S. Malasala, A. Polomoni, Md.N. Ahmad et al.
Journal of Molecular Structure 1234 (2021) 130168
1.85 (s, 4H); 13C NMR (125 MHz, DMSO- d6): δ 166.6, 154.7, 152.2,
149.5, 141.3, 135.4, 135.1, 134.0, 130.3, 130.0, 128.7, 127.0, 120.6,
117.6, 116.5, 115.1, 25.7, 25.6, 22.6, 22.4; HRMS (ESI): m/z calculated
for C23H19 N3O5S2 482.0766 found 482.0787 [M+H]+.
7.40–7.26 (m, 1H), 6.71 (dd, J = 8.0, 1.7 Hz, 1H), 3.45 (s, 3H), 3.10
(s, 2H), 2.83 (s, 2H), 1.85 (s, 4H); HRMS (ESI): m/z calculated for
C24H21N3O5S2 495.2048 found 495.2073 [M+H]+.
4.1.8. 2-(((4-nitrophenyl)sulfonyl)oxy)-4-((5,6,7,8-
4.1.3. 2-(((4-chlorophenyl)sulfonyl)oxy)-4-((5,6,7,8-
tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)amino)benzoic acid
(9g)
tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)amino)benzoic acid
(9b)
Off-white solid; yield 80 %; mp:160–164 °C; FT-IR (cm−1):
3325, 3062, 1650, 1585, 780, 710; 1H NMR (500 MHz, DMSO-d6):
δ 8.52–8.44 (m, 2H), 8.35 (s, 1H), 8.28 (s, 1H), 8.24–8.15 (m, 2H),
7.59 (d, J = 7.9 Hz, 2H), 7.36 (t, J = 8.1 Hz, 1H), 6.82–6.73 (m,
1H), 3.09 (s, 2H), 2.84 (s, 2H), 1.85 (s, 4H); 13C NMR (125 MHz,
DMSO- d6): δ 166.6, 154.6, 152.2, 151.5, 149.2, 141.4, 140.2, 134.2,
130.6, 130.3, 127.0, 125.5, 120.9, 117.7, 116.5, 114.9, 25.6, 25.6, 22.6,
22.4; HRMS (ESI): m/z calculated for C23H18 N4O7S2 527.0617 found
527.0640 [M+H]+.
Off-white solid; yield 80 %; mp:160–164 °C; FT-IR (cm−1):
3325, 3062, 1650, 1585, 780, 710; 1H NMR (500 MHz, DMSO-d6):
δ 8.37 (s, 1H), 8.26 (s, 1H), 7.92 (d, J = 8.6 Hz, 2H), 7.78 (d,
J = 8.6 Hz, 2H), 7.56 (d, J = 8.0 Hz, 2H), 7.35 (t, J = 8.0 Hz, 1H),
6.79–6.73 (m, 1H), 3.10 (s, 2H), 2.84 (s, 2H), 1.85 (s, 4H);13C NMR
(125 MHz, DMSO- d6): δ 166.6, 154.7, 152.2, 149.4, 141.3, 140.5,
134.1, 133.8, 130.7, 130.5, 130.2, 127.0, 120.7, 117.7, 116.6, 115.0, 25.7,
25.6, 22.6, 22.4; HRMS (ESI): m/z calculated for C23H18 ClN3O5S
516.0376 found 516.0398 [M+H]+.
4.1.9. 2-(((2,4-dichlorophenyl)sulfonyl)oxy)-4-((5,6,7,8-
tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)amino)benzoic acid
(9h)
4.1.4. 2-(((2-chlorophenyl)sulfonyl)oxy)-4-((5,6,7,8-
tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)amino)benzoic acid
(9c)
Off-white solid; yield 80 %; mp:160–164 °C; FT-IR (cm−1):
3325, 3062, 1650, 1585, 780, 710; 1H NMR (500 MHz, DMSO-
d6): δ 8.38 (s, 1H), 8.28 (s, 1H), 8.20 (d, J = 2.0 Hz, 1H), 7.94
(d, J = 8.6 Hz, 1H), 7.74–7.63 (m, 2H), 7.56–7.48 (m, 1H), 7.37 (t,
J = 8.2 Hz, 1H), 6.85 (dd, J = 8.1, 1.9 Hz, 1H), 3.10 (s, 2H), 2.84
(s, 2H), 1.85 (s, 4H); 13C NMR (125 MHz, DMSO- d6): δ 166.6,
154.6, 152.1, 149.2, 141.5, 141.2, 134.2, 134.1, 133.7, 132.7, 131.8,
130.3, 128.9, 127.0, 120.8, 117.7, 116.3, 114.4, 25.6, 25.6, 22.6, 22.4;
HRMS (ESI): m/z calculated for C23H17 Cl2N3O5S2 550.0065 found
550.0088 [M+H]+.
Off-white solid; yield 80 %; mp:160–164 °C; FT-IR (cm−1):
3325, 3062, 1650, 1585, 780, 710; 1H NMR (500 MHz, DMSO-d6):
δ 8.37 (s, 1H), 8.28 (s, 1H), 7.97 (dd, J = 7.9, 1.6 Hz, 1H), 7.91 (dd,
J = 8.0, 1.1 Hz, 1H), 7.82 (td, J = 7.8, 1.6 Hz, 1H), 7.71 (t, J = 2.2 Hz,
1H), 7.58 (td, J = 7.8, 1.2 Hz, 1H), 7.51 (dd, J = 8.2, 2.0 Hz, 1H), 7.35
(t, J = 8.2 Hz, 1H), 6.81 (ddd, J = 8.2, 2.4, 0.8 Hz, 1H), 3.10 (s, 2H),
2.84 (s, 2H), 1.85 (s, 4H); 13C NMR (125 MHz, DMSO- d6): δ 166.6,
154.6, 152.2, 149.3, 141.4, 136.9, 134.1, 133.0, 132.9, 132.8, 132.3,
130.2, 128.7, 127.0, 120.7, 117.7, 116.2, 114.6, 25.7, 25.6, 22.6, 22.4;
HRMS (ESI): m/z calculated for C23H18 ClN3O5S2 516.0376 found
516.0398 [M+H]+.
Experimental procedure for the synthesis of piperazine
linked thienopyrimidine derivatives: 13a-h
Equimolar amounts of intermediate
5
and piperazine
4.1.5. 2-(((4-bromophenyl)sulfonyl)oxy)-4-((5,6,7,8-
(10,1mmol) was taken into RBF and add the quantity of 10 ml 2-
proponal and refluxed for 10-12 h. On cooling intermediate 11 was
obtained which was treated with different arylsulphonylchlorides
(12a-h, 1 mmol) in the presence of DIPEA (1 mmol), DCM at room
temperature to acquire 13a-h derivatives.
tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)amino)benzoic acid
(9d)
Off-white solid; yield 80 %; mp:160–164 °C; FT-IR (cm−1):
3325, 3062, 1650, 1585, 780, 710; 1H NMR (500 MHz, DMSO-d6): δ
8.37 (s, 1H), 8.27 (s, 1H), 7.93 (d, J = 8.6 Hz, 2H), 7.83 (d, J = 8.6 Hz,
2H), 7.56 (t, J = 5.2 Hz, 2H), 7.36 (t, J = 8.1 Hz, 1H), 6.76 (dd,
J = 8.1, 1.5 Hz, 1H), 3.11 (s, 2H), 2.84 (s, 2H), 1.86 (s, 4H); 13C NMR
(125 MHz, DMSO- d6): δ 166.6, 154.6, 152.2, 149.4, 141.3, 134.2,
134.1, 133.5, 130.7, 130.2, 129.8, 127.0, 120.7, 117.7, 116.6, 114.9, 25.7,
25.6, 22.6, 22.4; HRMS (ESI): m/z calculated for C23H18 BrN3O5S2
561.0028 found 561.0016 [M+2]+.
