9734
I.O. Lebedyeva et al. / Tetrahedron 68 (2012) 9729e9737
(400.1 MHz, DMSO-d6), ppm:
d
¼1.18 (3H, t, 3J 6.8, CH2CH3),
148.5, 152.7, 155.3, 161.6, 164.6; HPLC/MS: 543.2 [MþH]þ. Anal. Calcd
for C25H25BrN4O3S (541.46): C, 55.46; H, 4.65; N, 10.35. Found: C,
55.55; H, 4.60; N, 10.48.
2.07e2.14 (2H, m, CH2), 2.81e2.85 (2H, m, CH2), 3.04e3.08 (2H, m,
CH2), 3.21 (3H, s, NCH3), 4.10 (2H, q, 3J 6.8, CH2CH3), 4.84 (1H, d, 2J
13.7, SCH), 4.99 (1H, d, 2J 13.7, SCH), 5.15 (1H, d, 3J 3.4, H-4), 7.20 (2H,
d, 3J 8.3, HeAr), 7.47 (2H, d, 3J 8.3, HeAr), 7.52 (2H, d, 3J 8.3, HeAr),
7.59 (2H, d, 3J 8.3, HeAr), 8.11 (1H, d, 3J 3.4, NH); HPLC/MS: 639.0
[MþH]þ. Anal. Calcd for C30H26BrClN4O3S (637.98): C, 56.48; H,
4.11; N, 8.78. Found: C, 56.59; H, 4.13; N, 8.68.
5.3.12. Ethyl 4-(4-bromophenyl)-6-({[4-(2-chlorophenyl)-3-cyano-
5,6,7,8-tetrahydroquinolin-2-yl]thio}methyl)-1-methyl-2-oxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylate (3l). Sand colored pow-
der, mp 215e218 ꢃC (dec, i-PrOH/DMF/H2O¼2:1:1), yield 72%. IR
(Nujol): 3360, 3210 (NH), 2200 (C^N),1705,1682 (2C]O) cmꢀ1; 1H
5.3.8. Ethyl 6-({[4-(4-chlorophenyl)-3-cyano-6,7-dihydro-5H-cyclo-
penta[b]pyridin-2-yl]thio}methyl)-4-(4-methoxyphenyl)-1-methyl-2-
oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (3h). White pow-
der, mp 98e100 ꢃC, yield 84%. IR (Nujol): 3300 (NH), 2220 (C^N),
NMR (400.1 MHz, DMSO-d6), ppm:
d
¼1.12 (3H, t, 3J 6.8, CH2CH3),
1.66e1.68 (2H, m, CH2), 1.78e1.82 (2H, m, CH2), 2.18e2.32 (2H, m,
CH2), 2.90e2.95 (2H, m, CH2), 3.21 (3H, s, NCH3), 4.07 (2H, q, 3J 6.8,
CH2CH3), 4.84 (1H, d, 2J 13.2, SCH), 4.98 (1H, d, 2J 13.2, SCH), 5.15
(1H, d, 3J 3.2, H-4), 7.20e7.21 (2H, m, HeAr), 7.42e7.56 (5H, m,
HeAr), 7.69 (1H, d, 3J 7.3, HeAr), 8.16 (1H, d, 3J 3.2, HN); HPLC/MS:
653.2 [MþH]þ. Anal. Calcd for C31H28BrClN4O3S (652.01): C, 57.11;
H, 4.33; N, 8.59. Found: C, 57.29; H, 4.40; N, 8.78.
