Synthesis of 6-mono- and 5,6-disubstituted 1,2,3-triazolo[4,5-d]pyrimidin- 7-ones

Article abstract of DOI:10.1023/A:1026004720790

The reactions of N-substituted 4-amino-3-benzyl-1,2,3-triazole-5- carboxamides with phosphorus oxochloride and dimethylformamide at 80°C or with triethyl orthoacetate and acetic anhydride at 160°C afforded 6-mono- or 5,6-disubstituted 1,2,3-triazolo[4.5-d

Full text of DOI:10.1023/A:1026004720790

1770
Russian Chemical Bulletin, International Edition, Vol. 52, No. 8, pp. 1770—1776, August, 2003
Synthesis of 6ꢀmonoꢀ and 5,6ꢀdisubstituted
1,2,3ꢀtriazolo[4,5ꢀd]pyrimidinꢀ7ꢀones
ꢀ
V. P. Kislyi, E. B. Danilova, and V. V. Semenov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5328. Eꢀmail: muskat@cacr.ioc.ac.ru
The reactions of Nꢀsubstituted 4ꢀaminoꢀ3ꢀbenzylꢀ1,2,3ꢀtriazoleꢀ5ꢀcarboxamides with
phosphorus oxochloride and dimethylformamide at 80 °C or with triethyl orthoacetate and
acetic anhydride at 160 °C afforded 6ꢀmonoꢀ or 5,6ꢀdisubstituted 1,2,3ꢀtriazolo[4.5ꢀd]pyriꢀ
midinꢀ7ꢀones in 30—85% and 65—90% yields, respectively.
Key words: 4ꢀaminoꢀ3ꢀbenzylꢀ1,2,3ꢀtriazoleꢀ5ꢀcarboxylic acid, 1,2,3ꢀtriazolo[4,5ꢀd]pyriꢀ
midinꢀ7ꢀones.
1,2,3ꢀTriazolo[4,5ꢀd]pyrimidines (TP) belonging to
8ꢀazapurines1 attract attention because some of these
compounds exhibit antiviral,2 antitumor,2—4 or herbiꢀ
cide activities5 or can be used in photomaterials.6 Earꢀ
lier, analogs of nucleosides, viz., compounds bearing a
carbohydrate residue in the triazole ring and unsubꢀ
stituted in the pyrimidine ring, have aroused particuꢀ
lar interest.1 In recent years, TPs containing substituꢀ
ents in the pyrimidine ring have also attracted attenꢀ
tion. The aim of the present study was to synthesize
5ꢀ and(or) 6ꢀsubstituted 1,2,3ꢀtriazolo[4,5ꢀd]pyrimidinꢀ
7ꢀones (1) starting from Nꢀsubstituted 4ꢀaminoꢀ3ꢀbenꢀ
zylꢀ1,2,3ꢀtriazoleꢀ5ꢀcarboxamides 2. The latter were
planned to prepare from the corresponding acid 3 (synꢀ
thesis of 3 has been described earlier7). However, refluxꢀ
ing of a mixture of acid 3, aniline, and dicyclohexylꢀ
carbodiimide (DCC) in acetonitrile for 2 h afforded only
compound 4, which is a product of addition of acid 3 to
DCC (Scheme 1).
The synthesis of amides from acids using DCC is
widely used, in particular, in peptide chemistry. Adducts 4
were sometimes isolated from the reactions of acids with
DCC in the absence of amines.8 However, to our knowlꢀ
edge, compounds of type 4 never remained unchanged
after refluxing with aniline in acetonitrile. Ester of acid 3
is also poorly reactive.7 Thus, heating with a solution of
ammonia in ethylene glycol at 100 °C for 24 h was reꢀ
quired for the preparation of the corresponding amide.
The reaction of acid 3 with POCl3 also did not give rise to
identified compounds.
We synthesized amides 2 from cyanoacetamides 5 in
high yields (Scheme 2, Table 1).
Scheme 1
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1679—1685, August, 2003.
