Novel synthesis of 1,8-alkanopyrido-[3,4-d]pyridazine: A new ring system

Article abstract of DOI:10.1023/A:1022657914710

Cycloalkylidenemalononitriles couple with various diazonium salts to yield the corresponding cycloalkeno[c]pyridazines, which react with trichloroacetonitrile to give the 1,8-alkanopyrido[3,4-d]pyridazines. The reaction of cycloalkenopyridazines with DMF dimethylacetal gives enamine derivatives, which can be converted to 1,8-alkanopyrido[3,4-d]pyridazines via treating with hydrazine hydrate or aromatic amines. Substituted cycloalkenopyridines react with diazoaminobenzene to afford the corresponding 1,8-alkanopyridopyridazines.

Full text of DOI:10.1023/A:1022657914710

Chemistry of Heterocyclic Compounds, Vol. 38, No. 12, 2002
NOVEL SYNTHESIS OF 1,8-ALKANOPYRIDO-
d
[3,4- ]PYRIDAZINE: A NEW RING SYSTEM
A. Z. A. Elassar1 and Y. M. Elkholy2
Cycloalkylidenemalononitriles couple with various diazonium salts to yield the corresponding
cycloalkeno[c]pyridazines, which react with trichloroacetonitrile to give the 1,8-alkanopyrido[3,4-d]-
pyridazines. The reaction of cycloalkenopyridazines with DMF dimethylacetal gives enamine
derivatives, which can be converted to 1,8-alkanopyrido[3,4-d]pyridazines via treating with hydrazine
hydrate or aromatic amines. Substituted cycloalkenopyridines react with diazoaminobenzene to afford
the corresponding 1,8-alkanopyridopyridazines.
Keywords: 1,8-alkanopyrido[3,4-d]pyridazines, cycloalkenopyridazines, cycloalkenopyridines.
Activated methylene nitriles are highly reactive reagents that have found extensive application in organic
synthesis [1-3]. Condensed azines comprise a very interesting class of compounds because of their biological and
medicinal activities [4-6]. In the last decade we have reported several novel syntheses of azines utilizing activated
nitriles as starting materials [7-9]. In conjunction with our interest, we report here on the reactivity of ylidene
derivatives 1a,b toward organic reagents of different types with the aim of preparing 1,8-alkanopyrido-
pyridazines. Thus, ylidene derivatives 1a,b readily coupled with diazonium salts 2a-d to give a product that was
established as having structure 3a-f. The mass spectrum of 3a showed m/z 281 and its IR revealed the presence
1
of NH and cyano groups at 3320 and 2212 cm-1, respectively. H NMR revealed the presence of aromatic
protons at δ 7.98-7.53 ppm. 13C NMR indicated the presence of one cyano group at δ 116.89 ppm. Signals of
other skeletal carbons appeared at the expected positions. The structures of 3b-f were established similarly.
( )n
NC
CN
_
+
N
N
RN2Cl
+
2a–d
NC
R
( )n
NH
3a–f
1a,b
CN
,
1 a n = 1, b n = 2; 2 a R = C6H4Cl-p, b R = C6H4NO2-m, c R =
S
S
;
3 a, b, e, f n = 1, c, d n = 2, a, d R = C6H4NO2-m, b, c R = C6H4Cl-p,
d R =
N
CONH2
S
,
e R =
f R =
N
S
__________________________________________________________________________________________
1
Department of Chemistry, Faculty of Science, University of Kuwait, P. O. Box 5969-Safat-13060,
2
Kuwait; e-mail: aelassar@yahoo.com. Department of Chemistry, Faculty of Science, Helwan University, Ain
Helwan, Cairo, Egypt. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1722-1729,
December, 2002. Original article submitted October 10, 2001.
0009-3122/02/3812-1521$27.00©2002 Plenum Publishing Corporation
1521

( )n
Cl3C–CN
Cl3C
Cl3C
Cl3C–CN
PhNHNNPh
1b
N
N
3a–d
N
N
CN
R
NH2
NH2
X
5
4a–e
4 a,d R = C6H4NO2-m, b, c R = C6H4Cl-p, e R = Ph; a-d X = NH, e X = O; a, b n = 1, c-e n = 2
Cycloalkanopyridazines 3a-d react readily under basic condition with trichloroacetonitrile to give
1,8-alkanopyrido[3,4-d]pyridazine derivatives 4a-d in good yields. The same reaction product, 4c, could be
obtained on treatment of 1b with trichloroacetonitrile to give 5 followed by coupling with arene diazonium salt
2a to give the final isolated product 4c in low yield. Moreover, a good yield was obtained via treating pyridine
derivative 5 with diazoaminobenzene in refluxing aqueous acetic acid/hydrochloric acid mixture to furnish the
oxo derivative 4e. The structures of 4a-e were established based on their elemental analyses and spectral data.
