Facile synthesis of some new pyrimidoquinolines

Article abstract of DOI:10.1080/00397911.2010.505701

The reaction of ethyl 5-oxo-2,5-dihydroisoxzole-4-carboxylate with derivatives of 2-chloroquinoline afforded the desired N-quinolinyl isoxazolones. Their reactions with triethylamine in chloroform produced the corresponding pyrimidoquinoline derivatives, through intramolecular cyclization.

Full text of DOI:10.1080/00397911.2010.505701

This article was downloaded by: [University of New Hampshire]
On: 22 February 2013, At: 11:51
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Facile Synthesis of Some New
Pyrimidoquinolines
Ahmad Poursattar Marjani a , Jabbar Khalafy a & Ali Reza Molla
Ebrahimlo b
a Chemistry Department, Faculty of Science, Urmia University,
Urmia, Iran
b Chemistry Department, Islamic Azad University, Khoy Branch, Khoy,
Iran
Version of record first published: 14 Jun 2011.
To cite this article: Ahmad Poursattar Marjani , Jabbar Khalafy & Ali Reza Molla Ebrahimlo (2011):
Facile Synthesis of Some New Pyrimidoquinolines, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 41:16, 2475-2482
To link to this article: http://dx.doi.org/10.1080/00397911.2010.505701
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Synthetic Communications1, 41: 2475–2482, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.505701
FACILE SYNTHESIS OF SOME NEW
PYRIMIDOQUINOLINES
Ahmad Poursattar Marjani,1 Jabbar Khalafy,1 and
Ali Reza Molla Ebrahimlo2
1Chemistry Department, Faculty of Science, Urmia University, Urmia, Iran
2Chemistry Department, Islamic Azad University, Khoy Branch, Khoy, Iran
GRAPHICAL ABSTRACT
Abstract The reaction of ethyl 5-oxo-2,5-dihydroisoxzole-4-carboxylate with derivatives of
2-chloroquinoline afforded the desired N-quinolinyl isoxazolones. Their reactions with
triethylamine in chloroform produced the corresponding pyrimidoquinoline derivatives,
through intramolecular cyclization.
Keywords Pyrimidoquinolines; N-quinolinyl isoxazolones; rearrangements; triethylamine
INTRODUCTION
The development of new methods for the synthesis of nitrogen-containing het-
erocycles is of extreme importance in organic chemistry. In past years, the syntheses
of imidazoles,[1,2] pyrimidines,[3] imidazopyridines,[4,5] and pyrimido- and pyrazolo-
quinolines[6] starting from isoxazoline-5-ones have been reported. Of these com-
pounds, pyrimidoquinolines are important because of their biological properties,
which are known to depend mainly on the nature and position of substituents
and include anticancer,[7] antimalarial,[8] antimicrobial,[9] anti-oxidant and
anti-inflammatory activities.[10,11]
Here we report the synthesis of pyrimidoquinolines by rearrangement of
N-quinolinyl isoxazol-5(2H)-ones, substituted on nitrogen with 2-chloroquinoline
derivatives, under mild base-catalyzed conditions.
Received April 17, 2010.
Address correspondence to Jabbar Khalafy, Chemistry Department, Faculty of Science, Urmia
University, Urmia 57154, Iran. E-mail: j.khalafi@mail.urmia.ac.ir, jkhalafi@yahoo.com
2475

2476
A. P. MARJANI, J. KHALAFY, AND A. R. M. EBRAHIMLO
RESULTS AND DISCUSSION
N-Arylation of ethyl 5-oxo-2,5-dihydroisoxzole-4-carboxylate with derivatives
of 2-chloroquinoline afforded the desired N-quinolinyl isoxazolones in good yields
(Scheme 1). While the formation (2a–e) appears trivial, the reaction generally pro-
ceeded best in the absence of solvent by heating the required reagents under nitrogen
atmosphere at 130 ꢀC.
The compounds 2a–e were prepared in 75–84% yield, and their structures were
confirmed by their spectral data and microanalyses.
