Substituted coumarin amidines: Useful building blocks for the preparation of [1]benzopyrano[4,3-b]pyridin-5-one and [1]benzopyrano[4,3-d]pyrimidin-5-one derivatives

Article abstract of DOI:10.1016/j.tet.2005.03.050

The synthesis of [1]benzopyrano[4,3-b]pyridin-5-ones 4a-f and 4g-j starting from 3-formylcoumarin and 3-cyanocoumarin N-functionalized amidines 3a-f and 3g-j, respectively, was reported. The ring-closure reaction mechanism, under basic or acidic media, wa

Full text of DOI:10.1016/j.tet.2005.03.050

Tetrahedron 61 (2005) 4957–4964
Substituted coumarin amidines: useful building blocks for the
preparation of [1]benzopyrano[4,3-b]pyridin-5-one and
[1]benzopyrano[4,3-d]pyrimidin-5-one derivatives
*
Egle M. Beccalli, Alessandro Contini and Pasqualina Trimarco
`
Istituto di Chimica Organica ‘A. Marchesini’, Facolta di Farmacia e Centro Interuniversitario di Ricerca sulle Reazioni Pericicliche e
`
Sintesi di Sistemi Etero e Carbociclici, Universita degli Studi di Milano, Via Venezian 21, 20133 Milano, Italy
Received 13 January 2005; revised 22 February 2005; accepted 10 March 2005
Available online 7 April 2005
Abstract—The synthesis of [1]benzopyrano[4,3-b]pyridin-5-ones 4a–f and 4g–j starting from 3-formylcoumarin and 3-cyanocoumarin
N-functionalized amidines 3a–f and 3g–j, respectively, was reported. The ring-closure reaction mechanism, under basic or acidic media, was
proposed. Furthermore, the reaction of 3-formylamidines 3a,c–f with ammonium acetate gave good yields of 2-substituted
[1]benzopyrano[4,3-d]pyrimidin-5-ones 7.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
In this context, we reported a preliminary communication5
on acetamidines bearing the 3-formylcoumarin group on
N-1 as a starting material to synthesize benzopyranopyridin-
5-ones.
In recent years nitrogen polyheterocycles containing a
coumarin nucleus have received increasing attention due to
their potential biological properties, and considerable efforts
have been undertaken to exploit synthetic routes to these
compounds. In particular, the coumarin nucleus is present in
compounds endowed with analgesic1 and antiplatelet2
properties, and in promising drugs useful as phospho-
diesterase VII inhibitors3 for the treatment of immunity-
associated diseases.
As a continuation of this study, we describe here, in full
detail, the synthesis of substituted 2-amino- and 2,4-
diaminobenzopyranopyridin-5-ones through acetamidines
bearing a 3-formyl or 3-cyano coumarin group on N-1.
With the purpose to extend this strategy to different
nitrogen polyheterocycle systems we report, for the first
time, a new synthetic approach to 2-substituted benzo-
pyranopyrimidin-5-ones. The key intermediates were again
the acetamidines substituted at N-1 with the 3-formyl
coumarin group.
The introduction of substituents in the C-3 position of the
coumarin moiety is of great importance as this generates
intermediates in the synthesis of heterocycles condensed
with the benzopyran-2-one nucleus.
In the last few years we focused our attention on tertiary
amidines bearing a 3-substituted coumarin group on N-1 as
synthons to give nitrogen fused triheterocycles, through
intramolecular cyclization reactions.
2. Results and discussion
Amidines 3a–j were prepared from azides 1a–b and
enamines 2a–f. The new azide 1b was achieved by reaction
of sodium azide with the corresponding 4-chloro-2-oxo-2H-
[1]benzopyran-3-carbonitrile.6 We performed the reactions
using equimolar amounts of 4-azido-3-formylcoumarin 1a7
or of 4-azido-3-cyanocoumarin 1b and the appropriate
enamine 2a–f,8–11 previously synthesized, in chilled
dichloromethane solution. These reaction conditions
allowed the isolation in good yields of the amidines 3a–f
and 3g–j, respectively (Scheme 1).
From acetamidines bearing a 3-nitrocoumarin group on N-1,
we recently developed an easy method for the preparation of
coumarin fused to imidazoles.4
Keywords: 3-Formylcoumarin amidines; 3-Cyanocoumarin amidines;
Enediamino tautomers; Aldols; Intramolecular cyclization.
*
Corresponding author. Tel.: C39 2 50314475; fax: C39 2 50314476;
e-mail: pasqualina.trimarco@unimi.it
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.03.050

4958
E. M. Beccalli et al. / Tetrahedron 61 (2005) 4957–4964
Scheme 1.
Despite the low reaction temperature, the 4,5-dihydro-
triazole A could never be isolated, owing to its thermal
instability as a result of the electron-withdrawing effect of
the N-1 substituent12 which facilitates the cleavage of the
N1–N2 bond and promotes amidine rearrangement.
nucleophilic character of the a-methylene group of
amidines,14b,c as well as the presence of formyl or cyano
groups linked to C-3 of the coumarin ring, to plan an
intramolecular condensation reaction.
The amidines 3a–d were heated in methanol at reflux under
basic conditions, and easily transformed into the expected
2-amino-benzopyranopyridinones 4a–d. In the case of
substrates 3e–f, in addition to the desired products 4e–f,
the aldol intermediates 5e–f and the side product 6, arising
from the hydrolytic reaction of amidine were also isolated
(Scheme 2).
The proposed structures of amidines 3a–f and 3g–j were
validated by spectral data, which were consistent with the
available literature data for similar substitution patterns in
coumarin derivatives.13
It is well known that the activation of the a-methylene group
of amidines, with respect to condensation reaction, is
attributed to the existence of amidine–enediamine
tautomerism.14
In aldol intermediate 5, the subsequent water loss should be
assisted by the substituent group bound to C-3.
Taking into account the structural features of amidines 3a–f
and 3g–j we proposed, at first, to take advantage of the
To determine the best conditions to favour this process,
and to enhance the yield of derivatives 4a–b,e–f, we decided
Scheme 2.

E. M. Beccalli et al. / Tetrahedron 61 (2005) 4957–4964
Table 1. Effect of experimental conditions on 4,5,6 ratio
4959
We furthermore investigated the possibility to react 3-cyano
substituted acetamidines 3g–j with the aim to achieve
2,4-diaminobenzopyranopyridin-5-ones. By heating aceta-
midines 3g–j in basic medium (methoxide for 3g–h and
tbutoxide for 3i–j, respectively), the expected tricyclic
derivatives 4g–j bearing an NH2 group on C-4 were
produced.
