Aminoazoles in heterocycles synthesis: II. Trifluoromethyl-containing diketones in the synthesis of pyrazolo[1,5-a]pyrimidines

Article abstract of DOI:10.1023/A:1012417816375

A regioselective synthesis was carried out of 7-trifluoromethylpyrazolo[1,5-a]pyrimidines by reaction of 3(5)aminopyrazoles with 1,3-diketones containing CF₃ group. The characteristic chemical shifts were established for C⁵ and C⁷ atoms of the pyrimidine ring and of substituents thereof in the ¹H, ¹³C, and ¹⁹F NMR spectra of pyrazolo[1,5-a]pyrimidines.

Full text of DOI:10.1023/A:1012417816375

Russian Journal of Organic Chemistry, Vol. 37, No. 6, 2001, pp. 852 858. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 6, 2001,
pp. 899 905.
Original Russian Text Copyright 2001 by Emelina, Petrov, Firsov.
Aminoazoles in Heterocycles Synthesis: II.*
Trifluoromethyl-containing Diketones in the Synthesis
of Pyrazolo[1,5-a]pyrimidines
E. E. Emelina, A. A. Petrov, and A. V. Firsov
St. Petersburg State University, St. Peresburg, 198504 Russia
Received July 20, 2000
Abstract A regioselective synthesis was carried out of 7-trifluoromethylpyrazolo[1,5-a]pyrimidines by
reaction of 3(5)aminopyrazoles with 1,3-diketones containing CF3 group. The characteristic chemical shifts
1
were established for C5 and C7 atoms of the pyrimidine ring and of substituents thereof in the H, 13C, and 19
F
NMR spectra of pyrazolo[1,5-a]pyrimidines.
3(5)-Aminopyrazoles are widely applied to pre-
paration of various polycyclic nitrogen-containing
heterocycles [2 5]. However the rules governing the
reactions between 3(5)-aminopyrazoles and nonsym-
metrical dielectrophiles yielding regioisomers of
pyrazolo[1,5-a]pyrimidines [3 9} are poorly studied,
and definite proofs of the regiostructure of com-
pounds obtained are seldom given. Note that the
unambiguous proof of the regiostructure of the
heterocycles formed is not an easy task. Just in a few
works was independently obtained every regioisomer
of pyrazolo[1,5-a]pyrimidines [1, 6, 10], and in [1,
10] were reported unambiguous proofs of their
structure based on 1H and 13C NMR spectra.
In the present study we investigated reactions of
substituted 3(5)-aminopyrazoles Ia h with trifluoro-
methyl-containing 1,3-diketones IIa c. The structure
of
pyrazolo[1,5-a]pyrimidines
obtained
was
1
determined from the H, 19F, and 13C NMR spectra.
The reaction of 3(5)aminopyrazoles Ib h with
1,1,1-trifluoropentane-2,4-dione (IIc) in ethanol gave
rise to two isomeric pyrazolopyrimidines, IIIb h,
and IVb h (Tables 1, 2).
Scheme.
I, III VI, R1 = XC6H4, R2 = H: X = 4-t-Bu (a), 4-Me (b), H (c), 4-Br (d), 4-Cl (e), 3-Br (f); R2 = Ph, R1 = H
(g), Me (h); R3 =Me (IIIb h, IVb h), Ph (Va h), t-Bu (VIc, d, f). II, R3 = Me (a), Ph (b), t-Bu (c).
Compounds
IIIb/IVb
IIIc/IVc
IIId/IVd
IIIe/IVe
IIIf/IVf
IIIg/IVg
IIIh/IVh
Isomers ratio, %
75/25
70/30
79/21
85/15
69/31
97/3
92/8
*
For communication I see [1].
1070-4280/01/3706-0852$25.00 2001 MAIK Nauka/Interperiodica

AMINOAZOLES IN HETEROCYCLES SYNTHESIS: II.
