Synthesis of 6H-thieno[3,2-b]pyridin-7-ones from N-(2-X-Carbonyl)-3-thienyl ketenimines (X = RS, ArO, R2N) via consecutive [1,5]-X sigmatropic rearrangement and 6π-electrocyclization

Article abstract of DOI:10.1055/s-2007-965874

N-(2-X-Carbonyl)-3-thienyl ketenimines (X = RS, ArO, R₂N) undergo cyclization under thermal conditions, through a [1,5]-X sigmatropic rearrangement followed by a 6π-electrocyclic ring closure of the resulting intermediate ketene, to provide 6H-thieno[3,2-b]pyridin-7-ones, bearing alkylthio, arylthio, aryloxy or amino groups at their 5-position. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-965874

590
PAPER
Synthesisof 6H-Thieno[3,2-b]pyridin-7-ones from N-(2-X-Carbonyl)-3-thienyl
Ketenimines (X = RS, ArO, R2N) via Consecutive [1,5]-X Sigmatropic
Rearrangement and 6p-Electrocyclization
Synthesis of
6H
-thieno
a
[3,2-
b
]pyri
t
din-7-o
e
nes o Alajarín,* Ángel Vidal,* María-Mar Ortín
Departamento de Química Orgánica, Facultad de Química, Universidad de Murcia, Campus de Espinardo, 30100 Murcia, Spain
Fax +34(968)364149; E-mail: alajarin@um.es
Received 6 September 2006; revised 11 November 2006
carbon to the central carbon atom of the ketenimine frag-
Abstract: N-(2-X-Carbonyl)-3-thienyl ketenimines (X = RS, ArO,
ment, followed by a 6p-electrocyclic ring closure. With
R2N) undergo cyclization under thermal conditions, through a [1,5]-
the aim of extending the versatility of this particular meth-
odology we decided to try its application for the synthesis
X sigmatropic rearrangement followed by a 6p-electrocyclic ring
closure of the resulting intermediate ketene, to provide 6H-
thieno[3,2-b]pyridin-7-ones, bearing alkylthio, arylthio, aryloxy or of 6H-thieno[3,2-b]pyridin-7-ones, by combination of an
amino groups at their 5-position.
acyl group and a ketenimine fragment at the adjacent C2
and C3 carbon atoms of a thiophene ring, respectively.
Here we present the results obtained in the thermally in-
duced cyclization of N-(2-X-carbonyl)-3-thienyl keten-
imines (X = RS, ArO, R2N), which in fact undergo a facile
[1,5]-X sigmatropic migration and subsequent 6p-electro-
cyclization to afford 6H-thieno[3,2-b]pyridin-7-ones. It is
interesting to note that this type of dihydrothieno[3,2-
b]pyridines have been not described up to now.
Key words: azides, ketenimines, rearrangements, ketenes,
thienopyridines
Fused pyridines attract considerable interest in organic
chemistry because of their various biological activities
and their practical usefulness as reagents for the fine and
industrial chemistry. Among these heterocyclic com-
pounds, thienopyridines are of special significance.1 Par-
The reaction of 3-azido-2-thiophenecarboxylic acid (1)
with thiols in CH2Cl2, utilizing DCC as coupling agent, af-
forded S-alkyl(aryl) 3-azidothiophene-2-thiocarboxylates
3a–d (X = SR1). The synthesis of 3-azidothiophene-2-
carboxylates 3e,f (X = OAr) was achieved by treatment of
3-azido-2-thiophenecarbonyl chloride (2) with phenols in
CH2Cl2, in the presence of a slight excess of 4-dimethyl-
aminopyridine. The preparation of the 3-azido-2-
thiophenecarboxamides 3g,h (X = NR1R2) was carried
out by acylation of secondary amines with 3-azido-2-
thiophenecarbonyl chloride (2), in pyridine. The treat-
ment of 3-azidothiophenes 3 with triphenylphosphane in
diethyl ether at room temperature gave triphenylphosp-
hazenes 4. The reaction of 3-(triphenylphosphoranylidene-
amino)thiophene-2-thiocarboxylates 4a–d (X = SR1), in
CH2Cl2 at room temperature, with a stoichiometric
amount of diphenylketene or methylphenylketene afford-
ed N-[2-alkyl(aryl)thiocarbonyl]-3-thienyl ketenimines
5a–e (X = SR1) via aza-Wittig reactions. The formation of
ketenimines 5a–e was established by IR spectroscopy; the
IR spectra of the reaction mixtures showed strong absorp-
tions around 2000 cm–1 attributable to the N=C=C group.
After stirring at room temperature for four hours, keten-
imines 5a–e were totally consumed, and column chroma-
tography of the final reaction mixtures allowed the
isolation of the 5-alkyl(aryl)thio-6H-thieno[3,2-b]pyri-
din-7-ones 6a–e (X = SR1) in moderate to good yields
(Scheme 1, Table 1). When CH2Cl2 solutions of the 3-
(triphenylphosphoranylideneamino)thiophene-2-carbox-
ylates 4e,f (X = OAr) and the 3-(triphenylphosphora-
nylideneamino)-2-thiophenecarboxamides 4g,h (X =
NR1R2) were treated with diphenylketene, the corre-
ticularly,
a
range of thieno[3,2-b]pyridines are
biologically active. It is known that derivatives of this
family act, for example, as (a) antihypertensive2 or anti-
bacterial,2 antiviral3 and anticancer4 agents, (b) protein ty-
rosine kinase inhibitors,5 (c) GABA brain receptor
ligands,6 or (d) potent inhibitors of VEGFR-2 kinase.7
Moreover, some thieno[3,2-b]pyridines are useful in the
diagnosis and treatment of anxiety,6,8 or the treatment of
intestinal dysfunctions.9 Different protocols have been re-
ported for the preparation of thieno[3,2-b]pyridines, most
of them based on the use of 3-aminothiophenes or their N-
derivatives as precursors.10
Ketenimines [R1N=C=CR2R3] are nitrogenated heterocu-
mulenes of great utility in organic synthesis for the con-
struction of nitrogenated heterocyclic compounds.11 As a
matter of fact, in the frame of our studies in the chemistry
of ketenimines we have successfully used this heterocu-
mulenic compounds as substrates in the synthesis of
isoquinolines,12 azeto[2,1-b]quinazolines,13 benzimid-
azo[1,2-b]isoquinolines,14 pyrido[1,2-a]benzimidazoles,15
imidazo[1,2-b]isoquinolines,16
benz[b]acridines,17
dibenz[b,h]acridines,18 indoles,19 1,4-benzoxazines,20 3,1-
benzoxazines,21 and 1,4-diazepin-5-ones.22
Recently, we have reported the conversion of N-(2-X-car-
bonyl)phenyl ketenimines (X = RS, RSe, ArO, R2N) into
quinolones,23 via the [1,5]-X migration of alkyl(aryl)thio,
arylseleno, aryloxy and amino groups from the carbonyl
SYNTHESIS 2007, No. 4, pp 0590–0596
Advanced online publication: 08.01.2007
DOI: 10.1055/s-2007-965874; Art ID: Z18306SS
x
x
.
