A synthesis of 5-hetaryl-3-(2-hydroxybenzoyl)pyrroles

Article abstract of DOI:10.1016/j.tet.2008.04.041

A facile and versatile procedure for the synthesis of 5-hetaryl-3-(2-hydroxybenzoyl)-1H-pyrroles and 4-(2-hydroxybenzoyl)-1H-pyrrole-2-carboxylic acid derivatives was established on the basis of TMSCl promoted recyclization of 3-formylchromone with various hetarylmethylamines and glycine derivatives.

Full text of DOI:10.1016/j.tet.2008.04.041

Tetrahedron 64 (2008) 5933–5943
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A synthesis of 5-hetaryl-3-(2-hydroxybenzoyl)pyrroles
,
,
b
,
a,c
Andrey S. Plaskon a b, Sergey V. Ryabukhin a , Dmitriy M. Volochnyuk
,
*
Alexander N. Shivanyuk a b, Andrey A. Tolmachev b
,
a ‘Enamine Ltd’, 23 A. Matrosova Street, 01103 Kyiv, Ukraine
b National Taras Shevchenko University, 62 Volodymyrska Street, 01033 Kyiv, Ukraine
c Institute of Organic Chemistry, National Academy of Sciences of Ukraine, 5 Murmanska Street, 02094 Kyiv, Ukraine
a r t i c l e i n f o
a b s t r a c t
Article history:
A facile and versatile procedure for the synthesis of 5-hetaryl-3-(2-hydroxybenzoyl)-1H-pyrroles and
4-(2-hydroxybenzoyl)-1H-pyrrole-2-carboxylic acid derivatives was established on the basis of TMSCl
promoted recyclization of 3-formylchromone with various hetarylmethylamines and glycine derivatives.
Ó 2008 Elsevier Ltd. All rights reserved.
Received 9 January 2008
Received in revised form 20 March 2008
Accepted 10 April 2008
Available online 12 April 2008
Keywords:
3-Formylchromone
Pyrroles
Hetarylmethylamines
Recyclization
Chlorotrimethylsilane
1. Introduction
The primary objective of the present study was to develop a facile
and versatile method for the synthesis of previously unknown
The pyrrole structural unit is widely found in natural
biomolecules (porphins, aminoacids, etc.) and a variety of phar-
macologically active compounds.1 Pyrroles have been employed as
antioxidants,2a antibacterial,2b,c ionotropic,2d,e antitumor,2f
anti-inflammatory,2g,h and antifungal agents,2i P38 kinase,3a prolyl-
4-hydroxylase,3b poly(ADP-ribose) polymerase inhibitors,3c estro-
5-hetaryl-2-hydroxybenzoylpyrroles through the recyclization
reaction of 3-formylchromone 1 with various hetarylmethyl-
amines.
2. Results and discussion
gen receptor
b
selective ligands,3d AT1-selective angiotensin II
receptor antagonists,3e and minor groove recognition elements.3f,g
At present, a variety of synthetic approaches to substituted pyrroles
exist. However, a search of the literature for effective methods for
the synthesis of pyrrole libraries to be employed in high-through-
put screening remains a challenge of medicinal chemistry.
The Paal–Knorr reactions of 1,4-diketones and primary amines
have been used extensively for the synthesis of various pyrrole
derivatives.1 Another, method is based on the reaction of 1,3-CCC-
bielectrophiles with 1,2-CN-binucleophiles.4–6 Acid and base cata-
lyzed recyclization reactions of 3-formylchromone7 with primary
and secondary amines have been used for the synthesis of
3(2-hydroxybenzoyl)pyrroles containing chromyl and carboxyl
groups in position 5 of the pyrrole ring although in rather low yield
(10–30%).4 Apparently, these synthetic drawbacks hamper combi-
natorial synthesis of drug like 3(2-hydroxybenzoyl)pyrroles.
We have demonstrated that chlorotrimethylsilane (TMSCl) is
a convenient reagent for the condensation reactions of carbonyl
compounds9 and recyclizations of 3-formylchromones.8 Thus,
TMSCl was considered as a potential promoter and water scavenger
in the reaction of 3-formylchromone with hetarylmethylamines
and glycine derivatives.
2.1. Reaction with primary hetarylmethylamines
3-Formylchromone 1 reacted with hetarylmethylamines 2 (DMF,
100 ꢀC, molar ratio 1:2) in the presence of 4 molar equiv of TMSCl to
give 5-hetaryl-1H-pyrrol-3-yl](2-hydroxyphenyl)methanones 3 in
68–91% yields (Scheme 1). The reaction between 1 and 2 strongly
depends on their molar ratio, such that at a 2:1 ratio, fused
chromonepyrroles 4 were formed exclusively in moderate yields.
The reaction of 1 with representative amines 2c,d, 2f–h, and 2l at
a 1:1 initial molar ratio gave mixtures of the corresponding pyrroles
3 and chromonopyrroles 4.
* Corresponding author. Tel.: þ380442289652; fax: þ380445373253.
E-mail address: ryabukhin@mail.enamine.net (S.V. Ryabukhin).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.04.041

5934
A.S. Plaskon et al. / Tetrahedron 64 (2008) 5933–5943
OH
2.3. Reaction with glycine derivatives
O
O
O
i
Het
O
Het
The TMSCl mediated [3þ3] cyclocondensation of 1 with glycine
derivatives 7 afforded pyrrole derivatives 8 in moderate yields
(Scheme 3). It should be noted that the use of TMSCl in the reaction
of glycine 7a avoided the previously described decarboxylation.4a–d
Compounds 8a,c,d were purified by precipitation of the crude
product with water followed by simple recrystallization, whereas
preparative HPLC was used for purification of pyrroles 8b and 8e.
+
NH2
N
H
1
2a-o
3a-o
Yields = 68-91%
O
O
O
Het
i
Het
O
N
+
2
NH2
O
O
1
2g,h
4g,h
OH
O
O
O
X
X
i
Yields = 54%, 64%
O
+
N
H
R
O
O
N
N
N
R
O
Me
N
N
7a-e
N
1
8a-e
N
N
a: X = OH, R = H (55%) b: X = OMe, R = Me (43%) c: X = NMe2, R = H (68%)
d: X = N(CH2)4, R = H (61%) e: X = NEt2, R = Me (45%)
N
N
S
g
N
d
H
m
a
j
Scheme 3. Reagents and conditions: (i) 4 equiv Me3SiCl, DMF, 100 ꢀC, 12–15 h.
N
N
N
N
N
The reaction of formylchromone 1 with N1,N2-dimethylglyci-
N
N
N
N
Me
namide or
L
-prolinamide proceeds as a [4þ1] recyclization10 and
S
N
OH
n
results in 9a (79%) and 9b (84%), respectively (Scheme 4).
The TMSCl mediated pyrrole synthesis is applicable to the fusion
of the pyrrole and the dihydroquinoxaline rings. The reaction of 3,4-
dihydroquinoxalin-2(1H)-one 10a or its sulfamide derivative 10b
gave the previously unknown 2-(2-hydroxybenzoyl)pyrrolo[1,2-
a]quinoxalin-4(5H)-ones 11a,b in 52 and 58% yields, respectively
(Scheme 4).
h
k
e
CF3
b
N
N
N
N
Cl
Ph
N
N
N
N
N
c
N
N
O
o
Me
i
l
f
CF3
Scheme 1. Reagents and conditions: (i) 4 equiv Me3SiCl, DMF, 100 ꢀC, 6–15 h.
2.4. Structure determination
2.2. Reaction with secondary hetarylmethylamines
The composition and structure of all the compounds obtained
were determined by LCMS, elemental analysis, 1H, 13C NMR and IR
spectroscopy. The signals in 1H and 13C NMR spectra were assigned
on the basis of 1H–13C HMQC and HMBC 2D NMR spectra of
representative compounds.
The reactions of formylchromone 1 with secondary hetaryl-
amines 5 (DMF, TMSCl, 100 ꢀC) led to [5-hetaryl-1-alkyl-1H-pyrrol-
3-yl](2-hydroxyphenyl)methanones 6 (Scheme 2) independent of
the molar ratio of reagents since the formation of compounds 4 is
not possible in this case.
The 1H NMR spectra of compounds 3 contain a characteristic set
of signals for the protons of ortho-acylated phenol ring and two
OH
O
O
Het
i
O
Het
R
+
N
H
N
R
O
5a-u
6a-u
1
O
j (R = Me, 99%)
k (R = Et, 99%)
N
O
N
l (R = i-Pr, 96%)
m (R = Bu, 89%)
n (R = sec-Bu, 91%)
o (R = (CH2)2OMe, 97%)
p (R = (CH2)2NMe2, 85%)
q (R = tetrahydrofuran-2-ylmethyl, 88%)
r (R = Bn, 99%)
N
R'
NH
a (R = Me, R' = H, 88%)
N
b (R = Me, R' = CHF2, 92%)
O
f (R = Me, 70%)
N
N
N
O
N
R1
s (R = Et, R1 = H, R2 = Cl, 99%)
t (R = Et, R1 = R2 = OMe, 82%)
c (R = Me, 65%)
NH
g (R = Me, 84%)
N
N
R2
N
O
N
N
S
d (R = Me, 71%)
h (R = Me, 61%)
S
NH
N
N
N
N
Ph
i (R = i-Pr, 83%)
O
O
u (R = Me, 97%)
e (R = i-Pr, 95%)
Scheme 2. Reagents and conditions: (i) 4 equiv Me3SiCl, DMF, 100 ꢀC, 6–15 h.

A.S. Plaskon et al. / Tetrahedron 64 (2008) 5933–5943
5935
10a,b
H
N
H
7g
R
O
O
R
N
NH2
O
O
O
O
N
H
N
N
O
N
i
i
11a,b
O
O
N
O
1
H
7f
O
9b (84%)
OH
i
N
H
N
H
a: R = H (52%)
b: R = SO2N(CH2)5 (58%)
O
N
O
N
O
9a (79%)
Scheme 4. Reagents and conditions: (i) 4 equiv Me3SiCl, DMF, 100 ꢀC, 15 h.
doublets (4JHH¼0.9–2.0 Hz) or broadened singlets for the protons of
the pyrrole fragment. The signals of the OH group appear in the
range of 10.9–11.3 ppm (DMSO-d6) and are magnetically deshiel-
ded due to the formation of the stable intramolecular hydrogen
bond to the adjacent carbonyl group. The NH protons of the pyrrole
ring emerge at 12.3–12.9 ppm (DMSO-d6). The 1H NMR spectra of
N-substituted pyrroles 6, 8, and 11 are similar to those of com-
pounds 3 except they do not contain the signals of the NH protons.
The 1H NMR spectra of compounds 4 contain a double set of
signals for the ortho-substituted aryl rings of the non-equivalent
chromone residues, a singlet for the methylene protons (3.85,
3.98 ppm) and two singlets of the pyrrole and pyranone fragments
(at 8.47, 8.62 and 8.76, 8.89 ppm, respectively) whereas no signal
was detected for the phenolic OH group. The structure of com-
by Iwasaki et al.11 Alkylation of the amine by 12a is likely to result in
compound 13, which can undergo retro-Michael reaction to give
enaminal 14. The TMSCl mediated intramolecular Knoevenagel
condensation9d of 14 to give 15 followed by hydrolysis would likely
givepyrroles3 and6. Anotherpossiblereactionpathwayinvolves the
activation of aldehyde group of 1 with TMSCl to give intermediate
12b. Reaction of amines with 12b could give rise to intermediate 16,
which can be transformed into compound 17 through the activation
of the keto group with TMSCl followed by retro-Michael reaction and
elimination of TMSOH. The formation of compounds 4 may proceed
through the alkylation of the primary amine with 2 mol of 12b
leading to intermediate 18. Elimination of TMSOH and intra-
molecular ring closure of the pyrrole ring can lead to 4.
pound 4 was unambiguously proved by the characteristic 1H–13
C
3. Conclusions
HMQC and HMBC correlations. Furthermore NOESY correlations
between the methylene protons and the proton of the pyrrole ring
are also in keeping with the proposed structure of compounds 4.
In conclusion, we have elaborated an efficient methodology for
the preparation of 5-hetaryl-3-(2-hydroxybenzoyl)pyrroles and
4-(2-hydroxybenzoyl)-1H-pyrrole-2-carboxylic acid derivatives
from 3-formylchromone, hetarylmethylamines, and glycine de-
rivatives using Me3SiCl as a promoter and water scavenger. This
allows simple insertion of hetaryl residues at position 2(5) of the
pyrrole ring, which previously has been achieved through com-
plicated multistep procedures. The methodology is applicable to
a wide variety of hetarylmethylamines and affords target com-
pounds in preparative yields using simple purification procedure.
2.5. A possible mechanism
A possible mechanism for the TMSCl mediated formation of
pyrroles 3, 4, and 6 is outlined in Scheme 5. TMSCl can activate
3-formylchromone 1 through addition to the C]O bonds. The
addition to the ketone bond may result in O-trimethylsilyl-3-for-
mylchromone chloride12a, whichhaspreviously been characterized
Me3Si
SiMe3
O
O
O
O
TMSCl
2, 5
O
O
H2O
O
O
3, 6
Het
-(TMS)2O
-HCl
-HCl
-(TMS)2O
-HCl
Het
O+
O
N
R'
Het
O
13
N
R'
N
R'
O
SiMe3
Cl-
12a
Me3Si 14
15
TMSCl
Me3Si
-(TMS)2O
-HCl
SiMe3
O
N
R'
TMSCl
-HCl
O
17
Het
O
O
OSIMe3
Me3Si
O
O
+
2, 5
-HCl
R'
N
Me3Si
Cl-
O
O
O
Het
12b
16
12b
N
O
Het
2TMSCl
R' = H
4
O
Me3Si
18
O
O
-2(TMS)2O
-HCl
Scheme 5.

5936
A.S. Plaskon et al. / Tetrahedron 64 (2008) 5933–5943
This synthetic methodology can also be used for the generation of
highly diverse combinatorial sets of novel pyrrole derivatives,
which exhibit a range of biological activities.
131.5 (5-Cpyrrole), 132.2 (3a,7a-CBIm), 134.1 (4-CAr), 142.9 (2-CBIm),
158.5 (2-CAr), 191.4 (C]O). IR (KBr), nmax (cmꢁ1): 3367 (br, OH, NH),
3122, 3101, 3057, 2970, 2881, 1639 (C]O), 1589, 1464, 1377, 1342,
1244, 1219, 1149, 893, 752, 708. APSI MS: Mþþ1¼304. Anal. Calcd
for C18H13N3O2: C, 71.28; H, 4.32; N, 13.85. Found: C, 71.45; H, 4.21;
N, 13.79.
4. Experimental
4.1. General
4.2.2. (2-Hydroxyphenyl)[5-(1-methyl-1H-benzimidazol-2-yl)-1H-
pyrrol-3-yl]methanone (3b)
All chemicals were obtained from commercially available sour-
ces and used without further purification (Aldrich, Fluka, ‘Enamine
Ltd’). DMF for the reactions was freshly distilled and dried by
standard methods, monitoring of water content in solvents (all
solvents have <0.05%, usually 0.02% of water) was performed using
Mettler Toledo DL31 KF Titrator. All solvents for the crystallizations
were used without additional purification.
