Synthesis of nitrogen-containing heterocycles 10 [1]. Reaction of 2-amino- 1H-imidazole derivatives with ethoxymethylene compounds

Article abstract of DOI:10.1002/jhet.5570390123

The direct annelation reaction of 4-substituted 2-amino-1-benzylideneamino-1H-imidazoles (1) or 2-amino-1-isopropylideneamino-1H-imidazole (8) with ethoxymethylenemalononitrile (I) gave successfully bicyclic imidazo[1,2-a]pyrimidine compounds 2 and 9 in high yields. The reactions of other ethoxymethylene compounds of lower reactivity, i.e., ethyl ethoxymethylenecyanoacetate (II) and diethyl ethoxymethylenemalonate (III), with 2-amino-1H-imidazoles under similar conditions afforded the corresponding enamines 3, 4 and 10, which, upon heating in the presence of an acid or a base, could readily be cyclized to form imidazopyrimidines except for 1-isopropylideneamino compound 10. In general, the 3-phenyl compounds (3b and 4b) did not cyclize to the type 2 compound resulting in a full recovery of the starting enamines.

Full text of DOI:10.1002/jhet.5570390123

Jan-Feb 2002
Synthesis of Nitrogen-Containing Heterocycles 10 [1].
Reaction of 2-Amino-1H-imidazole Derivatives
with Ethoxymethylene Compounds
Yoshiko Miyamoto
157
Department of Chemistry, School of Science, Kitasato University,
Kitasato, Sagamihara, Kanagawa 228-8555 Japan
Received July 23, 2001
The direct annelation reaction of 4-substituted 2-amino-1-benzylideneamino-1H-imidazoles (1) or
2-amino-1-isopropylideneamino-1H-imidazole (8) with ethoxymethylenemalononitrile (I) gave success-
fully bicyclic imidazo[1,2-a]pyrimidine compounds 2 and 9 in high yields. The reactions of other
ethoxymethylene compounds of lower reactivity, i.e., ethyl ethoxymethylenecyanoacetate (II) and diethyl
ethoxymethylenemalonate (III), with 2-amino-1H-imidazoles under similar conditions afforded the corre-
sponding enamines 3, 4 and 10, which, upon heating in the presence of an acid or a base, could readily be
cyclized to form imidazopyrimidines except for 1-isopropylideneamino compound 10. In general, the
3-phenyl compounds (3b and 4b) did not cyclize to the type 2 compound resulting in a full recovery of the
starting enamines.
J. Heterocyclic Chem., 39, 157 (2002).
In a previous paper [2], the author has reported the direct
diamino-1H-imidazole (14), which have rarely been used
as a starting material for the synthesis of new heterocycles.
The 1-isopropylidene- or 1-benzylideneamino-2-amino-
1H-imidazoles is considered as an already-cyclized
diaminomethylenehydrazone, including an imidazole ring.
The reaction of 4-substituted-1-benzylideneamino-2-
amino-1H-imidazoles (1) with ethoxymethylenemalo-
nonitrile (I) was performed by heating an equimolar mix-
ture of the starting materials in acetonitrile at 80° for 1
hour. The desired 1H-imidazo[1,2-a]pyrimidines (2) crys-
cyclization of diaminomethylenehydrazones with
ethoxymethylenemalononitrile (I) to bicyclic triazolopy-
rimidines. The author has also reported that treatment of
diaminomethylenehydrazones with ethyl ethoxymethyl-
enecyanoacetate (II) gave the corresponding 2,3-dihydro-
or 2,3-dehydro[1,2,4]triazolo[1,5-c]pyrimidines [3]. In
the present work, an attempt was made to extend this
cyclization to the reaction of ethoxymethylene compounds
(I-III) with 2-amino-1H-imidazoles (1, 8) and 1,2-

158
Y. Miyamoto
Vol. 39
tallized out of the solution and were easily isolated as crys-
talline compounds in good yields. 1-Isopropylidene-
aminoimidazole (8) gave similar bicyclic imidazopyrimi-
dine compounds (9) upon reacting with I at room tempera-
ture in the presence of acetone to prevent hydrolytic cleav-
age of the isopropylideneamino group.
