Acylimines of methyl trifluoropyruvate in cyclocondensation with C,N-bisnucleophiles

Article abstract of DOI:10.1007/s11172-006-0200-8

Reactions of acylimines of methyl trifluoropyruvate with C,N-bisnucleophiles gave fluoro-containing heterocycles including the 5-oxo-4,5-dihydro-1H-pyrrole fragment.

Full text of DOI:10.1007/s11172-006-0200-8

Russian Chemical Bulletin, International Edition, Vol. 54, No. 12, pp. 2851—2856, December, 2005
2851
Acylimines of methyl trif luoropyruvate
in cyclocondensation with C,Nꢀbisnucleophiles
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,
142432 Chernogolovka, Moscow Region, Russian Federation.
Fax: +7 (496) 785 7024. Eꢀmail: alaks@ipac.ac.ru
Reactions of acylimines of methyl trifluoropyruvate with C,Nꢀbisnucleophiles gave fluoroꢀ
containing heterocycles including the 5ꢀoxoꢀ4,5ꢀdihydroꢀ1Hꢀpyrrole fragment.
Key words: acylimines, methyl trifluoropyruvate, 3ꢀaminocrotononitrile, methyl 3ꢀaminoꢀ
crotonates, Nꢀsubstituted 3ꢀaminocyclohexenones, 6ꢀaminouracils, 6ꢀaminothiouracils,
3ꢀphenethylaminoꢀ1ꢀphenylbutꢀ2ꢀenꢀ1ꢀone, hexahydroꢀ1Hꢀpyrrolo[2,3ꢀd]pyrimidines, hexaꢀ
hydroꢀ1Hꢀindoles, dihydroꢀ1Hꢀpyrroles, 2,5ꢀdioxopyrrolidine, hexahydroꢀ6ꢀthiaꢀ1,5,8aꢀ
triazaindacenes, cyclocondensation.
Scheme 1
Acylimines of methyl trifluoropyruvate (MTFP) (1)
are known to act as 1,2ꢀbiselectrophiles in reactions with
C,Oꢀ and N,Nꢀbisnucleophiles (e.g., acetylacetone1
and benzamidine2) and undergo cyclocondensation into
furanones and dihydroimidazoles, respectively. Here we
present our data on reactions of acylimines 1 with various
C,Nꢀbisnucleophiles that yield fluoroꢀcontaining (includꢀ
ing fused) dihydropyrroles. Dihydropyrroles exhibit a
broad spectrum of biological activities: some of them were
found to be hypotensive agents,3 inhibitors of the biosynꢀ
thesis of cholesterol,4 and antihelminthics.5
In the present work, we studied reactions of acylimines
of MTFP 1 with a number of C,Nꢀbisnucleophiles.
The reaction of 4ꢀmethylbenzoylimine of MTFP 1a
with 6ꢀaminoꢀ1,3ꢀdimethyluracil 2a gave Cꢀalkylation
product 3, which was converted into pyrrolo[2,3ꢀd]pyriꢀ
midine 4a by heating in DMF in the presence of a cataꢀ
lytic amount of Et3N (Scheme 1).
6ꢀAminouracils 2, 6ꢀaminothiouracils 5, Nꢀsubstituted
3ꢀaminocyclohexenones 6, 3ꢀaminocrotononitrile 7, meꢀ
thyl 3ꢀaminocrotonates 8, and 3ꢀphenethylaminoꢀ1ꢀ
phenylbutꢀ2ꢀenꢀ1ꢀone 9 were studied as C,Nꢀbisnucleoꢀ
philes in cyclocondensation reactions with acylimines of
MTFP 1a—l (Scheme 2). The reactions of acylimines 1
with the above reagents follow a twoꢀstep scheme consistꢀ
ing of exothermic Cꢀalkylation and subsequent cyclizaꢀ
tion with elimination of MeOH.
