Synthesis of novel polyfunctional pyrrolo[2,1-a]isoquinolines based on 1,3-dipolar cycloaddition reactions

Article abstract of DOI:10.1007/s11172-019-2617-x

A series of 5-substituted 8-nitroisoquinolines was synthesized based on the reaction of 5-bromo-8-nitroisoquinohne with various nucleophiles. N-Alkylation products of 8-nitroisoquinolines were shown to undergo 1,3-dipolar cycloaddition to substituted alkenes and alkynes as dipolarophiles in the presence of a base to form new polyfunctional nitro-containing pyrrolo-[2,1-a]isoquinolines and their hydrogenated analogs.

Full text of DOI:10.1007/s11172-019-2617-x

Russian Chemical Bulletin, International Edition, Vol. 68, No. 9, pp. 1729—1734, September, 2019
1729
Synthesis of novel polyfunctional pyrrolo[2,1-a]isoquinolines
based on 1,3-dipolar cycloaddition reactions
M. A. Bastrakov and A. M. Starosotnikov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. E-mail: alexey41@list.ru
A series of 5-substituted 8-nitroisoquinolines was synthesized based on the reaction of
5-bromo-8-nitroisoquinoline with various nucleophiles. N-Alkylation products of 8-nitroiso-
quinolines were shown to undergo 1,3-dipolar cycloaddition to substituted alkenes and alkynes
as dipolarophiles in the presence of a base to form new polyfunctional nitro-containing pyrrolo-
[2,1-a]isoquinolines and their hydrogenated analogs.
Key words: pyrrolo[2,1-а]isoquinoline, nitro compounds, [3+2] cycloaddition, nucleo-
philic substitution.
The interest in pyrrolo[2,1-а]isoquinolines and their
tetrahydro derivatives is mainly due to the fact that these
compounds exhibit various biological activities, including
fungicidal1 and antibacterial.2 The pyrrolo[2,1-а]iso-
quinoline core is a part of many alkaloids.3,4 For example,
alkaloid Crispine A has a high antitumor activity,5 while
Oleracein E possesses an antioxidant activity.6 Lamellarins
exhibit antibacterial and antiproliferative effects, as well
as cytotoxicity and antitumor activity.7 In particular,
Lamellarin D has a strong cytotoxic effect8 and is a potent
inhibitor of Topoisomerase I.
example, multicomponent versions of the construction
of the pyrrolo[2,1-а]isoquinoline system were devel-
oped.10—12 The use of N-heterocyclic carbenes13 and
triphosphine14 as mediators of the process was reported.
Data on the approaches to the synthesis of pyrrolo[2,1-а]-
isoquinolines are summarized in reviews.15,16
Traditionally, the presence of a nitro group in phar-
macologically oriented molecules was considered undesir-
able.17 However, the works of the last 10 years devoted to
medicinal molecules containing a nitro group and sum-
marized in the review17 refute this point of view. In par-
ticular, we found that a number of benzofuroxan and
benzofurazan nitro derivatives exhibit a high inhibitory
activity against HIV-1 integrase.18,19 In addition, it is
known that natural nitro compounds have a broad struc-
tural diversity and a wide spectrum of biological activity.20
In the present work, we describe the synthesis of new
polyfunctional nitro derivatives of pyrrolo[2,1-а]iso-
quinoline and their hydrogenated analogs based on iso-
quinoline 1. 5-Bromo-8-nitroisoquinoline (2a) was syn-
thesized according to the known procedure21 (Scheme 1).
We found that the bromine atom in this compound is
quite readily replaced by various nucleophiles to form
products 2b—e.
Alkylation of compounds 2a—e with bromoacetophe-
none gives isoquinolinium salts 3a—e, which were further
involved into the reactions with alkenes and acetylenes in
the presence of Et3N (Scheme 2).
Reactions of 3a with dimethyl maleate and N-phenyl-
maleimide gave tetrahydropyrrolo[2,1-a]isoquinoline
derivatives 4a,b in high yields. It was found that the reac-
tion of salt 3a with dimethyl acetylenedicarboxylate is
accompanied by oxidative aromatization of the intermedi-
ate dihydro derivative, leading to pyrrolo[2,1-a]isoquino-
Such structures are often synthesized by the 1,3-dipo-
lar cycloaddition of N-alkylisoquinolinium salts to un-
saturated compounds in the presence of bases (see, for
example, Ref. 9). Recently, the synthesis methods of
pyrrolo[2,1-а]isoquinolines were actively improved. For
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1729—1734, September, 2019.
1066-5285/19/6809-1729 © 2019 Springer Science+Business Media, Inc.

