Med Chem Res
-SCH2CCH] (55), 39 [CH2CCH] (100); HREIMS m/z
[M]? calcd. for C9H7ClN4S 238.0079, found 238.0076.
combined, washed with water, dried over anhydrous sodi-
um sulfate, and evaporated in vacuo to give an oil residue.
In order to remove benzyl acetate and benzyl chloride, the
residue was triturated with ice-cold dry ether and the ether
layer was separated. The mixture of obtained oil (0.26 g,
1 mmol), and 25 % aqueous ammonia (2.5 ml) or diethy-
lamine (0.22 g, 3 mmol) in 10 % NaOH solution or aniline
(0.19 g, 2 mmol) in 2.5 ml of benzene was stirred at
40–45 °C for 2–6 h. The resulted solid was filtered off (in
the case of the reaction with ammonia, the excess of am-
monia was removed in vacuo and the residue was diluted
with water up to volume 2.5 ml) to give compounds 9a–c.
Products were purified by a column chromatography (alu-
minum oxide, CHCl3–EtOH, 99:1 v/v) to give:
Synthesis of 2-chloro-6-(4-N-pyrrolidinylbut-2-ynylthio)-7-
methylpurine 5b To a mixture of propargyl derivative 5a
(0.24 g, 1 mmol) and paraformaldehyde (0.06 g, 2 mmol) in
5 ml of dry dioxane, pyrrolidine (0.14 g, 2 mmol) and CuCl
(0.01 g) were added. The reaction mixture was stirred at
temperature 70 °C for 2 h. After cooling, the resulting solid
was filtered off and purified by column chromatography
(silica gel, CHCl3, CHCl3–EtOH, 99:1 v/v) to give compound
5b. It was obtained as a pale yellow solid (0.31 g, 96 %); mp
1
129–130 °C (EtOH); H NMR (CDCl3), d: 2.13 (m, 8H,
4CH2), 3.12 (t, J = 2.2 Hz, 2H, SCH2), 3.62 (t, J = 2.2 Hz,
2H, CCH2), 4.19 (s, 3H, NCH3), 8.25 (s, 1H, H-8); 13C NMR
(DMSO-d6), d: 18.77 (CH2, SCH2CC), 23.68 (2CH2), 34.86
(CH3, NCH3), 42.58 (CH2, CCH2), 51.86 (2CH2, NCH2),
79.15 (C, SCH2CC), 80.01 (C, SCH2CC), 123.16 (C, C-5),
151.08 (CH, C-8), 152.35 (C, C-2), 154.24 (C, C-6), 160.50
(C, C-4); CIMS m/z 322 [M?1]? (6.5), 324 [M?1?2] (2.5),
167 [M?1-SCH2CCCH2NC4H8] (9.5), 72 [C4H8NH2]?
(100); HRFABMS m/z [M?H]? calcd. for C14H17ClN5S
322.0893 found 322.0893.
2-Chloro-6-amine-7-methylpurine 9a was obtained as a
white solid (0.15 g, 82 %); mp 248–249 °C (EtOH), lit. mp
1
250 °C (Adams and Whitmore, 1945); H NMR (DMSO-
d6), d: 3.97 (s, 3H, NCH3), 7.46 (s, 2H, NH2), 8.20 (s, 1H,
H-8); 13C NMR (DMSO-d6), d: 34.29 (CH3, NCH3),
111.12 (C, C-5), 147.27 (CH, C-8), 153.03 (C, C-2), 153.17
(C, C-6), 161.50 (C, C-4); EIMS m/z 183 [M]? (100), 185
[M?2] (29); HREIMS m/z [M]? calcd. for C6H6ClN5
183.0311 found 183.0307.
Synthesis of 2-chloro-6-benzylthio-7-methylpurine 6 2-
Chloro-6-benzylthio-7-methylpurine 6 was prepared from
2-chloro-7-methyl-6-purinethione 1a (0.2 g, 1 mmol) by
alkylation with benzyl chloride (0.25 g, 2 mmol) at room
temperature in 4 % aqueous KOH solution (5 ml). After
30 min, the crude product was precipitated, filtered off,
washed with water, and crystallized from benzene. It was
obtained as a pale yellow solid (0.265 g, 91.5 %); mp
2-Chloro-6-diethylamine-7-methylpurine 9b was ob-
tained as a white solid (0.20 g, 84 %); mp 106–107 °C
(EtOH), lit. mp 107 °C (Adams and Whitmore, 1945); H
1
NMR (DMSO-d6), d: 1.17 (t, J = 7.7 Hz, 6H, 2 9 CH3
CH2N), 3.52 (q, J = 7.7 Hz, 4H, 2 9 CH3CH2N), 3 0.94 (s,
3H, NCH3), 8.37 (s, 1H, H-8); 13C NMR (DMSO-d6), d:
12.93 (2CH3, NCH2CH3), 35.63 (CH3, NCH3), 44.32 (2CH2,
NCH2CH3), 114.45 (C, C-5), 149.30 (CH, C-8), 151.81 (C,
C-2), 154.70 (C, C-6), 163.03 (C, C-4); EIMS m/z 239 [M]?
(19), 241 [M?2] (6); 210 [M-C2H5], (100); HREIMS m/z
[M]? calcd. for C10H14ClN5 239.0937 found 239.0935.
1
131–132 °C (benzene); H NMR (CDCl3), d: 4.07, (s, 3H,
NCH3), 4.64 (s, 2H, CH2), 7.38 (m, 5Harom), 7.98 (s, 1H,
H-8); 13C NMR (DMSO-d6), d: 33.39 (CH2, SCH2), 34.84
(CH3, NCH3), 122.72 (C, C-5), 127.98 (CH, p-CH), 128.99
(2CH, m-CH), 129.84 (2CH, o-CH), 137.12 (C, CCH2),
150.79 (CH, C-8), 152.26 (C, C-2), 155.46 (C, C-6), 160.33
(C, C-4); EIMS m/z 290 [M]? (100), 292 [M?2] (28.5),
2-Chloro-6-phenylamine-7-methylpurine 9c was obtained
as a white solid (0.18 g, 69 %); mp 202–203 °C. (EtOH);
1H NMR (CDCl3), d: 3.96 (s, 3H, NCH3), 6.84 (s, 1H, NH),
7.23 (t, J = 7.20 Hz, 1H, p-C6H5), 7.40 (t, J = 7.20 Hz,
2H, m-C6H5), 7.52 (d, J = 7.20 Hz, 2H, o-C6H5), 7.90 (s,
1H, H-8); 13C NMR (DMSO-d6), d: 34.63 (CH3, NCH3),
112.40 (C, C-5), 123.17 (2CH, m-CH), 124.61 (CH, p-CH),
129.06 (2CH, o-CH), 138.97 (C, CNH), 148.47 (CH, C-8),
149.75 (C, C-2), 152.29 (C, C-6), 162.07 (C, C-4); FABMS
m/z 260 [M?1]? (100), 262 [M?1?2] (31.5); HREIMS
m/z [M]? calcd. for C12H10ClN5 259.0625 found 259.0626.
?
199 [M-C6H5CH2] (87); HREIMS m/z [M?] calcd. for
C13H11ClN4S 290.0392 found 290.0385.
Chlorination and amination of 2-chloro-6-
benzylthio-7-methylpurine 6
The chlorinolysis was carried out by passing chlorine gas
into a stirred mixture composed of 2-chloro-6-benzylthio-
7-methylpurine 6 (0.29 g, 1 mmol), 3 ml of chloroform,
and 3 ml of 80 % acetic acid cooled at 5 °C. The passage
of chlorine gas was continued for 30 min, and then the
mixture was poured into 10 ml of ice water. The chloro-
form layer was separated, and aqueous layer was extracted
with chloroform (2 9 5 ml). The chloroform extracts were
General synthesis of 2-substituted 7-methyl-6-
purinesulfenamide 10a–e
A solution of commercial NaOCl (14.5 %, 1.7 ml) and
1.7 ml of water was cooled to 0 °C in an ice–NaCl bath.
123