Reaction of 2-aryl-4-cyano-1,3-oxazole-5-sulfonyl chlorides with 5-amino-1h-pyrazoles and 5-amino-1h-1,2,4-triazole

Article abstract of DOI:10.1007/s10593-014-1450-2

The reaction of 2-aryl-4-cyano-1,3-oxazole-5-sulfonyl chlorides with 5-amino-3-R-1H-pyrazoles and 5-amino-1H-1,2,4-triazole gave 5-[(3-R-5-amino-1H- pyrazol-1-yl)sulfonyl]-2-aryl-1,3-oxazole-4-carbo- nitriles and 5-[(5-amino-1H-1,2,4-triazol-1-yl)sulfonyl]-2-aryl-1,3-oxazole-4-carbonitriles. The action of sodium hydride on these carbonitriles leads to the elimination of sulfur dioxide and cyclocondensation to give new heterocyclic systems, namely, [1,3]oxazolo[5,4-d]pyrazolo[1,5-a]-pyrimidine and [1,3]oxazolo[5,4-d][1,2,4] triazolo[1,5-a]pyrimidine.

Full text of DOI:10.1007/s10593-014-1450-2

Chemistry of Heterocyclic Compounds, Vol. 50, No. 1, April, 2014 (Russian Original Vol. 50, No. 1, January, 2014)
REACTION OF 2-ARYL-4-CYANO-1,3-OXAZOLE-
5-SULFONYL CHLORIDES WITH 5-AMINO-
1H-PYRAZOLES AND 5-AMINO-1H-1,2,4-TRIAZOLE
A. N. Kornienko1, S. G. Pil'o1, A. P. Kozachenko1, V. M. Prokopenko1,
E. B. Rusanov2, and V. S. Brovarets1*
The reaction of 2-aryl-4-cyano-1,3-oxazole-5-sulfonyl chlorides with 5-amino-3-R-1H-pyrazoles and
5-amino-1H-1,2,4-triazole gave 5-[(3-R-5-amino-1H-pyrazol-1-yl)sulfonyl]-2-aryl-1,3-oxazole-4-carbo-
nitriles and 5-[(5-amino-1H-1,2,4-triazol-1-yl)sulfonyl]-2-aryl-1,3-oxazole-4-carbonitriles. The action
of sodium hydride on these carbonitriles leads to the elimination of sulfur dioxide and
cyclocondensation to give new heterocyclic systems, namely, [1,3]oxazolo[5,4-d]pyrazolo[1,5-a]-
pyrimidine and [1,3]oxazolo[5,4-d][1,2,4]triazolo[1,5-a]pyrimidine.
Keywords: 5-amino-1H-pyrazole, 5-amino-1H-1,2,4-triazole, 4-cyano-1,3-oxazole-5-sulfonyl chloride,
[1,3]oxazolo[5,4-d]pyrazolo[1,5-a]pyrimidin-9-amine, [1,3]oxazolo[5,4-d][1,2,4]triazolo[1,5-a]pyrimidin-
9-amine, sodium hydride.
The rapid development of the chemistry of functional derivatives of 1,3-oxazole in recent decades is
attributed to the finding of many bioactive 1,3-oxazole compounds among natural products [1-3]. Such
compounds include the antibiotics virginiamycin, madumycin II, griseoviridin, dendroamide A etc., possessing
not only strong bactericidal but also antiblastic activity [3-7]. 1,3-Oxazole-4-carbonitriles also display various
biological activity [8-11]. Furthermore, these compounds are convenient substrates for the synthesis of other
heterocyclic systems [12-14].
NH2
N
CN
SO2Cl
HN
C
N
O
Et3N
HN
NH
N
N
N
R
Ar
+
R
Ar
.
– SO2
H2N HCl
Ar
R
O
1
N
SO2
O
3
2
_______
*To whom correspondence should be addressed, e-mail: brovarets@bpci.kiev.ua.
1Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, 1
Murmanska St., Kyiv 02660, Ukraine.
2Institute of Organic Chemistry, National Academy of Sciences of Ukraine, 5 Murmanska St., Kyiv 02094,
Ukraine; e-mail: rusanov@ioch.kiev.ua.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 84-95, January, 2014. Original
article submitted January 2, 2014.
76
0009-3122/14/5001-0076©2014 Springer Science+Business Media New York

In recent work [15], we found that the reaction of available 2-aryl-4-cyano-1,3-oxazole-5-sulfonyl
chlorides 1 with amidines in the presence of Et3N proceeding through intermediates 2 at 20-25°C in THF gives
7-amino-2-aryl-1,3-oxazolo[5,4-d]pyrimidines 3.
