Y. Zhang et al.
Bioorganic & Medicinal Chemistry 38 (2021) 116114
4.2.14. (3-(((2-(2-methyl-4-(thiazole-4-carboxamido)-1H-indol-1-yl)-
6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)amino)methyl)phenyl)
boronic acid (25)
C25H28BN5O4S [M+Na]+ 528.1851, found 528.1843.
4.2.18. (3-(((2-(4-(but-2-ynamido)-2-methyl-1H-indol-1-yl)-5,6,7,8-
tetrahydroquinazolin-4-yl)amino)methyl)phenyl)boronic acid (29)
Compound 29 was synthesized from 17b and 2-butynoic acid ac-
cording to the procedure for preparing 20. 68% yield. 1H NMR (400
Compound 25 was synthesized from 16a and thiazole-4-carboxylic
acid according to the procedure for preparing 20. 78% yield. 1H NMR
–
–
(400 MHz, DMSO‑d6) δ 9.95 (s, 1H, CONH ), 9.30 (d, J = 2.0 Hz, 1H,
–
– –
MHz, DMSO‑d6) δ 10.30 (s, 1H, CONH ), 8.02 (d, J = 5.5 Hz, 2H,
thiazole), 8.53 (d, J = 2.0 Hz, 1H, thiazole), 8.04 (s, 2H, OH), 7.86 (t,
– –
–
– –
J = 6.1 Hz, 1H, NH ), 7.78 (d, J = 1.8 Hz, 1H, Ph), 7.70 (dt, J1 = 1.4
OH), 7.75 (s, 1H, NH ), 7.68 (d, J = 6.6 Hz, 1H, Ph), 7.65–7.61 (m,
Hz, J2 = 7.1 Hz, 1H, Ph), 7.57 (dd, J1 = 7.9 Hz, J2 = 11.3 Hz, 2H, Ph),
7.38–7.28 (m, 2H, Ph), 6.94 (t, J = 8.1 Hz, 1H, Ph), 6.39–6.35 (m, 1H, 3-
H of indole), 4.66 (d, J = 6.0 Hz, 2H, CH2Ph), 2.87 (t, J = 7.7 Hz, 2H,
CH2), 2.80 (t, J = 7.4 Hz, 2H, CH2), 2.48 (d, J = 1.0 Hz, 3H, Me), 2.12
(m, J = 7.8 Hz, 2H, CH2).13C NMR (100 MHz, DMSO‑d6) δ 171.45,
159.82, 159.10, 156.42, 155.76, 151.10, 139.07, 137.45, 137.28,
133.08, 133.01, 128.91, 128.74, 127.83, 125.62, 121.93, 121.84,
113.99, 113.59, 111.11, 101.69, 44.03, 34.17, 27.20, 21.69, 16.07.
HRMS calcd for C27H25BN6O3S [M+Na]+ 547.1698, found 547.1686.
1H, Ph), 7.48 (d, J = 8.3 Hz, 1H, Ph), 7.37 (d, J = 8.0 Hz, 1H, Ph),
7.34–7.26 (m, 2H, Ph), 6.82 (t, J = 8.0 Hz, 1H, Ph), 6.54 (s, 1H, 3-H of
indole), 4.65 (d, J = 6.2 Hz, 2H, CH2Ph), 2.68 (d, J = 4.6 Hz, 2H, CH2),
2.43 (s, 3H, Me), 2.06 (s, 3H, Me), 1.84 (m, J = 7.2 Hz, 4H, CH2). 13
C
NMR (100 MHz, DMSO‑d6) δ 162.09, 161.83, 154.36, 151.27, 139.22,
137.45, 136.66, 132.90, 132.85, 128.81, 128.67, 127.77, 121.65,
121.56, 114.26, 110.95, 109.72, 102.61, 84.54, 76.57, 44.30, 29.48,
22.50, 22.27, 16.10, 3.81. HRMS calcd for C28H28BN5O3 [M+Na]+
516.2182, found 516.2175.
