One-pot tandem complexity-generating reaction based on Ugi four component condensation and intramolecular cyclization

Article abstract of DOI:10.1016/j.tetlet.2007.02.015

A novel complexity-generating reaction is described, which can be used in a high-throughput parallel solution-phase combinatorial format. The synthetic pathway features the Ugi four component reaction followed by intramolecular cyclization via C-C bond fo

Full text of DOI:10.1016/j.tetlet.2007.02.015

Tetrahedron Letters 48 (2007) 2563–2567
One-pot tandem complexity-generating reaction based on Ugi
four component condensation and intramolecular cyclization
Andrey S. Trifilenkov,a Alexey P. Ilyin,a Volodymyr M. Kysil,b Yuri B. Sandulenkoa
and Alexandre V. Ivachtchenkob,*
aDepartment of Organic Chemistry, Chemical Diversity Research Institute, 114401 Khimki, Moscow Reg, Russia
bChemDiv, Inc., 11558 Sorrento Valley Rd., Suite 5, San Diego, CA 92121, USA
Received 11 April 2006; accepted 6 February 2007
Available online 9 February 2007
Abstract—A novel complexity-generating reaction is described, which can be used in a high-throughput parallel solution-phase com-
binatorial format. The synthetic pathway features the Ugi four component reaction followed by intramolecular cyclization via C–C
bond formation. Starting from readily available initial reactants, the described approach leads to generation of novel 3-oxoiso-
indoline-1-carboxamides with four points of diversity around the core scaffold. The scope and limitations of the involved chemistry
and some chemical transformations of the synthesized compounds are discussed.
Ó 2007 Published by Elsevier Ltd.
Multicomponent reactions can be carried out very effi-
ciently in solution and are suitable for the synthesis of
libraries of diverse small molecules. A classical example
is the four component Ugi condensation (U-4CC) be-
tween aldehyde, amine, isonitrile and carboxylic acid,
which has emerged as a powerful tool for rapid
identification and optimization of lead compounds in
drug discovery.1 A Combination of the classical Ugi
condensation with a postcondensation cyclization can
be used for introduction of additional complexity to
the generated scaffolds, and a wide number of recent
studies demonstrate the usefulness of this approach for
the synthesis of pharmaceutically relevant heterocyclic
structures. For example, U-4CC between (E)-cinnamal-
dehyde, chloroacetic acid, primary amine and isocya-
nide (structures I–IV) led to chloroacetamides V
(Scheme 1). Upon the addition of alkali into the reaction
media, compounds V underwent cyclization into b-lac-
tams VI.2 If 4-substituted benzaldehydes or naphthal-
dehyde R1–CHO were used in this reaction instead of
(E)-cinnamaldehyde, the resulting U-4CC-adducts VII
cyclized into 2,5-diketopiperazines VIII.3,4 Of note,
although the Ugi four component condensation was
successfully performed by employing aliphatic alde-
hydes I as starting materials, attempts to cyclize the
resulting products gave complex reaction mixtures.3
One of the useful modifications of this synthetic meth-
odology is the use of 2-fluoro-5-nitrobenzoic acid as
the carboxylic acid component in the Ugi coupling.
When bifunctional reagents IIIa–f such as 2-
aminoethanol and 2-aminophenol, or mono-Boc-substi-
tuted diamines such as hydrazine, ethylenediamine, 2-
aminomethylpyrrolidone and ortho-phenylenediamine,
are used in this condensation as amine components,
the reaction leads to standard U-4CC products 9a–f.
The latters then can undergo intramolecular O- or N-
arylation under elevated temperature in the presence
of bases to give the corresponding heterocyclic products
10a–f5,6 (Scheme 1). A modified variant of this method-
ology is the condensation of 2-fluoro-5-nitrobenzoic
acid with N-Boc-protected aminoaldehydes, primary
amines and isonitriles. For example, after consecutive
steps of condensation, deprotection of amino group
and cyclization, a series of 2,4-disubstituted 5-oxo-
2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-3-carboxami-
des were formed.7 All the mentioned approaches lead to
rare, diverse heterocyclic structures. As a rule, these
approaches are compatible with high-throughput
combinatorial format, and, therefore, represent
valuable methods in early stages of pharmaceutical
development.
Keywords: Ugi condensation; 3-Oxoisoindoline-1-carboxamides; Par-
allel synthesis; Library.
