Reactions of 1,3,5-triazinylnitroformaldoxime 4. synthesis of (5-R-1,2,4-oxadiazol-3-yl)-1,3,5-triazines

Article abstract of DOI:10.1007/s10593-012-0901-x

Heating 4-R-methoxy-1,3,5-triazin-2-ylnitroformaldoximes with nitriles leads not to the formation of 1,2,4-oxadiazoles but rather to dimerization of the intermediate 1,3,5-triazinylnitrile oxides to give furoxanes. The reaction of 4-R-6-methoxy-1,3,5-tria

Full text of DOI:10.1007/s10593-012-0901-x

Chemistry of Heterocyclic Compounds, Vol. 47, No. 10, January, 2012 (Russian Original Vol. 47, No. 10, October, 2011)
REACTIONS OF 1,3,5-TRIAZINYLNITROFORMALDOXIME
4.* SYNTHESIS OF (5-R-1,2,4-OXADIAZOL-3-YL)-
1,3,5-TRIAZINES
V. V. Bakharev1*, A. A. Gidaspov1, E. V. Selezneva1, V. E. Parfenov1,
I. V. Ul'yankina1, I. S. Nazarova1, Yu. T. Palatova1, and O. S. El'tsov2
Heating 4-R-methoxy-1,3,5-triazin-2-ylnitroformaldoximes with nitriles leads not to the formation of
1,2,4-oxadiazoles but rather to dimerization of the intermediate 1,3,5-triazinylnitrile oxides to give
furoxanes. The reaction of 4-R-6-methoxy-1,3,5-triazin-2-ylnitroformaldoximes with ammonia and
amines gives 1,3,5-triazinylamidoximes, which upon acylation and subsequent intramolecular
cyclization yield (5-R-1,2,4-oxadiazol-3-yl)-1,3,5-triazines.
Keywords: (5-R-1,2,4-oxadiazol-3-yl)-1,3,5-triazines, 1,3,5-triazinylamidoximes, 1,3,5-triazinylnitrile
oxides, 1,3,5-triazinylnitroformaldoximes, acylation, intramolecular cyclization.
The [3+2] cycloaddition of nitrile oxides to nitriles is one of the most commonly used methods for the
synthesis of 1,2,4-oxadiazoles [2, 3]. In previous work [1], we have developed a synthesis of the 3,5-disubsti-
tuted isoxazoles using the reaction of acetylenes with 1,3,5-triazinylnitrile oxides generated by the thermolysis
of the corresponding 1,3,5-triazin-6-ylnitroformaldoximes. In the present work, we have studied the possibility
of obtaining (5-R-1,2,4-oxadiazol-3-yl)-1,3,5-triazines using the analogous [3+2] cycloaddition reactions of
1,3,5-triazinylnitrile oxides to nitriles. The reaction was carried out by heating a solution or suspension of
nitroformaldoximes 1a-d in various nitriles. Formation of nitrogen oxides was observed upon heating, indicating
the release of nitrous acid and the formation of nitrile oxides. However, at the end of the reaction as indicated by
thin-layer chromatographic monitoring of the starting compounds 1a-d, 3,4-di-(4-R-6-methoxy-1,3,5-triazin-2-yl)-
furoxanes 2a-d were isolated instead of the expected 2-R-4-methoxy-6-(5-R-1,2,4-oxadiazol-3-yl)-1,3,5-tri-
azines (Scheme 1).
Thus, under the conditions described above, nitrile does not participate in the reaction but rather acts as a
solvent. Therefore, dimerization of the intermediate nitrile oxides occurs to give furoxanes 2a-d exclusively
analogous to the process described in our previous work [4] instead of formation of (5-R-1,2,4-oxadiazol-3-yl)-
1,3,5-triazines.
_______
*For Communication 3, see [1].
**To whom correspondence should be addressed, e-mail: knil@sstu.smr.ru.
1Samara State Technical University, 244 Molodogvardeyskaya St., 443100 Samara, Russia.
2Ural Federal University named after the First President of Russia B. N. Yeltsin, 19 Mira St., Yekaterinburg
620002, Russia; oleg-eltsov@yandex.ru.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1521-1531, October, 2011.
Original article submitted June 28, 2010, after revision submitted October 5, 2011.
1258
0009-3122/12/4710-1258©2012 Springer Science+Business Media, Inc.

Another commonly used method for the synthesis of 1,2,4-oxadiazoles is the intramolecular cyclization
of O-acylated amidoximes [1, 2]. In a series of 1,3,5-triazine derivatives, an example of such a synthesis was
described for 1,3,5-triazinecarbonitriles [5].
Scheme 1
R
R

N
N
N
N
– HNO2
N
C+
N
MeO
MeO
N
OH
N
O
NO2
1a–d
R1CN
R
N
R
R
N
N
N
N
MeO
MeO
N
N
N
N
R1
MeO
N
N
N+
N
O
O
O
2a–d
1a, 2a R = NMe2; 1b, 2b R = N(CH2)4; 1c, 2c R = N(CH2)5; 1d, 2d R = N(CH2CH2)2O;
R1 = Me, Bn
In contrast to the reaction of nitriles with hydroxylamine [5], the method for synthesizing of 1,3,5-tri-
azinylamidoximes using 1,3,5-triazinylnitroformaldoximes as starting materials is more general since it permits
the preparation of amidoximes substituted at the amino group. The reaction of nitroformaldoximes 1a-d with
ammonia and various amines in ethanol at 20-25°C gives 1,3,5-triazinylamidoximes 3a-h.
Scheme 2
R
HNR1R2
N
N
1a–d
N
MeO
N
OH
EtOH
NR1R2
3a–h
3a,b,c,d R1 = R2 = H; a R= NMe2; b R = N(CH2)4; c R = N(CH2)5; d R = N(CH2CH2)2O;
3e R = NMe2, R1 = H, R2 = Pr; 3f R = NMe2, R1 + R2 = (CH2)4;
3g R = N(CH2CH2)2O, R1 = H, R2 = Ph; 3h R = N(CH2)4, R1 = H, R2 = Ad
The resultant amidoximes 3a-d were acylated using acid chloroanhydrides (of benzoic and
adamantanecarboxylic acids) or acid anhydrides (of acetic and trifluoroacetic acids) in toluene at 20-25°C for
the synthesis of (5-R1-1,2,4-oxadiazol-3-yl)-1,3,5-triazines (Scheme 3). Triethylamine or pyridine were used as
a base for binding the evolved hydrogen chloride or corresponding acids. Products of acylation at the oxime
group oxygen atom 4a-l were obtained as a result with derivatives of acetic, benzoic, and adamantanecarboxylic
acids. The formation of O-acylated products was indicated by the position of the carbonyl group bands
(1730-1770 cm-1), which corresponds to the region for ester and not amide carbonyl groups, finding amino group
1
bands at 3200-3500 cm-1, and the presence of aminogroup signal in H NMR spectra. A signal of the carbonyl
1259

