Acylimines of hexafluoroacetone in cyclocondensation with C,N-binucleophiles

Article abstract of DOI:10.1007/s11172-006-0321-0

The reactions of acylimines of hexafluoroacetone with 1,3-C,N- binucleophiles giving rise to fluorine-containing 1,4-dihydropyrimidines, including fused compounds, were studied.

Full text of DOI:10.1007/s11172-006-0321-0

Russian Chemical Bulletin, International Edition, Vol. 55, No. 4, pp. 731—734, April, 2006
731
Acylimines of hexafluoroacetone in cyclocondensation with
C,Nꢀbinucleophiles
V. B. Sokolov,ꢀ A. Yu. Aksinenko, and I. V. Martynov
Institute of Physiologically Active Compounds, Russian Academy of Sciences,
142432 Chernogolovka, Moscow Region, Russian Federation.
Fax: +7 (495) 785 7024. Eꢀmail: alaks@ipac.ac.ru
The reactions of acylimines of hexafluoroacetone with 1,3ꢀC,Nꢀbinucleophiles giving rise
to fluorineꢀcontaining 1,4ꢀdihydropyrimidines, including fused compounds, were studied.
Key words: acylimines, hexafluoroacetone, 2ꢀaminocrotononitrile, Nꢀsubstituted 3ꢀaminoꢀ
cyclohexenones, 6ꢀaminouracils, 6ꢀaminothiouracils, 1,4ꢀdihydropyrimidines, 4,6,7,8ꢀtetraꢀ
hydroquinazolinꢀ5ꢀones, cyclocondensation, cyclization, bromination.
Scheme 1
Acylimines of hexafluoroacetone serve as synthons for
the synthesis of various heterocyclic compounds containꢀ
ing geminal trifluoromethyl groups and are used as
heterodienes and dienophiles in cycloaddition with niꢀ
triles,1,2 derivatives of trivalent phosphorus acids,3 and
cyclopentadiene4 as well as 1,3ꢀbielectrophilic reagents
in cyclocondensation with 1,3ꢀbinucleophiles5,6 to give
oxadiazines, oxazaphospholenes, azanorbornenes, and
dihydrotriazines, respectively. In the present study, we
examined the synthetic possibilities of acylimines of
hexafluoroacetone 1 as 1,3ꢀbielectrophilic reagents for
the preparation of 1,4ꢀdihydropyrimidines by cycloꢀ
condensation with 1,3ꢀC,Nꢀbinucleophiles. It should be
noted that 1,4ꢀdihydropyrimidines, including fluorineꢀ
containing derivatives, belong to a promising class of bioꢀ
logically active compounds. Some representatives of this
class are α1ꢀadrenoreceptor antagonists,7 cytostatics, and
compounds having the antiꢀHIV activity.8
The reactions of acylimines with 1,3ꢀC,Nꢀbinucleoꢀ
philes, viz., 2ꢀaminocrotononitrile, 6ꢀaminouracils,
6ꢀaminothiouracils, and Nꢀsubstituted 3ꢀaminocycloꢀ
hexenones, involve the following two steps (Scheme 1):
the addition of a binucleophile at the C=N bond of imine 1
followed by cyclization with water elimination. In the
case of 2ꢀaminocrotononitrile 2, we isolated and identified
the addition product, viz., the corresponding benzamide 3.
Heating of the latter in DMF in the presence of catalytic
amounts of Et3N afforded 1,4ꢀdihydropyrimidine 4a.
Cyclocondensation of imines 1a—k with 2ꢀaminoꢀ
crotononitrile 2, 6ꢀaminouracils 5a—d, 6ꢀaminothioꢀ
uracils 6a,b, and Nꢀsubstituted 3ꢀaminocyclohexenones
7a—c (equimolar amounts of the reagents were mixed
in DMF at 20 °C and, after completion of the exotherꢀ
mic reaction, the mixture was heated in the presence
of catalytic amounts of Et3N at 90—100 °C for 5 h
without isolation of intermediate addition products) afꢀ
forded 1,4ꢀdihydropyrimidines 4a—f, dihydropyrimiꢀ
do[4,5ꢀd]pyrimidineꢀ2,4ꢀdiones 8a—g, 2ꢀthioxotetraꢀ
hydropyrimido[4,5ꢀd]pyrimidinꢀ4ꢀones 9a,b, and tetraꢀ
hydroꢀ1Нꢀquinazolinꢀ5ꢀones 10a—d (Scheme 2).
