Synthesis of pyrrolo[2,3-c]2,7-naphthyridine derivatives by cascade heterocyclization reaction of 2-amino-4-cyanomethyl-6-dialkylamino-3,5- pyridinedicarbonitriles

Article abstract of DOI:10.1016/j.tet.2004.05.007

Alkylation of the title pyridinedicarbonitriles with N-substituted chloroacetamides was found to give 5,6-diamino-8-dialkylamino-2,3-dihydro-2-oxo- 1H-pyrrolo[2,3-c]2,7-naphthyridine-9-carbonitriles. The structure of obtained compounds was unambiguously confirmed by X-ray crystallographic study. The heterocyclization reaction proceeded regioselectively involving 3-CN group of the starting pyridines without participation of 5-CN. The reasons of the selectivity were discussed. An interaction of prepared naphthyridine derivatives with acetic acid anhydride and cyclohexanone yielded 2-dialkylamino-6,8,9,10- tetrahydro-5-methyl-9-oxopyrimido[4,5,6-ij]pyrrolo[2,3-c]2,7-naphthyridine-1- carbonitriles and 2-dialkylamino-4,5,6,8,9,10-hexahydro-9-oxospiro{pyrimido[4,5, 6-ij]pyrrolo[2,3-c]2,7-naphthyridine-5,1′-cyclohexane}-1-carbonitriles, respectively. All fused 2,7-naphthyridines obtained were derivatives of novel heterocyclic systems.

Full text of DOI:10.1016/j.tet.2004.05.007

Tetrahedron 60 (2004) 5777–5783
Synthesis of pyrrolo[2,3-c]2,7-naphthyridine derivatives by
cascade heterocyclization reaction of 2-amino-4-cyanomethyl-6-
dialkylamino-3,5-pyridinedicarbonitriles
a
b
Anton V. Tverdokhlebov,a Elizaveta V. Resnyanska, Alexander V. Zavada,
,
*
Andrey A. Tolmachev,c Alexander N. Kostyukd and Alexander N. Chernegad
aEnamine Ltd. Co., I. Kudri str. 31, apt. 17, 02042 Kiev, Ukraine
bChernigov State University of Technology, Shevchenko str. 95, 14027 Chernigov, Ukraine
cKiev National Taras Shevchenko University, Volodimirska str. 62, 01033 Kiev, Ukraine
dInstitute of Organic Chemistry NAS, Murmanskaya str. 5, 02094 Kiev, Ukraine
Received 15 February 2004; revised 13 April 2004; accepted 6 May 2004
Abstract—Alkylation of the title pyridinedicarbonitriles with N-substituted chloroacetamides was found to give 5,6-diamino-8-
dialkylamino-2,3-dihydro-2-oxo-1H-pyrrolo[2,3-c]2,7-naphthyridine-9-carbonitriles. The structure of obtained compounds was unam-
biguously confirmed by X-ray crystallographic study. The heterocyclization reaction proceeded regioselectively involving 3-CN group of the
starting pyridines without participation of 5-CN. The reasons of the selectivity were discussed. An interaction of prepared naphthyridine
derivatives with acetic acid anhydride and cyclohexanone yielded 2-dialkylamino-6,8,9,10-tetrahydro-5-methyl-9-oxopyrimido[4,5,6-ij]-
pyrrolo[2,3-c]2,7-naphthyridine-1-carbonitriles and 2-dialkylamino-4,5,6,8,9,10-hexahydro-9-oxospiro{pyrimido[4,5,6-ij]pyrrolo[2,3-c]-
2,7-naphthyridine-5,10-cyclohexane}-1-carbonitriles, respectively. All fused 2,7-naphthyridines obtained were derivatives of novel
heterocyclic systems.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
(Fig. 1, structure 2) could be suitable precursors for natural
compounds and their analogues. Therefore, the synthesis of
the naphthyridines of type 2 is of interest.
2,7-Naphthyridine nucleus is known to be a part of a large
number of alkaloids.1–11 Thus, alangimaridine,1 isoala-
marine,2 alamaridines,3 nauclefine,4,5 naulafine,6 normalin-
dine,7 eudistones,8 cystodytins,9 kuanoniamines10 and
meridine11 can be mentioned as examples of natural
condensed 2,7-naphthyridines. Many of these alkaloids
consist of 2,7-naphthyridine moiety fused at the sides i,j and
c8–11 (Fig. 1, structure 1). Hence the [c]fused 2,7-naph-
thyridines bearing functional groups at appropriate positions
While a considerable number of 2,7-naphthyridines of type
2 fused with six-membered rings has been described in the
literature (for reviews see12–16), corresponding derivatives
condensed with five-membered heterocycles have been less
investigated.17–28 Thus, pyrazolo-,17,21 isoxazolo-,21 cyclo-
penta-,18 thieno-,19,20,22–24,26–28 furo-,22–24 and imidazo-25
annulated 2,7-naphthyridines 2 were prepared. At the same
time 2,7-naphthyridines fused at the side c with pyrrole
nucleus are hitherto unknown. This prompted us to look for
approaches to the pyrrolonaphthyridines of type 2.
2. Results and discussion
Most of the above mentioned compounds 2 were obtained
by the central pyridine ring formation starting from the
suitable pyridine and five-membered cyclic precursors in
one or several steps.17–25 An alternative approach, inclu-
ding ring annulations to the readily available 2,7-naphthyri-
dine, was applied for thieno derivatives only.26,27 Over the
last years so called cascade reactions have had an increasing
Figure 1. Dashed lines establish annulated rings. ‘fg’ is a functional group.
Keywords: Cascade reactions; Nitriles; Chloroacetamides; Pyrrolo[2,3-c]-
2,7-naphthyridines; Spiro compounds.
