Syntheses and tautomerisations of amino-substitutedand pyrimidine-annulated pyrrolobenzodiazepines

Article abstract of DOI:10.3987/COM-04-10310

Different tautomers of 11-amino-substituted pyrrolo[2,1-c][1,4]benzodiazepinesand 2-substituted 4,7a,12b-triazadibenzo[e,g]azulene-1,8-diones were formed depending on the substitution pattern. Syntheses, spectroscopic investigations and an X-Ray analysis

Full text of DOI:10.3987/COM-04-10310

HETEROCYCLES, Vol. 65, No. 3, 2005
625
HETEROCYCLES, Vol. 65, No. 3, 2005, pp. 625 - 632
Received, 17th December, 2004, Accepted, 24th January, 2005, Published online, 28th January, 2005
SYNTHESES AND TAUTOMERISATIONS OF AMINO-SUBSTITUTED
AND PYRIMIDINE-ANNULATED PYRROLOBENZODIAZEPINES
Andreas Schmidt,*a Abbas Gholipour Shilabin,a and Martin Niegerb
a) Clausthal University of Technology, Institute of Organic Chemistry,
Leibnizstrasse
6,
D-38678
Clausthal-Zellerfeld,
Germany
E-mail: schmidt@ioc.tu-clausthal.de
b) University
of
Bonn,
Institute
of
Inorganic
Chemistry,
Gerhard-Domagk-Strasse 1, D-53121 Bonn, Germany
Abstract – Different tautomers of 11-amino-substituted pyrrolo[2,1-c][1,4]ben-
zodiazepines and 2-substituted 4,7a,12b-triazadibenzo[e,g]azulene-1,8-diones
were formed depending on the substitution pattern. Syntheses, spectroscopic
investigations and an X-Ray analysis are presented.
INTRODUCTION
Pyrrolo[2,1-c][1,4]benzodiazepines continue to be of interest from different points of view. Thus, some
representatives such as anthramycin (1) bind to specific sequences of DNA and have therefore potential
as regulators of gene expression with possible application as therapeutic agents.1 This ring system is also
found in some antitumor antibiotics produced by various Streptomyces species.2 In 1999, some new fused
pyrrolobenzodiazepines, circumdatins A (2), B (3), D (4) and E (5), were isolated from the fungus
Aspergillus ochraceus.3
O
R
N
O
O
R
N
H
N
CONH2
N
N
H
N
O
N
OH
H
Me
N
O
OMe
OH
H
O
MeO
OMe
4: R = OMe
5: R = H
2: R = OMe
3: R = H
1
Scheme 1

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HETEROCYCLES, Vol. 65, No. 3, 2005
The (S)-configuration of the α-C-atom of the pyrrolidine ring causes an isohelicity with the minor groove
of DNA, so that tautomerism involving this position plays a crucial role for the biological activities of this
class of compounds. In continuation of our work on benzodiazepines,4 pyrrolobenzodiazepines5,6 and
mesomeric betaines7 we became interested in studying possible tautomerisations of 11-amino-substituted
and pyrimidine-annulated pyrrolobenzodiazepines.
RESULTS AND DISCUSSION
We started the syntheses of our target molecules from the readily available monothiolactam (7)8 which was
reacted with ammonia, methylamine, and aniline in THF in the presence of mercury(II) chloride to give 8, 9,
and 10, respectively. The N-unsubstituted amidine (8) reacts quantitatively to the starting material (6) on
heating in water or dilute aqueous sodiumhydroxide. In contrast to 9 and 10, which exist as a mixture of the
tautomeric forms (A) and (B), respectively,6 only one tautomer of the amidine (8) in DMSO-d6 and MeOD
is observable. One broad H/D-exchangeable signal of two protons with a center of gravity at δ = 7.49
ppm in DMSO-d6 provides strong evidence for the formation of the tautomer (8A) under these conditions.
