A facile synthesis of ethyl-2-methyl-5-aryl-5H-chromeno-[3,4-c]pyridine-1-carboxylates

Article abstract of DOI:10.1081/SCC-100105383

Flav-4-ones on reaction with DMF/POCl₃ gave 4-chloro-2-aryl-2H-chromene-3-carbaldehydes which on reaction with ethyl-3-aminocrotonate give under Hantszch reaction conditions ethyl-2-methyl-5-aryl-5H-chromeno[3,4-c]pyridine-1-carboxylates in good yields.

Full text of DOI:10.1081/SCC-100105383

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A FACILE SYNTHESIS OF ETHYL-2-METHYL-5-ARYL-5H-
CHROMENO-[3,4-c]PYRIDINE-1-CARBOXYLATES
M. Venkati a & G. L. David Krupadanam b
a Department of Chemistry , Osmania University , Hyderabad, A. P., 500007, India
b Department of Chemistry , Osmania University , Hyderabad, A. P., 500007, India
Published online: 09 Nov 2006.
To cite this article: M. Venkati & G. L. David Krupadanam (2001) A FACILE SYNTHESIS OF ETHYL-2-METHYL-5-
ARYL-5H-CHROMENO-[3,4-c]PYRIDINE-1-CARBOXYLATES, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 31:17, 2589-2598, DOI: 10.1081/SCC-100105383
To link to this article: http://dx.doi.org/10.1081/SCC-100105383
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SYNTHETIC COMMUNICATIONS, 31(17), 2589–2598 (2001)
A FACILE SYNTHESIS OF ETHYL-
2-METHYL-5-ARYL-5H-CHROMENO-
[3,4-c]PYRIDINE-1-CARBOXYLATES
M. Venkati and G. L. David Krupadanam*
Department of Chemistry, Osmania University,
Hyderabad 500007, A. P., India
ABSTRACT
Flav-4-ones on reaction with DMF/POCl3 gave 4-chloro- 2-
aryl-2H-chromene-3-carbaldehydes which on reaction with
ethyl-3-aminocrotonate give under Hantszch reaction con-
ditions ethyl-2-methyl-5-aryl-5H-chromeno[3,4-c]pyridine-1-
carboxylates in good yields.
Severalflavanones, substituted chromanones and chromenes show a
variety of biological activities such as anticancer,1 gastroprotective,2 coro-
nary vasodilator3 and diuretic.4 In view of the potentialbioactivity shown by
these heterocyclics, in the present study several new pyridyl fused aryl sub-
stituted chromenes (6a–g) are synthesised by a modification of the Hantszch
reaction5 starting from 4-chloro-2-aryl-2H-chromene-3-carbaldehydes
(5a–g). Hantszch synthesis involves the reaction of aromatic or a,b-unsatu-
rated aldehydes with NH3 in ethylacetoacetate or ethyl-3-aminocrotonate to
give dihydropyridines and pyridines.6–12 Earlier, we reported the synthesis of
ethyl-2-methyl-5-oxo-[1]benzopyrano-[3,4-c]-pyridine-1-carboxylates13 (1) and
*Corresponding author.
2589
Copyright & 2001 by MarcelDekker, Inc.
www.dekker.com

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VENKATI AND KRUPADANAM
ethyl-2-methyl-5H-chromeno[3,4-c]pyridine-1-carboxylates.14 One of these
compounds, ethyl-9-hydroxy-2-methyl-5H-chromeno[3,4-c]pyridine-1-car-
boxylate (2) showed high activity in antituberculosis screening.15 Since
more lipophilic analogs of the new bioactive structure are expected to show
enhanced antituberculor activity, we planned the synthesis of aryl substituted
analogues of ethyl-2-methyl-5H-chromeno-[3H]-pyridine-1-carboxylates
(6a–g). Their synthesis and characterization is described in this paper.
20-Hydroxy chalcones 3a–g were obtained by the base catalyzed con-
densation of o-hydroxy acetophenones with substituted benzaldehydes.16
These were cyclised to the corresponding flav-4-ones (4a–g) by heating
in EtOH/HCl. The flavan-4-ones (4a–g) on reaction with DMF/POCl3
(Vilsmeier-Haack reaction)17 gave 4-chloro-2-aryl-2H-chromene-3-carbal-
dehydes (5a–g) in 85% yields.
