Synthesis of novel 1,2-functionally-substituted 6,7-dimethoxy-4-spirocyclo- pentanetetrahydroisoquinolines

Article abstract of DOI:10.1007/s10593-009-0385-5

1-[(3,4-Dimethoxyphenyl)cyclopentyl]methylamine has been used in the synthesis of 6,7-dimethoxy-4-spirocyclopentane-1,2,3,4-tetrahydroisoquinoline-1- carboxylic acid N-methylamide which is employed in the preparation of novel derivatives with substituents

Full text of DOI:10.1007/s10593-009-0385-5

Chemistry of Heterocyclic Compounds, Vol. 45, No. 9, 2009
SYNTHESIS OF NOVEL 1,2-FUNCTIONALLY-
SUBSTITUTED 6,7-DIMETHOXY-4-SPIROCYCLO-
PENTANETETRAHYDROISOQUINOLINES
A. A. Aghekyan1*, E. A. Arakelyan1, G. A. Panosyan1,
A. G. Khachatryan1, and E. A. Markaryan1
1-[(3,4-Dimethoxyphenyl)cyclopentyl]methylamine has been used in the synthesis of 6,7-dimethoxy-
4-spirocyclopentane-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid N-methylamide which is
employed in the preparation of novel derivatives with substituents in positions 1,2,6, and 7.
Keywords: 1-[(3,4-dimethoxyphenyl)cyclopentyl]methylamine, spirocyclopentane, tetrahydroiso-
quinoline, reduction.
Tetrahydroisoquinolines have long been known as biologically active substances [1] but interest in these
structures has not lessened and studies of their biological properties continue without losing interest to the
present day [2, 3].
The synthesis of isoquinolines containing methyl substituents in the one position and spiro rings in a
quaternary position has been reported previously [4, 5]. The aim of this work was to preserve the spiro ring in
the tetrahydroisoquinoline structure but to have functional groups like carbethoxy, amido, or hydroxymethyl in
position one in order to prepare novel derivatives.
Scheme 1
MeO
MeO
MeO
MeO
MeO
MeO
(COOEt)2
O
O
+
OMe
OMe
HN
HN
NH2
OEt
NH
2
O
O
1
3
_______
* To whom correspondence should be addressed, e-mail: edmar33@mail.ru, aaghekyan@mail.ru.
1 A. L. Mnjoyan Institute of Fine Organic Chemistry, National Academy of Sciences of the Republic of Armenia
Yerevan 0014, Armenian Republic.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1338-1344, September, 2009.
Original article submitted November 5, 2007.
0009-3122/09/4509-1069©2009 Springer Science+Business Media, Inc.
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The 1-[(3,4-dimethoxyphenyl)cyclopentyl]methylamine 1 [6] was used as the starting material and
condensed with diethyl oxalate to give the monoethyl ester of oxalic acid amide 2 together with a small amount
(~ 5%) of the symmetrical diamine 3 (Scheme 1).
Under Bischler-Napieralski reaction conditions amide 2 underwent cyclization to give 1-ethoxy-
carbonyl-4-spirocyclopentane-3,4-dihydroisoquinoline 4 and this was confirmed by the presence in the 1H NMR
spectrum of signals for two rather than the three aromatic protons seen in the starting compound 2 (Scheme 2).
Reduction of compound 4 with lithium aluminium hydride reduces both the double bond and also the ester
group to give the tetrahydroisoquinoline 5 containing a hydroxymethyl group at the one position. Attempts to
reduce the C=N bond in compound 4 selectively using sodium borohydride were unsuccessful and separation of
the tetrahydroisoquinoline could not be achieved due to the instability of the ester group in basic medium. In
order to retain a carbonyl fragment the dihydroisoquinoline 4 was treated with methylamine to give amide 6.
The same dihydroisoquinoline was separated after cyclization of the unsymmetrical oxalic acid diamide 7 which
was prepared via condensation of amidoester 2 with methylamine. The yields from both routes were virtually the
same (28% for the two stages).
