S.K. Sharma et al. / European Journal of Medicinal Chemistry 48 (2012) 16e25
23
40 ꢁC. The reaction mixture was then poured onto chipped ice
which produced a clear red solution. This was made basic with the
addition of 200 mL of 5 N sodium hydroxide which allowed the
separation of a yellow solid. This was diluted by the addition of
200 mL hot water and, after cooling the product was removed by
filtration and washed with cold water. The product was recrystal-
lized from aqueous dimethylformamide to yield 1H-indole-3-
carbaldehyde as faint orange needles.
Compound 4: Mp (ꢁC) 408e410; Yield e 80.10%; IR (KBr pellets)
cmꢀ1 3475 (NH str., indole), 1637 (C]O str., 30 amide), 1296 (CeN
str., aryl 20 amine), 1603(C]O str., oxo), 3098 (CH str., tetrahy-
dropyrimidine),1340(CeOeC str., ester),1247 (CH in plane bending,
Ar.), 1561 (C]C skeletal str., Ar.) 744 (CeCl), 1502(NeO str. NO2); 1H
NMR (MEOD): d 6.99e8.05 (m, 9H, ArH), 1.30 (t, 3H, CH3 of OC2H5),
3.66 (s, 1H, NH 20 amine), 3.65e3.33 (m, CH2 of OCH2CH3) Anal.
Calculated for C24H22ClN5O6: C, 56.31; H, 4.33; N, 13.68; Found: C,
56.26; H, 4.34; N, 13.75.
4.1.2. General procedure for the synthesis of 1-(2-chloro-acetyl)-
1H-indole-3-carbaldehyde
Compound 5: Mp (ꢁC) 402e404; Yield e 76.40%; IR (KBr pellets)
cmꢀ11658 (C]O str., 30 amide) 1335 (CeOeC str., ester), 1516 (C]C
A mixture of 1H-indole-3-carbaldehyde (0.1 mol), choloroacetyl
chloride (0.1 mol), in ethanol was heated under reflux for 10e12 h.
TLC was used to monitor the progress of the reaction. After
completion of reaction, the reaction mixture was poured on
crushed ice and filtered under suction; the precipitate thus ob-
tained was washed with water and recrystallized from ethanol.
skeletal str., Ar.); 1H NMR (MEOD):
d 7.99e8.06 (m, 9H, ArH) 1.30 (t,
3H, CH3 of OC2H5), 2.24 (s, 3H, CH3 Ar), 4.09 (s, 1H, NH 20 amine),
3.46e3.65 (m, CH2 of OCH2CH3) Anal. Calculated for C25H25N5O6: C,
61.09; H, 5.13; N, 14.25; Found: C, 6.01; H, 5.16; N, 14.28.
Compound 6: Mp (ꢁC) 428e430; Yield e 82.33%; IR (KBr pellets)
cmꢀ1 1612 (C]O str., 30 amide), 1205 (CeN str., aryl 20 amine),
1335(CeOeC str., ester), 1521 (C]C skeletal str., Ar.); 1H NMR
4.1.3. General procedure for the synthesis of 1-(2-substituted-
phenylamino-acetyl)-1H-indole-3-carbaldehyde
(MEOD): d 7.24e7.99 (m, 9H, ArH), 1.30 (t, 3H, CH3 of OC2H5), 2.23
(s, 3H, CH3 Ar.), 4.24e4.25 (m, 2H, CH2 of OC2H5), 4.24 (s, 1H, NH 20
amine); Anal. Calculated for C25H25N5O5S: C, 59.16; H, 4.96; N,
13.80; Found: C, 59.21; H, 4.98; N, 13.88.
A
mixture of 1-(2-chloro-acetyl)-1H-indole-3-carbaldehyde
(0.1 mol) and corresponding aniline (0.1 mol), in ethanol was
heated under reflux for 12e15 h. TLC was used to monitor the
progress of the reaction. After completion of reaction, the reaction
mixture was poured on crushed ice and filtered under suction, the
precipitate thus obtained was washed with water and recrystal-
lized from ethanol.