Cyclocondensation reactions of acylimines 1a—l with
nucleophiles 2b—d, 5a—g, 6a—d, 7, 8a—c, and 9 were
carried out by mixing equimolar amounts of the reꢀ
agents in DMF at 20 °C. After the exothermic reaction
was completed, the mixture was heated at 90—100 °C
for 5 h in the presence of a catalytic amount of Et3N,
without isolating intermediate adducts. The resulting hexaꢀ
hydroꢀ1Hꢀpyrrolo[2,3ꢀd]pyrimidines 4b—h and 10a—g,
hexahydroꢀ1Hꢀindoles 11a—e, and dihydroꢀ1Hꢀpyrroles
12a—c, 13a—e, and 14a,b were obtained in 65—86%
yields.
The compounds obtained are crystalline solids; their
compositions and structures were confirmed by elemental
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2755—2760, December, 2005.
1066ꢀ5285/05/5412ꢀ2851 © 2005 Springer Science+Business Media, Inc.

2852
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 12, December, 2005
Sokolov et al.
Scheme 2
Comꢀ
R
Comꢀ
R´
Comꢀ
R
R´
Comꢀ
R
R´
pound
pound
pound
pound
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
12a
12b
12c
14a
14b
4ꢀMeC5H4
Me
Et
Bui
2b
2c
2d
5a
5b
5c
5d
5e
5f
5g
6a
6b
6c
6d
8a
8b
8c
Ph
4b
4c
4d
4e
4f
4g
4h
10a
10b
10c
10d
10e
10f
10g
Me
Me
Bui
2ꢀFC6H4
4ꢀFC6H4
4ꢀFC6H4
2ꢀFuryl
Ph
Ph
4ꢀFC6H4
Ph
Ph
11a
11b
11c
11d
11e
13a
13b
13c
13d
13e
Ph
Ph
Ph
4ꢀMeC6H4
2ꢀThienyl
4ꢀFC6H4
2ꢀFC6H4
4ꢀFC6H4
2ꢀFC6H4
4ꢀFC6H4
Bu
4ꢀFC6H4
PhCH2CH2
All
CH2=C(Me)CH2
Ph
4ꢀMeC6H4
4ꢀMeC6H4
PhCH2
4ꢀFC6H4CH2
Bu
PhCH2
PhCH2CH2
4ꢀMeC6H4
4ꢀMeC6H4
H
Ph
Ph
2ꢀMeC6H4
2ꢀMeOC6H4
4ꢀClC6H4
2ꢀFC6H4
4ꢀFC6H4
2ꢀFuryl
2ꢀThienyl
Et
PhCH2CH2
Ph
All
CH2=C(Me)CH2
CH2=C(Me)CH2
Ph
PhCH2
4ꢀFC6H4CH2
4ꢀMeC6H4
H
PhCH2
PhCH2CH2
PhCH2
Ph
2ꢀFC6H4
4ꢀMeC6H4
4ꢀFC6H4
4ꢀFC6H4
2ꢀMeOC6H4
PhCH2
PhCH2CH2
4ꢀMeC6H4
H
PhCH2
PhCH2CH2
4ꢀClC6H4
2ꢀMeC6H4
Ph
2ꢀThienyl
analysis and NMR spectroscopy. In 19F NMR spectra,
signals for the trifluoromethyl group at δ 2—6 are inforꢀ
mative.
protons at δ 4.55 (J = 6.3 Hz) and a triplet for the NH
proton at δ 9.63 (J = 6.3 Hz).
Pyrrolo[2,3ꢀd]pyrimidines 10a,b containing the allyl
and methallyl thioamide fragments underwent cyclizaꢀ
tion in the presence of bromine into hexahydroꢀ6ꢀthiaꢀ
1,5,8aꢀtriazaindacenes 17a,b by analogy with allylureas6
(Scheme 4).
Thus, we studied the transformations of acylimines of
methyl trifluoropyruvate in cyclocondensation reactions
with C,Nꢀbisnucleophiles and developed a preparative
method for the synthesis of various novel fluoroꢀcontainꢀ
ing 1Hꢀpyrrolones, including fused ones.
