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d 8.85 (d, J ¼ 2.6 Hz, 1H), 8.46–8.39 (m, 1H), 8.15–8.08 (m, 2H), (dd, J ¼ 14.5, 6.9 Hz, 2H), 5.80 (dd, J ¼ 12.4, 5.0 Hz, 1H), 3.88 (dd, J
7.66–7.62 (m, 1H), 7.40 (t, J ¼ 8.9 Hz, 2H), 7.14 (d, J ¼ 2.6 Hz, ¼ 17.5, 12.4 Hz, 2H), 3.46 (s, 2H), 3.18 (dd, J ¼ 17.7, 5.1 Hz, 3H),
1H), 4.13 (s, 4H), 3.91 (d, J ¼ 4.5 Hz, 4H).
2.83 (s, 2H), 2.56 (s, 6H).
4-(2-(5-(4-Chlorophenyl)-1H-pyrazol-1-yl)thieno[2,3-d]
N1-(2-(3-(3,4-Dichlorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazol
pyrimidin-4-yl)morpholine (7d). A yellow solid, mp 280–282 ꢁC; -1-yl)thieno[2,3-d]pyrimidine-4-yl)-N1, N2,N2-trimethylethane-1,2-
1
ESI-MS m/z: [M + H]+: 397.8; H-NMR (400 MHz, DMSO) d 8.63 diamine (13e). A white solid, mp 262–263 C; ESI-MS m/z: [M +
ꢁ
(d, J ¼ 2.6 Hz, 1H), 8.19 (d, J ¼ 5.5 Hz, 1H), 7.86 (d, J ¼ 8.5 Hz, H]+: 525.5; 1H-NMR (400 MHz, DMSO) d 8.05 (d, J ¼ 5.4 Hz, 1H),
2H), 7.41 (dd, J ¼ 6.9, 4.8 Hz, 3H), 6.95 (d, J ¼ 2.7 Hz, 1H), 3.95– 7.77 (d, J ¼ 7.6 Hz, 2H), 7.62–7.50 (m, 2H), 7.48–7.37 (m, 3H),
3.84 (m, 4H), 3.72–3.62 (m, 4H).
7.20 (dd, J ¼ 20.5, 6.8 Hz, 2H), 5.77 (dd, J ¼ 12.2, 5.1 Hz, 1H),
3.88 (dd, J ¼ 17.7, 12.4 Hz, 1H), 3.79–3.70 (m, 1H), 3.53–3.43 (m,
1H), 3.26 (s, 3H), 3.14 (dd, J ¼ 17.7, 5.0 Hz, 1H), 2.20 (s, 2H), 2.11
(s, 6H).
5.5. General procedure for the preparation of target
compounds 10a–l
N1-(2-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol
-1-yl)thieno[2,3-d]pyrimidin-4-yl)-N1,N2,N2-ꢁtrimethylethane-1,2-
diamine (13f). A white solid, mp 287–289 C; ESI-MS m/z: [M +
H]+: 486.6; 1H-NMR (400 MHz, DMSO) d 8.04 (d, J ¼ 5.4 Hz, 1H),
7.70 (d, J ¼ 8.3 Hz, 2H), 7.30 (t, J ¼ 7.7 Hz, 2H), 7.26–7.19 (m,
3H), 7.16 (d, J ¼ 5.6 Hz, 1H), 7.00 (d, J ¼ 8.4 Hz, 2H), 5.82–5.71
Compounds 10a–l were synthesized according to the reported
procedures by our research group.13
5.6. General procedure for the preparation of target
compounds 13a–l
10a–l (chalcone) (0.001 mol) and 12 (N1-(2-mercaptothieno[2,3- (m, 1H), 3.92–3.84 (m, 2H), 3.80 (s, 3H), 3.46 (s, 2H), 3.17 (s, 1H),
d]pyrimidin-4-yl)-N1,N2,N2-trimethylethane-1,2-diamine) (0.001 3.09 (d, J ¼ 4.1 Hz, 1H), 3.05 (d, J ¼ 4.2 Hz, 1H), 2.85 (s, 2H), 2.56
mol) dissolved in 20 mL of acetic acid, concentrated H2SO4 is (s, 6H).
