Synthesis of functional 2-substituted 4-phenyl-9H-pyrimido[4,5-b]indoles

Article abstract of DOI:10.1023/A:1021688616234

A method was developed for the synthesis of 2-oxo-4-phenyl-2,3-dihydro-9H-pyrimido[4,5-b]indole as well as of 2-chloro- and 2-nitramino-4-phenylpyrimido[4,5-b]indoles. The replacement of the chlorine atom in 2-chloropyrimidoindole gave rise to a number of

Full text of DOI:10.1023/A:1021688616234

Russian Chemical Bulletin, International Edition, Vol. 51, No. 11, pp. 2129—2133, November, 2002
2129
Synthesis of functional 2ꢀsubstituted 4ꢀphenylꢀ9Hꢀpyrimido[4,5ꢀb]indoles
ꢀ
V. P. Borovik and O. P. Shkurko
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences,
9 prosp. Akad. Lavrent´eva, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383 2) 34 4752. Eꢀmail: oshk@nioch.nsc.ru
A method was developed for the synthesis of 2ꢀoxoꢀ4ꢀphenylꢀ2,3ꢀdihydroꢀ9Hꢀpyrimiꢀ
do[4,5ꢀb]indole as well as of 2ꢀchloroꢀ and 2ꢀnitraminoꢀ4ꢀphenylpyrimido[4,5ꢀb]indoles. The
replacement of the chlorine atom in 2ꢀchloropyrimidoindole gave rise to a number of its
functional derivatives (morpholino, azido, and cyano). The reaction of 2ꢀchloroꢀsubstituted
pyrimidoindole with hydrazine hydrate and catalytic hydrogenation of 2ꢀnitraminopyrimidoꢀ
indole were studied.
Key words: 2ꢀoxoꢀ4ꢀphenylꢀ2,3ꢀdihydroꢀ9Hꢀpyrimido[4,5ꢀb]indole, 2ꢀsubstituted 4ꢀpheꢀ
nylꢀ9Hꢀpyrimido[4,5ꢀb]indoles, diazotization, nucleophilic substitution, catalytic hydrogeꢀ
nation.
Functional pyrimido[4,5ꢀb]indole derivatives, in
particular, its amino derivatives, exhibit a broad spectrum
of biological activities, which opens up a possibility of
their use in the drug design.1—4 Previously,5 we have deꢀ
veloped a procedure for the synthesis of 2ꢀRꢀ4ꢀphenylꢀ
9Hꢀpyrimido[4,5ꢀb]indoles 1 based on the reaction of
2ꢀethoxy(3ꢀbenzylidene)indolenine tetrafluoroborate (2)
with amidines or guanidines (Scheme 1).
condensation of tetrafluoroborate 2 with urea afforded a
product whose purification led to large losses resulting in
a low yield of crystalline 2ꢀoxoꢀ4ꢀphenylꢀ2,3ꢀdihydroꢀ
9Hꢀpyrimido[4,5ꢀb]indole (1e). We found that diazotizaꢀ
tion of 2ꢀaminopyrimidoindole 1c in AcOH at 80 °C afꢀ
forded compound 1e in a yield of >90% and this comꢀ
pound can be used in subsequent syntheses without addiꢀ
tional purification (Scheme 2). It should be noted that
this reaction performed at ∼20 °C gave the nitric salt of
the starting amine 3. The formation of the latter is associꢀ
ated with protonation of the basic aminopyrimidine fragꢀ
ment by nitric acid, which was generated due to disproꢀ
Scheme 1
Scheme 2
R = Me (a), Ph (b), NH2 (c), NHSO2Ar (d)
The synthesis of 2ꢀoxo derivative 1e (R = OH) acꢀ
cording to Scheme 1 proved to be inefficient. Thus, direct
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1974—1977, November, 2002.
1066ꢀ5285/02/5111ꢀ2129 $27.00 © 2002 Plenum Publishing Corporation

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Russ.Chem.Bull., Int.Ed., Vol. 51, No. 11, November, 2002
Borovik and Shkurko
portionation of nitrous acid.6 This conclusion was conꢀ
firmed by the synthesis of authentic nitrate 3 upon the
direct addition of HNO3 to a solution of amino derivative
1c in AcOH. The structure of nitrate 3 was established by
NMR spectroscopy and Xꢀray diffraction analysis.7
The reaction of 2ꢀoxoꢀsubstituted compound 1e with
the Vilsmeier reagent afforded 2ꢀchloroꢀ4ꢀphenylꢀ9Hꢀ
pyrimido[4,5ꢀb]indole (4) in high yield. The Cl atom
in the latter compound is labile in reactions with nucleoꢀ
philic reagents. We used hydrazine hydrate, morpholine,
sodium azide, and potassium cyanide as nucleophilic reꢀ
agents (Scheme 3).