*
Corresponding author. Tel.: +1 858 794 4860; fax: +1 858 794
4931; e-mail addresses: atr@chemdiv.com; av@chemdiv.com
0040-4039/$ - see front matter Ó 2007 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2007.02.015

2564
A. S. Trifilenkov et al. / Tetrahedron Letters 48 (2007) 2563–2567
O
O
R3
Ph
R3
Ph
N
N
H
R2
N
H
N
R2
Cl
R1-CHO
+
Cl-CH2-COOH
O
O
V
VI
I
IIa
O
O
R2-NH2
III
+
R3-NC
R3
R1
R1
R3
N
IV
N
H
N
N
R2
R2
Cl
O
O
VII
VIII
O
O
O2N
CO2H
F
R1
R3
Base
-HF
R1
R3
R1-CHO
+
N
N
H
H
O
N
O
N
I
IIb
R2
F
R2-NH2
+
R3-NC
IV
IIIa-f
O2N
IXa-f
Xa-f
*
N
*
*
N
*
N
O
O
O
O
N
NH
=
O
O
O2N
O2N
O2N
a
b
c
*
*
*
N
O
O
O
N
N
N
N
N
O2N
O2N
O2N
H
H
d
e
f
Scheme 1. U-4CC followed by postcondensation intramolecular cyclization.
As a further modification of this useful synthetic strat-
egy, in this work we developed a synthetic approach to
3-oxoisoindoline-1-carboxamides (Scheme 2). The lat-
ters represent promising synthetic targets, since many
physiologically active compounds contain this heterocy-
clic fragment in their structures. At the first step, aro-
matic aldehydes 1a–u and 2-fluoro-5-nitrobenzoic acid
2 were reacted with primary amine 3 and isonitrile 4a
in methanol at 50 °C for 8–10 h. In a parallel set of reac-
tions, four arbitrary aldehydes 1a–d, 2-fluoro-5-nitro-
benzoic acid 2 and amine 3 were treated with isonitrile
4b under the same conditions. R1 aldehyde residues ex-
plored in this work are depicted in Figure 1. In both
reaction sets, we observed the conversion of the initial
reactants into the corresponding classical U-4CC-
adducts 5a–u and 6a–d.
Then we have found that compounds 5 and 6 can under-
go intramolecular cyclization leading to the correspond-
ing 3-oxoisoindoline-1-carboxamides 8 and 9.8 The
possible mechanism of this reaction is the SN2 attack
of the nucleophilic carbon atom at the electron-deficient
fluorine-substituted carbon atom resulting in C–C bond
formation. The reaction proceeds under elevated tem-
peratures (120 °C) in DMF media in the presence of
Et3N. The reaction was successful only in the case of
compounds 5a–l and 6a–d: the corresponding cycliza-
tion products 8a–l and 9a–d were obtained in 45–85%
yield (from initial 1–4). At the same time, according to
LCMS data, only trace amounts of 8m–u were observed
under the described conditions; the prolonged heating
caused thermal decomposition of the reaction mixture.
According to these observations, the intramolecular
cyclization is possible only in the case of aromatic or
heteroaromatic aldehydes R1–CHO, such as benzalde-
hydes possessing the electron-withdrawing substituents
or electron-deficient heteroaromatic aldehydes. Due to
their electron-deficient nature, such R1 substituents in-
crease the acidity of the C–H bond and favour the nucleo-
philic substitution.
According to LCMS analysis (ELSD detection,
254 nm), in all the studied cases the reaction mixtures
contained 60–100% of the condensation products 5a–u
and 6a–d. The major side-reaction was the intermolecu-
lar cyclization. Thus, in the case of condensation with
aldehydes 1f and 1h, the reaction mixtures contained
up to 35% of structures 8f and 8h. Another side-reaction
was the substitution of fluorine in compounds 5a–u and
6a–d with 4-methoxybenzylamine residue (up to 10% of
the corresponding products).
We also attempted to use 2-chloro-5-nitrobenzoic acid
as the carboxylic acid component in the Ugi coupling.