853
Boiling in acetic acid and fusion of the reagents
provides only pyrazolopyrimidines IIIb h.
duction of the trifluoromethyl group in positions 5
and 7 respectively changed C5(7) CF3 by 10 12 ppm,
whereas the effect on the chemical shift of C7(5) CF3
from the pyrimidine ring was small. Besides the
chemical shifts of the carbon atoms of the isomeric
pyrazolopyrimidines IIIb h, IVc are well consistent
with those of the model symmetrical 5,7-bis(trifluoro-
The determination of the regiostructure of pyrazol-
pyrimidines IIIb h and IVb h is based on compari-
son of the chemical shifts of protons and carbons
belonging to pyrimidine ring and methyl groups in
1
the H and 13C NMR spectra with the corresponding
methyl)-2-phenylpyrazolo[1,5-a]pyrimidine
(XI),
characteristic chemical shifts observed previously in
the NMR spectra of model 2-phenylpyrazolo[1,5-a]-
pyrimidines: 5-methyl- (VII) [10], 7-methyl- (VIII)
[10], 7-methyl-6-ethoxycarbonyl- (IX) [1], 5,7-di-
C, ppm: 145.5 q (C5CF3, JCF 37.0 Hz), 135.1 q
(C7CF3, JCF 38.5 Hz) (Table 3).
methyl- (X) [1, 10]: C5CH3 ( 2.6 2.7 ppm,
24
17 and
C
and 158 ppm ), C7CH3 ( 2.8 2.9 ppm,
C
147 ppm ).
Thus the observed signals of C5 and C7 atoms
from pyrimidine ring at CF3 group in pyrazolopyr-
imidines IIIb h, IVc, XI in the 13C NMR spectra
appear as characteristic quartets with considerably
different chemical shifts: C5CF3
147 ppm,
C
1
C7CF3
134 ppm.
The comparison of the chemical shifts in the H
and 13C NMR spectra of the model compounds
VII X (Table 3) and of pyrazolopyrimidines IIIb h
and IVb h (Tables 1, 2) shows that the proton signals
in the 2.64 2.70 ppm region and carbon signals at
25 and 158 ppm correspond to C5CH3 group of
pyrazolopyrimidines IIIb h, and the resonances at
2.89 2.91 and 17.2, 147.5 ppm belong to C7CH3
group of pyrazolopyrimidines IVb h.
C
The cyclocondensation of substituted aminopyr-
azoles Ia h with 4-phenyl-1,1,1-trifluorobutane-2,4-
dione by boiling in acetic acid ot by fusion also gives
rise to a single isomer of pyrazolopyrimidines. The
regiostructure of compounds Va h obtained was
proved by 13C NMR spectra with the use of the
previously assigned characteristic signals of the ipso-
atoms in the phenyl ring (C5Cipso
,
136 ppm,
C
1
C7Cipso
,
131 ppm) [1, 10], and also by
The above analysis of the characteristics of H and
comparisonCof the chemical shifts of C5 and C7 atoms
with those of the characteristic signals C7CF3, C5CF3
(Table 2). The presence of the characteristic quartet
13C NMR spectra from the isomeric pyrazolo-
pyrimidines IIIb h, IVb h showed that the reaction
of aminopyrazoles Ib h with 1,1,1-trifluoropentane-
2,4-dione affords in ethanol predominantly and in
acetic acid and at fusion solely IIIb h isomers with
trifluoromethyl group located in 7 position.
CCF3 at
phenyl group at
134 ppm and of signal Cipso of the
136 ppm permits an unambiguous
C
assignment of the compounds obtained to the 7-tri-
fluoromethyl-5-phenyl-containing isomers Va h.
The assignment of carbon signal from CF3 group
and from C5 and C7 atoms at the CF3 group of
pyrazolopyrimidines IIIb h, IVc, (Table 1, 2) is easy
since they appear as characteristic quartets with the
coupling constants J(C F) 280 Hz and J(C CF3)
37 Hz respectively. The comparison of the
13C NMR spectra of compounds IIIb h, IVc with
that of a model compound 5,7-dimethyl-2-phenyl-
pyrazolo[1,5-a]pyrimidine (XI) revealed that intro-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 6 2001

Table 1. Yields, melting points, 1H NMR spectra, and elemental analyses of pyrazolopyrimidines III VI, XI
1H NMR, , ppm (CDCl3)
Compd. Yield, mp,
C
Found, %
Calculated, %
a
no.
