Multicomponent synthesis of novel penta-heterocyclic ring systems incorporating a benzopyranopyridine scaffold

Article abstract of DOI:10.1055/s-0033-1340085

A simple one-pot method is reported for the synthesis of several novel series of chromeno[4′,3′:4,5]pyrido[2,3-d][1,2,4]triazolo[4,3-a] pyrimidine-6,14-diones, chromeno[4′,3′:4,5]pyr ido[2,3-d]thiazolo[3, 2-a]pyrimidine-6,14-diones, and chrom- eno[4′′,3′′: 4′,5′]pyrido[2′,3′:4,5]pyrimido[2,1-b][1,3]thiazine-6, 15-dione by a multicomponent reaction of salicylaldehyde, ethyl acetoacetate, and the appropriate fused heterocyclic amines in refluxing glacial acetic acid. The structures of the newly synthesized compounds were established by spectroscopy and elemental analyses. The mechanism of the single-step reaction was elucidated.

Full text of DOI:10.1055/s-0033-1340085

258▌
PAPER
paper
Multicomponent Synthesis of Novel Penta-Heterocyclic Ring Systems
Incorporating a Benzopyranopyridine Scaffold
Multicomponent Synthesis of Penta-Heterocycles
Sobhi M. Gomha, Sayed M. Riyadh*
Department of Chemistry, Faculty of Science, University of Cairo, Giza, 12613, Egypt
Fax 20(2)35676501; E-mail: riyadh1993@hotmail.com
Received: 02.09.2013; Accepted after revision: 10.10.2013
6H-chromeno[4′,3′:4,5]pyrido[2,3-d][1,2,4]triazolo-
[4,3-a]pyrimidine-6,14-diones 4a–g (Scheme 1).
Abstract: A simple one-pot method is reported for the synthesis of
several novel series of chromeno[4′,3′:4,5]pyrido[2,3-d][1,2,4]tri-
azolo[4,3-a]pyrimidine-6,14-diones, chromeno[4′,3′:4,5]pyr-
ido[2,3-d]thiazolo[3,2-a]pyrimidine-6,14-diones, and chrom-
eno[4′′,3′′:4′,5′]pyrido[2′,3′:4,5]pyrimido[2,1-b][1,3]thiazine-6,15-
dione by a multicomponent reaction of salicylaldehyde, ethyl aceto-
acetate, and the appropriate fused heterocyclic amines in refluxing
glacial acetic acid. The structures of the newly synthesized com-
pounds were established by spectroscopy and elemental analyses.
The mechanism of the single-step reaction was elucidated.
O
R
CHO
O
N
+
+
CO2Et
N
N
OH
H2N
N
piperidine
Ar
AcOH, reflux
1
2
3a–g
3, 4 R, Ar
Key words: multicomponent reactions, heterocycles, polycycles
a
b
c
d
e
f
Ph, Ph
COMe, Ph
O
O
R
Multicomponent reactions are among the best tools for
combinatorial chemistry.1 In these reactions, three or
more starting materials react to form a single product.
Among the advantages of multicomponent reactions are
higher productivities, simple procedures, and time saving.
Recent examples of multicomponent reactions include the
Biginelli reaction for rapid synthesis of dihydropyrimi-
dines,2,3 the Gewald reaction for the synthesis of amino-
thiophenes,4,5 and the Hantzsch dihydropyridine
synthesis.6,7
COMe, 4-MeC6H4
CO2Et, Ph
O
N
N
CONHPh, Ph
CONHPh, 4-MeC6H4
COPh, Ph
N
N
N
Ar
g
4a–g
Scheme 1
The structures of the products were confirmed by elemen-
tal analyses and spectroscopy. The IR spectra showed, in
each case, a single absorption band at 1713–1747 cm–1
which was assigned to the carbonyl group of the δ-lactone
and another band at 1640–1658 cm–1 corresponding to the
Benzopyranopyridines are regarded as important bioac-
tive heterocycles because they have diverse biological ac-
tivities, including antiinflammatory,8 antibacterial,9
antifungal,9 antiproliferative,10 and anticancer activities.11
Consequently, many synthetic pathways to such scaffold
have been reported. These include the thermal reaction of
4-amino-3-formylcoumarins with various active methy-
lene compounds under solvent-free conditions,12 Michael
additions of various naphthols to iminocoumarin deriva-
tives;13 and multicomponent reactions of aminopyrazoles,
ethyl acetoacetate, and salicylaldehyde.14,15 On the basis
of these precedents, we attempted to synthesize penta-het-
erocyclic ring systems incorporating the benzopyranopyr-
idine scaffold by a single-step multicomponent reaction.
