Synthesis of bis-spirocoupled pyrrolidinooxindoles derived from isatinylidene derivatives of thiazolotriazinones by [3+2] dipolar cycloaddition

Article abstract of DOI:10.1007/s11172-010-0343-5

Isatines react with 3,4-dihydro-2H-[1,3]thiazolo[3,2-a][1,3,5]triazin-6(7H) -ones to give their isatinylidene derivatives, which add azomethinylide, generated in situ from paraformaldehide and sarcosine, to yield bis-spirocoupled derivatives of pyrrolidin

Full text of DOI:10.1007/s11172-010-0343-5

Russian Chemical Bulletin, International Edition, Vol. 59, No. 10, pp. 1979—1982, October, 2010
1979
Synthesis of bisꢀspirocoupled pyrrolidinooxindoles
derived from isatinylidene derivatives of thiazolotriazinones
by [3+2] dipolar cycloaddition
A. A. Shvets and S. V. Kurbatov
Department of Chemistry, Southern Federal University,
7 ul. Zorge, 344090 RostovꢀonꢀDon, Russian Federation.
Fax: +7 (863) 297 5267. Eꢀmail: shvets@sfedu.ru
Isatines react with 3,4ꢀdihydroꢀ2Hꢀ[1,3]thiazolo[3,2ꢀa][1,3,5]triazinꢀ6(7H)ꢀones to give
their isatinylidene derivatives, which add azomethinylide, generated in situ from paraformꢀ
aldehide and sarcosine, to yield bisꢀspirocoupled derivatives of pyrrolidine. The [3+2] dipolar
cycloaddition reactions studied proceed absolutely diastereoselectively.
Key words: isatine, spiroheterocycle, spiropyrrolidinooxindole, azomethinylide, [3+2] diꢀ
polar cycloaddition.
It is known1—3 that pseudothiohidantoin 1 reacts with
Scheme 2
primary aliphatic and aromatic amines in the presence of
formaldehyde to form 3,4ꢀdihydroꢀ2Hꢀ[1,3]thiazoloꢀ
[3,2ꢀa][1,3,5]triazinꢀ6(7H)ꢀones 2, which, possessing an
active methylene group, readily form with aromatic aldeꢀ
hydes arylidene derivatives 3 (Scheme 1).
Scheme 1
2: R2 = 3ꢀBrC6H4 (a), 3,4ꢀ(OMe)2C6H3 (b), 4ꢀFꢀC6H4 (c),
3,5ꢀ(Me)2C6H3 (d); 4: R1 = Me (a), H (b), Br (c);
5: R1 = Me, R2 = 3ꢀBrC6H4 (a); R1 = H, R2 = 3,4ꢀ(OMe)2C6H3 (b),
4ꢀFꢀC6H4 (c); R1 = Br, R2 = 3,5ꢀ(Me)2C6H3 (d).
1
The study of compounds obtained by H NMR specꢀ
troscopy showed that the reactions result in the exclusive
formation of Zꢀisomers, that is confirmed, first, by the
absence of signals for possible Eꢀisomers in the 1H NMR
spectra and, second, by the presence of significantly downꢀ
field shift for the proton H(4´) found in the region
δ 8.7—9.0, which is due to the influence of the carbonyl
group C(6)O of the [1,3]thiazolo[3,2ꢀa][1,3,5]triazinꢀ
6(7H)ꢀone fragment (usually, chemical shifts of the sigꢀ
nals for the proton H(4) in isatines are found in the region
δ 7.5—7.6).4
R = Alk, Ar
We have studied reactions of 3ꢀarylꢀ3,4ꢀdihydroꢀ2Hꢀ
[1,3]thiazolo[3,2ꢀa][1,3,5]triazinꢀ6(7H)ꢀones 2 with
Nꢀmethylisatine derivatives 4a—c (Scheme 2). The conꢀ
densation was carried out in methanol in the presence of
40% aqueous KOH in catalytic amounts to give (7Z)ꢀ3ꢀ
arylꢀ7ꢀ(2ꢀoxoꢀ1,2ꢀdihydroꢀ3Hꢀindolꢀ3ꢀylidene)ꢀ3,4ꢀdiꢀ
hydroꢀ2Hꢀ[1,3]thiazolo[3,2ꢀa][1,3,5]triazinꢀ6(7H)ꢀones
5a—d in good yields.