An equimolar solution of 4-chloro-2-aryl-2H-chromene-3-carbalde-
hyde (5a) and ethyl-3-aminocrotonate in acetic acid was stirred at room
temperature for 24 h. The acetic acid was distilled off and the reaction
mixture poured onto ice. The crude product was purified using column
chromatography to give ethyl-2-methyl-5-(40-methylphenyl)-5H-chromene-
1
[3,4-c]-pyridine-1-carboxylate (6a) in 70% yield. The H NMR spectrum of
6a showed a signalpattern characteristic of a pyridylring fused to 3, 4
position of the chromene rather than the alternative 1,4-dihydropyridyl
substituted chromenes (7a–g). Similarly 6b–g were obtained from the reac-
tion of ethyl-3-aminocrotonate with 5b–g respectively.
The reaction of aromatic aldehydes and a,b-unsaturated carbonyl
compounds with ethyl-3-aminocrotonate generally gives dihydropyridines
and pyridines.6–9 Michaelreaction of 5a–g with ethyl-3-aminocrotonate
followed by an intramolecular condensation of the carbonyl and amino
group leads to the formation of the fused dihydropyridyl moiety (11a–g)
which by loss of HCl gives aromatised and fused pyridine ring 6a–g as
shown in Scheme 2.

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2591
Scheme 1.

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VENKATI AND KRUPADANAM
Scheme 2.
EXPERIMENTAL
Melting points were determined in sulfuric acid bath and are uncor-
rected IR spectra were recorded on FT-IR Perkin-Elmer 1605 spectrophot-
1
ometer and H NMR (200 MHz) and 13C NMR (50.3 MHz, CDCl3) were
recorded on a Varian Gemini 200 spectrometer using TMS as internalstan-
dard (Chemicalshifts in d ppm). Mass spectra were recorded on as VG

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ARYL–SUBSTITUTED CHROMENES
2593
micro mass 7070H instrument. UV spectra were recorded on as Shimadzu
UV-Visible Spectrophotometer (Model No. UV-1601). Elemental analysis
were done on a Elementar Vario EL instrument.
General procedure for the synthesis of 4-chloro-2-aryl-2H-chromene-
3-carbaldehydes (5a–g): To Flav-4-ones (4a–g) (10 mmoles) in dry dimethyl
formamide (50 mmoles) a freshly distilled dry phosphorus oxychloride
(9 mmoles) was added with constant stirring at 0ꢀC. The reaction mixture
was kept overnight and then poured on to crushed ice. The yellow com-
pound (4a–g) that separated was filtered, washed with water the product on
chromatography over silicagel by eluting with pet.ether gave 4a–g in 85%
yield. These were recrystallised from methanol to give yellow crystals.
4-Chloro-2-(4-methyl phenyl)-2H-3-chromene carbaldehyde (5a): m.p.
98ꢀC. IR (KBr): 1603 (C¼C). 1667 cm–1 (CHO). UV (MeOH): 210 nm
(log e 4.2), 292 nm (log e 4.0) and 307 nm (log e 4.0). 1H NMR: d 2.22
(40-CH3), 6.25 (s, H-2), 6.68 (bd, J ¼ 10 Hz, H-8), 6.95 (m, H-7), 7.0 (d,
J ¼ 10 Hz, H-30, 50), 7.10 (d, J ¼ 10 Hz, H20, 60), 7.30 (m, H-6), 7.65 (bd,
J ¼ 10 Hz, H-5), and 10.22 (s, 3-CHO). 13C NMR: d 21.0 (C-40-CH3), 74.9
(C-2), 117.5 (C-8), 120.0 (C-4a) 122.0 (C-6), 126.2 (C-3, C-7), 126.5 (C-20,
60), 129.2 (C-30, 50), 134.0 (C-5), 135.0 (C-40), 138.5 (C-10), 143.5 (C-4), 155.0
(C-8a), and 188.0 (CHO). MS: m/z 284 Mþ (25), 286 (8), 270 (24), 256 (100),
220 (20), and 206 (20). Anal. Calcd. for C17H13ClO2: C, 71.74, H, 4.62.