We have now studied the similar reaction of oxazoles 1 with 3-R-5-amino-1H-pyrazoles and 5-amino-
1H-1,2,4-triazole, which contain an amidine fragment. This reaction gives N-azolylsulfonation products, which
were isolated in 70-88% yield as pure compounds and characterized by elemental analysis and LC/MS (Tables 1
and 2). As indicated in the literature [16-21], the formation of two compounds (4 and 5) is possible in the
reaction of oxazoles 1 with 3-R-5-amino-1H-pyrazoles, while three alternative structures (6-8) may be formed
in the reaction with 5-amino-1H-1,2,4-triazole.
CN
R
N
O
Ar
S
N
N
H
O
N
H
H2N
HN
O
Et3N
4
1a,b
+
CN
THF, 20–25°С
NH2
N
N
R
O
Ar
S
O
O
N
N
R
5a–d
CN
N
N
O
S
O
6
Ar
N
N
O
N
H
H
CN
H2N
HN
NH2
N
N
Et3N
O
1a,b
+
N
Ar
S
THF, 20–25°С
N
N
O
O
N
N
N
O
7
CN
NH2
O
Ar
S
O
8a,b
N
N
1, 8 a Ar = Ph, b Ar = 4-MeC6H4;
5 a Ar = Ph, R = Me; b Ar = R = Ph; c Ar = 4-MeC6H4, R = Me; d Ar = 4-MeC6H4, R = Ph
It is difficult to determine which of these alternative structures is formed using only IR and NMR
spectroscopy. Furthermore, we cannot exclude the participation of the nitrile fragment in this reaction since
there is no CN group absorption band at 2220-2240 cm-1 in the IR spectra of the reaction products. Thus, an
X-ray structural analysis was carried out, which showed unequivocally that these products are sulfonylamides 5
and 8.
The major bond lengths and valence angles in 4-cyano-2-phenyl-1,3-oxazole fragment of carbonitrile
5b (Fig. 1) are virtually identical to the corresponding values for related structures containing this fragment [22,
23]. Thus, the C(1)–N(1) (1.293(3) Å) and C(2)–C(3) bond lengths (1.345(2) Å) are only slightly greater than
the lengths of the standard C=N (1.28 Å) and C=C double bonds (1.33 Å), while the other bond lengths in the
oxazole ring have values characteristic for delocalized bonds. The 2-phenyl-1,3-oxazole fragment itself is planar
and the mean deviation of the atoms from the plane is only 0.0297 Å. The 5-amino-3-phenylpyrazole fragment
77

is also almost planar (the mean deviation of the atoms from the plane is 0.050 Å) and forms a dihedral angle of
74.98(6)° with the 2-phenyl-1,3-oxazole fragment. We should note that the sulfur atom deviates from both the
2-phenyl-1,3-oxazole and 5-amino-3-phenylpyrazole fragments by -0.1333(27) and 0.7306(20) Å, respectively.
The sum of the valence angles at the atom N(3) is 354.38(17)°.
The lengths of the S–C and S–N bonds are 1.742(2) and 1.6562(18) Å, which is characteristic for such
compounds. The crystal features a shortened N(5)–H···O(2) contact, which may be considered as an
intramolecular hydrogen bond with the following parameters: N(5)···O(2), 2.833(3) Å; N(5)–H–O(2), 121(2)°.
There is also a very weak intermolecular N(5)–H···N(4a) hydrogen bond with parameters: N(5)···N(4), 3.146(3) Å;
N(5)–H–N(4), 160(2)°. (The letter a indicates the nitrogen atom related to the base atoms by the symmetry
operation 0.5-x, y-0.5, z).
The major bond lengths and valence angles in the 4-cyano-2-phenyl-1,3-oxazole fragment in
carbonitrile 8a (Fig. 2) are virtually identical to the corresponding values for carbonitrile 5b. The 2-phenyl-
1,3-oxazole fragment itself is planar, while the mean deviation of the atoms from the plane is 0.0412 Å. The
5-amino-1,2,4-traizole ring is planar (the mean deviation of the atoms from the plane is only 0.008 Å) and forms
a dihedral angle of 86.98(5)° with the 2-phenyl-1,3-oxazole fragment. The sulfur atom in carbonitrile 8a
deviates from the planes of the 2-phenyl-1,3-oxazole and 1,2,4-triazole rings by 0.0777(17) and 0.3648(28) Å,
respectively. These values are somewhat less than for these parameters in carbonitrile 5b. The configuration of
the N(3) atom in carbonitrile 8a is also more compressed and the sum of the valence angles at this atom is
357.31(16)°.
Fig. 1. Molecular structure of carbonitrile 5b with representation of the atoms by thermal vibration ellipsoids of
50% probability.
Fig. 2. Molecular structure of carbonitrile 8a with representation of the atoms by thermal vibration ellipsoids of
50% probability.
A shortened N(6)H···O(3) contact is observed in the crystal of carbonitrile 8a, which may be
considered as an intramolecular hydrogen bond with the following parameters: N(6)···O(3), 2.875(2) Å;
N(6)HO(3), 125.1(19)°. There is also a weak intermolecular N(6)H···N(5b) hydrogen bond with the
78

following parameters: N(6)···N(5), 3.031(3) Å; N(6)HN(5), 168(2)°. (The letter b indicates the nitrogen
atom related to the base atoms by the symmetry operation 1-x, 2-y, 2-z).
5-[(5-Amino-3-R-1H-pyrazol-1-yl)sulfonyl]-2-aryl-1,3-oxazole-4-carbonitriles 5a-d and 5-[(5-amino-
1H-1,2,4-triazol-1-yl)sulfonyl]-2-aryl-1,3-oxazole-4-carbonitriles 8a,b contain an electrophilic nitrile group and
nucleophilic primary amino group. Thus, these compounds can form seven-membered thiadiazepine rings A and
B (see analogies [17, 24]).
H2N
H2N
N
N
N
N
N
R
Ar
Ar
N
N
S
S
O
O
N
N
O
O
O
O
A
B
In order to check this proposal, carbonitriles 5a-d and 8a,b were treated with NaH in tetrahydrofuran
similar to the method described in our previous work [25]. Elemental analysis indicated that this reaction does
1
not give products containing sulfur. The H and 13C NMR spectral and LC/MS data (Tables 1 and 2) indicate
that the reaction is accompanied by the elimination of sulfur dioxide and formation of an oxazolopyrimidine
N
b
Na+
C
–
NaH
NH
а
N
5, 8
O
Ar
S
O
O
N
а
b
C
Na+
N
O
Na+
–
–
N
C
O
H
N
S
N
N
N
O
Ar
O
N
H
Ar
N
S
D
O
H
O
– SO2
N
Na+
– SO2
C
–
N
N
Ar
–
N
N
Na+
N
H
O
E
N
O
NH
Ar
–
N
Na+
I
N
O
N
Ar
H2O
N
H
F
NH2
H2O
N
NH2
N
O
N
Ar
N
Ar
N
O
N
J
G
79

system fused to a pyrazole or triazole ring. Initially, intermediate C probably is formed with a negative charge
on the exocyclic nitrogen atom. This intermediate can convert to final products G and J through two pathways.
Pathway a presupposes initial attack of the C-5 atom in the oxazole ring by the nucleophilic nitrogen atom and
formation of intermediate D. Subsequent loss of sulfur dioxide by analogy of the data in the literature [26] leads
to salt F. Then, this intermediate salt reacts with water to yield product G. Through pathway b, the nitrogen
atom in structure C initially attacks the electrophilic site of the CN group to give thiadiazepine intermediate H,
which then converts through intermediate I to yield product J.
The chain of transformations C→D→E→F→G presupposes formation of a linear tricyclic system, while
the chain C→H→I→J presupposes formation of an angular system. We should note that we have already obtained a
compound with angular structure J [25] but its spectral characteristics are not in accord with our product with
structure 9b. Thus, we favor the former variant with formation of new heterocyclic systems: 6-R-2-aryl[1,3]oxazolo-
[5,4-d]pyrazolo[1,5-a]pyrimidin-9-amines 9a-d and 2-aryl[1,3]oxazolo[5,4-d][1,2,4]triazolo[1,5-a]pyrimidin-
9-amines 10a,b.
NH2
NH2
NaH
NaH
N
O
N
N
O
N
N
5a–d
8a,b
N
N
Ar
R
Ar
THF,
50–60°С
THF,
50–60°С
N
N
10a,b
9a–d
9 a Ar = Ph, R = Me; b Ar = R = Ph; c Ar = 4-MeC6H4, R = Me;
d Ar = 4-MeC6H4, R = Ph; 10 a Ar = Ph, b 4-MeC6H4
Fig. 3. Molecular structure of pyrimidinamine 9d with representation of the atoms by thermal vibration
ellipsoids of 50% probability.
1
The H NMR spectra of these compounds show characteristic singlets for the pyrazole protons in
compounds 9a-d (6.14-6.86 ppm) and triazole protons in compounds 10a,b (8.42, 8.45 ppm, respectively). The
presence of a primary amino group in pyrimidinamines 9a-d and 10a,b was confirmed by finding a broadened
singlet at 8.63-9.15 ppm in the region characteristic for this group. X-ray structural analysis was carried out for
pyrimidinamines 9d (Fig. 3) and 10b (Fig. 4) to obtain unequivocal proof of the structures of these compounds
and determine their special features.