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Russ. Chem. Bull., Int. Ed., Vol. 68, No. 9, September, 2019
Bastrakov and Starosotnikov
Scheme 1
Compound
2b
2c
R
BnS
MeO
Yield (%)
37
Compound
2d
2e
R
Yield (%)
4-Cl—C6H4S
Pyrrolidin-1-yl
88
79
96
Reagents and conditions: i. BnSH (1 equiv.), Et3N, MeOH, 20 C, 24 h (for 2b); MeONa (2 equiv.), MeOH, 65 С, 10 h (for 2с);
4-Cl—C6H4SH (1 equiv.), Et3N, MeOH, 20 C, 24 h (for 2d), pyrrolidine (2 equiv.), MeOH, 65 C, 5 h (for 2e).
Scheme 2
3
a
b
c
R
Br
SBn
OMe
Yield (%)
3
d
e
R
Yield (%)
64
74
75
59
4-Cl—C6H4S
Pyrrolidin-1-yl
88
Reagents and conditions: i. PhCOCH2Br, EtOAc, 4 h, heating; ii. dipolarophile, Et3N, DMSO, 20 °С.
line 4c. When nonsymmetric dipolarophiles (methyl ac-
rylate and methyl propiolate) were used, only one regio-
isomer (4d and 4e, respectively) was formed, the structure
of which was established based on spectral data. The sig-
nals in the 1H and 13C NMR spectra of compound 4d were
assigned using 2D COSY, HMQC, and HMBC procedures.

Synthesis of novel pyrrolo[2,1-a]isoquinolines
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 9, September, 2019
1731
The 2D NOESY NMR spectrum of compound 4d exhib-
its cross-peaks (Fig. 1), allowing not only to determine
the position of the CO2Me group in the pyrrolidine ring,
but also to establish the stereochemical features of the
cycloaddition: the CO2Me and COPh groups are in the
anti-configuration with respect to the pyrrolidine ring.
The other 5-substituted 8-nitroisoquinolinium salts 2b—e
reacted with dimethyl maleate and N-phenylmaleimide
to give the expected adducts 4f—l (see Scheme 2). The
structures of all the synthesized compounds were estab-
lished based on a combination of spectral data (NMR and
IR spectroscopy, high resolution mass spectrometry).
In conclusion, a series of new polyfunctional pyr-
rolo[2,1-a]isoquinolines were synthesized by the 1,3-di-
polar cycloaddition reactions of N-phenacyl-5-R-8-
nitroisoquinolines with functionally substituted alkenes
and alkynes,. The addition to dipolarophiles containing
a triple bond is accompanied by oxidative aromatization
of intermediate dihydropyrrolo[2,1-a]isoquinolines. The
cycloaddition is regioselective in the case of nonsymmet-
ric dipolarophiles (acrylic and propiolic esters).
Experimental
Melting points were measured on a Stuart SMP20 instrument.
1H and 13C NMR spectra were recorded on Bruker AC-200
(1H, 200 MHz; 13C, 50 MHz), Bruker AM-300 spectrometers
(1H, 300 MHz; 13C, 75 MHz). All experiments were performed
using standard Bruker procedures. Chemical shifts are given
relative to Me4Si. Samples for NMR spectroscopy were prepared
in DMSO-d6 or CDCl3. IR spectra were recorded on a Bruker
Alpha spectrometer, the samples were prepared in pellets with
KBr. Electrospray ionization (ESI) high-resolution mass spectra
(HRMS) were recorded on a Bruker maXis instrument. The
measurements were carried out on positive (the capillary voltage was
4500 V) ions. The range of mass scanning was m/z 50—3000 Da,
using external calibration (Electrospray Calibrant Solution,
Fluka). A syringe injection was used for solutions in acetonitrile,
the flow rate was 3 μL min–1. The nebulizer gas was nitrogen
(4 L min–1), the interface temperature was 180 C. The reaction
progress and the purity of compounds were monitored by TLC
on Silica gel 60 F254 plates (Merk).
5-Bromo-8-nitroisoquinoline (2a). N-Bromosuccinimide
(17.8 g, 10 mmol) was added in portions to a solution of iso-
quinoline 1 (10.1 mL, 8.5 mmol) in concentrated H2SO4
(100 mL) at –10 C. The mixture was stirred for 2 h at 20 C,
followed by the addition of KNO3 (11.2 g, 11.1 mmol) and stand-
ing at room temperature for 48 h. Then, the mixture was poured
in ice and neutralized with saturated aqueous NH3, the precipi-
tate formed was collected by filtration and recrystallized from
MeOH. The yield was 14.2 g (65%). M.p. 134—135 C (Ref. 21:
1
137—139 C). H NMR (DMSO-d6), : 8.11 (d, 1 H, CHarom
J = 5.9 Hz); 8.33 (s, 2 H, 2 CHarom); 8.83 (d, 1 H, CHarom
J = 5.9 Hz); 9.76 (s, 1 H, CHarom).
,
,
5-(Benzylthio)-8-nitroisoquinoline (2b). Benzylmercaptane
(0.71 mL, 6 mmol) and Et3N (0.83 mL, 6 mmol) were added to
a suspension of bromide 2а (1.52 g, 6 mmol) in MeOH (25 mL).
The reaction mixture was stirred for 24 h at 20 C and poured
into water (150 mL), the precipitate formed was collected by
filtration and recrystallized from MeOH. The yield was 0.64 g
Fig. 1. Chemical shifts (δH and δC) and key correlations observed
in the 2D NOESY NMR spectrum of compound 4d.

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Russ. Chem. Bull., Int. Ed., Vol. 68, No. 9, September, 2019
Bastrakov and Starosotnikov
(37%). M.p. 138—139 C. 1H NMR (DMSO-d6), : 4.58 (s, 2 H,
CH2); 6.90—7.70 (m, 5 H, Ph); 7.88 (d, 1 H, CHarom, J = 8.3 Hz);
(d, 1 H, CHarom, J = 8.2 Hz); 8.98 (s, 2 H, 2 CHarom); 10.49
(s, 1 H, CHarom). 13C NMR (DMSO-d6), : 67.3, 120.4, 122.4,
128.0, 128.4, 128.8, 129.2, 129.3, 130.4, 133.6, 134.8, 134.9,
135.1, 138.7, 142.3, 145.5, 148.9, 190.6. IR, /cm–1: 1322 (NO2),
1506 (NO2); 1678 (C=O). HRMS: found m/z 415.1106 [M – Br]+;
C24H19N2O3S; calculated 415.1111.
8.08 (d, 1 H, CHarom, J = 5.6 Hz); 8.39 (d, 1 H, CHarom
,
J = 8.3 Hz); 8.71 (d, 1 H, CHarom, J = 5.9 Hz); 9.86 (s, 1 H,
CHarom). 13C NMR (DMSO-d6), : 35.5, 116.1, 124.7, 125.6,
127.7, 128.7, 129.1, 133.1, 135.4, 142.3, 144.1, 144.5, 148.3.
5-Methoxy-8-nitroisoquinoline (2c). Sodium methoxide
(0.66 g, 12 mmol) was added to a suspension of bromide 2а
(1.52 g, 6 mmol) in MeOH (25 mL ). The reaction mixture was
refluxed for 5 h, poured into water (150 mL), and extracted with
ethyl acetate (3×50 mL), the organic layer was concentrated, the
residue was dried in air. The yield was 1.18 g (96%). M.p.
148—150 C. 1H NMR (DMSO-d6), : 4.12 (s, 3 H, OMe); 7.32
(d, 1 H, CHarom, J = 8.8 Hz); 8.06 (d, 1 H, CHarom, J = 5.7 Hz);
5-Methoxy-8-nitro-2-(2-oxo-2-phenylethyl)isoquinolinium
1
bromide (3c). The yield was 59%. M.p. 186—187 C. H NMR
(DMSO-d6), : 4.27 (s, 3 H, OMe); 6.87 (s, 2 H, NCH2); 7.68
(t, 2 H, Ph, J = 7.6 Hz); 7.78—7.85 (m, 2 H, Ph, CHarom); 8.11
(d, 2 H, Ph, J = 7.6 Hz); 8.93—9.03 (m, 3 Н, CHarom); 10.55
(s, 1 H, CHarom). 13C NMR (DMSO-d6), : 58.6, 67.9, 113.1,
121.5, 121.7, 128.9, 129.6, 130.3, 133.4, 134.1, 135.2, 138.1,
138.9, 148.6, 159.5, 191.2. HRMS: found m/z 323.1024 [M – Br]+;
C18H15N2O4; calculated 323.1026.
8.53 (d, 1 H, CHarom, J = 8.7 Hz); 8.68 (d, 1 H, CHarom
,
J = 5.7 Hz); 9.92 (s, 1 H, CHarom). 13C NMR (DMSO-d6), :
57.6, 107.2, 115.0, 121.1, 128.2, 129.3, 138.1, 144.5, 147.9, 159.7.
5-(4-Chlorophenylthio)-8-nitroisoquinoline (2d). 4-Chloro-
thiophenol (0.87 g, 6 mmol) and Et3N (0.84 mL, 6 mmol) were
added to a suspension of bromide 2а (1.52 g, 6 mmol) in MeOH
(25 mL). The reaction mixture was stirred for 24 h, poured into
water, and acidified to рН 2. The precipitate formed was col-
lected by filtration. The yield was 1.67 g (88%). M.p. 133—134 C.
