2NO, 6), 300 (M＋－
C4H3NO, 3), 286 (M＋－C6H7O, 46). Anal. calcd for
C23H19N5O (381.40): C 72.42, H 5.02, N 18.36; found C
72.39, H 5.00, N 18.40.
1-(5-(4-Methoxyphenyl)-2-phenylpyrazolo[1,5-c]-
pyrimidin-7-yl)-3-methyl-1H-pyrazol-5-ol (6c) 0.80
1
180 ℃; H NMR (CDCl3, 500 MHz) δ: 2.45 (s, 3H,
1
g, yield 67%; m.p. 213—214 ℃; H NMR (DMSO-d6,
CH3), 6.94 (s, 1H, pyrimidine-H), 7.25—7.28 (m, 2H,
aromatic-H), 7.37—7.45 (m, 3H, aromatic-H), 7.81 (s,
1H, exchangeable NH), 7.96—7.99 (m, 4H, aromatic-H);
IR (KBr) υmax: 3213 (NH), 1739 (C＝O), 1612 (pyra-
zole ring－C＝N), 1504 (pyrimidine ＋ring C＝N), 1443 (C
500 MHz) δ: 2.01 (s, 3H, CH3), 3.77 (s, 3H, OCH3),
6.99 (s, 1H, pyrazole-H), 6.99—7.48 (m, 5H, aro-
matic-H), 7.40 (s, 1H, pyrazole-H), 7.50 (s, 1H,
pyrimidine-H), 8.01 (d, J＝8.4 Hz, 2H, aromatic-H),
8.07 (d, J＝8.4 Hz, 2H, aromatic-H), 10.13 (s, 1H, ex-
changeable aromatic C-OH); IR (KBr) υmax: 3263 (OH),
1666 (pyrazole ring C＝N), 1578 (pyrimidine＋ring C＝
＋
1
＝C) cm ; MS m/z (%): 346 (M , 100), 316 (M －
CH2O, 14), 300 (M＋－NO2, 22), 272 (M＋－CNO3, 26),
241 (M＋－C7H5O, 12), 210 (M＋－C7H6NO2, 16), 182
(M＋ －C7H6N3O2, 16). Anal. calcd for C19H14N4O3
(346.34): C 65.89, H 4.07, N 16.18; found C 65.90, H
－1
N),＋1447 (C＝C) cm ; MS m/z (%): 397 (M , 1), 357
(M －CH2O, 4), 331 (M＋－C4H2O, 100), 318 (M＋－
Chin. J. Chem. 2011, 29, 2451— 2460
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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2453

Atta
FULL PAPER
4.05, N 16.17.
5-(4-Methoxyphenyl)-3-nitro-2-phenylpyrazolo-
[1,5-c]pyrimidin-7(6H)-one (7c) 0.25 g, yield 69%;
C22H15N7O5 (457.40): C 57.77, H 3.31, N 21.44; found
C 57.79, H 3.28, N 21.47.
1-(3-Nitro-2-phenyl-5-p-tolylpyrazolo[1,5-c]pyri-
1
m.p. 172—173 ℃; H NMR (DMSO-d6, 500 MHz) δ:
midin-7-yl)-3-methyl-4-nitro-1H-pyrazol-5-ol
(8b)
3.82 (s, 3H, OCH3), 7.10 (d, J＝8.5 Hz, 2H, aro-
matic-H), 7.37 (s, 1H, pyrimidine-H), 7.47 (d, J＝9.2
Hz, 2H, aromatic-H), 7.51—7.54 (m, 3H, aromatic-H),
7.65 (d, J＝6.1 Hz, 2H, aromatic-H), 13.15 (s, 1H, ex-
changeable NH); IR (KBr) υmax: 3211 (NH), 1736 (C＝
O), 1624 (pyrazole ring C＝N), 1527 (pyrimidine ring
0.35 g, yield 74%; m.p. 137 — 138 ℃ ; 1H NMR
(DMSO-d6, 500 MHz) δ: 2.37 (s, 3H, CH3), 2.32 (s, 3H,
CH3), 7.32—7.68 (m, 5H, aromatic-H), 7.43 (s, 1H,
pyrimidine-H), 8.03 (d, J＝7.7 Hz, 2H, aromatic-H),
8.32 (d, J＝6.9 Hz, 2H, aromatic-H), 12.60 (s, 1H, ex-
changeable aromatic C-OH); IR (KBr) υmax: 3459 (OH),
1636 (pyrazole ring C＝N), 1544 (pyrimidine＋ring C＝
＋
－1
C＝N), 1447 (C＝C) cm ; MS m＋/z (%): 364 (M ＋2,
6), 349 (M＋＋2－CH3, 3), 345 (M －OH, 8), 331 (M＋
－CH3O, 51), 302 (M＋ －C2H4O2, 14), 213 (M＋ －
C7H5N2O2, 11), 198 (M＋－C8H8N2O2, 15). Anal. calcd
for C19H14N4O4 (362.34): C 62.98, H 3.89, N 15.46;
found C 62.90, H 3.91, N 15.44.
－1
N),＋1447 (C＝C) cm ; MS m/z (%): 471 (M , 2), ＋420
(M －H3O3, 4), 401 (M＋－C2NO2, 12), 400 (M －
C2HNO2, 17), 360 (M＋ －C4HNO3, 3), 359 (M＋ －
C4H2NO3, 2), 358 (M＋－C4H3NO3, 2), 357 (M＋－
C4H4NO3, 2). Anal. calcd for C23H17N7O5 (471.40): C
58.60, H 3.63, N 20.80; found C 58.63, H 3.65, N 20.77.
