Transformations of methyl 2-[(E)-2-(dimethylamino)-1-(methoxycarbonyl) ethenyl]-1-methyl-1H-indole-3-carboxylate

Article abstract of DOI:10.1002/hlca.200690248

A simple and efficient synthesis of novel 2-heteroaryl-substituted 1H-indole-2-carboxylates and γ-carbolines, compounds 1-3, from methyl 2-(2-methoxy-2-oxoethyl)-1-methyl-1H-indole-3-carboxylate (4) by the enaminone methodology is presented.

Full text of DOI:10.1002/hlca.200690248

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Helvetica Chimica Acta – Vol. 89 (2006)
Transformations of Methyl 2-[(E)-2-(Dimethylamino)-1-
(methoxycarbonyl)ethenyl]-1-methyl-1H-indole-3-carboxylate
by David Bevk, Urosˇ Grosˇelj, Anton Meden, Jurij Svete*, and Branko Stanovnik*
Faculty of Chemistry and Chemical Technology, University of Ljubljana, P. O. Box537,
SI-1001 Ljubljana, Slovenia
(phone: +38612419100; fax: +38612419220; branko.stanovnik@fkkt.uni-lj.si and
jurij.svete@fkkt.uni-lj.si)
A simple and efficient synthesis of novel 2-heteroaryl-substituted 1H-indole-2-carboxylates and g-
carbolines, compounds 1–3, from methyl 2-(2-methoxy-2-oxoethyl)-1-methyl-1H-indole-3-carboxylate
(4) by the enaminone methodology is presented.
Introduction. – Inhibition of the kinase insert domain receptor (KDR) may be use-
ful for the prevention and treatment of tumor-induced angiogenesis. A number of
potent and selective KDR inhibitors such as compounds I–IV (Fig. 1) have been iden-
tified. Compounds Ia–Ic, e.g., are potential drug candidates in a range of cancer indi-
cations [1–3], and an efficient synthesis of their key pharmacophore, i.e., 1H-indol-2-yl-
substituted 1H-quinolin-2-ones, has been described recently, starting from para-substi-
tuted nitrobenzene and 2-substituted 3-formylquinolines [4]. The novel flavono-indole
alkaloid lotthanongine (II) has been isolated from the roots of Trigonostemon rei-
dioides (Euphorbiaceae) [5], and four b-indoloquinoline alkaloids, bouchardatine
(III), rutaecarpine (IVa), 1-hydroxyrutaecarpine (IVb), and 1,2-dihydrorutaecarpine
(IVc), have been isolated from the aerial parts of Bouchardatia neurococca [6].
Conventional approaches to 2-arylindoles typically rely upon cross-coupling of
indol-2-yl halides, boronic acids, or stannates and silanes [7]. Although effective meth-
ods are available for the preparation of 1H-indol-2-ylboronic acid and silanes [8], the
major limitation with most of these approaches are the additional steps needed for
the preparation of coupling partners to enter Pd-catalyzed reactions. While a number
of other classical methods (e.g., those of Fischer, Madelung, Bischler, Reissert, Nenit-
zescu, or Leimgruber–Batcho [9]) have been successfully employed for the synthesis
of 2-substituted indoles, each has its limitation due to either construction of the starting
materials or harsh reaction conditions, which may interfere with other sensitive func-
tional groups often located in the target molecule. Therefore, mild synthetic methods
providing rapid assembly of the indole ring and tolerating a wide range of functional
groups continue to offer significant advantages.
A number of fluorescent 3-aryl-1-methylquinolinones, including 3-(1H-indol-2-yl)-
1-methylquinolin-2(1H)-one, have been synthesized by regiospecific photocoupling of
3-halo-1-methylquinolinones with aromatic and hetero-aromatic compounds [10]. And
a number of fluorescent 3-arylcoumarins, including 3-(1-methyl-1H-indol-2-yl)-2H-1-
ꢀ 2006 Verlag Helvetica Chimica Acta AG, Zürich

Helvetica Chimica Acta – Vol. 89 (2006)
2775
Fig. 1. Known inhibitors of the kinase insert domain receptor (KDR)
benzopyran-2-one, have been prepared by photo-coupling of 3-bromocoumarin with
aromatic and heteroaromatic compounds [11].