%
Formula
C
H
C
H
IIIb
82
167.5
2.42 s (3H, CH3C6H4), 2.67 s (3H, C5CH3), 6.97 s (C3H), 6.98 s (C6H), 61.90 4.21
7.27 7.94 m (4H, C6H4)
C15H12F3N3
C14H10F3N3
C14H9BrF3N3 47.21 2.55
C14H9C1F3N3 53.95 2.91
C14H9BrF3N3 47.21 2.55
62.02 4.15
60.65 3.63
IIIc
IIId
84
83
179.5 180 2.64 s (C5CH3), 6.97 s (2H, C3H, C6H), 7.48 8.05 m (5H, Ph)
188 189
60.59 3.77
2.69 s (3H, C5CH3), 6.95 s (1H, C3H), 7.01 s (1H, C6H), 7.57 7.90 m 47.00 2.60
(4H, C6H4)
IIIe
IIIf
85
86
83
184.5 185 2.68 s (3H, C5CH3), 6.94 s (1H, C3H), 7.01 s (1H, C6H), 7.42 7.96 m 53.90 2.99
(4H, C6H4)
159 160
116
2.68 s (3H, C5CH3), 6.97 s (1H, C3H), 7.05 s (1H, C6H), 7.34 8.16 m 47.25 2.60
(4H, C6H4)
IIIgb
2.75 s (3H, C5CH3), 7.07 s (1H, C6H), 7.25 8.10 m (5H, Ph), 8.51 s 60.45 3.75
C14H10F3N3
60.65 3.63
(1H, C3H)
IIIhb
IVc
84
126 127
2.67 s (6H, C2CH3, C5CH3), 7.00 s (1H, C6H), 7.36 7.71 m (5H, Ph) 62.10 4.20
2.89 s (3H, C7CH3), 6.95 s (1H, C3H), 7.14 s (1H, C6H), 7.50 7.98 m 60.53 3.71
(5H, Ph)
C15H12F3N3
C14H10F3N3
62.02 4.15
60.65 3.63
c
c
Va
83
137.5
1.40 s (9H, 3CH3), 7.14 s (1H, C3H), 7.57 s (1H, C6H), 7.49
8.18 m (9H, Ar)
69.72 5.22
C23H20F3N3
69.86 5.10
Vb
Vc
Vd
Ve
85
87
88
165 166
150
176 178
2.44 s(3H, CH3), 7.13 s(1H, C3H), 7.57 s (1H, C6H), 7.25 8.19 m (9H, Ar) 67.78 4.15
C20H14F3N3
C19H12F3N3
67.98 3.99
67.26 3.56
7.10 s (1H, C3H), 7.62 s (1H, C6H), 7.56 8.18 m (10H, Ar)
7.10 s (1H, C3H), 7.62 s (1H, C6H), 7.54 8.14 m (9H, Ar)
67.50 3.71
54.42 2.77 C19H11BrF3N3 54.57 2.65
60.95 3.10 C19H11ClF3N3 61.06 2.97
54.39 2.85 C19H11BrF3N3 54.57 2.65
87 154.5 156.5 7.11 s (1H, C3H), 7.61 s (1H, C6H), 7.37 8.20 m (9H, Ar)
Vf
87
85
85
78
79
169 170
201 202
133 135
94.5 96
93
7.10 s (1H, C3H), 7.62 s (1H, C6H), 7.32 8.20 m (9H, Ar)
7.62 s (1H, C6H), 8.55 s (1H, C2H), 7.30 8.29 m (10H, Ar)
2.72 s (3H, C2CH3), 7.60 s (1H, C6H), 7.30 8.29 m (10H, Ar)
Vgb
Vhb
VIc
VId
VIh
XI
67.28 3.62
67.83 4.15 C20Hi4F3N3 67.98 3.99
C17H16F3N3 63.94 5.05
1.46 (9H, t-Bu), 7.03 s (1H, C3H), 7.23 s (1H, C6H), 7.54 7.96 m (4H, Ar) 51.20 3.85 C17H15BrF3N3 51.26 3.80
C19H12F3N3
67.26 3.56
1.45 (9H, t-Bu), 7.03 s (1H, C3H), 7.23 s (1H, C6H), 7.49 8.05 m (5H, Ph) 63.52 5.09
81 115.5 117.5 1.45 s(9H, t-Bu), 2.74 s(3H, C2CH3), 7.21 s (1H, C6H), 7.30 7.89 m (5H, Ph) 64.80 5.50
C18H13F3N3
C14H7F6N3
64.86 5.44
50.77 2.11
75
128 129
7.36 s (1H, C3H), 7.45 s (1H, C6H),7.47 8.09
m
(5H, Ph)
50.25 2.43
a
Yields of compounds IIIb h (procedure b) and Va h (procedure c) were not optimized.
