Synthesis of 12-aryl-1-oxo-1,2,3,4,5,12-hexahydroindolo[2,1-b]quinazoline-6-carbonitriles by recyclization of 11-aryl-1-oxo-2,3,4,5,10b,11-hexahydro-1H-indolo[2,3-b] quinoline-10b-carbonitriles

Article abstract of DOI:10.1023/A:1021352502237

A general and convenient method for the synthesis of 12-aryl-1-oxo-1,2,3,4,5,12-hexahydroindolo[2,1-b]quinazoline-6-carbonitriles was proposed. The method is based on the recyclization of 11-aryl-1-oxo-2,3,4,5,10b,11-hexahydro-1H-indolo[2,3-b] quinoline-10b-carbonitriles. The structure of 12-(3-methoxyphenyl)-8-methyl-1-oxo-1,2,3,4,5,12-hexahydroindolo[2,1-b] quinazoline-6-carbonitrile was studied by X-ray diffraction analysis.

Full text of DOI:10.1023/A:1021352502237

Russian Chemical Bulletin, International Edition, Vol. 51, No. 10, pp. 1869—1874, October, 2002
1869
Synthesis of 12ꢀarylꢀ1ꢀoxoꢀ1,2,3,4,5,12ꢀhexahydroindoloꢀ
[2,1ꢀb]quinazolineꢀ6ꢀcarbonitriles by recyclization of 11ꢀarylꢀ1ꢀoxoꢀ
2,3,4,5,10b,11ꢀhexahydroꢀ1Нꢀindolo[2,3ꢀb]quinolineꢀ10bꢀcarbonitriles
B. V. Lichitsky,a D. V. Kozhinov,a L. G. Vorontsova,a Z. A. Starikova,b A. A. Dudinov,a and М. М. Krayushkina
ꢀ
aN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5328. Eꢀmail: mkray@ioc.ac.ru
bA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5085
A general and convenient method for the synthesis of 12ꢀarylꢀ1ꢀoxoꢀ1,2,3,4,5,12ꢀhexaꢀ
hydroindolo[2,1ꢀb]quinazolineꢀ6ꢀcarbonitriles was proposed. The method is based on the
recyclization of 11ꢀarylꢀ1ꢀoxoꢀ2,3,4,5,10b,11ꢀhexahydroꢀ1Нꢀindolo[2,3ꢀb]quinolineꢀ10bꢀ
carbonitriles. The structure of 12ꢀ(3ꢀmethoxyphenyl)ꢀ8ꢀmethylꢀ1ꢀoxoꢀ1,2,3,4,5,12ꢀhexahydroꢀ
indolo[2,1ꢀb]quinazolineꢀ6ꢀcarbonitrile was studied by Xꢀray diffraction analysis.
Key words: cyclic enehydrazino ketones, arylidenemalononitriles, 11ꢀarylꢀ1ꢀoxoꢀ
2,3,4,5,10b,11ꢀhexahydroꢀ1Нꢀindolo[2,3ꢀb]quinolineꢀ10bꢀcarbonitriles, recyclization, 12ꢀarylꢀ
1ꢀoxoꢀ1,2,3,4,5,12ꢀhexahydroindolo[2,1ꢀb]quinazolineꢀ6ꢀcarbonitriles, Xꢀray diffraction analysis.
Fused heterocyclic systems containing indole and pyꢀ
rimidine fragments compose some biologically active subꢀ
stances, in particular, antibiotic tryptanthrin.1—3 We have
previously4,5 found a new stereoselective rearrangement
of Nꢀarylaminoꢀsubstituted 1,4ꢀdihydropyridines, which
affords 11ꢀarylꢀ1ꢀoxoꢀ2,3,4,5,10b,11ꢀhexahydroꢀ1Hꢀ
indolo[2,3ꢀb]quinolineꢀ10bꢀcarbonitriles (1) containing
partially hydrogenated indole and pyridine fragments.
In this work we describe the recyclization of heterocyꢀ
clic system 1 to 12ꢀarylꢀ1ꢀoxoꢀ1,2,3,4,5,12ꢀhexahydroꢀ
indolo[2,1ꢀb]quinazolineꢀ6ꢀcarbonitriles (2) in 67—95%
yields. The recyclization occurs upon prolonged heating
of quinindolines 1 in ethanol in the presence of the strong
nonꢀnucleophilic base DBU. Quinazolines 2 that formed
are colorless or weakly colored highꢀmelting crystalline
compounds, which are virtually insoluble in ethanol to
facilitate substantially their isolation.