group carbon atom in the 13C NMR spectra was observed at 153-155 ppm (Table 1). Heating O-acetylated
amidoximes 4a-l at reflux in acetic acid leads to intramolecular cyclization, the elimination of water, and
formation of 2-R-4-methoxy-6-(5-R1-1,2,4-oxadiazol-3-yl)-1,3,5-triazines 5a-l.
In the case of trifluoroacetic anhydride, 1,3,5-triazin-2-yl-O-trifluoroacetoxyamidoximes were not
obtained due to formation of 2-R-4-methoxy-6-(5-trifluoromethyl-1,2,4-oxadiazol-3-yl)-1,3,5-triazines 5m-p as
a result of intramolecular cyclization under the acylation reaction conditions (Scheme 3).
The IR spectra of cyclization products 5a-p lack the characteristic bands for the carbonyl and free amino
13
groups found in the spectra of the starting acylated amidoximes 4a-l. At the same time, the C NMR spectra
given in Table 2 show signals for carbon atoms characteristic for the 1,2,4-oxadiazole ring [6, 7]. The presence
of a trifluoromethyl group in compounds 5m-p is confirmed by signals splitting of the trifluoromethyl group
carbon atom and C-5 carbon atom of the 1,2,4-oxadiazole ring into quartets.
Scheme 3
R
R
Ac2O

N
N
N
N
AcOH
N
N
MeO
N
MeO
N
OAc
Me
N
NH2
4a–d
5a–d
O
R
N
R
Et3N
or Py
N
R1COCl
N
N
O

3a–d
N
N
PhMe
AcOH
R1
MeO
N
MeO
N
O
R1
N
NH2
O
4e–l
5e–l
R
(CF3CO)2O
N
N
N
O
MeO
N
CF3
N
5m–p
4, 5 a,e,i,m R = NMe2; 4, 5 b,f,j,n R = N(CH2)4; 4, 5 c,g,k,o R = N(CH2)5;
4, 5 d,h,l,p R = N(CH2CH2)2O; 4, 5 e–h R1 = Ph, i–l R1 = Ad
Thus, we have shown that the thermolysis of 1,3,5-triazin-6-ylnitroformaldoximes in nitriles does not
lead to formation of (5-R-1,2,4-oxadiazol-3-yl)-1,3,5-triazines, but rather to dimerization of the 1,3,5-tri-
azinylnitrile oxides to give furoxanes. A three-step method was developed for the synthesis of (5-R-1,2,4-oxa-
diazol-3-yl)-1,3,5-triazines using 1,3,5-triazin-6-ylnitroformaldoximes as the starting compounds.
EXPERIMENTAL
1
The IR spectra were taken on an Avatar 360ESP spectrophotometer using KBr pellets. The H and
13C NMR spectra were taken in DMSO-d6 on a Bruker Avance II spectrometer at 400 and 100 MHz,
respectively, with TMS as internal standard. The elemental analyses were carried out on a Eurovector EA 3000
instrument.
1260

TABLE 1. 13C NMR Spectra (, ppm (J, Hz)) of 1,3,5-Triazine-2-carb-
oximidamides 4a-l
1,3,5-Triazine ring
Com-
pound
С=О (H2N)C=N
Other signals
СOMe СR С–C
4a
4b
4c
4d
4e
4f
171.7 169.4 167.5 154.3
171.5 169.4 167.4 154.3
171.9 169.3 167.8 154.4
172.0 169.3 167.9 154.2
171.1 167.0 166.3 154.3
170.8 166.8 163.9 154.1
166.7
164.5
165.8
166.2
163.9
163.8
20.9 (COCH3); 37.0, 37.4 (N(CH3)2);
55.5 (OCH3)
20.9 (COCH3); 25.7, 25.8 (CH2);
47.3, 47.7 (CH2N); 55.5 (OCH3)
20.9 (COCH3); 25.1, 26.4, 26.6 (CH2);
45.0, 45.4 (CH2N); 55.5 (OCH3)
20.9 (COCH3); 44.6, 45.0 (CH2N);
55.7 (OCH3); 66.9, 67.1 (OCH2)
36.4, 36.8 (N(CH3)2); 54.7 (OCH3);
129.0, 130.0, 133.0, 133.5 (Ph)
24.9, 25.0 (CH2); 46.6, 46.9 (CH2N);
54.7 (OCH3);
129.0, 129.7, 130.0, 133.6 (Ph)
4g
171.3 167.3 165.2 154.2
163.8
24.4, 25.6, 25.8 (CH2); 44.2, 44.8 (CH2N);
54.8 (OCH3);
129.0, 129.7, 130.0, 133.6 (Ph)
43.9, 44.3 (CH2N); 54.9 (OCH3); 66.2 (OCH2);
129.0, 129.6, 130.0, 133.6 (Ph)
4h
4i
171.3 167.3 165.6 154.0
173.8 170.9 166.9 153.5
163.8
166.0
27.8, 27.9, 39.3, 40.7 (Ad);
36.3, 36.6 (N(CH3)2); 54.7 (OCH3)
4j
173.8 170.8 166.8 153.6
173.8 171.2 167.3 153.5
163.9
165.1
27.9, 36.4, 38.7 (Ad); 24.9, 25.1 (CH2);
46.6, 46.9 (CH2N); 54.7 (OCH3)
4k
27.8, 36.3, 38.6 (Ad);
24.2, 25.4, 25.7 (CH2); 45.1, 45.3 (CH2N);
54.7 (OCH3)
4l
173.9 171.2 167.4 153.3
165.6
27.8, 36.3, 36.5, 38.0, 38.6 (Ad);
43.7, 44.2 (CH2N); 54.9 (OCH3); 66.1 (OCH2)
Nitroformaldoximes 1a-d were prepared by a procedure described in our previous work [4].
Reaction of Nitroformaldoximes 1a-d with Nitriles (General Method). A suspension of
nitroformaldoxime 1a-d (0.5 mmol) was heated at reflux in acetonitrile (20 ml) or heated at 100-110°C in
benzyl cyanide until thin-layer chromatography indicated the disappearance of starting compounds 1a-d (2-5 h).
The excess nitrile was distilled off at reduced pressure. The residue was treated with 20 ml water. The
precipitate was filtered off, washed twice with 10 ml water, and dried in the air. The furoxanes yields were: 91%
compound 2a, 88% compound 2b, 86% compound 2c, and 93% compound 2d. The melting points, IR and
1H NMR spectra were in accord with our previous data [4].
4-R-N'-Hydroxy-6-methoxy-1,3,5-triazine-2-carboximidamides 3a-h (General Method). 25%
Ammonium hydroxide (7.5 ml, 10 mmol) or corresponding amine (2.2 mmol) was added to a stirred suspension
of compounds 1a-d (1 mmol) in ethanol (10 ml). The reaction mixture was maintained at 20-25°C until the
starting compound disappeared as indicated by thin-layer chromatography. The oxime precipitate formed was
filtered off, washed with 5 ml ethanol, then twice with 5 ml water, and dried in the air.
N'-Hydroxy-4-dimethylamino-6-methoxy-1,3,5-triazine-2-carboximidamide (3a) was obtained from
compound 1a and ammonia in 89% yield (1.89 g); mp 210-212°C (decomp.). IR spectrum, , cm-1: 3488, 3394,
3272, 3207, 3126, 3014, 2952, 2937, 2902, 2877, 2823, 2806, 1594, 1577, 1517, 1459, 1403, 1369, 1309, 1257,
1213, 1187, 1085, 1039, 948, 877, 813, 744, 680. 1H NMR spectrum, , ppm: 3.11 (3H, s) and 3.19 (3H, s, N(CH3)2);
3.90 (3H, s, OCH3); 5.67 (2H, s, NH2); 10.26 (1H, s, NOH). Found, %: C 39.54; H 5.78; N 39.71. C7H12N6O2.
Calculated, %: C 39.62; H 5.70; N 39.60.
1261