For instance, the reaction of aldehyde 1f, acid 2b, amine

A. S. Trifilenkov et al. / Tetrahedron Letters 48 (2007) 2563–2567
2565
NC
O2N
CO2H
CH3OH
H2N
+
R1-CHO
+
+
( )n
Hal
O
1a-u
3
4a: n = 1
4b: n = 2
2a: Hal = F
2b: Hal = Cl
O
O
N
R1
( )n
NH
H
H
Et3N, DMF
-HHal
R1
O
N
O
O
O
N
O2N
( )n
Hal
8a-l: n = 1, 45-85% from 1-4
8m-u: n = 1, trace amounts
9a-d: n = 2, 56-75% from 1-4
O2N
5a-u: n = 1, Hal = F
6a-d: n = 2, Hal = F
8f: 73% from 5f, 72% from 7f
7f: n = 1, Hal = Cl
Scheme 2. Synthesis of 3-oxoisoindoline-1-carboxamides via U-4CC followed by postcondensation cyclization.
F
F
F
*
*
N
N
*
*
O
S
N
N
N
*
*
*
*
1b
1a
1c
1d
1e
1f
1g
1h
F
F
F
*
*
*
*
N
N
*
*
N
O
N
Br
CH3
Cl
N
N
*
1i
1j
1k
1l
1m
1n
1o
O
N
S
H3C
*
Br
*
*
*
N
N
N
N
N
CH3
Br
Cl
H3C
*
*
1p
1q
1r
1s
1t
1u
Figure 1. Aldehyde R1 residues studied in this work.
3 and isonitrile 4a resulted in formation of the classical
U-4CC product 7f (Scheme 2). Due to decreased electro-
philicity of the chlorine-substituted carbon atom as
compared to the fluorine-substituted one, the intramo-
lecular cyclization of 7f proceeded more slowly as com-
pared to 5f. Thus, according to LCMS data, almost
complete conversion of compound 5f was reached after
4 h from the initiation of the reaction, while only 80% of
7f were converted after 24 h. However, due to decreased
reactivity of chlorine-substituted compounds and, as a
consequence, a reduced probability of side-reactions,
the isolated yields of compound 8f from 2-fluoro- and
2-chloro-5-nitrobenzoic acids were almost equal (73%
and 72%, respectively). Therefore, both methods can
be recommended for the synthesis of the final cyclization
products.
Compounds 8 and 9 were obtained as racemic mixtures
of enantiomers. The assignment of all structures was
1
made on the basis of H NMR and mass-spectroscopy
data; satisfactory analytical data were obtained for all
the synthesized compounds. In many cases, pure crystal-
line substances could be obtained, thus allowing X-ray
crystallographic analysis of individual compounds. For
instance, the structure of 8h was established as N-cyclo-
hexyl-1-(2-pyridyl)-2-(4-methoxybenzyl)-5-nitro-3-oxo-
isoindoline-1-carboxamide by single crystal X-ray
analysis (Fig. 2). Single crystals of compounds suitable
for X-ray analysis were grown from diethyl ether.
For introduction of additional complexity to the gener-
ated heterocyclic scaffold, we attempted to reduce the
nitro group of the obtained 3-oxoisoindoline-

2566
A. S. Trifilenkov et al. / Tetrahedron Letters 48 (2007) 2563–2567
ity to the synthesized heterocyclic structures, the devel-
oped route provides a new valuable entry to a wide
variety of novel 3-oxoisoindoline-1-carboxamides. Com-
pounds synthesized in this work constitute examples of
conformationally rigid peptidomimetics, which are the
subject of increasing interest as potential new small mole-
cule therapeutics. Biological testing of the obtained
compounds is currently in progress.
Acknowledgement
The authors would like to thank Dr. Konstantin V. Bal-
akin (Chemical Diversity Research Institute) for help in
preparation of the manuscript.
Figure 2. ORTEP plot for compound 8h.
References and notes
1-carboxamides. Thus, we have found that the reaction
of a sample compound 9h with sodium dithionite
smoothly led to isoindol-5-ylsulfamic acid 10h.9 The lat-
ter was converted into the corresponding amine 11h
upon treatment with aqueous HCl. Alternatively, the ni-
tro group of compound 9h was reduced by treatment
with SnCl2 in aqueous HCl. Both methods gave compa-
rable yields of 11h10 (49% and 43%, respectively). Our
experiments demonstrated that the amino group of com-
pound 11h can be readily acylated and sulfonylated
upon treatment with acyl and sulfonyl chlorides, respec-
tively, or converted into the pyrrole moiety upon the
reaction with 2,5-dimethoxytetrahydrofurane (Scheme
3).11
1. (a) Ugi, I.; Lohberger, S.; Karl, R. In Comprehensive
Organic Synthesis; Pergamon: Oxford, 1991; Vol. 2,
Chapter 4.6; (b) Domling, A.; Ugi, I. Angew. Chem.
