Condensed isoquinolines 31. Reaction of 5-aryl-3-halo-12H-isoquino[2,3-a] quinazolines with electrophilic reagents

Article abstract of DOI:10.1007/s10593-008-0117-2

Treatment of 5-aryl-3-halo-12H-isoquino[2,3-a]quinazolines with electrophilic reagents readily forms their oxidation products. Acylation of the 3-chloro-5-phenyl-7,12-dihydroisoquino[2,3-a]quinazolinium perchlorate with Ac₂O in the presence of pyridine gave the product of electrophilic substitution at the C-7 atom 1-(3-chloro-5-phenyl-12H-isoquino[2,3-a]quinazolin- 7-yl)-1-ethanone. By the same route phenacyl bromides react with the anhydro base 1 to give 5-aryl-7-(2-aryl-2-oxoethyl)-3-halo-isoquino[2,3-a]quinazolin-13- ium bromides. These salts readily react with nucleophilic reagents to form the products of addition at the C-12 atom.

Full text of DOI:10.1007/s10593-008-0117-2

Chemistry of Heterocyclic Compounds, Vol. 44, No. 7, 2008
CONDENSED ISOQUINOLINES
31*. REACTION OF 5-ARYL-3-HALO-
12H-ISOQUINO[2,3-a]QUINAZOLINES
WITH ELECTROPHILIC REAGENTS
L. M. Potikha, V. M. Kisil, A. V. Turov, and V. A. Kovtunenko
Treatment of 5-aryl-3-halo-12H-isoquino[2,3-a]quinazolines with electrophilic reagents readily forms
their oxidation products. Acylation of the 3-chloro-5-phenyl-7,12-dihydroisoquino[2,3-a]quinazolinium
perchlorate with Ac2O in the presence of pyridine gave the product of electrophilic substitution at the C-
7 atom 1-(3-chloro-5-phenyl-12H-isoquino[2,3-a]quinazolin-7-yl)-1-ethanone. By the same route
phenacyl bromides react with the anhydro base 1 to give 5-aryl-7-(2-aryl-2-oxoethyl)-3-halo-
isoquino[2,3-a]quinazolin-13-ium bromides. These salts readily react with nucleophilic reagents to
form the products of addition at the C-12 atom.
Keywords: 5-aryl-12H-isoquino[2,3-a]quinazoline, 5-arylisoquino[2,3-a]quinazolin-13-ium bromides,
acylation, borohydride reduction, oxidation.
Secondary enamines are characterized by their high reactivity towards electrophilic reagents [2, 3]. We
have studied such reactions in a series of condensed isoquinolines in cases where the compounds have both a
secondary enamine fragment in the structure (benzimidazo[1,2-b]isoquinolin-11(5H)-one) and a methylene-
imine fragment (7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-one and 6,11-dihydro-13H-isoquino[3,2-b]-
quinazolin-13-one). It was also of interest to study the features of these reactions in a series of 5-aryl-12H-iso-
quino[2,3-a]quinazolines 1a,b whose structures also have two potentially reactive nucleophilic centers, i.e. the
C-7 atom (the β-carbon of the enamine fragment C(7)=C(6a)–N(13) and the N-6 atom (of the C(5)=N(6) imino
group). We have previously [4] found a number of similarities in the behavior of 5-arylisoquinoquinazolines
1a,b and their protonated 5-aryl-7,12-dihydroisoquino[2,3-a]quinazolinium perchlorate salts with the behavior
of other condensed isoquinolines [5-8] in oxidation reactions, i.e. a tendency for dehydrogenation at the benzyl
position (7 and 12) to form aromatic derivatives including those with a dimeric structure. It would be logical to
suggest a similar behavior dependence in electrophilic substitution reactions. However, the resolution of this
question proved difficult because of the extreme susceptibility of compounds 1a,b and 2a,b to oxidation. In the
presence of even weak bases (traces of water and alcohol) products of oxidation and their subsequent reaction
with bases are readily formed.