Neat reaction of the amidines (8 – 10) with 2-ethyl- and 2-benzyl-substituted bis(2,4,6-trichlorophenyl)
malonates in a Zincke apparatus resulted in the formation of the pyrimidine-annulated
pyrrolobenzodiazepines (11 – 16) and the leaving group 2,4,6-trichlorophenol which can be distilled off
during the reaction. Dependent on the substitution pattern 11 – 16 form different tautomers in solution as
well as in the solid state. Thus, only the 4,7a,12b-triazadibenzo[e,g]azulenes (11) and (12) resulting from
the N11-unsubstituted pyrrolobenzodiazepine (8) were isolated as optically active compounds. These two
new compounds form only one tautomer in DMSO-d6, MeOD, and CDCl3 at room temperature,
1
respectively, as evidenced by H NMR spectroscopy. A combination of HMBC and HSQC NMR
unambiguously proved the existence of enolic partial structures in 11 and 12 under these conditions, as
couplings between 4b-H and C-5, C-6, and C-4a were detected. The latest mentioned carbon atom C-4a
appears at δ = 157.4 ppm (11) and 158.0 ppm (12). The carbon atom C-2 is sp2 hybridized and appears at δ
= 103.5 ppm (11) and 101.6 ppm (12). The hydroxy group causes one broad, H/D-exchangeable signal at δ
= 11.45 ppm in DMSO-d6 and at δ = 6.34 ppmin CDCl3 in the 1H NMR spectra. NOESY experiments of 11,
which possesses the N-(3-oxopropenyl)formamidine chromophor, provide evidence for close proximities
between the hydroxy group at C-3 and the ethyl group as well as C-5 of the pyrrolidine ring.
In contrast to this, the pyrrolobenzodiazepines derived from the N11-substituted pyrrolobenzodiazepines
(9) and (10) form the tautomers 13 to 16 in DMSO-d6 at room temperature. No traces of cross-conjugated
mesomeric betaines, which would resemble the proposed structures of circumdatins A and B, or enols
were detectable. In 13 – 16, the carbon atom C-2, which appears between δ = 53.6 ppm and 55.8 ppm,
unambiguously is sp3 hybridized. HMBC and HSQC NMR measurements displayed couplings of C-2

HETEROCYCLES, Vol. 65, No. 3, 2005
627
with the ethyl group and the benzyl group, respectively.
O
R1-NH2,
HgCl2, THF
O
O
O
Lawesson´s
reagent
N
N
N
N
H
H
H
N
H
H
N
R1
reflux
N
H
N
N
N R1
H
O
S
H
8A: R1 = H
9A: R1 = Me
10A: R1 = Ph
6
8B - 10B
7
O
O
H2O, reflux
TCP
TCP
O
N
R2
170 -
190°C,
-2 TCP
(R1 = H)
H
N
N
O
numberings
O
O
N
3
OH
6
5
2
R2
N
7
8
11: R2 = Et (85%)
1
12: R2 = Bn (72%)
11a
11
H
N
R1
N
N
9
H
O
O
N
O
7
O
R2
9
6
N
4b
8
10
11
5
R1
N
N
N4a
1
12
4 N
O
(R1 = Me or Ph)
3
O
2
O
R2
13: R1 = Me, R2 = Et (78%)
14: R1 = Me, R2 = Bn (80%)
15: R1 = Ph, R2 = Et (79%)
16: R1 = Ph, R2 = Bn (88%)
TCP = 2,4,6-trichlorophenol
Scheme 2
In order to elucidate a structure in the solid state, we performed an X-Ray single crystal structure analysis of
the benzyl derivative (16).9 Single crystals were obtained by slow evaporation of a concentrated solution in
2-butanol. The molecular structure and the crystallographic numbering are shown in Figure 1 and relevant
bond distances and angles are given in the Tables 1 and 2. The molecule crystallized with one molecule of
2-butanol in the elemental cell which forms a hydrogen bond to the C12=O12 carbonyl group
[crystallographic numbering]. The carbon atom [C3] of the 1,3-diketo moiety is sp3 hybridized, as its bond
angles are 107.89(8)° [C2-C3-C4], 113.80(9)° [C31-C3-C4], and 112.05(9)° [C31-C3-C2], respectively.
2
The bond length C6-C7 was determined to be 132.93(15) pm and corresponds to a Csp =Csp2 double bond.
