S. Sana et al.
Bioorganic Chemistry 110 (2021) 104765
DMSO‑d6): δ 164.5, 157.5, 148.0, 142.1, 140.3, 139.8, 137.1, 131.8,
41.5; HRMS (ESI): m/z calculated for C31H28F2N7O2S 600.1993 found
600.2028 [M + H]+.
129.6, 124.3, 123.0, 116.4, 114.5, 97.0, 56.2, 44.6, 41.8.; HRMS (ESI):
m/z calculated for C25H25N8O4S 533.1719 found 533.1754 [M + H] +
.
7.1.4.20. (E)-3-([1,1′-Biphenyl]-4-yl)-1-(4-(2-amino-6-((5-(difluor-
omethoxy)-1H-benzo[d]imidazol-2-yl)thio)pyrimidin-4-yl)piperazin-1-yl)
7.1.4.15. (E)-1-(4-(2-Amino-6-((5-(difluoromethoxy)-1H-benzo[d]imida-
zol-2-yl)thio)pyrimidin-4-yl)piperazin-1-yl)-3-phenylprop-2-en-1-one
(17o). Off-white solid; yield 84%; mp:160–164 ◦C; FT-IR (cm ꢀ 1):
3325, 3062, 2887, 1650, 1585, 780, 710; 1H NMR (500 MHz, DMSO‑d6):
δ 13.20 (s, 1H), 7.73 (d, J = 7.1 Hz, 2H), 7.61 (d, J = 8.4 Hz, 1H), 7.53
(d, J = 15.4 Hz, 1H), 7.44–7.36 (m, 4H), 7.34–7.15 (m, 2H), 7.07 (d, J =
10.8 Hz, 1H), 6.57 (s, 2H), 6.15 (s, 1H), 3.78–3.57 (m, 8H); 13C NMR
(125 MHz, DMSO- d6): δ 165.1, 164.0, 162.9, 162.5, 142.2, 135.5,
130.0, 129.2, 128.5, 128.1, 119.3, 118.8, 118.6, 117.3, 115.3, 90.2,
44.2, 43.8, 43.4, 41.5; HRMS (ESI): m/z calculated for C25H24F2N7O2S
524.1680 found 524.1699 [M + H]+.
◦
prop-2-en-1-one (17t). White solid; yield 88%; mp: 192–196 C; FT-IR
(cmꢀ 1): 3346, 3119, 2986, 1689, 1654, 1527, 1203, 875; 1H NMR
(500 MHz, DMSO‑d6): δ 13.20 (s, 1H), 7.76 (d, J = 15.2 Hz, 1H), 7.61 (d,
J = 8.2 Hz, 1H), 7.48 (s, 1H), 7.38 (dd, J = 25.7, 7.3 Hz, 2H), 7.21 (dd, J
= 10.8, 4.1 Hz, 2H), 7.07 (d, J = 10.5 Hz, 1H), 6.56 (s, 2H), 6.13 (s, 1H),
3.87 (s, 3H), 3.82 (s, 3H), 3.68–3,56 (m, 8H); 13C NMR (125 MHz,
DMSO‑d6): δ 165.2, 164.9, 164.0, 162.5, 151.3, 149.0, 140.1, 126.8,
119.6, 119.1, 117.3, 116.5, 116.0, 115.3, 115.1, 111.0, 90.1, 56.6, 56.5,
45.3, 45.1, 43.1; HRMS (ESI): m/z calculated for C27H27BrF2N7O4S
662.0997 found 664.0980 [M + 2]+.