Light green solid (577 mg, 91%); mp 261–262 ꢀC (EtOH/DMF). 1H
NMR (400 MHz, DMSO-d6):
d
¼4.01 (s, 3H, NCH3), 6.92–7.03 (m, 2H,
3
3,5-HAr), 7.25 (m, 3H, 5,7-HBIm, 2-Hpyrrole), 7.45 (t, JHH¼7.9 Hz, 1H,
3
4-HAr), 7.53 (s, 1H, 4-Hpyrrole), 7.63 (dþt, JHH¼7.9 Hz, 2H, 6-HAr
,
6-HBIm), 7.73 (d, 3JHH¼7.9 Hz,1H, 4-HBIm),11.13 (s,1H, OH),12.64 (br s,
1H, NH).13C NMR (125 MHz, DMSO-d6):
d¼31.9 (CH3),110.8 (7-CBIm),
Melting points were measured with a Buchi melting points
apparatus and are uncorrected. The 1H NMR spectra (400 and
500 MHz) were recorded on a Varian Mercury-400 spectrometer
and Bruker Avance DRX 500 spectrometer with TMS as an internal
standard. 13C NMR spectra (125 MHz) and 2D NMR experiments
were recorded on a Bruker Avance DRX 500 spectrometer with TMS
as an internal standard. 19F NMR spectra (470 MHz) were recorded
on a Bruker Avance DRX 500 spectrometer with CFCl3 as an internal
standard. NMR experiments were recorded on a Bruker Avance DRX
500 spectrometer. LC/MS spectra were recorded using chroma-
tography/mass spectrometric system that consists of high-perfor-
mance liquid chromatograph ‘Agilent 1100 Series’ equipped with
diode-matrix and mass-selective detector ‘Aligent LC/MSD SL’.
According to HPLC–MS and 1H NMR data all the synthesized
compounds have purity >95%. IR spectra were recorded on
a Nexus-470 spectrometer for samples in KBr discs. Microanalyses
were performed in the Microanalytical Laboratory of the Institute
of Organic Chemistry, National Academy of Sciences of Ukraine.
Commercially unavailable hetarylmethylamines 2g,12a 2i and
5i,12b 2m–o,12c 5a,b,e,12d 5f,12e 5j–t12f were prepared according to
literature.
111.2 (4-Cpyrrole), 117.6 (3-CAr), 118.9 (4-CBIm), 119.5 (5-CAr), 122.5
(6-CBIm), 122.7 (5-CBIm), 123.8 (3-Cpyrrole), 124.3 (1-CAr), 125.5 (2-
Cpyrrole),129.2 (5-Cpyrrole),131.0 (6-CAr),134.0 (4-CAr),136.9 (7a-CBIm),
142.7 (2-CBIm), 146.3 (3a-CBIm), 159.0 (2-CAr), 191.9 (C]O). IR (KBr),
nmax (cmꢁ1): 3650–3100 (br, OH, NH), 3057, 3034, 2956,1614 (C]O),
1578,1487,1441,1385,1342,1271,1213,1134, 949, 891, 818, 798, 760,
741, 706, 677. APSI MS: Mþþ1¼318. Anal. Calcd for C19H15N3O2: C,
71.91; H, 4.76; N, 13.24. Found: C, 71.75; H, 4.87; N, 13.19.
4.2.3. (2-Hydroxyphenyl)(5-pyridin-2-yl-1H-pyrrol-3-yl)meth-
anone hydrochloride (3c)
Light green solid (529 mg, 88%); mp 146–147 ꢀC (MeCN). 1H
NMR (500 MHz, DMSO-d6):
d
¼6.93–6.99 (m, 2H, 3,5-HAr), 7.24 (m,
1H, 5-HPy), 7.27 (s,1H, 2-Hpyrrole), 7.44 (m, 2H, 4-Hpyrrole, 4-HAr), 7.72
(d, 3JHH¼7.9 Hz, 1H, 6-HAr), 7.81 (t, 3JHH¼7.9 Hz, 1H, 4-HPy), 7.88 (d,
3JHH¼7.9 Hz, 1H, 3-HPy), 8.55 (d, JHH¼4.6 Hz, 1H, 6-HPy), 11.22 (s,
3
1H, OH), 12.35 (s, 1H, NH). 13C NMR (125 MHz, DMSO-d6):
d
¼109.2
(4-Cpyrrole), 117.6 (3-CAr), 119.3 (3-CPy), 119.4 (5-CAr), 122.2 (3-Cpyr-
role), 123.9 (1-CAr), 125.4 (5-CPy), 128.6 (2-Cpyrrole), 131.0 (6-CAr),
133.3 (5-Cpyrrole), 134.0 (4-CAr), 137.7 (4-CPy), 149.3 (6-CPy), 150.0
(2-CPy), 159.3 (2-CAr), 192.2 (C]O). IR (KBr), nmax (cmꢁ1): 3226 (br,
OH, NH), 3138, 3051, 3007, 2983, 1618 (C]O), 1593, 1568, 1481,
1462, 1392, 1282, 1238, 1205, 1147, 893, 789, 754, 706, 673. APSI MS:
Mþþ1¼265. Anal. Calcd for C16H13ClN2O2: C, 63.90; H, 4.36; Cl,
11.79; N, 9.31. Found: C, 63.97; H, 4.30; Cl, 11.83; N, 9.34.
4.2. General procedure for the synthesis
of pyrroles 3, 6, 8, and 11
Hetarylmethylamines 2a–o, 5a–u or glycine derivatives 7a–e
and 10a,b (2a–o, 7a,c,dd4 mmol, 5a–u, 10a,bd2 mmol,
7b,ed2.6 mmol) and 3-formylchromone 1 (348 mg, 2 mmol) were
placed in 15 mL pressure tube and dissolved in DMF (2–4 mL).
Chlorotrimethylsilane (869 mg, 8 mmol) was added dropwise to
the solution. The tube was thoroughly sealed and heated on a
water-bath for 6–15 h. After cooling the flask was opened (caution!
excessive pressure inside) and the reaction mixture was poured into
water (15 mL) and allowed to stand at 20 ꢀC in an ultrasonic bath
for 1 h. The precipitate formed was filtered and washed with
a small amount of i-PrOH. Recrystallization from an appropriate
solvent yielded targeted compounds 3, 6, 8, and 11. Compounds 8b
and 8e were purified by preparative HPLC.
4.2.4. (2-Hydroxyphenyl)(5-pyridin-4-yl-1H-pyrrol-3-yl)meth-
anone hydrochloride (3d)
Yellow solid (427 mg, 71%); mp 184–185 ꢀC (MeCN). 1H NMR
3
(400 MHz, DMSO-d6):
d
¼6.95 (t, JHH¼8.3 Hz, 1H, 5-HAr), 7.01 (d,
3JHH¼8.3 Hz, 1H, 3-HAr), 7.45 (td, JHH¼8.3 Hz, JHH¼1.5 Hz, 1H,
3
4
3
4
4-HAr), 7.66 (dd, JHH¼8.3 Hz, JHH¼1.5 Hz, 1H, 6-HAr), 7.74 (m, 1H,
3
2-Hpyrrole), 7.80 (m, 1H, 4-Hpyrrole), 8.35 (d, JHH¼6.7 Hz, 2H, 3,5-
3
H
Py), 8.76 (d, JHH¼6.7 Hz, 2H, 2,6-HPy), 11.04 (s, 1H, OH), 13.33 (s,
1H, NH). 13C NMR (125 MHz, DMSO-d6):
d¼115.8 (4-Cpyrrole), 117.6
(3-CAr), 119.5 (5-CAr), 120.2 (3,5-CPy), 124.3 (1-CAr), 126.9 (3-Cpyrrole),
128.8 (2-Cpyrrole), 131.0 (6-CAr), 132.3 (5-Cpyrrole), 134.1 (4-CAr), 142.3
(2,6-CPy), 146.6 (4-CPy), 158.8 (2-CAr), 191.8 (C]O). IR (KBr), nmax
(cmꢁ1): 3650–3280 (br, OH, NH), 3145, 3051, 3043, 3032, 2991,
2935, 2900, 1633 (C]O), 1595, 1572, 1475, 1446, 1379, 1298, 1213,
1194, 1161, 893, 812, 766, 706, 690. APSI MS: Mþþ1¼265. Anal.
Calcd for C16H13ClN2O2: C, 63.90; H, 4.36; Cl,11.79; N, 9.31. Found: C,
63.86; H, 4.42; Cl, 11.80; N, 9.29.
Compounds 4g,h and 9a,b were obtained by the same
procedure.
4.2.1. [5-(1H-Benzimidazol-2-yl)-1H-pyrrol-3-yl](2-hydroxy-
phenyl)methanone (3a)
Gray solid (503 mg, 83%); mp 224–225 ꢀC (EtOH/DMF). 1H NMR
3
(500 MHz, DMSO-d6):
d
¼6.96 (t, JHH¼8.2 Hz, 1H, 5-HAr), 7.01 (d,
4.2.5. (2-Hydroxyphenyl)[5-(2-hydroxypyridin-4-yl)-1H-
pyrrol-3-yl]methanone (3e)
3JHH¼8.2 Hz, 1H, 3-HAr), 7.43–7.49 (m, 3H, 4-HAr, 5,6-HBIm), 7.62 (d,
3JHH¼8.2 Hz, 1H, 6-HAr), 7.71 (s, 1H, 2-Hpyrrole), 7.74 (m, 2H,
4,7-HBIm), 7.90 (s, 1H, 4-Hpyrrole), 8.52 (br s, 1H, NH), 10.88 (br s, 1H,
Pale yellow solid (459 mg, 82%); mp 292 ꢀC (EtOH/DMF). 1H
NMR (400 MHz, DMSO-d6):
d
¼6.57 (d, 3JHH¼7.0 Hz, 1H, 5-HPy), 6.67
OH), 13.00 (s, 1H, NH). 13C NMR (125 MHz, DMSO-d6):
d
¼114.1
(4,7-CBIm), 116.5 (4-Cpyrrole), 117.6 (3-CAr), 118.3 (3-Cpyrrole), 119.5 (5-
Ar), 124.6 (1-CAr), 125.8 (5,6-CBIm), 126.5 (2-Cpyrrole), 130.7 (6-CAr),
(s, 1H, 3-HPy), 6.91–7.01 (m, 2H, 3,5-HAr), 7.18 (s, 1H, 2-Hpyrrole), 7.34
(d, 3JHH¼7.0 Hz, 1H, 6-HPy), 7.45 (t, JHH¼7.7 Hz, 1H, 4-HAr), 7.59 (s,
3
3
C
1H, 4-Hpyrrole), 7.73 (d, JHH¼7.7 Hz, 1H, 6-HAr), 11.24 (s, 1H, OH),

A.S. Plaskon et al. / Tetrahedron 64 (2008) 5933–5943
5937
11.35 (br s, 1H, OH), 12.30 (s, 1H, NH). 13C NMR (125 MHz, DMSO-
d6):
¼102.5 (5-CPy), 111.1 (3-CPy), 112.0 (4-Cpyrrole), 117.6 (3-CAr),
4.2.9. (2-Hydroxyphenyl)[5-(4-methyl-4H-1,2,4-triazol-3-yl)-1H-
d
pyrrol-3-yl]methanone (3i)
119.5 (5-CAr), 123.7 (1-CAr), 125.5 (3-Cpyrrole), 129.6 (2-Cpyrrole), 130.7
(5-Cpyrrole), 131.2 (6-CAr), 134.2 (4-CAr), 135.9 (4-CPy), 142.9 (6-CPy),
159.4 (2-CAr), 163.2 (2-CPy), 192.2 (C]O). IR (KBr), nmax (cmꢁ1):
3650–3320 (br, OH), 3269 (NH), 3134, 2974, 2848, 1632 (C]O),
1595, 1564, 1524, 1487, 1443, 1421, 1336, 1267, 1213, 1555, 1136, 895,
841, 816, 766. APSI MS: Mþþ1¼281. Anal. Calcd for C16H13ClN2O3: C,
60.67; H, 4.14; Cl, 11.19; N, 8.84. Found: C, 60.80; H, 4.08; Cl, 11.15; N,
8.81.
Yellow solid (418 mg, 78%); mp 239–240 ꢀC (EtOH). 1H NMR
(500 MHz, DMSO-d6):
d
¼3.96 (s, 3H, NCH3), 6.94 (t, 3JHH¼8.1 Hz,1H,
5-HAr), 7.01 (d, 3JHH¼8.1 Hz, 1H, 3-HAr), 7.27 (s, 1H, 2-Hpyrrole), 7.43
3
3
(t, JHH¼8.1 Hz, 1H, 4-HAr), 7.63 (d, JHH¼8.1 Hz, 1H, 6-HAr), 7.64 (s,
1H, 4-Hpyrrole), 9.38 (s, 1H, 5-Htriazole), 10.99 (br s, 1H, OH), 12.90 (s,
1H, NH). 13C NMR (125 MHz, DMSO-d6):
d¼33.9 (CH3), 113.7
(4-Cpyrrole), 117.1 (3-Cpyrrole), 117.8 (3-CAr), 119.5 (5-CAr), 124.1
(1-CAr), 125.8 (5-Cpyrrole), 130.0 (2-Cpyrrole), 131.0 (6-CAr), 134.1 (4-
C
Ar), 145.5 (5-Ctriazole), 146.9 (3-Ctriazole), 159.1 (2-CAr), 191.8 (C]O).
4.2.6. (2-Hydroxyphenyl)[5-(2-pyrrolidin-1-ylpyridin-4-yl)-1H-
pyrrol-3-yl]methanone dihydrochloride (3f)
IR (KBr), nmax (cmꢁ1): 3410 (br, OH, NH), 3093, 2920, 1620 (C]O),
1595, 1485, 1444, 1363, 1269, 1209, 1151, 1065, 895, 812, 773. APSI
MS: Mþþ1¼269. Anal. Calcd for C14H12N4O2: C, 62.68; H, 4.51; N,
20.88. Found: C, 62.85; H, 4.38; N, 20.80.
Light green solid (601 mg, 74%); mp 227–228 ꢀC (MeCN). 1H
NMR (400 MHz, DMSO-d6):
d
¼2.03 (m, 4H, 2CH2), 3.59 (m, 4H,
2NCH2), 6.96 (t, 3JHH¼8.2 Hz, 1H, 5-HAr), 7.00 (d, 3JHH¼8.2 Hz, 1H, 3-
H
Ar), 7.31 (d, 3JHH¼7.6 Hz, 1H, 5-HPy), 7.45 (m, 2H, 6-HPy, 4-HAr), 7.55
4.2.10. [5-(6,7-Dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl)-1H-
pyrrol-3-yl](2-hydroxyphenyl)methanone (3j)
4
3
4
(d, JHH¼1.3 Hz, 1H, 2-Hpyrrole), 7.68 (dd, JHH¼7.6 Hz, JHH¼1.3 Hz,
1H, 6-HPy), 7.74 (d, 4JHH¼1.3 Hz, 1H, 4-Hpyrrole), 7.86 (d, 3JHH¼8.2 Hz,
Pale yellow solid (470 mg, 80%); mp 275–276 ꢀC (MeOH). 1H
1H, 6-HAr),11.10 (s,1H, OH),13.13 (s,1H, NH),13.19 (br s,1H, NH). 13
C
NMR (400 MHz, DMSO-d6):
d
¼2.73 (m, 2H, NCH2CH2), 2.88 (t,
NMR (125 MHz, DMSO-d6):
d
¼25.3, 49.0, 104.6 (3-CPy), 107.9 (5-
3JHH¼7.2 Hz, 2H, CH2), 4.19 (t, 3JHH¼7.2 Hz, 2H, NCH2), 6.92–7.00 (m,
3H, 3,5-HAr, 2-Hpyrrole), 7.45 (m, 2H, 4-Hpyrrole, 4-HAr), 7.70 (d,
3JHH¼7.5 Hz, 1H, 6-HAr), 11.12 (s, 1H, OH), 12.59 (s, 1H, NH). 13C NMR
C
Py), 114.0 (4-Cpyrrole), 117.6 (3-CAr), 119.5 (5-CAr), 124.1 (1-CAr), 126.1
(3-Cpyrrole), 129.5 (2-Cpyrrole), 130.9 (5-Cpyrrole), 131.0 (6-CAr), 134.1
(4-CAr), 136.6 (4-CPy), 144.2 (6-CPy), 150.3 (2-CPy), 159.0 (2-CAr),
191.9 (C]O). IR (KBr), nmax (cmꢁ1): 3640–3150 (br, OH, NH), 2926,
1653 (C]O), 1616, 1595, 1487, 1456, 1377, 1354, 1230, 1155, 941, 895.
APSI MS: Mþþ1¼334. Anal. Calcd for C20H21Cl2N3O2: C, 59.12; H,
5.21; Cl, 17.45; N, 10.34. Found: C, 59.20; H, 5.16; Cl, 17.40; N, 10.37.
(125 MHz, DMSO-d6):
d¼20.7 (NCH2CH2), 28.6 (CH2), 44.0 (NCH2),
108.8 (4-Cpyrrole), 117.6 (3-CAr), 119.5 (5-CAr), 121.5 (3-Cpyrrole), 124.0
(1-CAr), 125.2 (5-Cpyrrole), 128.8 (2-Cpyrrole), 131.0 (6-CAr), 134.0
(4-CAr), 143.9 (3-Ctriazole), 159.1 (2-CAr), 162.9 (5-Ctriazole), 191.9
(C]O). IR (KBr), nmax (cmꢁ1): 3650–3290 (br, OH, NH), 3130, 3055,
2966, 1614 (C]O), 1578, 1485, 1466, 1346, 1215, 1173, 891, 814, 756,
704. APSI MS: Mþþ1¼295. Anal. Calcd for C16H14N4O2: C, 65.30; H,
4.79; N, 19.04. Found: C, 65.41; H, 4.72; N, 19.01.
4.2.7. (2-Hydroxyphenyl)[5-(4-methyl-1,3-thiazol-2-yl)-1H-pyrrol-
3-yl]methanone (3g)
Light green solid (471 mg, 83%); mp 194–195 ꢀC (EtOH). 1H NMR
(500 MHz, DMSO-d6):
d
¼2.39 (s, 3H, CH3), 6.92–6.99 (m, 2H, 3,5-
4.2.11. (2-Hydroxyphenyl)[5-(6,7,8,9-tetrahydro-5H-[1,2,4]triazolo-
[4,3-a]azepin-3-yl)-1H-pyrrol-3-yl]methanone (3k)
H
Ar), 7.01 (s, 1H, 5-HTz), 7.21 (s, 1H, 2-Hpyrrole), 7.43 (m, 2H, 4-HAr
,
3
4-Hpyrrole), 7.67 (d, JHH¼7.5 Hz, 1H, 6-HAr), 11.09 (s, 1H, OH), 12.60
Pale yellow solid (438 mg, 68%); mp 216–217 ꢀC (EtOH). 1H NMR
(s, 1H, NH). 1H NMR (500 MHz, CDCl3):
d
¼2.45 (s, 3H, CH3), 6.81 (s,
(500 MHz, DMSO-d6):
d
¼1.63 (m, 2H, 5-HPHAz), 1.73 (m, 2H,
1H, 5-HTz), 6.94 (t, 3JHH¼8.1 Hz, 1H, 5-HAr), 7.05 (d, 3JHH¼8.1 Hz, 1H,
3-HAr), 7.15 (s, 1H, 2-Hpyrrole), 7.49 (t, 3JHH¼8.1 Hz,1H, 4-HAr), 7.50 (s,
1H, 4-Hpyrrole), 7.94 (d, 3JHH¼8.1 Hz, 1H, 6-HAr), 10.36 (br s, 1H, NH),
4-HPHAz), 1.82 (m, 2H, 6-HPHAz), 2.95 (m, 2H, 3-HPHAz), 4.17 (m, 2H,
7-HPHAz), 6.89 (s, 1H, 2-Hpyrrole), 6.95 (m, 2H, 3,5-HAr), 7.43 (t,
3JHH¼8.0 Hz, 1H, 4-HAr), 7.50 (s, 1H, 4-Hpyrrole), 7.68 (d, 3JHH¼8.0 Hz,
1H, 6-HAr), 11.10 (s, 1H, OH), 12.49 (s, 1H, NH). 13C NMR (125 MHz,
12.07 (s,1H, OH). 13C NMR (125 MHz, DMSO-d6):
d
¼17.3 (CH3),110.0
(4-Cpyrrole), 113.5 (5-CTz), 117.6 (3-CAr), 119.5 (5-CAr), 124.1 (1-CAr),
125.3 (3-Cpyrrole), 128.3 (5-Cpyrrole), 128.6 (2-Cpyrrole), 130.9 (6-CAr),
134.0 (4-CAr), 152.9 (4-CTz), 158.7 (2-CTz),158.9 (2-CAr), 191.8 (C]O).
IR (KBr), nmax (cmꢁ1): 3650–3310 (br, OH, NH), 3115, 3014, 2918,
1622 (C]O), 1593, 1512, 1483, 1454, 1390, 1362, 1273, 1238, 1190,
1161, 893, 814, 769, 719, 671. APSI MS: Mþþ1¼285. Anal. Calcd for
DMSO-d6):
d
¼25.6 (4-CPHAz), 26.3 (6-CPHAz), 28.4 (5-CPHAz), 30.2 (3-
CPHAz), 45.6 (7-CPHAz), 110.4 (4-Cpyrrole), 117.6 (3-CAr), 119.5 (5-CAr),
120.6 (3-Cpyrrole), 124.1 (1-CAr), 125.1 (5-Cpyrrole), 128.6 (2-Cpyrrole),
131.0 (6-CAr), 134.0 (4-CAr), 147.7 (3-CTriazole), 157.9 (5-CTriazole),
159.0 (2-CAr), 191.9 (C]O). IR (KBr), nmax (cmꢁ1): 3650–3300 (br,
OH, NH), 3107, 3039, 2941, 2916, 2899, 1622 (C]O), 1581, 1531,
1487, 1444, 1350, 1275, 1223, 1157, 897, 856, 816, 760, 706. APSI MS:
Mþþ1¼323. Anal. Calcd for C18H18N4O2: C, 67.07; H, 5.63; N, 17.38.
Found: C, 67.00; H, 5.67; N, 17.33.
C
15H12N2O2S: C, 63.36; H, 4.25; N, 9.85; S, 11.28. Found: C, 63.44; H,
4.34; N, 9.81; S, 11.31.
4.2.8. [5-(1,3-Benzothiazol-2-yl)-1H-pyrrol-3-yl](2-hydroxy-
phenyl)methanone (3h)
4.2.12. (2-Hydroxyphenyl)[5-(3-phenyl-1,2,4-oxadiazol-5-yl)-1H-
pyrrol-3-yl]methanone (3l)
Brown solid (499 mg, 78%); mp 170–171 ꢀC (EtOH/DMF). 1H
NMR (500 MHz, DMSO-d6):
d
¼6.93–7.01 (m, 2H, 3,5-HAr), 7.25 (m,
Beige solid (477 mg, 72%); mp 207–209 ꢀC (EtOH). 1H NMR
1H, 2-Hpyrrole), 7.38–7.48 (m, 2H, 5,6-HBTz), 7.51 (t, 3JHH¼7.8 Hz, 1H,
4-HAr), 7.58 (m, 1H, 4-Hpyrrole), 7.68 (d, 3JHH¼7.8 Hz, 1H, 6-HAr), 7.96
(d, 3JHH¼8.1 Hz, 1H, 7-HBTz), 8.09 (d, 3JHH¼8.1 Hz, 1H, 4-HBTz), 11.05
(s, 1H, OH), 12.95 (s, 1H, NH). 13C NMR (125 MHz, DMSO-d6):
(500 MHz, DMSO-d6):
d
¼6.99 (m, 2H, 3,5-HAr), 7.43 (d, 4JHH¼1.7 Hz,
3
1H, 2-Hpyrrole), 7.47 (t, JHH¼8.0 Hz, 1H, 4-HAr), 7.61 (m, 3H,
3,4,5-HPh), 7.66 (d, 3JHH¼8.0 Hz, 1H, 6-HAr), 7.76 (d, 4JHH¼1.7 Hz, 1H,
3
2-Hpyrrole), 8.08 (d, JHH¼7.8 Hz, 2H, 2,6-HPh), 10.94 (s, 1H, OH),
d
¼113.0 (4-Cpyrrole), 117.6 (3-CAr), 119.5 (5-CAr), 122.5 (7-CBTz), 122.8
13.24 (s, 1H, NH). 13C NMR (125 MHz, DMSO-d6):
d
¼115.8 (4-Cpyr-
(4-CBTz), 124.2 (1-CAr), 125.6 (6-CBTz), 125.8 (3-Cpyrrole), 127.1
(5-CBTz), 127.8 (2-Cpyrrole), 129.9 (5-Cpyrrole), 130.9 (6-CAr), 134.1 (4-
role), 117.6 (3-CAr), 118.0 (3-Cpyrrole), 119.6 (5-CAr), 124.4 (1-CAr), 126.3
(2-Cpyrrole), 126.6 (1-CPh), 127.6 (3,5-CPh), 129.7 (2,6-CPh), 130.9
(6-CAr), 131.1 (4-CPh), 132.1 (5-Cpyrrole), 134.1 (4-CAr), 158.6 (2-CAr),
168.4 (5-Coxadiazole), 169.6 (3-Coxadiazole), 191.5 (C]O). IR (KBr), nmax
(cmꢁ1): 3650–3320 (br, OH), 3240 (br, NH), 3128, 3062, 2926, 1637
(C]O), 1593, 1485, 1444, 1352, 1217, 1155, 897, 742, 690. APSI MS:
Mþþ1¼332. Anal. Calcd for C19H13N3O3: C, 68.88; H, 3.95; N, 12.68.
Found: C, 69.02; H, 3.83; N, 12.63.
C
Ar), 134.3 (7a-CBTz), 153.7 (3a-CBTz), 158.9 (2-CBTz), 159.3 (2-CAr),
191.7 (C]O). IR (KBr), nmax (cmꢁ1): 3650–3350 (br, OH), 3250 (br,
NH), 3061, 2926, 1620 (C]O), 1585, 1481, 1466, 1437, 1369, 1232,
1163, 922, 893, 758, 727, 706, 677. APSI MS: Mþþ1¼321. Anal. Calcd
for C18H12N2O2S: C, 67.48; H, 3.78; N, 8.74; S, 10.01. Found: C, 67.31;
H, 3.89; N, 8.81; S, 9.90.

5938
A.S. Plaskon et al. / Tetrahedron 64 (2008) 5933–5943
0
4.2.13. (2-Hydroxyphenyl)(5-[1,2,4]triazolo[4,3-a]pyridin-3-yl-1H-
pyrrol-3-yl)methanone (3m)
(5-CChr ), 126.9 (5-CChr), 128.0 (2-CChr), 128.8 (4-CTz), 129.7 (2-CTz),
0
0
134.7 (7-CChr ), 135.6 (7-CChr), 155.4 (2-Cpyrrole), 156.3 (8a-CChr ),
Light brown solid (547 mg, 90%); mp 283–284 ꢀC (EtOH). 1H
156.5 (8a-CChr), 159.1 (2-CChr ), 176.6 (C]OChr ), 176.7 (C]OChr). IR
(KBr), nmax (cmꢁ1): 3082, 2956, 2922, 1645 (C]O), 1616, 1574, 1466,
1398, 1350, 1319, 1217, 1153, 1103, 1045, 891, 760. APSI MS:
Mþþ1¼441. Anal. Calcd for C25H16N2O4S: C, 68.17; H, 3.66; N, 6.36;
S, 7.28. Found: C, 68.31; H, 3.55; N, 6.32; S, 7.37.
0
0
NMR (500 MHz, DMSO-d6):
d
¼6.93–7.01 (m, 2H, 3,5-HAr), 7.08 (t,
3JHH¼8.6 Hz, 1H, 6-HHet), 7.37 (s, 1H, 2-Hpyrrole), 7.45 (m, 2H, 4-HAr
,
7-HHet), 7.60 (s, 1H, 4-Hpyrrole), 7.75 (d, 3JHH¼7.8 Hz, 1H, 6-HAr), 7.85
(d, 3JHH¼8.6 Hz, 1H, 8-HHet), 8.71 (d, 3JHH¼7.8 Hz, 1H, 5-HHet), 11.18
(s, 1H, OH), 12.80 (s, 1H, NH). 13C NMR (125 MHz, DMSO-d6):
d
¼109.6 (8-CHet), 115.1 (6-CHet), 116.0 (4-Cpyrrole), 117.6 (3-CAr), 119.5
4.2.17. 2-(1,3-Benzothiazol-2-ylmethyl)-3-(4-oxo-4H-chromen-3-
yl)chromeno[2,3-c]pyrrol-9(2H)-one (4h)
(5-CAr), 120.1 (3-Cpyrrole), 124.0 (1-CAr), 125.0 (2-Cpyrrole), 125.5
(5-Cpyrrole), 128.4 (5-CHet), 129.1 (7-CHet), 131.1 (6-CAr), 134.1 (4-CAr),
140.4 (3-CHet), 150.1 (8a-CHet), 159.1 (2-CAr), 192.0 (C]O). IR (KBr),
nmax (cmꢁ1): 3650–3300 (br, OH, NH), 3134, 3059, 2900, 1635
(C]O), 1622, 1589, 1489, 1466, 1356, 1242, 1211, 1146, 1068, 893,
816, 750. APSI MS: Mþþ1¼305. Anal. Calcd for C17H12N4O2: C, 67.10;
H, 3.97; N, 18.41. Found: C, 66.97; H, 4.09; N, 18.35.
