Y. N. Mabkhot, N. A. Kaal, S. Alterary, M. S. Mubarak, A. Alsayari, and A. Bin Muhsinah
Vol 000
Yield 42%; mp 130–132°C. IR (KBr, cmÀ1) νmax = 3468,
3241 (NH), 2975, 2926, 1648 (C═O), 1582 (C═N),
1532, 1486, 1402, 1370, 1226, 1191, 1076, 1030. 1H-
NMR (300 MHz, CDCl3) δ: 1.30 (t, 3H, J = 6.1 Hz,
CH2CH3), 2.40 (s, 3H, CH3), 4.29 (q, 2H, J = 6.1 Hz,
CH2CH3), 6.64 (s, 1H, imidazole–NH), 6.91–7.58 (m,
9H, Ar–H), 7.61 (s, 1H, imidazole–H), 10.19 (s, 1H,
NH–Ph) ppm. 13C-NMR (75 MHz, CDCl3) δ: 13.4
(CH2CH3), 15.4 (CH3), 59.7 (CH2CH3), 109.6, 110.7
(2C), 111.2, 115.9, 119.1 (2C), 120.5, 122.2 (2C), 122.7,
130.0, 131.7 (2C), 132.1, 135.9, 138.5, 143.9, 153.5,
160.7, 164.7 (Ar–C), 189.1 (C═O) ppm. MS (EIMS) m/z:
417 (M++1, 10), 416 (M+, 60), 197 (100), 182 (30), 155
(20), 91 (95). Anal. calcd. for C23H20N4O2S (416.50): N,
13.45; H, 4.84; C, 66.33. Found: N, 13.31; H, 4.59; C,
66.15%.
J = 6.0 Hz, CH2CH3), 2.46 (s, 3H, CH3), 3.75 (s, 3H, O–
CH3), 3.80 (s, 2H, CH2), 4.36 (q, 2H, J = 6.0 Hz,
CH2CH3), 6.60–7.55 (m, 9H, Ar–H), 10.65 (s, 1H, NH),
10.97 (s, 1H, NH–CH2) ppm. Anal. calcd. for
C23H24N2O4S (424.51): N, 6.60; H, 5.70; C, 65.07.
Found: N, 6.46; H, 5.61; C, 64.94%.
Synthesis of compounds 9a–c. The following procedure
was employed for the synthesis of compounds 9a–c:
Compound 2 (0.382 g, 1 mmol) was treated with the
appropriate (1 mmol) urea derivatives in (10 mL)
ethanol as solvent and in the presence of trimethylamine
as a catalyst. The mixture was refluxed at 80°C for 8 h.
The solid was filtered on hot and recrystallized from
ethanol to afford the desired product. Using the same
general procedure, the following compounds were
prepared.
5-(2-Amino-oxazol-5-yl)-4-methyl-2-phenylamino-
thiophene-3-carboxylic acid ethyl ester (9a). Yield (26%);
Synthesis of compounds 7a–c.
These series of
thiophene compounds were produced according to the
following general method: A mixture of (0.382 g,
1 mmol) of compound 2 and (0093 g, 1 mmol) aniline,
(0.127 g, 1 mmol) p-chloroaniline, or (0.123 g, 1 mmol)
p-anisidine in (10 mL) ethanol and in the presence of
TEA (Et3N) was boiled under reflux for 8 h. The product
was filtered on hot and washed with cold ethanol to give
the desired derivatives 7a–c in a pure form. All physical
features and data of spectra of all derivatives 7a–c were
beige powder; mp 128–130°C. IR (KBr, cmÀ1
)
νmax = 3427, 3142 (NH and NH2), 3091, 1656 (C═O),
1
1586 (C═N). H-NMR (300 MHz, DMF-d7) δ: 1.39 (t,
3H, J = 6.0 Hz, CH2CH3), 2.48 (s, 3H, CH3), 4.38 (q,
2H, J = 6.1 Hz, CH2CH3), 4.92 (s, br, 2H NH2), 7.50–
7.70 (m, 6H, Ar–H + oxazole–H), 10.43 (s, 1H, NH)
ppm. 13C-NMR (75 MHz, CDCl3) δ: 13.2 (CH2CH3),
16.1 (CH3), 60.8 (CH2CH3), 110.1, 110.4, 111.4, 122.9,
123.0, 130.1, 132.8, 140.0, 145.0, 151.0, 160.6 (Ar–C),
189.8 (C═O) ppm. Anal. calcd. for C17H17N3O3S
(343.40): N, 12.24; H, 4.99; C, 59.46. Found: N, 12.10;
recorded below.
4-Methyl-2-phenylamino-5-(2-phenylamino-acetyl)-
thiophene-3-carboxylic acid ethyl ester (7a). Yield (72%);
beige powder; mp 108–110°C. IR (KBr, cmÀ1
)
H, 4.85; C, 59.31%.
