Reactions of 6-acetyl-4-methyl-5-(1-pyrrolyl)-2-phenylthieno-[2,3-d] pyrimidine in heterocyclic synthesis: Convenient route to some Schiff's bases, chalcones, pyridines, pyridin-2(1H)-ones and 2H-pyran-2-one derivatives incorporating a 5-(1-pyrrolyl)-2-ph

Article abstract of DOI:10.1002/jccs.200500048

Treatment of 6-acetyl-5-amino-4-methyl-2-phenylthieno[2,3-d]pyrimidine 3 with 2,5-dimethoxytetrahydrofuran afforded the 6-acetyl-5-(1-pyrrolyl)-4-methyl- 2-phenylthieno[2,3-d]pyrimidine 4, which can react with appropriate primary amines 5a-f to yield the

Full text of DOI:10.1002/jccs.200500048

Journal of the Chinese Chemical Society, 2005, 52, 313-325
313
Reactions of 6-Acetyl-4-methyl-5-(1-pyrrolyl)-2-phenylthieno-
[2,3-d]pyrimidine in Heterocyclic Synthesis: Convenient Route to Some
Schiff’s Bases, Chalcones, Pyridines, Pyridin-2(1H)-ones and
2H-Pyran-2-one Derivatives Incorporating a
5-(1-Pyrrolyl)-2-phenylthieno[2,3-d]pyrimidine Moiety
Yuh-Wen Hoa* (
) and Wei-Hua Yaob (
)
aDepartment of Textile Science, Nanya Institute of Technology, Chung-Li 32034, Taiwan, R.O.C.
bDepartment of Materials and Textiles, Oriental Institute of Technology, Pan-Chiao 22064, Taiwan, R.O.C.
Treatment of 6-acetyl-5-amino-4-methyl-2-phenylthieno[2,3-d]pyrimidine 3 with 2,5-dimethoxytetra-
hydrofuran afforded the 6-acetyl-5-(1-pyrrolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimidine 4, which can re-
act with appropriate primary amines 5a-f to yield the corresponding Schiff’s base derivatives 6a-f. The reac-
tion of acetyl compound 4 with appropriate arylaldehydes 14a-k and arylmethylidenemalononitriles 18a-f af-
forded the corresponding 6-(3-substituted-acryloyl)-5-(1-pyrrolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimi-
dines 15a-k and 6-[3-cyano-2-ethoxy-4-(4-substituted-phenyl)-pyridin-6-yl]-5-(1-pyrrolyl)-4-methyl-2-
phenyl-thieno[2,3-d]pyrimidines 21a-f under basic conditions, respectively. On the other hand, the 6-(3-
cyano-1,2-dihydro-4-substituted-2-oxopyridin-6-yl)-5-(1-pyrrolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimi-
dines 26a,b and 6-(3-substituted-amido-4-substituted-pyran-2-on-6-yl)-5-(1-pyrrolyl)-4-methyl-2-phenyl-
thieno[2,3-d]pyrimidines 30a-c were obtained by intramolecular cyclization of 6-(3-dimethylamino-3-
substituted-acryloyl)-5-(1-pyrrolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimidines 23a,b with cyanoacet-
amide 24 and N-acylglycines 27a,b, respectively.
Keywords: 6-Acetyl-5-(1-pyrrolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimidine; Schiff’s bases;
Chalcones; Pyridines; Pyridin-2(1H)-ones; 2H-Pyran-2-one derivatives.
INTRODUCTION
Thienopyrimidines have been the subject of many
Schiff’s bases, chalcones, pyridines, pyridin-2(1H)-ones and
2H-pyran-2-one derivatives incorporating a 5-(1-pyrrolyl)-
4-methyl-2-phenylthieno[2,3-d]pyrimidine moiety.
chemical and biological studies on account of their interest-
ing pharmacological properties.1-8 A number of syntheses for
substituted derivatives of this thienopyrimidine ring system,
featuring a variety of pharmacological effects, have been de-
veloped. On the other hand, several series of heterocyclic
compounds possessing a bridgehead pyrrolic moiety play a
vital role in many biological activities.9-13 Likewise, the pyr-
rolothione derivatives also possess a variety of pharmacolog-
ical activities.14-16 In view of these it was considered of inter-
est to synthesize some new heterocycles containing the pyr-
rolothienopyrimidine moiety in the hope that they may be bi-
ologically active. In a preceding paper17 we have described
the synthesis of some new pyrimido[2,3:4,3]pyrazolo[1,5-
a]pyrimidines from 5-cyano-1,6-dihydro-4-methyl-2-phen-
yl-6-thioxopyrimidine 1. In continuation of our studies, we
report herein the use of 6-acetyl-5-(1-pyrrolyl)-4-methyl-2-
phenylthieno[2,3-d]pyrimidine 4 for the synthesis of various
RESULTS AND DISCUSSION
All relevant reactions are depicted in Schemes I-III.
The reaction of 5-cyano-1,6-dihydro-4-methyl-2-phenyl-6-
thioxopyrimidine 1 with chloroacetone 2 in DMF in the pres-
ence of excess anhydrous potassium carbonate at room tem-
perature gave the 6-acetyl-5-amino-4-methyl-2-phenylthi-
eno[2,3-d]pyrimidine 318 (Scheme I). Treatment of com-
pound 3 with 2,5-dimethoxytetrahydrofuran in glacial acetic
acid produced the 6-acetyl-5-(1-pyrrolyl)-4-methyl-2-phen-
ylthieno[2,3-d]pyrimidine 4,19 which reaction with appropri-
ate primary amines 5a-d, 5f in pyridine and hydrazine hy-
drate 5e to afford the corresponding Schiff’s bases 6a-e
and/or oxime derivatives 6f, respectively (Scheme I). The IR
spectra of compound 4 indicated the absence of the NH2

314 J. Chin. Chem. Soc., Vol. 52, No. 2, 2005
Ho and Yao
Scheme I
CH
N
3
CH
N
3
CN
S
N
NH
DMF/K CO
2
2
3
+
N
ClCH2COCH3
Room teperature
2
COCH
3
S
3
H
1
CH COOH
3
OCH
CH O
CH
3
reflux
3
O
3
N
N
CH
3
C
N
S
N-R
H
RNH2
5a-f
OH
CH
N
3
N
-H2O
N
COCH
3
S
CH
N
3
4
N
C
N
CH
3
S
N-R
NH
2
6a-f
R= OH
Pyridine
reflux
5g
DMF
reflux
6f
R= OH
(CH3CO)2O
CH
N
3
Pyridine/reflux
6f
N
CH
3
N
N
C
N
N
S
CH
N
3
CH
3
N
S
9
CH
N
3
7
N
C
N
CH
3
S
N-OCOCH
3
8
a
b
c
d
e
f
5, 6
R
CH3 C2H5 C3H7 C4H9 NH2 OH
group. The 1H NMR spectra (CDCl3) of compound 4 revealed
two triplets at d 6.50 (2H, t) and 6.87 (2H, t), which were
readily assigned to the hydrogen attached at C3, C4 and C2, C5
of the pyrrolyl ring,20-21 respectively. The structures of 6a-f
were established on the basis of their elemental analysis and
spectral data. The IR spectra of 6a-f indicated the absence of
the C=O group absorption band, indicating the formation
Schiff’s base derivatives 6a-f. Under similar reaction condi-
tions, reaction of compound 4 with aniline 5g did not produce
the desired compound 7, but led only to the recovery of start-
ing material. Moreover, acetylation of oxime derivative 6f
with acetic anhydride in the presence of pyridine afforded
acetoxy derivative 8. Our attempts to cyclize 6f in DMF to the
compound 9 was unsuccessful.
Furthermore, condensation of compound 4 with mal-
ononitrile in glacial acetic acid containing ammonium ace-
tate afforded the 6-(2,2-dicyano-1-methylvinyl)-5-(1-pyr-
rolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimidine 10, which