1
amide carbonyl. H NMR revealed a singlet at δ = 2.91–
2.98 ppm, assignable to the methyl group on the fused
pyridine ring14 and another multiplet at δ = 7.40–7.68
ppm, with a four-proton intensity, assignable to the cou-
marin ring system.18 The 13C NMR spectra of compounds
4a–g confirmed the presence of the [1,2,4]triazolo[4,3-a]
pyrimidine ring system by exhibiting a peak at δ = 160.5–
161.5 ppm corresponding to the carbonyl group attached
to the sp3 nitrogen atom.19
We propose the following mechanism to account for the
formation of products 4a–g (Scheme 2). The three-com-
ponent reaction begins with condensation of salicylalde-
hyde (1) with ethyl acetoacetate (2). This is followed by
elimination of ethanol under basic condition to give 3-ace-
tyl-2H-chromen-2-one (5). Condensation of chromenone
5 with a 1,3-disubstituted 7-amino-[1,2,4]triazolo[4,3-
a]pyrimidin-5(1H)-one 3a–g gives the corresponding
nonisolable intermediate 6a–g. Subsequent autoxidation
of intermediates 6a–g gives the corresponding chrome-
no[4′,3′:4,5]pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine-
6,14-dione 4a–g as the final product.
We began by studying the three-component reaction of
salicylaldehyde (1), ethyl acetoacetate (2; ethyl 3-oxobu-
tanoate), and various 1,3-disubstituted 7-amino[1,2,4]tri-
azolo[4,3-a]pyrimidin-5(1H)-ones 3a–g16,17 in refluxing
acetic acid containing a few drops of piperidine. This re-
action gave the corresponding novel penta-heterocyclic
SYNTHESIS 2014, 46, 0258–0262
Advanced online publication: 07.11.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1340085; Art ID: SS-2013-Z0597-OP
© Georg Thieme Verlag Stuttgart · New York

PAPER
Multicomponent Synthesis of Penta-Heterocycles
259
O
CHO
OH
O
piperidine
+
CO2Et
O
O
O
N
R
2
5
1
N
N
N
H2N
Ar
3a–g
O
O
O
O
N
R
R
[O]
O
O
N
N
N
N
N
N
N
N
N
Ar
Ar
6a–g
4a–g
Scheme 2
The assigned structure and the proposed mechanism were rearrangement23 to give intermediate 11. This eliminated
confirmed by an alternative synthesis of 4a as a typical ex- hydrogen sulfide gas to give the desired product 4a.
ample of the series prepared in the multistep reaction.
To investigate the scope of these reactions with respect to
other amino fused-heterocyclic compounds we attempted
to react salicylaldehyde (1), ethyl acetoacetate (2) with 3-
Thus treatment of 3-acetyl-2H-chromen-2-one (5) with 6-
amino-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (7)20 in
refluxing acetic acid gave 7-methyl-10-thioxo-10,11-di-
hydro-6H-chromeno[4′,3′:4,5]pyrido[2,3-d]pyrimidine-
aryl-7-amino-5H-thiazolo[3,2-a]pyrimidin-5-ones 12a–
c24 and with 7-amino-2,3-dihydro-5H-[1,3]thiazolo[3,2-
6,12(9H)-dione (8). Heating of dione 8 with N-phenylben-
a]pyrimidin-5-one (14a)25 or 8-amino-3,4-dihydro-
zenecarbohydrazonoyl chloride (9)21 in 1,4-dioxane con-
2H,6H-pyrimido[2,1-b][1,3]thiazin-6-one (14b)25 under
taining triethylamine gave dione 4a as an authentic
the same conditions. These reactions gave the expected
products 13a–c, 15a, and 15b, respectively (Scheme 4).
product (Scheme 3). The conversion of 8 into product 4a
proceeded through S-alkylation22 to give S-alkylated
product (intermediate 10), which underwent a Smiles
O
O
O
O
O
AcOH
NH
O
NH
+
S
O
H2N
N
H
S
N
N
H
5
7
8
Cl
H
N
Et3N, 1,4-dioxane
Ph
O
N
Ph
9
O
O
N
O
O
NH
O
NH
Ph
H
H
N
Ph
N
N
Ph
N
N
N
S
N
S
Ph
10
11
O
O
Ph
O
N
N
N
N
N
4a
Ph
Scheme 3
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 258–262

260
S. M. Gomha, S. M. Riyadh
PAPER
140.3, 140.9, 143.3, 148.0, 148.9, 151.6, 161.3 (C=O), 166.5
(C=O).