Found: C, 71.71, H, 4.60%.
4,6-Dichloro-2-phenyl-2H-3-chromene carbaldehyde (5b): m.p. 114ꢀC.
IR (KBr): 1606 (C¼C), 1662 cm–1 (CHO). UV (MeOH): 207 nm (log e
1
4.8), 297 nm (log e 4.4) and 367 nm (log e 3.9). H NMR: d 6.45 (s, H-2),
6.83 (d, J ¼ 10 Hz, H-8), 7.25 (m, H-7, 20, 30, 40, 50 and 60), 7.68 (d, J ¼ 2 Hz,
H-5), and 10.26 (s, CHO). 13C NMR: d 26.0 (C-7), 75.3 (C-2), 118.5 (C-8),
121.5 (C-4a), 126.5 (C-20, 60), 127.0 (C-3), 127.5 (C-6), 128.5 (C-30, 50), 129.0
(C-40), 134.0 (C-5), 137.8 (C-11), 142.0 (C-4), and 153.8 (C-8a). MS: m/z 304
Mþ (40), 306 (26), 274 (100), 276 (66), 238 (10), 227 (5), and 176 (20). Anal.
Calcd. for C16H10Cl2O2: C, 62.97, H, 3.31. Found: C, 62.98, H, 3.30%.
4,6-Dichloro-2-(4-methoxy phenyl)-2H-3-chromene carbaldehyde (5c):
m.p. 126ꢀC. IR (KBr): 1601 (C¼C). 1660 cm–1 (CHO). UV (MeOH):
1
204 nm (log e 4.2), 296 nm (log e 4.6) and 374 nm (log e 4.2). H NMR: d
3.79 (40-OCH3), 6.30 (s, H-2), 6.80 (d, J ¼ 10 Hz, H-8), 6.75 (d, J ¼ 10 Hz,
H-30, 50), 7.20 (d, J ¼ 10 Hz, H-70, 60), 7.30 (dd, J ¼ 10, 2 Hz, H-7), 7.70 (d,
J ¼ 2 Hz, H-8), and 10.28 (s, CHO). 13C NMR: d 55.2 (40-OCH3), 75.0 (C-2),
114.0 (C-30, 50), 118.7 (C-8), 121.5 (C-4a), 126.0 (C-7), 127.0 (C-3), 127.5 (C-
6), 128.5 (C-20, 60), 130.0 (C-10), 134.1 (C-5), 142.0 (C-4), 153.8 (C-8a), and
160.3 (C-40). MS: m/z 333 Mþ (10), 335 (6), 304 (100), 306 (66), 298 (20), 227
(10), and 163 (10). Anal. Calcd. for C17H12Cl2O3: C, 60.90, H, 3.60. Found:
C, 60.92, H, 3.61%.

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VENKATI AND KRUPADANAM
4,6-Dichloro-2-(3,4-dimethoxyphenyl)-2H-3-chromenecarbaldehyde
(5d): m.p. 122ꢀC. IR (KBr): 1604 (C¼C), 1666 cm–1 (CHO). UV (MeOH):
211 nm (log e 5.0), 234 nm (log e 4.0), 294 nm (log e 4.6) and 371 nm (log e
4.1). 1H NMR: d 3.78 (s, OCH3), 6.28 (s, H-2), 6.65–6.82 (m, 4H, H-20,
50, 6, and H-8), 7.25 (dd, J ¼ 10 Hz, H-7), 7.68 (d, J ¼ 2 Hz, H-5), and
10.28 (s, CHO). 13C NMR: d 55.6 (OCH3), 55.7 (OCH3), 75.0 (C-2), 110.5
(C-20), 110.7 (C-50), 118.5 (C-8), 119.0 (C-60), 121.5 (C-4a), 125.8 (C-7), 127.0
(C-3), 127.5 (C-6), 130.0 (C-10), 134.0 (C-5), 141.8 (C-4), 149.0 (C-40), 149.5
(C-30), and 153.5 (C-8a). MS: m/z 362 Mþ (30), 344 (20), 334 (100), 336 (66),
281 (20), and 279 (20). Anal. Calcd. for C18H14Cl2O4: C, 59.21, H, 3.87.
