A novel one-step synthesis of benzo[b]furo[3,2-b]pyridines having an amino group at the 4-position from benzo[b]furo[3,2-d][1,3]oxazine

Article abstract of DOI:10.3987/COM-12-12615

A novel one-step synthesis of benzo[b]furo[3,2-b]pyridines having an amino group at the 4-position from benzo[b]furo[3,2-d][1,3]oxazine by treatment of various amines is described.

Full text of DOI:10.3987/COM-12-12615

HETEROCYCLES, Vol. 87, No. 1, 2013
177
HETEROCYCLES, Vol. 87, No. 1, 2013, pp. 177 - 191. © 2013 The Japan Institute of Heterocyclic Chemistry
Received, 31st October, 2012, Accepted, 14th November, 2012, Published online, 22nd November, 2012
DOI: 10.3987/COM-12-12615
A NOVEL ONE-STEP SYNTHESIS OF
BENZO[b]FURO[3,2-b]PYRIDINES HAVING AN AMINO GROUPAT THE
4-POSITION FROM BENZO[b]FURO[3,2-d][1,3]OXAZINE
Yukako Tabuchi, Yusa Kakumoto, Hitomi Uchimoto, Ikuo Kawasaki,*
Yoshitaka Ohishi, and Kiyoharu Nishide*
School of Pharmaceutical Sciences, Mukogawa Women’s University, 11-68
Koshien Kyuban-cho, Nishinomiya, Hyogo 663-8179, Japan; E-mail:
ikuo_k@mukogawa-u.ac.jp, nishide@mukogawa-u.ac.jp; Fax: +798 41 2792; Tel:
+798 45 9953
Abstract – A novel one-step synthesis of benzo[b]furo[3,2-b]pyridines having
an amino group at the 4-position from benzo[b]furo[3,2-d][1,3]oxazine by
treatment of various amines is described.
Benzo[b]furan derivatives with a fused pyridine ring show various bioactivities, for example, antibacterial
activity,1 inhibition of gyrase,2 and affinity for the adenosine A3 receptor.3 From them,
benzo[b]furo[3,2-b]pyridine with an amino group at the 4-position has been found as a basic structure of
several compounds showing activity against malaria.4 We have been interested in the preparation of
benzo[b]furan derivatives and their biological activities, and have reported several pharmaceutically
interesting compounds with activities, such as cysteinyl leukotriene 2 receptor antagonistic activity5
activity against human leukotriene B4 (BLT1, BLT2) receptors,6 poly(ADP-ribose)polymerase-1 inhibitory
activity,7 and growth inhibitory activity toward human pancreatic cancer cells.8
In continuing our research, we prepared several compounds having the benzo[b]furo[3,2-d][1,3]oxazine
skeleton, and some of them showed anti-osteoclastic bone resorption activity,9 selective estrogen receptor
modulators and growth inhibitory activity toward cancer cells.10 During our research program preparing
benzo[b]furo[3,2-d][1,3]oxazine derivatives, we discovered a novel one-step conversion from
benzo[b]furo[3,2-d][1,3]oxazine to benzo[b]furo[3,2-b]pyridine derivatives with an amino group at the

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4-position. Although several examples of conversion into a pyridine-fused polycyclic system from
1,3-oxazine derivatives have been reported,11 the products of these reactions were mostly
4-hydroxypyridine derivatives,11c-g and preparation of 4-aminobenzo[b]furo[3,2-b]pyridine derivatives
from 1,3-oxazine compounds by one-step conversion remains unknown.
In this paper, we report a novel one-step conversion into 4-aminobenzo[b]furo[3,2-b]pyridine derivatives
2 from (Z)-4-ylidenebenzo[b]furo[3,2-d][1,3]oxazine 1, which could be easily prepared on a multi-gram
scale.10
N
N
O
O
R'
MeO
N
R
O
MeO
CHO
1
2
Figure 1
In previous papers, we have reported the preparation of several butadiene derivatives containing the
benzo[b]furo[3,2-d][1,3]oxazine skeleton from 1, by reaction with phosphonate reagents in the presence
of NaH or TiCl4 (Scheme 1).9,10
In order to prepare other types of derivatives from 1, several reaction conditions were tried as shown in
Scheme 2. Treatment of aldehyde 1 with phenylmagnesium bromide or p-methoxyacetophenone in the
presence of TiCl4 and N-methylmorpholine afforded theketoamide 3 or the enol ketone 5 by opening of
the oxazine ring, but benzo[b]furo[3,2-d][1,3]oxazine derivatives 4 or 6 could not be found in these
reaction mixtures.

HETEROCYCLES, Vol. 87, No. 1, 2013
179
We supposed that the oxazine ring of benzo[b]furo[3,2-d][1,3]oxazine 1 could easily open under acidic
conditions, and tested the condensation under neutral reaction conditions. A reaction of aldehyde 1 with
p-bromoacetophenone
in
the
presence
of
piperidine
and
acetic
acid
gave
6-methoxy-4-(piperidin-1-yl)benzo[b]furo[3,2-b]pyridine 2a without the expected condensation product 7.
The structure of a new compound 2a has been supported by 1H-NMR, 13C-NMR, EIMS, IR and elemental
analysis data. In addition, HMBC experiments led to the indicated structure of the obtained product 2a
having a benzo[b]furo[3,2-b]pyridine skeleton, as shown in Figure 2.

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We decided therefore to investigate this one-step conversion to 6-methoxy-4-(piperidin-1-yl)benzo[b]-
furo[3,2-b]pyridine 2a from (Z)-(6-methoxy-(E)-2-styrylbenzo[b]furo[3,2-d][1,3]oxazin-4-ylideno)-
acetaldehyde 1. The optimized reaction conditions to give 2a were examined as shown in Table 1.
Reactions of 1 with piperidine (2.2 equiv.) in the presence of acetic acid (1.1, 0.5, 0.2 equiv.) in toluene
afforded 2a in yields of 34, 38, and 61%, respectively. Also obtained was 1-cinnamoylpiperidine 8a. The
reaction conditions in the absence of acetic acid were then examined. When two equivalents of piperidine
without acetic acid were used, the desired product 2a was obtained in the highest yield (85%).
N
O
HN
/ AcOH
+
N
O
N
toluene, reflux
MeO
N
O
O
MeO
8a
CHO
1
2a
Table 1
Yield (%)
Entry
AcOH
HN
2a
8a
1
2
3
4
5
6
7
2.2 eq.
2.2 eq.
2.2 eq.
1.0 eq.
2.0 eq.
3.0 eq.
4.0 eq.
1.1 eq.
0.5 eq.
0.2 eq.
\
34
38
61
22
85
83
74
61
50
54
34
82
83
77
\
\
\
Benzo[b]furo[3,2-d][1,3]oxazine compound 1 was treated with various secondary or primary amines
under the optimal reaction conditions to afford the corresponding benzo[b]furo[3,2-b]pyridine derivatives