RO
RO
MeO
MeO
LiAlH4
POCl3
2
NH
OH
N
COOEt
4
5 (R = Me)
11 (R = H)
MeNH2
HBr
MeNH2
MeO
MeO
POCl3
MeO
MeO
LiAlH4
MeO
MeO
O
NH
HN
N
CONHMe
O
NHMe
7
O
NH
Me
9
6
NaBH4
MeO
MeO
MeO
MeO
HBr
HO
HO
Py
NH
N
R
NH
RCOCl
O
COOH
O
NH
Me
O
NH
12
8
Me
10a–d
10 a R = Me, b R = 2-furyl, c R = Ph, d R = 4-O2NC6H4
Selective hydrogenation of the C=N double bond in compound 6 was achieved using sodium
borohydride to give the tetrahydroisoquinoline 8 with retention of the amide functional group in the 1 position.
The yield of the tetrahydroisoquinoline 8 can be increased by 5-7% if it is prepared from diamine 7 without
isolation of the intermediate dihydroisoquinoline 6.
Reduction of the dihydroisoquinoline 6 using lithium aluminium hydride also gave the tetrahydro-
isoquinoline 8 with a small admixture (~ 6%) of the fully hydrogenated product 9 and this could be separated due
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to the difference in solubilities of the hydrochloride 8 and the dihydrochloride 9 in absolute ethanol. The presence
of an active amino group in compound 8 allows the preparation of novel tetrahydroisoquinoline derivatives
containing a spiro ring. In particular, condensation of compound 8 with acetyl, benzoyl, p-nitrobenzoyl, or 2-furoyl
1
chlorides gave the series of amides 10a-d. Study of the H NMR spectra of these amides showed them to be
mixtures of diastereomers in the ratio 70:30, 80:20, and 70:30 for 10a,c,d respectively. In the case of compound
10b fractional recrystallization gave the main isomer. Formation of diastereomers in the N-acyl
tetrahydroisoquinoline series is apparently due to hindered rotation around the bond between the nitrogen atom
of the tetrahydroisoquinoline and the carbonyl group.
It was also of interest to study the demethylation process of the 6,7-dimethoxytetrahydroisoquinolines 5
and 8 to give the dihydroxyisoquinolines. Demethylation was carried out using hydrobromic acid. As a result of
this reaction compound 5 gave the 6,7-dihydroxytetrahydroisoquinoline hydrobromide 11 while demethylation
of compound 8 simultaneously gave hydrolysis of the amide group to form the amino acid hydrobromide 12.
EXPERIMENTAL
1
IR spectra were taken on a Carl Zeiss UR-20 instrument for a thin layer in vaseline oil and H NMR
spectra on a Varian Mercury 300 (300 MHz) instrument using DMSO-d6 diluted with carbon tetrachloride and
with TMS as internal standard. TLC was performed on Silufol UV-254 plates.
Ethyl Oxalate N-[1-(3,4-Dimethoxyphenyl)cyclopentylmethyl]amide (2). A solution of 3,4-di-
methoxyphenylcyclopentylmethylamide 1 (23.5 g, 100 mmol) in chloroform (50 ml) was added dropwise to a
refluxing solution of diethyl oxalate (29.2 g, 200 mmol) in chloroform (100 ml) and refluxed for 10 h.
Chloroform and excess diethyl oxalate were distilled off and the residue was distilled to give the monoamide 2
(20.0 g, 62.7%) with mp 68ºC (hexane) and bp 227-230ºC (1 mm Hg), Rf 0.51 (benzene–acetone, 3:1). IR
spectrum, ν, cm-1: 1580, 1600 (C=C Ar), 1640 (NC=O), 1710 (OC=O), 3300 (NH). 1H NMR spectrum, δ, ppm
(J, Hz): 1.34 (3H, t, J = 7.1, CH3); 1.62-1.97 (8H, m, C4H8); 3.31 (2H, d, J = 6.5, NCH2); 3.78 (3H, s, OCH3);
3.80 (3H, s, OCH3); 4.22 (2H, q, J = 7.1, OCH2); 6.73-6.80 (3H, m, C6H3); 7.49 (1H, br. t, J = 6.5, NH). Found,
%: C 64.51; H 7.72; N 4.23. C18H25NO2. Calculated, %: C 64.44; H 7.53; N 4.18.
