F.-C. Wang, et al.
BioorganicChemistryxxx(xxxx)xxxx
J = 15.6 Hz, 1H, COCH]), 7.42 (s, 2H, Ph 2′-H, 6′-H), 8.30 (d,
J = 15.6 Hz, 1H, CH]), 12.73 (s, 1H, NH). 13C NMR (150 MHz,
DMSO‑d6) δ: 16.14, 56.01, 56.38 (2C), 91.54 (2C), 110.65, 120.0,
125.06, 134.41, 136.26, 139.53, 149.97, 157.68, 158.93 (2C), 163.08,
163.34, 192.49. HRMS (ESI) m/z: calcd for C19H19N2O5S ([M+H]+):
387.1015; found: 387.1006.
140.56, 158.45, 163.14 (d, J = 247.05 Hz), 164.67, 168.27, 189.66.
HRMS (ESI) m/z: calcd for C16H12FN2O2S ([M+H]+): 315.0604; found:
315.0593.
4.1.4.11. (E)-6-Methyl-2-(3-(4-nitrophenyl)acryloyl)thieno[2,3-d]
pyrimidin-4(3H)-one (4k). Yield: 56% (57 mg), yellow solid, mp
284–286 °C. HPLC rt = 1.984 min (100%). 1H NMR (600 MHz,
CF3COOD) δ: 2.60 (s, 3H, CH3), 7.30 (s, 1H, thieno[2,3-d]pyrimidine
5-H), 7.89 (d, J = 15.6 Hz, 1H, COCH]), 8.31 (d, J = 15.6 Hz, 1H,
CH]), 8.70 (d, J = 4.8 Hz, 2H, Ph 2′-H, 6′-H), 9.03 (d, J = 4.8 Hz, 2H,
Ph 3′-H, 5′-H). 13C NMR (150 MHz, CF3COOD) δ: 16.21, 119.52,
121.46, 124.36 (2C), 126.23, 129.97 (2C), 140.23, 144.38, 145.95,
147.52, 148.97, 161.36 (overlapped with CF3COOD), 164.38, 182.15.
HRMS (ESI) m/z: calcd for C16H12N3O4S ([M+H]+): 342.0549; found:
342.0538.
4.1.4.6. (E)-2-(3-(4-Hydroxy-3-methoxyphenyl)acryloyl)-6-methylthieno
[2,3-d]pyrimidin-4(3H)-one (4f). Yield: 69% (71 mg), yellow solid,
mp > 330 °C. HPLC rt = 8.016 min (99%). 1H NMR (600 MHz,
DMSO‑d6) δ: 2.54 (d, J = 1.2 Hz, 3H, CH3), 3.88 (s, 3H, OCH3), 6.95
(d, J = 8.4 Hz, 1H, Ph 5′-H), 7.15 (d, J = 1.2 Hz, 1H, thieno[2,3-d]
pyrimidine 5-H), 7.29 (d, J = 15.6 Hz, 1H, COCH]), 7.59 (d,
J = 2.4 Hz, 1H, Ph 2′-H), 7.76 (dd, J = 8.4, 2.4 Hz, 1H, Ph 6′-H),
8.30 (d, J = 15.6 Hz, 1H, CH]), 10.28 (s, 1H, OH), 12.72 (br s, 1H,
NH). 13C NMR (150 MHz, DMSO‑d6) δ: 16.15, 56.14, 111.94, 115.57,
120.03, 124.82, 125.12, 129.09, 130.38, 134.14, 139.60, 148.45,
150.16, 153.19, 157.82, 163.41, 186.53. HRMS (ESI) m/z: calcd for
4.1.4.12. (E)-2-(3-(Furan-2-yl)acryloyl)-6-methylthieno[2,3-d]pyrimidin-
4(3H)-one (4l). Yield: 80% (69 mg), yellow solid, mp 294–296 °C.
HPLC rt = 3.837 min (95%). 1H NMR (600 MHz, DMSO‑d6) δ: 2.55
(d, J = 1.2 Hz, 3H, CH3), 6.84 (dd, J = 3.6, 1.2 Hz, 1H, furan 4′-H),
7.16 (d, J = 1.2 Hz, 1H, thieno[2,3-d]pyrimidine 5-H), 7.38 (d,
J = 15.6 Hz, 1H, COCH]), 7.83 (d, J = 3.6 Hz, 1H, furan 3′-H), 8.08
(d, J = 15.6 Hz, 1H, CH]), 8.15 (d, J = 1.2 Hz, 1H, furan 5′-H), 12.74
(s, 1H, NH). 13C NMR (150 MHz, DMSO‑d6) δ: 15.91, 113.52, 116.21,
119.05, 120.12, 127.27, 131.41, 142.03, 147.21, 147.72, 150.97,
156.68, 160.85, 181.41. HRMS (ESI) m/z: calcd for C14H11N2O3S ([M
+H]+): 287.0490; found: 287.0482.