Amidines 3
Compd. 4 yield (%)
Method Bc
Compd. 5a
yield (%)
Compd. 6a
yield (%)
Method Ab
a
b
c
d
e
f
46
58
94
85
70
88
—
—
60
66
0
0
0
0
36d/18e
38d/22e
28e
27e
35e
33e
13C NMR spectra of 4g–j showed a quaternary carbon at
about 150.6–151.7 ppm, as a diagnostic signal for C-4
linked to the amino group of the pyridine ring.15 In the IR
spectrum we also observed an absorption band in the range
1691–1698 cmK1, assigned to the stretching of the cou-
marin carbonyl group, whose frequency is lowered16 owing
to the intramolecular hydrogen bonding, with the neigh-
bouring amino function. The production of fused hetero-
cycles 4g–j can be rationalized as follows (Scheme 3).
a Compound formed only with method A.
b CH3ONa/CH3OH: see Section 4.
c p-TSA/toluene: see Section 4.
d Total yield: see Section 4.
e Yields of 4, 5, 6 from chromatographic column: see Section 4.
to perform the reaction of related amidines in acidic
medium.
The reaction of the amidines 3a–b,e–f in toluene at reflux,
containing a catalytic amount of p-toluensulfonic acid,
afforded the expected benzopyranopyridin-5-ones 4a–b,e–f.
Table 1 shows the results obtained under basic and acidic
media. Significant improvements in yields were achieved by
acidic reaction conditions (Table 1, method B), thus
confirming the hypothesis that the ring-closure reaction
occurs through isomerization of the amidine 3 into its
enediamino tautomer,14 followed by an intramolecular
condensation of the a-carbon with the formyl group. It is
plausible to postulate, in basic medium, a similar mecha-
nistic hypothesis.
In a basic medium, the iminic intermediate B arising from
the nucleophilic addition of the C-a amidinic carbon to the
cyano group, through rapid isomerization gave the desired
4-amino group.
The described success to synthesize 2-aminobenzopyrano-
pyridinones 4a–f from the corresponding 3-formyl acet-
amidines 3a–f prompted us to react the same compounds
to obtain 2-substituted benzopyranopyrimidin-5-ones 7.
As a synthetic route, we considered a mixture of 3-formyl
acetamidines 3a,c–f with an excess of ammonium acetate in
toluene at reflux. In a short reaction time, expected tricyclic
derivatives 7a–e were achieved in very good yield
(Scheme 4).
The structural assignments of 2-alkyl-benzopyranopyrimi-
1
din-5-ones 7a–e established by H and 13C NMR spectro-
scopy relating to the coumarin13a and pyrimidine17 nuclei,
were in agreement with the literature data.
In each case, we observed a typical pattern for the
coumarin13a moiety. 13C NMR spectra showed a first signal
at about 160 ppm, corresponding to a singlet17b at about 9.5
d related to CH-4 in HETCOR experiment, and a second
signal at 174.3–176.2 ppm associated to the lactone
carbonyl group, the latter validated also by IR (nujol)
stretching at about 1720 cmK1
.
In the 1H NMR spectra we noted a deshielding effect on the
Scheme 3.
Scheme 4.

4960
E. M. Beccalli et al. / Tetrahedron 61 (2005) 4957–4964
methylene group linked to C-2 of the pyrimidine nucleus
for the compounds 7a–e, relative to the starting amidines
3a,c–f, as a consequence of two nitrogen atoms in its ortho
position.
(decomp.); IR nmax (KBr) 2228 (CN), 2148 and 2130 (N3),
1
1722 (C]O) cmK1; H NMR d 7.36–7.44 (2H, m, H-6,
H-7); 7.71–7.79 (1H, m, H-5), 7.91 (1H, dd, JZ8.4, 1.4 Hz,
H-8); 13C NMR (DMSOd6): 90.5 (C-3), 112.8 (C-4a), 114.7
(CN), 118.1, 125.3, 126.3, 137.0 (CH), 153.5 (C-4), 157.7
(C-8a), 158.5 (C]O). Anal. Calcd for C10H4N4O2: C,
56.61; H, 1.90; N, 26.41; found: C, 56.49; H, 1.82; N, 26.59.
The achievement of fused heterocycles 7 can be rationalized
by the reaction path depicted in Scheme 4.
The reaction with ammonium acetate gave the imino
intermediate C, which rapidly underwent ring-closure
through addition to the C]N group of the amidine to give
an unstable 2,2-disubstituted-benzopyranopyrimidone D.
Morpholine elimination gave aromatic pyrimidine deriva-
tive 7.
4.2. General procedure for the preparation of amidines
3a–f
The suitable enamine 2a–f (10 mmol) was dissolved in
CH2Cl2 (20 mL). With careful monitoring of the internal
temperature (K40 8C, acetone–CO2 bath), an equimolar
amount of azide 1a, dissolved in CH2Cl2 (30 mL), was
slowly added dropwise with stirring. The mixture was kept
at K30 8C until disappearance (TLC: cyclohexane/EtOAc,
3:2) of the starting azide 1a. The stirring was continued until
room temperature was reached. The solvent was then
evaporated and the crude product purified by crystallization
from iPr2O to give pure 3a–f.
3. Conclusions
We have described new methods for the preparation of
both substituted 5H[1]benzopyrano[4,3-b]pyridin-5-ones
and 5H[1]benzopyrano[4,3-d]pyrimidin-5-ones in good
yields. At the same time, these synthetic routes represent
an expeditious access to polyheterocycles containing a
coumarin moiety, adding further proof of the utility of
substituted acetamidines as building blocks in organic
synthesis. Although the synthesis of a limited number of
derivatives is described in this paper, the flexibility of this
methodology should provide access to many variously
[1]benzopyrano[4,3-b]pyridin-5-ones and [1]benzopyrano-
[4,3-d]pyrimidin-5-ones.
4.2.1. N,N-Diethyl-N0-(3-formyl-2-oxo-2H-[1]benzo-
pyran-4yl)-2-phenyl-acetamidine 3b. Reaction time:
1.5 h. Yield 65%; pale yellow crystals, mp 127 8C; IR
1
nmax (Nujol) 1703 (C]O), 1668 (CHO) cmK1; H NMR:
1.24 (3H, t, JZ7.3 Hz, CH3), 1.29 (3H, t, JZ7.3 Hz, CH3),
3.30–4.11 (6H, m, CH2NCH2, CH2), 7.10–7.30 (5 HC2 H,
m, ArH, H-6, H-8), 7.53 (1H, td, JZ7.3, 1.8 Hz, H-7), 8.05
(1H, dd, JZ8.0, 1.8 Hz, H-5), 10.13 (1H, s, CHO); 13C
NMR: 11.8 (CH3), 13.8 (CH3), 38.0 (CH2), 44.1 (CH2N),
44.2 (CH2N), 100.2 (C-3), 117.2, 123.9, 126.9, 133.3 (CH),
120.4 (C-4a), 127.3, 128.5, 129.2 (ArCH) 134.8 (ArC),
154.3 (C-4), 157.2 (C-8a), 165.4 (N]C–N), 165.6 (C]O),
189.1 (CHO). Anal. Calcd for C22H22N2O3: C, 72.91; H,
6.12; N, 7.73; found: C, 72.68; H, 5.94; N, 7.89.
