Journal of Medicinal Chemistry
Article
2-((6-(4-(Methylsulfinyl)phenyl)thieno[3,2-d]pyrimidin-4-
yl)thio)acetic Acid (11m). Prepared using general procedure A,
with 4-(methylsulfinyl)phenylboronic acid. After purification, a
whitish solid was obtained (34 mg, 45%): mp 220.0−222.5 °C. H
DMSO-d6) δ 12.97 (s, 1H), 8.99 (s, 1H), 8.33 (s, 1H), 8.19−8.17 (m,
2H), 8.03−7.99 (m, 2H), 4.27 (s, 2H); 13C NMR (176 MHz,
DMSO) δ 169.6, 162.1, 159.1, 154.4, 149.6, 136.4, 133.5, 128.0,
127.8, 122.6, 118.6, 112.6, 31.8. HRMS (HESI) calcd for
C15H9N3O2S2 [M + H]+ 328.0214, found 328.0190.
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NMR (400 MHz, DMSO-d6) δ 12.94 (s, 1H), 8.98 (s, 1H), 8.24 (s,
1H), 8.20−8.16 (m, 2H), 7.87−7.83 (m, 2H), 4.27 (s, 2H), 2.82 (s,
3H); 13C NMR (176 MHz, DMSO) δ 169.3, 161.4, 159.2, 154.2,
150.2, 148.5, 133.9, 127.5, 127.1, 124.7, 121.4, 43.1, 31.5. HRMS
(HESI) calcd for C15H12N2O3S3 [M + H]+ 365.0088, found 365.0071.
2-((6-(4-Acetylphenyl)thieno[3,2-d]pyrimidin-4-yl)thio)-
acetic Acid (11n). Prepared using general procedure A, with 4-
acetylphenylboronic acid. After purification, a whitish solid was
2-((6-(4-(Ethoxycarbonyl)phenyl)thieno[3,2-d]pyrimidin-4-
yl)thio)acetic Acid (11u). Prepared using general procedure A, with
4-ethoxycarbonylphenylboronic acid. After purification, a pale orange
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solid was obtained (39 mg, 50%): mp 182.0−185.0 °C. H NMR
(400 MHz, DMSO-d6) δ 12.96 (s, 1H), 8.97 (s, 1H), 8.25 (s, 1H),
8.12 (d, J = 8.4 Hz, 2H), 8.06 (d, J = 8.4 Hz, 2H), 4.33 (q, J = 7.1 Hz,
2H), 4.25 (s, 2H), 1.34 (t, J = 7.1 Hz, 3H); 13C NMR (176 MHz,
DMSO) δ 169.3, 165.0, 161.6, 159.1, 154.1, 149.8, 136.0, 130.9,
130.0, 127.3, 127.0, 121.9, 61.0, 31.6, 14.1. HRMS (HESI) calcd for
C17H14N2O4S2 [M + H]+ 375.0473, found 375.0445.
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obtained (40 mg, 55%): mp 193.0−197.0 °C. H NMR (500 MHz,
DMSO-d6) δ 12.97 (s, 1H), 8.99 (s, 1H), 8.29 (s, 1H), 8.14 (d, J =
8.5 Hz, 2H), 8.10 (d, J = 8.5 Hz, 2H), 4.28 (s, 2H), 2.65 (s, 3H); 13C
NMR (176 MHz, DMSO) δ 197.3, 169.3, 161.5, 159.2, 154.2, 150.0,
137.6, 135.9, 129.2, 127.4, 127.0, 121.9, 31.5, 26.9. HRMS (HESI)
calcd for C16H12N2O3S2 [M + H]+ 345.0367, found 345.0357.
2-((6-(3-Morpholinophenyl)thieno[3,2-d]pyrimidin-4-yl)-
thio)acetic Acid (11o). Prepared using general procedure A, with 3-
morpholinophenylboronic acid. After purification, a pale orange solid
2-((6-(3-Fluorophenyl)thieno[3,2-d]pyrimidin-4-yl)thio)-
acetic Acid (11v). Prepared using general procedure A, with 3-
fluorophenylboronic acid. After purification, a white solid was
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obtained (39 mg, 58%): mp 194.0−196.5 °C. H NMR (400 MHz,
DMSO-d6) δ 12.96 (s, 1H), 8.97 (s, 1H), 8.22 (s, 1H), 7.91 (dt, J =
10.2, 2.2 Hz, 1H), 7.80 (dd, J = 7.7, 1.6 Hz, 1H), 7.60 (td, J = 8.0, 6.0
Hz, 1H), 7.38 (dd, J = 8.6, 2.6 Hz, 1H), 4.27 (s, 2H); 13C NMR (176
MHz, DMSO-d6) δ 169.2, 162.5 (d, J = 246.3 Hz), 161.5, 159.1,
154.1, 149.9 (d, J = 2.8 Hz), 134.1 (d, J = 8.4 Hz), 131.5 (d, J = 8.5
Hz), 127.1, 122.9 (d, J = 2.5 Hz), 121.3, 117.1 (d, J = 21.3 Hz), 113.6
(d, J = 23.7 Hz), 31.6; 19F NMR (376 MHz, DMSO-d6) δ −111.82 to
−111.92 (m, 1F). HRMS (HESI) calcd for C14H9FN2O2S2 [M + H]+
321.0167, found 321.0151.
