Modification of biologically active amides and amines with fluoro-containing heterocycles 5. Fluoro-containing heterocyclic derivatives of 2-amino-1,3,4-thiadiazoles

Article abstract of DOI:10.1007/s11172-011-0110-2

An approach to modification of biologically active 2-amino-1,3,4- thiadiazoles with fluoro-containing five-membered heterocycles was proposed. The approach involves reactions of imines (generated in situ from 2-amino-1,3,4-thiadiazoles and methyl trifluoropyruvate) with 1,3-binucleophiles such as 6-aminouracils, 6-aminothiouracils, N-substituted 3- aminocyclohexenones, N-substituted ureas, N-substituted benzamidines, and 3-aminocrotononitrile.

Full text of DOI:10.1007/s11172-011-0110-2

Russian Chemical Bulletin, International Edition, Vol. 60, No. 4, pp. 707—711, April, 2011
707
Modification of biologically active amides and amines
with fluoroꢀcontaining heterocycles
5*. Fluoroꢀcontaining heterocyclic derivatives of 2ꢀaminoꢀ1,3,4ꢀthiadiazoles
V. B. Sokolov, A. Yu. Aksinenko, T. A. Epishina, T. V. Goreva, and I. V. Martynov
Institute of Physiologically Active Compounds, Russian Academy of Sciences,
1 Severnyi pr., 142432 Chernogolovka, Moscow Region, Russian Federation.
Fax: +7 (496) 524 9508. Eꢀmail: alaks@ipac.ac.ru
An approach to modification of biologically active 2ꢀaminoꢀ1,3,4ꢀthiadiazoles with fluoroꢀ
containing fiveꢀmembered heterocycles was proposed. The approach involves reactions of
imines (generated in situ from 2ꢀaminoꢀ1,3,4ꢀthiadiazoles and methyl trifluoropyruvate) with
1,3ꢀbinucleophiles such as 6ꢀaminouracils, 6ꢀaminothiouracils, Nꢀsubstituted 3ꢀaminocycloꢀ
hexenones, Nꢀsubstituted ureas, Nꢀsubstituted benzamidines, and 3ꢀaminocrotononitrile.
Key words: 2ꢀaminoꢀ1,3,4ꢀthiadiazoles, methyl trifluoropyruvate, 1,3,4ꢀthiadiazolꢀ2ꢀ
ylimines, 6ꢀaminouracils, 6ꢀaminothiouracils, Nꢀsubstituted 3ꢀaminocyclohexenones, Nꢀsubꢀ
stituted ureas, Nꢀsubstituted benzamidines, 3ꢀaminocrotononitrile, fluoroꢀcontaining dihydroꢀ
1Hꢀpyrroles, hexahydroꢀ1Hꢀindoles, hexahydroꢀ1Hꢀpyrrolo[2,3ꢀd]pyrimidines, imidazolidineꢀ
2,4ꢀdiones, cyclocondensation.
1,3,4ꢀThiadiazole derivatives are successfully used as
herbicides2 and fungicides3 in agricultural chemistry and
as bactericides in medical practice.4 The 2ꢀaminoꢀ1,3,4ꢀ
thiadiazole fragment is also employed for molecular deꢀ
sign of biologically active compounds (e.g., sulfaethidole,
a streptocide derivative).5 The goal of the present study
was to modify 2ꢀaminoꢀ1,3,4ꢀthiadiazoles with trifluoroꢀ
methylꢀcontaining fiveꢀmembered heterocycles using
reactions of methyl trifluoropyruvate 1 and 1,3ꢀN,Nꢀ and
1,3ꢀC,Nꢀbinucleophiles with 2ꢀaminoꢀ1,3,4ꢀthiadiazoles
2a—c. The prerequisite for this work was the data from
systematic investigations of the behavior of acylimines
of methyl trifluoropyruvate in cyclocondensation reacꢀ
tions with 1,3ꢀN,Nꢀ and 1,3ꢀC,Nꢀbinucleophiles, which
yield trifluoromethylꢀcontaining fiveꢀmembered heteroꢀ
cycles,6—10 as well as modification of streptocide11 and
piracetam.12
Following known literature routes to Nꢀsubstituted
imines of methyl trifluoropyruvate, we failed to obtain the
starting biselectrophilic synthons (1,3,4ꢀthiadiazolꢀ2ꢀ
ylimines of methyl trifluoropyruvate (3a—c)) in the indiꢀ
vidual state.13 For this reason, imines 3a—c were generatꢀ
Scheme 1
* For Part 4, see Ref. 1.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 693—697, April, 2011.