1H NMR (DMSO-d6), : 7.43 (d, 1 H, CHarom, J = 8.3 Hz);
7.58 (s, 4 H, 4-Cl—C6H4); 8.17 (d, 1 H, CHarom, J = 5.9 Hz);
5-(4-Chlorophenylthio)-8-nitro-2-(2-oxo-2-phenylethyl)-
isoquinolinium bromide (3d). The yield was 64%. M.p. 205—206 C.
1H NMR (DMSO-d6), : 6.86 (s, 2 H, NCH2); 7.67—7.85
(m, 8 H, Ph); 8.12 (d, 2 H,2 CHarom, J = 7.6 Hz); 8.71 (d, 1 H,
CHarom, J = 8.4 Hz); 9.05—9.12 (m, 2 Н, 2 CHarom); 10.51
(s, 1 H, CHarom). 13C NMR (DMSO-d6), : 121.0, 123.1, 128.1,
128.9, 129.6, 129.9, 131.3, 133.8, 134.1, 135.2, 135.7, 136.0,
136.6, 139.6, 144.1, 145.2, 149.5, 191.0. HRMS: found m/z
435.0560 [M – Br]+; C23H16ClN2O3S; calculated 435.0565.
8-Nitro-2-(2-oxo-2-phenylethyl)-5-pyrrolidin-1-ylisoquin-
olinium bromide (3e). The yield was 88%. M.p. 244—245 С.
1H NMR (DMSO-d6), : 2.06 (br.s, 4 Н, 2 CH2); 3.89 (br.s,
8.33 (d, 1 H, CHarom, J = 8.3 Hz); 8.78 (d, 1 H, CHarom
,
J = 5.9 Hz); 9.85 (s, 1 H, CHarom). 13C NMR (DMSO-d6),
: 116.8, 120.0, 126.1, 128.8, 129.3, 130.9, 143.0, 144.3,
145.4, 148.8.
4 Н, 2 CH2); 6.77 (s, 2 Н, NCH2); 7.17 (d, 1 Н, CHarom
,
J = 9.6 Hz); 7.69 (t, 2 Н, Ph, J = 7.5 Hz); 7.81 (t, 1 Н, Ph,
J = 7.3 Hz); 8.11 (d, 2 Н, Ph, J = 7.6 Hz); 8.71—8.77 (m, 2 Н,
2 CHarom); 9.05 (d, 1 Н, CHarom, J = 7.1 Hz); 10.54 (s, 1 Н,
CHarom). 13С NMR (DMSO-d6), : 26.0, 53.8, 67.5, 112.4,
124.1, 125.3, 127.8, 128.8, 129.6, 131.6, 133.0, 134.2,
135.1, 135.5, 147.1, 151.6, 191.2. HRMS: found m/z 362.1510
[M – Br]+; C21H20N3O3; calculated 362.1499.
Synthesis of compounds 4a—l (general procedure). Triethyl-
amine (0.14 mL, 1 mmol) was added to a solution of isoquino-
linium salt 3 (1 mmol) and an unsaturated compound (dipolaro-
phile) (1 mmol) in DMSO (10 mL). The mixture was stirred for
24 h at room temperature and poured into water (50 mL). The
precipitate formed was collected by filtration, washed with water,
and dried in air.
Dimethyl 3-benzoyl-7-bromo-10-nitro-1,2,3,10b-tetrahydro-
pyrrolo[2,1-a]isoquinoline-1,2-dicarboxylate (4a). The yield was
91%. M.p. 133—134 C. 1H NMR (CDCl3), : 3.38 (s, 3 H,
OMe); 3.68 (s, 3 H, OMe); 3.92 (s, 2 Н, 2 CH); 5.46 (d, 1 H,
CH, J = 7.8 Hz); 5.63 (s, 1 Н, CH); 5.74 (d, 1 Н, CH, J = 2.7 Hz);
6.35 (d, 1 H, CH, J = 7.7 Hz); 7.51—7.66 (m, 5 H, Ph, 2 CHarom);
8.09 (d, 2 H, Ph, J = 7.6 Hz). 13C NMR (CDCl3), : 43.8, 52.0,
52.1, 52.6, 61.1, 66.9, 95.7, 121.7, 122.9, 124.5, 129.0, 129.1,
133.2, 134.0, 134.7, 135.5, 140.6, 147.1, 170.8, 171.8, 195.8. IR,
/cm–1:1341 (NO2), 1522 (NO2), 1745 (C=O). HRMS: found
m/z 515.0450 [M]+; C23H19BrN2O7; calculated 515.0448.