Introduction of a third nucleophilic site into C,Nꢀbisꢀ
nucleophiles radically changes the cyclocondensation
pathway in the aforementioned transformations. For inꢀ
stance, the reaction of pivaloylimine of MTFP 1n with
Nꢀfurfurylꢀ3ꢀaminocrotonanilide 15 yielded 2,5ꢀdioxoꢀ
pyrrolidine 16, which is a cyclocondensation product at
the amide rather than amino N atom (Scheme 3). This
structure was evident from signals for the FurCH2NH
1
group in the H NMR spectrum: a doublet for the CH2

Acylimines of MTFP and C,Nꢀbisnucleophiles
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 12, December, 2005 2853
Scheme 3
Experimental
1
H and 19F NMR spectra were recorded on a Bruker
DXP 200 spectrometer (200 and 188 MHz, respectively) in
DMSOꢀd6 with residual signals for the protons of the deuterated
solvent as the internal standard (1H) and with CF3COOH as the
external standard (19F). Melting points were determined in glass
capillaries. Acylimines of methyl trifluoropyruvate (1a—m)
were prepared according to a known procedure.1 The starting
6ꢀaminoꢀ and 6ꢀaminothiouracils7 and 3ꢀaminocyclohexenones8
were prepared as described earlier. Methyl 3ꢀaminocrotonate
and 3ꢀaminocrotononitrile (Aldrich) were used as purchased.
Methyl 2ꢀ(6ꢀaminoꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1,2,3,4ꢀtetraꢀ
hydropyrimidinꢀ5ꢀyl)ꢀ3,3,3ꢀtrifluoroꢀ2ꢀ(4ꢀmethylbenzoylamiꢀ
no)propionate (3). Aminouracil 2a (1.55 g, 0.01 mol) was added
to a solution of imine 1a (2.73 g, 0.01 mol) in DMF (20 mL).
After the exothermic reaction was completed, the reaction mixꢀ
ture was stirred for 1 h and poured into water (50 mL). The
precipitate that formed was filtered off and recrystallized from
50% EtOH to give compound 3 (3.7 g, 86%), m.p. 284—286 °C.
Found (%): C, 50.29; H, 4.31; N, 13.25. C18H19F3N4O. Calcuꢀ
lated (%): C, 50.49; H, 4.47; N, 13.08. 1H NMR, δ: 2.44 (s, 3 H,
Me); 3.32, 3.44 (both s, 3 H each, MeN); 3.81 (s, 3 H, MeO);
6.51 (s, 2 H, NH2); 7.29, 7.74 (both d, 2 H each, CHAr, J =
8.6 Hz); 12.09 (s, 1 H, NH). 19F NMR, δ: 2.56 (s).
Scheme 4
Nꢀ(1,3ꢀDimethylꢀ2,4,6ꢀtrioxoꢀ5ꢀtrifluoromethylꢀ
2,3,4,5,6,7ꢀhexahydroꢀ1Hꢀpyrrolo[2,3ꢀd]pyrimidinꢀ5ꢀyl)ꢀ
4ꢀmethylbenzamide (4a). A. A solution of amide 3 (2.14 g,
0.005 mol) and Et3N (0.2 mL) in DMF (10 mL) was heated at
90—100 °C for 5 h. The reaction mixture was cooled and poured
into water (50 mL). The precipitate that formed was filtered off
and recrystallized from 50% EtOH to give compound 4a (1.6 g,
72%), m.p. 196—198 °C.
R = H (a), Me (b)
Table 1. Yields, melting points, and elemental analysis data for compounds 4a—h, 10a—g,
11a—e, 12a—c, 13a—e, 14a,b, and 16
Comꢀ
pound
Yield
(%)
M.p./°C
Found
Calculated
Molecular
formula
(%)
C
H
N
4a
4b
4c
4d
4e
4f
83
79
84
78
76
80
75
77
196—198
310—312
262—264
191—193
309—311
331—333
273—275
317—319
50.37
50.52
48.79
48.92
46.72
46.64
52.81
52.69
53.69
53.58
53.62
53.58
55.31
55.47
51.52
51.44
3.66
3.81
3.13
3.01
2.77
2.61
4.29
4.18
2.82
2.70
2.55
2.70
3.23
3.39
2.76
2.64
14.32
14.14
15.33
15.21
14.38
14.50
13.51
13.65
12.63
12.50
12.41
12.50
11.89
11.76
13.21
13.33
C17H15F3N4O4
C15H11F3N4O4
C15H10F4N4O4
C18H17F3N4O4
C20H12F4N4O
C20H12F4N4O4
C22H16F4N4O4
C18H11F3N4O5
4g
4h
(to be continued)

2854
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 12, December, 2005
Sokolov et al.