N'-Hydroxy-4-methoxy-6-(pyrrolidin-1-yl)-1,3,5-triazine-2-carboximidamide (3b) was obtained
from compound 1b and ammonia in 82% yield (1.95 g); mp 268-270 (decomp.). IR spectrum, , cm-1: 3504,
3400, 3276, 3199, 3010, 2971, 2954, 2887, 1583, 1550, 1513, 1457, 1367, 1348, 1299, 1236, 1186, 1164, 1110,
1
1064, 962, 918, 873, 817, 784, 754, 698. H NMR spectrum, , ppm (J, Hz): 1.91 (4H, s, (CH2)2); 3.49 (2H, t,
J = 2.0) and 3.56 (2H, t, J = 2.0, N(CH2)2); 3.88 (3H, s, OCH3); 5.65 (2H, s, NH2); 10.25 (1H, s, NOH). Found,
%: C 45.32; H 5.99; N, 35.32. C9H14N6O2. Calculated, %: C 45.37; H 5.92; N 35.27.
TABLE 2. 13C NMR Spectra (, ppm (J, Hz)) of 6-Methoxy-4-(5-R1-1,2,4-
oxadiazol-3-yl)-1,3,5-triazin-2-amines 5a-p
1,2,4-Oxadiazole
1,3,5-Triazine ring
СOMe СR С–C
ring
Com-
pound
Other signals
C-3
C-5
5a
5b
5c
5d
5e
5f
171.2 167.3 166.4 164.3
170.6 167.0 163.8 163.3
171.4 167.3 165.2 164.4
171.5 167.2 165.8 164.6
171.3 168.0 166.5 164.3
170.9 167.9 164.2 164.0
178.6
178.3
178.6
178.6
176.6
176.5
12.4 (CH3); 36.4, 36.7 (N(CH3)2);
54.8 (OCH3)
12.2 (CH3); 24.7, 24.8 (CH2);
46.4, 46.7 (CH2N); 54.5 (OCH3)
12.5 (CH3); 24.3, 25.6, 25.7 (CH2);
44.3, 44.7 (CH2N); 54.8 (OCH3)
12.4 (CH3); 43.9, 44.3 (CH2N);
55.0 (OCH3); 66.1 (OCH2)
36.4, 36.7 (N(CH3)2); 54.7 (OCH3);
123.7, 128.4, 130.0, 133.8 (Ph)
24.9 (CH2); 46.8, 46.9 (CH2N);
54.8 (OCH3);
123.7, 128.4, 130.0, 133.9 (Ph)
5g
5h
171.5 168.0 165.4 164.5
171.6 167.9 165.9 164.6
176.5
176.6
24.4, 25.6, 25.8 (CH2);
44.4, 44.8 (CH2N); 54.9 (OCH3);
123.7, 128.4, 130.0, 133.9 (Ph)
44.1 (CH2N); 55.0 (OCH3);
66.2 (OCH2);
123.7, 128.4, 129.9, 133.8 (Ph)
5i
5j
171.1 167.1 166.3 164.3
170.9 167.0 164.2 164.1
186.3
186.2
27.6, 27.8, 35.7, 35.9, 38.9 (Ad);
36.4, 36.5 (N(CH3)2); 54.8 (OCH3)
27.6, 27.8, 35.7, 35.9, 36.4, 38.9
(Ad);
24.9, 24.9 (CH2); 46.7, 47.0 (CH2N);
54.8 (OCH3)
5k
5l
171.4 167.1 165.2 164.6
171.4 167.0 165.7 164.7
186.3
186.4
166.0
27.6, 27.8, 35.7, 35.9, 36.5, 39.3 (Ad);
24.3, 25.6, 25.8 (CH2);
44.3, 44.7 (CH2N); 54.8 (OCH3)
27.5, 27.8, 35.9, 36.5, 38.9 (Ad);
43.9, 44.3 (CH2N); 55.0 (OCH3);
66.1, 66.2 (OCH2)
5m
5n
171.1 167.7 166.1 162.7
170.9 167.7 163.9 162.6
36.4, 36.6 (N(CH3)2); 55.0 (OCH3);
(q, 2JC–F = 44) 116.0 (q, 1JC–F = 272, CF3)
166.0
24.9, 25.1 (CH2); 46.8, 47.0 (CH2N);
(q, 2JC–F = 44) 54.9 (OCH3);
116.0 (q, 1JC–F = 272, CF3)
5o
5p
171.4 167.8 165.1 163.1
171.4 167.7 165.3 163.1
166.0
25.5, 25.6, 25.7 (CH2);
(q, 2JC–F = 44) 44.4, 44.8 (CH2N); 55.0 (OCH3);
116.0 (q, 1JC–F = 272, CF3)
166.0
43.9, 44.4 (CH2N); 55.2 (OCH3);
(q, 2JC–F = 44) 66.0, 66.1, 66.2 (OCH2);
1262

