Pyrrolopyrimidines. 5*. Reaction of 6-amino-1,3-dimethyl-pyrrolo[3,4- d]pyrimidine-2,4(1H,3H)-diones with 1,3-diketones

Article abstract of DOI:10.1023/A:1026110808089

The reaction of 6-amino-1,3-dimethylpyrrolo[3,4-d]pyrimidine-2,4-dione with 1,3-diketones leads to formation of predominantly pyrimido[4′, 5′:3,4]pyrrolo[1,2-b]pyridazine-2,4(1H,3H)-diones and, to a lesser extent, pyrimido[5′,4′:3,4]pyrrolo[1,2-b]pyridazi

Full text of DOI:10.1023/A:1026110808089

Chemistry of Heterocyclic Compounds, Vol. 39, No. 7, 2003
PYRROLOPYRIMIDINES. 5*.
REACTION OF 6-AMINO-1,3-DIMETHYL-
d
PYRROLO[3,4- ]PYRIMIDINE-2,4(1H,3H)-
DIONES WITH 1,3-DIKETONES
E. B. Tsupak, M. A. Shevchenko, A. F. Pozharskii, and Yu. N. Tkachenko
The reaction of 6-amino-1,3-dimethylpyrrolo[3,4-d]pyrimidine-2,4-dione with 1,3-diketones leads to
formation of predominantly pyrimido[4',5':3,4]pyrrolo[1,2-b]pyridazine-2,4(1H,3H)-diones and, to a
lesser extent, pyrimido[5',4':3,4]pyrrolo[1,2-b]pyridazine-1,3(2H,4H)-diones. The ease and direction of
the cyclization reaction suggests a very π-electron rich pyrrole ring in the initial state, especially in the
position 7.
Keywords: N-aminopyrroles, acetylhydrazine, 1,3-diketones, pyrrolo[3,4-d]pyrimidine-2,4-diones,
1,3,6-trimethyluracil, Friedel–Crafts benzoylation, heterocyclization.
The reaction of 5-amino-1,3-dimethylpyrrolo[3,2-d]pyrimidine-2,4(1H,3H)-dione (1) with 1,3-diketones
R1COCH2COR2 leads to formation of the corresponding enamino ketones, of which the compound with
R1 = R2 = Me in the presence of boron trifluoride etherate undergoes ring closure to form the
pyrimidopyrrolopyridazine derivative [2].
In continuing this research, in this work we studied analogous conversions of the dione isomeric to 1,
6-amino-1,3-dimethylpyrrolo[3,4-d]pyrimidine-2,4(1H,3H)-dione (2), which has been described earlier in [3].
We established that, in contrast to compound 1, reaction of amine 2 with 1,3-diketones did not stop in the step
of formation of enamino ketones 3, which are not observed even in trace amounts, but rather leads to cyclization
products of the latter of the type 4 and 5. This indicates high reactivity of the pyrrole ring in pyrrolo[3,4-d]-
pyrimidinediones compared with their [3,2-d] isomers. So when amine 2 reacts with acetylacetone, two products
are formed: the yellow pyrimido[4',5':3,4]pyrrolo[1,2-b]pyridazinedione 4a (lmax for the long wavelength
absorption band, 391 nm) and its isomeric colorless pyrimido[5',4':3,4]pyrrolo[1,2-b]pyridazinedione 5a
(λmax 352 nm). In this case, independent of the reaction conditions (the presence or absence of solvent and acid
≥ 10:1) (see Scheme 1).
catalyst), the compound 4a predominates in the mixture (4a:5a
Probably both isomeric products are formed as a result of spontaneous electrophilic cyclization of
intermediate enamino ketones in the position 5 or 7 of the pyrrole ring. The reaction with benzoylacetone occurs
analogously: the yield of the colored (λmax 410 nm) pyrimido[4',5':3,4]pyrrolo[1,2-b]pyridazinedione 4b reaches
83%. In this case, its isomers 5b and 4c are also formed as minor products in 6% and 4% yields respectively;
_______
* For Communication 4, see [1].