4. Experimental
4.1. General
Melting points were determined using a Buchi 510
(capillary) or an Electrothermal 9100 apparatus and are
uncorrected. IR spectra were measured using Perkin–Elmer
FT-IR 16 P.C. (Nujol), and Perkin–Elmer FT-IR Spectrum
4.2.2. 4-{[2-(4-Bromophenyl)-1-morpholin-4-ylethyli-
dene]amino}-2-oxo-2H-[1]benzopyran-3-carbaldehyde
3c. Reaction time: 1 h. Yield 78%; pale yellow crystals, mp
1
One (KBr) spectrometers. H and 13C NMR spectra were
153 8C; IR nmax (Nujol) 1700 (C]O), 1660 (CHO) cmK1
;
1H NMR: 3.59–4.03 (10H, m, morph., CH2), 6.98 and 7.32
(4H, JZ8.4 Hz, ArH), 7.21–7.35 (2 H, m, H-6, H-8), 7.57
(1H, td, JZ8.4, 1.8 Hz, H-7), 7.97 (1H, dd, JZ8.4, 1.8 Hz,
H-5), 10.14 (1H, s, CHO); 13C NMR: 37.3 (CH2), 46.6
(CH2NCH2), 66.2 (CH2OCH2), 100.5 (C-3), 117.2, 124.1,
126.7, 133.2 (CH), 119.6 (C-4a), 121.5 (ArCBr), 129.8,
132.3 (ArCH), 136.4 (ArC), 154.3 (C-4), 157.9 (C-8a),
164.6 (N]C–N), 165.0 (C]O), 189.2 (CHO). Anal. Calcd
for C22H19BrN2O4: C, 58.04; H, 4.21; N, 6.15; found: C,
57.91; H, 4.02; N, 6.37.
recorded on EM Varian Gemini 200 and on Bruker Avance
300 spectrometers in CDCl3 solution unless otherwise
stated. Chemical shifts are expressed in ppm from internal
standard tetramethylsilane (d), coupling constants (J) are
given in Hz. Column chromatography was performed on
Kieselgel 60 (Merck) 0.063–0.200 mm with eluents and
ratios indicated in Section 4.
Materials. Azide 1a,7 enamines 2a,c,d,8 2b,9 2e,10 2f 11 and
compounds 3a,5 4a,5 5e5 have already been described.
4-Chloro-2-oxo-2H-[1]benzopyran-3-carbonitrile6 and
4-amino-3-formylcoumarin7 6 are known compounds.
4.2.3. 4-{[2-(4-Methoxyphenyl)-1-morpholin-4-ylethyli-
dene]amino}-2-oxo-2H-[1]benzopyran-3-carbaldehyde
3d. Reaction time: 3 h. Yield 63%; yellow crystals, mp
4.1.1. 4-Azido-2-oxo-2H-[1]benzopyran-3-carbonitrile
1b. NaN3 (1.092 g, 0.0168 mmol), protected from light,
was suspended in dry DMF (30 mL) and chilled in an ice
bath. A solution of 4-chloro-2-oxo-2H-[1]benzopyran-3-
carbonitrile (3.3 g, 0.016 mmol) in dry DMF (50 mL) was
added over 20 min. The mixture was then stirred a further
3 h at 0 8C before being poured onto ice. The red–orange
precipitate was filtered and recrystallized from ethanol to
give the azide 1b (2.9 g, 85%) as orange crystals, mp 171 8C
138 8C; IR nmax (Nujol) 1700 (C]O), 1658 (CHO) cmK1
;
1H NMR: 3.54–4.01 (10H, m, morph., CH2), 3.76 (3H, s,
OCH3), 6.76 and 7.00 (4H, JZ8.4 Hz, ArH), 7.20–7.29
(2H, m, H-6, H-8), 7.55 (1H, td, JZ7.3, 1.8 Hz, H-7), 7.98
(1H, dd, JZ8.4, 1.8 Hz, H-5), 10.12 (1H, s, CHO); 13C
NMR: 37.2 (CH2), 46.7 (CH2NCH2), 55.3 (OCH3),
66.1(CH2OCH2), 100.7 (C-3), 117.1, 124.0, 127.0, 133.6
(CH), 120.1 (C-4a), 114.4, 130.0 (ArCH), 129.6 (ArC),

E. M. Beccalli et al. / Tetrahedron 61 (2005) 4957–4964
4961
154.2 (C-4), 157.5 (C-8a), 158.6 (ArCOCH3) 164.7 (N]C–
N), 165.4 (C]O), 189.3 (CHO). Anal. Calcd for
C23H22N2O5: C, 67.97; H, 5.46; N, 6.89; found: C, 67.87;
H, 5.74; N, 7.01.
4.3.2. N0-(3-Cyano-2oxo-2H-[1]benzopyran-4yl)-N,N-
diethyl-2-phenyl-acetamidine 3h. Reaction time: 2 h.
Yield 83%; apricot powder from AcOEt, mp 140 8C; IR
nmax (KBr) 2214 (CN), 1715 (C]O) cmK1; 1H NMR: 1.15
(3H, t, JZ7.3 Hz, CH3), 1.35 (3H, t, JZ7.3 Hz, CH3), 3.30–
4.22 (6H, m, CH2NCH2 and CH2), 7.12–7.33 (5 HC2 H, m,
ArH, H-6, H-8), 7.58 (1H, td, JZ6.9, 1.8 Hz, H-7), 7.90
(1H, dd, JZ8.0, 1.8 Hz, H-5); 13C NMR: 12.4 (CH3), 13.8
(CH3), 38.3 (CH2), 44.4 (CH2N), 44.6 (CH2N), 79.7 (C-3),
117.4 (CN), 118.2 (C-4a), 117.4, 124.3, 126.0, 133.9 (CH),
127.6, 128.3, 129.3 (ArCH), 134.4 (ArC), 153.7 (C-4),
160.8 (C-8a), 162.9 (N]C–N), 163.0 (C]O). Anal. Calcd
for C22H21N3O2: C, 73.52; H, 5.89; N, 11.69; found: C,
73.41; H, 5.66; N, 11.94.
