d, J 8.1), 7.94–8.20 (4H, m), 7.91 (1H, d, J 7.6), 7.61 (1H, t,
J 7.6), 4.36 (3H, s, CH3), 4.18 (3H, s, CH3), 2.48 (2H, t, J 7.5,
COCH2), 1.62–1.73 (2H, m, COCH2CH2), 1.33–1.48 (2H, m,
CH2CH3), 0.96 (3H, t, J 7.3, CH2CH3); δC ([2H6]DMSO) 172.5,
152.6, 143.2, 142.2, 140.0, 139.3, 136.1, 135.9, 131.5, 130.0,
125.0, 112.7, 118.6, 117.8, 117.3, 115.6, 114.8, 113.3, 112.0,
107.4, 45.9, 36.4, 36.2, 27.2, 21.8, 13.8; m/z (ES-HRMS)
396.2072 [C26H26N3Oϩ requires 396.2070].
sodium hydroxide and the product extracted with CHCl3 (4 ×
50 cm3). Purification by column chromatography (0.25%
MeOH–CHCl3) gave 16 as a yellow solid (190 mg, 55%), mp
265–268 ЊC (Found: C, 58.41; H, 3.27; N, 6.44. C20H13N2I
requires C, 58.82; H, 3.19; N, 6.86%); νmax/cmϪ1 1597 (C᎐N);
᎐
δH ([2H6]DMSO) 8.78 (1H, dd, J 1.5 and 9.3), 8.32 (1H, d,
J 8.8), 8.27 (1H, d, J 2.0), 8.13 (1H, d, J 7.8), 7.89 (1H, t, J 8.0),
7.77 (1H, dd, J 1.8 and 8.5), 7.66–7.63 (2H, m), 7.44 (1H, d,
J 8.3), 7.29 (1H, t, J 8.0), 3.73 (3H, s, CH3); MS (ES) m/z 409.2
(M ϩ 1); m/z (ES-HRMS) 409.0214 [C20H14N2Iϩ requires
409.0202].
2-tert-Butylamido-8,13-dimethyl-8H-quino[4,3,2-kl]acri-
dinium iodide 14d. Method B, from 13d, the acridinium iodide
14d was isolated as a red powder (91%) without the need for
column chromatography. Washing the product with Et2O was
sufficient to obtain pure material, mp 179 ЊC (dec.); νmax/cmϪ1
3468 (NH), 1671 (C᎐O); δ ([2H6]DMSO) 9.89 (1H, s, NH),
8,13-Dimethyl-2-iodo-8H-quino[4,3,2-kl]acridinium iodide 17
Method B, from 16 (57 mg, 0.14 mmol) furnished 17 as a bright
red solid (65 mg, 85%), mp 240–243 ЊC; νmax/cmϪ1 1611 (C᎐N);
᎐
H
᎐
8.70 (1H, d, J 9.1), 8.63 (1H, d, J 1.4), 8.53 (1H, d, J 8.6), 8.41
(1H, d, J 8.0), 8.29 (1H, t, J 8.0), 7.96–8.19 (4H, m), 7.62 (1H, t,
J 7.3), 4.36 (3H, s, CH3), 4.17 (3H, s, CH3), 1.33 (9 H, s, t-Bu);
δC ([2H6]DMSO) 177.8, 152.8, 143.3, 142.5, 140.0, 139.2, 136.1,
135.8, 131.6, 129.8, 124.9, 122.6, 119.4, 117.9, 117.3, 115.8,
114.9, 113.4, 112.0, 108.3, 45.9, 38.5, 36.3, 27.1; m/z (ES-
HRMS) 396.2073 [C26H26N3Oϩ requires 396.2070].
δH ([2H6]DMSO) 8.55–8.45 (4H, m), 8.34 (1H, t, J 8.25), 8.23–
8.06 (4H, m), 7.65 (1H, t, J 7.25), 4.36 (3H, s, CH3), 4.21 (3H, s,
CH3); MS (ES) m/z 423.0 (Mϩ).
