8248
N.A. Liberto et al. / Tetrahedron 69 (2013) 8245e8249
2
H, J¼7.1 Hz, OCH
2
CH
3
), 5.28 (d,1H, J¼3.3 Hz, CH), 7.84e7.41 (m, 2H,
3H, OCH3), 3.95 (q, 2H, J¼7.1 Hz, OCH
2
CH
3
), 5.07 (d,1H, J¼3.0 Hz, CH),
CH, CH), 7.90 (br s, 1H, NH), 8.34e7.91 (m, 2H, CH, CH), 9.37 (s, 1H,
NH). C NMR (75 MHz, DMSO-d 14.7, 18.9, 54.2, 59.9, 99.1, 121.8,
6.85 (d, 2H, J¼8.7 Hz, CH, CH), 7.12 (d, 2H, J¼8.7 Hz, CH, CH), 7.67 (br s,
13
13
6
)
d
1H, NH), 9.15 (s, 1H, NH). C NMR (75 MHz, DMSO-d 14.8, 18.4,
6
) d
ꢁ1
122.6, 130.3, 133.8, 147.0, 147.6, 150.1, 158.2, 167.2. FTIR (ATR, cm ):
53.9, 55.7, 59.8,100.2,114.3,128.1,137.7,148.7,152.8,159.1,166.0. FTIR
ꢁ1
3
1
320, 3212, 3087, 2965,1701,1677,1620,1517,1458,1428,1378,1341,
260, 1215, 1110, 1081, 1003, 904, 819, 789, 735.
(ATR, cm ): 3237, 3105, 2960, 2837, 2160, 1722, 1647, 1613, 1583,
1511, 1366, 1277, 1256, 1218, 1174, 1085, 1030, 953, 834, 778.
4
.2.8. Ethyl 4-(4-chlorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-
4.2.14. Ethyl 6-methyl-2-oxo-4-p-tolyl-1,2,3,4-tetrahydropyrimidine-
pyrimidine-5-carboxylate (4h). Yield (0.748 g, 85%) as a yellow
5-carboxylate (4n). Yield (0.684 g, 83%) as a yellow solid; mp
ꢀ
ꢀ
22 1
ꢀ
ꢀ
24 1
solid; mp 209.4e211.4 C (lit.: 209e211 C).
DMSO-d CH ), 2.23 (s, 3H, CH
), 5.12 (d, 1H, J¼3.3 Hz, CH), 7.77e7.20 (m,
H NMR (300 MHz,
215.4e216.4 C (lit.: 214e216 C).
1.09 (t, 3H, J¼7.1 Hz, OCH CH ), 2.23 (s, 3H, CH
3.37 (q, 2H, J¼7.1 Hz, OCH CH ), 5.09 (d, 1H, J¼3.3 Hz, CH), 7.10 (s,
4H, aromatic), 7.68 (br s,1H, NH), 9.15 (s,1H, NH). C NMR (75 MHz,
H NMR (300 MHz, DMSO-d
6
)
6
)
d
1.04 (t, 3H, J¼7.1 Hz, OCH
CH
H, aromatic), 7.77 (br s, 1H, NH), 9.25 (s, 1H, NH). C NMR
¼14.7, 18.5, 54.1, 59.9, 99.4, 128.8, 129.1, 132.4,
2
3
3
), 3.93
d
2
3
3
), 2.49 (s, 3H, CH
3
),
(
4
(
1
q, 2H, J¼7.1 Hz, OCH
2
3
2
3
13
13
75 MHz, DMSO-d
44.4, 149.4, 152.6, 165.8. FTIR (ATR, cm ): 3232, 3113, 2978, 2169,
6
)
d
DMSO-d
6
)
d
14.8, 18.4, 21.3, 54.3, 59.9, 100.1, 126.8, 129.6, 137.1,
ꢁ
1
ꢁ1
142.6, 148.8, 152.9, 166.1. FTIR (ATR, cm ): 3234, 3109, 2977, 2929,
2166, 1699, 1644, 1459, 1365, 1285, 1216, 1085, 956, 776.