Compounds IIIg, IIIh, Vh, Vg contain a phenyl group in position 4.
b
c
1
Compounds IVb h were identified in mixtures with compounds IIIb h. Chemical shifts in H NMR spectra of compounds Vb, IVd h, , ppm, (IVb): 2.44 s
(3H, CH3C6H4), 2.94 s (3H, C7CH3), 7.00 s (1H, C3H), 7.15 s (1H, C6H), 7.30 8.10 m (4H, Ar); (IVd): 2.92 s (3H, C7CH3), 7.02 s (1H, C3H), 7.13 s (1H, C6H),
7.50 7.90 m (4H, Ar); (IVf): 2.94 s (3H, C7CH3), 7.03 s (1H, C3H), 7.14 s (1H, C6H), 7.40 8.00 m (4H, Ar); (IVe): 2.95 s (3H, C7CH3), 7.04 s (1H, C3H),
7.16 s (1H, C6H), 7.30 8.26 m (4H, Ar); (IVa c): 2 .90 s (3H, C7CH3), 7.07 s (1H, C3H), 7.22 8.14 m (5H, Ar), 8.60 s (1H, CH); (IVh): 2.74 s (3H, C2CH3), 2 .90
s (3H, C7CH3), 7.00 s (1H, C3H), 7.30 7.80 m (5H, Ar).

Table 2. 13C NMR Spectra ( C, ppm) pirazolo[1,5-a]pirimidines (III VI) in CDCl3
Compd.no.
R1
R3
R4
C2
C3
C3a
C5
c6a
c76b
Ar
5-R
-Rc
IIIb
4-CH3C6H4 CH3 CF3 157.73 93.85 150.91 158.28 106.91 133.87 21.76, 127.08, 129.87,
139.77
25.28
119.92
IIIc
IIIcd
IIId
Ph
Ph
CH3 CF3 156.9 93.4
CH3 CF3 155.9 93.6
150.1 157.7
150.1 159.4
106.4
108.4
133.08 126.4, 128.4, 129.0, 131.9 24.6
131.75 126.4, 129.0, 129.5, 131.9 24.53
119.15
119.50
119.82
4-BrC6H4 CH3 CF3 156.39 94.09 150.94 158.69 107.36 133.88 123.92, 128.64, 131.60,
132.32
25.34
25.32
25.35
24.64
IIIe
IIIf
IIIg
IIIh
IVce
Va
4-ClC6H4
CH3 CF3 156.36 94.09 150.94 158.66 107.32 133.88 128.37, 129.36, 131.16,
135.63
119.82
119.81
119.27
119.97
3-BrCgH4 CH3 CF3 155.99 94.37 150.89 158.76 107.52 133.94 123.34, 125.76, 130.02,
130.69, 132.59, 134.75
He
CH3 CF3 143.28 110.69 145.03 157.96 106.93 133.37 126.23, 126.43, 128.44,
130.86
Mee
Ph
CH3 CF3 154.29 110.35 147.12 158.37 106.87 133.47 127.18, 128.95,
129.52, 131.98
25.43, 14.71
CF3 CH3 157.00 95.01 148.00 146.04 102.69 147.54 126.36, 128.40, 129.06,
131.94
120.48 q [J (5-CF3) 17.21
277.8 Hz]