_______
* For Communication 30 see [1].
__________________________________________________________________________________________
Taras Shevchenko National University, Kiev 01033, Ukraine; e-mail: potikha_l@mail.ru. Translated
from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1044-1052, July, 2008. Original article submitted
June 14, 2007; revision submitted October 17, 2007.
838
0009-3122/08/4407-0838©2008 Springer Science+Business Media, Inc.

None the less, in some cases we have obtained and reliably established the structure of the products of
electrophilic substitution of 5-arylisoquino[2,3-a]quinazolines.
Hal
Hal
–
ClO4
+
N
N
N
Ar
N
1a,b
Ar
2a,b
Ar1COCH2Br
Ac2O
2a
Cl
Hal
Hal
–
Br
+
N
+
N
N
N
Ph
N
Ar
N
Ar
–
2ClO4
O
Ar
N
O
Me
Ar1
N
+
3
5a–c
4a,b
Hal
1, 2, 4 a Ar = Ph, Hal = Cl, b Ar = 4-BrC6H4, Hal = Br; 5 a Ar = Ph, Ar1 = 4-BrC6H4,
Hal = Cl, b Ar = 4-BrC6H4, Ar1 = Ph, Hal = Br; c Ar = Ar1 = 4-BrC6H4, Hal = Br
Heating a mixture of the isoquinoquinazolines 1a,b with acid chlorides in pyridine or dioxane gives
1
complex mixtures of oxidation and acylation products according to H NMR spectroscopic data. Acylation of
salt 2a with acetic anhydride in the presence of pyridine proved more successful and the reaction mixture gave a
modest yield of 1-(3-chloro-5-phenyl-12H-isoquino[2,3-a]quinazolin-7-yl)-1-ethanone (3). Spectroscopic data
1
identified the reaction product as the 7-acetyl derivatives. The H NMR spectrum of compound 3 showed a
three-proton singlet for the introduced acetyl group (2.55 ppm), the absence of a signal for the methine H-7
proton, and the aromatic proton signals shifted to low field of those in the unsubstituted isoquinoquinazoline 1a
[4] (see Table 1, mean ∆δ ~ 0.2 ppm). The greatest low field shift was observed for the H-8 proton at 8.07 ppm
(∆δ = 1.0 ppm) which falls in the deshielding region of the 7-acetyl substituent carbonyl group. The presence of
a carbonyl stretching vibration in the IR spectrum at low frequency (1630 cm-1) is due to donor effect of the
conjugated system of the 5-arylisoquino[2,3-a]quinazoline.
The reaction of the 5-arylisoquino[2,3-a]quinazolines 1a,b and their salts 2a,b with isocyanates and
aldehydes also leads to the formation of oxidation products according to 1H NMR spectroscopic data, mainly the
dimeric 3,3'-dihalo-5,5'-bis(aryl)[7,7']bi[isoquino[2,3-a]quinazoline]-13,13'-diium salts 4a,b. The same result
was obtained when attempting to alkylate compounds 1a,b with benzyl halides. Fusing compound 1a with
methyltosylate gave the 3,3'-dichloro-5,5'-biphenyl[7,7']bi[isoquino[2,3-a]quinazolinyl]-13,13'-diium perchlo-
rate 4a in high yield (65%). The formation of alkylation products of the isoquinoquinazolines 1a,b with
phenacyl bromides upon heating a mixture of the reagents in acetonitrile was unexpectedly successful. It should
be noted that an oxidation and not alkylation frequently occurs in this reaction in the case of condensed
isoquinolines [6, 9]. Oxidation also occurs in the reaction with 5-arylisoquino[2,3-a]quinazolines but gives the
5-aryl-7-(2-aryl-2-oxoethyl)-3-haloisoquino[2,3-a]quinazolin-13-ium bromides 5a-c.