1-(5-(4-Methoxyphenyl)-3-nitro-2-phenylpyra-
zolo[1,5-c]pyrimidin-7-yl)-3-methyl-4-nitro-1H-
pyrazol-5-ol (8c) 0.35 g, yield 71%; m.p. 177—178
℃; 1H NMR (DMSO-d6, 500 MHz) δ: 2.47 (s, 3H, CH3),
3.81 (s, 3H, OCH3), 7.05—7.64 (m, 5H, aromatic-H),
7.53 (s, 1H, pyrimidine-H), 8.04 (d, J＝7.6 Hz, 2H,
aromatic-H), 8.32 (d, J＝6.8 Hz, 2H, aromatic-H),
12.65 (s, 1H, exchangeable aromatic C-OH); IR (KBr)
υmax: 3462 (OH), 1625 (pyrazole ring C＝N), 1566
5-(4-Chlorophenyl)-3-nitro-2-phenylpyrazolo[1,5-
c]pyrimidin-7(6H)-one (7d) 0.25 g, yield 68%; m.p.
1
180—181 ℃; H NMR (CDCl3, 500 MHz) δ: 7.46 (s,
1H, pyrimidine-H), 7.55—7.59 (m, 3H, aromatic-H),
7.65 (d, J＝8.6 Hz, 2H, aromatic-H), 8.05 (d, J＝7.7 Hz,
2H, aromatic-H), 8.22 (d, J＝8.6 Hz, 2H, aromatic-H),
8.48 (s, 1H, exchangeable NH); IR (KBr) υmax: 3120
(NH), 1733 (C＝O), 1616 (pyrazole ring C＝N), 1535
－1
(pyrimidine ring C＝N), 1442＋(C＝C) cm ; MS m/z
(%): 370 (M＋＋3, 10), 369 (M ＋2, 11), 367 (M＋, 34),
337 (M＋－CH2O, 10), 257 (M＋－CHClNO3, 14), 232
(M＋－C7H5NO2, 16), 230 (M＋－C7H7NO2, 36), 203
(M＋－C7H6N3O2, 26), 189(M＋－C8H6N2O3, 17). Anal.
calcd for C18H11ClN4O3 (366.76): C 58.95, H 3.02, N
15.28; found C 58.97, H 3.01, N 15.30.
－1
(pyrimidine ring C＝N), 1474 (C＝C) cm ; MS m/＋z
(%): 487 (M＋, 1), 316 (M＋－C5H5N3O4, 18), 302 (M
－C6H7N3O4, 2), 301 (M＋－C6H8N3O4, 4), 207 (M＋－
C11H10N3O6, 31). Anal. calcd for C23H17N7O6 (487.40):
C 56.67, H 3.52, N 20.12; found C 56.70, H 3.50, N
20.14.
1-(5-Aryl-3-nitro-2-phenylpyrazolo[1,5-c]pyrimidin-
7-yl)-3-methyl-4-nitro-1H-pyrazol-5-ols (8a— 8d)
1-(5-(4-Chlorophenyl)-3-nitro-2-phenylpyrazolo-
[1,5-c]pyrimidin-7-yl)-3-methyl-4-nitro-1H-pyrazol-
1
General procedure A mixture of nitric acid (d
1.41, 1 mL) and sulfuric acid (d 1.84, 1 mL) in glacial
acetic acid (10 mL) was gradually added to a suspension
of 1-(5-aryl-2-phenylpyrazolo[1,5-c]pyrimidin-7-yl)-3-
methyl-1H-pyrazol-5-ols (6a—6d, 1 mmol) in glacial
acetic acid (10 mL) with stirring for 3 h at room tem-
perature. The reaction mixture was then poured onto
cold water with stirring and the yellow precipitated sol-
ids were filtered, washed with cold water, dried and
crystallized from EtOH to give the titled compounds 8a
—8d as yellow needles.
5-ol (8d) 0.35 g, yield 71%; m.p. 164—165 ℃; H
NMR (DMSO-d6, 500 MHz) δ: 2.47 (s, 3H, CH3), 7.31
—7.52 (m, 5H, aromatic-H), 7.53 (s, 1H, pyrimidine-H),
7.94 (d, J＝7.7 Hz, 2H, aromatic-H), 8.11—8.22 (m, 2H,
aromatic-H), 12.79 (s, 1H, exchangeable aromatic
C-OH); IR (KBr) υmax: 3459 (OH), 1634 (pyrazole ring
C＝N), 1551 (pyrimidine ＋ring C＝N),＋ 1474 (C＝C)
－1
cm ; MS m/z (%): 492 (M , 1), 398 (M －CClNO2, 4),
366 (M＋－CClNO4, 7), 320 (M＋－C4H4N4O4, 14), 316
(M＋－C4H2ClN3O3, 36), 301 (M＋－C4HClN3O4, 12).
Anal. calcd for C22H14ClN7O5 (491.80): C 53.72, H 2.87,
N 19.93; found C 53.75, H 2.89, N 19.90.
1-(3-Nitro-2,5-diphenylpyrazolo[1,5-c]pyrimidin-
7-yl)-3-methyl-4-nitro-1H-pyrazol-5-ol (8a) 0.35 g,
1
5-Aryl-7-(3,5-dimethyl-1H-pyrazol-1-yl)-3-iodo-2-
phenylpyrazolo[1,5-c]pyrimidines (9a, 9c, 9d)
yield 76%; m.p. 178—180 ℃; H NMR (DMSO-d6,
500 MHz) δ: 2.47 (s, 3H, CH3), 7.47—7.69 (m, 5H,
aromatic-H), 7.59 (s, 1H, pyrimidine-H), 8.05 (d, J＝7.7
Hz, 2H, aromatic-H), 8.34 (d, J＝6.7 Hz, 2H, aro-
matic-H), 12.67 (s, 1H, exchangeable aromatic C-OH);
IR (KBr) υmax: 3320 (OH), 1624 (pyrazole ring C＝N),
General procedure A solution of iodine
monochloride (0.2 g, 1.2 mmol) in acetic acid (10 mL)
was gradually added to a suspension of 5-aryl-7-(3,5-
dimethyl-1H-pyrazol-1-yl)-2-phenylpyrazolo[1,5-
c]pyrimidines (3a, 3c, 3d, 1 mmol) in acetic acid (10
mL) with stirring for 3 h at room temperature. The reac-
tion mixture was then poured onto crushed ice and the
precipitated 5-aryl-7-(3,5-dimethyl-1H-pyrazol-1-yl)-3-
iodo-2-phenylpyrazolo-[1,5-c]pyrimidines (9a, 9c, 9d)
－1
1504 (pyrimidine ring C＝N), 1467 (C＝C) cm ; MS
m/z (%): 457 (M＋, 1), 396 (M＋－CH3NO2, 1), 395 (M＋
－CH4NO2, 1), 361 (M＋－C4H2NO2, 5), 347 (M＋－
C4NO3, 3), 332 (M＋ －C4HN2O3, 15), 316 (M＋ －
C4H3N3O3, 2), 315 (M＋－C4H4N3O3, 1). Anal. calcd for
2454
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 2451— 2460

Study of the Reaction of 5-Aryl-7-hydrazino-2-phenylpyrazolo[1,5-c]pyrimidines
were filtered, washed with water, dried and crystallized
from EtOH as colorless needles.
