An efficient three-component synthesis of pyranoquinoline derivatives

Article abstract of DOI:10.1002/jhet.1614

Pyranoquinoline derivatives have been synthesized via three-component reaction of 4-hydroxy-1-methyl-2(1H)-quinolinone and dialkyl acetylenedicarboxylates in the presence of nucleophiles such as alkyl isocyanides and triphenylphosphine.

Full text of DOI:10.1002/jhet.1614

January 2014 An Efficient Three-Component Synthesis of Pyranoquinoline Derivatives
233
*
Sakineh Asghari and Samaneh Ramezani
Department of Organic Chemistry, Faculty of Chemistry,
University of Mazandaran, Babolsar, 47415, Iran
*
E-mail: s.asghari@umz.ac.ir
Received October 25, 2011
DOI 10.1002/jhet.1614
Published online 31 October 2013 in Wiley Online Library (wileyonlinelibrary.com).
R
HN
E
O
+
N
-
R= tBu, cyclohexyl
E= CO2Me, CO2Et, CO2 Bu
R
C
E
t
DMF / r.t.
OH
O
N
E
E
O
E
OH
O
N
H
H
PPh3
O
N
Me
+
DMF / r.t.
E
E
O
N
Me
O
Me
t
E= CO2Me, CO2Et
E= CO2 Bu
Pyranoquinoline derivatives have been synthesized via three-component reaction of 4-hydroxy-1-methyl-
2(1H)-quinolinone and dialkyl acetylenedicarboxylates in the presence of nucleophiles such as alkyl isocya-
nides and triphenylphosphine.
J. Heterocyclic Chem., 51, 233 (2014).
INTRODUCTION
triphenylphosphine 4 lead to products 6a–b and 7 in moder-
ate yields (Scheme 2). In the case of using tert-butyl
derivative of diester, the cyclization reaction did not occur
may be because of the hindrance of the tert-butyl group.
Therefore, the chain product 7 was obtained.
The reaction was carried out in the presence of alkyl
acetylenecarboxylates instead of dialkyl acetylenedicarboxy-
lates, but no result was found with acetylenic monoesters
probably because of the less electrophilicity of b carbon in
monoesters than diesters.
Pyranoquinoline moiety is a structural feature of many
natural bioactive alkaloids such as simulenoline [1],
huajiaosimuline [2], and flindersine [3]. In recent years,
pyranoquinoline derivatives have gained significant impor-
tance because of their diverse biological activities such as
anti-inflammatory [4], sterogenic [5], and anti-allergic [6]
and their pharmacological activities such as anti-coagulant
[7], coronary constricting [8], anti-fungal [9], and cancer
cell growth inhibitory activity [10]. In view of the highly
pronounced biological and pharmacological activities of
pyranoquinolines, several methods have been reported for
the synthesis of these tricyclic compounds [11–14]. Herein,
as part of our efforts to the synthesis of novel heterocyclic
systems [15–17], we describe an efficient approach for the
synthesis of pyranoquinoline derivatives via a three-
component reaction using 4-hydroxy-1-methyl-2(1H)-
quinolinone 1 and dialkyl acetylenedicarboxylates 2 in
the presence of nucleophiles such as alkyl isocyanides
3 and triphenylphosphine 4.
RESULTS AND DISCUSSION
On the basis of the chemistry of isocyanides [18–20], it
is conceivable that an initial addition of alkyl isocyanides 3
to dialkyl acetylenedicarboxylates 2 and subsequently the
protonation of 1:1 adduct 8 by the OH-acid 1 leads to 9,
which can be attacked by the conjugated base of 4-hydroxy-
1-methyl-2(1H)-quinolinone to generate intermediate 10.
This intermediate is converted to 11 by tautomerization,
and then a cyclization reaction occurs to produce 5
(Scheme 3).