Compounds 4 and 8—10 were prepared in the crystalꢀ
line state in 67—85% yields. Their compositions and strucꢀ
tures were confirmed by elemental analysis and NMR
spectroscopy. The 19F NMR spectra show characteristic
signals of the geminal trifluoromethyl groups at δ 2—6.
Like Nꢀallylthioureas,9 pyrimido[4,5ꢀd]pyrimidineꢀ4ꢀ
diones 9a,b containing the Nꢀallylthioamide fragment are
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 706—709, April, 2006.
1066ꢀ5285/06/5504ꢀ0731 © 2006 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 55, No. 4, April, 2006
Sokolov et al.
Scheme 2
brominated to form thiatetraazacyclopenta[a]naphthalꢀ
enones 11a,b (Scheme 3).
Therefore, acylimines of hexafluoroacetone can be
successfully used as 1,3ꢀbielectrophiles in the synthesis of
various previously unknown 4,4ꢀbis(trifluoromethyl)ꢀ1,4ꢀ
dihydropyrimidines, including fused derivatives. The ease
of the preparation of the latter is determined primarily by
the ease of the preparation of 1,3ꢀC,Nꢀbinucleophiles,
the available procedures for the synthesis of acylimines of
hexafluoroacetone,1,10 and the experimental simplicity of
the developed method.
Table 1. Yields, melting points, and elemental analysis data for
compounds 4a—f, 8a—g, 9a,b, and 10a—d
Comꢀ Yield M.p.
pound (%) /°С
Found
Calculated
Molecular
formula
(%)
N
C
H
4a
4b
4c
72 197—199 50.61 2.87 12.75 C14H9F6N3
50.46 2.72 12.61
76 176—178 39.69 2.44 15.66 C9H7F6N
39.86 2.60 15.50
81 192—194 51.73 3.05 12.27 C15H11F6N3
51.88 3.19 12.10
4d
4e
79 152—154 49.73 3.19 11.42 C15H11F6N3O
49.60 3.05 11.57
85 187—189 45.58 2.04 11.28 C14H8ClF6N3
45.73 2.19 11.43
4f
69 131—133 48.74 2.46 11.81 C14H8F7N3
47.88 2.30 11.96
75 296—298 43.76 2.07 13.51 C15H9F7N4O2
43.92 2.21 13.66
77 259—261 47.54 2.11 11.22 C20H10ClF7N4O2
47.40 1.99 11.06
76 311—313 50.15 2.21 11.28 C20H10F8N4O2
48.99 2.06 11.43
68 308—310 48.84 1.91 11.28 C20H10F8N4O2
48.99 2.06 11.43
83 311—313 47.24 2.13 11.22 C20H10ClF7N4O2
47.40 1.99 11.06
78 281—283 49.01 2.43 11.31 C20H11ClF6N4O2
49.15 2.27 11.46
1: R = Ph (a), Me (b), Et (c), 3ꢀMeC6H4 (d), 4ꢀMeOC6H4 (e),
3ꢀClC6H4 (f), 4ꢀClC6H4 (g), 2ꢀFC6H4 (h), 3ꢀFC6H4 (i), 4ꢀFC6H4 (j),
3ꢀpyridyl (k);
4: R = Ph (a), Me (b), 3ꢀMeC6H4 (c), 4ꢀMeOC6H4 (d),
3ꢀClC6H4 (e), 2ꢀFC6H4 (f);
8a
8b
8c
5: R´ = Ph (a), 4ꢀClC6H4 (b), 2ꢀFC6H4 (c), 4ꢀFC6H4 (d);
6, 9: R´ = All (a), methallyl (b);
7: R´ = PhCH2 (a), 2ꢀC5H4NCH2 (b), 3ꢀC5H4NCH2 (c);
8: R = Me, R´ = 4ꢀFC6H4 (a); R = 2ꢀFC6H4, R´ = 4ꢀClC6H4 (b);
R = 3ꢀFC6H4, R´ = 4ꢀFC6H4 (c); R = 4ꢀFC6H4, R´ = 2ꢀFC6H4 (d);