N'-Hydroxy-4-methoxy-6-(piperidin-1-yl)-1,3,5-triazine-2-carboximidamide (3c) was obtained from
compound 1c and ammonia in 79% yield (1.99 g); mp 202-204 (decomp.). IR spectrum, , cm-1: 3488, 3390,
3317, 3205, 3128, 3006, 2942, 2856, 1583, 1515, 1461, 1450, 1375, 1292, 1245, 1224, 1126, 1095, 1060, 1027,
1
997, 948, 931, 858, 815, 738, 675. H NMR spectrum, , ppm (J, Hz): 1.50-1.61 (6H, m, (CH2)3); 3.76 (2H, t,
J = 2.0) and 3.82 (2H, t, J = 2.0, N(CH2)2); 3.89 (3H, s, OCH3); 5.80 (2H, s, NH2); 10.31 (1H, br. s, NOH).
Found, %: C 47.56; H 6.48; N 33.39. C10H16N6O2. Calculated, %: C 47.61; H 6.39; H 33.31.
N'-Hydroxy-4-methoxy-6-(morpholin-1-yl)-1,3,5-triazine-2-carboximidamide (3d) was obtained
from compound 1d and ammonia in 84% yield (2.13 g); mp 207-209°C (decomp.). IR spectrum, , cm-1: 3496,
3473, 3386, 3346, 3274, 3234, 3133, 2998, 2969, 2927, 2858, 1577, 1521, 1473, 1448, 1371, 1303, 1286, 1236,
1
1220, 1143, 1112, 1068, 1020, 962, 867, 815, 742. H NMR spectrum, , ppm: 3.63-3.88 (8H, m,
2NCH2CH2O); 3.90 (3H, s, OCH3); 5.87 (2H, s, NH2); 10.32 (1H, br. s, NOH). Found, %: C 42.49; H 5.61;
N 33.12. C9H14N6O3. Calculated, %: C 42.52; H 5.55; N 33.05.
4-Dimethylamino-N'-hydroxy-6-methoxy-N-propyl-1,3,5-triazine-2-carboximidamide (3e) was
obtained from compound 1a and propylamine in 76% yield (1.93 g); mp 145-147°C. IR spectrum, , cm-1: 3373,
3131, 3004, 2950, 2929, 2873, 2856, 1675, 1583, 1513, 1461, 1450, 1373, 1317, 1288, 1261, 1236, 1213, 1151,
1
1130, 1097, 1043, 1027, 993, 973, 929, 883, 819, 781, 752. H NMR spectrum, , ppm (J, Hz): 0.80 (3H, t,
J = 9.0, CH3); 1.75 (2H, m, CH2); 3.08 (3H, s) and 3.15 (3H, s, N(CH3)2); 3.34-3.44 (2H, m, NCH2); 3.85 (3H, s,
OCH3); 5.63 (1H, m, NH); 10.25 (1H, s, NOH). Found, %: C 47.36; H 7.02; N 33.19. C10H18N6O2. Calculated,
%: C 47.23; H 7.13; N 33.05.
4-Dimethylamino-N'-hydroxy-6-methoxy-N-(pyrrolidin-1-yl)-1,3,5-triazine-2-carboximidamide (3f)
was obtained from compound 1a and pyrrolidine in 70% yield (1.86 g); mp 119-120°C. IR spectrum, , cm-1:
3245, 3197, 3128, 3004, 2929, 2883, 2861, 1654, 1573, 1517, 1457, 1375, 1349, 1292, 1220, 1141, 1130, 1081,
1
1025, 987, 946, 881, 856, 819, 779, 750, 742, 694. H NMR spectrum, , ppm (J, Hz): 1.77-1.85 (4H, m,
(CH2)2); 3.11 (3H, s) and 3.18 (3H, s, N(CH3)2); 3.55 (4H, t, J = 7.5, N(CH2)2); 3.82 (3H, s, OCH3); 10.15 (1H,
s, NOH). Found, %: C 49.49; H 6.93; N 31.54. C11H18N6O2. Calculated, %: C 49.61; H 6.81; N 31.56.
N'-Hydroxy-4-methoxy-6-(morpholin-1-yl)-N-phenyl-1,3,5-triazine-2-carboximidamide (3g) was
obtained from compound 1d and aniline in 78% yield (2.57 g); mp 189-190°C. IR spectrum, , cm-1: 3324,
3151, 2975, 2966, 2921, 2861, 1571, 1521, 1457, 1407, 1371, 1303, 1282, 1232, 1172, 1116, 1068, 1016, 987,
1
960, 902, 889, 848, 815, 777, 761, 694. H NMR spectrum, , ppm: 3.52-3.80 (8H, m, N(CH2CH2)2O); 3.86
(3H, s, OCH3); 6.82-7.21 (5H, m, H Ph); 7.72 (1H, s, NH); 9.98 (1H, s, NOH). Found, %: C 54.39; H 5.40;
N 25.60. C15H18N6O3. Calculated, %: C 54.54; H 5.49; N 25.44.
N-(1-Adamantyl)-N'-hydroxy-4-methoxy-6-(pyrrolidin-1-yl)-1,3,5-triazine-2-carboximidamide (3h)
was obtained from compound 1b and adamantylamine in 72% yield (2.68 g); mp 214-216°C. IR spectrum, ,
cm-1: 3321, 3112, 3197, 2908, 2848, 1585, 1540, 1511, 1457, 1411, 1375, 1340, 1290, 1272, 1238, 1182, 1116,
1
1095, 995, 977, 966, 819, 800. H NMR spectrum, , ppm: 1.99 (4H, m, (CH2)2); 1.65 (6H, s) and 2.08 (9H, s,
H Ad); 3.64-3.70 (4H, m, N(CH2)2); 4.02 (3H, s, OCH3); 5.21 (0.6H, s) and 5.60 (0.4H, s, NH); 13.40 (1H, s,
NOH). Found, %: C 61.15; H 7.63; N 22.71. C19H28N6O2. Calculated, %: C 61.27; H 7.58; N 22.56.
4-R-N-Acyloxy-6-methoxy-1,3,5-triazine-2-carboximidamides 4a-l (General Method). Triethyl-
amine (1.46 ml, 1.05 mmol) (for compounds 4a-d) or pyridine (0.85 ml, 1.05 mmol) (for compounds 4e-l) was added
to a stirred suspension of compound 3a-d (1 mmol) in toluene (30 ml) followed by the corresponding acid anhydride
(1.05 mmol). The reaction mixture was maintained at 20-25°C until starting carboximidamide 3 disappeared as
indicated by thin-layer chromatography. Toluene was evaporated off at reduced pressure and the residue was treated
with 40 ml water. The precipitate was filtered off, washed twice with 10 ml water, and dried in the air.
N-Acetoxy-4-dimethylamino-6-methoxy-1,3,5-triazine-2-carboximidamide (4a) was obtained from
compound 3a and acetic anhydride in 74% yield (1.88 g); mp 135-138°C. IR spectrum, , cm-1: 3494, 3388, 3265,
3205, 3139, 3023, 2937, 2879, 1762, 1648, 1616, 1577, 1521, 1473, 1417, 1375, 1309, 1209, 1081, 1041, 1001,
900, 817, 702, 642. 1H NMR spectrum, , ppm: 2.14 (3H, s, COCH3); 3.10 (3H, s) and 3.17 (3H, s, N(CH3)2); 3.88
(3H, s, OCH3); 6.81 (2H, s, NH2). Found, %: C 42.65; H 5.68; N 32.96. C9H14N6O3. Calculated, %: C 42.52;
H 5.55; N 33.05.
1263