*
Corresponding author. Tel./fax: þ380-44-558-6553;
e-mail address: atver@univ.kiev.ua
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.05.007

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A. V. Tverdokhlebov et al. / Tetrahedron 60 (2004) 5777–5783
importance in heterocyclic chemistry,29–32 since they allow
creation of two or more rings at once at the expense of
sequential chemical transformations induced one by
another. It seems to be the most economical method for
condensed heterocycles preparation. Thus, recently cascade
process involving Smiles rearrangement and two sequential
nucleophilic additions to nitrile has been used for
thieno[2,3-c]2,7-naphthyridine synthesis.28
Previously we have shown utility of the readily available
pyridines 4–6 for 2,7-naphthyridine derivative preparation
by alkoxide induced 1,5-dinitrile cyclization reaction.33
Continuing our researches in this field we assumed
compounds 4–6 to be suitable starting materials for the
target pyrrolonaphthyridines synthesis via cascade reaction
with chloroacetamides. Thus, alkylation of the malonodi-
nitrile, ethyl cyanoacetate and 2-benzothiazoleacetonitrile
with N-substituted chloroacetamides was reported to yield
aminopyrrolones 334–40 (Fig. 2). Therefore, the similar
alkylation of the pyridines 4–6 also containing a CH2CN
moiety should afford the intermediates 7 (Scheme 1) which
should undergo further cyclization to give desired pyrrolo-
naphthyridines. However, there are two possibilities for ring
closure in the intermediates 7 with participation of 3-CN or
5-CN leading to the isomers 8–10 or 11, respectively. Of
course, a mixture of products could also be formed.
Nevertheless, reaction of the derivatives 4–6 with N-sub-
Figure 3. X-ray molecular structure of compound 9b with the atom
numbering used in the crystallographic analysis.
stituted chloroacetamides in ethanol in the presence of
K2CO3 was found to result in the individual compounds
isolated in 50–70% yields. Since the isomers 8–10 and
11 were difficult to distinguish using spectral data the
structures 8-10 were assigned to the products on the basis
of X-ray crystallographic study carried out for derivative
9b (Fig. 3).
According to the crystal data† pyrrole and pyridine ring
N2–C6–C4–C3–C8–C7 of compound 9b are coplanar
˚
(with precision of 0.03 A). Phenyl substituent is turned out
from this plane at the angle 728. The ring N1–C1–C2–C3–
C4–C5 is slightly twisted. The atoms C1 and C5 are
˚
deviated from the other rings plane at 20.21 A and
˚
þ0.34 A, respectively. Probably, this distortion is caused
by interaction between amino groups, namely the formation
of the intramolecular hydrogen bond N4–H· · ·N5 with the
˚
length 3.01 A and the angle N4–H–N5 1508. Of course, the
Figure 2. X¼CN, CO2Et, 2-benzothiazolyl.
Scheme 1. R1¼a: 4-(i-Pr)C6H4, b: 4-CH3C6H4, c: 3,4-(MeO)2C6H3, d: 4-MeOC6H4CH2, e: 3-ClC6H4, f: 4-ClC6H4.
†
Crystallographic data (excluding structure factors) for the structure in this
paper have been deposited with the Cambridge Crystallographic Data
Center as supplementary publication number CCDC 230079. Copies of
the data can be obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge, CB2 1EZ, UK (fax:þ44-1223-336033 or
e-mail: deposit@ccdc.cam.ac.uk).

A. V. Tverdokhlebov et al. / Tetrahedron 60 (2004) 5777–5783
5779
Apparently, fused naphthyridines 13 and 14 are the
representatives of novel heterocyclic systems.
To summarize, the present investigation has resulted in a
convenient method for the synthesis of pyrrolo[2,3-c]2,7-
naphthyridines 8–10, the derivatives of a hitherto unknown
heterocyclic system. Furthermore, compounds 8–10 have
been converted easily into more complex novel condensed
and spirocyclic heterocycles 13, 14. It should be noted that
the starting materials 4–6 were obtained by amination of
2-amino-6-chloro-4-cyanomethyl-3,5-pyridinedicarbo-
nitrile (15) in quantitative yields.33 The chloropyridine
precursor 15 was in turn available from malonodinitrile and
inorganic materials in two steps.41 Hence derivatives 8–10
and 13, 14 have been prepared from malonodinitrile in four
and five steps, respectively. The other reagents used, such as
amines, chloroacetamides, acetic anhydride and cyclohexa-
none, are also of general access. The simpler and cheaper
sources for the preparation of complex heterocycles are
difficult to be proposed. Of course, the corner-stone of the
present synthetic pathway is the cascade heterocyclization
reaction of the pyridines 4–6 occurred regioselectively with
the 3-CN group. Moreover, potential of the pyridines 4–6 in
heterocyclic synthesis is believed not to be limited to the
present work and further research on their chemistry are in
progress.
Figure 4.
distortions of the pyridine ring are small and the aromaticity
of the naphthyridine moiety is not infringed.
It should be emphasized that there were no detectable
amounts of the isomers 11 in the reaction mixtures. Hence
the ring closure in the intermediates 7 proceeded regio-
selectively with participation of 3-CN. The selectivity was
explained in the terms of transition state energy. Thus,
nucleophilic additions to nitriles were assumed to occur
synchronously or quickly one after another. Therefore, the
transition states like 12 (Fig. 4) could be employed to
describe the addition process. The transition state 12a
corresponding to the heterocyclization with 3-CN is
additionally stabilized by intramolecular hydrogen bond.
On the other hand the bulky dialkylamino group is not only
unable to stabilize the alternative transition state 12b, but
seems to act destructively due to repulsion with neighbour-
ing substituent. Consequently, the energy of the transition
state 12a is lower and the reaction proceeds through it
resulting in pyrrolonaphthyridines 8–10. It is noteworthy
that predominant reactivity of 3-CN versus 5-CN in
heterocyclization reactions of compounds 4–6 and related
derivatives has been reported previously by us33 and other
researchers.41
3. Experimental
The pyridines 4–633 and chloroacetamides47 were prepared
as reported. Other reagents were commercially available.
All melting points were determined in open capillary tubes
in a Thiele apparatus and are uncorrected. 1H and 13C NMR
1
spectra were recorded on a Mercury 400 (400 MHz for H
and 100 MHz for 13C) spectrometer in DMSO-d6 solutions.