A plausible explanation for the formation of 6 is shown
in Scheme 4. According to the chemistry of trivalent phos-
phorus nucleophiles [21], the initial event is the nucleo-
philic addition of PPh3 4 to the acetylenic diester 2 to
form the zwitterion 12. Subsequent protonation of 1:1
The reaction of 4-hydroxy-1-methyl-2(1H)-quinolinone
1 and dialkyl acetylenedicarboxylates 2 in the presence of
alkyl isocyanides 3 proceeds in DMF at room temperature
to produce compounds 5a–e in good yields (Scheme 1).
Under similar conditions, the reactions of 1 with
dialkyl acetylenedicarboxylates 2 in the presence of
© 2013 HeteroCorporation

234
S. Asghari and S. Ramezani
Vol 51
Scheme 1
Scheme 3
R
H
HN
O
N
OH
E
C
E
E
+
-
+
O
DMF
r.t.
-
+
R
N C
C
E
R
N C
+
E
C
C
E
R N C
+ E
E +
O
O
N
H
8
3
2
Me
Me
O
N
Me
-
5
2
3
1
O
E
C
O
E
C
E
C
H
+
R
N C
R
N C
C
E
H
O
N
O
N
Me
Me
10
9
adduct 12 by the OH-acid 1 leads to 13. Then, the posi-
tively charged ion can be attacked by the conjugated base
of 1 to produce ylide 14, which is converted to 15 via
tautomerization and then [1,2]-proton transfer. Finally,
compound 15 with elimination of PPh3 leads to 7, which
undergoes a cyclization reaction to produce 6.
R
N
R
O
HN
C
C
C
H
E
OH
E
tautomerization
cyclization
E
E
H
O
N
O
N
The structures of the products were fully consistent with
their 1H NMR, 13C NMR, IR and mass spectra, and
elemental analysis.
Me
Me
11
5
1
The H NMR spectrum of 5a exhibited a sharp singlet
for tert-butyl at 1.58 ppm, a singlet for NCH3 at
3.70 ppm, two singlets for two methoxy groups at 3.74
and 3.76 ppm, a singlet for CH at 4.90 ppm, a multiplet
for aromatic protons at 7.33–8.04 ppm, and a singlet for
NH proton at 9.06 ppm. The 13C NMR spectrum of 5a
displayed 19 resonances in agreement with the proposed
structure. IR spectral data of 5a displayed four absorption
bands at 3380, 1731, 1683, and 1630 cmÀ1 indicating the
presence of NH and carbonyl groups, respectively. The
mass spectrum of 5a displayed a molecular ion peak at
m/z 400. The fragmentations involved the loss of side
chains such as CO2Me and C4H8.
at m/z 285. The 1H and 13C NMR spectra of 6b are similar
to those of 6a, except for the signals of the alkoxy groups.
The 1H NMR spectrum of 7 exhibited three singlets for 2
CMe3 and NCH3 groups at 1.44, 1.50, and 3.69 ppm; a
singlet for olefinic proton at 6.93 ppm; and a multiplet for
aromatic protons at 7.26–8.20 ppm. The 13C NMR spec-
trum of 7 displayed 18 resonances in agreement with the
proposed structure. The IR spectrum of 7 displayed four
absorption bands at 3316, 1713, 1690, and 1614 cmÀ1
,
indicating the presence of OH and carbonyl groups, respec-
tively. The mass spectrum of 7 displayed a molecular ion
peak at m/z 401.
The 1H and 13C NMR spectra of 5b–e are similar to those
of 5a, except for the signals of alkoxy and cyclohexyl groups.
The 1H NMR spectrum of 6a exhibited three singlets for
NCH3, OCH3, and CH groups at 3.75, 4.05, and 6.37 ppm
along with a multiplet for aromatic protons at 7.40–8.30 ppm.
The 13C NMR spectrum of 6a displayed 15 resonances in
agreement with the proposed structure. The IR spectrum
of 6a displayed three absorption bands at 1740, 1658, and
1598 cmÀ1, indicating the presence of carbonyl groups.
