S. Ahn and M.-K. Jeon
Tetrahedron 91 (2021) 132247
J ¼ 22.1 Hz), 47.2, 45.8, 28.7, 20.3 ppm; HRMS (EI): m/z calcd for
fluorophenyl)thieno[3,2-d]pyrimidine-2-carboxamide
(11j):
C
24H23FN4OS: 434.1577 [Mþ]; found: 434.1575.
m.p. 80 ꢀC; 1H NMR (400 MHz, CDCl3):
d
¼ 8.12 (br t, J ¼ 6.1 Hz, 1H),
4-(Benzylamino)-6-(4-chlorophenyl)-N-isobutylthieno[3,2-
7.70 (dd, J ¼ 8.8 and 5.1 Hz, 2H), 7.57 (s, 1H), 7.17 (t, J ¼ 8.6 Hz, 2H),
6.81 (s, 1H), 6.80 (m, 2H), 5.78 (br s, 1H), 3.87 (s, 3H), 3.85 (s, 3H),
3.74 (q, J ¼ 6.8 Hz, 2H), 3.04 (m, 1H), 2.90 (t, J ¼ 6.9 Hz, 2H), 1.00 (m,
d]pyrimidine-2-carboxamide (11d): m.p. 300 ꢀC; 1H NMR
(400 MHz, CDCl3):
d
¼ 8.04 (br t, J ¼ 6.3 Hz, 1H), 7.71 (s, 1H), 7.63 (d,
J ¼ 8.6 Hz, 2H), 7.44 (d, J ¼ 8.6 Hz, 2H), 7.40 (m, 3H), 7.37 (d,
J ¼ 7.6 Hz, 1H), 7.34 (m, 1H), 5.39 (br t, J ¼ 5.9 Hz, 1H), 4.92 (d,
J ¼ 5.5 Hz, 2H), 3.32 (t, J ¼ 6.5 Hz, 2H), 1.91 (m, 1H), 0.97 (d,
2H), 0.81 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3):
d
¼ 163.8 (d,
J ¼ 251.7 Hz), 163.5, 162.0, 159.4, 154.6, 149.1, 147.8, 131.8, 129.4,
129.3, 128.7 (d, J ¼ 8.5 Hz), 120.9, 120.4, 116.5 (d, J ¼ 22.0 Hz), 114.7,
112.3, 111.5, 56.1, 56.0, 41.1, 35.5, 24.4, 10.0 ppm; HRMS (EI): m/z
calcd for C26H25FN4O3S: 492.1631 [Mþ]; found: 492.1632.
J ¼ 6.7 Hz, 6H) ppm; 13C NMR (100 MHz, CDCl3):
d
¼ 163.6, 161.2,
156.7, 155.0, 149.1, 138.1, 135.9, 131.5, 129.6, 129.0, 127.9, 127.8, 121.6,
115.9, 47.2, 45.8, 29.8, 28.7, 20.3 ppm; HRMS (EI): m/z calcd for
C
4-(Cyclopropylamino)-6-(4-fluorophenyl)-N-(2-(thiophen-2-
yl)ethyl)thieno[3,2-d]pyrimidine-2-carboxamide (11k): m.p.
24H23ClN4OS: 450.1281 [Mþ]; found: 450.1282.