When the reaction of ethyl ethoxymethylenecyanoacetate
(II) with 2-aminoimidazoles (1,8) was carried out under the
conditions of the general procedure, the reaction stopped at
the initial condensation stage as was expected from the early
study [2] and the open-chain compounds 3 were obtained in
85-98 % yield. Compounds 3 thus produced were homoge-

Jan-Feb 2002
Synthesis of Nitrogen-Containing Heterocycles 10
159
neous upon isolation and found to have a Z form on the basis
of spectral data [4]. In order to promote the reaction toward
the bicyclic products 5 or 6, it was required to add an acid or
a base as a catalyst into the reaction medium. It was unex-
pectedly found that when the cyclization of 3 was performed
under the influence of acid, the cyanocarbon on the vinyli-
dene carbon of the side chain did act as the electrophilic cen-
ter that attacked the N-3 nitrogen of the imidazole ring to
give 5, whereas, in the presence of a base, nucleophilic
attack by the N-3 nitrogen occurred on the ethoxycarbonyl
carbon of 3a (Z=Me) to give 6a and thus the alternative
cyclization could be realized.
In the acid-catalized cyclization (Scheme 3), the proto-
nated cyano-nitrogen may generate a strong electrophilic
center at the cyano carbon, which may easily be subjected to
nucleophilic attack by the lone-pair of N-3 nitrogen of the
imidazole ring, without the unfavorable electron-withdraw-
ing effects of the adjacent phenyl group. The Z conformer
of 3 is evidently unfavorable to afford 5 unless the geometry
is inverted to the E form before cyclization. Under the con-
ditions of acid catalysis, the positive charge on the cyano
nitrogen should lower the bond order of the vinylic double
bond to which it is attached and thus make it possible to
approach the cyano group to the N-3 of the imidazole ring in
the transition state. While the cyclization of 3a, for exam-
ple, in hot acetic acid gave 5a only in 9 % yield, further
improvement in the yield of 5 could be achieved (38 %) by
conducting the reaction in a mixture of concentrated HCl
and methanol at the reflux temperature. On the other hand,
in the base-catalyzed cyclization of 3 (Scheme 4), the adja-
cent phenyl group (Z=Ph) will sterically block the approach
of the ethoxycarbonyl group. Furthermore, the phenyl
group will lower the nucleophilicity of the N-3 nitrogen in
contrast to the electron-donating effects of the methyl group
(Z=Me), thus the formation of 3-phenyl compound corre-
sponding to 6a being completely inhibited. Thus the base-
catalyzed cyclization of 3a (Z=Me) was performed in
methanol containing triethylamine at the reflux temperature
and the product 6a was obtained in 36 % yield. Similarly,
the bis(ethoxycarbonyl)vinylamino compound 4a under-
went the base-catalyzed cyclization to form 7a, whereas 4b
did not cyclize to 7b.
1-Isopropylideneamino-2-amino-4-phenyl-1H-imida-
zole (8) reacted with I at room temperature to give
1-isoprpopylideneaminoimidazopyrimidine (9) in moder-
ate yield. The imidazole 8 gave 2-cyanovinylaminoimida-
zole (10) in the reaction with II, but the resulting
cyanovinyl compound (10) failed to give 11 under the con-
Table 1
Analytical and Physical Data for 1,4-Disubstituted 2-Imidazolamimomethylene Compounds
1
Compd. Yield
MP
(ºC)
Formula
Calcd/Found
H N
MS,m/z(Rel.Int.)
H NMR Spectral Data
No.
