S. Chortani, et al.
BioorganicChemistry92(2019)103270
54.8, 63.2, 93.4, 113.1, 114.2, 123.1, 123.5, 125.5, 127.1, 127.6,
128.1, 129.7, 130.3, 133.0, 142.2, 151.7, 155.0, 158.9, 161.2, 165.4,
165.9.
Yield: 58%. mp: 96–98 °C. ES-HRMS [M+H]+ calcd. for
(C21H19ClN4O3)+
:
411.1224,
found:
411.1236.
1H
NMR
(300 MHz,CDCl3):
δ
(ppm) = 1.82 (s, 3H, CH3(a)), 2.11 (s, 3H,
CH3(b)), 2.79 (d, 1H, H4′′′, J = 18.6 Hz), 2.85 (d, 2H, H4′”
,
,
J = 18.6 Hz), 5.46 (d, 1H, H1″
,
J = 15.6 Hz.), 5.55 (d, 1H, H1″
4.1.5. General procedure for preparation of compounds 7–9(a-c)
A mixture of appropriate hydrazide 3 (1 mmol) and cyclic anhy-
dride (1 mmol) was stirred in reflux of dry dioxane in the presence of
catalytic amount of acetic acid (0.001 mmol, 0.06 mL). After 8 h, the
reaction mixture was cooled to room temperature and the dioxane was
removed in vacuo and the residue was purified by silica gel chroma-
tography (petroleum ether / ethyl acetate, 60:40) to yield compounds
7–9.
J = 15.6 Hz), 7.40 (d, 2H, H2′,6′
,
J = 9.0 Hz), 7.54 (td, 1H, H6,
J = 8.1 Hz, J = 1.2 Hz), 7.83 (td, 1H, H7, J = 8.4 Hz, J = 1.2 Hz),
7.98 (d, 1H, H8, J = 8.4 Hz), 8.27 (dd, 1H, H5, J = 8.4 Hz,
J = 1.2 Hz), 8.42 (d, 2H, H3′,5′
,
J = 9.0 Hz). 13C NMR (75 MHz,
CDCl3): δ (ppm) = 16.1, 26.9, 51.2, 63.9, 91.8, 114.9, 123.7, 126.7,
127.9, 128.4, 129.8, 130.1, 133.7, 136.5, 152.1, 155.8, 158.5, 166.1,
166.5.
4.1.4.3. 3-(2-(5-hydroxy-3,5-dimethyl-4,5-dihydro-1H-pyrazol-1-yl)-
4.1.5.1. N-(1,3-dioxoisoindolin-2-yl)-2-(4-oxo-2-phenylbenzopyrimidin-
3(4H)-yl)acetamide 7a. White solid, Yield: 57%. mp: 232–243 °C. ES-
HRMS [M+H]+ calcd. for (C24H16N4O4)+: 425.1249, found: 425.1261.
1H NMR (300 MHz, DMSO‑d6): δ (ppm) = 5.49 (s, 2H, H1″), 7.54 (m,
3H,Harom), 7.70 ((t, 1H, H6, J = 8.1 Hz), 7.97 (m, 6H, Harom), 8.32 (d,
1H, H5, J = 8.1 Hz), 8.60 (m, 2H, Harom), 11.20 (s, 1H, NH). 13C NMR
(75 MHz, DMSO‑d6): δ (ppm) = 63.6, 114.2, 123.5, 123.7, 127.1,
127.5, 128.4, 128.5, 129.7, 130.4, 134.4, 135.2, 137.0, 151.4, 158.8,
164.8, 166.7, 168.3.
2oxoethyl)-2(4-methoxyphenyl)benzopyrimidin-4(3H)-one
5c. White
solid, Yield: 66%. mp: 110–112 °C. ES-HRMS [M+H]+ calcd. for
(C22H22N4O4)+
:
407.1730,
found:
407.1742.
1H
NMR
(300 MHz,CDCl3):
δ
(ppm) = 1.84 (s, 3H, CH3(a)), 2.11 (s, 3H,
CH3(b)), 2.85 (d, 1H, H4′′′, J = 18.6 Hz), 3.03 (d, 1H, H4′”
J = 18.6 Hz), 3.87 (s, 3H, OCH3), 4.45 (s, 1H, OH), 5.46 (d, 1H, H1″
J = 15.6 Hz.), 5.58 (d, 1H, H1″, J = 15.6 Hz), 6.95 (d, 2H, H3′,5′
,
,
,
J = 6.9 Hz), 7.49 (t, 1H, H6, J = 7.2 Hz), 7.80 (td, 1H, H7, J = 8.4 Hz,
J = 1.2 Hz), 7.97 (d, 1H, H8, J = 8.4 Hz), 8.29 (d, 1H, H5, J = 7.5 Hz),
8.48 (d, 2H, H2′,6′
,
J = 6.9 Hz). 13C NMR (75 MHz, CDCl3):
δ
4.1.5.2. 2-(2-(4-chlorophenyl)-4-oxobenzopyrimidin-3(4H)-yl)-N-(1,3-
(ppm) = 15.6, 26.4, 50.7, 54.8, 63.3, 91.3, 113.1, 114.2, 123.1,
125.5, 127.1, 129.6, 130.0, 133.0, 151.8, 155.1, 158.9, 161.2, 165.4,
166.1.