839

TABLE 1. Spectroscopic Characteristics of the 5-Arylisoquinoquina-
zolines 3, 5-7
Com- IR spectrum,
1Н NMR spectrum, δ, ppm (J, Hz)
ArH Н-12
pound
ν, cm-1
Other signals
3
1630 (С=О),
1605 (C=N),
1520, 1375,
1325, 1285,
1000, 760,
690
8.07 (1Н, dd, oJ = 8.0, mJ = 1.6, Н-8);
7.86 (1Н, d, oJ = 8.5, Н-1);
5.10
(2Н, s)
2.55 (3Н, s, СН3)
7.68 (2Н, m, H-2',6');
7.65 (1Н, dd, oJ = 8.5, mJ = 2.4, Н-2);
7.57 (3Н, m, H-3'–H-5');
7.43 (1Н, d, mJ = 2.4, Н-4);
7.31 (1Н, d, oJ = 8.0);
7.17 (1Н, td, oJ = 8.0, mJ = 1.6, Н-9);
7.10 (1Н, td, oJ = 8.0, mJ = 1.6, Н-10)
5a
1685 (C=O),
1590 (C=N),
1545, 1350,
1210, 980,
760, 700
9.64 (1Н, d, oJ = 9.5, Н-1);
8.98 (1Н, d, oJ = 8.0, Н-11);
8.63 (1Н, d, oJ = 8.5, Н-8);
8.47 (1Н, dd, oJ = 9.5, mJ = 2.4, Н-2);
8.30 (1Н, t, oJ = 8.0, Н-9);
8.21 (1Н, d, mJ = 2.4, Н-4);
8.16 (1Н, t, oJ = 8.0, Н-10);
8.14 (2Н, d, oJ = 8.0, H-2'',6'');
7.76 (4Н, m, H-2',6',3'',5'');
7.66 (1Н, t, oJ = 8.0, H-4');
7.57 (2Н, t, oJ = 8.0, H-3',5')
11.73
(1Н, s)
5.68 (2Н, s, СН2)
5b
5c
6
1670 (C=O),
1590 (C=N),
1380, 1345,
1220, 990,
835, 760
9.65 (1Н, d, oJ = 9.5, Н-1);
8.95 (1Н, d, oJ = 8.0, Н-11);
8.60 (1Н, d, oJ = 8.0, Н-8);
8.58 (1Н, dd, oJ = 9.5, mJ = 2.4, Н-2);
8.32 (1Н, d, mJ = 2.4, Н-4);
8.30 (1Н, t, oJ = 8.0, Н-9);
8.21 (2Н, d, oJ = 7.5, H-2'',6'');
8.14 (1Н, t, oJ = 8.0, Н-10);
7.73 (5Н, m, H-2',3',5',6',4'');
7.59 (2Н, t, oJ = 7.5, H-3'',5'')
9.57 (1Н, d, oJ = 9.5, Н-1);
9.00 (1Н, d, oJ = 8.0, Н-11);
8.63 (1Н, d, oJ = 8.0, Н-8);
8.59 (1Н, dd, oJ = 9.5, mJ = 2.0, Н-2);
8.34 (1Н, d, mJ = 2.0, Н-4);
8.31 (1Н, t, oJ = 8.0, Н-9);
8.18 (1Н, t, oJ = 8.0, Н-10);
8.14 (2Н, d, oJ = 8.0, H-2'',6'');
7.77 (2Н, d, oJ = 8.0, H-3'',5'');
7.75 (4Н, m, H-2',3',5',6')
7.93 (2Н, d, oJ = 8.0, H-2'',6'');
7.60 (4Н, m, H-2',6',3'',5'');
7.51 (1Н, dd, oJ = 8.5, mJ = 2.0, Н-2);
7.41 (2Н, d, oJ = 8.0, H-3',5');
7.24 (1Н, d, oJ = 8.5, Н-1);
7.20 (1Н, d, mJ = 2.0, Н-4);
7.18 (1Н, d, oJ = 7.5, Н-11);
7.12 (1Н, t, oJ = 8.0, Н-9);
7.06 (1Н, t, oJ = 8.0, Н-10);
6.97 (1Н, d, oJ = 8.0, Н-8)
11.73
(1H, s)
5.71 (2Н, s, СН2)
5.69 (2Н, s, СН2)
4.35 (2Н, s, СН2)
1680 (C=O),
11.75
(1Н, s)
1580 (C=N),
1390, 1340,
1060, 990,
825, 745
1677 (C=O),
1590 (C=N),
1545, 1505,
1410, 1280,
1205, 990,
795, 750
5.00
(2Н, s)
7
1690 (C=O),
1593 (C=N),
1550, 1490,
1420, 1390,
1120 (C–O),
1005, 730
7.89 (2Н, d, oJ = 8.0, H-2'',6'');
7.66 (2Н, d, oJ = 8.0, H-2',6');
7.60 (1Н, d, oJ = 9.0, Н-1);
7.56 (4Н, m, H-3',5',3'',5'');
7.52 (1Н, dd, oJ = 9.0, mJ = 2.4, Н-2);
7.31 (2Н, m, Н-4,11);
6.49
(1Н, s)
4.73
(1Н, d, 2J = 16.8,
7-СНАНВ);
4.16
(1Н, d, 2J = 16.8,
7-СНАНВ);
3.29
(4Н, m, О–СH2);
2.38
7.26 (1Н, d, oJ = 8.0, Н-8);