(%)
C
+
3b
85
201-202
132-136
160-161
C
C
C
H
N O
68.56 4.97 18.17 385(M ,79),209(100)
68.33 4.98 18.12
1.39 (t, J=7.3, 3H, CH ),4.35 (q,J=7.3, 2H, CH ),
3 2
22 19
5
2
4
4
7.26 (s, 1H, C -H),7.30 (t, J=7.3, 1H,Ph),
5
7.40 (t, J=7.3, 2H, Ph),7.52 (m, 3H, Ph), 7.77
(t, J=8.3, 2H, Ph), 7.85 (m, 2H, Ph), 8.23 (s,1H,=CH),
8.39 (d, J=13, 1H, CH),11.70 (d, J=13, 1H, NH)
+
4a
4b
78
86
H
N O
61.61 5.99 15.13 370(M ,100),175(77)
1.33 (t, J=6.8, 3H, CH ),1.40 (t, J=6.8, 3H, CH ),
19 22
4
3
3
61.40 5.92 15.14
4.25 (q, J=6.8, 2H, CH ), 4.38 (q, J=6.8, 2H, CH ),
2 2
7.03 (s, 1H, C -H), 7.48 (m, 3H, Ph), 7.84 (m, 3H, Ph),
5
8.16 (s, 1H,=CH), 8.81 (d, J=13, 1H, CH),11.70 (d,
J=13, 1H, NH)
+
H
N O
66.65 5.59 12.96 432(M ,36),283(100)
1.37 (t, J=7.3, 3H, CH ), 1.41 (t, J=7.3, 3H, CH ),
24 24
4
3
3
66.78 5.61 12.89
4.29 (q, J=6.8, 2H, CH ), 4.40 (q, J=6.8, 2H, CH ),
2 2
7.26 (s, 1H, C -H), 7.30 (t, J=7.3, 1H, Ph), 7.42 (t,
5
J=7.3, 2H, Ph), 7.55 (m, 3H, Ph), 7.84 (d, J=8.3 ,2H,
Ph), 7.90 (m, 2H, Ph), 8.31 (s, 1H,=CH), 8.97 (d, J=13,
1H, CH), 11.75 (d, J=13, 1H, NH)

160
Y. Miyamoto
Vol. 39
Table 2
Analytical and Physical Data for 1H-Imidazo[1,2-a]pyrimidines
Compd.
No.
Yield
(%)
MpºC
Formula
Calcd/Found
H
MS,m/z(Rel.Int.)
C
N
+
2b
5b
7a
96
43
25
196-197
221-222
205-206
C
H
N
68.56 4.97 18.17
68.50 4.97 18.17
68.38 4.70, 14.50
68.32 4.72 14.37
62.95 4.98 17.27
62.94 5.00 17.28
338(M ,10),234(100)
20 14
6
+
C
H
N O
385(M ,32),281(100)
22 19
5
2
+
C
H
N O
324(M ,100),175(80)
17 16
4
3
Table 3
1
13
H and C NMR Chemical Shift Values of Imidazopyrimidine Ring Protons and Carbons
1
13
R
Z
X
Y
H NMR
H-2 H-7
C NMR(J in Hz)
C-3 C-5
C-2
C-6
C-7
C-8'
2b
5b
7a
9
Ph
Ph
CHPh
CHPh
NH
NH
O
CN
CO Et
CO Et
CN
7.11 9.01
7.58 8.88
7.14 9.42
7.76 8.36
111.4(d,202) 122.6
117.2(d,199) 123.2
113.9(d,199) 122.4
111.7(d,202) 125.9
154.2
157.0
157.0
119.3
86.8
155.7(d,184) 144.3
105.5 159.0(d,182) 142.5
105.1 159.4(d,184) 145.4
52.5
2
Me CHPh
Ph CMe
2
NH
164.8(d,162) 144.8
2
240D elemental analyzer at the Microanalytical Laboratory of
Kitasato University.
ditions for cyclization of the 1-benzylideneaminoimida-
zole (3). When the reaction of 8 with II was carried out in
acetonitrile at the reflux temperature, the reaction mixture
was found to contain both 10 and 1-aminoimidazole com-
pound (12) in an approximately equimolar proportion.
The isoprpopylideneamino group of 10 was highly suscep-
tible to hydrolysis in the reaction medium and the
hydrolyzate, 1-aminoimidazole compound (12), may spon-
taneously cyclize to a triazepine (13b). The formation of
13 was confirmed through an alternative route starting
from 1,2-diaminoimidazole (14).