2-tert-Butoxycarbonylamino-8-methyl-8H-quino[4,3,2-kl]-
acridine 18
Di-tert-butyl dicarbonate (Boc anhydride; 0.8 g, 3.7 mmol) was
added to a solution 2-amino-8-methyl-8H-quino-[4,3,2-kl ]-
acridine (1 g, 3.36 mmol) in THF (20 cm3). A 10% solution of
NaHCO3 (10 cm3) was added and the resulting mixture heated
under reflux for 3 h. After cooling, CHCl3 (50 cm3) was added,
the organic phase removed and washed with water (10 cm3).
The organic phase was purified by passing through a short bed
of silica, followed by washing with 3% MeOH–DCM to
leave 18 as a yellow solid (1.3 g, 97%), mp 245–248 ЊC;
νmax/cmϪ1 3213 (NH), 1720 (C᎐O); δ ([2H6]DMSO) 9.71
2-(4-Carboxy-n-butylamido)-8,13-dimethyl-8H-quino-
[4,3,2-kl]acridinium iodide methyl ester 14e. Method B,
from 13e, isolated as a red powder (40%), mp 176 ЊC (dec.);
νmax/cmϪ1 3430 (NH), 1728 (C᎐O, ester), 1689 (C᎐O, amide);
᎐
᎐
δH([2H6]DMSO) 10.59 (1H, s, NH), 8.46–8.56 (3H, m), 8.06–
8.28 (4H, m,), 7.91 (1H, d, J 8.2), 7.78 (1H, d, J 8.8), 7.60 (1H, t,
J 7.2), 4.30 (3H, s, CH3), 4.13 (3H, s, CH3), 3.62 (3H, s, CH3),
2.5 (2H, m, CH2), 2.41 (2H, t, J 7.0, CH2), 1.62–1.70 (4H, m,
2 × CH2); δC([2H6]DMSO) 173.2, 172.0, 152.5, 143.1, 142.1,
139.9, 139.1, 135.9, 135.8, 131.3, 129.6, 124.9, 122.6, 118.4,
117.7, 117.2, 115.5, 114.7, 113.2, 111.9, 107.2, 51.3, 45.9, 36.2,
᎐
H
(1H, br s, NH), 8.76 (1H, d, J 7.75), 8.42 (1H, d, J 9.0), 8.11
(1H, d, J 2.25), 8.02 (1H, d, J 8.0), 7.75 (1H, t, J 8.0), 7.63–7.56
(3H, m), 7.31–7.22 (2H, m), 3.7 (3H, s, NCH3), 1.56 (9H, s,
ϩ
33.1, 24.4, 24.1; m/z (ES-HRMS) 454.2146 [C28H28N3O3
requires 454.2131].
ϩ
3 × CH3); m/z (ES-HRMS) 398.1882 [C25H24N3O2 requires
398.1869).
2-Dodecanoylamido-8,13-dimethyl-8H-quino[4,3,2-kl]-
acridinium iodide 14f. Method B, from 13f, isolated as a red
powder (45%), mp 182–184 ЊC; νmax/cmϪ1 3435 (NH), 1689
(CO); δH([2H6]DMSO) 10.55 (1H, s, NH), 8.44–8.52 (3H, m),
8.02–8.24 (4H, m), 7.89 (1H, d, J 8.0), 7.78 (1H, d, J 8.7), 7.60
(1H, t, J 7.8), 4.29 (3H, s, CH3), 4.11 (3H, s, CH3), 2.45 (2H, t,
J 7.3, COCH2), 1.67 (2H, m, COCH2CH2), 1.25–1.33 (16H, m,
8 × CH2), 0.86 (3H, t, J 6.6, CH3), δC([2H6]DMSO) 172.4, 152.6,
143.2, 142.2, 140.0, 139.3, 136.0, 135.8, 131.5, 125.0, 122.6,
118.5, 117.7, 117.3, 115.6, 114.9, 113.3, 112.0, 107.2, 45.9, 36.6,
36.2, 29.1, 29.0, 29.0, 28.9, 28.8, 28.7, 31.3, 22.1, 14.0; m/z (ES-
HRMS) 494.3131 [C33H40N3Oϩ requires 494.3171].
2-tert-Butoxycarbonylamino-8,13-dimethyl-8H-quino[4,3,2-kl]-
acridinium iodide 19
By Method B, from 2-tert-butoxycarbonylamino-8-methyl-8H-
quino[4,3,2-kl ]acridine (0.2 g, 0.5 mmol) and methyl iodide
(10 cm3) for 7 days at 80 ЊC in a sealed tube, the crude quater-
nary salt was purified by column chromatography (10%
MeOH–CHCl3) to afford 19 as a bright red solid (200 mg,
73%), mp 183–185 ЊC; νmax/cmϪ1 3424 (NH), 1724 (C᎐O);
᎐
δH ([2H6]DMSO) 10.16 (1H, br s, NH), 8.65 (1H, d, J 10.0), 8.55
(1H, d, J 10.0), 8.39–8.25 (3H, m), 8.16 (1H, d, J 7.5), 8.08 (1H,
dd, J 2.5 and 10.0), 7.96 (1H, d, J 7.5), 7.62 (1H, d, J 7.5), 7.60
(1H, t, J 7.5), 4.35 (3H, s, CH3), 4.16 (3H, s, CH3), 1.58 (9H, s, 3
ϩ
2-Benzoylamido-8,13-dimethyl-8H-quino[4,3,2-kl]acridinium
iodide 14g. Method B, from 13g, isolated as a red powder
× CH3); m/z (ES-HRMS) 412.2002 [C26H26N3O2 requires
412.2025].
(18%), mp 180 ЊC (dec.); νmax/cmϪ1 3429 (NH), 1670 (C᎐O);
᎐
δH ([2H6]DMSO) 10.86 (1H, s, NH), 8.67 (2H, m), 8.56 (1H, d,
J 8.1), 7.94–8.38 (8H, m), 7.60–7.70 (4H, m), 4.37 (3H, s, CH3),
4.15 (3H, s, CH3); δC ([2H6]DMSO) 166.2, 152.6, 143.2, 142.1,
140.0, 139.1, 136.0, 135.8, 134.3, 132.2, 131.4, 129.8, 128.6,
127.8, 124.9, 122.7, 119.5, 118.2, 117.3, 115.7, 114.8, 113.4,
112.1, 108.6, 46.0, 36.2; m/z (ES-HRMS) 416.1765 [C28H22-
N3Oϩ requires 416.1763].
2-Amino-8,13-dimethyl-8H-quino[4,3,2-kl]acridinium chloride
20a
2-tert-Butoxycarbonylamino-8,13-dimethyl-8H-quino[4,3,2-kl ]-
acridinium iodide 19 or 2-acetylamino-8,13-dimethyl-8H-quino-
[4,3,2-kllacridinium iodide 14a (0.3 mmol) were dissolved in a
mixture of methanol (50 cm3) and 2 M HCl (50 cm3). The
resulting solution was stirred at 50 ЊC for 2 h. The methanol
was removed under vacuum and the aqueous phase basified (to
pH 10) with 5 M NaOH. The resulting precipitate was filtered
from solution and washed with water to yield 20a as a dark
purple solid (92%), mp 215–218 ЊC; νmax/cmϪ1 3410 (NH), 1608
2-Iodo-8-methyl-8H-quino[4,3,2-kl]acridine 16
A solution of sodium nitrite (87 mg, 1.26 mmol) in water
(2 cm3) was added dropwise to a solution of 2-amino-8-methyl-
8H-quino[4,3,2-kl ]acridine (250 mg, 0.84 mmol) in 2 M HCl
(50 cm3) at 0 ЊC. After stirring at 0 ЊC for 15 min, a solution of
KI (0.24 g, 1.47 mmol) in water (10 cm3) was added dropwise
and the resulting mixture heated for 0.5 h at 80 ЊC. After
cooling, the reaction mixture was basified (to pH 12) with 10%
(C᎐N); δ ([2H ]DMSO) 8.47 (1H, d, J 8.5), 8.40 (1H, d, J 8.8),
᎐
H
6
8.21–8.05 (4H, m), 7.75–7.67 (2H, m), 7.55 (1H, t, J 7.8), 7.07
(1H, d, J 2.5), 7.04 (1H, dd, J 2.5 and 8.8), 6.44 (2H, br s, NH2),
4.28 (3H, s, CH3), 4.08 (3H, s, CH3); m/z (ES-HRMS) 312.1499
[C23H22N3ϩ requires 312.1495].
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 2 2 0 – 2 2 8
226