( )n
( )n
R1NH2
7
R1HN
DMF / DMA
Me2N
3a–d
N
N
N
N
NC
NC
R
R
NH
6a–d
NH
8
1a,b
DMF / DMA
( )n
( )n
Me
N
N
N
Me
N
R1
R
NC
CN
10a,b
NH NH
9
( )n
( )n
HO
HC
R1NH
HC
N
N
N
N
O
R
R1
NC
NC
NH
NH
12a,b
11a,b
6 a, d R = C6H4NO2-m, b, c R = C6H4Cl-p, a, b n = 1, c, d n = 2; 7 a R1 = NH2, b R1 = Ph, c R1 = 2-pyridyl;
9 a-f R = C6H4NO2-m, a, b R1 = NH2, c, d R1 = Ph, e, f R1 = 2-pyridyl, a, c, e n = 1, b, d, f n = 2;
10 a n = 1, b n = 2; 11 a,b R = C6H4NO2-m, a n = 1, b n = 2
Furthermore, N,N-dimethylformamide dimethyl acetal (DMF/DMA) reacts with 3a-d to give 6a-d.
Enamines 6a,d react with hydrazine hydrate 7a or aromatic amines 7b,c to give via intermediate 8
pyridopyridazine derivatives 9a-f. The formation of intermediates of the type 8 involves probably the loss of
dimethylamine and is followed by cyclization under reaction conditions to give the final isolated product 9.
Alternatively, compounds 1a,b were treated with DMF/DMA in DMF and piperidine to give the condensation
products 10a,b. The latter coupled with arene diazonium salt 2b to give the aldehydes 11a,b. Compounds 11a,b
reacted with hydrazine hydrate in ethanol/DMF mixture to give the final isolated products 9a,b apparently
through the intermediate 12.
1522

TABLE 1. Physical and Analytical Data of Newly Synthesized Compounds
Found, %
——————
Com-
Empirical
formula
mp, °C
7
Color
8
Solvent
9
M.Wt./ m/z
Yield, %
11
Calculated, %
pound
C
3
H
N
5
S
6
1
2
4
10
C14H11N5O2
C14H11ClN4
C15H13ClN4
C15H13N5O2
C11H9N5S
60.01
59.77
4.00
3.94
25.02
24.90
147
140
165
123
200
175
>250
242
284
124
108
160
197
213
201
Brown
EtOH
281.3 (281)
270.74
78
70
72
76
66
65
71
63
75
73
70
69
75
78
64
3a
3b
3c
3d
3e
3f
62.32
3.99
20.65
Yellow
Yellow
Yellow
Brown
EtOH
EtOH
EtOH
EtOH
EtOH/DMF
DMF
62.10
4.10
20.69
63.36
63.26
4.50
4.61
19.85
19.67
284.77
61.00
4.32
23.73
295.33
60.99
4.44
23.71
54.32
54.29
4.00
3.73
28.58
28.78
13.43
13.18
243.32
C17H17N5OS
C16H11Cl3N6O2
C16H11Cl4N5
C17H13Cl4N5
C17H13Cl3N6O2
C17H13ClN4O
C11H10Cl3N3
C17H16N6O2
C17H16ClN5
C18H18ClN5
60.53
5.38
20.53
9.01
Pale-brown
Brown
339.46
60.14
5.05
20.63
9.44
45.32
45.14
2.60
2.61
19.76
19.74
425.68 (425)
415.12 (415)
429.15
4a
4b
4c
4d
4e
5
46.53
2.59
16.59
Yellow
Brown
DMF
46.29
2.67
16.87
47.58