4-(Benzylamino)-6-(4-cyanophenyl)-N-isobutylthieno[3,2-d]
138 ꢀC; 1H NMR (400 MHz, CDCl3):
d
¼ 8.25 (br t, J ¼ 5.3 Hz 1H), 7.70
pyrimidine-2-carboxamide (11e): m.p. 290 ꢀC; 1H NMR (400 MHz,
(dd, J ¼ 8.8 and 5.1 Hz, 2H), 7.59 (s, 1H), 7.19e7.13 (m, 3H), 6.95 (dd,
J ¼ 5.1 and 3.4 Hz,1H), 6.89 (d, J ¼ 3.2 Hz 1H), 5.83 (br s,1H), 3.78 (q,
J ¼ 6.6 Hz, 2H), 3.17 (t, J ¼ 6.7 Hz, 2H), 3.05 (m, 1H), 1.00 (m, 2H),
CDCl3):
d
¼ 8.02 (br t, J ¼ 6.3 Hz, 1H), 7.83 (s, 1H), 7.80 (d, J ¼ 8.8 Hz,
2H), 7.75 (d, J ¼ 8.8 Hz, 2H), 7.41 (m, 2H), 7.38 (m, 2H), 7.34 (m, 1H),
5.52 (br t, J ¼ 5.9 Hz, 1H), 4.92 (d, J ¼ 5.5 Hz, 2H), 3.33 (t, J ¼ 6.6 Hz,
2H), 1.91 (m, 1H), 0.97 (d, J ¼ 6.7 Hz, 6H) ppm; 13C NMR (100 MHz,
0.82 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3):
d
¼ 163.8 (d,
J ¼ 251.8 Hz), 163.6, 162.0, 159.4, 151.5, 141.6, 129.4, 128.7 (d,
J ¼ 8.4 Hz), 127.2, 125.6, 125.5, 124.0, 120.5, 116.5 (d, J ¼ 22.0 Hz),
115.3, 41.2, 30.2, 24.4, 10.0 ppm; HRMS (EI): m/z calcd for
CDCl3):
d
¼ 163.4, 161.1, 156.9, 155.3, 147.6, 137.8, 137.3, 133.1, 129.1,
128.1, 127.8, 127.2, 123.5, 118.3, 113.2, 47.2, 45.9, 29.8, 28.7,
20.3 ppm; HRMS (EI): m/z calcd for C25H23N5OS: 441.1623 [Mþ];
found: 441.1616.
C
22H19FN4OS2: 438.0984 [Mþ]; found: 438.0994.
6-(4-Chlorophenyl)-4-(cyclopropylamino)-N-(2-(pyrrolidin-
N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(cyclopropylamino)-6-
(4-methoxyphenyl)thieno[3,2-d]pyrimidine-2-carboxamide
1-yl)ethyl)thieno[3,2-d]pyrimidine-2-carboxamide (11l): m.p.
215 ꢀC; 1H NMR (400 MHz, CDCl3):
d
¼ 8.68 (br t, J ¼ 7.0 Hz,1H), 7.65
(11f): m.p. 110 ꢀC; 1H NMR (400 MHz, CDCl3):
d
¼ 8.30 (br t,
(d, J ¼ 8.5 Hz, 2H), 7.65 (s,1H), 7.43 (d, J ¼ 8.5 Hz, 2H), 6.47 (br s,1H),
3.73 (q, J ¼ 5.9 Hz, 2H), 3.08 (m, 1H), 2.99 (t, J ¼ 6.0 Hz, 2H), 2.89 (m,
4H), 1.89 (m, 4H), 1.03 (m, 2H), 0.85 (m, 2H) ppm; 13C NMR
J ¼ 5.9 Hz, 1H), 7.65 (d, J ¼ 8.8 Hz, 2H), 7.52 (s, 1H), 6.98 (d,
J ¼ 8.8 Hz, 2H), 6.88 (d, J ¼ 1.7 Hz, 1H), 6.83 (dd, J ¼ 7.9 and 1.7 Hz,
1H), 6.76 (d, J ¼ 7.9 Hz, 1H), 5.93 (s, 2H), 5.83 (br s, 1H), 4.59 (d,
J ¼ 6.0 Hz, 2H), 3.86 (s, 3H), 3.07 (m, 1H), 1.01 (m, 2H), 0.82 (m, 2H)
(100 MHz, CDCl3):
d
¼ 164.0, 161.9, 159.6, 154.6, 150.8, 135.8, 131.6,
129.5, 127.9, 120.8, 114.8, 54.9, 54.1, 38.2, 24.4, 23.6, 10.0 ppm;
HRMS (EI): m/z calcd for C22H24ClN5OS: 441.1390 [Mþ]; found:
441.1392.
ppm; 13C NMR (100 MHz, CDCl3):
154.3, 152.6, 148.0, 147.0, 132.3, 128.1, 125.7, 121.3, 118.9, 114.7, 114.3,
108.7, 108.3, 101.1, 55.6, 43.7, 24.4, 10.0 ppm; HRMS (EI): m/z calcd
for C25H22N4O4S: 474.1362 [Mþ]; found: 474.1365.
d
¼ 163.6, 162.1, 161.0, 159.3,
6-(4-Chlorophenyl)-4-(cyclopropylamino)-N-(2-(piperidin-
1-yl)ethyl)thieno[3,2-d]pyrimidine-2-carboxamide (11m): m.p.