The structures of compounds 2 were confirmed by the
1Н NMR spectroscopic and elemental analysis data
(Tables 1 and 2). The structure of 12ꢀ(3ꢀmethoxyꢀ
Table 1. Yields and elemental analysis data for compounds 2
Comꢀ
pound
Substituents
Yield
(%)
Found
Calculated
Molecular
formula
(%)
R
Ar
X
С
H
N
Br
—
2a
2b
2c
2d
2e
2f
Me
C6H5
Me
87
85
95
90
80
78
67
78.82
78.71
63.25
63.17
63.79
63.90
65.10
65.22
74.91
74.78
75.29
75.18
75.68
75.89
6.15
6.08
3.74
3.86
4.32
4.20
4.70
4.82
5.07
5.18
5.64
5.52
6.37
6.12
11.23
11.01
10.20
10.05
9.86
9.72
9.20
9.13
11.32
11.37
11.07
10.96
10.01
10.21
С25Н23N3О
H
H
4ꢀBrC6H4
4ꢀBrC6H4
H
Me
Me
H
19.01
19.10
18.60
18.48
17.50
17.36
—
C22H16BrN3O
C23H18BrN3O
C25H22BrN3O
C23H19N3O2
C24H21N3O2
C26H25N3O2
Me
H
4ꢀBrC6H4
3ꢀMeOC6H4
H
3ꢀMeOC6H4 Me
—
—
2g
Me 3ꢀMeOC6H4 Me
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1720—1725, October, 2002.
1066ꢀ5285/02/5110ꢀ1869 $27.00 © 2002 Plenum Publishing Corporation

1870
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 10, October, 2002
Lichitsky et al.
1
Table 2. Н NMR spectra (DMSOꢀd6, δ, J/Hz) of compounds 2
Comꢀ
pound
CMe2
(s, 3 H)
CH2
CH
(s, 1 Н)
NH
(br.s, 1 Н)
Ar
Me
(s, 3 H)
2a
2b
2c
2d
2e
0.85; 1.05
2.05 (d, 1 Н, J = 18);
2.25 (d, 1 H, J = 18);
2.55—2.65 (m, 2 H)
1.80—2.05 (m, 2 H);
2.25—2.35 (m, 2 H);
2.70—2.80 (m, 2 H)
1.80—2.05 (m, 2 H);
2.20—2.30 (m, 2 H);
2.60—2.70 (m, 2 H)
2.05 (d, 1 Н, J = 18);
2.25 (d, 1 H, J = 18);
2.55—2.65 (m, 2 H)
1.80—2.05 (m, 2 H);
2.25—2.35 (m, 2 H);
2.65—2.75 (m, 2 H)
6.40
6.48
6.42
6.40
6.45
11.25
11.25
11.45
11.20
11.25
6.85 (d, 1 H, J = 8);
7.10—7.30 (m, 7 H)
2.30
—
—
—
7.00—7.15 (m, 2 H);
7.25 (d, 2 H, J = 8);
7.30—7.50 (m, 4 H)
6.85 (d, 1 H, J = 8);
7.20—7.30 (m, 3 H);
7.45 (d, 2 H, J = 8)
6.85 (d, 1 Н, J = 8);
7.15—7.25 (m, 4 Н);
7.45 (d, 2 Н, J = 8)
3.70 (s, 3 Н, ОМе);
6.72 (m, 2 H);
2.30
2.30
—
0.90; 1.10
—
6.90 (s, 1 Н);
7.00—7.15 (m, 3 Н);
7.40 (m, 2 Н)
2f
—
1.80—2.05 (m, 2 H);
2.25—2.35 (m, 2 H);
2.70—2.80 (m, 2 H)
6.40
6.40
11.30
11.20
3.70 (s, 3 Н, ОМе);
6.70 (d, 2 H, J = 8);
7.25 (d, 2 H, J = 8);
7.30—7.50 (m, 4 Н)
3.65 (s, 3 Н, ОМе);
6.70—6.75 (m, 2 H);
6.85—6.90 (m, 2 H);
7.10—7.20 (m, 3 Н);
7.30 (d, 1 Н, J = 8)
2.30
2.30
2g
0.90; 1.10
2.10 (d, 1 Н, J = 18);
2.30 (d, 1 H, J = 18);
2.55—2.70 (m, 2 H)
C(21)
O(2)
C(18)
C(19)
C(17)
C(20)
C(16)
C(15)
C(12)
O(1)
C(1)
C(10)
C(9)
C(8)
C(3)
C(2)
C(10A)
C(6A)
C(12A)
C(4A)
N(5)
C(14)
N(11)
C(6)
C(4)
C(7)
C(5A)
C(13)
N(1)
Fig. 1. Structure of compound 2f.

