A.G. Golub et al. / European Journal of Medicinal Chemistry 46 (2011) 870e876
873
CH2), 7.40e7.50 (3H, m), 7.79e7.84 (3H, m), 8.75 (1H, s, 2-H), 12.80
(bs, OH). 13C NMR (100 MHz, DMSO-d6):
: 31.38, 95.42, 114.05,
126.36, 128.59, 129.10, 132.13, 143.41, 151.99, 161.96, 164.38, 169.28.
Anal. Calc. for C14H10N2O2S2: C, 55.61; H, 3.33; S, 21.21. Found: C,
55.60; H, 3.31; S, 21.20.
(400 MHz, DMSO-d6): d: 1.79 (4H, m, e(CH2)4e), 2.50 (2H, t), 2.58
d
(3H, s), 2.77e2.93 (4H, m, e(CH2)4e), 3.39 (2H, t). Anal. Calc. for
C14H16N2O2S2: C, 54.52; H, 5.23; S, 20.79. Found: C, 54.51; H, 5.22;
20.76.
2.1.4.19. 4-(5,6,7,8-Tetrahydro[1]benzothieno[2,3-d]pyrimidin-4-ylthio)
2.1.4.12. 2{[5-(4-Methylphenyl)thieno[2,3-d]pyrimidin-4-yl]thio}
butanoic acid (5s). Yield 81%; m.p. 153e154 ꢀC; 1H NMR (400 MHz,
propanoic acid (5l). Yield 81%; m.p. 159e160 ꢀC; 1H NMR (400 MHz,
DMSO-d6):
CH2), 2.84e3.05 (4H, m, e(CH2)4e), 3.32 (2H, t, CH2), 8.58 (1H, s, 2-
H), 11.94 (bs, OH). 13C NMR (100 MHz, DMSO-d6):
: 22.01, 22.08,
d: 1.88 (4H, m, e(CH2)4e), 1.95 (2H, t, CH2), 2.36 (2H, t,
DMSO-d6):
d
: 1.43 (3H, d, J ¼ 7.3 Hz, CH3), 2.42 (3H, s, CH3), 4.60 (1H,
q, J ¼ 7.3 Hz, J ¼ 7.3 Hz), 7.26 (2H, d, J ¼ 8.1 Hz, 4-CH3C6H4), 7.3 (2H,
d
d, J ¼ 8.1 Hz, 4-CH3C6H4), 7.58 (1H, s, 6-H), 8.75 (1H, s 2-H). 13C NMR
24.17, 25.26, 26.27, 28.05, 32.51, 95.46, 127.07, 127.70, 136.07, 151.01,
162.26, 164.40, 173.46. Anal. Calc. for C14H16N2O2S2: C, 54.52; H,
5.23; S, 20.79. Found: C, 54.51; H, 5.23; S, 20.76.
(100 MHz, DMSO-d6): d: 17.24, 20.98, 41.10, 95.44, 124.95, 125.46,
128.36, 129.71, 131.89, 135.06, 137.64, 151.33, 163.14, 166.05, 172.57.
Anal. Calc. for C16H14N2O2S2: C, 58.16; H, 4.27; S, 19.41. Found: C,
58.15; H, 4.26; H, 19.40.
2.1.4.20. 3-[(5,6-Dimethylthieno[2,3-d]pyrimidin-4-yl)thio]propanoic
acid (5t). Yield 87%; m.p. 189e190 ꢀC; 1H NMR (400 MHz, DMSO-
2.1.4.13. 2-{[5-(4-Methylphehyl)thieno[2,3-d]pyrimidin-4-yl]thio}
d6):
CH2), 8.61 (1H, s, 2-H), 12.19 (bs, OH). 13C NMR (100 MHz, DMSO-
d6): : 13.52,14.37, 24.17, 33.55, 95.44,124.92,128.53,133.18,150.88,
d: 2.47 (3H, s, CH3), 2.53 (3H, s, CH3), 2.69 (2H, t, CH2), 3.46 (2H,
butanoic acid (5m). Yield 84%; m.p.133e134 ꢀC; 1H NMR (400 MHz,
DMSO-d6):
d: 0.94 (3H, t, CH3), 1.71e1.89 (2H, m), 2.42 (3 H, s CH3),
d
4.59 (1H, t), 7.25 (2H, d, J ¼ 7.8, 4-CH3C6H4), 7.3 (2H, d, J ¼ 7.8,
162.21, 163.77, 172.54. Anal. Calc. for C11H12N2O2S2: C, 49.53; H,
4.51; S, 23.9. Found: C, 49.52; H, 4.50; S, 23.7.
