Convenient synthesis of 11-aryl-1,12-dihydro-11H-naphthopyrano[2,3-d] pyrimidin-12-ones

Article abstract of DOI:10.1080/00397910903419928

Various imidates 3 were successfully synthesized from naphthopyrans and ethyl orthoesters in moderate yields. These intermediates undergo rapid condensation with several primary amines to give the corresponding 11-aryl-1,12-dihydro-11H-naphthopyrano[2,3-d

Full text of DOI:10.1080/00397910903419928

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Convenient Synthesis of 11-Aryl-1,12-
dihydro-11H-naphthopyrano[2,3-
d]pyrimidin-12-ones
Kamar Mkaouar a , Fakher Chabchoub a , Abdelouahid Samadi b
José Louis Marco Contelles b & Mansour Salem a
,
a Laboratoire de Chimie Appliquée: Hétérocycles, Corps Gras et
Polymères, Faculté des Sciences de Sfax, Sfax, Tunisia
b Instituto de Química Orgánica (CSIC), Madrid, Spain
Available online: 15 Oct 2010
To cite this article: Kamar Mkaouar, Fakher Chabchoub, Abdelouahid Samadi, José Louis
Marco Contelles & Mansour Salem (2010): Convenient Synthesis of 11-Aryl-1,12-dihydro-11H-
naphthopyrano[2,3-d]pyrimidin-12-ones, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 40:22, 3405-3414
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Synthetic Communications1, 40: 3405–3414, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903419928
CONVENIENT SYNTHESIS OF 11-ARYL-1,12-DIHYDRO-
11H-NAPHTHOPYRANO[2,3-d]PYRIMIDIN-12-ONES
Kamar Mkaouar,1 Fakher Chabchoub,1 Abdelouahid Samadi,2
2
Jose Louis Marco Contelles, and Mansour Salem
1
´
Laboratoire de Chimie Appliquee: Heterocycles, Corps Gras et Polymeres,
1
´
Faculte des Sciences de Sfax, Sfax, Tunisia
´ ´
`
´
2
´
´
Instituto de Quımica Organica (CSIC), Madrid, Spain
Various imidates 3 were successfully synthesized from naphthopyrans and ethyl orthoesters
in moderate yields. These intermediates undergo rapid condensation with several primary
amines to give the corresponding 11-aryl-1,12-dihydro-11H-naphthopyrano[2,3-d]
pyrimidin-12-ones 4.
Keywords: Imidates; naphthopyranopyrimidinones; naphthopyrans; pyranopyrimidinones
INTRODUCTION
Considerable interest has been shown in several pyran ring systems, especially for
pyranopyrimidines, on account of their different types of interesting biological activi-
ties. It has been reported that various pyranopyrimidines exhibit antimicrobial,[1]
antibacterial,[2] antigenotoxic,[3] and antifungal activities.[4–6] Also, pyranopyrimidines
derivatives can have antiplatelet, antithrombotic,[7] analgesic, anti-inflammatory, and
antiphlogistic activity.[8–9] Moreover, the biological activities of fused pyrimidines have
led to intensive research on their synthesis.[10–20] We report here the synthesis of new
pyranopyrimidinones derivatives 4 using 2-amino-4-aryl-4H-naphtho[2,1-b]pyran-3-
ethoxycarbonyl 2 as a starting material.
RESULTS AND DISCUSSION
In continuation of our previous work,[3,10–12] it seemed interesting to use
naphthopyrans for the synthesis of new naphthopyranopyrimidinones. In the present
study, we began first by synthesizing 2-amino-4-aryl-4H-naphtho[2,1-b]pyran-3-
ethoxycarbonyl 2 by reacting a-cyanocinnamonitriles 1 with 2-naphthol under reflux
of ethanol (Scheme 1).
Received September 2, 2009.
Address correspondence to Kamar Mkaouar, Laboratoire de Chimie Appliquee: Heterocycles,
´ ´ ´
Corps Gras et Polymeres, Faculte des Sciences de Sfax, 3000 Sfax, Tunisia. E-mail: kmarmkaouar_
fourati@yahoo.fr
`
´
3405

3406
K. MKAOUAR ET AL.
Scheme 1. Reagents and conditions: EtOH=pyperidine, reflux, 5 h.
These compounds were obtained in good yields and will be opposed to several
orthoesters (ethyl orthoacetate or ethyl orthopropionate) to give the corresponding
2-[(ethoxyalkylidene)amino]-4-aryl-3-ethoxycarbonyl-4H-naphtho[2,1-b]pyrans 3.
