Stereoselective Synthesis of Functionalized Tetrahydro-β-Carbolines via Pictet-Spengler Reaction

Article abstract of DOI:10.1055/s-0034-1378727

A TFA-catalyzed Pictet-Spengler reaction of synthesized tryptophan propargyl ester with aromatic and heteroaromatic aldehydes resulted in cis-tetrahydro-β-carbolines with remarkably high stereocontrol under kinetically controlled conditions. In another approach, a diastereomeric mixture of tetrahydro-β-carboline hydrazides was synthesized. The tetrahydro-β-carboline hydrazides were prepared through the reaction of tryptophan hydrazide with carbonyl compounds via Pictet-Spengler reaction.

Full text of DOI:10.1055/s-0034-1378727

SYNLETT
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6
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2
1
4
1
4
3
7
-
2
0
9
6
© Georg Thieme Verlag Stuttgart · New York
2015, 26, 1955–1960
letter
1955
V. F. Vavsari et al.
Letter
Synlett
Stereoselective Synthesis of Functionalized Tetrahydro-β-Carbo-
lines via Pictet–Spengler Reaction
Vaezeh Fathi Vavsaria
Vahid Dianatia
Sorour Ramezanpoura
Saeed Balalaie*a,b
O
OH
H
N
O
O
O
N
Ar
NHR1
Pictet–Spengler
reaction
NH
NH
or
Ar
NR2
a Peptide Chemistry Research Center, K. N. Toosi University
of Technology, P. O. Box 15875-4416, Tehran, Iran
balalaie@kntu.ac.ir
Ar
NH
NH
b Medical Biology Research Center, Kermanshah University
of Medical Sciences, Kermanshah, Iran
L-tryptophan
R1 = H, Fmoc
2 = H, Boc
valuable functional groups
for additional reactions
R
Dedicated to Prof. Habib Bagheri on the occasion of his
birthday
Received: 10.04.2015
Accepted after revision: 11.05.2015
Published online: 09.07.2015
methods were developed for the construction of such struc-
tures8 in which the most direct method is the Pictet–Spen-
gler reaction (PSR).9
DOI: 10.1055/s-0034-1378727; Art ID: st-2015-d0259-l
Asymmetric synthesis centers on the use of chiral sub-
strates, catalysts, chiral auxiliaries, and/or solvents to result
in stereoselective reactions.10 Natural α-amino acids, such
as L-tryptophan, are suitable precursors for the asymmetric
synthesis.11 Recently, derivatives of L-tryptophan have been
used for the synthesis of indole alkaloids and were used for
the construction of cis-1,3-disubstituted tetrahydro-β-car-
boline via PSR.12
Abstract A TFA-catalyzed Pictet–Spengler reaction of synthesized
tryptophan propargyl ester with aromatic and heteroaromatic alde-
hydes resulted in cis-tetrahydro-β-carbolines with remarkably high ste-
reocontrol under kinetically controlled conditions. In another approach,
a diastereomeric mixture of tetrahydro-β-carboline hydrazides was syn-
thesized. The tetrahydro-β-carboline hydrazides were prepared through
the reaction of tryptophan hydrazide with carbonyl compounds via Pic-
tet–Spengler reaction.
In this paper, we wish to delineate the efficient asym-
metric synthesis of tetrahydro-β-carboline derivatives 3
and 4 (Figure 2) starting from L-tryptophan via PSR. The
stereoisomers of propargyl esters 3a–g and hydrazide tetra-
hydro-β-carbolines 4a–e have valuable functional groups
which can undergo further transformations. For example,
hydrazide functional groups can be converted into tetra-
zoles,13 α-hydrazino tetrazoles,14 hydrazino amides,15 spiro-
quinazolinones,16 pseudopeptides,17 and oxadiazole18
Key words tetrahydro-β-carboline, Pictet–Spengler reaction, L-trypto-
phan, asymmetric synthesis
Tetrahydro-β-carboline is an important structural
framework found in a variety of natural products, such as
compounds 11 and 22 (Figure 1), exhibiting significant bio-
logical activities including antimalaria,3 anti-HIV,4 antican-
cer,5 and antiallergic effects6 and also inhibition of brain
benzodiazepine receptors.7 In this regard, various synthetic
O
O
O
OH
O
O
NHFmoc
NHFmoc
1) Et2NH, MeCN
NH2
prop-2-yn, TBTU
2) reagent K
HOBt, DIPEA, DMF
N
N
N
H
Boc
Boc
6 (87%)
5
7 (66%)
reagent K = TFA, H2O, PhOH, ethanedithiol, triethylsilane and thioanisol
Scheme 1 Synthesis of Trp-O-propargyl using Fmoc-Trp(Boc)-OH
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1955–1960

