Synthesis and Reactions of Novel Pyrimido[4,5-c]pyridazine and s-Triazolo[3',4':2,3]pyrimido[4,5-c]pyridazine Derivatives

Article abstract of DOI:10.1007/s00706-003-0078-1

The reaction of 3-chloro-5,6-diphenylpyridazine-4-carbonitrile with potassium thiocyanate gave the corresponding isothiocyanate derivative. This was reacted with aromatic amines in ethanol to afford pyrimido[4,5-c]pyridazine derivatives. The reaction of the latter compounds with hydrazine hydrate led to the formation of 6-hydrazino derivatives. One hydrazino compound was reacted with a variety of reagents to produce other new pyrimidopyridazines as well as a number of s-triazolo derivatives.

Full text of DOI:10.1007/s00706-003-0078-1

Monatshefte f€ur Chemie 135, 45–53 (2004)
DOI 10.1007/s00706-003-0078-1
Synthesis and Reactions of Novel
Pyrimido[4,5-c]pyridazine and
s-Triazolo[39,49:2,3]pyrimido[4,5-c]pyridazine
Derivatives
ꢀ
Maisa I. Abdel Moneam
Chemistry Department, Faculty of Science, Assiut University, Assiut 71516, Egypt
Received May 25, 2003; accepted May 27, 2003
Published online October 6, 2003 # Springer-Verlag 2003
Summary. The reaction of 3-chloro-5,6-diphenylpyridazine-4-carbonitrile with potassium thiocyanate
gave the corresponding isothiocyanate derivative. This was reacted with aromatic amines in ethanol to
afford pyrimido[4,5-c]pyridazine derivatives. The reaction of the latter compounds with hydrazine
hydrate led to the formation of 6-hydrazino derivatives. One hydrazino compound was reacted with a
variety of reagents to produce other new pyrimidopyridazines as well as a number of s-triazolo
derivatives.
Keywords. Pyrimidopyridazine; s-Triazolopyrimidopyridazine; Heterocycles; Condensation.
Introduction
Pyridazine derivatives and heterocyclic annelated pyridazines continue to attract
attention due to their wide variety of interesting biological activities [1]. Synthesis
and utility of many pyridazine derivatives as analgesics, insecticidals [2], fungi-
cidals [3, 4] cardiotonics [5], and bactericidals [6] have been reported. In view of
the above mentioned benefits and in continuation of our work on the chemistry of
pyridazine compounds [7], we report herein the synthesis of pyrimidopyridazine
and triazolopyrimidopyridazine derivatives.
Results and Discussion
3-Chloro-5,6-diphenylpyridazine-4-carbonitrile (1), which was prepared according
to Ref. [8] was reacted with potassium thiocyanate in acetic acid to yield (5,6-
diphenyl-4-cyano pyridazin-2-yl)isothiocyanate (2). The reaction of 2 with different
ꢀ
Corresponding author. E-mail: maisaabdelmonem@hotmail.com

46
M. I. Abdel Moneam
arylamines, namely aniline, p-anisidine, and 4-chloroaniline afforded the pyrimido-
pyridazine derivatives 3a–3c [9]. Boiling of 2 in ethanol yielded the thiocarbamate
derivative 4 in good yield.
Further chemical confirmation of the pyrimidopyridazine constitution of 3a
was achieved using an alternative route for the synthesis. Thus, when 3-amino-
4-cyano-5,6-diphenylpyridazine [10] was allowed to react with phenyl isothiocya-
nate in pyridine for a long time, the pyrimidopyridazine 3a was produced in a
single step [11] (Scheme 1). When 3a was reacted with different alkylating agents,
namely ethyl chloroacetate, chloroacetonitrile, or chloroacetone in refluxing etha-
nol in the presence of sodium acetate, the corresponding S-alkylated derivatives
5a–5c were obtained in excellent yield. Reaction of 3a–3c with hydrazine hydrate
in refluxing ethanol afforded the corresponding hydrazino compounds 6a–6c.