N-Acetoxy-4-methoxy-6-(pyrrolidin-1-yl)-1,3,5-triazine-2-carboximidamide (4b) was obtained from
compound 3b and acetic anhydride in 70% yield (1.96 g); mp 172-174°C. IR spectrum, , cm-1: 3538, 3482,
3398, 3266, 3137, 2981, 2958, 2887, 1756, 1648, 1600, 1571, 1515, 1457, 1375, 1342, 1307, 1222, 1046, 1006,
896, 817, 676. 1H NMR spectrum, , ppm (J, Hz): 1.89 (4H, t, J = 2.8, (CH2)2); 2.14 (3H, s, COCH3); 3.48 (2H,
t, J = 2.8) and 3.56 (2H, t, J = 2.8, N(CH2)2); 3.89 (3H, s, OCH3); 6.78 (2H, s, NH2). Found, %: C 47.30; H 5.58;
N 30.12. C11H16N6O3. Calculated, %: C 47.14; H 5.75; N 29.98.
N-Acetoxy-4-methoxy-6-(piperidin-1-yl)-1,3,5-triazine-2-carboximidamide (4c) was obtained from
compound 3c and acetic anhydride in 64% yield (1.88 g); mp 139-141°C. IR spectrum, , cm-1: 3531, 3490,
3403, 3303, 3282, 2944, 2919, 2858, 1766, 1652, 1591, 1571, 1513, 1467, 1375, 1294, 1220, 1197, 1097, 1064,
1006, 896, 819, 700. 1H NMR spectrum, , ppm (J, Hz): 1.51-1.61 (6H, m, (CH2)3); 2.13 (3H, s, COCH3); 3.75
(2H, t, J = 2.0) and 3.84 (2H, t, J = 2.0, N(CH2)2); 3.88 (3H, s, OCH3); 6.82 (2H, s, NH2). Found, %: C 49.13;
H 6.01; N 28.37. C12H18N6O3. Calculated, %: C 48.97; H 6.16; N 28.55.
N-Acetoxy-4-methoxy-6-(morpholin-1-yl)-1,3,5-triazine-2-carboximidamide (4d) was obtained from
compound 3d and acetic anhydride in 65% yield (1.92 g); mp 164-166°C. IR spectrum, , cm-1: 3432, 3320,
2160, 2979, 2914, 2888, 2852, 1741, 1631, 1558, 1521, 1467, 1371, 1297, 1284, 1222, 1114, 1054, 1018, 1002,
1
958, 896, 821, 707. H NMR spectrum, , ppm: 2.13 (3H, s, COCH3); 3.65-3.76 (8H, m, N(CH2CH2)2O); 3.90
(3H, s, OCH3); 6.87 (2H, s, NH2). Found, %: C 44.56; H 5.62; N 28.41. C11H16N6O4. Calculated, %: C 44.59;
H 5.44; N 28.36.
N-Benzoyloxy-4-dimethylamino-6-methoxy-1,3,5-triazine-2-carboximidamide (4e) was obtained
from compound 3a and benzoyl chloride in 75% yield (2.37 g); mp 170-172°C. IR spectrum, , cm-1: 3417,
3320, 3062, 2954, 2927, 2807, 1731, 1635, 1585, 1569, 1521, 1467, 1417, 1313, 1259, 1247, 1211, 1087, 1066,
1037, 1025, 918, 885, 819, 711. 1H NMR spectrum, , ppm: 3.14 (3H, s) and 3.22 (3H, s, N(CH3)2); 3.92 (3H, s,
OCH3); 6.99 (2H, s, NH2); 7.53-8.18 (5H, m, H Ph). Found, %: C 53.02; H 5.19; N 26.68. C14H16N6O3.
Calculated, %: C 53.16; H 5.10; N 26.57.
N-Benzoyloxy-4-methoxy-6-(pyrrolidin-1-yl)-1,3,5-triazine-2-carboximidamide (4f) was obtained
from compound 3b and benzoyl chloride in 68% yield (2.33 g); mp 160-163°C. IR spectrum, , cm-1: 3485,
3347, 3025, 2975, 2950, 2875, 1734, 1625, 1560, 1517, 1465, 1456, 1373, 1342, 1294, 1259, 1240, 1105, 1091,
1
1068, 1025, 912, 819, 703. H NMR spectrum, , ppm: 1.91 (4H, s, (CH2)2); 3.50 (2H, s) and 3.60 (2H, s,
N(CH2)2); 3.92 (3H, s, OCH3); 6.89 (2H, s, NH2); 7.54-8.17 (5H, m, Ph). Found, %: C 56.29; H 5.45; N 24.50.
C16H18N6O3. Calculated, %: C 56.13; H 5.30; N 24.55.
N-Benzoyloxy-4-methoxy-6-(piperidin-1-yl)-1,3,5-triazine-2-carboximidamide (4g) was obtained
from compound 3c and benzoyl chloride in 64% yield (2.28 g); mp 174-176°C. IR spectrum, , cm-1: 3425,
3269, 3060, 3018, 2931, 2854, 1733, 1635, 1577, 1519, 1461, 1448, 1371, 1288, 1261, 1218, 1091, 1066, 1025,
1001, 919, 817, 705. 1H NMR spectrum, , ppm: 1.55-1.64 (6H, m, (CH2)3); 2.13 (3H, s, COCH3); 3.78 (2H, s)
and 3.87 (2H, s, N(CH2CH2)2); 3.82 (3H, s, OCH3); 6.92 (2H, s, NH2); 7.53-8.17 (5H, m, H Ph). Found, %:
C 57.36; H 5.73; N 23.69. C17H20N6O3. Calculated, %: C 58.29; H 5.66; N 23.58.
N-Benzoyloxy-4-methoxy-6-(morpholin-1-yl)-1,3,5-triazine-2-carboximidamide (4h) was obtained
from compound 3d and benzoyl chloride in 72% yield (2.58 g); mp 170-173°C. IR spectrum, , cm-1: 3433,
3288, 3072, 2966, 2917, 2854, 1735, 1637, 1575, 1523, 1469, 1448, 1371, 1317, 1280, 1257, 1230, 1116, 1066,
1
1024, 1010, 916, 877, 817, 705. H NMR spectrum, , ppm: 3.67-3.83 (8H, m, N(CH2CH2)2O); 3.93 (3H, s,
OCH3); 6.97 (2H, s, NH2); 7.53-8.18 (5H, m, Ph). Found, %: C 53.51; H 4.98; N 23.55. C16H18N6O4. Calculated,
%: C 53.63; H 5.06; N 23.45.
N-(Adamantane-1-carbonyl)oxy-4-dimethylamino-6-methoxy-1,3,5-triazine-2-carboximidamide (4i)
was obtained from compound 3a and andamantane-1-carbonyl chloride in 78% yield (2.92 g); mp 150-152°C.
IR spectrum, , cm-1: 3461, 3347, 2904, 2888, 1732, 1623, 1597, 1577, 1519, 1473, 1413, 1369, 1307, 1213,
1
1097, 1066, 952, 898, 819. H NMR spectrum, , ppm: 1.68 (6H, s) and 1.94 (9H, s, H Ad); 3.12 (3H, s) and
3.18 (3H, s, N(CH3)2); 3.89 (3H, s, OCH3); 6.58 (2H, s, NH2). Found, %: C 57.60; H 7.06; N 22.56. C18H26N6O3.
Calculated, %: C 57.74; H 7.00; N 22.44.
1264