8-Benzoyl-4-bromo-1-nitro-10-phenyl-11a,11b-dihydro-8H-
pyrrolo[3´,4´:3,4]pyrrolo[2,1-a]isoquinoline-9,11(8aH,10H)-
dione (4b). The yield was 95%. M.p. 162—163 C. 1H NMR
(CDCl3), : 4.19 (s, 2 H, 2 CH); 5.42 (d, 1 H, CH, J = 5.8 Hz);
5.60 (s, 1 H, CH); 5.92 (d, 1 H, CH, J = 7.6 Hz); 6.46 (d, 1 H,
CH, J = 7.5 Hz); 7.13 (d, 2 Н, Ph, J = 7.3 Hz); 7.39—7.89
(m, 8 H, Ph, 2 CHarom); 8.14 (d, 2 H, Ph, J = 7.3 Hz). 13C NMR
(CDCl3), : 45.9, 50.3, 58.8, 73.2, 100.6, 123.1, 125.8, 126.0,
8-Nitro-5-(pyrrolidin-1-yl)isoquinoline (2e). Pyrrolidine
(1 mL, 12 mmol) was added to a suspension of bromide 2а (1.52 g,
6 mmol) in MeOH (25 mL). The reaction mixture was refluxed
for 5 h and cooled, the precipitate formed was collected by filtra-
tion. The yield was 1.15 g (79%). M.p. 178—180 C. 1H NMR
(DMSO-d6), : 1.99 (m, 4 H, 2 CH2); 3.76 (m, 4 H, 2 CH2);
6.82 (d, 1 H, CHarom, J = 9.2 Hz); 8.24 (d, 1 H, CHarom
,
J = 5.6 Hz); 8.43 (d, 1 H, CHarom, J = 9.3 Hz); 8.52 (d, 1 H,
CHarom, J = 5.6 Hz); 10.12 (s, 1 H, CHarom). 13C NMR
(DMSO-d6), : 26.0, 53.4, 108.3, 119.1, 123.5, 126.5, 130.2,
142.1, 148.0, 152.3.
Synthesis of compounds 3a—e (general procedure). A mixture
of 5-R-8-nitroisoquinoline 2 (6 mmol) and 2-bromoaceto-
phenone (1.2 g, 6 mmol) in EtOAc (30 mL) was refluxed for 4 h.
The reaction mixture was cooled, the precipitate formed was
collected by filtration, washed with EtOAc (10 mL), and dried
in air.
5-Bromo-8-nitro-2-(2-oxo-2-phenylethyl)isoquinolinium bro-
mide (3a). The yield was 74%. M.p. 210—211 C. 1H NMR
(DMSO-d6), : 6.86 (s, 2 H, NCH2); 7.69 (t, 2 H, Ph, J = 7.3 Hz);
7.83 (t, 1 H, Ph, J = 7.1 Hz); 8.12 (d, 2 H, Ph, J = 7.4 Hz); 8.75
(d, 1 H, CHarom, J = 8.3 Hz); 8.86 (d, 1 H, CHarom, J = 8.3 Hz);
9.02 (d, 1 H, CHarom, J = 6.9 Hz); 9.10 (d, 1 H, CHarom
,
J = 6.8 Hz); 10.49 (s, 1 H, CHarom). 13C NMR (DMSO-d6), :
67.8, 121.3, 125.9, 128.9, 129.0, 129.6, 130.1, 134.1, 137.2, 140.1,
140.3, 146.1, 149.5, 191.0. HRMS: found m/z 371.0022 [M – Br]+;
C17H12BrN2O3; calculated 371.0026.
5-Benzylthio-8-nitro-2-(2-oxo-2-phenylethyl)isoquinolinium
1
bromide (3b). The yield was 75%. M.p. 195—196 C. H NMR
(DMSO-d6), : 4.76 (s, 2 H, SCH2); 6.81 (s, 2 H, NCH2);
7.30—7.80 (m, 7 H, Ph); 7.84 (d, 1 H, Ph, J = 7.3 Hz); 8.11
(d, 2 H, Ph, J = 7.6 Hz); 8.35 (d, 1 H, CHarom, J = 8.4 Hz); 8.80

Synthesis of novel pyrrolo[2,1-a]isoquinolines
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 9, September, 2019
1733
128.9, 129.1, 129.3, 129.4, 133.3, 133.5, 134.5, 139.2, 176.8,
192.6. IR, /cm–1: 1344 (NO2), 1524 (NO2), 1731 (C=O).
HRMS: found m/z 544.0506 [M]+; C27H18BrN3O5; calculated
544.0503.
