Synthesis of new 2-substituted 6,7-dimethoxy-1-(methylcarbamoyl)- 4-spirocyclopentane-1,2,3,4-tetrahydroisoquinolines

Article abstract of DOI:10.1134/S1070428013110122

New 2-(heterylmethyl) derivatives were synthesized from 6,7-dimethoxy-4-spirocyclopentane- 1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid N-methylamide and heterylmethyl chlorides. The reactions of 2-chloroacetyl-substituted tetrahydroisoquinoline with

Full text of DOI:10.1134/S1070428013110122

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 11, pp. 1632−1636. © Pleiades Publishing, Ltd., 2013.
Original English Text © A.A. Aghekyan, G.G. Mkryan, E.A. Markaryan, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 11, pp. 1651−1654.
Synthesis of New 2-Substituted
6,7-Dimethoxy-1-(methylcarbamoyl)-
4-spirocyclopentane-1,2,3,4-tetrahydroisoquinolines
A. A. Aghekyan, G. G. Mkryan, and E. A. Markaryan
R&D Center of Organic and Pharmaceutical Chemistry, National Academy of Sciences of Armenia,
Mndzhoyan Institute of Fine Organic Chemistry, Yerevan, 0014 Armenia
е-mail: aaghekyan@mail.ru
Received June 21, 2013
Abstract—New 2-(heterylmethyl) derivatives were synthesized from 6,7-dimethoxy-4-spirocyclopentane-
1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid N-methylamide and heterylmethyl chlorides. The reactions of
2-chloroacetyl-substituted tetrahydroisoquinoline with versatile secondary amines and heterylthiols afforded the
corresponding 2-aminoacetyl and 2-(heterylsulfanylacetyl) derivatives of tetrahydroisoquinoline series.
DOI: 10.1134/S1070428013110122
Tetrahydroisoquinoline derivatives possess a wide
range of biological actions depending on the nature of
substituents and their position in the heterocyclic ring.
Therefore the research in this field continues, the attempts
to vary the substituents introduced into the structure of
new 1,2,3,4-substituted tetrahydroisoquinoline is going
on [1]. Compounds containing a spirocyclopentane sub-
stituent and a carboxamide group in the positions 4 and 1
of the tetrahydroisoquinoline, respectively, have been the
objects of our research in recent years. Here we report on
the synthesis of new derivatives of tetrahydroisoquinoline
containing in the position 2 heterylmethyl, aminoacetyl,
and heterylsulfanylacetyl substituents. To this end we
carried out alkylation and acylation of 6,7-dimethoxy-
4-spirocyclopentane-1,2,3,4-tetrahydroisoquinoline-1-
carboxylic acid N-methylamide (I).
The alkylation of compound I with methyl 5-chlo-
romethylfuran-2-carboxylate and with chloromethylfu-
razan in a mixture dioxane–methanol, 10 : 1, afforded
2-(heterylmethyl)-substituted tetrahydroisoquinolines
IIa, IIb as crystalline substances.
H3CO
H3CO
Cl
Ht
N
Ht
NH
H3CO
H3CO
CONHCH3
IIa, IIb
CONHCH3
I
CH3
N
b).
(
(a),
COOCH3
Ht =
O
O
N
The acylation of compound I with chloroacetyl chlo-
ride gave 2-(chloroacetyl) derivative III, which was
subjected to condensation with secondary amines and
potassium phthalimide, and also with heterocyclic thiols.
The reactions with secondary amines (diethylamine,
pyrrolidine, piperidine, morpholine, 4-fluorobenzylpi-
1632

SYNTHESIS OF NEW 2-SUBSTITUTED 6,7-DIMETHOXY-1-(METHYLCARBAMOYL)-...
