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T. Liu et al. / European Journal of Medicinal Chemistry 73 (2014) 167e176
371 [M þ 1]þ. HRMS (ESI): m/z calcd for (C24H19ClN2 þ H)þ:
73 ꢀC. 1H NMR (500 MHz, CDCl3)
d
7.82 (s, 2H), 7.44 (d, J ¼ 8.2 Hz,
371.1315; found: 371.1318.
2H), 7.37 (dd, J ¼ 8.2, 5.7 Hz, 4H), 7.24 (d, J ¼ 8.4 Hz, 2H), 4.77 (s, 1H),
2.44e2.32 (m, 2H), 1.76 (dt, J ¼ 13.3, 6.7 Hz, 1H), 0.92 (dd, J ¼ 6.6,
5.1.6.9. N-Benzyl-1-(4-chlorophenyl)-1-(4-(pyridin-4-yl)phenyl)
1.3 Hz, 6H). 13C NMR (100 MHz, CDCl3)
d 142.1, 141.6, 132.80, 131.5,
methanamine 12f. Yellow solid (yield, 46%), mp: 77e79 ꢀC. 1H NMR
130.9, 129.5, 128.7, 128.7, 127.8, 126.0, 122.4, 66.6, 54.7, 28.3, 20.7.
(500 MHz, CDCl3)
d
8.63 (dd, J ¼ 4.7, 1.4 Hz, 2H), 7.59 (d, J ¼ 8.2 Hz,
ESI-MS (m/z): 340 [M
þ
1]þ. HRMS (ESI): m/z calcd for
2H), 7.53 (d, J ¼ 8.3 Hz, 2H), 7.47 (dd, J ¼ 4.6, 1.6 Hz, 2H), 7.42e7.39
(C20H22ClN3 þ H)þ: 340.1581; found: 340.1580.
(m, 2H), 7.37e7.27 (m, 7H), 4.90 (s, 1H), 3.76 (s, 2H). 13C NMR
(100 MHz, CDCl3)
d 150.2, 147.9, 147.2, 137.2, 133.2, 130.8, 129.5,
5.1.6.17. N-((4-(1H-Pyrazol-4-yl)phenyl)(4-chlorophenyl)methyl)-2-
128.9, 128.6, 128.4, 128.1, 127.5, 127.4, 127.3, 121.5, 65.2, 51.5. ESI-MS
(m/z): 385 [M þ 1]þ. HRMS (ESI): m/z calcd for (C25H21ClN2 þ H)þ:
385.1472; found: 385.1486.
methylpropan-2-amine 22c. White solid (yield, 33%), mp: 85e87 ꢀC.
1H NMR (500 MHz, CDCl3)
d
7.82 (s, 2H), 7.42 (d, J ¼ 8.2 Hz, 2H), 7.39
(d, J ¼ 8.4 Hz, 2H), 7.35 (d, J ¼ 8.2 Hz, 2H), 7.24 (d, J ¼ 8.4 Hz, 2H),
5.00 (s,1H),1.08 (s, 9H). 13C NMR (100 MHz, DMSO-d6)
138.7,137.1,
133.3, 132.6, 131.3, 130.2, 129.3, 128.8, 126.1, 121.3, 60.9, 59.9, 27.0.
d
5.1.6.10. N-((4-(9H-Purin-6-yl)phenyl)(4-chlorophenyl)methyl)
propan-2-amine 2. Yellow solid (yield, 20%), mp: 109e111 ꢀC. 1H
ESI-MS (m/z): 340 [M
þ
1]þ. HRMS (ESI): m/z calcd for
NMR (500 MHz, CDCl3)
d
8.93 (s, 1H), 8.64 (d, J ¼ 7.9 Hz, 2H), 8.26 (s,
(C20H22ClN3 þ H)þ: 340.1581; found: 340.1570.
1H), 7.62 (d, J ¼ 8.2 Hz, 2H), 7.44 (d, J ¼ 8.3 Hz, 2H), 7.29 (d,
J ¼ 8.3 Hz, 2H), 5.16 (s, 1H), 3.02e2.89 (m, 1H), 1.21 (t, J ¼ 6.8 Hz,
6H). ESI-MS (m/z): 378 [M þ 1]þ. HRMS (ESI): m/z calcd for
(C21H20ClN5 þ H)þ: 378.1485; found: 378.1480.
5.1.6.18. N-((4-(1H-Pyrazol-4-yl)phenyl)(4-chlorophenyl)methyl)
cyclopropanamine 22d. White solid (yield, 21%), mp: 62e64 ꢀC. 1H
NMR (500 MHz, CDCl3)
7.25 (m, 6H), 4.90 (s,1H), 2.12e2.05 (m, 1H), 0.45e0.35 (m, 4H). ESI-
d
7.83 (s, 2H), 7.45 (d, J ¼ 8.0 Hz, 2H), 7.35e
5.1.6.11. N-((4-(9H-Purin-6-yl)phenyl)(4-chlorophenyl)methyl)cyclo-
MS (m/z): 324 [M
þ
1]þ. HRMS (ESI): m/z calcd for
propanamine 3. White solid (yield, 47%), mp: 79e81 ꢀC. 1H NMR
(C19H18ClN3 þ H)þ: 324.1268; found: 324.1266.
