Synthesis and antituberculotic activity of some new imidazo[4,5-b]pyridine derivatives

Article abstract of DOI:10.1007/s10593-006-0249-1

The reactions of 2-acetylimidazo[4,5-b]pyridine hydrazone with some alkyl-and arylisothiocyanates and some orthoesters were carried out. Various new derivatives of the titled compound such as thiosemicarbazones, ethoxymethylenehydrazones, and derivatives of the new pyrido-[3′,2′: 4,5]imidazo[1,2-d][1,2,4]triazine ring system were obtained. Biological data for selected compounds are presented.

Full text of DOI:10.1007/s10593-006-0249-1

Chemistry of Heterocyclic Compounds, Vol. 42, No. 10, 2006
SYNTHESIS AND ANTITUBERCULOTIC ACTIVITY
OF SOME NEW IMIDAZO[4,5-b]PYRIDINE DERIVATIVES
L. Bukowski1, Z. Zwolska2, and E. Augustynowicz-Kopec2
The reactions of 2-acetylimidazo[4,5-b]pyridine hydrazone with some alkyl- and arylisothiocyanates
and some orthoesters were carried out. Various new derivatives of the titled compound such as
thiosemicarbazones, ethoxymethylenehydrazones, and derivatives of the new pyrido-
[3',2':4,5]imidazo[1,2-d][1,2,4]triazine ring system were obtained. Biological data for selected
compounds are presented.
Keywords: hydrazones, imidazo[4,5-b]pyridine, pyrido[3',2':4,5]imidazo[1,2-d][1,2,4]triazine, thio-
semicarbazones, antituberculotic activity.
It is known that thiosemicarbazones show various biological activites. To date many of them have been
applied in pharmacotherapy [1, 2]. Imidazo[4,5-b]pyridine derivatives have also revealed a broad spectrum of
biological activity and have been applied in pharmacotherapy [2]. These biological data prompted us to
synthesize a series of thiosemicarbazones fused with the imidazo[4,5-b]pyridine ring and to investigate their
biological activity.
First, the starting 2-acetylimidazo[4,5-b]pyridine (1) [3] was transformed to hydrazones 2-4 and
imines 5-8.
Scheme 1
O
N
Me
N
N
H
Ar–NH2
Me
H2N–NHR
1
S
Me
N
N
H2N–NH–C–NH2
N
H
N
H
N
Ar
NNHR
N
N
Me
N
S
2–4
5–8
N
H
C
NNH
NH2
N
9
2 R = H; 3 R = Ph; 4 R = 6-chloropyridazin-3-yl; 5 Ar = thiazol-2-yl; 6 Ar = pyridin-3-yl;
7 Ar = 4-methylpiperazin-1-yl; 8 Ar = [1,2,4]triazol-4-yl
__________________________________________________________________________________________
1
Department of Organic Chemistry, Medical University of Gdansk, 80-416 Gdansk, Poland.
2 Department of Microbiology, Institute of Tuberculosis and Pulmonary Diseases, 01-138 Warszawa, Poland;
e-mail: z.zwolska@igichp.edu.pl. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1571-1579,
October, 2006. Original article submitted March 3, 2005.
1358
0009-3122/06/4210-1358©2006 Springer Science+Business Media, Inc.