Synthesis of indolo[2,1ꢀb]quinazolines
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 10, October, 2002
1871
phenyl)ꢀ8ꢀmethylꢀ1ꢀoxoꢀ1,2,3,4,5,12ꢀhexahydroindoꢀ
lo[2,1ꢀb]quinazolineꢀ6ꢀcarbonitrile (2f) was established
by Xꢀray diffraction analysis (Fig. 1).
reaction mixture is acidified with an equivalent amount of
acetic acid after a time interval insufficient for the compleꢀ
tion of the reaction (TLC monitoring). The higher stabilꢀ
ity of anion 5 over that of the anion of initial heterocycle 3
seems to be the driving force of the rearrangement.
This recyclization also occurs in an acidic medium.
For example, refluxing of initial indoloquinolines 1 in a
mixture of acetic and trifluoroacetic acid affords amides 6.
The structures of compounds 6 were confirmed by the
transformation of the products of baseꢀcatalyzed reꢀ
cyclization of 2 into amides 6 on heating in a mixture of
acetic and trifluoroacetic acids (Scheme 2). The nitrile
function is transformed into the amide function, most
likely, under the action of a minor amount of water, which
is contained in the mixture of acids used.
The following scheme of formation of quinazolines 2
can be proposed. In the first stage, anion 3 is rapidly
generated, which is indicated by the fast dissolution of
initial compounds 1 in ethanol after the addition of an
equimolar amount of DBU. Then the anion undergoes
the tetrahydropyridine cycle opening to form anion 4,
which is recyclized to anion 5. The subsequent acidificaꢀ
tion of the reaction mixture with acetic acid affords prodꢀ
uct 2 in high yield (Scheme 1). The high rate of reꢀ
cyclization of 4 to 5 is confirmed by the isolation of a
mixture of initial compound 1 and product 2. The mixꢀ
ture contains no protonated forms of intermediate 4 if the
Scheme 1
2a
Ar
R
2b
Ph
Me
Me
2c
4ꢀBrC6H4
2d
2e
2f
2g
4ꢀBrC6H4 4ꢀBrC6H4
3ꢀMeOC6H4
3ꢀMeOC6H4
3ꢀMeOC6H4
H
H
H
Me
Me
Me
H
H
H
Me
Me
Me
X

1872
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 10, October, 2002
Lichitsky et al.
Scheme 2
Scheme 3
The rearrangement becomes impossible in the case of
compounds 7 bearing the methyl group at the nitrogen
atom. The reaction of 7 with DBU affords tetrahydroꢀ
indoloquinoline 8 due to the elimination of hydrogen
cyanide. Indoloquinolines 7 were synthesized according
to the scheme including the reaction of arylidene derivaꢀ
tives of malononitrile with enamino ketone 10 and proꢀ
longed refluxing of dihydropyridines 9 that formed in ethaꢀ
nol (Scheme 3). Products 7 can also be obtained directly
from arylidinemalononitriles and enamino ketone 10 withꢀ
out isolation of intermediate compounds 9.
The 1Н NMR spectra show that compounds 9 exist as
a mixture of two rotamers (А and В), like their analogs
containing no methyl group at the nitrogen atom.6
Rotamers А and В exhibit different chemical shifts for the
signals of protons in position 4 of the dihydropyridine
ring and protons of the amino group. Two rotamers can
be observed, probably, due to the hindered rotation about
the N—N bond because the molecule is sterically overꢀ
crowded. It is noteworthy that 1,4ꢀdihydropyridines bearꢀ
ing an aryl substituent in position 4 are characterized by
the sterically hindered boat conformation.7
molecule is planar (the rootꢀmeanꢀsquare deviation is
0.04 Å). The С(3) and С(12) atoms deviate from this
plane by 0.563 and 0.332 Å, respectively. The methoxyꢀ
phenyl substituent is pseudoꢀaxially oriented with respect
to cycle В. The benzene ring is turned out about the
С(12)—С(15) bond with respect to the framework of the
molecule by 88.40°. The methoxyl group is turned out by
8.38° with respect to the benzene ring.
