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P.M. Lukasik et al. / European Journal of Medicinal Chemistry 57 (2012) 311e322
107.82, 110.34, 120.63, 121.70, 122.19, 123.08, 124.97, 126.64, 128.32,
139.54, 139.59, 141.31, 158.02, 159.91, 160.33; Anal. RP-HPLC: tR
18.17 min (30e100% MeCN over 22 min, purity 96%); HRMS (m/z):
calcd for C18H14ClN5 requires 335.0938; found 335.9240 [M þ 1]þ.
IndeH, J ¼ 8.8 Hz), 8.06 (1H, d, PheH, J ¼ 8.0 Hz), 8.32 (1H, s, Phe
H), 8.56 (1H, d, PyrimeH, J ¼ 5.2 Hz), 8.74 (1H, d, IndeH, J ¼ 8.4 Hz),
9.97 (1H, s, NH); 13C NMR (DMSO-d6)
d 36.06, 108.07, 110.24, 115.91,
118.51, 121.74, 121.92, 122.32, 123.34, 126.64, 129.12, 139.49, 140.97,
141.30, 144.55, 157.98, 159.92, 160.47; Anal. RP-HPLC: tR 12.52 min
(30e100% MeCN over 22 min, purity 100%); HR-MS (m/z): calcd for
C18H16N6O2S 380.1055; found 379.0844 [M ꢂ 1]ꢂ.
5.1.25. N-(3-Chlorophenyl)-4-(1-methyl-1H-indazol-3-yl)
pyrimidin-2-amine (14f)
As an off-white crystalline solid (19% yield); mp 177e180ꢀ; 1H
NMR (DMSO-d6)
d
4.18 (3H, s, CH3), 7.04 (1H, ddd, PheH, J ¼ 7.6, 2.0,
5.1.30. 4-(4-(1-Ethyl-1H-indazol-3-yl)pyrimidin-2-ylamino)
benzenesulfonamide (14k)
0.8 Hz), 7.32 (1H, t, IndeH, J ¼ 8.0 Hz), 7.35 (1H, t, PheH, J ¼ 8.0 Hz),
7.51 (1H, t, IndeH, J ¼ 8.0 Hz), 7.53 (1H, d, PyrimeH, J ¼ 5.2 Hz), 7.64
(1H, dd, PheH, J ¼ 8.4,1.2 Hz), 7.76 (1H, d, PheH, J ¼ 8.4 Hz), 8.16 (1H,
t, PheH, J ¼ 2.0 Hz), 8.56 (1H, d, PyrimeH, J ¼ 5.2 Hz), 8.70 (1H, d,
As a white solid (50% yield); mp 229e232 ꢀC; 1H NMR (DMSO-
d6)
d
1.49 (3H, t, CH3, J ¼ 7.2 Hz), 4.58 (2H, q, CH2, J ¼ 7.2 Hz), 7.20
(2H, s, NH2), 7.33 (1H, td, IndeH, J ¼ 8.0, 0.8 Hz), 7.51 (1H, td, IndeH,
J ¼ 7.2, 0.8 Hz), 7.58 (1H, d, PyrimeH, J ¼ 5.2 Hz), 7.78 (2H, d, PheH,
J ¼ 8.8 Hz), 7.81 (1H, d, IndeH, J ¼ 8.8 Hz), 8.01 (2H, d, PheH,
J ¼ 8.8 Hz), 8.59 (1H, d, PyrimeH, J ¼ 5.2 Hz), 8.72 (1H, d, IndeH,
IndeH, J ¼ 8.0 Hz), 9.87 (1H, s, NH); 13C NMR (DMSO-d6)
d 36.07,
108.11, 110.37, 117.51, 118.34, 121.01, 121.64, 122.26, 122.94, 126.66,
130.11,133.06,139.57,141.34,142.08,158.15,159.82,160.25; Anal. RP-
HPLC: tR 18.55 min (30e100% MeCN over 22 min, purity 98%); HR-
MS (m/z): calcd for C18H14ClN5 335.0938; found 335.9348 [M þ 1]þ.
J ¼ 8.0 Hz), 10.06 (1H, s, NH); 13C NMR (DMSO-d6)
d 14.80, 43.82,
108.51, 110.30, 118.13, 121.81, 122.24, 123.13, 126.52, 126.61, 136.26,
139.61, 140.45, 143.67, 158.07, 159.71, 160.42; Anal. RP-HPLC: tR
13.48 min (30e100% MeCN over 22 min, purity 100%); HR-MS (m/
z): calcd for C19H18N6O2S 394.1212; found 394.8860 [M þ 1]þ.
5.1.26. 4-(1-Methyl-1H-indazol-3-yl)-N-(4-nitrophenyl)pyrimidin-
2-amine (14g)
As a bright yellow solid (48% yield); mp 266e269 ꢀC; 1H NMR
(DMSO-d6)
d
4.19 (3H, s, CH3), 7.36 (1H, t, IndeH, J ¼ 8.0 Hz), 7.52
5.1.31. 3-(4-(1-Ethyl-1H-indazol-3-yl)pyrimidin-2-ylamino)
benzenesulfonamide (14l)
(1H, t, IndeH, J ¼ 8.0 Hz), 7.64 (1H, d, PyrimeH, J ¼ 5.2 Hz), 7.78 (1H,
d, IndeH, J ¼ 8.8 Hz), 8.11 (2H, d, PheH, J ¼ 9.6 Hz), 8.25 (2H, d, Phe
H, J ¼ 9.6 Hz), 8.65 (1H, d, PyrimeH, J ¼ 5.2 Hz), 8.73 (1H, d, IndeH,
As a white crystalline solid (16% yield); mp 219e222 ꢀC; 1H NMR
(DMSO-d6)
d
1.48 (3H, t, CH3, J ¼ 7.2 Hz), 4.57 (2H, q, CH2, J ¼ 7.2 Hz),
J ¼ 8.0 Hz), 10.44 (1H, s, NH); 13C NMR (DMSO-d6)
d
36.10, 109.31,
7.32 (3H, m, NH2, IndeH), 7.47 (2H, t, IndeH, PheH, J ¼ 8.0 Hz), 7.52
(1H, d, PheH, J ¼ 8.0 Hz), 7.55 (1H, d, PyrimeH, J ¼ 5.2 Hz), 7.79 (1H,
d, IndeH, J ¼ 8.8 Hz), 8.07 (1H, d, PheH, J ¼ 8.4 Hz), 8.33 (1H, s, Phe
H), 8.56 (1H, d, PyrimeH, J ¼ 5.2 Hz), 8.74 (1H, d, IndeH, J ¼ 8.0 Hz),
110.42, 117.81, 121.72, 122.38, 122.96, 124.97, 126.72, 139.28, 140.40,
141.34, 147.22, 158.04, 159.30, 160.55; Anal. RP-HPLC: tR 18.15 min
(30e100% MeCN over 22 min, purity 98%); HR-MS (m/z): calcd for
C18H14N6O2 346.1178; found 346.9664 [M þ 1]þ.
9.98 (1H, s, NH); 13C NMR (DMSO-d6)
d 14.81, 43.81, 108.16, 110.14,
115.90, 118.50, 121.86, 121.91, 122.34, 123.45, 126.59, 129.12, 139.62,
140.42, 140.98, 144.55, 157.96, 159.92, 160.52; Anal. RP-HPLC: tR
13.35 min (30e100% MeCN over 22 min, purity 100%); HR-MS (m/z):
calcd for C19H18N6O2S requires 394.1212; found 394.8616 [M þ 1]þ.
5.1.27. 4-(1-Methyl-1H-indazol-3-yl)-N-(3-nitrophenyl)pyrimidin-
2-amine (14h)
As a bright yellow solid (68% yield); mp 248e251 ꢀC; 1H NMR
(DMSO-d6)
d
4.19 (3H, s, CH3), 7.30 (1H, t, IndeH, J ¼ 7.6 Hz), 7.52
(1H, t, IndeH, J ¼ 8.0 Hz), 7.59 (1H, d, PyrimeH, J ¼ 5.2 Hz), 7.63 (1H,
t, PheH, J ¼ 8.0 Hz), 7.77 (1H, d, IndeH, J ¼ 8.4 Hz), 7.84 (1H, ddd,
PheH, J ¼ 8.0, 2.4, 0.8 Hz), 8.17 (1H, ddd, PheH, J ¼ 8.4, 2.0, 0.8 Hz),
8.62 (1H, d, PyrimeH, J ¼ 5.2 Hz), 8.70 (1H, d, IndeH, J ¼ 8.0 Hz),
8.90 (1H, t, PheH, J ¼ 2.0 Hz), 10.17 (1H, s, NH); 13C NMR (DMSO-d6)
5.1.32. 4-(1-Ethyl-1H-indazol-3-yl)-N-(4-nitrophenyl)pyrimidin-2-
amine (14m)
As a bright yellow solid (37% yield); mp 227e229 ꢀC; 1H NMR
(DMSO-d6)
d
1.49 (3H, t, CH3, J ¼ 7.2 Hz), 4.58 (2H, q, CH2, J ¼ 7.2 Hz),
7.35 (1H, td, IndeH, J ¼ 8.0, 0.8 Hz), 7.51 (1H, td, IndeH, J ¼ 8.0,
0.8 Hz), 7.64 (1H, d, PyrimeH, J ¼ 5.2 Hz), 7.81 (1H, d, IndeH,
J ¼ 8.4 Hz), 8.10 (2H, d, PheH, J ¼ 9.6 Hz), 8.23 (2H, d, PheH,
J ¼ 9.2 Hz), 8.63 (1H, d, PyrimeH, J ¼ 5.2 Hz), 8.72 (1H, d, IndeH,
d
36.09, 108.60, 110.36, 112.68, 115.76, 121.68, 122.26, 123.00, 124.92,
126.68, 129.81, 139.41, 141.34, 141.88, 148.17, 158.13, 159.68, 160.45;
Anal. RP-HPLC: tR 17.32 min (30e100% MeCN over 22 min, purity
100%); HR-MS (m/z): calcd for C18H14N6O2 requires 346.1178; found
346.9461 [M þ 1]þ.