1066ꢀ5285/03/5208ꢀ1770 $25.00 © 2003 Plenum Publishing Corporation

Synthesis of 1,2,3ꢀtriazolo[4.5ꢀd]pyrimidines
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 8, August, 2003
1771
1
Table 1. Yields, melting points, and data from elemental analysis and H NMR spectroscopy of 4ꢀaminoꢀ3ꢀbenzylꢀ1,2,3ꢀtriazoleꢀ5ꢀ
carboxamides (2a—e)
Comꢀ Yield
pound (%)
M.p.
/°C
Found
Calculated
Molecular
formula
1H NMR (δ, J/Hz)
(%)
N
NH2
CH2
Ph
Other signals
C
H
(s, 2 Н) (s, 2 Н)
(m)
2a
2b
85
75
233—234
150—152
55.2 5.4 32.3
55.3 5.1 32.3
57.6 5.2 30.4
57.1 5.6 30.4
С10H11N5O 6.30
С11H13N5O 6.20
5.40
5.39
7.20—7.40
(5 Н)
7.20—7.40
(5 Н)
6.95, 7.20 (both br.s,
1 H each, CONH2)
2.80 (d, 3 Н, MeNHCO,
J = 4.6); 7.70 (br.s, 1 Н,
MeNHCO)
2c
86
182—186
66.0 5.7 22.8
65.5 5.1 22.8
С17H17N5O 6.18
5.40
7.20—7.35
(10 H)
4.47 (d, 2 H, PhCH2NHCO,
J = 6.2); 8.10 (br.s, 1 Н,
PhCH2NHCO)
2d
2e
79
91
205—207
180—182
65.9 5.3 23.2
66.4 5.5 22.8
63.2 5.5 22.0
63.1 5.3 21.7
С16H15N5O 6.50
С17H17N5O 6.45
5.48
5.45
7.00—7.80
(10 Н)
7.20—7.40
(5 Н)
9.90 (br.s, 1 Н,
NHCO)
3.95 (s, 3 Н, CH3O);
6.90—7.05 (m, 3 Н)
+ 8.35 (d, 1 Н, J = 8.9)
(2ꢀMeOC6H4); 9.05
(br.s, 1 Н, NH)
Scheme 2
Scheme 3
R = H (a), Me (b), CH2Ph (c), Ph (d), 2ꢀMeOC6H4 (e)
5ꢀUnsubstituted TPs were synthesized by heating
4ꢀaminoꢀ3ꢀphenylꢀ1,2,3ꢀtriazoleꢀ5ꢀcarboxamide with
HCONH2 at 180—200 °C.9 We extended this procedure
to amide 2a and prepared triazolopyrimidine 1a as the
reaction product. The reaction with the use of amide 2d
also gave 1a in low yield (Scheme 3). Apparently, this is
attributable to the fact that the attack of the amidine
amino group in the assumed intermediate 6 at the amide
group is more preferable than the attack of the amide NH
group at the amidine carbon atom.
At the same time, the reaction with POCl3 and DMF
(80 °C, 0.5 h) afforded a mixture of amidine 7d and TP 1d
(Scheme 4).
By varying the reaction conditions, it is possible to
selectively prepare either amidine 7d (40 °C, 0.5 h) or
TP 1d (80 °C, 4 h). The experimental conditions thus
found were used in the synthesis of amidines 7c,d and TP
1b—e (Table 2).
It should be noted that the Vilsmeier reaction of amide
2a afforded only amidine 7a, whereas the synthesis of TP
1e was accompanied by substantial resinification.
It is common practice to synthesize various fused pyꢀ
rimidines from heterocycles bearing the amino group and
the carboxamide group in the ortho position by heating in
acetic anhydride (or in any other anhydride).10 However,
amides 2 remained unconsumed upon refluxing in acetic
anhydride for 4 h, whereas the reactions in acetonitrile in

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Kislyi et al.
Scheme 4
Scheme 5
R = H (a), Me (b), CH2Ph (c), Ph (d), 2ꢀMeOC6H4 (e)
R = H (a), Me (b), CH2Ph (c), Ph (d)
the presence of mineral acids (H2SO4, HClO4) afforded
Nꢀacylated derivatives 8a—d in high yields (Scheme 5,
Table 3).
or dehydration to give nitrile generally takes place in the
series of other heterocycles.