Cipso 127.59, 129.52, 120.07
131.34, 136.61
4-(CH3)3C C6H5 CF3 158.25 95.09 151.21 155.50 103.63 134.45 126.18, 127.01, 129.87,
C6H4 153.07
Vb
4-CH3C6H4 C6H5 CF3 158.15 95.00 151.20 155.50 103.63 134.85 21.81, 127.11, 127.60
129.92, 139.87
Cipso 127.60, 129.50, 120.10
131.33, 136.80
Vc
Ph
C6H5 CF3 156.16 94.46 150.48 155.09 103.32 133.71 123.28, 127.91, 130.77,
1131.62
Cipso 126.86, 128.81, 119.21
131.62, 135.82
Vd
4-BrC6H4 C6H5 CF3 156.91 95.20 151.23 155.83 104.10 134.50 28.65, 124.03, 132.04
132.37
Cipso 127/62, 129.55, 118.97
131.51, 136.58

Table 2. (Contd.)
Compd.no.
Vd
R1
R3
R4
C2
C3
C3a
C5
c6a
c76b
Ar
5-R
-Rc
4-ClC6H4 C6H5
3-BrC6H4 C6H5
CF3 156.88 95.22 151.23 155.82 104.05 134.49 128.41, 129.43, 131.12
Cipso 127.62, 129.55, 118.87
131.52, 136.60
135.75
CF3 156.47 95.49 151.17 155.87 104.21 134.54 123.38, 125.76, 130.04
130.72, 132.66, 134.70
Ve
Cipso 127.63, 129.55, 118.91
131.53, 136.54
Vac
He
C6H5
C6H5
CF3 144.41 112.57 145.97 155.44 104.02 134.85 127.01, 127.25, 129.84
131.66
Cipso 127.70, 129.55, 118.97
131.58, 136.46
Vh
Mee
Ph
CF3 154.76 111.36 147.29 155.17 103.29 134.19 14.95 (C2CH3), 127.13, Cipso 127.61, 129.47, 120.14
128.02, 128.95, 132.09
131.34, 136.66
VIc
C(CH3)3 CF3 157.59 94.56 150.57 168.83 103.68 134.08 127.16, 129.19, 129.60, 29.77, 38.95
132.86
120.10
120.01
120.15
VId
4-BrC6H4 C(CH3)3 CF3 156.38 94.52 150.59 169.10 103.96 134.08 123.82, 128.64, 131.83, 29.76, 39.00
132.35
VIh
Med
C(CH3)3 CF3 154.13 110.16 146.57 168.58 103.38 133.65 126.82, 128.82, 129.20, 29.77, 39.07
132.34
a
Quartet, coupling constants for compounds IIIa h JCF 2.8 Hz, for compounds Va h JCF 3.3 Hz.
Quartet, coupling constants JCF 37 38.5 Hz.
Quartet, coupling constants JCF 274.8 Hz.
b
c
d
e
f
Solvent DMSO-d6.
R2
=
Ph.
13C NMR spectra of compounds IVb, d h were not registered because of low content of the isomer in the reaction mixture.
