Synthesis of tetra- and penta-heterocyclic compounds incorporated isoquinoline moiety

Article abstract of DOI:10.3987/COM-08-11481

7-Amino-2,3-dimethoxy-9-phenyl-5,6,9,6a-tetrahydropyridino[2,1-a]-isoquinoline-8,10-dicarbonitrile 5 was prepared via Michael addition reaction of benzylidenemalononitrile 2 with isoquinoline-1-carbonitrile 1. Reaction of 5 with triethyl orthoformate and

Full text of DOI:10.3987/COM-08-11481

HETEROCYCLES, Vol. 78, No. 2, 2009
337
HETEROCYCLES, Vol. 78, No. 2, 2009, pp. 337 -345. © The Japan Institute of Heterocyclic Chemistry
Received, 6th July, 2008, Accepted, 19th September, 2008, Published online, 25th September, 2008.
DOI: 10.3987/COM-08-11481
SYNTHESIS OF TETRA- AND PENTA-HETEROCYCLIC COMPOUNDS
INCORPORATED ISOQUINOLINE MOIETY
Tayseer A. Abdallah,* Hamdi M. Hassaneen, and Hayam A. Abdelhadi
Department of Chemistry, Faculty of Science, Cairo University, Giza 12613,
Egypt
Fax: +202 35727556; e-mail: tiseersu@yahoo.com
Abstract ― 7-Amino-2,3-dimethoxy-9-phenyl-5,6,9,6a-tetrahydropyridino[2,1-a]-
isoquinoline-8,10-dicarbonitrile 5 was prepared via Michael addition reaction of
benzylidenemalononitrile 2 with isoquinoline-1-carbonitrile 1. Reaction of 5 with
triethyl orthoformate and formamide led to the formation of the corresponding
4-ethoxymethylene and 4-aminopyrimidine derivatives of benzo[a]quinolizines 6
and 7, respectively. Compound 6 reacted with hydrazine to give imino-amino
compound 8. The latter compound reacted with formic acid, triethy1 orthoformate,
acetic anhydride or benzoy1 chloride to give the triazolopyrimidine derivatives 9,
10 and 11, respectively. Compound 8 reacted with hydrazonoy1 halides 12, 13 and
diethy1 oxalate to give triazinopyrimidine and triazolopyrimidine derivatives 16,
17 and 20, respectively.
INTRODUCTION
The considerable biological and medicinal activities of azoloazines have stimulated considerable interest
in the synthesis and chemistry of these compounds.1-4 Although several examples of the azoloazines
1-4
incorporated 1,2,4-triazole moiety have been reported in literature
there is no any example, to our
knowledge, reported contains 1,2,4-triazole ring fused with pyrimidopyridoisoquinoline ring. In
continuation of our previous work3-5, 7-10 on the use of isoquinoline derivatives for the synthesis of
heterocyclic compounds we wish to report the synthesis of some triazolo[1,5-e]pyrimidine and
triazino[2',3'-6,1]pyrimidine.
RESULTS AND DISCUSSION
Treatment of benzylidene malononitrile 2 with 6, 7-dimethoxy-3, 4-dihydroisoquinoline-1-carbonitrile 1
in boiling acetonitrile in the presence of piperidine afforded a single product as evidenced by TLC

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HETEROCYCLES, Vol. 78, No. 2, 2009
analysis. Structure 5 was assigned to the reaction product on the basis of elemental analyses and spectral
data (MS, IR, 1H and 13C NMR), for example the 1H NMR spectrum of the product revealed signals at δ
4.2 (s, 2H, NH2) and 4.3 (s,1H) ppm assignable to proton of pyridine ring in addition to the signals of the
dihydroisoquinoline moiety. Also the IR spectra showed two nitrile absorption bands at 2197 and 2185 in
addition to bands at 3415 and 3336 cm-1 characteristic to the amino group. From the previous data, the
product resulting from reaction of 2 with 1 was assigned 7-amino-2,3-dimethoxy-9-phenyl-5,6,9,6a-
tetrahydropyridino[2,1-a]isoquinoline-8,10-dicarbonitrile 5. The product 5 was also prepared in one step
by refluxing equimolar amounts of 1, benzaldehyde and malononitrile. The reaction started with Michael
addition to give 3 which upon cyclization led to the formation of 5.
MeO
CN
MeCN
PhCH=C
+
piperidine
N
CN
MeO
CH2CN
1
2
MeO
MeO
MeO
MeO
N
NH
CN
CN
H
CN
CN
H
NC
H
NC
H
Ph
H
Ph
3
MeO
MeO
MeO
N
NH
CN
N
NH2
CN
MeO
NC
H
NC
H
Ph
H
Ph
4
Scheme 1
5
Reaction of 5 with triethyl orthoformate in acetic anhydride at reflux afforded the ethoxymethyleneamino
1
derivative 6 in almost quantitative yield (Scheme 2). The H NMR spectrum of the product revealed
characteristic signals for ethoxy group at δ 1.4 (t, J = 7 Hz, 3H) and 4.4 (q, J = 7Hz, 2H) as well as a
signal at δ 7.9 ppm assignable to a proton of CHOEt. Also, the IR spectrum of 6 revealed the absence of
13
the bands of the amino group. The above data together with the C NMR confirmed that the product
assigned structure 6.
When compound 5 was refluxed with formamide it gave 7. The structure of the latter product was
established on the basis of its alternative synthesis from 6 and methanolic ammonia (Scheme 2). Both IR