(500 MHz, CDCl3)
d
8.98 (s, 1H), 8.74 (d, J ¼ 8.4 Hz, 2H), 8.28 (s, 1H),
7.55 (d, J ¼ 8.3 Hz, 2H), 7.32 (d, J ¼ 8.5 Hz, 2H), 7.27 (d, J ¼ 8.5 Hz,
2H), 4.99 (s, 1H), 2.11e2.08 (m, 1H), 0.48e0.36 (m, 4H). ESI-MS (m/
z): 376 [M þ 1]þ. HRMS (ESI): m/z calcd for (C21H18ClN5 þ H)þ:
376.1329; found: 376.1331.
5.1.6.19. N-((4-(1H-Pyrazol-4-yl)phenyl)(4-chlorophenyl)methyl)
cyclohexanamine 22e. White solid (yield, 54%), mp: 69e71 ꢀC. 1H
NMR (500 MHz, CDCl3)
d
7.81 (s, 2H), 7.43 (d, J ¼ 8.2 Hz, 2H), 7.35
(dd, J ¼ 8.5, 2.5 Hz, 4H), 7.29e7.24 (m, 2H), 5.01 (s, 1H), 2.44e2.32
(m, 1H), 1.95 (d, J ¼ 6.6 Hz, 2H), 1.69 (dd, J ¼ 9.2, 3.4 Hz, 2H), 1.21e
1.03 (m, 6H). ESI-MS (m/z): 366 [M þ 1]þ. HRMS (ESI): m/z calcd for
(C22H24ClN3 þ H)þ: 366.1737; found: 366.1696.
5.1.6.12. N-((4-(9H-Purin-6-yl)phenyl)(4-chlorophenyl)methyl)-2-
methylpropan-1-amine 17a. White solid (yield, 39%), mp: 87e
90 ꢀC. 1H NMR (500 MHz, CDCl3)
d
8.96 (s, 1H), 8.72 (d, J ¼ 8.1 Hz,
2H), 8.27 (s, 1H), 7.60 (d, J ¼ 8.3 Hz, 2H), 7.38 (d, J ¼ 8.5 Hz, 2H), 7.27
(d, J ¼ 8.3 Hz, 2H), 4.87 (s, 1H), 2.42 (d, J ¼ 6.6 Hz, 2H), 1.86e1.74 (m,
1H), 0.93 (dt, J ¼ 9.8, 4.9 Hz, 6H). ESI-MS (m/z): 392 [M þ 1]þ. HRMS
(ESI): m/z calcd for (C22H22ClN5 þ H)þ: 392.1642; found: 392.1652.
5.1.6.20. N-((4-(1H-Pyrazol-4-yl)phenyl)(4-chlorophenyl)methyl)an-
iline 22f. Yellow solid (yield, 25%), mp: 69e71 ꢀC. 1H NMR
(500 MHz, CDCl3)
d
7.85 (s, 2H), 7.47 (d, J ¼ 8.2 Hz, 2H), 7.35e7.29
(m, 6H), 7.13 (t, J ¼ 7.9 Hz, 2H), 6.72 (t, J ¼ 7.3 Hz, 1H), 6.55 (d,
J ¼ 8.2 Hz, 2H), 5.47 (s,1H). ESI-MS (m/z): 360 [M þ 1]þ. HRMS (ESI):
m/z calcd for (C22H18ClN3 þ H)þ: 359.1189; found: 359.1200.
5.1.6.13. N-((4-(9H-Purin-6-yl)phenyl)(4-chlorophenyl)methyl)cyclo-
hexanamine 17b. Yellow solid (yield, 32%), mp: 72e74 ꢀC. 1H NMR
(500 MHz, CDCl3)
d
9.02 (s, 1H), 8.71 (d, J ¼ 8.1 Hz, 2H), 8.30 (s, 1H),
7.58 (d, J ¼ 8.3 Hz, 2H), 7.37 (d, J ¼ 8.4 Hz, 2H), 7.26 (d, J ¼ 8.5 Hz,
2H), 5.12 (s, 1H), 2.44 (s, 1H), 2.03e1.91 (m, 2H), 1.69 (s, 2H), 1.20e
1.07 (m, 6H). ESI-MS (m/z): 418 [M þ 1]þ. HRMS (ESI): m/z calcd for
(C24H24ClN5 þ H)þ: 418.1798; found: 418.1801.