Green solid (609 mg, 64%); mp 298–299 ꢀC (EtOH/DMSO). 1H
NMR (500 MHz, DMSO-d6):
d
¼3.85 (s, 2H, CH2), 7.27 (m, 3H,
3
3
0
5,6,7-HBTz), 7.50 (t, JHH¼8.3 Hz, 1H, 6-HChr ), 7.59 (t, JHH¼8.3 Hz,
3
0
1H, 6-HChr), 7.67 (d, JHH¼8.3 Hz, 1H, 8-HChr ), 7.75–7.85 (m, 3H,
3
4
0
4-HBTz, 8-HChr, 7-HChr ), 7.91 (td, JHH¼8.1 Hz, JHH¼1.7 Hz, 1H,
3
4
0
7-HChr), 8.10 (dd, JHH¼8.1 Hz, JHH¼1.7 Hz, 1H, 5-HChr ), 8.16 (dd,
3JHH¼8.1 Hz, 4JHH¼1.7 Hz, 1H, 5-HChr), 8.47 (s, 1H, 2-Hpyrrole), 8.76 (s,
1
0
4.2.14. (2-Hydroxyphenyl){5-[6-(trifluoromethyl)[1,2,4]triazolo-
[4,3-a]pyridin-3-yl]-1H-pyrrol-3-yl}methanone (3n)
1H, 2-HChr ). H NMR (500 MHz, CF3COOD):
d
¼4.32 (s, 2H, CH2), 7.52
3
0
(t, JHH¼7.6 Hz, 1H, 5-HBTz), 7.62–7.72 (m, 3H, 6-HBTz, 6-HCh
,
Light brown solid (603 mg, 81%); mp 238–239 ꢀC (EtOH). 1H
6-HChr), 7.78 (m, 2H, 7-HBTz, 8-HChr ), 7.91 (m, 2H, 4-HBTz, 8-HChr),
0
3
3
0
NMR (400 MHz, DMSO-d6):
d
¼6.90–7.03 (m, 2H, 3,5-HAr), 7.47 (m,
7.97 (t, JHH¼7.6 Hz, 1H, 7-HChr ), 8.12 (t, JHH¼7.6 Hz, 1H, 7-HChr),
3
3
0
2H, 4-HAr, 2-Hpyrrole, 6-HAr), 7.65 (m, 2H, 4-Hpyrrole), 7.76 (d,
8.21 (d, JHH¼7.6 Hz, 1H, 5-HChr), 8.41 (d, JHH¼7.6 Hz, 1H, 5-HChr ),
3JHH¼7.8 Hz, 1H, 7-HHet), 8.05 (d, 3JHH¼7.8 Hz, 1H, 8-HHet), 8.91 (m,
8.61 (s, 1H, 2-Hpyrrole), 8.97 (s, 1H, 2-HChr ). 13C NMR (125 MHz,
0
1H, 5-HHet), 11.16 (s, 1H, OH), 12.80 (br s, 1H, NH). 13C NMR
CF3COOD):
C
d
¼21.9 (CH2), 109.1 (3-CChr ), 115.7 (7-CBTz), 118.5 (3-
0
2
0
(125 MHz, DMSO-d6):
6-CHet), 117.5 (4-Cpyrrole), 117.6 (3-CAr), 119.1 (3-Cpyrrole), 119.5 (5-
d
¼111.2 (8-CHet), 117.0 (q, JCF¼33.6 Hz,
Chr), 118.6 (8-CChr ), 118.7 (8-CChr), 121.7 (5-Cpyrrole), 122.0 (4a-CChr),
0
0
122.1 (4a-CChr ), 124.6 (4,6-CBTz), 125.7 (6-CChr), 126.8 (6-CChr ), 127.3
1
0
C
Ar), 123.8 (q, JCF¼271.1 Hz, CF3), 123.9 (1-CAr), 124.0 (5-Cpyrrole),
(5-CBTz), 128.0 (5-CChr ), 128.2 (2-CChr), 129.6 (5-CChr), 130.3 (7a-
125.3 (q, 3JCF¼6.7 Hz, 7-CHet), 125.5 (2-Cpyrrole), 129.5 (3-CHet), 131.1
C
BTz), 131.2 (3a-CBTz), 132.7 (2-CBTz), 136.2 (7-CChr ), 137.3 (7-CChr),
0
0
0
(6-CAr), 134.1 (4-CAr), 142.0 (8a-CHet), 149.6 (5-CHet), 159.1 (2-CAr),
156.9 (2-Cpyrrole), 157.2 (8a-CChr ), 157.6 (8a-CChr), 162.0 (2-CChr ),
192.0 (C]O). 19F NMR (470 MHz, DMSO-d6):
d¼ꢁ61.6 (CF3). IR
177.4 (C]OChr ), 181.1 (C]OChr). IR (KBr), nmax (cmꢁ1): 3082, 3062,
0
(KBr), nmax (cmꢁ1): 3650–3300 (br, OH, NH), 3126, 3041, 2980, 2875,
1655 (C]O), 1620, 1589, 1487, 1354, 1327, 1300, 1240 (C–F), 1174,
1144, 1061, 895, 810, 764, 710. APSI MS: Mþþ1¼373. Anal. Calcd for
3041, 1647 (C]O), 1608, 1572, 1466, 1400, 1346, 1321, 1119, 891, 760,
744. APSI MS: Mþþ1¼477. Anal. Calcd for C28H16N2O4S: C, 70.58; H,
3.38; N, 5.88; S, 6.73. Found: C, 70.46; H, 3.51; N, 5.95; S, 6.67.
C
18H11F3N4O2: C, 58.07; H, 2.98; N, 15.05. Found: C, 58.01; H, 3.09;
N, 14.96.
4.2.18. [5-(1H-Benzimidazol-2-yl)-1-methyl-1H-pyrrol-3-
yl](2-hydroxyphenyl)methanone (6a)
4.2.15. {5-[8-Chloro-6-(trifluoromethyl)[1,2,4]triazolo[4,3-a]-
pyridin-3-yl]-1H-pyrrol-3-yl}(2-hydroxyphenyl)methanone (3o)
Light brown solid (626 mg, 77%); mp 297–298 ꢀC (EtOH). 1H
Light green solid (558 mg, 88%); mp 211–212 ꢀC (EtOH/DMF). 1H
NMR (500 MHz, DMSO-d6):
d
¼4.17 (s, 3H, NCH3), 6.96 (t,
3JHH¼8.3 Hz, 1H, 5-HAr), 7.01 (d, JHH¼8.3 Hz, 1H, 3-HAr), 7.41–7.50
(m, 3H, 5,6-HBIm, 4-HAr), 7.56 (d, 4JHH¼1.4 Hz,1H, 2-Hpyrrole), 7.68 (d,
3JHH¼8.3 Hz, 1H, 6-HAr), 7.77 (m, 2H, 4,7-HBIm), 7.90 (d, 4JHH¼1.4 Hz,
1H, 4-Hpyrrole), 8.77 (br s, 1H, NH), 10.98 (br s, 1H, OH). 13C NMR
3
NMR (400 MHz, DMSO-d6):
d
¼6.98 (m, 2H, 3,5-HAr), 7.46 (m, 1H,
4-HAr), 7.51 (s, 1H, 2-Hpyrrole), 7.66 (s, 1H, 4-Hpyrrole), 7.75 (m, 1H,
6-HAr), 8.01 (s, 1H, 7-HHet), 8.90 (s, 1H, 5-HHet), 11.14 (s, 1H, OH),
12.86 (s, 1H, NH). 13C NMR (125 MHz, DMSO-d6):
d
¼111.7 (8-CHet),
(125 MHz, DMSO-d6):
d¼37.4 (CH3), 114.5 (4,7-CBIm), 117.8 (3-CAr),
2
117.1(q, JCF¼34.5 Hz, 6-CHet), 117.6 (3-CAr), 118.7 (4-Cpyrrole), 119.5
118.1 (4-Cpyrrole), 119.5 (5-CAr), 120.3 (3-Cpyrrole), 123.7 (5-Cpyrrole),
124.3 (1-CAr), 125.4 (5,6-CBIm), 126.5 (2-Cpyrrole), 131.0 (6-CAr), 133.6
(3a,7a-CBIm), 134.3 (4-CAr), 142.1 (2-CBIm), 159.4 (2-CAr), 191.3
(C]O). IR (KBr), nmax (cmꢁ1): 3413 (br, OH, NH), 3097, 3045, 2926,
1622 (C]O), 1595, 1481, 1442, 1389, 1354, 1246, 1200, 1159, 895,
750. APSI MS: Mþþ1¼318. Anal. Calcd for C19H15N3O2: C, 71.91; H,
4.76; N, 13.24. Found: C, 71.73; H, 4.89; N, 13.31.
(5-CAr), 122.3 (3-Cpyrrole), 123.0 (5-Cpyrrole), 123.2 (q, 1JCF¼271.5 Hz,
3
CF3), 124.1 (1-CAr), 124.7 (q, JCF¼6.7 Hz, 7-CHet), 125.6 (2-Cpyrrole),
129.7 (3-CHet), 131.1 (6-CAr), 134.1 (4-CAr), 143.7 (8a-CHet), 147.7
(5-CHet), 159.1 (2-CAr), 192.0 (C]O). 19F NMR (470 MHz, DMSO-d6):
d
¼ꢁ61.3 (CF3). IR (KBr), nmax (cmꢁ1): 3650–3340 (br, OH), 3169 (br,
NH), 3089, 3051, 2916, 1664 (C]O), 1624, 1589, 1487, 1466, 1356,
1315, 1298, 1242 (C–F), 1132, 893, 810, 752, 704, 677. APSI MS:
Mþþ1¼407. Anal. Calcd for C18H10ClF3N4O2: C, 53.15; H, 2.48; Cl,
8.72; N, 13.77. Found: C, 53.01; H, 2.61; Cl, 8.80; N, 13.82.
4.2.19. {5-[1-(Difluoromethyl)-1H-benzimidazol-2-yl]-1-methyl-
1H-pyrrol-3-yl}(2-hydroxyphenyl)methanone (6b)
Pale yellow solid (675 mg, 92%); mp 161–162 ꢀC (EtOH/DMF). 1H
4.2.16. 2-[(4-Methyl-1,3-thiazol-2-yl)methyl]-3-(4-oxo-4H-
chromen-3-yl)chromeno[2,3-c]pyrrol-9(2H)-one (4g)
NMR (400 MHz, DMSO-d6):
d
¼3.95 (s, 3H, NCH3), 6.94–7.02 (m, 3H,
3,5-HAr, 2-Hpyrrole), 7.38–7.49 (m, 3H, 5,6-HBIm, 4-HAr), 7.72 (d,
Light green solid (475 mg, 54%); mp 244–245 ꢀC (EtOH/DMSO).
3JHH¼8.0 Hz, 1H, 6-HAr), 7.76–7.84 (m, 2H, 4,7-HBIm), 7.87 (s, 1H,
1H NMR (500 MHz, DMSO-d6):
d
¼2.21 (s, 3H, CH3), 3.98 (s, 2H, CH2),
4-Hpyrrole), 8.02 (t, JHF¼58.0 Hz, 1H, CHF2), 11.04 (s, 1H, OH). 13C
2
3
1
0
7.15 (s, 1H, 5-HTz), 7.50 (t, JHH¼8.4 Hz, 1H, 6-HChr ), 7.61 (t,
NMR (125 MHz, DMSO-d6):
d
¼36.7 (CH3), 111.0 (t, JCF¼247.3 Hz,
3
JHH¼8.4 Hz, 1H, 6-HChr), 7.69 (d, 3JHH¼8.4 Hz, 1H, 8-HChr ), 7.82 (m,
CHF2), 112.9 (7-CBIm), 115.3 (4-Cpyrrole), 117.7 (3-CAr), 119.5 (5-CAr),
120.5 (4-CBIm), 122.2 (3-Cpyrrole), 123.6 (5-Cpyrrole), 124.0 (1-CAr),
124.7 (5-CBIm), 125.1 (6-CBIm), 131.0 (6-CAr), 131.4 (7a-CBIm), 134.1
(2-Cpyrrole), 134.4 (4-CAr), 143.0 (2-CBIm), 143.9 (3a-CBIm), 159.1
0
3
0
2H, 8-HChr, 7-HChr ), 7.93 (t, JHH¼8.4 Hz, 1H, 7-HChr), 8.06 (d,
3
3
0
JHH¼8.4 Hz, 1H, 5-HChr ), 8.13 (d, JHH¼8.4 Hz, 1H, 5-HChr), 8.62 (s,
1H, 2-Hpyrrole), 8.89 (s, 1H, 2-HChr ). 13C NMR (125 MHz, DMSO-d6):
0
d
¼12.8 (CH3), 23.7 (CH2), 114.2 (5-CTz), 115.87 (3-CChr), 115.93
(2-CAr), 191.3 (C]O). 19F NMR (470 MHz, DMSO-d6):
d¼ꢁ95.2 (d,
(3-CChr ), 119.0 (8-CChr ), 119.3 (8-CChr), 121.1 (5-Cpyrrole), 123.59
2JHF¼58.0 Hz, CHF2). IR (KBr), nmax (cmꢁ1): 3640–3310 (br, OH),
3126, 3099, 3055, 2954, 1620 (C]O), 1585, 1529, 1487, 1417, 1398,
0
0
0
0
(4a-CChr), 123.63 (4a-CChr ), 125.6 (6-CChr), 125.9 (6-CChr ), 126.0

A.S. Plaskon et al. / Tetrahedron 64 (2008) 5933–5943
5939
0
1338, 1286, 1217, 1157, 1120, 1093, 1038, 924, 897, 850, 766, 750, 710.
APSI MS: Mþþ1¼368. Anal. Calcd for C20H15F2N3O2: C, 65.39; H,
4.12; N, 11.44. Found: C, 65.52; H, 4.01; N, 11.50.
123.2 (3-Cpyrrole), 123.7 (5-Cpyrrole), 124.1 (1-CAr), 128.7 (2,6-CAr ),
130.8 (6-CAr), 133.8 (4-CAr), 134.1 (2-Cpyrrole), 159.0 (2-CAr), 161.3
0
(5-Cisoxazole), 162.4 (3-Cisoxazole), 162.6 (4-CAr ), 191.5 (C]O). IR (KBr),
nmax (cmꢁ1): 3650–3180 (br, OH), 3143, 3134, 3012, 2972, 2922,1622
(C]O),1583,1487,1433,1390,1344,1248,1225,1176,1161,1028, 943,
891, 837, 785, 758, 704, 669. APSI MS: Mþþ1¼375. Anal. Calcd for
4.2.20. (2-Hydroxyphenyl)(1-methyl-5-pyridin-4-yl-1H-pyrrol-3-
yl)methanone (6c)
Pale yellow solid (361 mg, 65%); mp 130–131 ꢀC (EtOH). 1H NMR
C22H18N2O4:C, 70.58; H, 4.85;N, 7.48. Found:C, 70.74;H, 4.76;N, 7.41.
(400 MHz,DMSO-d6):
d
¼3.82(s, 3H, NCH3), 6.91–7.00(m, 3H, 3,5-HAr,
3
3
2-Hpyrrole), 7.45 (t, JHH¼7.8 Hz, 1H, 4-HAr), 7.58 (dd, JHH¼4.8 Hz,
4JHH¼1.7 Hz, 2H, 3,5-HPy), 7.70 (s, 1H, 4-Hpyrrole), 7.73 (d, 3JHH¼7.8 Hz,
1H, 6-HAr), 8.61 (dd, 3JHH¼4.8 Hz, 4JHH¼1.7 Hz, 2H, 2,6-HPy), 11.21 (s,
4.2.24. [5-(6,7-Dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl)-1-
methyl-1H-pyrrol-3-yl](2-hydroxyphenyl)methanone (6g)
Light green solid (517 mg, 84%); mp 164–165 ꢀC (EtOH). 1H NMR
1H, OH). 13C NMR (125 MHz, DMSO-d6):
d¼36.5 (CH3), 112.2 (4-
(500 MHz, DMSO-d6):
d
¼2.79 (m, 2H, NCH2CH2), 3.14 (t, 3JHH¼7.1 Hz,
Cpyrrole), 117.7 (3-CAr), 119.4 (5-CAr), 122.6 (3,5-CPy), 123.4 (3-Cpyrrole),
2H, CH2), 3.95 (s, 3H, NCH3), 4.32 (t, 3JHH¼7.1 Hz, 2H, NCH2), 6.94 (t,
3
123.7 (1-CAr),131.0(6-CAr),133.1(5-Cpyrrole),133.8(2-Cpyrrole),134.1(4-
3JHH¼8.3 Hz, 1H, 5-HAr), 7.00 (d, JHH¼8.3 Hz, 1H, 3-HAr), 7.16 (d,
C
Ar), 139.1 (4-CPy),150.4 (2,6-CPy),159.4 (2-CAr), 191.8 (C]O). IR (KBr),
4JHH¼1.7 Hz, 1H, 2-Hpyrrole), 7.43 (t, 3JHH¼8.3 Hz, 1H, 4-HAr), 7.61 (d,
nmax (cmꢁ1): 3650–3160(br, OH), 3109, 3034, 2924,1624 (C]O),1599,
1581,1541,1477,1441,1396,1344,1284,1250,1205,1157, 893, 835, 818,
760, 704, 669. APSI MS: Mþþ1¼279. Anal. Calcd for C17H14N2O2:
C, 73.37; H, 5.07; N, 10.07. Found: C, 73.44; H, 5.01; N, 10.04.