MS (EI, 70 eV): m/z (%) = 472 (14) [M + 1]+, 471 (86) [M+], 193
CHO
OH
O
+
CO2Et
(27), 103 (26), 78 (100).
2
1
piperidine
O
Anal. Calcd for C28H17N5O3 (471.13): C, 71.33; H, 3.63; N, 14.85.
Found: C, 71.31; H, 3.43; N, 14.59.
O
N
12-Acetyl-7-methyl-10-phenyl-6H--chromeno[4′,3′:4,5] pyri-
do[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine-6,14-(10H)-dione (4b)
Pale-yellow crystals; yield: 0.32 g (73%); mp 262–264 °C (AcOH).
IR (KBr): 1728 (δ-lactone), 1680 (COCH3), 1648 (CO amide) cm–1.
O
N
Ar
N
N
n
O
O
5
S
H2N
14a,b
S
H2N
1H NMR (DMSO-d6): δ = 2.12 (s, 3 H, COCH3), 2.91 (s, 3 H, CH3),
12a–c
7.05–8.29 (m, 9 H, Ar-H).
13C NMR (DMSO-d6): δ = 22.6, 119.2, 120.4, 121.2, 121.8, 123.7,
124.6, 125.9, 128.6, 130.2, 130.7, 133.9, 136.2, 138.9, 140.3, 140.9,
143.3, 148.9, 151.6, 161.3 (C=O), 165.3 (C=O), 189.6 (COCH3).
MS (EI, 70 eV): m/z (%) = 438 (7) [M + 1]+, 437 (69) [M+], 395
(41), 278 (16), 223 (10), 153 (7), 78 (36), 43 (100).
O
O
N
N
Ar
O
O
N
O
O
N
n
S
Anal. Calcd for C24H15N5O4 (437.11): C, 65.90; H, 3.46; N, 16.01.
Found: C, 65.68; H, 3.49; N, 15.81.
N
N
S
15a n = 1
15b n = 2
13a Ar = Ph
13b Ar = 4-ClC6H4
13c Ar = 4-BrC6H4
12-Acetyl-7-methyl-10-(4-tolyl)-6H-chromeno [4′,3′:4,5]pyri-
do[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine-6,14(10H)-dione (4c)
Pale-yellow crystals; yield: 0.33 g (74%); mp 232–234 °C (AcOH).
Scheme 4
IR (KBr): 1736 (δ-lactone), 1683 (COCH3), 1642 (CO amide) cm–1.
1H NMR (DMSO-d6): δ = 2.08 (s, 3 H, Ar-CH3), 2.20 (s, 3 H,
COCH3), 2.93 (s, 3 H, CH3), 7.12–8.23 (m, 8 H, Ar-H).
MS (EI, 70 eV): m/z (%) = 451 (100) [M+], 278 (89), 223 (16), 122
(21), 43 (91).
In summary, we prepared several novel series of chrom-
eno[4′,3′:4,5]pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimi-
dine-6,14-diones,
chromeno[4′,3′:4,5]pyrido[2,3-
Anal. Calcd for C25H17N5O4 (451.13): C, 66.51; H, 3.80; N, 15.51.
Found: C, 66.48; H, 3.88; N, 15.31.
d]thiazolo[3,2-a]pyrimidine-6,14-diones, and chrom-
eno[4′′,3′′:4′,5′]pyrido[2′,3′:4,5]pyrimido[2,1-b][1,3]thia-
zine-6,15-diones by a one-pot multicomponent reaction.
Ethyl 7-Methyl-6,14-dioxo-10-phenyl-10,14-dihydro-6H-chro-
meno[4′,3′:4,5]pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine-
12-carboxylate (4d)
White crystals; yield: 0.31 g (67%); mp 214–216 °C (AcOH).
IR (KBr): 1747 (δ-lactone), 1701 (COOEt), 1640 (CO amide) cm–1.