7.20 (2Н, m, Н-9,10)
(2Н, m, N–СНАНВ);
2.24
(2Н, m, N–СНАНВ)
840

The structure of the alkylation products which is rather complex and not only possible was established
by a comparison of their spectroscopic data with the data of the more simple 3-chloroisoquino-5-phenyl-
[2,3-c]quinazolin-13-ium perchlorate [4] and dimer salts 4a,b [4]. The IR spectra of the compounds 5a-c showed
carbonyl group stretching vibrations in the range 1670-1685 cm-1, characteristic of an Ar–C=O system which
1
points to the presence of an acetophenone fragment in the molecule. Hence H and 13C NMR spectra were
measured with the use of homonuclear (COSY) and heteronuclear (HMBC and HMQC) 2D correlation
spectroscopy. In addition, for an evaluation of the steric proximity of the individual protons NOESY-1D and
NOESY spectra were used. For various spectra of compound 5b a whole series of analogies was found with the
corresponding spectra of compounds 4a,b and the 3-chloro-5-phenylisoquino[2,3-a]quinazolin-13-ium
perchlorate [4]. Hence in the proton spectrum a singlet with an unusually low field chemical shift of 11.73 ppm
was found. This signal has a correlation in the NOESY-1D spectrum with the signals at 9.65 and 8.95 ppm. This
points to the proximity of the protons in the molecule in agreement with its angular structure. Hence the unusual
chemical shift of the signal is explained on the one hand by the presence of the neighboring quaternary nitrogen
atom and on the other with a nonbonding interaction with the proton of the angularly annelated benzene ring.
This signal corresponds to the H-12 proton of the isoquinoquinazoline system and is observed in the region
characteristic of the isoquino[2,3-a]quinazoline aromatic system [4, 5, 7]. A positive assignment of the signals in
the proton spectrum can be made from the COSY spectrum. Here, clear correlations can be traced in three spin
systems, viz. the ABCD of the isoquinoline fragment, the ABC of the 3-bromoquinazoline fragment, and the
AA'BB' of the acetophenone fragment. The structure of the carbon skeleton of the molecule follows from its 2D
HMBC and HMQC spectra. In the HMQC spectrum there are correlations of all of the proton-bearing carbon
1
atoms in the molecule. Using the previously made assignment of signals in the H NMR spectra all of the
proton-bearing carbon atoms are readily located (see Table 2). A secure assignment of the majority of the
quaternary carbon atoms can be made on the basis of the correlations in the HMBC spectrum. Figure 1 shows
these signal assignments and the most significant correlations in the HMBC spectrum upon which they are
based.
