S.-X. Gu et al. / Bioorg. Med. Chem. 19 (2011) 7093–7099
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168.88; MS(EI) m/z 280 (M+); Anal. calcd for C16H16N4O: C, 68.55;
H, 5.75; N, 19.99. Found: C, 68.43; H, 5.87; N, 19.86.
1H, cyclopentyl H1), 6.01(d, J = 6.0 Hz, 1H, pyrimidine H5), 7.24
(brs, 1H, NH, deuterium-exchanged), 7.64 (d, J = 8.4 Hz, 2H,
ArH2,6), 7.83 (s, 1H, pyrimidine H6), 8.01 (d, J = 8.8 Hz, 2H, ArH3,5),
9.53 (s, 1H, NH, deuterium-exchanged); 13C NMR(100 MHz,
DMSO-d6) d (ppm) 23.48, 32.37, 51.67, 99.19, 101.19, 117.96,
119.86, 132.78, 145.90, 154.30, 159.22, 162.15; MS(ESI+) m/z 280
(M+H)+; Anal. calcd for C16H17N5: C, 68.79; H, 6.13; N, 25.0. Found:
C, 68.68; H, 6.27; N, 25.03.
4.1.2.3. 4-((4-(Cyclohexyloxy)-5-methylpyrimidin-2-yl)amino)
benzonitrile (1c). Yield 73%; white solid; mp 176.6–177.4 °C;
1H NMR(400 MHz, DMSO-d6)
d (ppm) 1.27–1.96 (m, 13H,
Me + cyclohexyl H2–11), 5.05–5.09 (m, 1H, cyclohexyl H1), 7.66 (d,
J = 8.8 Hz, 2H, ArH2,6), 7.91 (d, J = 8.8 Hz, 2H, ArH3,5), 8.07 (s, 1H,
pyrimidine H6), 9.86 (s, 1H, NH); 13C NMR(100 MHz, DMSO-d6) d
(ppm) 11.73, 23.32, 25.07, 31.15, 73.51, 101.75, 109.05, 117.85,
119.65, 132.86, 145.29, 157.09, 157.52, 166.75; MS(EI) m/z 308
(M+); Anal. calcd for C18H20N4O: C, 70.11; H, 6.54; N, 18.17. Found:
C, 70.04; H, 6.65; N, 18.11.
4.1.2.9. 4-((4-(Cyclopropylamino)pyrimidin-2-yl)amino)benzo-
nitrile (1i).
Yield 54%; white solid; mp 183.8–185.4 °C; 1H NMR(400 MHz,
DMSO-d6) d (ppm) 0.49–0.76 (m, 4H, cyclopropyl H2–5), 2.62 (m,
1H, cyclopropyl H1), 6.11 (d, J = 2.4 Hz, 1H, pyrimidine H5), 7.52–
8.07 (m, 6H, NH + ArH2,3,4,5 + pyrimidine H6), 9.61 (s, 1H, NH); 13C
4.1.2.4. 4-((4-(Cyclopentyloxy)-5-methylpyrimidin-2-yl)amino)
benzonitrile (1d).
NMR(100 MHz, DMSO-d6)
d (ppm) 6.47, 6.56, 23.25, 101.26,
Yield 68%; white solid; mp 154.2–155.1 °C; 1H NMR(400 MHz,
DMSO-d6) d (ppm) 1.61–2.01 (m, 11H, Me + cyclopentyl H2–9),
5.44 (s, 1H, cyclopentyl H1), 7.68 (d, J = 8.4 Hz, 2H, ArH2,6), 7.94
(d, J = 8.8 Hz, 2H, ArH3,5), 8.07 (s, 1H, pyrimidine H6), 9.87 (s, 1H,
NH); 13C NMR(100 MHz, DMSO-d6) d (ppm) 11.70, 23.44, 32.39,
78.27, 101.72, 109.18, 117.90, 119.69, 132.91, 145.29, 156.90,
157.50, 167.03; MS(EI) m/z 294 (M+); Anal. calcd for C17H18N4O:
C, 69.37; H, 6.16; N, 19.03. Found: C, 69.33; H, 6.23; N, 18.89.