4.2.4. 4-[(3-Methyl-1-morpholin-4-ylbutylidene)amino]-
2-oxo-2H-[1]benzopyran-3-carbaldehyde 3e. Reaction
time: 2 h. Yield 70%; yellow powder, mp 134 8C; IR nmax
1
(Nujol) 1699 (C]O), 1661 (CHO) cmK1; H NMR: 0.79
(3H, d, JZ6.6 Hz, CH3), 0.94 (3H, d, JZ6.6 Hz, CH3),
1.77–1.89 (1H, m, (CH3)2CH), 2.22–2.47 (2H, m, CH2),
3.60–4.08, (8H, m, morph.), 7.18–7.31 (2H, m, H-6, H-8),
7.55 (1H, td, JZ7.3, 1.8 Hz, H-7), 7.92 (1H, dd, JZ8.0,
1.4 Hz, H-5), 10.07 (1H, s, CHO); 13C NMR: 22.3 (CH3),
23.3 (CH3), 27.3 (CH), 39.6 (CH2), 54.5 (CH2NCH2), 66.4
(CH2OCH2), 99.8 (C-3), 117.2, 123.9, 127.0, 133.5 (CH),
119.9 (C-4a), 154.3 (C-4), 157.7 (C-8a), 165.4 (N]C–N),
167.8 (C]O), 188.8 (CHO). Anal. Calcd for C19H22N2O4:
C, 66.65; H, 6.48; N, 8.18; found: C, 66.78; H, 6.57; N, 7.97.
4.3.3. 4-[(3-Methyl-1-morpholin-4-ylbutylidene)amino]-
2-oxo-2H-[1]benzopyran-3-carbonitrile 3i. Reaction
time: 3 h. Yield 70%; pink powder from iPr2O, mp
1
139 8C; IR nmax (KBr) 2207 (CN), 1715 (C]O) cmK1; H
NMR: 0.80 (3H, d, JZ6.6 Hz, CH3), 1.00 (3H, d, JZ
6.6 Hz, CH3), 1.80–2.00 (1H, m, CH), 2.38–2.72 (2H, m,
CH2), 3.60–3.80 and 3.80–4.00 (8H, 2 m, morph.), 7.22–
7.38 (2H, m, H-6, H-8), 7.59 (1H, td, JZ8.4, 1.8 Hz, H-7),
7.79 (1H, dd, JZ8.0, 1.8 Hz, H-5); 13C NMR: 22.0 (CH3),
23.3 (CH3), 27.6 (CH), 39.9 (CH2), 48.3 (CH2NCH2), 66.6
(CH2OCH2), 79.7 (C-3), 117.1 (CN), 117.9 (C-4a), 117.5,
124.4, 126.2, 134.2 (CH), 153.8 (C-4), 160.8 (C-8a), 163.7
(N]C–N), 164.6 (C]O). Anal. Calcd for C19H21N3O3: C,
67.24; H, 6.24; N, 12.38; found: C, 67.43; H, 6.52; N, 12.13.
4.2.5. 4-[(1-Morpholin-4-yl-3-phenyl-propylidene)-
amino]-2-oxo-2H-[1]benzopyran-3-carbaldehyde 3f.
Reaction time: 2 h. Yield 69%; yellow powder, mp
108 8C; IR nmax (Nujol) 1700 (C]O), 1653 (CHO) cmK1
;
1H NMR: 2.60–2.99 (4H, m, CH2–CH2), 3.60–3.93 (8 H, m,
morph.), 7.02–7.27 (5 HC2 H, m, ArH, H-6, H-8), 7.54
(1H, td, JZ8.0, 1.8 Hz, H-7), 7.69 (1H, dd, JZ8.0, 1.8 Hz,
H-5), 10.08 (1H, s, CHO); 13C NMR: 32.3 (CH2), 33.3
(CH2), 46.5 (CH2NCH2), 66.1 (CH2OCH2), 99.7 (C-3),
117.1, 124.0, 126.8, 133.5 (CH), 119.6 (C-4a), 127.1, 128.4,
128.9 (ArCH), 139.1 (ArC), 154.2 (C-4), 157.6 (C-8a),
165.2 (N]C–N), 167.3 (C]O), 188.9 (CHO). Anal. Calcd
for C23H22N2O4: C, 70.75; H, 5.68; N, 7.17; found: C,
70.94; H, 5.54; N, 6.99.
4.3.4. 4-[(1-Morpholin-4-yl-3-phenylpropylidene)-
amino]-2-oxo-2H-[1]benzopyran-3-carbonitrile 3j.
Reaction time: 3 h. Yield 60%; pink powder from AcOEt,
mp 105 8C; IR nmax (KBr) 2210 (CN), 1716 (C]O) cmK1
;
1H NMR: 2.75–3.12 (4H, m, CH2–CH2), 3.60–3.97 (8H, m,
morph.), 7.02–7.36 (5 HC2 H, m, ArH, H-6, H-8), 7.45
(1H, dd, JZ8.0, 1.7 Hz, H-5), 7.58 (1H, td, JZ8.5, 1.7 Hz,
H-7); 13C NMR: 32.4 (CH2), 33.8 (CH2C6H5), 53.5
(CH2NCH2), 66.6 (CH2OCH2), 80.4 (C-3), 117.0 (CN),
117.7 (C-4a), 117.5, 124.6, 126.6, 134.3 (CH), 127.4, 128.6,
129.2 (ArCH), 138.7 (ArC), 153.8 (C-4), 160.7 (C-8a),
163.8 (N]C–N), 164.3 (C]O). Anal. Calcd for
C23H21N3O3: C, 71.30; H, 5.46; N, 10.85; found: C,
71.08; H, 5.39; N, 11.04.
4.3. General procedure for the preparation of amidines
3g–j
A solution of the appropriate enamine 2a–b,e–f (10 mmol)
in CH2Cl2 (20 mL) was added to a solution of an equimolar
amount of azide 1b dissolved in CH2Cl2 (30 mL), with
careful monitoring of internal temperature (K30 8C,
acetone–CO2 bath). The resulting dark red solution was
stirred at K30 8C until disappearance (TLC: cyclohexane/
EtOAc, 1:1) of the starting azide 1b. The stirring was
continued until room temperature was reached. The solvent
was then evaporated and the crude product purified by silica
gel column, eluent EtOAc/cyclohexane (3:7). The crude oil
crystallized from an appropriate solvent to give pure 3g–j.
4.4. General procedure for the synthesis of [1]benzo-
pyrano[4,3-b]pyridin-5-one derivatives 4a–f
Method A. A catalytic amount of sodium methoxide (0.5 ml,
30% solution) was added to a stirred suspension of the
appropriate 3-formylamidine 3a–f (4 mmol) in methanol
(100 mL). The mixture was heated at reflux until the starting
amidine disappeared. The solvent was evaporated under
reduced pressure and the crude residue was crystallized
from iPr2O to afford compounds 4a–d. In the case of
amidines 3e–f, after disappearance of the starting compound
(2 h) the crude reaction mixture was chromatographed on a
silica gel column (EtOAc/cyclohexane, 1:4) affording a first
fraction containing 4e–f, a second fraction of 4-amino-3-
formylcoumarin7 6 and finally the aldols 5e–f, respectively.
A catalytic amount of sodium methoxide (0.3 ml, 30%
solution) was added to the previously obtained aldols 5e–f.