The structure of 12ꢀ(3ꢀmethoxyphenyl)ꢀ8ꢀmethylꢀ1ꢀ
oxoꢀ1,2,3,4,5,12ꢀhexahydroindolo[2,1ꢀb]quinazolineꢀ6ꢀ
carbonitrile (2f) was studied by Xꢀray diffraction analysis
(Fig. 1, Tables 3 and 4). The basis of the molecule is a
tetracyclic framework consisting of three consequently
fused fragments, namely, cyclohexenone, pyrimidine, and
indole joint along the С(4а)—С(12а) and N(11)—С(5а)
bonds. The cyclohexenone fragment (А) has a sofa conꢀ
formation: the С(1), С(2), С(4), С(4а), and С(12а) atꢀ
oms lie in the same plane (with an accuracy of 0.03 Å),
and the С(3) atom deviates from this plane by 0.650 Å.
The pyrimidine fragment (В) also takes the sofa conforꢀ
mation, but much more flattened: the С(12) atom deviꢀ
ates from the plane of other five atoms, viz., С(12а),
С(4а), N(5), С(5а), and N(11) (the plane holds with an
accuracy of 0.01 Å), by 0.177 Å. The indole fragment
(С) is planar within 0.008 Å. The angles between the А,
В, and С fragments do not exceed 2—5°. Thus, except for
the С(3) and С(12) atoms, the tetracyclic fragment of the
The tetracyclic framework in molecule 2f is, in esꢀ
sence, a structural isomer with respect to the tetracyclic
framework in the earlier studied molecules of 9ꢀmethylꢀ
1ꢀoxoꢀ11ꢀ(4ꢀbromophenyl)ꢀ2,3,4,5,10b,11ꢀhexahydroꢀ
1Hꢀindolo[2,3ꢀb]quinolineꢀ10bꢀcarbonitrile and 9ꢀmeꢀ
thylꢀ1ꢀoxoꢀ11ꢀ(3,4,5ꢀtrimethoxyphenyl)ꢀ2,3,4,5,10b,11ꢀ
hexahydroꢀ1Hꢀindolo[2,3ꢀb]quinolineꢀ10bꢀcarbonitrile2
but, compared to the latter, it is considerably flattened.
All bond lengths in the structure are close to the average
statistical values.8
Thus, the recyclization of quinindolines 1 affords
12ꢀarylꢀ1ꢀoxoꢀ1,2,3,4,5,12ꢀhexahydroindolo[2,1ꢀb]quinꢀ
azolineꢀ6ꢀcarbonitriles (2). Nitriles 2 can be transformed
by acids into amides 6. The method was proposed for the
synthesis of 11ꢀarylꢀ6ꢀmethylꢀ4ꢀoxoꢀ2,3,4,6,10b,11ꢀ
hexahydroindolo[2,3ꢀb]quinolineꢀ10bꢀcarbonitriles (7),
which were transformed into 11ꢀarylꢀ6ꢀmethylꢀ2,3,4,6ꢀ
1Нꢀ1ꢀtetrahydroindolo[2,3ꢀb]quinolinones (8) under the
action of DBU.

Synthesis of indolo[2,1ꢀb]quinazolines
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 10, October, 2002
1873
temperature parameters, and geometric parameters of the molꢀ
ecule were deposited at the Cambridge Bank of Structural Data.
The main geometric parameters are presented in Tables 3 and 4.
Synthesis of 12ꢀarylꢀ1ꢀoxoꢀ1,2,3,4,5,12ꢀhexahydroindoꢀ
lo[2,1ꢀb]quinazolineꢀ6ꢀcarbonitriles (2) (general procedure). A
solution of compound 1 (1.0 mmol) and DBU (0.18 g, 1.2 mmol)
in ethanol (5 mL) was refluxed for 6 h. The reaction mixture was
cooled, and AcOH (0.1 mL) was added. The precipitate of prodꢀ
uct 2 that formed was filtered off and washed on the filter with
ethanol (5 mL). The melting points of compounds 2 are >330 °C.
The yields, elemental analysis results, and 1Н NMR spectroꢀ
scopic data of compounds 2 are presented in Tables 1 and 2.
Synthesis of 12ꢀarylꢀ1ꢀoxoꢀ1,2,3,4,5,12ꢀhexahydroindoꢀ
lo[2,1ꢀb]quinazolineꢀ6ꢀcarboxamides (6a—c) (general proceꢀ
dure). A solution of compound 1 or 2 (0.3 mmol) was refluxed
for 3 h in a mixture of acetic (1 mL) and trifluoroacetic (1 mL)
acids. The solvent was evaporated, and ethanol (2 mL) was
added to the residue. Precipitated product 6 was filtered off and
washed with ethanol (5 mL).
Experimental
1
Н NMR spectra were recorded on Bruker AMꢀ300
(300 MHz) and Bruker WMꢀ250 (250 MHz) instruments in
DMSOꢀd6. Melting points were measured on a Boetius heating
stage and were not corrected. All reaction mixtures were analyzed
and purity of isolated products was monitored by TLC on Silufol
UV 254 plates using a AcOEt—hexane mixture as the eluent.