47.57
3.00
3.05
16.36
16.32
DMF
46.34
3.01
19.00
Brown
DMF
439.71
46.43
2.98
19.11
51.22
51.59
3.53
3.31
14.00
14.16
Brown
DMF
395.69
45.66
3.75
14.36
Pale-brown
Brown
EtOH
EtOH
EtOH
EtOH
290.59
45.46
3.47
14.46
60.71
60.69
4.94
4.80
24.76
24.98
336.39 (336)
325.83
6a
6b
6c
62.41
4.83
21.43
Pale-brown
Yellow
62.66
4.95
21.49
63.93
63.60
5.41
5.34
20.41
20.61
339.86

TABLE 1 (continued)
1
2
3
4
5
6
7
8
9
10
11
C18H18N6O2
C15H13N7O2
C16H15N7O2
C21H16N6O2
C22H18N6O2
C20H15N7O2
C21H17N7O2
C15H11N5O3
C16H13N5O3
C16H13N3OS
C21H15N5O3S
C21H16N4OS
C22H15N5O4S
C22H16N4O2S
C22H17N5O3S
C22H18N4OS
C23H17N5O4S
C23H18N4O2S
61.39
61.69
5.01
5.18
23.74
23.98
189
157
168
>250
165
134
176
144
158
173
188
218
243
>250
206
233
195
212
Yellow
Yellow
Yellow
Brown
Brown
Brown
Brown
Red
EtOH
DMF
DMF
DMF
EtOH
EtOH
EtOH
350.42
66
79
72
74
76
71
73
69
72
64
70
71
74
73
74
73
72
70
6d
9a
55.69
4.31
30.63
323.35 (323)
337.38
55.71
4.06
30.32
57.01
56.95
4.53
4.49
29.01
29.06
9b
65.71
4.36
22.01
384.43
9c
65.60
4.20
21.86
66.31
66.31
4.81
4.56
21.38
21.09
398.46
9d
62.31
4.01
25.53
385.42
9e
62.32
3.93
25.44
63.31
63.13
4.39
4.29
24.63
24.55
399.45
9f
58.24
3.52
22.46
Acetone
Acetone
EtOH
DMF
309.31 (309)
323.34
11a
11b
14b
16a
16b
16c
16d
16e
16f
16g
16h
58.24
3.59
22.64
59.38
59.42
3.84
4.06
21.77
21.66
Red
65.00
4.34
14.01
11.00
10.85
Brown
295.39
65.25
4.44
14.22
60.51
60.41
3.45
3.62
16.98
16.77
7.83
Deep-yellow
Brown
417.48 (417)
372.48
7.68
67.60
4.05
14.91
8.31
8.60
DMF
67.71
4.33
15.04
59.37
59.30
3.13
3.40
16.01
15.72
7.28
Yellow
DMF
445.49
7.19
66.01
3.98
14.02
8.34
8.00
Brown
DMF
400.49
65.97
4.03
13.99
61.60
61.23
3.61
3.97
16.43
16.23
7.34
Deep-yellow
Brown
DMF
431.51
7.43
68.21
4.57
14.23
8.56
8.29
DMF
386.51
68.36
4.70
14.49
60.45
60.11
3.51
3.73
15.50
15.24
7.90
Yellow
DMF
459.52
7.97
66.89
4.00
13.80
7.32
7.73
Brown
DMF
414.52
66.63
4.38
13.51

TABLE 2. Spectral Data of Newly Synthesized Compounds
Com-
IR spectrum, ν, cm–1
1H NMR spectrum, δ, ppm
pound
1
2
3
3a*
3b
3c
3320 (NH), 2212 (CN)
3324 (NH), 2209 (CN)
3320 (NH), 2212 (CN)
3330 (NH), 2210 (CN)
3239 (NH), 2211 (CN)
7.98-7.53 (m, 4H, Ar); 6.25 (br, 1H, NH);
1.82-1.45 (m, 6H, 3CH2)
7.89-7.33 (m, 4H, Ar); 6.05 (br, 1H, NH);
1.81-1.45 (m, 6H, 3CH2)
