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M. Glänzel et al. / European Journal of Medicinal Chemistry 40 (2005) 1262–1276
(br, 1H, 4′-NH), 9–11 (br, 2H, 1-NH2), 12.05 (br, 1H, 4-NH).
13C-NMR (DMSO-d6) d 109.54 (C-9a), 113,12 (C-4a), 121.99
(C-3′), 123.00 (C-6′), 123.26 (C-5′), 124.55 (C-3), 125.74
(C-5, C-8), 130.65 (C-4′), 132.46 (C-6), 132.62 (C-7), 133.72
(C-10a), 133.98 (C-8a), 134.22 (C-1′), 138.96 (C-4), 139.72
(C-2′), 141.53 (C-2), 144.34 (C-1), 152.07 (C-2′′), 153.76
(C-4′′, C-6′′), 181.27 (C-10), 181.98 (C-9). ESI-MS (m/z):
408 (100%) [M-C3N3Cl2+H-SO3Na+H-Na]–, 488
[M-C3N3Cl2+H-2Na+H]–, 510 [M-C3N3Cl2+H-Na]–.
1-Amino-4-[4-(4,6-dichloro-[1,3,5]triazine-2-ylamino)-
3-sulfonatophenylamino]-9,10-dioxo-9,10-dihydroanthra-
cene-2-sulfonic acid disodium salt (13). Following the gen-
eral procedure B with 52 mg (0.28 mmol) of cyanuric chloride
(29), 150 mg (0.28 mmol) of 10 and RP-FCC performed with
a methanol/water (1:3) eluent (Rf = 0.57), 13 (136 mg, 71%)
was obtained as a blue solid [34]. 1H-NMR (DMSO-d6) [34],
13C-NMR (DMSO-d6) [34]. ESI-MS (m/z): 408 (100%)
[M-C3N3Cl2+H-SO3Na+H-Na]–, 488 [M-C3N3Cl2+H-
2Na+H]–, 510 [M-C3N3Cl2+H-Na]–.
(C-3′), 141.78 (C-4), 142.98 (C-2), 144.12 (C-1), 157.80
(C-4′′, C-6′′), 159.24 (C-2′′), 181.51 (C-9), 181.84 (C-10).
ESI-MS (m/z): 283 [M-2Na]2–, 566 (100%) [M-2Na+H]–, 588
[M-Na]–.
1-Amino-4-{4-[4-chloro-6-(2-sulfonatophenylamino)-
[1,3,5]triazine-2-ylamino]-2-sulfonatophenylamino}-9,10-
dioxo-9,10-dihydroanthracene-2-sulfonic acid trisodium
salt (18). A solution of 2-aminobenzenesulfonic acid (24)
(38 mg, 0.35 mmol) in water (10 ml) was added to a stirred
solution of 12 (50 mg, 0.07 mmol) in water (20 ml) and
acetone (10 ml). Then the temperature was increased to
40–60 °C and stirring was continued for approximately 4 h.
The pH was kept at 5–7 by dropwise addition of 2 M Na2CO3.
The formation of product was monitored by RP-TLC with a
mobile phase of methanol/water (2:3). After completion of
the reaction the solvents were evaporated to dryness and the
anhydrous residue was purified by FCC on RP-18 silica gel
(MeOH/H2O 2:3, Rf = 0.49) to give the blue solid 18 (50 mg,
1
81%). H-NMR (DMSO-d6) d 7.00 (t, 1H, 4′′′-H), 7.14 (d,
1-Amino-4-[4-(4,6-diamino-[1,3,5]triazine-2-ylamino)-
3-sulfonatophenylamino]-9,10-dioxo-9,10-dihydroanthra-
cene-2-sulfonic acid disodium salt (15). According to the
general procedure B, the solution of 41 mg (0.28 mmol) of
2-chloro-4,6-diamino- [1,3,5]-triazine (30) and 150 mg
(0.28 mmol) of 10 was stirred for 1 h at 0–5 °C and for addi-
tional 2 h at 60 °C. RP-FCC was performed with a methanol/
water (2:3) eluent (Rf = 0.37), 15 (114 mg, 63%) was obtained
as a blue solid. 1H-NMR (DMSO-d6) d 6.31 (s, 4H, 4′′-NH2,
6′′-NH2), 7.17 (dd, 1H, 6′-H), 7.51 (d, 1H, 2′-H), 7.83 (m,
2H, 6-H, 7-H), 7.93 (s, 1H, 3-H), 8.29 (m, 2H, 5-H, 8-H),
8.81 (d, 1H, 5′-H), 7–11 (br, 2H, 1-NH2), 9.50 (br, 1H, 4′-NH),
12.11 (br, 1H, 4-NH). 13C-NMR (DMSO-d6) d 108.89 (C-9a),
110,48 (C-4a), 120.27 (C-5′), 122.35 (C-2′), 122.40 (C-3),
124.02 (C-6′), 125.75 (C-5, C-8), 130.64 (C-1′), 132.36 (C-6),
132.63 (C-7), 133.55 (C-10a), 133.98 (C-4′), 134.06 (C-8a),
135.63 (C-3′), 141.81 (C-4), 142.93 (C-2), 144.07 (C-1),
164.13 (C-2′′), 167.07 (C-4′′, C-6′′), 181.49 (C-9), 181.75
(C-10). ESI-MS (m/z): 473 [M-C3N6H4-2Na+H]–, 488
[M-C3N5H3-2Na+H]–, 597 (100%) [M-2Na+H]–, 619
[M-Na]–.
1-Amino-4-[4-[1,3]diazine-2-ylamino)-3-sulfonatophe-
nylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonic
acid disodium salt (16). According to the general procedure
B, the solution of 32 mg (0.28 mmol) of 2-chloropyrimidine
(31) and 150 mg (0.28 mmol) of 10 was stirred for 1 h at
0–5 °C and for additional 2 h at 90 °C. RP-FCC was per-
formed with a methanol/water (2:3) eluent (Rf = 0.32), 16
(81 mg, 47%) was obtained as a blue solid. 1H-NMR (DMSO-
d6) d 6.88 (d, 1H, 5′′-H), 7.26 (dd, 1H, 6′-H), 7.56 (d, 1H,
2′-H), 7.83 (m, 2H, 6-H, 7-H), 7.94 (s, 1H, 3-H), 8.29 (m,
2H, 5-H, 8-H), 8.51 (d, 2H, 4′′-H, 6′′-H), 8.58 (d, 1H, 5′-H),
7–11 (br, 2H, 1-NH2), 10.03 (br, 1H, 4′-NH), 12.09 (br, 1H,
4-NH). 13C-NMR (DMSO-d6) d 108.89 (C-9a), 110,56
(C-4a), 112.61 (C-5′′), 119.67 (C-5′), 122.41 (C-3, C-2′),
124.33 (C-6′), 125.76 (C-5, C-8), 131.23 (C-1′), 132.37 (C-6),
132.67 (C-7), 133.54 (C-4′, C-10a), 134.01 (C-8a), 136.06
1H, 6′-H), 7.48 (t, 1H, 5′′′-H), 7.69 (d, 1H, 3′′′-H), 7.71 (d,
1H, 5′-H), 7.83 (m, 2H, 6-H, 7-H), 8.03 (d, 1H, 3′-H), 8.08
(s, 1H, 3-H), 8.27 (m, 2H, 5-H, 8-H), 8.39 (d, 1H, 6′′′-H), 7-9
(br, 2H, 1-NH2), 9.94 (s, 1H, 6′′-NH), 10.08 (s, 1H, 4′-NH),
11.5–12.5 (s, 1H, 4-NH). 13C-NMR (DMSO-d6) d 109.42
(C-9a), 112.64 (C-4a), 121.14 (C-3′), 121.83 (C-6′′′), 121.93
(C-4′′′), 122.03 (C-5′), 122.74 (C-6′), 124.53 (C-3), 125.66
(C-5), 125.78 (C-8), 126.54 (C-3′′′), 129.57 (C-5′′′), 132.35
(C-4′), 132.48 (C-6, C-7), 133.15 (C-1′), 133.76 (C-10a),
133.96 (C-8a), 134.53 (C-1′′′), 135.88 (C-2′′′), 139.43 (C-4),
140.54 (C-2′), 141.61 (C-2), 144.27 (C-1), 162.56 (C-2′′,
C-6′′), 168.30 (C-4′′), 180.99 (C-10), 181.84 (C-9). ESI-MS
(m/z): 772/774 (100%) [M(35Cl/37Cl)-3Na+2H]–, 794/796
[M(35Cl/37Cl)-2Na+H]–, 816/818 [M(35Cl/37Cl)-Na]–.
1-Amino-4-{4-[4,6-bis(2-sulfonatophenylamino)-
[1,3,5]triazine-2-ylamino]-3-sulfonato-phenylamino}-9,10-
dioxo-9,10-dihydroanthracene-2-sulfonic acid tetraso-
dium salt (19). A solution of 2-aminobenzenesulfonic acid
(24) (32 mg, 0.3 mmol) in water (10 ml) was added to a stirred
solution of CB 3GA (17) (50 mg, 0.06 mmol) in water (15 ml).
The mixture was heated at 90 °C for 5 h, keeping the pH at
5–7 by dropwise addition of 2 M Na2CO3. The formation of
product was monitored by RP-TLC using a mobile phase of
methanol/water (2:3). After completion of the reaction the
solvents were evaporated to dryness and the residue was puri-
fied by FCC on RP-18 silica gel using a methanol/water (1:2)
eluent (Rf = 0.34) to give 19 (52 mg, 88%) as a blue solid.
1H-NMR (DMSO-d6) d 6.96 (t, 2H, 4′′′-H), 7.23 (dd, 1H,
6′-H), 7.38 (t, 2H, 5′′′-H), 7.59 (d, 1H, 2′-H), 7.71 (dd, 2H,
3′′′-H), 7.84 (m, 2H, 6-H, 7-H), 8.02 (s, 1H, 3-H), 8.30 (m,
2H, 5-H, 8-H), 8.46 (d, 2H, 6′′′-H), 8.54 (d, 1H, 5′-H), 7–11
(br, 2H, 1-NH2), 9.88 (s, 1H, 4′-NH), 9.93 (s, 2H, 4′′-NH,
6′′-NH), 12.12 (s, 1H, 4-NH). 13C-NMR (DMSO-d6) d 108.98
(C-9a), 110.83 (C-4a), 120.52 (C-6′′′), 120.81 (C-4′′′), 121.45
(C-5′), 122.04 (C-2′), 122.56 (C-3), 123.78 (C-6′), 125.77
(C-5, C-8), 126.68 (C-3′′′), 129.03 (C-5′′′), 132.13 (C-1′),
132.39 (C-6, C-7), 132.69 (C-4′), 133.54 (C-10a), 134.01