Xꢀray diffraction study. Colorless triclinic crystals of
C24H21N3O2 were grown from a solution in an acetoniꢀ
trile—DMF mixture. Unit cell parameters: a = 6.373(4), b =
11.377(8), c = 13.689(9) Å, α = 84.058(12), β = 83.115(13), γ =
76.826(12)°, V = 956.4(11) Å3. The space group was P1–, Z = 2,
dcalc = 1.332 g cm–3, m.p. ∼200 °C, М = 383.44. Cell parameters
and intensities of 5344 independent reflections were measured
on a Bruker SMART fourꢀcircle automated diffractometer at
110 K (a graphite monochromator, MoꢀKα radiation, ϕ/ω scan
mode). Intensities of reflections were measured in the interval of
angles 1.84 > θ < 30.22°. In calculations 3712 reflections with
I > 2σ(I) were used. The structure was solved by the direct
method, during which all nonhydrogen atoms of the molecule
were revealed. The parameters of the structure were refined by
the F 2 values using the leastꢀsquares method in the anisotropic
approximation for nonhydrogen atoms. Hydrogen atoms were
localized in the difference electron density syntheses and then
refined isotropically by the leastꢀsquares method. The final diꢀ
vergence factor was R1 = 0.069 (wR2 = 0.168), and for all reflecꢀ
tions R1 = 0.093 (wR2 = 0.184). The Bruker SHELXTL program
packages were used in calculations. The coordinates of atoms,
12ꢀ(4ꢀBromophenyl)ꢀ8ꢀmethylꢀ1ꢀoxoꢀ1,2,3,4,5,12ꢀhexaꢀ
hydroindolo[2,1ꢀb]quinazolineꢀ6ꢀcarboxamide (6а). The yield was
35% (from 1с) and 53% (from 2с). M.p. 254—255 °C. 1Н NMR,
δ: 10.12 (s, 1 Н, NH); 7.70 (s, 1 Н, СОNHH); 7.42 (d, 2 Н, HAr
J = 8 Hz); 7.21—7.10 (m, 4 Н, HAr and СОNHH); 6.80 (d, 1 Н,
Ar, J = 8 Hz); 6.43 (s, 1 Н, СН); 2.90—2.65 (m, 2 Н, СН2);
,
H
2.40—2.20 (m, 2 Н, СН2); 0.35 (s, 3 Н, СН3); 2.05—1.75 (m,
2 Н, СН2). Found (%): С, 61.70; Н, 4.27; N, 9.56; Br, 17.45.
C
23H20BrN3O2. Calculated (%): С, 61.34; Н, 4.48; N, 9.33;
Br, 17.74.
Table 3. Bond lengths (d) in molecule 2f
Bond
d/Å
Bond
d/Å
Bond
d/Å
Bond
d/Å
O(1)—C(1)
1.230(2)
1.375(2)
1.425(2)
1.150(2)
1.371(2)
1.375(2)
1.359(2)
N(11)—C(10A) 1.409(2)
C(4A)—C(12A) 1.357(3)
C(8)—C(9)
1.409(3)
1.511(3)
1.400(3)
1.384(3)
1.522(3)
1.539(2)
O(2)—C(17)
O(2)—C(21)
N(1)—C(13)
N(5)—C(5A)
N(5)—C(4A)
N(11)—C(5A)
N(11)—C(12)
C(1)—C(12A)
C(1)—C(2)
1.471(2)
1.463(2)
1.522(3)
1.521(3)
1.528(3)
1.514(3)
C(5A)—C(6)
C(6)—C(13)
C(6)—C(6A)
C(6A)—C(7)
1.402(2)
1.410(2)
1.450(2)
1.405(2)
C(8)—C(14)
C(9)—C(10)
C(10)—C(10A)
C(12)—C(12A)
C(12)—C(15)
C(2)—C(3)
C(3)—C(4)
C(6A)—C(10A) 1.416(2)
C(7)—C(8) 1.392(3)
C(4)—C(4A)
Table 4. Bond angles (ω) in molecule 2f