1066ꢀ5285/11/6004ꢀ707 © 2011 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 60, No. 4, April, 2011
Sokolov et al.
Scheme 2
Comꢀ
pound
3a
3b
3c
8a
8b
10a
10b
10c
R
Comꢀ
pound
14a
14b
14c
R
Comꢀ
pound
4a
4b
4c
R´
Comꢀ
pound
6b
6c
6d
R
R´
Me
Et
Me
Et
EtS
Et
CH2Ph
CH2CH2Ph
CH2C6H4ꢀOMeꢀ4
CH2Ph
Me
Me
Et
CH2CH2Ph
CH2C6H4ꢀOMeꢀ4
CH2Ph
EtS
Me
EtS
Me
Et
16a
16b
11a
11b
6e
6f
Et
CH2CH2Ph
CH2Ph
CH2Ph
CH2CH2Ph
CH2CH2Ph
CH2Ph
EtS
CH2CH2Ph
EtS
Me
Me
Et
EtS
EtS
12a
12b
12c
12d
12e
EtS
CH2CH2Ph

Fluoroꢀcontaining 2ꢀaminoꢀ1,3,4ꢀthiadiazoles
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 4, April, 2011
709
The reaction mixture was stirred for 30 min and, after addition
of SOCl2 (1.19 g, 0.01 mol), for 1 h. Then phenethylurea (1.64 g,
0.01 mol) was added. The reaction mixture was stirred at 20 °C
for 1 h and poured into water (50 mL). The precipitate that
formed was filtered off and recrystallized from 50% EtOH. The
yield, melting point, elemental analysis data, and spectroscopic
characteristics of compound 5 are given in Tables 1 and 2.
ed in situ by successively adding pyridine, methyl trifluoroꢀ
pyruvate 2, and thionyl chloride to a solution of 2ꢀaminoꢀ
1,3,4ꢀthiadiazoles 2a—c in DMF. The generated imines
3a—c underwent cyclocondensation with 1,3ꢀC,Nꢀ and
1,3ꢀN,Nꢀbinucleophiles. The reactions of imines 3a—c
with 1,3ꢀbinucleophiles follow the cyclocondensation
mechanism involving (1) addition of the binucleophile to
the C=N bond and (2) heterocyclization with elimination of
methanol. In the case of 2ꢀaminoꢀ5ꢀethylsulfanyl[1,3,4]ꢀ
thiadiazole 2c and phenethylurea 4b, adduct 5 was isolatꢀ
ed in the individual state and characterized. When heated
in DMF at 90—100 °C for 2 h in the presence of catalytic
amounts of Et3N, adduct 5 underwent intramolecular
cyclization into imidazolidineꢀ2,4ꢀdione 6a (Scheme 1).
Reactions of in situ generated imines 3a—c with 1,3ꢀbiꢀ
nucleophiles such as Nꢀsubstituted ureas 4a—c, Nꢀbenzylꢀ
benzamidine 7, 3ꢀaminocrotononitrile 9, Nꢀsubstituted
3ꢀaminocyclohexenones 11a,b, 6ꢀaminouracil 13, and
6ꢀaminothiouracil 15 were carried out in DMF at 90—100 °C
for 2 h in the presence of catalytic amounts of Et3N withꢀ
out isolating intermediate adducts (Scheme 2). Cycloconꢀ
densation of imines 3a—c with binucleophiles 4a—c, 7, 9,
11a,b, 13, and 15 gave the corresponding heterocyclic comꢀ
pounds 6a—f, 8a,b, 10a—c, 12a,b, 14a—c, and 16a,b.
Fluoroꢀcontaining heterocyclic products 6, 8, 10, 12,
14, and 16 are crystalline solids; their compositions and
structures were determined from elemental analysis data
and 1H and 19F NMR spectra. The 19F NMR spectra
show characteristic signals at δ –0.7—0.9 for compound 6,
at δ 0.3—0.4 for compound 8, at δ 2.0—2.3 for compound
10, and at δ 3.6—3.9 for compounds 12, 14, and 16.