The bond angles N1-C6-N5, C6-C7-N11, and C7-C6-N5 are 114.82(9)°, 124.74(10)°, and 123.30(10)°,
respectively. The dioxopyrimidine moiety N1-C2-C3-C4-N5-C6 adopts a boat conformation with the
benzyl substituent in equatorial position.

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HETEROCYCLES, Vol. 65, No. 3, 2005
Figure 1: Molecular drawing of 4,7a,12b-triazadibenzo[e,g]azulene-1,3,8-trione (16).
Table 1. Selected atomic distances (pm) and angles (°) for (16).
Bond lengths
N1-C2
C2-C3
C3-C31
C2-O2
C3-C4
C4-O4
137.63(14)
153.22(14)
152.40(15)
121.34(13)
153.41(15)
121.51(13)
C4-N5
N5-C6
C6-N1
C7-N11
N11-C12
C12-O12
138.52(13)
142.36(13)
142.24(13)
141.05(14)
136.80(15)
123.16(14)
C12-C13
C13-C18
C18-N1
C18-C17
C13-C14
N5-C51
149.42(16)
139.72(15)
143.16(13)
139.27(15)
140.35(16)
143.18(14)
Bond angles
N1-C2-C3
C2-C3-C4
C3-C4-N5
O2-C2-C3
C3-C4-O4
C2-C3-C31
110.87(9)
107.89(8)
111.44(9)
125.38(10)
124.23(10)
112.05(9)
C4-N5-C6
C4-N5-C51
N5-C6-N1
C6-N1-C2
N1-C2-O2
N1-C6-C7
115.51(9)
123.74(9)
114.82(9)
116.95(9)
123.71(10)
121.85(10)
C6-C7-N11
C7-N11-C12
N11-C12-C13 120.84(10)
C12-C13-C18 125.44(10)
C13-C18-N1
124.74(10)
131.28(9)
119.64(9)
N11-C12-O12 118.71(10)
Table 2. Selected torsion angles for compound (16) (°).
N1-C2-C3-C4
N1-C2-C3-C31 -178.28(9)
-52.26(11)
C2-N1-C6-N5
C6-N1-C2-C3
N1-C6-C7-N11
N1-C6-C7-C8
C6-C7-N11-C12 -30.00(19)
C6-C7-N11-C10 159.49(11)
46.76(12)
3.03(12)
-0.74(17)
173.45(10)
N11-C12-C13-C18 32.90(17)
N11-C12-C13-C14 -148.09(11)
C12-C13-C18-C17 -178.68(11)
O12-C12-C13-C14 27.45(16)
O12-C12-C13-C18 -151.56(12)
C2-C3-C4-O4
C2-C3-C4-N5
C3-C4-N5-C6
C3-C4-N5-C51 -176.84(9)
C4-N5-C51-C52 -42.59(15)
-123.15(11)
56.00(11)
-9.41(12)
C12-C13-C18-N1
C6-N1-C18-C13
C18-N1-C6-N5
1.29(17)
- 60.62(13)
-122.19(10)
C7-N11-C12-O12 -178.65(11)
C7-N11-C12-C13 -3.04(18)
C4-N5-C6-N1
-42.62(12)

HETEROCYCLES, Vol. 65, No. 3, 2005
629
ACKNOWLEDGEMENTS
Prof. Dr. E. Niecke, Prof. Dr. K. H. Dötz, and Prof. Dr. F. Vögtle, University of Bonn, are gratefully
acknowledged for providing the X-ray crystallography facilities. The Deutsche Forschungsgemeinschaft
(DFG) is gratefully acknowledged for financial support.
EXPERIMENTAL
1
13
General methods: The H and C NMR spectra were recorded on a Bruker ARX-400 and DPX-200 in
1
DMSO-d6 (400 and 200 MHz for H NMR) unless otherwise noted. The chemical shifts are reported in
ppm relative to internal tetramethylsilane (δ = 0.00 ppm). FT-IR spectra were obtained on a Bruker
Vektor 22 in the range of 400 to 4000 cm-1 (2.5 % pellets in KBr). The GC-MS spectra were recorded on
a GC Hewlett-Packard 5980, Serie II in combination with a MS Hewlett-Packard 5989 B, and on a Varian
GC3900 with SAT2100T mass spectrometer.