Chemical shifts (d) are given in ppm downfield from
internal SiMe4. J values are in Hz. The purity of all
The possibility of additional ring annulation to the
compounds 8–10 using their amino groups was examined.
Thus, treatment of the derivatives 8a,b, 9e, 10f with excess
of acetic acid anhydride or cyclohexanone yielded pyri-
mido[4,5,6-ij]pyrrolo[2,3-c]2,7-naphthyridines 13a–d and
spirocyclic compounds 14a–d, respectively (Scheme 2).
The structures of compounds 13 and 14 were confirmed by
1H and 13C NMR data. Furthermore the similar transform-
ations are well known for 1,8-naphthalenediamine.42–46
1
compounds prepared was checked by H NMR.
3.1. Pyrrolo[2,3-c]2,7-naphthyridines 8–10. General
procedure
Powdered K2CO3 (0.41 g, 3.0 mmol) and chloroacetamide
(2.5 mmol) were added to a hot solution of the pyridines
4–6 (2.5 mmol) in absolute ethanol (10 ml) and the
Scheme 2.

5780
A. V. Tverdokhlebov et al. / Tetrahedron 60 (2004) 5777–5783
resulting mixture was refluxed for 30–40 min. After cooling
the precipitated solid was filtered, thoroughly washed with
water, dried and recrystallized from an appropriate solvent
to give compounds 8–10.
J¼7.2 Hz, HR1), 6.57 (2H, s, NH2), 4.74 (2H, s, N3-CH2),
3.73 (2H, s, 1-CH2), 3.70 (3H, s, OCH3), 3.67 (4H, m,
NCH2), 1.59 (6H, m, CH2CH2CH2). dC 179.5 (2-CO), 167.8
(9a-C), 159.0 (6-C), 157.6 (4-CR1), 155.0 (5-C), 153.3
(8-C), 139.5 (3a-C), 131.5 (1-CR1), 127.1 (2,6-CR1), 115.7
(3,5-CR1), 115.5 (CN), 98.5 (5a-C), 91.8 (9b-C), 68.6 (9-C),
57.3 (2,6-CNR2), 55.3 (OCH3), 47.2 (NCH2), 38.1 (1-C),
29.5 (3,5-CNR2), 26.1 (4-CNR2). Found: 65.1% C, 5.5% H,
22.0% N; C24H25N7O2 requires 65.0% C, 5.7% H, 22.1% N.
3.1.1. 5,6-Diamino-2,3-dihydro-2-oxo-8-(1-piperidinyl)-
3-[4-(i-propyl)phenyl]-1H-pyrrolo[2,3-c]2,7-naphthyri-
dine-9-carbonitrile (8a). Yield 64%. White needles. Mp
269 8C (from dioxane); nmax (KBr tablets) 3460, 3330,
2955, 2880, 2200, 1735, 1620, 1590, 1550, 1460, 1345,
1300, 1215, 1160, 1130, 1040, 850, 815, 710 cm21. dH 7.34
(2H, d, J¼6.8 Hz, HR1), 7.28 (2H, d, J¼6.8 Hz, HR1),
7.18 (2H, s, NH2), 6.55 (2H, s, NH2) 3.86 (2H, s, 1-CH2),
3.69 (4H, m, NCH2), 2.94 (1H, m, i-Pr), 1.59 (6H, m,
CH2CH2CH2), 1.23 (6H, d, J¼6.4 Hz, i-Pr). dC 178.2
(2-CO), 163.3 (9a-C), 156.4 (5-C), 156.1 (6-C), 151.7 (8-C),
142.3 (3a-C), 135.1 (1-CR1), 130.9 (4-CR1), 128.6 (3,5-CR1),
127.0 (2,6-CR1), 116.9 (CN), 97.9 (5a-C), 89.6 (9b-C), 70.8
(9-C), 52.2 (2,6-CNR2), 36.4 (1-C), 34.5 (i-Pr), 25.2
(3,5-CNR2), 22.0 (4-CNR2), 18.9 (i-Pr). Found: 67.9% C,
6.0% H, 22.4% N; C25H27N7O requires 68.0% C, 6.2% H,
22.2% N.
3.1.5. 5,6-Diamino-2,3-dihydro-8-(4-morpholinyl)-2-oxo-
3-[4-(i-propyl)phenyl]-1H-pyrrolo[2,3-c]2,7-naphthyri-
dine-9-carbonitrile (9a). Yield 62%. White powder. Mp
242 8C (from DMF); nmax (KBr tablets) 3420, 3360, 2920,
2195, 1725, 1650, 1575, 1490, 1350, 1275, 1205, 1170,
1115, 1030, 805, 720 cm21. dH 7.35 (2H, d, J¼8.0 Hz, HR1),
7.29 (2H, d, J¼8.0 Hz, HR1), 7.24 (2H, s, NH2), 6.57 (2H, s,
NH2), 3.86 (2H, s, 1-CH2), 3.69 (8H, m, NR2), 2.95 (1H, m,
i-Pr), 1.24 (6H, d, J¼8.0 Hz, i-Pr). dC 179.3 (2-CO), 160.0
(6-C), 159.2 (5-C), 158.4 (9a-C), 148.6 (8-C), 141.5 (3a-C),
136.2 (1-CR1), 132.7 (4-CR1), 127.7 (2,6-CR1), 127.4
(3,5-CR1), 115.6 (CN), 102.7 (5a-C), 96.2 (9b-C), 70.5
(9-C), 66.1 (OCH2), 51.9 (NCH2), 39.6 (1-C), 32.9 (i-Pr),
20.3 (i-Pr). Found: 64.9% C, 5.8% H, 22.1% N;
C24H25N7O2 requires 65.0% C, 5.7% H, 22.1% N.
