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Z. Brzozowski et al. / European Journal of Medicinal Chemistry 42 (2007) 1218e1225
4.5.1. 3-Amino-2-(4-chloro-2-mercapto-
followed by reflux for 5 h. After cooling to room temperature
the resulting suspension was left to stand overnight. The pre-
cipitate was collected by filtration, washed with water, dried
and recrystallized from 2-propanol (80 ml) to give 17 (1.7 g,
75%); m.p. 144e146 ꢂC dec. IR (KBr): 3350, 3300, 3255
(NH2, NH), 2120 (C^C), 1685 (C]O), 1645 (C]N),
5-methylbenzenesulfonyl)-1-(2-propynyl)guanidine (14)
Starting from benzodithiazine 12 (3.0 g), the title com-
pound 14 was obtained (2.6 g, 78%); m.p. 141e143 ꢂC. IR
(KBr) 3350, 3260 (NH2, NH), 2550 (SH), 2115 (C^C),
1650 (C]N), 1345, 1180 (SO2) cmꢀ1. H NMR (DMSO-d6)
1
1
d: 2.27 (s, 3H, CH3), 3.10 (s, 1H, C^CH), 3.95 (s, 2H,
CH2), 4.55 (s, 2H, NH2, disappearing on deuteration), 6.00
(s, 1H, SH, disappearing on deuteration), 7.57 (s, 1H, H-3),
7.70 (s, 1H, NH, disappearing on deuteration), 7.81 (s, 1H,
H-6), 8.16 (s, 1H, NH, disappearing on deuteration) ppm.
13C NMR (DMSO-d6) d: 18.95, 29.76, 73.09, 81.29, 130.15,
130.39, 131.39, 132.25, 135.86, 138.80, 156.34 ppm. Anal.
(C11H13ClN4O2S2) C, H, N.
1355, 1135 (SO2) cmꢀ1. H NMR (DMSO-d6) d: 2.30 (s,
3H, CH3), 3.05 (s, 1H, C^CH), 3.84 (s, 2H, NCH2), 4.53 (s,
2H, SCH2), 4.75 (s, 2H, NH2), 7.49 (s, 1H, NH), 7.53e7.56
(m, 2H, arom.), 7.65e7.68 (m, 2H, arom.), 7.84 (s, 1H, H-6,
PhSO2) 8.05e8.08 (m, 3H, HNeN and arom.) ppm. Anal.
(C19H19ClN4O3S2) C, H, N.
4.8. 3-Amino-2-[4-chloro-2-(cyanomethylthio)-5-
methylbenzenesulfonyl]-1-(2-propynyl)guanidine (18)
4.5.2. 3-Amino-2-[4-chloro-5-(phenylcarbamoyl)-
2-mercaptobenzenesulfonyl]-1-(2-propynyl)guanidine (15)
Starting from benzodithiazine 13 (4.1 g), the title compound
15 was obtained (3.3 g, 75%); m.p. 208e210 ꢂC. IR (KBr) 3330,
3300, 3245 (NH2, NH), 2560 (SH), 2125 (C^C), 1685 (C]O),
1575 (C]N), 1360, 1140 (SO2) cmꢀ1. 1H NMR (DMSO-d6) d:
3.02 (s, 1H, C^CH), 3.97 (s, 2H, NCH2C^C), 4.56 (s, 2H,
NH2), 5.98 (s, 1H, SH), 7.11 (m, 1H, Ph), 7.35 (m, 2H, Ph),
7.69 (m, 2H, Ph), 7.78 (s, 2H, HNeCeNH), 8.04 (s, 1H, H-3,
PhSO2), 8.21 (s, 1H, H-6, PhSO2), 10.53 (s, 1H, NHCO) ppm.
Anal. (C17H16ClN5O3S2) C, H, N.
To a solution of triethylamine (0.65 g, 6.4 mmol) and 3-
amino-2-(4-chloro-2-mercapto-5-methylbenzenesulfonyl)-1-(2-
propynyl)guanidine 14 (2.0 g, 6 mmol) in methanol (25 ml),
bromoacetonitrile (0.77 g, 6.4 mmol) was added. The reaction
mixture was stirred at room temperature for 4 h, followed by re-
flux for 2 h. The resulting solution was poured into water
(150 ml) and stirred at room temperature for 6 h. The precipitate
thus obtained was collected by filtration, washed successively
with water (5 ꢃ 5 ml) and 2-propanol (2 ꢃ 2 ml), and dried to
give 18 (3.1 g, 94%); m.p. 141e143 ꢂC. IR (KBr): 3350, 3285
(NH2, NH), 2245 (C^N), 2125 (C^C), 1645 (C]N), 1360,
4.6. 3-Amino-2-[4-chloro-2-(carbamoylmethylthio)-
5-methylbenzenesulfonyl]-1-(2-propynyl)guanidine (16)
1
1345, 1135 (SO2) cmꢀ1. H NMR (DMSO-d6) d: 2.36 (s, 3H
CH3), 3.08 (s, 1H, C^CH), 3.94 (s, 2H, CH2C^C), 4.35 (s,
2H, CH2CN), 4.56 (s, 2H, NH2), 7.57 (s, 1H, H-3, Ph), 7.75 (br
s, 1H, NH), 7.91 (s, 1H, H-6, Ph), 8.08 (s, 1H, HNeN) ppm.
Anal. (C13H14ClN5O2S2) C, H, N.
To a solution of triethylamine (1.6 g, 0.016 mol) and 3-
amino-2-(4-chloro-2-mercapto-5-methylbenzenesulfonyl)-1-
(2-propynyl)guanidine 14 (5.0 g, 0.015 mol) in methanol
(45 ml), chloroacetamide (1.5 g, 0.016 mol) was added. The
reaction mixture was stirred at room temperature for 4 h, fol-
lowed by reflux for 3 h. The resulting solution was poured into
water (60 ml) and stirred at room temperature for 2 h. The pre-
cipitate thus obtained was collected by filtration, washed with
water (6 ꢃ 10 ml) and 2-propanol (3 ꢃ 2 ml), and dried to give
16 (5.4 g, 92%); m.p. 188e190 ꢂC dec. IR (KBr) 3350, 3345,
3300 (NH2, NH), 2120 (C^C), 1690 (C]O), 1645 (C]N),
4.9. 2-[4-Chloro-2-(carbamolymethylthio)-5-methylben-
zenesulfonyl]-3-(5-nitrofurfurylideneamino)-1-(2-
propynyl)guanidine (19)
A mixture of aminoguanidine 16 (1.2 g, 3 mmol) and 5-
nitrofurane-2-carbaldehyde (0.46 g, 3.3 mmol) in ethanol
(20 ml) was stirred at reflux for 7 h. After cooling to room
temperature the resulting suspension was left overnight.
The precipitate was collected by filtration, washed with eth-
anol (4 ꢃ 2 ml) and dried initially at room temperature and
then at 90 ꢂC to give 19 (1.3 g, 85%); m.p. 210e212 ꢂC
dec. IR (KBr): 3415, 3395, 3275 (NH2, NH), 2125 (C^C),
1685 (C]O), 1655, 1625 (N]C, N]CH), 1350, 1170
1
1360, 1340, 1190 (SO2) cmꢀ1. H NMR (DMSO-d6) d: 2.31
(s, 3H, CH3), 3.09 (s, 1H, C^CH), 3.68 (s, 2H, NCH2),
3.96 (s, 2H, SCH2), 4.56 (s, 2H, H2NeN), 7.23 (s, 1H,
CONHa), 7.57 (s, 1H, H-3, Ph), 7.72 (s, 1H, CONHb), 7.85
(s, 1H, H-6, Ph), 8.06 (s, 1H, HNeN) ppm. Anal.
(C13H16ClN5O3S2) C, H, N.
4.7. 3-Amino-2-(4-chloro-5-methyl-2-phenacylthioben-
zenesulfonyl)-1-(2-propynyl)guanidine (17)
(SO2) cmꢀ1 1H NMR (DMSO-d6) d: 2.32 (s, 3H, CH3),
.
3.12 (s, 1H, C^CH), 3.69 (s, 2H, SCH2), 4.02 (d,
J ¼ 5.1 Hz, 2H, NCH2), 7.22 (s, 1H, CONHa), 7.38 (d,
J ¼ 3.9 Hz, 1H, H-3, furane), 7.55 (s, 1H, CONHb), 7.60
(s, 1H, H-3, PhSO2), 7.81 (d, J ¼ 3.9 Hz, 1H, H-4, furane),
7.91 (s, 1H, H-6, PhSO2), 8.33 (t, J ¼ 5.1 Hz, 1H, HNe
CH2), 8.45 (s, 1H, N]CH), 11.21 (s, 1H, HNeN) ppm.
Anal. (C18H17ClN6O6S2) C, H, N.
To an ice-cooled solution of triethylamine (0.6 g, 6 mmol)
and 3-amino-2-(4-chloro-2-mercapto-5-methylbenzenesul-
fonyl)-1-(2-propynyl)guanidine 14 (1.7 g, 5 mmol) in CH2
Cl2 (15 ml), phenacyl bromide (1.0 g, 5 mmol) was added
with stirring. After 0.5 h, the ice bath was removed and the re-
action mixture was stirred at room temperature for 3 h,