Jia et al.
(s, 3H), 3.32 (s, 3H), 2.55 (s, 3H). HRMS (AP-ESI) m/z:
calcd for C21H23N7O2S [M + H]+ 438.1707, found
438.1708.
(s, 1H), 11.22 (s, 1H), 8.07 (d, J = 6.9 Hz, 1H), 7.86 (s,
1H), 7.80 (m, 4H), 7.72 (d, J = 9.0 Hz, 1H), 7.14 (d,
J = 9.0 Hz, 1H), 6.61 (d, J = 7.2 Hz, 1H), 6.13 (d,
J = 9.0 Hz, 1H), 4.08 (s, 3H), 2.65 (s, 3H), 2.24 (s, 3H).
The compounds P1b-P1h and P2a-P2g were synthesized
following the general procedure as described above
(preparation of Pazopanib).
N-carbamimidoyl-4-((4-((2,3-dimethyl-2H-indazole-
6-yl)amino)pyrimidin-2-yl)amino)
benzenesulfonamide (P1g)
4-((4-((2,3-dimethyl-2H-indazole-6-yl)amino)
pyrimidin-2-yl)amino)benzenesulfonamide (P1b)
A white solid, yield: 88%, mp: 239–240 °C, ESI-MS m/z:
410.5 [M + H]+; 1H-NMR (600 MHz, DMSO-d6): d 10.25
(s, 1H), 10.18 (s, 1H), 8.06 (d, J = 6.3 Hz, 1H), 7.97 (s,
1H), 7.89 (d, J = 8.7 Hz, 2H), 7.72 (d, J = 8.7 Hz, 2H),
7.64 (d, 1H), 7.25 (s, 2H), 7.09 (d, 1H), 6.45 (d, 1H), 4.04
(s, 3H), 2.60 (s, 3H).
A white solid, yield: 90%, mp: 182–183 °C, ESI-MS m/z:
452.5 [M + H]+; 1H-NMR (300 MHz, DMSO-d6): d 11.45
(s, 1H), 11.21 (s, 1H), 8.07 (d, J = 7.2 Hz, 1H), 7.89
(s, 1H), 7.66-7.99 (m, 5H), 7.26 (d, J = 8.4 Hz, 1H),
6.94 (s, 4H), 6.67 (d, J = 6.6 Hz, 1H), 4.09 (s, 3H), 2.65
(s, 3H).
N4-(2,3-dimethyl-2H-indazole-6-yl)-N2-(4-
fluorophenyl)pyrimidine-2,4-diamine (P1h)
A white solid, yield: 95%, mp: 219–220 °C, ESI-MS m/z:
349.4 [M + H]+; 1H-NMR (300 MHz, DMSO-d6): d 11.06
(s, 1H), 10.76 (s, 1H), 7.97 (d, J = 7.2 Hz, 1H), 7.90 (s,
1H), 7.69 (d, J = 7.5 Hz, 1H), 7.56–7.60 (m, 2H), 7.23 (d,
2H), 7.14 (d, J = 8.7 Hz, 1H), 6.55 (d, J = 6.9 Hz, 1H),
4.04 (s, 3H), 2.61 (s, 3H).
4-((4-((2,3-dimethyl-2H-indazole-6-yl)amino)
pyrimidin-2-yl)amino)-N-(pyrimidin-2-yl)
benzenesulfonamide (P1c)
A white solid, yield: 92%, mp: 206–208 °C, ESI-MS m/z:
488.5 [M + H]+; 1H-NMR (300 MHz, DMSO-d6): d 11.23
(s, 1H), 10.19 (s, 1H), 8.48 (d, J = 4.8 Hz, 2H), 8.07 (d,
J = 6.9 Hz, 1H), 7.68–7.91 (m, 6H), 7.12 (d, J = 8.7 Hz,
1H), 7.04 (t, 1H), 6.61 (d, J = 7.2 Hz, 1H), 4.09 (s, 3H),
2.64 (s, 3H).