1956
V. F. Vavsari et al.
Letter
Synlett
Figure 1 Tetrahydro-β-carboline-based structures found in nature
whereas the propargyl group is a good precursor for click19
and Diels–Alder20 reactions.
In the synthesis of tetrahydro-β-carboline derivatives
3a–g via the PSR of L-tryptophan, a Boc/Fmoc protecting-
group strategy was adopted. According to the synthetic
route shown in Scheme 1, Boc/Fmoc-protected L-trypto-
phan 5 was treated with propargyl alcohol in the presence
of TBTU and HOBt as coupling agents to obtain propargyl
ester 6 in 87% yield (Scheme 1). Although, HOBt is formed
during the deprotection reaction, HOBt is used at the begin-
ning of the reaction to prevent the racemization of the re-
action (Scheme 4). Then, the Fmoc amine segment of com-
pound 6 was deprotected using diethylamine and acetoni-
trile. The ready removal of diethylamine from the reaction
mixture makes it a better base than piperidine for this reac-
O
O
NH
N
O
Ar
NH
NH
N
N
H
H
Ar
4
Ar
3
cis/trans = 1:2
Figure 2 The structure of functionalized tetrahydro-β-carbolines
O
NHFmoc
O
BF4
O
N
N
N
N
R
N
N
N
N
N
N
N
+
Me2N
NMe2
O
O
N
O
O
O
O
R
N
HOBt
NHFmoc
NHFmoc
TBTU
R
OH
O
N
NHFmoc
N
+
O
N
R
OH
Scheme 2 Proposed mechanism for the synthesis of Fmoc-Trp(O-propargyl)-OH
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1955–1960

1957
V. F. Vavsari et al.
Letter
Synlett
tion. Care was necessary during the deprotection of the Boc
amine group to avoid Friedel–Crafts reaction of the released
tert-butyl carbocation with the reactive indole ring. For this
purpose, the reagent K was chosen since it has a nucleophil-
ic component to trap the carbocation. Thus, Boc amine
deprotection was conducted by adding cooled reagent K to
the mixture. Finally, the pure tryptophan propargyl ester
(7)22 was achieved in overall yield of 66% in three reaction
steps. The proposed mechanism for the synthesis of Fmoc-
Trp(O-propargyl)-OH is illustrated in Scheme 2.
The PSR of tryptophan propargyl ester (7) with aromat-
ic and heteroaromatic aldehydes produced cis-tetrahydro-
β-carboline propargyl esters 3a–g23 with remarkably high
stereocontrol (Scheme 3), the exothermic reaction leading
to trans thermodynamic products. Therefore, the reaction
was performed at 0 °C to prevent the formation of trans iso-
mer. This reaction was accomplished using different alde-
hyde derivatives, and the results are summarized in Table 1.
In all cases, the reactions carried out at 0 °C gave the kinetic
products.
Table 2 Synthesis of Tetrahydro-β-carboline Hydrazides 4a–e Using
TFA as Catalysta
Entry
Aldehyde
Product
Yield (%)
1
2
3
4-ClC6H4CHO
4-MeOC6H4CHO
4-FC6H4CHO
4a
4b
4c
80
78
83
O
CHO
Br
4
4d
4e
85
65
5
O
a In all cases, the reaction time was 24 h.
The second aim of our approach was the synthesis of
cis- and trans-tetrahydro-β-carboline hydrazides 4a–e.
Firstly, tryptophan methyl ester (9) was produced in high
yield through the treatment of L-tryptophan (8) with thi-
onyl chloride and methanol (Scheme 4). Then, the trypto-
24
phan hydrazide (10)
was obtained by hydrazination of
O
O
NH2
tryptophan methyl ester (9) in methanol at room tempera-
ture. It is noteworthy that preservation of the enantiomeric
purity was observed during these steps.