Heterogeneous Reactions of [2,3-d]pyrimidine
J. Chin. Chem. Soc., Vol. 52, No. 2, 2005 315
Scheme II
CN
CH
CH
3
3
CH=C
N
C
N
N
COOEt
12
N
N
CH
3
CH COOH/CH COONa
3
3
N
S
N
S
C(CN)
CN
2
reflux
10
H
O
CNCH2CN
CH3COONH4
13
OHC
N(CH )
3 2
CH3COOH
reflux
CH
3
R-CHO
14a-k
DMF/piperidine
N
o
N
10 h
100 C
4
COCH=CHR
C H OH/NaOH
2
5
N
S
Room teperature
24 h
15a-k
CH
3
N
N
CH
3
N(CH )
CH=CH
3 2
C
C
N
N
S
O
N
CN
NC
CH
3
11
N
16
N
CH
3
CH COOH/CH COONa
3
3
CH
3
C=
N
S
reflux
N
O
N
17
a
b
c
d
e
f
14, 15
R
CH
OCH
N(CH )
N(C H )
2 5 2
3
3
3 2
O
14, 15
g
h
i
j
k
CH
3
R
CH
N
3
S
CH
3
then reacted with N,N-dimethylaminobenzaldehyde in DMF
in the presence of a catalytic amount of piperidine at 100 °C
for 10 h yielded the 6-(2-cyano-5-(4-dimethylaminophenyl)-
2,4-pentadienenitrile)-5-(1-pyrrolyl)-4-methyl-2-phenylthi-
eno[2,3-d]pyrimidine 11 (Scheme II). The IR spectra of com-
pounds 10 and 11 indicated the absence of the C=O group ab-
sorption band and showed the characteristic absorption bands
at 2220-2202 cm-1 for the CºN group. The 1H NMR spectra
(CDCl3) of compound 11 revealed a sharp singlet at d 3.09
(6H, s) assigned to the N(CH3)2 protons and at d 6.70 (1H, d)
and 7.74 (1H, d) assigned to the -CH=CH- of pentadieno-
nitrile moiety, and a multiplet at d 8.57-7.51 (9H, m) assigned
to the phenyl protons. Attempted cyclization of 4 with ethyl
benzylidinecyanoacetate 12 in glacial acetic acid to the com-
pound 13 was unsuccessful and the starting material was re-
covered.22-23 In addition, the 6-(3-substituted-acryloyl)-5-
(1-pyrrolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimidines
15a-k24 were obtained in good yields by condensation of
compound 4 with appropriate aldehydes 14a-k. The struc-
tures of chalcones 15a-k were established by examining

316 J. Chin. Chem. Soc., Vol. 52, No. 2, 2005
Ho and Yao
Scheme III
(CH O) CRN(CH )
3 2
3
2
Ar-CH=C(CN)
2
CH
CH
3
3
N
N
18a-f
22a,b
CN
4
N
N
CN
O
Xylene/
reflux
C H OH/C H ONa
2
5
2
5
COCH=CRN(CH )
3 2
N
S
N
S
reflux
Ar
23a,b
19
R CONHCH COOH
1
2
C H ONa
2
5
27a,b
(CH CO) O
CNCH CONH
3
2
2
2
reflux
C H OH C H O Na
2
5
2 5
reflux
24
N
OEt
CN
R
R
1
H N
O
O
2
Q
N(CH )
3 2
O
H
O
27a' R1 = CH3
27b' R1 = C6H5
Q
Ar
CN
H N
2
O
20
25
O
O
H
R
1
H
H O
-
2
-
2
O
N
CH
3
N(CH )
3 2
H O
2
-
Q
N
N
R
Ar
28
N
S
N
-HN(CH )
CN
3 2
CH
N
21a-f
3
OEt
N
N
N
O
O
R
1
CH
3
R
..
S
O
N
N
N
CN
Q =
H
Q
O
R
N
S
26a,b
29
a
b
c
18, 21
Ar
CH
3
N
CH
Cl
3
N
R
N
S
18, 21
Ar
d
e
f
O
NHCOR
1
30a-c
O
N(CH )
CN
3 2
a
b
c
30
R
H
H
CH3
a
b
22, 23, 26
R
CH3
R
1
H
CH3
spectral data and elemental analysis. The IR spectrum of
spectrum (CDCl3) of compounds 15a-k showed signals at d
5.88-5.47 (1H, d) and 8.15-7.74 (1H, d), which were assigned
to the protons -CH=CH- of propenyl moiety, respectively.
compounds 15a-k indicated the characteristic absorption
1
bands at 1688-1628 cm-1 for the CO group. The H NMR