__________________________________________________________________________________________
Rostov State University, Rostov-on-Don 344006, Russia; e-mail: zeb@chimfak.rsu.ru. Translated from
Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1096-1102, July, 2003. Original article submitted
October 10, 2001; revised January 30, 2003.
0009-3122/03/3907-0953$25.00©2003 Plenum Publishing Corporation
953

Scheme 1
O
O
5
4
Me
O
Me
O
H
6
N
MeCOCH2COR
3N
N
NH2
N
N
R = Me, Ph
R1
N 1
Me
2
2
7
N
Me
3
COR2
R
10
9
O
N
O
8
4
1
5
Me
Me
Me
6
N
N
7
N
N
3
2
N
N
+
7
6
8
R1
2
O
3
O
N 4
Me
1
5
10
Me
9
R2
5a,b
4 a R1 = R2 = Me; b R1 = Me, R2 = Ph; c R1 = Ph, R2 = Me; 5 a R = Me; b R = Ph
4a–c
they could not be separated due to their practically identical chromatographic mobility. However, there were no
doubts about their identification in the mixture based on the 1H NMR spectrum (Table 1).
1
The structure of compounds 4a-c and 5a,b is supported by the following arguments. In the H NMR
spectrum (Table 1) of compound 4b, the signals from protons of one of the N-methyl groups is found at
2.55 ppm, while as usual in various 6-substituted pyrrolopyrimidines of type 2, the N-methyl groups resonate in
the 3.1-3.6 ppm region. Obviously such an appreciable paramagnetic shift may be due to the anisotropic effect
of the spatially close 10-Ph substituent that is non-coplanar with the heterocyclic system, which is possible only
in isomer 4b. The similarity of the 1H NMR and UV spectra for compound 4b and the major product of reaction
with acetylacetone allows us to hypothesize that the latter has a structure related to compound 4a. Accordingly,
the colorless product with substantially different spectral characteristics is the isomer of the latter, 5a.
Thus in the cyclization reaction, the 7 position in the molecule of compound 2 is much more active than
the position 5 because it is more π-electron rich. In fact, the C(7) atom is conjugated with two electron-donor
atoms N(1) and N(6), while the C(5) atom is conjugated with a donor N(6) and an acceptor C(4)=O. The difference in
reactivity of the indicated carbon atoms is also illustrated well by an experiment on acidic deuteron exchange of
α-pyrrole protons in amine 2, which showed that the ratio of the activities of the positions 7 and 5 is ~12:1
(Table 2). Evidence for this comes from quantum-chemical calculations of the effective atomic charges for the
unsubstituted pyrrolo[3,4-d]pyrimidine-2,4-dione and the stabilization energies of σ complexes formed upon
1
13
addition of H+ and HCO+ cations to it (Table 3). The chemical shifts of the H and C nuclei in the NMR
spectra of amines 2 and 6 (Table 2) also reflect the familiar trend for heteroaromatic systems [4]: the more
electron-rich positions on the ring correspond to lower values of δ.
For the final experimental confirmation of the structure for the pyrimidopyrrolopyridazines obtained,
using the same 1,3-diketones we reacted 6-amino-1,3-dimethyl-5-phenylpyrrolo[3,4-d]pyrimidine-2,4-dione (6),
in the molecule of which cyclization is possible only at the position 7 (for synthesis of dione 6, see below). In
this case, we also could not detect formation of intermediate enamino ketones, and the only reaction product in
both cases, as we expected, proved to be the yellow pyrimidopyrrolopyridazine of type 4. However, we should
note that reaction of amine 6 with acetylacetone and benzoylacetone in alcohol, in contrast to compound 2,
requires the presence of traces of acid. Acid catalysis is also necessary to obtain hydrazone 7, while amine 2
reacts with benzaldehyde without a catalyst [3]. These data suggest decreased nucleophilicity of the N-amino
group in compound 6 compared with compound 2.