7.1.4.16. (E)-1-(4-(2-Amino-6-((5-(difluoromethoxy)-1H-benzo[d]imida-
zol-2-yl)thio)pyrimidin-4-yl)piperazin-1-yl)-3-(2-ethoxyphenyl)prop-2-en-
1-one (17p). Off-white solid; yield 80%; mp:162–165 ◦C; FT-IR (cmꢀ 1):
3325, 3062, 2767, 1650, 1585, 780, 710; 1H NMR (500 MHz, DMSO‑d6):
δ 13.20 (s, 1H), 7.79 (dd, J = 20.6, 11.5 Hz, 2H), 7.61 (d, J = 7.9 Hz,
1H), 7.37 (dd, J = 17.3, 11.1 Hz, 2H), 7.24 (d, J = 15.5 Hz, 1H),
7.17–6.98 (m, 3H), 6.98 (t, J = 7.4 Hz, 1H), 6.57 (s, 2H), 6.15 (s, 1H),
4.11 (dd, J = 13.7, 6.8 Hz, 2H), 3.76–3.55 (m, 8H), 1.38 (s, 3H); 13C
NMR (125 MHz, DMSO‑d6): 165.4, 164.2, 162.5, 157.3, 137.1, 131.5,
128.8, 123.9, 120.9, 119.5, 118.4, 117.3, 115.3, 112.9, 90.2, 64.1, 44.9,
44.3, 43.6, 41.5, 15.1; HRMS (ESI): m/z calculated for C27H28F2N7O3S
568.1942 found 568.1978 [M + H]+.
7.1.4.21. (E)-1-(4-(2-Amino-6-((5-(difluoromethoxy)-1H-benzo[d]imida-
zol-2-yl)thio)pyrimidin-4-yl)piperazin-1-yl)-3-(4-bromophenyl)prop-2-en-
1-one (17u). Off-white solid; yield 85%; mp: 190–194 ◦C; FT-IR (cmꢀ 1):
1
3369, 3285, 2981, 1695, 1656, 1635, 1253, 831; H NMR (500 MHz,
DMSO‑d6): δ 13.21 (s, 1H), 7.71 (d, J = 8.0 Hz, 2H), 7.62 (d, J = 7.9 Hz,
3H), 7.49 (d, J = 15.3 Hz, 1H), 7.36 (dd, J = 24.5, 17.1 Hz, 2H), 7.21 (s,
1H), 7.08 (d, J = 10.3 Hz, 1H), 6.57 (s, 2H), 6.15 (s, 1H), 3.85–3.57 (m,
8H); 13C NMR (125 MHz, DMSO‑d6): δ 164.3, 163.3, 162.2, 161.8,
141.4, 134.8, 129.3, 128.4, 127.7, 127.4, 118.6, 118.0, 117.9, 116.6,
114.5, 89.4, 43.5, 43.1, 42.6, 40.8; HRMS (ESI): m/z calculated for
C
25H23BrF2N7O2S 602.0785 found 604.0871 [M + 2]+.
7.1.4.22. (E)-1-(4-(2-Amino-6-((2-phenyl-1H-benzo[d]imidazol-5-yl)
amino)pyrimidin-4-yl)piperazin-1-yl)-3-(4-methoxyphenyl)prop-2-en-1-one
(18a). Off-white solid; yield 78%; mp: 198–201 ◦C; FT-IR (cmꢀ 1): 3367,
3251, 2891, 1692, 1675, 1643, 1425, 865; 1H NMR (500 MHz,
DMSO‑d6): δ 12.66 (s, 1H), 8.67 (s, 1H), 8.21–8.10 (m, 2H), 7.70 (dd, J
= 11.7, 8.0, Hz, 3H), 7.56–7.45 (m, 5H), 7.31 (dd, J = 11.9, 7.6 Hz, 1H),
7.15–7.11 (m, 1H), 6.98 (d, J = 8.4 Hz, 2H), 5.77 (s, 2H), 5.42 (s, 1H),
3.81 (s, 3H), 3.77–3.42 (m, 8H); 13C NMR (125 MHz, DMSO‑d6): δ 165.1,
163.8, 163.0, 160.0, 143.1, 142.2, 142.1, 130.0, 129.4, 129.2, 128.5,
128.5, 127.7, 126.7, 124.9, 110.0, 91.3, 62.8, 44.9, 44.1, 41.4; HRMS
(ESI): m/z calculated for C31H31N8O2 547.2570 found 547.2560 [M +
H]+.