Angle
ω/deg
Angle
ω/deg
Angle
ω/deg
C(17)—O(2)—C(21)
C(5A)—N(5)—C(4A)
C(5A)—N(11)—C(10A) 108.96(13)
C(5A)—N(11)—C(12) 124.84(14)
C(10A)—N(11)—C(12) 125.71(14)
O(1)—C(1)—C(12A)
O(1)—C(1)—C(2)
C(12A)—C(1)—C(2)
C(3)—C(2)—C(1)
117.62(16)
120.30(15)
N(11)—C(5A)—N(5)
N(11)—C(5A)—C(6)
N(5)—C(5A)—C(6)
C(5A)—C(6)—C(13)
C(5A)—C(6)—C(6A)
C(13)—C(6)—C(6A)
C(7)—C(6A)—C(10A)
C(7)—C(6A)—C(6)
C(10A)—C(6A)—C(6)
C(8)—C(7)—C(6A)
C(7)—C(8)—C(9)
120.39(15)
110.17(15)
129.43(16)
125.47(16)
106.35(15)
127.93(15)
118.92(16)
134.30(15)
106.77(14)
119.93(16)
119.57(16)
120.71(16)
119.72(17)
C(10)—C(9)—C(8)
C(10A)—C(10)—C(9)
121.74(17)
117.71(16)
C(10)—C(10A)—N(11) 130.15(15)
C(10)—C(10A)—C(6A) 122.11(15)
N(11)—C(10A)—C(6A) 107.72(15)
N(11)—C(12)—C(12A) 108.57(13)
N(11)—C(12)—C(15)
C(12A)—C(12)—C(15) 111.20(14)
C(4A)—C(12A)—C(1) 120.92(16)
C(4A)—C(12A)—C(12) 122.73(14)
120.86(17)
121.63(15)
117.50(16)
113.48(15)
110.84(16)
110.56(15)
121.38(16)
123.28(15)
115.34(16)
111.23(13)
C(2)—C(3)—C(4)
C(4A)—C(4)—C(3)
C(12A)—C(4A)—N(5)
C(12A)—C(4A)—C(4)
N(5)—C(4A)—C(4)
C(1)—C(12A)—C(12)
N(1)—C(13)—C(6)
C(16)—C(15)—C(20)
116.33(15)
179.3(2)
120.03(15)
C(7)—C(8)—C(14)
C(9)—C(8)—C(14)

1874
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 10, October, 2002
Lichitsky et al.
3,3,8ꢀTrimethylꢀ1ꢀoxoꢀ12ꢀphenylꢀ1,2,3,4,5,12ꢀhexahydroꢀ
indolo[2,1ꢀb]quinazolineꢀ6ꢀcarboxamide (6b). The yield was 43%
(from 1a) and 84% (from 2a). M.p. 195—197 °C. 1Н NMR, δ:
10.08 (s, 1 Н, NH); 7.67 (s, 1 Н, СОNHH); 7.30—7.05 (m, 7 Н,
HAr and СОNHH); 6.80 (d, 1 Н, HAr, J = 8 Hz); 6.40 (s, 1 Н,
СН); 2.80—2.7 (m, 2 Н, СН2); 2.35 (s, 3 Н, СН3); 2.25 (s, 1 Н,
СНН); 2.10 (s, 1 Н, СНН); 1.05 and 0.90 (both s, 6 Н, 2 СН3).
Found (%): С, 75.40; Н, 6.21; N, 10.78. C25H25N3O2. Calcuꢀ
lated (%): С, 75.16; Н, 6.31; N, 10.52.
ethanol (3 mL). The resulting solution was left for 12 h at ∼20 °C.
The precipitate that formed was filtered off and washed with
ethanol.
2ꢀAminoꢀ4ꢀ(4ꢀbromophenyl)ꢀ1ꢀmethylanilinoꢀ5ꢀoxoꢀ
1,4,5,6,7,8ꢀhexahydroquinolineꢀ3ꢀcarbonitrile (9a). The yield
1
was 65%. M.p. 170—172 °C. Н NMR, δ: 7.55 (A) and 7.45 (B)
(both s, 2 Н, СНAr); 7.35—7.10 (m, 4 Н, СНAr); 6.85 (m, 1 Н,
СНAr); 6.60 (m, 2 Н, СНAr); 6.93 (A) and 6.80 (B) (both s, 2 Н,
NH2); 4.48 (A) and 4.40 (B) (both s, 1 Н, СН); 3.30 (B) and 3.27
(A) (both s, 3 Н, NСН3); 2.70—2.50 (m, 2 Н, СН2); 2.25—2.05
(m, 2 Н, СН2); 1.90—1.50 (m, 2 Н, СН2). Found (%): С, 61.65;
Н, 4.53; N, 12.25; Br, 17.94. C23H21BrN4O. Calculated (%):
С, 61.48; Н, 4.71; N, 12.47; Br, 17.78.