1722, 1699, 1644, 1488, 1289, 1218, 1089, 1012, 958, 779, 684.
4.2.9. 4-(5-(Ethoxycarbonyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyri-
4.2.15. Ethyl 4-(4-(dimethylamino)phenyl)-6-methyl-2-oxo-1,2,3,4-
midin-4-yl)benzoic acid (4i). Yield (0.759 g, 83%) as a yellow solid;
tetrahydropyrimidine-5-carboxylate (4o). Yield (0.548 g, 60%) as
ꢀ
1
ꢀ
ꢀ
23 1
mp 277.1e278.8 C (lit.: not found). H NMR (300 MHz, DMSO-d
1.05 (t, 3H, J¼7.0 Hz, OCH CH ), 2.23 (s, 3H, CH ), 3.96 (q, 2H,
J¼7.0 Hz, OCH CH ), 5.18 (br s,1H, CH), 7.33 (d, 2H, J¼8.3 Hz, CH, CH),
.80 (br s, 1H, NH), 7.89 (d, 2H, J¼8.3 Hz, CH, CH), 9.26 (s, 1H, NH),
0.07 (sl, 1H, OH). 13C NMR (75 MHz, DMSO-d
14.7, 18.5, 54.5,
9.3, 99.3, 127.2, 130.4, 149.5, 150.2, 152.6, 165.8, 167.7, 171.1. FTIR
6
)
a yellow solid; mp 248.5e250.6 C (lit.: 249e250 C).
H NMR
), 2.21 (s, 3H,
CH ), 5.01 (d,
d
2
3
3
(300 MHz, DMSO-d
6
)
d
1.10 (t, 3H, J¼7.1 Hz, OCH
2
CH
3
2
3
CH ), 3.33 (s, 6H, N(CH
3
3
)
2
), 3.97 (q, 2H, J¼7.1 Hz, OCH
2
3
7
1H, J¼3.2 Hz, CH), 6.63 (d, 2H, J¼8.7 Hz, CH, CH), 7.02 (d, 2H, J¼8.7 Hz,
13
1
6
)
d
CH, CH), 7.58 (brs,1H, NH), 9.08 (s,1H, NH). C NMR (75 MHz, DMSO-
5
d
6
)
d
14.8,18.4, 43.4, 53.9, 59.8,100.5,112.9,127.5, 133.3,148.2,150.4,
ꢁ1
ꢁ1
(
ATR, cm ): 3286, 3215, 3074, 2929, 2166, 1702, 1646, 1609, 1579,
421, 1386, 1316, 1274, 1223, 1169, 1123, 1085, 907, 861, 770.
152.9, 166.1. FTIR (ATR, cm ): 3236, 3105, 2968, 2809, 2160, 1700,
1698, 1644, 1617, 1514, 1364, 1216, 1167, 1084, 1024, 990, 781, 659.
1
4
3
.2.10. Ethyl 4-(4-hydroxy-3-methoxyphenyl)-6-methyl-2-oxo-1,2,
4.2.16. Ethyl 4-(furan-2-yl)-6-methyl-2-oxo-1,2,3,4-tetrahyd-
,4-tetrahydropyrimidine-5-carboxylate (4j). Yield (0.806 g, 88%) as
ropyrimidine-5-carboxylate (4p). Yield (0.210 g, 28%) as a yellow
ꢀ
ꢀ
21 1
ꢀ
ꢀ
25 1
a yellow solid; mp 224.9e226.9 C (lit.: 226e228 C).
300 MHz, DMSO-d CH ), 2.21 (s, 3H,
1.07 (t, 3H, J¼7.1 Hz, OCH
CH ), 3.34 (s, 3H, OCH CH ), 5.03 (d,
), 3.97 (q, 2H, J¼7.1 Hz, OCH
H, J¼3.1 Hz, CH), 6.69e6.56 (m, 2H, CH, CH), 6.78 (s, 1H, CH), 7.63
H NMR
solid; mp 215.4e216.4 C (lit.: 214e216 C).