7.1.4.17. (E)-1-(4-(2-Amino-6-((5-(difluoromethoxy)-1H-benzo[d]imida-
zol-2-yl)thio)pyrimidin-4-yl)piperazin-1-yl)-3-(2,6-dimethoxyphenyl)prop-
2-en-1-one (17q). Off-white solid; yield 80%; mp:161–164 ◦C; FT-IR
1
(cmꢀ 1): 3325, 3262, 2898,1650, 1585, 780, 710; H NMR (500 MHz,
DMSO‑d6): δ 13.20 (s, 1H), 7.80 (d, J = 15.5 Hz, 1H), 7.61 (d, J = 8.1 Hz,
1H), 7.39 (d, J = 7.9 Hz, 2H), 7.23 (d, J = 14.6 Hz, 1H), 7.07 (d, J = 9.4
Hz, 1H), 6.99 (d, J = 10.2 Hz, 2H), 6.86 (s, 1H), 6.58 (s, 2H), 6.14 (s,
1H), 3.79 (d, J = 17.1 Hz, 6H), 3.61 (d, J = 27.9 Hz, 8H); 13C NMR (125
MHz, DMSO‑d6): δ 165.3, 163.7, 162.5, 153.7, 152.3, 137.9, 136.5,
124.6, 119.3, 118.6, 117.3, 116.9, 115.2, 114.4, 113.3, 113.2, 90.2,
56.5, 56.1, 46.1, 44.9, 41.7; HRMS (ESI): m/z calculated for
C
27H28F2N7O4S 584.1892 found 584.1924 [M + H]+.
7.1.4.23. (E)-1-(4-(2-Amino-6-((2-phenyl-1H-benzo[d]imidazol-5-yl)
amino)pyrimidin-4-yl)piperazin-1-yl)-3-(3,4,5-trimethoxyphenyl)prop-2-
en-1-one (18b). White solid; yield 86%; mp: 196–199 ◦C; FT-IR (cmꢀ 1):
7.1.4.18. (E)-1-(4-(2-Amino-6-((5-(difluoromethoxy)-1H-benzo[d]imida-
zol-2-yl)thio)pyrimidin-4-yl)piperazin-1-yl)-3-(3,4,5-trimethoxyphenyl)
prop-2-en-1-one (17r). Light brown solid; yield 78%; mp: 188–191 ◦C;
FT-IR (cmꢀ 1): 3367, 3114, 2898, 2609, 1859, 1563, 1394, 1275, 785; 1H
NMR (500 MHz, DMSO‑d6): δ 13.20 (s, 1H), 7.80 (d, J = 15.5 Hz, 1H),
7.61 (d, J = 8.1 Hz, 1H), 7.39 (d, J = 7.9 Hz, 2H), 7.23 (d, J = 14.6 Hz,
1H), 7.07 (d, J = 9.4 Hz, 1H), 6.99 (d, J = 10.2 Hz, 2H), 6.58 (s, 2H),
6.14 (s, 1H), 3.79–3.65 (m, 9H), 3.64–3.55 (m, 8H); 13C NMR (125 MHz,
DMSO‑d6): δ 165.2, 162.5, 159.7, 153.5, 147.5, 142.6, 139.4, 131.1,
119.3, 117.6, 117.6, 117.3, 115.2, 106.2, 91.2, 90.2, 60.5, 56.5, 44.5,
41.5; HRMS (ESI): m/z calculated for C28H30F2N7O5S 614.1997 found
614.2024 [M + H]+.