Table 1 (continued)
Comꢀ
pound
Yield
(%)
M.p./°C
Found
Calculated
Molecular
formula
(%)
C
H
N
10a
10b
10c
10d
10e
10f
79
82
73
75
72
75
78
81
69
74
76
77
83
81
85
86
80
68
71
65
72
69
71
263—265
301—303
211—213
298—300
305—307
287—289
265—267
158—160
193—195
196—198
226—228
241—243
238—240
268—270
221—223
228—230
241—243
143—145
154—156
143—145
157—159
169—171
198—200
49.91
49.76
50.78
50.94
48.96
48.87
54.91
54.78
52.84
52.72
50.93
50.81
53.71
53.88
62.66
62.55
62.65
62.78
66.81
66.37
66.48
66.37
59.85
59.73
45.81
45.98
48.77
48.93
55.57
55.73
49.83
50.01
50.13
50.01
58.50
58.67
59.31
59.48
58.50
58.67
68.11
68.29
62.48
62.64
59.73
59.62
3.11
3.19
3.43
3.56
3.31
3.19
3.14
3.28
3.11
2.95
2.77
2.64
3.62
3.49
5.82
5.97
5.21
5.08
5.48
5.36
5.45
5.36
4.42
4.58
3.69
3.86
2.48
2.64
3.59
3.74
3.21
3.36
3.19
3.36
4.19
4.03
4.18
4.34
4.19
4.03
4.55
4.71
4.09
4.25
5.11
5.22
13.77
13.65
13.37
13.20
12.55
12.66
12.29
12.17
11.84
11.71
11.41
11.29
11.31
11.42
6.48
6.63
6.02
6.14
5.81
5.95
5.82
5.95
6.17
C17H13F3N4O3S
C18H15F3N4O3S
C18H14F4N3O3S
C21H15F3N4O3S
C21H14F4N4O3S
C21H13F5N4O3S
C22H17F3N4O4S
C22H25F3N2O3
C25H23F3N2O3
C26H25F3N2O3
C26H25F3N2O3
C23H21F3N2O3S
C10H10F3N3O2
C14H9ClF3N3O2
C15H12F3N3O2
C15H12F4N2O4
C15H12F4N2O4
C22H18F4N2O4
C23H20F4N2O4
C22H18F4N2O4
C28H23F3N2O3
C.26H21F3N2O3S
С23H24F3N3O4
10g
11a
11b
11c
11d
11e
12a
12b
12c
13a
13b
13c
13d
13e
14a
14b
16
6.06
16.25
16.09
12.38
12.23
13.17
13.00
7.93
7.78
7.95
7.78
6.37
6.22
6.19
6.03
6.37
6.22
5.52
5.69
5.76
5.62
9.21
9.07
B. A solution of acylimine 1a (2.73 g, 0.01 mol) and
aminouracil 2a (1.55 g, 0.01 mol) in DMF (10 mL) was stirred
at 20 °C for 1 h. Then Et3N (0.2 mL) was added and the reaction
mixture was heated at 90—100 °C for 5 h, cooled, and poured
into water (50 mL). The precipitate that formed was filtered off
and recrystallized from 50% EtOH to give compound 4a (3.3 g,
83%), m.p. 196—198 °C.