To sum up, the reactions of 2ꢀaminoꢀ1,3,4ꢀthiadiazoles
with methyl trifluoropyruvate and 1,3ꢀC,Nꢀ and N,Nꢀbiꢀ
nucleophiles in the presence of the dehydrating system
Py/SOCl2 seem to be a promising synthetic way of modiꢀ
fying the amine function of biologically active heterylꢀ
amines with various trifluoromethylꢀcontaining fiveꢀmemꢀ
bered heterocycles.
Table 1. Yields, melting points, and elemental analysis data for
compounds 5, 6, 8, 10, 12, 14, and 16
Comꢀ Yield M.p./°C
pound (%)
Found
Calculated
Molecular
formula
(%)
N
C
H
5
86 154—155 44.05 4.35 15.11 C17H20F3N5O3S2
43.87 4.11 15.33
6a
88 (A) 183—184 44.54 3.74 16.23 C16H16F3N5O2S2
72 (B)
44.71 3.57 16.05
6b
83 180—182 46.75 3.66 18.17 C15H14F3N5O2S
46.58 3.84 18.01
6c
82 175—177 44.89 3.52 17.45 C15H14F3N5O3S
44.65 3.28 17.33
6d
69 172—174 46.75 3.66 18.17 C15H14F3N5O2S
46.92 3.88 18.36
6e
75 169—171 48.12 4.04 17.53 C16H16F3N5O2S
48.31 3.88 17.37
6f
78 153—155 43.16 3.38 16.78 C15H14F3N5O2S2
43.32 3.56 16.54
8a
73 180—182 55.68 3.74 16.23 C20H16F3N5OS
55.85 3.56 16.06
8b
75 168—170 52.82 3.80 14.67 C21H18F3N5OS2
52.61 4.02 14.44
10a
10b
10c
12a
12b
12c
12d
12e
14a
14b
14c
16a
16b
62 238—239 39.61 2.66 18.79 C10H8F3N5OS
39.45 2.48 18.95
68 224—226 41.64 3.18 22.07 C11H10F3N5OS
41.89 3.41 22.25
71 234—236 37.82 2.89 20.05 C11H10F3N5OS2
37.99 3.05 19.83
73 180—182 55.99 4.70 12.44 C21H21F3N4O2S
56.18 4.52 12.26
69 184—186 56.89 4.99 12.06 C22H23F3N4O2S
56.67 4.81 11.85
72 175—176 57.73 5.27 11.71 C23H25F3N4O2S
57.91 5.03 11.89
63 184—185 53.21 4.67 11.28 C22H23F3N4O2S2
53.38 4.52 11.03
68 167—168 54.10 4.94 10.97 C23H25F3N4O2S2
54.31 5.12 11.18
77 278—279 49.43 3.23 16.01 C18H14F3N5O3S
49.22 3.06 15.85
79 271—273 50.55 3.57 15.51 C19H16F3N5O3S
50.28 3.38 15.69
74 265—266 47.02 3.34 14.48 C19H16F3N5O3S2
46.84 3.16 14.69
82 245—246 44.64 3.08 15.31 C17H14F3N5O3S2
44.45 3.31 15.59
Experimental
1
H and 19F NMR spectra were recorded on a Bruker DXP
200 spectrometer (200.13 (1H) and 188.29 MHz (19F)) with
SiMe4 as the internal standard and CF3COOH as the external
standard, respectively. Melting points were determined in glass
capillaries. The starting reagents Nꢀsubstituted 3ꢀaminocycloꢀ
hexenones 11a,b were prepared according to a known proceꢀ
dure.14 6ꢀAminouracil 13 and 6ꢀaminothiouracil 15,15 Nꢀsubꢀ
stituted ureas 4a—c, 3ꢀaminocrotononitrile 9, methyl trifluoroꢀ
pyruvate 1, and 2ꢀaminoꢀ1,3,4ꢀthiadiazoles 2a—c (Aldrich) were
used as purchased.