The mass spectrum of 6a displayed a molecular ion peak
CONCLUSIONS
In conclusion, we have described a mild and efficient
method for the synthesis of pyranoquinoline derivatives
via a one-pot three-component reaction of 4-hydroxy-1-
methyl-2(1H)-quinolinone and dialkyl acetylenedicarboxy-
lates with alkyl isocyanides and PPh3 under neutral
conditions.
Scheme 2
O
H
E
OH
O
E
OH
H
DMF
r.t
+
+
PPh3
+
E
E
E
O
N
O
N
O
N
Me
Me
Me
7
1
2
6
4
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2014
An Efficient Three-Component Synthesis of Pyranoquinoline Derivatives
235
Scheme 4
H
O
RO2C
CO2R
..
PPh3 RO C
C C
CO2R
+
-
2
+
Ph3P
O
N
12
4
2
Me
-
OH
RO C
H
RO2C
CO2R
H
O
RO2C
O
2
H
RO2C
RO2C
+
tautomerization
Ph3P
Ph3P
Ph3P
O
N
O
N
O
N
Me
Me
Me
14
13
O
O
OR
OH
H
H
O
N
CO2ROH
-
RO2C
+
[1,2]-proton transfer
RO2C
cyclization
RO2C
Ph3P
H
O
O
N
O
N
Me
Me
Me
1
6
7
Calcd for C21H24N2O6 (400.40): C, 62.99; H, 6.03; N, 6.99. Found:
C, 62.92; H, 6.07; N, 6.97.
EXPERIMENTAL
Elemental analyses were performed using a F002 Heraeus
CHN-O-Rapid analyzer (Elementar Analysesysteme GmbH,
Hanau, Germany) using acetanilide as a standard. NMR spectra
were recorded with BRUCKER DRX-400 AVANCE spectrome-
ter (at 400.1 MHz for 1H and 100.6 MHz for 13C) with CDCl3 as
solvent. Mass spectra were recorded on a Finnigan-Matt 8430
mass spectrometer operating at an ionization potential of 70 eV.
IR spectra were recorded on a FTIR, Brucker, VECTOR 22 spec-
trometer. TLC was carried out on Fluka Silica gel TLC-cards. All
other reagents and solvents were used as received from commer-
cial suppliers. All of the coupling constants are given in hertz.
General procedure for the preparation of compound 5. To
a magnetically stirred solution of 4-hydroxy-1-methyl-2(1H)-
quinolinone (2mmol) and dialkyl acetylenedicarboxylate
(2mmol) in DMF (5 ml), 2 mmol of tert-butyl isocyanide was
added dropwise at room temperature over 10min. Then, the
reaction mixture was stirred for 24 h. The solvent was removed
under reduced pressure, and the residue was purified by column
chromatography with the use of hexane: ethyl acetate (60:40) as
eluent to take pure product 5a as a white powder.
Dimethyl 2-(tert-butylamino)-6-methyl-5-oxo-5,6-dihydro-4H-
pyrano[3,2-c]quinoline-3,4-dicarboxylate (5a, C21H24N2O6).
White powder, yield: 80%. mp 189–191 ꢀC. IR (KBr) (υmax/cmÀ1):
3380 (NH), 1731, 1683, and 1630 (3C═O). 1H NMR (400.1MHz,
CDCl3): d = 1.58 (s, 9H, CMe3), 3.70 (s, 3H, NCH3), 3.74 and
3.76 (2s, 6H, 2OCH3), 4.90 (s, 1H, CH), 7.33–8.04 (m, 4H,
aromatic protons), 9.06 (s, 1H, NH). 13C NMR (100.6 MHz,
CDCl3): d = 29.81 (NCH3), 30.55 (NCMe3), 36.59 (CH), 51.11
(NCMe3), 52.47 and 52.58 (2OCH3), 73.03 (NH–C═C),
108.16 (N–CO–C═C), 113.90, 114.47, 122.33, 122.68, 131.37
and 139.18 (aromatic carbons), 151.88 (N–CO–C═C), 160.37
and 161.31 (2CO), 169.93 (NH–C═C), 173.87 (NC═O). MS:
m/z (%): 400 (M+, 3), 341 [M+ À CO2Me, 53], 292 [M+ À
(2CH3OH + CH3 +NCH3), 100], 261 [M+ À (2CH3OH + 3CH3 +
NHCH3), 62], 225 [M+ À (CO2Me + C4H9), 18], 77 (Ph+, 23). Anal.