The thus formed carbonꢀcarbon double bond, bound
to the electronꢀwithdrawing groups, is a good dipolaroꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1928—1931, October, 2010.
1066ꢀ5285/10/5910ꢀ1979 © 2010 Springer Science+Business Media, Inc.

1980
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 10, October, 2010
Shvets and Kurbatov
Scheme 3
phile, and, therefore, isatinylidenes 5 can serve as conveꢀ
nient synthons for the synthesis of spiroheterocyclic skelꢀ
etons with β,β´ꢀspirocoupled oxindole and pyrrolidine
rings. Such a β,β´ꢀspirocoupled fragment is a part of many
natural alkaloids possessing pronounced biological activity,
for example, (–)ꢀhorsphiline 6, spirotryprostatin A 7,
pteropodine 8 (see Ref. 5).
The 1,3ꢀdipolar cycloaddition reactions of isatinylꢀ
idenes 5a—d leading to the bisꢀspirocoupled systems are
given in Scheme 3. The in situ decarboxylation of the conꢀ
densation product of sarcosine 9 and paraformaldehide
10, i.e., 5ꢀoxazolidinone 11 (see Ref. 6), resulted in the
generation of isomethinylide 12, serving as a dipole in the
[3+2] cycloaddition process.
The [3+2] dipolar cycloaddition reaction of 5a—d and
12 proceeds in high yields and leads to bisꢀspirocycloꢀ
adducts 13a—d.
5, 13
R1
Me
H
H
Br
R2
a
b
c
d
3´´´ ꢀBrC6H4
3´´´ ,4´´´ ꢀ(OMe)2C6H3
4´´´ ꢀFꢀC6H4
3´´´ ,5´´´ ꢀMe2C6H3
The cycloaddition results in developing two chiral cenꢀ
ters and this means that four stereoisomers 13 can be forꢀ
mally formed. However, due to the fact that addition of
azomethinylide 12 proceeds with equal probability from
"above" or "below" of the enantiotopic plane of dipolaroꢀ
phile 5 with simultaneous formation of spiroꢀnodes, only
two stereoisomers, i.e., enantiomers, are formed, which
are separated from the reaction mixture as a racemate.
The absence even trace amounts of other possible steꢀ
reoisomers in the 1H and 13C NMR spectra confirms comꢀ
plete diastereoselectivity of the cycloaddition process. In
δ 6.98—7.28, that indicates the absence of the double bond
between the indolone and thiazolone fragments and influꢀ
ence of the carbonyl group of the thiazolone fragment.
The carbon atoms involving into the formation of the spiroꢀ
nodes have characteristic chemical shifts in the 13C NMR
spectra: C(3´), in the region δ 61.9—62.11 and C(4´), about
δ 60.6.
Variation of substituents both at the nitrogen atoms
and in the oxindole core allows us to use this method for
the synthesis of a wide range of potentially biologically
active spiroheterocycles.
1
the H NMR spectra of compounds 13a—d, the pairs of
the diastereotopic groups CH2(2´) and CH2(5´) of the pyrꢀ
rolidine, as well as CH2(2″) and CH2(4″) of the [1,3]thiꢀ
azolo[3,2ꢀa][1,3,5]triazinꢀ6(7H)ꢀone rings are found as
ABꢀquartets in the regions δ 3.13—3.85 and 4.60—5.25,
respectively, that confirms the presence of stereogenic tetꢀ
racoordinated carbon atoms C(3´) and C(4´) in the moleꢀ
cules of compounds 13a—d. The signal for the hydrogen
atom H(4) is considerably upfield shifted to the region
Experimental
1
H and 13C NMR spectra were recorded on a Bruker DPXꢀ250
spectrometer (250 MHz for H and 62.5 MHz for 13C, respecꢀ
tively) in DMSOꢀd6 and CDCl3 using Me4Si as an internal stanꢀ
dard. Mass spectra were recorded on a FINNIGAN LCQ DECA
1

Bisꢀspirocoupled pyrrolidinooxindoles
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 10, October, 2010
1981
XP MAX instrument (ESI, 1.8 kV) at 180 °C. 3ꢀArylꢀ3,4ꢀdihyꢀ
droꢀ2Hꢀ[1,3]thiazolo[3,2ꢀa][1,3,5]triazinꢀ6(7H)ꢀones were obꢀ
tained according to the known procedure,1 isatine, 5ꢀmethylꢀ
isatine, and 5ꢀbromoisatine were methylated according to the
described procedure.7
Synthesis of (7Z)ꢀ3ꢀ(3ꢀaryl)ꢀ7ꢀ(1ꢀmethylꢀ2ꢀoxoꢀ1,2ꢀdihyꢀ
droꢀ3Hꢀindolꢀ3ꢀylidene)ꢀ3,4ꢀdihydroꢀ2Hꢀ[1,3]thiazolo[3,2ꢀa]ꢀ
[1,3,5]triazinꢀ6(7H)ꢀones 5a—d (general procedure). A 40%
aqueous solution of KOH (0.001 mL) was added to a solution of
equimolar amounts of the corresponding isatine 4a—c (0.01 mol)
and 3ꢀarylꢀ3,4ꢀdihydroꢀ2Hꢀ[1,3]thiazolo[3,2ꢀa][1,3,5]triazinꢀ
6(7H)ꢀone 3a—d (0.01 mol) in methanol (50 mL) at room temꢀ
perature. After 20 min, a precipitate formed was filtered off and
washed with methanol.
