A.T. Taher, et al.
Bioorganic Chemistry 89 (2019) 103023
4
.1.3.2. 6-(3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)-4-oxohex-5-
C
6
H
5
), 8.29 (s, 1H, pyrazole–CH). Anal. Calcd for C25
H
25
N
3
O (415): C,
3
enoic acid; (9b). White crystals; yield 75%; mp: 178–180 °C. IR (KBr,
72.27; H, 6.06; N, 10.11. Found, C, 72.29; H, 6.12; N, 10.24.
−
1
cm ): 3446 (OH, broad band), 3055 (CeH aromatic), 2958, 2945
1
(
CeH aliphatic), 1710, 1656 (C]O), 1616 (C]N). H NMR (CDCl
3
)
4.1.4.2. 7-(1,3-Diphenyl-1H-pyrazol-4-yl)-1-morpholinohept-6-ene-1,5-
δppm: 2.74 (t, 2H, CH
.66 (d, 1H, CH]CHeCO), 7.20 (d, 1H, CH]CHeCO), 7.50 (d, 2H,
-C ,6-H), 7.61 (s, 1H, OH, D O exchangeable),
2
CH
2
eCOOH), 2.97 (t, 2H, CH
2
CH
2
eCOOH),
dione; (13b). Yellow powder; yield 90%; mp: 158–160 °C. IR (KBr,
−
1
6
cm ): 3093, 3057 (CeH aromatic), 2962, 2852 (CeH aliphatic), 1716,
13
J = 8.4 Hz, 4-F-C
6
H
4
2
2
1650 (two C]O), 1614 (C]N), 1269, 1064 (CeOeC). C NMR
7
8
.62–7.66 (m, 5H, N-ArH), 7.77 (d, 2H, J = 8.4 Hz, 4-F-C
6
H
4
-C3,5-H),
(CDCl ) δppm: 18.83, 19.04, 24.80, 33.55 (2C), 76.50 (2C), 76.92,
3
.28 (s, 1H, pyrazole–CH). EI-Mass spectrum m/z (relative abundance
77.34, 117.52, 119.29 (2C), 125.48, 126.35, 127.21 (2C), 128.60,
128.72 (2C), 129.48 (2C), 133.36 (2C), 158.16, 187.78, 203.06. Anal.
+
%
): 366 (M+2, 0.32%), 365 (M+1, 0.17%), 364 (M , 0.35%), 77
(
100%). Anal. Calcd for (C21
H
2
17FN O
3
): C, 69.22, H, 4.70, N, 7.69.
Calcd for C26
H
27
N
3
3
O (429): C, 72.70; H, 6.34; N, 9.78. Found, C,
found, C, 69.28, H, 4.74, N, 7.82.
72.75; H, 6.36; N, 9.85.
4
.1.3.3. 6-(3-(4-bromophenyl)-1-phenyl-1H-pyrazol-4-yl)-4-oxohex-5-
4.1.4.3. 6-(1,3-diphenyl-1H-pyrazol-4-yl)-N-(1-hydroxy-2-methylpropan-
enoic acid; (9c). Yellowish white crystals; yield 65%; mp: 158–160 °C.
2-yl)-4-oxohex-5-enamide; (14a). Brownish red crystals; yield 80%; mp:
−
1
−1
IR (KBr, cm ): 3452 (OH, broad band), 3061 (CeH aromatic), 2954,
138–140 °C. IR (KBr, cm ): 3422 (OH), 3290 (NH), 3062 (CeH
1
2
924 (CeH aliphatic), 1710, 1653 (2C]O), 1635 (C]N). H NMR:
aromatic), 2954, 2854 (CeH aliphatic), 1739, 1663 (two C]O), 1643
1
(
DMSO‑d
6
)
δppm: 2.10 (t, 2H, CH
2
CH
2
eCOOH), 2.74 (t, 2H,
(C]N). H NMR (CDCl
3
) δppm: 1.24–1.37 (m, 6H, two CH ), 2.38 (s,
3
CH
2
CH
2
eCOOH), 6.50 (s, 1H, CH]CHeCO), 6.79 (s, 1H,
1H, OH,
CH CH eCONHe), 2.98 (t, 2H, J = 6.1 Hz, CH
(s, 2H, CH OH), 5.80 (s, 1H, NH, D O exchangeable), 6.60 (s, 1H,
CH]CHeCO), 6.64 (s, 1H, CH]CHeCO), 7.36 (d, 2H, J = 7.0 Hz,
-C3,5-H), 7.45 (d, 2H, J = 7.8 Hz, N-C -C3,5-H), 7.49 (d, 2H,
J = 7.0 Hz, C -C2,6-H), 7.53–7.76 (m, 2H, C -C -H, N-C -C -H),
D
2
O
exchangeable), 2.65 (t, 2H, J = 6.1 Hz,
CH]CHeCO), 7.24–7.50 (m, 5H, N-ArH), 7.57–7.90 (m, 4H, 3-Br-
2
2
2
CH eCOeNHe), 3.62
2
ArH), 7.92 (s, 1H, pyrazole–CH), 8.15 (s, 1H, OH, D
2
O exchangeable).