3JHH¼8.3 Hz,1H, 6-HAr), 7.79 (d, 4JHH¼1.7 Hz,1H, 4-Hpyrrole),10.94 (br
s, 1H, OH). 13C NMR (125 MHz, DMSO-d6):
d¼21.8 (NCH2CH2), 28.4
(CH2), 37.5 (NCH3), 46.7 (NCH2), 114.2 (4-Cpyrrole), 117.6 (3-CAr), 119.1
(3-Cpyrrole), 119.5 (5-CAr), 124.1 (1-CAr), 124.6 (5-Cpyrrole), 130.6 (6-
CAr), 133.8 (4-CAr), 135.0 (2-Cpyrrole), 143.4 (3-Ctriazole), 158.4 (2-CAr),
4.2.21. [5-(1,3-Benzothiazol-2-yl)-1-methyl-1H-pyrrol-3-yl](2-
hydroxyphenyl)methanone (6d)
162.0 (5-Ctriazole), 191.0 (C]O). IR (KBr), nmax (cmꢁ1): 3520 (OH),
3196 (br, OH), 3138, 3113, 2966, 2939,1603 (C]O),1572,1481, 1390,
1369, 1335, 1261, 1227, 1194, 1157, 1101, 989, 891, 810, 771, 710, 669.
APSI MS: Mþþ1¼309. Anal. Calcd for C17H16N4O2: C, 66.22; H, 5.23;
N, 18.17. Found: C, 66.30; H, 5.16; N, 10.40.
Light green solid (474 mg, 71%); mp 155–156 ꢀC (EtOH). 1H NMR
(400 MHz, DMSO-d6):
d
¼4.14 (s, 3H, NCH3), 6.98 (m, 2H, 3,5-HAr),
4
7.24 (d, JHH¼1.7 Hz, 1H, 2-Hpyrrole), 7.45 (m, 2H, 5,6-HBTz), 7.52 (t,
3JHH¼8.1 Hz, 1H, 4-HAr), 7.67 (t, JHH¼8.1 Hz, 1H, 6-HAr), 7.81 (d,
3
4JHH¼1.7 Hz, 1H, 4-Hpyrrole), 8.00 (d, JHH¼8.1 Hz, 1H, 7-HBTz), 8.10
4.2.25. (2-Hydroxyphenyl)[1-methyl-5-(6,7,8,9-tetrahydro-5H-
[1,2,4]triazolo[4,3-a]azepin-3-yl)-1H-pyrrol-3-yl]methanone (6h)
Light green solid (410 mg, 61%); mp 175–176 ꢀC (i-PrOH). 1H
3
(d, 3JHH¼8.1 Hz, 1H, 4-HBTz), 11.02 (br s, 1H, OH). 13C NMR (125 MHz,
DMSO-d6):
d
¼38.0 (CH3), 115.6 (4-Cpyrrole), 117.6 (3-CAr), 119.5 (5-
C
Ar), 122.4 (7-CBTz), 123.0 (2-CBTz), 123.9 (3-Cpyrrole), 124.2 (1-CAr),
NMR (400 MHz, DMSO-d6):
d
¼1.65 (m, 2H, 5-HPHAz), 1.71 (m, 2H, 4-
125.9 (6-CBTz), 127.1 (5-CBTz), 127.7 (2-Cpyrrole), 130.8 (6-CAr), 133.9
(5-Cpyrrole), 134.0 (4-CAr), 135.2 (7a-CBTz), 153.9 (3a-CBTz), 158.8
(2-CAr), 159.4 (2-CBTz), 191.2 (C]O). IR (KBr), nmax (cmꢁ1): 3650–
3150 (br, OH), 3062, 2926,1645,1620 (C]O),1587,1564,1489,1342,
1211, 1157, 955, 895, 750, 702. APSI MS: Mþþ1¼335. Anal. Calcd for
HPHAz), 1.81 (m, 2H, 6-HPHAz), 2.96 (m, 2H, 3-HPHAz), 3.73 (s, 3H,
4
NCH3), 4.02 (m, 2H, 7-HPHAz), 6.79 (d, JHH¼1.2 Hz, 1H, 2-Hpyrrole),
3
6.92–7.00 (m, 2H, 3,5-HAr), 7.44 (t, JHH¼7.8 Hz, 1H, 4-HAr), 7.68–
7.74 (m, 2H, 6-HAr, 4-Hpyrrole), 11.09 (s, 1H, OH). 13C NMR (125 MHz,
DMSO-d6):
d
¼25.5 (4-CPHAz), 26.4 (6-CPHAz), 28.3 (5-CPHAz), 30.2 (3-
C
19H14N2O2S: C, 68.25; H, 4.22; N, 8.38; S, 9.59. Found: C, 68.39; H,
CPHAz), 36.1 (NCH3), 45.6 (7-CPHAz), 113.3 (4-Cpyrrole), 117.6 (3-CAr),
4.10; N, 8.45; S, 9.47.
119.4 (5-CAr), 121.6 (3-Cpyrrole), 123.4 (5-Cpyrrole), 124.1 (1-CAr), 130.9
(6-CAr), 133.0 (2-Cpyrrole), 134.0 (4-CAr), 146.7 (3-Ctriazole), 157.6 (5-
4.2.22. [5-(1,3-Benzoxazol-2-yl)-1-isopropyl-1H-pyrrol-3-yl](2-
C
triazole), 159.0 (2-CAr), 191.5 (C]O). IR (KBr), nmax (cmꢁ1): 3650–
hydroxyphenyl)methanone (6e)
3300 (br, OH), 3109, 2939, 2918, 1620 (C]O), 1578, 1525, 1483,
1443, 1396, 1342, 1275, 1242, 1213, 1151, 893, 814, 756, 704, 669.
APSI MS: Mþþ1¼337. Anal. Calcd for C19H20N4O2: C, 67.84; H, 5.99;
N, 16.65. Found: C, 67.96; H, 5.88; N, 16.58.
Light green solid (657 mg, 95%); mp 135–136 ꢀC (EtOH/MeCN).
1H NMR (400 MHz, DMSO-d6):
CH(CH3)2), 5.76 (m, 1H, CH(CH3)2), 6.99 (m, 2H, 3,5-HAr), 7.33 (m,
d¼1.53 (d, JHH¼6.6 Hz, 6H,
3
3
1H, 2-Hpyrrole), 7.39 (m, 2H, 5,6-HBOx), 7.46 (t, JHH¼8.0 Hz,
1H, 4-HAr), 7.66 (d, 3JHH¼8.0 Hz, 1H, 6-HAr), 7.74 (d, 3JHH¼8.0 Hz, 1H,
4.2.26. (2-Hydroxyphenyl)[1-isopropyl-5-(5-phenyl-1,3,4-
7-HBOx), 7.78 (d, 3JHH¼8.0 Hz, 1H, 4-HBOx), 8.02 (d, 4JHH¼1.4 Hz, 1H,
oxadiazol-2-yl)-1H-pyrrol-3-yl]methanone (6i)
4-Hpyrrole), 10.97 (s, 1H, OH). 13C NMR (125 MHz, DMSO-d6):
d¼23.5
Beige solid (619 mg, 83%); mp 117–118 ꢀC (EtOH/MeCN). 1H NMR
3
(CH(CH3)2), 50.2 (CH(CH3)2), 111.0 (7-CBOx), 116.5 (4-Cpyrrole), 117.6
(3-CAr), 119.6 (5-CAr), 120.0 (4-CBOx), 120.9 (3-Cpyrrole), 124.3 (1-CAr),
124.6 (5-Cpyrrole), 125.3 (6-CBOx), 125.8 (5-CBOx), 129.8 (2-Cpyrrole),
130.9 (6-CAr), 134.1 (4-CAr), 141.8 (3a-CBOx), 149.4 (2-CBOx), 156.5
(7a-CBOx), 158.7 (2-CAr), 191.3 (C]O). IR (KBr), nmax (cmꢁ1): 3650–
3100 (br, OH), 2966, 2924,1626 (C]O),1583,1458,1392,1242,1215,
1153,1034, 748. APSI MS: Mþþ1¼347. Anal. Calcd for C21H18N2O3: C,
72.82; H, 5.24; N, 8.09. Found: C, 72.70; H, 5.20; N, 8.17.
(400 MHz, DMSO-d6):
d
¼1.53 (d, JHH¼6.8 Hz, 6H, CH(CH3)2), 5.45
3
(septet, JHH¼6.8 Hz, 1H, CH(CH3)2), 6.99 (m, 2H, 3,5-HAr), 7.38 (d,
4JHH¼1.5 Hz, 1H, 2-Hpyrrole), 7.47 (t, 3JHH¼8.1 Hz,1H, 4-HAr), 7.58–7.66
3
4
(m, 3H, 3,4,5-HPh), 7.68 (d, JHH¼8.1 Hz, 1H, 6-HAr), 7.99 (d, JHH
¼
1.5 Hz, 1H, 4-Hpyrrole), 8.11 (d, 3JHH¼8.1 Hz, 2H, 2,6-HPh), 11.00 (s, 1H,
OH). 13C NMR (125 MHz, DMSO-d6):
d¼23.4 (CH(CH3)2), 50.7
(CH(CH3)2), 115.8 (4-Cpyrrole), 117.6 (3-CAr), 118.2 (3-Cpyrrole), 119.6 (5-
Ar), 123.6 (1-CPh), 124.1 (1-CAr), 124.8 (5-Cpyrrole), 127.2 (2,6-CPh),
129.7 (4-CPh),129.9 (3,5-CPh),131.0 (6-CAr),132.5 (2-Cpyrrole),134.2 (4-
C
4.2.23. (2-Hydroxyphenyl){5-[3-(4-methoxyphenyl)isoxazol-5-yl]-
1-methyl-1H-pyrrol-3-yl}methanone (6f)
CAr), 158.6 (2-Coxadiazole), 158.9 (2-CAr), 163.1 (5-Coxadiazole), 191.4
(C]O). IR (KBr), nmax (cmꢁ1): 3650–3160 (br, OH), 3136, 3062, 2989,
2918, 1622 (C]O), 1606, 1589, 1487, 1446, 1394, 1348, 1236, 1205,
1053, 895, 758, 723, 694. APSI MS: Mþþ1¼374. Anal. Calcd for
Pale yellow solid (524 mg, 70%); mp 134–135 ꢀC (EtOH). 1H NMR
(500 MHz, DMSO-d6):
d
¼3.82 (s, 3H, OCH3), 3.95 (s, 3H, NCH3), 6.96
3
0
(m, 2H, 3,5-HAr), 7.08 (d, JHH¼8.3 Hz, 2H, 3,5-HAr ), 7.12 (1H, s,
C22H19N3O3:C,70.76;H, 5.13;N,11.25.Found:C,70.59;H, 5.25;N,11.31.
3
2-Hpyrrole), 7.33 (1H, s, 4-Hisoxazole), 7.45 (t, JHH¼7.8 Hz, 1H, 4-HAr),
3
7.67 (d, JHH¼7.8 Hz, 1H, 6-HAr), 7.76 (1H, s, 4-Hpyrrole), 7.87 (d,
4.2.27. 2-[4-(2-Hydroxybenzoyl)-1-methyl-1H-pyrrol-2-yl]quin-
azolin-4(3H)-one (6j)
3
JHH¼8.3 Hz, 2H, 2,6-HAr ), 11.04 (s, 1H, OH). 13C NMR (125 MHz,
0
DMSO-d6):
d
¼37.1 (NCH3), 55.8 (OCH3), 99.0 (4-Cisoxazole), 112.9
Pale yellow solid (683 mg, 99%); mp 236–237 ꢀC (EtOH/DMF). 1H
0
0
(4-Cpyrrole), 115.0 (3,5-CAr ), 117.7 (3-CAr), 119.4 (5-CAr), 121.2 (1-CAr ),
NMR (400 MHz, DMSO-d6):
d
¼4.14 (s, 3H, NCH3), 6.98 (m, 2H,

5940
A.S. Plaskon et al. / Tetrahedron 64 (2008) 5933–5943
3
3
3,5-HAr), 7.48 (m, 2H, 4-HAr, 6-HQnz), 7.68 (d, JHH¼8.0 Hz, 1H,
1.31 (m, 2H, CH2CH3), 1.75 (m, 2H, NCH2CH2), 4.65 (t, JHH¼7.3 Hz,
4
6-HAr), 7.69 (d, JHH¼1.2 Hz, 1H, 2-Hpyrrole), 7.76–7.82 (m, 2H, 7,8-
2H, NCH2), 6.98 (m, 2H, 3,5-HAr), 7.48 (m, 2H, 4-HAr, 6-HQnz), 7.62 (d,
4
H
Qnz), 7.82 (d, 4JHH¼1.2 Hz, 1H, 4-Hpyrrole), 8.12 (d, 3JHH¼8.0 Hz, 1H,
3JHH¼8.1 Hz, 1H, 6-HAr), 7.72 (d, JHH¼1.5 Hz, 1H, 2-Hpyrrole), 7.78
5-HQnz), 11.26 (s, 1H, OH), 12.38 (s, 1H, NH). 13C NMR (125 MHz,
(d, JHH¼8.1 Hz, 1H, 8-HQnz), 7.81 (t, JHH¼8.1 Hz, 1H, 7-HQnz), 7.86
3
3
4
3
DMSO-d6):
d
¼38.7 (qd, 1JCH¼141.6 Hz, 3JCH¼2.0 Hz, CH3), 116.4 (dd,
(d, JHH¼1.5 Hz, 1H, 4-Hpyrrole), 8.11 (d, JHH¼8.1 Hz, 1H, 5-HQnz),
11.25 (s, 1H, OH), 12.36 (s, 1H, NH). 13C NMR (125 MHz, DMSO-d6):
1JCH¼176.4 Hz, JCH¼5.5 Hz, 4-Cpyrrole), 117.7 (ddd, JCH¼163.1 Hz,
3
1
2JCH¼6.9 Hz, JCH¼5.5 Hz, 3-CAr), 119.4 (dd, JCH¼163.6 Hz, JCH
¼
d
¼11.2 (CH3), 24.7 (CH2CH3), 39.6 (NCH2CH2), 51.8 (NCH2), 117.5 (3-
3
1
2
7.8 Hz, 5-CAr), 121.3 (s, 4a-CQnz), 122.7 (dd, 2JCH¼6.4 Hz, 2JCH¼5.1 Hz,
C
C
Ar), 117.8 (4-Cpyrrole), 119.4 (5-CAr), 120.1 (4a-CQnz), 122.8 (3-
pyrrole), 123.3 (1-CAr), 125.1 (5-CQnz), 126.5 (5-Cpyrrole), 126.9
2
1
3-Cpyrrole), 123.4 (d, JCH¼6.0 Hz, 1-CAr), 126.3 (dd, JCH¼163.1 Hz,
2JCH¼8.3 Hz, 5-CQnz), 126.4 (dd, 2JCH¼7.3 Hz, 3JCH¼5.1 Hz, 5-Cpyrrole),
(6-CQnz), 128.4 (8-CQnz), 131.3 (6-CAr), 134.4 (4-CAr), 135.6 (7-CQnz),
139.6 (2-Cpyrrole), 147.8 (2-CQnz), 150.0 (8a-CQnz), 159.7 (2-CAr), 161.7
(C]OQnz), 191.6 (C]O). IR (KBr), nmax (cmꢁ1): 3650–3300 (br, OH,
NH), 3120, 3028, 2956, 1676 (C]OQnz), 1622 (C]O), 1579, 1483,
1227, 1157, 895, 766, 748, 704. APSI MS: Mþþ1¼388. Anal. Calcd for
1
2
126.8 (dd, JCH¼163.5 Hz, JCH¼7.4 Hz, 6-CQnz), 127.6 (dd,
1JCH¼162.7 Hz, JCH¼6.4 Hz, 8-CQnz), 131.3 (dd, JCH¼159.5 Hz,
2
1
2JCH¼8.3 Hz, 6-CAr), 134.4 (dd, JCH¼159.9 Hz, JCH¼8.7 Hz, 4-CAr),
1
2
1
2
135.0 (dd, JCH¼161.2 Hz, JCH¼9.2 Hz, 7-CQnz), 135.8 (dq,
1JCH¼187.0 Hz, JCH¼2.0 Hz, 2-Cpyrrole), 146.7 (s, 2-CQnz), 148.8 (dd,
C23H22N3O3: C, 71.30; H, 5.46; N, 10.85. Found: C, 71.17; H, 5.53; N,
3
2JCH¼8.2 Hz, JCH¼7.4 Hz, 8a-CQnz), 159.7 (m, 2-CAr), 162.3 (s,
10.94.