HETEROCYCLES, Vol. 87, No. 1, 2013
181
with an amino group at the 4-position, and the results are summarized in Table 2. Several kinds of amine
were successfully reacted with 1 to give 4-aminobenzo[b]furo[3,2-b]pyridines 2 in moderate to high
yields.
The proposed reaction mechanism for the formation of the benzo[b]furo[3,2-b]pyridine 2a from
benzo[b]furo[3,2-d][1,3]oxazine 1 is shown in Figure 3. The aldehyde group of 1 reacted with the amine
to form the iminium intermediate A. Adding one more molecule of the amine to the C-4 of A led to
opening of the oxazine ring of B to give C. The dihydropyridine ring was formed by conjugate addition of
amide nitrogen in C, and then, elimination of cinnamaminde from D by aromatization afforded
benzo[b]furo[3,2-b]pyridines 2.

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In conclusion, we developed a novel one-step synthesis of benzo[b]furo[3,2-b]pyridines with an amino
group attached at the 4-position from benzo[b]furo[3,2-d][1,3]oxazine compounds. We are currently
investigating the scope of this reaction and applications toward biologically active compounds.
EXPERIMENTAL
Melting points were measured with a Yanaco MP micro-melting-point apparatus and are uncorrected.
NMR spectra were measured on JEOL JNM-ECP500 (1H: 500 MHz, 13C: 125 MHz) or JEOL
JNM-ECP400 (1H: 400 MHz, 13C: 100 MHz), and the chemical shifts were expressed in parts per million
(ppm) downfield from tetramethylsilane as the internal standard. Mass spectra were measured on a JEOL
JMS DX-303 EI-MS spectrometer. Elemental analyses were performed on a CHN CORDER MT-3
(Yanaco). Silica gel (Merck Art. 7734) for column chromatography and Silica gel 60 PF254 (Nacalai
Tesque Inc.) for preparative TLC (PTLC) were used.
N-(2-Cinnamoyl-7-methoxybenzofuran-3-yl)cinnamamide (3): Phenylmagnesium bromide (32% in
THF, 1.08 mL, 2.1 mmol) was added to a stirred solution of 110 (0.20 g, 0.58 mmol) in THF (80 mL)
under N2 at 0 ˚C, and the mixture was refluxed for 6 h. The reaction mixture was poured into water and
acidified with 10% hydrochloric acid, then the solvent was concentrated under reduced pressure. The
products were extracted with CHCl3, washed with brine, dried over MgSO4, and the solvent was removed
under reduced pressure. The residue was purified by column chromatography (CHCl3/AcOEt 10:1) and
recrystallized from CHCl3/AcOEt to give 3 (0.04 g, 16%) as a yellow solid; mp 212.8-214.1 ˚C; 1H-NMR
(400 MHz, CDCl3) : 4.06 (3H, s, OCH3), 6.76 (1H, d, J = 15.4 Hz, PhCH=CH), 7.03 (1H, dd, J = 8.1
and 0.8 Hz, Bf 4 or 6-H), 7.25 (1H, t, J = 8.3 Hz, Bf 5-H), 7.40-7.46 (6H, m, Ph-H), 7.60-7.63 (2H, m,

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183
Ph-H), 7.72-7.76 (3H, m, Ph-H), 7.74 (1H, d, J = 15.8 Hz, PhCH=CH), 7.84 (1H, d, J = 15.8 Hz,
PhCH=CH), 7.94 (1H, d, J = 15.7 Hz, PhCH=CH), 8.30 (1H, dd, J = 8.5 and 0.8 Hz, Bf 4 or 6-H), 10.93
(1H, s, NH); 13C-NMR (100 MHz, CDCl3) : 56.1, 110.5, 119.8, 120.5, 121.2, 122.9, 123.6, 128.2, 129.0,
129.0, 130.3, 130.9, 132.8, 134.5, 134.7, 139., 143.5, 144.4, 144.9, 145.7, 163.7, 182.2; MS (EI) m/z: 423
(M+, 67), 293 (64), 216 (56), 131 (100), 103 (37); Anal. Calcd for C27H21NO4・1/2H2O; C, 74.99; H, 5.13;
N, 3.24. Found; C, 4.84; H, 5.13; N, 3.22.
N-(2-((Z)-3-Hydroxyacryloyl)-7-methoxybenzofuran-3-yl)cinnamamide
(5):
A
solution
of
titanium(IV) chloride (120 L, 1.18 mmol) in CCl4 (20 mL) was added to a stirred solution of
4’-methoxyacetophenone (43.5 mg, 0.29 mmol) in THF (4 mL) under N2 at 0 ˚C, then
(Z)-(6-methoxy-(E)-2-styrylbenzo[b]furo[3,2-d][1,3]oxazin-4-ylideno)acetaldehyde 1 (0.10 g, 0.29
mmol) in anhydrous THF (80 mL) and N-methylmorpholine (254 L, 2.32 mmol) were added to the
reaction mixture. The reaction mixture was stirred 67 h at room temperature, then poured into water and
the solvent was concentrated under reduced pressure. The products were extracted with CHCl3, washed
with brine, and dried over MgSO4, then the solvent was removed under reduced pressure. The crude
residue was recrystallized from hexane/AcOEt to give 5 (0.0173 g, 16%) as a yellow solid; mp
146.0-148.0 ˚C; 1H-NMR (400 MHz, CDCl3) : 4.02 (3H, s, OCH3), 6.37 (1H, d, J = 5.6 Hz, CH=CHOH
or CH=CHOH), 6.70 (1H, d, J = 15.9 Hz, PhCH=CH), 6.99 (1H, dd, J = 2.2 and 0.8 Hz, 4 or 6-H), 7.22
(1H, t, J = 8.2 Hz, 5-H), 7.40 - 7.44 (3H, m, Ph-H), 7.59 (1H, d, J = 5.1 Hz, CH=CHOH or CH=CHOH),
7.61-7.63 (2H, m, Ph-H), 7.83 (1H, d, J = 15.3 Hz, PhCH=CH), 8.21 (1H, dd, J = 8.2 and 1.0 Hz, 4 or
6-H), 10.43 (1H, s, NH), 14.09 (1H, br s, OH); 13C-NMR (100 MHz, CDCl3) : 56.1, 99.4, 110.5, 119.6,
120.3, 123.0, 123.6, 128.2, 128.9, 130.3, 132.0, 134.4, 136.5, 143.7, 145.1, 145.6, 163.5, 169.4, 185.8;
MS (EI) m/z: 363 (M+, 25), 233 (15), 131 (100), 103 (56), 77 (28); HRMS (EI) m/z: 363.1105 (Calcd for
C21H17NO5, 363.1107).
Preparation of benzo[b]furo[3,2-b]pyridines and cinnamamides: General Procedure
A solution of 1 (0.10 g, 0.290 mmol) and 2 equiv of amines in toluene (2.9 mL or 40 mL) was refluxed
for 1-9 h (TLC monitoring). The solvent was evaporated off and the residue was purified by PTLC and
recrystallized from hexane-AcOEt.
In the case of 2k and 2m, 20 equiv of diethylamine and 6 equiv of 2-thiophenylmethanamine were used,
respectively.
6-Methoxy-4-piperadinobenzo[b]furo[3,2-b]pyridine (2a): PTLC with [CHCl3/AcOEt (5:2)]; pale
yellow solid; yield 85%; mp 109.7-111.8 ˚C; 1H-NMR (400 MHz, CDCl3) : 1.69-1.82 (6H, m, piperidine
3, 4, 5-H), 3.69 (4H, t, J = 5.4 Hz, piperidine 2, 6-H), 4.06 (3H, s, OCH3), 6.69 (1H, d, J = 5.9 Hz, 3-H),
7.03 (1H, dd, J = 8.1 and 1.1 Hz, 7-H), 7.30 (1H, t, J = 7.9 Hz, 8-H), 7.76 (1H, dd, J = 7.7 and 1.1 Hz,

