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M. Glanzel et al. / European Journal of Medicinal Chemistry 38 (2003) 303ꢀ
/312
¨
solution of 35 mg (0.19 mmol) cyanuric chloride in
water (10 mL) and acetone (10 mL) was added to a
148.74 (C-3§), 162.85 (C-2ƒ), 163.88 (C-6ƒ), 168.20 (C-
4ƒ), 181,62 (C-9), 182.15 (C-10).
solution of 100 mg (0.19 mmol) 1 in water (10 mL) at 0ꢀ
5 8C. The resulting solution was stirred at 0ꢀ5 8C for 1 h
while 2 M sodium carbonate solution was added
dropwise to keep the pH in the range 5ꢀ7. The reaction
was monitored for completeness by reversed phase TLC
using a mobile phase of methanolꢀwater (2:3). After
/
/
6.1.2.4. 1-Amino-4-{4-[4-chloro-6-(4-
sulfophenylamino)-[1,3,5]triazin-2-ylamino]-3-sulfo-
phenylamino}-9,10-dioxo-9,10-dihydroanthracene-2-
sulfonic acid (4) (RB 2 para). A solution of 165 mg
(0.95 mmol) of sulphanilic acid in water (10 mL) was
added to the stirred solution of 130 mg (0.19 mmol) 2 in
/
/
completion of the reaction the solvent was evaporated
and the blue residue was purified by flash column
chromatography on reversed phase silica gel using a
water (20 mL) and acetone (10 mL) at 0ꢀ
/
5 8C. Then the
temperature was increased to 40ꢀ60 8C and stirring was
/
methanolꢀwater (1:3) eluent. The combined fractions
/
continued for ca. 2 h. A 2 M sodium carbonate solution
was added dropwise to keep the pH in the range of pH
were filtered and evaporated. The blue residue was dried
under vacuum.
1
C23H12N6O8Cl2S2Na2 [681.39] H-NMR (DMSO-d6)
5ꢀ/7. Reaction progress was monitored by reversed
phase TLC using a mobile phase of methanolꢀ
/
water
(2:3). Finally the solvent was evaporated and the blue
d 7.27 (dd, 1H, H-6?), 7.56 (d, 1H, H-2?), 7.83 (m, 2H,
H-6, H-7), 7.98 (s, 1H, H-3), 8.00 (d, 1H, H-5?), 8.27 (m,
residue was purified by flash column chromatography
2H, H-5, H-8), 10.7 (br, 1H, NH-4?), 9ꢀ11 (br, 2H,
/
on reversed phase silica gel using a methanolꢀwater
/
NH2-1), 12.0 (br, 1H, NH-4); 13C-NMR (DMSO-d6) d
109.19 (C-9a), 111,54 (C-4a), 121.16 (C-2?), 122.61 (C-3),
123.25 (C-6?), 125.63 (C-5?), 125.85 (C-5, C-8), 129.44
(C-4?), 132.58 (C-6), 132.99 (C-7), 133.46 (C-10a), 134.03
(C-8a), 135.00 (C-1?), 139.50 (C-3?), 140.62 (C-4), 142.69
(C-2), 144.27 (C-1), 152.91 (C-2ƒ), 154.27 (C-4ƒ, C-6ƒ),
181.77 (C-9), 182.46 (C-10).
(1:3) eluent. The combined fractions were filtered and
evaporated. The blue residue was dried under vacuum.
1
C29H17N7O11S3Na3Cl [840.10] H-NMR (DMSO-d6)
d 7.30 (dd, 1H, H-6?), 7.60 (m, 5H, H-2?, H-2§, H-3§, H-
5§, H-6§), 7.85 (m, 2H, H-6, H-7), 7.97 (s, 1H, H-3),
8.29 (m, 2H, H-5, H-8), 7-11 (br, 2H, NH2-1), 10.30 (s,
1H, NH-6ƒ), 10.35 (s, 1H, NH-4?), 12.04 (s, 1H, NH-4);
13C-NMR (DMSO-d6) d 109.11 (C-9a), 111.21 (C-4a),
119.68 (C-2§, C-6§), 121.50 (C-5?), 121.98 (C-2?), 122.47
(C-3), 123.92 (C-6?), 125.80 (C-3§, C-5§), 125.83 (C-5,
C-8), 131.19 (C-4?), 132.49 (C-6), 132.86 (C-7), 133.47
(C-1?,C-10a), 134.00 (C-8a), 137.22 (C-3?), 138.24 (C-
1§), 140.99 (C-4), 142.69 (C-2), 143.39 (C-4§), 144.17
(C-1), 162.89 (C-2ƒ), 163.73 (C-6ƒ), 168.29 (C-4ƒ), 181.69
(C-9), 182.25 (C-10).
6.1.2.3. 1-Amino-4-{4-[4-chloro-6-(3-
sulfophenylamino)-[1,3,5]triazin-2-ylamino]-3-sulfo-
phenylamino}-9,10-dioxo-9,10-dihydroanthracene-2-
sulfonic acid (3) (RB 2 meta). A solution of 165 mg
(0.95 mmol) of metanilic acid in water (10 mL) was
added to the stirred solution of 130 mg (0.19 mmol) 2 in
water (20 mL) and acetone (10 mL) at 0ꢀ
/
5 8C. Then the
temperature was increased to 40ꢀ60 8C and stirring was
/
continued for ca. 2 h. A 2 M sodium carbonate solution
was added dropwise to keep the pH in the range of pH
6.1.2.5. 1-Amino-4-{4-[4-chloro-6-(2-
sulfophenylamino)-[1,3,5]triazin-2-ylamino]-3-sulfo-
phenylamino}-9,10-dioxo-9,10-dihydroanthracene-2-
sulfonic acid (CB 3GA). The purchased CB 3GA was
purified by flash column chromatography on reversed
5ꢀ/7. Reaction progress was monitored by reversed
phase TLC using a mobile phase of methanolꢀ
/water
(2:3). Finally the solvent was evaporated and the blue
residue was purified by flash column chromatography
phase silica gel using a methanolꢀwater (1:3) eluent. The
/
on reversed phase silica gel using a methanolꢀ
/
water
combined fractions were filtered and evaporated. The
blue residue was dried under vacuum.
(1:3) eluent. The combined fractions were filtered and
evaporated. The blue residue was dried under vacuum.
1
C29H17N7O11S3Na3Cl [840.10] H-NMR (DMSO-d6)
1
C29H17N7O11S3Na3Cl [840.10] H-NMR (DMSO-d6)
d 7.09 (t, 1H, H-4§), 7.31 (dd, 1H, H-6?), 7.50 (t, 1H, H-
5§), 7.66 (d, 1H, H-2?), 7.77 (d, 1H, H-3§), 7.83 (m, 2H,
H-6, H-7), 8.06 (s, 1H, H-3), 8.26 (m, 2H, H-5, H-8),
8.30 (d, 1H, H-6§), 8.38 (d, 1H, H-5?), 7-11 (br, 2H,
NH2-1), 10.29 (s, 1H, NH-4?), 10.34 (s, 1H, NH-6ƒ),
11.99 (s, 1H, NH-4); 13C-NMR (DMSO-d6) d 109.30
(C-9a), 111.57 (C-4a), 121.08 (C-6§), 121.67 (C-2?),
122.05 (C-5?), 122.56 (C-4§), 122.71 (C-3), 123.52 (C-
6?), 125.71 (C-5, C-8), 126.80 (C-3§), 129.44 (C-5§),
130.73 (C-4?), 132.48 (C-6, C-7), 132.89 (C-6), 133.39 (C-
10a), 133.96 (C-1?, C-8a), 134.09 (C-1§), 136.17 (C-2§),
137.38 (C-3?), 140.65 (C-4), 142.45 (C-2), 144.17 (C-1),
d 7.33 (dd, 1H, H-6?), 7.36 (m, 1H, H-5§), 7.57 (d, 1H,
H-2?), 7.75 (br, 1H, H-4§), 7.83 (m, 3H, H-2§, H-6, H-
7), 7.98 (s, 1H, H-3), 8.29 (m, 2H, H-5, H-8), 8.5 (br, 1H,
H-5?), 7-11 (br, 2H, NH2-1), 10.26 (s, 1H, NH-6ƒ), 10.32
(s, 1H, NH-4?), 12.05 (s, 1H, NH-4); 13C-NMR (DMSO-
d6) d 109.04 (C-9a), 111.10 (C-4a), 118.37 (C-2§), 120.94
(C-6§), 121.15 (C-4§), 121.40 (C-5?), 121.85 (C-2?),
122.48 (C-3), 124.07 (C-6?), 125.77 (C-5, C-8), 127.68
(C-5§), 131.15 (C-4?), 132.43 (C-6), 132.79 (C-7), 133.30
(C-1?), 133.47 (C-10a), 134.00 (C-8a), 137.11 (C-3?),
137.35 (C-1§), 141.05 (C-4), 142.80 (C-2), 144.20 (C-1),