7.78-7.21 (m, 4H, Ar); 6.30 (br, 1H, NH);
2.82-1.17 (m, 8H, 4CH2)
7.97-7.43 (m, 4H, Ar); 6.20 (br, 1H, NH);
3d
3e
2.84-1.18 (m, 8H, 4CH2)
10.98 (br, 1H, NH); 7.99-7.46 (m, 2H, thiazolyl-H);
1.85-1.07 (m, 6H, 3CH2)
3406, 3329, 3225 (NH2
& NH), 2224 (CN),
1660 (CO)
7.48, 6.45 (br, 3H, NH & NH2); 2.66-1.55 (m, 14H, 7CH2)
3f
3401, 3358, 3325 (NH2
7.87-7.42 (m, 4H, Ar); 8.50, 6.25 (br, 3H, NH & NH2);
1.72-1.45 (m, 4H, 2CH2)
4a
4b
4c
4d
4e
5
& NH)
3411, 3345, 3320 (NH2
& NH)
7.98-7.32 (m, 4H, Ar); 8.40, 6.25 (br, 3H, NH & NH2);
1.71-1.50 (m, 4H, 2CH2)
3434, 3373, 3331 (NH2
7.76-7.01 (m, 4H, Ar); 8.40, 6.24 (br, 3H, NH & NH2);
1.85-1.06 (m, 6H, 3CH2)
& NH)
3422, 3331, 3321 (NH2,
& NH
7.88-7.24 (m, 4H, Ar); 8.42, 6.31 (br, 3H, NH & NH2);
1.82-1.06 (m, 6H, 3CH2)
3418, 3321 (NH2),
7.57-7.10 (m, 5H, Ar); 8.40 (br, 2H, NH2);
1.80-1.07 (m, 6H, 3CH2)
1659 (CO)
3422, 3328 (NH2),
2213 (CN)
8.05 (br, 2H, NH2); 1.85-105 (m, 8H, 4CH2)
3323 (NH), 2210 (CN)
3329 (NH), 2211 (CN)
3331 (NH), 2212 (CN)
3331(NH), 2212(CN)
7.93-7.15 (m, 4H, Ar); 6.98 (s, 1H, CH); 5.89 (br, 1H, NH);
2.45 (s, 6H, 2Me); 1.71-1.51 (m, 4H, 2CH2)
6a
6b
6c
6d
9a*2
7.67-7.15 (m, 4H, Ar); 6.98 (s, 1H, CH); 5.87 (br, 1H, NH);
2.45 (s, 6H, 2Me); 1.70-1.51 (m, 4H, 2CH2)
7.87-7.15 (m, 4H, Ar); 6.98 (s, 1H, CH); 5.89 (br, 1H, NH);
2.45 (s, 6H, 2Me); 1.83-1.08 (m, 6H, 3CH2)
7.98-7.13 (m, 4H, Ar); 6.97 (s, 1H, CH); 5.79 (br, 1H, NH);
2.46 (s, 6H, 2Me); 1.85-1.07 (m, 6H, 3CH2)
3412, 3334; 3226; 3215
(NH2, 2NH)
10.32 (br, 2H, NH2); 8.03 (s, 1H, pyridine-H);
7.89-7.10 (m, 4H, Ar); 6.95, 5.79 (br, 2H, 2NH);
1.85-1.07 (m, 4H, 2CH2)
3411, 3333; 3229; 3220
(NH2, 2NH)
10.02 (br, 2H, NH2); 8.13 (s, 1H, pyridine-H);
7.79-7.10 (m, 4H, Ar); 6.85, 5.77 (br, 2H, 2NH);
2.78-1.11 (m, 6H, 3CH2)
9b
3331, 3219 (2NH)
3331, 3219 (2NH)
3345, 3219 (2NH)
3365, 3223 (2NH)
8.69 (s, 1H, pyridine-H); 7.89-7.01 (m, 9H, Ar);
9c
6.85, 5.59 (br, 2H, 2NH); 1.85-1.07 (m, 4H, 2CH2)
8.57 (s, 1H, pyridine-H); 7.91-7.11 (m, 9H, Ar);
6.85, 5.77 (br, 2H, 2NH); 2.79-1.23 (m, 6H, 3CH2)
9d
8.78 (s, 1H, pyridine-H); 7.84-7.21 (m, 8H, pyridine & Ar);
9e
6.75, 5.59 (br, 2H, 2NH); 1.85-1.17 (m, 4H, 2CH2)
8.35 (s, 1H, pyridine-H); 7.91-7.12 (m, 8H, pyridine & Ar);
6.65, 6.09 (br, 2H, 2NH); 2.80-1.11 (m, 6H, 3CH2)