The reactions in the presence of strong mineral acid
but at higher temperature (100 °C, acetic anhydride,
HClO4, 1 h) gave compound 9.
This behavior of the CONH2ꢀsubstituted product is
anomalous. Thus, either cyclization to form pyrimidine
Under all the conditions used, attempts at subjecting
products 8a—d to cyclization giving rise to TP failed. An
attempt to use a mixture of POCl3 and DMF as a deꢀ
hydrating agent led to the generation of only 5ꢀunsubꢀ
stituted amide 2c from 8c (elimination of the COCH3
Table 2. Yields, melting points, and data from elemental analysis and 1H NMR spectroscopy of Vilsmeier reaction products 1a—e
and 7a,c,d
Comꢀ Yield
pound (%)
M.p.
/°C
Found
Calculated
Molecular
formula
1H NMR (δ, J/Hz)
(%)
CH*
CH2
Ph
Other signals
C
H
N
(s, 1 Н)
(s, 2 Н)
(m)
1b
1c
1d
1e
7a
7c
71
74
85
30
72
49
215—220
146—148
195—197
110—115
118—120
132—134
59.4 4.9 28.6
59.7 4.6 29.0
67.5 4.5 22.4
68.1 4.7 22.1
67.8 4.0 23.7
67.3 4.3 23.1
64.3 4.7 21.5
64.9 4.5 21.0
61.2 5.4 33.6
61.4 5.5 33.1
66.1 6.4 23.4
66.3 6.1 23.2
С12H11N5O
С18H15N5O
С17H13N5O
С18H15N5O2
С13H14N6
8.55
8.65
8.37
8.17
8.25
9.30
5.75
7.30—7.40 3.53 (s, 3 Н, CH3N)
(5 Н)
7.25—7.35 5.25 (s, 2 Н, NCH2Ph)
(10 Н)
5.80
5.78
5.85
5.38
5.40
7.20—7.60
(10 Н)
—
7.10—7.55 3.85 (s, 3 Н, MeO)
(5 Н)
7.30—7.40 3.05, 3.15
(5 Н)
(both s, 3 H each, Me2N)
С20H22N6O
7.15—7.35 4.50 (d, 2 Н, NCH2Ph,
(10 Н)
J = 6.21); 8.30 (br.s,
1 Н, CONH);
3.05, 3.15
(both s, 3 H each, Me2N)
7d
55
142—144
65.0 5.4 24.0
65.5 5.7 24.1
С19H20N6O
9.15
5.42
7.15—7.30 3.05, 3.15
(10 Н) (both s, 3 H each, Me2N);
8.30 (br.s, 1 Н, CONH)
* CH is the N=CH—NMe2 fragment for 7a,c,d or C(5) for 1b—e.

Synthesis of 1,2,3ꢀtriazolo[4.5ꢀd]pyrimidines
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 8, August, 2003
1773
1
Table 3. Yields, melting points, and data from elemental analysis and H NMR spectroscopy of acylated products 8b—g and 9
Comꢀ Yield
pound (%)
M.p.