11-Amino-1,2,3,11a-tetrahydrobenzo[e]pyrrolo[1,2-a][1,4]diazepin-5-one (8).
To a solution of thiolactam (7) (1.16 g, 5.0 mmol) in anhyd THF (50 mL) was added HgCl2 (1.63 g, 6.0
mmol) and pure anhydrous ammonia was bubbled through the mixture for 1 h at 60 °C. After cooling, the
resulting suspension was filtered off through a pad of Celite and eluted with methanol. The organic
solution was evaporated under reduced pressure at rt. Addition of an acetone/ether mixture afforded a
white solid which was washed with ether and recrystallized from anisole/methanol (0.925 g, 86%), mp
20
1
>240 °C (decomp) [α]D = +510.5° (c 1.0, DMSO); H NMR: δ = 7.79 (dd, J = 7.8, 1.5 Hz, 1H, 6-H),
7.49 – 7.54 (m, 1H, 7-H), 7.28 – 7.70 (br m, 2H, NH2), 7.22 (t, J = 7.5 Hz, 1H, 8-H), 7.15 (d, J = 7.5 Hz,
1H, 9-H), 4.22 (d, J = 7.8 Hz, 1H, 11a-H), 3.63 – 3.69 (m, 1H, 3-H), 3.35 – 3.42 (m, 1H, 3-H), 2.43 –
13
2.59 (m, 1H, 1-H), 2.08 – 2.18 (m, 1H, 1-H), 1.91 – 2.00 (m, 2H, 2-H); C NMR: δ = 24.0 (C-2), 26.7
(C-1), 47.4 (C-3), 55.1 (C-11a), 124.6, 125.1, 127.7, 131.0, 132.8, 141.3, 164.3, 165.4 (CO); IR (KBr)
1679, 1614, 1456 cm-1; MS m/z (rel. Int.) 215 (M+, 39), 70 (100). Anal. Calcd for C12H13N3O: C, 66.96; H,
6.09; N, 19.52. Found: C, 66.71; H, 6.27; N, 19.65.
General procedure for the reaction of the cycloamidines (8 – 10) with malonic esters. All of these
reactions were carried out in vacuo at 3×10-2 mbar. An equimolar mixture of the cycloamidine and the
corresponding 2-substituted bis(2,4,6-trichlorophenyl)malonate was heated in a Zincke apparatus for 10
min at 180-190 °C, whereupon 2,4,6-trichlorophenol was distilled off. The residue was treated with ether
(20 mL), the resulting precipitate was collected by filtration and washed with diethylether. The crude solid
was recrystallized from the solvents indicated below.

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HETEROCYCLES, Vol. 65, No. 3, 2005
2-Ethyl-3-hydroxy-4b,5,6,7-tetrahydro-4,7a,12b-triazadibenzo[e,g]azulene-1,8-dione (11).
Cycloamidine (8) (0.430 g, 2.0 mmol) and 2-ethyl bis(2,4,6-trichlorophenyl)malonate (0.982 g, 2.0
20
1
mmol) were used, yield 0.529 g (85%), mp >250 °C (nitromethane); [α]D = -6.1 ° (c 0.5, DMSO); H
NMR: δ = 11.46 (s, 1H, OH), 7.79 (dd, J = 7.6, 1.7 Hz, 1H, 9-H), 7.61 (td, J = 7.6, 1.7 Hz, 1H, 10-H),
7.51 – 7.55 (m, 1H, 11-H), 7.49 – 7.51 (m, 1H, 12-H), 4.48 – 4.50 (m, 1H, 4b-H), 3.61 – 3.66 (m, 1H,
7-H), 3.38 – 3.45 (m, 1H, 7-H), 2.74 – 2.81 (m, 1H, 5-H), 2.35 (q, J = 7.4 Hz, 2H, CH2), 2.01 – 2.12 (m,
13
2H, 5,6-H), 1.92 – 1.98 (m, 1H, 6-H), 1.00 (t, J = 7.4 Hz, 3H, CH3); C NMR: δ = 13.3 (CH3), 17.3
(CH2), 24.2 (C-6), 27.0 (C-5), 47.0 (C-7), 58.9 (C-4b), 103.5 (C-2), 129.2, 129.7, 129.8, 131.1, 132.7,
133.8, 157.4 (C-4a), 163.6, 163.9, 164.3; IR (KBr) 1650, 1554, 1458 cm-1; MS m/z (rel. Int.) 311 (M+,
100). Anal. Calcd for C17H17N3O3 · 0.5 H2O: C, 63.74; H, 5.66; N, 13.12. Found: C, 63.47; H, 5.44; N,
13.34.