(7Z)ꢀ3ꢀ(3ꢀBromophenyl)ꢀ7ꢀ(1,5ꢀdimethylꢀ2ꢀoxoꢀ1,2ꢀdihyꢀ
droꢀ3Hꢀindolꢀ3ꢀylidene)ꢀ3,4ꢀdihydroꢀ2Hꢀ[1,3]thiazolo[3,2ꢀa]ꢀ
[1,3,5]triazinꢀ6(7H)ꢀone (5a). The yield was 97%. Dark orange
crystals, m.p. 320—323 °C. Found (%): C, 53.77; H, 3.71;
Br, 17.05; N, 11.89. C21H17BrN4O2S. Calculated (%): C, 53.74;
H, 3.65; Br, 17.02; N, 11.94. 1H NMR (DMSOꢀd6), δ: 2.35 (s, 3 H,
C(5´)Me); 3.25 (s, 3 H, N(1´)Me); 5.05 (s, 2 H, C(4)H2); 5.39
(s, 2 H, C(2)H2); 6.40 (d, 1 H, H(4), Ar, J = 7.9 Hz); 6.75—6.90
(m, 3 H, H(2), H(4), H(5), Ar); 6.96 (d, 1 H, H(7´), J = 8.4 Hz);
7.43 (dd, 1 H, H(6´), J = 8.4 Hz, J = 2.1 Hz); 8.65 (d, 1 H,
H(4´), J = 2.1 Hz).
(7Z)ꢀ3ꢀ(3,4ꢀDimethoxyphenyl)ꢀ7ꢀ(1ꢀmethylꢀ2ꢀoxoꢀ1,2ꢀdihyꢀ
droꢀ3Hꢀindolꢀ3ꢀylidene)ꢀ3,4ꢀdihydroꢀ2Hꢀ[1,3]thiazolo[3,2ꢀa]ꢀ
[1,3,5]triazinꢀ6(7H)ꢀone (5b). The yield was 71%. Dark orange
crystals, m.p. 248 °C. Found (%): C, 60.60; H, 4.56; N, 12.89.
C22H20N4O4S. Calculated (%): C, 60.54; H, 4.62; N, 12.84.
1H NMR (DMSOꢀd6), δ: 3.22 (s, 3 H, N(1´)Me); 3.64 (s, 3 H,
OMe); 3.72 (s, 3 H, OMe); 4.99 (s, 2 H, C(4)H2); 5.36 (s, 2 H,
C(2)H2); 6.49 (dd, 1 H, H(7´), J = 8.7 Hz, J = 2.7 Hz); 6.75—6.87
(m, 2 H, H(2), H(5), Ar); 7.02—7.15 (m, 2 H, H(6), Ar, H(6´));
7.40 (dd, 1 H, H(5´), J = 8.6 Hz, J = 8.6 Hz); 8.77 (dd, 1 H,
H(4´), J = 8.6 Hz, J = 1.3 Hz).