2
2
EI-Mass spectrum m/z (relative abundance %): 427 (M+2, 0.85%), 426
+
(
(
M+1, 1.07%), 425 (M
,
0.59%), 55 (100%). Anal. Calcd for
C
6
H
4
6 5
H
C
21
H
17BrN
2
O
3
): C, 59.31, H, 4.03, N, 6.59. found, C, 59.35, H, 4.04,
6
H
4
6
H
4
4
6
H
5
4
N, 6.68.
7.79 (d, 2H, J = 7.8 Hz, N-C
6
H -C2,6-H), 8.28 (s, 1H, pyrazole–CH). EI-
5
Mass spectrum m/z (relative abundance %): 418.00 (M+1, 0.12),
+
4
.1.3.4. 7-(1,3-diphenyl-1H-pyrazol-4-yl)-5-oxohept-6-enoic acid; (9d).
417.00 (M , 0.18), 57.00 (100). Anal. Calcd for C25
H
27
N
3
O (417):
3
−
1
Yellow crystals; yield 80%; mp: 158–160 °C. IR (KBr, cm ): 3441 (OH,
C, 71.92; H, 6.52; N, 10.06. Found, C, 71.89; H, 6.56; N, 10.12.
broad band), 3055 (CeH aromatic), 2924, 2893 (CeH aliphatic), 1712,
1
1
651 (2C]O), 1620 (C]N). H NMR : (CDCl
3
) δppm: 1.99 (t, 2H,
4.1.4.4. N-(1-hydroxy-2-methylpropan-2-yl)-5-oxo-7-(1,3-diphenyl-1H-
CH
.71 (t, 2H, J = 7.2 Hz, CH
CH]CHeCO), 6.63 (d, 1H, CH]CHeCO), 7.33 (s, 1H, OH, D
exchangeable), 7.36–7.50 (m, 1H, C -C4-H), 7.51–7.61 (m, 5H, N-
ArH), 7.67 (d, 2H, C -C3,5-H), 7.78 (d, 2H, C -C ,6-H), 8.28 (s,
H, pyrazole–CH). EI-Mass spectrum m/z (relative abundance %): 362
2
CH
2
CH
2
eCOOH), 2.46 (t, 2H, J = 7.2 Hz, CH
2
CH
2
CH
2
eCOOH),
pyrazol-4-yl)hept-6-enamide; (14b). Yellowish white crystals; yield
−1
2
2
CH CH eCOOH, 6.57 (d, 1H,
2
2
80%; mp: 160–162 °C. IR (KBr, cm ): 3421 (OH), 3286 (NH), 3066
2
O
(CeH aromatic), 2966, 2873 (CeH aliphatic), 1730, 1662 (two C]O),
1
6
H
5
1639 (C]N). H NMR of compound δppm: 1.29–1.37 (m, 6H, two
6
H
5
6
H
5
2
CH
CH
CH
CH
3
2
2
2
), 1.68 (s, 1H, OH, D
2
O exchangeable), 1.97–2.01 (m , 2H,
1
CH
CH
CH
2
CH
2
CH
2
CH
2
2
2
e
COeNHe),
eCOeNHe),
eCOeNHe), 3.59 (s, 2H, CH
2.24
(t,
2H,
2H,
J = 6.9 Hz,
J = 6.9 Hz,
+
(
M+2, 0.36%), 361 (M+1, 1.04%), 360 (M , 2.01%), 77 (100%).
2.69
(t,
Anal. Calcd for (C22
H
20
N
2
O
3
): C, 73.32, H, 5.59, N, 7.77. found, C,
2
OH), 4.98 (s, 1H, NH, D
2
O
7
3.10, H, 6.19, N, 7.88.
exchangeable), 6.58 (s, 1H, CH]CHeCO), 6.63 (s, 1H, CH]CHeCO),
7
.34–7.39 (m, 5H, C
7.61–7.68 (m, 1H, N-C
H), 8.30 (s, 1H, pyrazole–CH). Anal. Calcd for C26
72.37; H, 6.77; N, 9.74. Found, C, 72.40; H, 6.81; N, 9.85.