1633
O
H3CO
H3CO
H3CO
O
O
Cl
Cl
NR1R2
I
Cl
N
N
H3CO
CONHCH3
CONHCH3
III
_
IV
а IVf
HSR3
H3CO
H3CO
O
SR3
N
CONHCH3
Va, Vb
IV, R1 = R2 = C2H5 (а); R1R2 = (CH2)4 (b), (CH2)5 (c), CH2CH2OCH2CH2 (d), (CH2CH2)2NCH2C6H4F-4 (e), 1,2-(C=O)2C6H4 (f); V,
R3 = 4,6-dimethylpyrimidin-2-yl (а), 5-phenyl-1,3,4-oxadiazol-2-yl (b).
perazine) were performed in a mixture dioxane–ethanol,
20 : 1, in the presence of catalytic amounts of KI. We
isolated 2-aminoacetyl-substituted compounds IVа–
IVe in 65–70% yields. The phthalimide derivative IVf
was obtained by condensation of substance III with
potassium phthalimide in ethanol. The corresponding
2-(heterylsulfanylacetyl)-substituted tetrahydroisoquino-
lines V were obtained by the reactions of chloroamide
III with pyrimidine- and oxadiazolethiols in alcohol in
the presence of KOH.
(I) was obtained by method [2].
Methyl 5-({6',7'-dimethoxy-1'-methylcarbamoyl-
1'Н-spiro[cyclopentane-1,4'-isoquinoline]-2'(3'H)-
yl}methyl)furan-2-carboxylate (IIa). A mixture of
1.1 g (36 mmol) of tetrahydroisoquinoline I, 0.63 g
(36 mmol) of methyl 5-chloromethylfuran-2-carboxylate,
0.36 g (36 mmol) of triethylamine, and a crystal of KI
in a mixture dioxane–methanol, 10 : 1, was heated at
60–65°C for 15 h. On distilling off the solvent the residue
was dissolved in 20 mL of 5% HCl, the impurity were
extracted with benzene. The acid solution was alkalin-
ized with 10% solution of NaOH, the reaction products
were extracted with benzene. The extract was dried with
anhydrous sodium sulfate, the solvent was distilled off,
the oily residue was crystallized from ether. Yield 0.8 g
(50%), mp 113–115°С (benzene–hexane, 1 : 1), Rf 0.55
The structure of all compounds synthesized was con-
firmed by the data of IR and 1Н NMR spectra, their purity
was checked by chromatography.
The ratio of diastereomers in compounds IV, V con-
taining two asymmetric sites was established by 1Н NMR
spectroscopy.
1
(benzene–acetone, 2 : 1). Н NMR spectrum, δ, ppm:
EXPERIMENTAL
1.48–2.14 m (8Н, С5Н8), 2.34 d, 2.80 d (1H each, NСН2,
2J 11.2 Hz), 2.72 d (3Н, NСН3, 3J 4.8 Hz), 3.64 d, 3.77 d
IR spectra were recorded on a spectrophotometer
Nicolet Avatar 330 FT-IR from mulls in mineral oil.
1Н NMR spectra were registered on a spectrometer Var-
ian Mercury-300, operating frequency 300 MHz, solvent
DMSO-d6, internal reference TMS. The melting points
were measured on a Boёtius heating microblock. TLC
was carried out on Silufol UV-254 plates, development
in iodine vapor.
2
(1H each, NСН2 -furyl, J 14.9 Hz), 3.74 s, 3.76 s (3Н
each, ОСН3), 3.84 s [3Н, С(О)ОСН3], 4.03 s (1Н, NСН),
6.51 d (1Н, Н4furyl, 3J 3.4 Hz), 6.64 s, 6.87 s (1H each, Н5
and Н8isoquinoline), 7.11 d (1Н, Н3furyl, 3J 3.4 Hz), 7.22 q
(1Н, NН, 3J 4.8 Hz). Found, %: С 65.35; Н 6.72; N 6.23.
С24Н30N2О6. Calculated, %: С 65.14; Н 6.83; N 6.33.
Hydrochloride, mp 162_164°С (ethanol).