3.1.2. 5,6-Diamino-2,3-dihydro-3-(4-methylphenyl)-2-
oxo-8-(1-piperidinyl)-1H-pyrrolo[2,3-c]2,7-naphthyri-
dine-9-carbonitrile (8b). Yield 69%. White powder. Mp
296 8C (from DMF); nmax (KBr tablets) 3465, 3340, 2970,
2200, 1735, 1595, 1450, 1300, 880, 760, 705, 630 cm21. dH
7.27 (4H, m, HR1), 7.12 (2H, s, NH2), 6.48 (2H, s, NH2),
3.86 (2H, s, 1-CH2), 3.69 (4H, m, NCH2), 2.36 (3H, s, CH3),
1.61 (6H, m, CH2CH2CH2). dC 176.8 (2-CO), 168.1 (9a-C),
160.6 (5-C), 159.7 (6-C), 152.9 (8-C), 138.2 (3a-C), 138.0
(4-CR1), 135.5 (1-CR1), 129.5 (3,5-CR1), 126.5 (2,6-CR1),
119.8 (CN), 99.3 (5a-C), 91.2 (9b-C), 68.8 (9-C), 57.1
(2,6-CNR2), 35.7 (1-C), 27.2 (3,5-CNR2), 20.1 (CH3), 17.4
(4-CNR2). Found: 67.0% C, 5.5% H, 23.9% N; C23H23N7O
requires 66.8% C, 5.6% H, 23.7% N.
3.1.6. 5,6-Diamino-2,3-dihydro-3-(4-methylphenyl)-8-(4-
morpholinyl)-2-oxo-1H-pyrrolo[2,3-c]2,7-naphthyri-
dine-9-carbonitrile (9b). Yield 65%. Colorless prisms. Mp
286 8C (from DMF); nmax (KBr tablets) 3395, 3345, 2980,
2220, 1745, 1560, 1465, 1305, 855, 775, 705, 670 cm21. dH
7.27 (4H, m, HR1), 7.23 (2H, s, NH2), 6.55 (2H, s, NH2),
3.86 (2H, s, 1-CH2), 3.68 (8H, m, NR2), 2.36 (3H, s, CH3).
dC 179.7 (2-CO), 161.7 (5-C), 158.8 (9a-C), 158.1 (6-C),
146.9 (8-C), 140.6 (3a-C), 138.7 (1-CR1), 137.9 (4-CR1),
129.7 (3,5-CR1), 129.3 (2,6-CR1), 114.4 (CN), 104.1 (5a-C),
89.7 (9b-C), 69.7 (9-C), 67.9 (OCH2), 53.6 (NCH2), 35.5
(1-C), 20.5 (CH3). Found 63.5% C, 5.2% H, 23.8% N;
C22H21N7O2 requires 63.6% C, 5.1% H, 23.6% N.
3.1.3. 5,6-Diamino-2,3-dihydro-3-(3,4-dimethoxyphenyl)-
2-oxo-8-(1-piperidinyl)-1H-pyrrolo[2,3-c]2,7-naphthyri-
dine-9-carbonitrile (8c). Yield 54%. Yellow prisms. Mp
172 8C (from EtOH); nmax (KBr tablets) 3430, 3330, 2980,
2850, 2200, 1730, 1620, 1520, 1490, 1280, 1140, 1025,
820 cm21. dH 7.17 (2H, s, NH2), 7.04 (1H, d, J¼8.4 Hz,
5-HR1), 6.98 (1H, d, J¼2.0 Hz, 2-HR1), 6.90 (1H, dd, J¼8.4,
2.0 Hz, 6-HR1), 6.55 (2H, s, NH2), 3.85 (2H, s, 1-CH2), 3.80
(3H, s, OCH3), 3.75 (3H, s, OCH3), 3.70 (4H, m, NCH2),
1.61 (6H, m, CH2CH2CH2). dC 179.2 (2-CO), 165.2 (9a-C),
159.9 (5-C), 154.6 (6-C), 152.3 (8-C), 150.2 (3-CR1), 149.3
(4-CR1), 142.7 (3a-C), 128.1 (1-CR1), 122.4 (CN), 117.4
(2-CR1), 116.2 (6-CR1), 111.9 (5-CR1), 97.7 (5a-C), 86.1
(9b-C), 69.5 (9-C), 56.4 (OCH3), 55.2 (OCH3), 52.1
(2,6-CNR2), 40.8 (1-C), 23.4 (3,5-CNR2), 22.6 (4-CNR2).
Found: 62.9% C, 5.4% H, 21.6% N; C24H25N7O3 requires
62.7% C, 5.5% H, 21.3% N.
3.1.7. 5,6-Diamino-2,3-dihydro-3-(3,4-dimethoxyphenyl)-
8-(4-morpholinyl)-2-oxo-1H-pyrrolo[2,3-c]2,7-naphthyri-
dine-9-carbonitrile (9c). Yield 57%. Light-brown powder.
Mp 201 8C (from EtOH); nmax (KBr tablets) 3415, 3345,
2935, 2220, 1740, 1600, 1550, 1450, 1270, 1130, 1035,
820 cm21. dH 7.23 (2H, s, NH2), 7.04 (1H, d, J¼8.1 Hz,
5-HR1), 6.98 (1H, d, J¼1.8 Hz, 2-HR1), 6.90 (1H, dd, J¼8.1,
1.8 Hz, 6-HR1), 6.57 (2H, s, NH2), 3.85 (2H, s, 1-CH2), 3.80
(3H, s, OCH3), 3.75 (3H, s, OCH3), 3.69 (8H, m, NR2). dC
178.8 (2-CO), 158.8 (5-C), 157.9 (6-C), 156.0 (9a-C), 152.2
(3-CR1), 152.0 (4-CR1), 150.2 (8-C), 143.9 (3a-C), 130.3
(1-CR1), 118.6 (6-CR1), 115.2 (CN), 109.5 (2-CR1), 107.7
(5-CR1), 98.6 (5a-C), 93.4 (9b-C), 68.5 (9-C), 63.5 (OCH2),
56.0 (OCH3), 55.9 (OCH3), 50.7 (NCH2), 41.4 (1-C).
Found: 59.6% C, 4.9% H, 21.1% N; C23H23N7O4 requires
59.9% C, 5.0% H, 21.3% N.
