4.1.50.
(R)-2,4-difluoro-N-(2-methoxy-5-(4-(3-
(t, JC-F = 26.1 Hz), 53.5, 49.3, 26.3. HRMS (ESI): m/z [M + H]+
methylmorpholino)thieno[2,3-d]pyrimidin-6-yl)pyridin-3-
calcd for C22H20F2N5O3S3, 536.0691, found 536.0692.
yl)benzenesulfonamide (6c)
4.1.54.
2,4-difluoro-N-(2-methoxy-5-(4-(piperidin-1-
Compound 6c was prepared from 9c in a yield of 39%,
according to the procedure of 6a. Yellow solid. H NMR (400
yl)thieno[2,3-d]pyrimidin-6-yl)pyridin-3-
yl)benzenesulfonamide (6g)
1
MHZ, DMSO-d6): δ 10.37 (s, 1H), 8.45 (d, J = 2.4 Hz, 1H), 8.40
(s, 1H), 8.01 (d, J = 2.4 Hz, 1H), 7.87 (s, 1H), 7.76 (td, J = 8.6,
6.3 Hz, 1H), 7.62 – 7.53 (m, 1H), 7.22 (td, J = 8.4, 2.1 Hz, 1H),
4.84 (q, J = 6.4 Hz, 1H), 4.44 – 4.24 (m, 1H), 4.06 – 3.89 (m,
1H), 3.79 – 3.67 (m, 2H), 3.64 (s, 3H), 3.60 – 3.46 (m, 2H), 1.31
(d, J = 6.8 Hz, 3H). 13C NMR (101 MHz, DMSO-d6) δ 168.3,
165.1 (dd, JC-F = 255, 11.9 Hz), 159.4 (dd, JC-F = 259, 13.7 Hz),
158.1, 157.1, 152.7, 142.0, 133.6, 133.0, 131.8 (d, JC-F = 10.7
Hz), 125.1 (dd, JC-F = 14.4, 3.6 Hz), 123.4, 119.9, 117.8, 116.9,
111.9 (dd, JC-F = 22.3, 3.4 Hz), 105.8 (t, JC-F = 26.3 Hz), 70.3,
66.2, 53.5, 48.4, 41.3, 14.5. HRMS (ESI): m/z [M + H]+ calcd for
C23H22F2N5O4S2, 534.1076, found 534.1071.
Compound 6g was prepared from 9g in a yield of 46%,
according to the procedure of 6a. Yellow solid. H NMR (400
1
MHZ, DMSO-d6): δ 10.37 (s, 1H), 8.46 (d, J = 2.4 Hz, 1H), 8.37
(s, 1H), 8.01 (d, J = 2.4 Hz, 1H), 7.84 (s, 1H), 7.77 (td, J = 8.6,
6.3 Hz, 1H), 7.64 – 7.54 (m, 1H), 7.23 (td, J = 8.4, 2.2 Hz, 1H),
3.96 – 3.84 (m, 4H), 3.65 (s, 3H), 1.77 – 1.58 (m, 6H). 13C NMR
(101 MHz, DMSO-d6) δ 168.0, 165.1 (dd, JC-F = 255, 11.9 Hz),
159.4 (dd, JC-F = 259, 13.5 Hz), 157.9, 157.4, 152.8, 141.9, 133.4,
132.6, 131.8 (d, JC-F = 10.8 Hz), 125.1 (dd, JC-F = 14.5, 3.4 Hz),
123.4, 119.8, 117.8, 116.8, 111.9 (dd, JC-F = 22.2, 3.1 Hz), 105.8
(t, JC-F = 26.2 Hz), 53.5, 47.6, 25.5, 24.0. HRMS (ESI): m/z [M +
H]+ calcd for C23H22F2N5O3S2, 518.1127, found 518.1133.
4.1.51. N-(5-(4-((2R,6S)-2,6-dimethylmorpholino)thieno[2,3-
d]pyrimidin-6-yl)-2-methoxypyridin-3-yl)-2,4-
difluorobenzenesulfonamide (6d)
4.1.55.