N-Methyl-6',7'-dimethoxy-2'-(4-methyl-1,2,5-
oxadiazol-3-ylmethyl)-2',3'-dihydro-1'Н-spiro-
6,7-Dimethoxy-4-spirocyclopentane-1,2,3,4-tetra-
hydroisoquinoline-1-carboxylic acid N-methylamide
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013

AGHEKYAN et al.
1634
cyclopentane-1,4'-isoquinoline-1'-carboxamide
(IIb) was obtained similarly to compound IIa from
tetrahydroisoquinoline I and 4-methyl-3-chloromethyl-
1,2,5-oxadiazole. Yield 55%, mp 118–120°С (ether),
Rf 0.49 (benzene–acetone, 2 : 1). 1Н NMR spectrum, δ,
ppm: 1.48_1.98 m (8Н, С5Н8), 2.29 d, 2.91 d (1H each,
NСН2, 2J 11.3 Hz), 2.40 s (3Н, СН3), 2.70 d (3Н, NСН3,
3J 4.8 Hz), 3.74 s, 3.77 s (3Н each, ОСН3), 3.76 d, 3.84 d
N-Methyl-6',7'-dimethoxy-2'-[2-(diethylamino)-
acetyl]-2',3'-dihydro-1'Н-spirocyclopentane-1,4'-
isoquinoline-1'-carboxamide (IVа). Stereoisomers
mixture, 70 : 30. Yield 67%, mp 155–157°С, Rf 0.52
(benzene–acetone, 1 : 1, ammonia vapor). 1Н NMR spec-
trum, δ, ppm: 0.99 t, 1.04 t (1.8Н and 4.2Н, NСН2СН3,
J 7.1 Hz), 1.31–2.18 m (8Н, С5Н8), 2.55 q, 2.56 q (1.2Н
and 2.8Н, NСН2СН3, J 7.1 Hz), 2.67 d, 2.68 d (0.9Н and
2.1Н, NНСН3, J 4.5 Hz), 2.75 d, 3.74 d, 3.92 d, 4.39 d
(0.3Н, 0.7Н, 0.7Н, 0.3Н, СОNСН2, 2J 13.0 Hz), 3.22 d,
3.25 d, 3.28 d, 3.40 d (0.3Н, 0.7Н, 0.7Н, 0.3Н, СОСН2N,
2J 13.5 Hz), 3.76 s, 3.78 s, 3.79 s, 3.80 s (2.1Н, 2.1Н,
0.9Н, 0.9Н, ОСН3), 5.49 s, 5.73 s (0.7Н, 0.3Н, СН),
6.70 s (1Н, Н5isoquinoline), 6.82 s, 6.88 s (0.3Н, 0.7Н,
Н8isoquinoline), 7.69 q, 7.92 q (0.3Н, 0.7Н, NН, J 4.5 Hz).
Found, %: С 66.40; Н 8.30; N 9.95. С23Н35N3О4. Cal-
culated, %: С 66.16; Н 8.45; N 10.06.
2
(1H each, NСН2-Het, J 14.3 Hz), 4.06 s (1Н, СН),
6.66 s, 6.73 s (1H each, Н5 and Н8 isoquinoline), 7.35 q (1Н,
3
NН, J 4.8 Hz). Found, %: С 62.70; Н 7.20; N 14.12.
С21Н28N4О4. Calculated, %: С 62.98; Н 7.05; N 13.99.