4-CH3C6H4), 7.58 (1H, s, 6-H), 8.75 (1H, s, 2-H). 13C NMR (100 MHz,
DMSO-d6):
d: 11.59, 20.95, 24.64, 47.42, 95.40, 125.08, 125.50,
128.33, 129.76, 131.89, 135.07, 137.68, 151.39, 163.21, 166.02, 72.00.
Anal. Calc. for C17H16N2O2S2: C, 59.28; H, 4.68; S, 18.62. Found: C,
59.27; H, 4.66; S, 18.60.
2.1.4.21. [(6-Methyl-5-phenylthieno[2,3-d]pyrimidin-4-yl)thio]acetic
acid (5u). Yield 82%; m.p. 174e175 ꢀC; 1H NMR (400 MHz, DMSO-
d6):
d: 2.35 (3H, s, CH3), 3.78 (2H, s, CH2), 7.32 (2H, m, C6H5), 7.47
(3H, m, C6H5), 8.66 (1H, s, 2-H). 13C NMR (100 MHz, DMSO-d6):
d
:
2.1.4.14. {[5-(4-Bromophenyl)thieno[2,3-d]pyrimidin-4-yl]thio}acetic
14.09, 31.71, 95.40, 127.02, 128.10, 128.45, 130.58, 130.91, 133.60,
136.39, 150.98, 161.75, 163.43, 169.44. Anal. Calc. for C15H12N2O2S2:
C, 56.94; H, 3.82; S, 20.27. Found: C, 56.93; H, 3.80; S, 20.26.
acid (5n). Yield 80%; m.p. 171e172 ꢀC; 1H NMR (400 MHz, DMSO-
d6):
J ¼ 8.2, 4-BrC6H4),7.84 (1H, s, 6-H), 8.84 (1H, s, 2-H), 12,67 (bs, OH).
13C NMR (100 MHz, DMSO-d6):
: 31.77, 95.43, 122.08, 125.67,
d: 3.98 (2H, s, CH2), 7.44 (2H, d, J ¼ 8.2, 4-BrC6H4), 7,69 (2H,d,
d
2.1.5. Substituted (thieno[2,3-d]pyrimidin-4-ylthio)carboxylic acids
6aeg
130.76, 131.98, 133.64, 134.04, 151.56, 163.15, 165.83, 169.26. Anal.
Calc. for C14H9BrN2O2S2: C, 44.10; H, 2.38; S. 16.82. Found: C, 44.07;
H, 2.36; S, 16.81.
Compounds 6aeg shown in Table 1 were synthesized on the base
of substituted 4-chlorothieno[2,3-d]pyrimidines 4. To a suspension
of 0.01 mol of 3-mercaptopropanoic acid or mercaptoacetic acid and
0.024 mol of potassium carbonate in 10 mL DMF the 4-chlorothieno
[2,3-d]pyrimidine was added. The mixture was heated on a boiling
water bath for 10 min. The resulting mixture was evaporated in
vacuum. The residue was diluted with water and acetic acid slowly to
pH ¼ 7. The solid acid was filtrated and crystallized from isopropyl
alcohol.
2.1.4.15. 4-(5,6,7,8-Tetrahydro[1]benzothieno[2,3-d]pyrimidin-4-ylthio)
methyl]benzoic acid (5o). Yield 83%; m.p. 257e258 ꢀC; 1H NMR
(400 MHz, DMSO-d6): d: 1.80 (4H, m, e(CH2)4e), 2.82e2.98 (4H, m,
e(CH2)4e), 4.67 (2H, s, CH2), 7.58 (2H, d, J ¼ 8.2), 7.88 (2H, d,
J ¼ 8.2), 8.76 (1H, s, 2-H), 12.92 (bs, OH). 13C NMR (100 MHz, DMSO-
d6):
d: 21.96, 25.22, 26.17, 32.22, 95.46, 126.87, 127.35, 128.96,
129.28, 129.55, 136.35, 142.28, 150.90, 161.36, 164.55, 166.71. Anal.
Calc. for C18H16N2O2S2: C, 60.65; H, 4.52; C, 17.99. Found: C, 60.64;
H, 4.50; S, 17.97.