However, all attempts to synthesize 2ꢀhydrazinoꢀ
pyrimidoindole 5 by the reaction of chloro derivative 4
with hydrazine hydrate failed. The reaction in DMSO at
temperatures below 90 °C did not lead to the replacement
of the Cl atom. The starting chloro derivative 4 disapꢀ
peared from the reaction mixture only when the temperaꢀ
ture was increased, an excess of hydrazine hydrate was
used, and the mixture was heated over a long period.
However, the reaction performed under these conditions
afforded a complex mixture of products from which only
2ꢀaminoꢀsubstituted derivative 1c (29%) and pyrimidoꢀ
indole 6 (14%) were isolated by preparative TLC. The
presence of 2ꢀhydrazineꢀsubstituted compound 5 in the
mixture was detected only from the line at m/z 275 ([M]+,
Irel 3%) in the mass spectrum. The reaction of chloro
derivative 4 with hydrazine hydrate in Nꢀmethylpyrrolꢀ
idone proceeded analogously. Only compounds 1c (20%)
and 6 (7%) were isolated from the reaction mixture by
preparative TLC. This result can be attributed to the fact
that 2ꢀhydrazineꢀcontaining derivative 5 contains the unꢀ
stable hydrazine group, which was subjected to reduction
and elimination under the reaction conditions.
Heating of 2ꢀchloropyrimidoindole 4 with other nuꢀ
cleophilic reagents in DMSO at 120 °C afforded the corꢀ
responding 2ꢀsubstituted pyrimidoindoles 7—9 in high
yields.
2ꢀNitraminoꢀ4ꢀphenylpyrimido[4,5ꢀb]indole (10),
which was prepared by the reaction of tetrafluoroborate 2
with nitroguanidine according to a procedure analogous
to that described previously,5 was also of interest for the
synthesis of 2ꢀsubstituted pyrimidoindoles. It was expected
that the reactions of 2ꢀnitraminoꢀsubstituted compound
10 with nucleophiles, such as hydrazine hydrate, morphoꢀ
line, hydroxylamine, etc., would give the corresponding
functional derivatives by analogy with the synthesis of
these derivatives from 2ꢀnitraminopyrimidines.8—10 Howꢀ
ever, unlike the latter compounds, 2ꢀnitraminopyrimidoꢀ
indole 10 reacted with none of the aboveꢀmentioned nuꢀ
cleophiles. There are several reasons for such a behavior.
First, as was exemplified by the chloro derivative, the
nucleophilic substitution in the pyrimidoindole series proꢀ
ceeds more difficultly than that in the pyrimidine series.
Second, deprotonation of the nitramino group under the
action of rather basic nucleophilic reagents and blocking
Scheme 3

2ꢀSubstituted 4ꢀphenylpyrimido[4,5ꢀb]indoles
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 11, November, 2002 2131
Scheme 4
2ꢀOxoꢀ4ꢀphenylꢀ2,3ꢀdihydroꢀ9Hꢀpyrimido[4,5ꢀb]indole (1e).
A solution of NaNO2 (0.72 g, 10.4 mmol) in water (4 mL) was
added dropwise with stirring to a solution of compound 1c (0.45 g,
1.7 mmol) in AcOH (16 mL) at 80 °C for 1—2 min. The reaction
mixture was stirred at this temperature for 3 h and then cooled
to 10—15 °C. The precipitate was separated, successively washed
with EtOH (2×3 mL) and water (5 mL), and dried. Compound
1e was obtained in a yield of 0.42 g (93%), m.p. >360 °C. The
sample for analysis was recrystallized from DMF. Found (%):
C, 73.70; H, 4.34; N, 16.20. C16H11N3O. Calculated (%):
C, 73.55; H, 4.24; N, 16.08. MS, m/z (Irel (%)): 261 [M]+ (83);
260 [M – 1]+ (100). IR, ν/cm–1: 1645 (C=O); 3400 (NH).
1H NMR (500 MHz), δ: 6.97 (ddd, 1 H, H(6), 3J = 8.0 Hz, 3J =
5.0 Hz, 4J = 3.0 Hz); 7.18 (d, 1 H, H(8), 3J = 7.5 Hz); 7.25—7.28
(m, 2 H, H(5), H(7)); 7.63—7.69 (m, 3 H, Ph); 7.75—7.78 (m,
2 H, Ph); 11.73 (br.s, 2 H, H(1), H(9)). 13C NMR (125 MHz),
δ: 100.85, 111.24, 119.64, 120.34, 120.78, 126.34, 128.69, 128.85,
131.03, 131.67, 139.95, 151.92, 157.08, 162.58.
2ꢀAminoꢀ4ꢀphenylꢀ9Hꢀpyrimido[4,5ꢀb]indole nitrate (3). Soꢀ
dium nitrite (0.08 g, 1.2 mmol) was added portionwise with
stirring to a solution of compound 1c (0.3 g, 1.15 mmol) in
AcOH (7 mL) at 20 °C for 20 min. The reaction mixture was
stirred at this temperature for 30 min. The precipitate that formed
was washed with water and dried in vacuo. Nitrate 3 was obꢀ
tained in a yield of 0.17 g (43%), m.p. 243—248 °C. The IR
spectrum and m.p. of the product were identical with those of an
authentic sample.7
of the nucleophilic attack at the reaction center of the
resulting anion must not be ruled out (cf. the acidities of
some nitraminopyrimidines: pKa < 4 11).
We attempted to prepare 2ꢀhydrazinopyrimidoindole
5 by catalytic hydrogenation of nitramino derivative 10
over Pd/C in EtOH. However, this reaction gave a mixꢀ
ture containing 2ꢀaminopyrimidoindole 1c as the major
product. The reaction mixture contained also insignifiꢀ
cant amounts of pyrimidoindole 6 and 2ꢀethoxypyrimidoꢀ
indole 11 (Scheme 4). We failed to isolate hydrazine deꢀ
rivative 5 although the mass spectrum of the mixture had
the corresponding line at m/z 275 ([M]+, Irel 4%).
Apparently, compound 1c was generated through
hydrogenolysis of the N—N bond in intermediate hydraꢀ
zine derivative 5. An analogous transformation of the hyꢀ
drazine group into the amino group was observed upon
chemical or catalytic reduction of hydrazinopyrimidines.12
The formation of compounds 6 and 11 can be interpreted
as elimination of the hydrazine group from hydrazine
derivative 5 accompanied by its substitution for the H
atom or the ethoxy group.
The structures of the new pyrimido[4,5ꢀb]indole deꢀ
1
rivatives were confirmed by H and 13C NMR spectrosꢀ
copy taking into account the known data.13
To summarize, we developed a convenient procedure
for the synthesis of 2ꢀoxoꢀ4ꢀphenylꢀ2,3ꢀdihydroꢀ9Hꢀ
pyrimido[4,5ꢀb]indole and of 2ꢀchloroꢀ4ꢀphenylpyrimiꢀ
do[4,5ꢀb]indole as the key compounds for the preparaꢀ
tion of different 2ꢀsubstituted pyrimidoindoles.
2ꢀChloroꢀ4ꢀphenylꢀ9Hꢀpyrimido[4,5ꢀb]indole (4). Comꢀ
pound 1e (1.95 g, 7.5 mmol) was added with stirring to the
Vilsmeier reagent, which was prepared from POCl3 (7 mL) and
DMF (23 mL), at 20 °C. Then the reaction mixture was heated
to 60 °C, stirred at this temperature for 5 h, cooled, and poured
onto ice. The precipitate that formed was refluxed in 15% HCl
(160 mL) for 1.5 h. The precipitate was separated, washed with a
solution of NaHCO3 and then with water until the reaction
mixture became neutral, and dried in vacuo. Pyrimidoindole 4
was obtained in a yield of 1.63 g (78%), m.p. 312—315 °C (from
xylene). Found (%): C, 68.30; H, 3.65; Cl, 12.80; N, 14.80.