N-Methyl-6',7'-dimethoxy-2'-(2-chloroacetyl)-
2',3'-dihydro-1'Н-spirocyclopentane-1,4'-iso-
quinoline-1'-carboxamide (III). To a benzene solution
of 4.5 g (40 mmol) of chloroacetyl chloride cooled to
10°С was added dropwise a mixture of 12.1 g (40 mmol)
of tetrahydroisoquinoline I and 3.2 g (40 mmol) of pyri-
dine. The reaction mixture was left overnight, then it was
filtered, the filtrate was washed in succession with 5%
aqueous HCl, with Н2О, 10% solution of NaOH, and
again with Н2О. The benzene solution was dried with
Na2SO4, the solvent was distilled off, the residue was
recrystallized from ethanol. Stereoisomers mixture, 60 :
40. Yield 10 g (65%), mp 190_192°С, Rf 0.55 (benzene–
acetone, 3 : 1). 1Н NMR spectrum, δ, ppm: 1.33–1.97 m,
2.08–2.18 m (7Н and 1Н, С5Н8), 3.10 d.d (0.4Н, 2J 13.0,
N-Methyl-6',7'-dimethoxy-2'-[2-(pyrrolidin-1-yl)
acetyl]-2',3'-dihydro-1'Н-spirocyclopentane-1,4'-
isoquinoline-1'-carboxamide (IVb). Stereoisomers
mixture, 60 : 40. Yield 65%, mp 110_112°С, Rf 0.58
1
(benzene–acetone, 1 : 1, ammonia vapor). Н NMR
spectrum, δ, ppm: 1.30–2.16 m [12Н, С5Н8, β,β'-СН2,
(С4Н8N)], 2.54 m (4Н, α,α'-СН2, С4Н8N), 2.67 d, 2.68 d
(1.2Н, 1.8Н, NСН3), 2.87 d, 3.73 d, 3.86 d, 4.39 d (0.4Н,
0.6Н, 0.6Н, 0.4Н, СОNСН2, 2J 13.0 Hz), 3.22 d, 3.28 d,
3.37 d (0.4Н, 0.6Н, 1Н, СОСН2N, 2J 13.0 Hz), 3.76 s,
3.78 s, 3.78 s, 3.79 s (1.8Н, 1.8Н, 1.2Н, 1.2Н, ОСН3),
5.49 s, 5.54 s (0.6Н, 0.4Н, Н5isoquinoline), 6.85 s, 6.89 s
(0.4Н, 0.6Н, Н8isoquinoline), 7.95 m (1Н, NН). Found, %:
С 66.20; Н 8.14; N 10.25. С23Н33N3О4. Calculated, %:
С 66.48; Н 8.00; N 10.11.
2
4J 1.5 Hz), 3.57 d (0.6Н, J 13.5 Hz), 3.74 d.d (0.6Н,
4
2
2J 13.5, J 1.5 Hz), 4.34 d (0.4Н, NСН2, J 13.0 Hz),
3.78 s, 3.78 s, 3.80 s (6Н, ОСН3), 4.14 d, 4.47 d (0.4 Н
each, 2J 12.7 Hz), 4.29 d, 4.33 d (0.6 Н each, NСН2Cl,
2J 13.0 Hz), 5.30 s, 5.54 s (0.4Н and 0.6Н, СН), 6.68 s,
6.73 s, 6.87 s, 7.06 s (0.6Н, 0.4Н, 0.4Н, 0.6Н, Нarom),
7.56 m (1Н, NН). Found, %: С 59.70; Н 6.78; Cl 9.40;
N 7.47. С19Н25ClN2О4. Calculated, %: С 59.92; Н 6.62;
Cl 9.31; N 7.36.
N-Methyl-6',7'-dimethoxy-2'-[2-(piperidin-1-yl)
acetyl]-2',3'-dihydro-1'Н-spirocyclopentane-1,4'-
isoquinoline-1'-carboxamide (IVc). Stereoisomers mix-
ture, 63:37. Yield 68%, mp 120–122°С, Rf 0.56 (benzene–
1
Compounds IVа–IVe. Amixture of 42 mmol of com-
pound III, 84 mmol of amine (diethylamine, pyrrolidine,
piperidine, morpholine, or 4-fluorobenzylpiperazine)
and 2–3 crystals of KI in 50 mL of a mixture ethanol–
dioxane, 20 : 1, was boiled for 10–12 h. The solvent was
distilled off, to the residue was added 50 mL of benzene
and 5% aqueous HCl till acid reaction. The water layer
was separated, alkalinized with 10% solution of NaOH,
the reaction products were extracted with benzene. The
extract was dried with anhydrous Na2SO4, the solvent was
distilled off, the residue was recrystallized from ether.