After distillation of compound 2 the residue was recrystallized from ethanol to give the diamide 3 (2.6 g,
5%); mp 166-168ºC, Rf 0.75 (benzene–acetone, 2:1). IR spectrum, ν, cm-1: 1590, 1605 (C=C Ar), 1690 (NC=O),
3390 (NH). 1H NMR spectrum, δ, ppm (J, Hz): 1.65-1.94 (16H, m, 2 C4H8); 3.27 (4H, d, J = 6.5, 2 NCH2); 3.78
(6H, s, 2 OCH3); 3.80 (6H, s, 2 OCH3); 6.70-6.79 (6H, m, 2 C6H3); 7.45 (2H, t, J = 6.5, 2 NH). Found, %:
C 68.58; H 7.51; N 5.54. C30H40N2O6. Calculated, %: C 68.70; H 7.63; N 5.34.
Oxalic Acid N-Methyl-N'-[1-(3,4-dimethoxyphenyl)cyclopentylmethyl]amide (7). A solution of
methylamine (1.3 g, 4 mmol) in absolute ethanol (50 ml) was added to a solution of the amidoester 2 (6.7 g,
2 mmol) in ethanol (50 ml) and left for 10 h at room temperature. The crystals formed were filtered and
recrystallized from ethanol to give the diamide 7 (4.8 g, 75.2%); mp 125-126ºC, Rf 0.44 (benzene–acetone, 3:1).
IR spectrum, ν, cm-1: 1590, 1610 (C=C Ar), 1657 and 1693 (NC=O, 3350 (NH). 1H NMR spectrum, δ, ppm (J,
Hz): 1.63-1.97 (8H, m, C4H8); 2.71 (3H, d, J = 5.0, NCH3); 3.31 (2H, d, J = 6.5, NCH2); 3.78 (3H, s, OCH3);
3.80 (3H, s, OCH3); 6.73-6.80 (3H, m, C6H3); 7.46 (1H, br. t, J = 6.5, NH); 8.45 (1H, br. q, J = 5.0, NH). Found,
%: C 63.95; H 7.81; N 8.82. C17H24N2O4. Calculated, %: C 63.71; H 7.50; N 8.75.
Ethyl 6,7-Dimethoxy-4-spirocyclopentane-3,4-dihydrosioquinoline-1-carboxylate (4). A mixture of
amidoester 2 (17.8 g, 53 mmol) and phosphorus oxychloride (50 ml) in acetonitrile (200 ml) was refluxed for
10 h. Solvent was distilled off, the residue was dissolved in water, and the product was basified with aqueous
ammonia to pH 8.0. It was extracted with benzene (3×100 ml), dried over sodium sulfate, solvent was distilled
off, and the residue was chromatographed on a II activity grade alumina column collecting the fraction with Rf
0.43 (benzene–diethyl ether, 2:1) to give the dihydroisoquinoline 4 (8.0 g, 47.6%). IR spectrum, ν, cm-1: 1585,
1071

1
1600 (C=C Ar), 1640 (C=N), 1720 (C=O). H NMR spectrum, δ, ppm (J, Hz): 1.41 (3H, t, J = 7.1, CH3);
1.66-1.83 (8H, m, C4H8); 3.59 (2H, s, NCH2); 3.80 (3H, s, OCH3); 3.88 (3H, s, OCH3); 4.35 (2H, q, J = 7.1,
OCH2); 6.78 (1H, s, CH arom); 7.10 (1H, s, CH arom). Found, %: C 68.02; H 7.55; N 4.25. C18H23NO4.
Calculated, %: C 68.13; H 7.32; N 4.41.
6,7-Dimethoxy-4-spirocyclopentane-3,4-dihydroisoquinoline-1-carboxylic Acid N-Methylamide
Hydrochloride (6·HCl). A. A mixture of the dihydroisoquinoline 4 (6.4 g, 20 mmol) and methylamine (1.2 g,
40 mmol) in ethanol (100 ml) was left for 6 h at room temperature. Solvent was distilled off and the residue was
dissolved in absolute diethyl ether and treated with an ether solution of hydrogen chloride to give the
hydrochloride 6 (4.0 g, 58.8%).