2
C]OQnz), 191.7 (s, C]O). IR (KBr), nmax (cmꢁ1): 3650–3300 (br, OH,
NH), 3178, 3124, 3039, 2958, 2926, 1726, 1672 (C]OQnz), 1614
(C]O), 1587, 1485, 1446, 1234, 1209, 1159, 893, 766. APSI MS:
Mþþ1¼346. Anal. Calcd for C20H15N3O3: C, 69.56; H, 4.38; N, 12.17.
Found: C, 69.49; H, 4.45; N, 12.20.
4.2.31. 2-[1-sec-Butyl-4-(2-hydroxybenzoyl)-1H-pyrrol-2-yl]-
quinazolin-4(3H)-one (6n)
Pale yellow solid (704 mg, 91%); mp 187–188 ꢀC (EtOH/DMF). 1H
3
NMR (400 MHz, DMSO-d6):
d
¼0.82 (t, JHH¼7.0 Hz, 3H, CH2CH3),
3
1.52 (d, JHH¼6.8 Hz, 3H, CHCH3), 1.78 (m, 1H, CH3CH2(A)), 1.91 (m,
1H, CH3CH2(B)), 5.63 (m, 1H, CHCH3), 7.00 (m, 2H, 3,5-HAr), 7.49 (t,
3JHH¼7.9 Hz, 2H, 4-HAr, 6-HQnz), 7.56 (d, 4JHH¼1.5 Hz, 1H, 2-Hpyrrole),
4.2.28. 2-[1-Ethyl-4-(2-hydroxybenzoyl)-1H-pyrrol-2-yl]qui-
nazolin-4(3H)-one (6k)
Pale yellow solid (711 mg, 99%); mp 258–260 ꢀC (EtOH/DMF). 1H
7.64 (d, JHH¼7.9 Hz, 1H, 6-HAr), 7.82 (m, 2H, 7,8-HQnz), 7.94 (d,
3
3
3
NMR (400 MHz, DMSO-d6):
d
¼1.41 (t, JHH¼6.8 Hz, 3H, CH2CH3),
4JHH¼1.5 Hz, 1H, 4-Hpyrrole), 8.13 (d, JHH¼7.9 Hz, 1H, 5-HQnz), 11.34
3
4.68 (q, JHH¼6.8 Hz, 2H, CH2CH3), 6.99 (m, 2H, 3,5-HAr), 7.49 (t,
(s, 1H, OH), 12.38 (s, 1H, NH). 13C NMR (125 MHz, DMSO-d6):
d¼11.0
3JHH¼8.0 Hz, 2H, 4-HAr, 6-HQnz), 7.65 (d, JHH¼8.0 Hz, 1H, 6-HAr),
(CH2CH3), 21.3 (CHCH3), 30.8 (CH2CH3), 55.3 (CHCH3), 116.5 (4-
pyrrole), 117.8 (3-CAr), 119.5 (5-CAr), 121.3 (4a-CQnz), 123.3 (3-
pyrrole),123.5 (1-CAr),125.8 (5-CQnz),126.3 (5-Cpyrrole),126.9 (6-CQnz),
127.6 (8-CQnz), 130.4 (7-CQnz), 131.5 (6-CAr), 134.5 (4-CAr), 135.0
(2-Cpyrrole), 146.8 (2-CQnz), 148.7 (8a-CQnz), 159.7 (2-CAr), 163.9
(C]OQnz), 191.8 (C]O). IR (KBr), nmax (cmꢁ1): 3650–3240 (br, OH,
NH), 3136, 3066, 2974, 2924, 1678 (C]OQnz), 1613 (C]O), 1597,
1583, 1485, 1254, 1232, 1153, 893, 812, 766, 752, 710. APSI MS:
Mþþ1¼388. Anal. Calcd for C23H21N3O3: C, 71.30; H, 5.46; N, 10.85.
Found: C, 71.21; H, 5.59; N, 10.89.
3
4
7.71 (d, JHH¼1.6 Hz, 1H, 2-Hpyrrole), 7.81 (m, 2H, 7,8-HQnz), 7.89 (d,
C
C
4JHH¼1.6 Hz, 1H, 4-Hpyrrole), 8.12 (d, 3JHH¼8.0 Hz, 1H, 5-HQnz), 11.29
(s, 1H, OH), 12.37 (br s, 1H, NH). 13C NMR (125 MHz, DMSO-d6):
d
¼17.3 (CH3), 45.3 (CH2), 116.8 (4-Cpyrrole), 117.7 (3-CAr), 119.5 (5-
C
Ar), 121.3 (4a-CQnz), 123.0 (3-Cpyrrole), 123.4 (1-CAr), 125.4 (5-CQnz),
126.3 (5-Cpyrrole), 126.8 (6-CQnz), 127.6 (8-CQnz), 131.3 (6-CAr), 134.4
(4-CAr), 134.7 (7-CQnz), 135.0 (2-Cpyrrole), 146.4 (2-CQnz), 148.8 (8a-
C
Qnz), 159.6 (2-CAr), 162.3 (C]OQnz), 191.6 (C]O). IR (KBr), nmax
(cmꢁ1): 3650–3220 (br, OH, NH), 3113, 2981, 2931, 1672 (C]OQnz),
1612 (C]O), 1583, 1566, 1487, 1443, 1346, 1306, 1230, 1157, 933,
895, 771, 756, 710. APSI MS: Mþþ1¼360. Anal. Calcd for
4.2.32. 2-[4-(2-Hydroxybenzoyl)-1-(2-methoxyethyl)-1H-pyrrol-2-
yl]quinazolin-4(3H)-one (6o)
C
21H17N3O3: C, 70.18; H, 4.77; N, 11.69. Found: C, 70.05; H, 4.88; N,
11.74.
Pale yellow solid (755 mg, 97%); mp 241–242 ꢀC (EtOH/DMF). 1H
NMR (400 MHz, DMSO-d6):
d
¼3.22 (s, 3H, OCH3), 3.73 (t,
3
4.2.29. 2-[4-(2-Hydroxybenzoyl)-1-isopropyl-1H-pyrrol-2-
3JHH¼5.4 Hz, 2H, OCH2), 4.84 (t, JHH¼5.4 Hz, 2H, NCH2), 6.99 (m,
3
yl]quinazolin-4(3H)-one (6l)
2H, 3,5-HAr), 7.48 (t, JHH¼7.8 Hz, 2H, 4-HAr, 6-HQnz), 7.63 (d,
Pale yellow solid (716 mg, 96%); mp 231–232 ꢀC (EtOH/DMF). 1H
3JHH¼8.1 Hz, 1H, 6-HAr), 7.71 (d, JHH¼1.6 Hz, 1H, 2-Hpyrrole), 7.75–
4
3
3
NMR (400 MHz, DMSO-d6):
d
¼1.51 (d, JHH¼6.8 Hz, 6H, CH(CH3)2),
7.85 (m, 3H, 4-Hpyrrole, 7,8-HQnz), 8.12 (d, JHH¼7.8 Hz, 1H, 5-HQnz),
3
5.80 (septet, JHH¼6.8 Hz, 1H, CH(CH3)2), 7.00 (m, 2H, 3,5-HAr),
11.25 (s, 1H, OH), 12.39 (br s, 1H, NH). 13C NMR (125 MHz, DMSO-
3
4
7.49 (t, JHH¼8.1 Hz, 2H, 4-HAr, 6-HQnz), 7.56 (d, JHH¼1.8 Hz, 1H,
d6):
d
¼49.6 (NCH2), 58.6 (OCH3), 71.9 (OCH2), 116.8 (4-Cpyrrole), 117.7
3
2-Hpyrrole), 7.65 (d, JHH¼8.1 Hz, 1H, 6-HAr), 7.82 (m, 2H, 7,8-HQnz),
(3-CAr), 119.5 (5-CAr), 121.3 (4a-CQnz), 122.8 (3-Cpyrrole), 123.4
(1-CAr), 125.6 (5-CQnz), 126.3 (5-Cpyrrole), 126.8 (6-CQnz), 127.5 (8-
4
3
7.97 (d, JHH¼1.8 Hz, 1H, 4-Hpyrrole), 8.13 (d, JHH¼8.1 Hz, 1H, 5-
H
Qnz), 11.36 (s, 1H, OH), 12.39 (s, 1H, NH). 13C NMR (125 MHz,
DMSO-d6):
CQnz), 131.2 (6-CAr), 134.4 (4-CAr), 135.0 (7-CQnz), 135.9 (2-Cpyrrole),
d
¼23.8 (CH(CH3)2), 50.1 (CH(CH3)2), 116.8 (4-Cpyrrole),
146.6 (2-CQnz), 148.7 (8a-CQnz), 159.6 (2-CAr), 162.3 (C]OQnz), 191.6
(C]O). IR (KBr), nmax (cmꢁ1): 3630–3300 (br, OH, NH), 3174, 3124,
2980, 2926, 1676 (C]OQnz), 1612 (C]O), 1597, 1579, 1483, 1346,
1302,1275,1230,1203,1161,1099, 928, 895, 822, 766, 754, 706. APSI
MS: Mþþ1¼390. Anal. Calcd for C22H19N3O4: C, 67.86; H, 4.92; N,
10.79. Found: C, 67.99; H, 4.83; N, 10.73.
117.8 (3-CAr), 119.5 (5-CAr), 121.3 (4a-CQnz), 123.1 (3-Cpyrrole), 123.3
(1-CAr), 125.9 (5-CQnz), 126.3 (5-Cpyrrole), 126.9 (6-CQnz), 127.7 (8-
C
Qnz), 130.2 (2-Cpyrrole), 131.5 (6-CAr), 134.5 (4-CAr), 135.0 (7-CQnz),
146.7 (2-CQnz), 148.7 (8a-CQnz), 159.8 (2-CAr), 162.4 (C]OQnz), 191.8
(C]O). IR (KBr), nmax (cmꢁ1): 3650–3300 (br, OH, NH), 3163, 3138,
3057, 2999, 2960, 2922, 1672 (C]OQnz), 1621 (C]O), 1597, 1581,
1485, 1443, 1346, 1232, 1153, 895, 812, 771, 748, 704. APSI MS:
Mþþ1¼374. Anal. Calcd for C22H19N3O3: C, 70.76; H, 5.13; N, 11.25.
Found: C, 70.61; H, 5.25; N, 11.32.
4.2.33. 2-[1-[2-(Dimethylamino)ethyl]-4-(2-hydroxybenzoyl)-1H-
pyrrol-2-yl]quinazolin-4(3H)-one hydrochloride (6p)
Pale yellow solid (745 mg, 85%); mp 257–258 ꢀC (EtOH/DMF). 1H
NMR (400 MHz, DMSO-d6):
d
¼2.82 (s, 6H, N(CH3)2), 3.60 (t,
4.2.30. 2-[1-Butyl-4-(2-hydroxybenzoyl)-1H-pyrrol-2-yl]quin-
3JHH¼7.1 Hz, 2H, CH2N(CH3)2), 5.08 (t, 3JHH¼7.1 Hz, 2H, NCH2), 6.99
azolin-4(3H)-one (6m)
(t, 3JHH¼8.3 Hz, 1H, 5-HAr), 7.02 (d, 3JHH¼8.3 Hz, 1H, 3-HAr), 7.50 (m,
3
Pale yellow solid (689 mg, 89%); mp 246–247 ꢀC (EtOH/DMF). 1H
2H, 4-HAr, 6-HQnz), 7.77 (d, JHH¼8.0 Hz, 1H, 6-HAr), 7.83 (m, 3H,
3
4
NMR (500 MHz, DMSO-d6):
d
¼0.89 (t, JHH¼7.2 Hz, 3H, CH2CH3),
2-Hpyrrole, 7,8-HQnz), 7.97 (d, JHH¼1.2 Hz, 1H, 4-Hpyrrole), 8.13 (d,

A.S. Plaskon et al. / Tetrahedron 64 (2008) 5933–5943
5941
3JHH¼8.0 Hz, 1H, 5-HQnz), 10.77 (br s, 1H, NH), 11.13 (s, 1H, OH), 12.41
(5-Cpyrrole), 126.9 (6-CQnz), 128.4 (8-CQnz), 131.2 (6-CAr), 134.4 (4-
CAr), 135.1 (2-Cpyrrole), 139.6 (7-CQnz), 147.6 (2-CQnz), 150.1 (8a-CQnz),
(br s, 1H, NH). 13C NMR (125 MHz, DMSO-d6):
d¼43.1 (N(CH3)2),
45.0 (NCH2), 56.8 (CH2N(CH3)2), 117.0 (4-Cpyrrole), 117.7 (3-CAr), 119.5
(5-CAr), 121.4 (4a-CQnz), 123.7 (3-Cpyrrole), 123.8 (1-CAr), 125.5
(5-CQnz), 126.2 (5-Cpyrrole), 127.0 (6-CQnz), 128.0 (8-CQnz), 131.1 (6-
159.5 (2-CAr), 161.7 (C]OQnz), 191.5 (C]O). IR (KBr), nmax (cmꢁ1):
3650–3280 (br, OH, NH), 3116, 3028, 2985, 2926, 1672 (C]OQnz),
1624 (C]O), 1608, 1578, 1487, 1446, 1225, 1159, 891, 760. APSI MS:
Mþþ1¼394. Anal. Calcd for C21H16ClN3O3: C, 64.05; H, 4.10; Cl, 9.00;
N, 10.67. Found: C, 64.18; H, 3.98; Cl, 9.07; N, 10.62.
C
Ar), 134.3 (4-CAr), 135.0 (7-CQnz), 135.9 (2-Cpyrrole), 146.3 (2-CQnz),
148.7 (8a-CQnz), 159.2 (2-CAr), 162.3 (C]OQnz), 191.4 (C]O). IR
(KBr), nmax (cmꢁ1): 3466 (br, OH, NH), 3180, 3138, 3097, 3045, 2933,
1682 (C]OQnz), 1620 (C]O), 1593, 1568, 1487, 1464, 1381, 1236,
1157, 893, 756. APSI MS: Mþþ1¼403. Anal. Calcd for C23H23ClN4O3:
C, 62.94; H, 5.28; Cl, 8.08; N,12.76. Found: C, 62.80; H, 5.42; Cl, 8.15;
N, 12.71.