The mixture heated for an additional time (5 h), yielding a
4.3.1. 4-[(1-Morpholin-4-yl-2-phenylethylidene)amino]-
2-oxo-2H-[1]benzopyran-3-carbonitrile 3g. Reaction
time: 2 h. Yield 60%; pale yellow crystals from AcOEt,
mp 215 8C; IR nmax (Nujol) 2206 (CN), 1700 (C]O) cmK1
;
1H NMR: 3.55–4.10 (10H, m, morph., CH2), 7.15–7.38
(5HC2 H, m, ArH, H-6, H-8), 7.61 (1H, td, JZ8.0, 1.8 Hz,
H-7), 7.89 (1H, dd, JZ8.1, 1.8 Hz, H-5); 13C NMR: 37.8
(CH2), 46.2 (CH2NCH2), 66.4 (CH2OCH2), 81.4 (C-3),
116.9 (CN), 117.9 (C-4a), 117.5, 124.6, 126.0, 134.3 (CH),
127.8, 128.2, 129.5 (ArCH), 133.9 (ArC), 153.7 (C-4),
160.3 (C-8a), 162.1 (N]C–N), 164.1 (C]O). Anal. Calcd
for C22H19N3O3: C, 70.76; H, 5.13; N, 11.25; found: C,
70.83; H, 5.34; N, 10.95.

4962
E. M. Beccalli et al. / Tetrahedron 61 (2005) 4957–4964
second batch of benzopyranopyridin-5-one 4e–f then
crystallized from iPr2O. The total yields of isolated and
purified products 4a–f,5e–f and 6 are listed in Table 1.
24.3 (2!CH3), 28.4 (CH), 51.2 (CH2NCH2), 67.0
(CH2OCH2), 112.1 (C-4a), 117.2, 124.61, 124.64, 131.5
(CH), 119.9 (C-10a), 136.6 (C-3), 137.0 (CH-4), 148.8
(C-6a), 153.0 (C-10b), 161.9 (C-2), 164.7 (C]O). Anal.
Calcd for C19H20N2O3: C, 70.35; H, 6.21; N, 8.64; found: C,
70.23; H, 6.08; N, 8.79.
Method B. A suspension of the appropriate 3-formylamidine
3a–b,e–f (4 mmol) in toluene (30 mL) containing a catalytic
(0.02 g) amount of p-TSA was heated at reflux until
disappearance of the starting amidine 3 (TLC: cyclohex-
ane/EtOAc, 1:1, about 6 h), and then the solvent evaporated
to dryness. The resulting solid residue was recrystallized
from iPr2O to give pure 4 derivatives. Analytical data are
shown above. The yields of isolated and purified compounds
4a–b,e–f are listed in Table 1.
4.4.5. 3-Benzyl-2-morpholin-4-yl-5H-[1]benzopyrano-
[4,3-b]pyridin-5-one 4f. Reaction time: 7 h. White crystals,
mp 174 8C; IR nmax (Nujol) 1721 (C]O) cmK1; 1H NMR:
3.51–3.58 (4H, m, CH2NCH2), 3.81–3.88 (4H, m,
CH2OCH2), 4.1 (2H, s, CH2), 7.14–7.60 (5H C3H, m,
ArH, H-7, H-8, H-9), 8.14 (1H, s, H-4), 8.48 (1H, dd, JZ
8.4, 1.4 Hz, H-10); 13C NMR: 38.3 (CH2), 50.1
(CH2NCH2), 66.9 (CH2OCH2), 111.2 (C-4a), 117.3,
124.6, 124.7, 131.7 (CH), 127.2, 129.0, 129.1 (ArCH),
119.8 (C-10a), 127.1 (C-3) 138.9 (ArC), 141.4 (CH-4),
149.5 (C-6a), 153.2 (C-10b), 161.6 (C-2), 164.5 (C]O).
Anal. Calcd for C23H20N2O3: C, 74.18; H, 5.41; N, 7.52;
found: C, 74.28; H, 5.45; N, 7.43.
4.4.1.
2-(Diethylamino)-3-phenyl-5H-[1]benzopyr-
ano[4,3-b]pyridin-5-one 4b. Reaction time: 1 h. Cream
crystals, mp 123 8C; IR nmax (Nujol) 1711 (C]O) cmK1; 1H
NMR: 1.12 (6H, t, JZ7.3 Hz, 2!CH3), 3.46 (4H, q, JZ
7.3 Hz, 2!CH2), 7.35–7.59 (5H C3H, m, ArH, H-7, H-8,
H-9), 8.14 (1H, s, H-4), 8.48 (1H, dd, JZ8.4, 1.4 Hz, H-10);
13C NMR: 13.0 (2!CH3), 44.8 (2!CH2N), 108.0 (C-4a),
117.3, 124.4, 124.7, 131.5 (CH), 120.1 (C-10a), 125.6 (C-3),
127.8, 128.0, 129.0 (ArCH), 140.3 (ArC), 141.3 (CH-4),
150.3 (C-6a), 153.5 (C-10b), 161.0 (C-2), 162.1 (C]O).
Anal. Calcd for C22H20N2O2: C, 76.72; H, 5.85; N, 8.13;
found: C, 76.81; H, 5.74; N, 7.95.
4.4.6. 3-Benzyl-4-hydroxy-2-morpholin-4-yl-3,4-dihy-
dro-5H-[1]benzopyrano[4,3-b]pyridin-5-one 5f. Reaction
time: 2 h. Pale yellow oil, IR nmax (Nujol) 3400 (OH), 1680
1
(C]O) cmK1; H NMR: 1.81 (1H, br s, OH), 2.40–2.52
(1H, m, CH-3), 2.65–3.00 (3H, m, CHNCH2, CH2Ph), 3.30–
3.80 (4HC1H, m, CH2OCH2, CHNCH2), 4.05–4.20 (2H,
m, CH2NCH2), 4.92 (1H, s, CH-4), 7.10–7.60 (5H C3H, m,
ArH, H-7, H-8, H-9), 8. 26 (1H, dd, JZ8.4, 1.8 Hz, H-10);
13C NMR: 37.0 (CH2), 41.8 (CH-3), 45.0 and 46.9
(CH2NCH2), 65.9 and 67.1 (CH2OCH2), 68.7 (CH-4),
99.6 (C-4a), 117.1, 124.0, 125.8, 132.1 (CH), 120.0
(C-10a), 127.7, 129.2, 129.7 (ArCH), 137.6 (ArC), 154.6
(C-6a), 154.8 (C-10b), 164.2 (C-2), 168.2 (C]O). Anal.
Calcd for C23H22N2O4: C, 70.75; H, 5.68; N, 7.17; found: C,
71.07; H, 5.84; N, 6.95.
4.4.2. 3-(4-Bromophenyl)-2-morpholin-4-yl-5H-[1]ben-
zopyrano[4,3-b]pyridin-5-one 4c. Reaction time: 0.5 h.