HETEROCYCLES, Vol. 78, No. 2, 2009
339
and 1H NMR spectroscopic data of the product were consistent with its assigned structure 7.
Treatment of 6 with hydrazine hydrate in ethanol at room temperature gave 8. The structure of 8 was
confirmed by its analytical and spectroscopic data and their chemical reactions outlined in schemes 2 and
3. Reaction of 8 with formic acid or triethyl orthoformate at reflux afforded 9. The formation of triazole
ring involving both amino and imino groups was evidenced by the absence of their absorption bands in
the IR spectrum of 9.
HCONH2
TEOF
5
MeO
MeO
MeO
MeO
N
N=CHOEt
CN
N
N
NH3 / MeOH
N
NC
NC
H
Ph
H
Ph
NH2
7
6
MeO
MeO
/pyridine
PhCOCl
Ac2O
NH2NH2
HCO2H
N
N
or
N
NH2
NC
orCH(OEt)3
H
Ph
NH
MeO
MeO
8
MeO
MeO
N
N
N
N
N
N
NC
H
N
Ph
N
N
NC
H
Ph
N
R
9
10, R=Me
11, R=Ph
Scheme 2
Also the 1H NMR spectrum of 9 revealed two characteristic signals at δ 8.3 (s,1H, triazolo-CH) and at δ
9.1 (s, 1H, pyrimidine-CH)ppm. Similarly, when compound 8 was refluxed in acetic anhydride or
benzoyl chloride in pyridine, it afforded the corresponding 10-methyl and 10-phenyl derivatives 10 and
1
11 which were assigned on both elemental analyses and spectroscopic data. For example, the H NMR
spectra of 10 and 11 revealed the absence of the proton in triazole ring at δ 8.3 appeared in compound 9;
instead, it showed a singlet signal at δ 2.5 ppm assignable to a methyl group in 10.
The reaction of 8 with C-acylhydrazonoyl halides 12a,b in refluxing chloroform in the presence of
triethylamine affordcd in cach case, a single product as evidenced by TLC analysis. The intermediates 15

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HETEROCYCLES, Vol. 78, No. 2, 2009
were discarded on the basis of imino-nitrogen are more basic, and in turn more nucleophilic, than that of
the amino group. The results of elemental analyses of the products were found to be consistent with 16A
and its tautomeric structure 16B, furthermore, the electronic absorption spectra of the isolated products
excludes the hydrazone structure 16A since they revealed a characteristic absorption maxima at λ 361
(log ε 4.43) and λ 400 (log ε 4.4) assignable to arylazo chromophore.13 Accordingly, the product obtained
from the reaction of 8 with 12a,b was assigned structure 16Ba, 16Bb.
X
+
RCO
8
N-NHPh
12,13
MeO
MeO
MeO
N
N
N
N
N
MeO
N
N
NC
NH
R
NC
NH2
H
Ph
H
Ph
NH
O
N-NHPh
C-COR
14
15
MeO
MeO
N-NHPh
MeO
MeO
N
N
N
N
N
NC
NH
N
H
Ph
17
NC
N
N
O
H
Ph
N
R
N
H
16A
N
NNHPh
Ph
MeO
N
N
N
MeO
N
12a,
12b,
13,
NC
NH
R
R=Me , X=Cl
R=C6H5, X=Br
H
Ph
R=OEt, X=Cl
16 B
N=NPh
a, R=Me, X=Cl
b, R=C6H5, X=Br
Scheme 3
1
The latter structure was further evidenced by spectroscopic data, for example the H NMR spectrum of
16B showed that a signal of δ 9.1ppm corresponding to NH disappeared upon shaking the solution of
16Ba with deuterium oxide. The IR spectrum of 16Bb exhibited an NH absorption band at 3212 cm-1.
C-Ethoxycarbonylhydrazonoyl halide 13 reacted under similar rection condition with 8 to give compound
17 and the IR spectrum of 17 showed two bands at 3209 and 1636 cm-1 assignable to the hydrazone NH