were filtered, washed with water, dried and crystallized
from EtOH as colorless needles.
3-Iodo-7-(4-iodo-3,5-dimethyl-1H-pyrazol-1-yl)-
2,5-diphenylpyrazolo[1,5-c]pyrimidine (10a) 0.45 g,
7-(3,5-Dimethyl-1H-pyrazol-1-yl)-3-iodo-2,5-
diphenylpyrazolo[1,5-c]pyrimidine (9a) 0.4 g, yield
1
1
yield 72%; m.p. 243—244 ℃; H NMR (DMSO-d6,
82%; m.p. 213—214 ℃; H NMR (DMSO-d6, 500
500 MHz) δ: 2.22 (s, 3H, CH3), 2.38 (s, 3H, CH3), 7.47
—7.53 (m, 6H, aromatic-H), 7.84 (d, J＝7.7 Hz, 2H,
aromatic-H), 8.12 (s, 1H, pyrimidine-H), 8.19 (d, J＝6.1
Hz, 2H, aromatic-H); IR (KBr) υmax: 1620 (pyrazole
ring C＝N), 1542 (pyrimidine ring C＝N), 1442 (C＝C)
MHz) δ: 2.22 (s, 3H, CH3), 2.38 (s, 3H, CH3), 6.23 (s,
1H, 1H-pyrazole-H), 7.46—7.53 (m, 6H, aromatic-H),
7.85 (d, J＝6.7 Hz, 2H, aromatic-H), 8.11 (s, 1H,
pyrimidine-H), 8.19 (d, J＝7.7 Hz, 2H, aromatic-H); IR
(KBr) υmax: 1620 (pyrazole ring C ＝ N), 1540
＋
＋
－1
－1
cm ; MS m/z (%): 618 (M ＋1, 100), 603 (M －CH2,
3), 577 (M＋－C2H2N, 6), 491 (M＋＋1－I, 68), 463 (M＋
－C2H3I, 7), 450 (M＋－C3H4I, 34), 363 (M＋－I2, 12),
348 (M＋－CH3I2, 7), 335 (M＋－C2H4I2, 10). Anal.
calcd for C23H17I2N5 (617.22): C 44.76, H 2.78, N 11.35;
found C 44.74, H 2.80, N 11.38.
(pyrimidine ring C＝N), 144＋6 (C＝C) cm ; MS m/z
(%): 493 (M＋＋2, 8), 492 (M＋＋1, 27), 491 (M＋, 100),
477 (M＋－CH2, 8), 463 (M －C2H4, 8), 449 (M＋－
C2H4N, 37), 364 (M＋－I, 46), 349 (M＋－CH3I, 15), 322
(M＋－C3H6I, 29). Anal. calcd for C23H18IN5 (491.33): C
56.22, H 3.69, N 14.25; found C 56.25, H 3.71, N 14.23.
7-(3,5-Dimethyl-1H-pyrazol-1-yl)-3-iodo-5-(4-
methoxyphenyl)-2-phenylpyrazolo[1,5-c]pyrimidine
3-Iodo-7-(4-iodo-3,5-dimethyl-1H-pyrazol-1-yl)-2-
phenyl-5-p-tolylpyrazolo[1,5-c]pyrimidine
(10b)
1
0.45 g, yield 71%; m.p. 199—200 ℃; 1H NMR (CDCl3,
500 MHz) δ: 2.39 (s, 3H, CH3), 2.42 (s, 3H, CH3), 2.47
(s, 3H, CH3), 7.30 (d, J＝8.4 Hz , 2H, aromatic-H), 7.46
—7.48 (m, 3H, aromatic-H), 7.78 (s, 1H, pyrimidine-H),
7.97—8.03 (m, 4H, aromatic-H); IR (KBr) υmax: 1612
(pyrazole ring C＝N), 1549 (pyrimidine r＋ing C＝N),
(9c) 0.4 g, yield 77%; m.p. 227—228 ℃; H NMR
(DMSO-d6, 500 MHz) δ: 2.21 (s, 3H, CH3), 2.34 (s, 3H,
CH3), 3.80 (s, 3H, OCH3), 6.22 (s, 1H, 1H-pyrazole-H),
7.05 (d, J＝8.5 Hz, 2H, aromatic-H), 7.47—7.53 (m, 3H,
aromatic-H), 7.84 (d, J＝6.9 Hz, 2H, aromatic-H), 7.95
(s, 1H, pyrimidine-H), 8.14 (d, J＝9.2 Hz, 2H, aro-
matic-H); IR (KBr) υmax: 1622 (pyrazole ring C＝N),
－1
1439 (C＝C) cm ; MS m/＋z (%): 632 (M ＋1, 100),
617 (M＋－CH2, 3), 591 (M －C2H2N, 5), 540 (M＋－
C7H7, 22), 490 (M＋－CH2I, 54), 464 (M＋－C2H2IN,
38), 449 (M＋－C3H5IN, 3), 413 (M＋－C7H7I, 16), 378
(M＋＋1－I2, 97). Anal. calcd for C24H19I2N5 (631.30):
C 45.66, H 3.03, N 11.09; found C 45.69, H 3.00, N
11.08.