1H NMR (DMSO-d6): δ = 1.44 (t, J = 7 Hz, 3 H, CH2CH3), 2.97 (s,
3 H, CH3), 4.56 (q, J = 7 Hz, 2 H, CH2CH3), 7.03–8.19 (m, 9 H, Ar-
H).
13C NMR (DMSO-d6): δ = 16.3, 23.4, 48.4, 118.4, 120.8, 122.2,
122.9, 123.6, 124.1, 127.3, 130.0, 130.7, 133.4, 136.6, 137.9, 140.3,
141.9, 143.3, 146.6, 150.6, 161.5 (C=O), 164.3 (C=O), 169.6
(C=O).
All melting points were determined on an electrothermal
Gallenkamp apparatus and are uncorrected. Solvents were generally
distilled and dried by standard procedures before use. The IR spec-
tra were recorded on KBr discs with a Pye Unicam SP300 instru-
1
ment. The H and 13C NMR spectra were recorded on a Varian
1
Mercury VXR-300 spectrometer (300 MHz for H NMR and 75
MHz for 13C NMR), and the chemical shifts were referenced to the
solvent DMSO-d6. The mass spectra were recorded on GCMS-
Q1000-EX Shimadzu and GCMS 5988-A HP spectrometers with an
ionizing voltage of 70 eV. Elemental analyses were carried out by
the Microanalytical Center of Cairo University, Giza, Egypt.
MS (EI, 70 eV): m/z (%) = 468 (6) [M + 1]+, 467 (100) [M+], 395
(31), 278 (7), 92 (34), 78 (33), 44 (18).
Penta-Heterocyclic Compounds 4a–g, 13a–c, and 15a,b;
General Procedure
Anal. Calcd for C25H17N5O5 (467.43): C, 64.24; H, 3.67; N, 14.98.
Found: C, 64.13; H, 3.69; N, 14.66.
Two drops of piperidine were added to a mixture of salicylaldehyde
(1; 0.122 g, 1mmol), MeCOCH2CO2Et (2; 0.130 g, 1mmol), and the
appropriate fused heterocyclic amine 3a–g, 12a–c, 14a, or 14b (1
mmol), and the mixture was stirred for 15 min. AcOH (10 mL) was
added and the mixture was refluxed for 12 h. The mixture was then
cooled and the product was collected by filtration, washed with
EtOH, and crystallized from an appropriate solvent.
7-Methyl-6,14-dioxo-N,10-diphenyl-10,14-dihydro-6H-chrome-
no[4′,3′:4,5]pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine-12-
carboxamide (4e)
White crystals; yield: 0.34 g (66%); mp 256–258 °C (DMF).
IR (KBr): 3460 (NH), 1732 (δ-lactone), 1643, 1631 (2 CO amide)
cm–1.
7-Methyl-10,12-diphenyl-6H-chromeno[4′,3′:4,5]pyrido[2,3-
d][1,2,4]triazolo[4,3-a]pyrimidine-6,14(10H)-dione (4a)
White microcrystals; yield: 0.32 g (67%); mp 322–324 °C (AcOH).
1H NMR (DMSO-d6): δ = 2.98 (s, 3 H, CH3), 7.07–8.00 (m, 14 H,
Ar-H), 11.97 (br s, 1 H, NH).
13C NMR (DMSO-d6): δ = 22.8, 114.8, 118.4, 121.6, 121.8, 123.6,
123.9, 124.3, 125.2, 125.9, 126.6, 130.2, 130.3, 133.4, 134.7, 137.2,
138.8, 140.6, 141.2, 143.9, 145.6, 151.4, 160.5 (C=O), 165.2
(C=O), 167.2 (C=O).
MS (EI, 70 eV): m/z (%) = 514 (19) [M+], 471 (37), 276 (19), 202
(33), 120 (10), 105 (63), 78 (54), 44 (100).
IR (KBr): 1739 (δ-lactone), 1658 (CO amide) cm–1.
1H NMR (DMSO-d6): δ = 2.97 (s, 3 H, CH3), 7.31–8.31 (m, 14 H,
Ar-H).
13C NMR (DMSO-d6): δ = 22.4, 114.6, 119.2, 120.4, 121.5, 122.7,
123.4, 124.6, 126.8, 128.6, 130.2, 130.7, 133.9, 134.7, 136.2, 138.9,
Synthesis 2014, 46, 258–262
© Georg Thieme Verlag Stuttgart · New York

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Multicomponent Synthesis of Penta-Heterocycles
261
Anal. Calcd for C29H18N6O4 (514.14): C, 67.70; H, 3.53; N, 16.33.
