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after column chromatography (chloroform), crystalliza-
tion from abs. Et2O, mp 77–81 ꢁC, MS ESI+386.3 (100,
M+H+), ESIꢀ384.2 (100, MꢀH+). 1H NMR (500 MHz,
CDCl3): 1.07 (6H, d, J = 6.6, (CH3)2CHCH); 1.66 (3H,
d, J = 7.6, (CH3)CHN); 1.67 (3H, d, J = 7.6,
CH(CH3)N); 2.06 (1H, m, br s, (CH3)2CHCH); 3.71–
3.99 (3H, m AB + m, CH2HOH + CHNH); 4.60 (2H,
bd, CH2Ar); 4.93 (1H, sept, J = 6.6, NCH(CH3)2);
5.52 (1H, br s, OH); 6.81 (1H, t, J = 7.3, Ar); 6.91
(1H, d, J = 8.0, Ar); 7.19 (1H, t, J = 7.4, Ar); 7.36
(1H, d, J = 8.0, Ar); 8.50 (1H, br s, NHCH2). The pro-
ton 2D-COSY experiments were used for the assignment
of signals. Anal. (C19H27N7O2) C, H, N.
sept, J = 6.6, NCH(CH3)2); 5.41 (1H, br s, OH); 6.78
(1H, dd, J = 8.0, J = 3.0, Ar); 6.88 (2H, m, Ar); 7.18
(1H, m, Ar). Anal. (C19H27N7O2) C, H, N.
4.2.28. 2-(trans-4-Aminocyclohexyl)amino-6-(3-hydroxy-
benzyl)amino-9-isopropyl-8-azapurine (14). Reaction in
1-butanol (120 ꢁC, 20 h, 6 amine eq.), 77% yield after
column chromatography (0–10% MeOH in chloroform
with a trace of NH4OH), crystallization from abs.
Et2O, mp 109–114 ꢁC, MS ESI+397.2 (100, M+H+).
1H NMR (500 MHz, CD3OD): 1.25–1.53 (4H, m,
C6H10); 1.60 (6H, d, J = 6.6, (CH3)2CH); 1.97–2.22
(4H, m, C6H10); 3.00 (1H, m, CHNH2); 3.83 (1H, m,
CHNH); 4.69 (2H, s, CH2Ar); 5.13 (1H, m, (CH3)2CH);
6.67 (1H, m, Ar); 6.82 (2H, m, Ar); 7.12 (1H, dd, J = 7.8,
J = 7.8, Ar). Anal. (C20H28N8O) C, H, N.
4.2.24.
2-(cis-2-Aminocyclohexyl)amino-6-(2-hydroxy-
benzyl)amino-9-isopropyl-8-azapurine (10). Reaction in
1-butanol (115 ꢁC, 6 amine eq., 2 h), 72% yield after col-
umn chromatography (0–5% MeOH in chloroform with
a trace of NH4OH), amorphous, MS ESI+397.4 (100,
M+H+), MS ESIꢀ395.4 (100, MꢀH+). 1H NMR
(500 MHz, CD3OD): 1.62 (6H, dd, J = 6.7, J = 2.7,
(CH3)2CH); 1.45–2.10 (8H, m, C6H10); 3.55 (1H, br s,
CHNH2); 4.44 (1H, br s, CHNH); 4.75 (2H, s, CH2Ar);
4.96 (1H, m, (CH3)2CH); 6.81 (2H, m, Ar), 7.11 (1H, dd,
J = 7.6, J = 7.6, Ar); 7.22 (1H, d, J = 7.2, Ar). Anal.
(C20H28N8O) C, H, N.
4.2.29. 6-(3-Hydroxybenzyl)amino-2-[1-(hydroxymethyl)
propyl]amino-9-isopropyl-8-azapurine (15). Reaction in
1-butanol (100 ꢁC, 8 h, 15 amine eq.), 73% yield after col-
umn chromatography (0–3% MeOH in chloroform), crys-
tallization from abs. Et2O/pentane, mp 105–109 ꢁC, MS
1
ESI+371.2 (100, M+H+). H NMR (300 MHz, CDCl3):
1.03 (3H, t, J = 7.3 Hz, CH3CH2); 1.56 (2H, bm,
CH2CH3); 1.64 (6H, d, J = 6,9 Hz, (CH3)2CH); 3.65
(1H, m, CHNH); 3.77–4.02 (2H, bm, AB, CH2OH);
4.77 (2H, br s, CH2Ar); 4.82 (1H, sept, J = 6.9 Hz,
CH(CH3)2); 5.30 (1H, br s, NH); 6.60 (1H, br s, NH);
6.78–6.88 (3H, m, Ar); 7.30 (1H, s, Ar). Anal.
(C18H25N7O2) C, H, N.