Methyl 2ꢀ(5ꢀethylsulfanyl[1,3,4]thiadiazolꢀ2ꢀylamino)ꢀ3,3,3ꢀ
trifluoroꢀ2ꢀ(3ꢀphenethylureido)propionate (5). Pyridine (1.56 g,
0.02 mol) and methyl trifluoropyruvate 1 (1.56 g, 0.01 mol) were
successively added to a stirred solution of 1.62 g (0.01 mol)
2ꢀaminoꢀ5ꢀethylsulfanyl[1,3,4]thiadiazole 2c in DMF (20 mL).
80 235—237 41.71 2.88 14.31 C17H14F3N5O3S3
41.50 2.63 14.13

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Russ.Chem.Bull., Int.Ed., Vol. 60, No. 4, April, 2011
Sokolov et al.
Table 2. 1H and 19F NMR spectra of compounds 5, 6, 8, 10, 12, 14, and 16 in DMSOꢀd6
Compound
1H NMR (δ, J/Hz)
19F NMR (δ (s))
5
1.36 (t, 3 H, Me, J = 7.5); 2.60 (t, 2 H, CH2, J = 6.8); 3.03—3.20 (m, 4 H, CH2 + CH2);
3.80 (s, 3 H, MeO); 6.50 (t, 1 H, NH, J = 6.8); 7.00—7.26 (m, 5 H, CHAr); 7.58, 8.46
(both s, 1 H, NH)
2.82
6a
6b
6c
6d
6e
6j
1.38 (t, 3 H, Me, J = 7.8); 2.92 (t, 2 H, CH2, J = 7.5); 3.14 (q, 2 H, CH2, J = 7.3); 3.68
(t, 2 H, CH2, J = 7.5); 7.06—7.34 (m, 5 H, CHAr); 9.19, 9.23 (both s, 1 H, NH)
2.54 (s, 3 H, Me); 2.98 (t, 2 H, CH2, J = 7.7); 3.72 (m, 2 H, CH2); 7.09—7.37 (m, 5 H,
CHAr); 9.13, 9.27 (both s, 1 H, NH)
2.55 (s, 3 H, Me); 3.79 (s, 3 H, MeO); 4.61 (m, 2 H, CH2); 6.84, 7.29 (both d, 2 H,
CHAr, J = 8.6); 9.15, 9.35 (both s, 1 H, NH)
1.30 (t, 3 H, Me, J = 7.6); 2.86 (q, 2 H, CH2, J = 7.6); 4.65 (m, 2 H, CH2); 7.11—7.42
(m, 5 H, CHAr); 9.16, 9.35 (both s, 1 H, NH)
1.31 (t, 3 H, Me, J = 7.5); 2.80—3.04 (m, 4 H, CH2 + CH2); 3.69 (m, 2 H, CH2);
7.07—7.35 (m, 5 H, CHAr); 9.15, 9.24 (both s, 1 H, NH)
1.39 (t, 3 H, Me, J = 7.6); 3.12 (q, 2 H, CH2, J = 7.6); 4.17 (m, 2 H, CH2); 7.00 (m,
2 H, CHAr); 7.15 (m, 3 H, CHAr); 7.68, 8.59 (both s, 1 H, NH)
2.30 (s, 3 H, Me); 4.77 (s, 2 H, CH2); 7.18—7.37 (m, 5 H, CHAr); 7.40—7.54 (m, 5 H,
CHAr); 8.94 (s, 1 H, NH)
1.40 (t, 3 Н, Ме, J = 7.3); 3.05 (q, 2 Н, СН2, J = 7.3); 4.79 (q, 2 Н, СН2, J = 10.3);
7.23, 7.24—7.54 (both m, 5 Н, СНAr); 7.49 (m, 5 Н, СНAr); 9.37 (s, 1 Н, NH)
2.28, 2.55 (both s, 3 Н, Ме); 9.02, 11.35 (both s, 1 Н, NH)
–0.75
–0.70
–0.92
–0.74
–0.58
–0.71
0.40
8a
8b
0.30
10a
10b
2.27
2.22
1.27 (t, 3 Н, Ме, J = 7.1); 2.22 (s, 3 H, Me); 2.84 (q, 2 Н, СН2, J = 7.1); 8.98, 11.28