R = 4ꢀFC6H4, R´ = 4ꢀClC6H4 (e); R = 4ꢀClC6H4, R´ = Ph (f);
R = 4ꢀClC6H4, R´ = 2ꢀFC6H4 (g);
8d
8e
10: R = Me, R´ = 2ꢀC5H4NCH2 (a); R = Me, R´ = 3ꢀC5H4NCH2 (b);
R = Et, R´ = PhCH2 (c); R = 3ꢀC5H4NCH2, R´ = PhCH2 (d)
8f
8g
9a
9b
10a
10b
10c
10d
77 292—294 47.53 2.14 11.19 C20H10ClF7N4O2
47.40 1.99 11.06
76 211—213 47.15 2.63 12.77 C17H12F6N4OS
47.01 2.78 12.90
79 196—197 48.09 2.31 12.34 C18H14F6N4OS
48.22 3.15 12.50
82 134—136 54.27 4.41 10.19 C19H19F6N3O
54.42 4.57 10.02
78 157—159 54.26 4.71 10.13 C19H19F6N3O
54.42 4.57 10.02
74 182—183 58.16 5.29 6.32 C21H22F6N2O
58.33 5.13 6.48
79 201—203 59.71 4.56 8.84 C24H21F6N3O
59.88 4.40 8.73
Scheme 3
11: R = H (a), Me (b)

Acylimines of HFA with C,Nꢀbinucleophiles
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 4, April, 2006
733
1
H, 3.16; N, 11.96. Н NMR, δ: 2.17 (s, 3 Н, Ме); 6.59 (br.s,
2 Н, NH2); 7.51 (m, 3 H, CHAr); 7.89 (d, 2 H, CHAr, J =
6.7 Hz); 8.62 (s, 1 Н, NH). 19F NMR, δ: 9.17 (s).
Experimental
The H and 19F NMR spectra were recorded on a Bruker
1
DXP 200 spectrometer in DMSOꢀd6. The melting points were
determined in a glass capillary. Acylimines of hexafluoroacetone
1a—k,10 the starting 6ꢀaminouracils, 6ꢀaminothiouracils,11 and
3ꢀaminocyclohexenones12 were synthesized according to proceꢀ
dures described earlier. Methyl ether and 2ꢀaminocrotononitrile
(Aldrich) were used without preliminary purification.
Nꢀ[3ꢀAminoꢀ2ꢀcyanoꢀ1,1ꢀbis(trifluoromethyl)butꢀ2ꢀ
enyl]benzamide (3). 2ꢀAminocrotononitrile 2 (0.82 g, 0.01 mol)
was added to a solution of imine 1a (2.69 g, 0.01 mol) in benzene
(20 mL). After completion of the exothermic reaction, the benꢀ
zene was evaporated and the residue was recrystallized from
a 1 : 1 benzene—hexane mixture. Benzamide 3 was obtained in a
yield of 3.2 g (91.1%), m.p. 161—162 °C. Found (%): C, 47.71;
H, 3.03; N, 1.79. C14H11F6N3O. Calculated (%): C, 47.87;
6ꢀMethylꢀ2ꢀphenylꢀ4,4ꢀbis(trifluoromethyl)ꢀ1,4ꢀdihydroꢀ
pyrimidineꢀ5ꢀcarbonitrile (4a). A. A solution of benzamide 3
(1.75 g, 0.005 mol) and Et3N (0.2 mL) in DMF (10 mL) was
heated at 90—100 °C for 5 h. Then the reaction mixture was
cooled and poured into water (50 mL). The precipitate that
formed was recrystallized from 50% EtOH and compound 4a
was obtained in a yield of 1.2 g (72%), m.p. 197—199 °C.
B. A solution of benzoylimine 1 (2.69 g, 0.01 mol) and
2ꢀaminocrotononitrile 2 (0.82 g, 0.01 mol) in DMF (10 mL)
was stirred at 20 °C for 1 h. Then Et3N (0.2 mL) was added. 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. Compound 4a
was obtained in a yield of 2.7 g (81%), m.p. 197—199 °C.
