Condensed isoquinolines 25. Alkylation of 6,11-dihydro-13H-isoquino[3,2-b] quinazolin-13-one

Article abstract of DOI:10.1007/s10593-007-0223-6

Interaction of 6,11-dihydro-13H-isoquino[2,3-b]quinazolin-13-one with alkylating agents occurs at two positions depending on their nature and the reaction conditions-at C₍₆₎ or N₍₅₎. Fusion with methyl tosylate leads to 5-methyl-13-o

Full text of DOI:10.1007/s10593-007-0223-6

Chemistry of Heterocyclic Compounds, Vol. 43, No. 11, 2007
CONDENSED ISOQUINOLINES
25*. ALKYLATION OF 6,11-DIHYDRO-
13H-ISOQUINO[3,2-b]QUINAZOLIN-
13-ONE
L. M. Potikha and V. A. Kovtunenko
Interaction of 6,11-dihydro-13H-isoquino[2,3-b]quinazolin-13-one with alkylating agents occurs at two
positions depending on their nature and the reaction conditions – at C(6) or N(5). Fusion with methyl tosylate
leads to 5-methyl-13-oxo-6,13-dihydro-11H-isoquino[3,2-b]quinazolin-5-ium salts, while interaction with
benzyl halides in the presence of i-PrONa gave 6-benzyl- and 6,6-dibenzyl-6,11-dihydro-13H-
isoquino[3,2-b]quinazolin-13-ones. Alkylation with olefins led to two types of products. In the case of
maleinimides and maleic acid anhydride Michael adducts at C(6) were formed and in the case of
cyanocinnamic acid esters the reaction was accompanied by intramolecular acylation at N(5) to give 1-aryl-
3,9-dioxo-3H,9H,11H-benzo[5,6][1,8]naphthyridino[1,8-ab]quinazoline-2-carbonitrile.
Keywords:
3,9-dioxo-3H,9H,11H-benzo[5,6][1,8]naphthyridino[1,8-ab]quinazoline-2-carbonitrile,
isoquino[3,2-b]quinazoline,
spiro[6,11-dihydro-13H-isoquino[3,2-b]quinazoline-6,2'-indan]-13-one,
alkylation.
We have previously studied alkylation, one of the characteristic reactions of enamines, using
benzimidazo[1,2-b]isoquinolin-11(5H)-one [2, 3] and 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-one [4, 5] as
examples. It seemed of interest to investigate the characteristics of this reaction for the linear isomer –
6,11-dihydro-13H-isoquino[3,2-b]quinaxolin-13-one (1) which had been shown previously [1] to be ambident as
nucleophilic agent with the example of reactions with carbonyls. We had previously [4] obtained the
hydrobromides of 6-benzyl-substituted derivatives of compound 1 by rearrangement of the corresponding
compounds with an angular structure. However, under the reaction conditions (170-180°C) the process was
accompanied by oxidation of both the starting materials and the final reaction products [6]. Thus this method of
rearrangement was not suitable for the preparation of the 5-substituted or disubstituted derivatives of
isoquino[3,2-b]quinazoline.
In the present work we have carried out the direct alkylation of the isoquinoquinazoline 1 by heating it
with 1 equiv. of benzyl halides in 2-propanol solution in the presence of i-PrONa. The yields of compounds 2
reached 70-80%. Use of a two-fold excess of a benzyl halide gave the formation of the disubstituted compound 3
under these conditions (Tables 1-3).
_______
* For Communication 24 see [1].
__________________________________________________________________________________________
Taras Shevchenko National University, Kiev 01033, Ukraine; e-mail: vkovtunenko@univ.kiev.ua.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No.11, 1698-1708, November 2007. Original article
submitted July 24, 2006.
0009-3122/07/4311-1445©2007 Springer Science+Business Media, Inc.
1445