954

TABLE 1. 1H NMR Spectra of Synthesized Compounds
Com-
Chemical shifts, δ, ppm (J, Hz)*
pound
2.37 (3Н, s, 8-CH3); 2.61 (3Н, d, J = 1.2, 10-CH3); 3.45 (3Н, s, 3-CH3);
3.69 (3Н, s, 1-CH3); 6.22 (1Н, br. d, J = 1.1, 9-Н); 8.12 (1Н, s, 5-H)
4a
4b
2.43 (3H, s, 8-CH3); 2.58 (3H, s, 1-CH3); 3.40 (3H, s, 3-CH3); 6.24 (1H, s, 9-H);
7.38-7.50 (5H, m, Ph); 8.17 (1H, s, 5-H)
4c +
5b
4c
– 2.73 (3H, s, 10-CH ); 3.47 (3H, s, 3-CH ); 3.76 (3H, s, 1-CH ); 6.79 (1H, s, 9-H);
3
3
7.93 (2H, dd, J1 = 8.0, J23 = 2.0, o-HPh); 8.30 (1H, s, 5-H)*2
5b – 2.56 (3H, s, 8-CH3); 3.27 (3H, s, 4-CH3); 3.50 (3H, s, 2-CH3); 6.74 (1H, s, 9-H);
general signal: 7.35-7.55 [9H, m, 5-H and 5HPh (5b) + 3HPh (4c)]
2.30 (3H, s, 8-CH3); 2.62 (3H, d, J = 1.0, 10-CH3); 3.40 (3H, s, 3-CH3);
3.72 (3H, s, 1-CH3); 6.22 (1H, br. d, J = 1.0, 9-H); 7.38–7.51 (3H, m, m- and p-HPh);
7.69 (2H, d, J = 8.0, o-HPh)
4d
2.39 (3H, s, 8-CH3); 2.61 (3H, s, 1-CH3); 3.38 (3H, s, 3-CH3); 6.29 (1H, s, 9-H);
4e
5a
6
7.43-7.53 (3H, m, m- and p-HPh); 7.78 (2H, d, J = 8.1, o-HPh)
2.47 (3Н, s, 8-CH3); 2.93 (3Н, d, J = 0.8, 10-CH3); 3.42 (3Н, s, 2-CH3);
3.47 (3Н, s, 4-CH3); 6.61 (1Н, br. d, J = 0.7, 9-Н); 7.36 (1Н, s, 5-H)
3.16 (3H, s, 3-CH3); 3.29 (3H, s, 1-CH3); 6.14 (2H, s, NH2); 6.82 (1H, s, 7-H);
7.40 (3H, m, m- and p-HPh); 7.60 (2H, m, o-HPh)
3.23 (3H, s, 3-CH3); 3.41 (3H, s, 1-CH3); 7.45 (3H, m, m-, p-HPh);
7
7.63 (3H, m, o-HPh and 7-H); 7.77 (1H, t, J = 8.0, m-HAr); 8.08 (1H, d, J = 7.7, p-HAr);
8.28 (1H, d, J = 8.1, o-HAr); 8.48 (1H, s, N=CH–Ph–H-2); 9.05 (1H, s, N=CH)
2.20 (3H, s, 6-CH3); 3.33 (3H, s, 3-CH3); 3.47 (3H, s, 1-CH3); 7.43 (2H, t, J = 7.4, m-HPh);
7.56 (1H, t, J = 7.3, p-HPh); 7.84 (2H, d, J = 7.0, o-HPh)
8
3.33 (3H, s, 3-CH3); 3.60 (3H, s, 1-CH3); 4.22 (2H, s, CH2); 7.45 (2H, t, J = 7.5, m-HPh);
9
7.58 (1H, t, J = 7.3, p-HPh); 7.83 (2H, d, J = 7.2, o-HPh)
1.86 (3H, s, COCH3); 3.17 (3H, s, 3-CH3); 3.29 (3H, s, 1-CH3); 6.96 (1H, s, 7-H);
7.35-7.45 (5H, m, Ph); 11.44 (1H, s, NH)
10
_______
* The spectra of compounds 4a,b,d,e, 4c + 5b, 5a, 8, 9 were taken in CDCl3,
the spectra of compounds 6, 7, and 10 were taken in DMSO-d6.
