Synthesis of 3-Amino-2-carboxamide Tetrahydropyrrolo[2,3- b ]quinolines

Article abstract of DOI:10.1055/s-0036-1588619

This article communicates the first synthesis of 3-amino-2-carboxamide pyrrolo[2,3-b]quinolines and fused-ring pyrrolopyridines in an efficient synthesis via a Thorpe-Ziegler transformation. The reported synthetic route allows for a wide range of nitrogen analogues of thienopyridines - compounds which have potent bioactivities but poor aqueous solubility.

Full text of DOI:10.1055/s-0036-1588619

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
© Georg Thieme Verlag Stuttgart · New York
2016, 27, A–D
letter
A
L. I. Pilkington et al.
Letter
Synlett
Synthesis of 3-Amino-2-carboxamide Tetrahydropyrrolo[2,3-b]quin-
olines
Lisa I. Pilkingtona
Natalie A. Haverkatea
Michelle van Rensburga
Johannes Reynissona
Euphemia Leungb
David Barker*a
CN
NH2
1. KF, DMSO, 120 °C
2. KOtBu, THF, reflux
HN
O
Cl
N
+
R'
N
H
N
R
N
RHN
R = Me, (CH2)3Ph, (CH2)3N(CH2CH2)2O
R' = various incl. H, Cl, Me, NO2
8 examples prepared, up to 54% (2 steps)
O
R'
a School of Chemical Sciences, University of Auckland,
Private Bag 92019, Auckland 1142, New Zealand
d.barker@auckland.ac.nz
b Auckland Cancer Society Research Centre and
Department of Molecular Medicine and Pathology,
University of Auckland, Private Bag 92019, Auckland
1142, New Zealand
Received: 04.08.2016
Accepted after revision: 13.09.2016
Published online: 11.10.2016
Previous syntheses of 3-amino-2-carboxamide pyrro-
lo[2,3-b]quinolines or other similar fused-ring pyrrolopyri-
dines are unreported in the literature; we herein report the
first synthesis of 3-amino-2-carboxamide pyrrolo[2,3-
b]quinolines allowing the preparation of analogues of bio-
active 3-amino-2-carboxamide thieno[2,3-b]quinolines.
To achieve our goal, we proposed to adapt our previous-
ly reported route towards thienopyridines; that route cen-
ters on the reaction between a bicyclic thiocarbonitrile and
bromoaniline and the concomitant cyclization of the result-
ing condensation product, to provide the final struc-
ture.1,4,6,10 The synthesis of nitrogen analogues requires the
use of chlorotetrahydroquinoline 1, which we envisioned
could be coupled with a primary amine 2 to give nitrile 3
which could undergo cyclization via a Thorpe–Ziegler reac-
tion (Scheme 1).
DOI: 10.1055/s-0036-1588619; Art ID: st-2016-d0513-l
Abstract This article communicates the first synthesis of 3-amino-2-
carboxamide pyrrolo[2,3-b]quinolines and fused-ring pyrrolopyridines
in an efficient synthesis via a Thorpe–Ziegler transformation. The re-
ported synthetic route allows for a wide range of nitrogen analogues of
thienopyridines – compounds which have potent bioactivities but poor
aqueous solubility.
Key words pyrrolo[2,3-b]quinolines, Thorpe–Ziegler, pyrrolo[2,3-
b]pyridines, thieno[2,3-b]pyridines, heterocycles
There has been extensive reporting on the significant
antiproliferative activities of thienopyridine derivatives
against a range of human cancer cell lines.1–9 Of particular
note is the potent activity of this family of compounds, with
some having GI50 values in the nanomolar range against tri-
ple negative breast cancer cell lines such as MDA-MB-
231/468.4 Despite these promising findings, in a recent re-
port that includes an investigation into the in vivo activity
of thienopyridines, it was noted that the poor aqueous solu-
bility of the compounds tested was a significant factor in
limiting the dose that could be tested.10 We envisioned that
the synthesis of nitrogen analogues of such a scaffold,
thereby synthesizing the corresponding pyrrolo[2,3-b]quin-
olines, could lead to compounds with improved solubility
(Figure 1).