4.2.37. 2-[1-Ethyl-4-(2-hydroxybenzoyl)-1H-pyrrol-2-yl]-6,7-
dimethoxyquinazolin-4(3H)-one (6t)
Beige solid (687 mg, 82%); mp 287 ꢀC (EtOH/DMF). 1H NMR
(400 MHz, DMSO-d6):
d
¼1.39 (t, 3JHH¼7.0 Hz, 3H, CH2CH3), 3.88 (s,
3
3H, OCH3), 3.92 (s, 3H, OCH3), 4.68 (q, JHH¼7.0 Hz, 2H, CH2CH3),
6.98 (m, 2H, 3,5-HAr), 7.11 (s,1H, 8-HQnz), 7.46 (s,1H, 5-HQnz), 7.48 (t,
3JHH¼7.8 Hz, 1H, 4-HAr), 7.64 (d, 4JHH¼1.3 Hz, 1H, 2-Hpyrrole), 7.82 (d,
4.2.34. 2-[4-(2-Hydroxybenzoyl)-1-(tetrahydrofuran-2-ylmethyl)-
1H-pyrrol-2-yl]quinazolin-4(3H)-one (6q)
Pale yellow solid (730 mg, 88%); mp 245–246 ꢀC (EtOH/DMF). 1H
3JHH¼7.8 Hz, 1H, 6-HAr), 7.85 (d, JHH¼1.3 Hz, 1H, 4-Hpyrrole), 11.34
4
NMR (400 MHz, DMSO-d6):
d
¼1.58 (m, 1H, 4-HTHF(A)), 1.78 (m, 2H,
(br s, 1H, OH), 12.31 (br s, 1H, NH). 13C NMR (125 MHz, DMSO-d6):
4-HTHF(B), 3-HTHF(A)), 1.96 (m, 1H, 3-HTHF(B)), 3.58 (m, 1H, 2-HTHF(A)),
3.66 (m, 1H, 2-HTHF(B)), 4.23 (m, 1H, NCH2(A)), 4.59 (m, 1H, NCH2(B)),
4.89 (m, 1H, 2-HTHF), 6.99 (m, 2H, 3,5-HAr), 7.48 (t, 3JHH¼8.1 Hz, 2H,
4-HAr, 6-HQnz), 7.63 (d, 3JHH¼8.1 Hz, 1H, 6-HAr), 7.67 (d, 4JHH¼1.5 Hz,
1H, 2-Hpyrrole), 7.74–7.84 (m, 3H, 4-Hpyrrole, 7,8-HQnz), 8.12 (d,
3JHH¼8.1 Hz, 1H, 5-HQnz), 11.25 (br s, 1H, OH), 12.44 (br s, 1H, NH).
d
¼17.4 (CH2CH3), 45.1 (CH2), 56.2 (OCH3), 56.5 (OCH3), 105.6
(4a-CQnz), 108.4 (8-CQnz), 114.2 (5-CQnz), 116.1 (4-Cpyrrole), 117.7 (3-
Ar), 119.4 (5-CAr), 122.9 (3-Cpyrrole), 123.4 (1-CAr), 125.6 (5-Cpyrrole),
C
131.3 (6-CAr), 134.2 (2-Cpyrrole), 134.4 (4-CAr), 136.5 (2-CQnz), 144.9
(6-CQnz), 149.0 (8a-CQnz), 155.2 (7-CQnz), 159.6 (2-CAr), 162.3
(C]OQnz), 191.6 (C]O). IR (KBr), nmax (cmꢁ1): 3650–3300 (br, OH,
NH), 3130, 3082, 3062, 3012, 2958, 1670 (C]OQnz), 1633 (C]O),
1608, 1497, 1431, 1390, 1281, 1238, 1221, 1159, 1101, 1003, 893, 814,
766. APSI MS: Mþþ1¼420. Anal. Calcd for C23H21N3O5: C, 65.86; H,
5.05; N, 10.02. Found: C, 65.99; H, 4.90; N, 9.96.
13C NMR (125 MHz, DMSO-d6):
d¼25.5 (4-CTHF), 28.7 (3-CTHF), 53.4
(NCH2), 67.7 (5-CTHF), 78.3 (2-CTHF), 116.6 (4-Cpyrrole), 117.7 (3-CAr),
119.4 (5-CAr), 121.2 (4a-CQnz), 122.8 (3-Cpyrrole), 123.5 (1-CAr), 125.9
(5-CQnz), 126.3 (5-Cpyrrole), 126.8 (6-CQnz), 127.5 (8-CQnz), 131.2
(6-CAr), 134.3 (4-CAr), 135.1 (7-CQnz), 135.8 (2-Cpyrrole), 146.8
(2-CQnz), 148.7 (8a-CQnz), 159.5 (2-CAr), 162.3 (C]OQnz), 191.6
(C]O). IR (KBr), nmax (cmꢁ1): 3650–3290 (br, OH, NH), 3169, 3113,
3064, 3032, 2974, 2953, 1672 (C]OQnz), 1610 (C]O), 1574, 1539,
1487, 1448, 1344, 1298, 1252, 1228, 1076, 893, 818, 775, 762. APSI
MS: Mþþ1¼416. Anal. Calcd for C24H21N3O4: C, 69.39; H, 5.10; N,
10.11. Found: C, 69.55; H, 4.98; N, 10.04.
4.2.38. 2-[4-(2-Hydroxybenzoyl)-1-methyl-1H-pyrrol-2-yl]-
thieno[3,2-d]pyrimidin-4(3H)-one (6u)
Beige solid (681 mg, 97%); mp 275–276 ꢀC (DMF). 1H NMR
3
(500 MHz, DMSO-d6):
d
¼4.08 (s, 3H, NCH3), 6.97 (t, JHH¼8.4 Hz,
1H, 5-HAr), 6.98 (d, 3JHH¼8.4 Hz,1H, 3-HAr), 7.39 (d, 3JHH¼5.2 Hz,1H,
3
4
4-Hthiophene), 7.46 (t, JHH¼8.4 Hz, 1H, 4-HAr), 7.62 (d, JHH¼1.4 Hz,
1H, 2-Hpyrrole), 7.78 (d, 3JHH¼8.4 Hz, 1H, 6-HAr), 7.79 (d, 4JHH¼1.4 Hz,
3
4.2.35. 2-[1-Benzyl-4-(2-hydroxybenzoyl)-1H-pyrrol-2-yl]quin-
azolin-4(3H)-one (6r)
1H, 4-Hpyrrole), 8.18 (d, JHH¼5.2 Hz, 1H, 5-Hthiophene), 11.26 (s, 1H,
OH), 12.54 (s, 1H, NH). 13C NMR (125 MHz, DMSO-d6):
d¼38.5 (CH3),
Pale yellow solid (834 mg, 99%); mp 259 ꢀC (DMF). 1H NMR
116.3 (4-Cpyrrole), 117.7 (3-CAr), 119.4 (5-CAr), 121.1 (4a-CThP), 122.7
(3-Cpyrrole), 123.4 (1-CAr), 125.8 (5-Cpyrrole), 126.2 (7-CThP), 131.2
(6-CAr), 134.3 (4-CAr), 135.6 (6-CThP), 135.7 (2-Cpyrrole), 148.4
(2-CThP), 157.8 (7a-CThP), 158.7 (C]OThP), 159.5 (2-CAr), 191.6 (C]O).
IR (KBr), nmax (cmꢁ1): 3650–3280 (br, OH), 3126, 3088, 3034, 3003,
2951, 1655 (C]OThP), 1626 (C]O), 1583, 1500, 1485, 1290, 1248,
1213, 1159, 889, 812, 789, 756, 735, 669. APSI MS: Mþþ1¼352. Anal.
Calcd for C18H13N3O3S: C, 61.53; H, 3.73; N, 11.96; S, 9.12. Found: C,
61.65; H, 3.64; N, 11.89; S, 9.20.
(400 MHz, DMSO-d6):
d
¼5.98 (s, 2H, CH2), 6.99 (m, 2H, 3,5-HAr),
3
7.18 (m, 3H, 2,4,6-HPh), 7.25 (t, JHH¼7.6 Hz, 2H, 3,5-HPh), 7.47 (m,
3
2H, 4-HAr, 6-HQnz), 7.66 (d, JHH¼8.0 Hz, 1H, 6-HAr), 7.75–7.82 (m,
4
3H, 2-Hpyrrole, 7,8-HQnz), 8.05 (d, JHH¼2.0 Hz, 1H, 4-Hpyrrole), 8.07
(d, 3JHH¼8.0 Hz, 1H, 5-HQnz), 11.17 (s, 1H, OH), 12.33 (s, 1H, NH). 13
C
NMR (125 MHz, DMSO-d6):
d
¼53.1 (NCH2), 117.2 (4-Cpyrrole), 117.7
(3-CAr), 119.5 (5-CAr), 121.2 (4a-CQnz), 123.3 (3-Cpyrrole), 123.8
(1-CAr), 125.5 (5-CQnz), 126.3 (5-Cpyrrole), 126.8 (6-CQnz), 127.3 (3,5-
C
Ph), 127.5 (8-CQnz), 127.8 (4-CPh), 128.9 (2,6-CPh), 131.2 (6-CAr),
134.3 (4-CAr), 135.1 (7-CQnz), 135.9 (2-Cpyrrole), 138.9 (1-CPh), 146.2
(2-CQnz), 148.6 (8a-CQnz), 159.3 (2-CAr), 162.2 (C]OQnz), 191.5
(C]O). IR (KBr), nmax (cmꢁ1): 3600–3300 (br, OH, NH), 3176, 3142,
3111, 3037, 2941, 1682 (C]OQnz), 1614 (C]O), 1585, 1547, 1498,
1487, 1462, 1443, 1342, 1302, 1228, 1211, 1155, 893, 812, 756, 725.
APSI MS: Mþþ1¼422. Anal. Calcd for C26H19N3O3: C, 74.10; H, 4.54;
N, 9.97. Found: C, 73.94; H, 4.68; N, 10.02.
4.2.39. 4-(2-Hydroxybenzoyl)-1H-pyrrole-2-carboxylic acid (8a)
Green solid (254 mg, 55%); mp 251–252 ꢀC (EtOH). 1H NMR
(400 MHz, DMSO-d6):
d
¼6.91–6.99 (m, 2H, 3,5-HAr), 7.08 (s, 1H, 5-
H
H
pyrrole), 7.43 (td, 3JHH¼7.8 Hz, 4JHH¼1.6 Hz,1H, 4-HAr), 7.50 (s,1H, 3-
pyrrole), 7.61 (dd, 3JHH¼7.8 Hz, 4JHH¼1.6 Hz, 1H, 6-HAr), 10.99 (1H, s,
OH), 12.54 (s, 1H, NH). 13C NMR (125 MHz, DMSO-d6):
d
¼116.0 (3-
Cpyrrole), 117.6 (3-CAr), 119.5 (5-CAr), 124.2 (1-CAr), 125.1 (4-Cpyrrole),
125.3 (2-Cpyrrole),129.5 (5-Cpyrrole),130.9 (6-CAr),134.0 (4-CAr),158.8
(2-CAr), 162.0 (COOH), 192.0 (C]O). IR (KBr), nmax (cmꢁ1): 3650–
3250 (br, OH), 3269 (br, OH), 3124, 2993, 1714 (C]Oacid), 1645
(C]O),1595,1556,1487,1340,1288,1259,1209,1190,1157, 895, 812,
758, 704, 675. APSI MS: Mþþ1¼232, Mþꢁ1¼230. Anal. Calcd for
4.2.36. 7-Chloro-2-[1-ethyl-4-(2-hydroxybenzoyl)-1H-pyrrol-2-
yl]quinazolin-4(3H)-one (6s)
Pale yellow solid (779 mg, 99%); mp 276 ꢀC (DMF). 1H NMR
(400 MHz, DMSO-d6):
d
¼1.39 (t, 3JHH¼7.2 Hz, 3H, CH2CH3), 4.65 (q,
3JHH¼7.2 Hz, 2H, CH2CH3), 6.98 (m, 2H, 3,5-HAr), 7.45–7.51 (m, 2H,
4,6-HAr), 7.69 (d, 4JHH¼2.0 Hz, 1H, 8-HQnz), 7.73 (d, 4JHH¼2.0 Hz, 1H,
C12H9NO4: C, 62.34; H, 3.92; N, 6.06. Found: C, 62.21; H, 4.05; N, 6.15.
3
4
2-Hpyrrole), 7.77 (d, JHH¼8.5 Hz, 1H, 6-HQnz), 7.89 (d, JHH¼2.0 Hz,
4.2.40. Methyl 4-(2-hydroxybenzoyl)-1-methyl-1H-pyrrole-2-
carboxylate (8b)
3
1H, 4-Hpyrrole), 8.09 (d, JHH¼8.5 Hz, 1H, 5-HQnz), 11.25 (s, 1H, OH),
12.41 (br s, 1H, NH). 13C NMR (125 MHz, DMSO-d6):
d
¼17.4 (CH3),
Pale yellow crystals (223 mg, 43%); mp 116–117 ꢀC (i-PrOH/
45.5 (CH2), 117.4 (4-Cpyrrole), 117.7 (3-CAr), 119.5 (5-CAr), 120.1
(4a-CQnz), 123.1 (3-Cpyrrole), 123.5 (1-CAr), 125.0 (5-CQnz), 126.7
hexane). 1H NMR (500 MHz, DMSO-d6):
(s, 3H, NCH3), 6.89–7.00 (m, 2H, 3,5-HAr), 7.16 (d, JHH¼1.2 Hz, 1H,
d
¼3.76 (s, 3H, OCH3), 3.91
4

5942
A.S. Plaskon et al. / Tetrahedron 64 (2008) 5933–5943
5-Hpyrrole), 7.43 (t, 3JHH¼7.9 Hz, 1H, 4-HAr), 7.58 (d, 3JHH¼7.9 Hz, 1H,
3JHH¼8.5 Hz,1H, 7-HChr), 8.09 (d, 3JHH¼8.5 Hz,1H, 5-HChr), 8.61 (s,1H,
4
6-HAr), 7.77 (d, JHH¼1.2 Hz, 1H, 3-Hpyrrole), 10.91 (s, 1H, OH). 13C
2-HChr). 13C NMR (125 MHz, DMSO-d6):
d
¼27.4 (CONCH3), 40.5
NMR (125 MHz, DMSO-d6):
d
¼37.5 (NCH3), 51.9 (OCH3), 117.6
(NCH3), 54.8 (CH2), 77.3 (CH),114.2 (3-CChr),119.2 (8-CChr),123.8 (4a-
CChr), 125.6 (5-CChr), 126.8 (6-CChr), 135.6 (7-CChr), 156.3 (2-CChr),
(3-CAr), 118.7 (3-Cpyrrole), 119.5 (5-CAr), 122.9 (4-Cpyrrole), 123.7 (2-
pyrrole), 124.2 (1-CAr), 130.7 (6-CAr), 134.0 (4-CAr), 135.5 (5-Cpyrrole),
C
160.9 (8a-CChr), 166.7 (CONCH3), 176.3 (C]OChr). IR (KBr), nmax
(cmꢁ1): 3055, 3022, 2980, 2933, 1726 (C]O), 1647 (C]OChr), 1572,
1464, 1396, 1363, 1317, 1128, 1012, 939, 885, 862, 758, 698. APSI MS:
Mþþ1¼259. Anal. Calcd for C14H14N2O3: C, 65.11; H, 5.46; N, 10.85.
Found: C, 65.22; H, 5.33; N, 10.89.