9f
3323 (NH), 2212 (CN),
1728 (CO)
10.45 (s, 1H, CHO); 7.98-7.23 (m, 4H, Ar);
11a
11b
14b
16a
6.23 (br, 1H, NH); 2.84-1.53 (m, 5H, 1CH & 2CH2)
3333 (NH), 2210 (CN),
10.50 (s, 1H, CHO); 7.97-7.20 (m, 4H, Ar);
1727 (CO)
6.05 (br, 1H, NH); 2.86-1.43 (m, 7H, 1CH & 3CH2)
3342, 3328 (NH2), 2210
(CN), 1661 (CO)
7.54-7.01 (m, 5H, Ar); 6.52 (br, 2H, NH2);
1.85-1.17 (m, 6H, 3CH2)
3343, 3332 (NH2), 1658
7.82-7.23 (m, 9H, Ar); 6.51 (br, 2H, NH2);
1.85-1.06 (m, 4H, 2CH2)
(CO)
1525

TABLE 2 (continued)
1
2
3
3342, 3329 (NH2), 1559
(CO)
7.72-7.23 (m, 10H, Ar); 6.53 (br, 2H, NH2);
1.85-1.07 (m, 4H, 2CH2)
16b
3343, 3329 (NH2), 1651,
7.91-7.21 (m, 9H, Ar); 6.54 (br, 2H, NH2);
16c
16d
16e
16f
1659 (2CO)
1.85-1.07 (m, 4H, 2CH2)
3343, 3328 (NH2), 1655,
1661 (2CO)
7.85-7.31 (m, 10H, Ar); 6.53 (br, 2H, NH2);
1.85-1.10 (m, 4H, 2CH2)
3348, 3335 (NH2), 1663
7.93-7.22 (m, 9H, Ar); 6.52 (br, 2H, NH2);
(CO)
2.85-1.37 (m, 6H, 3CH2)
3342, 3329 (NH2), 1659
(CO)
7.83-7.32 (m, 10H, Ar); 6.52 (br, 2H, NH2);
2.85-1.36 (m, 6H, 3CH2)
3342, 3328 (NH2), 1663,
7.93-7.22 (m, 9H, Ar); 6.50 (br, 2H, NH2);
16g
16h
1659 (2CO)
2.85-1.35 (m, 6H, 3CH2)
3331, 3328 (NH2), 1660,
1658 (2CO)
7.73-7.22 (m, 10H, Ar); 6.51 (br, 2H, NH2);
2.85-1.37 (m, 6H, 3CH2)
_______
* 13C NMR spectrum, δ, ppm: 165.16 (C-3); 157.12 (C-7a); 140.06, 139.12,
137.01, 135.11, 134.21, 129.61, 127.11, 124.10 (arom. carbons); 116.89
(CN); 28.66, 27.45, 25.98 (3CH2).
2
*
13C NMR spectrum, δ, ppm: 159.13, 158.78, 158.33, 157.02, 153.21,
149.12, 148.25, 147.68, 143.21, 138.21, 137.25, 135.01, 132.35 (arom.
carbons); 26.35, 27.60 (2CH2).
( )n
( )n
CN
( )n
CN
ArNHNNAr
S
S
S
RNCS
N
N
15a,b
1a,b
N
N
R
RHN
R
Ar
NC
NH2
NH2 O
13
14a–d
16a–h
14 a, c R = Ph, b, d R = COPh, a, b n = 1, c, d n = 2; 15 a Ar = Ph, b Ar = C6H4NO2-m;
16 a,c,e,g Ar = C6H4NO2-m, b,d,f,h Ar = Ph, a,b,e,f R = Ph, c,d,g,h R = COPh, a-d n = 1, e-h n = 2
The target ring system, 1,8-alkanopyrido[3,4-d]pyridazine, could be obtained via treating 1a,b with
phenylisothiocyanate or benzoylisothiocyanate to give 14a-d through the presumed intermediate 13.
Compounds 14a-d reacted with diazoaminobenzenes 15a,b in aqueous acetic acid/hydrochloric acid mixture to
afford the final isolated products 16a-h.