acetone, 1 : 1, ammonia vapor). Н NMR spectrum,
δ, ppm: 1.28–1.70 m, 1.73–1.94 m, 1.99–2.16 m [8Н,
4.4Н, 1.6Н, С5Н8 + (СН2)3 from С5Н10N], 2.35–2.47 m
[4Н, N(СН2)2 from С5Н10N], 2.67d, 2.69 d (1.8Н, 1.2Н,
NCH3, J 4.6 Hz), 2.84 d, 4.38 d (0.4 Н each, 2J 13.0 Hz),
3.74 d, 3.88 d (0.6Н each, СН2NСО, 2J 12.8 Hz), 3.00 d,
3.09 d, 3.22 d, 3.24 d (0.6Н, 0.4Н, 0.4Н, 0.6Н, СОСН2N,
2J 12.8 Hz), 3.76 s, 3.78 s, 3.79 s, 3.80 s (1.8Н, 1.8Н,
1.2Н, 1.2 Н, ОСН3), 5.46 s, 5.58 s (0.6Н, 0.4Н, СН),
6.68 s, 6.68 s (0.6Н, 0.4Н, С6Н2), 6.86 s, 6.89 s (0.4Н,
0.6Н, С6Н2), 7.91_7.96 m (1Н, NН). Found, %: С 67.35;
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013

SYNTHESIS OF NEW 2-SUBSTITUTED 6,7-DIMETHOXY-1-(METHYLCARBAMOYL)-...
1635
Н 8.11; N 9.63. С24Н35N3О4. Calculated, %: С 67.11;
Н 8.21; N 9.78.
(8Н, С5Н8), 2.68 d (2.1Н, J 4.2 Hz) and 2.76 d (0.9Н,
NCH3, J 4.2 Hz), 3. 06 d (0.3Н, J 13.1 Hz), 3.72 d (0.7Н,
J 14.1 Hz), 3.85 d (0.7Н, J 14.1 Hz), 4.30 d (0.3Н, NCH2,
J 13.1 Hz), 3.76 s (2.1Н), 3.79 s (2.1Н), 3.81 s (0.9Н),
3.82 s (0.9Н, ОСН3), 4.40 d (0.7Н, J 16.3 Hz), 4.54 d
(0.3Н, J 16.3 Hz), 4.69 d (0.3Н, J 16.3 Hz), 4.79 d (0.7Н,
СОСН2N, J 16.3 Hz), 5.47 s (0.3Н), 5.54 s (0.7Н, NCH),
6.72 s (0.7Н), 6.75 s (0.3Н), 6.87 s (0.3Н) and 6.94 s
(0.7Н, С6Н2), 7.74–7.89 m (4Н, С6Н4), 7.99 m (1Н,
NH). Found, %: С 65.70; Н 6.10; N 8.67. С27Н29N3О6.
Calculated, %: С 65.97; Н 5.95; N 8.55.
N-Methyl-6',7'-dimethoxy-2'-[2-(morpholin-4-yl)
acetyl]-2',3'-dihydro-1'Н-spirocyclopentane-1,4'-
isoquinoline-1'-carboxamide (IVd). Stereoisomers
mixture, 60:40. Yield 70%, mp 132–134°С, Rf 0.53 (ben-
zene–acetone, 1 : 1, ammonia vapor). 1Н NMR spectrum,
δ, ppm: 1.24–2.17 m (8Н, С5Н8), 2.40–2.52 m [4H,
N(CH2)2 morpholine], 2.67 d, 2.69 d (1.8Н, 1.2Н, NCH3,
J 4.5 Hz), 2.95 d, 4.39 d (0.4 Н each, 2J 13.0 Hz), 3.79 s
(1.2Н, СН2NСО), 3.13 d, 3.17 d, 3.23 d, 3.26 d (0.6Н,
0.4Н, 0.4Н, 0.6Н, NCH2CO, 2J 13.0 Hz), 3.52 m, 3.61 m
[1.6Н, 2.4Н, О(СН2)2], 3.76 s, 3.78 s, 3.79 s, 3.81 s
(1.8Н, 1.8Н, 1.2Н, 1.2Н, ОСН3), 5.47 s, 5.53 s (0.6Н,
0.4Н, СН), 6.68 s, 6.69 s (0.6Н, 0.4Н, С6Н2), 6.91 s,
6.93 s (0.6Н, 0.4Н, С6Н2), 7.75 br.q, 8.00 br.q (0.4Н,
0.6Н, NН, J 4.5 Hz). Found, %: С 64.31; Н 7.55; N 9.61.