Table 2. 1Н and 19F NMR spectra of compounds 4a—f, 8a—g, 9a,b, and 10a—d in DMSOꢀd6
Comꢀ
pound
δ (J/Hz)
1H
19F
4a
4b
4c
4d
2.38 (s, 3 Н, Ме); 7.53 (m, 3 H, CHAr); 7.93 (d, 2 H, CHAr, J = 7.1); 10.86 (s, 1 Н, NH)
2.04, 2.17 (both s, 3 H each, Ме); 9.81 (br.s, 1 Н, NH)
2.32, 2.45 (both s, 3 H each, Ме); 7.33, 7.68 (both m, 2 H each, CHAr); 10.81 (s, 1 Н, NH)
2.11 (s, 3 Н, Ме); 3.87 (s, 3 Н, МеO); 6.89, 7.84 (both d, 2 H each, CHAr, J = 8.0);
8.40 (s, 1 Н, NH)
2.68 (s)
2.52 (s)
2.73 (s)
3.59 (s)
4e
4f
2.34 (s, 3 Н, Ме); 7.47, 7.89 (both m, 2 H each, CHAr); 10.91 (s, 1 Н, NH)
2.29 (s, 3 Н, Ме); 7.24, 7.55 (both m, 2 H each, CHAr);
10.98 (s, 1 Н, NH)
2.02 (s, 3 H, Ме); 7.08 (m, 4 Н, CHAr);
9.73, 11.27 (both s, 1 H each, NH)
7.12—7.23 (m, 5 H, CHAr); 7.43 (d, 2 H, CHAr, J = 8.8); 7.53 (m, 1 H, CHAr);
9.81, 11.46 (both s, 1 H each, NH)
7.19 (m, 5 H, CHAr); 7.42 (m, 2 H, CHAr);
7.39 (m, 1 H, CHAr);
9.55, 11.39 (both s, 1 H each, NH)
7.09 (m, 2 H, CHAr); 7.29 (m, 3 H, CHAr);
7.48 (m, 2 H, CHAr); 7.71 (m, 1 H, CHAr);
9.60, 11.48 (both s, 1 H each, NH)
7.04 (m, 2 Н, CHAr); 7.23, 7.42 (both d, 2 H each, CHAr, J = 7.7); 7.63 (m, 2 Н, CHAr);
9.55, 11.34 (both s, 1 H each, NH)
7.21 (m, 2 Н, CHAr); 7.36 (d, 2 Н, CHAr, J = 7.7); 7.47 (m, 3 Н, CHAr);
7.63 (d, 2 Н, CHAr, J = 7.7); 9.58, 11.38 (both s, 1 H each, NH)
7.24 (m, 4 H, CHAr); 7.46, 7.73 (both m, 2 H each, CHAr);
9.71, 11.48 (both s, 1 H each, NH)
5.21 (m, 2 H, CH2N); 5.36 (m, 2 H, CH2=); 5.96 (m, 1 H, CH=); 7.55 (m, 3 H, CHAr);
7.94 (d, 2 Н, CHAr, J = 7.9); 9.99, 12.44 (both s, 1 H each, NH)
1.93 (s, 3 H, Ме); 4.51, 4.81 (both s, 1 H each, CH2N); 5.24 (s, 2 Н, CH2=);
7.47—7.64 (m, 3 Н, CHAr); 7.87 (d, 2 Н, CHAr, J = 6.8); 10.02, 12.60 (both s, 1 H each, NH)
1.01 (s, 6 H, Ме); 2.22 (s, 2 H, CH2); 2.26 (s, 3 H, Ме); 2.56, 5.09 (both s, 2 H each,
CH2); 7.28 (m, 2 Н, CHAr); 7.78 (t, 1 Н, CHAr, J = 7.6); 8.54 (d, 1 Н, CHAr, J = 7.6)
1.02 (s, 6 H, Ме), 2.25 (s, 2 H, CH2), 2.28 (s, 3 H, Ме), 2.56, 5.11 (both s, 2 H each, CH2);
7.35, 7.48 (both m, 1 H each, CHAr), 8.44 (s, 1 Н, CHAr), 8.55 (d, 1 Н, CHAr, J = 7.5)
0.94 (s, 6 H, Ме); 1.12 (t, 3 Н, Me, J = 7.5); 2.18 (s, 2 Н, CH2); 2.52—2.61 (m, 4 Н,
3.12 (s)
3.10 (s, 6 F);
–34.86 (m, 1 F)
4.82 (s, 6 F);
–29.05 (m, 1 F)
5.06 (s, 6 F);
–34.56 (m, 1 F)
5.48 (s, 6 F);
–34.64, –35.45
(both m, 1 F each)
5.16 (s, 6 F);
–28.14, –42.79
(both m, 1 F each)
5.46 (s, 6 F);
–28.43 (m, 1 F)
5.44 (s)
8a
8b
8c
8d
8e
8f
8g
5.30 (s, 6 F);
–43.04 (m, 1 F)
5.43 (s)
9a
9b
5.44 (s)
6.39 (s)
6.10 (s)
5.97 (s)
5.03 (s)
10a
10b
10c
10d
CH2 + CH2); 4.97 (s, 2 Н, CH2); 7.23 (d, 2 Н, CHAr, J = 8); 7.27—7.32 (m, 3 Н, CHAr
0.97, 1.03 (both s, 3 H each, Me); 2.17 (AB system, 2 H, CH2, J = 11.4); 2.48 (m, 2 H, CH2); 4.87
(s, 2 H, CH2); 7.23—7.41 (m, 6 H, CHAr); 8.22 (d, 1 H, CHAr, J = 7.8); 6.67 (m, 2 H, CHAr
)
)

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Russ.Chem.Bull., Int.Ed., Vol. 55, No. 4, April, 2006
Sokolov et al.