dioxoisoindolin-2-yl)acetamide
7b. White
solid,
Yield:
55%.
mp: > 300 °C. ES-HRMS [M+H]+ calcd. for (C24H15ClN4O4)+
:
459.0860, found: 459.0872. 1H NMR (300 MHz, DMSO‑d6):
δ
(ppm) = 5.39 (s, 2H, H1″), 7.56 (d, 2H, H2′,6′, J = 8,4 Hz), 7.63 (s,
1H, H8), 7.88 (m, 6H, Harom), 8.26 (d, 1H, H5, J = 8.1 Hz), 8.55 (d, 1H,
4.1.4.4. 3-(2-(5-hydroxy-3-methyl-5-phenyl-4, 5-dihydro-1H-pyrazol-1-
yl)-2oxoethyl)-2 -phenylbenzopyrimidin-4(3H)-one 6a. Yellow solid,
Yield: 65%. mp: 191–193 °C. ES-HRMS [M+H]+ calcd. for
H
3′,5′, J = 8.4 Hz), 11.10 (s, 1H, NH). 13C NMR (75 MHz, DMSO‑d6): δ
(ppm) = 68.5, 119.0, 128.3, 128.6, 132.2, 132.3, 133.3, 134.1, 134.9,
139.4, 140.5, 141.6, 133.4, 156.0, 162.5, 169.6, 170.3, 171.5.
(C26H22N4O3)+
:
439.1770,
found:
439.1782.
1H
NMR
(300 MHz,CDCl3): δ (ppm) = 2,15 (s, 3H, CH3(a)), 2.95 (d, 1H, H4′′′,
J = 18.6 Hz), 3.29 (d, 1H, H4′”
,
J = 18.6 Hz), 5.48 (d, 1H, H1″
,
4.1.5.3. N-(1,3-dioxoisoindolin-2-yl)-2-(2-(4-methoxyphenyl)-4-
J = 15.6 Hz.), 5.88 (d, 1H, H1″, J = 15.6 Hz), 7.04 (m, 3H, Harom),
7.34 (d, 2H, Harom, J = 7.0 Hz), 7.51 (m, 4H, Harom), 7.79 (t, 1H, H7,
J = 8.4 Hz), 7.96 (d, 1H, H8, J = 8.4 Hz), 8.23 (d, 1H, H5, J = 8.1 Hz),
8.56 (m, 2H, Harom). 13C NMR (75 MHz, CDCl3): δ (ppm) = 15.5, 53.5,
63.3, 93.4, 114.5, 123.0, 123.5, 126.0, 127.3, 127.5, 127.8, 128.1,
128.1, 129.8, 133.1, 137.6, 142.2, 151.6, 155.1, 159.1, 165.6, 165.8.
oxobenzopyrimidin-3(4H)-yl)acetamide 7c. White solid, Yield: 73%. mp:
232–234 °C. ES-HRMS [M+H]+ calcd. for (C25H18N4O5)+: 455.1355,
found: 455.1367. 1H NMR (300 MHz, DMSO‑d6): δ (ppm) = 3.88 (s, 3H,
OCH3), 5.46 (s, 2H, H1″), 7.10 (d, 2H, H3′,5′, J = 7.8 Hz), 7.65 (s, 1H,
H8), 7.96 (m, 6H, Harom), 8.28 (d, 1H, H5, J = 7.5 Hz), 8.54 (d, 1H,
H
2′,6′, J = 7.8 Hz), 11.15 (s, 1H, NH). 13C NMR (75 MHz, DMSO‑d6): δ
(ppm) = 55.3, 63.5, 113.8, 113.9, 123.5, 123.7, 125.3, 126.6, 127.3,
129.3, 130.1, 132.5, 134.4, 135.3, 1151.5, 158.6, 164.8, 165.2, 166.8.
4.1.4.5. 3-(2-(5-hydroxy-3-methyl-5-phenyl-4,5-dihydro-1H-pyrazol-1-
yl)-2oxoethyl)-2-(4-chlorophenyl)benzopyrimidin-4(3H)-one 6b. Yellow
solid, Yield: 52%. mp: 186–188 °C. ES-HRMS [M+H]+ calcd. for
4.1.5.4. N-(1,3-dioxo-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindol-
2(3H)-yl)-2-(4-oxo-2-phenylbenzopyrimidin-3(4H)-yl)acetamide
8a. White solid, Yield: 70%. mp: 242–244 °C. ES-HRMS [M+H]+
(C26H21ClN4O3)+
:
473.1380,
found:
473.1392.