*2 The signals at 2.73 ppm and 6.79 ppm were broadened due to spin–spin
coupling of the corresponding protons.
O
Ph
O
Ph
N
Me
O
N
Me
O
AcCH2COR
N
N
N
NH2
N
Me
Me
N
Me
6
R
4d,e
4 d R = Me, e R = Ph
O
Ph
Me
NO2
N
N
N
O
N
Me
7
The spectral characteristics of products 4d,e (λmax 403 nm and 423 nm respectively) are very similar to
those for pyrimidopyrrolopyridazines 4a,b, which supports the structure of the latter, and are appreciably
different from the characteristics of isomer 5a. The quantum-chemical calculation of the electronic absorption
955

TABLE 2. Data for Acidic Deuteron Exchange (DMSO-d6–CD3CO2D, 10:1,
100°C, 1 h) in Amine 2, Chemical Shifts of Its C(5), C(7) Atoms and Protons
Bonded With Them in 1NMR and 13C Spectra*
% D
1Н NMR spectrum, δ, ppm 13С NMR spectrum, δ, ppm
Compound
5-H
4
7-H
49
5-H
7-H
C(5)
C(7)
7.25
—
6.60
6.80
119.5
104.4
104.9
2
6
—
131.9*2
_______
1
13
* The signals were assigned based on comparison of the H and C NMR
spectra of compounds 2 and 6.
*2 The downfield shift of the signal relative to the C(5) signal of compound 2
is explained by the electron-acceptor and anisotropic effect of the 5-Ph
substituent.
spectra gives comparable results. The calculated values of the long wavelength λmax are 382 (4a), 388 (4b),
402 (4d), 407 (4e), 327, 358 nm (shoulder) (5a). The deeper color of diones 4a-d compared with dione 5a is
obviously connected with the presence of an extended chromophore chain N(1)···N(7), where N(1) is the donor and
1
N(7) is the acceptor. We note that in the H NMR spectra of compounds 4a,d and 5a we observe spin–spin
coupling between the 9-H proton and protons of the 10-CH3 group, which is apparent as doublets with
4JMe,H = 0.8-1.1 Hz (Table 1). An analogous phenomenon was observed previously for the pyrimidopyrrolo-
pyridazine obtained from amine 1 [2].
Earlier we synthesized the previously unknown amine 6 from 1,3,6-trimethyluracil, which subsequently
was benzoylated by a Friedel–Crafts reaction to form ketone 8, brominated at the methyl group to the
6-bromomethyluracil derivative 9, and then underwent ring closure when treated with acetylhydrazine to form
amide 10, which was subjected to acid hydrolysis.
O
O
Me
O
Me
O
COPh
Me
Br2
N
PhCOCl
ZnCl2
N
N
Me
Me
N
Me
8
O
O
N
Me
10
Ph
N
Me
O
COPh
+
Me
O
H2O , ∆
AcNHNH2
N
N
6
NHAc
N
Me
9
CH2Br
Thus the reactivities of 6-aminopyrrolo[3,4-d]pyrimidinediones 2, 6 and the previously studied
5-aminopyrrolo[3,2-d]pyrimidinedione 1 are considerably different, which is due to the increased π-electron
rich character of the pyrrole ring, especially for the 7 position, in diones 2, 6 and consequently their higher
activity with respect to electrophiles.