(both s, 1 Н, NH)
10c
12a
1.37 (t, 3 Н, Ме, J = 7.3); 2.25 (s, 3 H, Me); 3.11 (q, 2 Н, СН2, J = 7.3); 9.14, 11.32
(both s, 1 Н, NH)
0.99, 1.06 (both s, 3 Н, Ме); 2.13 (AB system, 2 Н, СН2, J = 15.09); 2.45 (d, 2 Н,
СН2, J = 4.2); 2.51 (s, 3 Н, Ме); 4.97 (AB system, 2 Н, СН2, J = 10.20); 7.24—7.51
(m, 5 Н, CHAr); 9.00 (s, 1 Н, NH)
2.03
3.81
12b
12c
0.97 (s, 6 H, Me); 2.07 (m, 2 H, CH2); 2.17 (m, 2 H, CH2); 2.96 (m, 2 H, CH2); 3.85
(m, 2 H, CH2); 7.15—7.43 (m, 5 H, CHAr); 8.92 (s, 1 H, NH)
0.94 (s, 6 H, Me); 1.30 (t, 3 H, Me, J = 7.7); 1.97—2.21 (m, 4 H, CH2); 2.85 (q, 2 H,
CH2, J = 7.7); 2.95 (t, 2 H, CH2, J = 6.8); 3.83 (t, 2 H, CH2, J = 6.8); 7.10—7.40 (m,
5 H, CHAr); 8.93 (s, 1 H, NH)
3.95
3.98
12d
12e
1.01, 1.07 (both s, 3 H, Me); 1.42 (t, 3 H, Me, J = 7.4); 2.16 (m, 2 H, CH2); 2.50 (m,
2 H, CH2); 3.14 (q, 2 H, CH2, J = 7.4); 4.93 (m, 2 H, CH2); 7.24—7.52 (m, 5 H, CHAr);
9.17 (s, 1 H, NH)
0.91 (s, 6 H, Me); 1.35 (t, 3 H, Me, J = 7.5); 1.98—2.15 (m, 4 H, CH2); 2.96 (t, 2 H,
CH2, J = 6.6); 3.11 (q, 2 H, CH2, J = 7.5); 3.86 (t, 2 H, CH2, J = 6.6); 7.14—7.42 (m,
5 H, CHAr); 9.09 (s, 1 H, NH)
3.89
3.93
14a
14b
14c
16a
16b
2.55 (s, 3 H, Me); 5.14 (m, 2 Н, CH2); 7.46 (m, 5 H, CHAr); 9.12 (s, 1 H, NH); 11.02
(s, 1 H, NH); 12.34 (s, 1 H, NH)
3.61
3.65
3.59
3.74
3.71
1.35 (t, 2 H, Me, J = 7.5); 2.89 (q, 2 H, CH2, J = 7.4); 5.01 (m, 2 Н, CH2); 7.38 (m,
5 H, CHAr); 9.13 (s, 1 H, NH); 11.0 (s, 1 H, NH); 12.32 (s, 1 H, NH)
1.45 (t, 2 H, Me, J = 7.4); 3.21 (q, 2 H, CH2, J = 7.4); 5.14 (m, 2 Н, CH2); 7.40 (m,
5 H, CHAr); 9.28 (s, 1 H, NH); 11.03 (s, 1 H, NH); 12.35 (s, 1 H, NH)
1.31 (t, 3 Н, Ме, J = 7.7); 2.88 (q, 2 Н, СН2, J = 7.7); 6.39, 6.49 (both m, 1 Н, СНAr);
7.52 (m, 1 Н, СНAr); 9.16, 12.42 (both s, 1 Н, NH)
1.37 (t, 3 Н, Ме, J = 7.2); 3.05 (q, 2 Н СН2, J = 7.2); 6.34, 6.45 (both m, 1 Н, СНAr);
7.49 (m, 1 Н, СНAr); 9.28, 12.40 (both s, 1 Н, NH)
5ꢀ(5ꢀEthylsulfanyl[1,3,4]thiadiazolꢀ2ꢀylamino)ꢀ3ꢀphenethylꢀ
Method B. Pyridine (1.56 g, 0.02 mol) and methyl trifluoroꢀ
pyruvate 1 (1.56 g, 0.01 mol) were successively added to a stirred
solution of compound 2c (1.62 g, 0.01 mol) in DMF (20 mL).