(7Z)ꢀ3ꢀ(4ꢀFluorophenyl)ꢀ7ꢀ(1ꢀmethylꢀ2ꢀoxoꢀ1,2ꢀdihydroꢀ
3Hꢀindolꢀ3ꢀylidene)ꢀ3,4ꢀdihydroꢀ2Hꢀ[1,3]thiazolo[3,2ꢀa][1,3,5]ꢀ
triazinꢀ6(7H)ꢀone (5c). The yield was 66%. Dark orange crysꢀ
tals, m.p. 292 °C. Found (%): C, 60.99; H, 3.93; F, 4.88; N, 14.14.
C20H15FN4O2S. Calculated (%): C, 60.90; H, 3.83; F, 4.82;
N, 14.20. 1H NMR (DMSOꢀd6), δ: 3.24 (s, 3 H, N(1´)Me); 5.02
(s, 2 H, C(4)H2); 5.39 (s, 2 H, C(2)H2); 7.05—7.20 (m, 6 H, Ar,
H(7´), H(6´)); 7.44 (dd, 1 H, H(5´), J = 7.9 Hz, J = 7.9 Hz);
8.80 (dd, 1 H, H(4´), J = 7.9 Hz, J = 1.2 Hz).
(7Z)ꢀ7ꢀ(5ꢀBromoꢀ1ꢀmethylꢀ2ꢀoxoꢀ1,2ꢀdihydroꢀ3Hꢀindolꢀ3ꢀ
ylidene)ꢀ3ꢀ(3,5ꢀdimethylphenyl)ꢀ3,4ꢀdihydroꢀ2Hꢀ[1,3]thiazoꢀ
lo[3,2ꢀa][1,3,5]triazinꢀ6(7H)ꢀone (5d). The yield was 86%. Dark
orange crystals, m.p. 274 °C. Found (%): C, 54.68; H, 4.05;
Br, 16.42; N, 11.67. C22H19BrN4O2S. Calculated (%): C, 54.66;
H, 3.96; Br, 16.53; N, 11.59. 1H NMR (DMSOꢀd6), δ: 2.19 (s, 6 H,
5ꢀMe, 3ꢀMe, Ar); 3.21 (s, 3 H, N(1´)Me); 5.00 (s, 2 H, C(4)H2);
5.39 (s, 2 H, C(2)H2); 6.40—6.70 (m, 3 H, Ar); 6.98 (d, 1 H,
H(7´), J = 8.2 Hz); 7.51 (dd, 1 H, H(6´), J = 8.2 Hz, J = 1.9 Hz);
8.97 (d, 1 H, H(4´), J = 1.9 Hz).
and paraformaldehide 10 (0.004 mol) were suspended in toluene
(40 mL). The reaction mixture was refluxed for 5—6 h. The
reaction progress was monitored by TLC on Silufolꢀ254 plate in
AcOEt with visualization in iodine vapors. After the reaction
reached completion, the reaction mixture was cooled, toluene
was evaporated at reduced pressure, the product was isolated by
column chromatography (Merck Silicagelꢀ60 (60—200 μm),
eluent: AcOEt).
3″ꢀ(3´´´ꢀBromophenyl)ꢀ1,1´,5ꢀtrimethylꢀ3″,4″ꢀdihydroꢀ2″Hꢀ
dispiro[indoleꢀ3,3´ꢀpyrrolidineꢀ4´,7″ꢀ[1,3]thiazolo[3,2ꢀa]ꢀ
[1,3,5]triazine]ꢀ2,6″(1H)ꢀdione (13a). The yield was 55%.