B. Obtained similarly to compound 4 from the diamine 7 (3.2 g, 10 mmol) and phosphorus oxychloride
(8 ml) in acetonitrile (50 ml) and converted to the hydrochloride by method A. Yield of the hydrochloride 6
1.1 g (36.6%); mp 176-178ºC (acetone), Rf 0.55 (benzene–acetone, 2:1; ammonia vapor). IR spectrum, ν, cm-1:
1
1590, 1600 (C=C Ar), 1640 (C=N), 1673 (NC=O), 3469 (NH). H NMR spectrum, δ, ppm (J, Hz): 1.80-1.95
(8H, m, C4H8); 2.82 (3H, br. d, J = 4.8, NCH3); 3.68 (2H, s, NCH2); 3.84 (3H, s, OCH3); 3.89 (3H, s, OCH3);
6.96 (1H, s, CH arom); 7.33 (1H, s, CH arom); 9.88 (1H, br. m, NH). Found, %: C 60.48; H 6.85; Cl 10.52;
N 8.11. C17H22N2O3·HCl. Calculated, %: C 60.23; H 6.79; Cl 10.47; N 8.27.
6,7-Dimethoxy-4-spirocyclopentane-1,2,3,4-tetrahydroisoquioline-1-carboxylic Acid N-Methyl-
amide (8). A. Sodium borohydride (1.1 g, 30 mmol) was added in small portions with stirring to a solution of
the dihydroisoquinoline 6 (3.0 g, 10 mmol) in methanol (100 ml) at 0-5ºC. It was left overnight. Solvent was
distilled off and the residue was treated with water and extracted with benzene (3×50 ml). The product was dried
over sodium sulfate, solvent distilled off, and the residue was recrystallized from diethyl ether to give the
tetrahydroisoquinoline 8 (2.0 g, 66.2%).
B. A mixture of diamide 7 (3.2 g, 10 mmol), phosphorus oxychloride (8 ml), and acetonitrile (50 ml) was
refluxed for 5 h. After distillation of the solvent the residue was dissolved in methanol and reduced as in method
A to give compound 8 (1.0 g, 33.3%); mp 100-102ºC, Rf 0.42 (benzene–acetone, 1:1). IR spectrum, ν, cm-1:
1580, 1605 (C=C Ar), 1680 (NC=O), 3300 (NH). Mp of hydrochloride 8·HCl 227-230ºC. 1H NMR spectrum, δ,
ppm (J, Hz): 1.76-2.05 (8H, m, C4H8); 2.78 (3H, d, J = 4.6, NCH3); 2.99, 3.59 (2H, two d, J = 12.5, NCH2); 3.78
(3H, s, OCH3); 3.79 (3H, s, OCH3); 5.14 (1H, s, NCH); 6.72 (1H, s, CH arom); 7.06 (1H, s, CH arom); 9.31 (1H,
br. q, J = 4.6, NH); 8.97 (1H, br. s, NH); 10.48 (1H, br. s, HCl). Found, %: C 67.32; H 7.65; N 9.45.
C17H24N2O3. Calculated, %: C 67.10; H 7.89; N 9.21.
1-Hydroxymethyl-6,7-dimethoxy-4-spirocyclopentane-1,2,3,4-tetrahydroisoquinoline
(5).
The
dihydroisoquinoline 4 (3.17 g, 10 mmol) in benzene (100 ml) was added dropwise to lithium aluminium hydride
(1.1 g, 30 mmol) in absolute diethyl ether (50 ml). The mixture was refluxed with stirring for 12 h and
decomposed with water. The product was filtered, solvent distilled off, and the residue was recrystallized from ether
to give the amino alcohol 5 (1.4 g, 50.5%); mp 70-72ºC, Rf 0.41 (butanol–acetic acid–water, 5:3:3). IR spectrum, ν,
cm-1: 1580, 1600 (C=C Ar), 3500-3300 (NH, OH). 1H NMR spectrum, δ, ppm (J, Hz): 1.61-1.91 (8H, m, C4H8); 2.31
(1H, br. s, NH); 2.56, 2.78 (2H, two d, J = 12.2, NCH2); 3.50, 3.59 (2H, dd, J = 8.4 and J = 10.7, OCH2); 3.74 (3H, s,
OCH3); 3.75 (1H, m, NCH); 3.75 (3H, s, OCH3); 4.18 (1H, br. s, OH); 6.55 (1H, s, CH arom); 6.65 (1H, s,
CH arom). Found, %: C 69.18; H 8.17; N 4.97. C16H23NO3. Calculated, %: C 69.31; H 8.30; N 5.05.