Heterogeneous Reactions of [2,3-d]pyrimidine
J. Chin. Chem. Soc., Vol. 52, No. 2, 2005 317
Moreover, attempted preparation of compound 17 via con-
densation of compound 4 with pyrazole 16 also failed.25-26
On the other hand, the reaction of compound 4 with
arylmethylidene-malononitriles 18a-f were also investi-
gated. Thus, the reaction of compound 4 with benzylidine-
malononitrile 18a in refluxing ethanol in the presence of an
equimolar amount of sodium ethoxide afforded a product of
molecular formula C31H23N5OS (86% yield, mp 149 °C).
Spectroscopic analyses revealed that 6-(3-cyano-2-ethoxy-4-
phenyl-pyridyl-6-yl)-5-(1-pyrrolyl)-4-methyl-2-phenylthi-
eno[2,3-d]pyrimidine 21a was obtained (Scheme III). The IR
spectrum of the reaction product showed the characteristic
compound 23b showed signals at d 2.07 (3H, s) and 4.77 (1H,
s), which were readily assigned to the 3-CH3 protons and 2-H
of acryloyl moiety, respectively. The study was extended to
investigate the behavior of enaminone derivatives 23a,b.
Intramolecular cyclization of enaminone derivatives 23a,b
gave different products depending on reaction conditions.
Thus, treatment of enaminone derivatives 23a,b with cyano-
acteamide 24 in sodium ethoxide solution afforded the corre-
sponding 6-(3-cyano-1,2-dihydro-4-substituted-2-oxopyr-
idyl-6-yl)-5-(1-pyrrol-yl)-4-methyl-2-phenylthieno[2,3-d]-
pyrimidines 26a,b,29 respectively (Scheme III). We propose
that the first step of the mechanism involves via initial addi-
tion of the active methylene in 24 to the activated double
bond in 23a,b to yield the non-isolable intermediate 25, fol-
lowed by deamination, and subsequent cyclization with loss
of water to afford the final products 26a,b. The structures of
compounds 26a,b were confirmed on the basis of their ele-
mental analysis and spectral data. The IR spectra of com-
pounds 26a,b showed the characteristic absorption band at
3234-3122 cm-1 for the NH group, at 2217-2193 cm-1 for the
CºN group and at 1720-1711 cm-1 for the C=O group. More-
over, the 1H NMR spectrum (DMSO-d6) of compound 26a re-
vealed signals at d 7.06 (1H, d) and 8.02 (1H, d), which were
assigned to the 5-H and 4-H of the pyridone ring, respec-
tively, was also confirmed by the mass spectrum m/z 409 (M+
100). The mass fragmentation pattern of compound 26a
showed the presence of a prominent ion peak [M-CN]+ at m/z
383. Also, the 1H NMR spectrum of compound 26b showed
signals at d 2.13 (3H, s) and 7.87 (1H, s), which were readily
assigned to the 4-CH3 protons and 5-H of the pyridone ring,
respectively.
1
absorption band at 2225 cm-1 for the CºN group. The H
NMR spectrum (CDCl3) of the reaction product, which
showed a triplet at d 1.56 (3H, t) and a quartet at d 4.64 (2H,
q) assigned to the ethoxy group (OCH2CH3), a single at d 7.41
(1H, s) assigned to the proton at the 5-position of the pyridine
ring and a multiplet at d 8.63-7.47 (10H, m) assigned to the
phenyl protons, was also confirmed by the mass spectrum m/z
513 (M+ 100). The mass fragmentation pattern of compound
21a showed the presence of the ion peaks [M-CH3]+ at m/z
498, [M-CH2CH3]+ at m/z 484 and [M-OCH2CH3]+ at m/z
468. The formation of 21a from the reaction of 4 with 18a is
assumed to proceed via initial addition of the methyl anionic
center of the acetyl group in 4 to the activated double bond in
18a to yield the non-isolable intermediate Michael adduct 19
then reacts with ethoxide to form the intermediate 20,27-28
which then undergoes intramolecular cyclization via loss of
water afforded the final product 21a. Under similar reaction
conditions, treatment of compound 4 with arylmethylidene-
malononitriles 18b-f afforded the corresponding 6-(3-cyano-
2-ethoxy-4-(4-substituted-phenyl)-pyridin-6-yl)-5-(1-pyr-
rolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimidines 21b-f, re-
spectively in good yields (Scheme III).
On the other hand, the reactivity of thienopyrimidines
23a,b towards N-acylglycines 27a,b was also investigated.
Thus, treatment of compound 23a with N-acetylglycine 27a
in refluxing acetic anhydride afforded a product of molecular
formula C24H18N4O3S (43% yield, mp 243 °C). Spectroscopic
analyses revealed that the corresponding 6-(3-acetamido-
pyran-2-on-6-yl)-5-(1-pyrrolyl)-4-methyl-2-phenyl-thieno-
[2,3-d]pyrimidine 30a was obtained (Scheme III). The IR
spectra of compound 30a revealed characteristic absorption
bands at 3266 cm-1 and 1728 cm-1 due to NH group and car-
bonyl group, respectively. In addition, the structure of com-
pound 30a was supported by the 1H NMR spectra, which re-
vealed two doublets at d 6.87 (1H, d) and 8.10 (1H, d) as-
signed to the 5-H and 4-H of oxopyran ring, respectively, a
singlet at 2.21 (3H, s) assigned to the CH3 protons of the
acetamido group and a broad singlet at d 8.02 (1H, br) as-
signed to the NH proton, was also confirmed by the mass
Next, reaction of compound 4 with dimethylformamide
dimethylacetal 22a and N,N-dimethylacetamide dimethyl-
acetal 22b in refluxing xylene afforded the corresponding
6-(3-substituted-3-dimethylamino-acryloyl)-5-(1-pyrrolyl)-
4-methyl-2-phenylthienenylthieno[2,3-d]pyrimidines 23a,b,
respectively. (Scheme III). The IR spectrum of compounds
23a,b indicated the characteristic absorption bands at 1628-
1626 cm-1 for the CO group. The 1H NMR spectra (CDCl3) of
compounds 23a,b revealed two sharp singlets at d 2.58 (3H,
s) and 3.08-2.71 (3H, s), which were assigned to the N(CH3)2
1
protons. In addition, the H NMR spectra (CDCl3) of com-
pound 23a revealed signals at d 4.41 (1H, d) and 7.15 (1H, d),
which were assigned to the protons -CH=CH- of acryloyl
1
moiety, respectively. Moreover, the H NMR spectrum of

