1106 J . Org. Chem., Vol. 65, No. 4, 2000
Sharma et al.
temperature. Rapid evolution of gas was observed, and the
resulting solution was stirred for 24 h at room temperature.
The mixture was cooled to 0 °C, dry triethylamine (9.6 mL,
68.9 mmol) was added to this stirred mixture over a period of
30 min, and then the solution was concentrated in vacuo and
the residue purified by silica gel column chromatography
eluting with dichloromethane to give 10 as a viscous brown
oil. Yield 68%; 1H NMR (CDCl3) δ 1.53 (m, 2 H), 2.10 (q, 4 H),
4.40 (t, J ) 7.1 Hz, 4 H), 7.20 (s, 2 H), 7.38 (s, 2 H); MS (m/z
rel. intensity) 495.918 (M+), 377.013 (85), 55.050 (100).
H), 8.15 (t, J ) 6.0 Hz, 2 H), 8.68 (s, 2 H), 10.68 (s, 2 H); HRMS
calcd for C37H55N14O8 823.432, found 823.432.
1,1′-(1,5-P e n t a m e t h yle n e )b is[N -[5-[[[(3,3-d im e t h yl-
a m in o )p r o p y l]c a r b o n y l]-1-m e t h y l-4-p y r r o l-3-y l]-4-
[[[2-a m i n o -4-m e t h y lt h i a z o l-5-y l]c a r b o n y l]a m i n o ]-
im id a zole]-2-ca r boxa m id e (16). Palladium charcoal (10%,
500 mg) was added to a solution of 14 (1.00 g, 1.25 mmol) in
anhydrous DMF:MeOH (1:1 v/v; 20 mL). Degassing of the
solution was done by argon, and then the mixture was
hydrogenated in a Parr shaker for 2 h at 50 psi. The catalyst
was then removed by filtration, and the filtrate was washed
several times with methanol. The combined filtrates were
evaporated under high vacuum to remove traces of the solvent.
The residual reduced product was redissolved in anhydrous
DMF (10 mL), and compound 5 (396.00 mg, 2.51 mmol) and
HOBt (474.91 mg, 3.51 mmol) were added to it with constant
stirring. A solution of DCC (723.04 mg, 3.51 mmol) in
anhydrous DMF (3 mL) was added slowly to this stirred
mixture, and the stirring was continued at 25 °C for an
additional 18 h. The reaction mixture was filtered, and the
solvent was removed in vacuo. The impure product was
purified on silica gel column chromatography, eluting with
CH2Cl2:MeOH:NH4OH (80:20:4,v/v/v) to give compound 16 as
a white solid.Yield 39%; mp 154-156 °C; 1H NMR (DMSO-d6)
δ 1.29 (m, 2 H), 1.60 (q, 2 H), 1.85 (q, 4 H), 2.15 (s, 12 H), 2.26
(t, J ) 7.0 Hz, 4 H),2.40 (s, 6 H), 3.20 (q, J ) 6.2 Hz, 4 H),
3.88 (s, 6 H), 4.41 (t, J ) 7.2 Hz, 4 H), 7.00 (d, J ) 1.7 Hz, 2
H), 7.27 (d, J ) 1.7 Hz, 2 H), 8.15 (t, J ) 5.5 Hz, 2 H), 8.60 (s,
2 H), 9.60 (s, 2 H), 10.64 (s, 2 H); HRMS calcd for C45H63N18O6S2
1015.461, found 1015.462.
1,1′-(1,7-Hep ta m eth ylen e)-2,2′-bis(tr ich lor oa cetyl)bis-
(im id a zole) (11). Obtained in a similar procedure as a viscous
1
dark yellow oil. Yield 67%; H NMR (CDCl3) δ 1.35 (m, 6 H),
1.80 (m, 4 H), 4.40 (t, J ) 7.1 Hz, 4 H), 7.18 (s, 2 H), 7.38 (s,
2 H); MS (m/z rel intensity) 523.950 (M+), 405.045 (85), 55.050
(100).
1,1′-(1,5-P en ta m eth ylen e)-2,2′-bis(tr ich lor oa cetyl)-4,4′-
d in itr obis(im id a zole) (12). A suspension of 10 (2.00 g, 4.04
mmol) in acetic anhydride (9.00 mL) and dichloromethane(35
mL) was cooled to -78 °C, and fuming nitric acid (0.65 mL)
was added to it dropwise over a period of 30 min. This
procedure was followed by the addition of concentrated sulfuric
acid (0.4 mL). The brown mixture was brought to room
temperature gradually and stirred for 3 h. The final reaction
mixture was diluted with dichloromethane, neutralized with
saturated sodium bicarbonate solution, extracted with di-
chloromethane (3 × 50 mL), dried over Na2SO4, and then
filtered and concentrated to a brown foam. The impure product
was purified by silica gel column chromatography eluting with
ethyl acetate-hexane (1:2) to give 12 as pale yellow crystals.
1,1′-(1,7-H e p t a m e t h yle n e )b is[N -[5-[[[(3,3-d im e t h yl-
a m in o )p r o p y l]c a r b o n y l]-1-m e t h y l-4-p y r r o l-3-y l]-4-
[[[2-a m i n o -4-m e t h y lt h i a z o l-5-y l]c a r b o n y l]a m i n o ]-
im id a zole]-2-ca r boxa m id e (17). The title compound was
prepared in a similar way as a white solid, yield 38%; mp 150-
1
Yield 70%; mp 132 °C; H NMR (CDCl3) δ 1.52 (m, 2 H), 2.10
(q, 4 H), 4.45 (t, J ) 7.1 Hz, 4 H), 8.01 (s, 2 H); MS (m/z rel.
intensity) 585.913 (M+), 465.411 (13.8), 55.050 (100).
1,1′-(1,7-Hep ta m eth ylen e)-2,2′-bis(tr ich lor oa cetyl)-4,4′-
d in itr obis(im id a zole) (13). The title compound was obtained
by a similar procedure as pale yellow crystals. Yield 70%; mp
1
153 °C; H NMR (DMSO-d6) δ 1.26 (m, 6 H), 1.60 (q, J ) 7.0
Hz, 4 H), 1.75 (m, 4 H), 2.15 (s, 12 H), 2.25 (t, J ) 7.0 Hz, 4
H),2.40 (s, 6 H),3.20 (t, J ) 6.2 Hz, 4 H), 3.80 (s, 6 H), 4.40 (t,
J ) 7.2 Hz, 4 H). 6.90 (d, J ) 1.6 Hz, 2 H), 7.20 (d, J ) 1.6 Hz,
2 H),7.46 (s, 4 H), 7.50 (s, 2 H), 8.10 (t, J ) 6.0 Hz, 2 H), 9.64
(s, 2 H), 10.06 (s, 2 H); HRMS calcd for C47H67N18O6S2
1043.493, found 1043.491.
1
120 °C; H NMR (CDCl3) δ 1.44 (m, 6 H), 1.92 (m, 4 H), 4.50
(t, J ) 7.1 Hz, 4 H), 7.98 (s, 2 H); MS (m/z rel. intensity)
613.520 (M+), 493.018 (13.8), 55.050 (100).
1,1′-(1,5-P en ta m eth ylen e)-2,2′bis[N-[(d im eth yla m in o)-
p r op yl]1-m et h yl-4-p yr r olyl]4,4′-d in it r ob is(im id a zole)-
2,2′-ca r boxa m id e (14). Palladium charcol (10%, 430 mg) was
added to N-[(dimethylamino)propyl]1-methyl-4-nitropyrrole-
carboxamide 3 (869 mg, 3.40 mmol) in anhydrous DMF:MeOH
(1:1, 10 mL). After being degassed with argon, the mixture
was hydrogenated in a Parr shaker at 50 psi for 2 h. The
catalyst was removed by filtration and washed thoroughly with
methanol, and the combined filtrates were evaporated in
vacuo. The residue was dried under high vacuum to remove
traces of residual solvent. To this residue dry DMF was
reintroduced, and the solution was cooled to 0 °C. A solution
of 12 (1.00 g, 1.70 mmol) in DMF:THF (10 mL, 1:1 v/v) was
added to the above solution under stirring over a duration of
30 min. The reaction mixture was brought to room tempera-
ture, and stirring was continued for 18 h. A TLC examination
at this time showed that the reaction was complete. The
solvent were evaporated in vacuo, and the impure product was
purified by silica gel column chromatography. Eluting with
CH2Cl2:MeOH:NH4OH (80:20:1, v/v/v) gave the pure product
14 as pale yellow crystals. Yield 62%; mp 120 °C; 1H NMR
(DMSO-d6) δ 1.28 (m, 2 H), 1.57 (q, 2 H), 1.85 (q, 4 H), 2.15 (s,
12 H), 2.25 (t, J ) 7.0 Hz, 4 H), 3.20 (q, J ) 6.2 Hz, 4 H), 3.89
(s, 6 H), 4.41 (t, J ) 7.2 Hz, 4 H). 6.95 (d, J ) 1.7 Hz, 2 H),
7.29 (d, J ) 1.7 Hz, 2 H), 8.15 (t, J ) 5.5 Hz, 2 H), 8.65 (s, 2
H), 10.62 (s, 2 H); HRMS calcd for C35H51N14O8 795.401, found
795.402.
1,1′-(1,5-P e n t a m e t h yle n e )b is[N -[5-[[[(3,3-d im e t h yl-
a m in o )p r o p y l]c a r b o n y l]-1-m e t h y l-4-p y r r o l-3-y l]-4-
[[[2-for m yla m in o-4-m eth ylth ia zol-5-yl]ca r bon yl]a m in o]-
im id a zole]-2-ca r boxa m id e (18). Compound 14 (1.00 g, 1.25
mmol) was reduced by palladium charcoal (500 mg) in a similar
way as described for 16. The reduced product was redissolved
in anhydrous DMF (10 mL), and 6 (465.00 mg, 2.50 mmol),
and HOBt (472.50 mg, 3.50 mmol) were added to it at room
temperature under nitrogen. A solution of DCC (721.00 mg,
3.50 mmol) in anhydrous DMF (3 mL) was added slowly to
this stirred mixture, and stirring was continued at 25 °C for
an additional 18 h. The reaction mixture was filtered, and the
solvent was removed in vacuo. The impure product was
purified on silica gel column chromatography, eluting with
CH2Cl2:MeOH:NH4OH (80:20:3,v/v/v) to give compound 18 as
a yellow-colored powder; yield 35%; mp 165-167 °C; 1H NMR
(DMSO-d6) δ 1.30 (m, 2 H), 1.85 (q, 4 H), 2.20 (s, 12 H), 2.25
(t, J ) 7.0 Hz, 4 H),2.45 (s, 6 H),3.20 (q, J ) 6.2 Hz, 4 H), 3.88
(s, 6 H), 4.45 (t, J ) 7.2 Hz, 4 H). 6.95 (d, J ) 1.7 Hz, 2 H),
7.25 (d, J ) 1.7 Hz, 2 H), 7.59 (s, 2 H, exchanged with D2O),
8.15 (t, J ) 5.5 Hz, 2 H), 8.55 (s, 2 H), 10.05 (s, 2 H, exchanged
with D2O), 10.42 (s, 2 H, exchanged with D2O); HRMS calcd
for C47H63N18O8S2 1071.451, found 1071.451.
1,1′-(1,7-H e p t a m e t h yle n e )b is[N -[5-[[[(3,3-d im e t h yl-
a m in o )p r o p y l]c a r b o n y l]-1-m e t h y l-4-p y r r o l-3-y l]-4-
[[[2-for m yla m in o-4-m eth ylth ia zol-5-yl]ca r bon yl]a m in o]-
im id a zole]-2-ca r boxa m id e (19). The title compound was
obtained in a similar way as a yellow powder, yield 35%; mp
1,1′-(1,7-Hep ta m eth ylen e)-2,2′bis[N-[(d im eth yla m in o)-
p r op yl]1-m et h yl-4-p yr r olyl]4,4′-d in it r ob is(im id a zole)-
2,2′-ca r boxa m id e (15). This compound was synthesized from
13 in a similar way as described for 14 as pale yellow crystals
15, yield 62%; mp 101 °C; 1H NMR (DMSO-d6) δ 1.30 (m, 6
H), 1.62 (q, 2 H), 1.90 (m, 4 H), 2.16 (s, 12 H), 2.28 (t, J ) 7.0
Hz, 4 H), 3.18 (q, J ) 6.8 Hz,4 H), 3.80 (s, 6 H), 4.48 (t, J )
7.0 Hz, 4 H). 7.00 (d, J ) 1.6 Hz, 2 H), 7.25 (d, J ) 1.6 Hz, 2
1
174-176 °C; H NMR (DMSO-d6) δ 1.25 (m, 6 H), 1.65 (q, 4
H), 1.80 (m, 4 H), 2.20 (s, 12 H), 2.30 (t, J ) 7.0 Hz, 4 H), 2.45
(s, 6 H),3.20 (t, J ) 6.2 Hz, 4 H), 3.85 (s, 6 H), 4.45 (t, J ) 7.0
Hz, 4 H). 6.95 (d, J ) 1.6 Hz, 2 H), 7.25 (d, J ) 1.6 Hz, 2 H),
7.60 (s, 2 H, exchanged with D2O) 8.15 (t, J ) 6.0 Hz, 2 H),