The rearrangement of N-quinolinyl isoxazolones (2a–e) by mild base triethyla-
mine led to synthesis of new pyrimidoquinoline derivatives 3a–e (Scheme 2). This
structure exists in the form of tautomers 3 Ð 4.
The pyrimidoquinolines 3a–e were formed in 70–80% yields, and their struc-
1
tures were confirmed by H NMR, 13C NMR, Fourier transform–infrared (FT-IR)
spectra and microanalyses. It is interesting that the rearrangements could be
achieved in good yield by triethylamine in chloroform under reflux conditions by
Scheme 1.
Scheme 2.

NEW PYRIMIDOQUINOLINES
2477
Scheme 3.
Scheme 4.
removing a vinyl hydrogen atom as shown in Scheme 3. There was no considerable
ester hydrolysis.
The rearrangement of a 2-methylisoxazolin-5-ones (5), unsubstituted at C-3,
has shown[12,13] that the system afforded ring-opened product 6. The mechanism
suggested, for which good evidence has been presented, is shown in Scheme 4.
An adaptation of this scheme in the present context leads to the pathway
shown in Scheme 3.
EXPERIMENTAL
1H and 13C NMR spectra were recorded with a Bruker spectrometer at 300 and
75.5 MHz, respectively. The spectra were measured in CDCl3 or CDCl3 þ dimethyl-
sulfoxide (DMSO-d6) using tetramethylsilane (TMS) as the internal standard. IR
spectra were recorded on a Thermonicolet (Nexus 670) FT-IR spectrometer, using
sodium chloride cells and measured as KBr disks. Mass spectra were recorded on

2478
A. P. MARJANI, J. KHALAFY, AND A. R. M. EBRAHIMLO
a Varian Matt 311 spectrometer, and relative abundances of fragments are quoted in
parentheses after the m=z values. Microanalyses were performed on a Leco Analyzer
932. Melting points were determined on a digital melting-point apparatus (Electro-
thermal) and remain uncorrected.
Ethyl 2-(3-Formylquinolin-2-yl)-5-oxo-2,5-dihydroisoxazole-4-
carboxylate (2a)
Ethyl 5-oxo-2,5-dihydroisoxazole-4-carboxylate[14] (100 mg, 0.64 mmol) and
2-chloro-3-formylquinoline[15] (122 mg, 0.64 mmol) were heated neat under nitrogen
in 130 ꢀC for 15 min. The resulting product was recrystallized from ethanol to afford
the ethyl 2-(3-formylquinolin-2-yl)-5-oxo-2,5-dihydroisoxazole-4-carboxylate (159 mg,
80%) as a pale yellow solid, mp 188–190 ꢀC. 1H NMR (CDCl3): d 1.43
(t, J ¼ 7.2 Hz, 3H, CH3), 4.43 (q, J ¼ 7.2 Hz, 2H, CH2), 7.68 (td, J1 ¼ 8.4 Hz,
J2 ¼ 1.2 Hz, 1H, ArH), 7.93 (td, J1 ¼ 8.4 Hz, J2 ¼ 1.2 Hz, 1H, ArH), 8.01 (dd,
J1 ¼ 8.4 Hz, J2 ¼ 1.2 Hz, 1H, ArH), 8.05 (dd, J1 ¼ 8.4 Hz, J2 ¼ 1.2 Hz, 1H, ArH),
8.93 (s, 1H, ArH), 9.62 (s, 1H, H-isoxazolone ring), 10.68 (s, 1H, CHO);
13C NMR (CDCl3): d 14.37, 61.33, 96.62, 121.21, 126.57, 128.31, 128.43, 129.68,
134.15, 142.16, 144.41, 147.78, 148.73, 160.81, 164.01, 187.47; FT-IR (KBr, cmꢁ1):
1808, 1708, 1691, 1560, 1494, 1440, 1208, 1031, 787, 776. Anal. calcd. for
C16H12N2O5: C, 61.54; H, 3.87; N, 8.97. Found: C, 61.69; H, 3.66; N, 9.01.
Ethyl 2-[3-(1,3-Dithiolan-2-yl)quinolin-2-yl]-5-oxo-
2,5-dihydroisoxazole-4-carboxylate (2b)
Using the corresponding quinoline[15] (170 mg, 0.64 mmol) by the same pro-
1
cedure gave 2b (185 mg, 75%) as a pale yellow solid, mp 175–176 ꢀC. H NMR
(CDCl3): d 1.41 (t, J ¼ 7.2 Hz, 3H, CH3), 3.98 (s, 4H, CH2CH2), 4.41 (q, J ¼ 7.2 Hz,
2H, CH2), 6.39 (s, 1H, CH), 7.62 (t, J ¼ 8.2 Hz, 1H, ArH), 7.78 (t, J ¼ 8.2 Hz, 1H,
ArH), 7.91 (d, J ¼ 8.4 Hz, 1H, ArH), 7.97 (d, J ¼ 8.4 Hz, 1H, ArH), 8.85 (s, 1H,
ArH), 9.41 (s, 1H, H-isoxazolone ring); 13C NMR (CDCl3): d 14.42, 39.43, 50.39,
61.08, 95.72, 127.71, 127.83, 128.01, 128.32, 130.56, 131.32, 139.36, 144.29, 145.47,
150.11, 161.12, 164.62; FT-IR (KBr, cmꢁ1): 1784, 1691, 1557, 1491, 1224, 1024,
777; MS m=z (%) 389 [(Mþ þ 1), 4], 388 (Mþ, 3), 344 (18), 316 (100), 272 (72), 244
(58), 211 (42), 169 (60), 128 (25). Anal. calcd. for C18H16N2O4S2: C, 55.65; H,
4.15; N, 7.21; S, 16.51. Found: C, 55.75; H, 4.03; N, 7.31; S, 16.62.
Ethyl 2-(3-Formyl-6-methylquinolin-2-
yl)-5-oxo-2,5-dihydroisoxazole-4-carboxylate (2c)
Using the corresponding quinoline[15] (100 mg, 0.48 mmol) by the same pro-
1
cedure gave 2c (126 mg, 80%) as a pale yellow solid, mp 199–201 ꢀC. H NMR
(CDCl3) d: 1.41 (t, J ¼ 7.2 Hz, 3H, CH3), 2.58 (s, 3H, CH3), 4.41 (q, J ¼ 7.2 Hz,
2H, CH2), 7.75 (d, J ¼ 8.4 Hz, 1H, ArH), 7.76 (s, 1H, ArH), 7.91 (d, J ¼ 8.4 Hz,
1H, ArH), 8.81 (s, 1H, ArH), 9.57 (s, 1H, H-isoxazolone ring), 10.63 (s, 1H,
CHO); 13C NMR (CDCl3) d: 14.38, 21.63, 61.27, 96.28, 121.19, 126.68, 128.08,
128.34, 136.58, 138.83, 141.22, 143.88, 146.34, 148.73, 160.87, 164.17, 187.62; FT-IR

NEW PYRIMIDOQUINOLINES
2479
(KBr, cmꢁ1): 1801, 1699, 1553, 1500, 1444, 1335, 1213, 1160, 1027, 950, 780; MS m=z
(%) 327 [(Mþ þ 1), 51], 326 (Mþ, 13), 253 (36), 237 (71), 211 (100), 209 (98), 183 (78),
142 (72), 115 (40). Anal. calcd. for C17H14N2O5: C, 62.57; H, 4.32; N, 8.59. Found:
C, 62.71; H, 4.22; N, 8.66.
Ethyl 2-(3-Formyl-8-methylquinolin-2-
yl)-5-oxo-2,5-dihydroisoxazole-4-carboxylate (2d)
Using the corresponding quinoline[15] (100 mg, 0.48 mmol) by the same pro-
1
cedure gave 2d (119 mg, 75%) as a pale yellow solid, mp 178–180 ꢀC. H NMR
(CDCl3): d 1.42 (t, J ¼ 6.9 Hz, 3H, CH3), 2.76 (s, 3H, CH3), 4.43 (q, J ¼ 6.9 Hz,
2H, CH2), 7.55 (t, J ¼ 7.8 Hz, 1H, ArH), 7.76 (d, J ¼ 7.8 Hz, 1H, ArH), 7.84 (d,
J ¼ 7.8 Hz, 1H, ArH), 8.87 (s, 1H, ArH), 9.55 (s, 1H, H-isoxazolone ring), 10.66
(s, 1H, CHO); 13C NMR (CDCl3): d 14.37, 17.68, 61.34, 99.40, 120.78, 126.67,
127.52, 128.11, 134.22, 136.81, 142.42, 143.29, 146.77, 148.32, 161.01, 163.99,
187.61; FT-IR (KBr, cmꢁ1): 1801, 1704, 1681, 1611, 1589, 1561, 1455, 1490, 1468,
1434, 1367, 1218, 1028, 947, 781. Anal. calcd. for C17H14N2O5: C, 62.57; H, 4.32;
N, 8.59. Found: C, 62.69; H, 4.29; N, 8.27.
Ethyl 2-(3-Formyl-6-methoxyquinolin-2-
yl)-5-oxo-2,5-dihydroisoxazole-4-carboxylate (2e)
Using the corresponding quinoline[15] (100 mg, 0.45 mmol) by the same pro-
1
cedure gave 2e (129 mg, 84%) as a pale yellow solid, mp 162–164 ꢀC. H NMR
(CDCl3): d 1.42 (t, J ¼ 6.9 Hz, 3H, CH3), 3.98 (s, 3H, OCH3), 4.41 (q, J ¼ 6.9 Hz,
2H, CH2), 7.24 (s, 1H, ArH), 7.56 (d, J ¼ 9 Hz, 1H, ArH), 7.92 (d, J ¼ 9 Hz, 1H,
ArH), 8.79 (s, 1H, ArH), 9.53 (s, 1H, H-isoxazolone ring), 10.64 (s, 1H, CHO);
13C NMR (CDCl3): d 14.37, 55.87, 61.23, 96.16, 106.31, 121.46, 127.38, 128.02,
129.84, 140.04, 142.89, 143.90, 148.83, 159.17, 160.93, 164.25, 187.64; FT-IR
(KBr, cmꢁ1): 1781, 1715, 1695, 1619, 1567, 1504, 1464, 1371, 1348, 1229, 1017,
835, 775. Anal. calcd. for C17H14N2O6: C, 59.65; H, 4.12; N, 8.18. Found: C,
59.51; H, 4.21; N, 8.43.
Ethyl 5-Formyl-3-hydroxy-1-oxo-1H-pyrimido[1,2-a]quinoline-2-
carboxylate (3a)
The isoxazolone (100 mg, 0.32 mmol) was refluxed in chloroform with triethy-
lamine (0.5 mL) for 4 h. The solvent was removed, the residue was dissolved in water
(2 mL), and the solution was acidified to pH 2 with concentrated HCl. The yellow
1
precipitate was filtered to give the compound 3a (80 mg, 80%), mp 169–171 ꢀC. H
NMR (CDCl3): d 1.52 (t, J ¼ 7.2 Hz, 3H, CH3), 4.57 (q, J ¼ 7.2 Hz, 2H, CH2),
7.64 (t, J ¼ 7.5 Hz, 1H, ArH), 7.83 (ddd, J1 ¼ 9 Hz, J2 ¼ 7.5 Hz, J3 ¼ 1.5 Hz, 1H,
ArH), 7.93 (dd, J1 ¼ 7.8 Hz, J2 ¼ 1.5 Hz, 1H, ArH), 8.61 (s, 1H, ArH), 9.52 (d,
J ¼ 9 Hz, 1H, ArH), 10.86 (s, 1H, CHO), 13.91 (s, 1H, OH, exchanged by D2O
addition); 13C NMR (CDCl3): d 14.35, 62.63, 90.34, 122.25, 123.33, 125.72,
127.61, 131.45, 133.46, 136.64, 141.84, 153.14, 159.87, 171.3, 171.68, 188.82; FT-IR

2480
A. P. MARJANI, J. KHALAFY, AND A. R. M. EBRAHIMLO
(KBr, cmꢁ1): 3451, 3060, 1698, 1620, 1576, 1525, 1488, 1333, 1213, 1093, 807. Anal.
calcd. for C16H12N2O5: C, 61.54; H, 3.87; N, 8.97. Found: C, 61.77; H, 3.52; N, 8.88.
