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N. V. Alekseeva et al.
boiling isopropyl alcohol, after which the filtrates were evap-
orated. The residues were combined and recrystallized from
25 ml of isopropyl alcohol to obtain 1.5 g (38%) of amide
VIa identical to that synthesized by method A.
crystallized from acetone to obtain cream-colored crystals of
amide VIe; yield, 2.0 g (68%); mass spectrum, m/z (Irel, %):
295 (16), 194 (63), 166 (55), 58 (100).
3-Carbazolecarboxylic acid (VII). To a solution of 12 g
(51 mmole) of 3-carbazolecarboxylic acid ethyl ester (IV) in
150 ml of ethanol was added a solution of 4.4 g (79 mmole)
of KOH in 20 ml of water and the mixture was boiled for
~5 h until consumption of the initial ester (TLC monitoring).
The solution was cooled and acidified with hydrochloric acid
to pH 2. The precipitated colorless crystals were separated
by filtration to obtain 9.8 g (92%) of acid VII m.p.,
270 – 274°C (published m.p., 274 – 276°C [7]); Rf, 0.29
(system A).
N-(Carbazolyl-3-carbonyl)glycine ethyl ester (VIII).
A suspension of 3.0 g (14 mmole) of 3-carbazolecarboxylic
acid (VII), 2.0 g (14 mmole) of glycine hydrochloride
ethylate [9], and 2.93 g (14 mmole) of dicyclohexylcarbo-
diimide in 20 ml of pyridine was stirred for 2 h at 0°C and al-
lowed to stand overnight in a refrigerator. Then, the precipi-
tate of dicyclohexylurea was separated by filtration, pyridine
was distilled off in vacuum, and the residue (containing ini-
tial acid VII and the product VIII) was dissolved in ethanol.
The solution was poured into 150 ml of saturated aqueous
sodium carbonate solution. The precipitate was separated by
filtration to obtain 3.2 g of a technical-purity product VIII.
Recrystallization from ethanol yields 2.4 g (58%) of com-
pound VIII in the form of colorless crystals; mass spectrum,
m/z (Irel, %): 296 (100), 250 (16), 194 (93), 166 (13).
The aqueous solution was acidified to isolate 0.4 g of the
initial acid VII (13%).
N-(2-Hydroxypropyl)carbazole-3-carboxamide (VIb).
A suspension of 6.0 g (25 mmole) of ester IV in a mixture of
5.7 ml (75 mmole) of 1,3-aminopropanol and 10 ml of ethyl-
ene glycol was heated for ~3 h at 160 – 165°C until the ini-
tial ester was consumed (TLC monitoring). The solvent and
excess 1,3-aminopropanol were distilled off in vacuum, after
which the residue was dissolved in isopropyl alcohol. The
solution was poured into ice-cold water and the mixture was
allowed to stand for 2 h. The precipitated product (5.3 g) was
separated by filtration and recrystallized from isopropyl alco-
hol to obtain colorless crystals of amide VIb; yield, 4.6 g
(68%); mass spectrum, m/z (Irel, %): 268 (20), 223 (30), 194
(100), 166 (33).
N-(2,3-Dihydroxypropyl)carbazole-3-carboxamide
(VIc). A suspension of 1.7 g (7 mmole) of ester IV and 1.2 g
(14 mmole) of 1-amino-2,3-dioxypropane in 5 ml of ethyl-
ene glycol was heated for 4 h at 160°C and diluted with
10 ml of isopropyl alcohol. The precipitated product was
separated and dried to obtain 1.3 g (65%) of light-yellow
crystals of amide VIc; mass spectrum, m/z (Irel, %): 284 (10),
266 (16), 194 (100), 166 (40).
N-[2-Diethylamino)ethyl]carbazole-3-carboxamide
hydrochloride (VId × HCl).
A
suspension of 2.4 g
(10 mmole) of ester IV in a mixture of 3.5 ml (30 mmole) of
N,N-diethylethylenediamine and 5 ml of ethylene glycol was
heated for ~20 h at 190°C until the initial ester was con-
sumed (TLC monitoring). The solvent and excess diamine
were distilled off in vacuum, after which the residue was dis-
solved in chloroform. The chloroform solution was treated
with diluted hydrochloric acid and the aqueous acid extract
was alkalized with sodium carbonate. The subsequent extrac-
tion with chloroform yielded 2.8 g of base VId. Chloroform
was distilled off and the residue of base VI was dissolved in
ethanol. Finally, a solution of hydrogen chloride in ethanol
was added to pH 4 and hydrochloride VId × HCl was precipi-
tated with diethyl ether. The oily product was dried in vac-
uum until solidification; yield, 2.0 g (57%); mass spectrum,
m/z (Irel, %): 309 (2), 307 (17), 194 (60), 166 (60), 86 (100).
N-[3-Dimethylamino)propyl]carbazole-3-carboxamid
e hydrochloride (VIe). A suspension of 2.4 g (10 mmole) of
N -(Carbazolyl-3-carbonyl)glycine
N-(2-hydroxy-
ethyl)aamide (IX). A mixture of 3.5 g (12 mmole) ester VIII
and 3.0 ml (50 mmole) ethanolamine in 70 ml of ethylene
glycol was heated for ~3 h on a bath at 140 – 150°C until ter-
mination of the reaction (TLC monitoring). The solvent and
excess ethanolamine were distilled in vacuum. The residue
was cooled and poured into an ice-cold sodium carbonate so-
lution, after which the mixture was allowed to stand for 2 h.
Then the precipitate was separated by filtration, washed with
water, and dried to obtain 3.3 g (89%) of compound IX in the
form of pink crystals; mass spectrum, m/z (Irel, %): 311 (13),
250 (13), 194 (100).
3-[N-(3-Hydroxypropyl)aminomethyl]carbazole hy-
drochloride (Ib × HCl). To a suspension of 0.4 g of lithium
aluminum hydride in 50 ml of anhydrous THF was gradually
(over 1.5 h) added with stirring and boiling a solution of
2.5 g (9 mmole) of amide VIb in 250 ml of the same solvent.
Every 0.5 h, additional 0.4 g portions of lithium aluminum
hydride were added to a total amount of 1.6 g (42 mmole)
LiAlH4, after which the mixture was boiled for 5 h with TLC
monitoring. Then the reaction mass was decomposed by
treating sequentially with 1.6 ml of water, 1.6 ml of a 15%
aqueous NaOH solution, and 4.8 ml of water [10] and stirred
for 2 h. The inorganic precipitate was separated by filtration.
The filtrate was washed with THF. THF was distilled off and
ester IV in
a
mixture of 3.1 ml (30 mmole) of
N,N-dimethyl-1,3-diaminopropane and 5 ml of ethylene gly-
col was heated for ~16 h at 190°C until the initial ester was
consumed (TLC monitoring). The solvent and excess
diamine were distilled off in vacuum, after which the residue
was dissolved in chloroform. The chloroform solution was
treated with diluted hydrochloric acid to extract hydrochlo-
ride VIe × HCl (0.5 g of acid VII remained in the chloro-
form). The aqueous acid extract was alkalized with sodium
carbonate and amide VIe was extracted with chloroform and
dried. The chloroform was distilled off and the residue was