C16H10ClN2. Calculated (%): C, 68.68; H, 3.60; Cl, 12.67;
N, 15.02. MS, m/z (Irel (%)): 279 [M]+ (72); 278 [M – 1]+
(100). IR, ν/cm–1: 3410 (NH). 1H NMR (400 MHz), δ: 7.23
(td, 1 H, H(6), J = 8.0 Hz, J = 1.2 Hz); 7.55 (td, 1 H, H(7),
3J = 8.0 Hz, 4J = 0.8 Hz); 7.61 (d, 1 H, H(8), 3J = 8.0 Hz);
7.65—7.70 (m, 3 H, Ph); 7.78 (d, 1 H, H(5), 3J = 8.0 Hz);
7.89—7.94 (m, 2 H, Ph); 12.50—13.00 (br.s, 1 H, NH).
13C NMR (100 MHz), δ: 109.80 (C(4a)); 112.33 (C(8)); 118.24
(C(4b)); 121.37 (C(6)); 121.92 (C(5)); 128.14 (C(7)); 128.78
Experimental
The IR spectra were recorded on a Specord Mꢀ80 spectromꢀ
eter in KBr pellets. The 1H and 13C NMR spectra were meaꢀ
sured on Bruker ACꢀ200, Bruker ACꢀ400, and Bruker DRXꢀ500
spectrometers in DMSOꢀd6 using the signals of the solvent at
δ 2.50 (1H) and 39.5 (13C) with respect to Me4Si as the internal
standard. The mass spectra were obtained on a Finnigan
MATꢀ8200 spectrometer (EI, 70 eV). The course of the reacꢀ
tions was monitored by TLC on Silufol UVꢀ254 plates; visualꢀ
ization was carried out with UV light. The solvents were dried
according to standard procedures.
3
4

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Borovik and Shkurko
(Co, Cm, Ph); 130.55 (Cp, Ph); 136.90 (Ci, Ph); 138.97 (C(8a));
155.14 (C(9a)); 157.69 (C(4)); 160.81 (C(2)).
(100 mg, 2 mmol) was added and the reaction mixture was
heated until the starting compound 4 was consumed (13 h),
after which the reaction mixture was cooled, poured into water
(100 mL), and extracted with AcOEt (4×25 mL). The combined
extracts were washed with water and concentrated to dryꢀ
ness under reduced pressure. The residue was chromatoꢀ
graphed on Silufol plates (CHCl3—EtOAc, 1 : 3, as the eluent).
Compound 1c was isolated in a yield of 15 mg (20%) and
compound 6 was isolated in a yield of 5 mg (7%) as described
above.
2ꢀNitraminoꢀ4ꢀphenylꢀ9Hꢀpyrimido[4,5ꢀb]indole (10).
Nitroguanidine (1.5 g, 14.4 mmol) was added to a solution of
MeONa, which was prepared from Na (1.0 g, 43 mmol) in
MeOH (50 mL). The reaction mixture was refluxed for 1 h and
cooled to ∼20 °C. Then tetrafluoroborate 2 5 (4.9 g, 14.2 mmol)
was added. The reaction mixture was refluxed with stirring for
5 h and cooled. The precipitates of NaBF4 and unconsumed
nitroguanidine were filtered off. The methanolic filtrate was
acidified with concentrated HCl to pH 5. The precipitate that
formed was separated, washed with water and EtOH (5 mL),
and dried in vacuo. Compound 10 was obtained in a yield of
1.7 g (39%). The sample for analysis was crystallized from DMF.
According to TLC (Rf 0.40, AcOEt—CHCl3, 1 : 1, as the eluꢀ
ent), the product was pure but it did not have a sharp m.p.
(noticeable melting of the crystals with decomposition was obꢀ
served at 280—320 °C). Found (%): C, 62.94; H, 3.77; N, 22.63.
2ꢀAzidoꢀ4ꢀphenylꢀ9Hꢀpyrimido[4,5ꢀb]indole (7). Sodium
azide (0.21 g, 3.2 mmol) was added to a solution of pyrimidoꢀ
indole 4 (0.3 g, 1.1 mmol) in dry DMSO (20 mL). The reaction
mixture was heated with stirring at 120 °C for 6 h, cooled to
∼20 °C, and poured into water (200 mL). The finely dispersed
precipitate that formed was separated and dried in vacuo.
Pyrimidoindole 7 was obtained in a yield of 0.29 g (95%), m.p.