Condensation of 6a with aromatic aldehydes in ethanol furnished 7-arylmethy-
lenehydrazino derivatives 7a–7c. When 7a was treated with thionyl chloride, it
underwent an intramolecular cyclization affording triazolopyrimidopyridazine 8
[12]. Condensation of 6a with acetophenone in refluxing ethanol containing a
Scheme 1. i: KSCN=CH3COOH; ii: EtOH; iii: ArNH2=EtOH; iv: PhNCS=pyridine; v: RCH2Cl=
EtOH=AcONa; vi: NH2NH2=EtOH

Novel Pyrimido[4,5-c]pyridazines and s-Triazolo[30,40:2,3]pyrimido[4,5-c]pyridazines
47
Scheme 2. i: ArCHO=EtOH; ii: SOCl2; iii: PhCOCH3=EtOH; iv: POCl3=DMF
Scheme 3. i: Ac2CH2=EtOH; ii: CH3COCH2CO2Et=EtOH=KOH; iii: CS2=pyridine; iv: NaNO2=
CH3CO2H; v: ClCH2CO2 Et=EtOH=AcONa

48
M. I. Abdel Moneam
Scheme 4. i: CH(OEt)3; ii: ClCO2Et=pyridine; iii: CH3CO2H; iv: EtOCH¼C(CN)CO2Et;
v: EtOCH¼C(CN)2=EtOH=AcOH
few drops of acetic acid afforded 5,6-dihydro-7-[2-(methylphenylmethylene)hydra-
zino-5-imino-3,4,6-tri-phenylpyrimido[4,5-c]pyridazine (9). Upon treatment of 9
with POCl3=DMF mixture (Vilsmeier reagent) at 60–70ꢁC, the pyrazolylpyrimi-
dopyridazine 10 was obtained [13]. Furthermore, the hydrazino derivative 6a was
condensed with acetylacetone or ethyl acetoacetate in refluxing ethanol in the
presence of KOH to afford pyrazolylpyrimidopyridazines 11 or 12.
Moreover, 6a was used as a versatile compound for building a new heterocyclic
system condensed with a pyridazine moiety. Thus, its reaction with carbon disul-
fide in pyridine and=or nitrous acid leads to the formation of the triazolopyrimi-
dopyridazine 13 and tetrazolopyrimidopyridazine 14. The thioxo derivative 13 was
easily S-alkylated with ethyl chloroacetate in refluxing ethanol in the presence of
sodium acetate to give the ester 15. Furthermore, the reaction of 6a with triethyl
orthoformate and=or ethyl chloroformate afforded 16 and 17. Compound 16 under-
went an intramolecular cyclization when stirred in acetic acid at room temperature
yielding triazolo[30,40:2,3]pyrimido[4,5-c]pyridazine (18). Finally, the reaction of
6a with ethyl ethoxymethylenecyanoacetate or ethoxymethylenemalonitrile in
refluxing ethanol in the presence of a few drops of AcOH yielded pyrazolyl-
pyrimidopyridazines 19 and 20.
Experimental
Uncorrected Melting points were determined using a Kofler melting point apparatus. IR spectra were
recorded on a Pye-Unicam spectrometer using KBr wafers. 1H NMR spectra were recorded on a Varian
390 NMR spectrometer at 90MHz using TMS as an internal standard. Mass spectra were recorded on

Novel Pyrimido[4,5-c]pyridazines and s-Triazolo[30,40:2,3]pyrimido[4,5-c]pyridazines
49
JEOL JMS 600 spectrometer. Elemental analyses were performed on a Perkin-Elmer 240C micro-
analyzer. They were found to agree favorably with the calculated values.
3-Chloro-5,6-diphenylpyridazine-4-carbonitrile (1) was prepared according to Ref. [8].
(5,6-Diphenyl-4-cyanopyridazine-2-yl)thiocyanate (2, C18H10N4S)
A mixture of 2.91g of 1 (0.01 mol) and 0.79 g of KSCN (0.01 mol) in acetic acid was stirred at room
temperature. The precipitated product was collected by filtration as orange crystals in 82% yield; mp
175–177ꢁC; IR: ꢀꢀ¼ 2220 (CꢂN) and 1590 (C¼N) cmꢃ1; EI: m=z ¼ 314, base peak at 288 (M-26).