HETEROCYCLES, Vol. 78, No. 2, 2009
341
and amido carbony1 groups, respectively. Its UV spectrum in ethanol revealed two bands in the regions
λmax250-300(log ε4.42) and λmax300-360(log ε 4.22) nm assignable to hydrazone chromophoure15
(Scheme 3). Refluxing of 8 with diethy1 oxalate afforded a single product whose elemental analysis and
mass spectra were consistent with C28H24N6O4 formula (Scheme 4).
CO2Et
8
+
CO2Et
MeO
MeO
MeO
MeO
N
N
N
N
N
N
O
N
NC
NC
NH2
NH
19
18
H
Ph
H
Ph
NH
EtO2C
C=O
CO2Et
-H2O
-H2O
MeO
MeO
MeO
MeO
N
N
N
N
N
N
N
O
NC
N
H
Ph
NC
N
N
OEt
H
Ph
21
CO2Et
-
20
OH
MeO
MeO
MeO
N
N
MeO
N
N
N
N
N
NC
NH
NC
-EtOH
N
H
Ph
N
H
Ph
O
9
O
22
Scheme 4
Thus, formula 22 was discarded for the isolated product. Two possible structures were assigned for the
resulting product 20 or 21. The former was assigned to be the isolated product on the basis of its
transformation to 9. Thus saponification of 20 gave 9 via decarboxylation of the resulting acid (Scheme
4). The structure of the product 20 was confirmed by it analytical and spectroscopic data.

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HETEROCYCLES, Vol. 78, No. 2, 2009
EXPERIMENTAL
!
All melting points were determined on a Gallenkamp electrothermal apparatus and are uncorrected. IR
spectra (KBr) were recorded on a Pye Unicam SP-300 IR spectrophotometer and Testscan Shimadzu
FTIR 8000 series 1H NMR and 13C NMR spectra were recorded on a Varian Gemini 200 and Varian EM
390 spectrometers for solution in deuterated chloroform using TMS as internal standard. Mass spectra
were recorded on a GCMS- QP 1000 Ex Shimadzu, Japan. Elemental analyses were carried out at the
Micro analytical Centre of Cairo University. The hydrazonoyl halides 12a14, 12b15 and 1316 were
prepared as previously described.
General procedure :
Synthesis of 7-amino-2,3-dimethoxy-9-phenyl-5,6,9,6a-tetrahydropyridino[2,1-a]isoquinoline-8,10-
dicarbonitrile 5.
To a solution of benzylidene malononitrile 2 (0.77g, 5mmol) and 6,7-dimethoxy-3,4-dihydroisoquinoline-
1-acetoniotrile 1 (1.15g, 5mmol) in acetonitrile (40 mL) was added 3-4 drops of piperidine at rt. The
reaction mixture was refluxed for 3 h, the solvent was evaporated under reduced pressure and the residue
was triturated with MeOH (10 mL) where it solidified the crude product was collected and crystallized
from MeCN to give 5: mp 210 ºC (MeCN); 78% yield; IR (KBr): υ 3415, 3336 (NH2), 2197, 2185 (CN)
1
cm-1; H NMR (CDCl3) δ 2.8 (m,2H), 3.4 (m ,1H), 3.8 (m, 1H), 3.8 (s, 3H), 3.9 (s, 3H), 4.2 (s, 2H), 4.3
13
(s,1H), 6.7(s,1H), 7.2-7.4 (m, 5H), 7.7 (s, 1H); C NMR (CDCl3): δ 41.1, 56.0 110.0, 110.6, 126.3,
127.7, 129.0 ( CH3 CH); 28.6, 41.9, 85.4, 120.4, 121.0, 129.2, 142.8, 145.4, 147.8, 151.1, 152.4, 167.2,
167.5 (CH2, C,CN); m/z 384. Anal. Calcd for C23H20N4O2: C, 71.84; H, 5.24; N, 14.58. Found: C, 72.06;
H, 5.02; N, 14.33 %.
Synthesis
of
2,3-dimethoxy-7-(N-ethoxymethylene)-9-phenyl-5,6,9,6atetrahydropyridino[2,1-a]
isoquinoline -8,10-dicarbonitrile 6.
7-Amino-2,3-dimethoxy-9-phenyl-5,6,9,6a-tetrahydropyridino[2,1-a]isoquinoline-8,10-dicarbonitrile
5
(1.9g, 5 mmol) was dissolved in acetic anhydride (30 mL), to the resulting solution, triethyl orthoformate
(0.74g, 5 mmol) was added and the mixture was refluxed for 5 h. The excess acetic anhydride was
distilled off under reduced pressure and the solid that precipitated on cooling was filtered and crystallized
from EtOH to give 6: mp 172 oC (EtOH); 86% yield; IR (KBr): υ 2198, 2183 (2CN), 1638 (N = CHOEt)
1
cm-1; H NMR (CDCl3): δ 1.4 (t, J = 7 Hz, 3H), 2.8 (m, 2H), 3.5 (m, 1H), 3.7 (m, 1H), 3.8 (s, 6H), 4.4 (q,
13
J = 7 Hz, 2H), 4.5 (s, 1H), 6.6 (s, 1H) , 7.1- 7.3 (m, 5H), 7.8 (s, 1H), 7.9 (s, 1H); C NMR (CDCl3): δ
13.8, 42.5, 56.1, 56.2, 110.4, 111.3, 127.4, 128.1, 129.3, 153.7 (CH3, CH); 27.0, 42.4, 64.4, 72.1, 81.9,
119.6, 120.1, 121.5, 131.0, 143.2, 145.6, 147.7, 151.4, 153.7, (CH2, C, CN); m/z 440. Anal. Calcd for
C26H24N4O3: C, 70.87; H, 5.49; N, 12.72. Found: C, 70.72; H, 5.36; N, 12.48 %.