2,6ꢀDimethylꢀ4,4ꢀbis(trifluoromethyl)ꢀ1,4ꢀdihydropyrimiꢀ
151—153 °C. Found (%): C, 41.17; H, 2.37; N, 10.47,
C18H13BrF6N4OS. Calculated (%): C, 41.00; H, 2.49; N, 10.63.
1Н NMR, δ: 1.82 (s, 3 H, Me); 4.02 (AB system, 2 H, CH2, J =
10.4 Hz); 4.24 and 4.80 (both d, 1 H each, CH2Br, J = 12.5 Hz);
7.55 (m, 3 H, CHAr); 7.93 (d, 2 H, CHAr, J = 8.0 Hz); 9.72 (s,
1 H, NH). 19F NMR, δ: 5.76 (s).
dineꢀ5ꢀcarbonitrile (4b), 6ꢀmethylꢀ2ꢀ(3ꢀtolyl)ꢀ4,4ꢀbis(trifluoroꢀ
methyl)ꢀ1,4ꢀdihydropyrimidineꢀ5ꢀcarbonitrile (4c), 2ꢀ(4ꢀmethꢀ
oxyphenyl)ꢀ6ꢀmethylꢀ4,4ꢀbis(trifluoromethyl)ꢀ1,4ꢀdihydropyriꢀ
midineꢀ5ꢀcarbonitrile (4d), 2ꢀ(3ꢀchlorophenyl)ꢀ6ꢀmethylꢀ4,4ꢀ
bis(trifluoromethyl)ꢀ1,4ꢀdihydropyrimidineꢀ5ꢀcarbonitrile (4e),
2ꢀ(2ꢀfluorophenyl)ꢀ6ꢀmethylꢀ4,4ꢀbis(trifluoromethyl)ꢀ1,4ꢀdiꢀ
hydropyrimidineꢀ5ꢀcarbonitrile (4f), 1ꢀ(4ꢀfluorophenyl)ꢀ7ꢀmethylꢀ
5,5ꢀbis(trifluoromethyl)ꢀ5,8ꢀdihydropyrimido[4,5ꢀd]pyrimidineꢀ
2,4(1H,3H )ꢀdione (8a), 1ꢀ(4ꢀchlorophenyl)ꢀ7ꢀ(2ꢀfluorophenyl)ꢀ
5ꢀbis(trifluoromethyl)ꢀ5,8ꢀdihydropyrimido[4,5ꢀd]pyrimidineꢀ
2,4(1H,3H )ꢀdione (8b), 7ꢀ(3ꢀfluorophenyl)ꢀ1ꢀ(4ꢀfluorophenyl)ꢀ
5,5ꢀbis(trifluoromethyl)ꢀ5,8ꢀdihydropyrimido[4,5ꢀd]pyrimidineꢀ
2,4(1H,3H )ꢀdione (8c), 1ꢀ(2ꢀfluorophenyl)ꢀ7ꢀ(4ꢀfluorophenyl)ꢀ
5,5ꢀbis(trifluoromethyl)ꢀ5,8ꢀdihydropyrimido[4,5ꢀd]pyrimidineꢀ
2,4(1H,3H )ꢀdione (8d), 1ꢀ(4ꢀchlorophenyl)ꢀ7ꢀ(4ꢀfluorophenyl)ꢀ
5,5ꢀbis(trifluoromethyl)ꢀ5,8ꢀdihydropyrimido[4,5ꢀd]pyrimidineꢀ
2,4(1H,3H )ꢀdione (8e), 7ꢀ(4ꢀchlorophenyl)ꢀ1ꢀphenylꢀ5,5ꢀ
bis(trifluoromethyl)ꢀ5,8ꢀdihydropyrimido[4,5ꢀd]pyrimidineꢀ
2,4(1H,3H )ꢀdione (8f), 7ꢀ(4ꢀchlorophenyl)ꢀ1ꢀ(2ꢀfluorophenyl)ꢀ
5,5ꢀbis(trifluoromethyl)ꢀ5,8ꢀdihydropyrimido[4,5ꢀd]pyrimidineꢀ
2,4(1H,3H )ꢀdione (8g), 1ꢀallylꢀ7ꢀphenylꢀ2ꢀthioxoꢀ5,5ꢀbis(triꢀ
fluoromethyl)ꢀ2,3,5,8ꢀtetrahydroꢀ1Hꢀpyrimido[4,5ꢀd]pyrimidinꢀ
4ꢀone (9a), 1ꢀ(2ꢀmethylallylꢀ2ꢀthioxo)ꢀ5,5ꢀbis(trifluoromethyl)ꢀ
7ꢀphenylꢀ2,3,5,8ꢀtetrahydroꢀ1Hꢀpyrimido[4,5ꢀd]pyrimidinꢀ4ꢀ
one (9b), 2,7,7ꢀtrimethylꢀ1ꢀ(pyridinꢀ2ꢀylmethyl)ꢀ4,4ꢀbis(triꢀ