While with ethyl orthoformiate, we noticed that the product did not match to
imidate 3. Indeed, different spectroscopic techniques have shown that compounds
30 were identified as 4-aryl-3-ethoxycarbonyl-2-formylamino-4H-naphtho[2,1-b]pyrans
(Scheme 2).
Starting from the key intermediate imidates 3 with an excess of the suitable
primary amine, under reflux of toluene, we obtained the pyranopyrimidinones 4
(Scheme 3), whose structure was confirmed by 1H NMR data by the disappearance of
signals related to the two ethoxy groups and the presence of signals introduced by amine.
Scheme 2. Reagents and conditions: CH3COOH, reflux, 24 h: (i) MeC(OEt)3 or EtC(OEt)3; (ii) CH(OEt)3.

SYNTHESIS OF NAPHTHOPYRANOPYRIMIDINONES
3407
Scheme 3. Reagents and conditions: (i) R0-NH2 in toluene, reflux, 48 h.
1
Structures of the target compounds (1–4) were confirmed by infrared (IR), H
NMR, and 13C NMR spectral data. In addition, all the new pyranopyrimidinone
derivatives have been determined with high-resolution mass spectra (HRMS) and
microanalyzed satisfactorily for C, H, and N.
In conclusion, we have synthesized and analyzed a series of 2-[(ethoxyalkyl-
idene)amino]-4-aryl-3-ethoxycarbonyl-4H-naphtho[2,1-b]pyrans 3 that are variously
substituted at the 2- and 4-phenyl moieties, by reacting 2-amino-4-aryl-4H-naphtho
[2,1-b]pyran-3-ethoxycarbonyl 2 with several orthoesters. Subsequently, these imi-
dates 3 were opposed to primary amines to give new naphthopyranopyrimidinone
4 derivatives.
EXPERIMENTAL
All melting points were determined on a Kofler-type microscope and are
uncorrected. IR spectra were recorded on a Perkin-Elmer Fourier transform
1
FT–IR spectrophotometer (4000–400 cmꢀ1) using KBr pellets. H NMR and 13C
NMR spectra were recorded at room temperature (rt) in CDCl3 or dimethylsulfoxide
(DMSO-d6) at 300, 400, or 500 MHz and at 75, 100, or 125 MHz, respectively, using
solvent peaks [CDCl3: 7.27 (D), 77.2 (C) ppm and DMSO-d6 2.50 (D) and 39.7 (C)
ppm] as internal reference. The assignment of chemical shifts is based on standard
NMR experiments (1H, 13C) using tetramethylsilane (TMS) as the internal standard.
Mass spectra (MS) were recorded on a gas chromatography (GC) MS spectrometer
with an atmospheric pressure electrospray (API-ES) ionization source. Elemental
´
analyses (C, H, and N) were performed at the Instituto de Quımica Organica
(Consejo Superior de Investigaciones Cientıficas, Spain). All solvents were dried
´
´
by standard methods.
General Procedure for 2-Amino-4-aryl-3-ethoxycarbonyl-4H-
naphtho[2,1-b]pyrans 2a–d
A mixture of a-cyanocinnamonitriles 1a–e (0.01 mmol) and 2-naphthol
(0.01 mmol) in ethanol (20 ml) was refluxed for 5 h with the presence of 0.2 equivalent

3408
K. MKAOUAR ET AL.
of piperidine. The solid product that formed was filtered, washed with cold ethanol,
dried, and recrystallized with a suitable solvent to give compounds 2a–e in good
yields.
Selected Data
2-Amino-3-ethoxycarbonyl-4-phenyl-4H-naphtho[2,1-b]pyran (2a). Yield
1
82%, mp 168–170 ꢁC; H NMR (DMSO-d6; 300 MHz) d: 1.23 (t, J ¼ 7.0 Hz, 3H),
4.08 (q, J ¼ 7.0 Hz, 2H), 5.51 (s, 1H), 7.00–8.02 (m, 11H, Ar-H), 7.67 (br, 2H,
NH2, cancelled by D2O); 13C NMR (DMSO-d6; 75 MHz) d: 14.91, 37.02, 59.39,
78.27, 117.20, 119.32, 123.64, 125.27, 126.42, 127.55, (double intensity): 128.21,
(double intensity): 128.59, 129.04, 129.42, 130.78, 131.25, 147.24, 147.38, 160.98,
168.65; IR (KBr) nCO: 1685, nNH : 3300–3438 cmꢀ1
.
