SYNTHESES OF COMPOUNDS ACTIVE TOWARD GLUTAMATE RECEPTORS: I.
1767
Methyl 5-indancarboxylate (VI). Thionyl
acetate was added, and the mixture was washed with
chloride, 6 ml, was added on cooling to a solu- 60 ml of water. The product was extracted into 30%
tion of 10 g (0.06 mol) of 5-indancarboxylic acid (V)
in 10 ml of dry benzene. The mixture was heated for
2 h under reflux until gaseous products no longer
evolved and was then heated for 1 h under reduced
pressure to remove excess thionyl chloride. 5-Indan-
carbonyl chloride thus obtained, 11.14 g (0.06 mol),
was added dropwise at 0 C under argon to a solution
of 3.24 g (0.065 mol) of sodium methoxide in 20 ml
of anhydrous methanol. The mixture was stirred for
3 h, poured ino ice water, and extracted with diethyl
ether (3 50 ml). The combined extracts were dried
over calcined sodium sulfate and evaporated, and the
remaining dark brown oily material was subjected to
flash chromatography on silica gel using petroleum
ether as eluent. Yield 9.64 g (90%), yellow oily sub-
stance (purity 99%, GLC).
aqueous NaOH (60 ml). The aqueous phase was
separated and acidified to pH 5 with hydrochloric
acid. Acid IX was extracted into ether (3 50 ml), the
combined extracts were dried over calcined sodium
sulfate and evaporated, and the residue was recrystal-
lized from benzene. Yield 0.28 g (65%), light brown
1
crystals, mp 252 C. H NMR spectrum (DMSO-d6),
, ppm: 2.43 m (1H, CH2), 2.54 m (1H, CH2), 3.10 d
(2H, CH2), 7.69 d (1H, Harom), 7.87 d (1H, Harom),
7.94 s (1H, Harom), 8.10 s (1H, NH), 8.43 s (1H, NH).
Methyl 2 ,4 -dioxoindan-1-spiro-5 -imidazoli-
dine-6-carboxylate (X). A solution of 0.83 g
(0.01 mol) in 3 ml of water was added to a solution
of 4.5 g (0.047 mol) of ammonium carbonate and
2 g (0.01 mol) of methyl 1-oxoindan-6-carboxylate
in 20 ml of DMF. The mixture was heated for 36 h at
90 C and cooled, 100 ml of ethyl acetate was added,
and the mixture was washed with 100 ml of water
and extracted with 100 ml of a 30% solution of
sodium hydroxide. The aqueous phase was separated
and acidified to pH 5 with hydrochloric acid. Ester
X was extracted into ether (3 50 ml), the combined
extracts were dried over calcined sodium sulfate and
evaporated, and the residue was recrystallized from
benzene. Yield 2 g (75%), light brown crystals,
Oxidation of methyl 5-indancarboxylate. A solu-
tion of 7 g (0.07 mol) of CrO3 in a mixture of 27 ml
of acetic acid and 11.6 ml of water was added over
a period of 30 min to a solution of 5 g (0.028 mol)
of methyl 5-indancarboxylate in 13.5 ml of glacial
acetic acid, which was stirred at room temperature.
The mixture was stirred for 12 h, diluted with 60 ml
of water, and extracted with ethyl acetate (4 50 ml).
The combined extracts were washed with a 10% solu-
tion of Na2CO3 (3 30 ml) and a concentrated solu-
tion of sodium chloride (30 ml), dried over calcined
sodium sulfate, and evaporated under reduced pres-
sure. The residue, a dark yellow oily substance, was
recrystallized from ethyl acetate petroleum ether and
was then purified by flash chromatography on silica
gel using petroleum ether ethyl acetate (85:15) as
eluent. We isolated 1.15 g (20%) of methyl 1-oxo-
indan-5-carboxylate (VII) and 1.44 g (25%) of
methyl 1-oxoindan-6-carboxylate (VIII) as colorless
crystalline substances with mp 111 C (for both
isomers); published data [5]: mp 111 112 C. 1H NMR
spectrum (CDCl3), , ppm: compound VII: 2.76 t
(2H, CH2), 3.20 t (2H, CH2), 3.95 s (3H, CH3), 7.56 d
(1H, Harom), 8.24 d (1H, Harom), 8.36 s (1H, Harom);
VIII: 2.76 t (2H, CH2), 3.20 t (2H, CH2), 3.95 s
(3H, CH3), 7.76 d (1H, Harom, 8.12 s (1H, Harom).
1
mp 250 C. H NMR spectrum (DMSO-d6), , ppm:
2.20 m (1H, CH2), 2.48 m (1H, CH2), 3.05 m (2H,
CH2), 3.85 s (CH3), 7.42 d (1H, Harom), 7.62 s (1H,
Harom), 7.95 d (1H, Harom), 8.55 s (1H, NH), 10.90 s
(1H, NH).
1-Aminoindan-1,6-dicarboxylic acid (XI). A mix-
ture of 0.5 g (0.0019 mol) of compound X and 0.61 g
(0.0019 mol) of Ba(OH)2 8H2O in 10 ml of water
was heated for 10 h under reflux. The mixture was
cooled to room temperature, 0.46 g (0.005 mol) of
ammonium carbonate was added, and the mixture was
refluxed for 2.5 h. The precipitate was filtered off,
and the filtrate was evaporated. The residue was
purified by cation-exchange chromatography on
Dowex 50 200 using a 10% solution of pyridine in
water as eluent. Yield 0.3 g (72%), yellowish crystals,
1
mp >300 C (cf. [5]). H NMR spectrum (D2O),
,
ppm: 2.22 m (1H, CH2), 2.55 m (1H, CH2), 2.96 t
(2H, CH2), 7.22 d (1H, Harom), 7.56 s (1H, Harom),
7.76 d (1H, Harom).
2 ,4 -Dioxoindan-1-spiro-5 -imidazolidine-5-car-
boxylic acid (IX). A solution of 0.13 g (0.0026 mol)
of sodium cyanide in 2 ml of water was added to
a solution of 0.73 g (0.0076 mol) of ammonium car-
bonate and 0.32 g (0.0017 mol) of methyl 1-oxoindan-
5-carboxylate in 3 ml of DMF. The mixture was
heated for 36 h at 90 C and cooled, 50 ml of ethyl
REFERENCES
1. Zefirova, O.N. and Zefirov, N.S., Russ. J. Org. Chem.,
2000, vol. 36, no. 9, pp. 1231 1258.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 12 2002