/°C
Found
Calculated
Molecular
formula
1H NMR (δ, J/Hz)
(%)
N
4ꢀCH3CONH
(br.s)
CH2
Ph
Other
signals
C
H
(s, 2 Н)
(m)
8b
8c
80
78
183—184 56.8 5.5 25.2 С13H15N5O2 2.1 (3 Н, Me);
57.1 5.5 25.6 9.95 (1 Н, NH)
5.42
7.20—7.35
(5 Н)
2.8 (d, 3 Н, J = 4.63);
8.2 (br.s, 1 Н,
MeNHCO)
4.44 (d, 2 H,
PhCH2NHCO,
J = 6.2);
178—180 65.1 5.5 20.5 С19H19N5O2 2.1 (3 Н, Me);
65.3 5.4 20.0 10.1 (1 Н, NH)
5.45
7.20—7.40
(10 Н)
8.8 (br.s, 1 Н,
PhCH2NHCO)
10.05 (s, 1 H,
PhNHCO)
2.82 (d, 3 H,
MeNHCO, J = 4.49);
8.2 (br.s, 1 Н,
MeNHCO)
8d
8e
85
85
156—158 64.4 5.4 23.7 С18H17N5O2 2.15 (3 Н, Me); 5.50
64.5 5.0 23.2 10.15 (1 Н, NH)
215—220 47.3 3.7 21.7 C13H12F3N5O211.5 (1 Н, NH) 5.45
47.7 3.7 21.4
7.05—7.80
(10 Н)
7.20—7.35
(5 Н)
8f
90
170—173 56.2 4.2 17.0 C19H16F3N5O211.6 (1 Н, NH) 5.50
56.6 4.0 17.4
7.15—7.40
(10 Н)
4.45 (d, 2 Н,
PhCH2NHCO,
J = 5.74);
8.80 (br.s, 1 Н,
PhCH2NHCO)
10.1 (br.s, 1 Н,
NHCO)
8g
9
87
75
165—170 55.0 3.9 18.5 C18H14F3N5O211.65 (1 Н, NH) 5.55
55.5 3.6 18.0
7.05—7.8
(10 Н)
7.20—7.35
(5 Н)
155—157 55.7 5.4 23.7 С14H15N5O3 2.1 (3 Н, Me);
55.8 5.0 23.2 10.25 (1 Н, NH)
5.50
2.4 (s, 3 H,
MeCONHCO);
9.95 (br.s, 1 Н,
MeCONHCO)
group occurred), whereas attempts to perform cyclization
under alternative conditions (heating in acetonitrile with
P2O5 or POCl3, refluxing in toluene in the presence of
TsOH with a water trap, heating in Si(OEt)4 and TsOH,
refluxing in pure SOCl2) led only to gradual accumulaꢀ
tion of the starting nonacylated triazoles 2.
The reactions with trifluoroacetic anhydride afforded
Nꢀtrifluoroacetyl derivatives 8e—g, which we also failed
to subject to cyclization with the formation of TP under
all the conditions used (Scheme 6).
Scheme 7
Scheme 6
R = Me (2b, 8e), CH2Ph (2c, 8f), Ph (2d, 8g)
R = H (1f, 2a), Me (1g, 2b), CH2Ph (1h, 2c, 10c), Ph (1i, 2d, 10d)

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Kislyi et al.
Triazolopyrimidines 1f—i were prepared by heatꢀ
ing amides 2a—d with MeC(OEt)3 in the presence of
acetic anhydride (160 °C, 4 h). When the reactions
were performed at low temperature (130—140 °C, 1 h),
compounds 10c,d were isolated in pure form, the latter
being, presumably, intermediates of these reactions
(Scheme 7).
The structures of the compounds synthesized were
confirmed by 1H NMR spectroscopy, mass spectrometry,
and IR spectroscopy. The CH2Ph fragment is a common
structural element of all the compounds synthesized. The
chemical shift of the CH2 unit for the monocyclic comꢀ
pounds varies within a narrow range (5.30—5.48 ppm),
whereas this shift for TP is in the range of 5.68—5.85 ppm,
which allows one to readily distinguish between bicyclic
and monocyclic structures. The characteristic feature of
compounds 8a—d containing the CH3CONH fragment is
an unusually strong broadening of the signal of the methyl
group at δ 2.1—2.15 (up to 40 Hz). The fact that the CN
group was formed from the CONH2 fragment in 7a was
confirmed by the IR spectrum in which the CN group is
observed at 2240 cm–1. The mass spectrometric study of
acids 2 and TPs is rather efficient because all these comꢀ
pounds, including even 4 ([М]+ (424)), give a pronounced
molecular ion. Scheme 8 shows the fragmentation of comꢀ
pound 4. Due to the presence of numerous parallel fragꢀ
mentation channels, all peaks, except for the peak of
PhCH2+ (100%) and the peak of cycloꢀC6H11 NH+ (67%),
Scheme 8

Synthesis of 1,2,3ꢀtriazolo[4.5ꢀd]pyrimidines
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 8, August, 2003
1775
After 15 min, a solution of benzyl azide (8.9 g, 67 mmol)
in alcohol (20 mL) was added to a suspension (the reaction
mixture immediately turned yellow). The reaction mixture was
refluxed for 1 h (the precipitate was completely dissolved and
then formed in the process of refluxing). The reaction mixture
was cooled to ∼20 °C. The precipitate was filtered off on a
Schott filter and reprecipitated from methanol by adding water
(1 : 1, v/v).