3.1.4. 5,6-Diamino-2,3-dihydro-3-[(4-methoxyphenyl)-
methyl]-2-oxo-8-(1-piperidinyl)-1H-pyrrolo[2,3-c]2,7-
naphthyridine-9-carbonitrile (8d). Yield 56%. White
powder. Mp 192 8C (from EtOH); nmax (KBr tablets)
3450, 3375, 2960, 2880, 2205, 1710, 1615, 1585, 1460,
1370, 1335, 1305, 1260, 1190, 1040, 920, 870 cm21. dH
7.27 (2H, d, J¼7.2 Hz, HR1), 7.11 (2H, s, NH2), 6.84 (2H, d,
3.1.8. 5,6-Diamino-2,3-dihydro-3-[(4-methoxyphenyl)-
methyl]-8-(4-morpholinyl)-2-oxo-1H-pyrrolo[2,3-c]2,7-
naphthyridine-9-carbonitrile (9d). Yield 51%. Colorless
needles. Mp 217 8C (from dioxane); nmax (KBr tablets)
3425, 3320, 2940, 2200, 1730, 1605, 1570, 1420, 1355,
1305, 1285, 1215, 1000, 940, 865 cm21. dH 7.31 (4H, m,

A. V. Tverdokhlebov et al. / Tetrahedron 60 (2004) 5777–5783
5781
NH2, HR1), 6.88 (2H, d, J¼8.0 Hz, HR1), 6.71 (2H, s, NH2),
4.77 (2H, s, N3–CH2), 3.76 (2H, s, 1-CH2), 3.73, (3H, s,
OCH3), 3.69 (8H, m, NR2). dC 179.3 (2-CO), 168.2 (9a-C),
160.3 (5-C), 159.2 (4-CR1), 156.6 (6-C), 146.5 (3a-C), 146.1
(8-C), 130.8 (2,6-CR1), 129.3 (1-CR1), 116.1 (CN), 115.8
(3,5-CR1), 103.1 (5a-C), 92.4 (9b-C), 67.9 (9-C), 64.3
(OCH2), 55.3 (OCH3), 55.1 (NCH2), 43.9 (N3–CH2) 36.4
(1-C). Found: 62.2% C, 5.1% H, 21.9% N; C23H23N7O3
requires 62.0% C, 5.2% H, 22.0% N.
1070, 850 cm21. dH 7.08 (2H, s, NH2), 7.02 (1H, dd, J¼8.4,
1.6 Hz, 6-HR1), 6.97 (1H, d, J¼1.6 Hz, 2-HR1), 6.89 (2H, d,
J¼8.4 Hz, 5-HR1), 6.50 (2H, s, NH2), 3.90 (2H, s, 1-CH2),
3.79 (3H, s, OCH3), 3.73 (3H, s, OCH3), 3.62 (4H, q, J¼
6.0 Hz, NR2), 1.19 (6H, t, J¼6.0 Hz, NR2). dC 179.5
(2-CO), 161.6 (9a-C), 158.6 (5-C), 157.8 (6-C), 157.5 (8-C),
156.8 (3-CR1), 148.9 (4-CR1), 144.8 (3a-C), 127.8 (1-CR1),
118.7 (CN), 118.2 (6-CR1), 115.7 (5-CR1), 111.7 (2-CR1),
98.1 (5a-C), 92.2 (9b-C), 70.8 (9-C), 58.7 (OCH3), 55.7
(OCH3), 41.9 (CNR2), 36.3 (1-C), 13.7 (CNR2). Found:
62.0% C, 5.9% H, 22.0% N; C23H25N7O3 requires 61.7% C,
5.6% H, 21.9% N.
3.1.9. 3-(3-Chlorophenyl)-5,6-diamino-2,3-dihydro-8-(4-
morpholinyl)-2-oxo-1H-pyrrolo[2,3-c]2,7-naphthyri-
dine-9-carbonitrile (9e). Yield 70%. Light-gray powder.
Mp .300 8C (from DMF); nmax (KBr tablets) 3420, 3300,
2915, 2220, 1740, 1610, 1490, 1470, 1280, 1170, 1120,
1050, 940, 790 cm21. dH 7.48 (2H, m, 4,6-HR1), 7.42 (1H, s,
2-HR1), 7.38 (1H, t, J¼6.6 Hz, 5-HR1), 7.11 (2H, s, NH2),
6.49 (2H, s, NH2), 3.86 (2H, s, 1-CH2), 3.71 (8H, m, NR2).
dC 181.1 (2-CO), 162.3 (6-C), 159.7 (5-C), 158.6 (9a-C),
149.4 (8-C), 147.1 (3a-C), 137.7 (1-CR1), 135.5 (3-CR1),
130.0 (4-CR1), 128.9 (6-CR1), 127.5 (5-CR1), 123.4 (2-CR1),
115.5 (CN), 104.7 (5a-C), 94.7 (9b-C), 66.3 (9-C), 65.4
(OCH2), 53.4 (NCH2), 37.5 (1-C). Found: 57.7% C, 4.2% H,
8.3% Cl, 22.6% N; C21H18ClN7O2 requires 57.9% C, 4.2%
H, 8.1% Cl, 22.5% N.
3.1.13. 5,6-Diamino-8-diethylamino-2,3-dihydro-3-[(4-
methoxyphenyl)methyl]-2-oxo-1H-pyrrolo[2,3-c]2,7-
naphthyridine-9-carbonitrile (10d). Yield 60%. White
powder. Mp 193 8C (from EtOH); nmax (KBr tablets) 3410,
3330, 2970, 2210, 1730, 1605, 1585, 1450, 1320, 1305,
1250, 1215, 1070, 945, 890 cm21. dH 7.28 (2H, d, J¼
7.6 Hz, HR1), 7.05 (2H, s, NH2), 6.84 (2H, d, J¼7.6 Hz,
HR1), 6.58 (2H, s, NH2), 4.73 (2H, s, N3–CH2), 3.76 (2H, s,
1-CH2), 3.70 (3H, s, OCH3), 3.61 (4H, q, J¼6.0 Hz, NR2),
1.18 (6H, t, J¼6.0 Hz, NR2). dC 177.1 (2-CO), 159.5 (6-C),
158.7 (4-CR1), 158.2 (8-C), 158.1 (5-C), 157.4 (9a-C), 146.5
(3a-C), 129.5 (2,6-CR1), 127.4 (1-CR1), 116.5 (CN), 115.2
(3,5-CR1), 99.1 (5a-C), 87.6 (9b-C), 68.4 (9-C), 59.1
(OCH3), 46.1 (CNR2), 43.7 (NCH2), 37.1 (1-C), 13.6
(CNR2). Found: 63.9% C, 6.0% H, 23.0% N; C23H25N7O2
requires 64.0% C, 5.8% H, 22.7% N.