Compounds 4a—h, 10a—g, 11a—e, 12a—c, 13a—e, 14a,b,
and 16 were obtained analogously from acylimines 1a—l
(0.01 mol) and the corresponding 1,3ꢀbisnucleophiles 2b—d,

Acylimines of MTFP and C,Nꢀbisnucleophiles
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 12, December, 2005 2855
Table 2. 1H and 19F NMR spectra of compounds 4a—h, 10a—g, 11a—e, 12a—c, 13a—e, 14a,b, and 16
Comꢀ
pound
δ (J/Hz)
1H
19F
4a
2.43 (s, 3 H, Me); 2.81, 3.43 (both s, 3 H each, MeN); 7.17, 7.55 (both d, 2 H each, CHAr, J = 8.1);
9.38, 11.01, 12.25 (all s, 1 H each, NH)
4.78 (s)
4b
4c
1.98 (s, 3 H, Me); 7.34 (m, 2 H, CHAr); 7.53 (m, 3 H, CHAr); 9.45, 11.07, 11.28 (all s, 1 H each, NH)
1.96 (s, 3 H, Me); 7.21—7.42 (m, 4 H, CHAr); 9.45, 11.07, 11.28 (all s, 1 H each, NH)
4.09 (s)
–33.67 (m, 1 F);
4.10 (s, 3 F)
4.13 (s)
4d
0.96 (d, 6 H, Me, J = 7.9); 2.08 (m, 3 H, CH2 + CH); 7.33 (m, 2 H, CHAr); 7.58 (m, 3 H, CHAr);
9.31, 11.05, 11.08 (all s, 1 H each, NH)
4e
7.12, 7.32, 7.48 (all m, 2 H each, CHAr); 7.63 (t, 2 H, CHAr, J = 7.6);
9.59, 11.24, 11.49 (all s, 1 H each, NH)
–34.95 (m, 1 F);
4.15 (s, 3 F)
4f
7.21 (t, 2 H, CHAr, J = 7.5); 7.33 (m, 3 Н, CHAr); 7.52, 8.04 (both m, 2 H each, CHAr);
9.79, 11.08, 11.34 (all s, 1 H each, NH)
–30.08 (m, 1 F);
4.75 (s, 3 F)
4g
2.98, 4.22 (both m, 2 H each, CH2); 7.08—7.38 (m, 7 Н, CHAr); 8.01 (t, 2 Н, CHAr, J = 7.8);
9.89, 10.92, 12.12 (all s, 1 H each, NH)
–29.75 (m, 1 F);
4.73 (s, 3 F)
4h
6.52 (m, 1 H, CHFur); 7.35 (m, 3 Н, CHAr + CHFur); 7.53 (m, 3 Н, CHAr); 8.72 (m, 1 H, CHFur);
9.45, 11.18, 11.42 (all s, 1 H each, NH)
4.59 (s)
10a
10b
10c
10d
10e
10f
5.21 (m, 1 H, H2C=); 5.36 (m, 3 H, CH2N + CH=); 5.98 (m, 1 H, H2C=); 7.55 (m, 3 H, CHAr);
7.98 (d, 2 H, CHAr, J = 7.4); 9.78, 11.96, 12.09 (all s, 1 H each, NH)
1.86 (s, 3 H, Me); 4.63 (m, 1 H, H2C=); 4.92 (m, 3 H, CH2N + H2C=); 7.47 (m, 3 H, CHAr);
7.93 (m, 2 H, CHAr); 9.91, 12.10, 12.42 (all s, 1 H each, NH)
1.82 (s, 3 H, Me); 4.85 (m, 4 H, CH2N + H2C=); 7.21 (m, 2 H, CHAr); 7.47, 7.61 (both m,
1 H each, CHAr); 9.66, 12.10, 12.41 (all s, 1 H each, NH)
2.41 (s, 3 Н, Ме); 7.23 (d, 2 Н, CHAr, J = 8.2); 7.36 (m, 2 Н, CHAr); 7.54 (m, 3 Н, CHAr);
7.84 (d, 2 Н, CHAr, J = 8.2); 9.71, 11.13, 11.39 (all s, 1 H each, NH)