8.58
139.2
Br
9.65
11.73
139.3
125.3
8.95
136.4
+
8.32
N
126
139
121.5
161.5
134.8
137.6
139
132.4
N
O
38.2
126.1
8.60
132.7
7.73
Br
5.71
132.7
7.73
197.1
137
8.21
129
129.6
7.59
134.4
7.73
Fig. 1. Structurally important HMBC correlations for compound 5b.
841

From the point of view of structure the most important correlation is that of the methylene group protons
with the carbonyl group carbon at δ = 197.1 and the two heterocyclic system carbon atoms at 132.4 and 139
ppm. This confirms the presence of the acetophenone fragment bonded at C-7. In full agreement with this
deduction is the observation of the marked homonuclear Overhauser effect for the methylene group protons with
the H-8 (4%) and H-2'',6'' protons in the experiment carried out on compound 5a.
The fact that the p-bromophenyl substituent in compound 5b is bonded to C-5 is confirmed by the
presence of the corresponding correlation of C-5 (161.5 ppm) with the o-protons at 7.73 ppm. There are also
correlations of this carbon with proton H-4 and with H-1 (via a W type interaction) completely analogous to that
in the spectra of compound 4 [4].
Additional evidence supporting the proposed structure for compounds 5a-c comes from the overall
similarity in the UV spectra of the dimer salts 4, 3-chloro-5-phenylisoquino[2,3-a]quinazolin-13-ium perchlorate
[4], and 7-[2-(4-bromophenyl)-2-oxoethyl]isoquinoquinazolinium bromide 5a which points to their
isoelectronicity. The spectrum of compound 5a differs from the rest only by the presence of a characteristic
π→π* ketonic band at 255 nm (ε·10-3 = 44.5).
The mass spectra of salts 5a,b were obtained by the HPLC-MS method (CI, acetonitrile, 0.05% formic
acid) and showed weak intensity peaks for the 7-[2-(aryl)-2-oxoethyl]-5-aryl-3-haloisoquino[2,3-a]quinazolin-
13-ium cations (35-40%) and stronger peaks corresponding to the products of the interaction of these cations
with water and their subsequent oxidation and decomposition. Such a result is fully in agreement, bearing in
mind the ready reaction of aromatic isoquino[2,3-a]quinazoline derivatives with nucleophiles seen before [4, 5]
in other examples. In fact, the reaction of salt 5c with sodium borohydride in alcohol readily gives the nucleophilic
addition product at the 12 position, i.e. 2-[3-bromo-5-(4-bromophenyl)-12H-isoquino[2,3-a]quin-azolin-7-yl]-1-(4-
1
bromophenyl)-1-ethanone (6). The H NMR spectrum (Table 1) shows a two-proton methylene group singlet
TABLE 2. Proton-Carbon and Proton-Proton Correlations for Compound 5b
1Н NMR
spectrum,
δ, ppm
COSY
correlations,
δ, ppm
13С NMR
spectrum, δ, ppm;
HMQC correlations
Atom
number
НМВС correlations, δ, ppm
1
9.65
8.58
—
8.65
9.65
—
161.5, 136.4, 125.3, 121.5, 139.2
122.2
139.2
125.3
131.9
121.5
161.5
139
2
136.4
3
—
4
8.32
—
—
139.2, 136.4, 125.3, 161.5
4a
5
—
—
—
—
—
6a
7
—
—
—
—
—
—
132.4
139
7a
8
—
—
—
8.60
8.30
8.14
8.95
—
8.28
8.14
8.30
8.14
—
137.6, 132.4, 126
126.1
137.6
131.4
131.6
126
9
139, 131.4
10
11
11a
12
13a
1'
126
139, 137.6, 126
—
11.73
—
—
139, 136.4, 131.6, 126
139.3
136.4
134.8
132.7
126.1
134.4
137
—
—
—
—
—
2',3'
4''
4'
7.73
—
134.8, 132.7, 129, 126.1, 161.5
—
—
—
—
—
—
1''
2''
3''
C=O
CH2
8.21
7.59
—
7.59
8.21
—
134.4, 129.6, 197.1
137, 129
129
129.6
197.1
38.2
—
5.71
—
197.1, 139, 132.4
842

for H-12 at 5.00 ppm and the aromatic protons of the isoquino[2,3-a]quinazoline system shifted to high field,
being seen in the same region as the unsubstituted derivative 1b [4]. This also agrees fully with the observed
change in the UV spectrum of a bathochromic shift by an average 5-10 nm and of 60 nm for the long
wavelength band when compared with the spectrum of the starting salt 5c.