3.1.10. 5,6-Diamino-8-diethylamino-2,3-dihydro-2-oxo-
3-[4-(i-propyl)phenyl]-1H-pyrrolo[2,3-c]2,7-naphthyri-
dine-9-carbonitrile (10a). Yield 63%. White needles. Mp
255 8C (from dioxane); nmax (KBr tablets) 3410, 3345,
2980, 2210, 1730, 1670, 1435, 1300, 1275, 1205, 1195,
1100, 1060, 800, 725 cm21. dH 7.37 (2H, d, J¼8.0 Hz, HR1),
7.32 (2H, d, J¼8.0 Hz, HR1), 7.11 (2H, s, NH2), 6.53 (2H, s,
NH2), 3.92 (2H, s, 1-CH2), 3.66 (4H, q, J¼6.4 Hz, NR2),
2.97 (1H, m, i-Pr), 1.27 (12H, m, NR2, i-Pr). dC 178.7
(2-CO), 159.9 (6-C), 158.3 (5-C), 157.5 (9a-C), 146.6 (8-C),
144.6 (3a-C), 134.8 (1-CR1), 133.5 (4-CR1), 130.7 (3,5-CR1),
126.4 (2,6-CR1), 117.1 (CN), 104.2 (5a-C), 91.5 (9b-C),
68.7 (9-C), 44.6 (CNR2), 36.3 (1-C), 35.8 (i-Pr), 21.9 (i-Pr),
14.1 (CNR2). Found: 67.0% C, 6.6% H, 22.9% N;
C24H27N7O requires 67.1% C, 6.3% H, 22.8% N.
3.1.14. 3-(4-Chlorophenyl)-5,6-diamino-8-diethylamino-
2,3-dihydro-2-oxo-1H-pyrrolo[2,3-c]2,7-naphthyridine-
9-carbonitrile (10f). Yield 69%. Yellow needles. Mp
242 8C (from DMF); nmax (KBr tablets) 3405, 3300, 2955,
2220, 1750, 1665, 1445, 1385, 1345, 1130, 1050, 840 cm21
.
dH 7.55 (2H, d, J¼8.4 Hz, HR1), 7.45 (2H, d, J¼8.4 Hz,
HR1), 7.11 (2H, s, NH2), 6.52 (2H, s, NH2), 3.91 (2H, s,
1-CH2), 3.64 (4H, q, J¼7.2 Hz, NR2), 1.20 (6H, t, J¼
7.2 Hz, NR2). dC 177.2 (2-CO), 167.6 (9a-C), 158.5 (5-C),
155.4 (6-C), 154.6 (8-C), 144.4 (3a-C), 135.1 (1-CR1), 133.9
(4-CR1), 127.1 (2,6-CR1), 124.9 (3,5-CR1), 116.8 (CN), 98.5
(5a-C), 91.3 (9b-C), 68.5 (9-C), 46.5 (CNR2), 36.2 (1-C), 9.9
(CNR2). Found: 59.9% C, 4.5% H, 23.2% N, 8.6% Cl;
C21H20ClN7O requires 59.8% C, 4.8% H, 23.2% N, 8.4%
Cl.
3.1.11. 5,6-Diamino-8-diethylamino-2,3-dihydro-3-(4-
methylphenyl)-2-oxo-1H-pyrrolo[2,3-c]2,7-naphthyri-
dine-9-carbonitrile (10b). Yield 66%. Colorless plates. Mp
225 8C (from DMF); nmax (KBr tablets) 3440, 3330, 2950,
2210, 1735, 1610, 1445, 1340, 1215, 1125, 810, 735, 705,
600 cm21. dH 7.28 (2H, d, J¼8.0 Hz, HR1), 7.24 (2H, d,
J¼8.0 Hz, HR1), 7.07 (2H, s, NH2), 6.47 (2H, s, NH2), 3.89
(2H, s, 1-CH2), 3.63 (4H, q, J¼6.4 Hz, NR2), 2.35 (3H, s,
CH3), 1.20 (6H, t, J¼6.4 Hz, NR2). dC 179.6 (2-CO), 164.5
(9a-C), 158.9 (6-C), 158.3 (5-C), 156.0 (8-C), 139.9 (3a-C),
136.1 (4-CR1), 133.5 (1-CR1), 128.7 (3,5-CR1), 126.4
(2,6-CR1), 119.1 (CN), 96.7 (5a-C), 89.1 (9b-C), 69.8
(9-C), 47.3 (CNR2), 37.9 (1-C), 17.5 (CH3), 9.5 (CNR2).
Found: 65.7% C, 5.9% H, 24.2% N; C22H23N7O requires
65.8% C, 5.8% H, 24.4% N.
3.2. Pyrimido[4,5,6-ij]pyrrolo[2,3-c]2,7-naphthyridines
13a–d. General procedure
A solution of pyrrolonaphthyridine 8a,b, 9e, 10f (2 mmol)
in acetic acid anhydride (5 ml) was refluxed for 30 min.
After cooling the precipitate formed was filtered, washed
with water and recrystallized from DMF to yield derivatives
13a–d.
3.2.1. 5-Methyl-9-oxo-2-(1-piperidinyl)-8-[4-(i-propyl)-
phenyl]-6,8,9,10-tetrahydropyrimido[4,5,6-ij]pyrrolo-
[2,3-c]2,7-naphthyridine-1-carbonitrile (13a). Yield 95%.