2-Amino-1-benzylideneamino-4-methyl-1H-imidazole (1a).
A mixture of benzaldehyde diaminomethylenehydrazone (1.62
g, 0.01 mol), α-chloroacetone (0.9 g) and triethylamine (2.02 g,
0.02 mol) was heated under reflux for 3 hours and the solvent was
removed under reduced pressure. The residue was taken up in
chloroform and the solution was thoroughly washed with water,
dried over anhydrous sodium sulfate and evaporated under
reduced pressure to give substantially pure compound as yellow
crystals (1.35g, 68 %), mp 195-199º. Recrystallization from
1
acetonitrile gave yellow needles (0.61 g, 40 %), mp 196-199º; H
The structures of 1H-imidazo[1,2-a]pyrimidine 2, 5-7, 9
and 2-vinylamino-1H-imidazoles 3 and 4 were confirmed
on the basis of the spectral data and the elemental analyses
which appear in Tables 1-3.
nmr (deuteriochloroform): δ 2.15 (s, 3H, CH ), 4.70 (s, 2H, NH ),
3
2
7.26 (s, 1H, C -H), 7.44 (m, 2H, Ph), 7.74 (m, 2H, Ph), 8.02 (s,
5
13
1H, =CH), C nmr (deuteriochloroform): δ 14.4(q), 100.6(d),
127.5(d), 128.9(d), 130.8(d), 133.4(s), 135.4(s), 145.6(d),
+
148.0(s); ms: m/z (relative intensity): 200(M , 55), 96(100).
Anal. Calcd. for C
Found: C, 65.87, H, 6.18, N, 27.89.
H N : C, 65.98; H, 6.04; N, 27.98.
11 12 4
EXPERIMENTAL
2-Amino-1-benzylideneamino-4-phenyl-1H-imidazole (1b).
Melting points were determined in open capillary tubes and are
1
13
In a similar manner as described for 1a, treatment of benzalde-
hyde diaminomethylenehydrazone (1.62 g, 0.01 mol) with
α-chloroacetophenone (1.6 g, 0.01 mol) in triethylamine (2.20 g,
0.02 mol) and ethanol (30 ml) afforded 1b as yellow crystals
(1.60 g, 61.1 %), mp 198-203º. Recrystallization from acetoni-
uncorrected. H and C nmr spectra were obtained with a JNM
EX-400 (400 MHz) or JNM FX-90Q (90 MHz) spectrometer.
The chemical shift values were recorded in parts per million
(ppm) on the δ scale with tetramethylsilane as the internal refer-
ence. The mass spectra (75 eV) were obtained on a JMS-D100
mass spectrometer. Preparative high-performance liquid chro-
matography (hplc) was carried out in a Kusano Kagaku KHLC-
201 instrument with a 300 X 22 mm glass column packed with
silica gel. Microanalyses were performed with a Perkin-Elmer
1
trile gave yellow needles (1.38 g, 55 %), mp 200-203º; H nmr
(deuteriochloroform): δ 6.21 (s, 2H, NH ), 7.21 (t, J=7.3, 1H,
2
Ph), 7.36 (t, J=7.3, 2H, Ph), 7.50 (m, 3H, Ph), 7.73 (d, J=7.3, Ph),
13
7.94 (m, 2H, Ph), 8.02 (s, 1H, C -H), 8.58 (s, 1H, =CH); C nmr
5

Jan-Feb 2002
Synthesis of Nitrogen-Containing Heterocycles 10
161
(deuteriochloroform): δ 101.2(d), 124.0(d), 126.2(d), 127.6(d),
Anal. Calcd. For C H N O : C, 63.14; H, 5.30; N, 21.66.
17 17 5 2
128.3(d), 128.7(d), 130.4(d), 133.7(s), 134.3(s), 136.6(s),
146.5(d), 149.5(s); ms: m/z (relative intensity): 262 (M , 66), 158
(100).
Found: C, 62.94; H, 5.27; N, 21.54.
+
Ethyl 1-Benzylideneamino-5-imino-3-methyl-1H-imidazo-
[1,2-a]pyrimidine-6-carboxylate (5a).