2ꢀAminoꢀ1ꢀmethylanilinoꢀ5ꢀoxoꢀ4ꢀphenylꢀ1,4,5,6,7,8ꢀhexaꢀ
hydroquinolineꢀ3ꢀcarbonitrile (9b). The yield was 70%. M.p.
187—189 °C. 1Н NMR, δ: 7.40—7.15 (m, 7 Н, CHAr); 6.85 (m,
1 H, CHAr); 6.62 (m, 2 H, CHAr); 6.47 (A) and 6.25 (B) (both s,
2 Н, NH2); 4.48 (A) and 4.40 (B) (both s, 1 Н, СН); 3.30 (B)
and 3.27 (A) (both s, 3 Н, NСН3); 2.70—2.50 (m, 2 Н,
СН2); 2.25—2.05 (m, 2 Н, СН2); 1.90—1.50 (m, 2 Н, СН2).
Found (%): С, 74.71; Н, 6.12; N, 15.19. C23H22N4O. Calcuꢀ
lated (%): С, 74.57; Н, 5.99; N, 15.12.
3ꢀ(2ꢀMethylꢀ2ꢀphenylhydrazino)cyclohexꢀ2ꢀenꢀ1ꢀone (10). A
solution of cyclohexaneꢀ1,3ꢀdione (2.24 g, 0.02 mol), Nꢀmeꢀ
thylꢀNꢀphenylhydrazine (2.32 g, 0.02 mol), and paraꢀtolueneꢀ
sulfonic acid (0.1 g) in benzene (30 mL) was refluxed for 3 h
with azeotropic distillation of water. The solvent was evapoꢀ
rated, and the residue was recrystallized from ethyl acetate. The
product was obtained in 60% yield (2.70 g). M.p. 139—141 °C.
1Н NMR, δ: 8.90 (s, 1 Н, NH); 7.25 (m, 2 Н); 6.85—6.75
(m, 3 Н); 4.98 (s, 1 Н, СН); 3.05 (s, 3 Н, СН3); 2.30—2.40
(m, 2 Н); 2.10—2.15 (m, 2 Н); 1.85—1.95 (m, 2 Н).
12ꢀ(3ꢀMethoxyphenyl)ꢀ1ꢀoxoꢀ1,2,3,4,5,12ꢀhexahydroindoꢀ
lo[2,1ꢀb]quinazolineꢀ6ꢀcarboxamide (6c). The yield was 38%
1
(from 1e) and 62% (from 2e). M.p. 251—252 °C. Н NMR, δ:
10.15 (s, 1 Н, NH); 7.85 (d, 1 Н, HAr, J = 8 Hz), 7.35 (d, 1 Н,
HAr, J = 8 Hz); 7.20—6.95 (m, 5 Н, HAr and СОNHH); 6.87 (s,
1 Н, HAr); 6.75—6.70 (m, 2 Н, HAr); 6.45 (s, 1 Н, СН);
2.95—2.60 (m, 2 Н, СН2); 2.35—2.25 (m, 2 Н, СН2); 2.00—1.75
(m, 2 Н, СН2). Found (%): С, 71.42; Н, 5.59; N, 10.71.
C
23H21N3O3. Calculated (%): С, 71.30; Н, 5.46; N, 10.85.
Synthesis of 11ꢀarylꢀ6ꢀmethylꢀ4ꢀoxoꢀ2,3,4,6,10b,11ꢀhexaꢀ
hydroꢀ1Hꢀindolo[2,3ꢀb]quinolineꢀ10bꢀcarbonitriles (7a,b) (genꢀ
eral procedure). А. A mixture of enaminone 10 (0.22 g, 1 mmol)
and benzylidenemalononitrile (0.23 g, 1 mmol) in ethanol (4 mL)
was refluxed for 6 h. The solution was cooled down, and the
precipitate that formed was filtered off and washed with cold
ethanol (5 mL).
B. A solution of compound 9 (0.5 mmol) was refluxed for 6 h
in ethanol (2 mL). The precipitate that formed was filtered off
and washed with ethanol.
11ꢀ(4ꢀBromophenyl)ꢀ6ꢀmethylꢀ4ꢀoxoꢀ2,3,4,6,10b,11ꢀhexaꢀ
hydroꢀ1Hꢀindolo[2,3ꢀb]quinolineꢀ10bꢀcarbonitrile (7а). The yield
was 48% (method А) and 63% (method B). M.p. 205—206 °C.