Recently a series of 2-substituted alkyl 3-(dimethylamino)prop-2-enoates (and
related enaminones) have been prepared as versatile reagents for the preparation of
various dehydro-alanine derivatives, heterocyclic systems, and natural-product ana-
logues. In extension, chiral cyclic enamino lactams and lactones, derived from an a-
amino acid and (+)-camphor, have been used in the synthesis of functionalized hetero-
cycles such as hetero-arylalanines, hetero-arylalaninols, hetero-arylpropanediols, 3-het-
eroaryl-substitued (+)-camphor derivatives, and heterocyclic compounds with and a-
amino acid or a dipeptide structural element incorporated into the ring system [12][13].
In the present paper, we describe an extension of our research on 2-substituted alkyl
3-(dimethylamino)prop-2-enoates and related enaminones. These versatile reagents
have been used for the preparation of various heterocyclic systems [12] and natural
products and their analogues such as 3-substituted indoles, dipodazines [14], aplysinop-
sins [15], and meridianins [16], or employed in combinatorial syntheses of heterocycles
and N-acyldehydroalanine esters [17]. Here, we present an efficient synthesis of the 2-
heteroaryl-substituted novel indoles 1–3 (Scheme)1).
1
)
For systematic names, see the Exper. Part.

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Helvetica Chimica Acta – Vol. 89 (2006)
Results and Discussion. – 1. Synthesis. As shown in the Scheme below, methyl 2-(2-
methoxy-2-oxoethyl)-1-methyl-1H-indole-3-carboxylate (4) [18] was transformed with
dimethylformamide dimethylacetal (DMF-DMA) in MeOH into the enamino-substi-
tuted compound 5 in 88% yield. The latter turned out to be a versatile intermediate
for a series of transformations: when 5 was heated with 2-aminopyridine in AcOH, cyc-
lization to the 4H-pyrido[1,2-a]pyrimidine derivative 1 occurred (27% yield). Similarly,
when 5 was heated in the presence of 1,3-dimethylbarbituric acid (=1,3-dimethylpyri-
midine-2,4,6(1H,3H,5H)-trione), the heterocyclic system 2 was obtained. Finally, 5
could be further transformed in H2O into the corresponding enol 6a. Analogously, in
the presence of alcohols (ROH) and AcCl, the enol ethers 6b–d were isolated in mod-
erate yields. With aromatic amines in MeOH/HCl, compound 5 afforded the enamines
7a–e in 61–98% yield, and the latter (7a,b) could be cyclized in MeOH/MeONa at
room temperature to afford the target compounds 3a,b.
2. Structure Determination. The structures of all compounds were determined by
spectroscopic methods and by elemental analyses. The geometry of the exocyclic C=
C bond in compounds 5 and 7c was established by NMR analysis on the basis of the
3J(C,H) coupling constants between the olefinic H-atom and the ester C=O group,
as determined from the antiphase splitting of cross-peaks in the HMBC spectrum. Gen-
erally, the 3J(C,H) value for nuclei on the same side of the C=C bond was smaller (2–6
Hz) than those for nuclei on opposite sides (8–12 Hz) [12].
3
In compound 5, a J(C,H) value of 5 Hz indicated an (E)-configured C=C bond
(Fig. 2). Similarly, for compound 7c, the magnitude of the coupling constant of the
major isomer (5 Hz) indicated (E)-configuration, whereas the minor isomer (11 Hz)
had the (Z)-configuration. Also, in the case of the enol ether 6b (3J(C,H)=3.2 Hz),
the proposed (E)-configuration was unequivocally confirmed by X-ray-diffraction
analysis (Fig. 3).