as well as the molecular ion by itself have low intensiꢀ
ties (<10%).
Experimental
The 1H NMR spectra were recorded on a Bruker WMꢀ250
instrument operating at 250 MHz in DMSOꢀd6. The IR spectra
were measured on a Specord M80 instrument in KBr. Cyanoꢀ
acetamides were prepared either by the reactions of cyanoacetic
ester with amines at ∼20 °C in alcohol or by heating a mixture of
cyanoacetic ester and anilines without a solvent at 180—200 °C
with distillation of the alcohol formed. Commercial dicycloꢀ
hexylcarbodiimide (DCC) was used without additional purifiꢀ
cation.
Reaction of acid 3 with dicyclohexylcarbodiimide. Synthesis
of cyclohexylamino(cyclohexylimino)methyl 5ꢀaminoꢀ1ꢀbenzylꢀ
1,2,3ꢀtriazoleꢀ4ꢀcarboxylate (4). A mixture of acid 3 (0.5 g,
2.3 mmol), DCC (0.5 g, 2.4 mmol), aniline (0.4 g, 4.3 mmol),
and acetonitrile (10 mL) was refluxed for 2 h, after which the
starting compounds were completely dissolved. The reaction
mixture was cooled and kept for some time. Then the precipitate
was filtered off. Compound 4 was obtained in a yield of 0.8 g
(79%), m.p. 182 °C. MS: М 424 (calculated for C23H32N6O2:
М 424). 1H NMR, δ: 4.4 (t, 1 H, NH—CH(CH2)2, 3J = 10.5 Hz);
The yields, melting points, and 1H NMR spectroscopic data
are given in Table 1.
Synthesis of triazolopyrimidinꢀ7ꢀones (1b—e) under the conꢀ
ditions of the Vilsmeier reaction (general procedure). A suspenꢀ
sion of amide 2b—e (5 mmol) in DMF (5 mL) was cooled to
0—2 °C and then POCl3 (0.85 mL, 1.42 g; 9.3 mmol) was added
dropwise with stirring. The resulting solution was stirred at 0 °C
for 5 min, at 25 °C for 10 min, and at 80 1 °C for 3 h. Then the
reaction solution was cooled to ∼20 °C and poured onto ice
(∼50 g). The precipitate that formed was filtered off and
reprecipitated from methanol by adding water (in the course of
dissolution in methanol, the mixture was neutralized by a 2 N
ammonia solution to pH 7).
The yields, melting points, and 1H NMR spectroscopic data
are given in Table 2.
Synthesis of 1ꢀbenzylꢀ5ꢀ(dimethylaminomethyleneamino)ꢀ
1,2,3ꢀtriazoleꢀ4ꢀcarboxamides (7c,d) (general procedure). A susꢀ
pension of amide 2c,d (5 mmol) in DMF (5 mL) was cooled to
0—2 °C. Then POCl3 (0.85 mL, 1.42 g, 9.3 mmol) was added
dropwise with stirring. The resulting solution was stirred at 0 °C
for 5 min, at 25 °C for 10 min, and at 80 1 °C for 0.5 h. Then
the solution was cooled to ∼20 °C and poured onto ice (∼50 g).
The precipitate that formed was filtered off and reprecipitated
from methanol by adding water (in the course of dissolution in
methanol, the mixture was neutralized by a 2 N ammonia soluꢀ
tion to pH 7).