2000, 39, 3168–3210.
2. Bossio, R.; Fernandez Marcos, C.; Marcaccini, S.; Pepino,
R. Tetrahedron Lett. 1997, 38, 2519–2520.
3. Marcaccini, S.; Pepino, R.; Pozo, M. C. Tetrahedron Lett.
2001, 42, 2727–2728.
4. Ilyin, A. P.; Trifilenkov, A. S.; Petrunin, V. N.; Dmitriev,
D. E.; Dorogov, M. V.; Balakin, K. V.; Ivachtchenko, A.
V. Izv. Vuzov. Khim. Techn. (Russia) 2006, 49, 117–123.
5. Zhu, J.; Bienayme, H. Multicomponent Reactions; Wiley-
VCH: Weinheim, 2005; p 468.
6. Tempest, P.; Ma, V.; Kelly, M. G.; Jones, W.; Hulme, C.
Tetrahedron Lett. 2001, 42, 4963–4968.
7. Tempest, P.; Pettus, L.; Gore, V.; Hulme, C. Tetrahedron
Lett. 2003, 44, 1947–1950.
In summary, in this work we have shown that 3-oxoiso-
indoline-1-carboxamides can be efficiently prepared by a
novel modification of four component Ugi reaction fol-
lowed by postcondensation intramolecular C–C bond
formation. Considering the availability of initial reac-
tants, convenient synthesis and isolation of products,
and amenability to introduction of additional complex-
8. General procedure for the preparation of 3-oxoisoindoline-1-
carboxamides 8a–l, 9a–d. The equimolar amounts of
aldehydes 1a–l, acid 2, 4-methoxybenzyl amine 3 and
isonitrile 4a,b (1.0 mmol of each component) were succes-
sively dissolved in methanol (3 mL). The reaction mixture
was stirred at 50 °C for 10 h. The solvent was evaporated
method A
O
O
Na2S2O4
Et3N
HCl, aq.
R-NH2
R
S
R-NO2
N
OH
10h
H
11h, 49% (method A
)
9h
43% (method B
)
SnCl2, HCl, aq.
method B
H3C
O
O
PhO-CH2-COCl
R
PhO
12h
R-NH2
N
11h
H
N
N
O
R =
R
N
O
O
O
O
HN
13h
*
Scheme 3. Chemical transformations of compound 9h.

A. S. Trifilenkov et al. / Tetrahedron Letters 48 (2007) 2563–2567
2567
in vacuo, then DMF (3 mL) and Et3N (2 mmol) were
added to the residue. The resulting mixture was stirred at
120 °C for 5 h. The reaction was followed by TLC (5%
MeOH in CH2Cl2). On completion, the reaction mixture
was cooled to rt and poured into water (15 mL). The
formed precipitate was filtered off and purified by recrys-
tallization from methanol. Satisfactory analytical data
were obtained for all the synthesized compounds.
dissolution of the solid material (approx. 2 h). The
solution was cooled to rt, and then a concentrated
solution of Na2CO3 was slowly added until pH 8 was
reached. The formed precipitate was filtered off, washed
with water twice and dried to afford 0.23 g of amine 11h.
Method B. Compound 8h (0.5 g, 1 mmol) was suspended
in a solution of SnCl2 (0.8 g, 3.5 mmol) in 10% aqueous
HCl (3 mL). The suspension was stirred at 70 °C until
complete dissolution of the solid material (approx. 1 h).
The solution was cooled to rt, and then a concentrated
solution of Na2CO3 was slowly added until pH 8 was
reached. The formed precipitate was filtered off and dried.
Chloroform (10 mL) was added, and the mixture was
stirred at reflux for 3 h. The solid particles were removed
by filtration, and the solvent was evaporated. The crude
residue was recrystallized from ether to afford 0.2 g of 11h.
Yield 49% (method A), 43% (method B); H1 NMR,
DMSO-d6, d ppm: 0.93–1.27 (5H, m, cyclohexyl); 1.43–
1.68 (5H, m, cyclohexyl); 3.42–3.58 (1H, m, CH cyclo-
hexyl); 3.62 (3H, s, CH3O); 4.50, 4.73 (2H, dd, CH2,
J = 15.8 Hz); 6.58, 6.72 (4H, dd, p-MeO–phenyl,
J = 8.1 Hz); 6.93–7.11 (3H, m, 3CHar); 7.17–7.25 (1H,
m, CHar); 7.41 (1H, d, CHar, J = 8.0 Hz); 7.56–7.71 (2H,
m, 2CHar); 8.41 (1H, d, CHPy, J = 3.6 Hz); NH2 in
exchange. LC–MS: M+ = 471.4.