NH2
CN
HN Ar'
H
N
Ar'
N
H
N
N
O
N
H
O
3
4
H
CN
Cl
N
Ar'
+
H2N
O
N
1
2
Scheme 1 Retrosynthetic plan towards N-unsubstituted thienopyri-
dine analogues
NH2
NH2
HN
HN
R
R
N
O
Initially, we decided to test our proposed methodology
on the synthesis of N-unsubstituted nitrogen analogues,
containing phenyl (4a) or 2-naphthyl (4b) carboxamide.
The required amines 2a,b were synthesized from the corre-
sponding N-aryl bromoacetamides1 5a,b, in two steps; for-
S
N
O
N
R'
thienoquinolones
target pyrrolo[2,3-b]quinolines
Figure 1 Target pyrrolo[2,3-b]quinolines
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–D

B
L. I. Pilkington et al.
Letter
Synlett
mation of azides 6a,b using NaN3 in DMSO, and hydrogena-
tion of 6a,b gave 2a,b in yields of 94% and 84%, respectively,
over two steps (Scheme 2).
H
H
N
N
i
Ar'
Ar'
RHN
1
+
Br
O
O
9
5
ii
H
H
H
N
N
N
ii
i
Ar'
Ar'
Br
N3
Ar'
H2N
O
O
O
NH2
CN
iii
HN Ar'
O
5
6
2
H
N
Ar'
N
R
N
N
+
N
O
R
O
CN
O
CN
Cl
iii, iv
v
11
10
9–11a; R = Me, Ar' = phenyl
9–11b; R = Me, Ar' = 2-naphthyl
9–11c; R = Me, Ar' = 2-chlorophenyl
N
N
H
1
7
8
9–11d; R = Me, Ar' = 2-methyl-3-chlorophenyl
9–11e; R = Me, Ar' = 2,3-dimethylphenyl
9–11f; R = Me, Ar' = 3-nitrophenyl
9–11g; R = 3-phenylpropyl, Ar' = phenyl
9–11h; R = 3-morpholinopropyl, Ar' = phenyl
vi
a; Ar' = phenyl
b; Ar' = 2-naphthyl
NH2
Scheme 3 Synthesis of N-substituted pyrrolo[2,3-b]quinolines. Reagents
and conditions: i) amine, EtOH, r.t., 24 h, 9a–h (68% to quant.); ii) KF (2.4
equiv), DMSO, 120 °C, 24 h, 10a–h (10–54%); iii) KOtBu (1.2 equiv),
THF, reflux, 30–60 min, 11a–h (64% to quant.).
CN
HN Ar'
O
H
N
Ar'
N
N
N
H
N
H
O
3
4
Utilizing the previously optimized coupling condi-
tions,12 the coupled products 10 were successfully synthe-
sized, however, once again with no cyclization products 11
seen, which is contrasting with the synthesis of thienopyri-
dines which are often formed in a single step.1,4,6,10 Cycliza-
tion conditions were tested using 10a18 (see Table 1 for a
summary of conditions tested); heating 10a with a number
of bases including NaHCO3, Na2CO3, Cs2CO3 in various sol-
vents did not induce cyclization, with only starting material
isolated after extended reaction times. When the reaction
was attempted with stronger base KOtBu, after four hours at
80 °C only degradation products were seen. The reaction
did not proceed at room temperature, even after five days,
however, using KOtBu in THF at 80 °C for just one hour, the
desired substituted pyrrolo[2,3-b]quinoline 11a19 was ob-
tained in quantitative yield. These conditions were then re-
peated for the remaining nitriles 10b–f,20 providing pyrro-
lo[2,3-b]tetrahydroquinolines 11b–f in 64% to quantitative
yields.
Scheme 2 Attempted synthesis of N-unsubstituted pyrrolo[2,3-b]pyri-
dines. Reagents and conditions: i) NaN3 (1.1 equiv), DMSO, r.t., 24 h, 6a
(quant.), 6b (88%); ii) Pd/C, H2 (atm.), MeOH, r.t., 18 h, 2a (94%), 2b
(95%); iii) Na (1 equiv), ethyl formate (1 equiv), EtOH (cat.), Et2O, r.t., 24
h, 66%; iv) cyanoacetamide (1 equiv), piperidinium acetate, H2O, reflux,
24 h, 48%; v) POCl3 (1.3 equiv), reflux, 24 h, 67%; vi) KF (2.4 equiv),
DMSO, 120 °C, 24 h, 3a (51%), 3b (50%).
Chloroquinoline 1 was formed through the chlorination,
using POCl3 of 7,11 itself formed following literature proce-
dures from cyclohexanone 8.1 Amination of chloride 1 with
amines 2a,b was performed in DMSO with KF (2.4 equiv) at
120 °C overnight12 to give coupled products 3a,b, respec-
tively. No cyclization products 4a,b were obtained. Unfortu-
nately, despite a large number of conditions attempted to
effect this cyclization to 4, including reactions with a num-
ber of different bases for extended reaction times with
heating, no cyclized products were isolated from the reac-
tion. A literature investigation provided very few examples
of successful cyclization of similar cyanopyridines, and no
examples without additional electron-withdrawing groups
on the pyridine ring.13–15 The Thorpe–Ziegler reaction of
these compounds is proposed to be difficult due to depro-
tonation of the amine rather than the α-amide protons
which is required for cyclization.16
Following the unsuccessful synthesis of the N-unsubsti-
tuted analogues 4, we wished to prepare analogues con-
taining an N-substituent, which we hoped would allow for
the cyclization to proceed. We began using a methyl sub-
stituent and methyl amines 9a–f were obtained in quanti-
tative yields through the direct amination of bromides 5a,b
prepared earlier as well as a number of other analogues 5c–
f using methylamine in EtOH (Scheme 3).17
Table 1 Summary of the Conditions Tested in the Formation of Pyrro-
lo[2,3-b]quinoline 10a
Base
NaHCO3
Solvent
Temp
Time
Result
EtOH
EtOH
MeCN
MeCN
THF
reflux
reflux
70 °C
50 °C
r.t.
4 d
3 d
5 d
6 h
5 d
1 h
4 h
no reaction
no reaction
no reaction
no reaction
no reaction
10a (quant.)
complex mixture
Na2CO3
Na2CO3
Cs2CO3
KOtBu
KOtBu
THF
80 °C
80 °C
KOtBu
THF
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–D

C
L. I. Pilkington et al.
Letter
Synlett
We then decided to explore whether this method could
be adapted to allow for other substituents attached to the
nitrogen atom; 3-phenylpropylamine and 3-morpholino-
amine were added to bromide 5a, giving amines 9g21 and
9h22 in 68% and 95% yields, respectively. These amines were
coupled12 and then cyclized20 to provide N-3-phenylpropyl
and N-3-morpholinopropyl analogues 11g and 11h, respec-
tively.
Acknowledgment
We wish to acknowledge the Auckland Medical Research Foundation
and the University of Auckland for funding for this work.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588619.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
o
nrtogI
f
rmoaitn
In addition to the substitution on the aryl ring, one of
the main points of variation that is extensively investigated
for thienopyridines is the size of the fused nonaromatic
ring. We wished to determine that if the method could be
applied to the generation of nitrogen analogues of other
heterocycles, thus the eight-membered bicycle 12 was
formed from cyclooctanone 13 firstly by conversion into
the α-hydroxymethylene salt and then its reaction with cy-
anoacetamide and piperidinium acetate, followed by acidi-
fication with acetic acid, to give bicyclic product 14 which
was then chlorinated to provide 12. Chloride 12 was then
coupled12 with amine 9a to give 15 which was then cy-
clized20 to give 16 in quantitative yield (Scheme 4).
References and Notes
(1) Leung, E.; Pilkington, L. I.; van Rensburg, M.; Jeon, C. Y.; Song,
M.; Arabshahi, H. J.; De Zoysa, G. H.; Sarojini, V.; Denny, W. A.;
Reynisson, J.; Barker, D. Bioorg. Med. Chem. 2016, 24, 1142.
(2) Reynisson, J.; Court, W.; O’Neill, C.; Day, J.; Patterson, L.;
McDonald, E.; Workman, P.; Katan, M.; Eccles, S. A. Bioorg. Med.
Chem. 2009, 17, 3169.
(3) Feng, L.; Reynisdóttir, I.; Reynisson, J. Eur. J. Med. Chem. 2012,
54, 463.
(4) Leung, E.; Hung, J. M.; Barker, D.; Reynisson, J. Med. Chem.
Comm. 2014, 5, 99.
(5) Arabshahi, H. J.; Leung, E.; Barker, D.; Reynisson, J. Med. Chem.
Comm. 2014, 5, 186.
(6) Hung, J. M.; Arabshahi, H. J.; Leung, E.; Reynisson, J.; Barker, D.
Eur. J. Med. Chem. 2014, 86, 420.
(7) Deng, X. Q.; Wang, H. Y.; Zhao, Y. L.; Xiang, M. L.; Jiang, P. D.;
Cao, Z. X.; Zheng, Y. Z.; Luo, S. D.; Yu, L. T.; Wei, Y. Q.; Yang, S. Y.
Chem. Biol. Drug Des. 2008, 71, 533.
O
CN
O
CN
Cl
i, ii
iii
iv
N
N
H
13
14
12
(8) Zeng, X. X.; Zheng, R. L.; Zhou, T.; He, H. Y.; Liu, J. Y.; Zheng, Y.;
Tong, A. P.; Xiang, M. L.; Song, X. R.; Yang, S. Y.; Yu, L. T.; Wei, Y.
Q.; Zhao, Y. L.; Yang, L. Bioorg. Med. Chem. Lett. 2010, 20, 6282.
(9) Zhou, R.; Huang, W. J.; Guo, Z. Y.; Li, L.; Zeng, X. R.; Deng, Y. Q.;
Hu, F. Y.; Tong, A. P.; Yang, L.; Yang, Y. L. Oncol. Rep. 2012, 28,
225.
NH2
CN
HN
v
H
N
N
N
N
O
N
O
Me
Me
(10) (a) Arabshahi, H. J.; van Rensburg, M.; Pilkington, L. I.; Jeon, C.
Y.; Song, M.; Gridel, L.-M.; Leung, E.; Barker, D.; Vuica-Ross, M.;
Volcho, K. P.; Zakharenko, A. L.; Lavrik, O. I.; Reynisson, J. Med.
Chem. Commun. 2015, 6, 1987. (b) Reynisson, J.; Jaiswal, J. K.;
Barker, D.; D’Mello, A.; Denny, S. W. A.; Baguley, B. C.; Leung, E.
Y. Cancer Cell Int. 2016, 16, 18.
(11) Dabaeva, V. V.; Bagdasaryan, M. R.; Noravyan, A. S.;
Dzhagatspanyan, I. A.; Nazaryan, I. M.; Akopyan, A. G. Pharm.
Chem. J. 2015, 49, 587.
16
15
Scheme 4 Synthesis of N-substituted fused-ring pyrrolopyridine. Re-
agents and conditions: i) Na (1 equiv), ethyl formate (1 equiv), EtOH
(cat.), Et2O, r.t., 24 h, 73%; ii) cyanoacetamide (1 equiv), piperidinium
acetate, H2O, reflux, 24 h, 61%; iii) POCl3 (1.3 equiv), reflux, 24 h, 58%;
iv) 9a, KF (2.4 equiv), DMSO, 120 °C, 18 h, 33%; v) KOtBu (1.2 equiv),
THF, reflux, 10 min, quant.
(12) General Procedure for the Coupling of Carbonitrile and
Amine
The methods reported here allow the synthesis of pyr-
rolo[2,3-b]tetrahydroquinolines and fused-ring pyrrolopyr-
idines in an efficient synthesis that allows for several points
of variation on the structure, including the size of the non-
aromatic fused ring, substitution on the pyrrolic nitrogen,
and substitution on the aryl ring. This methodology allows
for the synthesis of novel analogues of thieno[2,3-b]pyri-
dine compounds with additional substitution on the pyrro-
lo nitrogen. These additional substituents could incorpo-
rate functionalities that allow for improved solubility
and/or bioactivity; we are currently investigating the effect
of these changes, and results will be reported in due course.
A mixture of carbonitrile (1 equiv) and amine (1 equiv) were
dissolved in DMSO, and KF (2.4 equiv) was added under an
atmosphere of N2. The mixture was heated at 120 °C overnight,
before cooling to r.t. The reaction was diluted with EtOAc,
before being quenched with H2O. The mixture was then
extracted with EtOAc (2×), and the combined organic extracts
were washed with H2O (5×), brine, dried (MgSO4), and the
solvent removed in vacuo to give the crude product, which was
then purified using flash chromatography to give the desired
product.
(13) Vitorino, P.; Yeung, S.; Crow, A.; Bakke, J.; Smyczek, T.; West, K.;
McNamara, E.; Eastham-Anderson, J.; Gould, S.; Harris, S. E.;
Ndubaku, C.; Ye, W. Nature (London, U.K.) 2015, 519, 425.