Diethyl 2-(tert-butylamino)-6-methyl-5-oxo-5,6-dihydro-4H-
pyrano[3,2-c]quinoline-3,4-dicarboxylate (5b, C23H28N2O6).
White powder, yield: 85%. mp 150–152 ꢀC. IR (KBr) (υmax/cmÀ1):
3238 (NH), 1726, 1689, and 1630 (3C═O). 1H NMR (400.1 MHz,
CDCl3): d = 1.27 and 1.33 (t, 6H, 3JHH = 7.2 Hz, 2CH3), 1.57 (s, 9H,
CMe3), 3.73 (s, 3H, NCH3), 4.15 (m, 2H, OCH2), 4.17–4.25
(m, 2H, OCH2), 4.89 (s, 1H, CH), 7.32–8.04 (m, 4H, aromatic
protons), 9.08 (s, 1H, NH). 13C NMR (100.6 MHz, CDCl3): d = 14.20
and 14.55 (2CH3), 29.77 (NCH3), 30.56 (NCMe3), 36.74 (CH), 52.49
(NCMe3), 59.69 and 61.05 (2OCH2), 73.11 (NH–C═C), 108.35
(N–CO–C═C), 113.95, 114.41, 122.27, 122.70, 131.28 and 139.17
(aromatic carbons), 151.87 (N–CO–C═C), 160.28 and 161.38
(2CO), 169.63 (NH–C═C), 173.73 (NC═O). MS: m/z (%): 428
(M+, 2), 383 [M+À EtO, 45], 355 [M+ À CO2Et, 40], 327
[M+ À (EtO + C4H8), 100], 271 [M+ À (CO2Et + C4H8 +C2H4), 63],
225 [M+ À (2CO2Et + C4H9), 22], 57 (C4H9, 21). Anal. Calcd for
C23H28N2O6 (428.45): C, 64.48; H, 6.58; N, 6.54. Found: C, 64.51;
H, 6.56; N, 6.57.
Di(tert-butyl) 2-(tert-butylamino)-6-methyl-5-oxo-5,6-dihydro-
4H-pyrano[3,2-c]quinoline-3,4-dicarboxylate (5c, C27H36N2O6).
White powder, yield: 76%. mp 188–190 ꢀC. IR (KBr) (υmax/cmÀ1):
1
3249 (NH), 1726, 1667, and 1651 (3C═O). H NMR (400.1 MHz,
CDCl3): d = 1.46 (s, 9H, CMe3), 1.54 and 1.56 (2s, 18H, 2OCMe3),
3.73 (s, 3H, NCH3), 4.75 (s, 1H, CH), 7.30–8.04 (m, 4H, aromatic
protons), 9.00 (s, 1H, NH). 13C NMR (100.6 MHz, CDCl3):
d = 28.12 and 28.62 (2OCMe3), 29.71 (NCH3), 30.65 (NCMe3),
38.12 (CH), 52.27 (NCMe3), 74.79 (NH–C═C), 79.57 and 80.76
(2OCMe3), 109.03 (N–CO–C═C), 114.11, 114.30, 122.09, 122.76,
131.03 and 139.14 (aromatic carbons), 151.97 (N–CO–C═C),
160.15 and 161.36 (2CO), 169.22 (NH–C═C), 173.16 (NC═O).
MS: m/z (%): 484 (M+, 4), 383 [M+ À (3CH3 +C4H8), 48], 327
t
t
[M+ À (CO2 Bu + C4H8), 100], 271 [M+ À (CO2 Bu + 2C4H8), 70],
t
t
253 [M+ À (CO2 Bu + C4H9O+C4H9), 50], 225 [M+ À (2CO2 Bu +
C4H8), 20], 57 (C4H9, 80). Anal. Calcd for C27H36N2O6 (484.55): C,
66.93; H, 7.48; N, 5.78. Found: C, 66.97; H, 7.50; N, 5.73.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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S. Asghari and S. Ramezani
Vol 51
Dimethyl 2-(cyclohexylamino)-6-methyl-5-oxo-,5,6-dihydro-
57], 104 (NC7H6, 24). Anal. Calcd for C16H13NO5 (299.26): C,
64.22; H, 4.37; N, 4.68. Found: C, 64.25; H, 4.39; N, 4.65.
Di(tert-butyl) (E)-2-(4-hydroxy-1-methyl-2-oxo-1,2-dihydro-3-
4H-pyrano[3,2-c]quinoline-3,4-dicarboxylate (5d, C23H26N2O6).
White powder, yield: 88%. mp 190–192 ꢀC; IR (KBr) (υmax/cmÀ1):
1
3254 (NH), 1726, 1683, and 1651 (3C═O). H NMR (400.1 MHz,
quinolinyl)-2-butenedioate (7, C22H27NO6).
Yellow powder,
yield: 50%. mp 192–194 ꢀC. IR (KBr) (υmax/cmÀ1): 3316 (OH),
1713, 1690, and 1614 (3C═O). 1H NMR (400.1 MHz, CDCl3):
d = 1.43 and 1.50 (2s, 18H, 2CMe3), 3.68 (s, 3H, NCH3), 6.93
(s, 1H, CH), 7.26–8.20 (m, 4H, aromatic protons), 9.16 (s, 1H, OH).
13C NMR (100.6 MHz, CDCl3): d = 27.82 and 27.89 (2CMe3),
29.38 (NCH3), 82.96 and 83.37 (2OCMe3), 108.54 (N–CO–C═C),
113.67, 117.07, 121.76, 125.11, 131.59 and 139.70 (aromatic
carbons), 129.98 (═CH), 138.96 (C═CH), 158.38 (NC═O),
162.31 (C═C–OH), 166.78 and 167.50 (2CO). MS: m/z (%): 401
(M+, 2), 299 (M+À CO2tBu+1, 12), 225 [M+À (CO2tBu + C4H9O), 17],
CDCl3): d =1.40–2.13 (m, 10H, 5CH2cy), 3.70 (s, 3H, NCH3), 3.74
and 3.76 (2s, 6H, 2OCH3), 3.92–3.95 (m, 1H, CHcy), 4.88 (s, 1H, CH),
3
7.32–7.88 (m, 4H, aromatic protons), 8.74–8.75 (bd, 1H, JHH
=
7.6 Hz, NH). 13C NMR (100.6 MHz, CDCl3): d = 24.50, 24.56,
25.49, 33.49 and 33.79 (5CH2cy), 29.76 (NCH3), 36.78 (CH),
50.55 (CHcy), 51.04 and 52.48 (2OCH3), 72.30 (NH–C═C), 108.08
(N–CO–C═C), 113.96, 114.38, 122.24, 122.35, 131.44 and 139.18
(aromatic carbons), 151.66 (N–CO–C═C), 159.08 and 161.30
(2CO), 169.75 (NH–C═C), 173.95 (NC═O). MS: m/z (%): 426
(M+, 2), 367 (M+ À CO2Me, 100), 285 [M+ À (C6H10 +CO2Me), 17],
253 [M+ À (C6H10 +CO2Me + CH3OH), 51], 225 [M+ À (C6H11
+
195 [M+ À (CO2 Bu + C4H10O+NCH3), 8], 167 [M+ À (2CO2 Bu +
NHCH3 +2H)]. Anal. Calcd for C22H27NO6 (401.43): C, 65.82; H,
6.77; N, 3.49. Found: C, 65.79; H, 6.72; N, 3.46.
t
t
2CO2Me), 17], 83 (C6H11, 16). Anal. Calcd for C23H26N2O6 (426.44):
C, 64.78; H, 6.14; N, 6.57. Found: C, 64.81; H, 6.17; N, 6.60.
Diethyl 2-(cyclohexylamino)-6-methyl-5-oxo-5,6-dihydro-4H-
pyrano[3,2-c]quinoline-3,4-dicarboxylate (5e, C25H30N2O6).
White powder, yield: 85%. mp 177–178 ꢀC. IR (KBr) (υmax/cmÀ1):
3249 (NH), 1715, 1688, and 1646 (3C═O). 1H NMR (400.1 MHz,
CDCl3): d = 1.27 and 1.33 (2t, 6H, 3JHH =7.2Hz, 2CH3), 1.39–1.51
(m, 10H, 5CH2cy), 3.73 (s, 3H, NCH3), 3.92–3.96 (m, 1H, CHcy),
4.10–4.28 (2m, 4H, 2OCH2), 4.87 (s, 1H, CH), 7.30–7.87 (m, 4H,
Acknowledgment. This research was supported by the Research
Council of the University of Mazandaran in Iran.
3
aromatic protons), 8.31 (d, 1H, JHH =7.6Hz, NH). 13C NMR
REFERENCES AND NOTES
(100.6 MHz, CDCl3): d = 14.20 and 14.55 (2CH3), 24.51, 24.58,
25.51, 33.51 and 33.80 (5CH2cy), 29.76 (NCH3), 36.92 (CH), 50.51
(CHcy), 59.58 and 61.05 (2OCH2), 72.41 (NH–C═C), 108.25
(N–CO–C═C), 114.01, 114.31, 122.25, 122.27, 131.33 and 139.17
(aromatic carbons), 151.65 (N–CO–C═C), 158.99 and 161.37
(2CO), 169.45 (NH–C═C), 173.80 (NC═O). MS: m/z (%): 454
(M+, 2), 381 (M+ À CO2Et, 100), 299 [M+ À (CO2Et + C6H10), 11],
253 [M+ À (CO2Et + C6H10 + EtOH), 46], 225 [M+ À (2CO2Et +
C6H11), 16], 77 (Ph, 4). Anal. Calcd for C25H30N2O6 (454.49): C,
66.07; H, 6.65; N, 6.16. Found: C, 66.11; H, 6.68; N, 6.12.
[1] (a) Chen, I. S.; Tsai, I. W.; Teng, C. M.; Chem, J. J.; Chang,
Y. L.; Ko, F. N.; Lu, M. C.; Pezzuto, J. M. Phytochemistry 1997, 46,
525; (b) Michael, J. P. Nat Prod Rep 1999, 16, 697; (c) Brader, G.;
Bacher, M.; Greger, H.; Hofer, O. Phytochemistry 1996, 42, 881.
[2] (a) Wu, S. J.; Chen, I. S. Phytochemistry 1993, 34, 1659; (b)
Chen, I. S.; Wu, J. S.; Tsai, I. L.; Wu, T. S.; Ezzuto, J. M.; Lu, M. C.;
Chai, H.; Suh, N.; Teng, C. M. J Nat Prod 1994, 57, 1206.
[3] Ramesh, M.; Mohan, P. A.; Shanmuganm, P. Tetrahedron
1984, 40, 4041.
[4] Faber, K.; Stueckler, H.; Kappe, T. J. Heterocycl Chem 1984,
21, 1177.
Methyl 6-methyl-2,5-dioxo-5,6-dihydro-2H-pyrano[3,2-c]
[5] Johnson, J. V.; Rauckman, S.; Baccanari, P. D.; Roth, B. J
Med Chem 1989, 32, 1942.
[6] Yamada, N.; Kadowaki, S.; Takahashi, K.; Umezu, K.
Biochem Pharmacol 1992, 44, 1211.
[7] Anniyappan, M.; Muralidharan, D.; Perumal, P. T. Tetrahedron
Lett 2003, 44, 3653.
[8] Ravindranath, N.; Ramesh, C.; Reddy, M. R.; Das, B. Chemistry
lett 2003, 32, 3, 222.
[9] Badhwar, I. C.; Venkataraman, K. J Chem Soc 1932, 2420.