General Procedure for the Synthesis of 3a–3c
Method A: A suspension of 3.14 g of 2 (0.01 mol) and 0.01mol of the respective arylamine in 35cm3
of absolute ethanol was heated under reflux for 2–4 h, and then allowed to cool. The solid product was
collected by filtration and recrystallized from EtOH=CHCl3 to give yellow-orange crystals.
5-Imino-5,6,7,8-tetrahydro-3,4,6-triphenylpyrimido[4,5-c]pyridazine-7-thion (3a, C24H17N5S)
1
Yield 78%; mp 299–300ꢁC; IR: ꢀꢀ¼ 3450, 3350 (NH) 1600 (C¼N) cmꢃ1; H NMR (DMSO-d6):
ꢁ ¼ 7.5–8.2 (m, 15ArH), 11.2 (s, 2NH) ppm; 13C NMR (DMSO-d6): ꢁ ¼ 147.2, 156.4, 163.3 (3C¼N),
114.9, 134.8 (C¼C pyrimidine ring), 178.3 (C¼S), 137.7 (N–C), 124.5, 125.3, 127.0, 128.5, 129.0,
136.5 (aromatic) ppm.
5-Imino-5,6,7,8-tetrahydro-6-(4-methoxyphenyl)-
3,4-diphenylpyrimido[4,5-c]pyridazine-7-thion (3b, C25H19N5SO)
1
Yield 73%; mp 269–271ꢁC; IR: ꢀꢀ¼ 3450, 3350 (NH), 1590 (C¼N) cmꢃ1; H NMR (DMSO-d6):
ꢁ ¼ 3.4 (s, OCH3), 7.5–8.5 (m, 14ArH), 10.9 (s, 2NH) ppm.
6-(4-Chlorophenyl)-5-imino-5,6,7,8-tetrahydro-3,4-diphenylpyrimido[4,5-c]pyridazine-
7-thion (3c, C24H16N5SCl)
Yield 75%; mp 273–275ꢁC; IR: ꢀꢀ¼ 3450–3350 (NH), 1600 (C¼N) cmꢃ1
.
Method B: A mixture of 2.5 g of 3-amino-4-cyano-5,6-diphenylpyridazine (0.01 mol) and 1.35 g of
phenyl isothiocyanate (0.01 mol) in 20 cm3 of pyridine was heated under refux for 10–12h, and then
allowed to cool. The solid product was collected by filtration and recrystallized from EtOH=CHCl3 to
give yellow crystals. The products were identical with those synthesized by method A.
Ethyl N-(4-Cyano-5,6-diphenylpyridazin-3-yl)thiocarbamate (4, C20H16N4OS)
A sample of 2 g of 2 was boiled for 1 h in 30 cm3 of ethanol and the reaction mixture was then allowed
to cool. The solid product was filtered off and recrystallized from dioxane to give yellow crystals in
1
63% yield; mp 195–197ꢁC; IR: ꢀꢀ¼ 3310 (NH), 2220 (CꢂN) cmꢃ1; H NMR (CDCl3): ꢁ ¼ 1.5 (t,
J ¼ 7.0 Hz, CH3), 2.7 (q, J ¼ 7.0 Hz, CH2), 7.1–7.7 (m, 10ArH), 9.7 (s, NH) ppm; EI: m=z ¼ 360.5.
General Procedure for the Synthesis of 5a–5c
A mixture of 2 g of 3a (0.005mol), 0.005 mol of the corresponding halo compound and 0.015 mol of
sodium acetate in 30cm3 of ethanol was refluxed for 2 h, then allowed to cool, and poured into H2O.
The solid product was collected and recrystallized from ethanol to give white pale yellow crystals.

50
M. I. Abdel Moneam
Ethyl (5,6-Dihydro-5-imino-3,4,6-triphenylpyrimido[4,5-c]pyridazin-7-ylthio)acetate
(5a, C28H23N5O2S)
Yield 87%; mp 193–195ꢁC; IR: ꢀꢀ¼ 3350 (NH), 2900 (CH aliphatic), 1710 (C¼O), 1600 (C¼N)
cmꢃ1; 1H NMR (CDCl3): ꢁ ¼ 1.5 (t, J ¼ 7.0 Hz, CH3), 2.4 (q, J ¼ 7.0 Hz, CH2), 6.1 (s, CH2), 7.5–8.6
(m, 15ArH), 10.9 (s, NH) ppm.