5.64 (s, 2 H, CH2); 7.15—7.58 (m, 7 Н, CHAr); 8.05 (t, 2 Н, CHAr, J = 7.8);
9.99, 12.31, 12.48 (all s, 1 H each, NH)
5.66 (s, 2 H, CH2); 7.02—7.23 (m, 4 Н, CHAr); 7.35, 8.03 (both m, 2 H each, CHAr);
9.99, 12.28, 12.42 (all s, 1 H each, NH)
4.85 (s)
4.90 (s)
–32.18 (m, 1 F);
4.75 (s, 3 F)
4.85 (s)
–29.76 (m, 1 F);
4.95 (s, 3 F)
–34.78, –29.73
(both m, 1 F each);
4.95 (s, 3 F)
10g
11a
7.42 (s, 3 H, Me); 4.07 (s, 3 H, MeO); 7.06 (t, 1 H, CHAr, J = 7.9); 7.26 (m, 5 H, CHAr);
7.52 (t, 1 H, CHAr, J = 7.9); 7.91 (d, 1 H, CHAr, J = 7.9); 9.99, 12.28, 12.42 (all s, 1 H each, NH)
1.03 (t, 3 H, Me, J = 7.8); 1.16 (s, 6 H, Me); 1.42, 1.59 (both m, 2 H each, CH2);
2.19 (АВ system, 2 H, CH2, J = 10.6); 2.64 (s, 2 H, CH2); 3.57 (m, 2 H, CH2N);
7.38 (m, 3 Н, CHAr); 7.84 (d, 2 H, CHAr, J = 7.8); 9.61 (s, 1 H, NH)
3.08 (s)
5.11 (s)
11b
11c
1.02, 1.08 (both s, 3 H each, Me); 2.15 (АВ system, 2 H, CH2, J = 10.6); 2.46 (s, 2 H, CH2);
4.88 (s, 2 H, CH2N); 7.36 (m, 8 Н, CHAr); 7.95 (d, 2 H, CHAr, J = 7.8); 9.73 (s, 1 H, NH)
0.96, 1.02 (both s, 3 H each, Me); 2.12 (s, 2 H, CH2); 2.16 (АВ system, 2 H, CH2, J = 17.4);
2.94, 3.84 (both m, 2 H each, CH2); 7.22—7.38 (m, 5 H, CHAr); 7.46 (m, 3 H, CHAr);
7.94 (d, 2 H, CHAr, J = 7.4); 9.62 (s, 1 H, NH)
5.08 (s)
5.17 (s)
11d
1.04, 1.11 (both s, 3 H each, Me); 2.22 (АВ system, 2 H, CH2, J = 15.2); 2.37, 2.42 (both s, 3 H each,
Me); 2.49 (m, 2 H, CH2); 7.17 (d, 2 H, CHAr, J = 8.0); 7.28, 7.41 (both d, 2 H each, CHAr, J = 8.1);
7.55 (d, 2 H, CHAr, J = 8.0); 7.28, 7.41 (both d, 2 H each, CHAr, J = 8.1) 9.46 (s, 1 H, NH)
5.19 (s)
11e
12a
1.07, 1.14 (both s, 3 H each, Me); 2.28 (АВ system, 2 H, CH2, J = 15.2); 2.47 (s, 3 H, Me); 2.53 (m, 2 H,
CH2); 6.56 (m, 1 H, HC=); 7.21—7.40 (m, 4 H, CHAr); 7.42, 7.72 (m, 1 H, CHAr); 9.46 (s, 1 H, NH)
1.05 (t, 3 Н, Ме, J = 7.5); 2.18 (s, 3 Н, Ме); 2.27 (q, 2 Н, СН2, J = 7.5);
9.17, 11.03 (both s, 1 H each, NH)
4.59 (s)
2.83 (s)
12b
12c
2.28 (s, 3 H, Me); 7.46, 7.97 (both d, 2 H each, CHAr, J = 8.4); 7.99, 11.22 (both s, 1 H each, NH)
2.28, 2.44 (both s, 3 H each, Ме); 7.19, 7.36 (both m, 2 H each, CHAr); 9.88,
11.21 (both s, 1 H each, NH)
3.64 (s)
3.20 (s)
13a
13b
13c