1
3368, 3112, 2889, 1698, 1675, 1638, 1412, 890; H NMR (500 MHz,
DMSO‑d6): δ 12.69 (s, 1H), 8.73 (s, 1H), 8.16 (d, J = 7.5 Hz, 2H), 7.85 (s,
1H), 7.54 (t, J = 7.5 Hz, 2H), 7.51–7.44 (m, 3H), 7.31 (d, J = 8.3 Hz,
1H), 7.20 (d, J = 15.3 Hz, 1H), 7.06 (s, 2H), 5.91 (s, 2H), 5.43 (s, 1H),
3.86 (d, J = 13.5 Hz, 9H), 3.53 (s, 8H).; 13C NMR (125 MHz, DMSO‑d6): δ
172.3, 165.2, 163.7, 153.5, 153.0, 142.5, 139.5, 131.1, 130.8, 129.9,
129.3, 126.6, 117.7, 106.2, 75.8, 60.5, 56.4, 44.6, 43.3; HRMS (ESI): m/
z calculated for C33H35N8O4 607.2781 found 607.2810 [M + H]+.
7.1.4.24. (E)-1-(4-(2-Amino-6-((2-phenyl-1H-benzo[d]imidazol-5-yl)
amino)pyrimidin-4-yl)piperazin-1-yl)-3-(2-bromo-5-methoxyphenyl)prop-
2-en-1-one (18c). White solid; yield 82%; mp: 199–203 ◦C; FT-IR
(cmꢀ 1): 3366, 3217, 2936, 1696, 1685, 1587, 1243, 875; 1H NMR
(500 MHz, DMSO‑d6): δ 12.59 (s, 1H), 8.61 (s, 1H), 8.09–8.03 (m, 2H),
7.62 (dd, J = 11.7, 8.0 Hz, 3H), 7.60–7.53 (m, 3H), 7.46 (dd, J = 11.9,
7.6 Hz, 1H), 7.44 (m, 1H), 7.15–7.11 (m, 1H), 6.90 (d, J = 8.4 Hz, 2H),
5.71 (s, 2H), 5.35 (s, 1H), 3.74 (s, 3H), 3.68–3.23 (m, 8H); 13C NMR
(125 MHz, DMSO‑d6): δ 165.4, 165.3, 163.8, 163.5, 162.9, 162.9, 161.0,
160.9, 141.9, 130.2, 130.1, 130.1, 129.4, 129.3, 129.3, 116.0, 114.7,
820.7, 45.7, 43.9; HRMS (ESI): m/z calculated for C31H30BrN8O2
625.1675 found 625.1666 [M + 2]+.
7.1.4.19. (E)-1-(4-(2-Amino-6-((5-(difluoromethoxy)-1H-benzo[d]imida-
zol-2-yl)thio)pyrimidin-4-yl)piperazin-1-yl)-3-(3,4,5-trimethoxyphenyl)
prop-2-en-1-one (17s). Light brown solid; yield 72%; mp: 183–187 ◦C;
FT-IR (cmꢀ 1): 3368, 3112, 2920, 2651, 1851, 1556, 1389, 1285, 760; 1H
NMR (500 MHz, DMSO‑d6): δ 13.08 (s, 1H), 7.82 (s, 2H), 7.72 (d, J = 8.0
Hz, 4H), 7.58 (d, J = 15.3 Hz, 3H), 7.49 (t, J = 7.6 Hz, 2H), 7.40 (t, J =
7.3 Hz, 1H), 7.33 (d, J = 15.4 Hz, 1H), 7.23 (s, 2H), 6.56 (s, 2H), 6.11 (s,
1H), 3.79 (s, 2H), 3.60 (d, J = 27.8 Hz, 6H); 13C NMR (125 MHz,
DMSO‑d6): δ 165.1, 164.6, 162.5, 162.5, 144.3, 141.7, 141.6, 139.8,
134.7, 129.4, 129.2, 128.3, 127.4, 127.1, 118.5, 89.9, 44.6, 44.4, 43.4,
15