2
2-Amino-3-ethoxycarbonyl-4-(p-methylphenyl)-4H-naphtho[2,1-b]pyran
(2b). Yield 72%, mp 194–196 ꢁC; 1H NMR (DMSO-d6; 300 MHz) d: 1.24 (t,
J ¼ 7.0 Hz, 3H), 2.10 (s, 3H), 4.09 (q, J ¼ 7.0 Hz, 2H), 5.49 (s, 1H), 6.93–8.01 (m,
10H, Ar-H), 7.68 (br, 2H, NH2, cancelled by D2O); 13C NMR (DMSO-d6;
75 MHz) d: 14.92, 20.94, 36.64, 59.38, 78.39, 117.18, 119.48, 123.67, 125.20,
127.46, (double intensity): 128.09, (double intensity): 129.00, 129.13, 129.30,
130.82, 131.26, 135.39, 144.47, 147.20, 160.95, 168.73; IR (KBr) nCO: 1687, nNH
:
2
3320–3440 cmꢀ1
.
2-Amino-3-ethoxycarbonyl-4-(o-methoxylphenyl)-4H-naphtho[2,1-b]-
1
pyran (2c). Yield 60%, mp 188–190 ꢁC; H NMR (DMSO-d6; 300 MHz) d: 1.14 (t,
J ¼ 6.9 Hz, 3H), 3.80 (s, 3H), 4.01 (q, J ¼ 6.9 Hz, 2H), 5.82 (s, 1H), 6.72–8.25 (m,
10H, Ar-H), 7.68 (br, 2H, NH2, cancelled by D2O); 13C NMR (DMSO-d6;
75 MHz) d: 14.77, 31.34, 55.83, 59.18, 77.50, 111.63, 117.16, 119.59, 120.84,
123.77, 125.07, 127.32, 127.79, 128.91, 128.95, 130.55, 131.04, 131.38, 135.50,
147.36, 156.15, 161.48, 169.09; IR (KBr) nCO: 1690, nNH : 3339–3425 cmꢀ1
.
2
2-Amino-4-(o-chlorophenyl)-3-ethoxycarbonyl-4H-naphtho[2,1-b]pyran
(2d). Yield 65%, mp 170–172 ꢁC; 1H NMR (DMSO-d6; 300 MHz) d: 1.15 (t,
J ¼ 7.0 Hz, 3H), 4.05 (q, J ¼ 7.0 Hz, 2H), 5.82 (s, 1H), 7.00–8.20 (m, 10H, Ar-H),
7.79 (br, 2H, NH2, cancelled by D2O); 13C NMR (DMSO-d6; 75 MHz) d: 14.97,
34.62, 59.34, 77.22, 117.32, 118.58, 123.51, 125.33, 127.58, 127.92, 128.29, 129.18,
129.78, 129.99, 131.10, 131.13, 131.71, 131.97, 144.59, 147.38, 161.23, 168.78; IR
(KBr) nCO: 1692, nNH : 3341–3430 cmꢀ1
.
2
General Procedure for 2-[(Ethoxyalkylidene) Amino]-4-aryl-3-
ethoxycarbonyl-4H-naphtho[2,1-b]pyrans 3a–h
A solution of 2a–e (0.01 mmol) was treated with ethyl orthoester (0.06 mmol)
and acetic acid (0.5 ml). The mixture was heated, and the ethanol formed was con-
tinuously distilled at atmospheric pressure. Then we added a second portion of acetic
acid, and the main mixture was heated under reflux for 24 h. The solid product
formed was collected by filtration and recrystallized with a suitable solvent to give
compounds 3a–h and 30a, b.

SYNTHESIS OF NAPHTHOPYRANOPYRIMIDINONES
3409
Selected Data
2-[(Ethoxyethylidene)amino]-3-ethoxycarbonyl-4-phenyl-4H-naphtho-
[2,1-b]pyran (3a). Yield 81%, mp 120–122 ꢁC; 1H NMR (CDCl3; 300 MHz) d: 1.17
(t, J ¼ 7.1 Hz, 3H), 1.25 (t, J ¼ 7.2 Hz, 3H), 1.95 (s, 3H), 4.18 (q, J ¼ 7.1 Hz, 2H), 4.25
(q, J ¼ 7.2 Hz, 2H), 5.70 (s, 1H), 6.92–8.17 (m, 11H, Ar-H); 13C NMR (CDCl3;
75 MHz) d: 14.46, 14.59, 17.93, 37.60, 60.36, 63.49, 94.28, 117.41, 118.29, 123.89,
125.05, 126.41, 127.20, 127.23, 127.73, 128.46, 128.83, 129.13, 131.36, 131.47,
131.77, 146.25, 148.48, 159.37, 166.91, 167.59; IR (KBr) nCO: 1670 cmꢀ1
.