Anal. Calcd. for C
H N ; C, 73.26, H, 5.38; N, 21.36.
16 14 4
To a solution of 3a (0.1 g) in methanol (5 ml) was added 1 ml of
concentrated HCl solution. The mixture was heated under reflux
for 1 hour and then allowed to cool to ambient temperature. The
separated crystals were collected by filtration and converted to the
free base in usual manner to give 5a as a crystalline powder (0.09
g, 90 %). Recrystallization from methanol gave the analytically
Found: C, 73.27; H 5.60; N, 21.63.
2-Amino-1-isopropylideneamino-4-phenyl-1H-imidazol (8).
A mixture of 1,2-diamino-4-phenyl-1H-imidazole (14) (0.87 g, 5
mmol), acetone (10 ml), acetic acid (0.2 ml) and ethanol (5 ml) was
heated under reflux for 2 hours and then evaporated under reduced
pressure. The residue was partitioned between 10 % aqueous
sodium carbonate and chloroform. The organic phase was washed
with water, dried over sodium sulfate, and then evaporation under
reduced pressure to give pale yellow crystals (0.76 g, 71 %), mp
164-165º. Recrystallization from 2-propanol gave pale yellow
pure sample of 5a as yellow needles (0.031 g, 31 %), mp 168-170º;
1
H nmr (deuteriochloroform): δ 1.35 (t, 3H, J=7.3, CH CH ), 2.84
2
3
(s, 3H, CH ), 4.28 (q, 2H,J=7.3, CH CH ), 6.98 (s, 1H, C -H),
3
2
3
2
7.48 (m, 3H, Ph), 7.85 (m, 2H, Ph), 8.37 (s, 1H, N=CH), 8.95
13
(s,1H, NH), 9.26 (s, 1H, C -H); C nmr (deuteriochloroform): δ
7
1
prisms (0.66 g, 62 %), mp 167º; H nmr (deuteriochloroform): δ
14.4 (q), 14.7(q), 60.1(t), 101.4(s), 112.3(d), 123.5(s), 128.4(d),
128.9(d),131.9(d), 132.7(s), 145.6(s), 154.6(s), 155.2(d), 155.8(d),
2.21 (s, 3H, CH ), 2.20 (s, 3H, CH ), 4.65 (s, 2H, NH ), 6.91 (s, 1H,
3
3
2
+
C -H), 7.18 (t, J=7.8, 1H, Ph), 7.33 (t, J=7.8, 2H, Ph), 7.67 (t, J=7.8,
166.6(s); ms: m/z (relative intensity): 323(M , 32), 219(100).
5
13
2H, Ph); C nmr (deuteriochloroform): δ 20.1(q), 25.9(q),
Anal. Calcd. For C H N O : C, 63.14; H, 5.30; N, 21.66.
17 17
5 2
107.4(d), 124.3(d), 126.4(d), 128.5(d), 134.3(s), 135.5(s), 147.3(s),
170.4(s); ms m/z (relative intensity): 214(M , 35), 158(100).
Found: C, 62.89; H, 5.31; N, 21.81.
+
1-Benzylideneamino-6-cyano-3-methyl-5-oxo-1H-imdazo[1,2-a]-
pyrimidine (6a).
Anal. Calcd. for C
H N : C, 67.27; H, 6.58; N, 26.15.
12 14 4
Found: C, 67.27; H, 6.60; N, 26.36.
To a solution of 3a (0.1 g) in 5 ml of methanol was added 1 ml
of triethylamine. The mixture was heated under reflux for 7 hours
and then allowed to cool to ambient temperature. The separated
crystals were collected, washed with methanol, and then dried to
give 6a as a crystalline powder (0.035 g, 41 %). Recrystallization
1-Benzylideneamino-6-cyano-5-imino-3-methyl-1H-imi-
dazo[1,2-a]-pyrimidine (2a).
A solution of 1a (0.2 g, 0.01 mol), ethoxymethylenemalononi-
trile (I) (0.122 g, 0.01 mol) in acetonitrile (10 ml) was heated
under reflux for 1 hour and then cooled to ambient temperature.