－1
1542 (pyrimidine＋ring C＝N), 1444 (C＝C) cm ; ＋MS
m/z (%): 523 (M＋＋2, 7), 521 (M＋, 100＋), 507 (M －
CH2, 15), 479 (M －C2H4N, 19), 394 (M －I, 77), 378
(M＋－CH4I, 25), 353 (M＋－C3H5I, 19), 351 (M＋－
C2H5IN, 25). Anal. calcd for C24H20IN5O (521.35): C
55.29, H 3.87, N 13.43; found C 55.31, H 3.85, N 13.45.
5-(4-Chlorophenyl)-7-(3,5-dimethyl-1H-pyrazol-
1-yl)-3-iodo-2-phenylpyrazolo[1,5-c]pyrimidine (9d)
3-Iodo-7-(4-iodo-3,5-dimethyl-1H-pyrazol-1-yl)-5-
(4-methoxyphenyl)-2-phenylpyrazolo[1,5-c]-pyrim-
1
idine (10c) 0.45 g, yield 69%; m.p. 224—225 ℃; H
1
0.4 g, yield 75%; m.p. 219—220 ℃; H NMR (CDCl3,
NMR (CDCl3, 500 MHz) δ: 2.30 (s, 3H, CH3), 2.42 (s,
3H, CH3), 3.89 (s, 3H, OCH3), 7.18—8.20 (m, 9H, aro-
500 MHz) δ: 2.38 (s, 3H, CH3), 2.45 (s,3H, CH3), 6.15
(s, 1H, 1H-pyrazole-H), 7.77 (s, 1H, pyrimidine-H),
7.45—7.47 (m, 5H, aromatic-H), 7.98—8.06 (m, 4H,
aromatic-H); IR (KBr) υmax: 1603 (pyrazole ring C＝N),
matic-H), 7.90 (s, 1H, pyrimidine-H); IR (KBr) υmax
:
1607 (pyrazole ring C＝N), 1518 (pyrimidine ring C＝
＋
－1
N), 141＋2 (C＝C) cm ; MS m/z (%): 648 (M ＋1, 13),
522 (M ＋2－I, 100), 507 (M＋－CHI, 14), 480 (M＋－
C2H2IN, 6), 443 (M＋－C6H5I, 2), 395 (M＋－C6H9IN2O,
41), 379 (M＋－CH2I2, 14), 352 (M＋－C2H3I2N, 11).
Anal. calcd for C24H19I2N5O (647.20): C 44.54, H 2.96,
N 10.82; found C 44.51, H 2.99, N 10.80.
－1
1535 (pyrimidine ring C＝N), 1406 (C＝C) cm ; ＋MS
m/z (%): 528 (M＋＋＋2, 18), 526 (M＋, 100), 512 (M －
CH2, 6), 483 (M －C2H5N, 3), 447 (M＋－C3H7Cl, 6),
401 (M＋－C5H8N4, 17), 399 (M＋－I, 30), 383 (M＋－
C8H11Cl, 13), 357 (M＋－C9H11ClN, 9). Anal. calcd for
C23H17ClIN5 (525.77): C 52.54, H 3.26, N 13.32; found
C 52.51, H 3.24, N 13.30.
4-Iodo-1-(5-aryl-3-iodo-2-phenylpyrazolo[1,5-c]py-
rimidin-7-yl)-3-methyl-1H-pyrazol-5-ols (11a— 11d)
5-Aryl-3-iodo-7-(4-iodo-3,5-dimethyl-1H-pyrazol-1-
yl)-2-phenylpyrazolo[1,5-c]pyrimidines (10a— 10c)
General procedure A solution of iodine mono-
chloride (0.4 g, 2.4 mmol) in acetic acid (10 mL) was
gradually added to a suspension of (5-aryl-2-phenyl-
pyrazolo[1,5-c]pyrimidin-7-yl)-3-methyl-1H-pyrazol-
5-ols (6a—6d, 1 mmol) in acetic acid (10 mL) with stir-
ring for 3 h at room temperature. The reaction mixture
was then poured onto crushed ice and the precipitated
5-aryl-4-iodo-1-(3-iodo-2-phenylpyra-zolo[1,5-c]py-
rimidin-7-yl)-3-methyl-1H-pyrazol-5-ols (11a — 11d)
were filtered, washed with water, dried and crystallized
from EtOH as colorless needles.
General procedure A solution of iodine mono-
chloride (0.4 g, 2.4 mmol) in acetic acid (10 mL) was
gradually added to a suspension of 5-aryl-7-(3,5-dimeth-
yl-1H-pyrazol-1-yl)-2-phenylpyrazolo[1,5-c]pyrim-
idines (3a—3c, 1 mmol) in acetic acid (10 mL) with
stirring for 3 h at room temperature. The reaction mix-
ture was then poured onto crushed ice and the precipi-
tated 5-aryl-3-iodo-7-(4-iodo-3,5-dimethyl-1H-pyrazol-
1-yl)-2-phenylpyrazolo[1,5-c]pyrimidines (10a — 10c)
Chin. J. Chem. 2011, 29, 2451— 2460
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
2455

Atta
FULL PAPER
5-Aryl-3-bromo-7-(4-bromo-3,5-dimethyl-1H-pyra-
zol-1-yl)-2-phenylpyrazolo[1,5-c]pyrimidines (12a—
12d)
4-Iodo-1-(3-iodo-2,5-diphenylpyrazolo[1,5-c]-
pyrimidin-7-yl)-3-methyl-1H-pyrazol-5-ol
(11a)
0.45 g, yield 73%; m.p. 202 — 204 ℃ ; 1H NMR
(DMSO-d6, 500 MHz) δ: 2.47 (s, 3H, CH3), 7.13—7.50
(m, 6H, aromatic-H), 7.63 (s, 1H, pyrimidine-H), 7.79
(d, J＝7.4 Hz, 2H, aromatic-H), 8.21 (d, J＝8.2 Hz, 2H,
aromatic-H), 10.38 (s, 1H, exchangeable aromatic
C-OH); IR (KBr) υmax: 3210 (OH), 1620 (pyrazole ring
C＝N), 1551 (pyrimidine ring C＝N), 1450 (C＝C)
General procedure A solution of bromine (0.12
mL, 2.4 mmol) in acetic acid (10 mL) was gradually
added to a suspension of 5-aryl-7-(3,5-dimethyl-1H-
pyrazol-1-yl)-2-phenylpyrazolo[1,5-c]pyrimidines (3a
—3d, 1 mmol) in acetic acid (10 mL) with stirring for 3
h at room temperature. The precipitated 5-aryl-3-bromo-
7-(4-bromo-3,5-dimethyl-1H-pyrazol-1-yl)-2-phenylpy-
razolo[1,5-c]pyrimidines (12a — 12d) were filtered,
washed with water, dried and crystallized from EtOH as
colorless needles.
＋
＋
－1
cm ; MS m/z (%): 621 (M ＋2, 27), 364 (M －HI2,
14), 363 (M＋－H2I2, 62), 333 (M＋－CH4I2O, 9), 287
(M＋－C6H6I2, 20), 247 (M＋－C8H8I2N, 12). Anal. calcd
for C22H15I2N5O (619.20): C 42.67, H 2.44, N 11.31;
found C 42.70, H 2.46, N 11.29.
3-Bromo-7-(4-bromo-3,5-dimethyl-1H-pyrazol-1-
yl)-2,5-diphenylpyrazolo[1,5-c]pyrimidine (12a) 0.4
4-Iodo-1-(3-iodo-2-phenyl-5-p-tolylpyrazolo[1,5-
1
g, yield 77%; m.p. 215—216 ℃; H NMR (DMSO-d6,
c]pyrimidin-7-yl)-3-methyl-1H-pyrazol-5-ol
(11b)
500 MHz) δ: 2.24 (s, 3H, CH3), 2.37 (s, 3H, CH3), 7.45
—7.53 (m, 6H, aromatic-H), 7.89 (d, J＝7.7 Hz, 2H,
aromatic-H), 8.19 (d, J＝6.7 Hz, 2H, aromatic-H), 8.22
(s, 1H, pyrimidine-H); IR (KBr) υmax: 1624 (pyrazole
ring C＝N), 1543 (pyrimidine ring C＝N), 1447 (C＝C)
0.45 g, yield 71%; m.p. 199—200 ℃; IR (KBr) υmax
:
3220 (OH), 1612 (pyrazole ring C ＝ N), 1555
－1
(pyrimidine ring C＝N), 1447 (C＝C) cm ; MS m/z
(%): 635 (M＋＋2, 7), 633 (M＋, 11), 618 (M＋－CH3, 7),
601 (M＋－CH3OH, 3), 599 (M＋－CH6O, 17), 584 (M＋
－C2H9O, 6), 334 (M＋－C11H10INO, 26), 300 (M＋－
C6H7I2, 100). Anal. calcd for C23H17I2N5O (633.20): C
43.63, H 2.71, N 11.06; found C 43.60, H 2.75, N 11.10.
4-Iodo-1-(3-iodo-5-(4-methoxyphenyl)-2-phenyl-
pyrazolo[1,5-c]pyrimidin-7-yl)-3-methyl-1H-pyrazol-
＋
＋
－1
cm ; MS m/z (%): 527＋(M ＋4, 4), 525 (M ＋2, 38),
523 (M＋, 100), 509 (M －CH2, 4), 482 (M＋－C2H3N,
9), 446 (M＋－C6H5, 10), 445 (M＋－C6H6, 63), 428 (M＋
－CH3Br, 11), 363 (M＋－C5H6BrN, 11). Anal. calcd for
C23H17Br2N5 (523.22): C 52.80, H 3.27, N 13.39; found
C 52.78, H 3.30, N 13.40.
1
5-ol (11c) 0.45 g, yield 69%; m.p. 211—212 ℃; H
3-Bromo-7-(4-bromo-3,5-dimethyl-1H-pyrazol-1-
yl)-2-phenyl-5-p-tolylpyrazolo[1,5-c]pyrimidine (12b)
NMR (DMSO-d6, 500 MHz) δ: 2.47 (s, 3H, CH3), 3.82
(s, 3H, OCH3), 7.05—8.18 (m, 9H, aromatic-H), 7.53 (s,
1H, pyrimidine-H), 9.61 (s, 1H, exchangeable aromatic
C-OH); IR (KBr) υmax: 3240 (OH), 1605 (pyrazole ring
C＝N), 1551 (pyrimidine ring C＝N), 1408 (C＝C)
1
0.4 g, yield 74%; m.p. 217—218 ℃; H NMR (CDCl3,
500 MHz) δ: 2.39 (s, 3H, CH3), 2.41 (s, 3H, CH3), 2.45
(s, 3H, CH3), 7.29 (d, J＝7.9 Hz, 2H, aromatic-H), 7.45
—7.49 (m, 3H, aromatic-H), 7.81 (s, 1H, pyrimidine-H),
7.99 (d, J＝8.0 Hz, 2H, aromatic-H), 8.04 (d, J＝7.7 Hz,
2H, aromatic-H); IR (KBr) υmax: 1616 (pyrazole ring
C＝N), 1529 (pyrimidine ring C＝N), 143＋9 (C＝C)
＋
＋
－1
cm ; MS m/z (%): 506 (M －CH4I, 24), 359 (M －
C10H11IO2, 22), 350 (M＋－C11H10INO, 39), 331 (M＋－
C11H13INO2, 22), 317 (M＋－C6H6I2, 82), 301 (M＋－
C6H6I2O, 31), 288 (M＋ －C8H11I2, 34), 286 (M＋ －
C7H9I2O, 29), 246 (M＋－C9H9I2O2, 22). Anal. calcd for
C23H17I2N5O2 (649.20): C 42.55, H 2.64, N 10.79; found
C 42.57, H 2.60, N 10.82.
＋
－1
cm ; MS m/z (%): 541＋(M ＋4, 4), 539 (M ＋2, 38),
537 (M＋, 100), 523 (M －CH2, 4), 496 (M＋－C2H3N,
10), 459 (M＋－Br, 85), 457 (M＋－Br, 74), 442 (M＋－
CH3Br, 14), 418 (M＋－C3H3Br, 28), 416 (M＋－C3H3Br,
26). Anal. calcd for C24H19Br2N5 (537.20): C 53.65, H
3.56, N 13.04; found C 53.57, H 3.53, N 13.00.
1-(5-(4-Chlorophenyl)-3-iodo-2-phenylpyrazolo[1,
5-c]pyrimidin-7-yl)-4-iodo-3-methyl-1H-pyrazol-5-ol
(11d) 0.45 g, yield 69%; m.p. 204—205 ℃; 1H NMR
(DMSO-d6, 500 MHz) δ: 2.01 (s, 3H, CH3), 7.40 (s, 1H,
pyrimidine-H), 7.44—7.56 (m, 5H, aromatic-H), 7.98 (d,
J＝7.6 Hz, 2H, aromatic-H), 8.16 (d, J＝8.4 Hz, 2H,
aromatic-H), 10.17 (s, 1H, exchangeable aromatic
C-OH); IR (KBr) υmax: 3468 (OH), 1625 (pyrazole ring
C＝N), 1576 (pyrimidine ring C＝N), 1462 (C＝C)
3-Bromo-7-(4-bromo-3,5-dimethyl-1H-pyrazol-1-
yl)-5-(4-methoxyphenyl)-2-phenyl-pyrazolo[1,5-c]-
pyrimidine (12c) 0.4 g, yield 73%; m.p. 201—202
1
℃; H NMR (DMSO-d6, 500 MHz) δ: 2.56 (s, 6H,
2CH3), 3.60 (s, 3H, OCH3), 7.59 (s, 1H, pyrimidine-H),
7.14—7.93 (m, 5H, aromatic-H), 8.19 (d, J＝7.7 Hz, 2H,
aromatic-H), 8.21 (d, J＝7.6 Hz, 2H, aromatic-H); IR
(KBr) υmax: 1609 (pyrazole ring C ＝ N), 1539
＋
＋
－1
－1
cm ; MS m/z (%): 506 (M －C9H10NO, 49), 504 (M
(pyrimidine ring C＝N), 143＋7 (C＝C) cm ; MS m/z
－C8H5ClN, 100), 464 (M＋－C2H4ClI, 28), 462 (M＋－
CH2ClIO, 61), 446 (M＋－CH4ClINO, 11), 432 (M＋－
C4H3IN2O, 15), 377 (M＋－C9H7ClI, 6), 335 (M＋－
CH2ClI2O, 6), 319 (M＋－CH4ClI2NO, 10), 305 (M＋－
CH4ClI2N2O, 45). Anal. calcd for C22H14ClI2N5O
(653.60): C 40.43, H 2.16, N 10.71; found C 40.45, H
2.20, N 10.74.
(%): 55＋7 (M＋＋4, 4), 555 (＋M ＋2, 40), 553 (M＋,＋100),
539 (M －CH2, 4), 512 (M －C2H3N, 7), 475 (M －Br,
63), 473 (M＋－Br, 53), 458 (M＋－CH3Br, 10), 431
(M＋ －C7H10O, 17). Anal. calcd for C24H19Br2N5O
(553.20): C 52.10, H 3.46, N 12.66; found C 52.12, H
3.44, N 12.63.
3-Bromo-7-(4-bromo-3,5-dimethyl-1H-pyrazol-1-
2456
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 2451— 2460

Study of the Reaction of 5-Aryl-7-hydrazino-2-phenylpyrazolo[1,5-c]pyrimidines
yl)-5-(4-chlorophenyl)-2-phenyl-pyrazolo[1,5-c]-
pyrimidine (12d) 0.4 g, yield 71%; m.p. 222—223
3.89 (s, 3H, OCH3), 7.01—7.87 (m, 9H, aromatic-H),
7.53 (s, 1H, pyrimidine-H), 9.58 (s, 1H, exchangeable
aromatic C-OH); IR (KBr) υmax: 3320 (OH), 1686
(pyrazole ring C－＝N), 1593 (pyrimidine＋ring C＝N),
1
℃; H NMR (CDCl3, 500 MHz) δ: 2.39 (s, 3H, CH3),
2.45 (s, 3H, CH3), 7.83 (s, 1H, pyrimidine-H), 7.45—
7.49 (m, 5H, aromatic-H), 8.03—8.06 (m, 4H, aro-
matic-H); IR (KBr) υmax: 1616 (pyrazole ring C＝N),
1
1442 (C＝C) cm＋ ; MS m/z (%): 557 ＋(M ＋2, 1), 555
(M＋, 2), 541 (M －CH2, 59), 523 (M －CH3OH, 25),
494 (M＋－C2H5O2, 59), 474 (M＋－HBr, 24), 459 (M＋
－CH4Br, 100), 443 (M＋－CH4BrO, 21), 395 (M＋－Br2,
18), 381 (M＋－CH2Br2, 16), 364 (M＋－CH3Br2O, 17).
Anal. calcd for C23H17Br2N5O2 (555.20): C 49.75, H
3.09, N 12.61; found C 49.77, H 3.11, N 12.64.
－1
1539 (pyrimidine ring C＝N), 1433 (C＝C) cm ; MS
m/z (%): 561＋(M＋＋4, 14), 559 (M＋＋2, 51), 557 (M＋,
100), 543 (M －CH2, 4), 516 (M＋－C2H3N, 11), 480.5
(M＋－C2H3ClN, 39), 400 (M＋－C2H3BrClN, 4). Anal.
calcd for C23H16Br2ClN5 (557.70): C 49.54, H 2.89, N
12.56; found C 49.56, H 2.90, N 12.52.