2-Benzyl-3-hydroxy-4b,5,6,7-tetrahydro-4,7a,12b-triazadibenzo[e,g]azulene-1,8-dione (12).
Cycloamidine (8) (0.430 g, 2.0 mmol) and 2-benzyl bis(2,4,6-trichlorophenyl)malonate (1.106 g, 2.0
20
1
mmol) were used, yield 0.537 g (72%), mp >250 °C (methanol); [α]D = -29.6 ° (c 0.5, DMSO); H
NMR: δ = 11.71 (s, 1H, OH), 7.80 (dd, J = 7. 5, 1.1 Hz, 1H, 9-H), 7.59 – 7.64 (m, 1H, 10-H), 7.52 – 7.55
(m, 1H, 11-H), 7.48 (d, J = 8.0 Hz, 1H, 12-H), 7.21 – 7.27 (m, 4H, Ph), 7.12 – 7.15 (m, 1H, Ph), 4.50 (d,
J = 6.3 Hz, 1H, 4b-H), 3.58 – 3.69 (m, 1H, 7-H), 3.37 – 3.44 (m, 1H, 7-H), 3.17 (s, 2H, CH2), 2.75 – 2.77
(m, 1H, 5-H), 2.01 – 2.14 (m, 2H, 5,6-H), 1.92 – 1.97 (m, 1H, 6-H); 13C NMR: δ = 24.1 (C-6), 27.0 (C-5),
29.6 (CH2), 47.0 (C-7), 58.9 (C-4b), 101.6 (C-2), 126.6, 129.0, 129.2, 129.3, 129.7, 129.8, 131.1, 132.6,
133.8, 141.4, 158.0 (C-4a), 163.8, 164.2, 164.5; IR (KBr) 1667, 1626, 1604, 1558, 1458 cm-1; MS m/z (rel.
Int.) 373 (M+, 100). Anal. Calcd for C22H19N3O3 · 0.5 H2O: C, 69.10; H, 5.27; N, 10.99. Found: C, 68.89;
H, 5.33; N, 10.76.
2-Ethyl-4-methyl-4,5,6,7-tetrahydro-4,7a,12b-triazadibenzo[e,g]azulene-1,3,8-trione (13).
Cycloamidine (9) (0.458 g, 2.0 mmol) and 2-benzyl bis(2,4,6-trichlorophenyl)malonate (0.982 g, 2.0
20
1
mmol) were used, yield 0.507 g (78%), mp 185–187 °C (xylene); [α]D = 0 ° (c 1.0, CHCl3); H NMR
(CDCl3): δ = 8.05 (dd, J = 8.1, 1.6 Hz, 1H, 9-H), 7.59 (ddd, J = 8.1, 7.4, 1.6 Hz, 1H, 10-H), 7.38 – 7.42
(m, 1H, 11-H), 7.35 (dd, J = 8.2, 0.8 Hz, 1H, 12-H), 4.00 – 4.06 (m, 2H, 7-H), 3.25 – 3.28 (m, 1H, 2-H),
3.22 (s, 3H, NCH3), 2.72 – 2.77 (m, 2H, 5-H), 2.20 – 2.28 (m, 1H, 6-H), 2.09 (dd, J = 7.4/6.3 Hz, 2H,
CH2CH3), 2.04 – 2.16 (m, 1H, 6-H), 1.16 (t, J = 7.4 Hz, 3H, CH2CH3); 13C NMR (CDCl3): δ = 12.9 (CH3),
17.2 (CH2), 20.9 (C-6), 29.7 (C-5), 29.7 (NCH3), 49.7 (C-7), 53.6 (C-2), 120.6, 125.8, 127.7, 129.0, 129.7,
132.6, 133.6, 140.5, 165.6 (CO), 167.1 (CO), 168.4 (CO); IR (KBr) 1681, 1632, 1574, 1489, 1452 cm-1;
MS m/z (rel. Int.) 325 (M+, 100). Anal. Calcd for C18H19N3O3: C, 66.45; H, 5.89; N, 12.91. Found: C,

HETEROCYCLES, Vol. 65, No. 3, 2005
631
66.37; H, 5.92; N, 12.91.