4-((4-((2,3-dimethyl-2H-indazole-6-yl)(methyl)
amino)pyrimidin-2-yl)amino) benzenesulfonamide
(P2b)
4-((4-((2,3-dimethyl-2H-indazole-6-yl)amino)
pyrimidin-2-yl)amino)-N-(4-methylpyrimidin-2-yl)
benzenesulfonamide (P1d)
A white solid, yield: 96%, mp: 212–214 °C, ESI-MS m/z:
502.5 [M + H]+; 1H-NMR (300 MHz, DMSO-d6): d 11.47
(s, 1H), 11.37 (s, 1H), 8.29 (d, J = 5.1 Hz, 1H), 8.09 (d,
J = 7.2 Hz, 1H), 7.91 (d, J = 8.7 Hz, 2H), 7.84 (s, 1H),
7.67–7.78 (m, 4H), 7.21 (d, J = 8.7 Hz, 1H), 6.89 (d,
J = 5.1 Hz, 1H), 6.67 (d, J = 6.9 Hz, 1H), 4.11 (s, 3H),
2.66 (s, 3H), 2.25 (s, 6H).
A white solid, yield: 89%, mp: >270 °C, ESI-MS m/z:
424.5 [M + H]+; 1H-NMR (300 MHz, DMSO-d6): d 10.20
(s, 1H), 7.92 (d, J = 6.6 Hz, 1H), 7.82 (d, J = 9.0 Hz, 1H),
7.79 (s, 1H), 7.76 (s, 1H), 7.63 (d, J = 6.9 Hz, 1H), 7.563
(s, 1H), 7.22 (s, 2H), 6.92 (d, J = 9.0 Hz, 1H), 4.08
(s, 3H), 3.53 (s, 3H), 2.65 (s, 3H).
4-((4-((2,3-dimethyl-2H-indazole-6-yl)(methyl)
amino)pyrimidin-2-yl)amino)-N-(pyrimidin-2-yl)
benzenesulfonamide (P2c)
A white solid, yield: 84%, mp: 244–245 °C, ESI-MS m/z:
502.4 [M + H]+; 1H-NMR (300 MHz, DMSO-d6): d 11.08
(s, 1H), 8.50 (d, J = 4.8 Hz, 2H), 7.97 (s, 1H), 7.88 (d,
J = 9.0 Hz, 1H), 7.60–7.73 (m, 4H), 7.06 (t, 1H), 6.94 (d,
J = 8.7 Hz, 1H), 6.12 (s, 1H), 4.09 (s, 3H), 3.57(s, 3H),
2.64 (s, 3H). HRMS (AP-ESI) m/z: calcd for
C24H23N9O2S [M + H]+ 502.1768, found 502.1768.
4-((4-((2,3-dimethyl-2H-indazole-6-yl)amino)
pyrimidin-2-yl)amino)-N-(4,6-dimethylpyrimidin-2-
yl)benzenesulfonamide (P1e)
A white solid, yield: 86%, mp: 224–225 °C, ESI-MS m/z:
516.6 [M + H]+; 1H-NMR (300 MHz, DMSO-d6): d 11.09
(s, 1H), 11.04 (s, 1H), 8.05 (d, J = 7.2 Hz, 1H), 7.90
(d, J = 8.7 Hz, 2H), 7.83 (s, 1H), 7.69–7.76 (m, 4H), 7.11
(d, J = 8.7 Hz, 1H), 6.74 (s, 1H), 6.56 (d, J = 7.2 Hz, 1H),
4.08 (s, 3H), 2.64 (s, 3H), 2.19 (s, 6H).
4-((4-((2,3-dimethyl-2H-indazole-6-yl)(methyl)
amino)pyrimidin-2-yl)amino)-N-(4-methylpyrimidin-
2-yl)benzenesulfonamide (P2d)
4-((4-((2,3-dimethyl-2H-indazole-6-yl)amino)
pyrimidin-2-yl)amino)-N-(5-methylisoxazol-3-yl)
benzenesulfonamide (P1f)
A white solid, yield: 92%, mp: 216–217 °C, ESI-MS m/z:
491.5 [M + H]+; 1H-NMR (300 MHz, DMSO-d6): d 11.44
A white solid, yield: 80%, mp: >270 °C, ESI-MS m/z:
516.6 [M + H]+; 1H-NMR (300 MHz, DMSO-d6): d 10.75
(s, 1H), 8.31 (d, J = 5.4 Hz, 1H), 7.94 (d, J = 7.2 Hz, 1H),
7.86 (d, J = 8.7 Hz, 1H), 7.58-7.71 (m, 4H), 6.92 (d,
J = 8.7 Hz, 2H), 6.14 (s, 1H), 4.10 (s, 3H), 3.56 (s, 3H),
308
Chem Biol Drug Des 2014; 83: 306–316