Found: C, 59.20, H, 3.86%.
4,6-Dichloro-2-(4-methyl phenyl)-2H-3-chromenecarbaldehyde (5e):
m.p. 113ꢀC. IR (KBr): 1600 (C¼C). 1658 cm–1 (CHO). UV (MeOH):
1
206 nm (log e 4.8), 297 nm (log e 4.4) and 375 nm (log e 4.0). H NMR: d
6.25 (s, H-2), 6.82 (d, J ¼ 10 Hz, H-8), 7.08 (m, 4-H, H-30, 50, 20, and 60),
7.30 (dd, J ¼ 10, 2 Hz, H-7), 7.68 (d, J ¼ 2 Hz, H-5), and 10.25 (s, CHO).
13C NMR: d 20.9 (CH3), 75.0 (C-2), 118.6 (C-8), 121.0 (C-4a), 126.0
(C-7), 126.5 (C-20, 60), 127.0 (C-3), 127.5 (C-6), 129.0 (C-30, 50), 134.0
(C-5), 134.3 (C-40), 138.6 (C-10), 142.0 (C-4), and 153.8 (C-8a). MS: m/z
317 Mþ (21), 319 (14), 288 (100), 290 (66), 238 (5), and 189 (10). Anal.
Calcd. for C17H12Cl2O2: C, 63.96, H, 3.78. Found: C, 63.97, H, 3.79%.
4,8-Dichloro-2-(4-methyl phenyl)-2H-3-chromenecarbaldehyde (5f):
m.p. 153ꢀC. IR (KBr): 1599 (C¼C). 1660 cm–1 (CHO). UV (MeOH):
1
209 nm (log e 4.8), 306 nm (log e 4.6) and 362 nm (log e 4.1). H NMR: d
2.30 (s, 40-CH3), 6.50 (s, H-2), 6.96 (dd, J ¼ 10, 10 Hz, H-6), 7.08 (d,
J ¼ 10 Hz, H-30, 50), 7.20 (d, J ¼ 10 Hz, H-20, 60), 7.42 (dd, J ¼ 10, 2 Hz,
H-7), 7.63 (dd, J ¼ 10, 2 Hz, H-5), and 10.32 (s, 3-CHO). 13C NMR: d 21.0
(40-CH3), 75.2 (C-2), 120.2 (C-6), 120.5 (C-4a), 122.5 (C-8), 125.0 (C-7),
126.5 (C-20, 60), 128.0 (C-3), 129.2 (C-30, 50), 134.2 (C-40), 134.5 (C-5),
138.5 (C-10), 142.8 (C-4), and 151.0 (C-8a). MS: m/z 318 Mþ (18), 320
(12), 303 (15), 289 (100), 291 (80), 253 (10), 255 (10), 239 (15), and 189
(20). Anal. Calcd. for C17H12Cl2O2: C, 63.96, H, 3.78. Found: C, 63.97,
H, 3.79%.
4,8-Dichloro-2-(4-chloro phenyl)-2H-3-chromenecarbaldehyde (5g):
m.p. 125ꢀC. IR (KBr): 1602 (C¼C) 1662 cm–1 (CHO). UV (MeOH):
1
207 nm (log e 4.7), 306 nm (log e 3.4), and 360 nm (log e 3.9). H NMR: d
6.50 (s, H-2), 7.02 (dd, J ¼ 10, 10 Hz, H-6) 7.25 (m, H-20, 30, 50, and 60),
7.47 (dd, J ¼ 10, 2 Hz, H-7), 7.65 (dd, J ¼ 10, 2 Hz, H-5), and 10.35 (s,
CHO). 13C NMR: d 74.8 (C-2), 120.0 (C-4a), 122.7 (C-6), 122.8 (C-8),
125.0 (C-7), 127.9 (C-3), 134.5 (C-5), 135.0 (C-40), 136.2 (C-10), 143.5 (C-
4), 151.0 (C-8a), and 188.0 (CHO). MS: m/z 330 Mþ (30), 340 (25), 309

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2595
(100), 311 (90), 275 (15), 239 (25), and 176 (25). Anal. Calcd. for
C16H9Cl2O2: C, 56.58, H, 2.66. Found: C, 56.59, H, 2.67%.
General procedure for the synthesis of ethyl-2-methyl-5-aryl-
5H-chromene[3,4-c]pyridine-1-carboxylates (6a–g): 4-Chloro-2-aryl-2H-chro
mene-3-carbaldehyde (5a–g) (3 mmoles) and ethyl-3-amino crotonate
(3 mmoles) were dissolved in acetic acid (10 ml) and kept in constant stirring
at room temperature for 48 hours. The acetic acid was distilled off under
reduced pressure. Then the reaction mixture was poured on to crushed ice.
Pale yellow solid separated out. It was filtered and washed with water and
chromatographed over silica gel by eluting with pet either: chloroform 8:2 to
give 6a–g which were recrystallised methanol to give pale yellow crystals.
6a–g were obtained in 70% yield.
Ethyl-2-methyl-5-(4-methyl phenyl)-5H-chromene[3,4-c]pyridine-1-car-
boxylate (6a): m.p. 102ꢀC. IR (KBr): 1719 cm–1 (ester carbonyl). UV
(MeOH): 210 nm (log e 4.5), 275 nm (log e 4.7), and 333 nm (log e 4.7).
1H NMR: d 1.34 (t, J ¼ 8 Hz, CH3), 2.37 (s, CH3), 2.87 (s, CH3), 4.32
(q, J ¼ 8 Hz, OCH2), 6.23 (s, H-5), 6.90 (dd, J ¼ 10, 2 Hz, H-7), 7.2 (m,
H-8, H-9, 20, 30, 50, 6 aromatic), 7.62 (s, H-4), and 8.32 (dd, J ¼ 10, 2 Hz,
H-10). 13C NMR: d 14.0 (CH3), 21.0 (CH3 of 40-CH3), 25.0 (C-2 CH3), 61.0
(OCH2), 78.9 (C-5), 117.2 (C-7), 122.0 (C-9), 122.1 (C-10b), 124.0 (C-1),
125.1 (C-8), 125.5 (C-4a), 127.8 (C-20, 60), 129.0 (C-30, 50), 132.0 (C-10),
135.8 (C-40), 136.0 (C-4), 138.5 (C-10), 150.0 (C-10a), 155.8 (C-2), 159.5
(C-6a), and 166.4 (C¼O). MS: m/z 359 Mþ (80), 358 (40), 330 (15), 268
(100), and 240 (20). Anal. Calcd. for C23H21NO3: C, 76.85, H, 5.88, N, 3.90.
Found: C, 76.86, H, 5.89, N, 3.91%.
Ethyl-9-chloro-2-methyl-5-phenyl-5H-chromene[3,4-c]pyridine-1-carboxylate
(6b): m.p. 136ꢀC. IR (KBr): 1718 cm–1 (ester carbonyl). UV (MeOH):
1
228 nm (log e 4.7), 299 nm (log e 4.3), and 342 nm (log e 4.3). H NMR: d
1.33 (t, J ¼ 8 Hz, CH3), 2.87 (s, CH3-2), 4.30 (q, J ¼ 8 Hz, OCH3), 6.22 (s, H-
5), 6.85 (q, J ¼ 10 Hz, H-7), 7.22 (dd, J ¼ 10, 2.5 Hz, H-8), 7.32 (m, H5, H-20,
30, 40, 50, 60), 7.60 (s, H-4), and 8.32 (d, J ¼ 2.5 Hz, H-10). 13C NMR: d 14.1
(CH3), 25.0 (CH3-2), 61.0 (OCH2), 79.0 (C-5), 118.8 (C-7), 123.2 (C-10b),
124.8 (C-1), 125.0 (C-8), 125.5 (C-4a), 127.8 (C-9), 128.0 (C-20, 60), 128.2 (C-
30, 50), 128.5 (C-40), 132 (C-10), 136.1 (C-4), 138.5 (C-10), 148.5 (C-10a),
154.5 (C-2), 160.0 (C-6a), and 166.0 (C¼O). MS: m/z 379 Mþ (80), 381
(26), 350 (10), 302 (100), 304 (33), 274 (20), 228 (15), and 69 (40). Anal.