Fig. 2. 3J(C,H) Values for the discrimination of (E)- and (Z)-isomers of compounds 5–7

Helvetica Chimica Acta – Vol. 89 (2006)
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Helvetica Chimica Acta – Vol. 89 (2006)
Fig. 3. X-Ray crystal structure of 6b (ORTEP-III plot)
Experimental Part
General. All chemicals and reagents were purchased from Fluka or Aldrich. Compound 4 was pre-
pared according to a literature procedure [18]. Melting points (m.p.) were determined on a Kofler hot-
stage micro-melting-point apparatus. IR Spectra were recorded on a Perkin-Elmer-BX FT-IR spectro-
photometer; in cmꢀ1. 1H- and 13C-NMR Spectra were obtained on a Bruker Avance DPX-300 apparatus
at 300 (1H) and 75.5 (13C) MHz in CDCl3 or (D6)DMSO soln.; d in ppm rel. to Me4
analyses were performed on a Perkin-Elmer CHN Analyser 2400 II.
A
Methyl 2-[(E)-2-(Dimethylamino)-1-(methoxycarbonyl)ethenyl]-1-methyl-1H-indole-3-carboxylate
(5). A soln. of 4 (2.61 g, 10 mmol) and DMF-DMA (2 ml) in MeOH (30 ml) was heated at refluxfor
24 h. The solvent was evaporated in vacuo, and the residue was crystallized from MeOH/H2O: 3.86 g
(88%). Colorless needles. M.p. 165–1678 (MeOH/H2O). IR (KBr): 2940, 1700, 1600, 1430, 1390, 1280,
1210, 1090, 750. 1H-NMR (CDCl3): 2.73 (br. s, Me2
N); 3.62 (s, 3 H); 3.64 (s, 3 H); 3.88 (s, 3 H);
G
7.27–7.86 (m, 3 H of indole); 8.17 (s, HC=); 8.17–8.18 (m, 1 H of indole). 13C-NMR (CDCl3): 30.1;
31.3; 50.5; 51.1; 86.4; 107.0; 109.5; 121.6; 121.7; 122.3; 126.5; 136.3; 141.9; 152.4; 165.5; 169.1. Anal.
calc. for C17H20NO4: C 64.54, H 6.37, N 8.86; found: C 64.74, H 6.53, N 8.76.
Methyl 1-Methyl-2-(4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl)-1H-indole-3-carboxylate (1). Compound
5 (158 mg, 0.5 mmol), 2-aminopyridine (47 mg, 0.5 mmol), and AcOH (2 ml) were heated at refluxfor 8
h. After cooling, the precipitated product was filtered off and recrystallized from toluene: 45 mg (27%).
Yellow crystals. M.p.>3508 (toluene). IR (KBr): 3430, 3050, 1690, 1670, 1520, 1490, 1330, 1190, 1100, 790,
730. 1H-NMR (CDCl3): 3.71 (s, MeN); 3.81 (s, MeO); 7.28–7.43 (m, 5 H); 7.80–7.90 (m, 2 H); 8.53 (s, 1
H); 9.21–9.24 (m, 1 H). Anal. calc. for C19H15N3O3: C 68.46, H 4.54, N 12.61; found: C 68.68, H 4.38, N
12.66.
Methyl 2-(2,3,4,7-Tetrahydro-1,3-dimethyl-2,4,7-trioxo-2H-pyrano[2,3-d]pyrimidin-6-yl)-1-methyl-
1H-indole-3-carboxylate (2). A mixture of 5 (158 mg, 0.5 mmol), 1,3-dimethylbarbituric acid (78 mg,
0.5 mmol), and AcOH (2 ml) was heated at refluxfor 9 h. After cooling, the precipitated product was
filtered off and recrystallized from toluene/DMF: 100 mg (51%). Yellow crystals. M.p. 259–2608 (tolu-
ene/DMF). IR (KBr): 3470, 2960, 1770, 1710, 1670, 1580, 1530, 1440, 1290, 1190, 1110, 910, 770, 750,
1
480. H-NMR (CDCl3): 3.44 (s, MeN); 3.64 (s, MeN); 3.70 (s, MeN); 3.87 (s, MeO); 7.26–7.41 (m, 4 H
of indole); 8.14 (s, 1 H); 8.15–8.17 (m, 1 H of indole). Anal. calc. for C20H17N3O6: C 60.76, H 4.33, N
10.63; found: C 60.68, H 4.29, N 10.50.