Compound 7: Mp (ꢁC) 386e388; Yield e 78.25%; IR (KBr pellets)
cmꢀ1 3391 (NH str., indole), 1655 (C]O str., 30 amide), 1202 (CeN
str., aryl 20 amine), 1615 (C]O str., oxo), 1341 (CeOeC str., ester),
1458 (C]C skeletal str., Ar.); 1H NMR (MEOD):
d 6.65e8.04 (m, 10H,
ArH), 2.86e3.32 (m, CH2 of OCH2CH3), 4.89 (s, 1H, NH 20 amine);
Anal. Calculated for C24H23N5O6: C, 60.37; H, 4.86; N, 14.67; Found:
C, 60.38; H, 3.84; N, 14.74.
4.1.4. General procedure for the synthesis of 6-methyl-4-[1-(2-
substituted- phenylamino-acetyl)-1H-indol-3-yl]-2-oxo/thioxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl esters (1e16)
A mixture of 1-(2-substituted-phenylamino-acetyl)-1H-indole-
3-carbaldehyde (0.1 mol), urea or thiourea (0.2 mol), ethyl-
acetoacetate (0.1 mol) in ethanol was heated under reflux for
12e15 h in the presence of hydrochloric acid. TLC was used to
monitor the progress of the reaction. After completion of reaction,
the reaction mixture was poured on crushed ice and filtered under
suction, the precipitate was washed with water. The pure product
was obtained by recrystallization from ethanol.
Compound 8: Mp (ꢁC) 412e414; Yield e 79.00%; IR (KBr pellets)
cmꢀ1 1615 (C]O str., 30 amide) 1457 (C]S str., thioxo), 1345
(CeOeC str., ester); 1H NMR (MEOD):
d 6.65e8.57 (m, 10H, ArH),
1.32e1.54 (t, 3H, CH3 of OC2H5), 2.68e3.02 (m, CH2 of OCH2CH3)
Anal. Calculated for C24H23N5O5S: C, 58.41; H, 4.70; N, 14.19; Found:
C, 58.38; H, 4.74; N, 14.28.
Compound 9: Mp (ꢁC) 417e419; Yield e 82.50%; IR (KBr pellets)
cmꢀ1 3394 (NH str., indole), 1614 (C]O str., 30 amide), 1257 (CeN
str., aryl 20 amine), 1425(C]S str., thioxo), 3061(CH str., tetrahy-
dropyrimidine),1339(CeOeC str., ester),1257 (CH in plane bending,
Ar.), 1552 (C]C skeletal str., Ar.), 1525 (NeO str. NO2); 1H NMR
Compound 1: Mp (ꢁC) 412e414; Yield e 84.24%; IR (KBr pellets)
cmꢀ1 3398 (NH str., indole), 1612 (C]O str., 30 amide), 1268 (CeN
str., aryl 20 amine), 1420 (C]S str., thioxo), 2939 (CH str., tetrahy-
dropyrimidine), 1322 (CeOeC str.), 1236 (CH in plane bending, Ar.),
(MEOD): d 6.81e8.36 (m, 10H, ArH),1.28e1.56 (t, 3H, CH3 of OC2H5),
2.24e3.02 (m, CH2 of OCH2CH3) Anal. Calculated for C24H23N5O5S:
C, 58.41; H, 4.70; N, 14.19; Found: C, 58.48; H, 4.71; N, 14.18.