The precipitated crystals were collected, washed with acetonitrile,
and then dried to give yellow crystals (0.23 g, 83 %), mp 218-
220º. Recrystallization from methanol gave yellow needles (0.21
from methanol gave the analytically pure sample of as yellow
1
needles (0.031 g, 36 %), mp 238-240º; H nmr (DMSO-d ): δ
6
2.67 (s, 3H, CH ), 7.57 (m, 3H, Ph), 7.88 (m, 2H, Ph), 8.18 (s, 1H,
3
13
C -H, 8.45 (s, 1H, N=CH), 9.07 (s, 1H, C -H); C nmr (DMSO-
5
7
1
g, 76 %), mp 218-220º; H nmr (DMSO-d ): δ 2.72 (s, 3H, CH ),
d ): δ 12.2(q), 87.3(s), 111.8(d), 116.4(s), 121.5(s), 128.2(d),
6
3
6
7.12 (s, 1H, C -H), 7.57 (m, 3H, Ph), 7.85 (m,2H, Ph), 7.96 (s,1H,
129.1(d), 132.1(s), 132.1(d), 144.9(s), 157.4(s), 156.9(d),
7
13
+
=CH), 8.01 (s, 1H, NH), 9.01 (s, 1H, C -H); C nmr (DMSO-
159.1(d); ms: m/z (relative intensity): 277(M , 30), 174(100).
7
d ): δ 14.0(q), 85.8(s), 111.0(d), 117.1(s), 122.4(s), 128.1(d),
6
Anal. Calcd. for C H N O: C, 64.97 H, 4.00; N, 25.26.
15 11
5
129.0(d), 131.9(d), 132.4(s), 144.9(s), 153.2(s), 155.4(d),
Found: C, 64.87; H, 4.05; N, 25.00.
+
155.7(d); ms: m/z(relative intensity): 276(M , 12), 172(100).
6-Cyano-5-imino-1-isopropylideneamino-3-phenyl-1H-imi-
dazo[1,2-a]pyrimidine (9).
Anal. Calcd. For C
H N : C,65.22; H,4.35; N, 30.43.
15 12 6
Found: C, 65.19; H, 4.46; N, 30.27.
A mixture of 8 (0.15 g, 0.7 mmol) and I (0.10 g, 0.84 mmol)
was dissolved in a mixed solvent of acetonitrile (2 ml) and ace-
tone (2 ml) and the reaction mixture was allowed to stand at room
temperature with occasional agitation for 1 day. The crystals
gradually deposited from the solution, and were collected by fil-
tration to give 0.1 g (50 %) of analytically pure 9 as pale yellow
(1,4-Disubstituted Ethyl Imidazol-2-yl)aminomethylenecyano-
acetate.
General Procedure.
A mixture of 1 (0.001 mol) and active ethoxymethylene com-
pounds (0.001 mol) in acetonitrile (2 ml) was heated under reflux
for 1 hour. The solid product was recrystallize for acetonitrile to
give product.
1
needles, mp 148-151º; H nmr (deuteriochloroform): δ 1.99 (s,
3H, CH ), 2.23 (s, 3H, CH ), 7.49 (t, J=7.3, 2H, Ph), 7.73 (d,
3
3
J=7.3, 2H, Ph), 7.76 (s, 1H, C -H), 7.88 (t, J=7.3, 1H, Ph), 8.36
2
Ethyl (1-Benzylideneamino-4-methylimidazol-2-yl)amino-
methylenecyanoacetate (3a).
13
(s, 1H, C -H), 12.8 (s, 1H, NH); C nmr (deuteriochloroform): δ
7
20.4(q), 24.7(q), 52.5(d), 111.7(d), 116.5(s), 119.3(s), 124.3(d),
125.9(s), 127.4(s), 128.3(d), 128.9(d), 144.7(d), 164.8(d),
This compound was obtained in 98 % yield as yellow needles,
+
1
180.6(s): ms: m/z (relative intensity): 290(M , 24), 158(100).
mp 186-187º; H nmr(deuteriochloroform): δ 1.39 (t, J=7.3, 3H,
CH CH ), 4.36 (q, J=7.3, CH CH ), 7.05 (s, 1H, C -H), 7.50 (m,
Anal. Calcd. For C
H N : C, 66.19; H, 4.86; N, 28.95.