318 J. Chin. Chem. Soc., Vol. 52, No. 2, 2005
Ho and Yao
spectra m/z 442 (M+). The mass fragmentation pattern of
compound 30a showed the presence of the ion peaks [M-
CH3]+ at m/z 427, [M-COCH3]+ at m/z 399 and [M-NHCOCH3]+
at m/z 384. The formation of compound 30a from the reaction
of 23a with 27a is assumed that N-acetylglycine generated in
situ is cyclised into oxazolone 27a’29 which then reacts with
thienopyrimidine 23a via initial addition of the active methy-
lene in 27a’ to the activated double bond in 23a to yield the
intermediate 29. The latter can then rearrange into an insolu-
ble product 30a via an attack of carbonyl on the oxazolone
ring29 (Scheme III). Under similar reaction conditions, treat-
ment of compound 23a,b with hippuric acid 27b affords the
corresponding 6-(3-benzoylamino-4-substituted-pyran-2-
on-6-yl)-5-(1-pyrrolyl)-4-methyl-2-phenyl-thieno[2,3-d]pyr-
imidines 30b,c, respectively. The formation of compounds
30a-c from thienopyrimidines 23a,b with either N-acetyl
glycine or hippuric acid can thus be considered as an exten-
sion of the Kepe pyranone synthesis.30-32
chloroacetone 2 (0.93 g, 0.01 mol) were added. The reaction
mixture was stirred at room temperature for 4 h and then di-
luted with cold water (50 mL). The resulting solid product
was collected by filtration, washed with water and recrys-
tallized from ethyl acetate/ethanol to give 2.66 g of yellow
needles (94% yield), mp 210 °C; IR: n 3424, 3295 (NH2),
1663 (CO) cm-1; 1H NMR (CDCl3): d 2.47 (3H, s, COCH3),
3.07 (3H, s, CH3), 3.76 (2H, br, NH2), 8.58-8.55, 7.60-7.55
(5H, m, phenyl-H); MS: 283 (M+, 100), 268 (95), 240 (20),
212 (2), 165 (5), 160 (10), 137 (34), 110 (18), 77 (9). Anal.
Calcd. for C15H13N3OS: C, 63.60; H, 4.59; N, 14.84. Found:
C, 63.63; H, 4.50; N, 14.77%.
6-Acetyl-5-(1-pyrrolyl)-4-methyl-2-phenylthieno[2,3-d]-
pyrimidine (4)
A mixture of 6-acetyl-5-amino-4-methyl-2-phenylthi-
eno[2,3-d]pyrimidine 3 (2.83 g, 0.01 mol), 2,5-dimethoxy-
tetrahydrofuran (1.26 g, 0.01 mol), in glacial acetic acid (20
mL) was refluxed for 12 h. After cooling, the resulting solid
product was collected by filtration, washed with water, and
the crude product recrystallized from ethanol/glacial acetic
acid to give 2.96 g of gray white needles (89% yield), mp 204
°C; IR: n 1660 (CO) cm-1; 1H NMR (CDCl3): d 2.09 (3H, s,
COCH3), 2.20 (3H, s, CH3), 6.50 (2H, t, 3,4-H of pyrrolyl),
6.87 (2H, t, 2,5-H of pyrrolyl), 8.56-8.54, 7.51-7.49 (5H, m,
phenyl-H); MS: 333 (M+, 100), 318 (35), 290 (36), 277 (4),
223 (4), 185 (8), 166 (10), 160 (14), 116 (10), 103 (20), 77
(19), 51 (5). Anal. Calcd. for C19H15N3OS: C, 68.46; H, 4.50;
N, 12.61. Found: C, 68.33; H, 4.52; N, 12.59%.
In conclusion, 6-acetyl-5-(1-pyrrolyl)-4-methyl-2-phen-
ylthieno[2,3-d]pyrimidine 4 has been shown to be a useful
building block for the synthesis of some new Schiff’s bases
6a-f, chalcones 15a-k, pyridines 21a-f, pyridin-2(1H)-ones
26a,b and 2H-pyran-2-one derivatives 30a-c.
EXPERIMENTAL SECTION
All melting points were determined in a capillary tube
and are uncorrected. The IR spectra were recorded on potas-
sium bromide pellets on a JASCO FTIR-3 spectrometer. The
1H NMR spectra were obtained on a Bruker AM-300WB
FT-NMR spectrometer and chemical shifts are expressed in d
ppm using TMS as an internal standard. Electron impact mass
spectra were obtained at 70 eV by using a Finnigan Mat
TSQ-46C spectrometer. Microanalyses for C, H, and N were
performed on a Perkin-Elmer 240 elemental analyzer. 6-
Acetyl-5-amino-4-methyl-2-phenylthieno[2,3-d]pyrimidine
3, 6-acetyl-5-(1-pyrrolyl)-4-methyl-2-phenylthieno[2,3-d]-
pyrimidine 4 and 6-(3-substituted-acryloyl)-5-(1-pyrrolyl)-
4-methyl-2-phenyl-thieno[2,3-d]pyrimidines 15a-k were
prepared following the methods in the literature,18-19,24 re-
spectively.
Reactions of 6-acetyl-5-(1-pyrrolyl)-4-methyl-2-phenyl-
thieno[2,3-d]pyrimidine 4 with the primary amines 5a-d,
5f
General Procedure: A mixture of acetyl compound 4
(0.33 g, 1 mmol) and the primary amines 5a-d, 5f (1.1 mmol),
namely, methylamine, ethylamine, propylamine butylamine
and hydroxylamine hydrochloride, in pyridine (5 mL), was
refluxed for 10 h, and cooled. The separated solid was filtered
and recrystallized from an appropriate solvent into the corre-
sponding Schiff’s bases 6a-d, 6f respectively. The physical
constants and spectral data of compounds 6a-d, 6f are re-
corded in Tables 1, 2.
6-Acetyl-5-amino-4-methyl-2-phenylthieno[2,3-d]pyrimi-
dine (3)
Reactions of 6-acetyl-5-(1-pyrrolyl)-4-methyl-2-phenyl-
thieno[2,3-d]pyrimidine 4 with the hydrazine hydrate 5e
A mixture of acetyl compound 4 (0.33 g, 1 mmol) and
an excess of hydrazine hydrate 5e (4 mL, 85% solution 0.04
mol) was refluxed in absolute ethanol (10 mL) for 24 h. After
To a solution of 5-cyano-1,6-dihydro-4-methyl-2-phen-
yl-6-thioxopyrimidine 1 (2.27 g, 0.01 mol) in DMF (50 mL),
potassium carbonate anhydrous (2.76 g, 0.02 mol) and

Heterogeneous Reactions of [2,3-d]pyrimidine
J. Chin. Chem. Soc., Vol. 52, No. 2, 2005 319
Table 1. Physical and analytical data of compounds 6a-f
Element Analysis (%)
Yield
%
Mp
°C
Molecular
Calcd/Found
Compound
R
Formula
C20H18N4S
C21H20N4S
C22H22N4S
C23H24N4S
C19H17N5S
(recrystallization solvent)
C
H
N
6a
6b
6c
6d
6e
6f
CH3
C2H5
C3H7
C4H9
NH2
OH
97
pyridine/DMF
93
pyridine/DMF
64
pyridine/DMF
77
pyridine/DMF
78
179
220
192
198
164
69.36
69.46
70.00
70.16
70.58
70.56
71.13
71.12
65.70
65.52
5.20
5.55
5.55
5.58
5.88
5.78
6.18
6.36
4.89
4.91
4.59
4.52
16.18
16.22
15.55
15.32
14.97
15.01
14.43
14.44
20.17
20.30
16.09
16.22
DMF/ethanol
98
DMF/H2O
264 C19H16N4OS 65.51
65.48
Table 2. Spectral data of compounds 6a-f
Compound
MS
1H NMR
(CDCl3)
d (ppm)
(M+)
6a
346 (36), 333 (100), 318 (35),
290 (44), 277 (4), 228 (30),
187 (14), 160 (14), 116 (8),
103 (20), 77 (18), 56 (29).
360 (52), 333 (100), 318 (41),
301 (50), 290 (8), 277 (4),
228 (20), 199 (14), 160 (8),
116 (8), 103 (18), 77 (19),
68 (22).
374 (100), 359 (38), 345 (52),
332 (85), 318 (82), 302 (98),
290 (22), 275 (25), 251 (39),
213 (38), 172 (28), 116 (22),
103 (54), 77 (50), 68 (36),
52 (20).
1.66 (3H, s, CH3), 2.07 (3H, s, CH3), 2.20 (3H, s, CH3), 6.50 (2H, t,
3,4-H of pyrrolyl), 6.87 (2H, t, 2,5-H of pyrrolyl), 8.56-8.53, 7.52-
7.48 (5H, m, phenyl-H).
6b
6c
1.31 (3H, t, J = 1.5 Hz, CH3), 1.65 (3H, s, CH3), 2.06 (3H, s, CH3),
3.49 (2H, q, J = 1.5 Hz, CH2), 6.50 (2H, t, 3,4-H of pyrrolyl), 6.88
(2H, t, 2,5-H of pyrrolyl), 8.56-8.53, 7.51-7.48 (5H, m, phenyl-H).
1.02 (3H, t, J = 1.5 Hz, CH3), 1.65 (3H, s, CH3), 1.78-1.71 (2H, m,
CH2), 2.15 (3H, s, CH3), 3.40 (2H, t, J = 1.4 Hz, CH2), 6.42 (2H, t,
3,4-H of pyrrolyl), 6.83 (2H, t, 2,5-H of pyrrolyl), 8.54-8.52, 7.52-
7.47 (5H, m, phenyl-H).
6d
388 (98), 373 (60), 359 (24),
345 (48), 332 (78), 318 (74),
302 (100), 290 (18), 275 (24),
251 (36), 213 (34), 172 (24),
128 (16), 116 (18), 103 (50),
77 (44), 56 (43).
0.98 (3H, t, J = 2.1 Hz, CH3), 1.50-1.42 (2H, m, CH2), 1.65 (3H, s,
CH3), 1.73-1.68 (2H, m, CH2), 2.14 (3H, s, CH3), 3.44 (2H, t, J =
1.4 Hz, CH2), 6.42 (2H, t, 3,4-H of pyrrolyl), 6.83 (2H, t, 2,5-H of
pyrrolyl), 8.54-8.51, 7.48-7.47 (5H, m, phenyl-H).
6e
6f
347 (28), 331 (100), 316 (10),
290 (18), 282 (30), 253 (8),
228 (16), 213 (6), 165 (4),
122 (3), 103 (21), 77 (16),
56 (6).
348 (6), 331 (100), 317 (4),
290 (4), 239 (4), 228 (16),
213 (8), 165 (4), 103 (21),
77 (16), 56 (3).
1.76 (3H, s, CH3), 2.09 (3H, s, CH3), 6.53 (2H, t, 3,4-H of pyrrolyl),
6.84 (2H, t, 2,5-H of pyrrolyl), 8.27-8.14, 7.72-7.58 (5H, m, phenyl-
H).a
1.65 (3H, s, CH3), 2.08 (3H, s, CH3), 6.35 (2H, t, 3,4-H of pyrrolyl),
7.09 (2H, t, 2,5-H of pyrrolyl), 8.46-8.44, 7.55-7.52 (5H, m, phenyl-
H), 12.12 (1H, s, OH).b
a 1H NMR in CF3COOD
b 1H NMR in DMSO-d6