Reduction of 6,7-Dimethoxy-4-spirocyclopentane-3,4-tetrahdroisoquinoline-1-carboxylic Acid
N-Methylamide (6). A solution of the dihydroisoquinoline 6 (1.5 g, 5 mmol) in benzene (50 ml) was added
dropwise to lithium aluminium hydride (1.1 g, 30 mmol) in absolute diethyl ether (50 ml). The mixture was
refluxed with stirring for 20 h and decomposed with water. The product was filtered, the solvent distilled off,
and the residue was dissolved in absolute diethyl ether and treated with an ether solution of hydrogen chloride to
yield the hydrochloride. It was refluxed in ethanol and the dihydrochloride 9 (0.1 g, 5.6%) insoluble in the hot
alcohol was filtered off. Mp 265-267ºC, Rf 0.30 (benzene–acetic acid–water, 5:3:3). IR spectrum, ν, cm-1: 1590,
1
1605 (C=C Ar); 3250-3400 (NH, NH2). H NMR spectrum, δ, ppm (J, Hz): 1.56-1.91 (6H, m, C4H8);
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2.01-2.14 (2H, m, C4H8); 2.64 (3H, s, CH3); 3.12, 3.22 (2H, two d, J = 13.6, NCH2); 3.37(1H, dd, J = 14.2 and
J = 2.1, NCH2CH); 3.74 (1H, dd, J =14.2 and J = 9.3, NCH2CH); 3.77 (6H, s, 2OCH3); 4.78 (1H, dd, J = 9.3 and
J = 2.1, CH); 6.81 (1H, s, CH arom); 7.01 (1H, s, CH arom); 9.60 (4H, br. s, NH, HCl). Found, %: C 56.41; H
7.59; Cl 19.65; N 7.82. C17H26N2O2·2HCl. Calculated, %: C 56.20; H 7.76; Cl 19.56; N 7.71.
Cooling the alcohol solution gave crystals of the hydrochloride 6 which were filtered off to give 6·HCl
(0.9 g, 53.0%) with parameters agreeing with those reported before.
1-Hydroxymethyl-6,7-dihydroxy-4-spirocyclopentane-1,2,3,4-tetrahydroisoquinoline Hydrobromide
(11·HBr). A solution of the isoquinoline 5 (1.0 g, 3.6 mmol) in hydrobromic acid (30 ml) was refluxed for 4 h.
After cooling, the crystalline product was filtered off and washed with cold water to give the hydrobromide 11
1
(0.9 g, 75.0%); mp 272-273ºC. IR spectrum, ν, cm-1: 1590, 1610 (C=C Ar), 3200-3500 (NH, OH). H NMR
spectrum, δ, ppm (J, Hz): 1.73-2.02 (8H, m, C4H8); 2.99, 3.15 (1H, two m, NCH2); 3.73 (1H, dd, J = 12.1 and
8.6, OCH2); 3.93 (1H, dd, J = 12.1 and J = 4.0, OCH2); 4.34 (1H, m, NCH); 6.57 (1H, s, CH arom); 6.68 (1H, s,
CH arom); 8.40 (3H, br. s), 8.65 (1H, br. s), and 9.40 (1H, br. s, NH, OH, NBr). Found, %: C 51.05; H 5.89;
Br 24.13; N 4.51. C14H19NO3·HBr. Calculated, %: C 50.90; H 6.06; Br 24.24; N 4.24.