The desirable thiosemicarbazones were synthesized either by reaction of ketone 1 with
thiosemicarbazide (compound 9) or reaction of 2-acetylimidazo[4,5-b]pyridine hydrazone 2 with appropriate
isothiocyanates (compounds 10-18).
While the melting point of compounds 9-18 had being determined, it was observed that after meltdown
they recrystallized and melted again at about 280°C. This observation allowed us to suppose the possibility of
their cyclization. This fact was confirmed experimentally. All compounds 9-18 upon heating in boiling N,N-
dimethylaniline underwent intramolecular cyclization to the new heterocyclic system, the
pyridoimidazo[1,2,4]triazine reported by us previously [4].
As shown in Scheme 2 there are two possibilities of this cyclization: elimination of hydrogen sulfide to
give compound 19 containing at position 9 a substituted amino group, or elimination of the appropriate amine to
give product 20 containing at this position the thioxo group.
Since from all thiosemicarbazones 9-18 the same compound was obtained and it contained sulfur, one
can conclude that the result of cyclization was compound 20.
Scheme 2
Me
Me
N
N
ArNCS
S
N
H
N
H
NNH2
NNH
NH
C
Ar
N
N
2
10–18
∆
– ArNH2
– H2S
N
N
N
Me
Me
N
N
N
N
N
N
N
H
S
Ar–HN
19
20
10 Ar = Me; 11 Ar = CH2–CH=CH2; 12 Ar = C6H11; 13 Ar = Ph; 14 Ar = C6H4Cl-p;
15 Ar = C6H4CN-p; 16 Ar = C6H4OMe-p; 17 Ar = C6H4SMe-p; 18 Ar = C6H4CF3-p
Due to the tautomeric properties of the imidazo[4,5-b]pyridine system the cyclization may lead either to
compound 20 or to alternative product 20' (ring closure with participation of N(1) or N(3) atoms, Scheme 3). In
order to find its correct structure, synthesis of its S-methyl derivative (21) was carried out with MeI as an
alkylating agent. Compound 21 was then examined by NOE experiment. Since in this investigation a positive
effect between the S-methyl group protons of the 1,2,4-triazine ring and the α-proton of the pyridine ring was
observed, the structure of the tricyclic system 20 was supported (cyclization to N(3)). Looking for optimum
conditions for the synthesis of compound 21, methylation of thione 20 was carried out with MeI in ethanol or
DMF (in the presence of KOH) as well as with dimethyl sulfate in nitrobenzene. In the latter case the N-methyl
derivative 22 was obtained instead of the expected 21 (Scheme 3).
1359

Scheme 3
S
H
N
N
N
N
Me
N
or
Me
N
N
N
N
N
H
S
20'
20
Me2SO4
KOH
MeI
N
N
Me
N
Me
N
N
N
N
N
H
N
N
S
Me
MeS
NOE
22
21
In the next set of experiments the reactions of hydrazone 2 with chloroacetyl chloride and with some
ortho esters (triethyl orthoformate, triethyl orthoacetate, triethyl orthobenzoate) were investigated. As the result
of the first three reactions, products 23-25 were prepared (Scheme 4). Unexpectedly from the reaction of
hydrazone 2 with triethyl orthobenzoate a tricyclic compound 26 was obtained. Due to the already mentioned
tautomeric properties of the imidazo[4,5-b]pyridine system, the cyclization may lead to two isomeric forms 26
and 26' (or to their mixture). As in the NOE investigation of compound 26, a correlation between the γ-proton of
the pyridine ring and orthoprotons of the benzene ring was observed, and the structure of 26 was confirmed.
Compounds 2, 4, 5, 9, 10, 13, 14, 23, 24 chosen as examples were tested in vitro for their
antituberculotic activity against Mycobacterium tuberculosis H37Rv and two ''wild'' strains isolated from
tuberculotic patients: the 210 strain, resistant to isoniazid (INH), p-aminosalicylic acid (PAS), ethambutol
(ETB), and rifampicin (RFP), as well as the 192 strain, fully susceptible to the drugs administered.
TABLE 1. Antituberculotic Activity, MIC Values (µg/ml)
Mycobacterium
Compound
H37Rv
192
210
2
4
100
6.2
50
100
6.2
50
6.2
50
5
> 100
50
9
12.5
50
50
10
13
14
23
24
50
50
12.5
6.25
50
12.5
< 6.2
50
12.5
< 6.2
50
50
100
50
1360

Scheme 4
Me
N
O
C
ClCH2
Me
N
H
COCH2Cl
NNH
Cl
N
23
Me
NN
N
N
RC(OEt)3
OEt
N
H
C
R
N
N
H
NNH2
N
2
24, 25
C(OEt)3
N
N
Me
H
H
N
NOE
N
N
or
N
N
N
N
Me
N
Me
N
N
26'
26
N
COEt
N
N
H
27
24 R = H; 25 R = Me
The antibacterial activity of the compounds was determined in liquid Youmans medium containing 10%
bovine serum using the method previously described [3]. The lowest concentration of the investigated
compound, when no growth of strains could be observed, was taken as the MIC. The results obtained are given
in Table 1.
TABLE 2. Physical and Analytical Data of Compounds 2-26
Found, %
Com-
pound
Empirical
formula
mp, °C
(solvent)
Yield,
%
——————
Calculated, %
C
3
H
N
5
1
2
3
4
2
4
6
7
C8H9N5
54.61
54.84
5.03
5.18
40.12
39.98
293-294
(DMF–H2O)
90
80
71
C14H13N5
C12H10ClN7
66.82
66.91
5.16
5.21
28.11
27.87
240-242
(EtOH–H2O)
245-247
(DMF–H2O)
49.95
50.09
3.48
3.50
34.32
34.07
5
6
7
C11H9N5S
C13H11N5
C13H18N6
54.27
54.32
3.78
3.73
29.06
28.80
242-244
(H2O)
65
70
72
65.72
65.81
4.56
4.67
29.78
29.52
228-230
(EtOH)
224-225
(toluene)
60.31
60.44
6.93
7.02
32.76
32.54
1361