Dimethyl 3-benzoyl-7-methoxy-10-nitro-1,2,3,10b-tetra-
hydropyrrolo[2,1-a]isoquinoline-1,2-dicarboxylate (4h). The yield
was 88%. M.p. 78—80 C. 1H NMR (DMSO-d6), : 3.24 (s, 3 H,
OMe); 3.58 (s, 3 H, OMe); 3.70 (dd, 1 Н, CH, J = 7.9 Hz,
J = 5.0 Hz); 3.87 (s, 3 Н, OMe); 3.95 (dd, 1 Н, CH, J = 7.2 Hz,
J = 5.7 Hz); 5.26 (d, 1 Н, CH, J = 7.7 Hz); 5.53 (d, 1 Н, CH,
J = 5.2 Hz); 5.85 (d, 1 Н, CH, J = 5.5 Hz); 6.70 (d, 1 Н, CH,
J = 7.8 Hz); 7.02 (d, 1 Н, J = 9.2 Hz); 7.58 (t, 2 Н, Ph,
Dimethyl 3-benzoyl-7-bromo-10-nitropyrrolo[2,1-a]isoquin-
oline-1,2-dicarboxylate (4c). The yield was 39%. M.p.
243—244 C. 1H NMR (CDCl3), : 3.29 (s, 3 H, OMe); 3.83
(s, 3 H, OMe); 7.42—7.88 (m, 5 H, Ph); 7.79 (d, 1 H, CHarom
,
J = 7.4 Hz); 7.96 (d, 1 H, CHarom, J = 8.5 Hz); 8.13 (d, 1 H,
CHarom, J = 8.5 Hz); 9.05 (d, 1 H, CHarom, J = 7.8 Hz). 13C NMR
(CDCl3), : 52.4, 52.3, 113.8, 114.3, 118.4, 123.5, 126.0, 126.9,
127.7, 128.0, 128.3, 128.6, 129.1, 131.5, 132.0, 133.1, 138.9,
146.9, 164.3, 163.6, 186.7. IR, /cm–1: 1351 (NO2), 1531 (NO2),
1731 (C=O). HRMS: found m/z 511.0132 [M]+; C23H15BN2O7;
calculated 511.0135.
J = 7.4 Hz); 7.70 (t, 1 Н, Ph, J = 7.3 Hz); 7.86 (d, 1 Н, CHarom,
J = 9.2 Hz); 8.16 (d, 2 Н, Ph, J = 7.3 Hz). 13C NMR (DMSO-d6),
: 43.6, 52.1, 52.5, 52.7, 56.8, 60.8, 67.5, 89.2, 110.7, 122.0,
124.1, 129.3, 129.6, 134.3, 135.5, 139.2, 141.0, 156.6, 171.1,
171.8, 196.8. HRMS: found m/z 467.1436 [M]+; C24H22N2O8;
calculated 467.1449.
8-Benzoyl-4-methoxy-1-nitro-10-phenyl-11a,11b-dihydro-
8H-pyrrolo[3',4':3,4]pyrrolo[2,1-a]isoquinoline-9,11(8aH,10H)-
dione (4i). The yield was 88%. M.p. 123 C. 1H NMR (DMSO-d6),
: 3.88 (s, 3 Н, OMe); 3.95 (t, 1 Н, CH, J = 6.7 Hz); 4.13 (d, 1 Н,
CH, J = 7.9 Hz); 5.31 (d, 1 Н, CH, J = 7.5 Hz); 5.63 (d, 1 Н,
CH, J = 7.7 Hz); 6.88 (d, 1 Н, CH, J = 7.7 Hz); 7.06 (d, 1 Н,
CH, J = 9.3 Hz); 7.12 (d, 2 Н, Ph, J = 7.5 Hz); 7.39—7.61 (m,
6 Н, Ph, CHarom); 7.70 (t, 1 Н, Ph, J = 7.2 Hz); 7.97 (d, 1 Н,
CHarom, J = 9.2 Hz); 8.20 (d, 2 Н, Ph, J = 7.5 Hz). 13C NMR
(DMSO-d6), : 45.8, 51.1, 56.8, 58.2, 72.0, 93.6, 110.7, 123.1,
123.5, 124.9, 126.8, 128.9, 129.2, 129.5, 129.8, 132.8, 134.2,
134.4, 138.4, 140.8, 157.1, 174.8, 177.1, 194.6. HRMS: found
m/z 496.1495 [M]+; C28H21N3O6; calculated 496.1503.
Dimethyl 3-benzoyl-7-(4-chlorophenylthio)-10-nitro-
1,2,3,10b-tetrahydropyrrolo[2,1-a]isoquinoline-1,2-dicarboxyl-
ate (4j). The yield was 97%. M.p. 75—76 С. 1H NMR
(DMSO-d6), : 3.28 (s, 3 H, OMe); 3.58 (s, 3 H, OMe); 3.69
(dd, 1 Н, CH, J = 7.5 Hz, J = 5.5 Hz); 3.96 (t, 1 Н, CH,
J = 5.28 Hz); 5.30 (d, 1 Н, CH, J = 7.7 Hz); 5.50 (d, 1 Н, CH,
J = 5.3 Hz); 5.87 (d, 1 Н, CH, J = 5.4 Hz); 6.85 (d, 1 Н, CH,
Methyl (1R,3S)-3-benzoyl-7-bromo-10-nitro-1,2,3,10b-
tetrahydropyrrolo[2,1-a]isoquinoline-1-carboxylate (4d). The
yield was 50%. M.p. 167—168 C. 1H NMR (CDCl3), :
2.08—2.17 (m, 1 H, CH); 2.45 (dt, 1 H, CH, J = 11.9 Hz,
J = 1.8 Hz); 3.21 (s, 3 H, OMe); 3.36 (t, 1 H, CH, J = 6.0 Hz);
5.31 (dd, 1 H, CH, J = 9.4 Hz, J = 5.4 Hz); 5.54 (m, 2 H, 2 CH);
6.77 (d, 1 H, CH, J = 7.7 Hz); 7.51—7.60 (m, 5 H, Ph, 2 CH);
8.06 (d, 2 H, Ph, J = 7.4 Hz). 13C NMR (CDCl3), : 27.6, 48.7,
51.9, 60.7, 67.7, 95.8, 121.4, 124.0, 124.4, 128.8, 129.0, 132.8,
133.9, 134.5, 134.9, 140.5, 147.3, 173.5, 196.2. IR, /cm–1:1340
(NO2), 1517 (NO2), 1731 (C=O). HRMS: found m/z 479.0196
[M + Na]+; C21H17BrN2NaO5; calculated 479.0213.
Methyl 3-benzoyl-7-bromo-10-nitropyrrolo[2,1-a]isoquino-
line-1-carboxylate (4e). The yield was 51%. M.p. 210—212 C.
1H NMR (CDCl3), : 3.82 (s, 3 H, OMe); 7.50—8.00 (m, 9 H,
Ph, 4 CHarom); 9.74 (d, 1 H, CHarom, J = 7.8 Hz). 13C NMR
(CDCl3), : 52.0, 113.1, 115.2, 118.0, 123.9, 125.6, 127.4, 127.7,
128.0, 128.6, 129.3, 130.6, 131.5, 131.8, 132.4, 139.1, 147.3,
164.3, 186.2. IR, /cm–1: 1348 (NO2), 1535 (NO2), 1719 (C=O).
HRMS: found m/z 453.0071 [M]+; C21H13BrN2O5; calculated
453.0081.
Dimethyl 3-benzoyl-7-benzylthio-10-nitro-1,2,3,10b-tetra-
hydropyrrolo[2,1-a]isoquinoline-1,2-dicarboxylate (4f). The yield
was 39%. M.p. 118—119 C. 1H NMR (DMSO-d6), : 3.19
(s, 3 H, OMe); 3.59 (s, 3 H, OMe); 3.70 (t, 1 H, CH, J = 5.5 Hz);
3.97 (t, 1 H, CH, J = 7.9 Hz); 4.34 (s, 2 H, SCH2); 5.25 (d, 1 H,
CH, J = 7.8 Hz); 5.48 (d, 1 H, CH, J = 5.4 Hz); 5.87 (d, 1 H,
CH, J = 5.4 Hz); 6.83 (d, 1 H, CH, J = 7.8 Hz); 7.26—7.48
(m, 6 H, Ph, CHarom); 7.57—7.73 (m, 4 Н, Ph, CHarom); 8.16
(d, 2 H, Ph, J = 7.3 Hz). 13C NMR (DMSO-d6), : 35.3, 43.1,
51.6, 52.0, 52.2, 60.1, 67.0, 91.6, 112.0, 120.0, 130.0, 126.4,
127.3, 128.5, 128.6, 129.1, 131.8, 133.8, 134.9, 136.2, 137.3,
140.3, 144.7, 170.5, 171.2, 196.1. IR, /cm–1: 1326 (NO2), 1513
(NO2), 1736 (C=O). HRMS: found m/z 559.1507 [M]+;
C30H26N2O7S; calculated 559.1533.
Dimethyl 3-benzoyl-7-benzylthio-10-nitropyrrolo[2,1-a]-
isoquinoline-1,2-dicarboxylate (4g). The yield was 57%. M.p.