The major bond lengths and valence angles in the central tricyclic fragment in compound 9d (Fig. 3) are
characteristic for conjugated heterocyclic systems, and, on the whole, the geometrical characteristics are similar
to those for previously studied simpler heterocyclic systems [27, 28]. Thus, the valence angles for the five-
membered heterocycles fall in the range 103.52(13)-114.84(14)°, while these values for the pyrimidine ring are
111.34(14)-130.48(15)°. The distribution of the endocyclic angles in the central fragment are somewhat
unusual, which leads to their pairwise enhancement: N(3)–C(1)–C(2), 132.78(15)°; N(3)–C(4)–O(1),
122.55(14)°; N(1)N(2)C(6), 123.22(13)°; C(6)C(5)N(4), 131.67(14)°.
The C(6)N(5) bond is considerably shorter (1.326(2) Å) than the standard C–N single bond (1.45 Å)
due to strong conjugation of the lone electron pair of the N(5) atom with the heterocyclic -electron system. The
sum of the valence angles at the N(5) atom is 359.6(18)°.
80

As we might have expected, the central tricyclic fragment is virtually planar (the mean-square deviation
of the atoms from the plane is only 0.028 Å), while the phenyl and 4-methylphenyl substituents are twisted
relative to the tricyclic fragment by 27.93(5) and 7.74(5)°, respectively.
Fig. 4. Molecular structure of pyrimidinamine 10b with representation of the atoms by thermal vibration
ellipsoids of 50% probability.
Intermolecular N(5)–H···N(3a) and N(5)–H(2N)···N(4b) hydrogen bonds are formed in the crystal
with the following parameters: N(5)···N(3a), 3.018(2) Å; N(5)HN(3a), 142.0(17)°; N(5)···N(4b), 3.074(2)Å,
N(5)H(2N)N(4b), 158.8(17)°. (The letters a and b indicate nitrogen atoms related to the base atoms by
symmetry operations x, 1-y, z+0.5 and -x, y, 1.5-z, respectively.
The major bond lengths and valence angles in the central tricyclic fragment of pyrimidinamine 10b
(Fig. 4) are similar to those for pyrimidinamine 9d and are characteristic for conjugated heterocyclic systems.
Thus, the valence angles in the five-membered heterocycles fall in a somewhat broader range than in
pyrimidinamine 9d, 100.65(17)-117.71(19)°, while these values for the pyrimidine ring are 109.67(17)-
130.78(19)°. As in the case of compound 9d, the C(4)N(6) bond is shorter (1.324(3) Å) than the standard CN
single bond due to strong conjugation of the lone electron pair of the N(6) atom with the heterocyclic -electron
system. The sum of the valence angles at the N(5) atom is 359.6(18)°. The central tricyclic fragment is virtually
planar (the mean-square deviation of the atoms from the plane is only 0.016 Å), while the aryl substituent is
twisted relative to the central fragment by 9.0(5)°.
Intermolecular N(6)H(1N)···N(5a) hydrogen bonds are found in the crystal with the following
parameters: N(6)···N(5a), 2.872(3) Å, N(6)H(1N)N(5a), 174.8(18)°. (The letter a indicates the nitrogen atom
related to the base atoms by the symmetry operation 0.5+x, 0.5-y, z+0.5).
Thus, our study showed that the reaction of 2-aryl-4-cyano-1,3-oxazole-5-sulfonyl chlorides with 3-R-
5-amino-1H-pyrazoles and 5-amino-1H-1,2,4-triazoles proceeds regioselectively at the ring nitrogen atom N-1.
The products obtained upon the action of sodium hydride give new heterocyclic systems, namely,
[1,3]oxazolo[5,4-d]pyrazolo[1,5-a]pyrimidine and [1,3]oxazolo[5,4-d][1,2,4]triazolo[1,5-a]pyrimidine, whose
structures were confirmed by X-ray structural analysis.
EXPERIMENTAL
IR spectra were recorded on a Vertex 70 spectrometer in KBr pellets. The 1H and 13C NMR spectra were
recorded on a Bruker Avance DRX-500 spectrometer (500 and 125 MHz, respectively) in DMSO-d6 with TMS
as internal standard. The LC/MS spectra were recorded with an Agilent 1100 Series chromatograph equipped
with a diode matrix and Agilent LC/MSD SL mass-selective detector using a 4.6×15-mm column packed with
Zorbax SB-C18 (1.8 m) and solvents: A) 95:5 MeCN–H2O, 0.1% CF3CO2H, and B) 0.1% aqueous CF3CO2H.