Helvetica Chimica Acta – Vol. 89 (2006)
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Methyl 2-[(E)-2-Hydroxy-1-(methoxycarbonyl)ethenyl]-1-methyl-1H-indole-3-carboxylate (6a). A
soln. of 5 (158 mg, 0.5 mmol) and conc. HCl (20 drops) in MeOH (2 ml) was left standing at r.t. for 12
h. The precipitate was filtered off and recrystallized from MeOH/H2O: 100 mg (46%). Colorless crystals.
M.p. 127–1318 (MeOH/H2O). IR (KBr): 3200, 2950, 1690, 1440, 1400, 1190, 740. 1H-NMR (CDCl3): 3.64
(s, Me); 3.74 (s, Me); 3.87 (s, Me); 7.25–7.38 (m, 3 H of indole, =CH); 8.17–8.20 (m, 1 H of indole); 12.34
(d, J=12.8, OH). Anal. calc. for C15H15NO5: C 62.28, H 5.23, N 4.84; found: C 62.32, H 5.35, N 4.67.
Methyl 2-[(E)-2-Methoxy-1-(methoxycarbonyl)ethenyl]-1-methyl-1H-indole-3-carboxylate (6b).
MeOH (2 ml) was cooled to ꢀ308, and AcCl (0.5 ml) was added dropwise during mixing on an ice
bath. Then, 5 (158 mg, 0.5 mmol) was added, and the mixture was heated at reflux for 3 h: 118 mg
(78%). Colorless crystals. M.p. 164–1688 (MeOH). IR (KBr): 2950, 1720, 1690, 1640, 1400, 1250, 1210,
1120, 1100, 760, 750, 550. 1H-NMR (CDCl3): 3.63 (s, Me); 3.70 (s, Me); 3.86 (s, Me); 3.82 (s, Me);
7.24–7.30 (m, 2 H of indole); 7.34–7.37 (m, 1 H of indole); 7.74 (s, HC=); 8.16–8.19 (m, 1 H of indole).
13C-NMR (CDCl3): 30.4; 50.7; 51.8; 62.3; 103.1; 105.7; 109.7; 121.7; 121.8; 122.5; 126.5; 136.9; 138.3;
162.0; 165.3; 166.9. Anal. calc. for C16H17NO5: C 63.36, H 5.65, N 4.62; found: C 65.59, H 5.73, N 4.76.
Methyl 2-[(E)-2-Ethoxy-1-(ethoxycarbonyl)ethenyl]-1-methyl-1H-indole-3-carboxylate (6c). EtOH
(2 ml) was cooled to ꢀ308, and AcCl (0.5 ml) was added dropwise during mixing on an ice bath.
Then, compound 5 (158 mg, 0.5 mmol) was added, and the mixture was heated at reflux for 3 h: 106
1
mg (67%). Yellow oil. H-NMR (CDCl3): 1.19 (t, J=7.12, MeCH2O); 1.25 (t, J=7.08, MeCH2O); 3.61
(s, MeN); 3.84 (s, MeO); 4.08 (q, J=7.05, MeCH2
U
G
102.9; 105.5; 109.6; 121.6; 121.7; 122.3; 126.6; 136.8; 138.7; 160.7; 165.3; 166.5. HR-CI-MS: 331.1425 (M+,
C
N
G
PrOH (2 ml) was cooled to ꢀ308, and AcCl (0.5 ml) was added dropwise during mixing on an ice
bath. Then, compound 5 (158 mg, 0.5 mmol) was added, and the mixture was heated at reflux for 3 h:
92 mg (56%). Yellow oil. 1H-NMR (CDCl3): 0.76–0.92 (m, 2 Me(CH2)2
A
2
MeCH2CH2O); 3.61 (s, MeN); 3.83 (s, MeO); 3.98 (dd, J=6.7, 2.6, MeCH2
MeCH2CH2
A
ACHTREUNG
A
ACHTREUNG
A
ACHTREUNG
boxylate (7a). A soln. of 5 (158 mg, 0.5 mmol), 4-nitroaniline (69 mg, 0.5 mmol), and conc. HCl (25
drops) in MeOH (2 ml) was left standing at r.t. for 12 h. Then, H2O (2 ml) was added, and the precipitate
was filtered off and recrystallized from MeOH/H2O: 192 mg (94%). Colorless crystals. M.p. 180–1848
1
(MeOH/H2O). IR (KBr): 3430, 1690, 1630, 1590, 1520, 1340, 1240, 1100, 840, 750. H-NMR (CDCl3):
3.66 (s, Me); 3.74 (s, Me); 3.87 (s, Me); 7.08–7.13 (m, 2 arom. H); 7.29–7.38 (m, 3 arom. H); 7.59 (d,
J=12.5, HC=); 8.16–8.19 (m, 1 arom. H); 8.20–8.24 (m, 2 arom. H); 10.90 (d, J=12.5, NH). Anal.