Compound 10: Mp (ꢁC) 424e426; Yield e 83.40%; IR (KBr pellets)
cmꢀ1 3394 (NH str., indole), 1617 (C]O str., 30 amide), 1235 (CeN
str., aryl 20 amine), 1599 (C]O str., oxo), 3175 (CH str., tetrahy-
dropyrimidine), 1344 (CeOeC str., ester), 1235 (CH in plane
1521 (C]C skeletal str., Ar.); 1H NMR (MEOD):
d 1.27e1.308 (t, 3H,
CH3 of OC2H5), 3.92e4.07 (m, CH2 of OCH2CH3), 2.19 (s, 2H eNH
pyrimidine), 4.03 (s, 1H, NH 20 amine); Anal. Calculated for
C24H24N4O3S: C, 64.27; H, 5.39; N, 12.49; Found: C, 64.30; H, 5.35;
N, 12.48.
bending, Ar.), 1551 (C]C skeletal str., Ar.) 1524 (NeO str. NO2); 1
NMR (MEOD): 6.88e8.90 (m, 10H, ArH), 1.24e1.42 (t, 3H, CH3 of
H
Compound 2: Mp (ꢁC) 398e400; Yield e 81.00%; IR (KBr pellets)
cmꢀ1 3397 (NH str., indole), 1613 (C]O str., 30 amide), 1269 (CeN
str., aryl 20 amine), 1458 (C]S str., thioxo), 1322 (CeOeC str.), 1236
(CH in plane bending, Ar.), 1523 (C]C skeletal str., Ar.) 742 (CeCl);
d
OC2H5), 2.01e2.88 (m, CH2 of OCH2CH3); Anal. Calculated for
C24H23N5O6: C, 60.37; H, 4.86; N, 14.67; Found: C, 60.33; H, 4.84; N,
14.70.
1H NMR (MEOD):
d
6.90e7.88 (m, 9H, ArH), 1.25e1.29 (t, 3H, CH3 of
Compound 11: Mp (ꢁC) 406e408; Yield e 82.55%; IR (KBr pellets)
cmꢀ1 3353 (NH str., indole), 1618 (C]O str., 30 amide), 1304 (CeN
str., aryl 20 amine), 1597 (C]O str., oxo), 3053 (CH str., tetrahy-
dropyrimidine), 1329 (CeOeC str., ester), 1180 (CH in plane
bending, Ar.), 1597 (C]C skeletal str., Ar.) 1524 (NeO str. NO2); 1H
OC2H5), 3.33e3.64 (m, CH2 of OCH2CH3); Anal. Calculated for
C24H23ClN4O3S: C, 59.68; H, 4.80; N, 11.60; Found: C, 59.60; H, 4.84;
N, 11.58.
Compound 3: Mp (ꢁC) 420e422; Yield e 78.20%; IR (KBr pellets)
cmꢀ1 3474 (NH str., indole), 1636 (C]O str., 30 amide), 1268 (CeN
str., aryl 20 amine), 1420 (C]S str., thioxo), 3091 (CH str., tetrahy-
dropyrimidine),1340 (CeOeC str., ester),1247 (CH in plane bending,
Ar.), 1561 (C]C skeletal str., Ar.), 743 (CeCl),1502(NeO str. NO2); 1H
NMR (MEOD):
d 6.83e8.03 (m, 10H, ArH), 1.29e1.56 (t, 3H, CH3 of
OC2H5), 2.87e3.50 (m, CH2 of OCH2CH3); Anal. Calculated for
C24H23N5O6: C, 60.37; H, 4.86; N, 14.67; Found: C, 60.39; H, 4.84; N,
14.68.
NMR (MEOD):
d
6.99e8.04 (m, 9H, ArH), 1.30 (t, 3H, CH3 of OC2H5),
Compound 12: Mp (ꢁC) 392e394; Yield e 81.30%; IR (KBr pellets)
cmꢀ1 3395 (NH str., indole), 1694 (C]O str., 30 amide), 1237 (CeN
str., aryl 20 amine), 1617(C]O str., oxo), 1342(CeOeC str., ester),
1237 (CH in plane bending, Ar.), 1548 (C]C skeletal str., Ar.); 1H
2.05 (s, 2H, NH pyrimidine), 3.66 (s, 1H, NH 20 amine), 3.28e3.33
(m, CH2 of OCH2CH3); Anal. Calculated for C24H22ClN5O5S: C, 54.60;
H, 4.20; N, 13.26; Found: C, 54.63; H, 4.19; N, 13.25.