Methyl
thieno[3,2-d]pyrimidine-2-carboxamido)methyl)benzoate
(11g): m.p. 115 ꢀC; 1H NMR (400 MHz, CDCl3):
4-((4-(cyclopropylamino)-6-(4-methoxyphenyl)
200 ꢀC; 1H NMR (400 MHz, CDCl3):
d
¼ 8.54 (br t, J ¼ 5.8 Hz, 1H),
7.65 (d, J ¼ 8.6 Hz, 2H), 7.64 (s, 1H), 7.43 (d, J ¼ 8.6 Hz, 2H), 6.17 (br s,
1H), 3.67 (q, J ¼ 6.0 Hz, 2H), 3.04 (m, 1H), 2.73 (t, J ¼ 6.2 Hz, 2H),
2.61 (s, 4H), 1.66 (p, J ¼ 5.6 Hz, 4H), 1.48 (m, 2H), 1.03 (m, 2H), 0.84
d
¼ 8.52 (br t,
J ¼ 6.2 Hz,1H), 7.98 (d, J ¼ 8.1 Hz, 2H), 7.63 (d, J ¼ 8.8 Hz, 2H), 7.52 (s,
1H), 7.42 (d, J ¼ 8.1 Hz, 2H), 6.96 (d, J ¼ 8.8 Hz, 2H), 6.27 (br s, 1H),
4.73 (d, J ¼ 6.2 Hz, 2H), 3.89 (s, 3H), 3.85 (s, 3H), 3.06 (m, 1H), 1.00
(m, 2H) ppm; 13C NMR (100 MHz, CDCl3):
d
¼ 163.8, 161.9, 159.5,
154.7, 150.8, 135.8, 131.7, 129.5, 127.9, 120.9, 114.9, 57.4, 54.4, 36.5,
25.6, 24.4, 24.2, 10.0 ppm; HRMS (EI): m/z calcd for C23H26ClN5OS:
455.1547 [Mþ]; found: 455.1547.
(m, 2H), 0.83 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3):
d
¼ 166.9,
163.5, 161.2, 161.1, 159.2, 153.6, 153.1, 143.6, 130.0, 129.3, 128.1, 127.7,
125.5, 118.5, 114.7, 114.3, 55.5, 52.2, 43.5, 24.5, 9.9 ppm; HRMS (EI):
m/z calcd for C26H24N4O4S: 488.1518 [Mþ]; found: 488.1516.
4-(Cyclopropylamino)-N-(pyridin-4-ylmethyl)-6-(p-tolyl)
thieno[3,2-d]pyrimidine-2-carboxamide (11h): m.p. 150 ꢀC; 1H
6-(4-Cyanophenyl)-4-(cyclopropylamino)-N-(2-
morpholinoethyl)thieno[3,2-d]pyrimidine-2-carboxamide
(11n): m.p. 228 ꢀC; 1H NMR (400 MHz, CDCl3):
d
¼ 8.36 (br t,
J ¼ 5.3 Hz,1H), 7.84 (d, J ¼ 8.6 Hz, 2H), 7.77 (d, J ¼ 8.4 Hz, 2H), 7.77 (s,
1H), 5.95 (br s, 1H), 3.74 (t, J ¼ 4.6 Hz, 4H), 3.62 (q, J ¼ 6.0 Hz, 2H),
3.11 (m, 1H), 2.63 (t, J ¼ 6.2 Hz, 2H), 2.53 (t, J ¼ 4.6 Hz, 4H), 1.06 (m,
NMR (400 MHz, CDCl3):
d
¼ 8.57 (d, J ¼ 5.9 Hz, 2H), 8.50 (br t,
J ¼ 6.3 Hz, 1H), 7.63 (d, J ¼ 8.1 Hz, 2H), 7.61 (s, 1H), 7.30 d, J ¼ 5.9 Hz,
2H), 7.28 (d, J ¼ 8.1 Hz, 2H), 7.27 (s, 1H), 5.94 (br s, 1H), 4.72 (d,
J ¼ 6.4 Hz, 2H), 3.10 (m, 1H), 2.42 (s, 3H), 1.03 (m, 2H), 0.84 (m, 2H)
2H), 0.86 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3):
d
¼ 163.5, 161.6,
159.6, 154.9, 149.4, 137.3, 133.1, 127.2, 122.6, 118.3, 115.6, 113.2, 67.1,
ppm; 13C NMR (100 MHz, CDCl3):
d
¼ 164.1, 162.0, 159.6, 153.1,
57.3, 53.6, 36.4, 24.4, 10.0 ppm; HRMS (EI): m/z calcd for
154.0, 149.9, 147.9, 140.4, 130.2, 130.1, 126.7, 122.6, 119.6, 114.8, 42.7,
24.5, 21.5, 10.2 ppm; HRMS (EI): m/z calcd for C23H21N5OS: 415.1467
[Mþ]; found: 415.1469.