O
O
ArCHO, TFA
CH2Cl2, 0 °C
NH
Tryptophan hydrazide (10) was then reacted with cyclo-
hexanone derivative 11, and aromatic and/or heteroaro-
matic aldehydes in the presence of a catalytic amount of
TFA at room temperature to obtain tetrahydro-β-carboline
hydrazides 4a–e (Scheme 5).25 The results are summarized
in Table 2. 4-Bromobenzaldehyde, 4-hydroxybenzaldehyde,
2-propargyloxybenzaldehyde, and isobutyraldehyde failed
to react efficiently as mixtures of products were observed
and purification was not efficient.
N
N
H
H
Ar
3a–g (52–73%)
7
Scheme 3 Synthesis of tetrahydro-β-carbolines contained propargyl
ester 3a–g
Table 1 Synthesis of cis-Tetrahydro-β-carboline Propargyl Ester 3a–g
Using TFA as Catalyst
Ungemach and co-workers21 used 13C NMR spectrosco-
py to assign the stereochemistry of tetrahydro-β-carbo-
lines. Based on these results, the chemical shifts related to
C-1 and C-3 in the trans isomers would be expected to ap-
pear downfield compared to the cis isomers. On the other
hand, the 13C NMR chemical shifts of C-1 and C-3 in com-
pound 3a are similar to data reported for cis isomers of 12a
and 13 in the Ungemach publication (Figure 3). Hence, it
was concluded that 3a was a cis-tetrahydro-β-carboline and
it is reasonable that this result can be generalized to the
other derivatives 3b–g.
Entry
Aldehyde
Product
Time (h)
Yield (%)
1
2
3
4
5
6
PhCHO
3a
3b
3c
3d
3e
3f
6
73
52
66
62
67
64
4-ClC6H4CHO
4-MeOC6H4CHO
4-(i-Pr)C6H4CHO
3-O2NC6H4CHO
4-O2NC6H4CHO
5
4.5
5.5
5
6
S
7
3g
6.5
57
CHO
H
O
O
O
OMe
OH
N
NH2
NH2
NH2
NH2
NH2NH2, H2O
MeOH, r.t., 72 h
SOCl2, MeOH
–10 °C, 24 h
N
N
N
H
H
H
8
9 (95%)
10 (95%)
Scheme 4 Synthesis of tryptophan hydrazide (10)
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1955–1960

1958
V. F. Vavsari et al.
Letter
Synlett
O
O
O
O
O
OMe
NH
O
OMe
NH
56.8
56.9
57.3
52.3
3
NH
NH
1
58.6
58.7
58.7
54.9
N
N
H
N
N
H
H
H
3a
13
12b
12a
Ungemach structures
Figure 3 13C NMR chemical shifts of C-1 and C-3 in the structures of tetrahydro-β-carbolines
Moreover, investigation of the 1H NMR spectrum of
compound 4a showed that it has two stereogenic centers,
but one of them is fixed by tryptophan. Observation of two
resonances at δ = 4.89 and 4.08 ppm indicates that both cis
and trans isomers of compound 4a were formed. Compari-
son of cis-4a and trans-4a 13C NMR chemical shifts is shown
in Figure 4. The diastereomeric ratios were measured by 1H
NMR spectral data, it showed that the cyclization reaction
provided a cis/trans isomer ratio of 2:1.
O
NH
N
27.3
NH
Cl
N
H
Cl
cis-4a
In this paper we prepared two new derivatives of L-
tryptophan including tryptophan propargyl ester (7) and
tryptophan hydrazide (10). Then, these derivatives were
used in a Pictet–Spengler reaction in the presence of TFA.
The cis-tetrahydro-β-carboline propargyl esters obtained
were pure stereoisomers; whereas the tetrahydro-β-carbo-
line hydrazides were obtained as a mixture of cis and trans
isomers with a ratio of 2:1.
O
NH
N
26.6
NH
Cl
N
H
Cl
trans-4a
Figure 4 13C NMR chemical shifts of C-1 and C-3 in cis-4a and trans-4a
O
NH
2
ArCHO
N
NH
Ar
TFA, MeOH, r.t., 24 h
N
H
Ar
H
N
O
4a–d (cis/trans)
NH2
NH2
O
N
H
NH
N
10
2
NH
O
N
H
11
TFA, MeOH, r.t., 24 h
4e
Scheme 5 Reaction of tryptophan hydrazide (10) with aldehydes and 4-tert-butylcyclohexane to access 4a–e
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1955–1960

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V. F. Vavsari et al.