Colorless crystals, m.p. 136 °C. Found (%): C, 54.63; H, 4.55;
Br, 15.07; N, 13.41. C24H24BrN5O2S. Calculated (%): C, 54.76;
H, 4.60; Br, 15.18; N, 13.30. 1H NMR (CDCl3), δ: 2.13 (s, 3 H,
C(5)Me); 2.60 (s, 3 H, N(1´)Me); 3.13 (d, 1 H, C(2´)H2,
J = 10.4 Hz); 3.17 (s, 3 H, N(1)Me); 3.42 (d, 1 H, C(5´)H2,
J = 10.6 Hz); 3.59 (d, 1 H, C(2´)H2, J = 10.4 Hz); 3.82 (d, 1 H,
C(5´)H2, J = 10.6 Hz); 4.60 (d, 1 H, C(4″)H2, J = 15.8 Hz); 4.75
(d, 1 H, C(4″)H2, J = 15.8 Hz); 4.88 (d, 1 H, C(2″)H2, J = 12.7
Hz); 5.13 (d, 1 H, C(2″)H2, J = 12.7 Hz); 6.60—6.75 (d, m, 2 H,
H(7), HAr(6´´´ ), J = 7.9 Hz); 6.93—7.07 (m, 4 H, H(6), H(4),
HAr(2´´´ ) + HAr(4´´´ )); 7.08—7.15 (m, 1 H, HAr(5´´´ )). 13C NMR
(CDCl3), δ: 21.3 (C(5)CH3), 26.3 (N(1)CH3), 42.7 (N(1´)CH3),
60.6 (C(4´)), 61.7 (C(5´)), 61.9 (C(3´)), 62.4 (C(2´)), 63.6
(C(4″)), 65.6 (C(2″)), 108.1 (C(7)), 117.9 (CAr(6´´´ )), 123.2
(CAr(2´´´ ), CAr(4´´´ )), 123.7 (CAr(3´´´ )), 125.1 (C(4)), 126.2 (C(6)),
130.0 (C(3a)), 130.6 (CAr(5´´´ )), 132.3 (C(5)), 142.3 (C(7a)),
148.9 (CAr(1´´´ )), 150.4 (C(8a″)), 171.8 (C(2)), 177.2 (C(6″)).
MS (ESI), m/z: 527 [M + 1]+.
3″ꢀ(3´´´,4´´´ꢀDimethoxyphenyl)ꢀ1,1´ꢀdimethylꢀ3″,4″ꢀdihyꢀ
droꢀ2″Hꢀdispiro[indoleꢀ3,3´ꢀpyrrolidineꢀ4´,7″ꢀ[1,3]thiazoloꢀ
[3,2ꢀa][1,3,5]triazine]ꢀ2,6″(1H)ꢀdione (13b). The yield was
74%. Colorless crystals, m.p. 134 °C. Found (%): C, 60.86;
H, 5.61; N, 14.12. C25H27N5O4S. Calculated (%): C, 60.84;
H, 5.51; N, 14.19. 1H NMR (CDCl3), δ: 2.59 (s, 1 H, N(1´)Me);
3.11 (d, 1 H, C(2´)H2, J = 10.4 Hz); 3.17 (s, 3 H, N(1)Me); 3.39
(d, 1 H, C(5´)H2, J = 10.7 Hz); 3.60 (d, 1 H, C(2´)H2, J = 10.4 Hz);
3.73 (s, 3 H, OMe); 3.85 (s, d, 4 H, C(5´)H2, OMe, J =
= 10.7 Hz); 4.64 (d, 1 H, C(4″)H2, J = 15.8 Hz); 4.69 (d, 1 H,
C(4″)H2, J = 15.8 Hz); 4.97 (d, 1 H, C(2″)H2, J = 12.8 Hz); 5.03
(d, 1 H, C(2″)H2, J = 12.8 Hz); 6.28 (dd, 1 H, HAr(6´´´ ), J = 8.6 Hz,
J = 2.6 Hz); 6.35 (d, 1 H, HAr(2´´´), J = 2.6 Hz); 6.57 (m, 2 H,
HAr(5´´´ ); H(6)); 6.73 (d, 1 H, H(7), J = 7.7 Hz); 6.98 (d, 1 H,
H(4), J = 7.7 Hz); 7.16 (dd, 1 H, H(5), J = 7.7 Hz, J = 7.7 Hz).
13C NMR (CDCl3), δ: 26.2 (N(1)CH3), 42.7 (N(1´)CH3), 55.7
(C(3)OCH3), 56.0 (C(4)OCH3), 60.5 (C(4´)), 61.7 (C(5´)), 61.9
(C(3´)), 63.1 (C(2´)), 63.4 (C(4″)), 66.2 (C(2″)), 104.6 (CAr(2´´´ )),
108.1 (C(7)), 111.4 (CAr(5´´´ )), 111.5 (CAr(6´´´ )), 122.7 (C(5)),
123.3 (C(3a)), 124.1 (C(4)), 129.4 (C(6)), 141.3 (C(7a)), 144.5
(CAr(4´´´ )), 145.3 (CAr(1´´´ )), 149.3 (CAr(3´´´ )), 150.2 (C(8a″)),
172.0 (C(2)), 177.2 (C(6″)). MS (ESI), m/z: 493 [M + 1]+.