Table 3. 13C NMR spectra ( C, ppm) of model pyrazolo[l,5-a]pyrimidines (VII XI) in CDCl3
Compd.no. R1
VII [10] C6H5
VIII [10] C6H5
R3
H
R4
CH3 155.68 93.65 149.98 148.57
156.05 92.22 149.05 158.68
CH3 151.68 95.21 150.12 158.06
C2
C3
C3a
C5
c6a
107.40
108.39
110.75
108.29
c76b
146.03
133.84
150.27
145.17
Ar
5-R
-Rc
126.60, 128.75,
128.89, 133.05
126.13, 128.43,
128.59, 132.49
127.09, 129.20,
129.73, 132.76
126.51, 128.70,
128.73, 133.22
17.24
24.45
CH3
H
H
IX
X
C6H5
H
15.46
CH3 CH3 155.55 92.51 149.66 158.30
24.60
17.04
XI
C6H5
CF3 CF3 159.19 96.76 149.31 145.48 q (Jcp 101.76 q.q 135.09 q 126.94, 128.91,
37.0) (Jcp < 2) (Jcp 38.5) 130.07, 131.12
120.10
(Jcp 275.4)
q
118.93
(Jcp 275.4)
q

AMINOAZOLES IN HETEROCYCLES SYNTHESIS: II.
857
Even a bulky tert-butyl group does not hamper the
regioselectivity of the cyclocondensation of amino-
pyrazoles Ic, d, f with 5,5-dimethyl-1,1,1-trifluoro-
methylhexane-2,4-dione, and as a result of the reac-
tion arise substituted 5-tert-butyl-7-trifluoromethyl-
the reaction product. Aminopyrazoles Ia h react with
1,3-diketones IIa c in acetic acid or at fusion giving
rise to a single isomer in virtually quantitative
yield. This pyrazolo[1,5-a] pyrimidine contains the
trifluoromethyl group in 7 position.
pyrazolo[1,5-a]pyrimidines VIc, d, f,
(C7 CF3)
133.4 ppm (Table 2).
EXPERIMENTAL
The analysis of 19F NMR spectra of pyrazolo-
pyrimidines IIIc, IVc, Vc, VIc, XI showed that the
chemical shifts of fluorine atoms from the groups
C5CF3 and C7CF3 are quite similar and are not
1H and 13C NMR spectra were registered on
spectrometers Bruker AM-500, Bruker DPX300,
Bruker WP-200 (500, 300, 200 and 125.74, 75.47,
50.3 MHz respectively), 19F NMR spectra on spectro-
meter Bruker AM-500 (470.6 MHz, hexafluoro-
butadiene reference). CDCl3 and DMSO-d6 were used
as solvents.
characteristic ( C7CF3 65.64 IIIc, 65.50 Vc,
F
65.54 ppm VIc,
C5CF3 65.02 IVc,
C5CF3
F
and C7CF3 of moFdel compound XI 65.03 and
65.82 ppm respectively).
3(5)-Aminopyrazoles Ia h were prepared accord-
ing to procedures from [11, 12], compound IX as in
[13]. The preparation procedure for fluoro-containing
1,3-diketones IIa c was taken from [14].
The analysis of data from Tables 2, 3 revealed the
characteristic chemical shifts of the regioisomeric
pyrazolopyrimidines, especially those in the
13C NMR spectra, that permit unambiguous assign-
ment of isomer structure.
Pyrazolo[1,5-a]pyrimidines.
(a)
Equimolar
amounts of compounds I and II dissolved in ethanol
were mixed at 18 20 C, and then heated at reflux for
2 4 h. The ethanol was distilled off at reduced pres-
sure, and the compounds obtained were recrystallized
from ethanol.
, ppm
, ppm
C5 CH3
C5 CF3
C5CH3
158.5
146.0
25.0
155.7
136.5
C7 CH3
C7 CF3
C7CH3
147.5
133.5
17.2
146.0
131.0
C5 Cipso (Ph)
C5Cipso (Ph)
C7 Cipso (Ph)
C7Cipso (Ph)
(b) Equimolar amounts of compounds I and II
dissolved in acetic acid were mixed at 18 20 C, and
then heated at reflux for 2 4 h. The acetic acid was
distilled off at reduced pressure, and the compounds
obtained were recrystallized from ethanol.