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Acknowledgment
(17) Maghari, S.; Ramezanpour, S.; Balalaie, S.; Darvish, F.;
Rominger, F.; Bijanzadeh, H. R. J. Org. Chem. 2013, 78, 6450.
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Rominger, F.; Bijanzadeh, H. R. Tetrahedron 2013, 69, 2075.
(b) Zarghi, A.; Hajimahdi, Z. Expert Opin. Ther. Pat. 2013, 23,
1209.
(19) (a) Kumar, D.; Mishra, B. A.; Chandra Shekar, K. P.; Kumar, A.;
Akamatsu, K.; Kusaka, E.; Ito, T. Chem. Commun. 2013, 683.
(b) Tahoori, F.; Balalaie, S.; Sheikhnejad, R.; Sadjadi, M.; Boloori,
P. Amino Acids 2014, 46, 1033. (c) Tahoori, F.; Sheikhnejad, R.;
Balalaie, S.; Sadjadi, M. Amino Acids 2013, 45, 975.
We gratefully acknowledge the Iran National Science Foundation
(INSF) for financial support.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1378727.
S
u
p
p
ortioInfgrmoaitn
S
u
p
p
ortiInfogrmoaitn
(20) (a) Khoshkholgh, M. J.; Balalaie, S.; Gleiter, R.; Rominger, F. Tet-
rahedron 2008, 64, 10924. (b) Khoshkholgh, M. J.; Lotfi, M.;
Balalaie, S.; Rominger, F. Tetrahedron 2009, 65, 4228. (c) Ma, Z.;
Ni, F.; Woo, G. H. C.; Lo, S.-M.; Roveto, P. M.; Schaus, S. E.;
Snyder, J. K. Beilstein J. Org. Chem. 2012, 8, 829.
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(22) Synthesis of Tryptophan Propargyl Ester (7)
Fmoc-Trp(Boc)-OH (5, 5.27 g, 10 mmol) was added to O-(ben-
zotriazol-1-yl)-N,N,N′,N′-tetramethyluronium
tetrafluorobo-
rate (3.52 g, 11 mmol), N,N-diisopropylethylamine (3.9 mL, 22
mmmol), and hydroxybenzotriazole hydrate (1.48 g, 11 mmol)
in DMF, (5mL). The mixture was left at r.t. for 10 min, then prop-
argyl alcohol (1.2 mL, 20 mmol) was added and the reaction
mixture stirred for 3 h until completion (monitored by TLC). It
was diluted with EtOAc (50 mL) and then washed with Na2CO3
solution (3%), H2O, and finally brine three times in each case.
The organic phase was collected and dried over MgSO4 followed
by filtering and evaporation of the solvent to obtain pure 6 (2.98
g. 78%) as a pale yellow oil. In the Fmoc deprotection compound
6 was dissolved in MeCN (6 mL) and stirred at r.t. in the pres-
ence of Et2NH (10 mL). After completion of the reaction (1 h),
the solvent was evaporated under reduced pressure, the residue
was diluted twice with MeCN (10 mL), and the solvent was
removed under reduced pressure to remove the residual Et2NH.
The viscous oil obtained was purified by column chromatogra-
phy (gradient eluting from 100% PE to 50:50 PE–EtOAc) afford-
ing the pure intermediate as a viscous oil (90%). Finally, Boc
deprotection was accomplished by reagent K (a mixture of TFA,
PhOH, ethanedithiol, triethylsilane, and thioanisol in H2O). Puri-
fied intermediate was added to cooled reagent K (ice-water
bath, 20 mL). After 2 h, the TFA was removed, H2O was added
(20 mL), and the mixture was extracted with Et2O (40 mL), fol-
lowed by washing the organic extract with H2O, drying over
MgSO4, filtering, and removing the solvent under reduced pres-
sure to obtain pure tryptophan propargyl ester (7) as a yellow
oil (85%). 1H NMR (500 MHz, CDCl3): δ = 2.50 (t, J = 2.4 Hz,
C≡CH), 3.11 (dd, J = 14.4, 7.4 Hz, 1 H, ArCHH), 3.31 (dd, J = 14.4,
4.8 Hz, 1 H, ArCHH), 3.80 (dd, J = 7.4, 4.9 Hz, 1 H, ArCH2CH), 4.71
(d, J = 2.4 Hz, 2 H, OCH2C≡CH), 7.08–7.66 (m, 5 H, ArH), 8.17 (s, 1
H, indole NH) ppm. 13C NMR (125 MHz, CDCl3): δ = 25.9, 38.6,
53.8, 76.0, 76.4, 105.7, 111.7, 118.0, 119.7, 122.3, 125.6, 126.4,
136.3, 168.5 ppm.