2.39 (s, 3 Н, Ме); 3.62 (s, 3 Н, МеO); 7.12, 7.99 (both m, 2 H each, CHAr);
9.25, 10.83 (both s, 1 H each, NH)
2.41 (s, 3 Н, Ме); 3.67 (s, 3 Н, МеO); 7.19 (m, 2 Н, CHAr); 7.47, 7.63 (both m, 1 H each, CHAr);
8.73 (d, 1 H NH, J = 7.2); 10.96 (s, 1 Н, NH)
2.42 (s, 3 Н, Ме); 3.68 (s, 3 Н, МеO); 4.93 (s, 2 Н, CH2); 7.17 (m, 2 Н, CHAr);
7.35 (m, 5 Н, CHAr); 8.06 (m, 2 Н, CHAr); 9.49 (s, 1 Н, NH)
–30.82 (m, 1 F);
1.26 (s, 3 F)
–34.21 (m, 1 F);
2.68 (s, 3 F)
–30.21 (m, 1 F);
4.68 (s, 3 F)
(to be continued)

2856
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 12, December, 2005
Sokolov et al.
Table 2 (continued)
Comꢀ
pound
δ (J/Hz)
1H
19F
13d
13e
14a
14b
16
2.42 (s, 3 Н, Ме); 2.87 (m, 2 Н, CH2); 3.68 (s, 3 Н, МеO); 4.93 (s, 2 Н, CH2);
7.17 (m, 2 Н, CHAr); 7.35 (m, 5 Н, CHAr); 8.06 (m, 2 Н, CHAr); 9.49 (s, 1 Н, NH)
2.41 (s, 3 Н, Ме); 3.70 (s, 3 Н, МеO); 4.90 (AB system, 2 H, CH2, J = 17.0); 7.13 (t, 1 H,
HC=, J = 5.1); 7.36 (m, 5 Н, CHAr); 7.62, 8.19 (both d, 1 H each, HC=, J = 5.1); 9.47 (s, 1 Н, NH)
2.48 (s, 3 Н, Ме); 2.98, 3.87 (both m, 2 H each, CH2); 7.22—7.58 (m, 13 Н, CHAr);
7.98 (d, 2 Н, CHAr, J = 7.8); 9.63 (s, 1 Н, NH)
–35.12 (m, 1 F);
2.84 (s, 3 F)
4.82 (s)
5.16 (s)
5.24 (s)
5.48 (s)
2.45 (s, 3 Н, Ме); 2.94, 3.83 (both m, 2 H each, CH2); 7.14 (t, 1 H, HC=, J = 5.4);
7.43 (m, 10 Н, CHAr); 7.63, 8.17 (both d, 1 H each, HC=, J = 5.4); 9.50 (s, 1 Н, NH)
1.21 (s, 9 H, Me); 2.19 (s, 3 H, Me); 4.55 (d, 2 H, CH2NH, J = 6.3); 6.29 (d, 1 H, CHFur
J = 3.5); 6.36 (t, 1 H, CHFur, J = 3.5); 7.39 (d, 6 H, CHAr + CHFur); 8.67 (s, 1 H, NH);
9.63 (t, 1 H, CH2NH, J = 6.3)
,
5a—g, 6a—d, 7, 8a—c, 9, and 15 (0.01 mol). The yields, melting
points, and spectroscopic characteristics of the products are
given in Tables 1 and 2.
emy of Sciences (Program No. 10 of the Division of
Chemistry "Biomolecular and Medicinal Chemistry").
Nꢀ(7ꢀBromomethylꢀ2,4ꢀdioxoꢀ3ꢀtrifluoromethylꢀ
1,2,3,4,7,8ꢀhexahydroꢀ6ꢀthiaꢀ1,5,8aꢀtriazaindacenꢀ3ꢀyl)benzꢀ
amide (17a). Bromine (0.8 g, 0.005 mol) was added at 20 °C to a
suspension of pyrrolo[2,3ꢀd]pyrimidine 10a (2.05 g, 0.005 mol)
in EtOH (20 mL). The reaction mixture was stirred for 1 h,
diluted with water (50 mL), and neutralized with 10% NaOH.