158.7 (2-CAr), 161.0 (COOCH3), 191.4 (C]O). IR (KBr), nmax (cmꢁ1):
3650–3300 (br, OH), 3126, 2999, 2956, 1707 (C]Oester), 1622
(C]O), 1581, 1537, 1489, 1446, 1294, 1250, 1198, 1157, 1099, 893,
823, 758, 704, 667. APSI MS: Mþþ1¼260. Anal. Calcd for C14H13NO4:
C, 64.86; H, 5.05; N, 5.40. Found: C, 64.95; H, 4.98; N, 5.47.
4.2.45. (7aS)-3-(4-Oxo-4H-chromen-3-yl)hexahydro-1H-
pyrrolo[1,2-c]imidazol-1-one hydrochloride (9b)
4.2.41. 4-(2-Hydroxybenzoyl)-N,N-dimethyl-1H-pyrrole-2-
carboxamide (8c)
Beige solid (515 mg, 84%); mp 232–233 ꢀC (MeCN). 1H NMR
Light green solid (351 mg, 68%); mp 146–147 ꢀC (EtOH/MeCN).
(400 MHz, DMSO-d6):
d
¼1.97 (m, 2H, 7-H), 2.10 (m, 1H, 6-HA),
1H NMR (500 MHz, DMSO-d6):
d
¼3.10 (m, 6H, N(CH3)2), 6.89–6.98
2.21 (m, 1H, 6-HB), 3.66 (m, 2H, 5-H), 4.57 (m, 1H, 7a-H), 5.88 (m,
3
3
(m, 3H, 3,5-HAr, 5-Hpyrrole), 7.40 (d, 4JHH¼1.7 Hz, 1H, 3-Hpyrrole), 7.42
(t, 3JHH¼7.8 Hz, 1H, 4-HAr), 7.64 (d, 3JHH¼7.8 Hz, 1H, 6-HAr), 11.06 (s,
1H, 3-H), 7.59 (t, JHH¼8.6 Hz, 1H, 6-HChr), 7.76 (d, JHH¼8.6 Hz,
3
3
1H, 8-HChr), 7.90 (t, JHH¼8.6 Hz, 1H, 7-HChr), 8.11 (d, JHH¼8.6 Hz,
1H, 5-HChr), 8.61 (s, 1H, 2-HChr), 9.30 (s, 1H, NH), 12.37 (br s, 1H,
NH). 13C NMR (125 MHz, DMSO-d6, *signals of minor di-
1H, OH), 12.21 (s, 1H, NH). 13C NMR (125 MHz, DMSO-d6):
d¼36.3
(NCH3)2, 113.2 (3-Cpyrrole), 117.6 (3-CAr), 119.5 (5-CAr), 124.0 (1-CAr),
124.5 (4-Cpyrrole), 127.0 (2-Cpyrrole), 128.1 (5-Cpyrrole), 131.0 (6-CAr),
134.0 (4-CAr), 159.1 (2-CAr), 161.8 (CON), 192.2 (C]O). IR (KBr), nmax
(cmꢁ1): 3650–3300 (br, OH, NH), 3170, 3145, 3041, 2981, 2935, 1622
(C]O), 1601, 1587, 1564, 1481, 1385, 1352, 1271, 1163, 901, 760, 696,
669. APSI MS: Mþþ1¼259. Anal. Calcd for C14H14N2O3: C, 65.11; H,
5.46; N, 10.85. Found: C, 65.25; H, 5.36; N, 10.79.
astereomer):
and 57.7 (5-C), 64.3 and 65.4
and 115.1 (3-CChr), 119.1 and 119.2
Chr), 125.5 and 125.6 (5-CChr), 126.8 and 126.9
and 135.8 (7-CChr), 156.2 and 156.4 (2-CChr), 157.8 and 157.9
(8a-CChr), 170.8 and 170.9 (CON), 175.7 and 175.9 (C]OChr). IR
d
¼24.6
*
and 24.9 (6-C), 26.8
*
and 27.7 (7-C), 57.0
and 72.9 (3-C), 115.0
*
*
(7a-C), 71.4
*
*
*
(8-CChr), 123.7 and 123.8
*
(4a-
C
*
*
(6-CChr), 135.6
*
*
*
*
*
(KBr), nmax (cmꢁ1): 3448 (br, NH), 3055, 2989, 2943, 1732 (C]O),
1645 (C]OChr), 1624, 1608, 1460, 1402, 1350, 1309, 1182, 1165,
914, 795, 773. APSI MS: Mþþ1¼271. Anal. Calcd for C15H15ClN2O3:
C, 58.73; H, 4.93; Cl, 11.56; N, 9.13. Found: C, 58.87; H, 4.80; Cl,
11.48; N, 9.19.
4.2.42. (2-Hydroxyphenyl)[5-(pyrrolidin-1-ylcarbonyl)-1H-pyrrol-
3-yl]methanone (8d)
Light green solid (346 mg, 61%); mp 179–180 ꢀC (EtOH/MeCN).
1H NMR (500 MHz, DMSO-d6):
d
¼1.82 (m, 2H, CH2), 1.95 (m, 2H,
CH2), 3.49 (m, 2H, NCH2), 3.72 (m, 2H, NCH2), 6.88–7.03 (m, 3H, 3,5-
4
HAr
,
5-Hpyrrole), 7.40 (d, JHH¼1.5 Hz, 1H, 3-Hpyrrole), 7.43 (t,
4.2.46. 2-(2-Hydroxybenzoyl)pyrrolo[1,2-a]quinoxalin-4(5H)-
one (11a)
3JHH¼8.0 Hz, 1H, 4-HAr), 7.63 (d, JHH¼8.0 Hz, 1H, 6-HAr), 11.04 (s,
3
1H, OH), 12.23 (s, 1H, NH). 13C NMR (125 MHz, DMSO-d6):
d¼23.9
Beige solid (316 mg, 52%); mp>300 ꢀC (EtOHþDMF). 1H NMR
(CH2), 26.7 (CH2), 47.3 (NCH2), 48.2 (NCH2), 112.8 (3-Cpyrrole), 117.6
(3-CAr), 119.5 (5-CAr), 124.2 (1-CAr), 124.9 (4-Cpyrrole), 127.9 (2-
(400 MHz, DMSO-d6):
d
¼7.00 (m, 2H, 3,5-HAr), 7.22 (t,
3JHH¼8.3 Hz, 1H, 7-HQnx), 7.29 (d, 4JHH¼1.5 Hz, 1H, 5-Hpyrrole), 7.30–
3
C
pyrrole), 128.3 (5-Cpyrrole), 130.9 (6-CAr), 133.9 (4-CAr), 158.9 (2-CAr),
7.39 (m, 2H, 6,8-HQnx), 7.49 (t, JHH¼7.6 Hz, 1H, 4-HAr), 7.69 (d,
159.5 (CON),192.1 (C]O). IR (KBr), nmax (cmꢁ1): 3415 (br, OH), 3209
(br, NH), 2981, 2968, 1626 (C]O), 1589 (C]O), 1552, 1487, 1454,
1385, 1354, 1213, 1146, 895, 812, 754, 704. APSI MS: Mþþ1¼285.
Anal. Calcd for C16H16N2O3: C, 67.59; H, 5.67; N, 9.85. Found: C,
67.73; H, 5.55; N, 9.78.
3JHH¼7.6 Hz, 1H, 6-HAr), 8.26 (d, JHH¼8.3 Hz, 1H, 5-HQnx), 8.75 (d,
3
4JHH¼1.5 Hz, 1H, 3-Hpyrrole), 10.90 (s, 1H, OH), 11.47 (s, 1H, NH). 13
C
NMR (125 MHz, DMSO-d6):
d¼112.8 (8-CQnx), 116.5 (3-Cpyrrole),
117.2 (5-CQnx), 117.7 (3-CAr), 119.7 (5-CAr), 122.47 (4-Cpyrrole), 122.49
(8a-CQnx), 123.3 (5-Cpyrrole), 124.3 (1-CAr), 124.7 (4a-CQnx), 127.0 (2-
Cpyrrole), 127.5 (6-CQnx), 129.6 (7-CQnx), 131.3 (6-CAr), 134.4 (4-CAr),
4.2.43. N,N-Diethyl-4-(2-hydroxybenzoyl)-1-methyl-1H-pyrrole-2-
155.4 (CONH), 158.8 (2-CAr), 192.3 (C]O). IR (KBr), nmax (cmꢁ1):
3650–3320 (br, OH, NH), 3132, 3035, 2983, 2924, 2900, 1674
(C]O), 1626 (C]O), 1595, 1545, 1516, 1483, 1379, 1338, 1298, 1252,
1223, 1157, 895, 816, 754, 739. APSI MS: Mþþ1¼305. Anal. Calcd
for C18H12N2O3: C, 71.05; H, 3.97; N, 9.21. Found: C, 71.18; H, 3.86;
N, 9.15.
carboxamide (8e)
Pale yellow solid (270 mg, 45%); mp 84 ꢀC (i-PrOH/hexane). 1H
3
NMR (500 MHz, DMSO-d6):
d
¼1.14 (t, JHH¼7.0 Hz, 6H, 2CH2CH3),
3
3.45 (q, JHH¼7.0 Hz, 4H, 2CH2CH3), 3.69 (s, 3H, NCH3), 6.69 (d,
4JHH¼1.4 Hz, 1H, 5-Hpyrrole), 6.91–7.00 (m, 2H, 3,5-HAr), 7.43 (t,
3JHH¼8.0 Hz, 1H, 4-HAr), 7.58 (d, 4JHH¼1.4 Hz, 1H, 3-Hpyrrole), 7.68 (d,
3JHH¼8.0 Hz,1H, 6-HAr),11.10 (s,1H, OH).13C NMR (125 MHz, DMSO-
4.2.47. 2-(2-Hydroxybenzoyl)-7-(piperidin-1-
d6):
d
¼14.1 (CH2CH3), 36.0 (NCH3), 39.5 (CH2CH3), 110.9 (3-Cpyrrole),
ylsulfonyl)pyrrolo[1,2-a]quinoxalin-4(5H)-one (11b)
117.6 (3-CAr), 119.4 (5-CAr), 122.1 (4-Cpyrrole), 124.0 (1-CAr), 128.6 (5-
pyrrole), 130.9 (6-CAr), 132.5 (2-Cpyrrole), 134.0 (4-CAr), 159.1 (2-CAr),
White solid (523 mg, 58%); mp>300 ꢀC (EtOHþDMF). 1H NMR
C
(400 MHz, DMSO-d6):
d
¼1.36 (m, 2H, CH2), 1.55 (m, 4H, 2NCH2CH2),
162.3 (CON), 191.6 (C]O). IR (KBr), nmax (cmꢁ1): 3650–3200 (br,
OH), 3140, 2970, 2933, 1624 (C]O), 1591 (C]O), 1549, 1483,
1425, 1282, 1219, 1157, 897, 766. APSI MS: Mþþ1¼301. Anal. Calcd
for C17H20N2O3: C, 67.98; H, 6.71; N, 9.33. Found: C, 68.10; H, 6.60; N,
9.27.
2.83 (m, 1H, NCH), 2.92 (m, 3H, NCH), 7.01 (m, 2H, 3,5-HAr), 7.34 (d,
4JHH¼1.3 Hz, 1H, 5-Hpyrrole), 7.50 (m, 2H, 4-HAr, 8-HQnx), 7.67 (m, 2H,
3
6-HAr
,
6-HQnx), 8.51 (d, JHH¼8.3 Hz, 1H, 5-HQnx), 8.84 (d,
4JHH¼1.3 Hz, 1H, 3-Hpyrrole), 10.84 (s, 1H, OH), 11.63 (s, 1H, NH). 13
C
NMR (125 MHz, DMSO-d6):
d¼23.3 (CH2), 25.2 (NCH2CH2), 47.1
(NCH2), 113.5 (8-CQnx), 116.3 (3-Cpyrrole), 117.5 (5-CQnx), 117.7 (3-CAr),
119.7 (5-CAr), 121.9 (4-Cpyrrole), 123.4 (5-Cpyrrole), 124.3 (1-CAr), 124.8
(6-CQnx), 125.6 (8a-CQnx), 127.7 (2-Cpyrrole), 130.2 (7-CQnx), 131.3 (6-
4.2.44. 1,3-Dimethyl-2-(4-oxo-4H-chromen-3-
yl)imidazolidin-4-one (9a)
Colorless crystals (408 mg, 79%); mp 195–196 ꢀC (EtOH). 1H NMR
CAr),134.1 (4a-CQnx),134.5 (4-CAr),155.1 (CONH),158.7 (2-CAr),192.1
(500 MHz, DMSO-d6):
d
¼2.49 (s, 3H, NCH3), 2.63 (s, 3H, CONCH3),
(C]O). IR (KBr), nmax (cmꢁ1): 3670–3300 (br, OH, NH), 3142, 3074,
2941, 1701 (C]O), 1668, 1620 (C]O), 1587, 1485, 1360, 1333 (SO2),
1163 (SO2), 1092, 1053, 931, 893, 816, 758, 715, 604. APSI MS:
3.54 (m, 1H, CH2(A)), 3.84 (m, 1H, CH2(B)), 5.47 (m, 1H, CH), 7.55 (t,
3JHH¼8.5 Hz, 1H, 6-HChr), 7.73 (d, JHH¼8.5 Hz, 1H, 8-HChr), 7.87 (t,
3

A.S. Plaskon et al. / Tetrahedron 64 (2008) 5933–5943
5943
Mþþ1¼452. Anal. Calcd for C23H21N3O5S: C, 61.19; H, 4.69; N, 9.31;
101–110; (f) Renneberg, D.; Dervan, P. B. J. Am. Chem. Soc. 2003, 125, 5707–5716;
(g) Marques, M. A.; Doss, R. M.; Foister, S.; Dervan, P. B. J. Am. Chem. Soc. 2004,
126, 10339–10349.
S, 7.10. Found: C, 61.37; H, 4.57; N, 9.24; S, 7.18.
4. (a) Figueiredo, A. G. P. R.; Tome, A. C.; Silva, A. M. S.; Cavaleiro, J. A. S.
Tetrahedron 2007, 63, 910–917; (b) Ghosh, C. K.; Sahana, S.; Bandyopadhyay, C.
Indian J. Chem., Sect. B 1993, 32, 624–629; (c) Clarke, P. D.; Fitton, A. O.;
Kosmirak, M.; Suschitzky, H.; Suschitzky, J. L. J. Chem. Soc., Perkin Trans. 1 1985,
1747–1756; (d) Fitton, A. O.; Kosmirak, M.; Suschitzky, H.; Suschitzky, J. L.
Tetrahedron Lett. 1982, 23, 3953–3956; (e) Mataka, S.; Takahashi, K.; Tsuda, Y.;
Tashiro, M. Synthesis 1982, 157–159; (f) Terzidis, M.; Tsoleridis, C. A.; Stepha-
nidou-Stephanatou, J. Tetrahedron 2007, 63, 7828–7832.
Acknowledgements
The authors acknowledge V.V. Polovinko (Enamine Ltd) and
Dr. S.A. Alekseev (Kyiv National Taras Shevchenko University)
for spectral measurements.
5. (a) Klappa, J. J.; Geers, S. A.; Schmidtke, S. J.; MacManus-Spencer, L. A.; McNeill,
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A. Tetrahedron Lett. 2003, 44, 2417–2420; (c) Klappa, J. J.; Rich, A. E.; McNeill, K.
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References and notes
1. (a) Bean, G. P. Pyrroles: Part 1; Jones, R. A., Ed.; John Wiley and Sons: New York,
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