(6) Omura, K.; Choshi, T.; Watanabe, S.; Satoh, Y.; Nobuhiro, J.;
Hibino, S. Chem. Pharm. Bull. 2008, 56, 237.
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K.; Nagesh, N. Org. Biomol. Chem. 2014, 12, 2370. (d) Kamal, A.;
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(23) General Procedure of the Synthesis of cis-Tetrahydro-β-car-
boline Propargyl Esters 3a–g
The general procedure for PSR was followed by addition of tryp-
tophan propargyl ester (7, 2.42 g, 1 mmol) to a solution of the
appropriate aldehyde (1.2 mmol) in CH2Cl2 (10 mL) cooled in an
ice-bath (0 °C). Then, TFA (0.23 g, 2 mmol) was slowly added to
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J. Heterocycl. Chem. 2015, in press, doi: 10.1002/jhet.2138.
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the reaction mixture. After the reaction was complete (moni-
tored by TLC), it was quenched by the addition of CH2Cl2 (20 mL)
and a solution of NaHCO3 (10 mL, 10%). The organic phase was
separated, washed with brine, dried over MgSO4, filtered, and
the solvent removed under reduced pressure. The pure product
was obtained after thick-layer chromatography.
(25) General Procedure for the Synthesis of cis- and trans-Tetra-
hydro-β-carboline Hydrazide 4a–e
The general procedure of PSR was followed by addition of tryp-
tophan hydrazide (10, 218 mg, 1 mmol) to a solution of the
appropriate aldehyde (2 mmol) in MeOH (5 mL) containing a
catalytic amount of TFA (100 μL), and the mixture was stirred at
r.t. for 24 h monitoring by TLC. Then CH2Cl2 (10 mL) was added,
and the resultant precipitate of the product was collected by fil-
tration. Column chromatography was also used for further puri-
fication of 4b–e.
(1S,3S)-Prop-2-ynyl-1-phenyl-2,3,4,9-tetrahydro-1H-pyr-
ido[3,4b]indole-3-carboxylate (3a)
Pale oil, 73% yield. IR (KBr): ν = 3388, 3281, 2135, 1750 cm–1. 1H
NMR (500 MHz, CDCl3): δ = 2.06 (br s, 1 H, NH), 2.54 (t, J = 2.5
Hz, C≡CH), 3.05 (ddd, J = 15.0, 11.2, 2.2 Hz, 1 H, H4a), 3.15 (ddd,
J = 15.0, 4.2, 2.2 Hz, 1 H, H4b), 4.07 (dd, J = 11.2, 4.2 Hz, 1 H, H3),
4.81 (dABq, J = 15.6, 2.5 Hz, 2 H, OCH2C≡CH), 5.23 (s, 1 H, H1),
7.12–7.27 (m, 3 H, ArH), 7.39 (s, 5 H, ArH),7.52 (s, 1 H, indole
NH), 7.57 (m, 1 H, ArH) ppm. 13C NMR (125 MHz, CDCl3): δ =
25.7, 52.6, 56.8, 58.6, 75.4, 77.3, 108.7, 110.9, 118.2, 119.6,
121.9, 127.1, 128.6, 129, 134.6, 136.2, 140.7, 172.0 ppm. EI-MS:
m/z (%) = 331 23) [M+ + 1], 330 (87) [M+], 291 (26), 247 (56), 218
(100), 204 (11), 169 (24), 144 (30), 57 (13), 43 (26). Anal. Calcd
for C21H18N2O2 (330.38): C, 76.34; H, 5.49; N, 8.47. Found: C,
76.14; H, 5.36; N, 8.38; O, 9.53.
