Studies with pyridazines and condensed pyridazines: Routes for synthesis of 3-amino-5-aryl-2,5-dihydro-pyridazine, 10aH-pyridazino[1,6-a]quinazoline and thieno[3,4-d]pyridazinone

Article abstract of DOI:10.1002/jhet.5570440421

(Chemical Equation Presented) Novel routes to 3-aminopyridazines, 10aH-pyridazino[1,6-a]quinazoline and, thieno[3,4-d]pyridazine utilizing the reaction of 2-oxobutanal-1-arylhydrazones 3a,b with α,β-unsaturated nitriles are described. Condensation of 3 wi

Full text of DOI:10.1002/jhet.5570440421

Jul-Aug 2007
877
Studies with Pyridazines and Condensed Pyridazines: Routes for
Synthesis of 3-Amino-5-aryl-2,5-dihydro-pyridazine, 10aH-
Pyridazino[1,6-a]quinazoline and Thieno[3,4-d]pyridazinone
Suzan Ibrahim Aziz [a], Hany Fakhry Anwar*[a,b], Morsy Ahmed El-Apasery[c],
and Mohamed Hilmy Elnagdi[a]
[a] Chemistry Department, Faculty of Science, Cairo University; Giza; A. R. Egypt
[b] School of Pharmacy, Department of Chemistry, University of Oslo, P O Box 1068 Blindern, N-O316, Oslo, Norway
[c] Dying, Printing and Textile Auxiliaries Department, Textile Research Division, National Research Center,
12622 Dokki, Giza; A. R. Egypt
E-mail: hany.anwar@farmasi.uio.no
Received September 9, 2006
O
Ar1
N
O
X
Ar1
O
Ar1
X
X
Ar = o-C6H4COOMe
CN
N
N
NH
N
NH
Ar
N
NH2
O
Ar
O
NC
OEt
O
S
S
OEt
CN
O
NH2
N
H
OEt
N
N
N
N
O
N
O
N
O
S / Dioxane
Cl
Cl
Cl
Novel routes to 3-aminopyridazines, 10aH-pyridazino[1,6-a]quinazoline and, thieno[3,4-d]pyridazine
utilizing the reaction of 2-oxobutanal-1-arylhydrazones 3a,b with ꢀ,ꢁ-unsaturated nitriles are described.
Condensation of 3 with ethyl cyanoacetate afforded pyridazinones that reacted with sulphur yielding
thienopyradazinone 10. Reaction of 10 with maleic anhydride and acrylonitrile afforded products of
addition and hydrogen sulphide elimination. On other hand reacting 10 with enaminone and ethyl
propionate afforded the product of addition of the amino function to activated double bond
J. Heterocyclic Chem., 44, 877 (2007).
Reactivity of aldehydic hydrazones toward electrophilic
reagents as a result of hydrazone lone pair delocalization
has recently been intensively investigated [10-13], but to
our knowledge with exception of our recent report on
reactivity of 2-oxopropanal-1-arylhydrazones [14], no
other report on reactivity of such hydrazones in Michael
reaction has been made. The formed adducts were
assigned the pyridazine structure 6a,b and are believed to
be formed via intermediacy of acyclic 5a,b. On the other
hand reacting 3b with 4a,b resulted in formation of
tricyclic 8a,b formed most likely via intermediates 7a,b
that could not be isolated (Scheme 1). Formation of such
tricyclic products supports our suggested formation of
5a,b rather than possible isomeric 6H-pyridazine
derivatives. This finding thus parallel reported [14]
formation of 4H-pyridazines from reaction of 2-
oxopropanal-1-arylhydrazones with 4.
INTRODUCTION
The chemistry of pyridazines and condensed pyrida-
zines is now receiving considerable interest [1-4] As a
part of our programme directed at developing efficient
syntheses for biologically interesting polyfunctional
heteroaromatics utilizing inexpensive and readily
obtainable starting materials [5-8], we report here several
efficient synthetic routes to pyridazines utilizing 2-oxo-
butanal-1-arylhydrazones 3a,b as starting materials. The
required prepared 3a,b were readily obtained via coupling
3-oxopentanoic acid with aromatic diazonium salts
following a procedure reported for synthesis of 2-oxo-
pyruvaldhyde-1-arylhydrazones from reaction of aceto-
acetic acid with aromatic diazonium salts [9].
RESULTS AND DISCUSSION
In conjunction to our recent previous work [15] com-
pound 3a was condensed on heating with ethyl
cyanoacetate in presence of ammonium acetate for 15 min
to yield the pyridazinone 9. Compound 9 reacted with
Compounds 3a,b reacted with benzylidenemalono-
nitrile (4a) and with ethyl arylidenecyanoacetate 4b to
yield 1:1 adducts. These were assumed to result from
Michael addition to activated double bond in 4a,b.

878
S. I. Aziz, H. F. Anwar, M. A. El-Apasery, and M. H. Elnagdi.
Vol 44
Scheme 1
O
Ar1
O
O
Ar1
4a,b
CN
O
CN
COONa
ArN NCl
Na2CO3
COOH
H
X
X
N
N
NH
Ar
N
NH
Ar
NH
Ar
1
5
3a,b
2a,b
a, Ar = p-C6H4Cl
b, Ar = o-C6H4COOMe
Ar = o-C6H4Cl
Ar = o-C6H4COOMe
O
Ar1
X
O
Ar1
N
O
Ar1
X
X
N
N
N
NH2
N
NH
N
NH2
4-8 a, X = CN, Ar1 = C6H5
COOMe
b, X = COOEt, Ar1 = p-C6H4OMe
O
Cl
6a,b
8a,b
7
sulfur in dioxane in presence of piperidine to yield the
thieno[3,4-d]pyridazine 10 (Scheme 2).
carboxylate with acrylonitrile has been shown
earlier to afford 6-amino-8a-methyl-2,5-dioxo-4-
phenyl-4,5,8,8a-tetrahydro-2H-1-thia-3,4-diazaacenaph-
thylene-7-carbonitrile [22]. Although it was believed
earlier [23] that the reaction of condensed amino-
thiophenes with acetylenic esters affords thiepines
Elnagdi et al [24] has shown that the formed products are
actually C-1 alkylation products.
Scheme 2
O
S
CN
O
NC
OEt
NH2
S / Dioxane
3a
N
N
N
N
O
In conclusion, we could show that the readily
obtainable 1-(aryl-hydrazono)-butan-2-ones are versatile
starting for synthesis of pyridazines and condensed
pyridazines of biological interest.
Cl
Cl
9
10
Compound 10 reacted with maleic anhydride and
acrylonitrile to yield products of addition and hydrogen
sulphide elimination. These were assigned structure 12
and 14 and are assumed to be formed via cycloaddition. In
contrast to this compound 10 reacted with the enaminone
15 and with ethyl propiolate to yield only product of
addition of amino function at double bond affording 16,
17 and stereo-isomeric 18. While 16 existed solely in cis
form, compound 17 proved to be a 1:1 mixture of cis and
trans forms. Stereochemistry of the reaction products
could be readily concluded from J values of olefinic
protons (Scheme 3). Thus olefinic protons in 16 have J =
8.1 Hz while product of reaction with ethyl propiolate
revealed four olefinic doublets at ꢀ 5.03, 5.65, 8.08, 5.03
ppm. The doublets at 5.03 and 8.08 have J = 7.3 Hz while
others have J = 12.2 Hz with half integral per each signal.
It is of value to report that reaction of thienoazines with
dipolarophile has been reported by Elnagdi et al [16-20]
as well as Döpp et al [21] to afford either products of 4+2
cycloaddition, products of C-1 alkylation or product of
initial addition of aminofunction to the dipolarophile.
However reaction of methyl 5-amino-7-methyl-4-
oxo-3-phenyl-3,4-dihydro-thieno[3,4-d]pyridazine-1-
EXPERIMENTAL
All melting points are uncorrected. IR spectra were recorded
in KBr disks using a Pye Unicam SP-3000 IR spectrophotometer
and Testscan Shimadzu FT-IR 8000 series. H and 13C NMR
1
spectra were measured in DMSO-d6 at 400/100 and 300/75 MHz
1
on a Varian Gemini relative to DMSO (2.50 ppm for H and
39.5 ppm for 13C); chemical shifts are reported in ꢀ units (ppm).
Mass spectra were measured on
a GCMS-QP 1000-EX
Shimadzu. Microanalyses were performed on a LECO CHNS-
932 Elemental Analyzer.
1-(Aryl-hydrazono)-butan-2-one (3a,b). In
a beaker
equipped with a mechanical stirrer a solution of 3.5 g. (53
mmol) of 85 % potassium hydroxide in 112 ml of water with 6.5
g (0.05 mol) of methyl 3-oxo-pentanoate. The mixture is
allowed to stand at room temperature for 24 hrs. The solution
was cooled to 0 °C, and 4.5 ml of conc. HCl in 15 ml. of ice
water was added slowly with stirring. The diazonium salt
solution was added (50 mmol); prepared by adding a solution of
sodium nitrite (3.6 g into 10 ml H2O) to cold solution of aniline
hydrochloride derivatives (50 mmol of aniline derivatives in 20
ml concentrated HCl); over a period of 20 min, and the mixture
is made basic by the addition of 8.2 g. of sodium acetate
dissolved in 30 ml. of water. The temperature of the reaction
mixture is raised slowly to 50°C and maintained at this value for

Jul-Aug 2007
Studies with Pyridazines and Condensed Pyridazines
879
(brs, 1H, NH). Anal. calcd. for C12H14N2O3 C, 61.53; H, 6.02;
N, 11.96. Found C, 61.17; H, 6.33, N, 11.73 %
Scheme 3
O
O
3-Amino-2-(4'-chloro-phenyl)-5-aryl-6-propionyl-2,5-
dihydro-pyridazine-4-derivates (6a,b). A mixture of 3a (0.01
mol), benzylidenemalononitrile 4a, or ethyl 2-cyano-3-(4-
methoxy-phenyl)-acrylate 4b (0.01 mol) and piperidine (0.5 ml)
in ethanol (20 ml) was refluxed for 5 hrs. The solvent was then
evaporated under reduced pressure and the residue poured onto
water and neutralized by HCl. The product was collected by
filtration and crystallized from ethanol.
O
O
O
O
O
S
O
10
O
NH2
NH2
N
N
N
O
N
O
3-Amino-2-(4'-chloro-phenyl)-5-phenyl-6-propionyl-2,5-
dihydro-pyridazine-4-carbonitrile (6a). Brown crystal, (yield
82%, 2.9g) mp 177-178 °C; ir (KBr): ꢀmax 3473, 3309 (NH2),
2190 (CN) 1687 cm-1 (CO); ms (70 eV) m/z 364 (M+, 11%),
(307, 100%); 1H nmr (400 MHz, DMSO-d6): 0.93 (t, 3H, J = 7.3
Hz, CH3), 2.75 (q, 2H, J = 7.3 Hz, CH2), 4.73 (s, 1H, CH), 6.19
(brs, 2H, NH2), 7.16-7.36 (m, 5H, Ar-H), 7.56 (d, 2H, J = 8.6
Hz, CH), 7.58 (d, 2H, J = 8.6 Hz, CH),) 13C nmr (100 MHz;
DMSO-d6): 199.4, 151.3, 144.6, 142.9, 140.0, 133.0, 130.4,
130.0x2, 128.4x2, 128.3x2, 127.8x2, 121.5, 57.8, 37.2, 30.6, 8.9.
Anal. calcd. for C20H17ClN4O C, 65.84; H, 4.70; N, 15.36. Found
C, 65.41; H, 4.93; N, 15.58. %
Cl
Cl
S
12
11
CN
CN
NH2
NH2
CN
N
N
N
O
N
O
Cl
Cl
13
14
Ethyl 3-amino-2-(4'-chloro-phenyl)-5-(4-methoxy-phenyl)-
6-propionyl-2,5-dihydro-pyridazine-4-carboxylate (6b).
Yellow crystal, (yield 81%, 3.5 g), mp 150 °C; ir (KBr): ꢀmax
3365, 3270 (NH2), 1688, 1652 cm-1 (CO); ms (70 eV) m/z : 441
S
S
N
N
H
O
S
15
N
1
(M+, 7%), (369, 100%); H nmr (300 MHz, DMSO-d6): 0.95 (t,
O
O
N
3H, J = 8.7 Hz, CH3), 1.16 (t, 3H, J = 8.4 Hz, CH3), 2.80 (q, 2H,
J = 8.7 Hz, CH2), 3.68 (s, 3H, CH3), 4.05 (q, 2H, J = 8.4 Hz,
CH2), 5.13 (s, 1H, CH), 6.81-7.11 (m, 8H, Ar-H), 7.57 (brs, 2H,
NH2), 13C nmr (75 MHz; DMSO-d6): 198.6, 168.1, 158.0, 151.0,
147.0, 139.0, 135.0, 132.0, 129.5x2, 128.1x2, 127.3x2, 113.9x2,
76.3, 58.8, 54.9, 33.2, 29.6, 14.4, 8.1. Anal. calcd. for
C23H24ClN3O4 C, 62.51; H, 5.47; N, 9.51. Found C, 62.92; H,
5.33; N, 9.12 %
10aH-Pyridazino[1,6-a]quinazoline derivatives (8a,b). A
mixture of 3b (0.01 mol), benzylidenemalononitrile 4a, or ethyl
2-cyano-3-(4-methoxy-phenyl)-acrylate 4b (0.01 mol) and
piperidine (0.5 ml) in ethanol (20 ml) was refluxed for 7 hrs.
The solvent was then evaporated under reduced pressure and the
residue poured onto water and neutralized by HCl. The product
was collected by filtration and crystallized from ethanol.
6-Oxo-3-phenyl-2-propionyl-5,6-dihydro-3H-pyridazino[1,6-
a]quinazoline-4-carbonitrile (8a). Dark green solid (yield 80%,
78 g), mp 220-221 °C; ir (KBr): ꢀmax 3444 (NH), 2200 (CN),
1684, 1652 cm-1 (CO); ms (70 eV) m/z 356 (M+, 12.5%), (299,
43%), (279, 21%); 1H nmr (300 MHz, DMSO-d6): 0.93 (t, 3H, J
= 7.3 Hz, CH3), 2.75 (q, 2H, J = 7.3 Hz, CH2), 4.73 (s, 1H, CH),
6.19 (brs, 1H, NH), 7.24-7.37 (m, 5H, Ar-H) 7.80-7.98 (m, 4H,
Ar-H); 13C nmr (75 MHz, DMSO-d6): 198.0, 158.3, 145.0,
141.2, 140.7, 135.5, 129.0, 128.6x2, 127.8, 127.6x2, 127.2,
124.7, 117.3, 115.7, 114.9, 63.3, 36.9, 30.2, 7.7. Anal. calcd. for
C21H16N4O2 C, 70.77; H, 4.53; N, 15.72. Found C, 70.89; H,
4.12; N, 15.42 %
Cl
16
O
S
S
OEt
N
N
H
OEt
O
H
N
OEt
O
N
O
N
N
O
+
Cl
18
Cl
17
1:1
1 hr; the solid product, so formed, was collected by filtration and
crystallized from ethanol [9].
1-[(4'-Chloro-phenyl)-hydrazono]-butan-2-one (3a). Red
crystal, (yield 76%, 7.9 g) mp 130-131 °C; ir (KBr): ꢀmax 3236
(NH), 1650 cm-1 (CO); ms (70 eV) m/z: 210 (M+, 35%), (111,
1
100%); H nmr (300 MHz, DMSO-d6): 1.01 (t, 3H, J = 7.4 Hz,
CH3), 2.80 (q, 2H, J = 7.4 Hz, CH2), 6.98-7.10 (m, 4H, Ar-H),
7.30 (s, 1H, CH), 11.21 (brs, 1H, NH) 13C nmr (75 MHz;
DMSO-d6): 200.1, 142.0, 134.3, 131.4, 130.8x2, 114.4x2, 30.0,
9.5. Anal. calcd. for C10H11ClN2O C, 57.01; H, 5.26; N, 13.30.
Found C, 56.78; H, 5.10; N, 13.72 %
Methyl 2-[N'-(2-oxo-butylidene)-hydrazino]-benzoate (3b).
Orange crystal, (yield 74%, 8.6 g) mp 65 °C; ir (KBr): ꢀmax 3258
(NH), 1684 cm-1 (CO); ms (70 eV) m/z 234 (M+, 22%), (175,
Ethyl 3-(4-methoxyphenyl)-6-oxo-2-propionyl-5,6-dihydro-
3H-pyridazino[1,6-a]quinazoline-4-carboxylate (8b). Green
crystal (yield 82%, 3.5 g), mp 174-175 °C; ir (KBr): ꢀmax 3445
(NH), 1697, 1665 cm-1 (CO); ms (70 eV) m/z 433 (M+, 24.3%)
1
(360, 40%); H nmr (300 MHz, DMSO-d6): 0.97 (t, 3H, J = 8.4
1
35%); H nmr (300 MHz, DMSO-d6): 1.01 (t, 3H, J = 7.2 Hz,
CH3), 2.83 (s, 3H, CH3), 2.90 (q, 2H, J = 7.2 Hz, CH2), 7.00-
7.59 (m, 1H, Ar-H), 7.60-7.99 (m, 4H, CH and Ar-H), 11.34
Hz, CH3), 1.16 (t, 3H, J = 8.0 Hz, CH3), 2.97 (q, 2H, J = 8.4 Hz,
CH2), 3.67 (s, 3H, CH3), 4.10 (q, 2H, J = 8.0 Hz, CH2), 5.07 (s,
1H, CH), 6.81 (d, 2H, J = 9.45 Hz, Ar-H), ), 7.1 (d, 2H, J = 9.45

880
S. I. Aziz, H. F. Anwar, M. A. El-Apasery, and M. H. Elnagdi.
Vol 44
Hz, Ar-H), 7.38-7.43 (m, 1H Ar-H), 7.82-8.02 (m, 3H Ar-H),
11.66 (brs, 1H, NH), 13C nmr (75 MHz; DMSO-d6): 198.3,
167.9, 158.4, 157.3, 148.4, 141.6, 140.8, 135.9, 134.3, 129.0x2,
127.3, 124.8, 115.5, 115.3, 114.0x2, 79.8, 60.3, 55.0, 33.6, 30.3,
14.0, 7.8. Anal. calcd. for C24H23N3O5 C, 66.50; H, 5.35; N,
9.69. Found C, 66.74; H, 5.28; N, 10.02 %
2-(4'-Chloro-phenyl)-5-ethyl-3-oxo-2,3-dihydro-pyridazine-
4-carbonitrile (9). A mixture of 3a (0.01 mol), and cyanoacetic
acid ethyl ester (0.01 mol) were treated with ammonium acetate
(2 g), and acetic acid (15 ml) then refluxed for 15 min. The
solvent was then evaporated under reduced pressure and the
residue poured into water. The product was collected by
filtration and crystallized from ethanol, dark orange crystal,
(yield 71%, 1.8 g) mp 132-133 °C, ir (KBr): ꢀmax 2234 (CN),
1659 cm-1 (CO); ms (70 eV) m/z 259 (M+, 32%) (111, 100%);
1H nmr (300 MHz, DMSO-d6): 1.28 (t, 3H, J = 7.6 Hz, CH3),
2.77 (q, 2H, J = 7.6 Hz, CH2), 7.32 (d, 2H, J = 8.2 Hz, Ar-H),
7.43 (d, 2H, J = 8.2 Hz, Ar-H), 8.31 (s, 1H, CH). Anal. calcd.
for C13H10ClN3O. C, 60.12; H, 3.88; N, 16.18. Found C, 60.44;
H, 3.51; N, 15.79 %
7-Amino-2-(4'-chloro-phenyl)-5-methyl-2H-thieno[3,4-d]-
pyridazin-1-one (10). A mixture of 9 (0.01 mol), and elemental
sulfur (0.01 mol) in dioxane (15 ml) and piperidine (0.5 ml) was
refluxed for 5 hrs then poured onto water. The product was
collected by filtration and crystallized from ethanol, pale brown
crystal, (yield 62 %, 1.8 g); m.p. 212-213 °C, ir (KBr): ꢀmax
3406, 3304 (NH2), 1661 cm-1 (CO); ms (70 eV) m/z: 291 (M+,
35%), (258, 100%); 1H nmr (400 MHz, DMSO-d6): 2.44 (s, 3H,
CH3), 7.37 (brs, 2H, NH2), 7.47 (d, 2H, J = 8.7 Hz, Ar-H), 7.55
(d, 2H, J = 8.7 Hz, Ar-H), 8.04 (s, 1H, CH). Anal. calcd. for
C13H10ClN3OS C, 53.52; H, 3.45; N, 14.40; S, 10.99. Found C,
53.46; H, 3.46; N, 14.14; S, 10.82 %
General procedure 12, 14, 16, 17. A suspension of 10 (0.01
mol) in dioxan (15 ml) and acetic acid (2 ml) was treated with
maleic anhydride, acrylonitrile, enaminone 15 [25] or with ethyl
propiolate (0.01 mol). The reaction mixture was refluxed for 6
hrs then poured into water. The solid product was collected by
filtration and recrystallized from dioxan to yield 12, 14, 16 and
17, respectively
CH), 7.33-7.40 (m, 1H, CH), 7.51 (d, 2H, J = 10.1 Hz, Ar-H),
7.61 (d, 2H, J = 10.1 Hz, Ar-H), 7.89-7.93 (m, 2H, CH), 8.26 (s,
1H, CH), 13.03 (d, 1H, J = 12.3, NH), 13C nmr (100 MHz;
DMSO-d6): 182.7, 161.2, 156.9, 148.8, 145.3, 142.8, 142.7,
139.5, 134.4, 133.7, 130.7, 128.5x2, 128.1, 127.0, 126.4x2,
109.5, 97.0, 11.9. Anal. calcd. for C20H14ClN3O2S2 C, 56.13; H,
3.30; N, 9.82; S, 14.99. Found C, 56.26; H, 3.13; N, 9.78; S,
15.20 %
Ethyl 3-[3-(4'-chloro-phenyl)-7-methyl-4-oxo-3,4-dihydro-
thieno[3,4-d]pyridazin-5-ylamino]-acrylate (17). Dark green
solid, (yield 67%, 2.6 g) mp 199-200 °C, ir (KBr): ꢀmax: 3430
(NH), 1685, 1645 cm-1 (CO); ms (70 eV) m/z 389 (M+, 42%),
1
(316, 21%), (291, 100%); H nmr (400 MHz, DMSO-d6): 1.21
(t, 3H, J = 6.3 Hz, CH3) 2.28 (s, 3H, CH3), 4.09 (q, 2H, J = 6.3
Hz, CH2), 5.03 (d, 0 .5 H, J = 7.3 Hz, CH), 5.65 (d, 0 .5 H, J =
12.2 Hz, CH), 8.08 (d, 0 .5 H, J = 7.3 Hz, CH), 8.30 (d, 0 .5H, J
= 12.2 Hz, CH), 8.38 (s, 1H, CH), 7.48-7.62 (m, 4H, Ar-H),
10.97 (brs, 1H, NH), 13C nmr (100 MHz; DMSO-d6): 173.0,
161.0, 155.1, 152.0, 140.5, 140.4, 133.7, 132.6, 129.7x2, 129.6,
129.1x2, 128.8, 118.0, 25.7, 22.1, 16.0. Anal. calcd. for
C18H16ClN3O3S C, 55.45; H, 4.14; N, 10.78; S, 8.22. Found C,
55.14; H, 4.05; N, 11.08; S, 8.68 %
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9-Amino-2-(4'-chloro-phenyl)-5-methyl-2H-furo[3,4-g]-
phthalazine-1,6,8-trione (12). Yellow crystal, (yield 64%, 2.3
g); mp 230-231 °C, ir (KBr): ꢀmax 3448, 3321 (NH2), 1717, 1654
1
cm-1 (CO); ms (70 eV) m/z: 355 (M+, 100%), (283, 64%); H
nmr (300 MHz, DMSO-d6): 2.7 (s, 3H, CH3), 7.50-7.68 (m, 4H,
Ar-H), 8.40 (brs, 2H, NH2), 8.75 (s, 1H, CH). Anal. calcd. for
C17H10ClN3O4 C, 57.40; H, 2.83; N, 11.81. Found C, 57.17; H,
2.75; N, 11.47 %
5-Amino-3-(4'-chloro-phenyl)-8-methyl-4-oxo-3,4-dihydro-
phthalazine-6-carbonitrile (14). Yellow solid, (yield 66%, 2.0
g); m.p. 285-286 °C, ir (KBr): ꢀmax 3431, 3316 (NH2), 2211
(CO), 1654 cm-1 (CO); ms (70 eV) m/z 310 (M+, 100%), (291,
84%);1H nmr (300 MHz, DMSO-d6): 2.44 (s, 3H, CH3), 7.55-
7.63 (m, 4H, Ar-H), 7.79 (s, 1H, CH), 7.82 (brs, 2H, NH2), 8.49
(s, 1H, CH). Anal. calcd. for C16H11ClN4O C, 61.84; H, 3.57; N,
18.03. Found C, 61.38; H, 3.31; N, 18.32 %
2-(4'-Chloro-phenyl)-5-methyl-7-(3-oxo-3-thiophen-2-yl-
propenylamino)-2H-thieno[3,4-d]pyridazin-1-one (16). Dark
red solid, (yield 61%, 2.6 g); mp 216-217 °C, ir (KBr): ꢀmax 3437
(NH), 1689, 1658 cm-1 (CO); ms (70 eV) m/z : 427 (M+, 42%),
(315, 10%), (111, 100%);1H nmr (300 MHz, DMSO-d6): 2.63 (s,
3H, CH3), 6.21 (d, 1H, J = 8.1 Hz, CH), 7.21 (t, 1H, J = 4.2 Hz,
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