Calcd. for C22H18ClNO3: C, 69.58, H, 4.79, N, 3.69. Found: C, 69.57, H,
4.78, N, 3.68%.
Ethyl-9-chloro-2-methyl-5-(4-methoxy phenyl)-5H-chromene[3,4-c]pyri-
dine-1-carboxylate (6c): m.p. 158ꢀC. IR (KBr): 1710 cm–1 (ester carbonyl).
UV (MeOH): 205 nm (log e 4.5), 230 nm (log e 4.5), 277 nm (log e 4.0) and
344 nm (log e 4.0). 1H NMR: d 1.35 (t, J ¼ 8 Hz, CH3), 2.88 (s, CH3-2),

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VENKATI AND KRUPADANAM
3.80 (s, OCH3-40), 4.33 (q, J ¼ 8 Hz, OCH2), 6.22 (s, H-5), 6.85 (d, 2H,
J ¼ 10 Hz, H-30, 50), 6.82 (d, J ¼ 10 Hz, H-7), 7.2 (d, J ¼ 10 Hz, 2H, H-20, 60),
7.26 (dd, J ¼ 10 Hz, H-8), 7.63 (H-4) and 8.25 (d, J ¼ 2.5 Hz, H-10). 13C
NMR: d 14.2 (CH3), 25.0 (CH3-2), 55.3 (OCH3-40), 61.2 (OCH2), 79.0 (C-
5), 114.2 (C-30, 50), 119.0 (C-7), 123.5 (C-10b), 124.5 (C-1), 125.0 (C-8), 126.0
(C-4a), 127.0 (C-9), 129.2 (C-20, 60), 130.5 (C-10), 132.0 (C-10), 136.1 (C-4),
149.0 (C-10a), 154.2 (C-2), 160.0 (C-6a), 160.3 (C-40), and 166.5 (C¼O). MS:
m/z 409 Mþ (100), 408 (40), 380 (20), 302 (50), and 274 (20). Anal. Calcd. for
C23H20ClNO4: C, 67.41, H, 4.93, N, 3.42. Found: C, 67.40, H, 4.92, N,
3.41%.
Ethyl-9-chloro-2-methyl-5-(3,4-dimethoxy phenyl)-5H-chromene[3,4-c]
pyridine-1-carboxylate (6d): m.p. 172ꢀC. IR (KBr): 1711cm–1 (ester carbonyl).
UV (MeOH): 208 nm (log e 4.6), 229 nm (log e 4.4), 279 nm (log e 4.0) and
343 nm (log e 3.8). 1H NMR: d 1.37 (t, J ¼ 8 Hz, CH3), 2.88 (s, CH3-2),
3.80 (s, OCH3), 3.85 (s, OCH3), 4.32 (q, J ¼ 8 Hz, OCH2), 6.20 (s, H-5),
6.80 (m, 4H, H-7, 20, 50, 60), 7.25 (dd, H-8), 7.62 (s, H-4), and 8.28
(d, J ¼ 2 Hz, H-10). 13C NMR: d 14.0 (CH3), 25.0 (CH3-2), 56.0 (OCH3),
56.1 (OCH3), 61.2 (OCH2), 79.0 (C-5), 111.0 (C-50), 111.1 (C-20), 119.0
(C-7), 121.0 (C-60), 123.8 (C-10b), 124.5 (C-1), 125.0 (C-8), 126.0 (C-4a),
127.0 (C-9), 131.0 (C-10), 132.0 (C-10), 136.0 (C-4), 148.5 (C-10a), 149.4
(C-30), 149.5 (C-40), 154.0 (C-2), 160.0 (C-6a), and 166.0 (C¼O). MS: m/z
439 Mþ (40), 441 (13), 408 (20), 364 (20), 335 (60), 337 (40), 302 (20), and
149 (100). Anal. Calcd. for C24H22ClNO5: C, 65.51, H, 5.03, N, 3.18. Found:
C, 65.53, H, 5.04, N, 3.17%.