The eluent flow rate was 3 ml/min. The injection volume was 1 l. The UV detectors recorded at 215, 254, and
285 nm. The chemical ionization spectra were recorded at atmospheric pressure. Elemental analysis was carried
out in the Analytical Laboratory of the Institute of Bioorganic and Petrochemistry
81

TABLE 1. Physicochemical Characteristics of Compounds 5a-d, 8a,b,
9a-d, and 10a,b
Found, %
Calculated, %
——————
Com-
pound
Empirical
formula
Mp*, °С
Yield, %
C
H
N
S
C14H11N5O3S
C19H13N5O3S
C15H13N5O3S
C20H15N5O3S
C12H8N6O3S
C13H10N6O3S
C14H11N5O
C19H13N5O
C15H13N5O
C20H15N5O
C12H8N6O
51.08
51.06
3.32
3.37
21.18
21.26
9.75
9.74
172-174
205-206
200-201
202-203
210-211
209-210
262-264
>300
70
78
85
88
74
76
53
60
54
55
50
53
5a
58.21
3.40
17.95
8.14
5b
5c
58.30
3.35
17.89
8.19
52.39
52.47
3.77
3.82
20.52
20.40
9.35
9.34
59.18
3.79
17.37
7.89
5d
8a
59.25
3.73
17.27
7.91
45.49
45.57
2.50
2.55
26.65
26.57
10.13
10.14
47.15
3.12
25.58
9.75
8b
9a
47.27
3.05
25.44
9.71
63.30
63.39
4.15
4.18
26.46
26.40
—
—
—
—
—
—
69.70
4.00
21.42
9b
9c
69.72
4.00
21.39
64.49
64.51
4.61
4.69
25.13
25.07
299-300
>300
70.31
4.39
20.49
9d
10a
10b
70.37
4.43
20.52
57.05
57.14
3.11
3.20
33.45
33.32
>300
C13H10N6O
58.51
3.75
31.71
>300
58.64
3.79
31.56
_______
*Recrystallization solvents: acetonitrile for compounds 5a,b, 8a,b, and 9a,
ethanol for compounds 5c,d, and 1:1 acetonitrile–DMF for compounds 9b-d
and 10a,b.
of the National Academy of Sciences of Ukraine. The carbon and hydrogen contents were determined using the
Pregl gravimetric method, while nitrogen was determined using the Dumas gasometric micromethod. Sulfur was
determined by the Scheininger titrimetric method [29]. Melting points were determined on a Fisher–Johns
instrument. The reaction course and purity of the products were monitored by thin-layer chromatography on
Silufol UV-254 plates using 9:1 chloroform–methanol as the eluent with visualization by UV light.
Starting 2-aryl-4-cyano-1,3-oxazolo-5-sulfonyl chlorides 1a,b were obtained according to our previous
procedure [30]. 3-R-5-Amino-1H-pyrazoles were obtained according to Grandberg et al. [31]. Commercial
samples of 5-amino-1H-1,2,4-triazole and NaH were obtained from Aldrich.
5-[(5-Amino-3-R-1H-pyrazol-1-yl)sulfonyl]-2-aryl-1,3-oxazole-4-carbonitriles
5a-d
(General
Method). A solution of 5-amino-3-methyl-1H-pyrazole (4 mmol) or 5-amino-3-phenyl-1H-pyrazole in
anhydrous THF (10 ml) and Et3N (0.405 g, 4 mmol) was added with stirring to a solution of sulfonyl chloride
1a,b (4 mmol) in anhydrous THF (15 ml). The reaction mixture was maintained for 12 h at 20-25°C. The
precipitate was filtered off, and the solvent was removed at reduced pressure. The residue was treated with
water (20 ml). The precipitate formed was filtered off, washed with water (10 ml), dried, and purified by
recrystallization.
Compound 5a. 13С NMR spectrum, δ, ppm: 12.8 (CH3); 88.6; 109.4; 118.4 (CN); 123.1; 127.0; 129.2;
133.2; 148.7; 152.5; 158.0; 163.7.