N-(Adamantane-1-carbonyl)oxy-4-methoxy-6-(pyrrolidin-1-yl)-1,3,5-triazine-2-carboximidamide
(4j) was obtained from compound 3b and adamantane-1-carbonyl chloride in 66% yield (2.64 g); mp
169-171°C. IR spectrum, , cm-1: 3463, 3365, 2906, 2850, 1735, 1627, 1585, 1560, 1517, 1457, 1369, 1340,
1222, 1066, 892, 819. 1H NMR spectrum, , ppm (J, Hz): 1.70 (6H, s) and 1.95 (9H, s, H Ad); 1.92 (2H, s) and
1.98 (2H, s, (CH2)2); 3.50 (2H, t, J = 4.0) and 3.57 (2H, t, J = 4.0, N(CH2)2); 3.91 (3H, s, OCH3); 6.47 (2H, s,
NH2). Found, %: C 60.12; H 7.12; N 20.83. C20H28N6O3. Calculated, %: C 59.98; H 7.05; N 20.98.
N-(Adamantane-1-carbonyl)oxy-4-methoxy-6-(piperidin-1-yl)-1,3,5-triazine-2-carboximidamide (4k)
was obtained from compound 3c and adamantane-1-carbonyl chloride in 73% yield (3.03 g); mp 164-167°C. IR
spectrum, , cm-1: 3430, 3336, 3010, 2929, 2904, 2854, 1731, 1631, 1577, 1517, 1448, 1369, 1290, 1214, 1095,
1
1062, 907, 887, 819. H NMR spectrum, , ppm: 1.53 (2H, s) and 1.65 (4H, s, (CH2)3); 1.69 (6H, s) and 1.98
(9H, s, H Ad); 3.76 and 3.82 (4H, two s, NCH2); 3.89 (3H, s, OCH3); 6.57 (2H, s, NH2). Found, %: C 60.92;
H 7.44; N 20.19. C21H30N6O3. Calculated, %: C 60.85; H 7.30; N 20.27.
N-(Adamantane-1-carbonyl)oxy-4-methoxy-6-(morpholin-1-yl)-1,3,5-triazine-2-carboximidamide
(4l) was obtained from compound 3d and adamantane-1-carbonyl chloride in 65% yield (2.71 g); mp
141-143°C. IR spectrum, , ppm: 3454, 3346, 2965, 2906, 2850, 1735, 1625, 1581, 1521, 1467, 1448, 1375,
1286, 1238, 1216, 1118, 1066, 999, 898, 819. 1H NMR spectrum, , ppm: 1.65 (6H, s) and 1.97 (9H, m, H Ad);
3.65-3.87 (8H, m, N(CH2CH2)2O); 3.91 (3H, s, OCH3); 6.61 (2H, s, NH2). Found, %: C 57.80; H 6.70; N 20.06.
C21H30N6O3. Calculated, %: C 57.68; H 6.78; N 20.18.
6-Methoxy-4-(5-R1-1,2,4-oxadiazol-3-yl)-1,3,5-triazine-2-amines 5a-l (General Method).
A
suspension of compound 4a-l (0.5 mmol) in acetic acid (20 ml) was heated at reflux until disappearance of the
starting compound as indicated by thin-layer chromatography. At the end of the reaction, acetic acid was
distilled off at reduced pressure. The residue was treated with 20 ml water. The precipitate was filtered off,
washed twice with 10 ml water, and dried in the air.
N,N-Dimethylamino-6-methoxy-4-(5-methyl-1,2,4-oxadiazol-3-yl)-1,3,5-triazin-2-amine (5a) was
obtained in 82% yield (0.97 g); mp 157-160°C. IR spectrum, , cm-1: 3012, 2956, 2873, 1594, 1571, 1521,
1
1508, 1467, 1409, 1365, 1245, 1205, 1079, 1031, 991, 904, 821, 777. H NMR spectrum, , ppm: 2.65 (3H, s,
CH3); 3.14 (3H, s) and 3.17 (3H, s, N(CH3)2); 3.91 (3H, s, OCH3). Found, %: C 45.84; H 5.02; N 35.61.
C9H12N6O2. Calculated, %: C 45.76; H 5.12; N 35.57.
2-Methoxy-4-(5-methyl-1,2,4-oxadiazol-3-yl)-6-(pyrrolidin-1-yl)-1,3,5-triazine (5b) was obtained in
76% yield (1.00 g); mp 127-128°C (decomp.). IR spectrum, , cm-1: 2979, 2956, 2885, 1570, 1517, 1457, 1407,
1
1376, 1336, 1284, 1247, 1230, 1068, 991, 914, 898, 817, 777. H NMR spectrum, , ppm (J, Hz): 1.89-1.92
(4H, m, (CH2)2); 2.67 (3H, s, CH3); 3.49 (2H, t, J = 2.4) and 3.53 (2H, t, J = 2.4, N(CH2)2); 3.90 (3H, s, OCH3).
Found, %: C 50.56; H 5.47; N 31.90. C11H14N6O2. Calculated, %: C 50.38; H 5.38; N 32.04.
2-Methoxy-4-(5-methyl-1,2,4-oxadiazol-3-yl)-6-(piperidin-1-yl)-1,3,5-triazine (5c) was obtained in
71% yield (0.98 g); mp 134-136°C. IR spectrum, , cm-1: 3014, 3001, 2943, 2862, 1592, 1573, 1521, 1473,
1
1448, 1419, 1373, 1336, 1284, 1253, 1216, 1126, 1091, 1066, 1035, 987, 914, 891, 852, 819, 777. H NMR
spectrum, , ppm: 1.54-1.63 (6H, m, N(CH2)3); 2.67 (3H, s, CH3); 3.77 (2H, s) and 3.83 (2H, s, N(CH2)2); 3.90
(3H, s, OCH3). Found, %: C 52.04; H 5.79; N 30.53. C12H16N6O2. Calculated, %: C 52.17; H 5.84; N 30.42.
2-Methoxy-4-(5-methyl-1,2,4-oxadiazol-3-yl)-6-(morpholin-1-yl)-1,3,5-triazine (5d) was obtained in
80% yield (1.11 g); mp 163-165°C. IR spectrum, , cm-1: 2998, 2958, 2869, 1596, 1577, 1531, 1467, 1419,
1
1373, 1278, 1251, 1216, 1108, 1070, 1022, 991, 896, 813, 775. H NMR spectrum, , ppm: 2.67 (3H, s, CH3);
3.66-3.83 (8H, m, N(CH2CH2)2O); 3.92 (3H, s, OCH3). Found, %: C 47.57; H 4.99; N 30.31. C11H14N6O3.
Calculated, %: C 47.48; H 5.07; N 30.20.
N,N-Dimethylamino-4-methoxy-6-(5-phenyl-1,2,4-oxadiazol-3-yl)-1,3,5-triazin-2-amine (5e) was
obtained in 79% yield (1.18 g); mp 196-198°C. IR spectrum, , cm-1: 3076, 3010, 2929, 2871, 1598, 1560,
1525, 1471, 1409, 1371, 1255, 1207, 1076, 1045, 991, 904, 825, 815, 771, 715, 688. 1H NMR spectrum, , ppm:
3.16 (3H, s) and 3.23 (3H, s, N(CH3)2); 3.96 (3H, s, OCH3); 7.64-8.14 (5H, m, H Ar). Found, %: C 56.48;
H 4.79; N 28.04. C14H14N6O2. Calculated, %: C 56.37; H 4.73; N 28.17.
1265