For example: N1-Cyclohexyl-2-(4-methoxybenzyl)-5-nitro-
3-oxo-1-(4-pyridyl)-1-isoindolinecarboxamide (8f). Yield
73%; mp 127–129 °C; H1 NMR, DMSO-d6, d ppm:
0.89–1.26 (5H, m, cyclohexyl); 1.39–1.70 (5H, m, cyclo-
hexyl); 3.42–3.58 (1H, m, CH cyclohexyl); 3.63 (3H, s,
CH3O); 4.53, 4.77 (2H, dd, CH2, J = 15.9 Hz); 6.62, 6.84
(4H, dd, p-MeO–phenyl, J = 8.4 Hz); 7.14 (2H, d, 2CHPy
,
J = 4.9 Hz); 7.85–7.98 (2H, m, 2CHar); 8.42 (2H, d,
2CHPy, J = 4.9 Hz); 8.47 (1H, s, CHar); 8.52 (1H, d,
CHar, J = 8.4 Hz); LC–MS: M+ = 501,4.
N1-Cyclohexyl-2-(4-methoxybenzyl)-5-nitro-3-oxo-1-(2-pyr-
idyl)-1-isoindolinecarboxamide (8h). Yield 81%, mp 152–
154 °C; H1 NMR, DMSO-d6, d ppm: 0.93–1.25 (5H, m,
cyclohexyl); 1.45–1.68 (5H, m, cyclohexyl); 3.45–3.59 (1H,
m, CH cyclohexyl); 3.62 (3H, s, CH3O); 4.55, 4.81 (2H, dd,
CH2, J = 15.7Hz); 6.59, 6.75 (4H, dd, p-MeO–phenyl,
J = 8.7 Hz); 7.21–7.29 (2H, m, 2CHar); 7.61–7.70 (1H, m,
CHar); 7.91–8.04 (2H, m, 2CHar); 8.38–8.45 (2H, m,
2CHar); 8.52 (1H, d, CHar, J = 8.5 Hz).
11. N1-Cyclohexyl-2-(4-methoxybenzyl)-3-oxo-5-[(2-phenoxy-
acetyl)amino]-1-(2-pyridyl)-1-isoindolinecarboxamide (12h).
Phenoxyacetyl chloride (61.4 g, 0.36 mmol) was added to a
solution of amine 11h (0.15 g, 0.3 mmol) in 1.4-dioxane
(3 mL) freshly distilled over Na. The mixture was stirred at
80 °C for 5 h, then poured into 10% solution of Na2CO3
(10 mL). The resulting suspension was stirred at rt for 2 h.
The formed precipitate was filtered off, washed with water
twice and dried to give 181 g of 12h. Yield 85%; mp 123–
125 °C; H1 NMR, DMSO-d6, d ppm: 0.92–1.29 (5H, m,
cyclohexyl); 1.44–1.68 (5H, m, cyclohexyl); 3.43–3.60 (1H,
m, CH cyclohexyl); 3.62 (3H, s, CH3O); 4.50 (H, d,
CH(CH2), J = 15.3 Hz); 4.69–4.82 (3H, m, CH (CH2),
CH2); 6.58, 6.74 (4H, dd, p-MeO–phenyl, J = 8.2 Hz);
6.93–7.13 (4H, m, 4CHar); 7.16–7.39 (3H, m, 3CHar);
7.55–7.67 (2H, m, 2CHar); 7.74–7.85 (2H, m, 2CHar); 8.14
(1H, s, CHar); 8.42 (1H, d, CHPy, J = 4.2 Hz); LC–MS:
M+ = 603.5.