6
6
H
5
), 7.49 (d, 2H, J = 7.8 Hz, N-C
6
H -C3,5-H),
5
6
4.1.4. General procedure of synthesis of compounds (13–15)
H
5
-C -H), 7.79 (d, 2H, J = 7.8 Hz, N-C
4
H
5
-C2,6-
A mixture of triethylamine (1.01 g, 1.39 mL, 0.01 mol), dry methy-
H
29
N
3
3
O (431): C,
lene chloride (10 mL) and the appropriate pyrazole derivative 9aor 9d
(
0.01 mol) was stirred in an ice bath at −10 °C for 15 min. Ethyl
chloroformate (1.09 g, 0.78 mL, 0.01 mol) was added dropwise while
stirring. To an ice cooled solution of the appropriate amine; (namely:
morpholine or 2-amino-2-methyl-1-propanol) or N-(4-hydroxy phenyl)
acetamide (0.01 mol) in dry methylene chloride (10 mL) was added
dropwise over a period of 15 min and stirring was continued for 24 h at
room temperature. The solvent was evaporated under vacuum till
dryness and cooled. The residue was extracted twice with ethyl acetate
4.1.4.5. 4-Acetamidophenyl4-oxo-6-(1,3-diphenyl-1H-pyrazol-4-yl)hex-5-
enoate; (15a). Buff powder; yield 85%; mp: 158–160 °C. IR (KBr,
−1
cm ): 3317, 3209 (NH), 3059 (CeH aromatic), 2986, 2916 (CeH
aliphatic), 1755, 1700, 1658 (three C]O), 1612 (C]N), 1276, 1060
1
(CeOeC). H NMR δppm: 2.14 (s, 3H, NHCOCH
3
), 2.91 (t, 2H,
J = 6.3 Hz, CH
6.62 (s, 1H, CH]CHeCO), 6.67 (s, 1H, CH]CHeCO), 7.04 (d, 2H,
J = 8.7 Hz, anilide-C -C3,5-H), 7.27–7.38 (m, 5H, C ), 7.45 (s, 1H,
NH, D O exchangeable), 7.65–7.70 (m, 5H, N-C ), 7.79 (d, 2H,
J = 8.7 Hz, anilide-C -C2,6-H), 8.29 (s, 1H, pyrazole-CH). Anal. Calcd
for C29 (479): C, 72.64; H, 5.25; N, 8.76. Found, C, 72.71; H,
5.27; N, 8.84.
2
CH
2
COOe), 3.04 (t, 2H, J = 6.3 Hz, CH
2
CH
2
COOe),
(
(
20 mL). The organic layer was washed with 10% hydrochloric acid
15 mL), then washed with 5% sodium hydroxide (15 mL). The organic
6
H
4
6 5
6 5
H
H
2
layer was separated and dried over anhydrous sodium sulphate then
filtered. The filtrate was evaporated under reduced pressure till half its
volume and cooled. The crystalline solid was collected and re-
crystallized from ethanol.
H
6 4
H
25
N
3 4
O
4
.1.4.6. 4-Acetamidophenyl-7-(1,3-diphenyl-1H-pyrazol-4-yl)-5-oxohept-
4
.1.4.1. 1-Morpholino-6-(1,3-diphenyl-1H-pyrazol-4-yl)hex-5-ene-1,4-
6-enoate; (15b). Brownish yellow powder; yield 90%; mp: 156–158 °C.
−1
dione; (13a). Orange powder; yield 90%; mp: 78–80 °C. IR (KBr,
IR (KBr, cm ): 3387 (NH), 3066 (CeH aromatic), 2962 (CeH
−
1
cm ): 3061 (CeH aromatic), 2960, 2856 (CeH aliphatic), 1722,
aliphatic), 1747, 1700, 1678 (three C]O), 1597 (C]N), 1270, 1060
1
1
1
685 (two C]O), 1635 (C]N), 1273, 1064 (CeOeC). H NMR
(CeOeC). H NMR (CDCl
3
) δppm: 2.06–2.13 (m, 2H, CH
2
2
CH
2
2
CH
2
2
COO),
COO),
(
CDCl
3
) δppm: 2.69 (t, 2H, J = 6.3 Hz, CH
H, J = 6.3 Hz, CH CH eCOeNe), 3.46–3.57 (m, 4H, morph-C2,6-H),
.62–3.73 (m, 4H, morph-C3,5-H), 6.64 (s, 1H, CH]CHeCO), 6.69 (s,
H, CH]CHeCO), 7.25–7.50 (m, 5H, C ), 7.53–7.80 (m, 5H, N-
2
CH
2
eCOeNe), 3.00 (t,
2.18 (s, 3H, NHCOCH
2.77 (t, 2H, J = 7.05 Hz, CH
6.65 (s, 1H, CH]CHeCO), 7.23 (s, 1H, NH, D
7.34–7.39 (m, 3H, -C3,4,5-H), 7.45–7.52 (m, 5H, N-C
3
), 2.65 (t, 2H, J = 7.05 Hz, CH
CH CH
CH
CH
2
3
1
2
2
2
2
2
COO), 6.59 (s, 1H, CH]CHeCO),
2
O exchangeable),
),
6
H
5
C
6
H
4
H
6 5
10