SYNTHESIS OF 2-THIOXO-6-TRIFLUOROMETHYL-1,2-DIHYDROPYRIDINE-3-CARBONITRILE
123
not appear, probably due to a fast exchange with
deuterium. Mass spectrum, m/z (Irel, %): 205 [M + 1]+
(7), 203 [M – 1]+ (100), 106 [M – H – CF3+ – HCN]+
(10). Found, %: C 41.04; H 1.33; N 13.60. C7H3F3N2S.
Calculated, %: C 41.18; H 1.48, N 13.72.
c. Compound VIIIa. A stirred solution of 2.04 g of
pyridinethione V in 10 ml of DMF was treated at 20°C
with 5.6 ml of 10% aqueous KOH and 0.94 g of 2-
chloroacetamide (VIIa). The resulting mixture was
stirred for 4 h and left for a day. After that the reaction
mixture was diluted by half with water, and the
precipitate that formed was filtered off to obtain
amide VIIIa, yield 1.85 g (71%). Its melting point and
Rf were analogous to those of the sample synthesized
by method a.
Ethyl 5-cyano-6-thioxo-1,6-dihydropyridine-2-
carboxylate (VI) was obtained similarly to salt IV
from ethyl 4-ethoxy-2-oxobut-3-enoate (Ib). Yield 1.6
g (77%), mp 193–195°C (AcOH), yellow powder. IR
spectrum, ν, cm–1: 2225 (C≡N), 1730 (C=O). 1H NMR
spectrum, δ, ppm: 1.31 t (3H, Me, J 6.19 Hz), 4.33 q
(2H, CH2, J 6.19 Hz), 7.08 d (1H, C4H, J 8.02 Hz),
7.99 d (1H, C3H, J 8.02 Hz), 14.51 br.s (1H, NH).
Found, %: C 51.82; H 3.72; N 13.29. C9H8N2O2S.
Calculated, %: C 51.91; H 3.87; N 13.45.
d. Compound VIIIb was prepared analogously to
amide VIIIa from 2.67 g of bromoacetylcoumarin
VIIb. Yield 2.92 g (75%), the melting point and
chromatographic data were analogous to those of the
sample prepared by method a.
2-[(3-Cyano-6-trifluoromethylpyridin-2-yl)sulfa-
nyl]acetamide (VIIIa). a. 2-Chloroacetamide (VIIa),
0.94 g, was added at 20°C to a stirred solution of 3.05 g
of salt IV in 10 ml of DMF. The reaction mixture was
stirred for 4 h and left for a day. After that in was
diluted by half with water, and the precipitate that
formed was filtered off, washed with water, ethanol,
and hexane. Yield 1.93 g (74%), mp 168°C (AcOH),
colorless needles. IR spectrum, ν, cm–1: 3427, 3206
(NH2), 2232 (C≡N), 1623 (CONH). 1H NMR
spectrum, δ, ppm: 4.00 s (2H, CH2), 7.13 br.s (1H,
NH2), 7.56 br.s (1H, NH2), 7.78 d (1H, C4H, J 7.95 Hz),
8.49 d (1H, C5H, J 7.95 Hz). Mass spectrum, m/z (Irel,
%): 260 [M – 1]+ (91), 242 (59), 203 [M –
CH2CONH2]+ (100), 143 (8), 106 (11), 84 (19). Found,
%: C 41.14; H 2.05; N 15.87. C9H6F3N3OS. Calculated,
%: C 41.38; H 2.31; N 16.09.
3-Amino-4-trifluoromethylthieno[2,3-b]pyridine-
2-carboxamide (IX). A solution of 2.61 g of amide
VIIIa in 15 ml of DMF was treated with stirring at
20°C with 5.6 ml of 10% aqueous KOH, and the
resulting mixture was stirred for 5 h. After that it was
diluted by half with water, and the precipitate that
formed was filtered off and washed with water,
ethanol, and hexane. Yield 1.98 g (76%), mp 270°C
(BuOH), light yellow powder. At 210°C the substance
sublimes to form needles, under UV irradiation it
fluoresces. IR spectrum, ν, cm–1: 3410, 3390, 3324
(NH2), 1696 (C=O), 1662 [δ(NH2)]. 1H NMR
spectrum, δ, ppm: 7.41 br.s (4H, 2NH2), 7.92 d (1H,
C4H, J 8.02 Hz), 8.71 d (1H, C5H, J 8.02 Hz). Mass
spectrum, m/z (Irel, %): 263 [M + 2]+ (14), 262 [M + 1]+
(100), 219 (25), 138 (11), 101 (9), 83 (7). Found, %: C
41.25; H 2.18; N 15.94. C9H6F3N3OS. Calculated, %:
C 41.38; H 2.31; N 16.09.
b. 2-[2-Oxo-2-(2-oxo-2H-chromen-3-yl)ethylsulfa-
nyl]-6-trifluoromethylnicotinonitrile (VIIIb) was
prepared analogously to amide VIIIa from 2.67 g of
compound VIIb. Yield 3.47 g (89%), mp 170–172°C
(AcOH), colorless powder. IR spectrum, ν, cm–1: 2228
(C≡N), 1722 (C=O). 1H NMR spectrum, δ, ppm: 4.88 s
(2H, CH2), 7.31 d (1H, coumarin C5H, J 9.0 Hz), 7.43
d (1H, coumarin C8H , J 9.0 Hz), 7.50 d (1H, pyridine
C4H, J 8.0), 7.77 t (2H, coumarin C6H and C7H, J
9.0 Hz), 8.51 d (1H, pyridine C4H, J 8.0 Hz), 8.73 s
(1H, coumarin C4). Mass spectrum, m/z (Irel, %): 392
[M + 2]+ (15), 390 [M]+ (54), 388 [M – 2]+ (100), 372
(16), 284 (9), 259 (12), 218 (13), 202 (67), 190 (18),
150 (11), 124 (7), 94 (6). Found, %: C 55.20; H 2.14;
N 6.99. C18H9F3N2O3S. Calculated, %: C 55.39; H
2.32; N 7.18.
7-Trifluoromethyl-2-spirocyclopentane-1,2,3,4-
tetrahydropyrido[2',3':2,3]thieno[4,5-d]pyrimidin-
4-one (X). A mixture of 2.61 g of compound IX, 0.89 g
of cyclopentanone, and 25 ml of glacial acetic acid was
refluxed for 4 h. After cooling, yellow crystals formed
and were filtered off and washed with glacial acetic
acid and ether. Yield 2.26 g (69%), mp 220°C. At 170°C
the substance sublimes, under UV irradiation it
fluoresces. IR spectrum, ν, cm–1: 3324 (N–H), 1714
1
(C=O). H NMR spectrum, δ, ppm: 1.71 m (4H,
2CH2), 1.89 m (4H, 2CH2), 7.95 br.s (1H, NH), 7.98 d
(1H, C9H, J 8.0 Hz), 8.14 br.s (1H, CONH), 8.65 d
(1H, C8H, J 8.0 Hz). Mass spectrum, m/z (Irel, %): 326
[M – 1]+ (100). Found, %: C 51.29; H 3.55; N 12.74.
C14H12F3N3OS. Calculated, %: C 51.37; H 3.69; N
12.84.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 1 2009