4.2.25. 2-(trans-4-Aminocyclohexyl)amino-6-(2-hydroxy-
benzyl)amino-9-isopropyl-8-azapurine (11). Reaction in
neat amine (115 ꢁC, 4 h, 35 amine eq.), 84% yield after
column chromatography (0–8% MeOH in chloroform
with a trace of NH4OH), crystallization from CHCl3/
abs. Et2O, mp 120–123 ꢁC, MS ESI+397.4 (100,
M+H+), MS ESIꢀ395.4 (100, MꢀH+). 1H NMR
(500 MHz, CD3OD): 1.29–1.50 (4H, m, C6H10); 1.61
(6H, d, J = 6.6, CH3)2CH; 2.00–2.25 (4H, m, C6H10);
3.00 (1H, bt, CHNH2); 3.81 (1H, bm, CHNH); 4.62
(2H, s, CH2Ar); 4.90 (1H, sept, J = 6.6, (CH3)2CH);
6.81 (2H, m, Ar), 7.11 (1H, dd, J = 7.6, J = 7.6, Ar);
7.225 (1H, d, J = 7.2, Ar). Anal. (C20H28N8O) C, H, N.
4.2.30. 2-(trans-4-Aminocyclohexyl)amino-6-(4-hydroxy-
benzyl)amino-9-isopropyl-8-azapurine (16). Reaction in
neat amine (115 ꢁC, 4 h, 35 amine eq.), 84% yield after col-
umn chromatography (0–8% MeOH in chloroform with a
trace of NH4OH), crystallization from abs. Et2O, mp
118–122 ꢁC, MS ESI+397.2 (100, M+H+). 1H NMR
(500 MHz, CD3OD): 1.25–1.55 (4H, m, C6H10); 1.62
(6H, d, J = 6.8, (CH3)2CH); 2.00–2.20 (4H, m, C6H10);
3.08 (1H, m, CHNH2); 3.85 (1H, m, CHNH), 4.64 (2H,
s, CH2Ar); 5.10 (1H, m, (CH3)2CH); 5.43 (1H, s, NH);
6.750 (2H, d, J = 8.2, Ar); 7.210 (2H, d, J = 8.3, Ar). Anal.
(C20H28N8O) C, H, N.
4.2.26. 2,6-Bis[(2-Hydroxybenzyl)amino]-9-isopropyl-8-
azapurine (12). Reaction in NMP (100 ꢁC, 2 h), 68% yield
after column chromatography (chloroform), crystalliza-
tion from chloroform/abs. Et2O, mp 215–217 ꢁC, MS
4.2.31. 2-Hexylamino-9-isopropyl-6-(1-phenyl-2-hydroxy-
ethyl)amino-8-azapurine (17). Reaction in 1-butanol
(100 ꢁC, 2 h), 85% yield after column chromatography
(chloroform), amorphous, MS ESI+398.4 (100, M+H+).
1H NMR (400 MHz, CDCl3): 0.90 (3H, t, J = 6.7,
CH3CH2), 1.31 (6H, m, (CH2)3), 1.63 (2H, m,
CH2CH2N), 1.67 (6H, dd, J = 7.8, J = 7.8, (CH3)2CH);
3.32 (2H, dt, J = 6.6, J = 6.6, NHCH2); 4.07 (2H, m,
CH2OH); 5.00 (1H, sept, J = 7.8, (CH3)2CH); 5.58 (1H,
dd, J = 5.1, J = 5.1 CHPh); 7.28–7.49 (5H, m, Ph). Anal.
(C21H31N7O) C, H, N.
1
ESI+406.3 (100, M+H+), ESIꢀ404.3 (100, MꢀH+). H
NMR (500 MHz, CDCl3 + 20% CD3OD): 1.68 (6H, d,
J = 6.6, (CH3)2CH); 4.57 (2H, d, CH2Ar); 4.62 (2H, s,
CH2Ar); 4.98 (1H, sept, J = 6.7, (CH3)2CH); 6.83–6.92
(4H, m, Ar), 7.19 (2H, dd, J = 7.4, J = 7.4, Ar); 7.27
(2H, d, J = 6.8, Ar). Anal. (C21H23N7O2) C, H, N.
4.2.27. 6-(3-Hydroxybenzyl)amino-2-[1-(hydroxymethyl)-
2-methylpropyl]amino-9-isopropyl-8-azapurine
(13).
Reaction in 1-butanol (100 ꢁC, 22 h, 10 amine eq.),
67% yield after column chromatography (0–3% MeOH
in chloroform), crystallization from abs. EtOAc, mp
150–152 ꢁC, MS ESI+386.2 (100, M+H+), ESIꢀ384.2
4.2.32. 6-(3-Chlorophenyl)amino-2-[1-(hydroxymethyl)-2-
methylpropyl]amino-9-isopropyl-8-azapurine (18). Reac-
tion in 1-butanol (100 ꢁC, 22 h, 10 amine eq.), yield 56%
after column chromatography in chloroform, crystalliza-
tion from abs. Et2O, mp 160–163 ꢁC, MS ESI+390.2 (100,
M+H+). 1H NMR (300 MHz, CDCl3): 1.03 (3H, d,
J = 7.0, (CH3)2CHCH); 1.05 (3H, d, J = 7.0,
1
(100, MꢀH+). H NMR (500 MHz, CDCl3): 1.07 (6H,
d, J = 6.6, (CH3)2CHCH); 1.66 (3H, d, J = 7.6,
(CH3)CHN); 1.67 (3H, d, J = 7.7, CH(CH3)N); 2.06
(1H, m, br s, (CH3)2CHCH); 3.70–3.96 (3H, m AB+m,
CH2HOH + CHNH); 4.60 (2H, bd, CH2Ph); 4.93 (1H,