Ethyl 3-Hydroxy-5-(1,3-oxathiolan-2-yl)-1-oxo-1H-
pyrimido[1,2-a]quinoline-2-carboxylate (3b)
This compound was prepared by the same procedure as described for com-
pound 3a, using the corresponding isoxazolone 2b (100 mg, 0.26 mmol), to give 3b
as a pale yellow solid (70 mg, 70%), mp 173–175 ꢀC.1H NMR (CDCl3): d 1.51 (t,
J ¼ 7.2 Hz, 3H, CH3), 3.61 (s, 4H, CH2CH2), 4.54 (q, J ¼ 7.2 Hz, 2H, CH2), 6.31
(s, 1H, CH), 7.55 (t, J ¼ 7.8 Hz, 1H, ArH), 7.65 (ddd, J1 ¼ 9 Hz, J2 ¼ 7.8 Hz,
J3 ¼ 1.5 Hz, 1H, ArH), 7.75 (dd, J1 ¼ 7.8 Hz, J2 ¼ 1.5 Hz, 1H, ArH), 8.43 (s, 1H,
ArH), 9.42 (d, J ¼ 9 Hz, 1H, ArH), 13.75 (s, 1H, OH, exchanged by D2O addition);
13C NMR (CDCl3): d 14.41, 39.05, 50.17, 62.41, 89.97, 121.79, 124.04, 126.97, 128.9,
130.35, 134.07, 134.36, 136.8, 152.58, 160.45, 170.87, 171.82; FT-IR (KBr, cmꢁ1):
3500, 1716, 1627, 1578, 1521, 1483, 1342, 1222, 805, 758; MS m=z (%) 389
[(Mþ þ 1), 2], 388 (Mþ, 1), 373 (6), 343 (7), 316 (100), 271 (81), 211 (37), 168 (42),
129 (39), 115 (12). Anal. calcd. for C18H16N2O4S2: C, 55.65; H, 4.15; N, 7.21; S,
16.51. Found: C, 55.55; H, 4.32; N, 7.33; S, 16.42.
Ethyl 5-Formyl-3-hydroxy-8-methyl-1-oxo-
1H-pyrimido[1,2-a]quinoline-2-carboxylate (3c)
This compound was prepared by the same procedure as described for com-
pound 3a, using the corresponding isoxazolone 2c (100 mg, 0.31 mmol), to give 3c
1
as a pale yellow solid (75 mg, 75%), mp 182–184 ꢀC. H NMR (CDCl3): d 1.51 (t,
J ¼ 7.2 Hz, 3H, CH3), 2.54 (s, 3H, CH3), 4.56 (q, J ¼ 7.2 Hz, 2H, CH2), 7.63 (dd,
J1 ¼ 9 Hz, J2 ¼ 2.1 Hz, 1H, ArH), 7.69 (s, 1H, ArH), 8.55 (s, 1H, ArH), 9.43 (d,
J ¼ 9 Hz, 1H, ArH), 10.85 (s, 1H, CHO), 13.87 (s, 1H, OH, exchanged by D2O
addition); 13C NMR (CDCl3): d 14.38, 20.76, 62.6, 90.27, 122.06, 123.14, 125.58,
130.69, 134.74, 134.96, 137.89, 141.8, 152.95, 159.92, 171.12, 171.74, 188.99; FT-IR
(KBr, cmꢁ1): 3421, 1718, 1697, 1616, 1579, 1518, 1334, 1099; MS m=z (%) 327
[(Mþ þ 1), 100], 326 (Mþ, 90), 309 (19), 253 (55), 210 (23), 205 (13), 142 (11). Anal.
calcd. for C17H14N2O5: C, 62.57; H, 4.32; N, 8.59. Found: C, 62.45; H, 4.55; N, 8.66.