the catalyst. The reaction solution was heated on a 100–110 ꢁC
N1-(2-(3-(3,4-Dichlorophenyl)-5-(p-tolyl)-4,5-dihydro-1H-pyr-
oil bath, and the reaction was conrmed by TLC, and excess azol-1-yl)thieno[2,3-d]pyrimidin-4-yl)-N1,N2,N2-trimethylethane-
solvent was removed under reduced pressure. The precipitated 1,2-diamine (13g). A white solid, mp 269–270 ꢁC; ESI-MS m/z: [M
solid is suction ltered, washed with ethanol, dried, and + H]+: 539.5; H-NMR (400 MHz, DMSO) d 8.02 (d, J ¼ 5.4 Hz,
1
recrystallize with
compound 13a–1 is obtained.
a
suitable solvent mixture. The target 1H), 7.65 (d, J ¼ 8.0 Hz, 2H), 7.54 (d, J ¼ 8.3 Hz, 1H), 7.49 (s, 1H),
7.23 (dd, J ¼ 14.9, 6.7 Hz, 3H), 7.16 (d, J ¼ 8.3 Hz, 1H), 5.73 (dd, J
N1-(2-(3-(3,4-Dichlorophenyl)-5-(4-methoxyphenyl)-4,5-dihydro- ¼ 12.1, 5.2 Hz, 1H), 3.84 (dd, J ¼ 17.6, 12.2 Hz, 1H), 3.76–3.68
1H-pyrazol-1-yl)thieno[2,3-d]pyrimidin-4-yl)-N1,N2,N2-trimethyl- (m, 1H), 3.49–3.39 (m, 2H), 3.24 (s, 3H), 2.33 (s, 3H), 2.17 (s, 2H),
ethane-1,2-diamine (13a). A white solid, mp 232–233 ꢁC; ESI-MS 2.08 (s, 6H).
m/z: [M + H]+: 555.2; H-NMR (400 MHz, DMSO) d 8.14 (d, J ¼
N1-(2-(3-(4-Bromophenyl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazol-
1
5.5 Hz, 1H), 7.76 (d, J ¼ 8.5 Hz, 2H), 7.68–7.54 (m, 2H), 7.33–7.18 1-yl)thieno[2,3-d]pyrimidin-4-yl)-N1,N2,N2-trimethylethane-1,2-
(m, 2H), 7.07 (d, J ¼ 8.7 Hz, 2H), 6.02–5.74 (m, 1H), 4.03 (d, J ¼ diamine (13h). A white solid, mp 272–273 ꢁC; ESI-MS m/z: [M +
4.5 Hz, 2H), 3.89 (s, 1H), 3.86 (s, 3H), 3.62 (s, 1H), 3.46 (s, 3H), H]+:549.5; 1H-NMR (400 MHz, DMSO) d 8.08 (d, J ¼ 5.5 Hz, 1H),
3.28–3.17 (m, 2H), 2.84 (s, 6H).
7.65 (d, J ¼ 8.0 Hz, 2H), 7.50 (d, J ¼ 8.3 Hz, 2H), 7.24 (dd, J ¼
N1-(2-(5-(4-Bromophenyl)-3-(3,4-dichlorophenyl)-4,5-dihydro- 17.4, 8.2 Hz, 4H), 7.17 (d, J ¼ 5.4 Hz, 1H), 5.83 (dd, J ¼ 12.0,
1H-pyrazol-1-yl)thieno[2,3-d]pyrimidin-4-yl)-N1,N2,N2-trimethyl- 4.5 Hz, 1H), 3.86 (dd, J ¼ 17.7, 12.0 Hz, 2H), 3.40 (s, 3H), 3.10
ethane-1,2-diamine (13b). A white solid, mp 291–294 ꢁC; ESI-MS (dd, J ¼ 17.5, 4.4 Hz, 2H), 2.89 (s, 2H), 2.74 (d, J ¼ 7.9 Hz, 6H),
m/z: [M + H]+: 604.3; H-NMR (400 MHz, DMSO) d 8.05 (d, J ¼ 2.34 (s, 3H).