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was obtained (29 mg, 35%): mp 229.0−233.0 °C. H NMR (500
MHz, DMSO-d6) δ 12.94 (s, 1H), 8.95 (s, 1H), 8.13 (s, 1H), 7.46 (t,
J = 2.1 Hz, 1H), 7.41−7.34 (m, 2H), 7.12−7.07 (m, 1H), 4.26 (s,
2H), 3.77 (dd, J = 5.8, 3.8 Hz, 4H), 3.26−3.23 (m, 4H); 13C NMR
(176 MHz, DMSO) δ 169.3, 161.0, 159.4, 154.0, 152.4, 151.7, 132.6,
130.1, 126.7, 120.0, 117.3, 116.9, 112.7, 66.0, 48.0, 31.4. HRMS
(HESI) calcd for C18H17N3O3S2 [M + H]+ 388.0789, found 388.0780.
2-((6-(4-Morpholinophenyl)thieno[3,2-d]pyrimidin-4-yl)-
thio)acetic Acid (11p). Prepared using general procedure A, with 4-
morpholinophenylboronic acid. After purification, an orange solid was
2-((6-(2-Fluorophenyl)thieno[3,2-d]pyrimidin-4-yl)thio)-
acetic Acid (11w). Prepared using general procedure A, with 2-
fluorophenylboronic acid. After purification, a white solid was
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obtained (29 mg, 35%): mp 205.0−208.0 °C. H NMR (500 MHz,
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obtained (40 mg, 60%): mp 184.0−187.0 °C. H NMR (400 MHz,
DMSO-d6) δ 12.92 (s, 1H), 8.88 (s, 1H), 7.89 (s, 1H), 7.82 (d, J =
8.9 Hz, 2H), 7.06 (d, J = 8.9 Hz, 2H), 4.24 (s, 2H), 3.78−3.72 (m,
4H), 3.28−3.23 (m, 4H); 13C NMR (176 MHz, DMSO) δ 169.5,
160.2, 159.9, 154.0, 152.5, 152.3, 127.8, 125.9, 121.8, 117.1, 114.6,
65.9, 47.2, 31.4. HRMS (HESI) calcd for C18H17N3O3S2 [M + H]+
388.0790, found 388.0773.
DMSO-d6) δ 12.96 (s, 1H), 8.99 (s, 1H), 8.13−8.07 (m, 2H), 7.58 (s,
1H), 7.49 (dd, J = 11.7, 1.2 Hz, 1H), 7.43−7.39 (m, 1H), 4.27 (s,
2H); 13C NMR (176 MHz, DMSO-d6) δ 169.3, 161.5, 158.9 (d, J =
149.4 Hz), 158.4, 154.1, 144.3 (d, J = 3.5 Hz), 132.3 (d, J = 8.8 Hz),
129.8, 127.2 (d, J = 5.3 Hz), 125.6 (d, J = 3.2 Hz), 122.9 (d, J = 4.8
Hz), 119.7 (d, J = 11.7 Hz), 116.8 (d, J = 22.0 Hz); 19F NMR (376
MHz, DMSO-d6) δ −112.35 to −112.50 (m, 1F). HRMS (HESI)
calcd for C14H9FN2O2S2 [M + H]+ 321.0167, found 321.0142.
2-((6-(3,4-Difluorophenyl)thieno[3,2-d]pyrimidin-4-yl)thio)-
acetic Acid (11x). Prepared using general procedure A, with 3,4-
difluorophenylboronic acid. After purification, a white solid was
2-((6-(6-Acetylpyridin-3-yl)thieno[3,2-d]pyrimidin-4-yl)-
thio)acetic Acid (11q). Prepared using general procedure A, with
(6-acetylpyridin-3-yl)phenylboronic acid. After purification, a pale
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orange solid was obtained (22 mg, 30%): mp 181.0−184.0 °C. H
NMR (400 MHz, DMSO-d6) δ 12.98 (s, 1H), 9.36 (d, J = 2.4 Hz,
1H), 9.01 (s, 1H), 8.55 (dd, J = 8.2, 2.4 Hz, 1H), 8.41 (s, 1H), 8.08
(d, J = 8.2 Hz, 1H), 4.29 (s, 2H), 2.69 (s, 3H); 13C NMR (176 MHz,
DMSO) δ 198.6, 169.2, 161.8, 158.9, 154.2, 153.2, 147.0, 146.8,
135.3, 131.2, 127.7, 123.1, 121.5, 31.6, 25.7. HRMS (HESI) calcd for
C15H11N3O3S2 [M + H]+ 346.0320, found 346.0310.