2-[(Ethoxyethylidene)amino]-3-ethoxycarbonyl-4-(p-methylphenyl)-4H-
naphtho[2,1-b]pyran (3b). Yield 90%, mp 118–120 ꢁC; 1H NMR (CDCl3;
300 MHz) d: 1.32 (t, J ¼ 6.9 Hz, 3H), 1.40 (t, J ¼ 7.0 Hz, 3H), 1.98 (s, 3H), 2.24 (s,
3H), 4.18 (q, J ¼ 6.9 Hz, 2H), 4.38 (q, J ¼ 7.0 Hz, 2H), 5.80 (s, 1H), 7.03–8.08 (m,
10H, Ar-H); 13C NMR (CDCl3; 75 MHz) d: 14.19, 14.23, 17.33, 20.19, 37.49,
58.91, 62.03, 92.86, 115.94, 116.90, 122.38, 123.55, 125.75, (double intensity):
127.10, 127.36, 127.56, (double intensity): 127.87, 129.81, 130.23, 134.64, 141.85,
146.84, 157.82, 165.48, 166.19; IR (KBr) nCO: 1680 cmꢀ1
.
2-[(Ethoxyethylidene)amino]-3-ethoxycarbonyl-4-(o-methoxylphenyl)-
4H-naphtho[2,1-b]pyran (3c). Yield 84%, mp 144–146 ꢁC; 1H NMR (CDCl3;
300 MHz) d: 1.30 (t, J ¼ 7.2 Hz, 3H), 1.41 (t, J ¼ 7.1 Hz, 3H), 2.04 (s, 3H), 3.87 (s,
3H), 4.14 (q, J ¼ 7.2 Hz, 2H), 4.38 (q, J ¼ 7.1 Hz, 2H), 6.79 (s, 1H), 6.79–8.31 (m,
10H, Ar-H); 13C NMR (CDCl3; 75 MHz) d: 14.19, 14.33, 17.61, 33.85, 55.42,
59.88, 63.14, 92.98, 111.13, 117.06, 118.20, 120.73, 123.94, 124.49, 126.64, 127.73,
(double intensity): 128.35, 131.04, 131.20, 131.49, 134.11, 148.31, 156.33, 159.57,
166.76, 167.47; IR (KBr) nCO: 1665 cmꢀ1
.
2-[(Ethoxyethylidene)amino]-4-(o-chlorophenyl)-3-ethoxycarbonyl-4H-
naphtho[2,1-b]pyran (3d). Yield 40%, mp 120–122 ꢁC; 1H NMR (CDCl3;
300 MHz) d: 1.27 (t, J ¼ 7.0 Hz, 3H), 1.40 (t, J ¼ 7.0 Hz, 3H), 2.02 (s, 3H), 4.18 (q,
J ¼ 7.0 Hz, 2H), 4.20 (q, J ¼ 7.0 Hz, 2H), 6.20 (s, 1H), 6.97–8.36 (m, 10H, Ar-H);
13C NMR (CDCl3; 75 MHz) d: 14.26, 14.44, 17.80, 36.31, 60.04, 63.22, 93.36,
117.18, 117.97, 123.91, 124.83, 127.05, 127.14, 127.27, 127.39, 128.49, 129.05,
129.58, 131.29, 131.66, 132.24, 143.64, 148.25, 159.38, 166.40, 167.38; IR (KBr)
n
CO: 1670 cmꢀ1
.
2-[(Ethoxypropylidene)amino]-3-ethoxycarbonyl-4-phenyl-4H-naphtho-
[2,1-b]pyran (3e). Yield 89%, mp 176–178 ꢁC; 1H NMR (CDCl3; 300 MHz) d: 1.13
(t, J ¼ 7.2 Hz, 3H), 1.30 (t, J ¼ 7.2 Hz, 3H), 1.41 (t, J ¼ 7.2 Hz, 3H), 2.32 (q,
J ¼ 7.2 Hz, 2H), 4.18 (q, J ¼ 7.2 Hz, 2H), 4.38 (q, J ¼ 7.2 Hz, 2H), 5.83 (s, 1H),
7.08–8.08 (m, 11H, Ar-H); 13C NMR (CDCl3; 75 MHz) d: 09.32, 12.99, 13.17,
23.98, 37.87, 58.89, 61.98, 92.49, 115.92, 116.86, 122.38, 123.58, 125.20, 125.78, (dou-
ble intensity): 127.14, (double intensity): 127.22, 127.36, 127.65, 129.82, 130.22,
144.66, 146.92, 157.73, 165.52, 169.19; IR (KBr) nCO: 1690 cmꢀ1
.