956

TABLE 3. Effective Charges qeff on C(5) and C(7) Atoms in the Pyrrolo-
[3,4-d]pyrimidine-2,4-dione Molecule and the Stabilization Energies Est of
the Corresponding σ-Complexes
Atom
qeff, е
|Est| for H+, kcal/mol
|Est| for HCO+, kcal/mol
C(5)
C(7)
+0.102
-0.013
206.69
222.85
49.67
65.75
EXPERIMENTAL
1
The IR spectra were obtained on a Specord-75 spectrometer in vaseline oil. The H NMR spectra were
13
recorded on a Bruker DPX-250 (250 MHz) (Table 1), the C NMR spectra of amines 2 and 6 were taken in
DMSO-d6 on a Varian Unit-300 (75 MHz). The electronic absorption spectra of solutions of the compounds in
methanol (5·10-5 mol/l) were recorded on a Specord M-40 spectrometer. The melting points were determined in
open capillaries and were uncorrected. The course of the reactions and the purity of the compounds obtained
were monitored using TLC on Al2O3 (Brockmann activity II-III), eluent CHCl3 or CHCl3–EtOAc, 5:1;
visualization in UV light and iodine vapors. Amine 2 was obtained using the familiar procedure in [3]. We used
the software package in [5] for the quantum-chemical calculations. The effective charges were calculated by the
DGauss method in a 6-31G basis; the stabilization energies for the s complexes were calculated in a 3-21G
basis; the electronic absorption spectra were calculated by the ZINDO CI method for optimized (AM1)
conformation.
b
1,3,8,10-Tetramethylpyrimido[4',5':3,4]pyrrolo[1,2- ]pyridazine-2,4(1H,3H)-dione (4a) and
b
A mixture of
2,4,8,10-Tetramethylpyrimido[5',4':3,4]pyrrolo[1,2- ]pyridazine-1,3(2H,4H)-dione (5a).
amine 2 (1 g, 5.15 mmol) and acetylacetone (0.54 ml, 5.17 mmol) in alcohol (10 ml) was refluxed for 3 h. The
precipitate forming after cooling was filtered out and carefully ground; the impurity of product 5a was extracted
with hot ethylacetate (3-6 times, ~5 ml each, TLC monitoring); the residue was recrystallized from DMF.
Compound 4a (950 mg, 72%) was obtained. Yellow prisms with yellow-green fluorescence in UV light;
mp 235-237°C. IR spectrum, ν, cm-1: 1575 (C=C), 1605, 1685 (C=O), 3120 (C(5)–H). UV spectrum, λmax, nm
(log ε): 237.1 (4.54), 270.5 (4.21), 279.2 (4.22), 317 (3.71), 391 (3.44). Found, %: C 60.68; H 5.40. C13H14N4O2.
Calculated, %: C 60.47; H 5.43.
The alcoholic mother liquor and the extract (EtOAc) with the precipitate forming from it were
combined, the solvents were distilled off to dryness, the residue was chromatographed on a column (l = 50 cm,
d = 1.5 cm) with Al2O3 (Brockmann activity III), eluent CHCl3. From the eluate of the colorless band with blue
fluorescence in UV light, after evaporation and recrystallization of the residue from alcohol we obtained 26 mg
(1.9%) of compound 5a. Colorless crystals with mp 278-280°C (sublimes). The solutions of compound 5a have
an intense blue fluorescence in UV light. IR spectrum, ν, cm-1: 1375 (C=C), 1625, 1660, 1705 (C=N, C=O).
UV spectrum, λmax, nm (log ε): 264.8 (4.32), 318.5 (3.75), 351.6 (3.81). Found, %: C 59.88; H 5.62.
C13H14N4O2. Calculated, %: C 60.47; H 5.43.
b
1,3,8-Trimethyl-10-phenylpyrimido[4',5':3,4]pyrrolo[1,2- ]pyridazine-2,4(1H,3H)-dione (4b).
