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purity of the compounds was ꢀ95% according to the elemental
and anhydrous NaOH (280 mg) was placed in a steel vial in an
oven at 1008C for 24 h. The volatiles were then removed in vacuo
and the residue was suspended in H2O, neutralised with 1n HCl
and partitioned three times with CHCl3. The collected organic
layers were dried over anhydrous Na2SO4, filtered and concentrated
in vacuo. Compounds 11 and 12 were obtained as white solids
after silica gel normal column chromatography with elution with
CHCl3/CH3OH (97:3).
analysis data.
General procedure for the synthesis of the 9-ethyl-2-phenyl-
alkylaminoadenine derivatives 4 and 6: 2-Chloro-9-ethyladenine
(3; 200 mg, 1.0 mmol) and the suitable amine (3.5 mL) were placed
in a steel vial and heated at 1308C for 24–28 h until completion of
the reaction. The volatiles were then removed in vacuo and the
residue was subjected to chromatography on a silica gel column
with elution with the suitable solvent system to obtain compounds
4 and 6 as white solids.
2-(Benzylthio)-9-ethyl-9H-purin-6-amine (11): Obtained by the re-
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action of 10 with benzylthiol; yield 65%; mp: 145–1478C; H NMR
([D6]DMSO): d=1.39 (t, 3H, J=7.2 Hz, CH2CH3), 4.14 (q, 2H, J=
7.2 Hz, CH2CH3), 4.36 (s, 2H, CH2Ph), 7.19–7.44 (m, 7H, HPh and
NH2), 8.04 ppm (s, 1H, H8); elemental analysis: calcd for C14H15N5S:
C 58.93, H 5.30, N 24.54, found: C 59.04, H 5.35, N 24.49.
N2-Benzyl-9-ethyl-9H-purine-2,6-diamine (4): Obtained by the re-
action of 3 with benzylamine in a 28 h reaction time and by purifi-
cation with normal column chromatography with elution with
CHCl3/CH3OH (95:5); yield 65%; mp: 169–1738C; 1H NMR
([D6]DMSO): d=1.31 (t, 3H, J=7.2 Hz, CH2CH3), 3.97 (m, 2H,
CH2NH), 4.48 (q, 2H, J=7.2 Hz, CH2CH3), 6.65 (brs, 2H, NH2), 6.79 (t,
2H, J=5.6 Hz, NH), 7.14–7.37 (m, 5H, HPh), 7.71 ppm (s, 1H, H8);
elemental analysis: calcd for C14H16N6: C 62.67, H 6.01, N 31.32,
found: C 62.78, H 6.16, N 31.21.
9-Ethyl-2-(phenethylthio)-9H-purin-6-amine (12): Obtained by the
reaction of 10 with 2-phenethylthiol; yield 77%; mp: 152–1548C;
1H NMR ([D6]DMSO): d=1.42 (t, 3H, J=7.2 Hz, CH2CH3), 3.00 (m,
2H, CH2Ph), 3.31 (m, 2H, CH2S), 4.16 (q, 2H, J=7.2 Hz, CH2CH3),
7.19–7.24 (m, 7H, HPh and NH2), 8.05 ppm (s, 1H, H8); elemental
analysis: calcd for C15H17N5S: C 60.18, H 5.72, N 23.39, found: C
60.29, H 5.83, N 23.30.
9-Ethyl-N2-(3-phenylpropyl)-9H-purine-2,6-diamine (6): Obtained
by the reaction of 3 with 1-propylamine in a 24 h reaction time
and by purification with flash column chromatography with elution
with CHCl3/CH3OH (98:2); yield 70%; mp: 65–708C; 1H NMR
([D6]DMSO): d=1.35 (t, 3H, J=7.2 Hz, CH2CH3), 1.83 (m, 2H,
CH2CH2CH2), 2.64 (t, 2H, J=7.2 Hz, CH2Ph), 3.27 (m, 2H, CH2NH),
3.99 (q, 2H, J=7.2 Hz, CH2CH3), 6.30 (t, 1H, J=5.6 Hz, NH), 6.59
(brs, 2H, NH2), 7.25 (m, 5H, HPh), 7.71 ppm (s, 1H, H8); elemental
analysis: calcd for C16H20N6: C 64.84, H 6.80, N 28.36, found: C
64.97, H 6.87, N 28.29.
General procedure for the synthesis of the 8-bromo-9-ethyl-2-
substituted adenine derivatives 13–18: NBS (267 mg, 1.5 mmol)
was added to a solution of either 4–9, 11 or 12 (1.0 mmol) in anhy-
drous DMF (10 mL). The mixture was left under stirring at room
temperature for 20–50 min. The solvent was then removed in va-
cuo and the residue was purified on silica gel normal column chro-
matography with elution with the suitable eluent to obtain the
pure desired products as white solids.
N2-Benzyl-8-bromo-9-ethyl-9H-purine-2,6-diamine (13): Obtained
from 4; purified by silica gel normal column chromatography with
elution with CHCl3/CH3OH (98:2); yield 19%; mp: 156–1588C;
1H NMR ([D6]DMSO): d=1.25 (t, 3H, J=7.3 Hz, CH2CH3), 3.99 (q, 2H,
J=7.3 Hz, CH2CH3), 4.47 (d, 2H, J=6.5 Hz, NHCH2), 6.82 (brs, 2H,
NH2), 6.98 (t, 1H, J=6.5 Hz, NHCH2), 7.13–7.40 ppm (m, 5H, HPh);
elemental analysis: calcd for C14H15BrN6: C 48.43, H 4.35, N 24.20,
found: C 48.52, H 4.44, N 24.13.