5.1.6.21. 1-(4-(1H-Pyrazol-4-yl)phenyl)-N-benzyl-1-(4-chlorophenyl)
methanamine 22g. Yellow solid, yield 39%, mp: 63e69 ꢀC. 1H NMR
(500 MHz, CDCl3)
(m, 4H), 7.38e7.26 (m, 7H), 4.85 (s, 1H), 3.76 (s, 2H). 13C NMR
(100 MHz, CDCl3) 142.3, 141.8, 140.0, 132.8, 131.4, 128.9, 128.7,
d
7.83 (s, 2H), 7.46 (d, J ¼ 7.6 Hz, 2H), 7.44e7.38
5.1.6.14. 1-(4-(9H-Purin-6-yl)phenyl)-N-benzyl-1-(4-chlorophenyl)
d
methanamine 17c. White solid (yield, 33%), mp: 118e120 ꢀC. 1H
128.6, 128.5, 128.2, 127.8, 127.1, 126.1, 122.5, 65.4, 51.1. ESI-MS (m/z):
374 [M þ 1]þ. HRMS (ESI): m/z calcd for (C23H20ClN3 þ H)þ:
374.1424; found: 374.1454.
NMR (500 MHz, CDCl3)
d
8.97 (s, 1H), 8.74 (d, J ¼ 8.3 Hz, 2H), 8.28 (s,
1H), 7.62 (d, J ¼ 8.3 Hz, 2H), 7.39 (t, J ¼ 6.7 Hz, 2H), 7.36e7.32 (m,
4H), 7.28 (d, J ¼ 8.4 Hz, 3H), 4.93 (s, 1H), 3.78 (d, J ¼ 3.1 Hz, 2H). ESI-
MS (m/z): 426 [M
þ
1]þ. HRMS (ESI): m/z calcd for
5.1.6.22. 2-(((4-(1H-Pyrazol-4-yl)phenyl)(4-chlorophenyl)methyl)
(C25H20ClN5 þ H)þ: 426.1485; found: 426.1478.
amino)ethanol 22h. Yellow syrup (yield, 35%), 1H NMR (500 MHz,
CDCl3)
d
7.78 (s, 2H), 7.43 (d, J ¼ 7.6 Hz, 2H), 7.37e7.30 (s, 4H), 7.27
5.1.6.15. N-((4-(1H-Pyrazol-4-yl)phenyl)(4-chlorophenyl)methyl)
(s, 1H), 4.85 (s, 1H), 3.73 (s, 2H), 2.79 (s, 2H). ESI-MS (m/z): 328
[M þ 1]þ. HRMS (ESI): m/z calcd for (C18H18ClN3O þ H)þ: 328.1217;
found: 328.1212.
propan-2-amine 22a. Yellow solid (yield, 27%), mp: 78e80 ꢀC. 1H
NMR (500 MHz, CDCl3)
d
7.84e7.79 (m, 2H), 7.44 (d, J ¼ 8.1 Hz, 2H),
7.35 (dd, J ¼ 8.4, 3.1 Hz, 4H), 7.24 (d, J ¼ 8.4 Hz, 2H), 4.95 (s,1H), 2.75
(dt, J ¼ 12.7, 6.3 Hz, 1H), 1.09 (dd, J ¼ 6.2, 3.6 Hz, 6H). 13C NMR
(100 MHz, CDCl3)
d
141.5, 140.9, 132.9, 131.5, 130.9, 128.8, 128.7,
5.1.6.23. N1-((4-(1H-Pyrazol-4-yl)phenyl)(4-chlorophenyl)methyl)
128.0, 126.0, 122.3, 63.4, 46.7, 22.6. ESI-MS (m/z): 326 [M þ 1]þ.
HRMS (ESI): m/z calcd for (C19H20ClN3 þ H)þ: 326.1424; found:
326.1456.
ethane-1,2-diamine 22i. Yellow syrup (yield, 42%), 1H NMR
(500 MHz, CDCl3)
d
7.78 (s, 2H), 7.43 (d, J ¼ 8.0 Hz, 2H), 7.35 (t,
J ¼ 8.0 Hz, 4H), 7.28 (d, J ¼ 8.0 Hz, 2H), 4.81 (s, 1H), 3.72 (q,
J ¼ 7.0 Hz, 1H), 2.86 (t, J ¼ 5.6 Hz, 2H), 2.67 (t, J ¼ 5.6 Hz, 2H), 1.26 (t,
J ¼ 7.0 Hz, 2H). ESI-MS (m/z): 327 [M þ 1]þ. HRMS (ESI): m/z calcd
for (C18H19ClN4 þ H)þ: 327.1376; found: 327.1380.
5.1.6.16. N-((4-(1H-Pyrazol-4-yl)phenyl)(4-chlorophenyl)methyl)-2-
methylpropan-1-amine 22b. Yellow solid (yield, 40%), mp: 71e