x
x
.2
0
0
7
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of 6H-Thieno[3,2-b]pyridin-7-ones
591
For X = SR1
R1SH, DCC
PPh3
N3
N3
O
N
O
PPh3
CH2Cl2, 0 °C, 1 h; then r.t., 24 h
Et2O, r.t., 16 h
X
X
S
COOH
S
S
4a–d X = SR1
4e,f X = OAr
4g,h X = NR1R2
1
3a–d X = SR1
SOCl2
3e,f X = OAr
3g,h X = NR1R2
benzene, reflux, 5 h
For X = OAr
Ph(R3)C=C=O
ArOH, DMAP
– Ph3P=O
N3
Cl
O
CH2Cl2, r.t., 10 min
CH2Cl2, r.t., 24 h
For X = NR1R2
Ph
S
N
C C
R1R2NH
5a–e X = SR1
R3
2
X
pyridine, 0 °C, 1.5 h
5f,g X = OAr
S
5h,i X = NR1R2
O
For X = OAr, NR1R2
For X = SR1
CH2Cl2, r.t., 4 h
neat, sealed tube, 200 °C, 1 h
N
O
X
6a–e X = SR1
Ph
R3
6f,g X = OAr
6h,i X = NR1R2
S
Scheme 1 Synthesis of 5-substituted 6H-thieno[3,2-b]pyridin-7-ones 6
sponding N-(2-aryloxycarbonyl)-3-thienyl ketenimines The conversion of ketenimines 5 into the 6H-thieno[3,2-
5f,g (X = OAr) and N-(2-carboxamido)-3-thienyl keten- b]pyridin-7-ones 6 most likely occurs by [1,5] migration
imines 5h,i (X = NR1R2) were formed, respectively, of the electron rich group X [alkyl(aryl)thio, aryloxy or
which in contrast with ketenimines 5a–e remained unal- amino] from the carbonyl carbon to the electron-deficient
tered at room temperature. No conversion was observed central carbon atom of the ketenimine fragment to give
while heating a toluene or ortho-xylene solution of the the intermediate ketenes 7, which cyclize to the 6H-
C,C-diphenyl ketenimines 5f–i at reflux temperature for thieno[3,2-b]pyridin-7-ones 6 through a 6p-electrocyclic
48 hours. Then, ketenimines 5f,g and 5h,i were generated ring closure, that involves the conjugated 3-azatriene frag-
in CH2Cl2 at room temperature, and after removal the sol- ment of their 1-oxa-5-aza-1,2,4,6-heptatetraene system
vent to dryness, the mixtures containing these ketenimines (Scheme 2).
and triphenylphosphane oxide were heated at 200 °C, in a
sealed tube for one hour. The materials obtained from
Table 1 6H-Thieno[3,2-b]pyridin-7-ones 6
R3
Ph
Me
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Yield (%)
these thermal treatments were chromatographed, thus al-
lowing the isolation of the 5-aryloxy-6H-thieno[3,2-b]py-
ridin-7-ones 6f,g (X = OAr) and the 5-amino-6H-
thieno[3,2-b]pyridin-7-ones 6h,i (X = NR1R2) in accept-
able global yields for the conversion 4 → 6 (Scheme 1,
Table 1).
Compound
X
6a
6b
6c
6d
6e
6f
4-MeC6H4S
4-MeC6H4S
4-MeOC6H4S
4-MeOC6H4CH2S
PhCH2CH2S
4-MeC6H4O
3,4-(MeO)2C6H3O
Ph(Me)N
65
50
51
73
71
31
36
61
50
The structural characterization of thienopyridin-7-ones 6
relies on their analytical and spectroscopic data. In this re-
spect, their IR spectra display a strong absorption at 1651–
1669 cm–1 corresponding to the C=O vibration. In the 1H
NMR spectra of these compounds, the H2 proton reso-
nates as a doublet at d = 7.57–7.73, and the H3 proton is
observed as a doublet at d = 6.97–7.07. Their 13C NMR
spectra show the signals of the quaternary carbon atoms
C6 and C7 at d = 60.6–72.0 and d = 189.4–191.4, respec-
tively.
6g
6h
6i
(4-MeC6H4)(Me)N
Synthesis 2007, No. 4, 590–596 © Thieme Stuttgart · New York

592
M. Alajarín et al.
PAPER
13C NMR (100 MHz, CDCl3): d = 21.4, 121.5, 123.6 (s), 126.0 (s),
Ph
130.1, 132.3, 135.0, 140.0 (s), 140.2 (s), 181.3 (s).
N
O
C
C
N
C
X
[1,5]-X
R3
MS (EI, 70 eV): m/z (%) = 152 (100), 275 (9, [M+]).
X
Ph
R3
S
S
Anal. Calcd for C12H9N3OS2: C, 52.34; H, 3.29; N, 15.26. Found:
C, 52.49; H, 3.11; N, 15.02.
O
5
7
S-(4-Methoxyphenyl) 3-Azidothiophene-2-thiocarboxylate (3b)
Yield: 60%; yellow prisms; mp 68–70 °C (Et2O–n-hexane).
6π ERC
IR (Nujol): 2146, 2107, 1612, 1588, 1530, 1494, 1420, 1283, 1249,
1200, 1174, 1030, 960, 850, 818, 755 cm–1.
N
X
1H NMR (400 MHz, CDCl3): d = 3.83 (s, 3 H), 6.94–6.97 (m, 2 H),
Ph
S
7.00 (d, J = 5.3 Hz, 1 H), 7.38–7.41 (m, 2 H), 7.55 (d, J = 5.3 Hz, 1
R3
H).
O
6
13C NMR (100 MHz, CDCl3): d = 55.4, 114.9, 117.7 (s), 121.5,
126.0 (s), 132.3, 136.7, 140.2 (s), 160.9 (s), 181.8 (s).
Scheme 2 Proposed mechanism for the conversion 5 → 6
MS (EI, 70 eV): m/z (%) = 152 (100), 291 (12, [M+]).
Anal. Calcd for C12H9N3O2S2: C, 49.47; H, 3.11; N, 14.42. Found:
C, 49.36; H, 3.10; N, 14.21.
In summary, the thermally induced cyclization of the N-
(2-X-carbonyl)-3-thienyl ketenimines 5 has provided ex-
amples of thieno[3,2-b]pyridines saturated at their 6-posi-
tion, disubstituted at the C6 carbon atom, and bearing an
alkylthio, arylthio, aryloxy or amino group at the C5 car-
bon atom. Moreover, this process represents a novel reac-
tion sequence in ketenimine chemistry,23 involving a [1,5]
sigmatropic rearrangement followed by a 6p-electrocyclic
ring closure.
S-(4-Methoxybenzyl) 3-Azidothiophene-2-thiocarboxylate (3c)
Yield: 83%; yellow oil.
IR (neat): 2151, 2116, 1612, 1516, 1414, 1393, 1289, 1253, 1025,
1178, 1036, 966, 892, 824, 743 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.76 (s, 3 H), 4.23 (s, 2 H), 6.80–
6.84 (m, 2 H), 6.93 (dd, J = 5.3, 1.8 Hz, 1 H), 7.25–7.29 (m, 2 H),
7.48 (dd, J = 5.3, 1.8 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 33.2, 55.2, 114.0, 121.3, 126.2
All melting points were determined on a Kofler hot-plate mp appa-
ratus and are uncorrected. IR spectra were obtained as films or Nu-
jol emulsion on a Nicolet Impact 400 spectrophotometer. NMR
spectra were recorded on a Bruker Avance 300 (300 MHz and 75
MHz for 1H and 13C, respectively) or a on Bruker Avance 400 spec-
trometer (400 MHz and 100 MHz for 1H and 13C, respectively), in
CDCl3 as solvent, and the chemical shifts are expressed in ppm rel-
ative to TMS at d = 0.00 for 1H NMR and to CDCl3 at d = 77.10 for
13C NMR. The abbreveation ‘s’ is used to denote quaternary car-
bons in the 13C NMR data. Mass spectra were recorded on a
Hewlett-Packard 5993C spectrometer or on a VG-Autospec spec-
trometer. Microanalyses were performed on a Carlo Erba EA-1108
instrument.
(s), 129.1 (s), 130.2, 131.8, 139.8 (s), 158.8 (s), 182.0 (s).
Anal. Calcd for C13H11N3O2S2: C, 51.13; H, 3.63; N, 13.76. Found:
C, 51.39; H, 3.45; N, 13.59.
S-Phenethyl 3-Azidothiophene-2-thiocarboxylate (3d)
Yield: 84%; yellow oil.
IR (neat): 2148, 2110, 1621, 1530, 1425, 1391, 1290, 1196, 1175,
1074, 1033, 968, 884, 860, 823, 743 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.93–2.97 (m, 2 H), 3.25–3.29 (m,
2 H), 6.92 (d, J = 5.0 Hz, 1 H), 7.22–7.31 (m, 5 H), 7.50 (d, J = 5.0
Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 30.8, 36.0, 121.4, 126.5 (s),
126.6, 128.6, 128.7, 131.7, 139.7 (s), 140.0 (s), 182.4 (s).
3-Azido-2-thiophenecarboxylic acid (1),24 diphenylketene25 and
methylphenylketene26 were prepared according to literature proce-
dures.
MS (EI, 70 eV): m/z (%) = 105 (100), 289 (3, [M+]).
Anal. Calcd for C13H11N3OS2: C, 53.96; H, 3.83; N, 14.52. Found:
C, 53.78; H, 3.67; N, 14.33.
3-Azidothiophene-2-thiocarboxylates 3a–d; General Procedure
To a suspension, of 3-azido-2-thiophenecarboxylic acid (1; 0.34 g,
2 mmol) in anhyd CH2Cl2 (10 mL) cooled to 0 °C, was added DCC
(0.43 g, 2.1 mmol). Next, the corresponding thiol (2.1 mmol) was
added, and the mixture was stirred at 0 °C for 1 h, and at r.t. for 24
h. The precipitated dicyclohexyl urea was separated by filtration,
and washed with Et2O (2 × 5 mL). From the filtrate the solvent was
removed under reduced pressure and the resulting material was pu-
rified by column chromatography [silica gel; hexanes–Et2O (7:3)].
3-Azidothiophene-2-carboxylates 3e,f; General Procedure
A suspension of 3-azido-2-thiophenecarboxylic acid (1; 0.85 g, 5
mmol) in anhyd benzene (30 mL) was heated at reflux temperature.
Then a solution of SOCl2 in the same solvent (10 mL) was added
dropwise during 30 min. The mixture was heated at reflux temper-
ature for 5 h. After cooling to r.t., the solvent was removed under
reduced pressure, and to the resulting residue was added benzene
(60 mL), and the solvent was again removed under reduced pres-
sure. The resulting solid was dissolved in n-hexane–Et2O [50 mL,
(1:1)], and the solution heated to boiling. The hot solution was treat-
ed with a small amount of charcoal (0.25 g), and filtered. The sol-
vent was removed under reduced pressure to give 3-azido-2-
thiophenecarbonyl chloride (2) as a crystalline yellow solid, which
was used in the following step without further purification. To a so-
lution of 3-azido-2-thiophenecarbonyl chloride (2; 0.38 g, 2 mmol)
in anhyd CH2Cl2 (15 mL), were added DMAP (0.32 g, 2.6 mmol)
and the corresponding phenol (2 mmol). The mixture was stirred at
S-(4-Methylphenyl) 3-Azidothiophene-2-thiocarboxylate (3a)
Yield: 72%; yellow prisms; mp 105–106 °C (Et2O–n-hexane).
IR (Nujol): 2145, 2109, 1616, 1526, 1418, 1391, 1280, 1199, 1182,
965, 855, 825, 808, 756 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.38 (s, 3 H), 6.99 (d, J = 4.0 Hz,
1 H), 7.24 (d, J = 7.9 Hz, 2 H), 7.37 (d, J = 7.9 Hz, 2 H), 7.54 (d,
J = 4.0 Hz, 1 H).
Synthesis 2007, No. 4, 590–596 © Thieme Stuttgart · New York

PAPER
Synthesis of 6H-Thieno[3,2-b]pyridin-7-ones
593
r.t. for 24 h. Then n-hexane (25 mL) was added and the resulting
solid was filtered and washed with n-hexane (3 × 10 mL). From the
filtrate the solvent was removed under reduced pressure, and the re-
sulting material was purified by column chromatography on silica
gel.
3-Azido-2-[N-methyl-N-(4-methylphenyl)]thiophenecarbox-
amide (3h)
Yield: 90%; yellow prisms; mp 80–82 °C (Et2O–n-hexane).
IR (Nujol): 2140, 2110, 1636, 1538, 1530, 1455, 1382, 1300, 1281,
1183, 1080, 946, 836, 821, 770, 723 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.32 (s, 3 H), 3.41 (s, 3 H), 6.64
(d, J = 5.3 Hz, 1 H), 7.01–7.04 (m, 2 H), 7.08–7.11 (m, 2 H), 7.20
(d, J = 5.3 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 21.0, 38.3, 120.1, 121.7 (s),
126.9, 128.3, 129.7, 137.2 (s), 137.7 (s), 141.2 (s), 162.5 (s).
4-Methylphenyl 3-Azido-2-thiophenecarboxylate (3e)
Eluent: hexanes–Et2O (7:3); yield: 93%; colorless prisms; mp 54–
56 °C (Et2O–n-hexane).
IR (Nujol): 2157, 2107, 1727, 1538, 1506, 1426, 1399, 1226, 1200,
1166, 1047, 1021, 966, 864, 772, 726 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.35 (s, 3 H), 6.96 (d, J = 5.4 Hz,
1 H), 7.07–7.09 (m, 2 H), 7.18–7.20 (m, 2 H), 7.55 (d, J = 5.4 Hz, 1
MS (EI, 70 eV): m/z (%) = 91 (100), 272 (24, [M+]).
Anal. Calcd for C13H12N4OS: C, 57.34; H, 4.44; N, 20.57. Found:
C, 57.40; H, 4.31; N, 20.42.
H).
13C NMR (100 MHz, CDCl3): d = 20.9, 116.5 (s), 121.3, 122.4,
3-(Triphenylphosphoranylideneamino)thiophenes 4; General
Procedure
130.0, 132.1, 135.7 (s), 143.6 (s), 148.1 (s), 159.4 (s).
MS (EI, 70 eV): m/z (%) = 152 (100), 259 (10, [M+]).
To a solution of the corresponding 3-azidothiophene 3 (4 mmol) in
anhyd Et2O (40 mL), was added Ph3P (1.05 g, 4 mmol) in five por-
tions. The mixture was stirred at r.t. under N2 for 16 h. Then, the pre-
cipitated compound 4 was isolated by filtration, and was used in the
following step without further purification. For analytical samples,
compounds 4 were recrystallized from Et2O.
Anal. Calcd for C12H9N3O2S: C, 55.59; H, 3.50; N, 16.21. Found:
C, 55.45; H, 3.69; N, 16.03.
3,4-Dimethoxyphenyl 3-Azido-2-thiophenecarboxylate (3f)
Eluent: hexanes–Et2O (2:3); yield: 76%; colorless prisms; mp 97–
98 °C (Et2O–n-hexane).
S-(4-Methylphenyl) 3-(Triphenylphosphoranylidene-
amino)thiophene-2-thiocarboxylate (4a)
Yield: 91%; colorless prisms; mp 140–142 °C (Et2O).
IR (Nujol): 2106, 1731, 1544, 1517, 1449, 1428, 1393, 1269, 1246,
1229, 1193, 1157, 1128, 1057, 1027, 766 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.87 (s, 3 H), 3.89 (s, 3 H), 6.74–
6.78 (m, 2 H), 6.85–6.89 (m, 1 H), 6.98 (d, J = 5.4 Hz, 1 H), 7.58
(d, J = 5.4 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 56.0, 57.2, 105.8, 111.1, 113.0,
116.2 (s), 122.2, 132.2, 143.6 (s), 143.9 (s), 147.0 (s), 149.3 (s),
159.5 (s).
IR (Nujol): 1616, 1596, 1510, 1438, 1419, 1395, 1298, 1161, 1118,
1074, 911, 842, 806, 753, 722, 698 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.36 (s, 3 H), 6.06 (d, J = 5.4 Hz,
1 H), 7.12 (d, J = 5.4 Hz, 1 H), 7.20 (d, J = 7.9 Hz, 2 H), 7.44–7.50
(m, 8 H), 7.54–7.58 (m, 3 H), 7.82–7.88 (m, 6 H).
13C NMR (100 MHz, CDCl3): d = 21.4, 122.7 (d, J = 24.9 Hz) (s),
123.9 (d, J = 9.4 Hz), 127.0 (s), 128.9 (d, J = 12.4 Hz), 129.5, 129.9
(d, J = 100.3 Hz) (s), 131.9, 132.3 (d, J = 2.7 Hz), 132.8 (d, J = 10.0
Hz), 135.4, 138.6 (s), 156.1 (s), 181.4 (s).
MS (EI, 70 eV): m/z (%) = 124 (100), 305 (52, [M+]).
Anal. Calcd for C13H11N3O4S: C, 51.14; H, 3.63; N, 13.76. Found:
C, 50.97; H, 3.69; N, 13.55.
31P NMR (121.4 MHz, CDCl3/H3PO4): d = 9.5.
MS (EI, 70 eV): m/z (%) = 386 (100), 509 (3, [M+]).
3-Azido-2-thiophenecarboxamides 3g,h; General Procedure
A solution of the corresponding amine (10 mmol) in anhyd pyridine
(20 mL) was cooled to 0 °C and 3-azido-2-thiophenecarbonyl chlo-
ride (2; 1.88 g, 10 mmol), prepared as above, was added. The mix-
ture was stirred at 0 °C for 1.5 h. Then, H2O (300 mL) was added
and the resulting suspension was extracted with Et2O (3 × 100 mL).
The combined extracts were washed with H2O (2 × 100 mL) and aq
2 N HCl (2 × 150 mL), and dried (MgSO4). The solvent was re-
moved under reduced pressure and the resulting material was puri-
fied by column chromatography on silica gel using hexanes–Et2O
(1:1) as eluent.
Anal. Calcd for C30H24NOPS2: C, 70.70; H, 4.75; N, 2.75. Found:
C, 70.51; H, 4.58; N, 2.57.
S-(4-Methoxyphenyl) 3-(Triphenylphosphoranylidene-
amino)thiophene-2-thiocarboxylate (4b)
Yield: 78%; colorless prisms; mp 223–225 °C (Et2O).
IR (Nujol): 1650, 1617, 1597, 1514, 1433, 1393, 1301, 1250, 1165,
1112, 1078, 913, 804, 721, 698 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.82 (s, 3 H), 6.08 (d, J = 5.3 Hz,
1 H), 6.93–6.95 (m, 2 H), 7.15 (d, J = 5.3 Hz, 1 H), 7.46–7.52 (m, 8
H), 7.56–7.60 (m, 3 H), 7.83–7.88 (m, 6 H).
3-Azido-2-(N-methyl-N-phenyl)thiophenecarboxamide (3g)
Yield: 87%; yellow prisms; mp 44–45 °C (Et2O–n-hexane).
13C NMR (100 MHz, CDCl3): d = 55.4, 114.5, 123.9 (d, J = 9.1 Hz),
129.0 (d, J = 12.3 Hz), 132.0, 132.4, 132.9 (d, J = 10.0 Hz), 137.0,
160.2 (s), 182.0 (s).
31P NMR (121.4 MHz, CDCl3/H3PO4): d = 9.2.
IR (Nujol): 2143, 2106, 1633, 1595, 1534, 1498, 1276, 1104, 1027,
988, 952, 921, 835, 741, 721, 701 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.45 (s, 3 H), 6.64 (dd, J = 5.3, 0.8
Hz, 1 H), 7.13–7.16 (m, 2 H), 7.21 (dd, J = 5.3, 0.7 Hz, 1 H), 7.23–
7.25 (m, 1 H), 7.27–7.30 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 38.2, 120.1, 121.7 (s), 127.1,
127.3, 128.4, 129.1, 137.7 (s), 143.9 (s), 162.5 (s).
MS (EI, 70 eV): m/z (%) = 386 (100), 525 (3, [M+]).
Anal. Calcd for C30H24NO2PS2: C, 68.55; H, 4.60; N, 2.66. Found:
C, 68.43; H, 4.45; N, 2.49.
MS (EI, 70 eV): m/z (%) = 77 (100), 258 (8, [M+]).
S-(4-Methoxybenzyl) 3-(Triphenylphosphoranylidene-
amino)thiophene-2-thiocarboxylate (4c)
Yield: 87%; colorless prisms; mp 175–176 °C (Et2O).
Anal. Calcd for C12H10N4OS: C, 55.80; H, 3.90; N, 21.69. Found:
C, 55.67; H, 3.84; N, 21.58.
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IR (Nujol): 1590, 1512, 1449, 1435, 1397, 1306, 1249, 1236, 1169,
1118, 1077, 1038, 915, 835, 814, 758 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.78 (s, 3 H), 4.25 (s, 2 H), 6.02
(dd, J = 5.4, 0.8 Hz, 1 H), 6.81–6.86 (m, 2 H), 7.10 (d, J = 5.4 Hz,
1 H), 7.31–7.36 (m, 2 H), 7.39–7.46 (m, 6 H), 7.50–7.57 (m, 3 H),
7.75–7.83 (m, 6 H).
13C NMR (75 MHz, CDCl3): d = 32.6, 55.3, 113.8, 122.8 (d,
J = 25.0 Hz) (s), 123.9 (d, J = 9.3 Hz), 128.8 (d, J = 12.2 Hz), 129.9
(d, J = 100.3 Hz) (s), 130.3, 130.9 (s), 131.3, 132.2 (d, J = 2.8 Hz),
132.8 (d, J = 10.1 Hz), 155.8 (s), 158.4 (s), 182.7 (s).
J = 12.2 Hz), 130.4 (d, J = 100.8 Hz) (s), 130.5, 132.0 (d, J = 2.7
Hz), 132.7 (d, J = 10.1 Hz), 145.0 (s), 146.4 (s), 149.2 (s), 158.1 (s),
161.8 (d, J = 1.5 Hz) (s).
31P NMR (121.4 MHz, CDCl3/H3PO4): d = 5.3.
MS (EI, 70 eV): m/z (%) = 386 (100), 539 (3, [M+]).
Anal. Calcd for C31H26NO4PS: C, 69.00; H, 4.86; N, 2.60. Found:
C, 68.81; H, 4.68; N, 2.57.
3-(Triphenylphosphoranylideneamino)-2-(N-methyl-N-
phenyl)thiophenecarboxamide (4g)
Yield: 91%; colorless prisms; mp 159–161 °C (Et2O).
31P NMR (121.4 MHz, CDCl3/H3PO4): d = 9.0.
MS (EI, 70 eV): m/z (%) = 386 (100), 539 (3, [M+]).
IR (Nujol): 1621, 1594, 1522, 1456, 1435, 1423, 1404, 1346, 1271,
1172, 1109, 1072, 1027, 829, 720, 696 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.51 (s, 3 H), 5.89 (dd, J = 5.2, 0.9
Hz, 1 H), 6.87 (d, J = 5.2 Hz, 1 H), 7.00–7.13 (m, 5 H), 7.38–7.43
(m, 6 H), 7.48–7.57 (m, 9 H).
13C NMR (75 MHz, CDCl3): d = 38.4, 117.5 (d, J = 26.1 Hz) (s),
123.8 (d, J = 8.8 Hz), 124.8, 125.6, 126.1, 128.1, 128.5 (d, J = 12.1
Hz), 130.9 (d, J = 100.1 Hz) (s), 131.7 (d, J = 2.8 Hz), 132.6 (d,
J = 9.9 Hz), 145.7 (s), 149.1 (s), 167.3 (s).
Anal. Calcd for C31H26NO2PS2: C, 69.00; H, 4.86; N, 2.60. Found:
C, 68.81; H, 4.66; N, 2.55.
S-Phenethyl 3-(Triphenylphosphoranylideneamino)thiophene-
2-thiocarboxylate (4d)
Yield: 88%; colorless prisms; mp 153–154 °C (Et2O).
IR (Nujol): 1593, 1512, 1435, 1394, 1304, 1173, 1122, 1081, 1030,
998, 920, 815, 757, 718, 694, 626 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.97–3.02 (m, 2 H), 3.25–3.30 (m,
2 H), 6.03 (dd, J = 5.4, 0.8 Hz, 1 H), 7.10 (d, J = 5.4 Hz, 1 H), 7.19–
7.33 (m, 5 H), 7.42–7.49 (m, 6 H), 7.52–7.58 (m, 3 H), 7.77–7.85
(m, 6 H).
13C NMR (75 MHz, CDCl3): d = 30.1, 36.5, 123.2 (d, J = 24.7 Hz)
(s), 124.0 (d, J = 9.3 Hz), 126.1, 128.4, 128.7, 128.9 (d, J = 12.3
Hz), 130.0 (d, J = 100.4 Hz) (s), 131.3, 132.2 (d, J = 2.8 Hz), 132.8
(d, J = 10.1 Hz), 141.4 (s), 155.7 (s), 182.9 (s).
31P NMR (121.4 MHz, CDCl3/H3PO4): d = 3.3.
MS (EI, 70 eV): m/z (%) = 386 (100), 492 (18, [M+]).
Anal. Calcd for C30H25N2OPS: C, 73.15; H, 5.12; N, 5.69. Found:
C, 73.01; H, 5.01; N, 5.44.
3-(Triphenylphosphoranylideneamino)-2-[N-methyl-N-
(4-methylphenyl)]thiophenecarboxamide (4h)
Yield: 95%; colorless prisms; mp 208–210 °C (Et2O).
31P NMR (121.4 MHz, CDCl3/H3PO4): d = 8.7.
MS (EI, 70 eV): m/z (%) = 386 (100), 523 (11, [M+]).
IR (Nujol): 1616, 1605, 1523, 1432, 1270, 1157, 1130, 1110, 1074,
1028, 987, 763, 727, 714, 694, 603 cm–1.
Anal. Calcd for C31H26NOPS2: C, 71.10; H, 5.00; N, 2.67. Found:
C, 71.01; H, 4.78; N, 2.49.
1H NMR (300 MHz, CDCl3): d = 2.23 (s, 3 H), 3.48 (s, 3 H), 5.89
(dd, J = 5.2, 0.9 Hz, 1 H), 6.83–6.87 (m, 3 H), 6.96–7.00 (m, 2 H),
7.37–7.43 (m, 6 H), 7.49–7.58 (m, 9 H).
4-(Methylphenyl) 3-(Triphenylphosphoranylideneamino)-2-
thiophenecarboxylate (4e)
Yield: 80%; colorless prisms; mp 165–167 °C (Et2O).
13C NMR (75 MHz, CDCl3): d = 21.0, 38.6, 117.6 (d, J = 26.1 Hz)
(s), 123.8 (d, J = 8.7 Hz), 125.4, 126.1, 128.5 (d, J = 12.0 Hz),
128.7, 131.0 (d, J = 100.0 Hz) (s), 131.7 (d, J = 2.8 Hz), 132.6 (d,
J = 9.8 Hz), 134.4 (s), 143.2 (s), 148.9 (s), 167.2 (s).
31P NMR (121.4 MHz, CDCl3/H3PO4): d = 3.2.
MS (EI, 70 eV): m/z (%) = 386 (100), 506 (17, [M+]).
IR (Nujol): 1716, 1514, 1506, 1435, 1135, 1111, 1011, 918, 865,
819, 769, 752, 721, 693 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.33 (s, 3 H), 6.22 (d, 1 H, J = 5.3
Hz), 7.09-7.12 (m, 3 H), 7.15–7.17 (m, 2 H), 7.40–7.45 (m, 6 H),
7.49–7.53 (m, 3 H), 7.77–7.82 (m, 6 H).
13C NMR (100 MHz, CDCl3): d = 20.9, 110.2 (d, J = 23.1 Hz) (s),
122.1, 124.8 (d, J = 9.1 Hz), 128.8 (d, J = 12.3 Hz), 129.7, 130.4,
130.5 (d, J = 100.8 Hz) (s), 132.0 (d, J = 2.8 Hz), 132.7 (d, J = 10.0
Hz), 134.5 (s), 149.0 (s), 157.8 (s), 161.7 (s).
Anal. Calcd for C31H27N2OPS: C, 73.50; H, 5.37; N, 5.53. Found:
C, 73.33; H, 5.21; N, 5.39.
5-Alkyl(aryl)thio-6H-thieno[3,2-b]pyridin-7-ones 6a–e;
General Procedure
To a solution of the corresponding 3-(triphenylphosphoranylidene-
amino)thiophene-2-thiocarboxylate 4 (1 mmol) in anhyd CH2Cl2
(15 mL), was added a solution of methylphenylketene (0.13 g, 1
mmol) or diphenylketene (0.19 g, 1 mmol) in the same solvent (5
mL), and the mixture was stirred at r.t. for 4 h. The solvent was re-
moved under reduced pressure and the resulting material was puri-
fied by column chromatography on silica gel.
31P NMR (121.4 MHz, CDCl3/H3PO4): d = 4.5.
MS (EI, 70 eV): m/z (%) = 386 (100), 493 (4, [M+]).
Anal. Calcd for C30H24NO2PS: C, 73.00; H, 4.90; N, 2.84. Found:
C, 72.82; H, 4.78; N, 2.67.
3,4-(Dimethoxyphenyl) 3-(Triphenylphosphoranylidene-
amino)-2-thiophenecarboxylate (4f)
Yield: 95%; colorless prisms; mp 222–223 °C (Et2O).
5-(4-Methylphenylthio)-6,6-diphenyl-6H-thieno[3,2-b]pyridin-
7-one (6a)
Eluent: hexanes–Et2O (7:3); yield: 65%; yellow prisms; mp 198–
200 °C (Et2O).
IR (Nujol): 1714, 1505, 1463, 1427, 1401, 1192, 1174, 1144, 1132,
1026, 1003, 906, 864, 771, 718, 696 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.85 (s, 3 H), 3.87 (s, 3 H), 6.23
(dd, J = 5.4, 0.9 Hz, 1 H), 6.77–6.81 (m, 2 H), 6.86 (d, J = 8.6 Hz,
1 H), 7.14 (d, J = 5.4 Hz, 1 H), 7.43–7.47 (m, 6 H), 7.51–7.54 (m, 3
H), 7.78–7.83 (m, 6 H).
13C NMR (100 MHz, CDCl3): d = 55.9, 56.2, 106.7, 110.0 (d,
J = 24.0 Hz) (s), 111.2, 113.7, 124.8 (d, J = 9.2 Hz), 128.8 (d,
IR (Nujol): 1662, 1552, 1501, 1430, 1378, 1282, 1110, 1072, 1031,
1019, 835, 759, 740 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.38 (s, 3 H), 6.97 (d, J = 5.1 Hz,
1 H), 7.22 (d, J = 7.9 Hz, 2 H), 7.34–7.40 (m, 12 H), 7.57 (d, J = 5.1
Hz, 1 H).
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Synthesis of 6H-Thieno[3,2-b]pyridin-7-ones
595
13C NMR (100 MHz, CDCl3): d = 21.4, 71.9 (s), 122.9 (s), 125.8 (s),
127.0, 128.5, 128.6, 129.9, 130.3, 135.1, 135.5, 138.5 (s), 139.6 (s),
155.0 (s), 183.7 (s), 191.0 (s).
1H NMR (300 MHz, CDCl3): d = 2.95–3.01 (m, 2 H), 3.33–3.38 (m,
2 H), 7.20–7.34 (m, 16 H), 7.68 (d, J = 5.1 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 33.0, 34.9, 72.0 (s), 122.8 (s),
126.5, 126.6, 128.3, 128.4, 128.6, 128.7, 130.2, 135.7, 139.0 (s),
140.3 (s), 155.0 (s), 183.8 (s), 191.2 (s).
MS (EI, 70 eV): m/z (%) = 302 (100), 425 (55, [M+]).
Anal. Calcd for C26H19NOS2: C, 73.38; H, 4.50; N, 3.29. Found: C,
73.21; H, 4.41; N, 3.13.
MS (EI, 70 eV): m/z (%) = 105 (100), 439 (26, [M+]).
Anal. Calcd for C27H21NOS2: C, 73.77; H, 4.82; N, 3.19. Found: C,
73.59; H, 4.71; N, 3.05.
6-Methyl-5-(4-methylphenylthio)-6-phenyl-6H-thieno[3,2-
b]pyridin-7-one (6b)
Eluent: hexanes–Et2O (7:3); yield: 50%; yellow prisms; mp 118–
120 °C (Et2O–n-hexane).
5-Aryloxy-6H-thieno[3,2-b]pyridin-7-ones 6f,g and 5-amino-
6H-thieno[3,2-b]pyridin-7-ones 6h,i; General Procedure
A solution of the corresponding 3-(triphenylphosphoranylidene-
amino)-2-thiophenecarboxylate 4e,f (1 mmol) or 3-(triphenylphos-
phoranylideneamino)-2-thiophenecarboxamide 4g,h (1 mmol) in
anhyd CH2Cl2 (5 mL) was introduced in a glass tube, and a solution
of diphenylketene (0.19 g, 1 mmol) in the same solvent (2 mL) was
added. After stirring at r.t. for 10 min, the solvent was removed to
dryness under reduced pressure. The glass tube was sealed and the
mixture containing the corresponding ketenimine 5 and Ph3PO was
heated at 200 °C for 1 h. After cooling at r.t., the crude mixture was
dissolved in CH2Cl2 (20 mL) and transferred to a round-bottomed
flask. Finally, the solvent was removed under reduced pressure and
the resulting material was purified by column chromatography on
silica gel.
IR (Nujol): 1652, 1556, 1503, 1434, 1381, 1296, 1173, 1048, 975,
918, 836, 807, 728, 695 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.03 (s, 3 H), 2.40 (s, 3 H), 7.05
(d, J = 5.1 Hz, 1 H), 7.22 (d, J = 7.9 Hz, 2 H), 7.30–7.39 (m, 7 H),
7.68 (d, J = 5.1 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 21.5, 24.2, 60.6 (s), 122.5 (s),
125.1 (s), 127.2, 127.3, 128.3, 129.0, 129.9, 135.1, 135.8, 138.8 (s),
139.5 (s), 155.8 (s), 186.1 (s), 191.4 (s).
MS (EI, 70 eV): m/z (%) = 240 (100), 363 (93, [M+]).
Anal. Calcd for C21H17NOS2: C, 69.39; H, 4.71; N, 3.85. Found: C,
69.18; H, 4.61; N, 3.73.
5-(4-Methoxyphenylthio)-6,6-diphenyl-6H-thieno[3,2-b]pyri-
din-7-one (6c)
Eluent: hexanes–Et2O (1:1); yield: 51%; yellow prisms; mp 210–
212 °C (Et2O).
5-(4-Methylphenyloxy)-6,6-diphenyl-6H-thieno[3,2-b]pyridin-
7-one (6f)
Eluent: hexanes–Et2O (7:3); yield: 31%; yellow prisms; mp 181–
183 °C (Et2O).
IR (Nujol): 1662, 1591, 1557, 1497, 1455, 1430, 1253, 1174, 1115,
1026, 827, 773, 738, 699, 665 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.84 (s, 3 H), 6.94–6.96 (m, 2 H),
6.98 (d, J = 5.1 Hz, 1 H), 7.36–7.38 (m, 10 H), 7.40–7.42 (m, 2 H),
7.59 (d, 1 H, J = 5.1 Hz).
13C NMR (100 MHz, CDCl3): d = 55.4, 71.9 (s), 114.7, 119.9 (s),
122.9 (s), 127.0, 128.5, 128.6, 130.3, 135.5, 136.8, 138.5 (s), 155.0
(s), 160.6 (s), 184.2 (s), 191.1 (s).
IR (Nujol): 1669, 1615, 1591, 1506, 1495, 1438, 1266, 1225, 1188,
1053, 1022, 1008, 863, 755, 711, 697 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.33 (s, 3 H), 6.85–6.87 (m, 2 H),
7.06 (d, J = 5.1 Hz, 1 H), 7.12–7.14 (m, 2 H), 7.34–7.43 (m, 10 H),
7.72 (d, J = 5.1 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 21.0, 68.0 (s), 121.1, 122.9 (s),
127.0, 128.1, 128.6, 129.6, 129.9, 135.4 (s), 136.5, 139.2 (s), 150.2
(s), 155.5 (s), 173.7 (s), 189.5 (s).
MS (EI, 70 eV): m/z (%) = 302 (100), 441 (47, [M+]).
MS (EI, 70 eV): m/z (%) = 302 (100), 409 (72, [M+]).
Anal. Calcd for C26H19NO2S2: C, 70.72; H, 4.34; N, 3.17. Found: C,
70.61; H, 4.51; N, 3.03.
Anal. Calcd for C26H19NO2S: C, 76.26; H, 4.68; N, 3.42. Found: C,
76.42; H, 4.58; N, 3.19.
5-(4-Methoxybenzylthio)-6,6-diphenyl-6H-thieno[3,2-b]pyri-
din-7-one (6d)
Eluent: hexanes–Et2O (1:1); yield: 73%; yellow prisms; mp 160–
5-(3,4-Dimethoxyphenyloxy)-6,6-diphenyl-6H-thieno[3,2-b]py-
ridin-7-one (6g)
Eluent: hexanes–Et2O (2:3); yield: 36%; yellow prisms; mp 182–
183 °C (Et2O).
162 °C (Et2O).
IR (Nujol): 1666, 1608, 1542, 1510, 1434, 1301, 1250, 1176, 1118,
1034, 836, 739, 696, 666 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.78 (s, 3 H), 4.30 (s, 2 H), 6.80–
6.85 (m, 2 H), 7.14–7.17 (m, 4 H), 7.22–7.32 (m, 9 H), 7.68 (d,
J = 5.1 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 35.8, 55.3, 71.7 (s), 113.8, 122.9
(s), 126.5, 128.3, 128.4, 128.6 (s), 130.1, 130.7, 135.7, 138.7 (s),
154.9 (s), 158.9 (s), 183.3 (s), 191.1 (s).
IR (Nujol): 1658, 1613, 1507, 1440, 1267, 1230, 1175, 1144, 1119,
1044, 1008, 780, 747, 731, 700, 656 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.79 (s, 3 H), 3.85 (s, 3 H), 6.45
(d, J = 2.6 Hz, 1 H), 6.55 (dd, J = 8.7, 2.6 Hz, 1 H), 6.80 (d, J = 8.7
Hz, 1 H), 7.07 (d, J = 5.1 Hz, 1 H), 7.34–7.44 (m, 10 H), 7.73 (d,
J = 5.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 56.1, 56.2, 68.1 (s), 105.7, 111.1,
112.7, 123.0 (s), 127.0, 128.1, 128.6, 129.6, 136.5, 139.1 (s), 146.2
(s), 146.8 (s), 149.4 (s), 155.4 (s), 173.8 (s), 189.4 (s).
MS (EI, 70 eV): m/z (%) = 121 (100), 455 (8, [M+]).
MS (EI, 70 eV): m/z (%) = 302 (100), 455 (48, [M+]).
Anal. Calcd for C27H21NO2S2: C, 71.18; H, 4.65; N, 3.07. Found: C,
71.01; H, 4.46; N, 3.23.
