K.M. Amin et al.
Bioorganic Chemistry 110 (2021) 104792
3′,5′ Ar), 7.48 (d, 2H, J = 6.7 Hz, H-2′,6′ Ar), 7.78 (d, 1H, J = 8.8 Hz, H-5
Ar), 10.90 (s, 1H, NH, D2O exchang.). 13C NMR (DMSO‑d6) δ ppm: 26.75
(CH2CH2), 32.88, 33.72 (CH2CO), 70.30 (OCH2), 101.91, 113.23,
113.66, 123.97, 126.65, 127.52, 128.29, 128.65, 128.85, 129.00,
136.76, 139.07, 145.12, 153.86 (aromatic carbons), 161.18, 167.26,
4.1.8. General procedure for synthesis of compounds (13a-c)
A mixture of carboxazide compound 10 (0.32 g, 1 mmol), ethyl
acetoacetate (0.12 mL, 1 mmol), acetylacetone (0.1 mL, 1 mmol) or
ethoxymethylene malononitrile (0.12 g, 1 mmol), respectively and
anhydrous sodium acetate (0.16 g, 2 mmol) in absolute ethanol (30 mL)
was refluxed for 48 h. The precipitated solid was filtered, washed with
water to remove excess sodium acetate, dried and crystalized from ab-
solute ethanol.
–
174.52 (4C O). Anal. Calcd. for C22H18N2O6 (406.39) C, 65.02; H,
–
4.46; N, 6.89; Found C, 64.87; H, 4.78; N, 7.13.
4.1.6.2. 2-(7-Benzyloxy-2-oxo-2H-chromen-4-yl)-N-(2,5-dioxo-2,5-dihy-
dro-1H-pyrrol-1-yl)acetamide (11b). Buff powder, (yield 89%), m.p.
115–7 ◦C. IR (KBr, νmax/cmꢀ 1): 3421 (NH), 3032 (CH aromatic), 2931,
4.1.8.1. 1-[2-(7-Benzyloxy-2-oxo-2H-chromen-4-yl)acetyl]-3-methyl-1,2-
dihydropyrazol-5-one (13a). Buff powder, (yield 60%), m.p. 113–5 ◦C.
IR (KBr, νmax/cmꢀ 1): 3414 (NH), 3040 (CH aromatic), 2974, 2839 (CH
2877 (CH aliphatic), 1740, 1716, 1700, 1693 (4C = O), 1604, 1558 (NH,
C
C). 1H NMR (DMSO‑d6) δ ppm: 3.91 (s, 2H, CH2CO), 3.95 (s, 2H,
aliphatic), 1720, 1700, 1685 (3C = O), 1608, 1562 (NH, C C). H NMR
1
–
–
–
–
CH2CO), 5.24 (s, 2H, OCH2), 7.08 (s, 1H, H-3 Ar), 7.18–7.19 (m, 2H, H-
6,8 Ar), 7.26 (d, 2H, J = 3.2 Hz, CH = CH), 7.35 (t, 1H, J = 6.8 Hz, H-4′
Ar), 7.41 (t, 2H, J = 7.0 Hz, H-3′,5′ Ar), 7.48 (d, 2H, J = 6.8 Hz, H-2′,6′
Ar), 7.77 (d, 1H, J = 8.7 Hz, H-5 Ar), 10.21 (s, 1H, NH, D2O exchang.).
13C NMR (DMSO‑d6) δ ppm: 32.87, 33.97 (CH2CO), 70.27 (OCH2),
101.94, 113.16, 113.85, 123.72, 126.58, 127.55, 128.29, 128.66,
128.99, 134.22, 136.82, 139.29, 145.91, 153.87 (aromatic carbons),
161.11, 167.18, 168.34, 168.49 (4C = O). Anal. Calcd. for C22H16N2O6
(404.37) C, 65.34; H, 3.99; N, 6.93; Found C, 65.71; H, 4.17; N, 7.20.
(DMSO‑d6) δ ppm: 3.96 (s, 5H, CH3, CH2CO), 4.07 (s, 2H, CH2CO), 5.23
(s, 2H, OCH2), 7.10 (s, 1H, H-3 Ar), 7.19 (s, 1H, CH pyrazolinone), 7.21
(s, 1H, NH, D2O exchang.), 7.24 (d, 2H, J = 7.0 Hz, H-6,8 Ar), 7.35 (t,
1H, J = 7.1 Hz, H-4′ Ar), 7.41 (t, 2H, J = 7.3 Hz, H-3′,5′ Ar), 7.47 (d, 2H,
J = 7.4 Hz, H-2′,6′ Ar), 7.64 (d, 1H, J = 8.8 Hz, H-5 Ar). 13C NMR
(DMSO‑d6) δ ppm: 19.14 (CH3), 32.68, 34.71 (CH2CO), 70.31 (OCH2),
101.99, 107.25, 113.39, 113.64, 123.53, 126.58, 127.31, 128.32,
128.51, 128.78, 128.99, 136.78, 139.23, 145.22, 153.91 (aromatic
carbons), 161.22, 161.65, 169.31 (3C = O). Anal. Calcd. for C22H18N2O5
(390.39) C, 67.69; H, 4.65; N, 7.18; Found C, 67.96; H, 4.83; N, 7.39.