Ethyl-9-chloro-2-methyl-5-(4-methyl phenyl)-5H-chromene[3,4-c]pyri-
dine-1-carboxylate (6e): m.p. 149ꢀC. IR (KBr): 1718 cm–1 (ester carbonyl).
UV (MeOH): 276 nm (log e 4.3), 299 nm (log e 4.3), and 334 nm (log e 4.4).
1H NMR: d 1.35 (t, J ¼ 8 Hz, CH3), 2.38 (s, CH3), 2.87 (s, CH3), 4.32 (q,
J ¼ 8 Hz, OCH2), 6.22 (s, H-5), 6.84 (d, J ¼ 10 Hz, H-7), 7.20 (m, 5H, H-8,
H-20, 30, 50, 60), 7.63 (s, H-4), and 8.25 (d, J ¼ 2.5 Hz, H-10). 13C NMR: d 14.0
(CH3), 21.0 (CH3-40), 24.9 (CH3-2), 61.2 (OCH2), 79.0 (C-5), 119.0 (C-7),
123.5 (C-10b), 124.8 (C-1), 125.0 (C-8), 126.0 (C-4a), 127.5 (C-9), 128.0
(C-20, 60), 129.5 (C-30, 50), 130.0 (C-10), 135.5 (C-40), 136.0 (C-4), 138.6
(C-10), 148.8 (C-10a), 154.2 (C-2), 160.0 (C-6a), and 166.1 (C¼O). MS:
m/z 393 Mþ (100), 392 (30), 302 (90), 304 (30), 274 (25), 256 (5), and 228
(20). Anal. Calcd. for C23H20ClNO3: C, 70.13, H, 5.10, N, 3.56. Found: C,
70.14, H, 5.12, N, 3.55%.
Ethyl-7-chloro-2-methyl-5-(4-methyl phenyl)-5H-chromene[3,4-c]pyri-
dine-1-carboxylate (6f): m.p. 182ꢀC. IR (KBr): 1721 cm–1 (ester carbonyl).
UV (MeOH): 276 nm (log e 3.9), 304 nm (log e 4.0), and 333 nm (log e 4.0).
1H NMR: d 1.38 (t, J ¼ 8 Hz, CH3), 2.32 (s, CH3), 2.88 (s, CH3), 4.32
(q, J ¼ 8 Hz, OCH3), 6.35 (s, H-5), 6.96 (dd, J ¼ 10, 10 Hz, H-9), 7.15 (A2,

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2597
B2, 20, 30, 50, 60 aromatic J ¼ 10 Hz), 7.35 (dd, J ¼ 10, 2 Hz, H-8), 7.75 (s, H-4),
and 8.20 (dd, J ¼ 10, 2 Hz, H-10). 13C NMR: d 14.0 (CH3), 21.0 (CH3 of
40-CH3), 25.0 (C-2CH3), 61.2 (OCH2), 79.0 (C-5), 122.5 (C-9), 122.7 (C-10b),
124.0 (C-8), 124.8 (C-8), 125.2 (C-7), 125.5 (C-4a), 127.8 (C-20, 60), 129.5
(C-30, 50), 132.5 (C-10), 135.5 (C-40), 136.5 (C-4), 138.8 (C-10), 149.2 (C-10a),
152.0 (C-2), 160.2 (C-6a), and 166.5 (C¼O). MS: m/z 394 Mþ (100), 396
(33), 393 (40), 378 (30), 364 (20), 302 (90), 304 (20), and 274 (30). Anal.
Calcd. for C23H20ClNO3: C, 70.13, H, 5.11, N, 3.56. Found: C, 70.14, H,
5.12, N, 3.57%.