6,7-Dihydroxy-4-spirocyclopentane-1,2,3,4-tetrahydroisoquinoline-1-carboxylic Acid Hydrobromide
(12·HBr). was prepared similarly to compound 11·HBr from isoquinoline 8 (1.0 g, 3.3 mmol) to give a yield of
0.7 g (65.0%); mp 263-265ºC. IR spectrum, ν, cm-1: 1600, 1615 (C=C Ar); 1730 (C=O), 3300-3600 (NH, OH).
1H NMR spectrum, δ, ppm (J, Hz): 1.64-1.94 (7H, m, C4H8); 2.01-2.11 (1H, m, C4H8); 3.17, 3.34 (1H, two d,
J = 12.8, NCH2); 4.96 (1H, s, NCH); 6.69 (1H, s, CH arom); 6.86 (1H, s, CH arom); 8.70 (3H, br. s); 9.25 (1H,
br. s), and 9.77 (1H, br. s, NH, OH, HBr). Found, %: C 48.55; H 5.05; Br 23.27; N 4.29. C14H17NO4·HBr.
Calculated, %: C 48.83; H 5.23; Br 23.25; N 4.07.
Acylation of 6,7-Dimethoxy-4-spirocyclopentane-1,2,3,4-tetrahydroisoquinolinecarboxylic Acid
N-Methylamide (8). The corresponding acid chloride (5 mmol) was added dropwise to a solution of the
isoquinoline 8 (1.52 g, 5 mmol) and pyridine (0.4 g, 5 mmol) in benzene (50 ml). In the preparation of amide
10a the reaction mixture was held with stirring for 5 h at room temperature and for the remainder refluxed for
5 h with stirring. The pyridine hydrochloride was filtered off and the filtrate was washed with water, 10% HCl, a
10% solution of sodium carbonate, and again water. Distillation of solvent gave a crystalline precipitate which
was recrystallized from ethanol.
2-Acetyl-6,7-dimethoxy-4-spirocyclopentane-1,2,3,4-tetrahydroisoquinolinecarboxylic Acid N-Methyl-
amide (10a). Yield 1.0 g (58.8%); mp 125-126ºC, Rf 0.35 (benzene–acetone, 2:1). IR spectrum, ν, cm-1: 1600,
1610 (C=C Ar), 1660, 1680 (NHCO, NCO), 3320 (NH). 1H NMR spectrum, δ, ppm (J, Hz): 1.26-2.20 (8H, m,
C4H8); 2.09 (0.9H, s, C(O)CH3) and 2.11 (2.1H, s, C(O)CH3); 2.67 (2.1H, d, J = 4.5, NHCH3) and 2.69 (0.9H, d,
J = 4.5, NHCH3); 3.55, 3.77 (0.7H, two d, J = 13.5, NCH2) and 3.75, 4.39 (0.3H, two d, J = 13.0, NCH2); 3.76
(2.1H, s, OCH3); 3.78 (2.1H, s, OCH3) and 3.79 (1.8H, s, OCH3); 5.16 (0.3H, s, NCH) and 5.60 (0.7H, s, NCH);
6.69 (0.7H, s, CH arom) and 6.71 (0.3H, s, CH arom); 6.88 (1H, s, CH arom); 7.75 (0.3H, q, J = 4.5, NH) and
7.95 (0.7H, q, J = 4.5, NH) (Two isomers in the ratio 70:30). Found, %: C 65.64; H 7.40; N 8.22. C19H26N2O4.
Calculated, %: C 65.89; H 7.51; H 8.09.
2-Furoyl-6,7-dimethoxy-4-spirocyclopentane-1,2,3,4-tetrahydroisoquinolinecarboxylic Acid N-Methyl-
amide (10b). Yield 1.1 g (56.1%); mp 145-147ºC, Rf 0.51 (benzene–acetone, 2:1). IR spectrum, ν, cm-1: 1580,
1
1605 (C=C Ar), 1650 and 1670 (NC=O); 3400 (NH). H NMR spectrum, δ, ppm (J, Hz): 1.36-2.20 (8H, m,
C4H8); 2.71 (3H, d, J = 4.6, NCH3); 3.78 (3H, s, OCH3); 3.79 (3H, s, OCH3); 3.92, 4.32 (2H, two br. d, J = 13.0,
NCH2); 5.65 (1H, br. s, NCH); 6.54 (1H, dd, J = 3.4 and J = 1.8, H-4 furan); 6.70 (1H, s, CH arom); 6.93 (1H, s,
CH arom); 7.01 (1H, d, J = 3.4, H-3 furan); 7.63 (1H, d, J = 1.8, H-5 furan); 8.10 (1H, br. s, NH). Found, %:
C 66.15; H 6.39; N 7.21. C22H26N2O5. Calculated, %: C 66.30; H 6.53; N 7.03.