2-[(Ethoxypropylidene)amino]-3-ethoxycarbonyl-4-(p-methylphenyl)-
4H-naphtho[2,1-b]pyran (3f). Yield 30%, mp 110–112 ꢁC; 1H NMR (CDCl3;

3410
K. MKAOUAR ET AL.
75 MHz) d: 1.11 (t, J ¼ 7.2 Hz, 3H), 1.27 (t, J ¼ 7.2 Hz, 3H), 1.39 (t, J ¼ 7.2 Hz, 3H),
2.23 (s, 3H), 2.30 (q, J ¼ 7.2 Hz, 2H), 4.14 (q, J ¼ 7.2 Hz, 2H), 4.34 (q, J ¼ 7.2 Hz,
2H), 5.75 (s, 1H), 7.00–8.05 (m, 10H, Ar-H); IR (KBr) nCO: 1683 cmꢀ1
.
2-[(Ethoxypropylidene)amino]-3-ethoxycarbonyl-4-(o-methoxylphenyl)-
1
4H-naphtho [2,1-b]pyran (3g). Yield 83%, mp 162–164 ꢁC; H NMR (CDCl3;
300 MHz) d: 1.03 (t, J ¼ 7.2 Hz, 3H), 1.11 (t, J ¼ 7.2 Hz, 3H), 1.27 (t, J ¼ 7.2 Hz,
3H), 2.28 (q, J ¼ 7.2 Hz, 2H), 3.75 (s, 3H), 4.00 (q, J ¼ 7.2 Hz, 2H), 4.23 (q,
J ¼ 7.2 Hz, 2H), 5.99 (s, 1H), 6.66–7.61 (m, 10H, Ar-H); 13C NMR (CDCl3;
75 MHz) d: 10.83, 14.46, 14.65, 25.38, 34.09, 55.80, 60.08, 63.32, 93.24, 111.48,
117.37, 118.76, 121.06, 124.30, 124.78, 126.93, 127.99, (double intensity): 128.63,
131.32, 131.55, 131.88, 134.61, 148.69, 156.69, 159.60, 167.10, 170.60; IR (KBr)
n
CO: 1676 cmꢀ1
.
2-[(Ethoxypropylidene)amino]-4-(o-chlorophenyl)-3-ethoxycarbonyl-4-
H-naphtho[2,1-b]pyran (3h). Yield 80%, mp 178–180 ꢁC; 1H NMR (CDCl3;
300 MHz) d: 1.03 (t, J ¼ 7.2 Hz, 3H), 1.14 (t, J ¼ 7.2 Hz, 3H), 1.29 (t, J ¼ 7.2 Hz,
3H), 2.22 (q, J ¼ 7.2 Hz, 2H), 4.06 (q, J ¼ 7.2 Hz, 2H), 4.23 (q, J ¼ 7.2 Hz, 2H),
6.07 (s, 1H), 6.85–7.59 (m, 10H, Ar-H); 13C NMR (CDCl3; 75 MHz) d: 10.75,
14.44, 14.64, 25.56, 36.63, 60.32, 63.47, 93.51, 117.52, 118.45, 124.27, 124.36,
125.16, 127.38, 127.57, 127.72, 128.03, 128.82, 129.37, 131.53, 131.67, 132.46,
144.04, 148.61, 159.52, 166.79, 169.80; IR (KBr) nCO: 1680 cmꢀ1
.
3-Ethoxycarbonyl-4-phenyl-2-formylamino-4H-naphtho[2,1-b]pyran (3’a).
Yield 31%, mp 203–207 ꢁC; 1H NMR (CDCl3; 500 MHz) d: 1.38 (t, J ¼ 7.2 Hz,
3H), 4.28 (q, J ¼ 7.2 Hz, 2H), 5.65 (s, 1H), 7.09–8.00 (m, 11H), 9.25 (d, 1H), 10.80
(d, 1H); 13C NMR (CDCl3; 125 MHz) d: 14.29, 37.25, 61.02, 87.51, 116.24, 117.98,
123.35, 125.32, 126.75, 127.26, (double intensity): 128.29, (double intensity):
128.39, 128.65, 129.37, 130.71, 131.67, 144.65, 146.37, 152.25, 159.62, 167.76; IR
(KBr) nCO: 1680–1700, nNH: 3244 cmꢀ1
.