1H
NMR
(300 MHz,CDCl3): δ (ppm) = 2.10 (s, 3H, CH3(a)), 2.89 (d, 1H, H4′′′,
J = 18.9 Hz), 3.23 (d, 1H, H4′”
,
J = 18.9 Hz), 5.43 (d, 1H, H1″
,
calcd. for (C25H20N4O4)+
:
441.1563, found: 441.1572. 1H NMR
J = 15.6 Hz), 5.74 (d, 1H, H1″, J = 15.6 Hz), 7.05 (m, 3H, Harom),
7.28 (d, 2H, Harom, J = 6.9 Hz), 7.43 (m, 3H, Harom), 7.74 (td, 1H, H7,
J = 8.4 Hz, J = 1.5 Hz), 7.90 (d, 1H, H8, J = 8.4 Hz), 8.19 (dd, 1H, H5,
J = 8.1 Hz, J = 0.9 Hz), 8.46 (d, 2H, Harom, J = 8.7 Hz). 13C NMR
(75 MHz, CDCl3): δ (ppm) = 16.0, 53.9, 63.8, 93.9, 114.9, 123.6,
123.9, 126.7, 127.8, 128.1, 128.5, 128.6, 129.9, 133.7, 136.5, 136.6,
142.7, 152.0, 155.6, 158.5, 166.1, 166.3.
(300 MHz,CDCl3): δ (ppm) = 1.55 (d, 1H, H6′′′, J = 9.0 Hz), 1.76 (d,
1H, H6′′′, J = 9.0 Hz), 3.38 (s, 2H, H4′′′b,2′′′a), 3.46 (s, 2H, H4′′′a,2′′′b), 5.37
(s, 2H, H1″), 6.19 (s, 2H, H3′′′,4′′′), 7.53 (m, 4H, Harom), 7.88 (t, 1H, H7,
J = 8.1 Hz), 8.04 (d, 1H, H8, J = 7.8 Hz), 8.16 (d, 1H, H5, J = 8.1 Hz),
8.28 (s, 1H, NH), 8.54 (m, 2H, Harom). 13C NMR (75 MHz, CDCl3): δ
(ppm) = 44.3, 45.0, 51.7, 64.7, 114.4, 123.0, 126.9, 128.3, 128.5,
128.6, 130.8, 134.1, 134.7, 137.2, 152.3, 159.6, 165.1, 165.6, 173.3.
4.1.4.6. 3-(2-(5-hydroxy-3-methyl-5-phenyl-4, 5-dihydro-1H-pyrazol-1-
yl)-2oxoethyl)-2-(4-methoxyphenyl)benzopyrimidin-4(3H)-one
4.1.5.5. 2-(2-(4-chlorophenyl)-4-oxobenzopyrimidin-3(4H)-yl)-N-(1,3-dioxo-
3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindol-2(3H)-yl)acetamide 8b. White
solid, Yield: 58%. mp: 216–218 °C. ES-HRMS [M+H]+ calcd. for
6c. Yellow solid, Yield: 58%. mp: 160–162 °C. ES-HRMS [M+H]+
calcd. for (C27H24N4O4)+
:
469.1876, found: 469.1888. 1H NMR
(C25H19ClN4O4)+
:
475.1173, found: 475.1183. 1H NMR (300 MHz,
(300 MHz,CDCl3): δ (ppm) = 2.16 (s, 3H, CH3(a)), 2.95 (d, 1H, H4′′′,
J = 18.9 Hz), 3.29 (d, 1H, H4′”, J = 18.9 Hz), 3.90 (s, 3H, OCH3), 5.48
(d, 1H, H1″, J = 15.6 Hz.), 5.84 (d, 1H, H1″, J = 15.6 Hz), 7.01 (d, 2H,
DMSO‑d6): δ (ppm) = 1.45 (d, 1H, H6′′′, J = 8.4 Hz), 1.49 (d, 1H, H6′′′,
J = 8.4 Hz), 3.23 (s, 2H, H4′′′b,2′′′a), 3.38 (s, 2H, H4′′′a,2′′′b), 5.22 (s, 2H, H1″),
5.99 (s, 2H, H3′′′,4′′′), 7.49 (d, 2H, H2′,6′, J = 8,7 Hz), 7.62 (m, 1H, H6), 7.91
H
3′,5′, J = 9.0 Hz), 7.10 (m, 3H, Harom), 7.37 (d, 2H, Harom, J = 8.1 Hz),
(m, 2H, Harom), 8.21 (d, 1H, H5, J = 8.1 Hz), 8.84 (d, 2H, H3′,5′,
7.46 (t, 1H, H6, J = 7.8 Hz), 7.77 (td, 1H, H7, J = 8.1 Hz, J = 1.2 Hz),
7.92 (d, 1H, H8, J = 8.4 Hz), 8.22 (d, 1H, H5, J = 8.1 Hz), 8.52 (d, 2H,
J = 8.7 Hz), 10.77 (s, 1H, NH). 13C NMR (75 MHz, DMSO‑d6):
δ
(ppm) = 43.5, 44.3, 51.3, 63.6, 114.2, 123.5, 127.4, 127.5, 128.5,
130.1, 134.4, 134.6, 135.7, 135.8, 151.2, 157.7, 164.7, 165.5, 173.9.
H
2′,6′, J = 9.0 Hz). 13C NMR (75 MHz, CDCl3): δ (ppm) = 15.5, 53.4,
8