4.1.6.3. 2-(7-Benzyloxy-2-oxo-2H-chromen-4-yl)-N-(1,3-dioxoisoindolin-
2-yl) acetamide (11c). White powder, (yield 89%), m.p. 245–7 ◦C. IR
(KBr, νmax/cmꢀ 1): 3414 (NH), 3016 (CH aromatic), 2927, 2858 (CH
4.1.8.2. 7-Benzyloxy-4-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-2-oxoethyl]-
2H-chromen-2-one (13b). Buff powder, (yield 60%), m.p. 118–120 ◦C.
IR (KBr, νmax/cmꢀ 1): 3062 (CH aromatic), 2927, 2873 (CH aliphatic),
1
–
aliphatic), 1747, 1720, 1670 (4C = O), 1604, 1558 (NH, C C). H NMR
–
1701 (2C = O), 1635, 1620, 1562 (C N, NH, C C). 1H NMR
–
–
–
–
(DMSO‑d6) δ ppm: 3.99 (s, 2H, CH2CO), 4.15 (s, 2H, CH2CO), 5.25 (s,
2H, OCH2), 7.10 (s, 1H, H-3 Ar), 7.20–7.29 (m, 2H, H-6,8 Ar), 7.35 (t,
1H, J = 6.9 Hz, H-4′ Ar), 7.41 (t, 2H, J = 7.4 Hz, H-3′,5′ Ar), 7.49 (d, 2H,
J = 7.0 Hz, H-2′,6′ Ar), 7.83 (d, 1H, J = 8.7 Hz, H-5 Ar), 7.95–7.96 (m,
4H, H-3′’,4′’,5′’,6′’ Ar), 11.15 (s, 1H, NH, D2O exchang.). 13C NMR
(DMSO‑d6) δ ppm: 32.94, 33.71 (CH2CO), 70.32 (OCH2), 101.94,
113.25, 113.67, 124.05, 124.25, 126.64, 127.52, 128.33, 128.55,
128.69, 128.85, 128.99, 129.91, 135.79, 136.80, 139.14, 145.05,
153.91 (aromatic carbons), 161.22, 161.37, 165.45, 168.13 (4C = O).
Anal. Calcd. for C26H18N2O6 (454.43) C, 68.72; H, 3.99; N, 6.16; Found
C, 69.01; H, 4.16; N, 6.38.
(DMSO‑d6) δ ppm: 1.69 (s, 3H, CH3), 2.01 (s, 3H, CH3), 3.96 (s, 2H,
CH2CO), 4.08 (s, 2H, CH2CO), 5.24 (s, 2H, OCH2), 6.39 (s, 1H, CH
pyrazole), 7.10 (s, 1H, H-3 Ar), 7.17–7.21 (m, 2H, H-6,8 Ar), 7.35 (t, 1H,
J = 7.2 Hz, H-4′ Ar), 7.41 (t, 2H, J = 7.3 Hz, H-3′,5′ Ar), 7.47 (d, 2H, J =
7.1 Hz, H-2′,6′ Ar), 7.58 (d, 1H, J = 8.9 Hz, H-5 Ar). 13C NMR (DMSO‑d6)
δ ppm: 16.38 (CH3), 26.37 (CH3), 32.91, 35.30 (CH2CO), 70.31 (OCH2),
101.86, 113.28, 114.25, 123.21, 126.56, 127.57, 128.26, 128.53,
128.79, 128.99, 136.82, 139.31, 145.23, 147.43, 153.90, 155.87 (aro-
–
matic carbons), 161.22 (C N), 161.68, 169.31 (2C = O). Anal. Calcd.
–
for C23H20N2O4 (388.42) C, 71.12; H, 5.19; N, 7.21; Found C, 70.91; H,
5.47; N, 7.49.