4.1.10. 4-(4-(phenylsulfonyl)piperazin-1-yl)-5,6,7,8-
tetrahydrobenzo[4,5]thieno[2,3-d] pyrimidine
(13a)
Off-white solid; yield 80 %; mp:160–164 °C; FT-IR (cm−1):
3325, 3062, 1650, 1585, 780, 710; 1H NMR (500 MHz, Trifluo-
roacetic acid-d) δ 8.46 (s, 1H), 7.81 (dd, J = 19.6, 7.6 Hz, 2H),
7.77–7.69 (m, 1H), 7.64 (t, J = 7.8 Hz, 2H), 4.20 (s, 4H), 3.30 (d,
J = 41.6 Hz, 4H), 3.03–2.91 (m, 2H), 2.85 (s, 2H), 2.11–2.00 (m, 2H),
1.84 (s, 2H); 13C NMR (125 MHz, Trifluoroacetic acid-d) δ 160.1,
154.9, 143.6, 139.4, 134.9, 134.8, 133.7, 129.9, 129.9, 128.7, 127.5,
127.4, 118.8, 49.4, 46.0, 45.6, 28.0, 25.1, 22.2, 22.0; HRMS (ESI): m/z
calculated C20H22N402S2 416.1561 for found 415.1590 [M+H]+.
4.1.6. 2-(((4-(tert-butyl)phenyl)sulfonyl)oxy)-4-((5,6,7,8-
tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)amino)benzoic acid
(9e)
Off-white solid; yield 80 %; mp:160–164 °C; FT-IR (cm−1):
3325, 3062, 1650, 1585, 780, 710; 1H NMR (500 MHz, DMSO-d6):
δ 8.37 (s, 1H), 8.26 (s, 1H), 7.83 (d, J = 8.5 Hz, 2H), 7.69 (d,
J = 8.5 Hz, 2H), 7.62–7.47 (m, 2H), 7.34 (t, J = 8.1 Hz, 1H), 6.79–
6.71 (m, 1H), 3.10 (s, 2H), 2.83 (s, 2H), 1.85 (s, 4H), 1.27 (s, 8H);
13C NMR (125 MHz, DMSO- d6): δ 166.6, 158.7, 154.7, 152.2, 149.5,
141.3, 134.0, 132.2, 130.0, 128.6, 127.1, 127.0, 120.6, 117.6, 116.6,
115.1, 35.6, 31.0, 25.7, 25.6, 22.6, 22.4; HRMS (ESI): m/z calculated
for C27H27N3O5S2 538.0681 found 538.0709 [M+H]+.
4.1.11. 4-(4-((2-chlorophenyl)sulfonyl)piperazin-1-yl)-5,6,7,8-
tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine
(13b)
Off-white solid; yield 80 %; mp:160–164 °C; FT-IR (cm−1):
3325, 3062, 1650, 1585, 780, 710; 1H NMR (500 MHz, Trifluo-
roacetic acid-d) δ 8.55 (s, 2H), 8.17 (d, J = 7.9 Hz, 2H), 7.68 (d,
J = 3.4 Hz, 4H), 7.56 (dd, J = 4.7, 4.3 Hz, 2H), 4.39–4.13 (m, 11H),
3.63 (dd, J = 27.9, 23.2 Hz, 9H), 3.02 (t, J = 6.1 Hz, 5H), 2.93 (d,
J = 17.0 Hz, 5H), 2.14–2.05 (m, 5H), 1.96–1.85 (m, 5H); 13C NMR
(125 MHz, Trifluoroacetic acid-d) δ 160.2, 154.9, 143.5, 139.4, 135.6,
133.8, 132.8, 132.5, 132.2, 128.7, 127.7, 118.9, 49.8, 45.5, 28.0, 25.0,
22.1, 21.9; HRMS (ESI): m/z calculated C20H21ClN4O2S2 449.0794
for found 449.0821 [M+H]+.
4.1.7. 4-((5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-
yl)amino)-2-(tosyloxy)benzoic acid
(9f)
Off-white solid; yield 80 %; mp:156–159 °C; FT-IR (cm−1):
3325, 3062, 1650, 1585, 780, 710; 1H NMR (500 MHz, DMSO-d6):
δ 8.38 (d, J = 10.6 Hz, 1H), 8.25 (s, 1H), 7.91 (t, J = 15.1 Hz, 2H),
7.83 (t, J = 7.4 Hz, 1H), 7.70 (t, J = 7.8 Hz, 2H), 7.63–7.47 (m, 1H),
10