(5,6-Dihydro-5-imino-3,4,6-triphenylpyrimido[4,5-c]pyridazin-7-ylthio)acetonitril
(5b, C26H18N6S)
1
Yield 81%; mp 173–175ꢁC; IR: ꢀꢀ¼ 3340 (NH); 2220 (CꢂN) and 1590 (C¼N) cmꢃ1; H NMR
(CDCl3): ꢁ ¼ 3.5 (s, CH2), 7.5–8.3 (m, 15ArH), 11.1 (s, NH) ppm.
(5,6-Dihydro-5-imino-3,4,6-triphenylpyrimido[4,5-c]pyridazin-7-ylthio)aceton
(5c, C27H21N5OS)
Yield 85%; mp 181–183ꢁC; IR: ꢀꢀ¼ 3350 (NH), 2900 (CH aliphatic), 1700 (C¼O), 1590 (C¼N)
1
cmꢃ1; H NMR (DMSO-d6): ꢁ ¼ 2.9 (s, CH3), 4.1 (s, CH2), 7.3–8.5 (m, 15ArH), 11.2 (s, NH) ppm.
General Procedure for the Synthesis of 6a–6c
A mixture of 0.01 mol of 3a–3c and hydrazine hydrate (5cm3) was heated under reflux for 6 h, then
20cm3 of absolute ethanol were added and the mixture was refluxed for additional 1 h. The solid
product was collected and recrystallized from ethanol to give orange crystals.
5,6-Dihydro-7-hydrazino-5-imino-3,4,6-triphenylpyrimido[4,5-c]pyridazine (6a, C24H19N7)
Yield 77%; mp 195–197ꢁC; IR: ꢀꢀ¼ 3400, 3350 (NH2, NH), 1610 (C¼N) cmꢃ1; 1H NMR (DMSO-d6):
ꢁ ¼ 5.7 (s, NH2), 7.0–7.9 (m, 15ArH), 9.5–10.2 (2s, 2NH) ppm.
5,6-Dihydro-3,4-diphenyl-7-hydrazino-5-imino-6-(4-methoxyphenyl)pyrimido[4,5-c]pyridazine
(6b, C24H21N7O)
Yield 72%; mp 218–220ꢁC; IR: ꢀꢀ¼ 3400, 3340 (NH2, NH), 1610 (C¼N) cmꢃ1; 1H NMR (DMSO-d6):
ꢁ ¼ 3.5 (s, CH3), 5.5 (s, NH2), 7.3–7.9 (m, 14ArH), 9.6, 10.2 (2s, 2NH) ppm.
5,6-Dihydro-3,4-diphenyl-7-hydrazino-5-imino-6-(4-chlorophenyl)pyrimido[4,5-c]pyridazine
(6c, C24H18N7Cl)
Yield 75%; mp 263–265ꢁC; IR: ꢀꢀ¼ 3410, 3330 (NH2, NH), 1590 (C¼N) cmꢃ1
.
General Procedure for the Synthesis of 7a–7c
A mixture of 0.01 mol of 6a and 0.01 mol of the appropriate aromatic aldehyde in 30 cm3 of ethanol
was refluxed for 3 h, and then allowed to cool to room temperature. The solid product was collected
and recrystallized from diluted CH3COOH to give yellow crystals.
7-Benzylidenehydrazino-5,6-dihydro-5-imino-3,4,6-triphenylpyrimido[4,5-c]pyridazine
(7a, C31H23N7)
1
Yield 77%; mp >300; IR: ꢀꢀ¼ 3450, 3350 (NH), 1610 (C¼N) cmꢃ1; H NMR (DMSO-d6): ꢁ ¼
7.1–7.7 (m, 20ArH), 8.3 (s, N¼CH), 10.5 (s, 2NH) ppm.