C
17H15N2O4S ([M+H]+): 343.0753; found: 343.0744.
4.1.4.7. (E)-2-(3-(4-Methylphenyl)acryloyl)-6-methylthieno[2,3-d]
pyrimidin-4(3H)-one (4g). Yield: 64% (60 mg), yellow solid, mp
264–267 °C. HPLC rt = 1.865 min (100%). 1H NMR (600 MHz,
DMSO‑d6) δ: 2.42 (s, 3H, CH3), 2.55 (d, J = 1.2 Hz, 3H, CH3), 7.17
(d, J = 1.2 Hz, 1H, thieno[2,3-d]pyrimidine 5-H), 7.33 (d, J = 15.6 Hz,
1H, COCH]), 7.42 (d, J = 8.4 Hz, 2H, Ph 3′-H, 5′-H), 8.05 (d,
J = 8.4 Hz, 2H, Ph 2′-H, 6′-H), 8.32 (d, J = 15.6 Hz, 1H, CH]),
12.77 (s, 1H, NH). 13C NMR (150 MHz, DMSO‑d6) δ: 15.74, 21.26,
119.63, 124.80, 128.88 (2C), 129.61 (2C), 129.87, 134.19, 134.49,
139.38, 144.56, 149.57, 157.36, 162.92, 187.85. HRMS (ESI) m/z:
calcd for C17H15N2O2S ([M+H]+): 311.0854; found: 311.0841.
4.1.4.13. (E)-6-Methyl-2-(3-(thiophen-2-yl)acryloyl)thieno[2,3-d]
pyrimidin-4(3H)-one (4m). Yield: 61% (55 mg), yellow solid, mp
308–311 °C. HPLC rt = 6.879 min (99%). 1H NMR (600 MHz,
DMSO‑d6) δ: 2.59 (d, J = 1.2 Hz, 3H, CH3), 7.24 (dd, J = 4.8, 3.6 Hz,
1H, thiophene 4′-H), 7.25 (d, J = 1.2 Hz, 1H, thieno[2,3-d]pyrimidine
5-H), 7.68 (d, J = 15.6 Hz, 1H, COCH]), 7.75 (d, J = 3.6 Hz, 1H,
thiophene 3′-H), 7.88 (d, J = 4.8 Hz, 1H, thiophene 5′-H), 8.07 (d,
J = 15.6 Hz, 1H, CH]), 12.49 (s, 1H, NH). 13C NMR (150 MHz,
DMSO‑d6) δ: 15.92, 117.66, 120.13, 127.32, 129.14, 131.68, 134.62,
138.32, 139.55, 142.03, 147.72, 156.69, 160.82, 181.36. HRMS (ESI)
m/z: calcd for C14H11N2O2S2 ([M+H]+): 303.0262; found: 303.0251.
4.1.4.8. (E)-2-(3-(4-Bromophenyl)acryloyl)-6-methylthieno[2,3-d]
pyrimidin-4(3H)-one (4h). Yield: 61% (69 mg), yellow solid,
mp > 330 °C. HPLC rt = 5.571 min (100%). 1H NMR (600 MHz,
DMSO‑d6) δ: 2.59 (d, J = 1.2 Hz, 3H, CH3), 7.26 (d, J = 1.2 Hz, 1H,
thieno[2,3-d]pyrimidine 5-H), 7.68 (d, J = 8.4 Hz, 2H, Ph 2′-H, 6′-H),
7.83 (d, J = 8.4 Hz, 2H, Ph 3′-H, 5′-H), 7.86 (d, J = 16.2 Hz, 1H,
COCH]), 8.03 (d, J = 16.2 Hz, 1H, CH]), 12.54 (s, 1H, NH). 13C NMR
(150 MHz, DMSO‑d6) δ: 15.92, 120.15, 120.20, 124.78, 127.41, 130.98
(2C), 132.09 (2C), 133.39, 142.18, 144.18, 147.66, 156.70, 160.77,
181.95. HRMS (ESI) m/z: calcd for C16H12BrN2O2S ([M+H]+):
374.9803, 376.9782; found: 374.9795, 376.9765.
4.1.4.14. (E)-6-Methyl-2-(3-(pyridin-2-yl)acryloyl)thieno[2,3-d]
pyrimidin-4(3H)-one (4n). Yield: 56% (50 mg), yellow solid,
mp > 330 °C. HPLC rt = 3.272 min (95%). 1H NMR (600 MHz,
DMSO‑d6) δ: 2.60 (d, J = 1.2 Hz, 3H, CH3), 7.27 (d, J = 1.2 Hz, 1H,
thieno[2,3-d]pyrimidine 5-H), 7.48 (ddd, J = 7.8, 4.8, 1.2 Hz, 1H,
pyridine 4′-H), 7.85 (d, J = 7.8 Hz, 1H, pyridine 6′-H), 7.87 (d,
J = 15.6 Hz, 1H, COCH]), 7.92 (td, J = 7.8, 1.8 Hz, 1H, pyridine 5′-
H), 8.41 (d, J = 15.6 Hz, 1H, CH]), 8.73 (d, J = 4.8 Hz, 1H, pyridine
3′-H), 12.57 (s, 1H, NH). 13C NMR (150 MHz, DMSO‑d6) δ: 15.94,
120.20, 122.80, 125.38, 126.29, 127.45, 137.42, 142.33, 143.86,
147.67, 150.27, 152.08, 156.73, 160.80, 182.31. HRMS (ESI) m/z:
calcd for C15H12N3O2S ([M+H]+): 298.0650; found: 298.0641.
4.1.4.9. (E)-2-(3-(4-Chlorophenyl)acryloyl)-6-methylthieno[2,3-d]
pyrimidin-4(3H)-one (4i). Yield: 57% (57 mg), yellow solid, mp
220–223 °C. HPLC rt = 1.844 min (100%). 1H NMR (600 MHz,
DMSO‑d6) δ: 2.58 (d, J = 1.2 Hz, 3H, CH3), 7.25 (d, J = 1.2 Hz, 1H,
thieno[2,3-d]pyrimidine 5-H), 7.67 (d, J = 8.4 Hz, 2H, Ph 2′-H, 6′-H),
7.83 (d, J = 8.4 Hz, 2H, Ph 3′-H, 5′-H), 7.85 (d, J = 16.2 Hz, 1H,
COCH]), 8.03 (d, J = 16.2 Hz, 1H, CH]), 12.53 (s, 1H, NH). 13C NMR
(150 MHz, DMSO‑d6) δ: 15.92, 120.14, 120.17, 124.77, 127.40, 130.96
(2C), 132.07 (2C), 133.38, 142.16, 144.16, 147.64, 156.69, 160.75,
181.93. HRMS (ESI) m/z: calcd for C16H12ClN2O2S ([M+H]+):
331.0308, 333.0279; found: 331.0302, 333.0268.
4.1.4.15. (E)-6-Methyl-2-(3-(pyridin-3-yl)acryloyl)thieno[2,3-d]
pyrimidin-4(3H)-one (4o). Yield: 76% (68 mg), yellow solid, mp
221–224 °C. HPLC rt = 1.821 min (99%). 1H NMR (600 MHz,
DMSO‑d6) δ: 2.59 (s, 3H, CH3), 7.27 (s, 1H, thieno[2,3-d]pyrimidine
5-H), 7.51 (dd, J = 7.8, 4.8 Hz, 1H, pyridine 5′-H), 7.92 (d,
J = 16.2 Hz, 1H, COCH]), 8.13 (d, J = 16.2 Hz, 1H, CH]), 8.36 (d,
J = 7.8 Hz, 1H, pyridine 4′-H), 8.65 (d, J = 4.8 Hz, 1H, pyridine 6′-H),
9.0 (s, 1H, pyridine 2′-H), 12.58 (s, 1H, NH). 13C NMR (150 MHz,
CF3COOD) δ: 16.26, 120.98, 126.05, 128.15, 128.76, 130.09, 134.80,
138.84, 143.17, 143.61, 145.53, 147.94, 157.54, 161.63, 182.67.
4.1.4.10. (E)-2-(3-(4-Fluorophenyl)acryloyl)-6-methylthieno[2,3-d]
pyrimidin-4(3H)-one (4j). Yield: 45% (42 mg), yellow solid, mp
217–219 °C. HPLC rt = 3.511 min (98%). 1H NMR (600 MHz,
DMSO‑d6) δ: 2.55 (s, 3H, CH3), 7.17 (s, 1H, thieno[2,3-d]pyrimidine
5-H), 7.34 (d, J = 15.6 Hz, 1H, COCH]), 7.44 (t, J = 8.4 Hz, 2H, Ph 3′-
H, 5′-H), 8.23 (dd, J = 8.4, 6.0 Hz, 2H, Ph 2′-H, 6′-H), 8.31 (d,
J = 15.6 Hz, 1H, CH]), 12.77 (s, 1H, NH). 13C NMR (150 MHz,
DMSO‑d6) δ: 15.92, 115.96 (d, J = 21.6 Hz, 2C), 119.87, 123.86 (d,
J = 1.8 Hz), 125.12, 130.70 (d, J = 8.55 Hz, 2C), 131.65, 132.71,
HRMS (ESI) m/z: calcd for
C
15H12N3O2S ([M+H]+): 298.0650;
found: 298.0642.
10