TABLE 2 (continued)
1
2
3
4
5
6
7
8
C10H9N7
52.69
52.85
3.90
3.99
43.27
43.15
284-286
(dioxane)
30
9
C9H10N6S
C10H12N6S
C12H14N6S
C15H20N6S
C15H14N6S
C15H13ClN6S
C16H13N7S
C16H16N6OS
C16H16N6S2
C16H13F3N6S
C9H7N5S
45.98
46.15
4.16
4.30
36.24
35.88
235-237
(DMF–H2O)
266-268
(DMF–H2O)
87
63
71
73
68
72
70
84
82
71
62
69
54
45
72
63
22
10
11
12
13
14
15
16
17
18
20
21
22
23
24
25
26
48.26
48.38
4.80
4.87
34.05
33.86
52.47
52.54
5.11
5.15
30.80
30.64
221-223
(EtOH)
56.89
56.95
6.32
6.37
26.62
26.57
239-242
(DMF–H2O)
58.13
58.05
4.46
4.55
27.18
27.09
214-216
(DMF–H2O)
52.16
52.25
3.64
3.80
24.53
24.37
230-232
(DMF–H2O)
57.23
57.31
3.78
3.91
29.52
29.24
230-231
(DMF–H2O)
190-194
(DMF–H2O)
56.41
56.46
4.62
4.74
24.96
24.70
53.86
53.93
4.48
4.53
23.65
23.59
203-205
(DMF–H2O)
50.69
50.78
3.42
3.46
22.38
22.21
235-237
(DMF–H2O)
49.62
49.77
3.18
3.25
32.46
32.25
291-293
(EtOH)
C10H9N5S
51.72
51.94
3.81
3.92
30.53
30.29
248-250
(EtOH)
C10H9N5S
51.80
51.94
3.76
3.92
30.64
30.29
236-238
(DMF–H2O)
308-310
(DMF–H2O)
C10H10ClN5O
C11H13N5O
C12H15N5O
C15H11N5
47.53
47.72
3.84
4.00
28.07
27.83
57.02
57.13
5.46
5.67
20.72
20.68
185-188
(acetone)
58.64
58.76
6.03
6.16
28.68
28.56
202-204
(acetone)
68.76
68.95
4.18
4.24
26.93
26.81
276-278
(acetone)
TABLE 3. IR and MS Data for Compounds 2-26
Com-
pound
IR spectrum, ν, cm-1
m/z (I, %)
1
2
3
2
3
4
3375, 3305 (NH2),
3158, 2898,
1648 (C=N)
175 [M]+ (100), 146 (83), 145 (63), 144 (58), 120 (12),
119 (13), 93 (32), 92 (11), 66 (19), 64 (11), 57 (13), 44 (12)
3500-2700 (NH),
1604 (C=N)
251 [M]+ (100), 252 (20), 250 (11), 235 (12), 234 (10),
146 (38), 145 (22), 144 (21), 119 (12), 93 (21), 92 (23),
91 (23), 77 (96), 65 (46), 39 (36)
287 [M]+ (13), 289 (4), 274 (20), 272 (75), 225 (10),
224 (100), 169 (20), 146 (36), 145 (29), 144 (25), 119 (48),
92 (20), 73 (20), 64 (23), 39 (17)
243 [M]+ (6), 161 (93), 146 (19), 133 (46), 119 (88), 92 (48),
65 (12), 64 (24), 43 (100), 42 (10), 39 (13), 38 (17)
237 [M]+ (20), 236 (100), 222 (9), 196 (17), 169 (8), 119 (8),
92 (6), 78 (38), 64 (7), 52 (6), 51 (24), 39 (13)
258 [M]+ (4), 188 (9), 174 (5), 160 (11), 119 (28), 99 (92),
98 (52), 97 (15), 83 (12), 71 (20), 70 (30), 69 (13), 58 (12),
57 (31), 56 (100), 55 (19), 44 (15)
3467 (NH), 3081,
1677 (C=N)
5
6
7
3362, 3059, 2969,
1693
3425, 3053, 2976,
1631
3450, 3051, 2969,
2937, 2821, 1609
1362