82

TABLE 2. Spectral Characteristics of Compounds 5a-d, 8a,b, 9a-d, and 10a,b
Mass
Com-
IR spectrum, ν, cm-1
1Н NMR spectrum, δ, ppm (J, Hz)
spectrum,
m/z [M+H]+
330
pound
5a
1167, 1209, 1331, 1393, 2.02 (3Н, s, СН3); 5.28 (1Н, s, СН pyrazole);
1448, 1545, 1594, 1634; 6.45 (2Н, s, NH2); 7.62-7.74 (3Н, m, H Ar);
3303, 3472 (NH2)
8.00 (2Н, d, J = 6.8, H Ar)
5b
1172, 1200, 1330, 1404, 5.88 (1Н, s, СН pyrazole); 6.66 (2Н, s, NH2);
1449, 1480, 1547, 1568, 7.42-7.44 (3H, m, H Ar);
1621; 3315, 3460 (NH2) 7.61-7.70 (3Н, m, H Ar);
7.77 (2Н, d, J = 6.5, H Ar);
392
7.98 (2Н, d, J = 8.0, H Ar)
5c
5d
8a
8b
1166, 1205, 1267, 1329, 2.05 (3Н, s, СН3); 2.41 (3Н, s, СН3);
1405, 1494, 1550, 1582, 5.23 (1Н, s, СН pyrazole), 6.41 (2Н, s, NH2);
1637; 3142, 3448 (NH2) 7.45 (2Н, d, J = 7.6, H Ar);
7.89 (2Н, d, J = 7.6, H Ar)
344
406
317
331
1171, 1201, 1327, 1401, 2.38 (3Н, s, СН3); 5.86 (1Н, s, СН pyrazole);
1477, 1494, 1570, 1622; 6.57 (2Н, s, NH2); 7.39-7.44 (5H, m, H Ar);
3328, 3470 (NH2)
7.74-7.76 (2Н, m, H Ar);
7.88 (2Н, d, J = 7.6, H Ar)
1176, 1218, 1283, 1336, 7.63-7.73 (5Н, m, H Ar, NH2);
1425, 1481, 1516, 1548, 7.79 (1Н, s, СН triazole);
1647, 1603; 3148, 3387 7.88 (2Н, d, J = 6.8, H Ar)
(NH2)
1137, 1174, 1217, 1280, 2.42 (3Н, s, СН3); 7.46 (2Н, d, J = 7.6, H Ar);
1332, 1428, 1492, 1516, 7.70 (2Н, s, NH2); 7.78 (1Н, s, СН triazole);
1551, 1609, 1647; 3160, 7.92 (2Н, d, J = 7.6, H Ar)
3391 (NH2)
9a
9b
1071, 1263, 1280, 1360, 2.42 (3Н, s, СН3); 6.15 (1Н, s, СН pyrazole);
266
328
1563, 1521, 1675, 2924; 7.60-7.62 (5H, m, H Ar);
3116, 3301 (NH2)
8.09-8.11 (2Н, m, H Ar); 8.63 (2Н, br. s, NH2)
1051, 1262, 1282, 1362, 6.86 (1Н, s, СН pyrazole);
1446, 1560, 1612, 1681; 7.45-7.52 (3Н, m, H Ar);
3153, 3306 (NH2)
7.62-7.64 (3H, m, H Ar);
8.10-8.13 (4Н, m, H Ar); 8.77 (2Н, br. s, NH2)
9c
1047, 1265, 1280, 1361, 2.34 (3Н, s, СН3); 2.36 (3Н, s, СН3);
1501, 1563, 1621, 1677, 6.14 (1Н, s, СН pyrazole);
2919; 3126, 3303 (NH2) 7.40 (2Н, d, J = 7.6, H Ar);
7.99 (2Н, d, J = 7.6, H Ar);
280
342
8.64 (2Н, br. s, NH2)
9d
1051, 1262, 1361, 1442, 2.42 (3Н, s, СН3); 6.86 (1Н, s, СН pyrazole);
1502, 1562, 1620, 1675; 7.43-7.55 (5Н, m, H Ar);
3139, 3299 (NH2)
8.08 (2Н, d, J = 7.6, H Ar);
8.12 (2Н, d, J = 7.6, H Ar);
8.72 (2Н, br. s, NH2)
10a
10b
1044, 1277, 1372, 1409, 7.63 (3Н, s, H Ar); 8.14 (2Н, s, H Ar);
1478, 1543, 1599, 1679; 8.42 (1Н, s, СН triazole); 8.97 (2Н, br. s, NH2)
3334 (NH2)
253
267
1045, 1224, 1280, 1412, 2.41 (3Н, s, СН3); 7.41 (2Н, d, J = 7.6, H Ar);
1543, 1598, 1682, 2925; 8.01 (2Н, d, J = 7.6, H Ar);
3092, 3345 (NH2)
8.45 (1Н, s, СН triazole); 9.15 (2Н, br. s, NH2)
Compound 5c. 13С NMR spectrum, δ, ppm: 14.0 (CH3); 21.4 (CH3); 89.4; 110.1; 119.1 (CN); 121.0;
127.5; 130.3; 144.4; 148.8; 152.9; 158.3; 164.3.