2-Benzoyl-6,7-dimethoxy-4-spirocyclopentane-1,2,3,4-tetrahydroisoquinolinecarboxylic Acid N-Methyl-
amide (10c). Yield 1.2 g (60.3%); mp 245-246ºC (benzene), Rf 0.58 (benzene–acetone, 1:1). IR spectrum, ν, cm-1:
1
1595, 1615 (C=C Ar), 1640, 1660 (NC=O), 3350 (NH). H NMR spectrum, δ, ppm (J, Hz): 0.96-2.20 (8H,
1073

m, C4H8); 2.67 (0.6H, d, J = 4.5, NCH3) and 2.75 (2.4H, d, J = 4.5, NCH3); 3.78 (6H, s, 2OCH3); 3.14 (0.2H, d,
J = 13.2, NCH2) and 3.48 (0.8H, d, J = 13.2, NCH2); 3.86 (0.8H, d, J = 13.2, NCH2) and 4.56 (0.2H, d, J = 13.2,
NCH2); 4.87 (0.2H, s, NCH) and 5.84 (0.8H, s, NCH); 6.68 (0.8H, s, CH arom) and 6.72 (0.2H, s, CH arom);
6.80 (0.2H, s, CH arom) and 6.96 (0.8H, s, CH arom); 7.31-7.44 (5H, m, C6H5); 7.61 (0.2H, br. q, J = 4.5, NH)
and 8.20 (0.8H, br. q, J = 4.5, NH). (Two isomers in the ratio 80:20). Found, %: C 70.78; H 7.12; N 6.68.
C24H28N2O4. Calculated, %: C 70.55; H 6.93; N 6.86.
6,7-Dimethoxy-2-(4-nitrobenzoyl)-4-spirocyclopentane-1,2,3,4-tetrahydroisoquinolinecarboxylic
Acid N-Methylamide (10d). Yield 1.4 g (63.5%); mp 165-166ºC, Rf 0.55 (benzene–acetone, 1:1). IR spectrum,
1
ν, cm-1: 1590, 1605 (C=C Ar), 1640 and 1650 (NC=O), 3350 (NH). H NMR spectrum, δ, ppm (J, Hz):
0.98-2.20 (8H, m, C4H8); 2.66 (0.9H, d, J = 4.5, NCH3) and 2.76 (2.1H, d, J = 4.5, NCH3); 3.20, 4.53 (0.6H, two
d, J = 13.2, NCH2) and 3.31, 3.92 (1.4H, two d, J = 13.2, NCH2); 3.70, 3.78, 3.79, and 3.80 (6H, s, 2OCH3);
4.77 (0.3H, s, NCH) and 5.82 (0.7H, s, NCH); 6.67 (0.7H, s, CH arom) and 6.71 (0.3H, s, CH arom); 6.74
(0.3H, s, CH arom) and 6.99 (0.7H, s, CH arom); 7.58 (0.6H, d, J = 8.6, CH arom) and 7.65 (1.4H, d, J = 8.6,
CH arom); 8.27 (0.6H, d, J = 8.6, CH arom) and 8.31 (1.4H, d, J = 8.6, CH arom); 7.54 (0.3H, br. q, J = 4.5,
NH) and 8.28 (0.7H, br. q, J = 4.5, NH). (Two isomers in the ratio 70: 30). Found, %: C 63.65; H 5.81; N 9.11.
C24H27N3O6. Calculated, %: C 63.54; H 5.97; N 9.27.
This work was carried out with the financial support of the International Science Technology Centre
(grant A-960).
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