O
N
O
N
N
N
CH2Ar
ArH2C
CH2Ar
2a–c
3
O
N
O
N
N
N
1
4
_
ClO4
O
O
N
+
N
N
N
Me
Me
6
5
2 a Ar = Ph, b Ar = 2-MeC6H4, c Ar = 3-O2NC6H4; 3 Ar = Ph
Attempts to synthesize benzyl derivatives of isoquino[3,2-b]quinazoline by other methods – fusing a
mixture of the reagents and heating in polar solvents (acetonitrile and DMF) in the presence or absence of bases
– led to resinification or the formation of multicomponent mixtures of oxidation products.
The 6-benzoisoquino[3,2-b]quinazolines 2a-c were identical to those we had prepared previously [4]. In
1
the H NMR spectrum of 6,6-dibenzylisoquino[3,2-b]quinazoline 3 (Table 2) the protons of the methylene
2
groups of the benzyl groups were nonequivalent and were observed as an AB spin system with J = 13.5 Hz.
This results, as in the case of the isomeric 7,7-dibenzyl-7,12-dihydro-5H-isoquino(2,3-a)quinazolin-5-ones [4],
from spatially restricted rotation of the bulky substituents around the C(6)–C(α′) and C(6)–C(α″) bonds.
The necessity to use bases for the synthesis of the benzyl derivatives 2 and 3 is explained by the nature
of isoquino[3,2-b]quinazoline 1 is an activated "imine". In the presence of a strong base it is converted into a
deprotonated form – a carbanion. However the tautomeric conversion of compound 1 into an "enamine" in polar
solvents or at high temperature is not excluded. The alkylation of compound 1 with o-xylylene dibromide may
serve as an indirect test of this hypothesis. On fusing (160-170°C) an equimolar mixture of the reagents we
obtained a small yield (30%) of spiro[6,11-dihydro-13H-isoquino[3,2-b]quinazoline-6,2'-9-indan]-13-one (4).
This compound is formed considerably more readily and with higher yield (63%) on carrying out the reaction in
2-propanol in the presence of i-PrONa. As in the case of the isomeric spiro[7,12-dihydro-5H-isoquino[2,3-a]-
1
quinazoline-7,2′-indan]-5-one [4], in the H NMR spectrum of the spiroindane 4 the protons of the methylene
groups C(2′)H2 and C(6′)H2 are observed as AB spin systems with 2J = 11.0 Hz and ∆δ = 0.82 ppm.
Fusion of isoquinoquinazoline 1 with methyl tosylate also gave a product of alkylation (55% yield)
which was isolated from the reaction mixture as 5-methyl-13-oxo-6,13-dihydro-11H-isoquino[3,2-b]quinazolin-
5-ium perchlorate (5). Reaction of morpholine with this salt gave deprotonation at position 6 to give 5-methyl-
5,13-dihydro-11H-isoquino[3,2-b]quinazolin-13-one (6). Formation of the product of N-alkylation in the
reaction with methyl tosylate is completely natural as in the "imine" form for isoquinoquinazoline 1 or the
"enamine" form (according to the HSAB principle). The structures of compounds 5 and 6 were confirmed
spectroscopically. It should be noted that deprotonation of salt 5 occurs readily even with such weak bases as
1446

Table 1. IR Spectra of Derivatives of Isoquino[3,2-b]quinazolines 3-8
Com-
pound
Com-
pound
IR spectrum, ν, cm-1
IR spectrum, ν, cm-1
3
1663 (br., С=О), 1600 (C=N),
1580, 1560, 1470, 1445, 778, 750,
720, 690
7c
1705 (С=О), 1687 (C=O),
1603 (C=N), 1400, 1250 (C–O),
1163, 1030, 730
4
5
6
1670 (C=O), 1590 (C=N),
1455, 1387, 1170, 755
7d
7e
7f
1713 (С=О), 1684 (C=O),
1600 (C=N), 1385, 1165, 770
1715 (C=O), 1620 (C=N),
1090, 755
1710 (С=О), 1670 (C=O),
1590 (C=N), 1380, 1155, 760
1620 (C=N), 1565, 1490, 1455,
1380, 740
1723 (С=О), 1687 (C=O),
1605 (C=N), 1382, 1345 (NO2),
1170
7a
7b
3220 (NH), 1705 (C=O),
1670 (C=O), 1600 (C=N),
1190, 1165, 765
7g
8
1713 (С=О), 1680 (C=O),
1608 (C=N), 1405, 1197, 1166,
780
1710 (C=O), 1670 (C=O),
1590 (C=N), 1380, 1190,
1155, 760
3420 (NH), 1725 (С=О),
1685 (С=О), 1590, 1520, 1495,
1475, 1500, 1370 (С–О), 847
1
polar solvents. Thus the H NMR spectrum of salt 5 in DMSO-d6 appears as the spectrum of a mixture of two
compounds – the salt 5 and the anhydro base 6 – as indicated by the presence of signals of the aliphatic and
aromatic protons of the protonated and deprotonated forms (Table 2).
O
O
N
N
H
+
N
N
H
H
H
O
O
ap-
sc-
O
N
N
R
7a–g
1
O
R
O
O
N
N
N
N
H
.
.
.
NC
Ar
CO2Et
O
O
O
12
8
O
N
O
N
O
8
8
N
N
N
+
N
3
3
1
1
Ar
O
O
Ar
Ar
CN
CN
11a–c
10
9a,b
7 a R = H, b R = CH2Ph, c R = 4-MeOC6H4, d R = 4-MeC6H4, e R = Ph, f R = 4-O2NC6H4,
g R = α-naphthyl; 9, 11 a Ar = 4-MeOC6H4, b Ar = 4-ClC6H4, c Ar = 4-Me2NC6H4
1447

1448

1449

Isoquino[3,2-b]quinazoline 1 also readily forms products of alkylation by interaction with activated
olefins. Fusing an equimolar mixture of 1 with maleimides or maleic anhydride gave the Michael adducts – 1-R-
3-(13-oxo-6,13-dihydro-11H-isoquino[3,2-b]quinazolin-6-yl)-2,5-pyrrolidinediones 7a-g and 3-(13-oxo-5,13-
dihydro-11H-isoquino[3,2-b]quinazolin-6-yl)dihydro-2,5-furandione (8). It should be noted that in the case of
isoquino[3,2-b]quinazoline 1 this reaction occurs quite easily (20-40 min at 120-150°C) and with high yield (60-
80%). Whereas for other condensed 3-aminoisoquinolines – benzimidazo[1,2-b]isoquinolin-11(5H)-one,
which exists predominantly in the "enamine" form [3] and 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-one,
which exists as a mixture of tautomers [7] – alkylation products were not formed with these olefins. One possible
reason for this is the difference in reactivity of these heterocycles as proton donors in reaction with proton
acceptors – anhydride and imides of dicarboxylic acids. The structures of the pyrrolidinediones 7a-g were
established on the basis of their 1H NMR spectra. In the aliphatic proton resonance region signals of 6 protons in
the form of AB and ABX systems were observed. Vicinal coupling constant of H-6′ and H-3 J = 0.8-1.0 Hz is
1
characteristic [8] for unshielded conformations with trans and cis positions of the interacting protons. The H
NMR spectrum of 1-benzyl-2,5-pyrrolidinedione 7b permit the conclusion that an antiperiplanar conformation is
predominant for compounds 7a-g. A peculiarity of the spectrum of compound 7b is the presence at stronger
field, in comparison with signals of the other aromatic protons, of a one-proton doublet (6.56 ppm), assigned by
us to the resonance of H-4' on the basis of a COSY HH experiment. Analysis of a molecular models of 7b shows
that the structure which has H-4′ extremely close to the benzyl substituent so that it falls within the region of
shielding of the benzene ring, corresponds to the form 7ap.
The maximum yields of 1-(4-nitrophenyl)-2,5-pyrrolidinedione 7f and 1-(α-naphthyl)-2,5-pyrrolidine-
dione 7g were obtained by fusion at higher temperatures (140-150°C) than for the remaining pyrrolidinediones.
1
In the H NMR spectra of these compounds double sets of aliphatic and aromatic protons were observed, with
small differences in chemical shifts and similar coupling constants (Table 2). We have observed similar patterns
in products of alkylation with other N-arylmaleimides 7c-e which had not been crystallized. In the case of 1-(4-
nitrophenyl)-2,5-pyrrolidinedione 7f one of the components of the mixture (J6′,3 = 1.0 Hz) was obtained in pure
form after many crystallizations of the mixture from DMF. These data show that the product of the reaction of
compound 1 with maleimides is a mixture of two conformers with cis and trans positions of the interacting
protons. This hypothesis was confirmed by the results of chromato-mass spectrometry studies of mixtures of
isomers of compounds 7f,g which showed the presence of a unique peak on the chromatogram, the m/z of which
corresponds to the expected value. The vicinal coupling constant J6′,3 = 3.0 Hz of the second component of the
mixture corresponds to the synclinal conformation 7sc. Using the modified Karplus equation [9] we determined
the values of the dihedral angles H–C(6)–C(3)–H from the coupling constants, 173 (J6′,3 = 1.0 Hz, 7ap) and 49°
(J6′,3 = 3.0 Hz, 7sc).
The observed appearance of atropoisomerism is explained by restricted rotation around the C(6′)–C(3)
bond. Probably the transition temperature between the two forms is 130-160°C. For example, in the spectrum
pyrrolidinedione 7a (ap-form), which was initially heated in boiling nitrobenzene for 20 min, signals of two
isomers are also observed. It should be noted that the transition between the ap- and sc-forms evidently occurs at
1
a lower temperature in an acid medium. For example in the H NMR spectra of compounds 7a-e in CF3CO2D
(7ap according to the data of spectra in DMSO-d6), signals for both forms were observed with the content of 7sc
< 15%. The explanation for this observation was found from a study of the structure of the fusion product of
compound 1 with maleic acid anhydride (furandione) 8. In the 1H NMR spectrum of compound 8 a broad signal
was observed at 12.50 ppm for proton, which exchanged with D2O, and in the IR spectrum there was a broad
band in the region of 3450 cm-1 which indicate the presence of the N(5)H group in the structure. In the aliphatic
proton resonance region there is a two-proton singlet of the methylene group C(11)H2 and signals of the protons
of the furandione ring in the form of an A2X spin system. The formation of the "enamine" form for
1450

6-alkylisoquino[3,2-b]quinazoline in this case is explained by the electron-acceptor influence of the substituent.
It is probable that a similar structure occurs on protonation of the pyrrolidinediones 7 as an intermediate in the
conversion of the ap- and sc-forms.
Alkylation with the olefin at atom C(6) also occurs on reaction between isoquino[3,2-b]quinazoline 1 and
cyanocinnamic acid esters. However, in this case the reaction does not stop at the stage of formation of the
Michael product, but is accompanied by intramolecular acylation at atom N(5) and oxidation of the cyclic adduct
which leads to the derivatives of a new heterocyclic system – 1-(4-aryl)3,9-dioxo-3H,9H,11H-benzo[5,6][1,8]-
naphthyridino[1,8-ab]quinazoline-2-carbonitriles, 9a,b. The cyano group remains unchanged in the reaction
products: stretching bands are observed in the IR spectra in the region of 2210 cm-1. The absence in the 1H NMR
spectra of proton signals of the isoquino[3,2-b]quinazoline unit at atoms C(6) and N(5) indicates the formation of
5,6-disubstituted derivative. In the aromatic proton resonance region we observed two doublets in weak field at
9.20 and 8.27 ppm. The latter (in the region characteristic for H-1 of the isoquinoquinazoline starting material) is
assigned to the signal of a proton peri to a carbonyl group H-8, while the proton at weaker field is assigned to a
proton falling in the region of deshielding by the carbonyl group of a pyridine ring annelated to isoquino-
[3,2-b]quinazoline. A doublet in strong field at 6.37 ppm corresponds to the resonance of a proton screened by
the benzene ring of the pyridine unit. However, the enumerated data do not allow an unambiguous conclusion on
the structures of the products as products of C-alkylation or N-alkylation. Although it is known [3, 10, 11]
Table 3. Characteristics of the Compounds Synthesized
Found, %
——————
Calculated, %
Com-
pound
Empirical
formula
Yield,
%
mp, °C*
C
H
N
3
C30H24N2O
84.00
84.08
82.19
82.26
56.20
56.29
77.78
77.84
69.51
69.56
74.42
74.47
71.80
71.83
74.37
74.47
74.04
74.10
6.91
6.95
76.37
76.42
69.30
69.36
75.12
75.16
71.60
71.65
5.61
5.65
5.10
5.18
4.12
4.17
5.32
5.38
4.33
4.38
4.83
4.86
4.65
4.69
4.80
4.86
4.50
4.54
3.86
3.89
4.42
4.49
4.00
4.07
3.91
3.97
3.19
3.24
6.56
6.54
8.00
7.99
7.73
7.72
10.70
10.68
12.17
12.17
9.68
9.65
3.32
3.31
9.68
9.65
10.00
9.97
12.10
12.01
8.93
8.91
8.10
8.09
9.76
9.74
9.63
9.64
156-158
231-232
224-226
147-149
280-281
211-213
258-261
274-276
275-277
253-255
197-200
175-178
284-287
317-320
66
30*2
55
60
80
85
79
85
83
85
60
75
35
30
4
C24H18N2O
5
C17H15ClN2O5*3
C17H14N2O
6
7a
7b
7с
7d
7е
7f
7g
8
C20H15N3O3
C27H21N3O3
C27H21N3O4
C27H21N3O3
C26H19N3O3
C26H18N4O5
C30H21N3O3
C20H14N2O4
C27H17N3O3
C26H14ClN3O2*4
9a
9b
_______
* Solvents for crystallization: i-PrOH (compound 3), DMF (compounds 4,
6-9), MeCN (compound 5).
*2 Yield by method B 63%.
*3 Found, %: Cl 8.15, calculated %: Cl 8.13.
*4 Found, %: Cl 9.78, calculated, %: Cl 9.77.
1451

that alkylation of natural products (cyclic "imines" and "enamines") with derivatives of cyanocinnamic acid
occurs predominantly at carbon atoms, it should be taken into consideration an alternate structure 10 as a product
of C-alkylation and N-alkylation. The final choice of 9 resulted from a study of the structure of by-products of
this reaction. We have examined different conditions – fusion or heating mixtures of reagents in polar solvents,
with or without bases. In all cases a mixture of reaction products was formed, the content of 9 in which depended
on the conditions used and the nature of the substituents in the benzene ring of the cyanocinnamic ester. The
basically by-products of this reaction, and in the case of ethyl 2-cyano-3-(4-dimethylamino)phenyl-2-propenoate,
were 6-arylidene-6,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-ones 11a-c. These compounds were isolated
from the reaction mixtures and their spectroscopic characteristics and physical constants coincided completely
with compounds prepared previously [1]. The content of 6-arylidene derivatives in the reaction mixture
increased with increasing electron-donor strength of the substituent in the benzene ring of the cyanocinnamic
ester and also when the reaction was carried out by fusion. In solution in the presence of base and with
increasing electron-acceptor strength of the substituent, the fraction of products of oxidation of isoquino[3,2-
b]quinazoline increased. On fusing the base 1 with ethyl 3-(4-chlorophenyl)-2-cyano-2-propenoate at 150-160°C
a mixture was obtained the basic components of which were compounds 9b, 11b, and 12 according to 1H NMR
data. A mixture of signals of 5 aliphatic protons, the δ values and coupling constants of which are characteristic
of products of C(6) alkylated type of the pyrrolidinediones 7, indicates the formation of 6-alkyl-6,11-dihydro-
13H-isoquino[3,2-b]quinazolin-13-one 12. The protons of the C(11)H(2) methylene group are observed as two
2
doublets with geminal J = 17.0 Hz and ∆δ = 0.63 ppm. In our view the formation of 12 in this reaction can be
considered as strong evidence for structure
9
for the derivatives of benzo[5,6][1,8]naphthyri-
ino[1,8-]quinazolines. The optimal yield of compound 9a was obtained by carrying out the reaction in DMF in
the presence of Et3N, and of 9b by fusion at 180-190°C.
EXPERIMENTAL
Melting points were determined with a Boetius block and were not corrected. IR spectra of KBr disks
1
were recorded with a Pye-Unicam SP3-300 instrument. H NMR spectra of DMSO-d6 solutions with TMS as
internal standard were recorded with a Varian Mercury 400 (400 MHz) instrument. Mass spectra were recorded
by the HPLC method on an Agilent/100 Series instrument (CI, acetonitrile, 0.05% formic acid). The course of
reactions and the purity of the products were monitored by TLC on Silufol UV-254 plates.
Yields, physicochemical characteristics, and elemental analysis data of the synthesized compounds are
given in Table 3.
6-Arylmethyl-6,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-ones, 2a-c. Isoquino[3,2-b]quinazoline 1
(1 g, 4.03 mmol) was added to a solution of i-PrONa (0.33g, 4.0 mmol) in 2-propanol (15 ml). The mixture was
heated with stirring while most of the solid had not dissolved. Benzyl chloride (4.0 mmol) in 2-propanol (2 ml)
was then added dropwise and the mixture was heated and stirred for 30 min. The solvent was evaporated on
rotary evaporator and water (10 ml) was added to the residue. The precipitate formed was filtered off, thoroughly
washed with water and a small amount of 2-propanol.
Compound 2a. Yield: 1.09 g (80%); mp 146-147°C (DMF, 148°C [5]).
Compound 2b. Yield: 1.06 g (75%); mp 170-172°C (DMF, 171°C [5]).
Compound 2c. Yield: 1.07 g (69%); mp 143-145°C (DMF, 145°C [5]).
6,6-Dibenzyl-6,11-dihydro-13H-isoquino[3,2-b]quinazoline-13-one (3). The reaction was carried out
analogously to the synthesis of compounds 2a-c using i-ProNa (0.66 g, 8.1 mmol) and benzyl chloride (1 ml,
8.0 mmol).
1452