2-Methoxy-6-(5-phenyl-1,2,4-oxadiazol-3-yl)-4-(pyrrolidin-1-yl)-1,3,5-triazine (5f) was obtained in
72% yield (1.17 g); mp 184-186°C. IR spectrum, , cm-1: 3052, 2966, 2887, 1589, 1531, 1498, 1459, 1450, 1405,
1361, 1342, 1278, 1238, 1224, 1159, 1058, 989, 815, 773, 719, 692. 1H NMR spectrum, , cm-1 (J, Hz) : 1.95 (4H,
t, J = 6.8, N(CH2)2); 3.57 (2H, t, J = 6.8) and 3.61 (2H, t, J = 6.8, N(CH2)2); 3.96 (3H, s, OCH3); 7.65- 8.16 (5H, m,
H Ar). Found, %: C 59.13; H 4.95; N 26.04. C16H16N6O2. Calculated, %: C 59.25; H 4.97; N 25.91.
2-Methoxy-6-(5-phenyl-1,2,4-oxadiazol-3-yl)-4-(piperidin-1-yl)-1,3,5-triazine (5g) was obtained in
75% yield (1.27 g); mp 163-165°C. IR spectrum, , cm-1: 3068, 3010, 2939, 2858, 1610, 1579, 1560, 1525,
1465, 1448, 1411, 1284, 1218, 1099, 1058, 987, 817, 771, 717, 692. 1H NMR spectrum, , ppm: 1.58-1.66 (6H,
m, CH2); 3.81 (2H, s) and 3.88 (2H, s, N(CH2)2); 3.94 (3H, s, OCH3); 7.64-8.16 (5H, m, H Ar). Found, %:
C 60.22; H 5.26; N 24.90. C17H18N6O2. Calculated, %: C 60.34; H 5.36; N 24.84.
2-Methoxy-4-(morpholin-1-yl)-6-(5-phenyl-1,2,4-oxadiazol-3-yl)-1,3,5-triazine (5h) was obtained in
81% yield (1.38 g); mp 198-200°C. IR spectrum, , cm-1: 3002, 2962, 2906, 2856, 1610, 1571, 1533, 1502,
1
1459, 1411, 1373, 1288, 1228, 1112, 1058, 1008, 987, 892, 819, 771, 715, 686. H NMR spectrum, , ppm:
3.70-3.85 (8H, m, N(CH2CH2)2O); 3.97 (3H, s, OCH3); 7.65-8.15 (5H, m, H Ph). Found, %: C 56.58; H 4.67;
N 24.53. C16H16N6O3. Calculated, %: C 56.47; H 4.74; N 24.69.
4-[5-(1-Adamantyl)-1,2,4-oxadiazol-3-yl]-N,N-dimethylamino-6-methoxy-1,3,5-triazin-2-amine (5i)
was obtained in 64% yield (1.14 g); mp 144-145°C. IR spectrum, , cm-1: 3023, 2931, 2912, 2852, 1581, 1560,
1535, 1508, 1450, 1413, 1363, 1292, 1251, 1203, 1087, 1072, 999, 783. 1H NMR spectrum, , ppm: 1.63 (6H, s)
and 2.05 (9H, s, H Ad); 3.15 (3H, s) and 3.19 (3H, s, N(CH3)2); 3.92 (3H, s, OCH3). Found, %: C 60.49; H 6.83;
N 23.49. C18H24N6O2. Calculated, %: C 60.66; H 6.79; N 23.58.
2-[5-(1-Adamantyl)-1,2,4-oxadiazol-3-yl]-4-methoxy-6-(pyrrolidin-1-yl)-1,3,5-triazine (5j) was
obtained in 68% yield (1.30 g); mp 136-138°C. IR spectrum, , cm-1: 2904, 2854, 1587, 1548, 1521, 1457,
1
1411, 1369, 1340, 1282, 1232, 1182, 1083, 1054, 999, 900, 817, 781. H NMR spectrum, , ppm: 1.65 (5H, s)
and 2.06 (9H, s, H Ad); 1.93 (4H, s, CH2); 3.54 (2H, s) and 3.57 (2H, s, N(CH2)2); 3.93 (3H, s, OCH3). Found,
%: C 62.76; H 6.97; N 22.07. C20H26N6O2. Calculated, %: C 62.81; H 6.85; N 21.97.
2-[5-(1-Adamantyl)-1,2,4-oxadiazol-3-yl]-4-methoxy-6-(piperidin-1-yl)-1,3,5-triazine (5k) was
obtained in 70% yield (1.38 g); mp 145-148°C. IR spectrum, , cm-1: 3010, 2921, 2854, 1592, 1533, 1511,
1
1450, 1407, 1378, 1348, 1284, 1220, 1083, 1052, 997, 985, 892, 856, 813, 781. H NMR spectrum, , ppm:
1.55-1.64 (6H, m, 3CH2); 1.75 (6H, s) and 2.05 (9H, s, H Ad); 3.78 (2H, s) and 3.83 (2H, s, N(CH2)2); 3.91 (3H,
s, OCH3). Found, %: C 63.54; H 7.25; N 21.02. C21H28N6O2. Calculated, %: C 63.62; H 7.12; N 21.20.
2-[5-(1-Adamantyl)-1,2,4-oxadiazol-3-yl]-4-methoxy-6-(morpholin-1-yl)-1,3,5-triazine (5l) was
obtained in 69% yield (1.37 g); mp 154-156°C. IR spectrum, , cm-1: 2912, 2854, 1587, 1535, 1508, 1473,
1450, 1378, 1284, 1257, 1228, 1108, 1083, 1054, 997, 985, 894, 815, 783. 1H NMR spectrum, , ppm: 1.64 (6H,
s) and 2.05 (9H, s, H Ad); 3.67-3.83 (8H, m, N(CH2CH2)2O); 3.93 (3H, s, OCH3). Found, %: C 60.16; H 6.70;
N 21.21. C20H26N6O3. Calculated, %: C 60.29; H 6.58; N 21.09.
4-Methoxy-6-(5-trifluoromethyl-1,2,4-oxadiazol-3-yl)-1,3,5-triazin-2-amines 5m-p (General Method).
Triethylamine (1.46 ml, 1.05 mmol) or pyridine (0.85 ml, 1.05 mmol) was added to a stirred suspension of
compounds 3a-d (1 mmol) in toluene (30 ml) followed by the addition of trifluoroacetic acid anhydride (1.47 ml,
1.05 mmol). The reaction mixture was maintained at 20-25°C until the starting compound disappeared as
indicated by thin-layer chromatography. Toluene was evaporated off at reduced pressure and the residue was
treated with 40 ml water. The precipitate was filtered off, washed twice with 10 ml water, and dried in the air.
N,N-Dimethylamino-4-methoxy-6-(5-trifluoromethyl-1,2,4-oxadiazol-3-yl)-1,3,5-triazin-2-amine (5m)
was obtained from compound 3a in 70% yield (2.03 g); mp 101-103°C. IR spectrum, , cm-1: 3000, 2937, 2881,
1592, 1535, 1508, 1471, 1407, 1369, 1340, 1286, 1220, 1170, 1149, 1079, 992, 983, 896, 813, 783, 757.
1H NMR spectrum, , ppm: 3.18 (3H, s) and 3.22 (3H, s, N(CH3)2); 3.96 (3H, s, OCH3). Found, %: C 37.34;
H 3.19; N 28.82. C9H9F3N6O2. Calculated for, %: C, 37.25; H 3.13; N 28.96.
2-Methoxy-4-(pyrrolidin-1-yl)-6-(5-trifluoromethyl-1,2,4-oxadiazol-3-yl)-1,3,5-triazine (5n) was
obtained from compound 3b in 63% yield (1.99 g); mp 105-107°C. IR spectrum, , cm-1: 2981, 2960, 2887,
1266