The reaction mixture was stirred for 30 min and, after addition
of SOCl2 (1.19 g, 0.01 mol), for 1 h. Then phenethylurea 4b
(1.64 g, 0.01 mol) and Et3N (0.1 g) were added. The reaction
5ꢀtrifluoromethylimidazolidineꢀ2,4ꢀdione (6a). Method A. A soluꢀ
tion of urea 5 (0.46 g, 0.001 mol) in Et3N (0.05 g) was heated at
90—100 °C for 2 h. The reaction mixture was cooled and poured
into water (50 mL). The precipitate that formed was filtered off
and recrystallized from 50% EtOH.

Fluoroꢀcontaining 2ꢀaminoꢀ1,3,4ꢀthiadiazoles
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 4, April, 2011
711
mixture was stirred at 20 °C for 1 h, heated at 90—100 °C for 2 h,
cooled, and poured into water (50 mL). The precipitate that
formed was filtered off and recrystallized from 50% EtOH. The
yield, melting point, elemental analysis data, and spectroscopic
characteristics of compound 6a are given in Tables 1 and 2.
5ꢀ(5ꢀMethyl[1,3,4]thiadiazolꢀ2ꢀylamino)ꢀ3ꢀphenethylꢀ5ꢀtriꢀ
fluoromethylimidazolidineꢀ2,4ꢀdione (6b), 3ꢀ(4ꢀmethoxybenzyl)ꢀ
5ꢀ(5ꢀmethyl[1,3,4]thiadiazolꢀ2ꢀylamino)ꢀ5ꢀtrifluoromethylimidꢀ
azolidineꢀ2,4ꢀdione (6c), 3ꢀbenzylꢀ5ꢀ(5ꢀethyl[1,3,4]thiadiazolꢀ2ꢀ
ylamino)ꢀ5ꢀtrifluoromethylimidazolidineꢀ2,4ꢀdione (6d), 5ꢀ(5ꢀ
ethyl[1,3,4]thiadiazolꢀ2ꢀylamino)ꢀ3ꢀphenethylꢀ5ꢀtrifluoromethꢀ
ylimidazolidineꢀ2,4ꢀdione (6e), 3ꢀbenzylꢀ5ꢀ(5ꢀethylsulfanylꢀ
[1,3,4]thiadiazolꢀ2ꢀylamino)ꢀ5ꢀtrifluoromethylimidazolidineꢀ2,4ꢀ
dione (6f), 3ꢀbenzylꢀ5ꢀ(5ꢀmethyl[1,3,4]thiadiazolꢀ2ꢀylamino)ꢀ2ꢀ
This work was financially supported by the Division of
Chemistry and Materials Science of the Russian Acadeꢀ
my of Sciences (Program "Medicinal and Biomedicinal
Chemistry").
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phenylꢀ5ꢀtrifluoromethylꢀ4,5ꢀdihydroimidazolꢀ4ꢀone
(8a),
3ꢀbenzylꢀ5ꢀ(5ꢀethylsulfanyl[1,3,4]thiadiazolꢀ2ꢀylamino)ꢀ2ꢀpheꢀ
nylꢀ5ꢀtrifluoromethylꢀ4,5ꢀdihydroimidazolꢀ4ꢀone (8b), 2ꢀmethylꢀ
4ꢀ(5ꢀmethyl[1,3,4]thiadiazolꢀ2ꢀylamino)ꢀ5ꢀoxoꢀ4ꢀtrifluoromethꢀ