118.02, 119.88, 132.79, 132.88, 145.85, 159.20, 163.84; MS(ESI+)
m/z 253 (M+H)+; Anal. calcd for C14H13N5: C, 66.92; H, 5.21; N,
27.87. Found: C, 66.88; H, 5.32; N, 27.82
4.1.2.10. 4-((4-(Cyclohexylamino)-5-methylpyrimidin-2-yl)
amino)benzonitrile (1j).
Yield 56%; light yellow solid; mp 202.1–203.2 °C; 1H
NMR(400 MHz, DMSO-d6) d (ppm) 1.12–1.92 (m, 13H, Me + cyclo-
hexyl H2–11), 3.94 (m, 1H, cyclohexyl H1), 6.34 (d, 1H, J = 7.6 Hz,
NH), 7.62 (d, J = 8.8 Hz, 2H, ArH2,6), 7.69 (s, 1H, pyrimidine H6),
7.96 (d, J = 8.8 Hz, 2H, ArH3,5), 9.46 (s, 1H, NH); 13C NMR(100 MHz,
DMSO-d6) d (ppm) 13.34, 25.25, 25.47, 32.38, 49.50, 100.76,
106.05, 117.51, 119.88, 132.72, 146.11, 153.60, 157.79, 160.30;
MS(EI) m/z 307 (M+); Anal. calcd for C18H21N5: C, 70.33; H; 6.89;
N; 22.78. Found: C, 70.14; H, 7.03; N, 22.69.
4.1.2.5. 4-((4-(Cyclohexyloxy)-6-methylpyrimidin-2-yl)amino)
benzonitrile (1e).
Yield 59%; white solid; mp 141.8–142.5 °C; 1H NMR(400 MHz,
DMSO-d6) d (ppm) 1.23–1.99 (m, 10H, cyclohexyl H2–11), 2.27 (s,
3H, Me), 4.96–5.01 (m, 1H, cyclohexyl H1), 6.20 (s, 1H, pyrimidine
H5), 7.68 (d, J = 8.8 Hz, 2H, ArH2,6), 7.94 (d, J = 8.8 Hz, 2H, ArH3,5),
9.99 (s, 1H, NH); 13C NMR(100 MHz, DMSO-d6) d (ppm) 23.37,
23.54, 25.02, 31.30, 73.79, 98.76, 102.12, 118.18, 119.60, 132.89,
145.14, 158.73, 168.22, 169.12; MS(EI) m/z 308 (M+); Anal. calcd
for C18H20N4O: C, 70.11; H, 6.54; N, 18.17. Found: C, 70.06; H,
6.62; N, 18.08.
4.1.2.11. 4-((4-(Cyclopentylamino)-5-methylpyrimidin-2-yl)
amino)benzonitrile (1k).
Yield 55%; light yellow solid; mp 195.7–197.4 °C; 1H
NMR(400 MHz, DMSO-d6) d (ppm) 1.52–1.98 (m, 11H, Me + cyclo-
pentyl H2–9), 4.37–4.42 (m, 1H, cyclopentyl H1), 6.44 (d, J = 6.8 Hz,
1H, NH), 7.63 (d, J = 8.8 Hz, 2H, ArH2,6), 7.70 (s, 1H, pyrimidine H6),
7.97 (d, J = 8.8 Hz, 2H, ArH3,5), 9.46 (s, 1H, NH); 13C NMR(100 MHz,
DMSO-d6) d (ppm) 13.37, 23.61, 32.12, 52.10, 100.73, 106.30,
117.54, 119.92, 132.78, 146.11, 153.34, 157.80, 160.86; MS(EI)
m/z 293 (M+); Anal. calcd for C17H19N5: C, 69.60; H, 6.53; N,
23.87. Found: C, 69.47; H, 6.79; N, 23.76.
4.1.2.6. 4-((4-(Cyclopentyloxy)-6-methylpyrimidin-2-yl)amino)
benzonitrile (1f).