TABLE 3 (continued)
1
2
3
8
3420, 3049, 2970,
1590
227 [M]+ (22), 172 (100), 171 (42), 161 (49), 146 (17),
145 (48), 144 (56), 130 (27), 119 (88), 118 (17), 104 (27),
92 (57), 84 (25), 65 (31), 64 (49), 52 (25), 43 (71), 42 (28),
41 (25), 40 (36), 39 (40)
9
3481, 3402, 3174,
1693, 1614, 1278,
1120
234 [M]+ (58), 217 (10), 178 (9), 174 (29), 146 (100),
145 (22), 144 (15), 119 (18), 93 (20), 92 (11), 66 (15),
64 (10), 60 (17), 43 (9), 39 (14)
248 [M]+ (81), 179 (93), 175 (12), 174 (36), 161 (18),
147 (17), 146 (100), 145 (42), 144 (28), 120 (22), 119 (43),
93 (36), 92 (20), 91 (13), 74 (82), 66 (26), 64 (19), 42 (21)
274 [M]+ (4), 162 (10), 161 (100), 160 (10), 146 (28),
10
11
3460-2600, 1685,
1558, 1279, 1230
3500-2650 (NH),
1642 (C=C), 1590
(C=N), 1275 (C=S)
145 (20), 144 (16), 120 (17), 119 (43), 92 (8), 56 (8), 41 (14)
12
13
3276, 2931, 2852,
1589, 1491, 1271
316 [M]+ (16), 162 (17), 161 (100), 146 (26), 145 (11),
120 (14), 119 (18), 98 (12), 35 (9)
310 [M]+ (10), 217 (73), 179 (21), 175 (11), 146 (39),
145 (14), 144 (11), 136 (10), 135 (17), 119 (20), 93 (100),
91 (18), 77 (16), 66 (30), 65 (21), 64 (13), 39 (19)
3600-2500, 1652,
1513, 1278, 1189
14
15
16
17
18
20
3600-2500, 1680,
1550, 1280, 1200
344 [M]+ (4), 217 (64), 188 (10), 175 (9), 146 (14), 145 (11),
144 (10), 135 (11), 129 (26), 127 (100), 119 (19), 92 (23),
91 (13), 64 (15), 44 (13), 39 (15)
3432, 3267, 3073,
2227, 1665, 1538,
1271
217 [M–118] (100), 188 (15), 160 (10), 144 (9), 135 (14),
119 (13), 118 (84), 91 (21), 64 (11)
3460, 3184, 2960,
1655, 1590, 1514,
1247, 1032
217 [M–108] (12), 288 (21), 254 (40), 239 (47), 165 (38),
150 (34), 123 (64), 122 (38), 108 (100), 92 (15), 80 (34),
77 (18), 64 (15), 52 (10), 43 (10), 39 (10)
356 [M]+ (4), 218 (16), 217 (100), 188 (31), 175 (9), 145 (13),
144 (15), 139 (69), 135 (21), 124 (91), 119 (12), 108 (14)
3450, 3183, 2917,
1655, 1508, 1271,
1192
3254, 3059, 2933,
1656, 1531, 1275
378 [M]+ (84), 218 (28), 217 (100), 190 (15), 188 (26),
179 (49), 174 (26), 161 (51), 146 (90), 145 (54), 135 (15),
120 (17), 119 (33), 111 (18), 93 (20), 91 (17)
217 [M]+ (100), 219 (12), 188 (64), 145 (28), 144 (26),
136 (36), 135 (85), 118 (15), 117 (13), 108 (40), 103 (20),
92 (22), 59 (25), 56 (19), 52 (16), 39 (34)
231 [M]+ (100), 233 (6), 230 (13), 204 (11), 186 (10),
145 (17), 144 (28), 135 (10), 117 (12)
3448, 3055, 2922,
1546, 1393, 1358,
1303, 1267
21
22
2997, 2919, 1554,
1436, 1403
3474, 3375, 3075,
2985, 1630, 1545,
1256, 1070
231 [M]+ (100), 233 (7), 217 (22), 203 (13), 198 (17),
172 (10), 171 (18), 162 (14), 146 (12), 144 (21), 135 (28),
108 (18), 103 (17)
23
24
25
3600-2600, 1685,
1608
251 [M]+ (48), 253 (15), 202 (24), 175 (28), 174 (97),
147 (41), 146 (100), 144 (46), 119 (27), 93 (89), 78 (26),
77 (18), 66 (58), 44 (20), 43 (21), 39 (51)
231 [M]+ (11), 203 (42), 185 (15), 174 (31), 161 (12),
160 (15), 147 (18), 146 (100), 145 (16), 144 (15), 119 (51),
93 (21), 39 (15)
245 [M]+ (18), 188 (39), 187 (46), 174 (10), 161 (58),
160 (28), 147 (17), 146 (100), 145 (27), 144 (18), 120 (22),
119 (78), 93 (21), 92 (13), 66 (15), 57 (12), 43 (77), 42 (20),
41 (15), 39 (16)
261 [M]+ (100), 260 (45), 246 (44), 220 (30), 219 (17),
193 (29), 117 (16), 103 (11), 77 (12), 76 (11)
3436, 3064, 2984,
2924, 1629, 1247,
1054
3449, 3064, 2978,
1642, 1052
26
3058, 2924, 1618
EXPERIMENTAL
Melting points are uncorrected. IR spectra – Specord 75 spectrophotometer (pellets in KBr); 1H NMR –
Varian Gemini 200 (200 MHz) or Varian Unity 500 (500 MHz) Plus spectrometers with TMS as an internal
1363