C
23H24N6O2S: 448.1681 [Mþ]; found: 448.1689.
6-(4-Cyanophenyl)-4-(cyclopropylamino)-N-(2-(1-
methylpyrrolidin-2-yl)ethyl)thieno[3,2-d]pyrimidine-2-
4-(Cyclopropylamino)-N-(2-methoxyphenethyl)-6-(p-tolyl)
carboxamide (11o): m.p. 124 ꢀC; 1H NMR (400 MHz, CDCl3):
thieno[3,2-d]pyrimidine-2-carboxamide (11i): m.p. 126 ꢀC; 1H
d
¼ 8.37 (br t, J ¼ 6.1 Hz, 1H), 7.83 (d, J ¼ 8.5 Hz, 2H), 7.76 (d,
NMR (400 MHz, CDCl3):
d
¼ 8.20 (br t, J ¼ 5.6 Hz, 1H), 7.58 (d,
J ¼ 8.6 Hz, 2H), 7.76 (s, 1H), 6.33 (br s, 1H), 3.66 (m, 1H), 3.44 (m,
J ¼ 7.6 Hz, 3H), 7.25 (d, J ¼ 8.3 Hz, 2H), 7.19 (dd, J ¼ 7.7 and 1.7 Hz,
1H), 7.16 (dd, J ¼ 7.4 and 1.7 Hz, 1H), 6.87 (t, J ¼ 8.4 Hz, 2H), 5.09 (br
s, 1H), 3.84 (s, 3H), 3.70 (q, J ¼ 6.5 Hz, 2H), 3.05 (m, 1H), 2.94 (t,
J ¼ 6.8 Hz, 2H), 2.40 (s, 3H), 0.99 (m, 2H), 0.88 (m, 2H) ppm; 13C
2H), 3.11 (m, 1H), 2.71 (m, 1H), 2.54 (s, 3H), 2.17 (m, 2H), 1.95 (m,
1H), 1.87 (m, 2H), 1.77 (m, 1H), 1.06 (m, 2H), 0.88 (m, 2H) ppm; 13
C
NMR (100 MHz, CDCl3):
d
¼ 163.6, 161.7, 159.8, 154.7, 149.6, 137.4,
133.1, 127.2, 122.5, 118.4, 115.5, 113.2, 65.2, 56.5, 39.9, 37.2, 32.0,
30.2, 24.4, 21.9, 10.2 ppm; HRMS (EI): m/z calcd for C24H26N6OS:
446.1889 [Mþ]; found: 446.1895.
NMR (100 MHz, CDCl3):
d
¼ 161.6, 158.7, 157.7, 154.4, 152.0, 140.7,
130.6, 130.0, 129.7, 128.0, 127.3, 126.6, 126.5, 120.6, 117.9, 114.5,
110.4, 55.4, 40.0, 30.3, 24.8, 21.5, 9.3 ppm; HRMS (EI): m/z calcd for
C
4-((Benzo[d][1,3]dioxol-5-ylmethyl)amino)-N-cyclopropyl-6-
(4-methoxyphenyl)thieno[3,2-d]pyrimidine-2-carboxamide
26H26N4O2S: 458.1776 [Mþ]; found: 458.1778.
4-(Cyclopropylamino)-N-(3,4-dimethoxyphenethyl)-6-(4-
(11p): m.p. 230 ꢀC; 1H NMR (400 MHz, CDCl3):
d
¼ 7.93 (br d,
11