SYNTHESIS AND BIOLOGICAL ACTIVITY
2015
1
0.01 mol of compound 7a or 7b and 0.01 mol of potassium
70%, mp 65‒67°C. H NMR spectrum, δ, ppm: 1.90‒2.02
hydroxide in 10 mL of water. After 3 h, the precipitate
m (4H, CH CH ), 2.22 s (3H, CH ), 2.72 s (3H, SCH ),
2
2
3
3
was filtered off and dried.
3.43‒3.55 m (4H, CH NCH ), 5.45 s (2H, OCH ), 5.84 s
2 2 2
13
(
1H, 5-H). C NMR spectrum, δ , ppm: 13.9, 23.5, 24.8,
4
-([4-Ethyl-5-(methylthio)-4H-1,2,4-triazol-3-yl]-
C
45.8, 55.4, 93.1, 159.1, 163.1, 162.5, 167.6, 167.7. Found,
methoxy}-6-methyl-2-(pyrrolidin-1-yl)pyrimidine
1
%: C 50.67; H 5.45; N 22.59. C H N O S. Calculated,
(
8a). Yield 68%, mp 85‒87°C. H NMR spectrum, δ,
13 17
5
2
%: C 50.80; H 5.58; N 22.79.
ppm: 1.33 t (3H, NCH CH , J = 7.2 Hz), 1.92‒2.03 m
2
3
(
4H, CH CH ), 2.21 s (3H, CH ), 2.70 s (3H, SCH ),
Methyl 2-{[5-({[6-methyl-2-(pyrrolidin-1-yl)-
2 2 3 3
3
.51‒3.59 m (4H, CH NCH ), 3.96 q (2H, NCH CH ,
pyrimidin-4-yl]oxy}methyl)-1,3,4-oxadiazol-2-yl]-
sulfanyl}acetate (10b). Yield 68%, mp 75‒78°C. H
2
2
2
3
1
3
1
J = 7.1 Hz), 5.45 s (2H, OCH ), 5.78 s (1H, 5-H). C
2
NMR spectrum, δ , ppm: 14.3, 14.6, 23.5, 24.9, 45.9,
NMR spectrum, δ, ppm: 1.92‒2.00 m (4H, CH CH ),
C
2
2
5
6.2, 93.1, 150.6, 150.7, 159.3, 167.6, 167.9. Found, %:
2.22 s (3H, CH ), 3.44‒3.52 m (4H, CH NCH ), 3.74
3 2 2
C 53.69; H 6.52; N 24.81. C H N OS. Calculated, %:
s (3H, OCH ), 4.12 s (2H, SCH ), 5.46 s (2H, OCH ),
1
5
22
6
3
2
2
1
3
C 53.87; H 6.63; N 25.13.
-{[4-Phenyl-5-(methylthio)-4H-1,2,4-triazol-3-yl]-
methoxy}-6-methyl-2-(pyrrolidin-1-yl)pyrimidine
5.85 s (1H, 5-H). C NMR spectrum, δ , ppm: 23.5,
C
2
1
4.8, 33.2, 45.8, 52.1, 55.5, 93.1, 159.0, 163.0, 163.4,
66.9, 167.6, 167.7. Found, %: C 49.22; H 5.13; N 19.01.
4
1
C H N O S. Calculated, %: C 49.31; H 5.24; N 19.17.
(
8b). Yield 72%, mp 67‒69°C. H NMR spectrum, δ,
15 19 5 4
ppm: 1.90‒1.98 (4H, CH CH ), 2.20 s (3H, CH ), 2.67 s
2-{[5-({[6-Methyl-2-(pyrrolidin-1-yl)pyrimidin-
4-yl]oxy}methyl)-1,3,4-oxadiazol-2-yl]sulfanyl}
acetamide (10c). Yield 60%, mp 165‒167°C. H NMR
2
2
3
(
3H, SCH ), 3.43‒3.53 m (4H, CH NCH ), 5.30 s (2H,
3 2 2
1
OCH ), 5.64 s (1H, 5-H), 7.32‒7.55 m (5H, C H ). Found,
2
6
5
%
: C 59.87; H 5.91; N 22.19. C H N OS. Calculated,
spectrum, δ, ppm: 1.91‒2.02 m (4H, CH CH ), 2.22 s (3H,
1
9
22
6
2
2
%
: C 59.66; H 5.80; N 21.97.
-{[5-(Thioxo)-1,3,4-oxadiazole-2-yl]methoxy}-
-methyl-2-(pyrrolidin-1-yl)pyrimidine (9).
