A R T I C L E S
Archer and Krische
NMR (75 MHz, CDCl3): δ 170.8, 168.2, 166.0, 157.7, 155.9, 131.5,
128.6, 114.1, 67.9, 66.6, 43.6, 41.9, 38.9, 31.8, 29.6, 29.5, 29.4, 29.3,
28.3, 26.0, 22.6, 14.1. HRMS calcd for C49H79N6O6: 847.6061.
Found: 847.6070. IR (neat): 2924, 2854, 1714, 1537, 1510, 1442, 1410,
29.3, 26.0, 22.6, 14.1. HRMS calcd for C47H72N10O4Cl: 875.5423.
Found: 875.5439. IR (neat): 3425, 3156, 2924, 2854, 1687, 1637, 1574,
1510, 1408, 1362, 1294, 1247, 1176, 1118, 1013, 989, 810 cm-1. mp
(capillary) 89-93 °C.
1365, 1302, 1246, 1175, 1117, 1069, 1013, 886, 836, 813, 738 cm-1
.
Trimer (9c). This was prepared from 8b according to general method
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mp (capillary) 47-50 °C.
C. Yield 77%. Rf ) 0.5 (25% acetone-hexanes). H NMR (500 MHz,
Boc-Protected Dimer (8b). This was prepared from 8a according
to general method B. Yield 76%. Rf ) 0.5 (25% acetone-hexanes). 1H
NMR (300 MHz, CDCl3): δ 7.04 (d, 4H, J ) 8.5 Hz), 6.96 (d, 4H, J
) 8.5 Hz), 6.78 (d, 4H, J ) 8.2 Hz), 6.70 (d, 4H, J ) 8.5 Hz), 5.94
(s, 1H), 4.96 (s, 1H), 4.11 (s, 2H), 3.98 (s, 2H), 3.83 (m, 8H), 3.70 (m,
8H), 3.49 (s, 2H), 3.23 (s, 2H), 2.57-2.80 (m, 8H), 1.70 (s, 8H), 1.48
(s, 9H), 1.24 (m, 56H), 0.854 (t, 12H, J ) 6.9 Hz). 13C NMR (75
MHz, CDCl3): δ 168.4, 166.8, 157.8, 156.2, 131.5, 128.6, 128.2, 114.2,
114.0, 79.7, 67.9, 66.7, 43.7, 41.3, 40.5, 39.4, 32.2, 31.8, 29.6, 29.4,
29.3, 28.5, 26.1, 26.0, 22.6, 14.1. MS (CI+, CH4) m/z (relative
intensity): 1507 (M+, 45), 1466 (8), 1464 (10), 1422 (10), 1392 (7),
1364 (23), 1336 (56), 1322 (12), 1292 (14), 1263 (31), 1236 (100),
1222 (5), 1206 (5), 1162 (6), 1002 (9). IR (neat): 3434, 3154, 2925,
2854, 1690, 1650, 1573, 1510, 1471, 1428, 1409, 1357, 1302, 1246,
1176, 1117, 1069, 1015, 887, 835, 813, 738 cm-1. mp (capillary) 119-
121 °C.
16 mM in d8-toluene, 100 °C): δ 9.80 (br s, 3H), 7.08 (d, J ) 8.6 Hz,
4H), 7.03 (d, J ) 8.6 Hz, 4H), 6.82 (d, J ) 8.6 Hz, 4H), 6.78 (d, J )
8.6 Hz, 4H), 6.30 (br s, 1H), 6.10 (br s, 1H), 4.28 (s, 2H), 4.21 (s, 2H),
3.78 (m, 8H), 3.61 (m, 8H), 3.48 (m, 4H), 2.85-2.71 (m, 8H), 1.66
(m, 8H), 1.37 (br m, 8H), 1.26 (br m, 48H), 0.87 (m, 12H). 13C NMR
(125 MHz, 16 mM in d8-toluene, 100 °C): δ 171.17, 171.09, 169.58,
169.36, 168.04, 167.01, 166.93, 159.16, 132.29, 132.22, 115.34, 115.38,
68.84, 68.81, 66.88, 44.68, 41.59, 40.84, 40.31, 32.46, 30.16, 30.14,
30.04, 29.85, 26.75, 23.13, 14.18. HRMS calcd for C87H133N15O7Cl:
1535.0200. Found: 1535.0222. IR (neat): 3500, 3424, 3117, 2924,
2854, 1691, 1639, 1567, 1511, 1471, 1440, 1408, 1356, 1297, 1247,
1176, 1117, 1086, 1015, 989, 921, 885, 810, 704, 594 cm-1. mp
(capillary) 171-175 °C.
Tetramer (9d). This was prepared from 8c according to general
method C. Yield 99%. Rf ) 0.6 (25% acetone-hexanes). 1H NMR (500
MHz, 11 mM in d8-toluene, 100 °C): δ 9.85 (br s, 4H), 7.18 (d, J )
8.4 Hz, 4H), 7.10 (d, J ) 8.4 Hz, 4H), 6.84 (m, 8H), 6.80 (d, J ) 8.6
Hz, 4H), 6.45 (br s, 2H), 6.18 (br s, 1H), 4.34 (s, 2H), 4.32 (s, 2H),
4.23 (s, 2H), 3.80 (m, 12H), 3.64 (m, 8H), 3.48 (m, 4H), 2.87-2.78
(m, 12H), 1.68 (m, 12H), 1.38 (br m, 12H), 1.27 (br s, 78H), 0.87 (m,
18H), 0.45 (s, 2H). 13C NMR (125 MHz, 11 mM in d8-toluene, 100
°C): δ 171.29, 171.24, 169.73, 168.17, 159.27, 132.48, 132.45, 132.39,
129.78, 129.61, 129.57, 115.45, 115.40, 69.02, 68.99, 68.94, 67.04,
44.79, 42.04, 41.73, 40.91, 40.42, 40.27, 32.59, 30.31, 30.25, 30.20,
29.99, 26.90, 23.26, 14.33. MS (ESI) m/z (relative intensity): 2211
(5), 2195 (M+, 20), 2194 (95), 2193 (100), 2192 (85), 2164 (25), 2037
(4), 1997 (5), 1534 (5), 1517 (12), 1516 (20), 1099 (25), 1085 (8). IR
(neat): 3424, 3119, 2924, 2854, 1691, 1638, 1566, 1511, 1470, 1426,
1408, 1355, 1298, 1247, 1176, 1144, 1117, 1081, 1015, 991, 968, 922,
810, 707 cm-1. mp (capillary) 220-224 °C.
Boc Trimer (8c). This was prepared from 8b according to general
method B. Yield 87%. 1H NMR (300 MHz, 34 mM in CDCl3): δ 9.54
(br s, 1H), 9.31 (br m, 2H), 6.98-7.07 (m, 12H), 6.71-6.81 (m, 12H),
6.07 (br s, 1.5H), 4.99 (br s, 0.7H), 4.13 (br s, 4H), 3.99 (s, 2H), 3.70-
3.85 (m, 20H), 3.53 (br s, 2H), 3.48 (br s, 2H), 3.24 (br s, 2H), 2.57-
2.76 (m, 12H), 1.70 (m, 12H), 1.23-1.54 (m, 99H), 0.85 (t, J ) 6.9
Hz, 18H). 13C NMR (75 MHz, 34 mM in CDCl3): δ 157.8, 131.5,
114.0, 67.9, 31.8, 29.6, 29.4, 29.3, 28.5, 26.0, 22.6, 14.1. HRMS calcd
for C129H201N16O12: 2166.5650. Found: 2166.5610. MS (FAB, NBA)
m/z (relative intensity): 2167 (M+, 2.7), 1516 (1.4), 1310 (3.5), 1179
(1.9), 857 (5), 717 (5), 694 (9), 660 (100), 605 (10), 551 (15), 533
(17), 520 (27). IR (neat): 3429, 3120, 2924, 2854, 1691, 1649, 1570,
1510, 1470, 1423, 1356, 1301, 1246, 1175, 1118, 1080, 1014, 993,
811, 711, 539 cm-1. mp (capillary) 173-179 °C.
4-(3,5-Bis-decyloxy-benzyloxy)-6-morpholin-4-yl-[1,3,5]triazin-2-
ylamine (9a). To a solution of 5a (0.100 g, 0.182 mmol) in CHCl3 (3
mL, 60mM) was added morpholine (0.050 mL, 0.573 mmol), and the
mixture was refluxed under air for 45 min. The reaction mixture was
then washed with aqueous citric acid (15% w:v, 5 mL), and the organic
layer which separated was dried over Na2SO4, filtered through cotton,
and evaporated to dryness in vacuo. Purification by column chroma-
tography (SG60, 15 cm3, 2:3:5 ethyl acetate-CHCl3-hexanes) yielded
9a (0.080 g, 73%) as a white solid. Rf ) 0.3 (33% ethyl acetate in
hexanes). 1H NMR (300 MHz, CDCl3): δ 6.52 (m, 2H), 6.35 (m, 1H),
5.23 (s, 2H), 5.02 (s, 2H), 3.89 (t, 4H, J ) 6.5 Hz), 3.77 (m, 4H), 3.67
(m, 4H), 1.73 (quintet, 4H, J ) 6.8 Hz), 1.40-1.24 (m, 28H), 0.86 (t,
6H, J ) 6.4). 13C NMR (75 MHz, CDCl3): δ 170.8, 168.1, 166.2,
160.3, 138.6, 106.2, 100.8, 68.3, 68.0, 66.7, 43.8, 31.9, 29.6, 29.4, 29.3,
29.2, 26.0, 22.7, 14.1. MS (ESI+) m/z (relative intensity): 602.4 (8),
601.5 (30), 600.5 (M+, 100), 403.7 (7). HRMS calcd for C34H58N5O4:
600.4489. Found: 600.4494. IR (neat): 2954, 2923, 2853, 1649, 1600,
1573, 1541, 1479, 1437, 1412, 1351, 1303, 1281, 1266, 1177, 1120,
1069, 1015, 811 cm-1. mp (capillary) 119-122 °C.
5-Dimethylamino-naphthalene-1-sulfonic Acid (3-Hydroxy-pro-
pyl)-amide. A solution of 5-(dimethylamino)-naphthalene-1-sulfonyl
chloride (1.50 g, 5.56 mmol) in CH2Cl2 (50 mL) was combined with
a solution of 3-aminopropan-1-ol (0.64 mL, 8.34 mmol) in 2 M aqueous
Na2CO3 (30 mL), and the resulting biphasic, yellow mixture was
vigorously stirred for 1 h. The reaction mixture was acidified cautiously
with 100 mL of 15% aqueous citric acid and shaken. The organic phase
was separated, dried over Na2SO4, decanted, and evaporated to dryness
in vacuo, yielding the title compound as a pale yellow solid (1.58 g,
1
92%). Rf ) 0.4 (66% ethyl acetate-hexanes). H NMR (300 MHz, d6-
DMSO): δ 8.44 (d, 1H, J ) 8.7 Hz), 8.29 (d, 1H, J ) 8.7 Hz), 8.09
(dd, 1H, J ) 1.1, 7.4 Hz), 7.80 (br s, 1H), 7.59 (m, 2H), 7.24 (d, 1H,
J ) 7.4 Hz), 4.37 (s, 1H), 3.29 (s, 2H), 2.84-2.79 (m, 8H), 1.47
(quintet, 2H, J ) 7.0 Hz). 13C NMR (75 MHz, d6-DMSO): δ 151.3,
136.0, 129.3, 129.1, 129.0, 128.3, 127.8, 123.6, 119.1, 115.1, 58.0,
45.1, 39.9, 32.5. MS (CI+, CH4) m/z (relative intensity): 349 (3), 337
(14), 311 (7), 310 (16), 309 (M + 1, 100), 308 (7). IR (neat): 3503,
3297, 2944, 2873, 2833, 1587, 1574, 1477, 1312, 1142, 1073, 944,
790, 625 cm-1. mp (capillary) 117-119 °C.
N-[3-(4-Amino-6-morpholin-4-yl-[1,3,5]triazin-2-yloxy)-2,2-bis-
(4-decyloxy-benzyl)-propyl]-6-chloro-[1,3,5]triazine-2,4-diamine (9b).
This was prepared from 8a according to general method C. Yield 97%.
5-Dimethylamino-naphthalene-1-sulfonic Acid [3-(4,6-Dichloro-
[1,3,5]triazin-2-yloxy)-propyl]-amide. 5-Dimethylamino-naphthalene-
1-sulfonic acid (3-hydroxy-propyl)-amide (1.58 g, 5.12 mmol) was
dissolved in CHCl3 (50 mL), followed by 2,6-lutidine (1.31 mL, 11.3
mmol) and cyanuric chloride (1.88 g, 10.2 mmol). The resulting pale
orange solution was refluxed for 6 h, and allowed to cool. After washing
the reaction mixture with 15% aqueous citric acid (100 mL), the organic
layer was separated dried over Na2SO4, decanted, and evaporated to
dryness in vacuo. Purification was achieved by column chromatography
(SiO2, 60 cm3/g crude product), eluting with 1:1:2 CHCl3:ethyl acetate:
hexanes, followed by 2:1:1 CHCl3:ethyl acetate:hexanes, affording the
1
Rf ) 0.4 (25% acetone in hexanes). H NMR (300 MHz, CDCl3): δ
6.97 (d, 4H, J ) 8.5 Hz), 6.75 (d, 4H, J ) 8.5 Hz), 6.08 (t, 1H, J )
5.9 Hz), 4.13 (s, 2H), 3.89 (t, 4H, J ) 6.2 Hz), 3.71 (s, 8H), 3.54 (d,
2H, J ) 5.4 Hz), 2.77 (part A of AB system, 2H, J ) 14.1 Hz), 2.60
(part B of AB system, 2H, J ) 13.6 Hz), 1.74 (quintet, 4H, J ) 7.2,
6.4 Hz), 1.42-1.24 (m, 28H), 0.85 (t, 6H, J ) 6.2 Hz). 13C NMR (75
MHz, CDCl3): δ 169.8, 169.4, 168.0, 166.4, 165.6, 165.4, 157.9, 131.6,
128.0, 114.1, 73.0, 67.9, 66.6, 43.7, 40.3, 39.8, 31.8, 29.6, 29.5, 29.4,
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5082 J. AM. CHEM. SOC. VOL. 124, NO. 18, 2002