2
3
2
3
5
16 14 6
3H, Ph), 7.84 (m, 2H, Ph), 8.18 (s, 1H, =CH), 8.33 (d, J=13, CH-
NH), 11.49 (d, J=13, CH-NH). C nmr (deuteriochloroform): δ
Found: C, 66.36; H, 4.98; N, 29.02.
13
Ethyl (4-Phenyl-1-isopropylideneaminoimidazol-2-yl)amino-
methyenecyanoacetate (10).
14.2(q), 14.3(q), 61.5(t), 78.6(s), 103.6(d), 116.9(s), 128.1(d),
129.2(d), 131.8(d), 132.3(s), 136.6(s), 139.9(s), 148.7(d),
+
149.5(d), 166.8(s). ms: m/z (relative intensity): 323(M , 72),
A solution of 8 (0.17, 0.001 mol) and ethyl ethoxymethyl-
enecyanoacetate (II) (0.203 g, 0.0012 mol) in acetone (2 ml) was
147(100).

162
Y. Miyamoto
Vol. 39
allowed to stand at room temperature. During 24 hours, crystals
gradually deposited from the solution, and were collected by fil-
tration to give 0.13 g (89 %) of analytically pure 10 as pale yel-
free base in the usual manner to give 13b as a crystalline powder
1
(0.09 g, 86%), mp 188º(d); H nmr (DMSO-d ): δ 1.23 (t, 3H,
6
J=7.1, CH CH ), 4.29 (q, 2H,J=7.1, CH CH ), 7.33 (t, J=7.3,
2
3
2
3
1
low needles, mp 168º; H nmr (deuteriochloroform): δ 1.37 (t,
1H,Ph), 7.44 (t, J=7.3 and 7.8, 2H, Ph), 7.82 (s, 1H, C -H), 7.89
8
13
J=7.3, 3H, CH ), 2.20 (s, 3H, CH ), 2.32 (s, 3H, CH ), 4.31 (q,
(d, 2H, Ph), 8.91 (s, 1H, C -H), 12.01 (s, 2H, C -H); C nmr
3
3
3
2
6
J=7.3, 2H, CH ), 7.12 (s, 1H, C -H), 7.26 (t, J=7.3, 1H, Ph), 7.39
(DMSO-d ): δ 13.9(q), 61.4(t), 78.4(s), 116.1(s), 116.4(d),
2
5
6
(t, J=7.8, 2H, Ph), 7.73 (d, J=7.8, 1H, Ph), 8.43 (d, J=13, 1H,
CH), 10.99 (d, J=13, 1H, NH); C nmr (deuteriochloroform): δ
124.3(s), 124.4(d), 127.6(s), 127.7(d), 128.6(d), 139.6(s),
150.8(d), 165.3(s); ms: m/z (relative intensity): 297(M , 23),
13
+
14.2(q), 20.5(q), 26.3(q), 61.5(t), 78.1(s), 109.5(q), 117.0(s),
124.6(d), 127.3(d), 128.7(d), 133.1(s), 137.4(s), 139.2(s),
150.2(d), 166.9(s), 172.0(s); ms: m/z (relatuve intensity):
296(100).
Anal. Calcd. For C H N O : C, 60.60; H, 5.08; N, 23.56.
Found: C, 60.31; H, 4.82; N, 23.68.
15 15
5 2
+
337(M , 57), 209(100).
6-Amino-7-cyano-2-phenyl-1H-imidazo[1,2-b][1,2,4]triazepine
(13a).
Anal. Calcd. for C H N O : C, 64.08; H, 5.68; N, 20.76.
18 12
5 2
Found: C, 64.18; H, 5.69; N, 20.76.