HETEROCYCLES, Vol. 78, No. 2, 2009
343
Synthesis of 4-amino-8,9-dimethoxy-5-phenyl-5,11,12,12a-tetrahydroisoquinolino[2',1'-6,1] pyridine
[2,3-d] pyrimidine-6-carbonitrile 7.
Method A: A mixture of 5 (1.9g, 5 mmol) and formamide (10 mL) was refluxed for 3 h. The reaction
mixture was cooled and added to cold water with stirring. The solid formed was collected and crystallized
o
from DMF to give 7: mp 225 C (DMF); 83% yield; IR (KBr): υ 3500, 3300 (NH2), 2198 (CN) cm-1;
Anal. Calcd for C24H21N5O2: C, 70.04; H, 5.14; N, 17.03. Found: C, 70.36; H, 4.81; N, 17.25 %.
Method B: A compound 6 (2.2 g, 5 mmol) was treated with methanolic ammonia (10 mL) at rt for 6 h.
The solid that separated was collected and crystallized from DMF to give a compound which identical in
all respects (mp, mixed mp, IR) with that compound prepared by method A .
Synthesis
of
3-amino-8,9-dimethoxy-4-imino-5-phenyl-5,11,12,12a-tetrahydroisoquinolino[2',1'-
6,1]pyridine[2,3-d] pyrimidine-6-carbonitrile 8.
A mixture of 6 (2.2 g, 5 mmol) and hydrazine hydrate (5 mL) was stirred for 4 h in EtOH (20 mL) at rt.
The solid that separated was filtered and crystallized from AcOH to give product 8: mp 199 oC (AcOH);
63% yield; IR (KBr): υ 3311, 3142, 3060 (NH, NH2), 2181 (CN) cm-1; 1H NMR (CDCl3): δ 2.8 (m, 2H),
3.7 (m, 1H), 3.8 (s, 3H), 3.9 (s, 3H), 4.5 (m, 1H), 4.6 (s,1H), 4.8 (s, 2H), 5.9 (s, 1H), 6.7 (s, 1H), 7.2-7.3
(m, 5H), 7.8 (s,1H), 8.0 (s, 1H); 13C NMR (DMSO): 55.5, 55.6, 120.9, 122.0, 126.0, 127.1, 127.3, 128.4,
131.6, 149.5, 150.6, (CH3, CH); 28.4, 79.9, 97.1, 110.8, 110.9, 119.3, 143.9, 145.6, 146.2, 146.5,
154.0(CH2, C, CN); m/z 426. Anal. Calcd for C24H22N6O2: C, 67.57; H, 5.20; N, 19.71. Found: C, 67.81;
H, 5.43; N, 19.94 %.
Synthesis of 4,5-dimethoxy-8-phenyl-1,2,8,11a,13b-pentahydroisoquinoline[2',1'-6,11]pyridino[2,3-
d]1,2,4-triazolo[1,5-e]pyrimidine-7-carbonitrile 9.
A solution of compound 8 (2.1g, 5 mmol) in formic acid or triethyl othoformate (5 mL) was refluxed for
5 h. The reaction mixture was cooled and the solid that precipitated was collected and crystallized from
EtOH to give product 9: mp 233 °C (EtOH); 66% yield; IR (KBr): υ 2183 (CN) cm-1; 1H NMR (CDC13):
δ 3.0 (m, 2H), 3.9 (s, 3H), 4.0 (s, 3H), 4.1 (m, 1H), 4.5 (m, 1H), 5.5 (s, 1H), 6.8 (s, 1H), 7.2-7.5 (m, 5H),
7.9 (s, 1H), 8.3 (s, 1H), 9.1 (s, 1H). Anal. Calcd for C25H20N6O2: C, 68.77; H, 4.62; N, 19.26. Found: C,
68.52; H, 4.43; N, 19.50%.
Synthesis
of
4,5-dimethoxy-10-methyl-8-phenyl-1,2,8,11a,13b-pentahydroisoquinoline[2',1'-6,1]
pyridino[2,3-d]1,2,4-triazolo[1,5-e]pyrimidine-7-carbonitrile 10.
A solution of 8 (2.1g, 5 mmol) in acetic anhydride (20 mL) was refluxed for 3 h. The mixture was cooled
and the solid that separated was collected and crystallized from AcOH to give product 10: mp 246 °C
(AcOH); 67% yield; IR (KBr): υ 2185 (CN) cm-1; 1H NMR (CDC13): δ 2.5 (s, 3H), 2.9 (m, 2H), 3.9 (m,
1H), 3.9 (s, 3H), 4.0 (s, 3H), 4.4 (m, 1H), 5.4 (s, 1H), 6.7 (s, 1H), 7.2-7.5 (m, 5H), 7.8 (s, 1H), 8.9 (s, 1H);