2,4-difluoro-N-(2-methoxy-5-(4-(pyrrolidin-1-
yl)thieno[2,3-d]pyrimidin-6-yl)pyridin-3-
yl)benzenesulfonamide (6h)
Compound 6d was prepared from 9d in a yield of 78%,
according to the procedure of 6a. Yellow solid. H NMR (400
Compound 6h was prepared from 9h in a yield of 20%,
according to the procedure of 6a. Yellow solid. H NMR (400
1
1
MHZ, DMSO-d6): δ 10.38 (s, 1H), 8.47 (d, J = 2.4 Hz, 1H), 8.39
(s, 1H), 7.97 (d, J = 2.4 Hz, 1H), 7.86 (s, 1H), 7.77 (td, J = 8.6,
6.4 Hz, 1H), 7.62 – 7.51 (m, 1H), 7.22 (td, J = 8.5, 2.3 Hz, 1H),
4.48 (d, J = 12.5 Hz, 2H), 3.71 – 3.60 (m, 5H), 2.84 (dd, J = 13.1,
10.7 Hz, 2H), 1.19 (d, J = 6.2 Hz, 6H). 13C NMR (101 MHz,
DMSO-d6) δ 168.1, 165.1 (dd, JC-F = 255, 11.8 Hz), 159.4 (dd, JC-
F = 259, 13.6 Hz), 157.9, 157.4, 152.6, 142.0, 133.3, 131.8 (d, JC-
F = 11.0 Hz), 125.1 (dd, JC-F = 14.3, 3.7 Hz), 123.3, 119.9, 117.5,
117.1, 111.9 (dd, JC-F = 22.4, 3.4 Hz), 105.8 (t, JC-F = 26.3 Hz),
71.0, 53.5, 51.6, 18.7. HRMS (ESI): m/z [M + H]+ calcd for
C24H24F2N5O4S2, 548.1232, found 548.1242.
MHZ, DMSO-d6): δ 10.35 (s, 1H), 8.42 (d, J = 1.9 Hz, 1H), 8.31
(s, 1H), 7.99 (d, J = 2.0 Hz, 1H), 7.89 (s, 1H), 7.77 (td, J = 8.5,
6.3 Hz, 1H), 7.66 – 7.50 (m, 1H), 7.23 (td, J = 8.4, 2.3 Hz, 1H),
3.82 (br s, 4H), 3.64 (s, 3H), 2.01 (br s, 4H). 13C NMR (151
MHz, DMSO-d6) δ 167.0, 165.1 (dd, JC-F = 254, 11.8 Hz), 159.4
(dd, JC-F = 258, 13.4 Hz), 157.8, 155.0, 153.3, 141.7, 133.3, 131.8
(d, JC-F = 10.7 Hz), 131.6, 125.1 (dd, JC-F = 14.3, 3.3 Hz), 123.6,
119.8, 118.1, 116.7, 111.9 (dd, JC-F = 22.2, 2.7 Hz), 105.8 (t, JC-F
= 26.0 Hz), 53.5, 48.7, 25.0 (br s).HRMS (ESI): m/z [M + H]+
calcd for C22H20F2N5O3S2, 504.0970, found 504.0976.
4.1.56. 2,4-difluoro-N-(2-methoxy-5-(4-(4-methoxypiperidin-
1-yl)thieno[2,3-d]pyrimidin-6-yl)pyridin-3-
yl)benzenesulfonamide (6i)
4.1.52.
N-(5-(4-(2,6-dimethylmorpholino)thieno[2,3-
d]pyrimidin-6-yl)-2-methoxypyridin-3-yl)-2,4-
difluorobenzenesulfonamide (6e)
Compound 6i was prepared from 9i in a yield of 75%,
according to the procedure of 6a. Yellow solid. H NMR (400
Compound 6e was prepared from 9e in a yield of 67%,
according to the procedure of 6a. Yellow solid. H NMR (400
1
1
MHz, DMSO-d6) δ 10.37 (s, 1H), 8.47 (d, J = 2.4 Hz, 1H), 8.39
(s, 1H), 8.03 (d, J = 2.4 Hz, 1H), 7.87 (s, 1H), 7.77 (td, J = 8.6,
6.4 Hz, 1H), 7.64 – 7.55 (m, 1H), 7.23 (td, J = 8.4, 2.3 Hz, 1H),
4.26 – 4.15 (m, 2H), 3.69 – 3.58 (m, 5H), 3.58 – 3.50 (m, 1H),
3.31 (s, 3H), 2.04 – 1.93 (m, 2H), 1.64 – 1.50 (m, 2H). 13C NMR
(101 MHz, DMSO-d6) δ 168.0, 165.1 (dd, JC-F = 255, 11.8 Hz),
159.4 (dd, JC-F = 259, 13.6 Hz), 158.0, 157.4, 152.8, 142.0, 133.6,
132.8, 131.8 (d, JC-F = 10.6 Hz), 125.1 (dd, JC-F = 14.3, 3.7 Hz),
123.4, 119.8, 117.8, 116.9, 111.9 (dd, JC-F = 22.3, 3.4 Hz), 105.8
(t, JC-F = 26.2 Hz), 74.9, 55.0, 53.5, 44.0, 30.4. HRMS (ESI): m/z
[M + H]+ calcd for C24H24F2N5O4S2, 548.1232, found 548.1231.