Note that since the nitrogen atom in the
C5(R)=N group is more electronegative than the
nitrogen from the = C 7(R) N < group of the pyr-
azolo[1,5-a]pyrimidines then the C5 atom is less
shielded than C7 and therefore the former has a larger
chemical shift in the 13C NMR spectra. Consequently
the carbon atoms of the methyl and trifluoromethyl
groups and also ipso-atoms of the phenyl groups
attached to C5 atom (in compounds IIIb h, Va h) are
located more downfield than the signals of the same
groups linked to C7 atom {compound IVc, model
compounds (Table 3), and data from [1, 10]}
(Table 1). It is not correct to extend this statement to
the protons of the methyl group and fluorine atoms
of the trifluoromethyl group of the pyrazolo[1,5-a]-
pyrimidines. This invalid assumption in [8, 9] led to
erroneous conclusions on regiostructure of trifluoro-
methyl-containing pyrazolopyrimidines synthesized
in that study.
(c) Equimolar amounts of compounds I and II
were mixed and heated at 160 C till the end of the
reaction (TLC monitoring). The products were re-
crystallized from ethanol.
REFERENCES
1. Petrov, A.A., Emelina, E.E., and Firsov, A.V.,
Zh. Org. Khim., 2000, vol. 36, no. 7, pp. 1058 1063.
2. Filler, R., Organofluorine Chemicals and Their
Industrial Applications, Banks, R.E., Ed., Horwood:
Chichester, 1979, pp. 123 153.
3. Elnagdi, M.H., Elmoghayar, M.R.H., and
Elgemeie, G.E.H., Adv. Heterocycl. Chem.,
Katritzky, A.R., Ed., New York: Academic Press,
1987, vol. 41, pp. 319 376.
4. Elnagdi, M.H., Abdel-Galid, F.M., and Riad, B.Y.,
Heterocycles, 1983, vol. 20, no. 12, pp. 2437 2470.
5. Novinson, T., Miller, J.P., Scholten, M.B., Ro-
bins, R.K., Simon, L.N., O,Brien, D.E., and
Meyer, R.B., Jr., J. Med. Chem., 1975, vol. 18,
no. 5, pp. 460 464.
Thus significant alterations in the structure of the
trifluoromethyl-containing 1,3-diketone IIa c [R3 =
Me, Ph, t-Bu, R4 = CF3] and aminopyrazole Ia h
(the presence of a bulky phenyl group in 3 or 4
position) did not affect the regioisomeric structure of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 6 2001

858
EMELINA et al.
6. Maquestiau, A., Target, H., and vanden Eyden, J.-J.,
pp. 1093 1097.
Bull. Soc. Chim. Belg., 1992, vol. 101, no. 2,
pp. 131 136.
11. German Patent 145750, 1981. Chem. Abstr., 1981,
vol. 95, 80952m.
7. Quiroga, J., Insuasty, B., Rincon, R., Larra-
hondo, M., Hanold, N., and Meier, H., J. Hetero-
cyclic Chem., 1994, vol. 31, no. 6, pp. 1333 1335.
8. Balicki, R., Pol. J. Chem., 1981, vol. 55, no. 10,
pp. 1995 2005.
9. Joshi, K.C. and Dubey, K., J. pr. Chem., 1979,
vol. 321, no. 2, pp. 341 344.
10. Chimichi, S., Cosimelli, B., Bruni, F., and Selle-
ri, S., Canad. J. Chem., 1992, vol. 70, no. 4,
12. Grandberg, I.I., Din Vei-Py, and Kost, A.N., Zh.
Org. Khim, 1961, vol. 31, no. 7, pp. 2311 2315.
13. Auzzi, G., Checchi, S., Costanzo, A., Pecori
Vettori, L., Bruni, F., Pirisino, R., and Ciot-
toly, G.B., Farmaco Ed. Sci., 1979, vol. 34, no. 6,
pp. 478 485.
14. Henne, A.L., Newman, M.S., Quill, L.L., and
Stamiforh, R.A., J. Am. Chem. Soc., 1947, vol. 69,
p. 1819.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 6 2001