320 J. Chin. Chem. Soc., Vol. 52, No. 2, 2005
Ho and Yao
cooling, the resulting solid product was collected by filtration
and washed with water. The physical constants and spectral
data of compound 6e is recorded in Tables 1, 2.
yield), mp 138 °C; IR: n 2202 (CN) cm-1; 1H NMR (CDCl3): d
2.08 (3H, s, CH3), 3.09 (6H, s, N(CH3)2), 6.50 (2H, t, 3,4-H of
pyrrolyl), 6.88 (2H, t, 2,5-H of pyrrolyl), 6.70 (1H, d, J = 2.0
Hz, -CH=), 7.74 (1H, d, J = 2.0 Hz, =CH-), 8.57-8.55, 7.52-
7.51 (9H, m, phenyl-H); MS: 512 (M+,10), 464 (100), 421
(8), 397 (2), 332 (52), 318 (18), 290 (14), 232 (5), 146 (10),
134 (46), 78 (17). Anal. Calcd. for C31H24N6S: C, 72.65; H,
4.68; N, 16.40. Found: C, 72.49; H, 4.60; N, 16.48%.
Reaction of oxime derivative 6f with acetic anhydride
A mixture of oxime derivative 6f (0.35 g, 1 mmol),
pyridine (10 mL) and acetic anhydride (10 mL) was refluxed
for 4 h. After cooling, the resulting solid product was col-
lected by filtration, washed with water. and recrystallized
from acetic acid/ethanol to give 0.25 g of gray white needles
General procedure of 6-(3-substituted-acryloyl)-5-(1-
pyrrolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimidines
(15a-k)
1
8 (64% yield), mp 225 °C; IR: n 1701 (CO) cm-1; H NMR
(CDCl3): d 1.84 (3H, s, CH3), 2.22 (3H, s, COCH3), 2.27 (3H,
s, CH3), 6.44 (2H, br, 3,4-H of pyrrolyl), 6.82 (2H, br, 2,5-H
of pyrrolyl), 8.55, 7.51-7.50 (5H, m, phenyl-H); MS: 390
(M+, 23), 347 (2), 331 (80), 317 (9), 302 (10), 290 (4), 264
(3), 225 (40), 185 (8), 213 (45), 199 (38), 165 (31), 116 (38),
104 (70), 77 (100), 51 (38). Anal. Calcd. for C21H18N4O2S: C,
64.61; H, 4.61; N, 14.35. Found: C, 64.56; H, 4.72; N,
14.32%.
A mixture of compound 4 (0.33 g, 1 mmol), appropriate
aldehydes 14a-k (1.0 mmol) and NaOH (2.2 mmol) in abso-
lute ethanol (10 mL) was stirred at room temperature for 24 h.
The mixture was acidified with dilute acetic acid and the pre-
cipitated product was collected by filtration, washed with wa-
ter, and the crude product recrystallized from THF/ethanol.
The physical constants and spectral data of compounds 15a-k
are recorded in Tables 3, 4.
6-(2,2-Dicyano-1-methylvinyl)-5-(1-pyrrolyl)-4-methyl-2-
phenylthieno[2,3-d]pyrimidine (10)
General procedure of 6-[3-cyano-2-ethoxy-4-(4-substi-
tuted-phenyl)-pyridin-6-yl]-5-(1-pyrrolyl)-4-methyl-2-
phenylthieno[2,3-d]pyrimidines (21a-f)
A mixture of compound 4 (0.33 g, 1 mmol), malono-
nitrile (0.07 g, 1 mmol) and ammonium acetate (0.82 g, 1.1
mmol) was refluxed in glacial acid (8 mL) for 5-6 h. After
cooling, the resulting solid product was collected by filtra-
tion, washed with water, and the crude product recrystallized
from ethanol/acetic acid to give 0.25 g (66% yield), mp 173
A mixture of compound 4 (0.33 g, 1 mmol), arylmethyl-
idenemalononitrile 18a-f (1 mmol) and sodium ethoxide
(0.07 g, 1 mmol) was refluxed in absolute ethanol (10 mL) for
10 h. After cooling, the mixture was poured into water, acidi-
fied with hydrochloric acid, and the precipitated product was
collected by filtration, washed with water, and the crude
product recrystallized from THF/ethanol. The physical con-
stants and spectral data of compounds 21a-f are recorded in
Tables 5, 6.
1
°C; IR: n 2220, 2200 (CN) cm-1; H NMR (CDCl3): d 2.08
(3H, s, CH3), 2.21 (3H, s, CH3), 6.50 (2H, t, 3,4-H of pyr-
rolyl), 6.87 (2H, t, 2,5-H of pyrrolyl), 8.57-8.55, 7.52-7.50
(5H, m, phenyl-H); MS: 381 (M+, 15), 355 (20), 333 (100),
317 (26), 302 (2), 290 (19), 264 (4), 237 (4), 229 (7), 186
(10), 160 (14), 116 (8), 103 (44), 77 (38), 51 (9). Anal. Calcd.
for C22H15N5S: C, 69.29; H, 3.93; N, 18.37. Found: C, 69.33;
H, 3.72; N, 18.32%.
6-(3-Dimethylamino-acryloyl)-5-(1-pyrrolyl)-4-methyl-2-
phenylthieno[2,3-d]pyrimidine (23a)
To a solution of compound 4 (3.3 g, 0.01 mol) in dry
xylene (40 mL), dimethylformamide dimethylacetal 22a
(1.20 g, 0.01 mol) was added. The reaction was heated under
reflux for 6 h. The solvent was removed by evaporation under
reduced pressure and the remainder was left to cool. The solid
product so formed was collected by filtration, washed with
petroleum ether (bp 40-60 °C), and the crude product was
recrystallized from ethanol to give 3.22 g (83% yield) of 23a,
mp 212 °C; IR: n 1628 (C=O) cm-1; 1H NMR (CDCl3): d 2.23
(3H, s, CH3), 2.58 (3H, s, NCH3), 3.08 (3H, s, NCH3), 4.41
(1H, d, J = 2.3 Hz, -COCH=), 6.50-6.43 (2H, m, 3,4-H of
pyrrolyl), 6.87 (2H, t, 2,5-H of pyrrolyl), 7.75 (1H, d, J = 2.4
6-[2-Cyano-5-(4-dimethylaminophenyl)-2,4-pentadiene-
nitrile)]-5-(1-pyrrolyl)-4-methyl-2-phenylthieno[2,3-d]-
pyrimidine (11)
To a mixture of compound 10 (0.25 g, 0.65 mmol) and
4-(dimethylamino)benzaldehyde (0.10 g, 0.65 mmol) in dry
DMF (5 mL), a few drops of piperidine was added. The reac-
tion mixture was heated at 100 °C for 10 h. After cooling, the
mixture was poured into water, acidified with hydrochloric
acid, and the precipitated product was collected by filtration,
washed with water, and the crude product recrystallized from
ethanol/THF to give 0.30 g of red violet needles 11 (90%

Heterogeneous Reactions of [2,3-d]pyrimidine
J. Chin. Chem. Soc., Vol. 52, No. 2, 2005 321
Table 3. Physical and analytical data of compounds 15a-k
Element Analysis (%)
Calcd/Found
Yield
%
Mp
°C
Molecular
Formula
Compd.
R
C
H
N
15a
15b
15c
15d
15e
15f
15g
15h
15i
phenyl
4-CH3C6H4
4-CH3OC6H4
(CH3)2NC6H4
(C2H5)2NC6H4
furyl
93
96
95
87
93
92
98
93
95
94
95
169
165
245
263
229
130
262
152
148
286
278
C26H19N3OS
C27H21N3OS
C27H21N3O2S
C28H24N4OS
C30H28N4OS
C24H17N3O2S
C24H17N3OS2
C29H25N3OS
C32H23N3OS
C38H28N4OS
C36H23N3OS
74.10 4.51 09.97
74.18 4.55 10.09
74.48 4.82 09.65
74.16 4.58 09.66
71.84 4.65 09.31
71.56 4.78 09.33
72.41 5.17 12.06
72.12 5.36 12.14
73.17 5.69 11.38
73.11 5.74 11.30
70.07 4.13 10.21
70.11 4.21 10.30
67.44 3.98 09.83
67.35 4.01 09.88
75.16 5.39 09.07
75.22 5.45 09.08
77.26 4.62 08.45
77.22 4.65 08.56
77.55 4.76 09.52
77.48 4.52 09.22
79.26 4.22 07.70
79.33 4.62 07.79
thienyl
2,4,6-(CH3)3C6H2
biphenyl
15j
15k
(C6H5)2NC6H4
pyrenyl
Hz, =CH-), 8.56-8.53, 7.51-7.49 (5H, m, phenyl-H); MS: 388
(M+, 30), 371 (19), 357 (10), 344 (10), 322 (11), 289 (22), 274
(12), 239 (5), 187 (4), 160 (8), 142 (8), 116 (8), 104 (18), 98
(100), 77 (22), 55 (28). Anal. Calcd. for C22H20N4OS: C,
68.04; H, 5.15; N, 14.43. Found: C, 68.23; H, 5.23; N,
14.49%.
6-(3-Cyano-1,2-dihydro-2-oxopyridin-6-yl)-5-(1-pyrrolyl)-
4-methyl-2-phenylthieno[2,3-d]pyrimidine (26a)
A mixture of compound 23a (0.39 g, 1 mmol), cyano-
acetamide 24 (0.084 g, 1 mmol) and sodium ethoxide (0.14 g,
2.0 mmol) was refluxed in absolute ethanol (10 mL) for 10 h.
After cooling, the mixture was poured into water, acidified
with hydrochloric acid, and the precipitated product was col-
lected by filtration, washed with water, and the crude product
recrystallized from ethanol to give 0.4 g (98% yield) of 26a,
mp 245 °C; IR: n 3243 (NH), 2193 (CºN), 1720 (C=O) cm-1;
1H NMR (DMSO-d6): d 2.06 (3H, s, CH3), 6.50-6.48 (2H, m,
3,4-H of pyrrolyl), 6.97 (2H, m, 2,5-H of pyrrolyl), 7.06 (1H,
d, J = 1.0 Hz, 5-H of oxopyridyl), 8.02 (1H, d, J = 1.0 Hz, 4-H
of oxopyridyl), 8.45-8.44, 7.53-7.51 (5H, m, phenyl-H); MS:
409 (M+, 100), 383 (50), 355 (41), 333 (37), 290 (46), 250
(13), 185 (7), 116 (8), 104 (18), 77 (19), 56 (4). Anal. Calcd.
for C23H15N5OS: C, 67.48; H, 3.66; N, 17.11. Found: C,
67.23; H, 3.66; N, 17.01%.
6-(3-Dimethylamino-3-methyl-acryloyl)-5-(1-pyrrolyl)-4-
methyl-2-phenyl-thieno[2,3-d]pyrimidine (23b)
This compound was synthesized from compound 4 (3.3
g, 0.01 mol) and N,N-dimethylacetamide dimethylacetal 22b
(1.34 g, 0.01 mol) in a manner similar to that described for the
preparation of 23a. It was recrystallized from ethanol/THF to
give 3.09 g (77% yield), mp 260 °C; IR: n 1626 (C=O) cm-1;
1H NMR (CDCl3): d 2.07 (3H, s, CH3), 2.20 (3H, s, CH3),
2.58 (3H, s, NCH3), 2.71 (3H, s, NCH3), 4.77 (1H, s,
-COCH=), 6.50-6.40 (2H, m, 3,4-H of pyrrolyl), 6.88-6.83
(2H, m, 2,5-H of pyrrolyl), 8.56-8.52, 7.52-7.47 (5H, m,
phenyl-H); MS: 402 (M+, 18), 369 (9), 331 (22), 304 (17),
289 (12), 239 (5), 187 (6), 160 (8), 116 (4), 111 (18), 70 (18),
56 (25). Anal. Calcd. for C23H22N4OS: C, 68.65; H, 5.47; N,
13.93. Found: C, 68.53; H, 5.33; N, 14.01%.
6-(3-Cyano-1,2-dihydro-4-methyl-2-oxopyridin-6-yl)-5-(1-
pyrrolyl)-4-methyl-2-phenylthieno[2,3-d]pyrimidine (26b)
This compound was synthesized from compound 23b
(0.40 g, 1.0 mmol) cyanoacetamide 24 (0.084 g, 1 mmol) and