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HETEROCYCLES, Vol. 78, No. 2, 2009
13C NMR (DMSO): 14.2, 55.6, 55.7, 121.5, 121.8, 127.4, 128.8, 129.0, 131.6, 131.9, 146.6, 150.8, (CH3,
CH); 28.2, 79.8, 99.2, 110.9, 119.1, 138.9, 143.0, 144.9, 146.2, 151.1, 151.7, 166.1(CH2, C, CN); m/z
450. Anal. Calcd for C26H22N6O2: C, 69.30; H, 4.92; N, 18.66. Found: C, 69.46; H, 4.75; N, 18.48 %.
Synthesis of 4,5-dimethoxy-8,10-phenyl-1,2,8,11a,13b-pentahydroisoquinoline[2',1'-6,l]pyridino[2,3-
d]1,2,4-triazolo[1,5-e]pyrimidine-7-carbonitrile 11.
To a solution of 8 (2.1 g, 5 mmol) in pyridine (10 mL) benzoyl chloride (0.7 mL, 5 mmol) was added.
The mixture was refluxed for 4 h, then cooled and poured into cooled hydrochloric acid (10%) with
stirring. The solid that precipitated was collected, washed with cold water and finally crystallized from
DMF to give product 11: mp 276 °C (DMF); 65% yield; IR (KBr): υ 2186 (CN) cm-1; 1H NMR (CDC13):
δ 3.0 (m, 2H), 3.9 (s, 3H), 4.0 (s, 3H), 4.1 (m, 1H), 4.5 (m, 1H), 5.6 (s, 1H), 6.8 (s,1H), 7.3 (s, 1H), 7.2-
8.8 (m, 10H), 9.1 (s, 1H); m/z 512. Anal. Calcd for C31H24N6O2: C, 72.62; H, 4.72; N, 16.40. Found: C,
72.40; H, 4.51; N, 16.17 %.
Synthesis of 11,12-dimethoxy-2-phenylazo-14-phenyl-8,14,4a-trihydro-4H-benzo[a] 1,2,4-triazino[2',3'-
6,1]pyrimidine[4,5-f]quinolizine-13-carbonitrile 16 and 17 ( general procedure ).
To a hot solution of 8 (2.1g, 5 mmol) and the appropriate hydrazonoyl halide (5 mmol) in CHCl3 (30 mL)
was added triethylamine (0.7 mL, 5 mmol). The reaction mixture was refluxed for 18 h, and then the
solvent was evaporated under reduced pressure. The crude product was collected and crystallized from
DMF to give the products 16 and 17.
11,12-dimethoxy-2-phenylazo-3-methyl-14-phenyl-8,14a,4a-trihydro-4H-benzo-[a]1,2,4-triazino[2',3'-
6,1] pyrimidine[4,5-f]quinolizine-13-cabonitrile 16Ba.
1
mp 297°C (DMF); 61% yield; IR (KBr): υ 3212 (NH), 2187 (CN) cm-1; H NMR (DMSO-d6): δ 2.1 (s,
3H), 3.0 (m,2H), 3.7 (s, 3H), 3.8 (s, 3H), 4.0 (m, 1H ) , 4.3 (m, 1H), 5.2 (s,1H), 6.8 (s,1H), 7.1 (s,1H),
7.2-7.8 (m, 9H), 8.3 (s,1H), 8.5 (s, 1H), 9.1 (s, 1H, NH); m/z 568. Anal. Calcd for C33H28N8O2: C, 69.68;
H, 4.96; N, 19.71. Found: C, 69.91; H, 4.83; N, 19.54 %.
11,12-dimethoxy-3,14-diphenyl-2-phenylazo-8,14a,4a-trihydro-4H-benzo[a]1,2,4-triazino[2,3-6,1]-
pyrimidine[4,5-f]quinolizine-13-carbonitrile 16 Bb.
mp 250 °C (DMF); 65% yield; IR (KBr): υ 3213 (NH), 2189 (CN) cm-1; m/z 630. Anal. Calcd for
C38H30N8O2: C, 72.34; H, 4.79; N, 17.77. Found: C, 72.15; H, 4.63; N, 18.06 %.
11,12-dimethoxy-3-oxo-11,12-dimethoxy-2-phenylhydrazo-14-phenyl-8,14,4a-trihydro-2H,4H-benzo-
[a]1,2,4-triazino[2',3'-6,1]pyrimidine[4,5-f]quinolizine-13- carbonitrile 17.
1
mp 190 °C (DMF); 64% yield; IR (KBr): υ 3309, 3209 (2NH), 2190 (CN); 1636 (CO) cm-1; H NMR