The precipitate that formed was filtered off and recrystalꢀ
lized from 50% EtOH to give indacene 17a (1.9 g, 78%),
m.p. 293—295 °C. Found (%): C, 41.85; H, 2.33; N, 11.56.
C17H12BrF3N4O3S. Calculated (%): C, 41.73; H, 2.47; N, 11.45.
1H NMR, δ: 3.94 (m, 2 H, CH2N); 4.51 (m, 3 H,
CH2Br + CHS); 7.48 (m, 3 H, CHAr); 7.90 (d, 2 H, CHAr, J =
7.0 Hz); 9.87 (s, 1 H, NH). 19F NMR, δ: 6.37 (s).
References
1. S. N. Osipov, V. B. Sokolov, A. F. Kolomiets, I. V. Martynov,
and A. V. Fokin, Izv. Akad. Nauk SSSR, Ser. Khim., 1987,
1185 [Bull. Acad. Sci. USSR, Div. Chem. Sci., 1987, 36, 1098
(Engl. Transl.)].
2. V. B. Sokolov, A. Yu. Aksinenko, T. A. Epishina, T. V. Goreva,
and I. V. Martynov, Izv. Akad. Nauk, Ser. Khim., 2005, 462
[Russ. Chem. Bull., Int. Ed., 2005, 54, 472].
3. P. R. Bovv, D. W. Reitz, J. T. Collins, T. S. Chamberlain,
G. M. Olins, V, M. Corpus, E. G. McMhon, M. A. Palomo,
J. P. Koepke, G. J. Smits, D. E. Graw, and J. F. Graw,
J. Med. Chem., 1993, 36, 101.
4. P. A. Procopiou, C. D. Draper, J. L. Hutson, G. G. A. Inglis,
B. C. Ross, and N. S. Watson, J. Med. Chem., 1993, 36, 3658.
5. R. D. Haugwitz, R. G. Angel, G. A. Jacobs, B. V. Maurer,
and V. L. Narayanan, J. Med. Chem., 1982, 25, 969.
6. V. M. Fedoseev and Yu. M. Evdokimov, Zh. Obshch. Khim.,
1964, 34, 1551 [J. Gen. Chem. USSR, 1964, 34 (Engl. Transl.)].
7. W. Hatzenlaub and W. Pfleiderer, Lieb. Ann. Chem.,
1979, 1847.
Nꢀ(7ꢀBromomethylꢀ7ꢀmethylꢀ2,4ꢀdioxoꢀ3ꢀtrifluoromethylꢀ
1,2,3,4,7,8ꢀhexahydroꢀ6ꢀthiaꢀ1,5,8aꢀtriazaindacenꢀ3ꢀyl)benzꢀ
amide (17b) was obtained analogously from compound 10b
(2.12 g). The yield was 2.1 g (83%), m.p. 313—315 °C.
Found (%): C, 43.11; H, 2.68; N, 11.26. C18H14BrF3N4O3S.
1
Calculated (%): C, 42.96; H, 2.80; N, 11.13. H NMR, δ: 1.83
(s, 3 H, Me); 4.02 (AB system, CH2N, J = 10.1 Hz); 4.23, 4.68
(both d, 1 H each, CH2Br, J = 12.0 Hz); 7.47 (m, 3 H, CHAr);
7.94 (d, 2 H, CHAr, J = 7.4 Hz); 9.89 (s, 1 H, NH). 19F NMR,
δ: 6.34 (s).
8. D. Enders, A. S. Demir, H. Puff, and S. Franken, Tetraꢀ
hedron Lett., 1987, 3795.
This work was financially supported by the Division of
Chemistry and Materials Science of the Russian Acadꢀ
Received July 18, 2005;
in revised form October 6, 2005