4-(o-Chlorophenyl)-3-ethoxycarbonyl-2-formylamino-4H-naphtho[2,1-b]-
1
pyran (3’b). Yield 75%, mp 173–176 ꢁC; H NMR (CDCl3; 300 MHz) d: 1.20 (t,
J ¼ 7.0 Hz, 3H), 4.15 (q, J ¼ 7.0 Hz, 2H), 5.95 (s, 1H), 7.09–8.00 (m, 11H, Ar-H),
9.15 (d, 1H), 10.90 (d, 1H); 13C NMR (CDCl3; 75 MHz) d: 14.81, 34.83, 61.49,
87.24, 116.72, 118.31, 124.19, 125.86, (double intensity): 127.83, 128.52, 129.06,
130.05, 130.28, 131.47, 131.96, 131.99, 132.62, 142.84, 146.81, 153.18, 160.02,
168.41; IR (KBr) nCO: 1696–1676, nNH: 3207 cmꢀ1
.
General Procedure for 11-Aryl-1,12-dihydro-11H-
naphthopyrano[2,3-d]pyrimidin-12-ones 4a–j
The appropriate primary amine (0.01 mmol) was added to the suitable imidate
3 (0.01 mmol), and the mixture was stirred at reflux of toluene (10 ml) for 48 h. After
cooling, the precipitated solid was filtered, washed with cold ether, and dried to
obtain compounds 4a–j.

SYNTHESIS OF NAPHTHOPYRANOPYRIMIDINONES
3411
Selected Data
11-(o-Chlorophenyl)-1,12-dihydro-2-methyl-1-phenyl-11H-naphthopyr-
1
ano[2,3-d]pyrimidin-12-one (4a). Yield 67%, mp 314–317 ꢁC; H NMR (CDCl3;
300 MHz) d: 2.21 (s, 3H), 6.24 (s, 1H), 6.99–7.80 (m, 15H, Ar-H); 13C NMR (CDCl3;
75 MHz) d: 23.94, 34.66, 101.67, 117.56, 123.94, 125.07, 127.02, 127.14, 127.31, (dou-
ble intensity): 127.76, 127.95, 128.54, (double intensity): 128.88, 129.48, 129.65,
130.01, 130.99, 131.48, 131.83, 132.56, 133.20, 137.07, 141.42, 148.18, 158.76,
162.41. Anal. calcd. for C28H19ClN2O2: C, 74.58; H, 4.25; N, 6.21; Cl, 7.86. Found:
C, 74.35; H, 4.21; N, 6.32; Cl, 7.75. IR (KBr) nCO: 1678 cmꢀ1; MS (APCIþ): m=z 451
(M þ H)þ.
1-Benzyl-11-(o-chlorophenyl)-1,12-dihydro-2-methyl-11H-naphthopyr-
1
ano[2,3-d]pyrimidin-12-one (4b). Yield 30%, mp 230–232 ꢁC; H NMR (CDCl3;
500 MHz) d: 2.47 (s, 3H), 4.90 (d, J ¼ 7.2 Hz, 1H), 5.61 (d, J ¼ 7.2 Hz, 1H), 6.32 (s,
1H), 7.05–7.83 (m, 15H, Ar-H); 13C NMR (CDCl3; 125 MHz) d: 22.98, 34.67, 47.14,
101.03, 116.57, 117.50, 123.86, 125.02, (double intensity): 126.45, 127.10, 127.26,
127.75, 127.94, 128.48, (double intensity): 128.93, 129.60, 129.87, 131.38, 131.39,
131.71, 133.05, 135.05, 141.49, 148.05, 159.01, 159.72, 162.35. Anal. calcd. for
C29H21ClN2O2: C, 74.91; H, 4.55; N, 6.03; Cl, 7.63. Found: C, 74.66; H, 4.62; N,
5.80; Cl, 7.74; IR (KBr) nCO: 1672 cmꢀ1; MS (APCIþ): m=z 465 (M þ H)þ.
1,12-Dihydro-11-(o-methoxyphenyl)-2-methyl-1-phenyl-11H-naphtho-
pyrano[2,3-d]pyrimidin-12-one (4c). Yield 77%, mp 290–292 ꢁC; 1H NMR
(CDCl3; 500 MHz) d: 2.20 (s, 3H), 3.82 (s, 3H), 6.15 (s, 1H), 6.77–7.51 (m, 15H,
Ar-H); 13C NMR (CDCl3; 125 MHz) d: 23.91, 32.04, 55.80, 101.32, 111.66, 117.31,
117.33, 120.76, 123.87, 124.63, 126.76, 127.71, 127.76, 127.93, 128.29, 128.77,
129.31, 129.90, 129.92, 131.13, 131.31, 131.52, 132.12, 137.20, 148.19, 156.82,
158.02, 160.46, 162.47. Anal. calcd. for C29H22N2O3: C, 78.01; H, 4.97; N, 6.27.