С23Н33N3О5. Calculated, %: С 64.02; Н 7.71; N 9.74.
N-Methyl-6',7'-dimethoxy-2'-[2-(5-phenyl-1,3,4-
oxadiazol-2-ylsulfanyl)acetyl]-2',3'-dihydro-1'Н-
spirocyclopentane-1,4'-isoquinoline-1'-carboxamide
(Vа). To a solution of 0.6 g (34 mmol) of 5-phenyl-1,3,4-
oxadiazole-2-thiol and 0.2 g of KОН in 15 mL of anhy-
drous ethanol was added a solution of 1.2 g (32 mmol)
of compound III in 20 mL of ethanol, and the mixture
was boiled for 3 h. The mixture was left overnight, the
precipitated crystals were filtered off, washed with water
on the filter, then with 10% water solution of KОН, again
with water, dried, and recrystallized from ethanol. Ste-
reoisomers mixture, 60 : 40. Yield 53%, mp 260–262°С,
Rf 0.53 (benzene–acetone, 2 : 1). 1Н NMR spectrum, δ,
ppm: 1.34_2.21 m (8Н, С5Н8), 2.69 d, 2.73 d (1.8Н, 1.2Н,
NCH3, J 4.5 Hz), 3.13 d, 4.38 d (on 0.4Н, 2J 12.9 Hz),
3.74 d, 3.82 d (0.6 Н each, СН2NСО, 2J 14.2 Hz), 4.40 d,
4.46 d, 4.66 d, 4.69 d (0.6Н, 0.4Н, 0.4Н, 0.6Н, SСН2,
2J 15.6 Hz), 5.41 s, 5.61 s (0.4Н, 0.6Н, СН), 3.76 s,
3.78 s, 3.79 s, 3.80 s (1.8Н, 1.8Н, 1.2Н, 1.2Н, ОСН3),
6.71 s, 6.73 s (0.6Н, 0.4Н, Н5isoquinoline), 6.92 s, 6.97 s
(0.4Н, 0.6Н, Н8isoquinoline), 7.47–7.57 m, 7.98 m (3Н, 2Н,
С6Н5), 7.93 q, 7.98 q (0.4Н, 0.6Н, NН, J 4.5 Hz). Found,
%: С 62.24; Н 5.60; N 10.63; S 6.25. С27Н30N4О5S.
Calculated, %: С 62.05; Н 5.79; N 10.72; S 6.14.