4-Bromo-1-(3-bromo-5-(4-chlorophenyl)-2-
phenylpyrazolo[1,5-c]pyrimidin-7-yl)-3-methyl-1H-
pyrazol-5-ol (13d) 0.40 g, yield 71%; m.p. 237—238
℃; 1H NMR (DMSO-d6, 500 MHz) δ: 2.47 (s, 3H, CH3),
7.48 — 7.54 (m, 3H, aromatic-H), 7.55 (s, 1H,
pyrimidine-H), 7.66 (d, J＝7.7 Hz, 2H, aromatic-H),
7.78 (d, J＝6.9 Hz, 2H, aromatic-H), 7.83 (d, J＝6.9 Hz,
2H, aromatic-H), 12.25 (s, 1H, exchangeable aromatic
C-OH); IR (KBr) υmax: 3468 (OH), 1641 (pyrazole ring
C＝N), 1582 (pyrimidine ring C＝N), 1435 (C＝C)
4-Bromo-1-(5-aryl-3-bromo-2-phenylpyrazolo[1,5-c]-
pyrimidin-7-yl)-3-methyl-1H-pyrazol-5-ols (13a —
13d)
General procedure A solution of bromine (0.12
mL, 2.4 mmol) in acetic acid (10 mL) was gradually
added to a suspension of 1-(5-aryl-2-phenylpyra-
zolo[1,5-c]pyrimidin-7-yl)-3-methyl-1H-pyrazol-5-ols
(6a—6d, 1 mmol) in acetic acid (10 mL) with stirring
for 3 h at room temperature. The precipitated 4-bromo-
1-(5-aryl-3-bromo-2-phenylpyrazolo[1,5-c]pyrimidin-7-
yl)-3-methyl-1H-pyrazol-5-ols (13a—13d) were filtered,
washed with water, dried and crystallized from EtOH as
colorless needles.
＋
＋
－1
cm ; MS m/z (%): 546 (M －CH2, 52), 544 (M －
CH4, 95), 541 (M＋－H3O, 100), 465 (M＋－CH3Br, 7),
463 (M＋－HBrO, 15), 383 (M＋－HBr2O, 11). Anal.
calcd for C22H14Br2ClN5O (559.60): C 47.22, H 2.52, N
12.51, found C 47.25, H 2.50, N 12.48.
4-Bromo-1-(3-bromo-2,5-diphenylpyrazolo[1,5-
c]pyrimidin-7-yl)-3-methyl-1H-pyrazol-5-ol
(13a)
Results and discussion
0.40 g, yield 75%; m.p. 221 — 223 ℃ ; 1H NMR
(DMSO-d6, 500 MHz) δ: 2.47 (s, 3H, CH3), 7.29—8.23
(m, 10H, aromatic-H), 7.55 (s, 1H, pyrimidine-H),
10.69 (s, 1H, exchangeable aromatic C-OH); IR (KBr)
υmax: 3348 (OH), 1616 (pyrazole ring C＝N), 1554
Condensation of 5-aryl-7-hydrazino-2-phenylpyra-
zolo[1,5-c]pyrimidines (1a—1d), which were readily
obtained from ethyl phenylpropiolate,29,30 with
1,3-dicarbonyl compounds was studied. Thus, treatment
of 1a—1d with acetylacetone under reflux for 1 h af-
forded the respective dehydrative cyclized products 3a
—3d rather than the hydrazone derivatives 2a—2d as
confirmed from their spectral and elemental analyses.
－1
(pyrimidine ring C＝N), 1447 (C＝C) cm ; MS m/z
(%): 445 (M＋－Br, 10), ＋444 (M＋－HBr, 7), 366 (M＋＋－
C4HBrNO, 20), 365 (M －C4H2BrNO, 8), 364 (M －
C4H3BrNO, 19). Anal. calcd for C22H15Br2N5O (525.20):
C 50.31, H 2.88, N 13.33; found C 50.30, H 2.90, N
13.35.
1
Their H NMR spectra showed the absence of both NH
and NH2 protons as well as the CH2 protons of the
starting materials. Moreover, a new characteristic
singlet signals corresponding to the two methyl groups
as well as H-4 of the newly synthesized pyrazole ring
moity were assigned at δH 2.41—2.47 and 6.16—6.18,
respectively. The singlets at δH 6.92—6.99 and 7.74—
7.87 were due to H-3 and H-4 of the pyrazolopyrimidine
moiety (Scheme 1).
4-Bromo-1-(3-bromo-2-phenyl-5--p-tolylpyra-
zolo[1,5-c]pyrimidin-7-yl)-3-methyl-1H-pyrazol-5-ol
(13b) 0.40 g, yield 74%; m.p. 168—170 ℃; 1H NMR
(DMSO-d6, 500 MHz) δ: 2.47 (s, 3H, CH3), 2.36 (s, 3H,
CH3), 7.29—7.57 (m, 5H, aromatic-H), 7.56 (s, 1H,
pyrimidine-H), 7.66 (d, J＝6.2 Hz, 2H, aromatic-H),
7.86 (d, J＝6.1 Hz, 2H, aromatic-H), 9.63 (s, 1H, ex-
changeable aromatic C-OH); IR (KBr) υmax: 3430 (OH),
1680 (pyrazole ring C＝N), 1585 (pyrimidine ＋ring C＝
On the other hand, condensation of 1a—1d with
equimolar amounts of ethyl acetoacetate at room tem-
perature in ethanol afforded the respective hydrazone
derivatives ethyl 3-(2-(5-aryl-2-phenylpyrazolo[1,5-c]-
pyrimidin-7-yl)hydrazono)butanoates 4a—4d rather
than the respective hydrazides 5a—5d as confirmed
from their spectral analyses. Their IR spectra showed a
characteristic sharp absorption band at 1730—1742
－1
N), 1442 (C＝C) cm＋ ; MS m/z (%):＋540 (M ＋1, 1),
539 (M＋, 1), 538 (M －1, 1), 521 (M －H2O, 66), 458
(M＋－HBr, 32), 443 (M＋－CH4Br, 36), 299 (M＋－
C4H2Br2NO, 25), 282 (M＋－C4H5Br2N2O, 16). Anal.
calcd for C23H17Br2N5O (539.20): C 51.23, H 3.18, N
12.99; found C 51.20, H 3.20, N 13.00.