322 J. Chin. Chem. Soc., Vol. 52, No. 2, 2005
Table 4. Spectral data of compounds 15a-k
Ho and Yao
Compd.
IR
MS
1H NMR
(CDCl3)
d (ppm)
n (cm-1)
(M+)
15a
15b
15c
1667 (C=O)
1663 (C=O)
1688 (C=O)
421
435
451
2.20 (3H, s, CH3), 5.80 (1H, d, J = 3.1 Hz, COCH=), 6.63-6.42 (2H, m, 3,4-H
of pyrrolyl), 6.87-6.80 (2H, m, 2,5-H of pyrrolyl), 8.57-8.55, 7.55-7.21 (11H,
m, =CH- and phenyl-H).
2.27 (3H, s, CH3), 2.39 (3H, s, CH3), 6.02 (1H, d, J = 3.0 Hz, COCH=), 6.61-
6.51 (2H, m, 3,4-H of pyrrolyl), 7.09-6.87 (2H, m, 2,5-H of pyrrolyl), 7.79
(1H, d, J = 3.0 Hz, =CH-), 8.59-8.58, 7.81-7.33 (9H, m, phenyl-H).
2.33 (3H, s, CH3), 3.84 (3H, s, OCH3), 5.75 (1H, d, J = 3.1 Hz, COCH=), 6.60
(2H, t, 3,4-H of pyrrolyl), 6.87 (2H, d, J = 1.0 Hz, 3,5-H of phenyl), 6.99 (2H,
t, 2,5-H of pyrrolyl), 7.28 (2H, d, J = 1.0 Hz, 2,6-H of phenyl), 7.76 (1H, d, J =
3.0 Hz, =CH-), 8.59-8.55, 7.52-7.51 (5H, m, phenyl-H).
15d
15e
1628 (C=O)
1628 (C=O)
464
492
2.27 (3H, s, CH3), 3.06 (6H, s, N(CH3)2), 5.70 (1H, d, J = 3.1 Hz, COCH=),
6.59-6.50 (2H, m, 3,4-H of pyrrolyl), 6.98-6.87 (2H, m, 2,5-H of pyrrolyl),
6.70 (2H, d, J = 1.0 Hz, 3,5-H of phenyl), 7.25 (2H, d, J = 1.5 Hz, 2,6-H of
phenyl l), 7.75 (1H, d, J = 3.1 Hz, =CH-), 8.57-8.54, 7.51-7.50 (5H, m, phenyl-
H).
1.21 (6H, t, J = 1.4 Hz, CH3), 2.27 (3H, s, CH3), 3.41 (4H, q, J = 1.4 Hz, CH2),
5.68 (1H, d, J = 3.1 Hz, COCH=), 6.59-6.49 (4H, m, 3,4-H of pyrrolyl and 3,5-
H of phenyl), 6.98-6.87 (2H, m, 2,5-H of pyrrolyl), 7.24 (2H, d, J = 1.0 Hz,
2,6-H of phenyl), 7.74 (1H, d, J = 3.0 Hz, =CH-), 8.56-8.53, 7.50-7.49 (5H, m,
phenyl-H).
15f
15g
15h
1667 (C=O)
1641 (C=O)
1643 (C=O)
411
427
463
2.28 (3H, s, CH3), 5.88 (1H, d, J = 3.1 Hz, COCH=), 6.59-6.48 (3H, m, 3,4-H
of pyrrolyl and 4-H of furyl), 6.87 (2H, m, 2,5-H of pyrrolyl), 7.00 (1H, d, J =
2.0 Hz, 3-H of furyl), 8.15 (1H, d, J = 3.0 Hz, =CH-), 8.63-8.54, 7.58-7.48 (6H,
m, 5-H of furyl and phenyl-H).
2.11 (3H, s, CH3), 5.47 (1H, d, J = 3.2 Hz, COCH=), 6.63-6.39 (3H, m, 3,4-H
of pyrrolyl and 4-H of thienyl), 7.06-7.03 (2H, m, 2,5-H of pyrrolyl), 7.13 (1H,
d, J = 1.0 Hz, 3-H of thienyl), 7.80 (1H, d, J = 3.0 Hz, =CH-), 8.48-8.45, 7.54-
7.44 (6H, m, 5-H of thienyl and phenyl-H).
2.10 (3H, s, CH3), 2.22 (3H, s, CH3), 2.28 (3H, s, CH3), 2.42 (3H, s, CH3), 5.88
(1H, d, J = 4.0 Hz, COCH=), 6.51-6.45 (2H, m, 3,4-H of pyrrolyl), 6.88-6.84
(2H, m, 2,5-H of pyrrolyl), 7.39 (1H, d, J = 1.2 Hz, =CH-), 8.58-8.53, 7.54-
7.51 (7H, m, phenyl-H).
15i
15j
15k
1667 (C=O)
1631 (C=O)
1679 (C=O)
497
588
545
2.18 (3H, s, CH3), 5.75 (1H, d, J = 3.0 Hz, COCH=), 6.50 (2H, t, 3,4-H of
pyrrolyl), 6.86 (2H, t, 2,5-H of pyrrolyl), 8.65-8.54, 7.63-7.38 (15H, m, =CH-
and phenyl-H).
2.30 (3H, s, CH3), 5.71 (1H, d, J = 3.0 Hz, COCH=), 6.55 (2H, t, 3,4-H of
pyrrolyl), 6.98-6.94 (4H, m, 3,5-H of phenyl and 2,5-H of pyrrolyl), 7.74 (1H,
d, J = 3.0 Hz, =CH-), 8.59-8.57, 7.53-7.13 (17H, m, phenyl-H).
2.06 (3H, s, CH3), 5.79 (1H, d, J = 3.1 Hz, COCH=), 6.51 (2H, m, 3,4-H of
pyrrolyl), 6.90 (2H, m, 2,5-H of pyrrolyl), 8.62-8.42, 8.32-8.05 (15H, m, =CH-,
phenyl-H and pyrenyl-H).
sodium ethoxide (0.14 g, 2.0 mmol) in a manner similar to
that described for the preparation of 26a. It was recrystallized
from ethanol/THF to give 0.18 g (43% yield), mp 146 °C; IR:
356 (42), 333 (100), 290 (90), 246 (14), 228 (20), 202 (34),
187 (18), 160 (24), 104 (79), 77 (62), 56 (28). Anal. Calcd. for
C24H17N5OS: C, 68.08; H, 4.01; N, 16.54. Found: C, 68.23; H,
4.12; N, 16.55%.
1
n 3122 (NH), 2217 (CºN), 1711 (C=O) cm-1; H NMR
(DMSO-d6): d 2.10 (3H, s, CH3), 2.13 (3H, s, CH3), 6.40-6.26
(2H, m, 3,4-H of pyrrolyl), 6.93-6.84 (2H, m, 2,5-H of
pyrrolyl), 7.87 (1H, s, 5-H of oxopyridyl), 8.47-8.45,
7.47-7.41 (5H, m, phenyl-H); MS: 423 (M+, 60), 385 (71),
6-(3-Acetamidopyran-2-on-6-yl)-5-(1-pyrrolyl)-4-methyl-
2-phenylthieno[2,3-d]pyrimidine (30a)
A mixture of N-acetylglycine 27a (0.12 g, 1 mmol) in