2.1.5.1. 3-{[5-(4-Methylphenyl)thieno[2,3-d]pyrymidin-4-yl]thio}
propanoic acid (6a). Yield 85%; m.p. 161e162 ꢀC; 1H NMR
(400 MHz, DMSO-d6):
(2H, t, CH2), 7.21 (2H, d, J ¼ 7.8, 4-CH3C6H4) 7.26 (2H, d, J ¼ 7.8,
4-CH3C6H4), 7.50 (1H, s, 6-H), 8.76 (1H, s, 2-H), 12.12 (bs, OH). 13
NMR (100 MHz, DMSO-d6): : 20.95, 24.42, 33.54, 95.39, 124.80,
125.79, 125.29, 129.76, 132.00, 135.19, 137.53, 151.62, 163.99, 165.85,
172.56. Anal. Calc. for C16H14N2O2S2: C, 58.16; H, 4.27; S, 19.41.
Found: C, 58.15; H, 4.26; S, 19.40.
d: 2.42 (3H, s, CH3), 2.56 (2H, t, CH2), 3.29
2.1.4.16. 3-{[5-(4-Chlorophenyl)thieno[2,3-d]pyrimidin-4-yl]thio}
propanoic acid (5p). Yield 85%; m.p. 168e169 ꢀC; 1H NMR
C
(400 MHz, DMSO-d6):
d, J ¼ 7.8, 4-ClC6H4), 7.44 (2H, d, J ¼ 7.8, 4-ClC6H4), 7.62 (1H, s, 6-H),
8.78 (1H, s, 2-H), 12.14 (bs, OH). 13C NMR (100 MHz, DMSO-d6):
d: 2.57 (2H, t, CH2), 3.32 (2H, t, CH2), 7.39 (2H,
d
d:
24.43, 33.54, 95.49, 125.45, 127.67, 131.56, 133.37, 133.77, 151.60,
163.85, 165.94, 172.38. Anal. Calc. for C15H11ClN2O2S2: C, 51.53; H;
3.16; S, 18.28. Found: C, 51.50; H, 3.15; S, 18.27.
2.1.5.2. 3-{[5-(3,4-Dimethylphenyl)thieno[2,3-d]pyrimidin-4-yl]thio}
propanoic acid (6b). Yield 84%; m.p. 133e134 ꢀC; 1H NMR
2.1.4.17. 3-{[(5,6-Dimethylthieno[2,3-d]pyrimidin-4-yl)thio]methyl}
(400 MHz, DMSO-d6): d: 2.30 (3H, s, CH3), 2.32 (3H, s, CH3), 2.57
benzoic acid (5q). Yield 80%; m.p. 116e117 ꢀC; 1H NMR (400 MHz,
(2H, t, CH2), 3.29 (2H, t, CH2), 7.07e7.17 (3H, m, 3,4-(CH3)2C6H3),
DMSO-d6):
7.39 (1H, t), 7.63 (1H, d), 7.82 (1H, d), 8.04 (1H, s), 8.65 (1H, s, 2-H),
12.60 (bs, OH). 13C NMR (100 MHz, DMSO-d6):
: 19.51, 14.37, 95.37,
d: 2.47 (3H, s, CH3), 2.52 (3H, s, CH3), 4.64 (2H, s, CH2),
7.46 (1H, s, 6-H), 8.75 (1H, s, 2-H), 12.10 (bs, OH). 13C NMR
(100 MHz, DMSO-d6): d: 19.27, 19.37, 24.42, 33.53, 95.39, 124.60,
d
125.78, 127.27, 128.78, 130.93, 130.93, 132.29, 135.45, 136.21, 150.78,
151.59, 164.00, 165.86, 172.58. Anal. Calc. for C17H16N2O2S2: C,
59.28; H, 4.68; S, 18.62. Found: C, 59.27; H, 4.67; S, 18.60.
124.90, 128.04, 128.56, 129.85, 130.95, 133.45, 137.77, 150.90, 161.82,
163.85, 166.90. Anal. Calc. for C16H14N2O2S2: C, 58.16; H, 4.27; S,
19.41. Found: C, 58.15; H, 4.26; S, 19.40.
2.1.5.3. [(6-Methylthieno[2,3-d]pyrimidin-4-yl)thio]acetic acid (6c). Yield
2.1.4.18. 3-[(2-Methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-
80%; m.p. 171e172 ꢀC; 1H NMR (400 MHz, DMSO-d6):
CH3), 4.09 (2H, s, CH2), 7.11 (1H, s, 5-H), 8.67 (1H, s, 2-H), 12.69 (bs, OH).
d
: 2.64 (3H, s,
4-yl)thio]propanoic acid (5r). Yield 83%; m.p. 177e178 ꢀC; 1H NMR