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9-H), 8.32 (1H, d, J = 5.9 Hz, 2-H); 13C-NMR (100 MHz, CDCl3) : 24.5 (piperidine C4), 25.6 (OCH3),
49.4 (piperidine C3, 5), 56.3 (piperidine C2, 6), 107.0 (C3), 110.7 (C7), 113.1 (C9), 123.9 (C8), 125.7
(C9a), 140.0 (C4a), 142.9 (C4), 144.3 (C9b), 145.3 (C5a), 145.7 (C6), 146.6 (C2); IR (KBr) : 2928,
1632, 1594, 1410, 1267, 1178 cm-1; MS (EI) m/z: 282 (M+, 100), 241 (11), 226 (18), 198 (2); Anal. Calcd
for C17H18N2O2・2/3 H2O: C, 69.37; H, 6.62; N, 9.52. Found: C, 69.18; H, 6.40; N, 9.42.
6-Methoxy-4-morpholinobenzo[b]furo[3,2-b]pyridine (2b): PTLC with [CHCl3/AcOEt (5:2)]; pale
1
yellow solid; yield 80%; mp 177.1-180.7 ˚C; H-NMR (400 MHz, CDCl3) : 3.67 (4H, t, J = 4.8 Hz,
morpholine 3, 5-H), 3.95 (4H, t, J = 4.8 Hz, morpholine 2, 6-H), 4.04 (3H, s, OCH3), 6.69 (1H, d, J = 5.9
Hz, 3-H), 7.04 (1H, dd, J = 8.1 and 0.7 Hz, 7-H), 7.32 (1H, t, J = 7.9 Hz, 8-H), 7.78 (1H, dd, J = 7.9 and
13
0.9 Hz, 9-H), 8.37 (1H, d, J = 5.9 Hz, 2-H); C-NMR (100 MHz, CDCl3) : 48.3, 56.1, 66.7, 106.6,
110.7, 113.0, 124.1, 125.3, 142.5, 144.5, 145.4, 145.7, 146.7; IR (KBr) : 1597, 1273, 1202, 1120, 987
cm-1; MS (EI) m/z: 284 (M+, 85), 226 (100), 211 (16), 198 (2), 183 (17); Anal. Calcd for C17H16N2O3・
9/10 H2O: H, 6.07; C, 64.00; N, 9.27. Found: H, 5.81; C, 63.94; N, 9.23.
6-Methoxy-4-(4-methylpiperazin-1-yl)benzo[b]furo[3,2-b]pyridine (2c): PTLC with [CHCl3/MeOH
(5:2) and MeOH]; white solid; yield 84%; mp 157.0-158.5 ˚C; 1H-NMR (400 MHz, CDCl3) : 2.38 (3H, s,
CH3), 2.66 (4H, t, J = 5.1 Hz, piperazine-H), 3.73 (4H, t, J = 5.0 Hz, piperazine-H), 4.05 (3H, s, OCH3),
6.69 (1H, d, J = 5.9 Hz, 3-H), 7.04 (1H, dd, J = 8.0 and 1.1 Hz, 7-H), 7.32 (1H, t, J = 7.9 Hz, 8-H), 7.77
13
(1H, dd, J = 7.9 and 0.9 Hz, 9-H), 8.36 (1H, d, J = 5.5 Hz, 2-H); C-NMR (100 MHz, CDCl3) : 46.1,
47.8, 54.7, 56.0, 106.8, 110.5, 112.9, 123.8, 125.3, 139.8, 142.3, 144.2, 145.2, 145.5, 146.5; IR (KBr) :
2799, 1594, 1461, 1267, 1178, 1086 cm-1; MS (EI) m/z: 297 (M+, 100), 282 (22), 255 (23), 226 (68), 70
(89); Anal. Calcd for C17H19N3O2・1/5H2O: C, 67.84; H, 6.50; N, 13.96. Found: C, 68.10; H, 6.40; N,
13.81.
6-Methoxy-4-(4-acetylpiperazin-1-yl)benzo[b]furo[3,2-b]pyridine (2d): PTLC with [CHCl3/MeOH
(5:2) and MeOH]; pale yellow solid; yield 66%; mp 192.5-194.3 ˚C; 1H-NMR (400 MHz, CDCl3) : 2.17
(3H, s, COCH3), 3.62-3.89 (8H, m, piperazine-H), 4.06 (3H, s, OCH3), 6.70 (1H, d, J = 5.5 Hz, 3-H), 7.06
(1H, dd, J = 8.1 and 0.7 Hz, 7-H), 7.34 (1H, t, J = 7.9 Hz, 8-H), 7.77 (1H, dd, J = 7.9 and 1.0 Hz, 9-H),
8.39 (1H, d, J = 5.5 Hz, 2-H); 13C-NMR (100 MHz, CDCl3) : 21.2, 40.9 (CH2), 45.9 (CH2), 47.5 (CH2),
48.1 (CH2), 56.0, 106.9, 110.6, 112.9, 124.1, 125.2, 139.7, 141.8, 144.5, 145.3, 145.6, 146.6, 169.0; IR
(KBr) : 3010, 1649, 1594, 1430, 1249, 1191 cm-1; MS (EI) m/z: 325 (M+, 58), 282 (20), 253 (100), 240
(33), 226 (27), 212 (22), 56 (37), 43 (30); Anal. Calcd for C18H19N3O3・1/4 H2O: C, 65.54; H, 5.96; N,
12.74. Found: C, 65.83; H, 5.93; N, 12.49.
1
(E)-1-(4-Acetylpiperazin-1-yl)-3-phenylprop-2-en-1-one (8d): pale yellow oil; yield 83%; H-NMR