Ethyl 5-Formyl-3-hydroxy-10-methyl-1-oxo-
1H-pyrimido[1,2-a]quinoline-2-carboxylate (3d)
This compound was prepared by the same procedure as described for com-
pound 3a, using the corresponding isoxazolone 2d (100 mg, 0.31 mmol), to give 3d
1
as a pale orange solid (71 mg, 71%), mp 229–231 ꢀC. H NMR (CDCl3þDMSO-
d6): d 1.33 (t, J ¼ 7.5 Hz, 3H, CH3), 2.66 (s, 3H, CH3), 4.30 (q, J ¼ 7.5 Hz, 2H,
CH2), 7.30 (t, J ¼ 7.5 Hz, 1H, ArH), 7.55 (d, J ¼ 6.9 Hz, 1H, ArH), 7.64 (s, 1H,
ArH), 7.69 (d, J ¼ 7.5 Hz, 1H, ArH), 8.45 (s, 1H, CHO), 11.62 (s, 1H, OH,
exchanged by D2O addition); 13C NMR (CDCl3 þ DMSO-d6): d 14.32, 17.99,
61.31, 98.06, 113.90, 124.92, 125.10, 126.78, 132.38, 135.64, 139.41, 143.23, 148.20,
148.27, 160.40, 163.82, 184.32; FT-IR (KBr, cmꢁ1): 3448, 1693, 1675, 1627, 1615,

NEW PYRIMIDOQUINOLINES
2481
1568, 1330, 1283, 1254, 826, 746, 604. Anal. calcd. for C17H14N2O5: C, 62.57; H,
4.32; N, 8.59. Found: C, 62.66; H, 4.21; N, 8.73.
Ethyl 5-Formyl-3-hydroxy-8-methoxy-1-oxo-
1H-pyrimido[1,2-a]quinoline-2-carboxylate (3e)
This compound was prepared by the same procedure as described for com-
pound 3a, using the corresponding isoxazolone 2e (100 mg, 0.3 mmol), to give 3e
1
as a pale green solid (79 mg, 79%), mp 166–168 ꢀC. H NMR (CDCl3): d 1.29 (t,
J ¼ 7.2 Hz, 3H, CH3), 3.87 (s, 3H, OCH3), 4.28 (q, J ¼ 7.2 Hz, 2H, CH2), 7.39 (d,
J ¼ 9 Hz, 1H, ArH), 7.70 (s, 1H, ArH), 8.61 (s, 1H, ArH), 9.39 (d, J ¼ 9 Hz, 1H,
ArH), 10.59 (s, 1H, CHO), 12.82 (s, 1H, OH, exchanged by D2O addition); 13C
NMR (CDCl3): d 14.57, 56.17, 61.31, 93.99, 113.01, 121.62, 123.24, 125.14,
126.06, 130.97, 140.83, 150.73, 157.47, 160.54, 165.35, 166.95, 189.89; FT-IR
(KBr, cmꢁ1): 3481, 1729, 1694, 1615, 1582, 1526, 1469, 1439, 1336, 1247, 1226,
1099, 1039, 827. Anal. calcd. for C17H14N2O6: C, 59.65; H, 4.12; N, 8.18. Found:
C, 59.42; H, 4.09; N, 8.25.
CONCLUSION
This study shows a new and facile synthetic pathway to the pyrimidoquinoline
system, allowing large substitution patterns. Furthermore, starting from a suitable
substrate, the synthesis of other heterocyclic compounds is possible, which may have
pharmaceutical applications.
ACKNOWLEDGMENT
The authors are grateful for support of this work from the University of
Urmia.