MHZ, DMSO-d6): δ 10.39 (s, 1H), 8.50 (d, J = 2.3 Hz, 1H), 8.42
(s, 1H), 7.99 (d, J = 2.4 Hz, 1H), 7.91 (s, 1H), 7.77 (td, J = 8.6,
6.3 Hz, 1H), 7.63 – 7.54 (m, 1H), 7.28 – 7.18 (m, 1H), 4.51 (d, J
= 12.3 Hz, 2H), 3.75 – 3.61 (m, 5H), 2.87 (dd, J = 13.2, 10.6 Hz,
2H), 1.20 (d, J = 6.2 Hz, 6H). 13C NMR (101 MHz, DMSO-d6) δ
168.1, 165.1 (dd, JC-F = 255, 11.8 Hz), 159.4 (dd, JC-F = 259, 13.6
Hz), 157.9, 157.4, 152.6, 142.0, 133.34, 133.26, 131.8 (d, JC-F
=
10.7 Hz), 125.1 (dd, JC-F = 14.4, 3.7 Hz), 123.3, 119.8, 117.5,
117.1, 111.9 (dd, JC-F = 22.3, 3.3 Hz), 105.8 (t, JC-F = 26.2 Hz),
71.0, 53.5, 51.6, 18.7. HRMS (ESI): m/z [M + H]+ calcd for
C24H24F2N5O4S2, 548.1232, found 548.1237.
4.1.57. 2,4-difluoro-N-(2-methoxy-5-(4-(3-methoxyazetidin-1-
yl)thieno[2,3-d]pyrimidin-6-yl)pyridin-3-
yl)benzenesulfonamide (6j)
4.1.53.
2,4-difluoro-N-(2-methoxy-5-(4-
thiomorpholinothieno[2,3-d]pyrimidin-6-yl)pyridin-3-
yl)benzenesulfonamide (6f)
Compound 6j was prepared from 9j in a yield of 44%,
according to the procedure of 6a. Yellow solid. H NMR (400
Compound 6f was prepared from 9f in a yield of 39%,
according to the procedure of 6a. Yellow solid. H NMR (400
1
1
MHZ, DMSO-d6): δ 10.42 (s, 1H), 8.50 (d, J = 2.3 Hz, 1H), 8.39
(s, 1H), 8.06 (d, J = 2.3 Hz, 1H), 7.83 (td, J = 8.5, 6.4 Hz, 1H),
7.74 (s, 1H), 7.71 – 7.58 (m, 1H), 7.29 (td, J = 8.5, 2.2 Hz, 1H),
4.66 (br s, 2H), 4.52 – 4.44 (m, 1H), 4.30 (br s, 2H), 3.70 (s, 3H).
13C NMR (151 MHz, DMSO-d6) δ 166.3, 165.1 (dd, JC-F = 254,
11.7 Hz), 159.4 (dd, JC-F = 258, 13.6 Hz), 158.0, 156.7, 153.5,
MHZ, DMSO-d6): δ 10.37 (s, 1H), 8.46 (d, J = 2.4 Hz, 1H), 8.41
(s, 1H), 8.01 (d, J = 2.4 Hz, 1H), 7.80 (s, 1H), 7.76 (td, J = 8.6,
6.3 Hz, 1H), 7.80 – 7.72 (m, 1H), 7.22 (td, J = 8.4, 2.2 Hz, 1H),
4.24 – 4.12 (m, 4H), 3.64 (s, 3H), 2.84 – 2.73 (m, 4H). 13C NMR
(101 MHz, DMSO-d6) δ 168.1, 165.1 (dd, JC-F = 255, 12.0 Hz),
159.4 (dd, JC-F = 258, 13.4 Hz), 158.0, 157.3, 152.7, 142.1, 133.6,
133.3, 131.8 (d, JC-F = 11.0 Hz), 125.1 (dd, JC-F = 14.4, 3.7 Hz),
123.3, 119.8, 117.5, 117.0, 111.9 (dd, JC-F = 22.3, 3.5 Hz), 105.8
141.9, 133.52, 133.47, 131.8 (d, JC-F = 10.7 Hz), 125.1 (dd, JC-F
=
14.3, 3.2 Hz), 123.4, 119.8, 116.3, 116.0, 111.9 (dd, JC-F = 22.0,
2.3 Hz), 105.8 (t, JC-F = 26.1 Hz), 69.7, 58.4 (br s), 55.5, 53.5.