Benzoylacetone (260 mg, 1.60 mmol) was added to amine 2 (300 mg, 1.55 mmol) in boiling alcohol (3 ml), and
the mixture was refluxed for 30 min. The precipitate forming after cooling was filtered out, washed with
alcohol, and recrystallized from DMF. We obtained 402 mg (81%) of product 4b. Yellow rhombic;
mp 224-226°C. IR spectrum, ν, cm-1: 1420 (C=C), 1540, 1680 (C=O). UV spectrum, λmax, nm (log ε): 238.5
(4.39), 273.5 (4.26), 317.5 (3.50), 409.6 (3.35). Found, %: C 67.77; H 5.13. C18H16N4O2. Calculated, %:
C 67.50; H 5.00.
957

The alcoholic mother liquor was evaporated to dryness; the residue was washed with ether (1-2 ml) and
chromatographed on a column (l = 50 cm, d = 1.5 cm) with Al2O3 (Brockmann activity III), eluent CHCl3. From
the eluate of the band with the highest Rf value (with blue fluorescence in UV light), after evaporation we
1
obtained 50 mg of a mixture of compounds 5b and 4c (according to H NMR data, 5b:4c, 3:2). Mixture of
compounds 4c and 5b. Found, %: C 66.96; H 4.83. C18H16N4O2. Calculated, %: C 67.50; H 5.00.
5-Benzoyl-1,3,6-trimethylpyrimidine-2,4-dione (8). A mixture of 1,3,6-trimethyluracil (10 g,
64 mmol), benzoyl chloride (7.4 ml, 64 mmol), and ZnCl2 (8.8 g, 64 mmol) in benzene (80 ml) was refluxed for
20 h; then water (50 ml) was added and the benzene was distilled off. After cooling, the precipitate was filtered
out, triturated with ether (20 ml); the product 8 that did not dissolve was filtered out, recrystallized from
2-propanol, and washed on the filter with ether. Yield 7.5 g (45%). Colorless needles; mp 135-136°C.
IR spectrum, ν, cm-1: 1605, 1630 (C=N), 1660, 1700 (C=O). Found, %: C 65.32; H 5.26. C14H14N2O3.
Calculated, %: C 65.10; H 5.43.
5-Benzoyl-6-bromomethyl-1,3-dimethylpyrimidine-2,4-dione (9). A solution of bromine (1.24 g,
7.75 mmol) in CHCl3 (10 ml) was added dropwise to a solution of ketone 8 (2 g, 7.75 mmol) in dry CHCl3
(10 ml) with stirring and heating on a water bath (50°C), the addition being made at such a rate that the reaction
mixture could become colorless after each drop, and then the mixture was boiled until rapid evolution of HBr
stopped (~1 h). The residue after distillation of the solvent was triturated with water (5 ml); the precipitate was
filtered out, washed with water (50 ml), and recrystallized from 2-propanol. We obtained 2.05 g (79%) of
product 9. Colorless needles; mp 169-171°C. IR spectrum, ν, cm-1: 1660, 1705 (C=O). Found, %: C 50.05;
H 3.95; Br 23.81. C14H13BrN2O3. Calculated, %: C 49.85; H 3.85; Br 23.73.
d
Acetyl-
6-Acetylamino-1,3-dimethyl-5-phenylpyrrolo[3,4- ]pyrimidine-2,4(1H,3H)-dione (10).
hydrazine (134 mg, 1 mmol) and triethylamine (0.125 ml, 0.89 mmol) were added to a solution of compound 9
(300 mg, 0.89 mmol) in alcohol (10 ml); the mixture obtained was refluxed for 2 h, then cooled down to 0°C,
and 192 mg (58%) of product 10 was filtered out that was sufficiently pure for further use. By recrystallization
of the latter from alcohol, we obtained an analytical sample. Colorless prisms; mp 276-278°C. IR spectrum,
ν, cm-1: 1570, 1635 (C=N), 1670, 1700 (C=O), 3200 (N–H). Found, %: C 61.23; H 5.24. C16H16N4O3.