1695, 1674 (2C]O) cmꢀ1 1H NMR (399.97 MHz, DMSO-d6), ppm:
;
d
¼1.14 (3H, t, 3J 6.8, CH2CH3), 2.03e2.09 (2H, m, CH2), 2.77e2.81
(2H, m, CH2), 3.03e3.08 (2H, m, CH2), 3.21 (3H, s, NCH3), 3.73 (3H, s,
OCH3), 4.07 (2H, q, 3J 6.8, CH2CH3), 4.84 (1H, d, 2J 11.6, SCH), 5.01
(1H, d, 2J 11.6, SCH), 5.13 (1H, d, 3J 3.4, H-4), 6.89 (2H, d, 3J 7.7, HeAr),
7.17 (2H, d, 3J 7.7, HeAr), 7.59 (2H, d, 3J 7.3, HeAr), 7.64 (2H, d, 3J 7.3,
HeAr), 8.03 (1H, d, 3J 3.4, NH). Anal. Calcd for C31H29ClN4O4S
(589.11): C, 63.20; H, 4.96; N, 9.51. Found: C, 63.01; H, 5.00; N, 9.38.
5.3.13. Ethyl 4-(4-bromophenyl)-6-({[4-(4-chlorophenyl)-3-cyano-
5,6,7,8-tetrahydroquinolin-2-yl]thio}methyl)-1-methyl-2-oxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylate (3m). Off-white pow-
der, mp 194e196 ꢃC (i-PrOH/DMF/H2O¼2:1:1), yield 81%. IR
(Nujol): 3210 (NH), 2220 (C^N), 1710, 1686 (2C]O) cmꢀ1; 1H NMR
5.3.9. Ethyl 6-{[(3-cyano-5,6,7,8-tetrahydroquinolin-2-yl)thio]methyl}-
2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate (3i). Light
yellow powder, mp 245e246 ꢃC (dec), yield 57% (yield lowered to 43%
when DMF was replaced with EtOH). IR (Nujol): 3391, 3227 (NH),
(400.1 MHz, DMSO-d6), ppm:
d
¼1.13 (3H, t, 3J 7.1, CH2CH3),
1.64e1.67 (2H, m, CH2), 1.77e1.81 (2H, m, CH2), 2.34e2.37 (2H, m,
CH2), 2.90e2.93 (2H, m, CH2), 3.20 (3H, s, NCH3), 4.08 (2H, q, 3J 7.1,
CH2CH3), 4.84 (1H, d, 2J 13.0, SCH), 4.99 (1H, d, 2J 13.0, SCH), 5.16
(1H, d, 3J 3.7, H-4), 7.21 (2H, d, 3J 8.3, HeAr), 7.43 (2H, d, 3J 8.3,
HeAr), 7.53 (2H, d, 3J 8.3, HeAr), 7.61 (2H, d, 3J 8.3, HeAr), 8.15 (1H,
2221 (C^N), 1716, 1682 (2C]O) cmꢀ1; H NMR (500.1 MHz, DMSO-
1
d6), ppm:
d
¼1.10 (3H, t, 3J 6.8, CH2CH3), 1.70e1.74 (2H, m, CH2),
1.78e1.81 (2H, m, CH2), 2.69e2.72 (2H, m, CH2), 2.82e2.85 (2H, m,
CH2), 4.03 (2H, q, 3J 6.8, CH2CH3), 4.50 (1H, d, 2J 13.2, SCH), 4.57 (1H, d,
2J 13.2, SCH), 5.15 (1H, d, 3J 3.5, H-4), 7.20e7.30 (5H, m, Ph), 7.87 (1H, br
s, HN-3), 7.97 (1H, s, H-4quinolin-2-yl), 9.20 (1H, s, HN-1); 13C NMR
d, 3J 3.7, HN); 13C NMR (100.6 MHz, DMSO-d6), ppm:
d
¼13.8, 21.5,
21.7, 26.1, 27.6, 29.8, 32.8, 51.8, 60.1, 103.9, 104.9, 114.8, 120.5, 127.0,
128.2, 128.7, 130.0, 131.2, 133.5, 133.9, 142.5, 148.4, 152.5, 152.7,
155.9, 161.4, 164.5. Anal. Calcd for C31H28BrClN4O3S: C, 57.11; H,
4.33; N, 8.59 (652.01). Found: C, 57.07; H, 4.37; N, 8.48.
(100.6 MHz, DMSO-d6), ppm:
d
¼13.8, 21.5, 21.7, 26.8, 29.2, 31.9, 54.0,
59.6, 101.1, 103.2, 115.6, 126.1, 127.2, 128.2, 128.9, 141.8, 143.9, 147.1,
151.5, 156.5, 161.5, 164.5; HPLC/MS: 449.3 [MþH]þ. Anal. Calcd for
C24H24N4O3S (448.55): C, 64.27; H, 5.39; N, 12.49. Found: C, 64.15; H,
5.43; N, 12.48.
5.3.14. Ethyl 6-{[(6-tert-butyl-3-cyano-5,6,7,8-tetrahydroquinolin-2-
yl)thio]methyl}-4-(4-methoxyphenyl)-1-methyl-2-oxo-1,2,3,4-
tetrahydropyrimidine-5-carboxylate (3n). White powder, mp
224e226 ꢃC (dec) (acetone), yield 74%. IR (Nujol): 3240 (NH), 2220
5.3.10. Ethyl 6-{[(3-cyano-5,6,7,8-tetrahydroquinolin-2-yl)thio]methyl}-
1-methyl-4-(3-nitrophenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-
carboxylate (3j). White powder, mp 211e212 ꢃC (EtOH/AcOH), yield
(C^N), 1710, 1685 (2C]O) cmꢀ1 1H NMR (400.1 MHz, DMSO-d6),
;
ppm:
d
¼0.92 (9H, s, C(CH3)3), 1.12 (3H, t, 3J 6.8, CH2CH3), 1.36e1.43
70%. IR (KBr): 3408, 3229 (NH), 2221 (C^N), 1707, 1685 (2C]O) cmꢀ1
;
(2H, m, CH), 2.00e2.02 (1H, m, CH), 2.42e2.46 (1H, m, CH),
2.77e2.99 (3H, m, CH), 3.17 (3H, s, NCH3), 3.73 (3H, s, OCH3), 4.06
(2H, q, 3J 6.8, CH2CH3), 4.80 (1H, d, 2J 13.2, SCH), 4.93 (1H, d, 2J 13.2,
SCH), 5.12 (1H, d, 3J 2.4, H-4), 6.87 (2H, d, 3J 7.6, HeAr), 7.16 (2H, d, 3J
7.6, HeAr), 7.95 (1H, s, H-4quinolin-2-yl), 8.01 (1H, br s, HN); 13C NMR
1H NMR (500.1 MHz, DMSO-d6), ppm:
d
¼1.14 (3H, t, 3J 6.9, CH2CH3),
1.71e1.74 (2H, m, CH2), 1.79e1.81 (2H, m, CH2), 2.70e2.72 (2H, m, CH2),
2.81e2.83 (2H, m, CH2), 3.21 (3H, s, NCH3), 4.10 (2H, q, 3J 6.9, CH2CH3),
4.86 (1H, d, 2J 13.4, SCH), 4.92 (1H, d, 2J 13.4, SCH), 5.34 (1H, d, 3J 3.7, H-
4), 7.66 (1H, dd, 3J 7.8, 8.3, HeAr), 7.72 (1H, d, 3J 7.8, HeAr), 7.93 (1H, s,
H-4quinolin-2-yl), 8.10 (1H, s, HeAr), 8.14 (1H, d, 3J¼8.3, HeAr), 8.22 (1H, d,
(100.6 MHz, DMSO-d6), ppm:
d
¼13.8, 23.2, 26.9, 27.6, 28.5, 29.6,
31.9, 33.1, 43.1, 51.7, 54.9, 59.9, 103.2, 105.7, 113.6, 115.5, 127.1, 129.0,
135.2, 142.1, 147.6, 152.8, 155.4, 158.4, 161.5, 164.6; HPLC/MS: 549.3
[MþH]þ. Anal. Calcd for C30H36N4O4S (548.71): C, 65.67; H, 6.61; N,
10.21. Found: C, 65.50; H, 6.54; N, 10.38.
3J¼3.7, HN); 13C NMR (125.8 MHz, DMSO-d6), ppm:
¼14.3, 22.1, 22.4,
d
27.5, 28.3, 30.4, 32.7, 52.4, 60.8, 104.1, 104.8, 116.2, 121.5, 123.1, 129.6,
130.8, 133.2, 142.5, 146.0, 148.3, 150.0, 153.2, 155.9, 162.2, 165.24. Anal.