5-[(5-Amino-1H-1,2,4-triazol-1-yl)sulfonyl]-2-aryl-1,3-oxazole-4-carbonitriles
8a,b
(General
Method) were obtained similar to oxazoles 5a-d from sulfonyl chlorides 1a,b and 5-amino-1H-1,2,4-triazole.
Compound 8a. 13С NMR spectrum, δ, ppm: 110.0; 120.1 (CN); 123.8; 127.7; 129.7; 133.8; 148.2;
154.4; 157.5; 164.5.
6-R-2-Aryl[1,3]oxazolo[5,4-d]pyrazolo[1,5-a]pyrimidin-9-amines 9a-d (General Method). NaH
(0.048 g, 2 mmol) was added with stirring to a solution of oxazole 5a-d (2 mmol) in anhydrous THF (15 ml).
The reaction mixture was stirred for 2 h at 20-25°C. The temperature was then raised to 50-60°C. The mixture
83

was maintained at this temperature for 0.5 h. The suspension was left overnight and then treated with water
(20 ml). The precipitate formed was filtered off, washed with water (10 ml), dried, and purified by
recrystallization.
Compound 9a. 13С NMR spectrum, δ, ppm: 14.7 (CH3); 92.5; 105.2; 126.6; 129.5; 131.5; 142.0; 144.3;
148.0; 154.0; 156.7; 160.2.
13
Compound 9с. С NMR spectrum, δ, ppm: 14.7 (CH3); 21.2 (CH3); 92.4; 105.2; 123.9; 126.6; 130.0;
141.6; 141.8; 148.0; 153.9; 157.0; 160.2.
2-Aryl[1,3]oxazolo[5,4-d][1,2,4]triazolo[1,5-a]pyrimidin-9-amines 10a,b (General Method) were
obtained analogously to pyrimidinamines 9a-d from oxazoles 8a,b.
Compound 10а. 13С NMR spectrum, δ, ppm: 107.9; 126.6; 127.2; 129.8; 132.2; 143.4; 154.3; 155.0;
158.3; 163.2.
X-ray structural study of compounds 5b, 8a, 9d, and 10b was carried out at room temperature on a
Bruker Smart Apex II diffractometer with MoK radiation and a graphite monochromator. The structures were
solved by the direct method and refined by the method of least squares using the Bruker SHELXTL programs
[32].
The unit cell parameters for orthorhombic crystals of compound 5b (C19H13N5O3S, M 391.4), space
group Pbcn: a 21.1512(7), b 11.4815(4), c 14.6393(5) Å; V 3555.1(2) Å3; Z 8; dcalc 1.463 g/cm3;  0.215 mm-1;
F(000) 1616. We used a monocrystal of compound 5b with linear dimensions 0.10×0.11×0.1 mm. A set of
33272 reflections was recorded (max 26.49°, sphere segment -26 ≤ h ≤ 25, -14 ≤ k ≤ 14, -18 ≤ l ≤ 18), of which
3676 reflections were independent (Rint 0.0585). A correction for absorption was introduced by the
multiscanning method using the SADABS program (Tmin/Tmax = 0.7570/0.9697). The hydrogen atoms were
determined objectively from the Fourier difference map and refined isotropically. A total of 2454 reflections
with I > 2(I) were used in the refinement (306 refined parameters, 8.0 reflections per parameter). We used the
weighting scheme  = 1/[2(Fo ) + (0.0212P)2 + 3.088P], where P = (Fo + 2Fc2)/3. The final probability
factors: R1(F) 0.0418, wR2 (F2) 0.0781 for reflections with I > 2(I) and R1(F) 0.0771, wR2(F2) 0.0925, GOOF
0.973 over all reflections. A correction for isotropic extinction 0.00143(15) was taken into account. The residual
electron density from the Fourier difference map after the final refinement cycle was 0.22 and -0.35 e/Å3. The
complete crystallographic data set was deposited at the Cambridge Crystallographic Data Center (CCDC deposit
919590).