General procedure for the synthesis of the 9-ethyl-2-phenylal-
koxyadenine derivatives 7 and 9: Anhydrous NaOH (200 mg,
5 mmol) was added to a mixture of 2-chloro-9-ethyladenine (3)
(200 mg, 1.0 mmol) suspended in the suitable alcohol (9.0 mL). The
mixture was heated at 85–1058C for 3–4 h. The solvent was then
removed in vacuo and the residue was suspended in H2O, neutral-
ised with 2n HCl and then partitioned with CHCl3 three times. The
combined organic layers were dried over anhydrous Na2SO4, fil-
tered and concentrated in vacuo. Compounds 7 and 9 were ob-
tained after purification with silica gel flash column chromatogra-
phy with elution with the appropriate solvent system.
8-Bromo-9-ethyl-N2-phenethyl-9H-purine-2,6-diamine (14): Ob-
tained from 5; purified by silica gel normal column chromatogra-
phy with elution with EtOAc/C6H12/CH3OH (60:39:1); yield 62%
(cryst. CH3CN/CH3OH); mp: 182–1838C; 1H NMR ([D6]DMSO): d=
1.30 (t, 3H, J=7.2 Hz, CH2CH3), 2.84 (t, 2H, J=7.5 Hz, NHCH2), 3.45
(m, 2H, CH2Ph), 4.02 (q, 2H, J=7.2 Hz, CH2CH3), 6.45 (m, 1H,
NHCH2), 6. 58 (brs, 2H, NH2), 7.28 ppm (m, 5H, HPh) elemental
analysis: calcd for C15H17BrN6: C 49.87, H 4.74, N 23.26, found: C
49.99, H 4.76, N 23.19.
2-Benzyloxy-9-ethyl-9H-purin-6-amine (7): Obtained by reaction
of 3 with benzyl alcohol in a 4 h reaction time and by column
chromatography with elution with CHCl3/CH3OH (95:5); yield 49%;
white solid (cryst. CH3OH); mp: 168–1708C; 1H NMR ([D6]DMSO):
d=1.37 (t, 3H, J=7.2 Hz, CH3), 4.08 (q, 2H, J=7.2 Hz, CH2CH3), 5.32
(s, 2H, OCH2Ph), 7.25 (s, 2H, NH2), 7.34–7.50 (m, 5H, HPh),
7.98 ppm (s, 1H, H8); elemental analysis: calcd for C14H15N5O: C
62.44, H 5.61, N 26.01, found: C 62.57, H 5.71, N 25.92.
8-Bromo-9-ethyl-N2-(3-phenylpropyl)-9H-purine-2,6-diamine (15):
Obtained from 6; purified by silica gel normal column chromatog-
raphy with elution with cHex/EtOAc/CH3OH (70:29:1); yield 54%
(cryst. CH3OH); mp: 122–1248C; 1H NMR ([D6]DMSO): d=1.28 (t,
3H, J=7.2 Hz, CH2CH3), 1.83 (m, 2H, CH2CH2CH2), 2.64 (t, 2H, J=
7.2 Hz, CH2Ph), 3.27 (m, 2H, CH2NH), 4.00 (q, 2H, J=7.2 Hz,
CH2CH3), 6.49 (t, 1H, J=7.8 Hz, NH), 6.80 (brs, 2H, NH2), 7.24 ppm
(m, 5H, HPh); elemental analysis: calcd for C16H19BrN6: C 51.21, H
5.10, N 22.39, found: C 51.29, H 5.17, N 22.30.
9-Ethyl-2-(3-phenylpropoxy)-9H-purin-6-amine (9): Obtained by
the reaction of 3 with 1-propylalcohol in a 4 h reaction time and
by column chromatography with elution with CHCl3/CH3OH (95:5);
yield 83%; white solid (cryst. CH3CN); mp: 131–1338C; 1H NMR
([D6]DMSO): d=1.38 (t, 3H, J=7.2 Hz, CH3), 2.00 (m, 2H, CH2CH2O),
2.74 (t, 2H, J=7.06 Hz, CH2Ph), 4.07 (q, 2H, J=7.2 Hz, CH2CH3),
4.22 (t, 2H, J=6.4 Hz, CH2O), 7.13–7.37 (m, 7H, HPh and NH2),
7.96 ppm (s, 1H, H8); elemental analysis: calcd for C16H19N5O: C
64.63, H 6.44, N 23.55, found: C 64.68, H 6.55, N 23.43.
2-(Benzyloxy)-8-bromo-9-ethyl-9H-purin-6-amine (16): Obtained
from 7 with a 20 min reaction time; purified by silica gel flash
column chromatography with elution with cHex/CHCl3/CH3OH
(59:40:1); yield 66% (cryst. CHCl3); mp: 208–2108C; 1H NMR
([D6]DMSO): d=1.30 (t, 3H, J=7.0 Hz, CH3), 4.08 (q, 2H, J=7.0 Hz,
General procedure for the synthesis of the 9-ethyl-2-phenylal-
kylthioadenine derivatives 11 and 12: A suspension of 2-iodo-9-
ethyladenine (10; 289 mg, 1.0 mmol) in the suitable thiol (5.8 mL)
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ChemMedChem 2016, 11, 1 – 12
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