2-Benzyl-4-methyl-4,5,6,7-tetrahydro-4,7a,12b-triazadibenzo[e,g]azulene-1,3,8-trione (14).
Cycloamidine (9) (0.458 g, 2.0 mmol) and 2-benzyl bis(2,4,6-trichlorophenyl)malonate (0.982 g, 2.0
20
1
mmol) were used, yield 0.619 g (80%), mp 185–187 °C (xylene); [α]D = 0 ° (c 1.0, CHCl3); H NMR
(CDCl3): δ = 8.01 (dd, J = 7.7, 1.1 Hz, 1H, 9-H), 7.55 – 7.59 (m, 1H, 10-H), 7.21 – 7.42 (m, 7H, Ph), 3.91
– 4.01 (m, 2H, 7-H), 3.57 – 3.60 (m, 1H, 2-H), 3.42 (d, J = 5.7 Hz, 2H, CH2Ph), 3.19 (s, 3H, NCH3), 2.62
13
– 2.72 (m, 2H, 5-H), 2.14 – 2.19 (m, 1H, 6-H), 1.95 – 2.06 (m, 1H, 6-H); C NMR (CDCl3): δ = 20.7
(C-6), 29.3 (C-5), 29.7 (CH2Ph), 35.7 (NCH3), 49.7 (C-7), 54.9 (C-2), 120.2, 125.7, 126.8, 127.8, 128.8,
129.0, 129.2, 130.1, 132.7, 133.7, 140.4, 140.6, 165.5 (CO), 166.7 (CO), 168.0 (CO); IR (KBr) 1721,
1682, 1644, 1597, 1487, 1450 cm-1; MS m/z (rel. Int.) 387 (M+, 100). Anal. Calcd for C23H21N3O3: C,
71.30; H, 5.46; N, 10.85. Found: C, 71.46; H, 5.48; N, 10.61.
2-Ethyl-4-phenyl-4,5,6,7-tetrahydro-4,7a,12b-triazadibenzo[e,g]azulene-1,3,8-trione (15).
Cycloamidine (10) (0.582 g, 2.0 mmol) and 2-benzyl bis(2,4,6-trichlorophenyl)malonate (0.982 g, 2.0
mmol) were used, yield 0.612 g (79%), mp 201–202 °C (n-butanol); [α]D20 = 0 ° (c 1.0, CHCl3); 1H NMR
(CDCl3): δ = 8.07 – 8.09 (m, 1H, 9-H), 7.61 – 7.66 (m, 1H, 10-H), 7.41 – 7.46 (m, 2H, Ph), 7.27 – 7.34
(m, 2H, Ph), 7.08 – 7.20 (m, 3H, Ph), 3.94 – 3.98 (m, 2H, 7-H), 3.47 (td, J = 6.2, 0.8 Hz, 1H, 2-H), 2.44 –
2.50 (m, 1H, 6-H), 2.08 – 2.15 (m, 2H, CH2CH3), 1.82 – 2.02 (m, 3H, 5,6-H), 1.19 (td, J = 7.5, 0.8 Hz,
13
3H, CH2CH3); C NMR (CDCl3): δ = 12.9 (CH3), 17.3 (CH2), 20.4 (C-6), 29.8 (C-5), 50.0 (C-7), 54.5
(C-2), 119.1, 124.5, 124.8, 126.7, 128.0, 129.2, 129.6, 131.7, 132.9, 133.9, 139.1, 139.9, 165.6 (CO),
166.9 (CO), 167.0 (CO); IR (KBr) 1724, 1684, 1635, 1600, 1490, 1453 cm-1; MS m/z (rel. Int.) 387 (M+,
100). Anal. Calcd for C23H21N3O3: C, 71.30; H, 5.46; N, 10.85. Found: C, 70.93; H, 5.58; N, 10.72.