4.2.15. (3-(((2-(4-(furan-2-carboxamido)-2-methyl-1H-indol-1-yl)-6,7-
dihydro-5H-cyclopenta[d]pyrimidin-4-yl)amino)methyl)phenyl)boronic
acid (26)
4.2.19. (3-(((2-(4-(furan-2-carboxamido)-2-methyl-1H-indol-1-yl)-
5,6,7,8-tetrahydroquinazolin-4-yl)amino)methyl)phenyl)boronic acid (30)
Compound 30 was synthesized from 17b and furan-2-carboxylic acid
according to the procedure for preparing 20. 67% yield. 1H NMR (400
Compound 26 was synthesized from 16a and furan-2-carboxylic acid
according to the procedure for preparing 20. 82% yield. 1H NMR (400
MHz, DMSO‑d6) δ 9.98 (s, 1H, CONH ), 8.05 (s, 2H, OH), 7.94 (d, J
–
–
–
–
–
–
– –
MHz, DMSO‑d6) δ 9.98 (s, 1H, CONH ), 8.04 (s, 2H, OH), 7.94 (d, J
= 1.7 Hz, 1H, furan), 7.78 (s, 1H, NH ), 7.70 (d, J = 7.0 Hz, 1H, Ph),
– –
= 1.7 Hz, 1H, furan), 7.85 (t, J = 6.1 Hz, 1H, NH ), 7.78 (s, 1H, Ph),
7.64 (s, 1H, Ph), 7.56 (d, J = 8.3 Hz, 1H, Ph), 7.38 (d, J = 3.5 Hz, 1H,
furan), 7.33 (d, J = 4.8 Hz, 1H, Ph), 7.29 (d, J = 7.5 Hz, 1H, Ph), 7.23 (d,
J = 7.7 Hz, 1H, Ph), 6.88 (t, J = 8.0 Hz, 1H, Ph), 6.71 (dd, J1 = 1.8 Hz, J2
= 3.5 Hz, 1H, furan), 6.37 (s, 1H, 3-H of indole), 4.67 (d, J = 5.9 Hz, 2H,
CH2Ph), 2.68 (t, J = 5.9 Hz, 2H, CH2), 2.45 (s, 3H, Me), 1.93–1.77 (m,
4H, CH2).13C NMR (100 MHz, DMSO‑d6) δ 164.31, 164.06, 158.92,
156.63, 150.42, 148.19, 141.47, 139.76, 139.06, 136.72, 135.13,
135.09, 130.92, 130.72, 129.99, 125.56, 123.84, 118.24, 117.04,
114.69, 113.59, 111.91, 105.21, 46.55, 34.19, 27.81, 24.73, 24.50,
18.24. HRMS calcd for C29H28BN5O4 [M+Na]+ 544.2131, found
544.2121.
7.70 (d, J = 7.3 Hz, 1H, Ph), 7.61 (d, J = 8.3 Hz, 1H, Ph), 7.36 (dd, J1 =
5.0 Hz, J2 = 8.2 Hz, 2H, Ph), 7.31 (t, J = 7.4 Hz, 1H, furan), 7.23 (d, J =
7.6 Hz, 1H, Ph), 6.91 (t, J = 8.0 Hz, 1H, Ph), 6.71 (dd, J1 = 1.8 Hz, J2 =
3.5 Hz, 1H, furan), 6.38 (s, 1H, 3-H of indole), 4.66 (d, J = 5.8 Hz, 2H,
CH2Ph), 2.87 (t, J = 7.8 Hz, 2H, CH2), 2.80 (t, J = 7.3 Hz, 2H, CH2), 2.47
(s, 3H, Me), 2.11 (m, 2H, CH2).13C NMR (100 MHz, DMSO‑d6) δ 171.44,
159.81, 156.71, 156.48, 148.19, 146.00, 139.08, 137.59, 136.89,
133.08, 133.01, 128.92, 128.54, 127.83, 123.39, 121.67, 116.11,
114.84, 113.49, 112.49, 111.42, 103.13, 44.03, 34.18, 27.20, 21.69,
16.11. HRMS calcd for C28H26BN5O4 [M+Na]+ 530.1974, found
530.1964.
4.2.20. (3-(((2-(2-methyl-4-(methylsulfonamido)-1H-indol-1-yl)-7,8-
dihydro-5H-pyrano[4,3-d]pyrimidin-4-yl)amino)methyl)phenyl)boronic
acid (31)
4.2.16. (3-(((2-(4-(isoxazole-5-carboxamido)-2-methyl-1H-indol-1-yl)-
6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)amino)methyl)phenyl)
boronic acid (27)
Compound 31 was synthesized from 16c and methanesulfonyl
Compound 27 was synthesized from 16a and isoxazole-5-carboxylic
acid according to the procedure for preparing 20. 79% yield. 1H NMR
(400 MHz, DMSO‑d6) δ 7.81 (d, J = 1.9 Hz, 1H, isoxazole), 6.96 (s, 1H,
Ph), 6.89–6.76 (m, 1H, Ph), 6.72 (t, J = 9.0 Hz, 1H, Ph), 6.62–6.46 (m,
3H, Ph), 6.34 (d, J = 1.9 Hz, 1H, Ph), 6.17 (t, J = 7.6 Hz, 1H, 3-H of