DMSO-d CH ), 2.21 (s, 3H, CH
1.12 (t, 3H, J¼7.1 Hz, OCH
(q, 2H, J¼7.1 Hz, OCH CH ), 5.17 (br s, 1H, CH), 6.07 (br s, 1H,
J¼3.2 Hz, CH), 6.34 (s, 1H, CH), 7.54 (d, 2H, J¼1.8 Hz, CH), 7.75 (br s,
H NMR (300 MHz,
(
6
)
d
2
3
6
)
d
2
3
3
), 4.01
3
3
2
3
2
3
1
13
13
(
br s, 1H, NH), 8.91 (s, 1H, NH), 9.11 (s, 1H, OH). C NMR (75 MHz,
6
1H, NH), 9.25 (s, 1H, NH). C NMR (75 MHz, DMSO-d ) d 14.8, 18.4,
DMSO-d 14.8, 18.4, 54.2, 56.2, 59.8, 100.2, 111.4, 115.9, 118.9,
6
)
d
48.3, 59.9, 97.4, 105.9, 111.0, 142.8, 149.9, 153.1, 156.6, 165.5. FTIR
(ATR, cm ): 3339, 3215, 3095, 2991, 2902, 2162, 1696, 1642, 1455,
ꢁ
1
ꢁ1
136.6, 146.6, 147.9, 148.6, 152.9, 166.1. FTIR (ATR, cm ): 3286, 3215,
3
1
074, 2929, 2166, 1702, 1646, 1609, 1579, 1421, 1386, 1316, 1274,
223, 1169, 1123, 1085, 907, 861, 770.
1417, 1364, 1313, 1295, 1228, 1144, 1096, 1009, 923, 881, 730.
4
.2.17. Ethyl 6-methyl-2-oxo-4-(thiophen-2-yl)-1,2,3,4-tetrahydro-
4
.2.11. Ethyl 4-(4-hydroxy-3,5-dimethoxyphenyl)-6-methyl-2-oxo-
pyrimidine-5-carboxylate (4q). Yield (0.207 g, 26%) as a yellow
ꢀ
ꢀ
19 1
1,2,3,4-tetrahydropyrimidine-5-carboxylate (4k). Yield (0.762 g,
solid; mp 210.0e211.5 C (lit.: 209e210 C).
DMSO-d CH ), 2.21 (s, 3H, CH
1.16 (t, 3H, J¼7.2 Hz, OCH
(q, 2H, J¼7.2 Hz, OCH CH ), 5.40 (d,1H, J¼3.6 Hz, CH), 7.00e6.81 (m,
1H, CH), 7.33 (d,1H, J¼1.3 Hz, CH), 7.35 (d.1H, J¼1.3 Hz, CH), 7.92 (br
H NMR (300 MHz,
ꢀ
1
7
5%) as a yellow solid; mp 169.8e171.7 C (lit.: not found). H NMR
CH ), 2.22 (s, 3H,
), 3.99 (q, 2H, J¼7.1 Hz, OCH CH ), 5.07
6
)
d
2
3
3
), 4.06
(
300 MHz, DMSO-d
6
)
d
1.10 (t, 3H, J¼7.1 Hz, OCH
2
3
2
3
CH
3
), 3.68 (s, 6H, OCH
3
, CH
3
2
3
13
(
1
d, 1H, J¼3.2 Hz, CH), 6.46 (s, 2H, CH, CH), 7.64 (br s, 1H, NH), 8.32 (s,
s,1H, NH), 9.31 (s, 1H, NH). C NMR (75 MHz, DMSO-d
6
) d 14.8,18.4,
13
H, NH), 9.13 (s, 1H, OH). C NMR (75 MHz, DMSO-d
6
) d 14.9, 18.4,
50.0, 60.0, 100.1, 124.2, 125.3, 127.4, 149.5, 149.4, 152.9, 165.7. FTIR
ꢁ
1
5
4.4, 56.6, 59.8, 99.4, 104.4, 135.6, 148.4, 148.7, 152.9, 166.1. FTIR
(ATR, cm ): 3330, 3232, 3105, 2159, 2034, 1696, 1450, 1364, 1225,
1158, 1094, 1023, 778, 706.