Compound 6, 0.01 mol, was added to a solution of
CH ), 3.43–3.55 m (4H, CH NCH ), 3.99 s (2H, SCH ),
3 2 2 2
5
.45 s (2H, OCH ), 5.85 s (1H, 5-H), 7.08 br.s and 7.55
2
4
1
3
br.s (2H, NH ). C NMR spectrum, δ , ppm: 23.5, 24.8,
6
2
C
3
5.9, 45.8, 55.5, 93.2, 159.1, 163.1, 164.1, 167.0, 167.6,
1
67.8. Found, %: C 47.82; H 5.11; N 23.75. C H N O S.
0.01 mol of potassium hydroxide in 25 mLof ethanol, and
14 18
6
3
Calculated, %: C 47.99; H 5.18; N 23.98.
0
.011 mol of carbon disulfide was then added dropwise.
The mixture was refluxed for 2 h, the solvent was distilled
off, the residue was dissolved in water and neutralized
with acetic acid, and the precipitate was filtered off.
Compounds 11 and 12 (general procedure). A mix-
ture of 0.01 mol of compound 9 and 0.02 mol of dieth-
ylamine or morpholine in propan-1-ol was refluxed for
10 h. The solvent was removed, the residue was treated
with water, and the precipitate was filtered off and dried.
1
Yield 82%, mp 185‒187°C. H NMR spectrum, δ, ppm:
1
.91‒2.00 m (4H, CH CH ), 2.22 s (3H, CH ), 3.45‒3.53
2 2 3
m (4H, CH NCH ), 5.30 s (2H, OCH ), 5.86 s (1H, 5-H),
2
2
2
2-{[6-Methyl-2-(pyrrolidin-1-yl)pyrimidin-4-yl]-
1
3
1
0.25 br.s (1H, NH). C NMR spectrum, δ , ppm: 23.5,
C
oxy}-N'-(morpholine-4-carbothioyl)acetohydrazide
2
4.8, 45.9, 55.6, 93.2, 104.5, 159.0, 167.6, 167.9, 177.9.
1
(
11). Yield 78%, mp 170‒172°C. H NMR spectrum,
Found, %: C 49.01; H 5.08; N 23.69. C H N O S.
1
2
15
5
2
δ, ppm: 1.89‒2.01 m (4H, CH CH ), 2.22 s (3H, CH ),
2
2
3
Calculated, %: C 49.13; H 5.15; N 23.87.
3
.48‒3.56 m (4H, CH NCH ), 3.61‒3.68 m and 3.81‒3.88
2 2
Compounds 10a–10c (general procedure). Dimethyl
sulfate, methyl chloroacetate, or chloroacetamide,
.01 mol, was added dropwise to the potassium salt
prepared from 0.01 mol of compound 9 and 0.01 mol of
potassium hydroxide in 15 mL of DMF. The mixture was
left overnight at room temperature and was then heated
for 2 h at 70‒80°C until pH 7. The solvent was removed,
the residue was treated with 10–20 mL of water, and the
precipitate was filtered off and dried.
m [8H, N(CH CH ) O], 4.80 s (2H, OCH ), 5.89 s (1H,
2 2 2 2
1
3
5-H), 9.30‒9.82 br.s (2H, NHNH). C NMR spectrum,
δC, ppm: 23.5, 24.9, 45.8, 48.2, 65.6, 93.5, 159.2, 165.7,
167.2, 168.0, 182.8. Found, %: C 50.63; H 6.41; N 22.30.
C H N O S. Calculated, %: C 50.51; H 6.36; N 22.09.
0
1
6
24
6
3
N,N-Diethyl-2-(2-{[6-methyl-2-(pyrrolidin-1-yl)py-
rimidin-4-yl]oxy}acetyl)hydrazine-1-carbothioamide
1
(
12). Yield 70%, mp 115‒117°C. H NMR spectrum,
δ, ppm: 1.22 t (3H, NCH CH , J = 6.9 Hz), 1.90‒2.01
2
3
4-{[5-(Methylthio)-1,3,4-oxadiazole-2-yl]methoxy}-
m (4H, CH CH ), 2.22 s (3H, CH ), 3.45‒3.55 m (4H,
2 2 3
6
-methyl-2-(pyrrolidin-1-yl)pyrimidine (10a). Yield
CH NCH ), 3.68 q (2H, NCH CH , J = 6.9 Hz), 4.82 s
2 2 2 3
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 10 2019