Found: C, 77.87; H, 5.12; N, 6.21. IR (KBr) nCO: 1677 cmꢀ1; MS (APCIþ): m=z
447 (M þ H)þ.
1-Benzyl-1,12-dihydro-11-(o-methoxyphenyl)-2-methyl-11H-naphtho-
pyrano[2,3-d]pyrimidin-12-one (4d). Yield 41%, mp 238–240 ꢁC; 1H NMR
(CDCl3; 500 MHz) d: 2.42 (s, 3H), 3.85 (s, 3H), 4.80 (d, J ¼ 7.2 Hz, 1H), 5.56 (d,
J ¼ 7.2 Hz, 1H), 6.21 (s, 1H), 6.76–7.72 (m, 15H, Ar-H); 13C NMR (CDCl3;
125 MHz) d: 23.01, 32.25, 47.13, 55.90, 101.04, 111.71, 117.12, 117.35, 120.75,
123.89, 124.65, (double intensity): 126.52, 126.79, 127.70, (double intensity):
128.04, 128.31, 128.82, 128.91, 131.04, 131.30, 131.56, 132.20, 135.29, 148.15,
156.89, 158.37, 160.10, 162.44. Anal. calcd. for C30H24N2O3: C, 78.24; H, 5.25; N,
6.08. Found: C, 77.98; H, 5.08; N, 6.01; IR (KBr) nCO: 1670 cmꢀ1. MS (APCIþ):
m=z 461 (M þ H)þ.
1-Cyclohexyl-1,12-dihydro-11-(o-methoxyphenyl)-2-methyl-11H-naph-
1
thopyrano[2,3-d]pyrimidin-12-one (4e). Yield 30%, mp 184–186 ꢁC; H NMR
(CDCl3; 300 MHz) d: 2.20 (s, 3H), 4.18 (s, 3H), 5.72 (s, 1H), 6.47–9.49 (m, 20H,
Ar-H); 13C NMR (CDCl3; 75 MHz) d: 24.92, 25.01, 25.33, 25.72, 25.87, 28.91,
34.20, 48.02, 55.32, 109.47, 116.91, 119.84, 122.32, 123.00, 124.42, 126.65, 127.34,
128.28, (double intensity): 128.39, (double intensity): 130.51, 130.85, 131.31,

3412
K. MKAOUAR ET AL.
134.97, 147.07, 152.05, 158.50, 168.97. Anal. calcd. for C29H28N2O3: C, 76.97; H,
6.24; N, 6.19. Found: C, 76.99; H, 6.31; N, 6.35; IR (KBr) nCO: 1651 cmꢀ1
.
1-Furan-2-yl-1,12-dihydro-11-phenyl-2-methyl-11H-naphthopyrano[2,3-
d]pyrimidin-12-one (4f). Yield 25%, mp 257–259 ꢁC; 1H NMR (CDCl3; 500 MHz)
d: 2.70 (s, 3H), 4.82 (d, J ¼ 7.2 Hz, 1H), 5.46 (d, J ¼ 7.2 Hz, 1H), 5.90 (s, 1H), 6.31
(dd, 1H), 6.39 (d, J ¼ 2 Hz, 1H), 7.10–7.93 (m, 12H, Ar-H); 13C NMR (CDCl3;
75 MHz) d: 22.99, 36.73, 101.57, 109.83, 110.71, 116.50, 117.41, 123.64, 124.90,
126.65, 127.06, (double intensity): 128.35, 128.43, (double intensity): 128.46,
129.33, 131.03, 131.46, (double intensity): 142.55, 143.75, 148.08, 148.45, 158.17,
159.30, 162.01. Anal. calcd. for C27H20N2O3: C, 77.13; H, 4.79; N, 6.66. Found:
C, 76.89; H, 4.72; N, 6.85. IR (KBr) nCO: 1667 cmꢀ1; MS (APCIþ): m=z 421
(M þ H)þ.