1Н NMR, δ: 7.65—7.30 (m, 5 Н); 7.15—7.00 (m, 2 Н); 6.32 (d,
1 Н, J = 8 Hz); 4.20 (s, 1 Н, СН); 3.45 (s, 3 Н, NMe); 2.80—2.70
(m, 2 Н); 2.40—2.20 (m, 2 Н); 2.05—1.95 (m, 2 Н). Found (%):
С, 63.70; Н, 4.26; N, 9.79; Br, 18.29. C23H18BrN3O. Calcuꢀ
lated (%): С, 63.90; Н, 4.20; N, 9.72; Br, 18.48.
References
6ꢀMethylꢀ4ꢀoxoꢀ11ꢀphenylꢀ2,3,4,6,10b,11ꢀhexahydroꢀ1Hꢀ
indolo[2,3ꢀb]quinolineꢀ10bꢀcarbonitrile (7b). The yield was 45%
(method А) and 53% (method B). M.p. 181—182 °C. 1Н NMR,
δ: 7.50—7.30 (m, 6 Н); 7.15—7.10 (m, 1 Н); 6.20 (d, 1 Н, J =
8 Hz); 4.12 (s, 1 Н, СН); 3.45 (s, 3 Н, NMe); 2.80—2.70
(m, 2 Н); 2.40—2.20 (m, 2 Н); 2.05—1.95 (m, 2 Н). Found (%):
С, 78.30; Н, 5.30; N, 11.67. C23H19N3O. Calculated (%):
С, 78.16; Н, 5.42; N, 11.89.
11ꢀ(4ꢀBromophenyl)ꢀ6ꢀmethylꢀ2,3,4,6ꢀtetrahydroꢀ1Нꢀ1ꢀ
indolo[2,3ꢀb]quinolinone (8). A solution of compound 7 (0.15 g,
0.35 mmol) and DBU (0.15 g, 1 mmol) in benzene (4 mL) was
refluxed for 6 h. The solvent was evaporated, and ethanol (2 mL)
was added to the residue. The precipitate that formed was filꢀ
tered off and washed with ethanol (5 mL). Compound 5 was
obtained in 53% yield (0.08 g). M.p. 280—281 °C. 1Н NMR, δ:
7.75—7.65 (m, 3 Н); 7.50 (t, 1 Н); 7.05 (t, 1 Н); 6.40 (d, 1 Н,
J = 8 Hz); 3.93 (s, 3 Н, NMe); 3.35—3.25 (m, 2 Н); 2.50—2.60
(m, 2 Н); 2.05—2.15 (m, 2 Н). Found (%): С, 65.45; Н, 4.16;
N, 6.79; Br, 19.49. C22H17BrN2O. Calculated (%): С, 65.20;
Н, 4.23; N, 6.91; Br, 19.71.
1. E. Fiedler, U. P. Fiedler, and A. Gerhard, Arch. Microbiol.,
1976, 107, 249.
2. J. Bergman, J.ꢀO. Lindström, and U. Tilstam, Tetrahedron,
1985, 41, 2879.
3. J. Symoeus and G. Cauwenbergh, Prog. Drug Res.,
1983, 27, 63.
4. B. V. Lichitsky, V. N. Nesterov, A. A. Dudinov, and M. M.
Krayushkin, Izv. Akad. Nauk, Ser. Khim., 2000, 1320 [Russ.
Chem. Bull., Int. Ed., 2000, 49, 1381].
5. B. V. Lichitsky, D. V. Kozhinov, V. N. Nesterov, L. G.
Vorontsova, Z. A. Starikova, A. A. Dudinov, and M. M.
Krayushkin, Izv. Akad. Nauk, Ser. Khim., 2002, 1713 [Russ.
Chem. Bull., Int. Ed., 2002, 51, 1862].
6. B. V. Lichitsky, V. N. Yarovenko, I. V. Zavarzin, and M. M.
Krayushkin, Izv. Akad. Nauk, Ser. Khim., 2000, 1254 [Russ.
Chem. Bull., Int. Ed., 2000, 49, 1251].
7. S. Goldmann and J. Stoltefuss, Angew. Chem., Ed. Engl., 1991,
30, 1559.
8. H. Allen, O. Kennard, D. G. Watson, L. Brammer, A. G.
Orpen, and R. Taylor, J. Chem. Soc., Perkin Trans. 2, 1987, S1.
Synthesis of 2ꢀaminoꢀ4ꢀarylꢀ1ꢀmethylanilinoꢀ5ꢀoxoꢀ
1,4,5,6,7,8ꢀhexahydroquinolineꢀ3ꢀcarbonitriles (9a,b) (general
procedure). A mixture of benzylidenemalononitrile (1 mmol)
and enamino ketone 6 (1 mmol) was boiled for 5—10 min in
Received December 5, 2001;
in revised form March 19, 2002