214—216 C. 1H NMR (DMSO-d6), : 3.23 (s, 3 H, OMe); 3.66
(s, 3 H, OMe); 4.58 (s, 2 H, SCH2); 7.21—7.87 (m, 12 H, 2 Ph,
2 CHarom); 8.27 (d, 1 H, CHarom, J = 8.4 Hz); 8.91 (d, 1 H,
CHarom, J = 7.8 Hz). 13C NMR (DMSO-d6), : 36.1, 51.9, 52.1,
110.5, 112.6, 116.0, 123.2, 125.4, 126.0, 126.5, 126.7, 127.7,
128.5, 128.7, 128.9, 129.1, 132.9, 133.2, 135.6, 138.2, 142.8,
143.9, 163.0, 163.8, 185.9. IR, /cm–1: 1345 (NO2), 1521 (NO2),
1741 (CO2Me), 1723 (C=O). HRMS: found m/z 555.1222 [M]+;
C30H22N2O7S; calculated 555.1220.
J = 7.7 Hz); 7.13 (d, 1 Н, CH, J = 8.7 Hz); 7.30 (d, 2 Н, CHarom
,
J = 8.4 Hz); 7.47 (d, 2 Н, CHarom, J = 8.3 Hz); 7.58 (t, 2 Н, Ph,
J = 7.8 Hz); 7.69 (t, 1 Н, Ph, J = 7.7 Hz); 8.14 (d, 2 Н, Ph,
J = 7.5 Hz). 13C NMR (DMSO-d6), : 43.7, 52.3, 52.6, 52.7,
60.6, 67.4, 92.2, 121.1, 121.6, 129.3, 129.6, 130.3, 132.0, 132.1,
133.4, 133.5, 134.3, 134.9, 135.3, 141.6, 170.9, 171.6, 196.6.
HRMS: found m/z 579.1003 [M]+; C29H23ClN2O7S; calculated
579.0987.
8-Benzoyl-4-(4-chlorophenylthio)-1-nitro-10-phenyl-
11a,11b-dihydro-8H-pyrrolo[3',4':3,4]pyrrolo[2,1-a]isoquinol-
ine-9,11(8aH,10H)-dione (4k). The yield was 79%. M.p. 156 C.
1H NMR (DMSO-d6), : 3.97 (t, 1 Н, CH, J = 7.6 Hz); 4.13
(d, 1 Н, CH, J = 8.0 Hz); 5.27 (d, 1 Н, CH, J = 7.5 Hz); 5.66
(d, 1 Н, CH, J = 7.7 Hz); 6.07 (s, 1 Н, CH); 7.03—7.77 (m, 15 Н,
Ph, CHarom); 8.20 (d, 2 Н, Ph, J = 7.5 Hz). 13C NMR
(DMSO-d6), : 45.6, 51.3, 57.9, 71.8, 96.6, 122.4, 122.7, 126.9,
129.0, 129.3, 129.4, 129.8, 130.0, 131.7, 132.6, 133.2, 133.8,
134.2, 134.5, 135.1, 140.9, 147.6, 174.8, 176.8, 194.2. HRMS:
found m/z 608.1021 [M]+; C33H22ClN3O5S; calculated 608.1041.
Dimethyl 3-benzoyl-10-nitro-7-pyrrolidin-1-yl-1,2,3,10b-
tetrahydropyrrolo[2,1-a]isoquinoline-1,2-dicarboxylate (4l). The
yield was 93%. M.p. 171—173 C. 1H NMR (DMSO-d6), :
3.27 (br.s, 7 H, OMe, 2 NCH2); 3.57 (s, 3 H, OMe); 3.65 (dd,
1 Н, CH, J = 7.6 Hz, J = 5.5 Hz); 3.97 (t, 1 Н, CH, J = 7.5 Hz;
5.20 (d, 1 Н, CH, J = 7.9 Hz); 5.45 (d, 1 Н, CH, J = 5.2 Hz);
5.80 (d, 1 Н, CH, J = 5.7 Hz); 6.57 (d, 1 Н, CH, J = 7.9 Hz);
6.75 (d, 1 Н, CHarom, J = 9.4 Hz); 7.57 (t, 2 Н, Ph, J = 7.6 Hz);

1734
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 9, September, 2019
Bastrakov and Starosotnikov
7.70 (t, 1 Н, Ph, J = 7.3 Hz); 7.77 (d, 1 Н, CHarom, J = 9.2 Hz);
8.17 (d, 2 Н, Ph, J = 7.6 Hz). 13C NMR (DMSO-d6), : 25.6,
43.6, 52.1, 52.4, 52.6, 61.2, 67.8, 94.8, 113.8, 122.0, 123.3, 124.5,
129.4, 129.6, 134.3, 135.5, 137.0, 138.6, 150.2, 171.2, 171.9,
196.4. HRMS: found m/z 506.1914 [M]+; C27H27N3O7; calcu-
lated 506.1922.
11. F. Dumitrascu, E. Georgescu, F. Georgescu, M. M. Popa,
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Received April 27, 2019;
in revised form May 31, 2019;
accepted June 27, 2019