J ¼ 8.0 Hz), 10.43 (1H, s, NH); 13C NMR (DMSO-d6)
d 14.78, 43.85,
109.38, 110.31, 117.79, 121.83, 122.38, 123.06, 124.95, 126.65, 139.40,
140.38, 140.46, 147.22, 157.99, 159.29, 160.58; Anal. RP-HPLC: tR
19.40 min (30e100% MeCN over 22 min, purity 100%); HR-MS (m/z):
calcd for C19H16N6O2 requires 360.1335; found 359.1286 [M ꢂ 1]ꢂ.
5.1.28. 4-(4-(1-Methyl-1H-indazol-3-yl)pyrimidin-2-ylamino)
benzenesulfonamide (14i)
As a white solid (43% yield); mp 240e242 ꢀC; 1H NMR (DMSO-
d6)
d
4.19 (3H, s, CH3), 7.20 (2H, s, NH2), 7.34 (1H, t, IndeH,
5.1.33. 4-(1-Ethyl-1H-indazol-3-yl)-N-(3-nitrophenyl)pyrimidin-2-
amine (14n)
J ¼ 7.6 Hz), 7.52 (1H, t, IndeH, J ¼ 7.6 Hz), 7.56 (1H, d, PyrimeH,
J ¼ 5.2 Hz), 7.77 (3H, m, PheH, IndeH), 8.00 (1H, d, PheH,
J ¼ 8.8 Hz), 8.59 (1H, d, PyrimeH, J ¼ 5.2 Hz), 8.72 (1H, d, IndeH,
As a bright yellow solid (67% yield); mp 217e220 ꢀC; 1H NMR
(DMSO-d6)
d
1.49 (3H, t, CH3, J ¼ 7.2 Hz), 4.58 (2H, q, CH2, J ¼ 7.2 Hz),
J ¼ 8.4 Hz), 10.06 (1H, s, NH); 13C NMR (DMSO-d6)
d
36.08,
7.27 (1H, td, IndeH, J ¼ 8.0, 0.8 Hz), 7.50 (1H, td, IndeH, J ¼ 8.0,
1.2 Hz), 7.59 (1H, d, PyrimeH, J ¼ 5.2 Hz), 7.63 (1H, d, PheH,
J ¼ 8.4 Hz), 7.81 (1H, d, IndeH, J ¼ 8.4 Hz), 7.84 (1H, ddd, PheH,
J ¼ 8.0, 2.4, 0.8 Hz), 8.17 (1H, ddd, PheH, J ¼ 8.0, 2.4, 0.8 Hz), 8.61
(1H, d, PyrimeH, J ¼ 5.2 Hz), 8.70 (1H, d, IndeH, J ¼ 8.0 Hz), 8.91
(1H, t, PheH, J ¼ 2.0 Hz), 10.17 (1H, s, NH); 13C NMR (DMSO-d6)
108.44, 110.40, 118.15, 121.71, 122.24, 123.04, 126.53, 126.68, 136.28,
139.50, 141.34, 143.67, 158.09, 159.72, 160.39; Anal. RP-HPLC: tR
12.32 min (30e100% MeCN over 22 min, purity 100%); HR-MS (m/
z): calcd for C18H16N6O2S 380.1055; found 380.8972 [M þ 1]þ.
5.1.29. 3-(4-(1-Methyl-1H-indazol-3-yl)pyrimidin-2-ylamino)
benzenesulfonamide (14j)
d 14.80, 43.83, 108.68, 110.26, 112.67, 115.74, 121.79, 122.28, 123.09,
124.91, 126.62, 129.80, 139.54, 140.46, 141.89, 148.17, 158.11, 159.68,
160.49; Anal. RP-HPLC: tR 18.53 min (30e100% MeCN over 22 min,
purity 100%); HR-MS (m/z): calcd for C19H16N6O2 requires 360.1335;
found 360.9510 [M þ 1]þ.
As a white solid (13% yield); mp 231e234 ꢀC; 1H NMR (DMSO-
d 4.18 (3H, s, CH3), 7.32 (3H, m, NH2, IndeH), 7.47 (1H, td, Inde
d6)
H, J ¼ 7.6, 1.2 Hz), 7.51e7.55 (3H, m, PheH, PyrimeH), 7.75 (1H, d,