Pale-yellow powder. Mp .300 8C (from DMF); nmax (KBr
tablets) 2980, 2955, 2890, 2205, 1750, 1670, 1640, 1600,
1530, 1450, 1325, 1205, 1160, 1120, 1040, 920, 840,
685 cm21. dH 12.78 (1H, br s, NH), 7.37 (2H, d, J¼8.0 Hz,
HR1), 7.33 (2H, d, J¼8.0 Hz, HR1), 3.85 (2H, s, 10-CH2),
3.1.12. 5,6-Diamino-8-diethylamino-2,3-dihydro-3-(3,4-
dimethoxyphenyl)-2-oxo-1H-pyrrolo[2,3-c]2,7-naph-
thyridine-9-carbonitrile (10c). Yield 58%. Yellow
powder. Mp 132 8C (from EtOH); nmax (KBr tablets)
3450, 3335, 2930, 2210, 1750, 1630, 1475, 1240, 1175,

5782
A. V. Tverdokhlebov et al. / Tetrahedron 60 (2004) 5777–5783
3.72 (4H, m, NCH2), 2.97 (1H, m, i-Pr), 2.31 (3H, s, 5-CH3),
1.62 (6H, m, CH2CH2CH2), 1.25 (6H, d, J¼6.8 Hz, i-Pr). dC
169.2 (9-CO), 151.8 (5-C), 150.3 (6a-C), 147.7 (3a-C),
146.3 (2-C), 145.4 (7a-C), 131.5 (4-CR1), 130.8 (1-CR1),
127.6 (3,5-CR1), 122.1 (2,6-CR1), 117.7 (10b-C), 107.1
(CN), 96.8 (10c-C), 89.2 (10a-C), 65.1 (1-C), 53.4 (2,6-
CNR2), 33.1 (i-Pr), 26.2 (3.5-CNR2), 26.1 (10-C), 24.5 (4-
CNR2), 16.3 (5-CH3), 15.8 (i-Pr). Found: 69.4% C, 5.7% H,
21.0% N; C27H27N7O requires 69.7% C, 5.9% H, 21.1% N.
in cyclohexanone (5 ml) was heated at 100 8C for 1 h. After
cooling water (10 ml) was added resulting in a dark oil
separation. The liquid was decanted; the oil was dissolved in
ethanol and then precipitated again by water as pale crystals,
which were filtered and recrystallized from an appropriate
solvent to give compounds 14a–d.
3.3.1. 4,5,6,8,9,10-Hexahydro-9-oxo-2-(1-piperidinyl)-8-
[4-(i-propyl)phenyl]-sprio{pyrimido[4,5,6-ij]pyrrolo-
[2,3-c]2,7-naphthyridine-5,10-cyclohexane}-1-carbo-
nitrile (14a). Yield 68%. White powder. Mp 278 8C (from
dioxane); nmax (KBr tablets) 3300, 2965, 2890, 2205, 1725,
3.2.2. 5-Methyl-8-(4-methylphenyl)-9-oxo-2-(1-piperi-
dinyl)-6,8,9,10-tetrahydropyrimido[4,5,6-ij]pyrrolo-
[2,3-c]2,7-naphthyridine-1-carbonitrile (13b). Yield
99%. Yellow plates. Mp .300 8C (from DMF); nmax (KBr
tablets) 3300, 2955, 2875, 2210, 1725, 1645, 1590, 1535,
1455, 1330, 1215, 1170, 825 cm21. dH 12.84 (1H, br s, NH),
7.30 (4H, m, HR1), 3.85 (2H, s, 10-CH2), 3.72 (4H, m,
NCH2), 2.37 (3H, s, CH3), 2.31 (3H, s, CH3), 1.62 (6H, m,
CH2CH2CH2). dC 170.9 (9-CO), 153.5 (5-C), 151.1 (2-C),
150.2 (6a-C), 144.7 (3a-C), 137.8 (7a-C), 135.1 (4-CR1),
134.6 (1-CR1), 125.1 (2,6-CR1), 124.4 (3,5-CR1), 120.4
(10b-C), 108.7 (CN), 100.9 (10c-C), 94.5 (10a-C), 62.3
(1-C), 47.2 (2,6-CNR2), 26.5 (10-C), 23.4 (3.5-CNR2), 17.7
(CH3), 17.6 (4-CNR2), 9.9 (5-CH3). Found: 68.8% C, 5.5% H,
22.3% N; C25H23N7O requires 68.6% C, 5.3% H, 22.4% N.
1650, 1535, 1495, 1295, 1200, 1155, 1065, 875, 760 cm21
.
dH 8.06 (1H, s, NH), 7.77 (1H, s, NH), 7.34 (2H, d, J¼
8.0 Hz, HR1), 7.27 (2H, d, J¼8.0 Hz, HR1), 3.81 (2H, s,
10-CH2), 3.69 (4H, m, NCH2), 2.94 (1H, m, i-Pr), 1.71 (4H,
m, 20,60-CH2), 1.60 (10H, m, NR2, 30,50-CH2), 1.30 (2H, m,
40-CH2), 1.22 (6H, d, J¼6.8 Hz, i-Pr). dC 177.1 (9-CO),
160.6 (10b-C), 158.4 (3a-C), 156.6 (2-C), 156.4 (6a-C),
143.4 (7a-C), 136.7 (4-CR1), 135.6 (1-CR1), 127.6 (3,5-CR1),
124.4 (2,6-CR1), 117.6 (CN), 98.2 (10c-C), 88.3 (10a-C),
73.2 (5-C), 69.7 (1-C), 50.1 (2,6-CNR2), 39.5 (20,60-C), 36.6
(10-C), 36.5 (i-Pr), 23.9 (40-C), 23.6 (3,5-CNR2), 20.5 (i-Pr),
19.9 (30,50-C), 19.7 (4-CNR2). Found: 71.3% C, 6.9% H,
18.7% N; C31H35N7O requires 71.4% C, 6.8% H, 18.8% N.