3.55 (m,
1 H, N—CH(CH2)2); 2.00—1.10 (m, 10 H,
two cyclohexyl rings); 5.51 (s, 2 H, CH2Ph); 7.30—7.50 (m,
5 H, Ph); 6.60 (br.s, 2 H, NH2); 7.90 (br.s, 1 H, NH of cycloꢀ
hexyl). Found (%): C, 65.5; H, 7.9; N, 20.0. C23H32N6O2. Calꢀ
culated (%): C, 65.09; H, 7.55; N, 19.81.
Synthesis of 5ꢀaminoꢀ1ꢀbenzylꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxꢀ
amides (2a—e) (general procedure). Cyanoacetamide (45 mmol)
was added with stirring to a solution of KOH (2.8 g, 50 mmol) in
alcohol (30 mL) (weak cooling of the solution was observed).
Table 4. Yields, melting points, and data from elemental analysis and 1H NMR spectroscopy of products of condensation with triethyl
orthoacetate 3f—i and 10c,d
Comꢀ Yield
pound (%)
M.p.
/°C
Found
Calculated
Molecular
formula
1H NMR (δ, J/Hz)
(%)
N
C—CH3
(s, 3 Н)
OCH2CH3
CH2
Ph
Other
signals
C
H
(s, 2 Н)
(m)
1f
90
40
65
72
62
185—187 59.2 4.9 28.7 С12H11N5O 2.45
59.7 4.6 29.0
135—138 60.8 4.9 27.8 С13H13N5O 2.68
61.2 5.1 27.4
170—175 68.7 5.0 20.8 С19H17N5O 2.58
68.9 5.1 21.1
152—156 69.0 4.8 21.8 С18H15N5O 2.25
68.1 4.7 22.1
—
—
—
—
5.75
5.78
5.68
5.73
5.30
7.25—7.35
(5 Н)
7.20—7.30
(5 Н)
7.15—7.40
(10 Н)
7.20—7.60
(10 Н)
12.5 (br.s, 1 H,
NHCO)
1g
1h
1i
3.6 (s, 3 H,
MeNHCO)
5.4 (s, 2 H,
CH2NCO)
—
10b
160—165 59.5 6.0 23.5 С15H19N5O2 1.65
59.8 6.3 23.3
1.35 (t, 3 Н);
4.30 (d, 2 Н,
J = 7.0)
7.20—7.40
(5 Н)
2.80 (d, 3 Н,
MeNHCO,
J = 4.1);
7.90 (br.s, 1 H,
MeNHCO)
4.45 (d, 2 Н,
PhCH2NHCO,
J = 6.2);
10c
48
115—117 66.4 6.2 18.7 С21H23N5O2 1.65
66.8 6.1 18.6
1.35
5.33
7.15—7.35
(10 Н)
(t, 3 Н);
4.30 (d, 2 Н,
J = 7.0)
8.4 (br.s, 1 H,
PhCH2NHCO)

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Kislyi et al.
The yields, melting points, and 1H NMR spectroscopic data
are given in Table 2.
(4.4 mmol) were mixted with acetic anhydride (1 g, 9.8 mmol)
and MeC(OEt)3 (0.89 g, 7.4 mmol) in a flask equipped with a
thermometer. The reaction mixture was heated to 160 °C and
kept at this temperature for 4 h, 1 mL of the solution being
distilled from the reaction mixture. After cooling, the reaction
mixture that solidified was dissolved in hot ethanol and again
cooled. The precipitate that formed was filtered off on a Schott
filter. The yields, melting points, and 1H NMR spectroscopic
data are given in Table 4.
Acetylation of 5ꢀacetylaminoꢀ1ꢀbenzylꢀ1,2,3ꢀtriazoleꢀ4ꢀ
carboxamides. Synthesis of 5ꢀacetylaminoꢀ1ꢀbenzylꢀ1,2,3ꢀtriꢀ
azoleꢀ4ꢀ(NꢀR)ꢀcarboxamides (8a—d) (general procedure).
Amides 2b—d (3.6 mmol) were suspended in acetonitrile (5 mL).