238—243 °C (from xylene). Found (%): C, 66.74; H, 3.56;
N, 28.85. C16H10N6. Calculated (%): C, 67.12; H, 3.52; N, 29.36.
MS, m/z (Irel (%)): 286 [M]+ (23); 258 [M – 28]+ (100). IR,
ν/cm–1: 2137 (N3); 3414 (NH).
2ꢀMorpholinoꢀ4ꢀphenylꢀ9Hꢀpyrimido[4,5ꢀb]indole (8) was
prepared analogously to compound 7 from pyrimidoindole 4
(0.3 g, 1.1 mmol) and morpholine (0.29 g, 3.3 mmol) in a yield
of 0.31 g (86%), m.p. 254—258 °C (from xylene). Found (%):
C, 72.30; H, 5.38; N, 16.69. C20H18N4O. Calculated (%):
C, 72.70; H, 5.49; N, 16.96. MS, m/z (Irel (%)): 330 [M]+ (80);
329 [M – 1]+ (19); 300 [M – 30]+ (40); 299 [M – 31]+ (100).
2ꢀCyanoꢀ4ꢀphenylꢀ9Hꢀpyrimido[4,5ꢀb]indole (9) was preꢀ
pared analogously to compound 7 from pyrimidoindole 4 (0.2 g,
0.7 mmol) and KCN (0.14 g, 2.1 mmol) in a yield of 0.17 g
(91%), m.p. 316—318 °C (from xylene). Found (%): C, 74.97;
H, 3.66; N, 21.16. C17H10N4. Calculated (%): C, 75.54; H, 3.73;
N, 20.73. MS, m/z (Irel (%)): 270 [M]+ (55); 269 [M – 1]+
(100). IR, ν/cm–1: 2243 (C≡N); 3400, 3500 (NH).
Reaction of 2ꢀchloroꢀ4ꢀphenylꢀ9Hꢀpyrimido[4,5ꢀb]indole (4)
with hydrazine hydrate. A. Hydrazine hydrate (99%, 0.13 g,
2.6 mmol) was added to a solution of pyrimidoindole 4 (0.36 g,
1.3 mmol) in dry DMSO (20 mL). The reaction mixture was
heated with stirring at 100—110 °C for 7 h. Then hydrazine
hydrate (0.5 g, 10 mmol) was added and the reaction mixture
was heated until the starting compound 4 was consumed (9 h),
after which the reaction mixture was cooled and poured into
water (200 mL). The precipitate that formed was separated,
washed with water until the washings became neutral, and dried
in vacuo. A crude product was obtained in a yield of 0.32 g,
m.p. 200—300 °C.
C
16H11N5O2. Calculated (%): C, 62.90; H, 3.60; N, 22.90. MS,
m/z (Irel (%)): 305 [M]+ (8); 259 [M – 46]+ (100). IR, ν/cm–1
1353 (NO2); 3230, 3240 (NH). 1H NMR (500 MHz), δ: 7.20 (t,
:
3
3
1 H, H(6), J = 8.0 Hz); 7.51 (t, 1 H, H(7), J = 8.0 Hz); 7.56
3
(d, 1 H, H(8), J = 8.0 Hz); 7.66—7.69 (m, 3 H, Ph); 7.71 (d,
1 H, H(5), 3J = 8.0 Hz); 7.90—7.94 (m, 2 H, Ph); 12.76 (br.s,
1 H, NH); 14.20—14.70 (br.s, 1 H, NH). 13C NMR (50 MHz),
δ: 108.05 (C(4a)); 112.2 (C(8)); 118.8 (C(4b)); 121.3 and 121.6
(C(5), C(6)); 127.6 (C(7)); 128.6 and 128.7 (Co, Cm, Ph); 130.7
(Cp, Ph); 136.0 (Ci, Ph); 139.4 (C(8a)); 152.6 (C(9a)); 157.5
and 158.0 (C(2), C(4)).
Hydrogenation of 2ꢀnitraminoꢀ4ꢀphenylꢀ9Hꢀpyrimiꢀ
do[4,5ꢀb]indole (10). A weighed sample of 2ꢀnitraminopyrimidoꢀ
indole 10 (0.2 g, 0.65 mmol) was hydrogenated over 4% Pd/C in
EtOH (20 mL) at 35—40 °C until the starting compound disapꢀ
peared (TLC control). The catalyst was separated, the solution
was concentrated to dryness under reduced pressure, and
the residue (104 mg) was chromatographed on Silufol plates
(CHCl3—EtOAc, 1 : 3). 2ꢀAminopyrimidoindole 1c was isolated
from the lower zone (Rf 0.30) in a yield of 79 mg (47%).