ylꢀ4,5ꢀdihydroꢀ1Hꢀpyrroleꢀ3ꢀcarbonitrile (10a), 4ꢀ(5ꢀethylꢀ
[1,3,4]thiadiazolꢀ2ꢀylamino)ꢀ2ꢀmethylꢀ5ꢀoxoꢀ4ꢀtrifluoromethylꢀ
4,5ꢀdihydroꢀ1Hꢀpyrroleꢀ3ꢀcarbonitrile (10b), 4ꢀ(5ꢀethylsulfanylꢀ
[1,3,4]thiadiazolꢀ2ꢀylamino)ꢀ2ꢀmethylꢀ5ꢀoxoꢀ4ꢀtrifluoromethylꢀ
4,5ꢀdihydroꢀ1Hꢀpyrroleꢀ3ꢀcarbonitrile (10c), 1ꢀbenzylꢀ6,6ꢀdiꢀ
methylꢀ3ꢀ(5ꢀmethyl[1,3,4]thiadiazolꢀ2ꢀylamino)ꢀ3ꢀtrifluoroꢀ
methylꢀ3,5,6,7ꢀtetrahydroꢀ1Hꢀindoleꢀ2,4ꢀdione (12a), 6,6ꢀdiꢀ
methylꢀ3ꢀ(5ꢀmethyl[1,3,4]thiadiazolꢀ2ꢀylamino)ꢀ1ꢀphenethylꢀ3ꢀ
trifluoromethylꢀ3,5,6,7ꢀtetrahydroꢀ1Hꢀindoleꢀ2,4ꢀdione (12b),
3ꢀ(5ꢀethyl[1,3,4]thiadiazolꢀ2ꢀylamino)ꢀ6,6ꢀdimethylꢀ1ꢀphenethꢀ
ylꢀ3ꢀtrifluoromethylꢀ3,5,6,7ꢀtetrahydroꢀ1Hꢀindoleꢀ2,4ꢀdione
(12c), 1ꢀbenzylꢀ3ꢀ(5ꢀethylsulfanyl[1,3,4]thiadiazolꢀ2ꢀylamino)ꢀ
6,6ꢀdimethylꢀ3ꢀtrifluoromethylꢀ3,5,6,7ꢀtetrahydroꢀ1Hꢀindoleꢀ
2,4ꢀdione (12d), 3ꢀ(5ꢀethylsulfanyl[1,3,4]thiadiazolꢀ2ꢀylamino)ꢀ
6,6ꢀdimethylꢀ1ꢀphenethylꢀ3ꢀtrifluoromethylꢀ3,5,6,7ꢀtetrahydroꢀ
1Hꢀindoleꢀ2,4ꢀdione (12e), 7ꢀbenzylꢀ3ꢀ(5ꢀmethyl[1,3,4]thiaꢀ
diazolꢀ2ꢀylamino)ꢀ3ꢀtrifluoromethylꢀ3,7ꢀdihydroꢀ1Hꢀpyrroloꢀ
[2,3ꢀb]pyrimidineꢀ2,4,6ꢀtrione (14a), 7ꢀbenzylꢀ3ꢀ(5ꢀethyl[1,3,4]ꢀ
thiadiazolꢀ2ꢀylamino)ꢀ3ꢀtrifluoromethylꢀ3,7ꢀdihydroꢀ1Hꢀpyrroꢀ
lo[2,3ꢀb]pyrimidineꢀ2,4,6ꢀtrione (14b), 7ꢀbenzylꢀ3ꢀ(5ꢀethylꢀ
sulfanyl[1,3,4]thiadiazolꢀ2ꢀylamino)ꢀ3ꢀtrifluoromethylꢀ3,7ꢀdiꢀ
hydroꢀ1Hꢀpyrrolo[2,3ꢀb]pyrimidineꢀ2,4,6ꢀtrione (14c), 3ꢀ(5ꢀ
ethyl[1,3,4]thiadiazolꢀ2ꢀylamino)ꢀ7ꢀfurfurylꢀ6ꢀthioxoꢀ3ꢀtrifluoroꢀ
methylꢀ3,7ꢀdihydroꢀ1Hꢀpyrrolo[2,3ꢀb]pyrimidineꢀ2,4ꢀdione
(16a), and 3ꢀ(5ꢀethylsulfanyl[1,3,4]thiadiazolꢀ2ꢀylamino)ꢀ7ꢀ
furfurylꢀ6ꢀthioxoꢀ3ꢀtrifluoromethylꢀ3,7ꢀdihydroꢀ1Hꢀpyrroꢀ
lo[2,3ꢀb]pyrimidineꢀ2,4ꢀdione (16b) were obtained as described
above for compound 6a (method B). The yields, melting points,
elemental analysis data, and spectroscopic characteristics of comꢀ
pounds 6, 8, 10, 12, 14, and 16 are given in Tables 1 and 2.
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Received November 17, 2010