Then acetic anhydride (1.1 g, 11 mmol) and two drops of 57%
perchloric acid were added. The suspension was heated to 60 °C
and kept at this temperature for 30 min. Then the reaction
mixture was cooled. The precipitate that formed was filtered off
and recrystallized from ethanol (in the course of heating, the
solution was neutralized with an aqueous solution of ammonia
to pH 7).
Synthesis of Nꢀsubstituted 1ꢀbenzylꢀ5ꢀ(1ꢀethoxyethyleneꢀ
amino)ꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxamides (10) (general procedure).
Acid 2 (4.4 mmol) was mixed with acetic anhydride (1 g,
9.8 mmol) and MeC(OEt)3 (0.89 g, 7.4 mmol) in a flask equipped
with a thermometer. The reaction mixture was heated to 140 °C
and kept at this temperature for 2 h. The reaction mixture was
cooled, poured into water, and neutralized with aqueous ammoꢀ
nia to pH 7. The precipitate that formed was filtered off on a
Schott filter and recrystallized from toluene. The yields, melting
The yields, melting points, and 1H NMR spectroscopic data
are given in Table 3.
Synthesis of Nꢀsubstituted acetylamide of 1ꢀbenzylꢀ5ꢀtriꢀ
fluoroacetylaminoꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxylic acid (9). A 57%
perchloric acid solution (0.3 mL) was added to a suspension of
4ꢀaminoꢀ3ꢀbenzylꢀ1,2,3ꢀtriazoleꢀ5ꢀcarboxamide (2a) (1 g,
4.6 mmol), which was preliminarily recrystallized from acetic
acid, in acetic anhydride (8 mL). The reaction mixture was
heated to 100 °C. After 1 h, the mixture was cooled. The preꢀ
cipitate was filtered off and recrystallized from ethanol (in the
course of heating, the solution was neutralized with aqueous
ammonia to pH 7). The yield was 0.6 g (43%). The melting
1
points, and H NMR spectroscopic data are given in Table 4.
References
1. A. Albert, Adv. Heterocycl. Chem., 1986, 39, 118.
2. Eur. Pat. 335355; Chem. Abstr., 1990, 112, 179713.
3. US Pat. 4931559; Chem. Abstr., 1991, 114, 43491.
4. US Pat. 307115; Chem. Abstr., 1990, 112, 36390.
5. M. V. Subramanian and B. C. Gerwick, ACS Symp. Ser.,
1989, 389, 277; Chem. Abstr., 1989, 111, 19341.
6. Jpn. Kokai 10 213887; Chem. Abstr., 1998, 129, 233188.
7. J. R. E. Hoover and A. R. Day, J. Am. Chem. Soc., 1956,
78, 5832.
8. Comprehensive Organic Chemistry, Ed. P. G. Sammes,
Pergamon Press, Oxford, 1979, 5, 105.
9. A. Dornow and J. Helberg, Chem. Ber., 1960, 93, 2001.
10. A. Albert, Adv. Heterocycl. Chem., 1982, 32, 1.
1
points and H NMR spectroscopic data are given in Table 3.
Trifluoroacetylation of amides 2b—d. Synthesis of 1ꢀbenzylꢀ
5ꢀtrifluoroacetylaminoꢀ1,2,3ꢀtriazoleꢀ4ꢀ(NꢀR)ꢀcarboxamides
(8e—h) (general procedure). Trifluoroacetic anhydride (1.95 g,
9.3 mmol) was added to a suspension of amides 2b—d (3 mmol)
in acetonitrile (4 mL). The suspension was heated to 45—50 °C
and kept at this temperature for 60 min. The resulting solution
was concentrated on a rotary evaporator and the residue was
recrystallized from ethanol (in the course of heating, the soluꢀ
tion was neutralized with aqueous ammonia to pH 7).
The yields, melting points, and 1H NMR spectroscopic data
are given in Table 3.
Synthesis of 5ꢀmethylꢀsubstituted 1,2,3ꢀtriazolo[4,5ꢀd]pyriꢀ
midinꢀ7ꢀones (1f—i) (general procedure). Aminotriazoles 2
Received March 28, 2003;
in revised form April 28, 2003