5-(2-Amino-thiazol-5-yl)-4-methyl-2-phenylamino-
νmax = 3317, 3465 (NH), 2976, 2928, 1651, 1629 (C═O),
1585, 1547, 1488, 1399, 1374, 1282, 1244, 1195, 1078,
1026. 1H-NMR (300 MHz, CDCl3) δ: 1.41 (t, 3H,
J = 6.1 Hz, CH2CH3), 2.47 (s, 3H, CH3), 3.63 (s, 2H,
CH2), 4.36 (q, 2H, J = 6.1 Hz, CH2CH3), 7.05–7.50 (m,
10H, Ar–H), 10.30 (s, 1H, NH–CH2), 10.66 (s, 1H, NH–
Ph) ppm. MS (EIMS) m/z: 396 (M++1, 5), 395 (M+, 10),
86 (100). Anal. calcd. for C22H22N2O3S (394.49): N,
7.10; H, 5.62; C, 66.98. Found: N, 7.01; H, 5.53; C,
thiophene-3-carboxylic acid ethyl ester (9b). Yield (96%);
beige powder; mp 210–212°C. IR (KBr, cmÀ1
)
νmax = 3399, 3243, 3150 (NH and NH2), 2974, 2926,
1645 (C═O), 1586 (C═N), 1525, 1493, 1402, 1373,
1343, 1244, 1197, 1113, 1073. 1H-NMR (300 MHz,
CDCl3) δ: 1.29 (t, 3H, J = 6.1 Hz, CH2CH3), 2.45 (s, 3H,
CH3), 4.26 (q, 2H, J = 6.1 Hz, CH2CH3), 6.52 (s, 2H,
NH2), 7.13 (s, 1H, thiazole–CH), 7.26–7.55 (m, 5H, Ar–
H), 9.92 (s, 1H, NH–Ph) ppm. 13C-NMR (75 MHz,
CDCl3) δ: 13.2 (CH2CH3), 15.4 (CH3), 59.6 (CH2CH3),
100.5, 110.0, 113.9, 116.2, 118.0, 120.1, 120.4, 130.1,
131.8, 140.0, 140.2, 164.9 (Ar–C), 166.9 (C═O) ppm.
MS (EIMS) m/z: 359 (M+, 10), 344 (35), 327 (15), 172
(25), 140 (50), 43 (100), 43 (100%). Anal. calcd. for
C17H17N3O2S2 (359.47): N, 11.69; H, 4.77; C, 56.80.
66.79%.
5-[2-(4-Chloro-phenylamino)-acetyl]-4-methyl-2-
phenylamino-thiophene-3-carboxylic acid ethyl ester (7b).
Yield (36%); beige powder; mp 202–204°C. IR (KBr,
cmÀ1) νmax = 3450, 3320 (NH), 1654 (C═O), 1616 (C═).
1H-NMR (300 MHz, CDCl3) δ: 1.40 (t, 3H, J = 6.0 Hz,
CH2CH3), 2.74 (s, 3H, CH3), 3.75 (s, 2H, CH2), 4.36 (q,
2H, J = 6.0 Hz, CH2CH3), 6.53–7.55 (m, 9H, Ar–H),
10.65 (s, 1H, NH), 10.92 (s, 1H, NH–CH2) ppm. Anal.
calcd. for C22H21ClN2O3S (428.93): N, 6.53; H, 4.94; C,
Found: N, 11.44; H, 4.63; C, 56.65%.
5-(2-Amino-3H-imidazol-4-yl)-4-methyl-2-phenylamino-
thiophene-3-carboxylic acid ethyl ester (9c). Yield (16%);
pale beige powder; mp 90–92°C. IR (KBr, cmÀ1
)
61.60. Found: N, 6.34; H, 4.75; C, 61.52%.
5-[2-(4-Methoxy-phenylamino)-acetyl]-4-methyl-2-
phenylamino-thiophene-3-carboxylic acid ethyl ester (7c).
νmax = 3404, 3216, 3165 (NH and NH2), 3165, 1656
1
(C═O), 1618 (C═N). H-NMR (300 MHz, DMSO-d6) δ:
1.41 (t, 3H, J = 6.0 Hz, CH2CH3), 2.74 (s, 3H, CH3),
4.36 (q, 2H, J = 6.0 Hz, CH2CH3), 4.93 (s, br, NH2),
7.13–7.51 (m, 5H, Ar–H), 10.16, 10.64 (s, 1H, NH) ppm.
Yield (36%); greenish yellow powder; mp 184–186°C.
IR (KBr, cmÀ1) νmax = 3451, 3348 (NH), 1650 (C═O),
1
1632 (C═O). H-NMR (300 MHz, CDCl3) δ: 1.42 (t, 3H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet