Diastereoselective Synthesis of Functionalized Tetrahydropyrimidin-2-thiones
3.76 (s, 3H, OCH3), 3.47-3.44 (m, 7H, OCH3, CH2),
Methyl 4-morpholinyl-6-(4-t-butylphenyl)-2-thi-
3.09-3.06 (m, 1H, CH), 2.91-2.89 (m, 2H, CH2),
2.45 - 2.43 (m, 2H, CH2); 13C NMR (150 MHz,
DMSO-d6) δ: 177.6, 170.6, 147.4, 146.4, 128.8, 119.8,
115.0, 111.0, 73.8, 66.6, 57.4, 55.6, 51.6, 48.1, 47.1; IR
(KBr) ν: 3456, 3200, 3040, 2838, 1732, 1599, 1538,
1521, 1496, 1468, 1438, 1372, 1315, 1281, 1247, 1205,
1190, 1175, 1157, 1128, 1104, 1063, 1034, 996, 929,
oxohexahydropyrimidine-5-carboxylate (1e) White
solid, 74%, m.p. 184-186 ℃; H NMR (600 MHz,
1
DMSO-d6) δ: 8.48 (s, 1H, NH), 8.35 (s, 1H, NH), 7.35
(d, J=7.8 Hz, 2H, ArH), 7.19 (d, J=8.4 Hz, 2H, ArH),
4.62 (d, J=9.6 Hz, 1H, CH), 4.32 (d, J=9.0 Hz, 1H,
CH), 3.45 (s, 3H, OCH3), 3.38 (brs, 4H, CH2), 3.10-
3.07 (m, 1H, CH), 2.82-2.80 (m, 2H, CH2), 2.41-
2.39 (m, 2H, CH2), 1.27 (s, 9H, CH3); 13C NMR (150
MHz, DMSO-d6) δ: 177.6, 170.5, 150.3, 135.8, 126.6,
125.0, 73.2, 66.5, 56.8, 51.7, 47.9, 47.2, 45.8, 34.2, 31.1;
IR (KBr) ν: 3271, 3170, 2969, 2847, 1741, 1555, 1512,
1446, 1416, 1374, 1311, 1264, 1227, 1206, 1178, 1159,
1107, 1068, 1049, 1000, 956, 921, 854, 835, 786, 764
cm−1; HRMS (ESI) calcd for C20H29N3NaO3S ([M+
Na]+): 414.1822, found 414.1824.
910, 859, 828, 788 cm−1; HRMS (ESI) calcd for
+
C17H23N3NaO5S ([M + Na] ): 404.1251, found
404.1253.
Methyl
4-morpholinyl-6-(4-methoxyphenyl)-2-
(1b)
thioxohexahydropyrimidine-5-carboxylate
1
White solid, 53%, m.p. 197-199 ℃; H NMR (600
MHz, DMSO-d6) δ: 8.43 (s, 1H, NH), 8.27 (s, 1H, NH),
7.20 (d, J=7.2 Hz, 2H, ArH), 6.88 (d, J=7.2 Hz, 2H,
ArH), 4.56 (d, J=9.0 Hz, 1H, CH), 4.37 (d, J=9.0 Hz,
1H, CH), 3.74 (s, 3H, OCH3), 3.43-3.37 (m, 7H,
OCH3, CH2), 3.06-3.03 (m, 1H, CH), 2.87 (brs, 2H,
CH2), 2.44 (brs, 2H, CH2); 13C NMR (150 MHz,
DMSO-d6) δ: 177.6, 170.5, 159.0, 130.1, 128.4, 113.6,
73.7, 66.6, 56.9, 55.0, 51.7, 48.2, 47.1; IR (KBr) ν: 3443,
3263, 3179, 2837, 1738, 1614, 1555, 1513, 1443, 1373,
1314, 1287, 1252, 1210, 1177, 1159, 1108, 1069, 1029,
1000, 917, 854, 830, 794, 763 cm−1; HRMS (ESI) calcd
for C17H23N3NaO4S ([M + Na] + ): 388.1301, found
388.1305.
Methyl
4-morpholinyl-6-(3-methoxyphenyl)-2-
(1f)
thioxohexahydropyrimidine-5-carboxylate
1
White solid, 41%, m.p. 172-174℃; H NMR (600
MHz, DMSO-d6) δ: 8.50 (s, 1H, NH), 8.41 (s, 1H, NH),
7.25-7.22 (m, 1H, ArH), 6.86-6.85 (m, 2H, ArH),
6.82 (d, J=7.2 Hz, 1H, ArH), 4.61 (d, J=9.6 Hz, 1H,
CH), 4.32 (d, J=9.0 Hz, 1H, CH), 3.75 (s, 3H, OCH3),
3.46 (s, 3H, OCH3), 3.39 (brs, 4H, CH2), 3.14-3.11 (m,
1H, CH), 2.84-2.82 (m, 2H, CH2), 2.41-2.40 (m, 2H,
CH2); 13C NMR (150 MHz, DMSO-d6) δ: 177.6, 170.5,
159.1, 140.3, 129.3, 119.2, 113.5, 112.5, 73.3, 66.5,
57.1, 55.1, 51.7, 47.7, 47.2; IR (KBr) ν: 3452, 3264,
2970, 2857, 1738, 1601, 1555, 1513, 1490, 1435, 1372,
1315, 1262, 1209, 1162, 1106, 1069, 1032, 1000, 916,
852, 794, 766 cm−1; HRMS (ESI) calcd for C17H23N3-
NaO4S ([M+ Na]+): 388.1301, found 388.1302.
Methyl 4-morpholinyl-6-(4-methxylphenyl)-2-thi-
oxohexahydropyrimidine-5-carboxylate (1c) White
1
solid, 64%, m.p. 188-191 ℃; H NMR (600 MHz,
DMSO-d6) δ: 8.45 (s, 1H, NH), 8.31 (s, 1H, NH), 7.15
-7.14 (m, 4H, ArH), 4.58 (d, J=9.6 Hz, 1H, CH), 4.36
(d, J=9.0 Hz, 1H, CH), 3.44-3.42 (m, 7H, OCH3,
CH2), 3.06-3.03 (m, 1H, CH), 2.85-2.84 (m, 2H,
CH2), 2.43-2.42 (m, 2H, CH2), 2.28 (s, 3H, CH3); 13C
NMR (150 MHz, DMSO-d6) δ: 177.6, 170.5, 137.2,
135.5, 128.9, 127.0, 126.4, 73.5, 66.6, 57.1, 48.1, 47.1,
20.7; IR (KBr) ν: 3440, 3269, 3175, 2851, 1739, 1631,
1554, 1512, 1446, 1375, 1314, 1264, 1210, 1178, 1160,
1109, 1032, 1002, 919, 855, 820, 794, 763 cm−1; HRMS
(ESI) calcd for C17H23N3NaO3S ([M+Na]+): 372.1352;
found 372.1354.
Methyl 4-morpholinyl-6-phenyl-2-thioxohexahy-
dropyrimidine-5-carboxylate (1g) White solid, 47%,
1
m.p. 185-187 ℃; H NMR (600 MHz, DMSO-d6) δ:
8.50 (s, 1H, NH), 8.43 (s, 1H, NH), 7.35-7.32 (m, 2H,
ArH), 7.30-7.27 (m, 3H, ArH), 4.63 (d, J=9.6 Hz, 1H,
CH), 4.35 (d, J=9.0 Hz, 1H, CH), 3.45 (s, 3H, OCH3),
3.39 (brs, 4H, CH2), 3.12-3.09 (m, 1H, CH), 2.83-
2.81 (m, 2H, CH2), 2.42-2.40 (m, 2H, CH2); 13C NMR
(150 MHz, DMSO-d6) δ: 177.7, 170.4, 138.7, 128.3,
128.0, 127.0, 73.3, 66.5, 57.2, 51.7, 47.9, 47.2; IR (KBr)
ν: 3259, 3168, 2956, 2860, 1738, 1554, 1511, 1460,
1434, 1365, 1311, 1265, 1225, 1209, 1170, 1153, 1104,
1069, 1028, 999, 915, 854, 768 cm−1; HRMS (ESI)
calcd for C16H21N3NaO3S ([M+Na]+): 358.1196, found
358.1195.
Methyl 4-morpholinyl-6-(4-isopropylphenyl)-2-
thioxohexahydropyrimidine-5-carboxylate
(1d)
1
White solid, 79%, m.p. 199-201 ℃; H NMR (600
MHz, DMSO-d6) δ: 8.46 (s, 1H, NH), 8.33 (s, 1H, NH),
7.20-7.18 (m, 4H, ArH), 4.61 (d, J=9.0 Hz, 1H, CH),
4.33 (d, J=8.4 Hz, 1H, CH), 3.45 (s, 3H, OCH3), 3.39
(brs, 4H, CH2), 3.09-3.06 (m, 1H, CH), 2.88-2.86 (m,
1H, CH), 2.82-2.80 (m, 2H, CH2), 2.41-2.39 (m, 2H,
CH2), 1.18 (d, J=6.0 Hz, 6H, CH3); 13C NMR (150
MHz, DMSO-d6) δ: 177.6, 170.5, 148.1, 136.2, 126.9,
126.2, 73.2, 66.5, 56.9, 51.7, 47.9, 47.2, 33.1, 23.9, 23.8;
IR (KBr) ν: 3271, 3178, 2965, 2852, 1740, 1554, 1512,
1445, 1375, 1315, 1264, 1208, 1193, 1178, 1159, 1108,
1065, 1001, 957, 920, 854, 836, 789, 764 cm−1; HRMS
(ESI) calcd for C19H27N3NaO3S ([M+Na]+): 400.1665,
found 400.1666.
Methyl 4-morpholinyl-6-(4-fluorophenyl)-2-thi-
oxohexahydropyrimidine-5-carboxylate (1h) White
1
solid, 18%, m.p. 192-194 ℃; H NMR (600 MHz,
DMSO-d6) δ: 8.51 (s, 1H, NH), 8.46 (s, 1H, NH), 7.35
-7.32 (m, 2H, ArH), 7.18-7.15 (m, 2H, ArH), 4.64 (d,
J=9.6 Hz, 1H, CH), 4.34 (d, J=9.0 Hz, 1H, CH), 3.45
(s, 3H, OCH3), 3.40 (brs, 4H, CH2), 3.16-3.13 (m, 1H,
CH), 2.84-2.82 (m, 2H, CH2), 2.41-2.39 (m, 2H,
CH2); 13C NMR (150 MHz, DMSO-d6) δ: 177.6, 170.4,
1
3
161.7 (d, JCF=249.5 Hz), 134.8, 129.3 (d, JCCCF=8.1
2
Hz), 115.0 (d, JCCF=21.6 Hz), 73.3, 66.5, 56.4, 51.7,
Chin. J. Chem. 2014, 32, 172—178
© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
173