Found: C, 67.65; H, 3.50; N, 16.16.
7-Methyl-11,12-dihydro-6H,14H-chromeno[4′,3′:4,5]pyri-
do[2,3-d][1,3]thiazolo[3,2-a]pyrimidine-6,14-dione (15a)
White solid; yield: 0.25 g (73%); mp 194–196 °C (EtOH).
7-Methyl-6,14-dioxo-N-phenyl-10-(4-tolyl)-10,14-dihydro-6H-
chromeno[4′,3′:4,5]pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimi-
dine-12-carboxamide (4f)
IR (KBr): 1738 (δ-lactone), 1682 (CO amide) cm–1.
1H NMR (DMSO-d6): δ = 2.78 (s, 3 H, CH3), 3.67 (t, J = 7 Hz, 2 H,
CH2), 4.46 (t, J = 7 Hz, 2 H, CH2), 7.12–8.01 (m, 4 H, Ar-H).
White crystals; yield: 0.4 g (75%); mp 241–243 °C (DMF).
MS (EI, 70 eV): m/z (%) = 337 (13) [M+], 213 (17), 119 (97), 91
(81), 78 (100).
IR (KBr): 3449 (NH), 1713 (δ-lactone), 1674, 1642 (2CO amide)
cm–1.
1H NMR (DMSO-d6): δ = 2.43 (s, 3 H, Ar-CH3), 2.98 (s, 3 H, CH3),
7.17–8.34 (m, 13 H, Ar-H), 11.22 (br s, 1 H, NH).
Anal. Calcd for C17H11N3O3S (337.05): C, 60.52; H, 3.29; N, 12.46;
S, 9.50. Found: C, 60.47; H, 3.20; N, 12.35; S, 9.39.
MS (EI, 70 eV): m/z (%) = 528 (2) [M+], 471 (30), 278 (14), 105
(11), 78 (35), 43 (100).
7-Methyl-12,13-dihydro-6H,11H,15H-chrome-
no[4′′,3′′:4′,5′]pyrido[2′,3′:4,5]pyrimido[2,1-b][1,3]thiazine-
6,15-dione (15b)
Anal. Calcd for C30H20N6O4 (528.15): C, 68.18; H, 3.81; N, 15.90.
Found: C, 68.13; H, 3.62; N, 15.68.
White solid; yield: 0.27 g (78%); mp 177–179 °C (EtOH).
IR (KBr): 1740 (δ-lactone), 1674 (CO amide) cm–1.
12-Benzoyl-7-methyl-10-phenyl-6H-chromeno[4′,3′:4,5]pyri-
do[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine-6,14(10H)-dione (4g)
Yellow crystals; yield: 0.38 (77%); mp 274–276 °C (DMF).
IR (KBr): 1737 (δ-lactone), 1680 (ArCO), 1641 (CO amide) cm–1.
1H NMR (DMSO-d6): δ = 2.92 (s, 3 H, CH3), 6.97–8.28 (m, 14 H,
Ar-H).
1H NMR (DMSO-d6): δ = 2.03 (m, 2 H, CH2), 2.71 (s, 3 H, CH3),
2.98 (t, J = 6 Hz, 2 H, CH2), 4.27 (t, J = 7 Hz, 2 H, CH2), 7.12–8.01
(m, 4 H, Ar-H).
MS (EI, 70 eV): m/z (%) = 351 (54) [M+], 213 (34), 119 (100), 105
(87), 78 (64).
Anal. Calcd for C18H13N3O3S (351.07): C, 61.53; H, 3.73; N, 11.96;
S, 9.13. Found: C, 61.53; H, 3.73; N, 11.96; S, 8.99.
MS (EI, 70 eV): m/z (%) = 499 (20) [M+], 405 (8), 105 (65), 77
(100).
Anal. Calcd for C29H17N5O4 (499.13): C, 69.74; H, 3.43; N, 14.02.
Found: C, 69.79; H, 3.35; N, 13.82.
7-Methyl-10-thioxo-9,10,11,12-tetrahydrochrome-
no[4′,3′:4,5]pyrido[2,3-d]pyrimidine-6,12-dione (8)
AcOH (20 mL) was added to a mixture of 3-acetylcoumarin (5)
(0.188 g, 1 mmol) and 6-amino-2-thioxo-2,3-dihydropyrimidin-
4(1H)-one (7; 0.143 g, 1 mmol), and the mixture was refluxed for
12 h then cooled. The product was collected by filtration, washed
with EtOH, and crystallized (AcOH) to give white microcrystals;
yield: 0.24 g (76%); mp 347–349 °C.