2-Benzyl-4-phenyl-4,5,6,7-tetrahydro-4,7a,12b-triazadibenzo[e,g]azulene-1,3,8-trione (16).
Cycloamidine (10) (0.582 g, 2.0 mmol) and 2-benzyl bis(2,4,6-trichlorophenyl)malonate (0.982 g, 2.0
20
1
mmol) were used, yield 0.790 g (88%), mp 187–188 °C (2-propanol); [α]D = 0 ° (c 1.0, CHCl3); H
NMR (CDCl3): δ = 8.06 – 8.08 (m, 1H, 9-H), 7.63 – 7.67 (m, 1H, 10-H), 7.42 – 7.48 (m, 4H, Ph), 7.22 –
7.35 (m, 5H, Ph), 7.15 – 7.19 (m, 1H, Ph), 7.06 – 7.09 (m, 2H, Ph), 3.87 – 3.98 (m, 2H, 7-H), 3.81 (t, J =
6.0 Hz, 1H, 2-H), 3.47 (d, J = 6.0 Hz, 2H, CH2Ph), 2.39 – 2.45 (m, 1H, 5-H), 1.82 – 1.97 (m, 3H, 5, 6-H);
13C NMR (CDCl3): δ = 20.2 (C-6), 29.3 (C-5), 29.8 (CH2Ph), 50.0 (C-7), 55.8 (C-2), 118.7, 124.5, 125.8,
126.8, 128.1, 128.9, 129.2, 129.4, 129.7, 130.2, 132.1, 132.9, 134.0, 139.1, 139.8, 140.6, 165.5 (CO),
166.4 (CO), 166.6 (CO); IR (KBr) 1735, 1695, 1633, 1619, 1574, 1496, 1454 cm-1; MS m/z (rel. Int.) 449
.
(M+, 100). Anal. Calcd for C28H23N3O3 0.5 2-propanol): C, 73.89; H, 5.68; N, 8.76. Found: C, 73.70; H,
5.67; N, 8.66.

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HETEROCYCLES, Vol. 65, No. 3, 2005
REFERENCES AND NOTES
1. D. E. Thurston and D. S. Bose, Chem. Rev., 1994, 94, 433.
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Tsunkawa, H. Kamei, M. Konishi, T. Miyaki, T. Oki, and H. Kawaguchi, J. Antibiot., 1988, 41,
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9. Crystallographic data have been deposited with the Cambridge Crystallographic Data Centre as
supplementary publication no. CCDC-258313. Copies of the data can be obtained free of charge on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: (+44)1223-336-033; e-mail:
deposit@ccdc.cam.ac.uk). Some crystal data of 16: C28H23N3O3 – 0.5 2-butanol; M = 486.55; space
group P-1 (no. 2); dimensions 0.50 x 0.30 x 0.20 mm, a = 10.9276(1), b = 11.6818(1), c =
11.6878(1) Å; α = 106.467(1)°, β = 115.771(1)°, γ = 99.841(1)°; V = 1211.44(2) Å3, Dc = 1.334 Mg
m-3, Z = 2, µ(MoKα) = 0.088 mm-1; T = 123(2) K; F(000) = 514, 23952 reflections were collected in
a Nonius KappaCD diffractometer (2Θmax. = 55°, -14 ≤ h ≤ 14, -15 ≤ k ≤ 15, -15 ≤ l ≤ 15), 5427
symmetry independent reflections (Rint = 0.0292) were used for the structure solution (direct
methods)10 and refinement (full-matrix least-squares on F2,11 330 parameters, 16 restraints),
non-hydrogen atoms were refined anisotropically, H atoms localized by difference electron density,
and were defined using a riding model; wR2 (all data) = 0.1008 [R1 = 0.0387 for 4856 I>2σ(I)].
10. G. M. Sheldrick, SHELXS-97, Acta Cryst., 1990, A46, 467.
11. G. M. Sheldrick, SHELXL-97, University of Göttingen, 1997.