Prins et al.
(FAB): m/z 837.2 ([M + H]+, calcd 837.1). Anal. Calcd for
5-N-[4-Am in o-6-(R)-1-p h en yleth yla m in o-1,3,5-tr ia zin -
2-yl]a m in o-17-N-[4-a m in o-6-(3-a m in o-2,2-d im et h ylp r o-
p yla m in o)-1,3,5-tr ia zin -2-yl]a m in o-25,26,27,28-tetr a p r o-
p oxyca lix[4]a r en e (6). Compound 6 was obtained as a white
solid (87%) following a similar procedure as described for
C
51H61O4N7‚0.2H2O: C 72.95, H 7.37, N 11.68; found C 72.97,
H 7.23, N 11.28.
5-N-[4-Am in o-6-(R)-1-p h en yleth yla m in o-1,3,5-tr ia zin -
2-yl]am in o-17-N-[4-am in o-6-(3-(am in om eth yl)ph en ylm eth -
ylam in o)-1,3,5-tr iazin -2-yl]am in o-25,26,27,28-tetr apr opoxy-
ca lix[4]a r en e (5a ). To an ice-cold solution of 4a (0.72 g, 0.86
mmol) and DIPEA (0.37 mL, 2.15 mmol) in THF (40 mL) was
added cyanuric chloride (0.17 g, 0.95 mmol), and the solution
was stirred for 3 h at 0 °C. A stream of ammonia gas was then
bubbled through the solution for a period of 2 h, while the
temperature was maintained at 0 °C. The solvent was removed
under reduced pressure, and the residue was partitioned
between CH2Cl2 and H2O. The organic layer was washed with
H2O and brine, dried (MgSO4), and the solvent was removed
under reduced pressure. The resulting intermediate compound
4a I was obtained as a white solid and used without further
purification or analysis. Compound 4a I (0.16 g, 0.17 mmol) was
stirred overnight at 70 °C in m-xylylenediamine (4.0 mL, 30.3
mmol). After cooling the mixture to room temperature, H2O
(20 mL) was added, and the white precipitate that formed was
collected, washed with H2O, and redissolved in CH2Cl2. After
drying over Na2SO4, the solvent was evaporated under reduced
pressure. Purification by flash column chromatography (SiO2,
CH2Cl2/MeOH/NH4OH ) 90/9.5/0.5%) gave 5a as a white solid
(0.12 g, 68%). 1H NMR (300 MHz, THF-d8) δ 8.0-7.0 (m, 15H),
6.5-6.0 (m, 8H), 5.8-5.4 (m, 4H), 5.3 (br s, 1H), 4.57 (d, 2H,
1
compound 5a . H NMR (300 MHz, CDCl3) δ 7.4-7.3 (m, 6H),
7.0-6.8 (m, 7H), 6.4-6.2 (m, 6H), 5.3-5.0 (m, 7H), 4.44 and
2
3.13 (ABq, 8H, J HH ) 12.8 Hz), 4.00 and 3.71 (2 br s, 8H),
3.21 (s, 2H), 2.44 (s, 2H), 2.0-1.8 (m, 8H), 1.53 (d, 3H, 3J HH
)
3
5.4 Hz), 1.09 (t, 6H, J HH ) 7.2 Hz), 1.0-0.9 (m, 12H). MS
(FAB): m/z 1030.5 ([M + H]+, calcd 1030.6). No satisfactory
elemental analysis of this compound could be obtained.
Tetr a m ela m in e 2c. To a refluxing solution of 1,4-diami-
nobutane bis(p-nitrophenyl) dicarbamate13 (0.08 g, 0.19 mmol)
in acetone (50 mL) was added a solution of 6 (0.40 g, 0.38
mmol) and DIPEA (68 µL, 0.38 mmol) in CH2Cl2 (10 mL). The
reaction mixture was refluxed overnight, after which the
solvent was evaporated. Purification using flash column chro-
matography (SiO2, CH2Cl2/CH3OH ) 92/8) gave 2c as a white
solid (0.35 g, 41%). 1H NMR (300 MHz, THF-d8) δ 7.8 (br s,
4H), 7.4-7.1 (m, 18H), 6.5-6.3 (m, 16H), 6.1-6.0 (br s, 4H),
5.7 (br s, 6H), 5.4-5.3 (br s, 4H), 4.43 and 3.12 (ABq, 16H,
2J HH ) 12.8 Hz), 3.93 and 3.74 (2 br s, 16H), 3.2-3.1 (m, 8H)
2.96 (s, 4H), 2.0-1.9 (m, 16H), 1.5-1.4 (br s, 10H), 1.09 and
3
0.96 (2 t, J HH ) 7.2 Hz, 24H), 0.86 (s, 12H). MS (FAB): m/z
2201.2 ([M + H]+, calcd 2201.3). Anal. Calcd for C124H158N28O10‚
H2O: C 67.12, N 17.68, H 7.27; found: C 67.10, N 17.42, H
7.14.
2
3J NH ) 12.1 Hz), 4.43 and 3.06 (ABq, 8H, J HH ) 13.2 Hz), 4.4
(br s, 2H), 3.94 (br s, 4H), 3.73 (br s, 4H), 2.45 (br s, 2H) 2.10-
5-N-[4-Am in o-6-(R)-1-p h en yleth yla m in o-1,3,5-tr ia zin -
2-yl]a m in o-17-N-[4-a m in o-6-(3-(4-N-(p-n itr op h en oxyca r -
b on yla m in o)b u t ylu r e id o)-2,2-d im e t h ylp r op yla m in o)-
1,3,5-t r ia zin -2-yl]a m in o-25,26,27,28-t et r a p r op oxyca lix-
[4]a r en e (7). To a refluxing solution of 1,4-diaminobutane
bis(p-nitrophenyl) dicarbamate13 (1.0 g, 2.4 mmol) in acetone
(300 mL) was added a solution of 6 (0.25 g, 0.24 mmol) and
DIPEA (46 µL, 0.26 mmol) in CH2Cl2 (20 mL). The reaction
mixture was refluxed overnight, after which the solvent was
evaporated. The product was extracted from the residue
(excess of dicarbamate) with CH2Cl2. Subsequently, purifica-
tion using flash column chromatography (SiO2, CH2Cl2/CH3-
3
3
1.60 (m, 8H), 1.49 (d, 3H, J HH ) 7.0 Hz), 1.09 (t, 6H, J HH
)
6.0 Hz), 0.95 (br s, 6H). MS (FAB): m/z 1064.5 ([M + H]+,
calcd 1064.6). Anal. Calcd for C62H73O4N13: calcd C 69.97, N
17.11, H 6.91; found C 69.98, N 17.01, H 6.91.
5-N-[4-Am in o-6-(S)-1-p h en ylet h yla m in o-1,3,5-t r ia zin -
2-yl]am in o-17-N-[4-am in o-6-(3-(am in om eth yl)ph en ylm eth -
ylam in o)-1,3,5-tr iazin -2-yl]am in o-25,26,27,28-tetr apr opoxy-
ca lix[4]a r en e (5b). Compound 5b was obtained as a white
solid (71%) following the procedure described for compound
1
5a starting from 10. The H NMR spectrum of 5b is identical
to that of compound 5a . MS (FAB): m/z 1064.6 ([M + H]+,
calcd 1064.6). C62H73O4N13: calcd C 69.97, N 17.11, H 6.91;
found: C 70.16, N 17.05, H 6.96.
1
OH ) 92/8) gave 7 as a white solid (120 mg, 42%). H NMR
3
(300 MHz, CDCl3) δ 8.23 (d, 2H, J HH ) 8.4 Hz), 7.3-7.2 (m,
Tetr a m ela m in e 2a . A solution of 5a (0.13 g, 0.12 mmol),
4a I (0.12 g, 0.11 mmol), and DIPEA (0.1 mL, 57 mmol) in THF
(5 mL) was refluxed for 7 days. The solvent was removed under
reduced pressure, and the residue was redissolved in CH2Cl2,
washed with H2O and brine, and dried over Na2SO4. Evapora-
tion of the solvent under reduced pressure gave compound 2a
(0.15 g, 62%) as a white solid after flash column chromatog-
raphy (SiO2, CH2Cl2/MeOH/NH4OH ) 92.5/7.0/0.5%). 1H NMR
(300 MHz, THF-d8) δ 7.64 (br s, 4H), 7.4-6.8 (br m, 22H), 6.4-
6.0 (br s, 16H), 5.6-5.4 (br s, 8H), 5.21 (br s, 2H), 4.41 (br s,
4H), 4.30 and 2.93 (ABq, 16H, 2J HH ) 13.2 Hz), 3.79 (br s, 8H),
7H), 7.1-6.8 (m, 6H), 6.5-6.2 (m, 6H), 5.95 (s, 1H), 5.62 (s,
2
1H), 5.3-4.8 (br m, 6H), 4.45 and 3.12 (ABq, 8H, J HH ) 12.8
Hz), 4.04 and 3.68 (2 br s, 8H), 3.3-3.2 (m, 6H), 2.88 (s, 2H),
2.0-1.8 (m, 8H), 1.5 (br s, 7H), 1.09 (t, 6H, 3J HH ) 7.2 Hz), 0.9
(m, 12H). MS (FAB): m/z 1171.7 ([M - C6H4NO2 + H]+, calcd
1170.6). No satisfactory elemental analysis of this compound
could be obtained.
Hexa m ela m in e 3a . A mixture of 7 (100 mg, 0.08 mmol),
831 (38 mg, 0.038 mmol), and DIPEA (7.2 µL, 0.041 mmol) in
CH2Cl2 (15 mL) was refluxed overnight. After evaporation of
the solvent, compound 3a was obtained after flash column
chromatography (SiO2, CH2Cl2/CH3OH ) 92/8) as a white solid
3
3.62 (br s, 8H), 2.0-1.7 (m, 16H), 1.36 (d, 6H, J HH ) 6.9 Hz),
3
3
0.95 (t, 12H, J HH ) 7.0 Hz), 0.84 (t, 12H, J HH ) 7.0 Hz). MS
1
(115 mg, 79%). H NMR (300 MHz, THF-d8) δ 7.8 (br s, 6H),
(FAB): m/z 1992.7 ([M + H]+, calcd 1992.1). Anal. Calcd for
7.3-7.0 (m, 26H), 6.5-6.0 (m, 28H), 5.7 (br s, 8H), 5.3 (br s,
C
116H134N24O8‚2H2O: C 68.67, N 16.57, H 6.86; found: C 68.87,
2
6H), 4.41 and 3.14 (ABq, 24H, J HH ) 12.8 Hz), 3.92 and 3.75
N 16.45, H 6.62.
(2 br s, 24H), 3.2-3.1 (m, 16H), 2.96 (s, 8H), 2.0-1.9 (m, 24H),
1.5-1.4 (br s, 14H), 1.09 and 0.96 (2 t, 3J HH ) 7.2 Hz), 0.86 (s,
24H). MS (FAB): m/z 3352.1 ([M + H]+, calcd 3350.9). Anal.
Calcd for C186H244N44O16: C 66.64, N 18.38, H 7.34; found: C
66.84, N 18.39, H 7.51.
Tetr a m ela m in e 2b. Compound 2b was obtained as an off-
white solid (82%) following the procedure described for com-
1
pound 2a . The H NMR spectrum of 2b is identical to that of
compound 2a . MS (FAB): m/z 1992.4 ([M + H]+, calcd 1992.1).
Anal. Calcd for C116H134N24O8: C 69.93, N 16.87, H 6.78;
found: C 69.76, N 16.57, H 6.68.
J O0201023
4820 J . Org. Chem., Vol. 67, No. 14, 2002