N1-Cycloheptyl-2-(4-methoxybenzyl)-5-nitro-3-oxo-1-(2-
thienyl)-1-isoindolinecarboxamide (9a). Yield 59%, mp 98–
101 °C; H1 NMR, DMSO-d6, d ppm: 0.61–0.81 (2H, m,
cycloheptyl); 1.12–1.58 (10H, m, cycloheptyl); 3.43–3.61
(1H, m, CH cycloheptyl); 3.79 (3H, s, CH3O); 3.91, 5.06
(2H, dd, CH2, J = 15.1 Hz); 5.74 (1H, d, CHar,
J = 7.5 Hz);6.78–7.05 (4H, m, 4CHar); 7.24–7.42 (3H, m,
3CHar); 7.86 (1H, d, CHar, J = 8.5 Hz); 8.40 (1H, d, CHar,
J = 8.5 Hz); 8.71 (1H, s, CHar); LC–MS: M+ = 520.4.
9. N-[1-[(Cyclohexylamino)carbonyl]-2-(4-methoxybenzyl)-
3-oxo-1-(2-pyridyl)-2,3-dihydro-1H-isoindol-5-yl]sulfamic
acid (10h). Na2S2O4 (0.6 g, 3.5 mmol) and Et3N (1 mL,
7 mmol) were added to a solution of 8h (0.5 g, 1 mmol) in
ethanol (5 mL). The resulting mixture was stirred at 60 °C
for 2 h, and the solvent was evaporated in vacuo. The
crude residue was dissolved in CH2Cl2 (10 mL), the
solution was successively washed with water (5 mL), 2%
aqueous HCl (5 mL) and with water again (5 mL). The
organic layer was dried over Na2SO4 and kept at 0 °C
overnight. The formed precipitate was filtered off, washed
with CH2Cl2 and dried to afford 0.33 g of 10h. Yield 60%,
mp 170–172 °C; H1 NMR, DMSO-d6, d ppm: 0.93–1.27
(5H, m, cyclohexyl); 1.44–1.67 (5H, m, cyclohexyl); 3.44–
3.59 (1H, m, CH cyclohexyl); 3.61 (3H, s, CH3O); 4.50,
4.75 (2H, dd, CH2, J = 16.2 Hz); 6.58, 6.71 (4H, dd, p-
MeO–Phenyl, J = 8.5 Hz); 7.09 (1H, d, CHar, J = 7.8 Hz);
7.15 (1H, d, CHar, J = 8.3 Hz); 7.20–7.29 (2H, m, 2CHar);
7.51 (1H, d, CHar, J = 8.3 Hz); 7.59–7.67 (1H, m, CHar);
7.77 (1H, d, CHar, J = 8.1 Hz); 8.41 (1H, d, CHPy, J =
4.3 Hz); NH, SO3H in exchange. LC–MS: M+ = 551.5.
10. N-Cyclohexyl-1-(2-pyridyl)-2-(4-methoxybenzyl)-5-amino-
3-oxoisoindoline-1-carboxamide 11h. Method A. Com-
pound 10h was suspended in 10% aqueous HCl (5 mL),
and the suspension was stirred at 60 °C until complete
N1-Cyclohexyl-2-(4-methoxybenzyl)-3-oxo-1-(2-pyridyl)-
5-(1H-pyrrol-1-yl)-1-isoindolinecarboxamide (13h). 2,5-
Dimethoxytetrahydrofuran (64.8 mL, 0.50 mmol) was
added to a solution of amine 11h (0.20 g, 0.42 mmol) in
acetic acid (2 mL). The mixture was stirred at 70 °C for
0.5 h, then poured into water (10 mL). The formed
precipitate was filtered off, washed with water, dried and
recrystallized from hexane to afford 0.10 g of 13h. Yield
45%; mp 123–125 °C; H1 NMR, DMSO-d6, d ppm: H1
NMR, DMSO-d6, d ppm: 0.95–1.31 (5H, m, cyclohexyl);
1.46–1.69 (5H, m, cyclohexyl); 3.49–3.59 (1H, m, CH
cyclohexyl); 3.62 (3H, s, CH3O); 4.54, 4.80 (2H, dd, CH2,
J = 15.9 Hz); 6.30 (2H, s, 2CH pyrrol); 6.59, 6.75 (4H, dd,
p-MeO–phenyl, J = 8.3 Hz); 7.13 (1H, d, CHar,
J = 8.3 Hz); 7.19–7.28 (1H, m, CHPy); 7.52 (2H, s, 2CH
pyrrol); 7.58–7.68 (1H, m, CHPy); 7.76 (1H, d, CHar,
J = 8.2 Hz); 7.81–7.93 (2H, m, 2CHar); 8.44 (1H, d, CHPy
,
J = 4.5 Hz); LC–MS: M+ = 521.3.