fluoromethyl)ꢀ4,6,7,8ꢀtetrahydroꢀ1Нꢀquinazolinꢀ5ꢀone (10a),
2,7,7ꢀtrimethylꢀ1ꢀ(pyridinꢀ3ꢀylmethyl)ꢀ4,4ꢀbis(trifluoromethyl)ꢀ
4,6,7,8ꢀtetrahydroꢀ1Нꢀquinazolinꢀ5ꢀone (10b), 1ꢀbenzylꢀ2ꢀ
ethylꢀ7,7ꢀdimethylꢀ4,4ꢀbis(trifluoromethyl)ꢀ4,6,7ꢀtetrahydroꢀ
1Нꢀquinazolinꢀ5ꢀone (10c), and 1ꢀbenzylꢀ7,7ꢀdimethylꢀ2ꢀ(pyriꢀ
dinꢀ3ꢀyl)ꢀ4,4ꢀbis(trifluoromethyl)ꢀ4,6,7,8ꢀtetrahydroꢀ1Нꢀquinꢀ
azolinꢀ5ꢀone (10d) were prepared analogously to pyrimidinone
4a from acylimines 1a—k (0.01 mol) and the corresponding
binucleophiles 5a—d, 6a,b, and 7a,c (0.01 mol). The yields, the
melting points, and the spectroscopic characteristics of comꢀ
pounds 4a—f, 8a—g, 9a,b, and 10a—d are given in Tables 1 and 2.
2ꢀBromomethylꢀ8ꢀphenylꢀ6,6ꢀbis(trifluoromethyl)ꢀ1,2,6,9ꢀ
tetrahydroꢀ3ꢀthiaꢀ4,7,9,9bꢀtetraazacyclopenta[a]naphthalenꢀ5ꢀ
one (11a). Bromine (0.8 g, 0.005 mol) was added to a suspension
of pyrimidinone 9a (2.17 g, 0.005 mol) in EtOH (20 mL) at 20 °C.
The reaction mixture was stirred for 1 h, diluted with Н2O
(50 mL), and neutralized with a 10% NaOH solution. The preꢀ
cipitate that formed was filtered off and recrystallized from
50% EtOH. Compound 11a was obtained in a yield of 2.1 g
(82%), m.p. 144—146 °C. Found (%): C, 38.62; H, 2.33;
N, 10.77. C17H11BrF6N4OS. Calculated (%): C, 39.78; H, 2.16;
This study was financially supported by the Division
of Chemistry and Materials Science of the Russian Acadꢀ
emy of Sciences (Program No. 10 of Basic Research
"Biomolecular and Medicinal Chemistry").
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1
N, 10.92. Н NMR, δ: 3.69 (m, 2 H, CH2Br); 4.37 (m, 1 H,
CHS); 4.49 and 4.71 (both m, 1 H each, CH2N); 7.61 (m, 3 H,
CHAr); 7.94 (m, 2 H, CHAr); 9.67 (s, 1 H, NH). 19F NMR,
δ: 5.95 (s).
2ꢀBromomethylꢀ2ꢀmethylꢀ8ꢀphenylꢀ6,6ꢀbis(trifluoromeꢀ
thyl)ꢀ1,2,6,9ꢀtetrahydroꢀ3ꢀthiaꢀ4,7,9,9bꢀtetraazacycloꢀ
penta[a]naphthalenꢀ5ꢀone (11b) was prepared analogously to 11a
from compound 9b (2.24 g) in a yield of 2.2 g (83%), m.p.
Received June 16, 2005;
in revised form November 17, 2005