1
5.4 Hz, 1H), 7.69 (d, J ¼ 8.6 Hz, 2H), 7.64 (d, J ¼ 8.5 Hz, 2H), 7.55
N1-(2-(3,5-Diphenyl-4,5-dihydro-1H-pyrazol-1-yl)thieno[2,3-d]
(d, J ¼ 8.2 Hz, 1H), 7.51 (s, 1H), 7.25–7.08 (m, 2H), 5.79 (dd, J ¼ pyrimidin-4-yl)-N1,N2,N2-trimethylethane-1,2-diamine (13i). A
12.0, 5.0 Hz, 1H), 3.86 (dd, J ¼ 17.7, 12.3 Hz, 2H), 3.63 (s, 2H), white solid, mp 225–227 ꢁC; ESI-MS m/z: [M + H]+: 456.6; H-
1
3.48 (s, 1H), 3.15 (dd, J ¼ 17.5, 5.4 Hz, 2H), 2.57 (d, J ¼ 2.6 Hz, NMR (400 MHz, DMSO) d 8.14 (d, J ¼ 5.5 Hz, 1H), 7.86 (d, J ¼
2H), 2.37 (s, 6H).
6.9 Hz, 2H), 7.53 (dd, J ¼ 15.7, 8.1 Hz, 3H), 7.39 (t, J ¼ 7.5 Hz,
N1-(2-(3,5-Bis(4-uorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)thieno 2H), 7.30 (dd, J ¼ 14.4, 6.4 Hz, 4H), 5.90 (dd, J ¼ 11.9, 4.4 Hz,
[2,3-d]pyrimidin-4-yl)-N1,N2,N2-tri-methylethane-1,2-diamine (13c). 1H), 3.98 (dd, J ¼ 17.6, 12.1 Hz, 2H), 3.41 (s, 3H), 3.18 (dd, J ¼
A white solid, mp 256–257 ꢁC; ESI-MS m/z: [M + H]+: 492.5; 1H-NMR 17.5, 4.6 Hz, 2H), 2.88 (s, 2H), 2.60 (s, 6H).
(400 MHz, DMSO) d 8.03 (d, J ¼ 5.5 Hz, 1H), 7.84–7.75 (m, 2H), 7.48
N1-(2-(3-(4-Fluorophenyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-
(d, J ¼ 8.2 Hz, 2H), 7.28 (t, J ¼ 8.6 Hz, 2H), 7.18 (t, J ¼ 7.7 Hz, 3H), pyrazol-1-yl)thieno[2,3-d]pyrimidin-4-yl)-N1,N2,N2-trimethylethane-
5.75 (dd, J ¼ 12.3, 4.4 Hz, 1H), 3.86 (dd, J ¼ 17.6, 12.1 Hz, 1H), 3.73 1,2-diamine (13j). A white solid, mp 286–287 ꢁC; ESI-MS m/z: [M +
(d, J ¼ 7.0 Hz, 1H), 3.55 (d, J ¼ 13.6 Hz, 1H), 3.41 (s, 2H), 3.17 (s, H]+: 504.2; 1H-NMR (400 MHz, DMSO) d 8.08 (d, J ¼ 5.2 Hz, 1H),
1H), 3.08 (dd, J ¼ 17.5, 4.7 Hz, 1H), 2.36 (s, 2H), 2.20 (s, 6H).
7.71 (d, J ¼ 8.9 Hz, 2H), 7.21–7.09 (m, 4H), 7.01 (d, J ¼ 8.8 Hz, 3H),
N1-(2-(3-(3,4-Dichlorophenyl)-5-(4-uorophenyl)-4,5-dihydro-1H- 5.84 (d, J ¼ 7.0 Hz, 1H), 3.91 (d, J ¼ 17.0 Hz, 2H), 3.81 (s, 3H), 3.73
pyrazol-1-yl)thieno[2,3-d]pyrimidin-4-yl)-N1,N2,N2-trimethylethane-
(s, 2H), 3.17 (s, 1H), 3.10 (d, J ¼ 13.5 Hz, 3H), 2.85 (s, 1H), 2.74 (s,
1,2-diamine (13d). A white solid, mp 244–247 ꢁC; ESI-MS m/z: [M + 6H).
H]+: 543.4; H-NMR (400 MHz, DMSO) d 8.06 (d, J ¼ 5.5 Hz, 1H),
N1-(2-(3-(4-Bromophenyl)-5-(4-uorophenyl)-4,5-dihydro-1H-pyr-
1
7.83–7.77 (m, 2H), 7.58–7.51 (m, 2H), 7.29 (t, J ¼ 8.8 Hz, 2H), 7.19 azol-1-yl)thieno[2,3-d]pyrimidin-4-yl)-N1,N2,N2-trimethylethane-1,2-
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RSC Adv., 2019, 9, 29579–29589 | 29587