HETEROCYCLES, Vol. 87, No. 1, 2013
185
(400 MHz, CDCl3) : 2.14 (3H, s, COCH3), 3.51-3.75 (8H, m, piperazine-H), 6.85 (1H, d, J = 15.4 Hz,
PhCH=CH), 7.36-7.40 (3H, m, Ph-H), 7.52-7.54 (2H, m, Ph-H), 7.71 (1H, d, J = 15.4 Hz, PhCH=CH);
13C-NMR (100 MHz, CDCl3) : 21.2, 41.3, 46.0, 116.4, 127.7, 128.7, 129.7, 134.9, 143.4, 165.6, 169.1;
IR (KBr) : 2922, 1645, 1430, 1219, 997 cm-1; MS (EI) m/z: 258 (M+, 47), 243 (14), 131 (100), 103 (63),
85 (84), 77 (38); HRMS (EI) m/z: 258.1370 (Calcd for C15H18FN2O2, 258.1368).
4-(4-Benzylpiperazin-1-yl)-6-methoxybenzo[b]furo[3,2-b]pyridine (2e): PTLC with [hexane/AcOEt
(1:10)]; yellow solid; yield 58%; mp 63.3-65.8 ˚C; 1H-NMR (400 MHz, CDCl3) : 2.69 (4H, t, J = 4.9 Hz,
piperazine), 3.60 (2H, s, PhCH2), 3.72 (4H, t, J = 5.2 Hz, piperazine), 4.03 (3H, s, OCH3), 6.67 (1H, d, J
= 5.9 Hz, 3-H), 7.03 (1H, dd, J = 8.1 and 0.8 Hz, 7-H), 7.28-7.39 (6H, m, 8-H, Ph-H), 7.76 (1H, dd, J =
7.9 and 0.9 Hz, 9-H), 8.34 (1H, d, J = 5.8 Hz, 2-H); 13C-NMR (100 MHz, CDCl3): 48.0, 52.8, 56.1, 63.1,
106.8, 110.7, 113.0, 123.9, 125.4, 127.2, 128.3, 129.2, 137.7, 139.9, 142.5, 144.2, 145.3, 145.7, 146.5; IR
(KBr) : 2956, 1594, 1458, 1437, 1270, 1198 cm-1; MS (EI) m/z: 373 (M+, 100), 282 (18), 227 (80), 146
(29), 91 (50); Anal. Calcd for C23H23N3O2・1/2 H2O: C, 67.46; H, 6.65; N, 10.26. Found: C, 67.42; H,
6.69; N, 10.28.
6-Methoxy-4-(4-(pyridin-4-yl)piperazin-1-yl)benzo[b]furo[3,2-b]pyridine
(2f):
PTLC
with
1
[CHCl3/AcOEt (5:2) and MeOH]; white solid; yield 90%; mp 224.0-225.0 ˚C; H-NMR (400 MHz,
CDCl3) : 3.60-3.62 (4H, m, piperazine-H), 3.86-3.88 (4H, m, piperazine-H), 4.07 (3H, s, OCH3), 6.73
(1H, d, J = 5.5 Hz, 3-H), 6.74 (2H, dd, J = 5.0 and 1.7 Hz, pyridine), 7.06 ( 1H, dd, J = 7.9 and 0.9 Hz,
7-H), 7.34 (1H, t, J = 7.9 Hz, 8-H), 7.78 (1H, dd, J = 7.9 and 0.9 Hz, 9-H), 8.34 (2H, dd, 4.8 and 1.5 Hz,
13
pyridine), 8.40 (1H, d, J = 5.8 Hz, 2-H); C-NMR (100 MHz, CDCl3) : 45.8, 47.4, 56.1, 106.8, 108.5,
110.7, 113.0, 124.2, 125.3, 139.8, 141.9, 144.7, 145.4, 145.7, 146.7, 150.5, 154.7; IR (KBr) : 1591, 1512,
1406, 1243, 1202 cm-1; MS (EI) m/z: 360 (M+, 100), 226 (44), 133 (35), 106 (37); Anal. Calcd for
C21H20N4O2・5/6H2O: C, 66.02; H, 5.91; N, 14.67. Found: C, 66.20; H, 5.79; N, 14.53.
(E)-3-Phenyl-1-(4-(pyridin-4-yl)piperazin-1-yl)prop-2-en-1-one (8f): pale yellow solid; yield 46%; mp
1
136.0-138.4 ˚C; H-NMR (400 MHz, CDCl3) : 3.40-3.43 (4H, m, piperazine-H), 3.85 (4H, br s,
piperazine-H), 6.67 (2H, d, J = 6.2 Hz, pyridine 3, 5-H), 6.88 (1H, d, J = 15.3 Hz, PhCH=CH), 7.36-7.41
(3H, m, Ph-H), 7.52-7.55 (2H, m, Ph-H), 7.72 (1H, d, J = 15.4 Hz, PhCH=CH), 8.32 (2H, d, J = 5.9 Hz,
13
pyridine 2, 6-H); C-NMR (100 MHz, CDCl3) : 41.5, 44.9, 45.9, 108.4, 116.5, 127.8, 128.8, 129.8,
135.0, 143.4, 150.3, 154.5, 165.6; IR (KBr) : 1645, 1594, 1441, 1226, 990 cm-1; MS (EI) m/z: 293 (M+,
76), 202 (20), 162 (51), 133 (100), 131 (56), 103(47); Anal. Calcd for C18H19N3O・1/5 H2O: C, 72.80; H,
6.58; N, 14.15. Found: C,73.06; H, 6.55; N, 13.98.
6-Methoxy-4-(4-(pyridin-2-yl)piperazin-1-yl)benzo[b]furo[3,2-b]pyridine
(2g):
PTLC
with

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[hexane/AcOEt (1:2)]; pale yellow solid; yield 78%; mp 132.8-135.7 ˚C; 1H-NMR (400 MHz, CDCl3) :
3.80-3.87 (8H, m, piperazine), 4.07 (3H, s, OCH3), 6.67-6.72 (2H, m, 3', 5'-H), 6.74 (1H, d, J = 5.5 Hz,
3-H), 7.05 (1H, d, J = 8.1 Hz, 7-H), 7.33 (1H, t, J = 7.9 Hz, 8-H), 7.53 (1H, ddd, J = 8.6, 7.0 and 1.9 Hz,
4'-H), 7.78 (1H, dd, J = 7.7 and 1.1 Hz, 9-H), 8.24 (1H, dd, J = 4.9 and 2.0 Hz, 6'-H), 8.38 (1H, d, J = 5.5
13
Hz, 2-H); C-NMR (100 MHz, CDCl3): 45.0, 47.7, 56.1, 106.8, 107.1, 110.7, 113.0, 113.7, 124.0,
125.4, 137.5, 139.8, 142.2, 144.4, 145.3, 145.7, 146.6, 148.0, 159.2; IR (KBr) : 1587, 1434, 1270, 1239
cm-1; MS (EI) m/z: 360 (M+, 48), 254 (100), 227 (42), 107 (71); Anal. Calcd for C21H20N4O2・1/4 H2O: C,
69.12; H, 5.66; N, 15.35. Found: C, 69.23; H, 5.50; N, 15.20.
(E)-3-Phenyl-1-(4-(pyridin-2-yl)piperazin-1-yl)prop-2-en-1-one (8g): pate yellow solid; yield 75%; mp
1
141.4-142.6 ˚C; H-NMR (400 MHz, CDCl3) : 3.64-3.83 (8H, m, piperazine), 6.65-6.68 (2H, m,
pyridine 3, 5-H), 6.91 (1H, d, J = 15.4 Hz, PhCH=CH), 7.34-7.41 (3H, m, Ph 2, 6-H, pyridine 4-H),
7.49-7.55 (3H, m, Ph 3, 4, 5-H), 7.71 (1H, d, J = 15.7 Hz, PhCH=CH), 8.21 (1H, dd, J = 5.5 and 1.8 Hz,
pyridine 6-H); 13C-NMR (100 MHz, CDCl3): 41.7, 41.8, 45.2, 107.1, 113.8, 117.0, 127.7, 128.8, 129.7,
135.2, 137.6, 143.0, 148.0, 159.0, 165.6; MS (EI) m/z: 293 (M+, 78), 162 (23), 133 (89), 131 (35), 120
(47), 107 (100), 103 (31).; HRMS (EI) m/z: 293.1528 (Calcd for C18H19N3O, 293.1528).
6-Methoxy-4-(4-phenylpiperazin-1-yl)benzo[b]furo[3,2-b]pyridine (2h): PTLC with [CHCl3/AcOEt
1
(5:2)]; pale yellow solid; yield 49%; mp 232.0-233.4 ˚C; H-NMR (400 MHz, CDCl3) : 3.41-3.43 (4H,
m, piperazine-H), 3.84-3.87 (4H, m, piperazine-H), 4.05 (3H, s, OCH3), 6.73 (1H, d, J = 5.9 Hz, 3-H),
6.89-6.94 ( 1H, m, Ph-H), 6.99-7.05 (3H, m, 7-H, Ph-H), 7.28-7.34 (3H, m, 8-H, Ph-H), 7.78 (1H, d, J =
13
7.3 Hz, 9-H), 8.38 (1H, d, J = 5.5 Hz, 2-H); C-NMR (100 MHz, CDCl3) : 48.0, 49.2, 56.2, 107.0,
110.7, 113.0, 116.5, 117.1, 120.3, 124.0, 125.4, 129.2, 142.3, 144.5, 145.4, 145.7, 146.7, 151.1; IR (KBr)
: 1638, 1587, 1492, 1236, 990 cm-1; MS (EI) m/z: 359 (M+, 100), 226 (33), 132 (70), 105 (50), 77 (13);
Anal. Calcd for C22H21N3O2: C, 73.52; H, 5.89; N, 11.69. Found: C, 73.32; H, 5.87; N, 11.48.
4-(4-(4-Fluorophenyl)piperazin-1-yl)-6-methoxybenzo[b]furo[3,2-b]pyridine (2i): PTLC with
1
[CHCl3/AcOEt (5:2)]; whote solid; yield 66%; mp 202.6-203.8 ˚C; H-NMR (400 MHz, CDCl3) : 3.35
(4H, t, J = 5.1 Hz, piperazine), 3.87 (4H, t, J = 5.1 Hz, piperazine), 4.06 (3H, s, OCH3), 6.74 (1H, d, J =
5.9 Hz, 3-H), 6.93-7.03 (4H, m, Ph-H), 7.06 (1H, dd, J = 8.1 and 0.8 Hz, 7-H), 7.33 (1H, t, J = 7.9 Hz,
8-H), 7.78 (1H, dd, J = 7.7 and 1.1 Hz, 9-H), 8.39 (1H, d, J = 5.5 Hz, 2-H); 13C-NMR (100 MHz, CDCl3)
: 48.1, 50.3, 56.2, 107.0, 110.7, 113.1, 115.7, 118.4, 124.1, 125.3, 140.0, 142.3, 144.5, 145.4, 145.7,
146.6, 147.8, 157.6; IR (KBr) : 1591, 1516, 1273, 1236, 1202 cm-1; MS (EI) m/z: 377 (M+, 100), 253 (8),
226 (28), 150 (48), 123 (36); Anal. Calcd for C22H10FN3O2・1/4 H2O: C, 69.19; H, 5.41; N, 11.00. Found:
C, 69.46; H, 5.55; N, 10.98.
(E)-1-(4-(4-Fluorophenyl)piperazin-1-yl)-3-phenylprop-2-en-1-one (8i): pale yellow solid; yield 77%;

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187
1
mp 170.0-172.5 ˚C; H-NMR (400 MHz, CDCl3) : 3.13-3.15 (4H, m, piperazine), 3.85 (4H, br s,
piperazine), 6.87-6.92 (3H, m, PhCH=CH, Ph-H), 6.96-7.01 (2H, m, Ph-H), 7.34-7.41 (3H, m, Ph-H),
13
7.52-7.55 (2H, m, Ph-H), 7.70 (1H, d, J = 15.4 Hz, PhCH=CH); C-NMR (100 MHz, CDCl3): 42.2,
45.9, 50.5, 50.8, 115.6, 115.8, 116.9, 118.5, 118.6, 127.7, 128.8, 129.7, 135.2, 143.1, 147.6, 147.6, 156.4,
158.8, 165.5; MS (EI) m/z: 310 (M+, 86), 179 (27), 150 (100), 131 (21), 103 (19); HRMS (EI) m/z:
310.1480 (Calcd for C19H19FN2O, 310.1481).
4-(4-(2-Fluorophenyl)piperazin-1-yl)-6-methoxybenzo[b]furo[3,2-b]pyridine (2j): PTLC with
[CHCl3/AcOEt (5:2) and hexane/AcOEt (1:50)]; pale yellow solid; yield 57%; mp 165.5-168.5 ˚C;
1H-NMR (400 MHz, CDCl3) : 3.33 (4H, t, J = 5.0 Hz, piperazine), 3.87 (4H, t, J = 5.0 Hz, piperazine),
4.05 (3H, s, OCH3), 6.74 (1H, d, J = 5.5 Hz, 3-H), 6.95-7.11 (4H, m, Ph-H), 7.04 (1H, dd, J = 8.0 and 0.9
Hz, 7-H), 7.32 (1H, t, J = 7.9 Hz, 8-H), 7.78 (1H, dd, J = 7.7 and 1.1 Hz, 9-H), 8.38 (1H, d, J = 5.9 Hz,
13
2-H); C-NMR (100 MHz, CDCl3) : 48.2, 50.4, 50.4, 56.2, 107.0, 110.7, 113.0, 116.1, 116.4, 119.1,
119.1, 122.9, 123.9, 124.0, 124.5, 124.6, 125.4, 139.7, 139.9, 140.0, 142.4, 144.5, 145.4, 145.7, 146.7,
154.6, 157.1; IR (KBr) : 2833, 1597, 1499, 1270, 1198, 990 cm-1; MS (EI) m/z: 377 (M+, 100), 226 (36),
150 (58); Anal. Calcd for C22H20FN3O2・3/10 H2O: C, 68.94; H, 5.42; N, 11.01. Found: C, 67.22; H, 5.34;
N, 10.82.
(E)-1-(4-(2-Fluorophenyl)piperazin-1-yl)-3-phenylprop-2-en-1-one (8j): pale yellow solid; yield 89%;
mp 111.6-112.6 ˚C; 1H-NMR (400 MHz, CDCl3) : 3.11 (4H, t, J = 5.1 Hz, piperazine), 3.84-3.89 (4H, m,
piperazine), 6.91 (1H, d, J = 15.4 Hz, PhCH=CH), 6.91-7.09 (4H, m, Ph-H), 7.32-7.40 (3H, m, Ph 3, 4,
5-H), 7.50-7.56 (2H, m, Ph 2, 6-H), 7.70 (1H, d, J = 15.4 Hz, PhCH=CH); 13C-NMR (100 MHz,
CDCl3): 42.3, 46.1, 50.4, 51.1, 116.2, 116.4, 117.0, 119.3, 119.3, 123.1, 123.2, 124.5, 124.6, 127.7,
128.8, 129.7, 135.3, 139.5, 139.6, 143.0, 154.6, 157.1, 165.5; MS (EI) m/z: 310 (M+, 63), 150 (100), 131
(17), 103 (18); HRMS (EI) m/z: 310.1481 (Calcd for C19H19FN2O, 310.1481).
6-Methoxy-4-(N,N-diethylamino)benzo[b]furo[3,2-b]pyridine (2k): PTLC with [CHCl3/AcOEt (5:2)];
yellow oil; yield 64%; 1H-NMR (400 MHz ; CDCl3) : 1.32 (6H, t, J = 7.3 Hz, CH2CH3), 3.73(4H, q, J =
7.3 Hz, CH2CH3), 4.05 (3H, s, OCH3), 6.51 (1H, d, J = 5.8 Hz, 3-H), 7.01 (1H, dd, J = 8.0 and 1.1 Hz,
7-H), 7.29 (1H, t, J = 8.1 Hz, 8-H), 7.77 (1H, dd, J = 8.8 and 1.1 Hz, 9-H), 8.25 (1H, d, J = 5.9 Hz, 2-H);
13C-NMR (100 MHz, CDCl3): 13.3, 45.4, 56.4, 105.1, 110.8, 113.1, 123.6, 125.6, 138.4, 140.8, 143.8,
145.2, 145.6, 146.2; IR (KBr) : 2969, 1597, 1434, 1202, 1069 cm-1; MS (EI) m/z: 270 (M+, 25), 255 (58),
156 (49), 91 (50), 61 (100), 43 (56); Anal. Calcd for C16H18N2O2・1/2 H2O: C, 68.80; H, 6.96; N, 10.03.
Found: C, 68.80; H, 6.78; N, 9.86.
6-Methoxy-4-(N-pyridin-4-ylmethylamino)benzo[b]furo[3,2-b]pyridine
(2l):
PTLC
with
1
[CHCl3/MeOH (10:1) and (10:3)]; brown oil; yield 45%; H-NMR (400 MHz, CDCl3) : 4.07 (3H, s,