EXPERIMENTAL
All melting points are uncorrected. IR spectra were recorded in KBr with an IR spectrophotometer
1
Shimadzu 408. H NMR and 13C NMR spectra were recorded on a Varian EM-390 MHz spectrometer (390
MHz) using TMS as internal reference and chemical shifts are expressed as ppm. Mass-spectra were measured
on a Shimadzu GCMS-QP 1000 Ex mass-spectrometer. Microanalytical data were obtained from the
Microanalytical Data Unit at Cairo University, Egypt. Compounds 14a,c,d were prepared as described
previously [10, 11]. Characteristics of newly synthesized compounds are presented in Tables 1 and 2.
1526

Preparation of Cycloalkeno[c]pyridazine Derivatives 3a-f. A solution of the diazonium salts
(prepared from 0.01 mol of aromatic or heteroaromatic amine with the appropriate quantities of sodium nitrite
and hydrochloric acid) was added to cycloalkylidenemalononitrile 1a or 1b (0.01 mol) in ethanol (50 ml)
containing sodium hydroxide (0.50 g). The reaction mixture was stirred at room temperature 2 h. The solid
product formed was collected by filtration and recrystallized from ethanol.
Preparation of 1,8-Alkanopyrido[3,4-d]pyridazines 4a-e. A (compounds 4a-d). To a solution of
compound 3a-d (0.01 mol) in DMF, trichloroacetonitrile (0.01 mol) and a few drops of piperidine were added.
The reaction mixture was refluxed for 1 h. The reaction product was treated with ice-cold water and the solid
product formed was filtered off and recrystallized from DMF.
B (compound 4e). A mixture of 5 (0.01 mol), diazoaminobenzene (0.01 mol), acetic acid (15 ml),
hydrochloric acid (15 ml), and a few drops of water was refluxed for 3 h and then allowed to cool. The reaction
product was neutralized using sodium bicarbonate solution. The solid product so formed was collected by
filtration, washed with ice-cold water several times, dried, and recrystallized from DMF.
Preparation of Tetrahidroisoquinoline 5. A solution of ylidene derivative 1b (0.01 mol) in DMF
(20 ml), trichloroacetonitrile (0.01 mol), and a few drops of piperidine was refluxed for 2 h. The reaction
mixture was evaporated under vacuum and the solid product formed was collected by filtration and
recrystallized from ethanol.
Preparation of N,N-Dimethylaminomethylidenecycloalkeno[c]pyridazines 6a-d. A solution of
pyridazines 3a-d (0.01 mol) in DMF (25 ml) was treated with DMF/DMA (0.01 mol) and a few drops of
piperidine. The reaction mixture was refluxed for 2 h, then treated with cold water. The reaction product was
collected by filtration and recrystallized from ethanol.
Preparation of N-Substituted Pyrido[3,4-d]pyridazines 9a-f. A. To a solution of 6a-d (0.01 mol) in
DMF (25 ml), hydrazine hydrate (aniline or 2-aminopyridine) (0.01 mol) was added. The reaction mixture was
refluxed for 2 h. Ice-cold water was added and the solid product so formed was collected by filtration and
recrystallized from proper solvent.
B. To a solution of 11a or 11b (0.01 mol) in DMF (25 ml), hydrazine hydrate (0.01 mol) was added.
The reaction mixture was heated under reflux for 2 h. Ice-cold water added and the solid product so formed was
collected by filtration and recrystallized from the proper solvent.
Synthesis of Cycloalkenepyridazinealdehydes 11a,b. A solution of diazonium salt (prepared as
described in the preparation of 3a-d) was added dropwise with intensive stirring for 2 h to a solution of 10a or
10b (0.01 mol) in DMF and a solution of NaOH (0.1 g dissolved in 10 ml of water). The solid product so
formed was collected by filtration and recrystallized from acetone.
Preparation of Hydroisoquinoline 14b. To a solution of 1a (0.01 mol) in ethanol (25 ml) benzoyl
isothiocyanate (0.01 mol) and a few drops of piperidine were added. The reaction mixture was refluxed for 3 h.
The solid product formed upon treating the reaction mixture with ice-cold water was collected by filtration and
recrystallized from ethanol.
Preparation of Thioxopyridopyridazinones 16a-h.
A
mixture of 14a-d (0.01 mol),
diazoaminobenzene (0.01 mol), acetic acid (15 ml), hydrochloric acid (15 ml), and a few drops of water was
refluxed for 3 h and then allowed to cool. The reaction product was neutralized with sodium bicarbonate
solution. The solid product so formed was collected by filtration, washed with ice-cold water several times,
dried, and recrystallized from DMF.
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