Pyrimidoindole 6 was isolated from the medium zone (Rf 0.60)
in a yield of 12 mg (7.5%). 2ꢀEthoxyꢀ4ꢀphenylꢀ9Hꢀpyrimiꢀ
do[4,5ꢀb]indole (11) was isolated from the upper zone (Rf 0.80)
in a yield of 11 mg (6%), m.p. 245—255 °C. Highꢀresolution
mass spectrum, found: m/z 289.12149 [M]+. C18H15N3O. Calꢀ
The product (79 mg) was chromatographed on Silufol plates
(CHCl3—AcOEt, 1 : 1, as the eluent). The individual compounds
were eluted from different zones with EtOH. Aminopyrimidoꢀ
indole 1c was isolated from the lower zone (Rf 0.30) in a yield of
23 mg (29%). The IR spectrum and m.p. of this compound were
identical with those (6) of an authentic sample. 4ꢀPhenylꢀ9Hꢀ
pyrimido[4,5ꢀb]indole was isolated from the upper zone (Rf 0.70)
in a yield of 11 mg (14%), m.p. 215—220 °C. Highꢀresolution
mass spectrum, found: m/z 245.0942 [M]+. C16H11N3. Calcuꢀ
lated: M = 245.0953. 1H NMR (400 MHz), δ: 7.19 (td, 1 H,
H(6), 3J = 7.5 Hz, 4J = 1.1 Hz); 7.52 (td, 1 H, H(7), 3J = 7.7 Hz,
3
4J = 0.9 Hz); 7.60 (d, 1 H, H(8), J = 8.0 Hz); 7.62—7.67 (m,
3 H, Ph); 7.80 (d, 1 H, H(5), 3J = 8.0 Hz); 7.88—7.94 (m, 2 H,
Ph); 8.98 (s, 1 H, H(2)); 12.52 (br.s, 1 H, NH). 13C NMR
(50 MHz), δ: 110.3 (C(4a)); 112.0 (C(8)); 118.6 (C(4b)); 120.7
(C(6)); 122.0 (C(5)); 127.7 (C(7)); 128.7 (Cm, Ph); 128.7
(Co, Ph); 130.0 (Cp, Ph); 138.3, 138.6 (Ci, C(8a)); 154.2 (C(2));
156.1 (C(9a)); 159.0 (C(4)).
culated: M = 289.12150. H NMR (200 MHz), δ: 1.39 (t, 3 H,
1
Me, 3J = 7.0 Hz); 4.46 (q, 2 H, CH2, 3J = 7.0 Hz); 7.12 (td, 1 H,
H(6), 3J = 7.5 Hz, 4J = 1.1 Hz); 7.40 (td, 1 H, H(7), 3J = 8.0 Hz,
4J = 0.7 Hz); 7.48 (d, 1 H, H(8), 3J = 7.5 Hz); 7.60—7.65 (m,
3 H, Ph); 7.67 (d, 1 H, H(5), 3J = 7.5 Hz); 7.87—7.93 (m, 2 H,
Ph); 12.24 (br.s, 1 H, NH). 13C NMR (50 MHz), δ: 14.5 (Me);
62.5 (CH2); 105.9 (C(4a)); 111.6 (C(8)); 119.2 (C(4b)); 120.5
and 120.8 (C(5), C(6)); 126.2 (C(7)); 128.6 (Co, Cm, Ph); 130.0
(Cp, Ph); 138.1 (Ci, Ph); 138.4 (C(8a)); 158.9 (C(9a)); 160.8
(C(4)); 162.6 (C(2)).
B. Hydrazine hydrate (99%, 46 mg, 0.9 mmol) was added to
a solution of pyrimidoindole 4 (84 mg, 0.3 mmol) in dry
Nꢀmethylpyrrolidone (6 mL). The reaction mixture was heated
with stirring at 100—110 °C for 17 h. Then hydrazine hydrate

2ꢀSubstituted 4ꢀphenylpyrimido[4,5ꢀb]indoles
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 11, November, 2002 2133
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Received March 7, 2002;
in revised form May 13, 2002