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OCH3), 4.61 (2H, d, J = 5.8 Hz, CH2), 5.38 (1H, t, J = 5.9 Hz, NH), 6.46 (1H, d, J = 5.5 Hz, 3-H), 7.06
(1H, dd, J = 8.1 and 0.8 Hz, 7-H), 7.31 (2H, d, J = 5.9 Hz, 3’,5’-H), 7.34 (1H, t, J = 7.9 Hz, 8-H), 7.78
(1H, dd, J = 7.9 and 0.9 Hz, 9-H), 8.29 (1H, d, J = 5.5 Hz, 2-H), 8.60 (2H, dd, J = 4.4 and 0.8 Hz,
13
2’,6’-H); C-NMR (100 MHz, CDCl3): 45.88, 56.18, 103.25, 110.26, 113.25, 121.90, 124.20, 125.78,
138.49, 139.34, 142.83, 145.65, 145.68, 146.89, 146.93, 150.26; IR (KBr) : 3256, 1642, 1611, 1345,
1198, 1055 cm-1; MS (EI) m/z: 305 (M+, 100), 227 (37), 212 (18), 186 (17); Anal. Calcd for C18H15N3O2:
C, 70.81; H, 4.95; N, 13.76. Found: C, 70.68; H, 4.99; N, 13.54.
6-Methoxy-4-(N-thiophen-2-ylmethylamino)benzo[b]furo[3,2-b]pyridine
(2m):
PTLC
with
[CHCl3/AcOEt (1:1)]; yellow solid; yield 65%; mp 160.4-163.3 ˚C; 1H-NMR (400 MHz, CDCl3) : 4.05
(3H, s, OCH3), 4.73 (2H, dd, J = 5.4 and 0.7 Hz, CH2), 5.24 (1H, t, J = 5.4 Hz, NH), 6.66 (1H, d, J = 5.4
Hz, 3-H), 6.98 (1H, dd, J = 5.1 and 3.3 Hz, thiophene-H), 7.03 (1H, dd, J = 8.0 and 0.7 Hz, 7-H),
7.06-7.07 (1H, m, thiophene-H), 7.25 (1H, dd, J = 5.1 and 1.5 Hz, thiophene-H), 7.32 (1H, t, J = 7.9 Hz,
8-H), 7.77 (1H, dd, J = 7.9 and 1.0 Hz, 9-H), 8.34 (1H, d, J = 5.5 Hz, 2-H); 13C-NMR (100 MHz, CDCl3)
: 42.1, 56.2, 103.3, 110.2, 113.2, 124.1, 125.3, 125.9, 126.0, 127.1, 138.6, 139.6, 140.5, 142.7, 145.6,
145.7, 146.94; IR (KBr) : 3263, 1638, 1488, 1267, 1198 cm-1; MS (EI) m/z: 310 (M+, 71), 97 (100); Anal.
Calcd for C17H14N2O2・1/2 H2O: C, 63.93; H, 4.73; N, 8.77. Found: C, 63.89; H, 4.51; N, 8.62.
1
N-(Thiophen-2-ylmethyl)cinnamamide (8m): yellow solid; yield 68%; mp 115.1-118.0 ˚C; H-NMR
(400 MHz, CDCl3) : 4.74 (2H, d, J = 5.5 Hz, CH2), 6.01 (1H, br s, NH), 6.39 (1H, d, J = 15.4 Hz,
PhCH=CH), 6.95 (1H, dd, J = 5.2 and 3.3 Hz, thiophene-H), 7.00-7.02 (1H, m, thiophene-H), 7.23 (1H,
dd, J = 5.2 and 1.1 Hz, thiophene-H), 7.33-7.38 (3H, m, Ph 3, 4, 5-H), 7.47-7.49 (2H, m, Ph 2, 6-H), 7.66
(1H, d, J = 15.4Hz, PhCH=CH); 13C-NMR (100 MHz, CDCl3): 38.5, 120.2, 125.3, 126.2, 126.9, 127.8,
128.8, 129.8, 134.8, 140.8, 141.6, 165.5; MS (EI) m/z: 243 (M+, 100), 131 (67), 112 (20), 103 (45), 77
(29); HRMS (EI) m/z: 243.0720 (Calcd for C14H13NOS, 243.0718).
6-Methoxy-4-(N-phenylamino)benzo[b]furo[3,2-b]pyridine (2n): PTLC with [CHCl3/AcOEt (10:1)];
1
cream solid; yield 94%; mp 147.6-149.7 ˚C; H-NMR (400 MHz; CDCl3) : 4.09 (3H, s, OCH3), 6.71
(1H, s, NH), 7.08 (1H, dd, J = 8.7 and 0.7 Hz, 7-H), 7.13 (1H, d, J = 5.9 Hz, 3-H), 7.18 (1H, t, J = 8.4 Hz,
8-H), 7.31-7.44 (5H, m, Ph-H), 7.80 (1H, dd, J = 7.7 and 0.7 Hz, 9-H), 8.35 (1H, d, J = 5.5 Hz, 2-H);
13C-NMR (100 MHz, CDCl3): 56.2, 104.5, 110.4, 113.2, 121.5, 124.2, 124.3, 125.8, 129.6, 136.6, 138.9,
139.1, 143.5, 145.6, 145.7, 146.7; IR (KBr) : 3406, 1638, 1601, 1502, 1430, 1273 cm-1; MS (EI) m/z:
290 (M+, 100), 289 (11), 219 (7), 247 (5); Anal. Calcd for C18H14N2O2・1/3 H2O: C, 72.96; H, 4.99; N,
9.45. Found: C, 72.92; H, 4.74; N, 9.25.
6-Methoxy-4-(N-4-fluorophenylamino)benzo[b]furo[3,2-b]pyridine (2o): PTLC with [CHCl3/AcOEt
1
(5:2)]; reddish brown solid; yield 50%; mp 160.2-163.9 ˚C; H-NMR (400 MHz, CDCl3) : 4.09 (3H, s,