ꢁ
1
(
1
ATR, cm ): 3610, 3228, 3119, 2981, 2162, 1726, 1706, 1648, 1517,
426, 1319, 1283, 1217, 1119, 1091, 1024, 777, 698.
4.2.18. Ethyl 4-butyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-
4
.2.12. Ethyl 4-(3-methoxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-
5-carboxylate (4r). Yield (0.276 g, 38%) as a yellow solid; mp
ꢀ
ꢀ
26 1
pyrimidine-5-carboxylate (4l). Yield (0.655 g, 75%) as a yellow solid;
mp 220.4e221.4 C (lit.: 220e221 C). H NMR (300 MHz, DMSO-d
d
164.1e165.7 C (lit.: 165e167 C).
DMSO-d
0.82 (t, 3H, J¼6.6 Hz, CH
11, OCH CH ),1.42e1.25 (m, 2H, CH ), 2.14 (s, 3H, CH
3H, H-4, OCH CH ), 7.32 (br s, 1H, NH), 8.93 (s, 1H, NH). C NMR
(75 MHz, DMSO-d 14.4,14.9,17.7,18.4, 39.6, 50.4, 59.7,100.0,148.9,
H NMR (300 MHz, DMSO-
), 1.22e1.08 (m, 7H, H-10, H-
), 4.09e3.94 (m,
ꢀ
ꢀ
23 1
6
)
d
6
6
)
d
3
1.09 (t, 3H, J¼7.1 Hz, OCH
2
CH
3
), 2.22 (s, 3H, CH
3
), 3.70 (s, 3H, OCH
3
),
2
3
2
3
13
3
.97 (q, 2H, J¼7.1 Hz, OCH CH
2
3
), 5.09 (d,1H, J¼3.2 Hz, CH), 6.86e6.68
2
3
(
1
1
m, 3H, CH, CH, CH), 7.22(t,1H, J¼7.5Hz,CH), 7.72(brs,1H, NH), 9.19(s,
H, NH).13CNMR(75MHz, DMSO-d
14.8,18.4,54.4,55.6,59.9,99.8,
12.8, 113.0, 118.9, 130.3, 146.9, 149.1, 152.8, 159.8, 166.0. FTIR (ATR,
6
)d
ꢁ1
6
)
d
153.5, 166.1. FTIR (ATR, cm ): 3242, 3113, 2932, 2161, 1717, 1700,
1671, 1643, 1462, 1391, 1367, 1332, 1281, 1230, 1219, 1087, 884, 775.
ꢁ1
cm ):3235,3097, 2937, 2841, 2191,1699,1648,1597,1493,1427,1329,
276, 1255, 1222, 1119, 1037, 862, 772, 751.
1
4.2.19. Ethyl 4-ethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-
5
-carboxylate (4s). Yield (0.167 g, 26%) as a yellow solid; mp
ꢀ
ꢀ
27 1
4.2.13. Ethyl 4-(4-methoxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahyd-
181.0e182.3 C (lit.: 180e183 C).
0.81 (t, 3H, J¼6.6 Hz, H-10),1.06 (t, 3H, J¼6.6 Hz, OCH
2H, J¼6.6 and 1.8 Hz, CH ), 2.15 (s, 3H, CH ), 4.11e4.01(m, 3H, H-4,
OCH CH ), 7.20 (br s, 1H, NH), 8.98 (s, 1H, NH). C NMR (75 MHz,
H NMR (300 MHz, DMSO-d
6
)
ropyrimidine-5-carboxylate (4m). Yield (0.745 g, 86%) as a yellow
d
2
CH ),1.17 (q,
3
ꢀ
ꢀ
19 1
solid; mp 203.2e205.1 C (lit.: 203e205 C). H NMR (300 MHz,
DMSO-d CH ), 2.22 (s, 3H, CH3), 3.69 (s,
1.08 (t, 3H, J¼7.1 Hz, OCH
2
3
13
6
)
d
2
3
2
3