Heterogeneous Reactions of [2,3-d]pyrimidine
J. Chin. Chem. Soc., Vol. 52, No. 2, 2005 323
Table 5. Physical and analytical data of compounds 21a-f
Element Analysis (%)
Calcd/Found
Yield
%
Mp
°C
Molecular
Formula
Compd.
Ar
C
H
N
21a
21b
21c
21d
21e
21f
phenyl
4-CH3C6H4
4-ClC6H4
86
84
71
95
88
93
149
151
147
199
163
132
C31H23N5OS
C32H25N5OS
C31H22ClN5OS
C32H22N6OS
C33H28N6OS
C37H27N5OS
72.51
72.46
72.86
72.99
67.94
67.88
71.37
71.12
71.22
71.52
75.38
75.48
4.48
4.55
4.74
4.58
4.01
4.11
4.08
4.36
5.03
4.91
4.58
4.52
13.64
13.42
13.28
13.32
12.78
12.69
15.61
15.44
15.10
15.30
11.88
11.97
4-CNC6H4
(CH3)2NC6H4
biphenyl
Table 6. Spectral data of compounds 21a-f
Compd.
IR
MS
1H NMR
(CDCl3)
n (cm-1)
(M+)
d (ppm)
21a
2225 (CN) 513 (100), 498 (5), 484 (36), 1.56 (3H, t, J = 1.8 Hz, CH3), 2.35 (3H, s, CH3), 4.64 (2H,
468 (4), 423 (2), 357 (1),
290 (3), 242 (2), 213 (1),
140 (1), 103(1).
q, J = 2.1 Hz, OCH2), 6.53-6.49 (2H, m, 3,4-H of pyrrolyl),
6.98-6.87 (2H, m, 2,5-H of pyrrolyl), 7.41 (1H, s, 5-H of
pyridyl), 8.63-8.54, 7.53-7.47 (10H, m, phenyl-H).
1.56 (3H, t, J = 1.7 Hz, CH3), 2.33 (3H, s, CH3), 2.44 (3H,
s, CH3), 4.62 (2H, q, J = 2.1 Hz, OCH2), 6.66-6.39 (4H, m,
3,4-H of pyrrolyl and 3,5-H of phenyl), 6.97-6.87 (2H, m,
2,5-H of pyrrolyl), 8.62-8.54, 7.51-7.17 (8H, m, 5-H of
pyridyl and phenyl-H).
21b
21c
21d
2225 (CN) 527 (100), 512 (30),
498 (44), 487 (10), 472 (8),
393 (3), 357 (2), 335 (10),
290 (11), 249 (8), 185 (1),
105 (5), 77 (1).
2217 (CN) 547.5 (100), 532 (5),
1.54 (3H, t, J = 2.3 Hz, CH3), 2.34 (3H, s, CH3), 4.63 (2H,
518 (40), 507 (18), 493 (12), q, J = 2.1 Hz, OCH2), 6.65-6.39 (4H, m, 3,4-H of pyrrolyl
477 (4), 363 (1), 335 (5),
290 (9), 242 (22), 162 (1),
104 (2), 77 (1).
and 3,5-H of phenyl), 6.97-6.86 (2H, m, 2,5-H of pyrrolyl),
8.61-8.51, 7.51-7.27 (8H, m, 5-H of pyridyl and phenyl-H).
2217 (CN) 538 (10), 531 (100),
1.46 (3H, t, J = 1.4 Hz, CH3), 2.18 (3H, s, CH3), 4.53 (2H,
516 (36), 502 (20), 484 (10), q, J = 2.0 Hz, OCH2), 6.53-6.27 (4H, m, 3,4-H of pyrrolyl
451 (5), 422 (16), 381 (10),
316 (22), 290 (80), 263 (4),
185 (4), 160 (1), 128 (16),
104 (4).
and 3,5-H of phenyl), 7.03-6.92 (2H, m, 2,5-H of pyrrolyl),
8.46-8.42, 7.47-7.39 (8H, m, 5-H of pyridyl and phenyl-H).a
21e
21f
2217 (CN) 556 (100), 541 (9), 527 (16), 1.53 (3H, t, J = 1.4 Hz, CH3), 2.30 (3H, s, CH3), 3.06 (6H,
511 (5), 466 (5), 422 (1),
333 (3), 316 (10), 290 (2),
264 (4), 147 (1), 134 (11),
77 (1).
s, N(CH3)2), 4.60 (2H, q, J = 2.0 Hz, OCH2), 6.56-6.38 (2H,
m, 3,4-H of pyrrolyl), 6.88-6.85 (2H, m, 2,5-H of pyrrolyl),
6.74 (2H, d, J = 2.0 Hz, 3,5-H of phenyl), 7.40 (2H, d, J =
1.8 Hz, 2,6-H of phenyl), 8.55-8.52, 7.50-7.46 (6H, m, 5-H
of pyridyl and phenyl-H).
2208 (CN) 589 (100), 574 (4), 564 (83), 1.56 (3H, t, J = 1.3 Hz, CH3), 2.33 (3H, s, CH3), 4.65 (2H,
560 (38), 549 (24), 535 (16), q, J = 2.1 Hz, OCH2), 6.60-6.39 (4H, m, 3,4-H of pyrrolyl
512 (4), 423 (2), 380 (3),
330 (2), 312 (18), 290 (5),
280 (4), 178 (2), 167 (16),
152 (4), 77 (2).
and 3,5-H of phenyl), 6.92-6.86 (2H, m, 2,5-H of pyrrolyl),
8.64-8.50, 7.70-7.41 (13H, m, 5-H of pyridyl and phenyl-
H).
a 1H NMR in DMSO-d6

324 J. Chin. Chem. Soc., Vol. 52, No. 2, 2005
Ho and Yao
acetic anhydride (5 mL) was heated for ten minutes; com-
pound 23a (0.39 g, 1 mmol) was added. The reaction mixture
was refluxed for 10 h. After cooling, the resulting solid prod-
uct was collected by filtration, washed with ethanol and wa-
ter, and the crude product was recrystallized from etha-
nol/acetic acid to give 0.19 g (43% yield), mp 243 °C; IR: n
3266 (NH), 1728 (C=O) cm-1; 1H NMR (CDCl3): d 2.21 (3H,
s, CH3), 2.32 (3H, s, CH3), 6.53-6.50 (2H, m, 3,4-H of
pyrrolyl), 6.78 (2H, t, 2,5-H of pyrrolyl), 6.87 (1H, d, J = 1.4
Hz, 5-H of pyranyl), 8.02 (1H, br, NH), 8.10 (1H, d, J = 1.6
Hz, 4-H of pyranyl), 8.56-8.54, 7.52-7.47 (5H, m, phenyl-H);
MS: 442 (M+, 22), 427 (5), 399 (24), 384 (71), 355 (13), 331
(32), 318 (71), 290 (22), 246 (14), 232 (18), 222 (100), 208
(54), 194 (28), 179 (21), 121 (43), 106 (88), 77 (59), 56 (19).
Anal. Calcd. for C24H18N4O3S: C, 65.15; H, 4.07; N, 12.67.
Found: C, 65.19; H, 4.12; N, 12.55%.
ACKNOWLEDGEMENT
We are grateful to the Nanya Institute of Technology for
financial support.
Received June 28, 2004.
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