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189
OCH3), 6.60 (1H, br s, NH), 6.95 (1H, d, J = 5.5 Hz, 3-H), 7.07-7.14 (3H, m, 7, 3’, 5’-H), 7.29 (2H, dd, J
= 9.0 and 4.6 Hz, 2’, 6’-H), 7.36 (1H, t, J = 7.9 Hz, 8-H), 7.80 (1H, dd, J = 7.3 and 0.7 Hz, 9-H), 8.34 (1H,
13
d, J = 5.9 Hz); C-NMR (100 MHz, CDCl3): 56.2, 104.2, 110.5, 113.3, 116.5, 124.3, 124.3, 125.8,
134.9, 137.1, 138.8, 143.6, 145.7, 145.8, 146.8, 159.9; IR (KBr) : 3645, 1642, 1560, 1509, 1273, 1205
cm-1; MS (EI) m/z: 308 (M+, 100.00), 293 (6.36), 237 (10.89); Anal. Calcd for C18H13FN2O2: C, 70.12; H,
4.25; N, 9.09. Found: N, 69.99; H, 4.11; N, 9.01.
6-Methoxy-4-(N-4-chlorophenylamino)benzo[b]furo[3,2-b]pyridine
(2p):
PTLC
with
1
[CHCl3/AcOEt(1:1)]; pale orange solid; yield 50%; mp 186.5-187.9 ˚C; H-NMR (400 MHz, CDCl3) :
4.09 (3H, s, OCH3), 6.66 (1H, br s, NH), 7.07 (1H, d, J = 5.9 Hz, 3-H), 7.09 (1H, dd, J = 8.0 and 1.1 Hz,
7-H), 7.26 (2H, d, J = 8.8 Hz, 2’, 6’-H), 7.35-7.39 (3H, m, 8, 3’, 5’-H), 7.80 (1H, dd, J = 7.9 and 1.0 Hz,
13
9-H), 8.37 (1H, d, J = 5.5 Hz, 2-H); C-NMR (100 MHz, CDCl3): 56.3, 104.7, 110.6, 113.3, 122.7,
124.3, 125.8, 129.5, 129.7, 136.2, 137.8, 139.0, 143.9, 145.7, 145.8, 146.8; IR (KBr) : 3329, 1642, 1594,
1492, 1386, 1198 cm-1; MS (EI) m/z: 326 (M+2, 33), 324 (M+, 100), 309 (5), 289 (2); Anal. Calcd for
C18H13BrN2O2: C, 58.56; H, 3.55; N, 7.59. Found: C, 58.42; H, 3.55; N, 7.46.
6-Methoxy-4-(N-4-bromophenylamino)benzo[b]furo[3,2-b]pyridine (2q): PTLC with [CHCl3/AcOEt
1
(10:1)]; yellow solid; yield 51%; mp 40.0-42.0 ˚C; H-NMR (400 MHz, CDCl3) : 4.09 (3H, s, OCH3),
6.66 (1H, br s, NH), 7.08-7.10 (2H, m, 3, 7-H), 7.20 (2H, d, J = 8.8 Hz, 2’, 6’-H), 7.37 (1H, t, J = 8.1 Hz,
8-H), 7.52 (2H, d, J = 8.8 Hz, 3’, 5’-H), 7.80 (1H, dd, J = 7.8 and 0.9 Hz, 9-H), 8.37 (1H, d, J = 5.1 Hz,
2-H); 13C-NMR (100 MHz, CDCl3): 56.2, 104.7, 110.5, 113.3, 116.9, 122.9, 124.3, 125.7, 132.7, 136.0,
138.3, 139.0, 143.9, 145.7, 145.8, 146.8; IR (KBr) : 3270, 1649, 1580, 1488, 1273, 1195 cm-1; MS (EI)
m/z: 370 (M+2, 98), 368 (M+, 100), 289 (9); Anal. Calcd for C18H13FN2O2・3/4 H2O: C, 67.18; H, 4.54; N,
8.70. Found: C, 69.86; H, 4.52; N, 8.56.
6-Methoxy-4-(N-3-fluorophenylamino)benzo[b]furo[3,2-b]pyridine (2r): PTLC with [CHCl3/AcOEt
1
(10:1)]; pale yellow solid; yield 65%; mp 141.6-145.8 ˚C; H-NMR (400 MHz, CDCl3) : 4.08 (1H, s,
OCH3), 6.79 (1H, br s, NH), 6.82-6.87 (1H, m, 4’-H), 7.03 (3H, m, 7-H and 5’, 6’-H), 7.18 (1H, d, J = 5.5
Hz, 3-H), 7.32-7.38 (2H, m, 8, 2’-H), 7.79 (1H, dd, J = 7.9 and 1.0 Hz, 9-H), 8.40 (1H, d, J = 5.5 Hz,
2-H); 13C-NMR (100 MHz, CDCl3): 56.2, 105.1, 107.9, 110.6, 110.8, 113.3, 116.4, 124.4, 125.7, 130.8,
135.7, 139.0, 141.0, 143.9, 145.7, 145.8, 146.7, 163.5; IR (KBr) : 3031, 1645, 1594, 1492, 1434, 1202
cm-1; MS (EI) m/z: 308 (M+, 100), 237 (12); Anal. Calcd for C18H13FN2O2・3/4 H2O; C, 67.18; H, 4.54; N,
8.70. Found: C, 69.86; H, 4.52; N, 8.56.
6-Methoxy-4-(N-methyl-N-phenylamino)benzo[b]furo[3,2-b]pyridine (2s): PTLC with [CHCl3/AcOEt
1
(10:1)]; pale yellow solid; yield 63%; mp 64.9-67.3 ˚C; H-NMR (400 MHz, CDCl3) : 3.75 (3H, s,
NCH3), 3.91 (3H, s, OCH3), 6.68 (1H, d, J = 5.5 Hz, 3-H), 7.02 (1H, dd, J = 7.9 and 1.0 Hz, 7-H),

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7.20-7.26 (3H, m, 2’, 4’, 6’-H), 7.30 (1H, t, J = 7.9 Hz, 8-H), 7.40 (1H, dd, J = 8.4 and 7.3 Hz, 3’, 5’-H),
13
7.77 (1H, dd, J = 7.9 and 0.9 Hz, 9-H), 8.28 (1H, d, J = 5.5 Hz, 2-H); C-NMR (100 MHz, CDCl3):
40.9, 56.7, 109.5, 112.1, 113.1, 123.9, 124.3, 125.1, 125.6, 129.5, 139.8, 141.0, 144.8, 145.5, 145.6, 146.1,
146.9; IR (KBr) : 3399, 1594, 1495, 1389, 1273 cm-1; MS (EI) m/z: 304 (M+, 100), 288 (4); Anal. Calcd
for C19H16N2O2・3/5H2O: C, 72.41; H, 5.50; N, 8.89. Found: C, 72.51; H, 5.34; N, 8.86.
ACKNOWLEDGEMENTS
The authors thank the staff of the Instrument Analysis Center of Mukogawa Women’s University for the
1H-NMR and MS measurements and elemental analyses.
REFERENCES
1. K. Gorlitzer, C. Kramer, and Ch. Boyle, Pharmazie, 2000, 55, 651.
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