Novel Pyrimido[4,5-c]pyridazines and s-Triazolo[30,40:2,3]pyrimido[4,5-c]pyridazines
51
7-(4-Methoxybenzylidenehydrazino)-5,6-dihydro-5-imino-3,4,6-
triphenylpyrimido[4,5-c]pyridazine (7b, C32H25N7O)
Yield 79%; mp >300ꢁC; IR: ꢀꢀ¼ 3450, 3350 (NH), 1605 (C¼N) cmꢃ1; 1H NMR (DMSO-d6): ꢁ ¼ 3.2
(s, –OCH3), 7.2–7.7 (m, 19ArH), 8.3 (s, –N¼CH), 10.7 (s, 2NH) ppm.
7-(p-Chlorobenzylidenehydrazino)-5,6-dihydro-5-imino-3,4,6-
triphenylpyrimido[4,5-c]pyridazine (7c, C31H22N8O2)
Yield 69%; mp >300ꢁC; IR: ꢀꢀ¼ 3410, 3350 (NH), 1610 (C¼N) cmꢃ1
.
5,6-Dihydro-5-imino-3,4,6,9-tetraphenyl-s-triazolo[30,40:2,3]pyrimido[4,5-c]
pyridazine (8, C31H21N7)
A mixture of 1.5g of 7a (0.003 mol) and 10cm3 of thionyl chloride was refluxed for 5 h, and then
excessive thionylchloride was removed by evaporation. Cold saturated sodium bicarbonate was added
and the reaction mixture was extracted several times with ether. The ether layer was washed with water
and dried over anhydrous magnesium sulphate. The residue left after evaporation of the solvent, was
recrystallized from dioxane to give yellow crystals in 54% yield; mp >300; IR: ꢀꢀ¼ 3350 (NH), 1590
1
(C¼N) cmꢃ1; H NMR (DMSO-d6): ꢁ ¼ 7.2–8.5 (m, 20ArH), 10.3 (s, NH) ppm.
5,6-Dihydro-7-[2-(methylphenylmethylen)hydrazino-5-imino-3,4,6-
triphenylpyrimido[4,5-c]-pyridazine (9, C32H25N7)
A mixture of 2 g of 6a (0.005mol) and 0.6 g of acetophenone (0.005 mol) in 20cm3 of absolute ethanol
and a few drops of acetic acid was heated under reflux for 5 h. Upon cooling the precipitated product
was filtered off and recrystallized from ethanol to give yellow crystals in 65% yield; mp 303–305ꢁC;
1
IR: ꢀꢀ¼ 3250 (NH), 1590 (C¼N) cmꢃ1; H NMR (DMSO-d6): ꢁ ¼ 2.3 (s, CH3), 7.1–8.5 (m, 20ArH),
9.5, 11.1 (2s, 2NH) ppm.
5,6-Dihydro-5-imino-7-(3-phenyl-4-carboxaldehydepyrazol-1-yl)-3,4,6-triphenyl-
pyrimido[4,5-c]pyridazine (10, C34H23N7O)
To a Vilsmeier reagent which was prepared from DMF (10 cm3) and POCl3 (0.012mol), 2 g of 9
(0.004 mol) were added. The mixture was stirred at 60–70ꢁC for 6 h, and then poured into an ice=H2O
mixture. The product which separated upon neutralization with NaHCO3 solution was filtered off
and recrystallized from ethanol to give pale yellow crystals in 52% yield; mp 318–320ꢁC; IR:
1
ꢀꢀ¼ 3350 (–NH), 1640 (C¼O), 1590 (C¼N) cmꢃ1; H NMR (DMSO-d6): ꢁ ¼ 7.1–7.8 (m, 20ArH),
8.2 (s, CH pyrazole), 9.1 (s, CHO), 9.9 (s, NH) ppm.
5,6-Dihydro-7-(3,5-dimethylpyrazol-1-yl)-5-imino-3,4,6-triphenylpyrimido[4,5-c]pyridazine
(11, C29H23N7)
A mixture of 2 g of 6a (0.005mol) and 0.5g of acetylacetone (0.005 mol) was refluxed in ethanol
(30 cm3) for 6 h. The solid product was separated from the hot mixture, filtered off and recrystallized
from acetic acid to give yellow crystals in 78% yield; mp 277–279ꢁC; IR: ꢀꢀ¼ 3400 (NH), 1610 (C¼N)
1
cmꢃ1; H NMR (CF3COOD): ꢁ ¼ 2.4, 2.7 (2s, 2CH3), 6.2 (s, CH pyrazol), 7.5–8.9 (m, 15ArH)
ppm.