Anal. Calcd for C27H21NO4S: C, 71.19; H, 4.65; N, 3.07. Found: C,
71.01; H, 4.88; N, 2.92.
6,6-Diphenyl-5-phenethylthio-6H-thieno[3,2-b]pyridin-7-one
(6e)
5-(N-Methyl-N-phenylamino)-6,6-diphenyl-6H-thieno[3,2-
b]pyridin-7-one (6h)
Eluent: hexanes–Et2O (1:1); yield: 61%; yellow prisms; mp 206–
208 °C (Et2O).
Eluent: hexanes–Et2O (3:2); yield: 71%; yellow prisms; mp 158–
159 °C (Et2O).
IR (Nujol): 1665, 1547, 1498, 1429, 1274, 1119, 1033, 1002, 915,
891, 793, 770, 740, 695, 667, 647 cm–1.
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IR (Nujol): 1651, 1530, 1505, 1490, 1447, 1410, 1259, 1215, 1111,
1035, 1028, 785, 730, 717, 696 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.27 (s, 3 H), 6.51–6.54 (m, 2 H),
6.90–6.95 (m, 2 H), 6.99–7.05 (m, 2 H), 7.18–7.24 (m, 6 H), 7.28–
7.33 (m, 4 H), 7.61 (d, J = 5.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 43.5, 67.8 (s), 116.5 (s), 126.3,
126.5, 127.5, 127.7, 128.3, 128.8, 129.2, 136.4, 137.7 (s), 145.3 (s),
160.2 (s), 170.7 (s), 189.5 (s).
(4) (a) Munchhof, M. J.; Sobolov-Jaynes, S. B.; Marx, M. A. US
Pat. Appl. US 6492383, 2002; Chem. Abstr. 2002, 138,
24721. (b) Munchhof, M. J.; Sobolov-Jaynes, S. B. PCT Int.
Appl. WO 9924440, 1999; Chem. Abstr. 1999, 131, 5266.
(5) Boschelli, D. H.; Zhang, N.; Barrios, S. A. C.; Durutlic, H.;
Wu, B. US Pat. Appl. US 2004242883, 2004; Chem. Abstr.
2004, 142, 6510.
(6) Cai, G.; Liu, G. PCT Int. Appl. WO 9943681, 1999; Chem.
Abstr. 1999, 131, 184940.
MS (EI, 70 eV): m/z (%) = 408 (100, [M+]).
(7) Munchhof, M. J.; Beebe, J. S.; Casavant, J. M.; Cooper, B.
A.; Doty, J. L.; Higdon, R. C.; Hillerman, S. M.; Soderstrom,
C. I.; Knauth, E. A.; Marx, M. A.; Rossi, A. M. K.; Sobolov,
S. B.; Sun, J. Bioorg. Med. Chem. Lett. 2004, 21.
(8) (a) Webb, T. R.; McCarthy, J. R. PCT Int. Appl. WO
9847903, 1998; Chem. Abstr. 1998, 129, 330658. (b) Cai,
G.; Liu, G.; Albaugh, P. A. PCT Int. Appl. WO 0077008,
2000; Chem. Abstr. 2001, 134, 42071.
(9) (a) Yamazaki, T.; Yano, T. Jpn. Kokai Tokkyo Koho JP
08143573, 1996; Chem. Abstr. 1996, 125, 158629.
(b) Murayama, A.; Ogawa, S.; Yamazaki, S.; Tobe, A. Eur.
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134449.
Anal. Calcd for C26H20N2OS: C, 76.44; H, 4.93; N, 6.86. Found: C,
76.32; H, 4.88; N, 6.79.
5-[N-Methyl-N-(4-methylphenyl)amino]-6,6-diphenyl-6H-
thieno[3,2-b]pyridin-7-one (6i)
Eluent: hexanes–Et2O (1:1); yield: 50%; yellow prisms; mp 190–
192 °C (Et2O).
IR (Nujol): 1652, 1531, 1497, 1449, 1412, 1262, 1211, 1146, 1113,
1032, 1019, 840, 781, 732, 701 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.21 (s, 3 H), 3.27 (s, 3 H), 6.36–
6.39 (m, 2 H), 6.70–6.72 (m, 2 H), 7.00 (d, J = 5.1 Hz, 1 H), 7.17–
7.22 (m, 6 H), 7.27–7.31 (m, 4 H), 7.61 (d, J = 5.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 21.0, 43.6, 67.8 (s), 116.5 (s),
126.3, 127.3, 127.4, 128.2, 129.2, 129.4, 136.3 (s), 136.4, 137.9 (s),
142.7 (s), 160.3 (s), 170.8 (s), 189.5 (s).
(10) For examples of methods of preparation of thieno[3,2-
b]pyridines, see reviews cited in reference 1.
(11) (a) Dondoni, A. Heterocycles 1980, 14, 1547. (b) Barker,
M. W.; McHenry, W. E. In The Chemistry of Ketenes,
Allenes, and Related Compounds, Part 2; Patai, S., Ed.;
Wiley Interscience: Chichester, 1980, 701. (c) Alajarín, M.;
Vidal, A.; Tovar, F. Targets Heterocycl. Syst. 2000, 4, 293.
(12) (a) Molina, P.; Vidal, A.; Barquero, I. Synthesis 1996, 1199.
(b) Molina, P.; Vidal, A.; Tovar, F. Synthesis 1997, 963; and
references cited therein.
MS (EI, 70 eV): m/z (%) = 422 (100, [M+]).
Anal. Calcd for C27H22N2OS: C, 76.75; H, 5.25; N, 6.63. Found: C,
76.59; H, 5.21; N, 6.58.
(13) (a) Alajarín, M.; Molina, P.; Vidal, A. Tetrahedron Lett.
1996, 37, 8945. (b) Alajarín, M.; Vidal, A.; Tovar, F.;
Arrieta, A.; Lecea, B.; Cossío, F. P. Chem. Eur. J. 1999, 5,
1106. (c) Alajarín, M.; Vidal, A.; Tovar, F.; Ramírez de
Arellano, M. C. Tetrahedron: Asymmetry 2004, 15, 489.
(d) Alajarín, M.; Sánchez-Andrada, P.; Vidal, A.; Tovar, F.
J. Org. Chem. 2005, 70, 1340; and references cited therein.
(14) Alajarín, M.; Vidal, A.; Tovar, F.; Conesa, C. Tetrahedron
Lett. 1999, 40, 6127.
Acknowledgment
This work was supported by the DGES and FEDER (Project
CTQ2005-02323/BQU), and the Fundación Séneca-CARM (Pro-
ject 00458/PI/04). One of us (M.-M. O.) thanks Fundación Caja
Murcia for a fellowship.
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Synthesis 2007, No. 4, 590–596 © Thieme Stuttgart · New York