(14) Dyke, H. J.; Gancia, E.; Gazzard, L. J.; Goodacre, S. C.; Lyssikatos, J.
P.; Macleod, C.; Williams, K. WO 2009151589, 2009.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–D

D
L. I. Pilkington et al.
Letter
Synlett
(15) Daghish, M.; Schulze, A.; Reichelt, C.; Ludwig, A.; Leistner, S.;
Heinicke, J.; Kroedel, A. WO 2006100095, 2006.
(C-1′), 157.8 (C-9a), 161.0 (C-8a), 168.8 (C=O). MS (ESI+): m/z (%)
= 321 (20) [MH+], 218 (100). HRMS (ESI+): m/z calcd for
(16) Yakovlev, M. Y.; Kadushkin, A. V.; Granik, V. G. Pharm. Chem. J.
1996, 30, 107.
(17) General Procedure for the Synthesis of N-Methyl Phenylacet-
amides
C19H21N4O: 321.1710; found 321.1706.
(20) General Procedure for the Synthesis of Pyrrolo[2,3-b]quino-
lines
Uncyclized nitrile (1 equiv) was dissolved in dry THF and KOtBu
(1.2 equiv) added under an atmosphere of N2. The mixture was
heated at 70 °C until completion, monitored by TLC, then cooled
to r.t. before being quenched with H2O and extracted with
EtOAc (2×). The combined organic extracts were washed with
brine, dried (MgSO4), and the solvent removed in vacuo to give
the desired compound.
Methylamine in 33% EtOH (55 equiv) was added to the N-aryl
bromoacetamide (1 equiv). The mixture was stirred at r.t. over-
night and solvent removed in vacuo to give the desired com-
pound. The resulting phenylacetamides were used in the next
reaction without further purification.
(18) 2-[(3-Cyano-5,6,7,8-tetrahydroquinolin-2-yl)(methyl)-
amino]-N-phenylacetamide (10a)
(21) N-Phenyl-2-[(3-phenylpropyl)amino]acetamide (9g)
The reaction was carried out following the general procedure
using 2-bromo-N-phenylacetamide (5a, 1.00 g, 4.67 mmol) and
3-phenylpropylamine (2.53 g, 18.7 mmol) in EtOH (25 mL) to
give the title compound 9g (0.856 g, 68%) as an orange oil. IR
(ATR): νmax = 3285, 3026, 2858, 1667, 1600, 1442, 1252 cm–1. 1H
NMR (400 MHz, CDCl3): δ = 1.81–1.90 (2 H, m, H-2), 1.92 (1 H, s,
NH), 2.68–2.73 (4 H, m, H-1 and H-3), 3.36 (2 H, s, NCH2C=O),
7.09 (1 H, t, J = 7.4 Hz, H-4′), 7.11–7.35 (7 H, m, H-3′ and ArH),
7.58 (2 H, d, J = 7.4 Hz, H-2′), 9.30 (1 H, s, NH). 13C NMR (100
MHz, CDCl3): δ = 31.7 (C-2), 33.5 (C-3), 49.8 (C-1), 53.0
(NCH2C=O), 119.4 (C-2′), 124.0 (C-4′), 126.0 (ArCH), 128.3
(ArCH), 128.4 (ArCH), 129.0 (ArCH), 137.6 (C-1′), 141.5 (C-1′′),
169.8 (C=O). MS (ESI+): m/z (%) = 269 (100) [MH+], 148 (65).
HRMS (ESI+): m/z calcd for C17H21N2O: 269.1648; found [MH+]:
269.1651.