O
Br
_
Br
Br
N
Br
O
NH
+
N
N
N
NaBH4
N
Ar
N
Ar
N
Ar
O
O
O
Ar1
Ar1
Ar1
6
5c
7
Ar = Ar1 = 4-BrC6H4
The 7-(2-aryl-2-oxoethyl)isoquinoquinazolinium bromides 5a-c, like other aromatic isoquino[2,3-a]-
quinazoline aromatic derivatives [4, 5], react readily with amines. We have characterized the reaction product of
salt 5c with morpholine as 2-[3-bromo-5-(4-bromophenyl)-12-(4-morpholino)-12H-isoquino[2,3-a]quin-azolin-
1
7-yl]-1-(4-bromophenyl)-1-ethanone (7). A feature of the H NMR spectrum of compound 7 (Table 1) is the
2
presence of the 7-CH2 methylene group as two AB type doublets with J = 16.8 Hz. The N–CH2 methylene
group protons of the morpholine fragment are also non-equivalent and appear as two multiplets with ∆δ = 0.14
ppm. This data and the low field positioning of the H-12 proton signal as a singlet at 6.49 ppm identify the
structure as the product of addition of the amine at position 12.
EXPERIMENTAL
Melting points for the compounds synthesized were determined on a Boetius type heating block and are
1
not corrected. IR spectra (KBr tablets) were recorded on a Pye-Unicam SP3-300 instrument and H and 13C
NMR spectra on a Varian Mercury 400 instrument (400 and 100 MHz respectively) using DMSO-d6 and with
TMS as internal standard. UV spectra were taken on a Specord M-400 instrument.
The mass spectra of compounds 5a,b were obtained on an Agilent/100 Series HPLC-MS instrument (CI,
acetonitrile, 0.05% formic acid) and are given as the cations of these salts [M-Br]+. Because of the instability of
the latter only the polyisotopic fragment ions [M-2Br]+ were recorded. Salts 5a,b were extremely unstable,
particularly in the presence of nucleophiles including water. As a result of the absence of reliable data for the
reaction of salts 5 under conditions to those used for recording the mass spectra some of the peaks, particularly
those of low intensity are not considered. Monitoring of the reaction course and the purity of the products
obtained was carried out by TLC on Silufol UV-254 plates.
1-(3-Chloro-5-phenyl-12H-isoquino[2,3-a]quinazolin-7-yl)-1-ethanone (3). A mixture of the
isoquinoquinazoline 2a (4.43 g, 10 mmol) and acetic anhydride (5 ml) was heated to reflux and pyridine (10 ml)
was added. After cooling it was diluted with water (60 ml). The precipitate was filtered off, washed with water
and then alcohol. Yield 1.19 g (31%); mp 175-177ºC (acetone). UV spectrum (MeOH), λmax, nm (ε·10-3): 207
(83.6), 229 (74.0), 265 (51.1), 285 (51.8), 350 (54.0), 515 (17.8). Found, %: C 74.83; H 4.33; Cl 9.21; N 7.30.
C24H17ClN2O. Calculated, %: C 74.90; H 4.45; Cl 9.21; N 7.28.