indole), 5.58 (s, 1H, isoxazole), 3.92 (s, 2H, CH2Ph), 2.54 (s, 2H, CH2),
2.13 (t, J = 7.7 Hz, 2H, CH2), 2.05 (t, J = 7.4 Hz, 3H, Me), 1.43 (m, 2H,
CH2). 13C NMR (100 MHz, DMSO‑d6) δ 170.14, 162.25, 159.23, 155.19,
154.29, 150.25, 137.89, 137.06, 136.44, 131.01, 127.72, 127.26,
126.70, 125.85, 122.55, 120.43, 114.96, 113.05, 110.22, 105.46,
100.53, 42.99, 32.52, 25.53, 20.51, 13.08. HRMS calcd for
chloride according to the procedure for preparing 17. 64% yield. 1H
– –
–
NMR (400 MHz, DMSO‑d6) δ 9.89 (s, 1H, NH ), 7.96 (s, 2H, OH),
7.85 (d, J = 1.7 Hz, 1H, Ph), 7.69 (s, 1H, Ph), 7.61 (d, J = 7.0 Hz, 1H,
Ph), 7.55 (s, 1H, Ph), 7.47 (d, J = 8.3 Hz, 1H, Ph), 7.29 (d, J = 3.5 Hz,
1H, Ph), 7.24 (dd, J1 = 2.4 Hz, J2 = 4.2 Hz, 1H, Ph), 6.28 (s, 1H, 3-H of
indole), 4.59 (d, J = 5.9 Hz, 2H, NHCH2), 3.52 (dd, J1 = 5.5 Hz, J2 = 8.4
– –
Hz, 1H, NH ), 3.30 (s, 3H, Me) 2.60 (t, J = 5.9 Hz, 2H, CH2), 2.36 (s,
3H, Me), 1.82–1.68 (m, 4H, CH2). 13C NMR (100 MHz, DMSO‑d6) δ
171.65, 159.23, 155.17, 138.83, 137.61, 137.57, 137.24, 133.01,
132.80, 128.71, 128.59, 127.84, 122.19, 115.76, 111.60, 108.64,
105.97, 102.76, 64.40, 63.16, 44.42, 40.48
C
27H25BN6O4 [M+Na]+ 531.1927, found 531.1919.
HRMS calcd for
530.1678.
C
24H26BN5O5S [M+Na]+ 530.1644, found
4.2.17. (3-(((2-(2-methyl-4-(methylsulfonamido)-1H-indol-1-yl)-5,6,7,8-
tetrahydroquinazolin-4-yl)amino)methyl)phenyl)boronic acid (28)
Compound 28 was synthesized from 17b and methanesulfonyl
chloride according to the procedure for preparing 17. 75% yield. 1H
4.2.21. (3-(((2-(4-(but-2-ynamido)-2-methyl-1H-indol-1-yl)-7,8-dihydro-
5H-pyrano[4,3-d]pyrimidin-4-yl)amino)methyl)phenyl)boronic acid (32)
Compound 32 was synthesized from 16c and 2-butynoic acid ac-
cording to the procedure for preparing 20. 67% yield. 1H NMR (400
–
–
NMR (400 MHz, DMSO‑d6) δ 9.40 (s, 1H, CONH ), 8.04 (s, 2H,
–
–
–
–
OH), 7.74 (s, 1H, Ph), 7.69–7.60 (m, 1H, Ph), 7.51 (d, J = 8.3 Hz, 1H,
MHz, DMSO‑d6) δ 10.32 (s, 1H, CONH ), 8.23 (s, 2H, OH), 7.75 (s,
1H, Ph), 7.72–7.60 (m, 1H, Ph), 7.54 (d, J = 8.3 Hz, 1H, Ph), 7.38 (d, J =
7.8 Hz, 1H, Ph), 7.34–7.24 (m, 1H, Ph), 6.85 (t, J = 8.1 Hz, 1H, Ph), 6.56
(s, 1H, 3-H of indole), 4.64 (d, J = 5.8 Hz, 1H, CH2Ph), 4.60 (s, 2H,
OCH2), 3.99 (t, J = 5.6 Hz, 2H, OCH2CH2), 2.75 (t, J = 5.8 Hz, 2H,
OCH2CH2), 2.44 (s, 3H, Me), 2.06 (s, 3H, Me).13C NMR (100 MHz,
DMSO‑d6) δ 166.59, 159.36, 159.21, 155.23, 151.29, 138.83, 133.02,
132.85, 128.72, 127.82, 121.83, 121.64, 114.46, 111.07, 108.57,
Ph), 7.33–7.24 (m, 2H, Ph), 6.95 (dd, J1 = 0.9 Hz, J2 = 7.8 Hz, 1H, Ph),
6.84 (t, J = 8.0 Hz, 1H, Ph), 6.58 (d, J = 1.3 Hz, 1H, 3-H of indole), 4.64
(d, J = 5.9 Hz, 2H, CH2Ph), 2.89 (s, 3H, Me), 2.66 (s, 2H, CH2),
2.45–2.37 (s, 3H, Me), 1.83 (d, J = 6.8 Hz, 4H, CH2).13C NMR (100 MHz,
DMSO‑d6) δ 162.10, 161.84, 154.31, 139.21, 137.63, 137.22, 132.91,
132.80, 128.64, 128.52, 127.79, 123.66, 122.03, 115.61, 111.51,
109.80, 102.36, 44.28, 31.95, 29.47, 22.25, 16.11. HRMS calcd for
9