(22) 2-[(3-Morpholinopropyl)amino]-N-phenylacetamide (9h)
The reaction was carried out following the general procedure
using 2-bromo-N-phenylacetamide (5a, 0.700 g, 2.59 mmol)
and 3-morpholinopropylamine (2.24 g, 15.5 mmol) in EtOH (10
mL) to give the title compound 9h (0.791 g, quant.) as an orange
oil. IR (ATR): νmax = 3285, 2944, 2855, 1674, 1600, 1442, 1254,
1115 cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.69–1.74 (3 H, m, H-
2 and NH), 2.41–2.45 (6 H, m, H-3, NCH2CH2O), 2.71–2.75 (2 H,
m, H-1), 3.36 (2 H, s, NCH2C=O), 3.68–3.71 (4 H, m, NCH2CH2O),
7.09 (1 H, t, J = 7.4 Hz, H-4′), 7.32 (2 H, t, J = 7.4 Hz, H-3′), 7.56 (2
H, d, J = 7.4 Hz, H-2′), 9.30 (1 H, s, NH). 13C NMR (100 MHz,
The reaction was carried out following the general procedure
using carbonitrile 1 (0.100 g, 0.520 mmol), 9a (80.0 mg, 0.520
mmol), KF (73.0 mg, 1.26 mmol), and dry DMSO (2.5 mL) and
purified with flash chromatography (n-hexanes–EtOAc = 2:1) to
give the title compound 10a (85.0 mg, 51%) as a white solid; mp
159–161 °C. IR (ATR): νmax = 3268, 3093, 2933, 2211, 1672,
1547, 1415, 1251, 1209 cm–1 1H NMR (400 MHz, CDCl3): δ =
.
1.79–1.90 (4 H, m, H-6 and H-7), 2.67 (2 H, t, J = 5.4 Hz, H-5),
2.83 (2 H, t, J = 5.4 Hz, H-8), 3.41 (3 H, s, NCH3), 4.26 (2 H, s,
NCH2C=O), 7.07–7.11 (1 H, m, H-4′), 7.32 (2 H, m, H-3′), 7.49–
7.53 (2 H, m, H-2′), 7.53 (1 H, s, H-4), 9.17 (1 H, br s, NH). 13C
NMR (100 MHz, CDCl3): δ = 22.5 (C-6 and C-7), 27.2 (C-5), 33.0
(C-8), 40.0 (NCH3), 57.5 (NCH2C=O), 91.5 (C-3), 118.2 (CN),
119.6 (C-2′), 123.7 (C-4a), 124.2 (C-4′), 129.0 (C-3′), 137.9 (C-1′),
144.8 (C-4), 157.4 (C-2), 160.6 (C-8a) 168.5 (C=O). MS (ESI+):
m/z (%) = 343 (100) [MH+], 321 (5). HRMS (ESI+): m/z calcd for
C19H20N4NaO: 343.1529; found: 343.1524.
(19) 3-Amino-1-methyl-N-phenyl-5,6,7,8-tetrahydro-1H-pyr-
rolo[2,3-b]quinoline-2-carboxamide (11a)
The reaction was carried out following the general procedure
using 10a (0.100 g, 0.310 mmol), KOtBu (40.0 mg, 0.310 mmol)
and THF (2 mL) to give the title compound 11a (90.0 mg, 90%) as
a dark brown solid; mp 102–105 °C. IR (ATR): νmax = 3282, 2930,
1728, 1598, 1443, 1259 cm–1. 1H NMR (400 MHz, (CD3)2CO): δ =
1.73–1.82 (4 H, m, H-6 and H-7), 2.64–2.70 (4 H, m, H-5 and H-
8), 3.42 (3 H, s, NCH3), 4.40 (2 H, s, NH2), 7.04 (1 H, t, J = 7.4 Hz,
H-4′), 7.28 (2 H, t, J = 7.4 Hz, H-3′), 7.58 (1 H, s, H-4), 7.63 (2 H, d,
J = 7.4 Hz, H-2′), 9.30 (1 H, br s, NH). 13C NMR (100 MHz,
(CD3)2CO): δ = 23.39 and 23.41 (C-6 and C-7), 27.6 (C-5), 33.6
(C-8), 40.3 (NCH3), 119.6 (C-3a), 120.2 (C-2), 120.3 (C-2′), 122.9
(C-3), 124.2 (C-3′), 129.5 (C-4), 129.6 (C-4′), 140.1 (C-4a), 145.3
CDCl3):
δ = 26.6 (C-2), 48.9 (C-1), 53.1 (NCH2C=O), 53.8
(NCH2CH2O), 57.1 (C-3), 67.0 (NCH2CH2O), 119.4 (C-2′), 124.1
(C-4′), 129.0 (C-3′), 137.6 (C-1′), 169.9 (C=O). MS (ESI+): m/z (%)
= 278 (100) [MH+], 128 (55). HRMS (ESI+): m/z calcd for
C
15H24N3O2: 278.1863; found [MH+]: 278.1860.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–D