calc. for C21H19N3O6: C 61.61, H 4.68, N 10.26; found: C 61.75, H 4.81, N 10.17.
Methyl
1-Methyl-2-{(Z)-1-(methoxycarbonyl)-2-[(3-nitrophenyl)amino]ethenyl}-1H-indole-3-car-
boxylate (7b). A soln. of 5 (158 mg, 0.5 mmol), 3-nitroaniline (69 mg, 0.5 mmol), and conc. HCl (25
drops) in MeOH (2 ml) was left standing at r.t. for 12 h. Then, H2O (2 ml) was added, and the precipitate
was filtered off and recrystallized from MeOH/H2O: 200 mg (98%). Colorless crystals. M.p. 155–1608
1
(MeOH/H2O). IR (KBr): 3430, 1700, 1670, 1530, 1350, 1220, 1100, 790, 730. H-NMR (CDCl3): 3.67 (s,
Me); 3.73 (s, Me); 3.88 (s, Me); 7.28–7.39 (m, 5 arom. H); 7.47–7.52 (m, 1 arom. H); 7.59 (d, J=12.7,
HC=); 7.88–7.92 (m, 2 arom. H); 8.16–8.19 (m, 1 arom. H); 10.79 (d, J=12.7, NH). Anal. calc. for
C21H19N3O6: C 61.61, H 4.68, N 10.26; found: C 61.54, H 4.75, N 10.12.
(E)- and (Z)-Isomers of Methyl 1-Methyl-2-{1-(methoxycarbonyl)-2-[(4-methylphenyl)amino]-
A
(72 mg, 0.5 mmol), and conc. HCl (20 drops) in MeOH (2 ml) was left standing at r.t. for 12 h. Then,
H2O (2 ml) was added, and the precipitate was filtered off and recrystallized from MeOH/H2O. Yield:
115 mg (61%); (Z/E) 57:43. Colorless crystals. M.p. 116–1688 (MeOH/H2O). IR (KBr): 3200, 1690,
1440, 1400, 1190, 1140, 1100, 760, 740. 1H-NMR (CDCl3; (Z)-isomer): 2.31 (s, Me); 3.64 (s, Me); 3.70
(s, Me); 3.85 (m, 3 arom. H); 6.95–6.98 (m, 2 arom. H); 7.12–7.14 (m, 2 arom. H); 7.27–7.43 (m, 3

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Helvetica Chimica Acta – Vol. 89 (2006)
arom. H); 7.53 (d, J=13.2, HC=); 8.17–8.20 (m, 1 arom. H); 10.56 (d, J=13.2, NH). 1H-NMR (CDCl3;
(E)-isomer): 2.29 (s, Me); 3.64 (s, Me); 3.72 (s, Me); 3.84 (s, Me); 6.39 (d, J=14.1, NH); 6.83–6.86 (m, 2
arom. H); 7.08–7.10 (m, 2 arom. H); 7.27–7.43 (m, 3 arom. H); 8.24–8.27 (m, 1 arom. H); 8.36 (d,
J=14.1, HC=). Anal. calc. for C22H22N2O4: C 69.83, H 5.86, N 7.40; found: C 70.08, H 6.14, N 7.34.
(E)- and (Z)-Isomers of Methyl 2-{2-[(4-Bromophenyl)amino]-1-(methoxycarbonyl)ethenyl}-1-meth-
yl-1H-indole-3-carboxylate (7d). A soln. of 5 (158 mg, 0.5 mmol), 4-bromoaniline (86 mg, 0.5 mmol), and
conc. HCl (20 drops) in MeOH (2 ml) was left standing at r.t. for 12 h. Then, H2O (2 ml) was added, and
the precipitate was filtered off and recrystallized from MeOH/H2O. Yield: 209 mg (94%); (Z/E) 38 :62.
Colorless crystals. M.p. 189–1978 (MeOH/H2O). IR (KBr): 3280, 1690, 1620, 1440, 1220, 1100, 820, 790,
750. 1H-NMR (CDCl3; (Z)-isomer): 3.63 (s, Me); 3.72 (s, Me); 3.84 (s, Me); 6.44 (d, J=13.8, NH);
6.80–6.85 (m, 2 arom. H); 7.26–7.35 (m, 3 arom. H); 7.37–7.41 (m, 2 arom. H); 8.22–8.26 (m, 1
1
arom. H); 8.31 (d, J=13.8, HC=). H-NMR (CDCl3; (E)-isomer): 3.64 (s, Me); 3.70 (s, Me); 3.86 (s,
Me); 6.92–6.97 (m, 2 arom. H); 7.26–7.35 (m, 3 arom. H); 7.42–7.45 (m, 2 arom. H); 7.51 (d, J=13.0,
HC=); 8.16–8.19 (m, 1 arom. H); 10.59 (d, J=13.0, NH). Anal. calc. for C21H19N2O4Br: C 56.90, H
4.32, N 6.32; found: C 57.08, H 4.52, N 6.33.
Methyl 1-Methyl-2-[(Z)-1-(methoxycarbonyl)-2-(naphthalen-1-ylamino)ethenyl]-1H-indole-3-car-
boxylate (7e). A soln. of 5 (158 mg, 0.5 mmol), naphthalene-1-amine (72 mg, 0.5 mmol), and conc. HCl
(20 drops) in MeOH (2 ml) was left standing at r.t. for 12 h. The precipitate was collected by filtration
and recrystallized from toluene/heptane: 145 mg (70%). Colorless crystals. M.p. 168–1708 (toluene/hep-
1
tane). IR (KBr): 3460, 1700, 1680, 1620, 1440, 1200, 1100, 790. H-NMR (CDCl3): 3.69 (s, Me); 3.77 (s,
Me); 3.87 (s, Me); 7.25–7.46 (m, 5 arom. H); 7.53–7.62 (m, 3 arom. H); 7.77 (d, J=12.6, HC=);
7.86–7.89 (m, 1 arom. H); 8.16–8.22 (m, 2 arom. H); 11.42 (d, J=12.6, NH). Anal. calc. for
C25H22N2O4: C 72.45, H 5.35, N 6.76; found: C 72.61, H 5.50, N 6.54.
Methyl 2,5-Dihydro-5-methyl-2-(4-nitrophenyl)-1-oxo-1H-pyrido[4,3-b]indole-4-carboxylate (3a).
Na (40 mg) was dissolved in MeOH (2 ml), and the resulting soln. was added dropwise to a suspension
of 7a (100 mg, 0.24 mmol) in MeOH (2 ml). The mixture was kept 4 h at r.t., and the precipitate was col-
lected by filtration and recrystallized from MeOH/DMF: 46 mg (50%). Yellow crystals. M.p. 237–2388
(MeOH/DMF). IR (KBr): 1710, 1670, 1520, 1350, 1250, 1080, 750. 1H-NMR ((D6)DMSO): 3.89 (s,
Me); 3.99 (s, MeO); 7.32–7.38 (m, 1 arom. H); 7.45–7.51 (m, 1 arom. H); 7.73–7.76 (m, 1 arom. H);
7.87–7.92 (m, 2 arom. H); 8.20–8.24 (m, 1 arom. H); 8.30 (s, HꢀC(3)); 8.38–8.43 (m, 2 arom. H).
Anal. calc. for C20H15N3O5: C 63.66, H 4.01, N 11.14; found: C 63.53, H 4.18, N 11.04.
Methyl 2,5-Dihydro-5-methyl-2-(3-nitrophenyl)-1-oxo-1H-pyrido[4,3-b]indole-4-carboxylate (3b). A
soln. of Na (40 mg) in MeOH (2 ml) was added dropwise to a suspension of 7b (73 mg, 0.18 mmol) in
MeOH (2 ml). The mixture was kept for 24 h at r.t. The precipitate was collected by filtration and recrys-
tallized from MeOH/DMF: 67 mg (quant.). Colorless crystals. M.p. 280–2828 (MeOH/DMF). IR (KBr):
1720, 1680, 1530, 1350, 1280, 1080, 750. 1H-NMR ((D6)DMSO): 3.89 (s, Me); 4.00 (s, MeO); 7.32–7.37 (m,
1 arom. H); 7.45–7.51 (m, 1 arom. H); 7.73–7.76 (m, 1 arom. H); 7.83–7.88 (m, 1 arom. H); 8.04–8.08
(m, 1 arom. H); 8.21–8.23 (m, 1 arom. H); 8.34 (s, HꢀC(3)); 8.35–8.38 (m, 1 arom. H); 8.48–8.49 (m, 1
arom. H). Anal. calc. for C20H15N3O5: C 63.66; H 4.01; N 11.14; found: C 63.78; H 4.08; N 11.10.
X-Ray Crystal Structure of 6b2). Single-crystal X-ray-diffraction data of methyl 2-[(E)-2-methoxy-1-
(methoxycarbonyl)ethenyl]-1-methyl-1H-indole-3-carboxylate (6b) were collected at r.t. on a Nonius
Kappa CCD diffractometer using the Nonius Collect software [19]. DENZO and SCALEPACK [20]
were used for indexing and scaling of the data, and the structure was solved by means of SIR97 [21].
Refinement was done with the Xtal3.4 [22] program package. The crystal structure was refined on F val-
ues using the full-matrixleast-squares procedure. The non-H-atoms were refined anisotropically, and the
positions of the H-atoms were geometrically calculated, their positional and isotropic atomic-displace-
2
)
The crystallographic data for compound 6b have been deposited with the Cambridge Crystallo-
graphic Data Centre as deposition number CCDC-608868. The data can be obtained, free of charge,
at http://www.ccdc.cam.ac.uk/data_request/cif.

Helvetica Chimica Acta – Vol. 89 (2006)
2781
Table. X-Ray Crystallographic and Refinement Data for 6b
Formula
Mr
C16
303.31
N
G
Crystal system
Space group
a, b, c [Š]
a=b=g [8]
V [Š3]
orthorhombic
P 212121
8.0709(2), 10.7386(3), 17.6925(5)
90.0000
1533.41(7)
4
1.314
0.098
Z
1 [Mg mꢀ3
]
m [mmꢀ1
]
Crystal dimension [mm]
Temperature [K]
Wavelength [Š]
qmax [8]
0.40”0.30”0.25
293(1)
0.71073
27.48
Total reflections
Independent reflections
Rint
17035
2043
0.055
Observed reflections
Reflection parameters
Threshold criterion
Final R and Rw
1591
199
I>2.0s(I)
0.048, 0.044
0.0005
ꢀ0.25, 0.24
(D/s)max
D1max, D1min (e Š
ꢀ3
)
ment parameters not being refined. Absorption corrections were not necessary. The Regina [23] weight-
ing scheme was used. The resulting crystal data and details concerning data collection and refinement are
collected in the Table. For an ORTEP-III [24] representation, see Fig. 3.
Financial support from the Slovenian Research Agency, Slovenia (grants P0-0502-0103, P1-0179, and
J1-6689-0103-04) is gratefully acknowledged. Financial support by the pharmaceutical companies LEK,
Ljubljana, and KRKA, Novo Mesto, is fully appreciated. We kindly acknowledge financial contributions
of the Ministry of Science and Technology, Republic of Slovenia, which enabled the Laboratory of Inor-
ganic Chemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, to purchase
the Nonius X-ray diffractometer (grants X-2000 and PS-511-103).
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Received August 3, 2006