REFERENCES
1. Khalafy, J.; Prager, R. H.; Smith. J. A. The chemistry of 5-oxodihydroisoxazoles, part 23:
Photochemical and thermal reactions of isoxazol-5(2H)-ones substituted at C-3 or C-4
with nitrogen, oxygen, or sulfur. J. Chem. Res., Miniprint 1999, 518–536.
2. Beccalli, E. M.; Marchesini, A. Pyrazin-2(1H)-ones from 3,4-disubstituted
4-aminoisoxazol-5(4H)-ones. Synthesis 1991, 861–862.
3. Prager, R. H.; Rosenzweig, T. K.; Sing, Y. The chemistry of 5-oxodihydroisoxazoles, III:
Synthesis of further annelated pyrimidines. Aust. J. Chem. 1992, 45, 1825–1832.
4. Baradarani, M. M.; Khalafy, J.; Khadivi, S.; Poursattar Marjani, A. Base-induced
rearrangements of N-substituted 3-arylaminoisoxazol-5(2H)-ones to 2-arylaminoimidazo
[1,2-a]pyridines. Chem. Heterocycl. Comp. 2008, 44, 594–599; Khim. Geterotsikl. Soedin.
2008, 44, 751–757.
5. Khalafy, J.; Prager, R. H. Some unusal reaction of 3-phenylaminoisoxazol-5(2H)-ones.
J. Sci. I. R. Iran 2000, 11, 32–38.
6. El-Gazzar, A. B. A.; El-Enany, M. M.; Mahmoud, M. N. Synthesis, analgesic,
anti-inflammatory, and antimicrobial activity of some novel pyrimido[4,5-b]quinoline-4-
ones. Bioorg. Med. Chem. 2008, 16, 3261–3273.

2482
A. P. MARJANI, J. KHALAFY, AND A. R. M. EBRAHIMLO
7. Dlugosz, A.; Dus, D. Synthesis and anticancer properties of pyrimido[4,5-b]quinolines.
Farmaco 1996, 51, 364–374.
8. Joshi, A. A.; Viswanathan, C. L. Recent developments in antimalarial drug discovery.
Anti-infect. Agent. Med. Chem. 2006, 5, 105–122.
9. El-Sayed, O. A.; Al-Bassam, B. A.; Hussein, M. E. Synthesis of some novel quinoline-3-
carboxylic acids and pyrimidoquinoline derivatives as potential antimicrobial agents.
Arch. Pharm. Pharm. Med. Chem. 2002, 335, 403–410.
10. El-Sayed, O. A.; Al-Turki, T. M.; Al-Daffiri, H. M.; Al-Bassam, B. A.; Hussein, M. E.
Pyrimidoquinoline derivatives as anti-inflammatory and antimicrobial agents. Boll. Chim.
Farm. 2004, 143, 227–238.
11. El-Gazzar, A. B. A.; Hafez, H. N.; Nawwar, G. A. M. New acyclic nucleosides analogues
as potential analgesic, anti-inflammatory, anti-oxidant, and anti-microbial derived from
pyrimido[4,5-b]quinolines. Eur. J. Med. Chem. 2009, 44, 1427–1436.
12. Woodman, D. J.; Borman, C. H.; Tontapanish, N.; Stonebraker, P. M. Novel reactions of
3-unsubstituted 3-isoxazolin-5-ones. J. Org. Chem. 1969, 34, 2981–2983.
13. Woodman, D. J.; Stonebraker, P. M. Observation of ketenimine carboxylates and their
conversion to four-membered heterocycles. J. Am. Chem. Soc. 1976, 98, 6036–6037.
14. Claisen, L. Untersuchungen uber die Oxymethylenverbindungen. (Zweite Abhandlung).
¨
Justus Liebigs Ann. Chem. 1879, 297, 1–98.
15. Meth-Cohn, O.; Narine, B.; Tarnowski, B. A versatile new synthesis of quinolines and
related fused pyridines, part 5. The synthesis of 2-chloroquinoline-3-carbaldehydes. J.
Chem. Soc., Perkin Trans. 1 1981, 1520–1530.