Spiro[6,11-dihydro-13H-isoquino[3,2-b]quinazoline-6,2′-indan]-13-one (4). A.
A
mixture of
isoquinoquinazoline 1 (1 g, 4.03 mmol) and o-xylylene dibromide (1.06 g, 4.0 mmol) were fused on an oil bath
at 160-170°C for 5 h. The melt was triturated with 2-propanol (10 ml) and the solid was filtered off and washed
with 2-propanol.
B. The product was obtained by the method used for 2 using i-PrONa (0.66 g, 8.1 mmol) and o-xylylene
dibromide (1.06 g, 4.0 mmol).
5-Methyl-13-oxo-6,13-dihydro-11H-isoquino[3,2-b]quinazolinium Perchlorate (5). A mixture of
isoquinoquinazoline 1 (1 g, 4.03 mmol) and MeOTs (1.11 g, 6.0 mmol) was fused on an oil bath at 135-140°C
for 2h. The melt was dissolved on heating in 2-propanol and a saturated solution of NaClO4 (5 ml) was added,
followed by water (10 ml). The precipitate was filtered off and washed with water and acetone.
5-Methyl-5,13-dihydro-11H-isoquino[3,2-b]quinazolin-13-one (6). A mixture of perchlorate 5 (1 g,
2.76 mmol) and morpholine (1.5 ml) was heated until the solid had dissolved completely. The solution was
cooled and water (25 ml) added. The precipitate was filtered off and washed thoroughly with water and
2-propanol.
1-R-3-(13-Oxo-6,13-dihydro-11H-isoquino[3,2-b]quinazolin-6-yl)-2,5-pyrrolidinediones 7a-g.
A
mixture of isoquinoquinazoline 1 (1 g, 4.03 mmol) and the corresponding maleimide (5.0 mmol) was fused on an
oil bath at 120-130°C (or 140-150°C for 7f,g) for 40 min. The melt was triturated with acetone (10 ml). The
solid substance was filtered off and washed with acetone.
Compound 7f. Mass spectrum, m/z (Irel, %): 467 [M+1]+ (100).
Compound 7g. Mass spectrum, m/z (Irel, %): 472 [M+1]+ (100).
3-(13-Oxo-5,13-dihydro-11H-isoquino[3,2-b]quinazolin-6-yl)dihydro-2,5-furandione
(8)
was
obtained by the method described for 7 using maleic anhydride (0.49 g, 5.0 mmol) at 120-125°C (20 min).
1-(4-Methoxyphenyl)-3,9-dioxo-3H,9H,11H-benzo[5,6][1.8]naphthyridino[1,8-ab]quinazoline-2-carbo-
nitrile (9a). A mixture of compound 1 (1 g, 4.03 mmol), triethylamine (3ml), and ethyl 2-cyano-3-(4-
methoxyphenyl)-2-propenoate (1.27 g, 5.5 mmol) in DMF (10 ml) was boiled for 5 h. The solution was cooled
and aqueous ethanol (20 ml) was added. The precipitate was filtered off and washed with ethanol. IR spectrum,
1
ν, cm-1: 2210 (CN), 1700 (C=O), 1645 (C=O), 1600, 1505, 1445, 1253 (C–O), 1170, 773, 750. H NMR
o
m
o
spectrum, δ, ppm (J, Hz): 9.23 (1H, d, J = 9.5, H-5); 8.27 (1H, dd, J = 1.6, J = 8.0, H-8); 7.89 (1H, td,
mJ = 1.6, oJ = 8.0, H-6); 7.66 (1H, d, oJ = 8.0, H-7); 7.44 (2H, d, oJ = 8.8, H-2′,6′); 7.38 (1H, d, oJ = 7.6, H-12),
7.11 (1H, t, J = 7.6, H-14); 7.02 (2H, d, oJ = 8.8, H-3′,5′); 6.90 (1H, t,oJ = 7.6, H-13); 6.37 (1H, d, J = 8.0, H-5);
5.24 (2H, s, C(11)H2); 3.88 (3H, s, OCH3).
1-(4-Chlorophenyl)-3,9-dioxo-3H,9H,11H-benzo[5,6][1,8]naphthyridino[1,8-ab]quinazoline-2-carbo-
nitrile (9b). A mixture of isoquinoquinazoline 1 (1g, 4.03 mmol) and ethyl 3-(4-chlorophenyl)-2-cyano-
2-propenoate (1.18 g, 5.0 mmol) was fused on an oil bath at 180-190°C for 4 h. The melt was triturated with
acetone (10 ml), the solid was filtered off and washed with acetone. IR spectrum, ν, cm-1: 2210 (CN), 1695
1
o
(C=O), 1665 (C=O), 1340, 780, 758. H NMR spectrum, δ, ppm (J, Hz): 9.20 (1H, d, J = 9.5, H-5), 8.27 (1H,
m
o
m
o
o
dd, J = 1.6, J = 8.0, H-8), 7.91 (1H, td, J = 1.6, J = 8.0, H-6), 7.72 (1H, d, J = 8.0, H-7), 7.58 (4H, m,
H-2′,3′,5′,6′), 7.43 (1H, d, oJ = 7.6, H-12), 7.13 (1H, t, oJ = 7.6, H-14), 6.97 (1H, t, oJ = 7.6, H-13), 6.37 (1H, d,
J = 8.0, H-15), 5.26 (2H, s, C(11)H2).
REFERENCES
1.
2.
L. M. Potikha and V. A. Kovtunenko, Khim. Geterotsikl. Soedin., 1509 (2007). [Chem. Heterocycl,
Comp., 43, 1280 (2007)].
L. M. Potikha, N. V. Shkilna, V. M. Kisel and V. A. Kovtunenko, Khim. Geterotsikl. Soedin., 1214
(2004). [Chem. Heterocycl. Comp., 40, 1052 (2004)].
1453