HETEROCYCLES, Vol. 78, No. 2, 2009
345
(CDC13): δ 3.7 (m, 1H), 3.8 (s, 3H), 3.9 (s, 3H ), 4.0 (m, 2H), 4.4 (m, 1H), 5.1 (s, 1H), 6.6-8.2 (m, 15H);
m/z 570. Anal. Calcd for C32H26N8O3: C, 67.33; H, 4.59; N, 19.64. Found: C, 67.54; H, 4.30; N, 19.44 %.
Synthesis of ethyl 7-cyano-4,5-dimethoxy-8-phenyl-1,2,8,11a,13b-pentahydroisoquinoline[2',1'-6,1]-
pyridino[2,3-d]1,2,4-triazolo[1,5-e]pyrimidine-10-carboxylate 20.
To a solution of 8 (2.1 g, 5 mmol) in EtOH (30 mL), diethyl oxalate (0.73 g, 5 mmol) was added. The
reaction mixture was refluxed for 3 h, then cooled and the product that separated was coolected and
crystallized from DMF to give product 20: mp 235 °C (DMF); 60% yield; IR (KBr): υ 2195 (CN), 1715
(CO) cm-1; 1H NMR (CDC13): δ 1.4 (t, J = 7 Hz, 3H), 3.0 (m, 2H), 3.9 (s, 6H, 2CH3), 4.1 (m, 1H), 4.4 (m,
1H ) 4.5 (q, J = 7 Hz, 2H), 5.6 (s, 1H), 6.8 (s,1H), 7.2-7.5 (m, 5H),7.9 (s, 1H), 9.2 (s, 1H); m/z 508. Anal.
Calcd for C28H24N6O4: C, 66.11; H, 4.75; N, 16.53. Found: C, 66.35; H, 4.97; N, 16.32 %.
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