Yield 57%; white solid; mp 158.7–159.4 °C; 1H NMR(400 MHz,
DMSO-d6) d (ppm) 1.59–1.98 (m, 8H, cyclopentyl H2–9), 2.28 (s,
3H, Me), 5.38 (d, J = 2.8 Hz, 1H, cyclopentyl H1), 6.22(s, 1H, pyrim-
idine H5), 7.71 (d, J = 8.8 Hz, 2H, ArH2,6), 7.96 (d, J = 8.8 Hz, 2H,
ArH3,5), 10.01 (s, 1H, NH); 13C NMR(100 MHz, DMSO-d6) d (ppm)
23.40, 23.47, 32.35, 78.26, 98.84, 102.09, 118.23, 119.66, 132.99,
145.15, 158.74, 168.13, 169.40; MS(EI) m/z 294 (M+); Anal. calcd
for C17H18N4O: C, 69.37; H, 6.16; N, 19.03. Found: C, 69.30; H,
6.24; N, 18.97.
4.1.2.12. 4-((4-(Cyclopropylamino)-5-methylpyrimidin-2-yl)
amino)benzonitrile (1l).
Yield 51%; white solid; mp 152.4–152.7 °C; 1H NMR(400 MHz,
DMSO-d6) d (ppm) 0.57–0.82 (m, 4H, cyclopropyl H2–5), 1.90 (s,
3H, Me), 2.80–2.82 (m, 1H, cyclopropyl H1), 6.91 (d, J = 2.0 Hz,
1H, NH), 7.63 (d, J = 8.8 Hz, 2H, ArH2,6), 7.71 (s, 1H, pyrimidine
H6), 8.10 (d, J = 8.4 Hz, 2H, ArH3,5), 9.55 (s, 1H, NH); 13C
NMR(100 MHz, DMSO-d6) d (ppm) 6.49, 13.26, 24.08, 100.73,
106.13, 117.66, 119.98, 132.81, 146.16, 153.63, 157.88, 162.26;
MS(ESI+) m/z 266 (M+H)+; Anal. calcd for C15H15N5: C, 67.90; H,
5.70; N, 26.40. Found: C, 67.84; H, 5.85; N, 26.35.
4.1.2.7. 4-((4-(Cyclohexylamino)pyrimidin-2-yl)amino)benzoni-
trile (1g).
Yield 51%; white solid; mp 219.0–220.5 °C; 1H NMR(400 MHz,
DMSO-d6) d (ppm) 1.16–1.98 (m, 10H, cyclohexyl H2–11), 3.82
(brs, 1H, cyclohexyl H1), 6.01(d, J = 6.0 Hz, 1H, pyrimidine H5),
7.24 (brs, 1H, NH), 7.63 (d, J = 8.8 Hz, 2H, ArH2,6), 7.82 (s, 1H,
pyrimidine H6), 7.99 (d, J = 8.4 Hz, 2H, ArH3,5), 9.53 (s, 1H, NH);
13C NMR(100 MHz, DMSO-d6) d (ppm) 24.74, 25.39, 32.41, 48.82,
101.22, 117.93, 119.81, 132.73, 145.88, 159.20, 161.71, MS(ESI+)
m/z 294 (M+H)+; Anal. calcd for C17H19N5: C, 69.60; H, 6.53; N,
23.87. Found: C, 69.52; H, 6.67; N, 23.83.
4.1.2.13. 4-((4-(Cyclohexylamino)-6-methylpyrimidin-2-yl)
amino)benzonitrile (1m).
Yield 53%; white solid; mp 200.8–201.1 °C; 1H NMR(400 MHz,
DMSO-d6) d (ppm) 1.14–1.98 (m, 10H, cyclohexyl H2–11), 2.13 (s,
1H, Me), 3.79 (brs, 1H, cyclohexyl H1), 5.87 (s, 1H, pyrimidine
H5), 7.08 (brs, 1H, NH), 7.62 (d, J = 8.4 Hz, 2H, ArH2,6), 8.00 (d,
J = 8.4 Hz, 2H, ArH3,5), 9.54 (s, 1H, NH); 13C NMR(100 MHz,
DMSO-d6) d (ppm) 23.35, 24.80, 25.43, 32.54, 48.98, 96.88, 96.95,
101.03, 117.82, 119.86, 132.71, 146.06, 159.05, 162.36; MS(EI)
4.1.2.8. 4-((4-(Cyclopentylamino)pyrimidin-2-yl)amino)benzo-
nitrile (1h).
Yield 54%; white solid; mp 203.6–204.9 °C; 1H NMR(400 MHz,
DMSO-d6) d (ppm) 1.45–1.97 (m, 8H, cyclopentyl H2–9), 4.25 (brs,