Acid-mediated cyclotransformations of 4a-substituted 4H-4a,5- dihydroindeno[1,2-b]pyridines as a new route to 9a-substituted 1H-fluorenes

Article abstract of DOI:10.1007/s10593-007-0032-y

4a-Substituted dihydroindenopyridines undergo cleavage of the C _(9b)=N bond in water-containing acidic medium, resulting in the formation of diastereomeric ethyl α-acetyl-β-(2,3-dihydro-1,3-dioxo- 1H-inden-2-yl)-β-phenylpropionates and 9a-substituted 1,9a-dihydrofluore- none derivatives. The cyclization of α-acetyl-β-(2,3-dihydro-1,3- dioxo-1H-inden-2-yl)-β-phenyl-propionates with benzylammonium acetate affords 3-benzylamino-1,9a-dihydrofluorenones. The methanobenzo[a]azulene compound is also found among cyclization products.

Full text of DOI:10.1007/s10593-007-0032-y

Chemistry of Heterocyclic Compounds, Vol. 43, No. 2, 2007
ACID-MEDIATED CYCLOTRANSFORMATIONS OF 4a-SUBSTITUTED
4H-4a,5-DIHYDROINDENO[1,2-b]PYRIDINES AS A NEW ROUTE TO
9a-SUBSTITUTED 1H-FLUORENES
S. Stupnikova, Dz. Muceniece, V. Lūsis
4a-Substituted dihydroindenopyridines undergo cleavage of the C(9b)=N bond in water-containing acidic
medium, resulting in the formation of diastereomeric ethyl α-acetyl-β-(2,3-dihydro-1,3-dioxo-1H-inden-
2-yl)-β-phenylpropionates and 9a-substituted 1,9a-dihydrofluore- none derivatives. The cyclization of α-
acetyl-β-(2,3-dihydro-1,3-dioxo-1H-inden-2-yl)-β-phenyl- propionates with benzylammonium acetate
affords 3-benzylamino-1,9a-dihydrofluorenones. The methanobenzo[a]azulene compound is also found
among cyclization products.
Keywords: 4a-substituted 1H-4a,5-dihydroindenopyridines, 9a-substituted 1H-fluorenes, methanobenzo-
[a]azulene, cyclotransformation, recyclization.
Naturally occurring and synthetic estrogens have a broad therapeutic utility, including relief of
menopausal symptoms, treatment of osteoporosis, and prevention of cardiovascular disease. Due to the fact that
estrogen is therapeutically very valuable, great interest has been paid to compounds that mimic the estrogen-like
behavior in estrogen-responsive tissues [1, 2]. Tetrahydro-3-oxo-9a-substituted-1H-fluorene derivatives are tried
Ph
O
R
Ph
O
R
COOEt
Me
COOEt
Me
N
O
H2N
O
1 a–c
Ph
O
Ph
R
R
COOEt
COMe
COOEt
+
+
COMe
O
O
2 a–c
3 a–c
Ph
O
Ph
O
O
O
R
COOEt
COOEt
+
+
+
R1
H
O
6
4a–c, 5a,b
7
1−5 a R = Me, b R = CH2CH=CH2; 1c−4c R = CH2C≡CH; 4 a−c R1 = NH2, 5 a,b R1 = OH;
__________________________________________________________________________________________
Latvian Institute of Organic Synthesis Riga LV-1006, Latvia; e-mail: lusis@osi.lv, e-mail:
stupnikova@osi.lv, e-mail: muceniece@osi.lv. Translated from Khimiya Geterotsiklicheskikh Soedinenii. No. 2,
pp. 249-258, February, 2007. Original article submitted September 26, 2006.
0009-3122/07/4302-0197©2007 Springer Science+Business Media, Inc.
197

as agents for the treatment of brain edema caused by traumatic head injury [3]. Up to now a significant
biological activity is revealed only within a narrow range of structural types of these compounds; therefore
synthesis of new 9a-substituted fluorene derivatives is a logical way to establish the structure-activity
relationships in this class of compounds. Besides, hydrofluorenones bearing an angular 9a-substituent are
versatile building blocks of plant hormones within a gibberellin framework [4-6]. The main route to
tetrahydrofluorenones is step-by-step ring annulation [3]. We have studied the hydrolysis of easily available 4a-
substituted 5-oxo-1H-4a,5-dihydroindeno[1,2-b]pyridines as an alternative route to 9a-substituted fluorenes.
In our studies 4a-allyl, propargyl, and ethoxycarbonylmethyl derivatives of dihydroindeno-
[1,2-b]pyridine have been selected as more suitable candidates for feasible gibbane ring construction.
Compounds with trans-location of 4,4a-substituents [7] can be prepared by alkylation of the appropriate 5-oxo-
1H-4,5-dihydroindenopyridine [8].
Acid hydrolysis of dihydroindenopyridines 1a−c resulted in the cleavage of the azometine C(9b)=N bond,
which was followed by hydrolysis of the enamine moiety (main path) and accompanied by recyclization or retro-
Michael reaction to a smaller extent. Hydrolysis of the open-chain intermediate afforded 2-alkyl-2-
butanoylindandione diastereomers 2 and 3.
The arrangement of substituents in the side chain of indandiones 2 and 3 was determined by NMR
spectroscopy. The singlet corresponding to the isomer 2 acetyl group is shifted upfield under the influence of
theindandione carbonyl function in comparison with the same singlet of isomer 3.
11.2 Hz
10.8 Hz
Ph
Ph
H
COOEt
H
H
COMe
H
2'-C
2'-C
2.37 ppm
COMe
COOEt
1.82 ppm
2
3
Open-chain enamine hydrolysis proceeds in parallel with intramolecular interaction between the terminal
CH3 and indandione CO groups. The interaction results in the formation of 9a-substituted 3-aminofluorenones 4,
unfortunately in low yield. A similar intramolecular condensation of indandione derivatives 2 or 3 affords
fluorenedione 6 or the corresponding enol 5. Besides the disubstituted indandiones and recyclization products 4-6,
2-monosubstituted indandione 7 was found among the 4a-propargylindenopyridine 1c hydrolysis products. 2-(3-
Oxobutyl)indandiones 2 and 3 can be converted into fluoren-3-one derivative 6 according to the methods
described in [9].
The enolates of ketones 6 are often used to construct the bridge between fluorene C(2) and C(9a) atoms.
The electronic features of the mentioned enolates are similar to these of aminofluorenones 4. Therefore, we tried
to improve the outcome of these compounds by cyclization of indandione derivatives 2 and 3 with excess of
ammonium acetate in acetic acid medium. 4a-Substituted indeno[1,2-b]pyridines 1a-c were formed as the main
reaction products in all the cases studied. However, the formation of 3-amino-9a-methylfluorenone 4a (yield up
to 15%) was also observed.
If propargyl derivatives 2c and 3c were used as starting compounds, besides indenopyridine 1c, a
gibbane-type bridged tetracycle, namely, 7,8,9,9a-tetra- hydro-7,9a-methanobenzo[a]azulene 8, was isolated
(yield 9%).
To suppress the pyridine ring formation, ammonium acetate was replaced by benzylammonium acetate.
Under such conditions the formation of 3-amino- fluorenone derivative becames predominant and the
corresponding benzyl- amino derivatives of 9a-methyl- and 9a-allylfluorenones 9a,b were isolated in 60% yield.
198

Ph
Ph
N
O
O
R
R
COOEt
Me
COOEt
NH4OAc
Ph
+
COMe
O
1a–c
4a
2a–c, 3a–c
CH2
O
COOEt
+
+
O
8
N-Benzylaminofluorene formation proceeds simultaneously with cyclization, leading to 3-oxofluo-renone
derivatives 6. Transformation of 3-oxo- compounds 6 into aminoderivatives 9 did not proceed under the reaction
conditions. Tetracyclic diketone 8 as a minor product was isolated after cyclization of propargylindandione 2c
and 3c.
Ph
O
R
COOEt
NHBn
BnNH3OAc
2a–c, 3a–c
+
Ph
9a–c
8
O
R
COOEt
O
+
+
6a–c
Debenzylation of fluorenes 9a can be achieved by action of formic acid in the presence of Pd/C catalyst
in methanol under reflux. Ammonium formate applied instead of formic acid under similar conditions at room
temperature caused the hydrogenation of C(4)=C(4a) bond and afforded benzylamino derivative 10b.
Debenzylation as the second process proceeded under reflux and compound 10a was formed.
Ph
Ph
O
O
Me
Me
COOEt
R
COOEt
NHBn
HCOOH
HCOONH4
4a
9a
10a,b
10 a R = NH2, b R = NHBn
Reduction of 3-(N-benzylamino)fluorenone 9a with NaBH4 resulted in the formation of 9-hydroxy-
diastereomers 11 and 12. Substituents arrangement of compounds 11 and 12 was determined by NMR studies. In
the 13C NMR spectrum the signal corresponding to isomer 12 9a-methyl group was shifted up-field (20.6 ppm)
under the influence of the hydroxyl group in comparison with the same signal of isomer 11 (28.5 ppm), and the
9-H and 9a-CH3 groups of isomer 11 exhibited a nuclear Overhauser effect. These facts assigned trans location
of 9-OH and 9a-CH3 groups in 11 and cis-location of these groups in 12, respectively.
199

OH Ph
Me
OH
Ph
Me
COOEt
NHBn
COOEt
NHBn
NaBH4
9a
+
11
12
The behavior of 4a-indenopyridine 13 was different under acid hydrolysis conditions. The first act, i.e.,
hydrolytic breakage of the pyridine ring, was the same, but further transformation of open-chain enamine was
different: 2,2-disubstituted indandione 16 as well as retro-Michael product 17 were formed as minors. The main
course was an intramolecular interaction between the amino function and the ester carbonyl group, leading to
amide formation and azepine ring closure. Spiro(azepine-4,2'-indandione) was isolated as lactam 14 as well as its
enol form 15.
COOEt
O
Ph
Ph
COOEt
Me
O
COOEt
Me
H+
H2N
COOEt
H2O
N
O
13
O
O
COOEt
COOEt
Ph
Ph
Me
Me
N
H
+
N
+
O
O
O
O
OH
14
Ph
15
COOEt
COMe
O
H
COOEt
+
+
COOEt
O
O
16
17
Simultaneous existence of both forms is surprising, but transformation into the N-methyl derivative
confirmed that treatment of azepinone derivatives 14 or 15 with NaH followed by interaction with methyl iodide
gave the same product, i.e., azepinone 18 in both cases.
COOEt
COOEt
Ph
Ph
O
O
O
O
Me
Me
14
15
NaH
MeI
N
N
Me
–
Na+
O
O
18
The transformation of 4a-allyl- and 4a-propargyl-5-oxo-1H-4a,5-dihydro- indeno[1,2-b]pyridines into 9a-
substituted 1H-fluorene-9-one derivatives has been achieved via the acid-catalyzed pyridine ring
opening/recyclization scheme. The cyclotransformation of 4a-ethoxycarbonylmethylindenopyridine did not give
the expected gibbane skeleton. Instead, the hydrolytic breakage of the pyridine ring leads to the formation of
spiro(azepine-4,2'-indandione) derivatives.
200

EXPERIMENTAL
13
1H and C NMR spectra were recorded on Brucker WH-90 (90 MHz, compounds 2a-c, 3b,c, 4b,c, 5b,
1
1
6a,c, 7,8,9a,b, 14-18, H), Varian Mercury-200 (200 and 50 MHz, compounds 14, H and 13C; 200 MHz,
compounds 6b, 9c, 10a,b, H), and Varian INOVA 600 (600 and 150 MHz, compounds 11, 12, H and 13C),
spectrometers in DMSO-d6 (compounds 7, 17) and CDCl3 (all other compounds) using TMS as internal standard.
IR spectra were recorded on a Perkin−Elmer 580 spectrometer as nujol mulls. Exact mass was determined on
MS-50 AEI (70 eV) or on Waters-Quattro-Micro (electrospray) instrument.
1
1
Hydrolysis of ethyl 4-allyl-2-methyl-5-oxo-4-phenyl-4a,5-dihydro-4H-indeno[1,2-b]pyridine-
3-carboxylate (1b). To a solution of 4a-allylindenopyridine 1b (4.0 g, 10 mmol) in aqueous ethanol (EtOH/H2O,
4:1, 250 ml) conc. HCl (5 ml, 52 mmol) was added. After reflux for 7 h the additional amount of conc. HCl (2
ml, 21 mmol) was added and refluxing was continued for 4 h. The reaction mixture, cooled and diluted with
water (300 ml), was extracted with CH2Cl2 (4×50 ml). The combined organic extracts were dried and
evaporated. The oily residue was treated with ether (100 ml) to obtain diastereomer 3b (0.47 g after
crystallization from methanol). The filtrate was evaporated and the residue was chromatographed (ethyl
acetate−petroleum ether, 3:20). From the first fraction 3-hydroxyfluorenone 5b (0.02 g, 0.5%) was obtained,
from the second – diastereomer 3b (0.35 g). The third fraction was an unresolved mixture of diastereomers 2b
and 3b. From the fourth fraction diastereomer 2b (0.33 g) was isolated, the fifth one afforded 3-oxofluorenone
6b (0.02 g, 0.5%), and the sixth gave 3-aminofluorenone 4b (0.11 g, 3%). Resolution (ethanol-ethyl
acetate−petroleum ether, 1:10:150) of diastereomers 2b and 3b mixture gave additionally 0.7 g of 3b (overall
yield 38%) and 0.45 g of 2b (overall yield 23%).
Ethyl trans-α-acetyl-β-(2-allyl-2,3-dihydro-1,3-dioxo-1H-inden-2-yl)-β-phenylpropionate (2b). White
solid. Mp 92–94oC (MeOH). IR spectrum, ν, cm-1: 1740 and 1703 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 1.15
(3H, t, J = 7.0, OCH2CH3); 1.82 (3H, s, COCH3); 2.47 (2H, d, J = 6.6, 2-CH2); 4.00 (2H, q, J = 7.0, OCH2CH3); 4.23
(1H, d, J = 11.2, H-3); 4.71 (1H, d, J = 11.2, H-2); 4.71-5.27 (3H, m, CH2=CH); 6.89-7.22 (5H, m, Ph); 7.49-8.00
(4H, m, H-4',5',6',7'). Found, %: C 73.80; H 5.95. C25H24O5. Calculated, %: C 74.24; H 5.98.
Ethyl cis-α-acetyl-β-(2-allyl-2,3-dihydro-1,3-dioxo-1H-inden-2-yl)-β-phenylpropionate (3b). White
solid. Mp 93-94°C (MeOH). IR spectrum, ν, cm–1: 1742, 1720, 1700 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 0.73
(3H, t, J = 7.0, OCH2CH3); 2.08-2.68 (5H, m, 2-CH2, COCH3); 3.69 (2H, q, J = 7.0, OCH2CH3); 4.29 (1H, d, J =
11.2, H-3); 4.58-4.78 (2H, m, CH2=CH); 4.91 (1H, d, J = 11.2, H-2); 4.91–5.46 (1H, m, CH2=CH); 6.87-7.18 (5H, m,
C6H5); 7.58-8.02 (4H, m, H-4',5',6',7'). Found, %: C 74.14; H 5.94. C25H24O5. Calculated, %: C 74.24; H 5.98.
Ethyl 9a-allyl-3-amino-9-oxo-1-phenyl-9,9a-dihydro-1H-fluorene-2-carboxylate (4b). Dark yellow solid.
Mp 187-188oC (i-PrOH). IR spectrum, ν, cm-1: 3420, 3300 (NH2); 1705, 1668 (C=O). 1H NMR spectrum, δ, ppm (J,
Hz): 1.17 (3H, t, J = 7.0, OCH2CH3); 2.64 (2H, d, J = 6.8, 9a-CH2); 4.08 (2H, m, OCH2CH3); 4.47 (1H, s, H-1);
4.92 (1H, m, CH2=CH); 5.02 (1H, m, CH2=CH); 5.31-5.87 (1H, m, CH2=CH); 6.56 (1H, s, H-4); 6.94-7.93
(11H, m, 4-C6H5, H-5,6,7,8, 3-NH2). Mass spectrum, (ES), m/z (I, %): calculated – 386 [M+H]+, 408 [M+Na]+;
found – 385.9 [M+H]+, 407.9 [M+Na]+.
Ethyl 9a-allyl-3-hydroxy-9-oxo-1-phenyl-9,9a-dihydro-1H-fluorene-2-carboxylate (5b). Yellow solid.
Mp 145–147°C (MeOH). IR spectrum, ν, cm-1: 1710 and 1659 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 1.18 (3H,
t, J = 7.0, OCH2CH3); 2.62 (2H, d, J = 6.8, 9a-CH2); 4.15 (2H, m, OCH2CH3); 4.33 (1H, s, H-1); 4.92 (1H, m,
CH2=CH); 5.02 (1H, m, CH2=CH); 5.31-5.86 (1H, m, CH2=CH); 6.69 (1H, s, H-4); 6.91-7.20 (5H, m, C6H5);
7.31-8.00 (4H, m, H-5,6,7,8). Found, %: C 77.42; H 5.75. C25H22O4. Calculated, %: C 77.70; H 5.74.
Ethyl 9a-allyl-3,9-dioxo-1-phenyl-2,3,9,9a-tetrahydro-1H-fluorene-2-carboxylate (6b). White solid. Mp
149-150°C (MeOH). IR spectrum, ν, cm-1: 1728, 1658, 1640 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 0.94 (3H, t,
J = 7.0, OCH2CH3); 2.70 (1H, dd, J = 7.3, J = 13.0, 9a-CH2); 2.76 (1H, dd, J = 7.3, J = 13.0, 9a-CH2); 3.90-4.03
(1H, d, J = 13.0, H-2 and 2H, q, J = 7.0, OCH2CH3,); 4.31 (1H, d, J = 13.0, H-1); 4.66-4.94 (2H, m, CH2=CH); 5.02-
5.25 (1H, m, CH2=CH); 6.59 (1H, s, H-4); 7.24-7.44 (5H, m, C6H5); 7.58-7.85 (4H, m, H-5,6,7,8). Found, %: C
77.59; H 5.61. C25H22O4. Calculated, %: C 77.70; H 5.74.
201

Ethyl 2-methyl-5-oxo-4-phenyl-4a-prop-2-ynyl-4a,5-dihydro-4H-indeno[1,2-b]pyridine-3-carboxylate
(1c) was hydrolyzed following the same procedure as described for 1b, and the 4a-prop-2-ynylindenopyridine (1.90
g, 5 mmol) 1c was refluxed with conc. HCl for 14 h. Three fractions were obtained after chromatography (ethyl
acetate−petroleum ether, 3:20). The first fraction was a mixture of indandione 7 and the starting material, the second
one being the mixture of diastereomers 2c and 3c. The third fraction afforded 3-aminofluorenone 4c (0.02 g, 1% after
crystallization from methanol). The chromatography of the mixtures mentioned afforded indandione 7 (0.05 g, 5%)
and 4a-prop-2-ynylindenopyridine 1c (0.01 g, 0.5%, elution with petroleum ether−chloroform, 2:1), as well as both
diastereomers 2c (0.36 g, 18%) and 3c (0.46 g, 23%, elution with ethanol−ethyl acetate−petroleum ether, 1:30:150).
Ethyl trans-α-acetyl-β-(2,3-dihydro-1,3-dioxo-2-(prop-2-ynyl)-1H-inden-2-yl)-β-phenylpropionate (2c).
White solid. Mp 106-110°C (EtOH). IR spectrum, ν, cm-1: 3289 (≡CH); 2105 (C≡C); 1740, 1730, 1703 (C=O).1H
NMR spectrum, δ, ppm (J, Hz): 1.18 (3H, t, J = 7.0, OCH2CH3); 1.55 (1H, t, J = 2.2, ≡CH); 1.81 (3H, s, COCH3);
2.55 (2H, d, J = 2.2, CH2C≡); 3.93 (1H, q, J = 7.0, OCH2CH3); 3.95 (1H, q, J = 7.0, OCH2CH3); 4.20 (1H, d, J =
11.2, H-3); 4.63 (1H, d, J = 11.2, H-2); 6.95−7.24 (5H, m, C6H5); 7.62-8.00 (4H, m, H-4',5',6',7'). Found, %:
C 74.26; H 5.48. C25H22O5. Calculated, %: C 74.61; H 5.51.
Ethyl cis-α-acetyl-β-(2,3-dihydro-1,3-dioxo-2-(prop-2-ynyl)-1H-inden-2-yl)-β-phenylpropionate (3c).
White solid. Mp 81-85°C (MeOH/hexane). IR spectrum, ν, cm-1: 3282 (≡CH); 2105 (C≡C); 1748, 1735, 1710 (C=O).
1H NMR spectrum, δ, ppm (J, Hz): 0.81 (3H, t, J = 7.0, OCH2CH3); 1.62 (1H, t, J = 2.6, ≡CH); 2.33 (3H, s, COCH3);
2.46 (1H, dd, J = 2.6, J = 16.2, CH2C≡); 2.72 (1H, dd, J = 2.6, J = 16.2, CH2C≡); 3.74 (2H, q, J = 7.0, OCH2CH3);
4.24 (1H, d, J = 11.0, H-3); 4.84 (1H, d, J = 11.0, H-2); 6.91-7.20 (5H, m, C6H5); 7.62-8.00 (4H, m, H-
4',5',6',7'). Found, %: C 74.47; H 5.46. C25H22O5. Calculated, %: C 74.61; H 5.51.
Ethyl 3-amino-9-oxo-1-phenyl-9a-(prop-2-ynyl)-9,9a-dihydro-1H-fluorene-2-carboxylate (4c). Dark
yellow solid. Mp 162-164°C (MeOH/hexane). IR spectrum, ν, cm–1: 3480, 3350 (NH2); 3260 (C≡H); 1718, 1662
(C=O). 1H NMR spectrum, δ, ppm (J, Hz): 1.07 (3H, t, J = 7.0, OCH2CH3); 1.71 (1H, t, J = 2.2, ≡CH); 2.73 (1H, dd,
J = 2.2, J = 15.8, CH2C≡); 2.98 (1H, dd, J = 2.2, J = 15.8, CH2C≡); 4.04 (1H, q, J = 7.0, OCH2CH3); 4.09 (1H, q, J =
7.0, OCH2CH3); 4.44 (1H, s, H-1); 6.29-6.78 (2H, bs, NH2); 6.55 (1H, s, H-4); 6.93-7.88 (9H, m, 4-C6H5, H-5,6,7,8).
Mass spectrum (AEI), m/z (Irel, %): 383 [M]+. (10), 338 [M−OEt]+ (100), 310 [M−COOEt]+ (46).
2-(Prop-2-ynyl)indan-1,3-dione (7). White solid. Mp 109-110°C (MeOH). IR spectrum, ν, cm-1: 3250
(≡CH); 1745, 1710 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 1.78 (1H, t, J = 2.4, ≡CH); 2.78–3.22 (3H, m, H-2, 2-
CH2); 7.73-8.13 (4H, m, H-4,5,6,7). Mass spectrum (AEI), m/z (Irel, %): 184 [M]+. (100), 156 (62), 128 (47), 104(97).
Ethyl 4a-ethoxycarbonylmethyl-5-oxo-4-phenyl-4a,5-dihydro-4H-indeno[1,2-b]pyridine-3-carboxylate
(13) (2.15 g, 5 mmol) was hydrolyzed with conc. HCl (2.4 eq) for 5 h as described for compound 1b. Extraction
and evaporation of the reaction mixture followed by treatment with MeOH afforded azepinol 15 (0.70 g). After
column chromatography (CHCl3) of filtrate, the evaporated two fractions were collected as a mixture of
indandiones 16 and 17, as well as a mixture of azepines 14 and 15. Repeated chromatography afforded 0.14 g
(14%) of 17 and 0.04 g (2%) of 16 (ethyl acetate–petroleum ether, 3:20) from the first fraction; from the second
fraction 0.09 g (4%) of 14 and 0.08 g (overall yield 42%) of 15 (ethyl acetate–petroleum ether, 7:20) were
isolated.
Spiro(6-ethoxycarbonyl-7-methyl-2-oxo-5-phenyl-1H-2,3,4,5-tetrahydroazepine-4,2'-indan-1',3'-dione)
(15). White solid. Mp ~200°C (decomposition), MeOH. IR spectrum, ν, cm-1: 3300 (NH); 1798, 1728
1
(C=O); 1640 (N–C=O). H NMR spectrum, δ, ppm (J, Hz): 1.14 (3H, t, J = 7.0, OCH2CH3); 2.27 (3H, s, 7-
CH3); 2.33 (1H, d, J = 17.0, 3-CH2); 2.69 (1H, d, J = 17.0, 3-CH2); 4.02 (2H, q, J = 7.0, OCH2CH3); 4.71
(1H, s, H-5); 4.86 (1H, bs, NH); 7.07-7.60 (5H, m, C6H5); 7.60-7.99 (4H, m, H-4',5',6',7'). Mass spectrum
(AEI), m/z (Irel, %): 403 [M]+. (20), 374 (24), 348 [M–OEt]+ (36), 330 [M–COOEt]+ (34), 298 (100), 284
(44).
202

Spiro(6-ethoxycarbonyl-2-hydroxy-7-methyl-5-phenyl-1H-2,3,4,5-tetrahydroazepine-4,2'-indan-
1',3'-dione) (14). White solid. Mp 200-210°C (decomposition), MeOH. IR spectrum, ν, cm–1: 3233 (OH);
1760, 1730, 1670 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 1.13 (3H, t, J = 7.0, OCH2CH3); 2.51 (3H, s, 7-CH3);
3.04 (1H, d, J = 18.0, 3-CH2); 3.38 (1H, d, J = 18.0, 3-CH2); 4.06 (2H, q, J = 7.0, OCH2CH3); 4.42 (1H, s, H-5);
6.83 (5H, m, C6H5); 7.24-7.38 (2H, m, H-5',6'); 7.51-7.80 (2H, m, H-4',7'). 13C NMR spectrum, δ, ppm: 14.1
(OCH2CH3); 20.5 (H3CC=); 38.2 (C-3); 44.7 (C-5); 59.1 (C-4); 59.9 (OCH2CH3); 95.5 (C-7); 100.7 (C-6); 122.8;
123.5; 126.8; 127.5; 129.0; 130.7; 135.7; 138.2; 148.5; 151.5 (arom. protons), 167.3 (COOEt); 173.7 (C-2); 202.2
(C=O). Mass spectrum (AEI), m/z (Irel, %): 403 [M]+. (19), 358 [M–OEt]+ (23), 330 [M–COOEt]+ (81), 298 (100),
284 (72). Found, %: C 71.34; H 5.22; N 3.34. C24H21NO5. Calculated, %: C 71.45; H 5.25; N 3.47.
Ethyl α-acetyl-β-(2,3-dihydro-1,3-dioxo-2-(ethoxycarbonyl)methyl-1H-inden-2-yl)-β-phenylpropionate
1
(16). White solid. Mp 139-142°C (MeOH). IR spectrum, ν, cm-1: 1744, 1723, 1709 (C=O). H NMR spectrum, δ,
ppm (J, Hz): 0.70 (3H, t, J = 7.0, CH2COOCH2CH3); 1.00 (3H, t, J = 7.0, COOCH2CH3); 2.34 (3H, s, COCH3); 2.76
(1H, d, J = 17.2, H-3); 3,09 (1H, d, J = 17.2, H-2); 3.67 (2H, q, J = 7.0, CH2COOCH2); 3.85 (2H, q, J = 7.0,
COOCH2); 4.13 (1H, d, J = 10.4, 2'-CH2); 4.47 (1H, d, J = 10.4, 2'-CH2); 6.99 (5H, s, C6H5); 7.58–7.98 (4H, m, H-
4',5',6',7'). Found, %: C 69.03; H 5.87. C26H26O7. Calculated, %: C 69.32; H 5.82.
Ethyl (1,3-dioxoindan-2-yl)acetate (17). White solid. Mp 94-96°C (MeOH). IR spectrum, ν, cm-1:
1
1750, 1710 (C=O). H NMR spectrum, δ, ppm (J, Hz): 1.00 (3H, t, J = 7.0, OCH2CH3); 3.04 (2H, d, J = 3.8,
2-CH2); 3.71 (1H, t, J = 3.8, CH); 3.93 (2H, q, J = 7.0, OCH2CH3); 8.00 (4H, s, H-4',5',6',7'). Found, %: C 66.89;
H 5.21. C13H12O4. Calculated, %: C 67.23; H 5.21.
Hydrolysis of ethyl 4a-methyl-5-oxo-4-phenyl-4a,5-dihydro-4H-indeno[1,2-b]pyridine-3-carboxylate
(1a). As described above, 4a-methylindenopyridine 1a (1.00 g, 3.0 mmol) was refluxed with conc. HCl (2.6 eq)
for 5 h. After the usual workup and repeated chromatography (ethyl acetate−petroleum ether, 3:20, and
ethanol−ethyl acetate−petroleum ether, 1:7.5:40, for resolution of diastereomers) 3-hydroxyfluorenone 5a
(0.04 g, 4%), diastereomer 2a (0.48 g, 46%), diastereomer 3a (0.21 g, 20%), and 3-aminofluorenone 4a (0.05 g,
5%) were isolated.
Ethyl cis-α-acetyl-β-(2,3-dihydro-1,3-dioxo-2-methyl-1H-inden-2-yl)-β-phenylpropionate (2a). White
solid. Mp 65-66°C (50% aq. MeOH). IR spectrum, ν, cm-1: 1745, 1724, 1705 (C=O). 1H NMR spectrum, δ, ppm
(J, Hz): 0.76 (3H, t, J = 7.0, OCH2CH3); 1.10 (3H, s, 4a-CH3); 2.34 (3H, s, COCH3); 3.72 (2H, q, J = 7.0,
OCH2CH3); 4.25 (1H, d, J = 11.2, H-3); 4.88 (1H, d, J = 11.2, H-2); 6.90-7.28 (5H, m, C6H5); 7.61-7.97 (4H, m,
H-4',5',6',7'). Found, %: C 73.12; H 6.02. C23H22O5. Calculated, %: C 73.00; H 5.86.
Spiro(6-ethoxycarbonyl-1,7-dimethyl-2-hydroxy-5-phenyl-1H-2,3,4,5-tetrahydroazepine-4,2'-
indan-1',3'-dione) (18). A (from 15). A mixture of spirocompound 15 (0.40 g, 1.0 mmol) and NaH (0.05 g, 60%
dispersion in mineral oil, 1.2 mmol) was stirred in dry DMF (2 ml) at room temperature for 15 min. MeI (0.12
ml, 2.0 mmol) was introduced into the dark red suspension and stirring was continued for 1 h. Then the water-
diluted (20 ml) reaction mixture was extracted with EtOAc (5×10 ml). The combined organic extract was
washed with brine (3×15 ml), dried, and evaporated. The residue was treated with EtOH to obtain
spirocompound 18 (0.27 g, 65%, crystallyzed from EtOH) as a yellow solid, mp 129–130oC. IR spectrum, ν,
1
cm-1:1742, 1720, 1700 (C=O). H NMR spectrum, δ, ppm (J, Hz): 1.17 (3H, t, J = 7.0, OCH2CH3); 2.67 (3H,
d, 5J = 1.2, 7-CH3); 2.95 (2H, s, 3-CH2); 3.38 (3H, s, N−CH3); 4.11 (2H, q, J = 7.0, OCH2CH3); 4.39 (1H, bs,
H-5); 6.75-7.13 (5H, m, C6H5); [7.40-7.82 (2H, m) and 8.00-8.20 (1H, m) H-4',5',6',7']. Found, %: C 71.47; H
5.55; N 3.28. C25H23NO5. Calculated, %: C 71.93; H 5.55; N 3.36.
B (from 14). In a manner similar to Method A, NaH and MeI were sequentially added to the solution of
spirocompound 14 in DMF to obtain compound 18 (51%).
Reaction of ethyl cis-α-acetyl-β-(2-allyl-2,3-dihydro-1,3-dioxo-1H-inden-2-yl)-β-phenylpropionate
(3b) with NH4OAc. A mixture of compound 3b (0.40 g, 1 mmol) and NH4OAc (0.40 g, 5 mmol) in AcOH
(1 ml) was heated at 100°C for 4 h, then cooled to room temperature and diluted with water (50 ml).
Indenopyridine 1b (0.32 g, 84%) was filtered off. Mp 150-152°C (149-150°C [8]).
203

Following the above procedure, 4a-allylindenopyridine 1b (92%, mp 150-152°C (149-150°C [8])) was
prepared from compound 2c, and 1c (92%, mp 194-195°C (195-197°C [8])) − from compound 3c.
Reaction of ethyl trans-α-acetyl-β-(2,3-dihydro-1,3-dioxo-2-(prop-2-ynyl)-1H-inden-2-yl)-β-phenyl-
propionate (2c) with NH4OAc. Compound 2c (0.36 g, 0.9 mmol) and NH4OAc (0.40 g, 4.9 mmol) were heated
for 10 h following the same procedure as in the case of ester 3b. The solid obtained was treated with petroleum
ether (50 ml) and crystallized from ethanol to give 4a-(prop-2-ynyl)indenopyridine 1c (0.21 g). The filtrate was
evaporated and subjected to column chromatography (ethyl acetate−petroleum ether, 3:20) to yield benzoazulene
8 (0.03 g, 9%) and compound 1c (0.04 g, overall yield 72%).
Ethyl 6,10-dioxo-8-methylene-11-phenyl-7,8,9,9a-tetrahydro-7,9a-methanobenzo[a]azulene-7-carboxy-
1
late (8). White solid. Mp 135-1136°C (MeOH). IR spectrum, ν, cm-1: 1740, 1710, 1665 (C=O). H NMR
spectrum, δ, ppm (J, Hz): 1.07 (3H, t, J = 7.0, OCH2CH3); 2.55 (1H, d, J = 14.4, 9-CH2); 3.31 (1H, dt, J = 2.2,
J = 14.4, 9-CH2); 4.19 (2H, q, J = 7.0, OCH2CH3); 4.58 (1H, s, H-11); 5.29 (1H, bs, =CH2); 5.78 (1H, bs, =CH2);
6.44 (1H, s, H-5); 7.09 (5H, s, 11-C6H5); 7.33-8.00 (4H, m, Ar). Found, %: C 78.12; H 5.08. C25H20O4. Calculated,
%: C 78.11; H 5.24.
Reaction of ethyl α-acetyl-β-(2-allyl-2,3-dihydro-1,3-dioxo-1H-inden-2-yl)-β-phenylpropionates
(2b and 3b) with benzylammonium acetate. A mixture of ethyl cis- and trans-(2-allyl-1H-inden-
2yl)propionates 2b and 3b (2.00 g, 5 mmol) and benzylammonium acetate (3.6 M in AcOH, 12 eq, 16 ml) in
glacial AcOH was heated with stirring at 65-70°C for 6.5 h. After cooling to room temperature the red reaction
mixture was diluted with water (40 ml) and extracted with CH2Cl2 (4×30 ml). The organic phase was dried and
evaporated (addition of toluene, 2×50 ml facilitated the evaporation of acetic acid). The red-brown residue was
chromatographed (ethyl acetate−petroleum ether−CH2Cl2, 1:2:7) to obtain 3-benzylaminofluorenone 9b (1.45 g,
62%) and 3-oxofluorenone 5b (0.12 g, 6%).
Ethyl 9a-allyl-3-benzylamino-9-oxo-1-phenyl-9,9a-dihydro-1H-fluorene-2-carboxylate (9b). Yellow
solid. Mp 73-74°C (i-PrOH). IR spectrum, ν, cm-1: 3300 (NH); 1720, 1665 (C=O). 1H NMR spectrum, δ, ppm (J,
Hz): 1.28 (3H, t, J = 7.0, OCH2CH3); 2.61 (2H, d, J = 7.1, CH2); 4.02 (1H, q, J = 7.0, OCH2CH3); 4.04 (1H, q, J
= 7.0, OCH2CH3); 4.43 (1H, s, H-1); 4.50–4.99 (4H, m, =CH2, CH2Ph); 5.10–5.67 (1H, m, =CH); 6.76 (1H, s, H-
4); 6.88–7.09 (5H, m, C6H5); 7.09–7.69 (m, 9H, Ar); 9.42 (1H, bs, NH). Found, %: C 80.70; H 6.06; N 2.66.
C32H29NO3. Calculated, %: C 80.82; H 6.15; N 2.95.
Reaction of ethyl trans-α-acetyl-β-(2,3-dihydro-1,3-dioxo-2-methyl-1H-inden-2-yl)-β-phenyl-
propionate (2a) with benzyl ammonium acetate was performed as described above. 3-Benzyl-
aminofluorenone 9a (1.51 g, 63%) and 3-oxofluorenone 6a (0.27 g, 14%) were obtained
from ethyl-2-methyl-1H-indene-2-propionate 2a (2.00 g, 5 mmol) and benzyl ammonium acetate (9 ml, 6 eq).
Ethyl 3-benzylamino-9a-methyl-9-oxo-1-phenyl-9,9a-dihydro-1H-fluorene-2-carboxylate (9a).
Yellow solid. Mp 124-125°C (MeOH). IR spetrum, ν, cm-1: 3280 (NH); 1725, 1718 (C=O). 1H NMR spectrum,
δ, ppm (J, Hz): 1.10 (3H, t, J = 7.2, OCH2CH3); 1.35 (3H, s, 9a-CH3); 4.01 (2H, q, J = 7.2, OCH2CH3); 4.34
(1H, s, H-1); 4.63 (2H, d, J = 6.9, CH2Ph); 6.77 (1H, s, H-4); 6.83-7.74 (14H, m, Ar). Found, %: C 79.85;
H 5.96; N 2.88. C30H27NO3. Calculated, %: C 80.15; H 6.05; N 3.12.
Ethyl 9a-methyl-3,9-dioxo-1-phenyl-2,3,9,9a-tetrahydro-1H-fluorene-2-carboxylate (6a). White
1
solid. Mp 177-178°C (MeOH). IR spectrum, ν, cm-1: 1730, 1720, 1660 (C=O). H NMR spectrum, δ, ppm (J,
Hz): 0.92 (3H, t, J = 7.2, OCH2CH3); 1.42 (3H, s, 9a-CH3); [3.90 (1H, d, J = 12.4) and 4.19 (1H, d, J = 12.4) H-1
and H-2]; 3.94 (2H, q, J = 7.2, OCH2CH3); 6.50 (1H, s, H-4); 7.32 (5H, s, C6H5); 7.50-7.94 (4H, m, H-5,6,7,8).
Found, %: C 76.39; H 5.49. C23H20O4. Calculated, %: C 76.65; H 5.59.
Reaction of ethyl α-acetyl-β-(2,3-dihydro-1,3-dioxo-2-(prop-2-ynyl)-1H-inden-2-yl)-β-phenyl-
propionates (2c and 3c) with benzyl ammonium acetate was performed as described above.
3-Benzylaminofluorenone 9c (0.63 g, 27%), benzoazulene 8 (0.26 g, 13%), and 3-oxofluorenone 6c (0.09 g, 5%)
were obtained from ethyl 2-(prop-2-ynyl)-1H-inden-2-ylpropionates 2c and 3c (2.00 g, 5 mmol) and benzyl
ammonium acetate (18 eq, 25 ml).
204

Ethyl
3-benzylamino-9-oxo-1-phenyl-9a-(prop-2-ynyl)-9,9a-dihydro-1H-fluorene-2-carboxylate
(9c). Yellow solid. Mp 117–119oC (MeOH). IR spectrum, ν, cm–1: 3440 (NH); 3280 (≡CH); 1730 and 1665
1
(C=O). H NMR spectrum, δ, ppm (J, Hz): 1.15 (3H, t, J = 7.1, OCH2CH3); 1.70 (1H, t, J = 2.6, ≡CH); 2.79
(1H, dd, J = 16.3, J = 2.6, CH2–C≡); 2.93 (1H, dd, J = 16.3, J = 2.6, CH2–C≡); 4.04 (2H, m, OCH2CH3); 4.45
(1H, s, H-1); 4.70 (2H, m, CH2Ph); 6.87 (1H, s, H-4); 6.94-7.79 (14H, m, arom. prot.); 9.47 (1H, bs, NH).
Found, %: C 81.15; H 5.69; N 2.73. C32H27NO3. Calculated, %: C 81.16; H 5.75; N 2.96.
Ethyl 3,9-dioxo-1-phenyl-9a-(prop-2-ynyl)-2,3,9,9a-tetrahydro-1H-fluorene-2-carboxylate (6c).
White solid. Mp 168-169°C (MeOH). IR spectrum, ν, cm-1: 3280 (≡CH); 1750, 1720 (C=O). 1H NMR spectrum,
δ, ppm (J, Hz): 0.92 (3H, t, J = 7.0, OCH2CH3); 1.99 (1H, t, J = 2.6, ≡CH); 2.48 (1H, dd, J = 16.3, J = 2.6,
CH2–C≡); 3.45 (1H, dd, J = 16.3, J = 2.6, CH2–C≡); 3.94 (2H, q, J = 7.02, OCH2CH3); [3.99 (1H, d,
J = 13.0) and 4.59 (1H, d, J = 13.0) H-1 and H-2]; 6.61 (1H, s, H-4); 7.32 (5H, s, C6H5); 7.46–7.99 (4H, m,
H-5,6,7,8). Found, %: C 78.13; H 5.19. C25H20O4. Calculated, %: C 78.11; H 5.24.
Ethyl
3-amino-9a-methyl-9-oxo-1-phenyl-9,9a-dihydro-1H-fluorene-2-carboxylate
(4a)
by
reduction of ethyl 3-benzylamino-9a-methyl-9-oxo-1-phenyl-9,9a-dihydro-1H-fluorene-2-carboxylate (9a).
A solution of 3-benzylaminofluorenone 9a (1.00 g, 2 mmol) in methanol (60 ml) was refluxed with Pd/C (0.3 g,
three portions of 0.1 g were added after every 10 h) and HCOOH (5.5 ml) for 32 h. The hot reaction mixture was
filtered off and filtrate was evaporated. The residue crystallized from MeOH gave 3-aminofluorenone 4a (0.67 g,
84%). Mp 183-184°C (184-186°C [8]).
Ethyl
3-benzylamino-9a-methyl-9-oxo-1-phenyl-4,4a,9,9a-tetrahydro-1H-fluorene-2-carboxylate
(10b). To 3-benzylaminofluorenone 9a (100 mg, 0.22 mmol) dissolved in MeOH (20 ml) Pd/C (26 mg) and
HCOONH4 (80 mg, 1.27 mmol) were added. After being stirred for 3.5 h the reaction mixture was filtered off
and the filtrate was evaporated. The yellow oil obtained was crystallyzed from MeOH to give fluorenone 10b
1
(80 mg, 81%) as a white solid, mp 99-100°C. IR spectrum, ν, cm-1: 3280 (NH); 1720, 1650 (C=O). H NMR
spectrum, δ, ppm, (J, Hz): 1.21 (3H, t, J = 7.1, OCH2CH3); 1.45 (3H, s, 9a-CH3); 2.62 (1H, dd, J = 15.9, J =
8.8, CH2); 3.05 (1H, t, J = 8.8, H-4); 3.25 (1H, dd, J = 15.9, J = 8.8, CH2); 4. 09 (2H, m, OCH2CH3); 4.50 (1H,
s, H-1); 4.61 (2H, d, J = 6.5, CH2Ph); 6.87 (5H, s, C6H5); 7.14-7.52 (9H, m, H-5,6,7,8, C6H5); 9.64 (1H, t, J =
6.5, NH). Mass spectrum (ES), m/z (I, %): calculated − 452 [M+H]+, 474 [M+Na]+; found − 451.9 [M+H]+,
473.9 [M+Na].
Ethyl 3-amino-9a-methyl-9-oxo-1-phenyl-4,4a,9,9a-tetrahydro-1H-fluorene-2-carboxylate (10a).
3-Benzylaminofluorenone (200 mg, 0.44 mmol) dissolved in MeOH (20 ml), Pd/C (20 mg) and HCOONH4 (120
mg, 1.90 mmol) were refluxed for 4.5 h. The hot reaction mixture was filtered off and the filtrate was
evaporated. The residue crystallyzed from MeOH afforded fluorene 10a (70 mg, 44%) as a white solid, mp
153-154°C. IR spectrum, ν, cm–1: 3420, 3310 (NH2), 1700, 1660 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 1.21
(3H, t, J = 7.1, OCH2CH3); 1.48 (3H, s, 9a-CH3); 2.82 (1H, dd, J = 16.2, J = 9.4, CH2); 3.01 (1H, dd, J = 16.2, J
= 9.0, CH2); 3.31 (1H, dd, J = 9.4, J = 9.0, H-4a); 4.10 (2H, m, OCH2CH3); 4.44 (1H, s, H-1); 6.46 (2H, bs,
NH2); 6.89 (5H, s, C6H5); 7.17-7.59 (4H, m, H-5,6,7,8). Found, %: C 76.45; H 6.41; N 3.72. C23H23NO3.
Calculated, %: C 76.43; H 6.41; N 3.88.
Reduction of ethyl 3-benzylamino-9a-methyl-9-oxo-1-phenyl-9,9a-dihydro-1H-fluorene-2-carboxylate
(9a) with NaBH4. 3-Benzylaminofluorenone 9a (0.8 g, 1.8 mmol) and NaBH4 (0.68 g, 17.9 mmol) in i-PrOH
(30 ml) were refluxed for 8.5 h. A fresh portion of NaBH4 (0.34 g, 8.95 mmol) was added and refluxing was
continued for additional 9 h. After cooling to room temperature and diluting with water (40 ml) the reaction
mixture was extracted with EtOAc (4×30 ml). The combined organic extract was washed with water (2×20 ml),
dried and evaporated. Chromatography (CH2Cl2) of the yellow oil obtained gave starting material 9a (0.04 mg,
5%), 9-hydroxyfluorenone 11 (0.30 g, 38%, after drying in vacuo), and 9-hydroxy- fluorenone 12 (0.24 mg,
30%, after drying in vacuo).
205

Ethyl 3-benzylamino-9-hydroxy-9a-methyl-1-phenyl-9,9a-dihydro-1H-fluorene-2-carboxylate (11).
1
Yellow solid. Mp 98-100°C (i-PrOH). IR spectrum, ν, cm-1: 3560 (NH), 3480 (OH), 1655 (C=O). H NMR
spectrum, δ, ppm (J, Hz): 0.69 (1H, bs, OH); 1.21 (3H, s, 9a-CH3); 1.23 (3H, t, J = 7.3, OCH2CH3); 4.07 (2H, m,
OCH2CH3); 4.18 (1H, s, H-1); 4.61 (1H, dd, J = 15.6, J = 6.3, CH2Ph); 4.64 (1H, dd, J = 15.6, J = 6.3, CH2Ph);
4.97 (1H, s, H-9); 6.74 (1H, s, H-4); 7.03-7.10 (3H, m, CH(1-C6H5)p, 2 CH(1-C6H5)m); 7.26 (1H, m,
CH(Ph−CH2N)p); 7.28-7.32 (2H, m, 2 CH(1-C6H5)o); 7.32-7.37 (6H, m, H-6,7, 2 CH(Ph−CH2N)o;
2 CH(Ph−CH2N)m); 7.43 (1H, m, H-8); 7.56 (1H, m, H-5); 9.42 (1H, m, NH). 13C NMR spectrum, δ, ppm: 14.3
(OCH2CH3); 28.5 (9a-CH3); 46.5 (C-1), 46.9 (CH2Ph); 48.8 (C-9a); 58.9 (OCH2CH3); 83.9 (C-9); 94.6 (C-2);
108.7 (C-4); 122.0 (C-5); 126.4 (CH(1-C6H5)p); 126.5 (C-8); 126.8 (2×CH(Ph−CH2N)o); 127.2
(CH(Ph−CH2N)p); 128.3 (2 × CH(1-C6H5)m); 128.7 (2 CH(1-C6H5)o); 128.8 (2 CH(Ph−CH2N)m); 129.2 (C-6);
131.1 (C-7); 136.4 (C-4b); 139.4 (CH(Ph−CH2N)i); 144.9 (CH(1-C6H5)i); 148.9 (C-8a); 153.5 (C-3); 157.3
(C-4a); 170.5 (C=O). Found, %: C 79.40; H 6.71; N 2.70. C30H29NO3. Calculated, %: C 79.80; H 6.47; N 3.10.
Ethyl 3-benzylamino-9-hydroxy-9a-methyl-1-phenyl-9,9a-dihydro-1H-fluorene-2-carboxylate (12).
1
Yellow solid. Mp 140-141°C (i-PrOH). IR spectrum, ν, cm-1: 3460 (NH), 3420 (OH); 1650 (C=O). H NMR
spectrum, δ, ppm (J, Hz): 1.12 (3H, t, J = 7.2, OCH2CH3); 1.22 (3H, s, 9a-CH3); 1.94 (1H, bs, OH); 4.01 (2H, m,
OCH2CH3); 4.24 (1H, s, H-1); 4.60-4.67 (3H, m, CH2Ph, H-9); 6.60 (1H, s, H-4); 7.07 (1H, m, CH(1-C6H5)p);
7.11-7.19 (4H, m, 2 CH(1- C6H5)o); 2×CH(1-C6H5)m); 7.23-7.32 (4H, m, H-6,7,8 CH(Ph−CH2N)p); 7.35-7.37
(4H, m, 2×CH(Ph−CH2N)o); 2×CH(Ph−CH2N)m); 7.42 (1H, d, J = 7.4, H-5); 9.46 (1H, m, NH). 13C NMR
spectrum, δ, ppm: 14.3 (OCH2CH3); 20.6 (9a-CH3); 46.9 (CH2Ph); 47.0 (C-1); 50.7 (C-9a); 58.9 (OCH2CH3);
76.0 (C-9); 92.1 (C-2); 107.9 (C-4); 121.9 (C-5); 124.6 (C-8); 126.0 (CH(1-C6H5)p); 126.7 (2×CH(Ph−CH2N)o);
127.1 (CH(Ph−CH2N)p); 127.8 (2×CH(1-C6H5)m); 127.9 (C-6); 128.5 (2×CH(Ph−CH2N)m); 128.8
(2×CH(1-C6H5)o); 130.4 (C-7), 135.1 (C-4b); 139.5 (CH(Ph−CH2N)i); 142.3 (CH(1-C6H5)i); 148.3 (C-8a); 154.0
(C-3); 155.1 (C-4a); 170.8 (C=O). Found, %: C 79.58; H 6.35; N 2.83. C30H29NO3. Calculated, %: C 79.80;
H 6.47; N 3.10.
We thank the European Social Fund for financial support.
REFERENCES
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S. P. Roher, WO Pat. 99704; Chem. Abstr., 143, 399829 (2005).
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344288 (2001).
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