－1
4-Bromo-1-(3-bromo-5-(4-methoxyphenyl)-2-
phenylpyrazolo[1,5-c]pyrimidin-7-yl)-3-methyl-1H-
pyrazol-5-ol (13c) 0.40 g, yield 71%; m.p. 176—178
℃; 1H NMR (DMSO-d6, 500 MHz) δ: 2.47 (s, 3H, CH3),
cm for ester carbonyl group－whereas, that of NH was
1
1
absorbed at 3435—3468 cm . Furthermore, the H
NMR spectra of 4a—4d showed a characteristic signals
of the ethyl ester group that resonated as triplet at δH
Chin. J. Chem. 2011, 29, 2451— 2460
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
2457

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FULL PAPER
1.22—1.30 and a quartet at δH 4.07—4.22 corre-
sponding to CH3 and CH2 protons, respectively, in
agreement with the formation the hydrazone 4a—4d
rather than hydrazide 5a—5d that also, was confirmed
from the presence of only one exchangeable NH proton
at δH 9.44—9.81. Moreover, the assignment of singlet
signal at δH 3.54—3.61 characteristic for the methylene
protons confirmed the assigned hydrazone structure
rather than the cyclized products 6a—6d. Furthermore,
the MS spectra of 4a—4d also confirmed the assigned
structure (cf. Experimental). Cyclization of 4a—4d was
attempted by boiling in glacial acetic acid for 2 h to give
1-(5-aryl-2-phenylpyrazolo[1,5-c]pyrimidin-7-yl)-3-
methyl-1H-pyrazol-5-ols (6a—6d). Their structures
were achieved from their elemental analyses and spec-
tral data. Their IR spectra showed the absence of ab-
sorption bands characteristic for ester and NH groups,
nation reactions on both compounds 3a—3d and 6a—
6d were studied with the aim that introduction of such
substituted groups may enhance their biological proper-
ties as well as study the more reactive position for
electrophilic substitution reactions on such ring system.
Thus, nitration of 3a—3d with a mixture nitric acid and
sulfuric acid in glacial acetic acid at room temperature
gave the unexpected 5-aryl-3-nitro-2-phenylpyrazolo-
[1,5-c]pyrimidin-7(6H)ones (7a—7d) as confirmed
from their spectral data. The MS spectra of compounds
7a—7d showed a molecular ion peak in agreement with
losing of dimethylpyrazole moiety and introduction of
1
only one nitro group. Moreover, the H NMR spectra
showed the absence of both signals of the two methyl
groups. Furthermore, an exchangeable NH proton was
assigned at δH 7.81—13.15 and only a singlet signal of
the pyrimidine unit was resonated at δH 6.94—7.46
which confirmed that nitration reaction took place at
pyrazole ring as well as an oxidative cleavage of the
3,5-dimethylpyrazole moiety took place to give 7a—7－d.
1
which were also disappeared from their H NMR spec-
tra. Also, singlet of the methylene protons was omitted
and instead two characteristic singlets of H-4 of the cy-
clized pyrazole ring and its C5-OH proton were as-
signed at δH 6.99—7.14 and 10.13—10.31, respectively.
In the present investigation the nitration and haloge-
1
The amidic carbonyl absorption at 1717—1739 cm
also, supports the assigned structure. On the other hand,
under similar reaction conditions, nitration of 6a—6d
Scheme 1 Synthesis of pyrazolylpyrazolopyrimidines
2458
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 2451— 2460

Study of the Reaction of 5-Aryl-7-hydrazino-2-phenylpyrazolo[1,5-c]pyrimidines
1
afforded the respective dinitro derivatives 8a—8d as
spectra, H NMR spectra as well as their elemental
analyses (cf. Experimental). The introduction of
monoiodo group at C-3 of the pyrazolopyrimidine moi-
ety rather than C-4 of the pyrazole side chain proves that
it is the more reactive position to electrophilic substitu-
tion reaction. Furthermore, the pyrazole ring is also
more reactive to electrophilic substitution reaction rather
than the pyrimidine ring since the second electrophilic
substitution step took place at the side chain pyrazole
ring moiety, with the formation of either dinitro, diiodo
or dibromo derivatives.
established from their spectral analyses. Their mass
spectra showed a molecular ion peaks (m/z 457—492) in
agreement with the introduction of two nitro groups;
1
whereas, their H NMR spectra showed the disappear-
ance of singlet signals corresponding to the two pyra-
zoles ring protons and the presence of an exchangeable
aromatic C-OH at δH 12.60—12.79 and only a singlet
signal of the pyrimidine unit at δH 7.43—7.59 (Scheme
2).
Iodination of 3a, 3c, 3d with 1 mol equiv. of iodine
monochloride in acetic acid at room temperature gave
the respective monoiodo derivatives; 5-aryl-7-(3,5-
dimethyl-1H-pyrazol-1-yl)-3-iodo-2-phenylpyrazolo-
[1,5-c]pyrimidines (9a, 9c, 9d), whereas with excess of
ICl compounds 3a—3c and 6a—6d afforded the diiodo
derivatives 10a—10c and 11a—11d, respectively.
Alternatively, bromination of 3a—3d as well as 6a—6d
with excess bromine in glacial acetic acid at room
temperature also afforded the dibromides 12a—12d and
13a—13d, respectively. The structures of the synthe-
sized products 9—13 were established from their mass
Conclusions
In conclusion, a library of functionalized pyra-
zolylpyrazolopyrimidines and their substituted analogs
has been successively achieved. The strategy for con-
structing the target compounds is based on the hetero-
cyclisation of 5-aryl-7-hydrazino-2-phenylpyrazolo-
[1,5-c]pyrimidines (1a—1d)29,30 with three-carbon do-
nors such as acetylacetone and ethyl acetoacetate.
Scheme 2 Electrophilic substitution reactions of pyrazolylpyrazolopyrimidines
Chin. J. Chem. 2011, 29, 2451— 2460
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
2459

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