52
M. I. Abdel Moneam
5,6-Dihydro-5-imino-7-(3-methyl-5-oxo-pyrazol-1-yl)-3,4,6-
triphenylpyrimido[4,5-c]pyridazine (12, C28H21N7O)
A mixture of 2 g of 6a (0.005mol) and 0.65g of ethyl acetoacetate (0.005mol) in ethanol (30 cm3) was
refluxed for 5 h. After cooling the solid product was filtered off and recrystallized from ethanol=CHCl3
1
to give yellow crystals in 71% yield; mp >300ꢁC; IR: ꢀꢀ¼ 3100 (NH), 1670 (C¼O) cmꢃ1; H NMR
(DMSO-d6): ꢁ ¼ 2.1 (s, CH3), 4.5 (s, CH2), 7.5–8.9 (m, 15ArH), 9.3 (s, NH) ppm.
4,5-Dihydro-5-imino-4,6,7-triphenyl-s-triazolo[30,40:2,3]pyrimido[4,5-c]pyridazine-
1(2H)-thione (13, C25H17N7S)
A sample of 2 g of 6a (0.005 mol) and carbon disulphide (3cm3) in pyridine (20 cm3) was heated on a
water bath for 8 h, and then allowed to cool. The solid product was collected and recrystallized from
1
dioxane to give yellow crystals in 65% yield; mp 255ꢁC; IR: ꢀꢀ¼ 3310 (NH), 1610 (C¼N) cmꢃ1; H
NMR (DMSO-d6): ꢁ ¼ 7.5–8.4 (m, 15ArH), 9.8, 10.3 (2s, 2NH) ppm.
5,6-Dihydro-5-imino-3,4,6-triphenyltetrazolo[50,10:2,3]pyrimido[4,5-c]pyridazine
(14, C24H16N8)
To a cooled sample of 0.5 g of 6a in glacial acetic acid (15 cm3), a cold solution of sodium nitrite (0.3g
in 5 cm3 of H2O) was added dropwise with stirring. Stirring was continued for 3 h at room temperature,
the solid product was filtered off, and recrystallized from dioxane to give pale brown crystals in 62%
1
yield; mp 285ꢁC (decomposed); IR: ꢀꢀ¼ 3310 (NH), 1610 (C¼N) cmꢃ1; H NMR (CF3COOD):
ꢁ ¼ 7.3–7.8 (m, 15ArH) ppm. EI: m=z ¼ 416.5.
4,5-Dihydro-1-ethoxycarbonylmethylthio-5-imino-4,6,7-triphenyl-s-triazolo[30,40:2,3]-
pyrimido[4,5-c]pyridazine (15, C28H23N7O2S)
A mixture of 4.47g of 13 (0.01 mol), 1.5 g of ethyl chloroacetate (0.01 mol), and 0.98g of sodium
acetate (0.012mol) in 30cm3 of ethanol was heated under reflux for 4 h, and then allowed to cool. The
solid product was collected by filtration as white crystals in 77% yield; mp 193–192ꢁC; IR: ꢀꢀ¼ 3410
1
(–NH), 1715 (C¼O) cmꢃ1; H NMR (CDCl3): ꢁ ¼ 1.5 (t, J ¼ 7.0 Hz, CH3), 4.2 (q, J ¼ 7.0 Hz, CH2),
4.7 (s, CH2), 7.3–8.1 (m, 15ArH), 9.7 (s, NH) ppm.