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obtained (32 mg, 45%): mp 206.0−209.0 °C. H NMR (500 MHz,
DMSO-d6) δ 12.96 (s, 1H), 8.97 (s, 1H), 8.20−8.16 (m, 2H), 7.83
(dd, J = 8.2, 3.9 Hz, 1H), 7.66−7.60 (m, 1H), 4.27 (s, 2H); 13C NMR
(176 MHz, DMSO) δ 169.3, 161.3, 159.1, 154.1, 150.9 (dd, J = 120.7,
12.8 Hz), 149.5 (dd, J = 117.2, 12.8 Hz), 149.0, 129.6−129.5 (m),
127.1, 124.1−123.9 (m), 121.3, 118.6 (d, J = 17.7 Hz), 116.1 (d, J =
18.8 Hz), 31.5; 19F NMR (376 MHz, DMSO-d6) δ −135.61 to
−135.88 (m, 1F), −136.89 to −137.13 (m, 1F). HRMS (HESI) calcd
for C14H8F2N2O2S2 [M + H]+ 339.0073, found 339.0058.
2-((6-(Thiophen-2-yl)thieno[3,2-d]pyrimidin-4-yl)thio)acetic
Acid (11r). Prepared using general procedure A, with 2-thienylbor-
onic acid. After purification, a pale orange solid was obtained (29 mg,
45%): mp 179.0−182.0 °C. 1H NMR (500 MHz, DMSO-d6) δ 12.95
(s, 1H), 8.93 (s, 1H), 7.85 (s, 1H), 7.83 (dd, J = 5.0, 1.2 Hz, 1H),
7.80 (dd, J = 3.7, 1.2 Hz, 1H), 7.26−7.23 (m, 1H), 4.25 (s, 2H); 13C
NMR (176 MHz, DMSO) δ 169.4, 160.9, 159.3, 154.3, 144.7, 134.7,
129.8, 129.0, 128.3, 126.3, 119.3, 31.5. HRMS (HESI) calcd for
C12H8N2O2S3 [M + H]+ 308.9826, found 308.9811.
2-((6-(3-Fluoro-4-(methylthio)phenyl)thieno[3,2-d]-
pyrimidin-4-yl)thio)acetic Acid (11y). Prepared using general
procedure A, with 3-fluoro-4-(methylthio)phenylboronic acid. After
purification, a pale yellow solid was obtained (32 mg, 42%): mp
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203.0−206.0 °C. H NMR (400 MHz, DMSO-d6) δ 12.95 (s, 1H),
2-((6-(Benzo[b]thiophen-2-yl)thieno[3,2-d]pyrimidin-4-yl)-
thio)acetic Acid (11s). Prepared using general procedure A, with
benzo[b]thien-2-ylboronic acid. After purification, a pale orange solid
8.95 (s, 1H), 8.17 (s, 1H), 7.92 (dd, J = 11.4, 2.0 Hz, 1H), 7.80 (dd, J
= 8.1, 2.0 Hz, 1H), 7.51−7.44 (m, 1H), 4.26 (s, 2H), 2.57 (s, 3H);
13C NMR (176 MHz, DMSO) δ 169.3, 161.1, 159.3, 158.6 (d, J =
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was obtained (30 mg, 40%): mp >250 °C. H NMR (500 MHz,
242.1 Hz), 154.1, 149.8 (d, J = 2.5 Hz), 129.9 (d, J = 8.1 Hz), 128.7
(d, J = 17.1 Hz), 127.3 (d, J = 3.3 Hz), 126.8, 123.3 (d, J = 2.8 Hz),
120.6, 112.9 (d, J = 23.4 Hz), 31.5, 13.5; 19F NMR (376 MHz,
DMSO-d6) δ −112.48 (dd, J = 11.4, 8.1 Hz). HRMS (HESI) calcd for
C15H11FN2O2S3 [M + H]+ 367.0044, found 367.0027.
DMSO-d6) δ 12.97 (s, 1H), 8.98 (s, 1H), 8.16 (s, 1H), 8.08−8.06 (m,
1H), 7.98 (s, 1H), 7.96−7.93 (m, 1H), 7.48−7.46 (m, 2H), 4.27 (s,
2H); 13C NMR (176 MHz, DMSO) δ 169.3, 161.2, 159.0, 154.3,
144.4, 139.6, 134.4, 126.9, 126.3, 125.4, 124.8, 124.7, 122.7, 121.2,
31.6. HRMS (HESI) calcd for C16H10N2O2S3 [M + H]+ 358.9982,
found 358.9971.
2-((6-(3-Fluoro-4-methoxyphenyl)thieno[3,2-d]pyrimidin-4-
yl)thio)acetic Acid (11z). Prepared using general procedure A, with
3-fluoro-4-methoxyphenylboronic acid. After purification, a pale
2-((6-(4-Cyanophenyl)thieno[3,2-d]pyrimidin-4-yl)thio)-
acetic Acid (11t). Prepared using general procedure A, with 4-
cyanophenylboronic acid. After purification, a pale brown solid was
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yellow solid was obtained (29 mg, 40%): mp 209.0−211.5 °C. H
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obtained (34 mg, 50%): mp 226.0−230.0 °C. H NMR (500 MHz,
NMR (400 MHz, DMSO-d6) δ 12.94 (s, 1H), 8.93 (s, 1H), 8.06 (s,
N
J. Med. Chem. XXXX, XXX, XXX−XXX