3″ꢀ(4´´´ꢀFluorophenyl)ꢀ1,1´ꢀdimethylꢀ3″,4″ꢀdihydroꢀ2″Hꢀ
dispiro[indoleꢀ3,3´ꢀpyrrolidineꢀ4´,7″ꢀ[1,3]thiazolo[3,2ꢀa]ꢀ
[1,3,5]triazine]ꢀ2,6″(1H)ꢀdione (13c). The yield was 64%. Colorꢀ
less crystals, m.p. 184 °C. Found (%): C, 61.22; H, 4.89; F, 4.15;
N, 15.62. C23H22FN5O2S. Calculated (%): C, 61.18; H, 4.91;
F, 4.21; N, 15.51. 1H NMR (CDCl3), δ: 2.60 (s, 1 H, N(1´)Me);
3.12 (d, 1 H, CH2(2´), J = 10.4 Hz); 3.19 (s, 3 H, N(1)Me); 3.41
(d, 1 H, C(5´)H2, J = 10.6 Hz); 3.62 (d, 1 H, C(2´)H2, J = 10.4 Hz);
3.85 (d, 1 H, C(5´)H2, J = 10.6 Hz); 4.61 (d, 1 H, C(4″)H2,
J = 15.8 Hz); 4.70 (d, 1 H, C(4″)H2, J = 15.8 Hz); 4.98 (d, 1 H,
Synthesis of 3″ꢀ(3ꢀaryl)ꢀ1,1´ꢀdimethylꢀ3″,4″ꢀdihydroꢀ2″Hꢀ
dispiro[indoleꢀ3,3´ꢀpyrrolidineꢀ4´,7″ꢀ[1,3]thiazolo[3,2ꢀa][1,3,5]ꢀ
triazine]ꢀ2,6″(1H)ꢀdiones 13a—d (general procedure). The corꢀ
responding (7Z)ꢀ3ꢀ(3ꢀaryl)ꢀ7ꢀ(1ꢀmethylꢀ2ꢀoxoꢀ1,2ꢀdihydroꢀ3Hꢀ
indolꢀ3ꢀylidene)ꢀ3,4ꢀdihydroꢀ2Hꢀ[1,3]thiazolo[3,2ꢀa][1,3,5]ꢀ
triazinꢀ6(7H)ꢀone 5a—d (0.001 mol), sarcosine 9 (0.004 mol),

1982
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 10, October, 2010
Shvets and Kurbatov
C(2″)H2, J = 13.0 Hz); 5.04 (d, 1 H, C(2″)H2, J = 13.0 Hz); 6.63
(dd, 1 H, H(6), J = 7.6 Hz, J = 7.6 Hz); 6.66—6.90 (m, 5 H,
H(7), Ar); 7.03 (d, 1 H, H(4), J = 7.6 Hz); 7.21 (dd, 1 H, H(5),
J = 7.6 Hz, J = 7.6 Hz). 13C NMR (CDCl3), δ: 26.2 (N(1)CH3),
42.7 (N(1´)CH3), 60.5 (C(4´)), 61.8 (C(5´)), 62.1 (C(2´)),
62.6 (C(3´)), 63.2 (C(4″)), 66.1 (C(2″)), 108.3 (C(7)), 116.0
(d, CAr(3´´´ ), CAr(5´´´ ), J = 22.5 Hz); 121.4 (d, CAr(2´´´ ), CAr(6´´´ ),
J = 8.1 Hz); 122.8 (C(5)), 123.4 (C(3a)), 124.2 (C(4)), 129.5
(C(6)), 143.6 (d, CAr(1´´´ ), J = 2.6 Hz), 144.6 (C(7a)), 150.3
(C(8a″)), 158.0 (d, CAr(4´´´ ), J = 242.1 Hz), 172.0 (C(2)), 177.2
(C(6″)). MS (ESI), m/z: 451 [M + 1]+.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 09ꢀ03ꢀ00726ꢀa),
the Ministry of Education and Science and Federal Agency
of Education (Analytical Departmental Specially Purposed
Program "Development of Scientific Potential of the Higher
School" 2.2.1.1/2348), and the Support Foundation for
Development of Small Enterprises in the Field of Science
and Technology (Project No. 9653/10).