3.
4.
5.
6.
7.
L. M. Potikha, N. V. Shkilna, V. M. Kisel, and V. O. Kovtunenko, Khim. Geterotsikl. Soedin., 1362
(2004). [Chem. Heterocycl. Comp., 40, 1179 (2004)].
V. M. Kisel, L. M. Potikha, and V. A. Kovtunenko, Khim. Geterotsikl. Soedin., 643 (2000). [Chem.
Heterocycl. Comp., 36, 560 (2000)].
V. M. Kisel, L. M. Potikha, and V. A. Kovtunenko, Khim. Geterotsikl. Soedin., 131 (2001). [Chem.
Heterocycl. Comp., 37, 125 (2001)].
L. M. Potikha, V. A. Kovtunenko, A. V. Tarasevich, J. G. Wolf, and Ch. Andre, Khim. Geterotsikl.
Soedin., 430 (2007). [Chem. Heterocycl. Comp., 43, 347 (2007)].
L. M. Potikha, V. A. Kovtunenko, and V. M. Kisil, Khim. Geterotsikl. Soedin., 562 (2007). [Chem.
Heterocycl. Comp., 43, 460 (2007)].
8.
9.
10.
11.
H. Gunter, Introduction to 1H NMR Spectroscopy [Russian translation]. Mir, Moscow, 1984, p.114.
C. A. G. Haasnoot, F. A. A. M. de Leeuw, and C. Altona, Tetrahedron, 36, 2783 (1980).
V. G. Granik, V. A. Makarov, and C. Parkanyi, Adv. Heterocycl. Chem., 72, 283 (1999).
P. W. Hickmott, Tetrahedron, 38, 3363 (1982).
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