1616, 1587, 1575, 1521, 1473, 1405, 1369, 1338, 1267, 1230, 1186, 1172, 1149, 1058, 993, 892, 813, 781, 756.
1H NMR spectrum, , ppm (J, Hz): 1.95 (4H, t, J = 6.4, (CH2)2); 3.54 (2H, t, J = 6.4) and 3.57 (2H, t, J = 6.4,
N(CH2)2); 3.95 (3H, s, OCH3). Found, %: C 41.65; H 3.39; N 26.66. C11H11F3N6O2. Calculated, %: C 41.78;
H 3.51; N 26.57.
2-Methoxy-4-(piperidin-1-yl)-6-(5-trifluoromethyl-1,2,4-oxadiazol-3-yl)-1,3,5-triazine (5o) was
obtained from compound 3c in 75% yield (2.48 g); mp 99-101°C. IR spectrum, , cm-1: 3010, 2944, 2933, 2860,
1591, 1500, 1473, 1452, 1415, 1378, 1340, 1286, 1272, 1213, 1170, 1157, 1105, 1029, 991, 894, 810, 779, 756.
1H NMR spectrum, , ppm (J, Hz): 1.58-1.67 (6H, m, (CH2)3); 3.77 (2H, t, J = 4.0) and 3.85 (2H, t, J = 4.0,
N(CH2)2); 3.95 (3H, s, OCH3). Found, %: C 43.49; H 3.90; N 25.61. C12H13F3N6O2. Calculated, %: C 43.64;
H 3.97; N 25.45.
2-Methoxy-4-(morpholin-1-yl)-6-(5-trifluoromethyl-1,2,4-oxadiazol-3-yl)-1,3,5-triazine (5p) was
obtained from compound 3d in 76% yield (2.52 g); mp 100-102°C. IR spectrum, , cm-1: 3014, 2971, 2906,
2858, 1579, 1506, 1463, 1415, 1371, 1340, 1276, 1261, 1230, 1174, 1147, 1110, 1045, 993, 898, 854, 813, 781,
1
757. H NMR spectrum, , ppm: 3.71-3.87 (8H, m, N(CH2CH2)2O); 3.97 (3H, s, OCH3). Found, %: C 39.72;
H 3.50, N 25.20. C11H11F3N6O3. Calculated, %: C 39.77; H 3.34; N 25.29.
This research was carried out as part of the Federal Targeted Program "Scientific and scientific-
pedagogical personnel of the innovative Russia" 2009-2013.
REFERENCES
1.
2.
3.
4.
V. V. Bakharev, A. A. Gidaspov, E. V. Peresedova, D. B. Krivolapov, E. V. Mironova, and
I. A. Litvinov, Khim. Geterotsikl. Soedin., 1345 (2009). [Chem. Heterocycl. Comp., 45, 1075 (2009)].
H. Feuer (editor), Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis: Novel Strategies in
Synthesis, 2nd ed., Wiley, Hoboken, New Jersey (2008).
J. C. Jochims, in: A. R. Katritzky and C. W. Rees (editors), Heterocyclic Chemistry II, vol. 4, Pergamon,
Oxford (1996), p. 179.
V. V. Bakharev, A. A. Gidaspov, E. V. Peresedova, V. G. Granik, N. B. Grigor'ev, V. I. Levina,
I. S. Severina, A. Yu. Shchegolev, D. E. Dmitriev, and A. B. Sheremetev, Izv. Akad. Nauk, Ser. Khim.,
1900 (2009).
5.
A. A. Chesnyuk, S. N. Mikhailichenko, L. D. Konyushkin, S. I. Firgang, and V. N. Zaplishnyi, Izv.
Akad. Nauk, Ser. Khim., 1845 (2005).
6.
7.
T. E. Young and W. T. Beidler, J. Org. Chem., 50, 1182 (1985).
M. Tamura, Y. Ise, Y. Okajima, N. Nishiwaki, and M. Ariga, Synthesis, 3453 (2006).
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