A solution of 1,2-diamono-4-phenyl-1H-imidazole (14) (0.174
g, 0.001 mol), I (0.07g, 0.001 mol) in acetonitrile (5 ml) was
heated under reflux for 1 hour and then allowed to cool to ambi-
ent temperature. The separated crystals were collected, washed
with acetonitrile, and then dried to give 13a as yellow crystals
(0.24 g, 96 %), mp 181-182º. Recrystallization from acetonitrile
Ethyl (1-Amino-4-phenylimidazol-2-yl)aminomethyenecyanoac-
etate (12).
A solution of 8(0.17 g, 0.001 mol) and II (0.203 1.2 mol) in
acetone (2 ml) was heated under reflux for 30 minutes and then
allowed to cool to ambient temperature. The separated crystals
were isolated by filtration and washed acetone to give 10 (0.12 g,
37 %), mp 178º. The filtrate was evaporated to give yellow oil.
The oil was crystallized from chloroform and the crystals found
1
gave yellow needles (0.20 g, 80 %), mp 184-185º; H nmr
(DMSO-d ): δ 6.07 (s, 1H, NH), 7.34 (t, J=7.3, 1H, Ph), 7.45 (t,
6
J=7.3 and J=7.8, 2H, Ph), 7.67 (s, 1H, C -H), 7.71 (d, J=7.8, 2H,
8
13
were collected by filtration to give 0.06 g, (20 %) of 12 as pale
Ph), 8.46 (s, 1H, C -H), 12.68 (s, 2H, C -NH); C nmr (DMSO-
2
6
1
yellow crystals with mp 197-198º; H nmr(DMSO-d ): δ 1.29 (t,
d ): δ 51.6(s), 115.9(d), 117.8(s), 119.6(s), 124.1(s), 124.1(d),
6
6
J=7.3, 3H, CH ), 4.25 (q, J=7.3, 2H,CH ), 6.17 (bs,2H, NH ),
7.20 (t, J=7.3, 1H, Ph), 7.35 (t, J=7.3 and 7.8, 2H, Ph), 7.55 (s,
127.6(s), 128.1(d), 128.9(d), 148.5(d), 164.8(d); ms m/z(relative
intensity): 250(M , 47), 249(100).
3
2
2
+
1H, C -H), 7.76 (d, J=7.8, 2H, Ph), 8.38 (d, J=13, 1H, CH), 11.13
Anal. Calcd. for C H N : C, 62.39; H, 4.03; N, 33.58.
Found: C, 62.14; H, 4.01; N, 33.48.
5
13 10 6
13
(d, J=13, 1H, NH); C nmr(DMSO-d ): 14.0(q), 61.0(t), 75.5(s),
6
116.3(d), 117.1(s), 124.0(d), 126.4(d), 128.4(d), 133.7(s),
134.6(s), 140.2(s), 150.5(d), 166.1(s); ms m/z (relative intensity):
297(M , 100), 250(96).
REFERENCES AND NOTES
+
Anal. Calcd. for C H N O : C, 60.60; H, 5.09; N, 23.59.
Found: C, 60.49; H, 5.11; N, 23.50.
15 15
5 2
[1] Part 9: Y. Miyamoto, J. Heterocyclic Chem., 37, 1587 (2000).
[2] Y. Miyamoto, R. Kobana and C. Yamazaki, Chem. Pharm.
Bull. 36(6), 1963 (1988).
[3] Y. Miyamoto and C. Yamazaki, J. Heterocyclic Chem., 26,
763 (1989).
6-Amino-7-ethoxycarbonyl-2-phenyl-1H-imidazo[1,2-b]-
[1,2,4]triazepine (13b).
To a solution of 10 (0.1 g) in methanol (2 ml) was added 0.2 ml
of concentrated HCl. The mixture was heated under reflux for 1
hour and then allowed to cool to ambient temperature. The sepa-
rated crystals were collected by filtration and converted to the
[4] The carbonyl frequencies in the internal (ir) spectra of 3
appears in the range of 1690-1675 cm , which corresponds to the inter-
nally bonded bands of the bis(ethoxycarbonyl)vinylamino compounds 4.
Thus the geometry about the CH=C bond of 3 should be Z form.
-1