White crystals, mp 141 8C; IR nmax (KBr) 1725
1
(C]O) cmK1; H NMR: 3.44–3.52 (4H, m, CH2NCH2),
3.68–3.76 (4H, m, CH2OCH2), 7.33–7.60 (3H, m, H-7, H-8,
H-9), 7.48 and 7.63 (4H, JZ8.8 Hz, ArH), 8.26 (1H, s, H-4),
8.48 (1H, dd, JZ8.4, 1.8 Hz, H-10); 13C NMR: 48.9
(CH2NCH2), 66.4 (CH2OCH2), 110.1 (C-4a), 117.2, 124.4,
124.6, 131.8 (CH), 119.4 (C-10a), 122.3 (ArCBr), 125.1
(C-3), 129.1, 132.4 (ArCH), 137.9 (ArC), 141.1 (CH-4),
150.3 (C-6a), 153.3 (C-10b), 161.3 (C-2), 162.7 (C]O).
Anal. Calcd for C22H17BrN2O3: C, 60.43; H, 3.92; N, 6.41;
found: C, 60.27; H, 3.76; N, 6.18.
4.5. General procedure for the synthesis of 4-amino-[1]-
benzopyrano[4,3-b]pyridin-5-one derivatives 4g–h
A suspension of cyano amidine 3g or 3h (3.0 mmol) in
methanol (40 mL) was added to a well-stirred solution of Na
(0.076 g, 3.3 mmol) in methanol (15 mL). The reaction
mixture was heated at reflux until disappearance (TLC:
cyclohexane/EtOAc 2:3) of the starting amidine: 1 h for 4g
and 2 h for 4h. The mixture was cooled to room temperature
and afforded a solid product which was recrystallized from
methanol to give 4g or 4h, respectively.
4.4.3. 3-(4-Methoxyphenyl)-2-morpholin-4-yl-5H-[1]-
benzopyrano[4,3-b]pyridin-5-one 4d. Reaction time:
0.5 h. Cream crystals, mp 165 8C; IR nmax (Nujol) 1708
1
(C]O) cmK1; H NMR: 3.43–3.50 (4H, m, CH2NCH2),
3.68–3.74 (4H, m, CH2OCH2), 3.88 (3H, s, OCH3), 6.99 and
7.50 (4H, JZ8.4 Hz, ArH), 7.27–7.58 (3H, m, H-7, H-8,
H-9), 8.19 (1H, s, H-4), 8.42 (1H, d, JZ8.4 Hz, H-10); 13C
NMR: 48.7 (CH2NCH2), 55.4 (OCH3), 66.5 (CH2OCH2),
110.1 (C-4a), 117.1, 124.4, 124.5, 131.5 (CH), 119.6
(C-10a), 126.4 (C-3), 114.6, 128.7 (ArCH), 131.2 (ArC),
140.7 (CH-4), 149.7 (C-6a), 153.2 (C-10b), 159.6
(ArCOCH3), 161.5 (C-2), 162.0 (C]O). Anal. Calcd for
C23H20N2O4: C, 71.12; H, 5.19; N, 7.21; found: C, 70.97; H,
5.06; N, 7.06.
4.5.1. 4-Amino-2-morpholin-4-yl-3-phenyl-5H-[1]benzo-
pyrano[4,3-b]pyridin-5-one 4g. Yield 92%, white crystals,
mp 194 8C; IR nmax (Nujol) 3429 and 3300 (NH2), 1691
1
(C]O) cmK1; H NMR: 3.25–3.35 (4H, m, CH2NCH2),
3.52–3.59 (4H, m, CH2OCH2), 5.35 (2H, br s, NH2), 7.31–
7.60 (5H C3H, m, ArH, H-7, H-8, H-9), 8.47 (1H, dd, JZ
8.0, 1.8 Hz, H-10); 13C NMR (DMSOd6): 48.8 (CH2NCH2),
66.5 (CH2OCH2), 96.5 (C-4a), 106.4 (C-10a), 117.1,
125.1, 125.4, 132.6 (CH), 120.1 (C-3), 128.6, 130.5, 130.8
(ArCH), 135.6 (ArC), 151.5 (C-4), 152.8 (C-6a), 155.1
(C-10b), 161.3 (C-2), 162.7 (C]O). Anal. Calcd for
C22H19N3O3: C, 70.76; H, 5.13; N, 11.25; found: C,
70.78; H, 5.24; N, 11.38.
4.4.4.
3-Isopropyl-2-morpholin-4-yl-5H-[1]benzo-
pyrano[4,3-b]pyridin-5-one 4e. Reaction time: 7 h. Ivory
powder, mp 175 8C; IR nmax (Nujol) 1721 (C]O) cmK1; 1H
NMR: 1.34 (6H, d, JZ6.9 Hz, 2!CH3), 3.20 (1H, quint,
JZ6.9 Hz, CH), 3.46–3.66 (4H, m, CH2NCH2), 3.90–3.98
(4H, m, CH2OCH2), 7.20–7.60 (3H, m, H-7, H-8, H-9), 8.37
(1H, s, H-4), 8.48 (1H, dd, JZ8.0, 1.4 Hz, H-10); 13C NMR:

E. M. Beccalli et al. / Tetrahedron 61 (2005) 4957–4964
4963
4.5.2. 4-Amino-2-(diethylamino)-3-phenyl-5H-[1]benzo-
pyrano[4,3-b]pyridin-5-one 4h. Yield 60%, white crystals,
mp 180 8C; IR nmax (KBr) 3487 and 3354 (NH2), 1695
(C]O) cmK1; 1H NMR: 0.99 (6H, t, JZ6.9 Hz, 2!CH3),
3.46 (4H, q, JZ6.9 Hz, 2!CH2), 5.40 (2H, br s, NH2),
7.30–7.46 (5H, m, ArH) 7.48–7.57 (3H, m, H-7, H-8, H-9),
8.46 (1H, dd, JZ8.0, 1.4 Hz, H-10); 13C NMR: 13.4 (2!
CH3), 44.7 (2!CH2N), 96.5 (C-4a), 104.9 (C-10a), 116.8,
124.3, 125.2, 131.3 (CH), 120.7 (C-3), 128.1, 130.0, 130.9
(ArCH), 136.6 (ArC), 151.7 (C-4); 153.1 (C-6a), 154.9
(C-10b), 160.4 (C-2), 163.6 (C]O). Anal. Calcd for
C22H21N3O2: C, 73.52; H, 5.89; N, 11.69; found: C,
73.77; H, 5.84; N, 11.56.
(see after) until disappearance of the starting amidine 3
(TLC: cyclohexane/EtOAc, 4:1), then evaporated to dry-
ness. The residue was poured into water and extracted with
CH2Cl2 (3!40 mL). The combined organic layers were
washed twice with water (2!40 mL) and dried over
Na2SO4, filtered and evaporated to dryness. The resulting
solid was recrystallized from iPr2O to give pure 7
derivatives.