Calcd for C25H25N5O5S (507.57): C, 59.16; H, 4.96; N, 13.80. Found: C,
59.25; H, 5.01; N, 12.88.
5.3.15. Ethyl 6-{[(3-cyano-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)thio]
methyl}-1-methyl-4-(3-nitrophenyl)-2-oxo-1,2,3,4-tetrahydropyrimi-
dine-5-carboxylate (3o), solvate with DMF 1:1. Off-white powder, mp
120e122 ꢃC (AcOH/DMF), yield 75%. IR (Nujol): 3325 (NH), 2230
5.3.11. Ethyl 4-(4-bromophenyl)-6-{[(3-cyano-5,6,7,8-tetrahydroq-
uinolin-2-yl)thio]methyl}-1-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-
5-carboxylate (3k). Off-white powder, mp 202e204 ꢃC (i-PrOH/DMF/
H2O¼2:1:1), yield 86%. IR (Nujol): 3360 (NH), 2221 (C^N), 1705, 1677
(C^N), 1706e1674 (3C]O) cmꢀ1 1H NMR (500.1 MHz, DMSO-d6),
;
ppm:
d
¼1.14 (3H, t, 3J 6.9, CH2CH3), 2.09e2.12 (2H, m, CH2),
(2C]O) cmꢀ1; 1H NMR (400.1 MHz, DMSO-d6), ppm:
d
¼1.11 (3H, t, 3J
2.65e2.68 (2H, m, CH2), 2.74 (3H, s, DMF), 2.90 (3H, s, DMF),
3.08e3.10 (2H, m, CH2), 3.23 (3H, s, NCH3), 4.11 (2H, q, 3J 6.9, CH2CH3),
4.97 (1H, d, 2J 13.0, SCH), 5.04 (1H, d, 2J 13.0, SCH), 5.36 (1H, br s, H-4),
7.66e7.69 (1H, m, HeAr), 7.74 (1H, d, 3J 7.8, HeAr), 7.96 (1H, s, DMF),
8.11 (1H, s, HeAr), 8.16 (1H, d, 3J 8.3, HeAr), 8.31 (1H, br s, HN), 8.49
7.1, CH2CH3), 1.71e1.72 (2H, m, CH2), 1.78e1.80 (2H, m, CH2),
2.68e2.71 (2H, m, CH2), 2.81e2.84 (2H, m, CH2), 3.17 (3H, s, NCH3),
4.06 (2H, q, 3J 7.1, CH2CH3), 4.80 (1H, d, 2J 13.2, SCH), 4.93 (1H, d, 2J 13.2,
SCH), 5.15 (1H, d, 3J 2.9, H-4), 7.20 (2H, d, 3J 8.3, HeAr), 7.52 (2H, d, 3J
8.3, HeAr), 7.93 (1H, s, H-4quinolin-2-yl), 8.16 (1H, d, 3J 2.9, HN); 13C NMR
(1H, s, H-4quinolin-2-yl); 13C NMR (125.8 MHz, DMSO-d6), ppm:
d¼14.3,
(100.6 MHz, DMSO-d6), ppm:
51.9, 60.1, 103.5, 104.9, 115.6, 120.6, 128.3, 129.0, 131.3, 141.9, 142.6,
d
¼13.9, 21.6, 21.9, 27.0, 27.8, 29.8, 32.2,
21.1, 28.7, 30.5, 31.3, 32.6, 36.3, 37.9, 52.4, 60.9, 105.3, 107.4, 115.3,
121.5, 123.1, 124.8, 130.9, 133.3, 140.3, 145.9, 148.3, 149.3, 153.2, 162.8,