Ethyl-7-chloro-2-methyl-5-(4-chlorophenyl)-5H-chromene[3,4-c]pyridine-1-
carboxylate (6g): m.p. 131ꢀC. IR (KBr): 1728 cm–1 (ester carbonyl). UV
1
(MeOH): 277 nm (log e 4.2), 304 nm (log e 4.3), and 332 nm (log e 4.2). H
NMR: d 1.40 (t, J ¼ 8 Hz, CH3), 2.90 (s, CH3, C-2), 4.36 (q, J ¼ 8 Hz, OCH3),
6.38 (s, H-5), 7.00 (dd, J ¼ 10, 10 Hz, H-9), 7.30 (m, 5H, H-20, 60, 30, 50, and
H-8), 7.78 (s, H-4), and 8.20 (dd, J ¼ 10, 2 Hz, H-10). 13C NMR: d 14.3
(CH3), 25.0 (C-2 CH3), 61.3 (OCH2), 78.5 (C-5), 122.2 (C-9), 122.4
(C-10b), 124.0 (C-1), 124.2 (C-8), 124.6 (C-7), 129.0 (C-20, 60), 129.2 (C-30,
50), 132.5 (C-10), 135.0 (C-40), 136.5 (C-4), 137.1 (C-10), 149.2 (C-10a), 151.5
(C-2), 160.5 (C-6a), and 166.0 (C¼O). MS: m/z 413 Mþ (80), 415 (52), 380
(10), 302 (100), 304 (33), 274 (15), and 228 (5). Anal. Calcd. for C22H17
Cl2NO3: C, 63.77, H, 4.13, N, 3.38. Found: C, 63.78, H, 4.14, N, 3.40%.
REFERENCES
1. Atassi, G.; Briet, P.; Berthelon, J.J., and Collonges, F. Eur. J. Med.
Chem. Chemther. 1985, 20, 393; Chem. Abstr. 1986, 104, 122574.
2. Ares, J.J.; Outt, E.P.; Randall, L.J.; Murray, D.P.; Weissshaar S.P.;
O’Brien, M.L.; Ems, L.B.; Kakodkar, V.S.; Kelm, R.G.; Kershaw,
C.W.; Werchowski, M.K.; Parkinson, A. J. Med. Chem. 1995, 38, 4937.
3. Re, P.D.; Sagramora, L.; Mancini, U.; Valanti, P.; Cima, L. J. Med.
Chem. 1970, 13, 527.
4. Setnikar, I.; Cova, A.; Magistretti, M. J. Arzneimittel-Forsch. 1975,
25, 1916.
5. Hartough, L.; Murray, M. J. Am. Chem. Soc. 1946, 68, 1389.
6. Watanabe, Y.; Shiota, K.; Hoshike, T.; Ozaki, S. Synthesis 1983, 7, 761.
7. Friedrich, B.; Wulf, V. South African Patent. 1968, 6801, 482; Chem.
Abstr. 1969, 70, 96641d.
8. Collie. J.N.; Liebigs, J. Ann. Chem. 1884, 226, 854.
9. Rieche, A.; Bichoff, C. Chem, Ber. 1963, 96, 2607.
10. Chatterjea, J.N. J. Indian. Chem. Soc. 1952, 29, 323.
11. Mumm, O.; Bohme, O. Ber. 1921, 54, 721.

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2598
VENKATI AND KRUPADANAM
12. Kao, V.S.; Robinson, R. J. Chem. Soc. 1955, 2865.
13. Gangadhar, N.; David Krupadanam, G.L. J. Indian. Chem. 1998,
37B, 686.
14. Ramdas, S.; David Krupadanam, G.L. Synth. Commun. 2000,
30, 1103.
15. This compound (ethyl-9-hydroxy-2-methyl-5H-chromeno[3,4-c]pyri-
dine-1-carboxylate) (2) was screened at TAACF (Tuberculosis
Antimicrobial Acquisition and coordinating facility), Alabama
U.S.A., At a MIC of 6.25 mg/ml, it exhibited 96% Inhibition in the
Assay Bactec.
16. Barry Old, K.; Main, L. J. Chem. Soc. Perkin Trans II. 1982, 1309.
17. Moorty, S.R.; Sundramurthy, V.; Subba Rao, N.V. J. Indian. Chem.
1973, 11, 854.
Received in the UK May 22, 2000

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