5,6-Dihydro-7-ethoxymethylenehydrazino-5-imino-3,4,6-triphenylpyrimido[4,5-c]-pyridazine
(16, C27H23N7O)
A mixture of 2 g of 6a (0.005 mol), triethyl orthoformate (3cm3), and 1 cm3 of glacial acetic acid was
heated under reflux for 3 h, and then cooled. The solid product was filtered off and recrystallized from
acetic acid to give pale yellow crystals in 64% yield; mp 185ꢁC; IR: ꢀꢀ¼ 3410, 3350 (NH), 2900 (CH
1
aliphatic), 1590 (C¼N) cmꢃ1; H NMR (DMSO-d6): ꢁ ¼ 1.5 (t, J ¼ 7.0 Hz, CH3), 3.7 (q, J ¼ 7.0 Hz,
CH2), 7–7.5 (m, 15ArH), 11.1 (s, 2NH) ppm.
Ethyl [5,6-Dihydro-5-imino-3,4,6-triphenylpyrimido[4,5-c]pyridazine-7-yl]carbazate
(17, C27H23N7O2)
A mixture of 2 g of 6a (0.005 mol), ethyl chloroformate (10 cm3), and 2.0 cm3 of pyridine was refluxed
for 4 h, the excess ethyl chloroformate was removed by distillation and the solid product which formed
after adding ethanol was crystallized from dioxane to give pale yellow crystals in 71% yield; mp
173–175ꢁC; IR: ꢀꢀ¼ 3400, 3150 (NH), 1710 (C¼O), 1600 (C¼N) cmꢃ1; 1H NMR (DMSO-d6): ꢁ ¼ 1.3
(t, J ¼ 7.0 Hz, CH3), 4.1 (q, J ¼ 7.0 Hz, CH2), 7.3–8.1 (m, 15ArH) 10.5 (s, 2NH); 11.2 (s, NH) ppm.

Novel Pyrimido[4,5-c]pyridazines and s-Triazolo[30,40:2,3]pyrimido[4,5-c]pyridazines
5,6-Dihydro-3,4,6-triphenyl-s-triazolo[30,40:2,3]pyrimido[4,5-c]pyridazine (18, C25H17N7)
53
A sample of 2 g of 16 in glacial acetic acid (10 cm3) was stirred at room temperature for about 4 h. The
solid product which formed during stirring was collected and recrystallized from acetic acid to give
dirty white crystals in 52% yield; mp >300; IR: ꢀꢀ¼ 3300 (NH), 1610 (C¼N) cmꢃ1; EI: m=z ¼ 415.
5,6-Dihydro-5-imino-7-(5-amino-4-ethoxycarbonylpyrazol-1-yl)-3,4,6-triphenyl-
pyrimido[4,5-c]pyridazine (19, C30H24N8O2)
A mixture of 2 g of 6a (0.005 mol) and 0.85 g of ethyl ethoxymethylene cyanoacetate (0.005mol) in
30cm3 of ethanol was refluxed in the presence of 1 cm3 of glacial acetic acid for 4 h. After cooling the
solid product was filtered off and recrystallized from dioxane to give brown crystals in 67% yield; mp
260–263ꢁC; IR: ꢀꢀ¼ 3300 (NH), 3400, 3480 (NH2), 1690 (C¼O) cmꢃ1; 1H NMR (DMSO-d6): ꢁ ¼ 1.5
(t, J ¼ 7.0 Hz, CH3), 2.5 (q, J ¼ 7.0 Hz, CH2), 5.5 (s, NH2), 7.2–7.9 (m, 15ArH) ppm.
5,6-Dihydro-5-imino-7-(5-amino-4-cyanopyrazol-1-yl)-3,4,6-triphenylpyrimido[4,5-c]-
pyridazine (20, C28H19N9)
A mixture of 2 g of 6a (0.005 mol) and 0.6 g of ethoxymethylenemalonitrile (0.005mol) in 30cm3 of
ethanol was refluxed in the presence of 1 cm3 of glacial acetic acid for 4 h. After cooling the brown
solid product was collected and recrystallized from dioxane to give brown crystals in 53% yield; mp
1
253–255ꢁC; IR: ꢀꢀ¼ 3100, 3300, 3450 (NH, NH2), 2220 (CꢂN) cmꢃ1; H NMR (DMSO-d6): ꢁ ¼
4.5 (s, NH2), 7.3–7.9 (m, 15ArH), 9.3 (s, NH) ppm.
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