N-Methyl-6',7'-dimethoxy-2'-{2-[(4-fluoro-
benzyl)piperazin-1-yl]acetyl}-2',3'-dihydro-1'Н-
spirocyclopentane-1,4'-isoquinoline-1'-carboxamide
(IVe). Stereoisomers mixture, 60:40. Yield 65%, mp
175–177°С, Rf 0.50 (benzene–acetone, 1:1, ammonia va-
por). 1Н NMR spectrum, δ, ppm: 1.28–2.14 m (8Н, С5Н8),
2.36–2.58 m (8Н, С4Н8N2), 2.61 d, 2.67 d (1.2Н, 1.8Н,
NCH3, J 4.6 Hz), 2.88 d, 4.37 d (0.4 Н each, 2J 13.1 Hz),
3.75 d, 3.82 d (0.6 Н each, СН2NСО, 2J 12.8 Hz), 3.09 d,
3.26 d (0.6 Н each,2J 12.9 Hz), 3.12 d, 3.27 d (0.4 Н each,
NCH2CO, 2J 13.1 Hz), 3.52 s, 3.53 s (0.8Н, 1.2Н, СН2Аr),
3.76 s, 3.78 s, 3.79 s, 3.80 s (1.8Н, 1.8Н, 1.2Н,1.2Н,
ОСН3), 5.46 s, 5.52 s (0.6Н, 0.4Н, СН), 6.68 s, 6.68 s
(0.6Н, 0.4Н, Н5isoquinoline), 6.86 s, 6.89 s (0.4Н, 0.6Н,
Н8isoquinoline), 6.96–7.03 m, 7.05–7.11 m, 7.18–7.25 m,
7.33–7.40 m (0.8Н, 1.2Н, 1.2Н, 0.8Н, С6Н4), 7.79 br.q,
7.95 br.q (0.4Н, 0.6Н, NН, J 4.6 Hz). Found, %: С 66.65;
Н 7.48; F 3.40; N 10.60. С30Н39FN4О4. Calculated, %:
С 66.89; Н 7.30; F 3.53; N 10.40.
N-Methyl-6',7'-dimethoxy-2'-[2-(4,6-dimethyl-
pyrimidin-2-ylsulfanyl)acetyl]-2',3'-dihydro-1'Н-
spirocyclopentane-1,4'-isoquinoline-1'-carboxamide
(Vb) was similarly obtained from compound III
and 4,6-dimethylpyrimidine-2-thiol. Stereoisomers
mixture, 70:30. Yield 51%, mp 222–224°С (ethanol),
Rf 0.48 (benzene–acetone, 1 : 1). 1Н NMR spectrum, δ,
ppm: 1.46–2.00 m (8Н, С5Н8), 2.24 s, 2.36 s (1.8Н, 4.2Н,
СН3), 2.67 d, 2.71 d (2.1Н, 0.9Н, NСН3, J 4.6 Hz), 3.76 s,
3.78 s, 3.78 s, 3.79 s (2.1Н, 0.9Н, 2.1Н, 0.9Н, ОСН3),
2'-[2-(1,3-Dioxoisoindolin-2-yl)acetyl]-N-methyl-6-
',7'-dimethoxy-2',3'-dihydro-1'Н-spiro-cyclopentane-
1,4'-isoquinoline-1'-carboxamide (IVf). A mixture of
0.6 g (16 mmol) of compound III and 0.3 g (16 mmol) of
potassium phthalimide in 30 mLof ethanol was boiled for
12 h. The precipitated crystals were filtered off, washed
with hot water 2–3 times, with acetone, and recrystal-
lized from ethanol. Stereoisomers mixture, 70 : 30. Yield
0.43 g (56%), mp 238–240°С (ethanol), Rf 0.52 (benzene–
acetone, 1 : 1). 1Н NMR spectrum, δ, ppm: 1.28–2.23 m
2
3.00 d, 4.44 d (0.3 Н each, J 13.0 Hz), 3.78 d, 3.85 d
(0.7 Н each, NСН2, 2J 13.7 Hz), 3.80 d, 4.16 d, 4.20 d,
4.33 d (0.3Н, 0.7Н, 0.7Н, 0.3Н, SСН2, 2J 15.4 Hz), 5.60 s
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013

AGHEKYAN et al.
1636
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(1Н, СН), 6.70 s, 6.72 s, 6.78 s (1Н, 0.3Н, 0.7Н, С6Н2),
6.90 s (1Нpyrimidin), 7. 84 br.q, 7.97 br.q (0.3Н, 0.7Н, NН,
J 4.6 Hz). Found, %: С 61.80; Н 6.50; N 11.67; S 6.74.
С25Н32N4О4S. Calculated, %: С 61.96; Н 6.66; N 11.56;
S 6.62.
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013