2-Ethyl-1,12-dihydro-11-(p-methylphenyl)-1-phenyl-11H-naphthopyr-
1
ano[2,3-d]pyrimidin-12-one (4g). Yield 63%, mp 264–266 ꢁC; H NMR (CDCl3;
400 MHz) d: 1.04 (t, J ¼ 7.1 Hz, 3H), 2.10 (s, 3H), 2.22 (q, J ¼ 7.1 Hz, 2H), 5.68 (s,
1H), 6.93–7.95 (m, 15H, Ar-H); 13C NMR (CDCl3; 100 MHz) d: 10.16, 20.53,
28.42, 35.63, 100.72, 116.56, 117.42, 123.45, 125.02, 125.34, 127.26, 128.11, 128.24,
128.35, 128.60, 128.91, 128.92, 129.15, 129.53, 129.54, 129.60, 130.44, 131.11,
135.68, 136.76, 141.15, 147.82, 159.45, 161.89, 162.02; IR (KBr) nCO: 1671 cmꢀ1
;
MS (APCIþ): m=z 445 (M þ H)þ.
1-Benzyl-2-ethyl-11-(p-methylphenyl)-1,12-dihydro-11H-naphthopyr-
1
ano[2,3-d]pyrimidin-12-one (4h). Yield 45%, mp 204–206 ꢁC; H NMR (CDCl3;
300 MHz) d: 1.27 (t, J ¼ 7.2 Hz, 3H), 2.22 (s, 3H), 2.71 (q, J ¼ 7.2 Hz, 2H), 4.92 (d,
1H), 5.60 (d, 1H), 5.94 (s, 1H), 7.01–7.98 (m, 15H, Ar-H); 13C NMR (CDCl3;
75 MHz) d: 11.16, 21.45, 28.45, 36.88, 46.92, 102.01, 117.22, 117.95, 124.18,
125.34, (double intensity): 126.84, 127.50, 128.14, 128.81, (double intensity):
128.87, 129.37, 129.50; 129.67, 131.60, 131.95, 135.93, 136.63, 141.48, 148.68,
160.03, 162.43, 163.17. Anal. calcd. for C31H26N2O2: C, 81.20; H, 5.72; N, 6.11.
Found: C, 81.08; H, 5.77; N, 6.05. IR (KBr) nCO: 1664 cmꢀ1; MS (APCIþ): m=z
459 (M þ H)þ.
2-Ethyl-1,12-dihydro-11-(o-methoxyphenyl)-1-phenyl-11H-naphthopyr-
1
ano[2,3-d]pyrimidin-12-one (4i). Yield 72%, mp 281–283 ꢁC; H NMR (CDCl3;
300 MHz) d: 1.30 (t, J ¼ 7.2 Hz, 3H), 2.41 (q, J ¼ 7.2 Hz, 2H), 3.84 (s, 3H), 6.18 (s,
1H), 6.79–7.50 (m, 15H, Ar-H); 13C NMR (CDCl3; 75 MHz) d: 11.37, 29.20,
32.42, 56.29, 101.65, 112.13, 117.86, 121.21, 124.34, 125.06, 125.73, 127.18, 128.34,
128.48, 128.66, 129.18, 129.47, 129.69, 130.24, 130.29, 131.60, 131.74, 131.98,
132.71, 137.24, 148.74, 157.26, 161.19, 162.25, 163.07. Anal. calcd. for
C30H24N2O3: C, 78.24; H, 5.25; N, 6.08. Found: C, 77.94; H, 5.46; N, 5.83. IR
(KBr) nCO: 1678 cmꢀ1; MS (APCIþ) m=z 461 (M þ H)þ.
1-Benzyl-2-ethyl-1,12-dihydro-11-(o-methoxyphenyl)-11H-naphthopyr-
1
ano[2,3-d]pyrimidin-12-one (4j). Yield 43%, mp 234–236 ꢁC; H NMR (CDCl3;
300 MHz) d: 1.30 (t, J ¼ 7.2 Hz, 3H), 2.69 (q, J ¼ 7.2 Hz, 2H), 3.90 (s, 3H), 4.90 (d,
1H), 5.64 (d, 1H), 6.24 (s, 1H), 6.83–8.30 (m, 15H, Ar-H); 13C NMR (CDCl3;
75 MHz) d: 11.16, 28.40, 32.53, 46.67, 56.39, 101.37, 112.16, 117.69, 117.87,

SYNTHESIS OF NAPHTHOPYRANOPYRIMIDINONES
3413
121.20, 124.35, 125.07, (double intensity): 126.78, 127.20, 128.02, 128.42, 128.73,
129.20, (double intensity): 129.30, 131.49, 131.72, 132.01, 132.82, 136.06, 148.68,
157.29, 160.74, 162.35, 163.00. Anal. calcd. for C31H26N2O3: C, 78.46; H, 5.52; N,
5.90. Found: C, 78.62; H, 5.54; N, 5.71. IR (KBr) nCO: 1668 cmꢀ1; MS (APCIþ):
m=z 475 (M þ H)þ.
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