4.7.1. 2-Benzyl-5H-[1]benzopyrano[4,3-d]pyrimidin-5-
one 7a. Reaction time: 1 h. Yield 63%, cream crystals,
mp 131 8C; IR nmax (Nujol) 1720 (C]O) cmK1; 1H NMR:
4.49 (2H, s, CH2), 7.27–7.50 (5H C2H, m, ArH, H-7, H-9),
7.71 (1H, td, JZ7.3, 1.4 Hz, H-8), 8.63 (1H, dd, JZ7.7,
1.4 Hz, H-10), 9.53 (1H, s, H-4); 13C NMR (DMSOd6): 46.4
(CH2), 113.7 (C-4a), 118.2 (C-10a), 118.1, 125.3, 125.8,
135.3 (CH), 127.4, 129.2, 130.0 (ArCH), 138.2 (ArC), 154.8
(C-6a), 158.3 (C-10b), 159.8 (C-2), 160.7 (CH-4), 174.4
(C]O). Anal. Calcd for C18H12N2O2: C, 74.99; H, 4.20; N,
9.72; found: C, 74.87; H, 4.24; N, 9.76.
4.6. General procedure for the synthesis of 4-amino-[1]-
benzopyrano[4,3-b]pyridin-5-one derivatives 4i–j
A suspension of cyano amidine 4i or 4j (3.0 mmol) in
tbutanol (40 mL) was added to a well-stirred solution of
tBuOK (0.38 g, 3.3 mmol) in tbutanol (10 mL). The
reaction mixture was heated at reflux until disappearance
(TLC: cyclohexane/EtOAc 2:3) of the starting amidine
(about 2 h) and evaporated to dryness. The residue was
poured into water and extracted with CH2Cl2 (3!40 mL).
The combined organic layers were washed twice with water
(2!40 mL) and dried over Na2SO4, filtered and evaporated
to dryness. The crude product was recrystallized from
methanol to give 4i or 4j, respectively.
4.7.2. 2-(4-Bromobenzyl)-5H-[1]benzopyrano[4,3-d]pyri-
midin-5-one 7b. Reaction time: 0.5 h. Yield 89%, cream
crystals, mp 185 8C; IR nmax (KBr) 1746 (C]O) cmK1; 1H
NMR: 4.44 (2H, s, CH2), 7.34 and 7.48 (4H, JZ8.4 Hz,
ArH), 7.39–7.49 (2H, m, H-7, H-9), 7.71 (1H, td, JZ7.7,
1.8 Hz, H-8), 8.59 (1H, dd, JZ7.7, 1.8 Hz, H-10), 9.53 (1H,
s, H-4); 13C NMR: 46.0 (CH2), 112.5 (C-4a), 117.7 (C-10a),
121.1 (ArCBr), 117.6, 125.2, 125.4, 134.6 (CH), 131.2,
131.8 (ArCH), 136.1 (ArC), 154.5 (C-6a), 158.5 (C-10b),
159.5 (C-2), 160.8 (CH-4), 174.3 (C]O). Anal. Calcd for
C18H11BrN2O2: C, 58.88; H, 3.02; N, 7.63; found: C, 58.67;
H, 3.00; N, 7.55.
4.6.1. 4-Amino-3-isopropyl-2-morpholin-4-yl-5H-[1]ben-
zopyrano[4,3-b]pyridin-5-one 4i. Yield 56%, pale yellow
crystals, mpO300 8C; IR nmax (KBr) 3465 (NH2), 1698
(C]O) cmK1; 1H NMR: 1.44 (6H, d, JZ7.3 Hz, 2!CH3),
3.28–3.34 (4H, m, CH2NCH2), 3.57 (1H, quint, JZ7.3 Hz,
CH), 3.88–3.94 (4H, m, CH2OCH2), 5.90 (2H, br s, NH2),
7.30–7.38 (2H, m, H-7, H-9), 7.52 (1H, td, JZ7.8, 1.4 Hz,
H-8), 8.47 (1H, dd, JZ7.8, 1.4 Hz, H-10); 13C NMR: 19.9
(2!CH3), 26.5 (CH), 51.8 (CH2NCH2), 67.4 (CH2OCH2),
99.4 (C-4a), 113.9 (C-10a), 116.9, 124.6, 125.3, 131.6 (CH),
120.6 (C-3), 150.6 (C-4), 152.7 (C-6a), 156.4 (C-10b),
164.1 (C-2), 165.1 (C]O). Anal. Calcd for C19H21N3O3: C,
67.24; H, 6.24; N, 12.38; found: C, 67.42; H, 6.25; N, 12.36.
4.7.3. 2-(4-Methoxybenzyl)-5H-[1]benzopyrano[4,3-d]-
pyrimidin-5-one 7c. Reaction time: 1 h. Yield 82%,
cream crystals, mp 110 8C; IR nmax (Nujol) 1723
1
(C]O) cmK1; H NMR: 3.78 (3H, s, OCH3), 4.39 (2H, s,
CH2), 6.87 and 7.37 (4H, JZ8.8 Hz, ArH), 7.35–7.47 (2H,
m, H-7, H-9), 7.65 (1H, td, JZ7.3, 1.8 Hz, H-8), 8.58 (1H,
dd, JZ7.8, 1.8 Hz, H-10), 9.48 (1H, s, H-4); 13C NMR: 45.8
(CH2), 55.5 (OCH3), 112.3 (C-4a), 117.8 (C-10a), 129.3
(ArC), 117.5, 125.2, 125.4, 134.4 (CH), 114.2, 130.4
(ArCH), 154.4 (C-6a), 158.3 (C-10b), 158.7 (ArCOCH3),
159.6 (C-2), 160.7 (CH-4), 175.2 (C]O). Anal. Calcd for
C19H14N2O3: C, 71.69; H, 4.43; N, 8.80; found: C, 71.69; H,
4.41; N, 8.74.
4.6.2. 4-Amino-3-benzyl-2-morpholin-4-yl-5H-[1]benzo-
pyrano[4,3-b]pyridin-5-one 4j. Yield 64%, pale yellow
crystals, mp 135 8C; IR nmax (KBr) 3435 and 3342 (NH2),
1697 (C]O) cmK1
;
1H NMR: 3.35–3.49 (4H, m,
CH2NCH2), 3.75–3.85 (4H, m, CH2OCH2), 4.06 (2H, s,
CH2), 5.35 (2H, br s, NH2), 7.20–7.40 (5H C2H, m, ArH,
H-7, H-9), 7.54 (1H, td, JZ8.0, 1.4 Hz, H-8), 8.51 (1H, d,
JZ8.0 Hz, H-10); 13C NMR: 33.0 (CH2), 50.7 (CH2NCH2),
67.2 (CH2OCH2), 98.2 (C-4a), 104.9 (C-10a), 116.8, 124.5,
125.2, 131.6 (CH), 120.4 (C-3), 127.3, 127.8, 129.5 (ArCH),
137.0 (ArC), 151.3 (C-4), 152.7 (C-6a), 156.4 (C-10b),
163.6 (C-2), 165.1 (C]O). Anal. Calcd for C23H21N3O3: C,
71.30; H, 5.46; N, 10.85; found: C, 71.21; H, 5.47; N, 10.94.