References
5ꢀBromoꢀ3″ꢀ(3´´´,5´´´ꢀdimethylphenyl)ꢀ1,1´ꢀdimethylꢀ3″,4″ꢀ
dihydroꢀ2″Hꢀdispiro[indoleꢀ3,3´ꢀpyrrolidineꢀ4´,7″ꢀ[1,3]thiazoloꢀ
[3,2ꢀa][1,3,5]triazine]ꢀ2,6″(1H)ꢀdione (13d). The yield was
53%. Colorless crystals, m.p. 175 °C. Found (%): C, 55.63;
H, 4.91; Br, 14.62; N, 13.06. C25H26BrN5O2S. Calculated (%):
C, 55.56; H, 4.85; Br, 14.78; N, 12.96. 1H NMR (CDCl3), δ:
2.23 (s, 6 H, C(3´´´ )Me, C(5´´´ )Me, Ar); 2.59 (s, 3 H, N(1´)Me);
3.13 (d, 1 H, C(5´)H2, J = 10.4 Hz); 3.17 (s, 3 H, N(1)Me); 3.38
(d, 1 H, C(2´)H2, J = 10.7 Hz); 3.58 (d, 1 H, C(5´)H2, J = 10.4 Hz);
3.79 (d, 1 H, C(2´)H2, J = 10.7 Hz); 4.56 (d, 1 H, C(4″)H2,
J = 15.8 Hz); 4.72—4.90 (m, 2 H, C(4″)H2, C(2″)H2); 5.25
(d, 1 H, C(2″)H2, J = 12.6 Hz); 6.49 (s, 2 H, HAr(6´´´ ), HAr(2´´´ ));
6.60—6.72 (m, 2 H, HAr(4´´´ ), H(7)); 7.28 (d, 1 H, H(4),
J = 1.6 Hz); 7.33 (dd, 1 H, H(5), J = 8.2 Hz, J = 1.9 Hz).
13C NMR (CDCl3), δ: 21.5 (2 C, C(5)CH3, C(3)CH3, Ar), 26.3
(N(1)CH3), 42.6 (N(1´)CH3), 60.9 (C(4´)), 61.8 (C(5´)), 62.1
(C(3´)), 62.8 (C(2´)), 63.3 (C(4″)), 62.6 (C(2″)), 109.6 (C(7)),
115.4 (C(5)), 117.3 (2 C, CAr(2´´´ ), CAr(6´´´ )), 125.1 (C(4)), 125.8
(C(3a)), 127.7 (CAr(4´´´ )), 132.4 (C(6)), 139.1 (2 C, CAr(3´´´ ),
CAr(5´´´ )), 143.8 (C(7a)), 147.2 (CAr(1´´´ )), 149.9 (C(8″a)), 171.6
(C(2)), 176.6 (C(6″)). MS (ESI), m/z: 541 [M + 1]+.
1. S. Yu. Solov´evaꢀYavits, S. M. Ramsh, A. I. Ginak, Khim.
Geterotsikl. Soedin., 1981, 4, 477 [Chem. Heterocycl. Compd.
(Engl. Transl.), 1981, 17, 340].
2. S. Yu. Solov´eva, S. M. Ramsh, A. I. Ginak, Khim. Geteroꢀ
tsikl. Soedin., 1983, 9, 1204 [Chem. Heterocycl. Compd.
(Engl. Transl.), 1984, 19, 961].
3. S. M. Ramsh, N. L. Medvedskii, S. O. Uryupov, Khim.
Geterotsikl. Soedin., 2006, 7, 1905 [Chem. Heterocycl. Compd.
(Engl. Transl.), 2006, 42, 948].
4. J. F. M. da Silva, S. J. Garden, A. C. Pinto, J. Braz. Chem.
Soc., 2001, 12, 273.
5. H. Wagner, B. Kreutzkamp, K. Jurcie, Planta Medica,
1985, 419.
6. V. Nair, K. C. Sheela, N. P. Rath, Chem. Lett., 2000, 29, 980.
7. G. I. Zhungietu, M. A. Rekhter, Izatin i ego proizvodnye
[Isatine and its Derivatives], Shtiintsa, Kishinev, 1977, 36 pp.
(in Russian).
The authors are grateful to D. V. Zimakov (South
Scientific Center of RAS) for the recording and interpreꢀ
tation of mass spectra.
Received April 12, 2010;
in revised form July 19, 2010