7-Methyl-12-phenyl-6H,14H-chromeno[4′,3′:4,5]pyrido[2,3-
d][1,3]thiazolo[3,2-a]pyrimidine-6,14-dione (13a)
White solid; yield: 0.31 g (75%); mp 273–275 °C (1,4-dioxane).
IR (KBr): 1736 (δ-lactone), 1643 (CO amide) cm–1.
1H NMR (DMSO-d6): δ = 2.76 (s, 3 H, CH3), 6.89–7.72 (m, 9 H,
Ar-H), 7.79 (s, 1 H, thiazole-H).
MS (EI, 70 eV): m/z (%) = 411 (15) [M+], 274 (100), 188 (51), 119
(34), 91 (23).
IR (KBr): 3414, 3252 (2 NH), 1743 (δ-lactone), 1689 (CO amide)
cm–1.
1H NMR (DMSO-d6): δ = 2.91 (s, 3 H, CH3), 6.91–8.36 (m, 4 H,
Ar-H), 12.42 (br s, 1 H, NH), 13.36 (br s, 1 H, NH).
MS (EI, 70 eV): m/z (%) = 311 (100) [M+], 294 (9), 197 (3), 143
(20), 115 (23), 77 (18).
Anal. Calcd for C23H13N3O3S (411.07): C, 67.14; H, 3.18; N, 10.21;
S, 7.79. Found: C, 67.11; H, 3.03; N, 10.13; S, 7.66.
12-(4-Chlorophenyl)-7-methyl-6H,14H-chrome-
Anal. Calcd for C15H9N3O3S (311.04): C, 57.87; H, 2.91; N, 13.50;
S, 10.30. Found: C, 57.76; H, 2.87; N, 13.38; S, 10.23.
no[4′,3′:4,5]pyrido[2,3-d][1,3]thiazolo[3,2-a]pyrimidine-6,14-
dione (13b)
White solid; yield: 0.37 g (84%); mp 364–366 °C (EtOH–1,4-diox-
ane).
IR (KBr): 1728 (δ-lactone), 1637 (CO amide) cm–1.
7-Methyl-10,12-diphenyl-6H-chromeno[4′,3′:4,5]pyrido[2,3-
d][1,2,4]triazolo[4,3-a]pyrimidine-6,14(10H)-dione (4a); Alter-
native Synthesis
Et3N (0.14 mL, 1 mmol) was added to a mixture of equimolar
amounts of dione 8 (0.311 g, 1 mmol) and PhC(Cl)=NNHPh (9;
0.23 g, 1 mmol) in 1,4-dioxane (15 mL). The mixture was refluxed
until all the starting materials disappeared (TLC) and H2S gas
ceased to evolve (12 h). The solvent was evaporated and the residue
was treated with MeOH. The solid that formed was collected by fil-
tration and crystallized (AcOH) to give an authentic sample of com-
pound 4a; yield: 0.31 g (65%).
1H NMR (DMSO-d6): δ = 2.78 (s, 3 H, CH3), 6.80–7.71 (m, 8 H,
Ar-H), 7.86 (s, 1 H, thiazole-H).
MS (EI, 70 eV): m/z (%) = 447 (10) [M + 2]+, 445 (34) [M+], 326
(20), 259 (59), 145 (28), 114 (67), 43 (100).
Anal. Calcd for C23H12ClN3O3S (445.03): C, 61.96; H, 2.71; N,
9.42; S, 7.19. Found: C, 61.87; H, 2.69; N, 9.22; S, 7.05.
12-(4-Bromophenyl)-7-methyl-6H,14H-chrome-
no[4′,3′:4,5]pyrido[2,3-d][1,3]thiazolo[3,2-a]pyrimidine-6,14-
dione (13c)
Supporting Information for this article is available online at
White solid; yield: 0.36 g (73%); mp 287–289 °C (1,4-dioxane).
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
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IR (KBr): 1743 (δ-lactone), 1647 (CO amide) cm–1.
1H NMR (DMSO-d6): δ = 2.79 (s, 3 H, CH3), 6.84–7.78 (m, 8 H,
Ar-H), 7.87 (s, 1 H, thiazole-H).
References
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