Calculated, %: C 61.54; H 5.13.
d
A suspension of
6-Amino-1,3-dimethyl-5-phenylpyrrolo[3,4- ]pyrimidine-2,4(1H,3H)-dione (6).
amide 10 (463 mg, 1.48 mmol) in 10% aqueous HCl solution (4 ml) was refluxed with rapid stirring for 2 h
30 min and then cooled down; a 10% aqueous solution of KOH was added until the pH was about ~8, and the
mixture was stirred for another 30 min. The precipitate was filtered out, washed with 5 ml water, and dried; it
was heated twice with CHCl3 (2 × 2 ml), each time filtering after cooling. We obtained 350 mg (83%) of pure
1
(according to H NMR data) product 6. Colorless crystals; mp 233-235°C. IR spectrum, ν, cm-1: 1525 (C=C),
1595 (C=N), 1635, 1675 (C=O), 3300 (NH2). Found, %: C 61.85; H 5.10. C14H14N4O2. Calculated, %: C 62.21;
H 5.22.
m
d
1,3-Dimethyl-6-( -nitrobenzylidene)amino-5-phenylpyrrolo[3,4- ]pyrimidine-2,4(1H,3H)-dione (7).
m-Nitrobenzaldehyde (84 mg, 0.56 mmol) was added to ground amine 6 (150 mg, 0.56 mmol) in alcohol (2 ml)
containing traces of HCl while boiling; the mixture was refluxed for another 10 min. After cooling, the
precipitate was filtered out, washed with hot alcohol (3-5 ml), and recrystallized from DMF. Product 7 (135 mg,
60%) was obtained. Orange crystals; mp 278-280°C. IR spectrum, ν, cm-1: 1630, 1675 (C=O), 3080 (C(7)–H).
Found, %: C 62.36; H 4.15. C21H17N5O4. Calculated, %: C 62.53; H 4.22.
b
1,3,8,10-Tetramethyl-5-phenylpyrimido[4',5':3,4]pyrrolo[1,2- ]pyridazine-2,4(1H,3H)-dione (4d).
A mixture of amine 6 (180 mg, 0.67 mmol) and acetylacetone (0.1 ml, 0.8 mmol) in alcohol (3 ml) was refluxed
for 1 h in the presence of traces of HCl. The precipitate forming after cooling was filtered out and recrystallized
from DMF, and we obtained 176 mg (79%) of product 4d. Yellow crystals; mp 267-269°C. IR spectrum,
ν, cm-1: 1510 (C=N), 1605, 1675 (C=O). UV spectrum, λmax, nm (log ε): 246 (4.51), 335 (3.88), 403 (3.48).
Found, %: C 68.18; H 5.60. C19H18N4O2. Calculated, %: C 68.32; H 5.69.
958

b
1,3,8-Trimethyl-5,10-diphenylpyrimido[4',5':3,4]pyrrolo[1,2- ]pyridazine-2,4(1H,3H)-dione (4e)
was obtained similarly to dione 4d from amine 6 (300 mg, 1.12 mmol) and benzoylacetone (190 mg, 1.20 mmol)
in a yield of 413 mg (94%). Silky dark yellow crystals; mp 241-243°C. IR spectrum, ν, cm-1: 1595 (C=N), 1660,
1690 (C=O). UV spectrum, λmax, nm (log ε): 252.4 (4.48), 341 (3.82), 423 (3.40). Found, %: C 73.05; H 5.13.
C24H20N4O2. Calculated, %: C 72.73; H 5.05.
This research was carried out with the financial support of the "Universities of Russia. Basic Research"
program. Grant No. UR 05.01.041.
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