[10] Kamperdick, C.; Van, N. H.; Van, S. T.; Adam, G. Phytochemistry
1999, 50, 177.
[11] Weinreb, S. M. Comprehensive Organic Synthesis, Trost,
B. M.; Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol 5; 401.
[12] (a) Babu, G.; Perumal, P. T. Tetrahedron Lett 1998, 39, 3225.
[13] Watters, W. H.; Ramachandran, V. N. J Chem Res (S) 1997,
184; (b) Dandia, A.; Gautam, S.; Jain, A. K. J. Fluorine Chem 2007,
128, 1454.
[14] McLaughlin, M. J.; Hsung, R. P. J Org Chem 2001, 66, 1049.
[15] Asghari, S.; Tajbakhsh, M.; Taghipour, V. Tetrahedron Lett
2008, 49, 1824.
[16] Asghari, S.; Qandalee, M. Acta Chim Slov 2007, 54, 638.
[17] Asghari, S.; Salimi, A.; Qandalee, M. Monatsh Chem 2008,
139, 1217.
quinoline-4-carboxylate (6a, C15H11NO5).
Yellow powder,
yield: 60%. mp 160–162 ꢀC. IR (KBr) (υmax/cmÀ1): 1740, 1658,
and 1598 (3C═O). 1H NMR (400.1 MHz, CDCl3): d = 3.75
(s, 3H, NCH3), 4.05 (s, 3H, OCH3), 6.37 (s, 1H, CH), 7.40–8.30
(m, 4H, aromatic protons). 13C NMR (100.6 MHz, CDCl3): d = 29.34
(NCH3), 53.39 (OCH3), 105.05 (N–CO–C═C), 112.66, 113.15,
114.77, 123.32, 124.37 and 140.09 (aromatic carbons), 134.10
(═CH), 147.41 (C–CO2Et), 158.40, 159.45 and 159.50 (3CO),
166.05 (C═C–O). MS: m/z (%): 285 (M+, 100), 254 (M+ À CH3O,
39), 226 (M+ À CO2Me, 42), 170 [M+ À (CO2Me + C4H8), 50], 104
(NC7H6, 32). Anal. Calcd for C15H11NO5 (285.24): C, 63.16; H,
3.88; N, 4.91. Found: C, 63.18; H, 3.85; N, 4.94.
Ethyl 6-methyl-2,5-dioxo-5,6-dihydro-2H-pyrano[3,2-c]
quinoline-4-carboxylate (6b, C16H13NO5). Yellow powder,
yield: 58%. mp 184–186 ꢀC. IR (KBr) (υmax/cmÀ1): 1740, 1656,
and 1598 (3C═O). 1H NMR (400.1 MHz, CDCl3): d =1.44 (t, 3H,
3JHH =7.2Hz, CH3), 3.75 (s, 3H, NCH3), 4.52 (q, 2H, 3JHH =7.2Hz,
OCH2), 6.36 (s, 1H, CH), 7.28–8.29 (m, 4H, aromatic protons). 13C
NMR (100.6 MHz, CDCl3): d = 14.04 (CH3), 29.83 (NCH3), 62.73
(OCH2), 105.05 (N–CO–C═C), 112.58, 113.15, 114.73, 123.24,
124.34 and 140.25 (aromatic carbons), 134.05 (═CH), 147.80
(C–CO2Et), 158.26, 158.51 and 159.43 (3CO), 165.53 (C═C–O).
MS: m/z (%): 299 (M+, 67), 254 (M+ À EtOH, 37), 227
[M+ À (CO2Et + CO2H), 100], 170 [M+ À (CO2Et + C2H2 + NHCH3),
[18] Ugi, I. Angew Chem Int Ed 1982, 21, 810.
[19] Marcaccini, S.; Torroba, T. Org Prep Proced Int 1993, 25, 141.
[20] Domling, A.; Ugi, I. Angew Chem Int Ed 2000, 39, 3168.
[21] Zbiral, E. Synthesis 1979, 755.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet