Plant coumarins: VII. Amination of oreoselone trifluoromethanesulfonate

Article abstract of DOI:10.1134/S1070428011090235

Amination of oreoselone trifluoromethanesulfonate with N-substituted piperazines, anabasine, aniline derivatives, quinolin- and isoquinolinamines, and amino acids of the penicillin and cephalosporin series in the presence of palladium complexes gave the c

Full text of DOI:10.1134/S1070428011090235

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 9, pp. 1390–1403. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © A.V. Lipeeva, E.E. Shul’ts, M.M. Shakirov, G.A. Tolstikov, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 9,
pp. 1367–1379.
Plant Coumarins: VII.* Amination of Oreoselone
Trifluoromethanesulfonate
A. V. Lipeeva, E. E. Shul’ts, M. M. Shakirov, and G. A. Tolstikov
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences,
pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia
e-mail: schultz@nioch.nsc.ru
Received February 24, 2011
Abstract—Amination of oreoselone trifluoromethanesulfonate with N-substituted piperazines, anabasine,
aniline derivatives, quinolin- and isoquinolinamines, and amino acids of the penicillin and cephalosporin series
in the presence of palladium complexes gave the corresponding N-substituted 3-aminofurocoumarins. The yield
of the amination products depended on the catalytic system and base used.
DOI: 10.1134/S1070428011090235
Various amino- and amido-substituted coumarins
produced by Streptomyces sp. attract attention due to
their valuable biological activity [2]. Natural and syn-
thetic aminocoumarins are promising from the view-
point of medicinal chemistry for the design of new
antibiotics and antitumor and antiviral agents [3].
Introduction of a nitrogen-containing functional group
into psoralen molecule changes its phototoxicity and in
some cases enhances photoantiproliferative activity
[4]. Furthermore, extensive search for selective mono-
aminooxidase (MAO-A) inhibitors and antidepressants
is performed in the series of amino-substituted furo-
coumarins [5, 6].
according to Buchwald–Hartwig; and Ganina et al.
[12] reported on palladium-catalyzed reactions of 4-tri-
fluoromethylsulfonyloxy-substituted coumarins with
amides and NH-heterocycles. As applied to furo-
coumarins, only amination of 2-(1,3-dibromopropan-2-
ylidene)oreoselone was reported [13]. This compound
reacted with various amines and amino acid deriva-
tives in the presence of palladium complexes to pro-
duce 2-(1,3-diaminopropan-2-ylidene)-substituted
furocoumarins, whereas its amination with di- and
polyamines afforded macrocyclic compounds contain-
ing furocoumarin fragments. Amination of furocou-
marins at the 3-position was not studied.
Classical procedures for the synthesis of amino-
coumarins are based on addition–elimination reactions
of 4-halo- or 4-trifluoromethyl-substituted coumarins
with aliphatic or aromatic amines [7] and reduction of
3-nitrocoumarins into 3-aminocoumarins with subse-
quent functionalization at the nitrogen atom [5, 8].
Although considerable attention has been given in the
recent time to amination and amidation of various
halogen derivatives and trifluoromethanesulfonates,
catalyzed by transition metals [9], only a few examples
of preparation of nitrogen-containing coumarin deriva-
tives via the above reactions have been reported. Wang
et al. [10] described the synthesis of 3-amino-4-sul-
fanylcoumarins by palladium-catalyzed amination of
3-bromo-4-tosyloxycoumarins; N-substituted 3-amino-
coumarins were synthesized by Audisio et al. [11]
The present work was aimed at synthesizing furo-
coumarins having a substituted amino group on C3 via
palladium-catalyzed amination of oreoselone trifluoro-
methanesulfonate (I). Compound I is readily prepared
in two steps from an accessible plant furocoumarin,
peucedanin, by hydrolysis with a solution of hydro-
chloric acid in methanol and subsequent treatment with
trifluoroacetic anhydride [1].
First of all, we examined amination of oreoselone
trifluoromethanesulfonate (I) with substituted anilines
IIa–IIl (Scheme 1), specifically with those containing
piperidino (IIb, IIl), fluoro (IId–IIh), and trifluoro-
methyl groups (IIe–IIl). Furocoumarins modified with
a 2-piperidinoaniline fragment attract interest taking
into account that some furfurylpiperidinoaniline deriv-
atives were found to act as selective cFMS tyrosine
kinase inhibitors (potential anti-inflammatory agents)
* For communication VI, see [1].
1390

PLANT COUMARINS: VII.
1391
Scheme 1.
R2
R3
R1
R4
R5
TfO
R4
R3
Pd(OAc)2, BINAP
NH2
R5
Me
Me
HN
Et3N, DMF, 110°C
+
Me
Me
O
O
O
R1
R2
O
O
O
I
IIa, IIc–IIl
IIIa, IIIc–IIIl
R1 = R2 = R3 = R4 = R5 = H (a); R1 = R3 = R4 = R5 = H, R2 = Cl (c); R1 = R3 = R4 = R5 = H, R2 = F (d); R1 = F, R2 = R3 = R4 = H,
R5 = CF3 (e); R1 = CF3, R2 = R3 = R5 = H, R4 = F (f); R1 = CF3, R2 = R4 = R5 = H, R3 = F (g); R1 = R4 = R5 = H, R2 = CF3, R3 = F (h);
R1 = R4 = R5 = H, R2 = CF3, R3 = Me (i); R1 = R4 = R5 = H, R2 = CF3, R3 = MeS (j); R1 = morpholino, R2 = R3 = R5 = H, R4 =
CF3 (k); R1 = piperidino, R2 = R3 = R4 = H, R5 = CF3 (l).
[14] and that heterocyclic anilinopiperidine derivatives
were reported to activate adrenoreceptors [15]. Modifi-
cation of furocoumarins with fluorine-containing
anilines was performed in view of important role of
fluorinated substituents in medicinal chemistry (as
a rule, replacement of hydrogen by fluorine changes
the selectivity and affinity for various receptors and
enhances biological activity) [16].
Pd(OAc)2/BINAP (2/8 mol %), and cesium carbonate
as base (solvent toluene) [17] was characterized by
considerably lower yield of the target product. Thus
the most efficient were Pd(OAc)2/BINAP as catalytic
system and triethylamine as base.
The results of amination of compound I with
anilines IIa–IIl under the optimal conditions are col-
lected in table. It is seen that the yield of the amination
product depends on the substituents in the aromatic
ring of II. The highest yield (74%, IIIj) was obtained
in the reaction of I with aniline IIj having an electron-
donor methylsulfanyl group in the para-position. In
this case the reaction was complete in 4 h, whereas
reactions with other anilines required 5 to 7 h. Fairly
high yields of the amination products were observed in
the reactions with unsubstituted aniline (IIa), 2-piper-
idinoaniline (IIb), and 5-methyl-3-trifluoromethylani-
line (IIi). The presence of electron-withdrawing sub-
stituents in the ortho and meta positions of the aniline
molecule reduced the yield of the amination products
(cf. the data for anilines IIb and IIl). The lowest yields
were obtained in the amination of oreoselone trifluoro-
methanesulfonate (I) with anilines IIe and IIg, each
The reaction conditions were optimized using the
amination of oreoselone trifluoromethanesulfonate (I)
with 2-piperidinoaniline (IIb) as model reaction
(Scheme 2). Palladium(II) acetate was used as source
of palladium, and BINAP, (o-Tol)3P, Xantphos, and
t-Bu3P were tried as ligands. When the reaction was
carried out in DMF in the presence of 1.3 equiv of tri-
ethylamine (115°C, 7 h) the yield of 3-(2-piperidino-
phenylamino)-7H-furo[3,2-g]chromen-7-one (IIIb)
was 64, 58, 50, and 26%, respectively. In the latter
case, 8% of unchanged trifluoromethanesulfonate I
was recovered from the reaction mixture. Replacement
of DMF by acetonitrile and lowering the temperature
(85°C, 10 h) did not result in increased yield of IIIb.
The amination of I using a different catalytic system,
Scheme 2.
3''
2''
3'
4'
4''
1''N
2'
1'
5'
TfO
NH2
N
6'
Me
Me
HN
Pd/L, i–vi
4
9
5
3
+
Me
Me
6
2
O
O
O
7
1
8
O
O
O
I
IIb
IIIb
i: Pd(OAc)2, BINAP, Et3N, DMF; ii: Pd(OAc)2, (o-Tol)3P, Et3N, DMF; iii: Pd(OAc)2, (t-Bu)3P, Et3N, DMF; iv: Pd(OAc)2, BINAP,
Et3N, MeCN; v: Pd(OAc)2, BINAP, Cs2CO3, toluene; vi: Pd(OAc)2, Xantphos, Et3N, DMF.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

LIPEEVA et al.
1392
Yields of 3-arylaminofurocoumarins IIIa and IIIc–IIIl in the amination of oreoselone trifluoromethanesulfonate (I)
Amine
Reaction time, h
Product
Yield, %
Aniline (IIa)
6
6
6
7
6
7
6
5
4
6
6
IIIa
IIIc
IIId
IIIe
IIIf
IIIg
IIIh
IIIi
62
58
55
28
37
31
48
66
74
45
49
3-Chloroaniline (IIc)
3-Fluoroaniline (IId)
2-Fluoro-6-trifluoromethylaniline (IIe)
5-Fluoro-2-trifluoromethylaniline (IIf)
4-Fluoro-2-trifluoromethylaniline (IIg)
4-Fluoro-3-trifluoromethylaniline (IIh)
4-Methyl-3-trifluoromethylaniline (IIi)
4-Methylsulfanyl-3-trifluoromethylaniline (IIj)
2-Morpholino-5-trifluoromethylaniline (IIk)
2-Piperidino-6-trifluoromethylaniline (IIl)
IIIj
IIIk
IIIl
having two electron-withdrawing substituents in the
ortho and para or meta positions.
isolated after heating of a mixture of compounds I and
IIj in the presence of pyridine for 6 h.
Taking into account high reactivity of aniline IIj,
we made an attempt to obtain 3-anilinooreoselone
derivative IIIj under classical addition–elimination
conditions (heating in dioxane in the presence of
a base). However, only the initial compounds were
The reactions of trifluoromethanesulfonate I with
quinolin-6-amine (IV), quinolin-8-amine (V), and iso-
quinolin-5-amine (VI) in DMF in the presence of
Pd(OAc)2/BINAP as catalytic system and triethyl-
amine gave the corresponding substituted furocou-
Scheme 3.
2'
N
1'
8'
3'
7'
6'
H2N
4'
5'
I
+
HN
Me
Me
N
O
O
O
IV
VII
6'
5'
4'
NH2
7'
N
3'
8'
1'
I
+
HN
N
2'
Me
Me
O
O
O
V
VIII
7'
8'
1'
NH2
6'
5'
N2'
I
+
HN
3'
4'
N
Me
Me
O
O
O
VI
IX
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

PLANT COUMARINS: VII.
1393
Scheme 4.
R
R
N
H
4'
N
5'
6'
3'
(XIa, XIb)
(X)
4''
5''
2'
HN
1'
3''
2''
N
HN
i, ii
N
N
i–iii
6''
H
1''
Me
Me
I
N
i-Pr
O
O
O
O
O
O
XII
XIIIa, XIIIb
R = t-BuOCO (a), Me (b); i: Pd(OAc)2, BINAP, Et3N, DMF; ii: Pd(OAc)2, Xantphos, Et3N, DMF;
iii: Pd(OAc)2, t-Bu3P, Et3N, DMF.
marins VII–IX in 45, 32, and 48% yield, respectively
(Scheme 3). Reduced yield in the reaction with quino-
lin-8-amine (V) should be noted. Cyclic secondary
amines, in particular anabasine (X) and N-substituted
piperazines XIa and XIb reacted with compound I to
produce the corresponding amination products in high
yield. In the reactions of I with alkaloid X in DMF
in the presence of Pd(OAc)2/BINAP and Pd(OAc)2/
Xantphos as catalytic system, compound XII was ob-
tained in 68 and 53% yield, respectively.
45%). The yield of the amination product did not
increase when N-Boc-piperazine XIa was added in
portions in 30 min after mixing the initial coumarin
with the catalyst and base according to the recommen-
dations given in [18]. The use of tri-tert-butylphos-
phine as ligand was also inefficient: the yield of com-
pound XIIIa was 35%.
With a view to obtain analogs of lactam antibiotics
containing a furocoumarin fragment, we performed
amination of trifluoromethanesulfonate I with amines
of the penam and cepham series. Combination of
coumarin and β-lactam fragments in a single molecule
seems to be promising taking into accounts modern
trends in improvement of penicillins via conjugation
with peptides, catechols, and isochromans [19, 20]. By
reactions of I with 6-aminopenicillanic acid (XIV) and
its methyl ester XV in DMF (Pd(OAc)2/BINAP,
The amination of I with N-Boc-protected pipera-
zine XIa in the presence of Pd(OAc)2/BINAP
(4/8 mol %) afforded 42% of 3-(4-Boc-piperazin-1-yl)-
7H-furo[3,2-g]chromen-7-one (XIIIa) (Scheme 4).
Analogous results were obtained in the reactions of I
with piperazines XIa and XIb carried out in the pres-
ence of Pd(OAc)2/Xantphos (4/8 mol %) (yield 40–
Scheme 5.
ROCO
2'
O
1'
Me
Me
3'
N
7'
H
4'
6'
H2N
S
S
5'
Me
Me
i, ii
4
5
6
7
NH
I
+
H
3
N1
2
Me
Me
O
COOR
O
O
O
XIV, XV
XVI, XVII
COOR
2'
R'
O
1'
N
6'
3'
4'
8'
H
S
5
7'
H2N
O
5'
S
4
3
i
6
7
NH
I
+
H
8
N1
2
Me
R'
COOR
XVIII–XX
O
Me
O
O
XXI–XXIII
XIV, XVI, R = H; XV, XVII, R = Me; XVIII–XXII, R′ = MeC(O)OCH2; XVIII, XXI, R = H; XIX, XXII, R = Me;
XX, XXIII, R = R′ = Me; i: Pd(OAc)2, BINAP, Et3N, DMF; ii: Pd(OAc)2, BINAP, (i-Pr)2NH, DMF.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

LIPEEVA et al.
1394
1
4/8 mol %; Et3N) we obtained 48–66% of furocou-
marins XVI and XVII containing a penicillin fragment
(Scheme 5). Our attempt to raise the yield of amination
product XVI and reduce tarring in the reaction of I
with amine XIV by replacing triethylamine by diiso-
propylamine was not successful. The amination of
oreoselone trifluoromethanesulfonate I with 7-amino-
cephalosporanic acid (XVIII), 7-amino(deacetoxy)-
cephalosporanic acid (XIX), and 7-amino(deacetoxy)-
cephalosporanic acid methyl ester (XX) under analo-
gous conditions gave compounds XXI–XXIII in 36–
42% yield. The lowest yield was observed in the
amination of compound I with 7-aminocephalospo-
ranic acid (XVIII).
600 spectrometers (600.30 MHz for H and
150.96 MHz for 13C). The H and 13C chemical shifts
1
were measured relative to the residual proton signal
and carbon signal of the solvent (CHCl3, δ 7.24;
CDCl3, δC 76.90 ppm); the 19F chemical shifts were
determined relative to C6F6 (δF 0.00 ppm) as internal
reference. Signal multiplicities in the 13C NMR spectra
were determined using J modulation technique.
Signals in the NMR spectra of compounds VIII, XVI,
XVII, and XXII were assigned on the basis of carbon–
proton shift correlation experiments (COXH,
COLOC). The IR spectra were obtained on a Bruker
Vector-22 instrument from samples prepared as KBr
pellets. The electronic absorption spectra were record-
ed on an HP 8453 UV-Vis spectrophotometer. The
optical rotations [α]D20 were measured at room tempera-
ture (20–23°C) on a PolAAr3005 polarimeter. The
elemental compositions were determined on a Carlo
Erba 1106 CHN analyzer.
The structure of the synthesized compounds was
determined on the basis of their spectral parameters
and elemental compositions. The amination products
displayed in the electronic spectra absorption bands
typical of furocoumarins. In particular, the UV spectra
of all compounds IIIa–IIIl, VII–IX, XII, XIIIa,
XIIIb, XVI, XVII, and XXI–XXIII contained absorp-
tion bands with their maxima at λ 244–253, 280–295,
and 333–338 nm. 3-Anilino, 3-quinolinyl, and 3-iso-
quinolinyl derivatives were characterized by a larger
number of absorption bands and increased intensity of
absorption maxima at λ 240–300 nm. For example,
absorption maxima at λ 223, 228, 234, 252, 297, 308,
342, and 353 nm were observed in the UV spectrum of
The products were isolated by column chromatog-
raphy on silica gel (0.035–0.070 mm, Acros Organics)
or neutral aluminum oxide using chloroform or chloro-
form–ethanol (50:3) as eluent. The progress of reac-
tions was monitored by TLC on Silufol UV-254 plates
using chloroform or chloroform–ethanol (50:3) as
eluent; spots were visualized by treatment with iodine
vapor and under UV light.
1
The solvents (acetonitrile, dimethylformamide,
toluene, dioxane) and triethylamine were distilled in
a stream of argon just before use. The ligands
[(o-Tol)3P, (R)-(+)-BINAP, (t-Bu)3P, Xantphos], diiso-
propylamine, and trifluoromethanesulfonic anhydride
were commercial products (Alfa Aesar). 6-Aminopeni-
cillanic acid methyl ester (XV) and 7-aminodeacetoxy-
cephalosporanic acid methyl ester (XX) were synthe-
sized according to the procedure described in [20]; the
spectral parameters of compound XV were consistent
with those given in [20]. Palladium(II) acetate was pre-
pared as reported in [21], and oreoselone trifluoro-
methanesulfonate (I) was synthesized from peucedanin
according to [1].
compound IX. The H and 13C NMR spectra of the
amination products contained only one set of signals
from the furocoumarin fragment and the corresponding
substituent and were consistent with the assumed
structure.
In the IR spectra of lactam derivatives XVI, XXI,
XXII, absorption bands at 1730–1770 (β-lactam car-
bonyl), 1690–1720 (COOH, COCH3, C7=O), and
3460–3435, 3190, 3090, 3062 cm–1 (NH, OH) were
present. Protons in the lactam ring of XVI and XVII
(5′-H, 6′-H) and XXI–XXIII (6′-H, 7′-H) resonated
1
in the H NMR spectra at δ 4.52–5.15 and 4.88–
5.48 ppm, respectively (3J = 4.6–5.0 Hz).
Thus the amination of oreoselone trifluoromethane-
sulfonate with various amines gives N-substituted
3-aminofurocoumarin derivatives which attract interest
as potential pharmacologically active compounds.
2-Isopropyl-3-phenylamino-7H-furo[3,2-g]chro-
men-7-one (IIIa). Oreoselone trifluoromethanesul-
fonate (I), 200 mg (0.5 mmol), was dissolved in 3 ml
of anhydrous dimethylformamide, 93 mg (1 mmol) of
aniline (IIa), 2.2 mg (2 mol %) of palladium(II)
acetate, 34 mg (8 mol %) of BINAP, and 0.07 ml
(0.65 mmol) of triethylamine were added under stirring
in a stream of argon, and the mixture was heated for
6 h at 115°C until initial compound I disappeared
EXPERIMENTAL
The NMR spectra were recorded on Bruker AV-300
1
(300.13 MHz for H and 75.47 MHz for 13C), AV-400
(400.13 MHz for 1H and 100.78 MHz for 13C), and AV-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

PLANT COUMARINS: VII.
1395
(TLC) and evaporated. The residue was subjected to
column chromatography on silica gel to isolate 105 mg
(62%) of compound IIIa as a yellow oily substance. IR
spectrum, ν, cm–1: 3360, 3090, 3061, 2978, 2928,
2880, 2854, 1732, 1627, 1578, 1452, 1429, 1350,
1321, 1288, 1248, 1211, 1140, 1072, 1047, 959, 901,
868, 824, 746, 696. UV spectrum (EtOH), λmax, nm
(logε): 201 (4.29), 250 (4.30), 285 (3.84), 337 (3.72).
1H NMR spectrum (CDCl3), δ, ppm: 1.26 d [6H,
(CH3)2CH, J = 7 Hz], 3.09 m [1H, CH(CH3)2],
3.88 br.s (1H, NH), 6.32 d (1H, 6-H, J = 9.7 Hz), 6.87 t
(1H, 4′-H), 7.19 s (1H, 9-H), 7.27 m (2H, 2′-H, 6′-H),
7.36 m (2H, 3′-H, 5′-H), 7.50 s (1H, 4-H), 7.75 d (1H,
5-H, J = 9.7 Hz). 13C NMR spectrum (CDCl3), δC,
ppm: 20.72 q [(CH3)2CH], 23.40 d [CH(CH3)2],
100.40 d (C9), 114.35 d (C6), 114.54 d (C4a), 115.33 s
(C3a), 121.79 d (C4), 125.59 d (C2′, C6′), 126.10 d (C4′),
127.44 d (C3′, C5′), 136.11 d (C1′), 143.26 d (C2),
144.55 d (C5), 151.26 s and 159.13 s (C8a, C9a),
161.24 s (C7). Found, %: C 74.37; H 6.12; N 6.92.
C25H26N2O3. Calculated, %: C 74.60; H 6.51; N 6.96.
was heated for 7 h at 115°C until the initial compound
disappeared (TLC) and evaporated. The residue was
subjected to column chromatography on silica gel to
isolate (in succession) 52 mg (26%) of compound IIIb
and 15 mg (8%) of initial trifluoromethanesulfonate I.
d. Compound I, 200 mg (0.5 mmol), was dissolved
in 6 ml of anhydrous acetonitrile, 176 mg (1 mmol) of
aniline IIb, 2.2 mg (2 mol %) of palladium(II) acetate,
34 mg (8 mol %) of BINAP, and 0.07 ml (0.65 mmol)
of triethylamine were added under stirring in a stream
of argon, and the mixture was heated for 10 h at 85°C
and evaporated. The residue was subjected to column
chromatography on silica gel to isolate (in succession)
48 mg (24%) of compound IIIb and 28 mg (14%) of
initial trifluoromethanesulfonate I.
e. Compound I, 200 mg (0.5 mmol), was dissolved
in 6 ml of anhydrous toluene, 176 mg (mmol) of
aniline IIb, 325 mg (1 mmol) of cesium carbonate,
2.2 mg (2 mol %) of palladium(II) acetate, and 34 mg
(8 mol %) of BINAP were added in succession under
stirring in a stream of argon, and the mixture was
heated for 7 h at 110°C until initial compound I
disappeared (TLC; strong tarring was observed) and
evaporated. The residue was subjected to column
chromatography on silica gel to isolate 34 mg (18%) of
compound IIIb.
2-Isopropyl-3-(2-piperidinophenylamino)-7H-
furo[3,2-g]chromen-7-one (IIIb). a. Oreoselone tri-
fluoromethanesulfonate (I), 200 mg (0.5 mmol), was
dissolved in 3 ml of anhydrous dimethylformamide,
176 mg (1 mmol) of 2-piperidinoaniline (IIb), 2.2 mg
(2 mol %) of palladium(II) acetate, 34 mg (8 mol %) of
BINAP, and 0.07 ml (0.65 mmol) of triethylamine
were added under stirring in a stream of argon, and the
mixture was heated for 6 h at 115°C until initial com-
pound I disappeared (TLC) and evaporated. The resi-
due was subjected to column chromatography on silica
gel, and compound IIIb was precipitated from the elu-
ate by addition of diethyl ether. Yield 128 mg (64%).
f. Compound I, 200 mg (0.5 mmol), was dissolved
in 3 ml of anhydrous DMF, 176 mg (1 mmol) of
aniline IIb, 2.2 mg (2 mol %) of palladium(II) acetate,
44 mg (8 mol %) of Xantphos, and 0.07 ml
(0.65 mmol) of triethylamine were added under stirring
in a stream of argon, and the mixture was heated for
7 h at 115°C until initial compound I disappeared
(TLC) and evaporated. Column chromatography of the
residue on silica gel gave 100 mg (50%) of compound
IIIb. mp 128–129°C (from diethyl ether). IR spectrum,
ν, cm–1: 3339, 3065, 2963, 2852, 2794, 1731, 1608,
1500, 1432, 1426, 1212, 1138, 1048, 869, 744, 601.
UV spectrum (EtOH), λmax, nm (logε): 216 (4.45), 249
b. Compound I, 200 mg (0.5 mmol), was dissolved
in 3 ml of anhydrous DMF, 176 mg (1 mmol) of
aniline IIb, 2.2 mg (2 mol %) of palladium(II) acetate,
34 mg (8 mol %) of tris(o-tolyl)phosphine, and 0.07 ml
(0.65 mmol) of triethylamine were added under stirring
in a stream of argon, and the mixture was heated for
7 h at 115°C until the initial compound disappeared
(TLC) and evaporated. The residue was subjected to
column chromatography on silica gel to isolate 116 mg
(58%) of compound IIIb.
1
(4.35), 290 (3.97), 334 (3.71). H NMR spectrum
(CDCl3), δ, ppm: 1.40 d [6H, (CH3)2CH, J = 7.0 Hz],
1.57 m (4H, 3″-H, 5″-H), 3.08 m [1H, CH(CH3)2],
3.16 m (6H, 2″-H, 4″-H, 6″-H), 3.97 br.s (1H, NH),
6.44 d (1H, 6-H, J = 9.8 Hz), 6.72 d (1H, 3′-H, J =
7.6 Hz), 6.74 t (1H, 5′-H, J = 7.6 Hz), 6.91 t (1H, 4′-H,
J = 7.6 Hz), 6.99 d (1H, 6′-H, J = 7.6 Hz), 7.42 s (1H,
9-H), 7.59 s (1H, 4-H), 7.78 d (1H, 5-H, J = 9.8 Hz).
13C NMR spectrum (CDCl3), δC, ppm: 20.67 q
[(CH3)2CH], 24.22 t (C3″, C5″), 29.84 d [CH(CH3)2],
33.20 t (C4″), 53.66 t (C2″, C6″), 100.18 d (C9), 114.90 s
c. Compound I, 200 mg (0.5 mmol), was dissolved
in 3 ml of anhydrous DMF, 176 mg (1 mmol) of
aniline IIb, 2.2 mg (2 mol %) of palladium(II) acetate,
10 mg (8 mol %) of tris(tert-butyl)phosphine, and
0.07 ml (0.65 mmol) of triethylamine were added
under stirring in a stream of argon, and the mixture
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

LIPEEVA et al.
1396
(C3′), 115.42 s (C4a), 118.32 d (C6), 119.03 s (C3a),
119.64 d (C4′), 120.17 d (C4), 124.09 d (C5′, C6′),
124.10 s (C3), 140.59 s and 141.39 s (C1′, C2′),
143.43 d (C5); 152.41 s, 153.08 s, 156.97 s (C2, C8a,
C9a), 160.45 s (C7). Found: N 6.92%. C25H26N2O3. Cal-
culated: N 6.96%.
(C5′), 143.05 s (C1′), 143.73 d (C5); 146.44 s, 157.69 s,
159.63 s, 159.91 s (C2, C7, C8a, C9a); 165.60 d (C3′,
JCF = 274.6 Hz). Found, %: C 71.03; H 3.99; F 5.28;
N 4.03. C20H16FNO3. Calculated, %: C 71.21; H 4.78;
F 5.63; N 4.15.
3-(2-Fluoro-6-trifluoromethylphenylamino)-2-
isopropyl-7H-furo[3,2-g]chromen-7-one (IIIe) was
synthesized as described above in a from 200 mg
(0.5 mmol) of compound I and 178 mg (1 mmol) of
2-fluoro-6-trifluoromethylaniline (IIe) (reaction time
7 h). Yield 60 mg (28%), oily substance. IR spectrum,
ν, cm–1: 3426, 2979, 1732, 1633, 1650, 1580, 1458,
1429, 1348, 1199, 1139, 1114, 1047, 958, 867, 821,
761, 740, 678. UV spectrum (EtOH), λmax, nm (logε):
204 (4.55), 252 (4.69), 280 (4.23), 338 (4.09).
1H NMR spectrum (CDCl3), δ, ppm: 1.23 d [6H,
(CH3)2CH, J = 7.0 Hz], 3.10 m [1H, CH(CH3)2],
4.08 br.s (1H, NH), 6.25 d (1H, 6-H, J = 9.8 Hz),
6.53 m (1H, 3′-H), 6.98 m (1H, 4′-H), 7.04 d (1H,
5′-H, J = 7.6 Hz), 7.09 s (1H, 9-H), 7.41 s (1H, 4-H),
7.64 d (1H, 5-H, J = 9.8 Hz). 13C NMR spectrum
(CDCl3), δC, ppm: 20.29 q [(CH3)2CH], 25.93 d
[CH(CH3)2], 100.52 d (C9), 113.99 d (C3′), 114.63 d
(C6), 114.75 d (C4′), 115.88 s (C4a), 117.80 s (C6′),
121.57 d (C4), 122.61 q (CF3), 122.86 d (C5′), 124.15 s
(C3a), 125.72 s (C3), 142.85 s (C1′), 143.53 d (C5);
153.06 s, 156.96 s, 157.57 s, 160.38 s (C2, C7, C8a,
C9a); 163.57 d (C2′). Found, %: C 61.03; H 4.09;
F 15.28; N 3.13. C21H15F4NO3. Calculated, %:
C 62.23; H 3.73; F 18.75; N 3.46.
3-(3-Chlorophenylamino)-2-isopropyl-7H-furo-
[3,2-g]chromen-7-one (IIIc) was synthesized as de-
scribed above in a from 200 mg (0.5 mmol) of com-
pound I and 127 mg (1 mmol) of 3-chloroaniline (IIc).
Yield 109 mg (58%), mp 113–114°C (from diethyl
ether). IR spectrum, ν, cm–1: 3464, 3370, 3060, 2970,
2930, 2874, 1723, 1652, 1623, 1596, 1538, 1484,
1450, 1397, 1319, 1255, 1142, 1121, 1098, 1077, 992,
888, 853, 824, 770, 681. UV spectrum (EtOH), λmax
,
nm (logε): 223 (4.12), 242 (4.33), 288 (3.89), 333
1
(3.69). H NMR spectrum (CDCl3), δ, ppm: 1.27 d
[6H, (CH3)2CH, J = 7.0 Hz], 3.09 m [1H, CH(CH3)2],
4.05 br.s (1H, NH), 6.31 d (1H, 6-H, J = 9.8 Hz),
6.97 d.d (1H, 4′-H, J = 7.5, 2.2 Hz), 7.19 s (1H, 9-H),
7.26 t (1H, 5′-H, J = 7.5 Hz), 7.38 d.d (1H, 6′-H, J =
7.5, 1.6 Hz), 7.50 s (1H, 4-H), 7.75 d (1H, 5-H, J =
9.8 Hz), 7.99 d.d (1H, 2′-H, J = 2.2, 1.6 Hz). 13C NMR
spectrum (CDCl3), δC, ppm: 20.39 q [(CH3)2CH],
25.28 d [CH(CH3)2], 99.04 d (C9), 114.21 d (C6),
114.40 s (C4a), 114.96 d (C2′), 121.65 d (C4), 121.81 s
(C3a), 123.72 d (C6′), 125.10 s (C3), 129.41 d (C4′),
134.06 d (C5′), 138.37 s (C3′), 143.10 d (C5), 144.41 s
(C1′); 151.12 s, 157.79 s, 160.45 s (C2, C7, C8a, C9a).
Found, %: Cl 10.58; N 4.13. C20H16ClNO3. Calculated,
%: Cl 10.02; N 3.96.
3-(5-Fluoro-2-trifluoromethylphenylamino)-2-
isopropyl-7H-furo[3,2-g]chromen-7-one (IIIf) was
synthesized as described above in a from 200 mg
(0.5 mmol) of compound I and 178 mg (1 mmol) of
5-fluoro-2-trifluoromethylaniline (IIf). Yield 80 mg
(37%), oily substance. IR spectrum, ν, cm–1: 3438,
3060, 2939, 2881, 1731, 1660, 1633, 1579, 1429,
1250, 1201, 1139, 1115, 1047, 868, 821, 601. UV
spectrum (EtOH), λmax, nm (logε): 202 (4.3), 250
3-(3-Fluorophenylamino)-2-isopropyl-7H-furo-
[3,2-g]chromen-7-one (IIId) was synthesized as de-
scribed above in a from 200 mg (0.5 mmol) of com-
pound I and 111 mg (1 mmol) of 3-fluoroaniline (IId).
Yield 99 mg (55%), mp 115–116°C. IR spectrum, ν,
cm–1: 3365, 3081, 2971, 2929, 2878, 1720, 1696, 1625,
1508, 1456, 1430, 1340, 1330, 1052, 905, 879, 825,
665. UV spectrum (EtOH), λmax, nm (logε): 221 (4.09),
1
1
238 (4.21), 286 (3.77), 330 (3.65). H NMR spectrum
(4.44), 285 (3.99), 334 (3.84). H NMR spectrum
(CDCl3), δ, ppm: 1.27 d [6H, (CH3)2CH, J = 7.0 Hz],
3.08 m [1H, CH(CH3)2], 3.81 br.s (1H, NH), 6.31 d
(1H, 6-H, J = 9.7 Hz), 6.66 m (1H, 4′-H), 6.88 m (1H,
2′-H, JHF = 9.8 Hz), 7.08 d.d (1H, 6′-H, J = 7.8,
1.6 Hz), 7.19 s (1H, 9-H), 7.35 m (1H, 5′-H, J = 2.2,
1.6 Hz), 7.50 s (1H, 4-H), 7.74 d (1H, 5-H, J =
9.7 Hz). 13C NMR spectrum (CDCl3), δC, ppm: 20.50 q
[(CH3)2CH], 25.23 d [CH(CH3)2], 104.87 d (C9),
(CDCl3), δ, ppm: 1.24 d [6H, (CH3)2CH, J = 7.0 Hz],
3.05 m [1H, CH(CH3)2], 4.08 br.s (1H, NH), 6.28 d
(1H, 6-H, J = 9.8 Hz), 6.57 d (1H, 6′-H, J = 8.8 Hz),
7.00 d.d (1H, 4′-H, J = 8.8, 7.8 Hz), 7.16 s (1H, 9-H),
7.54 s (1H, 4-H), 7.66 t (1H, 3′-H, J = 7.8 Hz), 7.71 d
(1H, 5-H, J = 9.8 Hz). 13C NMR spectrum (CDCl3), δC,
ppm: 20.66 q [(CH3)2CH], 23.02 d [CH(CH3)2],
99.43 d (C9), 111.01 d and 111.47 d (C4′, C6′), 112.74 s
(C2′); 114.29 d and 114.48 d (C6, C3′), 115.56 s (C4a),
116.79 s (C3a), 122.16 q (CF3, J = 287.8 Hz), 123.73 d
(C4), 125.72 s (C3), 139.32 s (C1′), 143.21 d (C5);
109.10 d (C2′, JCF = 9.5 Hz), 110.09 d (C4′, JCF
=
9.2 Hz), 111.19 d (C6′), 114.14 d (C6), 115.88 s (C4a),
119.30 d (C4), 121.61 s (C3a), 130.65 s (C3), 141.49 d
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PLANT COUMARINS: VII.
1397
144.49 s, 151.20 s, 159.86 s, 160.49 s (C2, C7, C8a,
C9a); 163.45 d (C5′, JCF = 261.7 Hz). Found, %:
C 59.93; H 3.39; F 17.08; N 3.23. C21H15F4NO3. Cal-
culated, %: C 62.23; H 3.73; F 18.75; N 3.46.
C7, C8a, C9a). 19F NMR spectrum, δF, ppm: 32.51 m
(CF3), 100.43 d (F). Found, %: C 62.02; H 3.99;
F 18.35; N 3.06. C21H15F4NO3. Calculated, %:
C 62.23; H 3.73; F 18.75; N 3.46.
3-(4-Fluoro-2-trifluoromethylphenylamino)-2-
isopropyl-7H-furo[3,2-g]chromen-7-one (IIIg) was
synthesized as described above in a from 200 mg
(0.5 mmol) of compound I and 178 mg (1 mmol) of
4-fluoro-2-trifluoromethylaniline (IIg) (reaction time
7 h). Yield 67 mg (31%), oily substance. IR spectrum,
ν, cm–1: 3440, 3061, 2927, 1731, 1659, 1633, 1550,
1429, 1348, 1288, 1250, 1201, 1140, 1115, 958, 868,
821. UV spectrum (EtOH), λmax, nm (logε): 200 (4.75),
2-Isopropyl-3-[4-methyl-3-(trifluoromethyl)-
phenylamino]-7H-furo[3,2-g]chromen-7-one (IIIi)
was synthesized as described above in a from 200 mg
(0.5 mmol) of compound I and 175 mg (1 mmol) of
4-methyl-3-trifluoromethylaniline (IIi) (reaction time
5 h). Yield 141 mg (66%), mp 121–122°C (from
diethyl ether). IR spectrum, ν, cm–1: 3430, 3403, 2931,
1731, 1650, 1633, 1321, 1288, 1250, 1201, 1139, 958,
868, 820, 761, 707. UV spectrum (EtOH), λmax, nm
(logε): 201 (4.61), 239 sh (4.32), 252 (4.33), 300 sh
1
252 (4.89), 284 (4.44), 334 (4.29). H NMR spectrum
1
(4.06), 337 (3.91), 350 sh (3.85). H NMR spectrum
(CDCl3), δ, ppm: 1.38 d [6H, (CH3)2CH, J = 7.0 Hz],
3.27 m [1H, CH(CH3)2], 3.92 br.s (1H, NH), 6.42 d
(1H, 6-H, J = 9.8 Hz), 7.00 d (1H, 6′-H, J = 8.6 Hz),
7.03 d (1H, 5′-H, J = 8.6 Hz), 7.14 s (1H, 9-H), 7.15 s
(1H, 3′-H), 7.58 s (1H, 4-H), 7.80 d (1H, 5-H, J =
9.8 Hz). 13C NMR spectrum (CDCl3), δC, ppm: 20.64 q
[(CH3)2CH], 23.83 d [CH(CH3)2], 100.09 d (C9),
111.66 d (C3), 112.16 s (C5′), 114.46 d and 114.63 d
(C6, C4a), 116.55 s (C3a), 118.32 d (C3′), 121.32 s (C6′),
122.87 d (C2′), 122.95 q (CF3, J = 286.1 Hz), 123.92 d
(C4), 136.35 s (C1′), 144.65 d (C5); 143.37 s, 151.37 s,
158.06 s, 161.19 s (C2, C7, C8a, C9a); 160.64 d (C4′,
JCF = 259.7 Hz). Found, %: C 60.03; H 4.09; F 18.28;
N 3.33. C21H15F4NO3. Calculated, %: C 62.23; H 3.73;
F 18.75; N 3.46.
(CDCl3), δ, ppm: 1.23 d [6H, (CH3)2CH, J = 7.0 Hz],
2.25 s (3H, CH3), 3.11 m [1H, CH(CH3)2], 3.74 br.s
(1H, NH), 6.25 d (1H, 6-H, J = 9.8 Hz), 7.04 d (1H,
5′-H, J = 7.2 Hz), 7.10 s (1H, 9-H), 7.22 d.d (1H, 6′-H,
J = 7.2, 2.0 Hz), 7.39 d (1H, 2′-H, J = 2.0 Hz), 7.42 s
(1H, 4-H), 7.64 d (1H, 5-H, J = 9.8 Hz). 13C NMR
spectrum (CDCl3), δC, ppm: 20.57 q [(CH3)2CH,
4′-CH3], 26.24 d [CH(CH3)2], 100.81 d (C9), 110.65 d
(C2′), 114.35 s (C4a), 115.84 d (C6), 116.95 d (C4),
117.80 s (C4′), 119.32 s (C3a), 122.01 q (CF3), 123.61 d
(C6′), 125.31 s (C3), 131.15 s (C3′), 132.51 d (C5′),
136.16 s (C1′), 143.80 d (C5); 143.90 s, 152.39 s,
157.20 s, 160.76 s (C2, C7, C8a, C9a). Found, %:
F 14.00; N 3.06. C22H18F3NO3. Calculated, %: F 14.20;
N 3.49.
3-(4-Fluoro-3-trifluoromethylphenylamino)-2-
isopropyl-7H-furo[3,2-g]chromen-7-one (IIIh) was
synthesized as described above in a from 200 mg
(0.5 mmol) of trifluoromethanesulfonate I and 178 mg
(1 mmol) of 4-fluoro-3-trifluoromethylaniline (IIh).
Yield 103 mg (48%), mp 123–124°C (from diethyl
ether). IR spectrum, ν, cm–1: 3428, 3062, 2852, 1729,
1626, 1574, 1483, 1325, 1290, 1141, 1103, 910, 825,
753, 701. UV spectrum (EtOH), λmax, nm (logε): 202
2-Isopropyl-3-[4-methylsulfanyl-3-(trifluoro-
methyl)phenylamino]-7H-furo[3,2-g]chromen-7-one
(IIIj) was synthesized as described above in a from
200 mg (0.5 mmol) of compound I and 207 mg
(1 mmol) of 4-methylsulfanyl-3-trifluoromethylaniline
(IIj) (reaction time 4 h). Yield 170 mg (74%), mp 138–
139°C (from diethyl ether). IR spectrum, ν, cm–1:
3337, 3185, 3058, 2962, 2952, 1735, 1727, 1681,
1624, 1573, 1483, 1350, 1334, 1289, 1252, 1139,
1120, 1101, 1043, 908, 823, 745, 724, 695. UV
spectrum (EtOH), λmax, nm (logε): 206 (4.38), 239
(4.26), 251 (4.28), 295 sh (3.91), 337 (3.86), 350 sh
1
(4.48), 253 (4.25), 297 (3.90), 337 (3.90). H NMR
spectrum (CDCl3), δ, ppm: 1.20 d [6H, (CH3)2CH, J =
7.0 Hz], 3.02 m [1H, CH(CH3)2], 4.04 br.s (1H, NH),
6.24 d (1H, 6-H, J = 9.8 Hz), 7.12 s (1H, 9-H), 7.40 m
(1H, 5′-H), 7.43 s (1H, 4-H), 7.47 d.d (1H, 6′-H, J =
8.6, 2.2 Hz), 7.67 d (1H, 5-H, J = 9.8 Hz), 8.20 m (1H,
2′-H). 13C NMR spectrum (CDCl3), δC, ppm: 20.28 q
[(CH3)2CH], 21.85 d [CH(CH3)2], 99.92 d (C9),
110.10 d (C2′), 114.09 d (C6), 114.31 s (C4a), 114.50 d
(C5′), 117.27 d (C3′), 117.79 d (C4), 119.91 q (CF3, J =
287.6 Hz), 120.56 s (C3a), 121.75 d (C6′), 128.63 s
1
(3.80). H NMR spectrum (CDCl3), δ, ppm: 1.28 d
[6H, (CH3)2CH, J = 7.0 Hz], 2.55 s (3H, CH3S),
3.09 m [1H, CH(CH3)2], 3.74 br.s (1H, NH), 6.31 d
(1H, 6-H, J = 9.8 Hz), 7.19 s (1H, 9-H), 7.21 d.d (1H,
6′-H, J = 7.5, 1.2 Hz), 7.46 d (1H, 5′-H, J = 7.5 Hz),
7.48 s (1H, 4-H), 7.75 d (1H, 5-H, J = 9.8 Hz), 7.82 s
(1H, 2′-H, J = 1.2 Hz). 13C NMR spectrum (CDCl3),
δC, ppm: 19.48 q (CH3S), 20.29 q [(CH3)2CH], 25.93 d
[CH(CH3)2], 100.52 d (C9), 113.23 d (C2′), 113.34 s
(C3), 137.37 s (C1′), 143.38 d (C5), 154.18 d (C4′, JCF
269.6 Hz); 143.22 s, 144.47 s, 157.89 s, 160.77 s (C2,
=
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

LIPEEVA et al.
1398
(C4a), 115.57 d (C6), 116.04 d (C4), 116.75 s (C4′),
118.99 s (C3a), 120.07 d (C6′), 122.01 q (CF3), 125.04 s
(C3), 126.18 d (C5′), 130.80 s (C3′), 134.40 s (C1′),
143.56 d (C5); 145.12 s, 152.23 s, 156.95 s, 160.39 s
(C2, C7, C8a, C9a). Found, %: F 14.00; N 3.06;
S 7.12. C22H18F3NO3S. Calculated, %: F 13.15;
N 3.23; S 7.40.
5′-H, J = 7.7, 1.2 Hz), 7.50 s (1H, 4-H), 7.67 d (1H,
5-H, J = 9.8 Hz). 13C NMR spectrum (CDCl3), δC,
ppm: 20.63 q [(CH3)2CH], 21.44 d [CH(CH3)2],
99.76 d (C9), 107.85 s (C3), 113.93 d (C3a), 114.26 d
(C6), 114.45 s (C4a), 115.57 d (C6), 116.52 d (C6′),
116.74 d (C2′), 117.41 s (C4′), 118.65 q (CF3), 122.47 d
(C4), 125.36 d (C5′), 128.48 s (C1′), 144.46 d (C5);
143.17 s, 151.17 s, 157.98 s, 160.65 s (C2, C7, C8a,
C9a). Found, %: F 11.56; N 5.33. C26H25F3N2O3. Cal-
culated, %: F 12.11; N 5.95.
2-Isopropyl-3-[2-morpholino-5-(trifluoromethyl)-
phenylamino]-7H-furo[3,2-g]chromen-7-one (IIIk)
was synthesized as described above in a from 200 mg
(0.5 mmol) of compound I and 246 mg (1 mmol) of
2-morpholino-5-trifluoromethylaniline (IIk) (reaction
time 6 h). Yield 113 mg (45%), oily substance. IR
spectrum, ν, cm–1: 3463, 3297, 3078, 2969, 2855,
2743, 1738, 1626, 1578, 1531, 1483, 1470, 1436,
1354, 1331, 1285, 1246, 1157, 1140, 1031, 910, 852,
828, 758, 639. UV spectrum (EtOH), λmax, nm (logε):
228 (3.99), 231 (4.02), 252 (4.21), 295 (3.79), 339
2-Isopropyl-3-(quinolin-6-ylamino)-7H-furo-
[3,2-g]chromen-7-one (VII). Compound I, 200 mg
(0.5 mmol), was dissolved in 3 ml of anhydrous DMF,
144 mg (1 mmol) of quinolin-6-amine (IV), 2.2 mg
(2 mol %) of palladium(II) acetate, 34 mg (8 mol %) of
BINAP, and 0.07 ml (1.3 equiv) of triethylamine were
added under stirring in a stream of argon, and the mix-
ture was heated for 6 h at 115°C (TLC) and evaporat-
ed. The product was isolated by column chromatog-
raphy on silica gel. Yield 88 mg (45%), mp 130–131°C
(from diethyl ether). IR spectrum, ν, cm–1: 3408, 3319,
3186, 3059, 2958, 2850, 1730, 1676, 1630, 1581,
1506, 1431, 1378, 1335, 1294, 1224, 1182, 1136, 1101,
1059, 960, 902, 874, 835, 791, 754, 656. UV spectrum
(EtOH), λmax, nm (logε): 207 (4.41), 244 (4.58), 274
(3.90), 285 (3.89), 321 (3.67), 335 (3.62), 351 (3.88).
1H NMR spectrum (CDCl3), δ, ppm: 1.23 d [6H,
(CH3)2CH, J = 7.0 Hz], 3.05 m [1H, CH(CH3)2],
6.27 d (1H, 6-H, J = 9.8 Hz), 7.15 s (1H, 9-H), 7.23–
7.33 m (2H, 3′-H, 7′-H), 7.46 s (1H, 4-H), 7.70 d (1H,
5-H, J = 9.8 Hz), 7.75 d (1H, 8′-H, J = 8.8 Hz), 7.85 d
(1H, 5′-H, J = 1.8 Hz), 7.87 d.d (1H, 4′-H, J = 5.8,
0.8 Hz), 9.05 d.d (1H, 2′-H, J = 5.8, 1.6 Hz). 13C NMR
spectrum (CDCl3), δC, ppm: 20.75 q [(CH3)2CH],
22.08 d [CH(CH3)2], 99.52 d (C9), 110.20 d (C3′),
114.69 s (C4a), 115.13 d (C6), 117.18 d (C4), 120.83 s
(C3a), 121.23 d, 121.79 d (C5′, C8′), 125.97 s (C3),
130.50 d (C7′), 131.00 s (C4a′), 137.90 d (C4′), 139.14 s
(C8a′), 141.77 d (C6′), 142.20 d (C2′), 144.55 d (C5),
151.26 s (C8a), 156.95 s (C9a), 157.98 s (C2), 160.63 s
(C7). Found, %: C 75.12; H 4.71; N 6.80. C23H18N2O3.
Calculated, %: C 74.58; H 4.90; N 7.56.
1
(3.80), 361 sh (3.71). H NMR spectrum (CDCl3), δ,
ppm: 1.19 d [6H, (CH3)2CH, J = 7.0 Hz], 3.00 m [1H,
CH(CH3)2], 3.40–3.70 m (9H, NCH2CH2O, NH),
6.23 d (1H, 6-H, J = 9.8 Hz), 6.92 d (1H, 3′-H, J =
8.8 Hz), 7.11 s (1H, 9-H), 7.31 d.d (1H, 4′-H, J = 8.8,
1.9 Hz), 7.42 s (1H, 4-H), 7.47 s (1H, 6′-H, J =
1.9 Hz), 7.66 d (1H, 5-H, J = 9.8 Hz). 13C NMR spec-
trum (CDCl3), δC, ppm: 29.61 q [(CH3)2CH], 31.05 d
[CH(CH3)2], 50.98 t (CH2N), 67.41 t (CH2O), 100.86 d
(C9), 107.17 d (C6′), 113.72 s (C4a), 113.99 d (C3′),
114.56 d (C6), 115.55 d (C4), 119.50 d (C4′), 120.86 q
(CF3), 124.31 s (C3a), 125.26 s (C5′), 127.31 s (C3),
140.20 s and 141.22 s (C1′, C2′), 143.53 d (C5);
142.32 s, 152.99 s, 159.87 s, 160.94 s (C2, C7, C8a,
C9a). Found, %: F 11.97; N 6.48. C25H23F3N2O4. Calcu-
lated, %: F 12.06; N 5.93.
2-Isopropyl-3-[2-piperidino-6-(trifluoromethyl)-
phenylamino]-7H-furo[3,2-g]chromen-7-one (IIIl)
was synthesized as described above in a from 200 mg
(0.5 mmol) of compound I and 244 mg (1 mmol) of
2-piperidino-6-trifluoromethylaniline (IIl) (reaction
time 6 h). Yield 123 mg (49%), mp 132–133°C (from
diethyl ether). IR spectrum, ν, cm–1: 3400, 3180, 3066,
2952, 2854, 1726, 1672, 1624, 1571, 1555, 1484,
1466, 1450, 1392, 1351, 1331, 1289, 1191, 1143, 1101,
1080, 946, 910, 824, 756, 742, 700. UV spectrum
(EtOH), λmax, nm (logε): 203 (4.46), 254 (4.40), 299
Compounds VIII and IX were synthesized in
a similar way.
1
(4.00), 307 (3.99), 345 (4.02). H NMR spectrum
2-Isopropyl-3-(quinolin-8-ylamino)-7H-furo-
[3,2-g]chromen-7-one (VIII) was synthesized from
200 mg (0.5 mmol) of compound I and 144 mg
(1 mmol) of quinolin-8-amine (V). Yield 63 mg (32%).
IR spectrum, ν, cm–1: 3451, 3352, 3063, 3038, 2963,
2874, 2853, 1726, 1711, 1680, 1628, 1600, 1576,
(CDCl3), δ, ppm: 1.20 d [6H, (CH3)2CH, J = 7.0 Hz],
1.42–1.58 m (6H, CH2), 3.02 m [1H, CH(CH3)2],
3.02–3.35 m (5H, NCH2, NH), 6.24 d (1H, 6-H, J =
9.8 Hz), 6.41 d.d (1H, 3′-H, J = 7.8, 1.2 Hz), 7.06 t
(1H, 4′-H, J = 7.8 Hz), 7.12 s (1H, 9-H), 7.38 d.d (1H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

PLANT COUMARINS: VII.
1399
1528, 1506, 1500, 1472, 1371, 1155, 1142, 1120, 1103,
1043, 822, 791, 758, 748. UV spectrum (EtOH), λmax
2 mol % of palladium(II) acetate, 8 mol % of BINAP,
and 0.07 ml (1.3 equiv) of triethylamine were added
under stirring in a stream of argon, and the mixture
was heated for 7 h at 115°C until initial compound I
disappeared (TLC) and evaporated. The residue was
subjected to column chromatography on silica gel to
isolate 132 mg (68%) of compound XII.
,
nm (logε): 205 (4.32), 250 (4.51), 299 (3.68), 307
1
(3.99), 338 (4.18), 351 (4.15). H NMR spectrum
(CDCl3), δ, ppm: 1.27 d [6H, (CH3)2CH, J = 7.0 Hz],
3.15 m [1H, CH(CH3)2], 4.04 br.s (1H, NH), 6.24 d
(1H, 6-H, J = 9.6 Hz), 6.83 d (1H, 5′-H, J = 7.1 Hz),
7.01 d (1H, 7′-H, J = 7.1 Hz), 7.19 m (2H, 3′-H, 6′-H),
7.22 s (1H, 9-H), 7.43 s (1H, 4-H), 7.64 d (1H, 5-H,
J = 9.6 Hz), 7.93 d (1H, 4′-H), 8.59 d (1H, 2′-H).
13C NMR spectrum (CDCl3), δC, ppm: 20.07 q
[(CH3)2CH], 25.69 d [CH(CH3)2], 100.10 d (C9),
110.10 d (C5′), 115.11 s (C6), 115.79 d (C7′), 115.94 s
(C4a), 116.46 d (C4), 120.96 d (C3′), 126.08 d (C3a),
127.16 d (C6′), 128.66 s (C3), 134.74 s (C4a′), 136.03 d
(C4′), 138.01 s (C8a), 140.56 s (C8′), 143.71 d (C5),
147.06 d (C2′), 151.94 s, 153.08 s (C8a, C9a), 156.90 s
(C2), 160.78 s (C7). Found, %: C 74.42; H 4.62;
N 7.10. C23H18N2O3. Calculated, %: C 74.58; H 4.90;
N 7.56.
b. Compound I, 200 mg (0.5 mmol), was dissolved
in 3 ml of anhydrous DMF, 160 mg (1 mmol) of ana-
basine (X), 44 mg (8 mol %) of Xantphos, 4.4 mg
(4 mol %) of palladium(II) acetate, and 0.07 ml
(1.3 equiv) of triethylamine were added under stirring
in a stream of argon, and the mixture was stirred for
7 h at 115°C and evaporated. By column chromatog-
raphy on silica gel we isolated 118 mg (53%) of com-
pound XII, mp 135–136°C, [α]D20 = –33.6° (c = 1.0,
CHCl3). IR spectrum, ν, cm–1: 3431, 3054, 2980, 2931,
2854, 1732, 1631, 1579, 1456, 1429, 1388, 1348,
1321, 1288, 1201, 1140, 1115, 1047, 920, 868, 819,
720. UV spectrum (EtOH), λmax, nm (logε): 202 (4.53),
1
2-Isopropyl-3-(isoquinolin-5-ylamino)-7H-furo-
[3,2-g]chromen-7-one (IX) was synthesized from
200 mg (0.5 mmol) of trifluoromethanesulfonate I and
144 mg (1 mmol) of isoquinolin-5-amine (VI). Yield
95 mg (48%). IR spectrum, ν, cm–1: 3516, 3070, 3059,
3040, 2877, 1729, 1713, 1677, 1630, 1576, 1511,
1484, 1357, 1335, 1280, 1246, 1160, 1145, 1107, 1047,
1031, 980, 960, 950, 920, 823, 772, 759, 639. UV
spectrum (EtOH), λmax, nm (logε): 223 (3.94), 228
(3.96), 234 (4.05), 252 (4.30), 297 (3.81), 308 (3.83),
250 (4.47), 284 (3.99), 332 (3.82). H NMR spectrum
(CDCl3), δ, ppm: 1.27 d [6H, (CH3)2CH, J = 7.0 Hz],
1.40–1.68 m (4H, 5′-H, 6′-H), 1.70–1.90 m (2H, 3′-H),
2.72 m (1H, 6′-H), 3.14 m [2H, 6′-H, CH(CH3)2],
3.67 d.d (1H, 2′-H, J = 3.8, 1.2 Hz), 6.28 d (1H, 6-H,
J = 9.8 Hz), 6.12 m (1H, 5″-H), 7.28 s (1H, 9-H),
7.48 s (1H, 4-H), 7.72 d (1H, 5-H, J = 9.8 Hz), 7.33 m
(1H, 4″-H), 8.33 m (1H, 6″-H), 8.49 br.s (1H, 2″-H).
13C NMR spectrum (CDCl3), δC, ppm: 20.07 q
[(CH3)2CH], 23.41 d [CH(CH3)2], 23.89 t (C4″), 25.72 t
(C5′), 32.36 t (C3′), 46.41 t (C6′), 58.96 d (C2′), 100.26 d
(C9), 110.64 s (C4a), 115.29 d (C6), 115.86 s (C3a),
119.95 d (C4), 123.51 d (C5″), 126 s (C3), 134.94 d
(C4″), 140.47 s (C3″), 141.44 d (C5), 148.57 d and
148.93 d (C2″, C6″); 143.48 s, 152.02 s, 156.76 s,
160.19 s (C2, C7, C8a, C9a). Found, %: C 73.30; H 6.06;
N 7.12. C24H24N2O3. Calculated, %: C 74.21; H 6.23;
N 7.21.
1
342 (3.99), 353 (3.99). H NMR spectrum (CDCl3), δ,
ppm: 1.24 d [6H, (CH3)2CH, J = 7.0 Hz], 3.04 m [1H,
CH(CH3)2], 3.92 br.s (1H, NH), 6.25 d (1H, 6-H, J =
9.7 Hz), 7.14 s (1H, 9-H), 7.28 t (1H, 7′-H, J =
7.7 Hz), 7.41 d (1H, 6′-H, J = 7.7 Hz), 7.43 d (1H,
8′-H, J = 7.7, 1.6 Hz), 7.45 s (1H, 4-H), 7.71 d (1H,
5-H, J = 9.7 Hz), 8.21 d (1H, 4′-H, J = 6.2 Hz),
8.37 d.d (1H, 3′-H, J = 6.2, 0.8 Hz), 8.75 br.s (1H,
1′-H). 13C NMR spectrum (CDCl3), δC, ppm: 20.20 q
[(CH3)2CH], 25.94 d [CH(CH3)2], 100.52 d (C9),
104.84 d (C6′), 109.55 d (C8′), 113.15 s (C4a); 114.11 d,
115.57 d, 116.60 d (C4, C6, C4′); 124.93 s (C3a), 125.76 s
(C8a′), 127.86 s (C3), 130.63 d (C7′), 132.57 s (C4a′),
142.93 s (C5′), 143.20 d (C3′), 143.52 d (C5), 145.82 s
(C9a), 153.06 s (C8a), 156.91 s (C2), 161.29 s (C7),
164.24 s (C1′). Found, %: C 75.07; H 5.06; N 7.60.
C23H18N2O3. Calculated, %: C 74.58; H 4.90; N 7.56.
tert-Butyl 4-(2-isopropyl-7-oxo-7H-furo[3,2-g]-
chromen-3-yl)piperazine-1-carboxylate (XIIIa).
a. Compound I, 200 mg (0.5 mmol), was dissolved in
3 ml of anhydrous DMF, 186 mg (1 mmol) of tert-
butyl piperazine-1-carboxylate (XIa), 2.2 mg
(2 mol %) of palladium(II) acetate, 34 mg (8 mol %) of
BINAP, and 0.07 ml (1.3 equiv) of triethylamine were
added under stirring in a stream of argon, and the
mixture was heated for 7 h at 115°C until initial com-
pound I disappeared (TLC) and evaporated. The resi-
due was subjected to column chromatography on silica
gel to isolate 88 mg (43%) of compound XIIIa.
2-Isopropyl-3-[2-(pyridin-3-yl)piperidin-1-yl]-
7H-furo[3,2-g]chromen-7-one (XII). a. Compound I,
200 mg (0.5 mmol), was dissolved in 3 ml of anhy-
drous DMF, 160 mg (1 mmol) of anabasine (X),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

LIPEEVA et al.
1400
due was subjected to column chromatography on silica
b. Compound I, 200 mg (0.5 mmol), was dissolved
gel. Yield 71 mg (44%), mp 132–133°C. IR spectrum,
ν, cm–1: 3435, 3100, 3057, 2980, 2931, 2881, 2854,
2802, 1732, 1689, 1632, 1620, 1581, 1462, 1429,
1388, 1348, 1300, 1288, 1250, 1203, 1140, 1100,
1047, 900, 868, 822, 779, 760, 700, 680, 626. UV
spectrum (EtOH), λmax, nm (logε): 203 (4.14), 250
in 3 ml of anhydrous DMF, 167 mg (0.9 mmol) of tert-
butyl piperazine-1-carboxylate (XIa), 44 mg (8 mol %)
of Xantphos, 4.4 mg (4 mol %) of palladium(II)
acetate, and 0.07 ml (1.3 equiv) of triethylamine were
added under stirring in a stream of argon, and the mix-
ture was heated for 7 h at 115°C and evaporated. The
residue was subjected to column chromatography on
silica gel to isolate 92 mg (45%) of XIIIa. When
140 mg (0.75 mmol) of piperazine XIa was added in
70-mg portions through a time interval of 2 h (the first
portion was added in 30 min after addition of all other
reagents), the yield of XIIIa was 82 mg (40%).
1
(4.31), 284 (3.86), 331 (3.70). H NMR spectrum
(CDCl3), δ, ppm: 1.34 d [6H, (CH3)2CH, J = 7.0 Hz],
2.21 s (3H, CH3), 2.32 m (4H, 3′-H, 5′-H), 2.84 m (4H,
2′-H, 6′-H), 3.22 m [1H, CH(CH3)2], 6.37 d (1H, 6-H,
J = 9.7 Hz), 7.36 s (1H, 9-H), 7.53 s (1H, 4-H), 7.76 d
(1H, 5-H, J = 9.7 Hz). 13C NMR spectrum (CDCl3), δC,
ppm: 20.23 q [(CH3)2CH], 25.86 d [CH(CH3)2],
45.13 q (CH3), 46.36 t (C2′, C6′), 54.65 t (C3′, C5′),
100.44 d (C9), 109.09 s (C3a), 114.26 s (C4a), 115.50 d
(C6), 118.91 d (C4), 120.23 s (C3), 143.52 d (C5);
144.82 s, 152.66 s, 156.75 s, 160.31 (C2, C7, C8a, C9a).
Found, %: C 68.85; H 6.35; N 8.45. C19H22N2O3. Cal-
culated, %: C 69.92; H 6.79; N 8.58.
c. Compound I, 200 mg (0.5 mmol), was dissolved
in 3 ml of anhydrous DMF, 186 mg (1 mmol) of piper-
azine XIa, 2.2 mg (2 mol %) of palladium(II) acetate,
10 mg (8 mol %) of tris(tert-butyl)phosphine, and
0.07 ml (1.3 equiv) of triethylamine were added under
stirring in a stream of argon, and the mixture was
heated for 7 h at 115°C and evaporated. Column chro-
matography of the residue on silica gel gave 72 mg
(35%) of XIIIa, mp 152–153°C (from diethyl ether).
IR spectrum, ν, cm–1: 3434, 3080, 2979, 2933, 2860,
1732, 1691, 1635, 1579, 1550, 1470, 1429, 1390,
1367, 1348, 1286, 1249, 1211, 1197, 1171, 1140, 1117,
1047, 1009, 868, 820, 790, 602. UV spectrum (EtOH),
λmax, nm (logε): 212 (3.99), 250 (4.26), 285 (3.77), 330
(2S,5R,6R)-6-(2-Isopropyl-7-oxo-7H-furo[3,2-g]-
chromen-3-ylamino)-3,3-dimethyl-7-oxo-4-thia-1-
azabicyclo[3.2.0]heptane-2-carboxylic acid (XVI).
Compound I, 200 mg (0.5 mmol), was dissolved in
3 ml of anhydrous DMF, 216 mg (1 mmol) of
6-aminopenicillanic acid (XIV), 4.4 mg (4 mol %) of
palladium(II) acetate, 34 mg (8 mol %) of BINAP, and
0.07 ml (1.3 equiv) of triethylamine were added under
argon, and the mixture was heated for 6 h at 115°C
until initial compound I disappeared (TLC) and evap-
orated. The residue was subjected to column chroma-
tography on silica gel, and a fraction containing com-
pound XVI was ground with diethyl ether. Yield
145 mg (66%), mp 214–215°C (from diethyl ether),
[α]D20 = –86.4° (c = 0.2, H2O–EtOH, 2:1). IR spectrum,
ν, cm–1: 3430, 3190, 3090, 3062, 2965, 2930, 2874,
1760, 1727, 1710, 1628, 1576, 1483, 1466, 1392,
1355, 1301, 1249, 1187, 1154, 1143, 1104, 1044, 978,
933, 900, 878, 830, 745, 705, 698. UV spectrum
(CHCl3–EtOH, 1:1), λmax, nm (logε): 253 (4.54), 296
1
(3.62). H NMR spectrum (CDCl3), δ, ppm: 1.37 d
[6H, (CH3)2CH, J = 7.0 Hz], 1.43 s (9H, t-Bu), 2.77 m
(4H, 2′-H, 6′-H), 3.14 m [1H, CH(CH3)2], 3.35 m (4H,
3′-H, 5′-H), 6.39 d (1H, 6-H, J = 9.7 Hz), 7.39 s (1H,
9-H), 7.55 s (1H, 4-H), 7.78 d (1H, 5-H, J = 9.7 Hz).
13C NMR spectrum (CDCl3), δC, ppm: 20.25 q
[(CH3)2CH], 25.89 d [CH(CH3)2], 28.36 q [C(CH3)3],
45.77 t (C3′, C5′), 50.35 t (C2′, C6′), 77.51 s [C(CH3)3],
100.44 d (C9), 107.05 s (C3a), 115.55 s (C4a), 116.69 d
(C6), 120.26 d (C4), 121.40 s (C3), 143.39 d (C5);
143.52 s, 152.20 s, 154.74 s, 156.83 s, 160.26 s (C2,
C7, C8a, C9a, C=O). Found, %: C 65.89; H 6.70;
N 6.45. C23H28N2O5. Calculated, %: C 66.97; H 6.84;
N 6.79.
1
(4.13), 310 (4.11), 342 (4.14), 354 (4.15). H NMR
spectrum (DMSO-d6), δ, ppm: 1.33 d [6H, (CH3)2CH,
J = 7.0 Hz], 1.49 s and 1.68 s (3H each, CH3), 3.26 m
[1H, (CH3)2CH], 4.14 s (1H, 2′-H), 4.55 d (1H, 5′-H,
J = 4.7 Hz), 5.38 m (1H, 6′-H, J5′,6′ = 4.7 Hz), 6.44 d
(1H, 6-H, J = 9.8 Hz), 7.72 s (1H, 9-H), 7.85 s (1H,
4-H), 8.19 d (1H, 5-H, J = 9.8 Hz). 13C NMR spectrum
(DMSO-d6), δC, ppm: 20.13 q [(CH3)2CH], 25.60 d
[CH(CH3)2], 26.89 q (CH3), 31.02 q (CH3), 60.37 d
(C6′), 63.20 d (C5′), 67.22 s (C3′), 70.26 d (C2′),
100.56 d (C9), 116.27 s and 116.50 s (C3a, C4a),
2-Isopropyl-3-(4-methylpiperazin-1-yl)-7H-furo-
[3,2-g]chromen-7-one (XIIIb). Compound I, 200 mg
(0.5 mmol), was dissolved in 3 ml of anhydrous DMF,
90 mg (0.9 mmol) of 4-methylpiperazine (XIb), 44 mg
(8 mol %) of Xantphos, 0.07 ml (1.3 equiv) of triethyl-
amine, and 4.4 mg (4 mol %) of palladium(II) acetate
were added under stirring in a stream of argon, and the
mixture was heated for 7 h at 115°C until initial com-
pound I disappeared (TLC) and evaporated. The resi-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

PLANT COUMARINS: VII.
1401
117.92 d (C6), 120.39 d (C4), 126.10 s (C3), 144.45 d
(C5), 151.98 s and 152.43 s (C8a, C9a), 156.56 s (C2),
159.87 s (C7), 169.50 s (C7′), 178.44 s (2′-C=O). Found,
%: C 59.60; H 4.77; N 6.08; S 6.89. C22H22N2O6S.
Calculated, %: C 59.72; H 5.01; N 6.33; S 7.25.
and evaporated. The residue was subjected by column
chromatography on silica gel. Yield 89 mg (36%),
mp 188–189°C (from diethyl ether), [α]D20 = –209.6°
(c = 0.5, H2O–EtOH, 2:1). IR spectrum, ν, cm–1: 3456,
3190, 3063, 2962, 2923, 2853, 1772, 1730, 1626,
1574, 1501, 1485, 1466, 1391, 1350, 1325, 1290,
1254, 1186, 1141, 1103, 1049, 943, 910, 876, 846, 826,
744, 710, 698. UV spectrum (EtOH), λmax, nm (logε):
204 (4.06), 222 (3.95), 251 (4.17), 297 (3.70), 308
Methyl (2S,5R,6R)-6-(2-isopropyl-7-oxo-7H-
furo[3,2-g]chromen-3-ylamino)-3,3-dimethyl-7-oxo-
4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
(XVII). Compound I, 200 mg (0.5 mmol), was dis-
solved in 3 ml of anhydrous DMF, 230 mg (1 mmol) of
6-aminopenicillanic acid methyl ester (XV), 4.4 mg
(4 mol %) of palladium(II) acetate, 34 mg (8 mol %) of
BINAP, and 0.07 ml (1.3 equiv) of triethylamine were
added under argon, and the mixture was heated for 6 h
at 115°C until initial compound I disappeared (TLC)
and evaporated. The residue was subjected to column
chromatography on silica gel. Yield 104 mg (48%),
mp 184–185°C (from diethyl ether), [α]D20 = +206.4°
(c = 0.5, CHCl3). IR spectrum, ν, cm–1: 3326, 2976,
2958, 2931, 2875, 1783, 1739, 1675, 1579, 1506,
1456, 1432, 1324, 1286, 1213, 1135, 1116, 1072, 1047,
1029, 929, 871, 819, 752, 665. UV spectrum (EtOH),
λmax, nm (logε): 192 (3.31), 209 (3.74), 243 (3.68), 250
1
(3.68), 343 (3.79), 353 (3.80). H NMR spectrum
(DMSO-d6), δ, ppm: 1.27 d [6H, (CH3)2CH, J =
7.0 Hz], 2.09 s (3H, CH3), 3.09 m [1H, (CH3)2CH],
3.52–3.69 m (2H, 4′-H), 4.96 m (2H, CH2), 5.15 m
(1H, 6′-H), 5.45 m (1H, 7′-H), 6.40 d (1H, 6-H, J =
9.8 Hz), 7.19 s (1H, 9-H), 7.43 s (1H, 4-H), 7.77 d
(1H, 5-H, J = 9.8 Hz). 13C NMR spectrum (DMSO-d6),
δC, ppm: 20.15 q (CH3), 20.39 q [(CH3)2CH], 22.26 t
(C4′), 23.34 d [CH(CH3)2], 65.25 d (C7′), 67.51 d (C6′),
71.20 t (CH2), 99.30 d (C9), 106.95 s (C4a), 113.90 s
(C3a), 114.33 d (C6), 123.60 s (C2′), 123.63 d (C4),
125.83 s (C3), 129.24 s (C3′), 144.53 d (C5), 146.93 s
and 150.84 s (C8a, C9a), 156.30 s (C2), 158.66 s (C7),
163.16 s (C8′), 165.41 s and 169.78 s (C=O). Found,
%: C 57.46; H 4.89; N 5.09; S 6.67. C24H22N2O8S.
Calculated, %: C 57.82; H 4.45; N 5.62; S 6.43.
1
(3.71), 287 (3.20), 330 (3.12). H NMR spectrum
(CDCl3), δ, ppm: 1.36 d [6H, (CH3)2CH, J = 7.0 Hz],
1.46 s and 1.61 s (3H each, CH3), 3.24 m [1H,
(CH3)2CH], 3.74 s (3H, OCH3), 4.41 d (1H, NH),
4.37 s (1H, 3′-H), 4.54 d (1H, 5′-H, J = 4.8 Hz),
5.48 m (1H, 6′-H), 6.40 d (1H, 6-H, J = 9.8 Hz), 7.40 s
(1H, 9-H), 7.56 s (1H, 4-H), 7.79 d (1H, 5-H, J =
9.8 Hz). 13C NMR spectrum (CDCl3), δC, ppm: 20.40 q
[(CH3)2CH], 23.35 d [CH(CH3)2], 27.24 q (CH3),
30.44 q (CH3), 51.94 q (OCH3), 65.14 d (C6′), 67.09 d
(C5′), 68.33 s (C3′), 75.79 d (C2′), 100.30 d (C9),
109.41 s (C4a), 114.34 d (C6), 114.93 d (C4), 121.25 s
(C3a), 123.23 s (C3), 142.44 d (C5), 144.54 s (C9a),
150.85 s (C8a), 157.39 s (C2), 160.64 s (C7), 165.52 s
(C7′), 171.44 s (2′-C=O). Found, %: C 60.32; H 5.08;
N 5.93; S 7.00. C23H24N2O6S. Calculated, %: C 60.51;
H 5.30; N 6.14; S 7.02.
(6R,7R)-7-(2-Isopropyl-7-oxo-7H-furo[3,2-g]-
chromen-3-ylamino)-3-methyl-8-oxo-5-thia-1-aza-
bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (XXII).
Compound I, 200 mg (0.5 mmol), was dissolved in
3 ml of anhydrous DMF, 214 mg (1 mmol) of 7-amino-
(deacetoxy)cephalosporanic acid (XIX), 4.4 mg
(4 mol %) of palladium(II) acetate, 34 mg (8 mol %) of
BINAP, and 0.07 ml (1.3 equiv) of triethylamine were
added under argon, and the mixture was heated for 6 h
at 115°C until initial compound I disappeared (TLC)
and evaporated. The residue was subjected to column
chromatography on silica gel. Yield 95 mg (42%),
mp 181–182°C (from diethyl ether), [α]D20 = –180.0°
(c = 0.1, H2O–EtOH, 2:1). IR spectrum, ν, cm–1: 3435,
3190, 3090, 3062, 3048, 2980, 2937, 1777, 1732,
1716, 1633, 1579, 1501, 1470, 1454, 1388, 1348,
1321, 1286, 1250, 1211, 1198, 1140, 1115, 1068, 1047,
902, 869, 835, 810, 780, 765, 745, 698, 648, 626, 602.
UV spectrum (EtOH), λmax, nm (logε): 200 (4.30), 221
(4.19), 251 (4.41), 295 (3.94), 306 (3.92), 342 (4.03),
(6R,7R)-3-(Acetoxymethyl)-7-(2-isopropyl-7-oxo-
7H-furo[3,2-g]chromen-3-ylamino)-8-oxo-5-thia-1-
azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (XXI).
Compound I, 200 mg (0.5 mmol), was dissolved in
3 ml of anhydrous DMF, 272 mg (1 mmol) of
7-aminocephalosporanic acid (XVIII), 4.4 mg
(4 mol %) of palladium(II) acetate, 34 mg (8 mol %) of
BINAP, and 0.07 ml (1.3 equiv) of triethylamine were
added under argon, and the mixture was heated for 8 h
at 120°C until initial compound I disappeared (TLC)
1
351 (4.04). H NMR spectrum (DMSO-d6), δ, ppm:
1.31 d [6H, (CH3)2CH, J = 7.0 Hz], 1.96 s (3H, CH3),
3.23 m [1H, (CH3)2CH], 3.58 m (2H, 4′-H), 4.69 d.d
(1H, 6′-H, J = 5.0, 1.8 Hz), 4.95 m (1H, 7′-H), 6.46 d
(1H, 6-H, J = 9.8 Hz), 7.77 s (1H, 9-H), 7.87 s (1H,
4-H), 8.20 d (1H, 5-H, J = 9.8 Hz). 13C NMR spectrum
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

LIPEEVA et al.
1402
(DMSO-d6), δC, ppm: 19.77 q (CH3), 20.02 q
[(CH3)2CH], 25.71 d [CH(CH3)2], 29.07 t (C4′),
57.72 d (C7′), 62.30 d (C6′), 100.41 d (C9), 107.83 s
(C4a), 115.31 d (C6), 115.95 s (C3a), 118.23 s (C2′),
123.75 d (C4), 124.50 s (C3), 126.16 s (C3′), 144.43 d
(C5), 152.17 s and 152.53 s (C8a, C9a), 156.63 s (C2),
159.81 s (C7), 165.57 s and 169.41 s (C=O). Found, %:
C 59.32; H 4.89; N 5.93; S 7.00. C22H20N2O6S. Cal-
culated, %: C 59.99; H 4.58; N 6.36; S 7.28.
1H NMR spectrum (CDCl3), δ, ppm: 1.31 d [6H,
(CH3)2CH, J = 7 Hz], 2.03 s (3H, CH3), 3.16 m (1H,
NH), 3.23 m [1H, (CH3)2CH], 3.55 d and 3.75 d (1H
each, 4′-H, J = 18.0 Hz), 3.91 s (3H, OCH3), 4.63 d
(1H, 6′-H, J = 4.6 Hz), 4.88 m (1H, 7′-H), 6.36 d (1H,
6-H, J = 9.8 Hz), 7.36 s (1H, 9-H), 7.54 s (1H, 4-H),
7.79 d (1H, 5-H, J = 9.8 Hz). 13C NMR spectrum
(CDCl3), δC, ppm: 19.27 q (CH3), 20.08 q [(CH3)2CH],
25.78 d [CH(CH3)2], 29.49 t (C4′), 59.02 d (C7′),
51.04 q (OCH3), 63.37 d (C6′), 100.45 d (C9), 109.51 s
(C4a), 115.21 d (C6), 116.58 s (C3a), 118.93 d (C4),
119.99 s (C2′), 125.94 s (C3), 136.53 s (C3′), 143.80 d
(C5), 151.98 s and 152.92 s (C8a, 9a), 156.91 s (C2),
160.73 s (C7), 166.43 s (C8′), 172.56 s (C=O). Found,
%: C 59.88; H 4.75; N 5.81; S 6.90. C23H22N2O6S.
Calculated, %: C 60.78; H 4.88; N 6.16; S 7.06.
7-Amino(deacetoxy)cephalosporanic acid methyl
ester (XX). Acid XIX, 300 mg (1.4 mmol), was dis-
persed in a mixture of diethyl ether with methylene
chloride (2:3), 20 ml of a solution of diazomethane in
diethyl ether (prepared from 1.5 g of nitrosomethylurea
according to [22]) was added dropwise under stirring,
and the mixture was left to stand for 16 h. The precip-
itate of unreacted acid XIX (130 mg) was filtered off,
the filtrate was evaporated, the residue was treated
with diethyl ether, and the precipitate was filtered off.
Yield 140 mg, mp 210–211°C, [α]D20 = –105.8° (c =
1.0, CHCl3). IR spectrum, ν, cm–1: 3424, 2960, 2927,
1783, 1741, 1672, 1508, 1457, 1438, 1369, 1328,
1294, 1213, 1159, 1133, 755. UV spectrum (EtOH),
λmax, nm (logε): 204 (2.74), 245 (2.80), 296 (2,41), 322
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 10-03-93162-Mong_a).
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