5-Aryl-7-(2-aryl-2-oxoethyl)-3-haloisoquino[2,3-a]quinazolin-13-ium Bromides (5a-c). The
phenacyl bromide (20 mmol) was added to a solution of the 5-arylisoquinoquinazoline 1a,b (10 mmol) in
843

acetonitrile (30ml) and refluxed for 3-5 h. After this time the solution had changed color from blue to yellow
and a yellow precipitate formed. The product was cooled, the precipitate filtered off, washed with acetone, and
recrystallized from acetic acid.
Compound 5a. Yield 3.28 g (53%); mp 278-280ºC (AcOH). UV spectrum (MeOH), λmax, nm (ε·10-3):
208 (61.9), 228 (54.1), 255 (44.5), 317 (44.5), 520 (7.7). Mass spectrum (CI), m/z (Irel, %): 542.0 [M-2Br]+ (31),
539.2 [M-2Br]+ (40), 536.8 [M-2Br]+ (60), 98.4 (100). Found, %: C 58.15; H 3.00; Br 25.84; Cl 5.71; N 4.56.
C30H19Br2ClN2O. Calculated, %: C 58.23; H 3.10; Br 25.83; Cl 5.73; N 4.53.
Compound 5b. Yield 3.38 g (51%). Mp 195-198ºC (AcOH). Mass spectrum (CI), m/z (Irel, %): 601.0
[M-2Br+H2O]+ (100), 585.2 [M-2Br]+ (15), 582.6 [M-2Br]+ (35), 581.3 [M-2Br]+ (17), 99.2 (50), 99 (50), 583
[M-Br]+ (35), 601 [M-Br+H2O]+ (100). Found, %: C 54.25; H 2.80; Br 36.14; N 4.25. C30H19Br3N2O.
Calculated, %: C 54.33; H 2.89; Br 36.14; N 4.22.
Compound 5c. Yield 4.6 g (62%). Mp 298-300ºC (AcOH). Found, %: C 48.45; H 2.37; Br 43.09; N
3.80. C30H18Br4N2O. Calculated, %: C 48.55; H 2.44; Br 43.07; N 3.77.
2-[3-Bromo-5-(4-bromophenyl)-12H-isoquino[2,3-a]quinazolin-7-yl]-1-(4-bromophenyl)-1-ethanone
(6). NaBH4 (0.38 g, 10 mmol) was added portionwise to a suspension of the 5-(4-bromophenyl)isoquino-
quinazolinium salt 5c (2.2 g, 5 mmol) in methanol (20 ml) and heated for 1 h. After cooling the solution formed
a dark-blue precipitate of compound 6. The precipitate was filtered off, thoroughly washed with a 15% solution
of sodium carbonate and water, and recrystallized from 2-propanol. Yield 1.13 g (34%); mp 183-184ºC
(2-propanol). UV spectrum (MeOH), λmax, nm (ε·10-3): 210 (163.3), 232 (185.5), 256 (163.3), 322 (126.2), 360
(81.6), 600 (26.0). Found, %: C 54.25; H 2.80; Br 36.14; N 4.25. C30H19Br3N2O. Calculated, %: C 54.33;
H 2.89; Br 36.14; N 4.22.
2-[3-Bromo-5-(4-bromophenyl)-12-(4-morpholino)-12H-isoquino[2,3-a]quinazolin-7-yl]-1-(4-bromo-
phenyl)-1-ethanone (7). The 5-(4-bromophenyl)isoquinoquinazolinium salt 5c (2.2 g, 5 mmol) was dissolved
with heating in morpholine (10 ml). Heating was continued for a further 3 min and then left overnight. The
solution was diluted with water (100 ml) and the precipitate was filtered off, washed with water, and then
alcohol. Yield 0.75 g (20%); mp 175-177ºC (2-propanol). Found, %: C 54.43; H 3.45; Br 32.02; N 5.67.
C34H26Br3N3O2. Calculated, %: C 54.57; H 3.50; Br 32.03; N 5.62.
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