(S,E)-N′-(4-Chlorobenzylidene)-1-(4-chlorophenyl)-2,3,4,9-
tetrahydro-1H-pyrido[3,4-b]indole-3-carbohydrazide (4a)
1
White solid. IR (KBr): ν = 3349, 1694 cm–1. H NMR (300 MHz,
DMSO-d6): δ (cis/trans = 1:2) =3.10–3.40 [m, 4 H, H4a,a′ (for two
diastereomers)], 3.25–3.45 [m, 2 H, H3 (for two diastereomers)],
4.08 [t, 1 H, J = 6.7 Hz, H1 (cis)], 4.89 [t, 1 H, J = 6.3Hz, H1 (trans)],
6.98 [t, 1 H, HAr (for two diastereomers)], 7.07 [t, 1 H, HAr (for
two diastereomers)], 7.21 [br s, 1 H, NH (trans)], 7.30 [d, 1 H, J =
7.8 Hz, HAr (trans)], 7.36 [d, 1 H, J = 8.1 Hz, HAr (cis)], 7.44 [d, 2
H, J = 8.1 Hz, HAr (for two diastereomers)], 7.51 [d, 2 H, J = 8.1
Hz, HAr (for two diastereomers)], 7.53 [d, 2 H, J = 8.1 Hz, HAr
(for two diastereomers)], 7.56 [d, 2 H, J = 8.1 Hz, HAr (for two
diastereomers)], 7.66 [d, 1 H, J = 7.5 Hz, HAr (cis)], 7.74 [d, 1 H,
J = 8.4 Hz, HAr (trans)], 8.02 [br s, 1 H, NH (cis)], 8.22 [br s, 1 H,
=CH (cis)], 8.32 [br s, 1 H, =CH (trans)], 10.99 [s, 1 H, NH amide
(trans)], 11.06 [s, 1 H, NH amide (cis)], 11.95 [br s, 1 H, NH
indole (trans)], 12.18 [br s, 1 H, NH indole (cis)] ppm. 13C NMR
(24) Synthesis of Tryptophan Hydrazide (10)
Hydrazine monohydrate (80%, 0.16 mL, 3.4 mmol) was added to
a mixture of tryptophan methyl ester (9, 218 mg, 1 mmol) in
MeOH (2.5 mL), and the mixture was stirred for 72 h, monitor-
ing by TLC. After evaporation of the solvent, a yellow oil was
obtained. IR (KBr): ν = 3420, 1681 cm–1 1H NMR (300 MHz,
.
DMSO-d6): δ = 2.77 (dd, 1 H J = 7.5, 15 Hz, Ha), 3.05 (dd, 1 H J =
6.0, 15 Hz, Ha′), 3.48 (t, 1 H J = 7.2 Hz, CHN), 4.46 (br s, 4 H,
NHNH2, CHNH2), 7.15 (s, 1 H, CHindol), 6.96 (t, 1 H, J = 6.8 Hz,
HAr), 7.04 (d, 1 H J = 7.0 Hz, HAr), 7.34 (d, 1 H J = 8.0 Hz, HAr),
7.55 (d, 1 H, J = 8.0 Hz, HAr), 11.00 (s, 1 H, NHNH2), 11.04 (s, 1 H,
NHIndole) ppm. 13C NMR (75 MHz, DMSO-d6): δ = 31.3, 54.3,
110.5, 111.6, 118.4, 118.6, 121.0, 124.0, 128.0, 136.3, 174.0
ppm.
(75 MHz, DMSO-d6): δ = 26.6 [C4a,a′ (trans)], 27.3 [C4a,a′ (cis)],
50.3, 52.3 [C1′, C3 (for two diastereomers)], 106.7, 108.9, 111.7,
115.3, 117.9, 118.5, 119.3, 121.2, 124.8, 127.0, 128.6, 128.8,
128.9, 129.0, 132.5, 132.7, 134.6, 134.9, 136.3, 144.1, 147.3 (for
two diastereomers), 158.0 [C=N (cis)], 158.4 [C=N (trans)], 158.4
[C=O (cis)], 158.4 [C=O (trans)] ppm. ESI-HRMS: m/z calcd for
C
18H17ClN4O [(M – C7H3Cl) + H]+: 341.11627; found: 341.11629.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1955–1960