4.1.7. 4-[(4-Amino-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]-7-
benzyloxy-2H-chromen-2-one (12)
4.1.8.3. 5-Amino-1-[2-(7-benzyloxy-2-oxo-2H-chromen-4-yl)acetyl]-1H-
pyrazole-4-carbonitrile (13c). Brown powder, (yield 65%), m.p. 79–81
◦C. IR (KBr, νmax/cmꢀ 1): 3340, 3217 (NH2), 3028 (CH aromatic), 2916,
Carbon disulfide (0.08 mL, 1.5 mmol) was added to ice cold mixture
of potassium hydroxide (0.08 g, 1.5 mmol) and carboxazide compound
10 (0.32 g, 1 mmol) in absolute ethanol (30 mL). The mixture was
stirred at room temperature for 12 h. Ether (20 mL) was added to this
mixture, the separated solid was filtered and washed with ether. The
obtained precipitate was refluxed with hydrazine hydrate 99% (0.1 mL,
2 mmol) in absolute ethanol (20 mL) for 24 h, then cooled and poured
onto ice. The obtained solid was filtered, dried and crystalized from
absolute ethanol.
2873 (CH aliphatic), 2206 (CN), 1716, 1708 (2C = O), 1620, 1597, 1562
1
–
–
–
(C N, NH, C C). H NMR (DMSO‑d ) δ ppm: 3.91 (s, 2H, CH CO), 3.93
–
6
2
(s, 2H, CH2CO), 5.23 (s, 2H, OCH2), 7.09 (s, 1H, H-3 Ar), 7.19–7.25 (m,
3H, CH pyrazole, H-6,8 Ar), 7.34 (t, 1H, J = 7.1 Hz, H-4′ Ar), 7.40 (t, 2H,
J = 7.3 Hz, H-3′,5′ Ar), 7.46 (d, 2H, J = 7.1 Hz, H-2′,6′ Ar), 7.74 (d, 1H, J
= 7.9 Hz, H-5 Ar), 10.39 (s, 2H, NH2, D2O exchang.). 13C NMR
(DMSO‑d6) δ ppm: 32.89, 33.93 (CH2CO), 70.29 (OCH2), 101.96,
110.67, 113.21, 113.83, 123.77, 126.59, 127.47, 128.30, 128.54,
Yellowish brown powder, (yield 70%), m.p. 230–2 ◦C. IR (KBr, νmax
/
cmꢀ 1): 3417, 3336 (NH2, NH), 3062 (CH aromatic), 2927, 2860 (CH
128.66, 128.99, 136.81, 139.24, 145.73, 153.91 (CN, aromatic car-
–
–
–
–
–
–
aliphatic), 1708 (C O), 1640, 1606, 1580, 1535 (C N, NH, C C),
–
bons), 161.15 (C N), 161.45, 167.10 (2C=O). Anal. Calcd. for
–
1284 (C S). 1H NMR (DMSO‑d6) δ ppm: 3.98 (s, 2H, NH2, D2O
–
–
C
22H16N4O4 (400.39) C, 66.00; H, 4.03; N, 13.99; Found C, 66.24; H,
exchang.), 4.29 (s, 2H, CH2), 5.23 (s, 2H, OCH2), 7.10 (s, 1H, H-3 Ar),
7.16–7.18 (m, 2H, H-6,8 Ar), 7.34 (t, 1H, J = 7.1 Hz, H-4′ Ar), 7.40 (t,
2H, J = 7.3 Hz, H-3′,5′ Ar), 7.47 (d, 2H, J = 7.2 Hz, H-2′,6′ Ar), 7.64 (d,
1H, J = 9.0 Hz, H-5 Ar), 13.47 (s, 1H, NH, D2O exchang.). 13C NMR
(DMSO‑d6) δ ppm: 32.88 (CH2), 70.31 (OCH2), 101.99, 113.33, 123.81,
126.60, 128.30, 128.50, 128.54, 128.79, 128.99, 136.79, 139.26,
4.24; N, 14.23.
4.1.9. General procedure for synthesis of compounds (14a,b)
A mixture of carboxazide compound 10 (0.32 g, 1 mmol) and
appropriate isothiocyanate derivatives (methyl and phenyl isothiocya-
nate) (1 mmol) in absolute ethanol (30 mL) was refluxed for 12 h. The
precipitated solid was filtered, dried and crystallized from absolute
ethanol.
–
145.50, 149.46, 153.99 (aromatic carbons), 161.20 (C N), 161.58
–
–
–
–
–
(C O), 166.45 (C S). Anal. Calcd. for C19H16N4O3S (380.42) C, 59.99;
H, 4.24; N, 14.73; Found C, 60.21; H, 4.53; N, 14.97.
4.1.9.1. 1-[2-(7-Benzyloxy-2-oxo-2H-chromen-4-yl)acetyl]-4-methyl-
thiosemicarbazide (14a). White powder, (yield 95%), m.p. 228–230 ◦C.
10