TABLE 4. 1H NMR Data for Compounds 20-26
Compound
Solvent
Chemical shifts, δ, ppm (J, Hz)
20
DMSO-d6
2.68 (3H, s, CH3); 7.63 (1H, dd, J = 5, C(3) H);
8.83 (1H, d, J = 6, C(4) H); 9.55 (1H, d, J = 5, C(2) H);
14.32 (1H, s, NH)
21
22
23
24
25
CDCl3
DMSO-d6
DMSO-d6
CD3OD
CDCl3
2.99 (3H, s, CH3); 3.02 (3H, s, SCH3);
7.55 (1H, dd, J = 5, C(3) H); 8.69 (1H, d, J = 8, C(4) H);
8.96 (1H, d, J = 5, C(2) H)
2.76 (3H, s, CH3); 4.47 (3H, s, NCH3);
7.85 (1H, t, J = 6, C(3) H); 9.04 (1H, d, J = 7, C(4) H);
10.55 (1H, d, J = 8, C(2) H)
2.38 (3H, s, CH3); 4.97 (2H, s, CH2);
7.26 (1H, dd, J = 5, C(6) H); 7.94-8.02 (1H, br.s, C(7) H);
8.38 (1H, d, J = 3.5, C(5) H)
1.40 (3H, t, J = 7, CH2CH3); 2.53 (3H, s, CH3);
4.39 (2H, q, J = 7, CH2CH3); 7.33 (1H, dd, J = 5, J = 7, C(6) H);
8.02 (1H, br. s); 8.41 (2H, d, J = 5, C(5) H); 8.46 (1H, s, CHO)
1.38 (3H, t, J = 7, CH2CH3); 2.18 (3H, s, CH3);
2.55 (3H, s, CH3); 4.33 (2H, q, J = 7, CH2CH3);
7.26 (1H, dd, J = 5, J = 8, C(6) H); 8.11 (1H, d, J = 8, C(7) H);
8.43 (1H, d, J = 7, C(5) H)
26
DMSO-d6
2.94 (3H, s, CH3); 7.08 (1H, d, J = 8, C(4) H);
7.38 (1H, dd, J = 5, C(3) H); 7.69-7.86 (5H, m, ArH);
8.80 (1H, d, J = 4, C(2) H)
standard; MS spectra – Varian MAT-711 apparatus with direct inlet, ionization energy 70 eV. The characteristics
of the synthesized compounds are given in Tables 2-4.
1-(3H-Imidazo[4,5-b]pyridin-2-yl)ethan-1-one hydrazones 2-4. Compound 1 [3] (0.64 g, 4 mmol) and
an appropriate hydrazine (6 mmol) in anhydrous ethanol (30 ml) were refluxed with stirring for 1 h. The solid
precipitate after cooling or after evaporation of the solvent was filtered off and recrystallized.
2-(1-Aryliminoethyl)imidazo[4,5-b]pyridines 5-8. Compound 1 [3] (2 mmol) and an appropriate amine
(3 mmol) were heated at 155-165°C with stirring for 15 min. After cooling the solid obtained was washed with
ether and recrystallized.
2-Acetylimidazo[4,5-b]pyridine Thiosemicarbazone (9). A suspension of compound 1 [3] (0.32 g,
2 mmol) and thiosemicarbazide (0.23 g, 2.5 mmol) in anhydrous ethanol (10 ml) was refluxed with stirring for
5 h. The precipitate obtained after cooling was filtered off and recrystallized.
2-Acetylimidazo[4,5-b]pyridine Arylthiosemicarbazones 10-18. Compound 2 (0.52 g, 3 mmol) and an
appropriate isothiocyanate (4 mmol) in anhydrous pyridine (15 ml) were heated at 100-105°C with stirring for 5
h. The solvent was then removed in vacuo, and the residue was treated with a small amount of methanol, filtered
off, and recrystallized from the proper solvent.
6-Methyl-9(8H)-thioxopyrido[3',2':4,5]imidazo[1,2-d][1,2,4]triazine
(20).
The
proper
thiosemicarbazone (2 or 10-18, 2 mmol) in N,N-dimethylaniline (10 ml) was refluxed for 4-5 h. Then, the
solvent was removed in vacuo, a small amount of benzene was added to the residue, and the solid was filtered
off and recrystallized.
6-Methyl-9-(methylthio)pyrido[3',2':4,5]imidazo[1,2-d][1,2,4]triazine (21).
A
suspension of
powdered KOH (3 mmol) and compound 20 (2 mmol) in anhydrous ethanol (12 ml) was stirred at room
temperature until a solution was obtained. It was then cooled to 0-2°C, and a cooled solution of methyl iodide
(3.2 mmol) in anhydrous ethanol (3 ml) was added dropwise during 10 min. Next, the reaction mixture was
heated at 40-50°C for 6 h and, after cooling, the solid was filtered off and recrystallized.
6,8-Dimethyl-9-thioxopyrido[3',2':4,5]imidazo[1,2-d][1,2,4]triazine (22). To a stirred solution of
compound 20 (2 mmol) in nitrobenzene (10 ml) (heated at 130-135°C) a solution of dimethyl sulfate (3 mmol) in
nitrobenzene (2 ml) was added dropwise during 10 min. The stirring was then continued at the same
1364

temperature for 4 h. After cooling, the formed solid was filtered off, washed with ether, dissolved in a small
amount of H2O, and alkalized with NH3. The resultant precipitate was filtered off and recrystallized.
2-Chloro-N'-[1-(3H-imidazo[4,5-b]pyridin-2-yl)ethylidene]acetohydrazide (23). Compound
2
(0.52 g, 3 mmol) and triethylamine (4 mmol) in anhydrous THF (10 ml) were stirred at room temperature for
20 min. Next, chloroacetyl chloride (3.5 mmol) was added dropwise during 10 min and the stirring was
continued for an additional 20 min. The reaction mixture was then refluxed for 1 h, and the formed solid was
filtered off, dissolved in a small amount of water, and alkalized with NH3. The resultant precipitate was filtered
off and recrystallized.
Ethyl-N-[1-(3H-imidazo[4,5-b]pyridin-2-yl)ethylidene]hydrazonoformate (24), Ethyl N-[1-(3H-
Imidazo[4,5-b]pyridin-2-yl)ethylidene]hydrazonoacetate (25). Compound 2 (0.52 g, 3 mmol), dry DMF
(8 ml), and triethyl orthoformate or triethyl orthoacetate (3 ml) were refluxed for 5 h. The reaction mixture was
then concentrated under vacuum, and the residue was washed with a small amount of acetone, filtered off, and
recrystallized.
9-Methyl-6-phenylpyrido[2',3':4,5]imidazo[1,2-d][1,2,4]triazine (26). Compound 2 (0.52 g, 3 mmol),
dry DMF (8 ml), and triethyl orthobenzoate (4 ml) were refluxed for 5 h. The reaction mixture was then
concentrated under vacuum, and the residue was washed with a small amount of acetone, filtered off, and
recrystallized.
We are grateful to Dr. P. Sowinski, head of the Inter-University NMR Laboratory in Gdansk, for helpful
discussion.
REFERENCES
1.
2.
S. N. Pandeya and J. R. Dimmock, Pharmazie, 48, 659 (1993).
M. Negver, Organic-Chemical Drugs and Their Synonyms, 7 Ed., Academie-Verlag, Berlin, Vol. 1-4
(1994).
3.
4.
L. Bukowski, M. Janowiec, and Z. Zwolska, Z. Andrzejczyk, Pharmazie, 54, 651 (1999).
L. Bukowski, Khim. Geterotsikl. Soed., 937 (2002). [Chem. Heterocycl. Comp., 38, 828 (2002)].
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