4.7.4. 2-Isobutyl-5H-[1]benzopyrano[4,3-d]pyrimidin-5-
one 7d. Reaction time: 1 h. Yield 85%, white crystals, mp
117 8C; IR nmax (Nujol) 1723 (C]O) cmK1; 1H NMR: 1.05
(6H, d, JZ6.6 Hz, 2!CH3), 2.45 (1H, ept, JZ6.6 Hz, CH),
3.05 (2H, d, JZ7.3 Hz, CH2), 7.39–7.50 (2H, m, H-7, H-9),
7.69 (1H, td, JZ7.7, 1.8 Hz, H-8), 8.64 (1H, dd, JZ7.7,
1.4 Hz, H-10), 9.53 (1H, s, H-4), 13C NMR: 22.6 (2!CH3),
28.5 (CH), 49.1 (CH2), 112.1 (C-4a), 117.9 (C-10a), 117.5,
125.1, 125.3, 134.3 (CH), 154.4 (C-6a), 157.9 (C-10b),
159.7 (C-2), 160.1 (CH-4), 176.2 (C]O). Anal. Calcd for
C15H14N2O2: C, 70.85; H, 5.55; N, 11.02; found: C, 70.77;
H, 5.48; N, 10.98.
4.7. General procedure for the synthesis of [1]benzo-
pyrano[4,3-d]pyrimidin-5-one derivatives 7a–e
A solution of the amidine 3a,c–f (20 mmol) in toluene
(25 mL) was added to ammonium acetate (100 mmol). The
resulting mixture was heated at reflux for the reported time
4.7.5. 2-(2-Phenylethyl)-5H-[1]benzopyrano [4,3-d]pyri-
midin-5-one 7e. Reaction time: 3 h. Yield 94%, cream

4964
E. M. Beccalli et al. / Tetrahedron 61 (2005) 4957–4964
crystals, mp 105 8C; IR nmax (Nujol) 1720 (C]O) cmK1; 1H
NMR: 3.31–3.35 and 3.45–3.46 (4H, 2!m, CH2-CH2),
7.18–7.53 (5HC2H, m, ArH, H-7, H-9), 7.70 (1H, td, JZ
7.7, 1.8 Hz, H-8), 8.63 (1H, dd, JZ7.7, 1.8 Hz, H-10), 9.53
(1H, s, H-4); 13C NMR: 34.0 (CH2C6H5), 41.6 (CH2), 112.3
(C-4a), 117.8 (C-10a), 117.6, 125.2, 125.3, 134.5 (CH),
126.3, 128.4, 128.5, (ArCH), 140.9 (ArC), 154.4 (C-6a),
158.1 (C-10b), 159.8 (C-2), 160.3 (CH-4), 175.7 (C]O).
Anal. Calcd for C19H14N2O2: C, 75.48; H, 4.67; N, 9.27;
found: C, 75.40; H, 4.64; N, 9.25.
5. Beccalli, E. M.; Contini, A.; Trimarco, P. Tetrahedron Lett.
2004, 45, 3447–3449.
6. Checchi, S.; Pecori Vettori, L.; Vincieri, F. Gazz. Chim. Ital.
1968, 98, 1488–1502.
7. Steinfu
¨hrer, T.; Hantschmann, A.; Pietsch, M.; Weibenfels, M.
Liebigs Ann. Chem. 1992, 23–28.
8. Broekhof, N. L. J. M.; Jonkers, F. L.; van der Gen, A.
Tetrahedron Lett. 1979, 2433–2436.
9. Mannich, C.; Davidsen, H. Chem. Ber. 1936, 69, 2106–2122.
10. Knorr, R.; Loew, P.; Hassel, P. Synthesis 1983, 785–786.
11. Fisher, G. B.; Lee, L.; Klettke, F. W. Synth. Commun. 1994,
24, 1541–1546.
Acknowledgements
ˇ
12. Kadaba, P. K.; Stanovnik, B.; Tisler, M. Adv. Heterocycl.
Chem. 1984, 37, 339 and references cited therein.
13. (a) Rabaron, A.; Didry, J. R.; Kirkiacharian, B. S.; Plat, M. M.
Org. Magn. Reson. 1979, 12, 284–288. (b) Michalik, M.;
Peseke, K.; Radeglia, R. J. Prakt. Chem. 1981, 323, 506–510.
(c) Michalik, M.; Kreutzmann, J. Sulfur Lett. 1986, 4, 73–78.
(d) Ivanov, I. C.; Karagiosov, S. K.; Simeonov, M. F. Liebigs
Ann. Chem. 1992, 203–207.
This work was supported by MIUR (Ministero dell’Istru-
zione e della Ricerca Universitaria). The authors thank Mrs.
D. Nava for recording NMR spectra and HETCOR
experiment as well as Dr. V. Bertacche for recording IR
spectra.
14. (a) Boyd, G. V. In Patai, S., Rappoport, Z., Eds.; The
Chemistry of Amidines and Imidates; Interscience: London,
1991; Vol. 2, p 370; and references cited therein. (b) Pfau, M.;
Chiriacescu, M.; Revial, G. Tetrahedron Lett. 1993, 34,
327–330. (c) Cado, F.; Di Martino, J. L.; Jacquault, P.;
Bazureau, J. P.; Hamelin, J. Bull. Soc. Chim. Fr. 1996, 133,
587–595.
References and notes
1. Heber, D.; Berghaus, T. J. Heterocycl. Chem. 1994, 31,
1353–1359.
2. Bruno, O.; Brullo, C.; Ranise, A.; Schenone, S.; Bondavalli,
F.; Barocelli, E.; Ballabeni, V.; Chiavarini, M.; Tognolini, M.;
Impicciatore, M. Bioorg. Med. Chem. Lett. 2001, 1397–1400.
3. Eggenweiler, M.; Rochus, J.; Wolf, M.; Gassen, M.; Poeschke,
O., Merck Patent Gmbh, Germany, PCT Int. Appl. 2001;
Chem. Abstr., 2001, 134, 331619.
15. Rasala, D. J. Phys. Org. Chem. 1993, 6, 307–315.
˘ ´
16. Kettermann, V.; Svetlık, J.; Kratkly, C. Acta Cryst. 2001, C57,
590–592.
17. (a) Abbotto, A.; Alanzo, V.; Bradamante, S.; Pagani, G. A.
J. Chem. Soc. Perkin Trans. 2 1991, 481–488. (b) Ivanov, I. C.;
Karagiosov, S. K.; Alexandrova, S. V. C.R. Acad. Bulg. Sci.
1998, 51, 61–62.
4. Beccalli, E. M.; Contini, A.; Trimarco, P. Eur. J. Org. Chem.
2003, 3976–3984.