2
2
The unit cell parameters of monoclinic crystals of oxazole 8a (C12H8N6O3S, M 316.30), space group P21/n:
a 9.5927(6), b 11.6543(7), c 12.3822(8) Å;  103.073(3)°; V 1348.41(15) Å3; Z 4; dcalc 1.558 g/cm3;  0.264 mm-1;
F(000) 648. We used a monocrystal of compound 8a with linear dimensions 0.10×0.11×0.10 mm. A set of
18299 reflections was recorded (max 26.54°, sphere segment -11 ≤ h ≤ 12, -14 ≤ k ≤ 14, -15 ≤ l ≤ 14), of which
2800 reflections were independent (Rint 0.0355). A correction for absorption was introduced using the multi-
scanning method with the SADABS program (Tmin/Tmax = 0.8487/0.9741). The hydrogen atoms were found
objectively from the Fourier difference map and refined isotropically. A total of 2227 reflections with I > 2(I)
were used in the refinement (231 refined parameters, 9.6 reflections per parameter). We used the weighting
scheme  = 1/[2(Fo ) + (0.0423P)2 + 0.6192P], where P = (Fo + 2Fc2)/3. The final probability factors R1(F2)
0.0367, wR2(F2) 0.0866 for reflections with I > 2(I) and R1(F) 0.0511, wR2(F2) 0.0965, GOOF 1.043 for all the
reflections. The residual electron density from the Fourier difference map after the final refinement cycle was
0.21 and -0.38 e/Å3. The complete crystallographic data set was deposited at the Cambridge Crystallographic
Data Center (CCDC deposit 919588).
2
2
The unit cell parameters of monoclinic crystals of pyrimidinamine 9d (C20H15N5O, M 341.37), space
group C2/c: a 36.3582(10), b 7.2706(3), c 12.9087(4) Å;  105.637(2)°; V 3286.07(19) Å3; Z 8; dcalc 1.38 g/cm3;
 0.09 mm-1; F(000) = 1424. We used a monocrystal of compound 9d with linear dimensions 0.50×0.20×0.14 mm.
A set of 16806 reflections was recorded (max 27.48°, sphere segment -46 ≤ h ≤ 46, -9 ≤ k ≤ 9, -16 ≤ l ≤ 16), of which
3781 reflections were independent (Rint 0.0528). A correction for absorption was introduced using the multiscanning
method with the SADABS program (Tmin/Tmax = 0.7541/0.9875). The positions of the hydrogen atoms at the carbon
84

atoms were calculated geometrically and refined using the rider model, while the positions of the hydrogen atoms at
the N(5) atom were found objectively from the Fourier difference map and refined isotropically. A total of 2412
reflections with I > 2(I) were used in the refinement (243 refined parameters, 9.9 reflections per parameter). We
used the weighting scheme  = 1/[2(Fo2) + (0.0579P)2 + 0.1453P], where P = (Fo2 + 2Fc2). The final probability
factors R1(F) 0.0498, wR2(F2) 0.1127 for reflections with I > 2(I) and R1(F) 0.0874 and wR2(F2) 0.1253, GOOF
1.039 for all the reflections. The residual electron density from the Fourier difference map after the final refinement
cycle was 0.20 and -0.23 e/Å3. The complete crystallographic data set was deposited at the Cambridge
Crystallographic Data Center (CCDC deposit 953028).
The unit cell parameters of monoclinic crystals of pyrimidinamine 10b (C13H10N6O, M 266.27), space
group P21/n: a 8.1949(4), b 10.5929(5), c 14.0631(7) Å;  104.350(3)°; V 1182.7(1) Å3; Z 4; dcalc 1.495 g/cm3;
 0.103 mm-1; F(000) 552. We used a monocrystal of compound 10b with linear dimensions 0.11×0.14×0.31 mm. A
set of 11449 reflections was recorded (max 26.65°, sphere segment -10 ≤ h ≤ 10, -13 ≤ k ≤ 13, -17 ≤ l ≤ 17), of
which 2480 were independent (Rint 0.0632). A correction for absorption was introduced using the multiscanning
method with the SADABS program (Tmin/Tmax = 0.7541/0.9887). The positions of the hydrogen atoms at the
carbon atoms were calculated geometrically and refined using the rider model, while the positions of the
hydrogen atoms at the N(6) atom were found objectively from the Fourier difference map and refined
isotropically. A total of 1497 reflections with I > 2(I) were used in the refinement (201 refined parameters,
7.44 reflections per parameter). We used the weighting scheme  = 1/[2(Fo ) + (0.0524P)2 + 0.061P], where
2
P = (Fo + 2Fc2)/3. The final probability factors R1(F) 0.0509, wR2(F2) 0.1003 for the reflections with I > 2(I)
2
and R1(F) 0.1021, wR2(F2) 0.1196, GOOF 1.003 for all the independent reflections. The residual electron
density from the Fourier difference map after the final refinement cycle was 0.17 and -0.24 e/Å3. The complete
crystallographic data set was deposited at the Cambridge Crystallographic Data Center (CCDC deposit 971133).
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