3.2.3. 8-(3-Chlorophenyl)-5-methyl-2-(4-morpholinyl)-9-
oxo-6,8,9,10-tetrahydropyrimido[4,5,6-ij]pyrrolo[2,3-c]-
2,7-naphthyridine-1-carbonitrile (13c). Yield 91%. Pale-
green powder. Mp .300 8C (from DMF); nmax (KBr tablets)
2975, 2220, 1745, 1585, 1475, 1400, 1305, 1270, 1195,
1125, 1055, 970, 820 cm21. dH 12.96 (1H, br s, NH), 7.59
(1H, s, 2-HR1), 7.54 (2H, m, 4,6-HR1), 7.47 (1H, t, J¼
7.2 Hz, 5-HR1), 3.83 (2H, s, 10-CH2), 3.70 (4H, m, OCH2),
3.67 (4H, m, NCH2), 2.33 (3H, s, CH3). dC 172.6 (9-CO),
151.1 (5-C), 149.9 (3a-C), 148.6 (6a-C), 147.8 (2-C), 139.9
(3-CR1), 138.3 (7a-C), 133.2 (1-CR1), 125.9 (4-CR1), 125.8
(10b-C), 125.4 (5-CR1), 125.3 (2-CR1), 123.4 (6-CR1), 108.8
(CN), 96.8 (10c-C), 87.6 (10a-C), 67.8 (OCH2), 64.3 (1-C),
46.6 (NCH2), 26.9 (10-C), 18.5 (5-CH3). Found: 60.0 C,
4.1% H, 7.9% Cl, 21.2% N; C23H18ClN7O2 requires 60.1%
C, 4.0% H, 7.7% Cl, 21.3% N.
3.3.2. 4,5,6,8,9,10-Hexahydro-8-(4-methylphenyl)-9-oxo-
2-(1-piperidinyl)-sprio{pyrimido[4,5,6-ij]pyrrolo[2,3-c]-
2,7-naphthyridine-5,10-cyclohexane}-1-carbonitrile
(14b). Yield 76%. Pale-pink powder. Mp .300 8C (from
DMF–H2O mixture); nmax (KBr tablets) 3300, 2955, 2875,
2205, 1725, 1620, 1520, 1465, 1335, 1205, 1160, 1035, 810,
725 cm21. dH 8.06 (1H, s, NH), 7.77 (1H, s, NH), 7.28 (2H,
d, J¼8.8 Hz, HR1), 7.22 (2H, d, J¼8.8 Hz, HR1), 3.80 (2H, s,
10-CH2), 3.68 (4H, m, NCH2), 2.35 (3H, s, CH3), 1.70 (4H,
m, 20,60-CH2), 1.60 (10H, m, NR2, 30,50-CH2), 1.29 (2H, m,
40-CH2). dC 174.8 (9-CO), 164.2 (10b-C), 159.8 (2-C),
156.2 (6a-C), 155.6 (3a-C), 141.7 (7a-C), 137.7 (4-CR1),
132.0 (1-CR1), 129.9 (3,5-CR1), 128.4 (2,6-CR1), 121.2
(CN), 94.0 (10c-C), 90.7 0(10a-C), 68.8 (5-C), 67.9 (1-C),
49.4 (2,6-CNR2), 37.3 (2 ,60-C), 34.7 (10-C), 26.4 (3,5-
CNR2), 25.1 (4-CNR2), 24.7 (40-C), 21.3 (CH3), 20.9 (30,50-
C). Found: 70.7% C, 6.2% H, 19.9% N; C29H31N7O requires
70.6% C, 6.3% H, 19.9% N.
3.2.4. 8-(4-Chlorophenyl)-2-diethylamino-5-methyl-9-
oxo-6,8,9,10-tetrahydropyrimido[4,5,6-ij]pyrrolo[2,3-c]-
2,7-naphthyridine-1-carbonitrile (13d). Yield 94%.
Yellow prisms. Mp .300 8C (from DMF); nmax (KBr
tablets) 2955, 2210, 1750, 1650, 1445, 1365, 1330, 1160,
1105, 1030, 840 cm21. dH 12.83 (1H, br s, NH), 7.57 (2H, d,
J¼8.8 Hz, HR1), 7.48 (2H, d, J¼8.8 Hz, HR1), 3.90 (2H, s,
10-CH2), 3.67 (4H, q, J¼7.2 Hz, NR2), 2.31 (3H, s, CH3);
1.23 (6H, t, J¼7.2 Hz, NR2). dC 168.7 (9-CO), 156.5 (5-C),
151.1 (2-C), 146.5 (6a-C), 145.4 (3a-C), 141.5 (7a-C), 132.7
(1-CR1), 129.1 (4-CR1), 121.6 (3,5-CR1), 119.7 (2,6-CR1),
119.4 (10b-C), 107.5 (CN), 95.0 (10c-C), 92.8 (10a-C), 61.0
(1-C), 37.6 (CNR2), 25.2 (10-C), 10.8 (5-CH3), 2.7 (CNR2).
Found: 62.1% C, 4.3% H, 7.8% Cl, 22.0% N; C23H20ClN7O
requires 62.0% C, 4.5% H, 8.0% Cl, 22.0% N.
3.3.3. 8-(3-Chlorophenyl)-4,5,6,8,9,10-hexahydro-2-(4-
morpholinyl)-9-oxosprio{pyrimido[4,5,6-ij]pyrrolo[2,3-c]-
2,7-naphthyridine-5,10-cyclohexane}-1-carbonitrile
(14c). Yield 76%. White powder. Mp 288 8C (from DMF–
H2O mixture); nmax (KBr tablets) 3420, 3335, 2975, 2885,
2210, 1750, 1625, 1495, 1450, 1335, 1285, 1190, 1120,
1045, 970, 800 cm21. dH 8.21 (1H, s, NH), 7.88 (1H, s, NH),
7.53 (2H, m, 2,5-HR1), 7.46 (1H, d, J¼7.2 Hz, 4-HR1), 7.39
(1H, d, J¼7.6 Hz, 6-HR1), 3.82 (2H, s, 10-CH2), 3.70 (8H,
m, NR2), 1.72 (4H, m, 20,60-CH2), 1.58 (4H, m, 30,50-CH2),
1.31 (2H, m, 40-CH2). dC 179.9 (9-CO), 160.6 (6a-C), 160.4
(10b-C), 156.6 (2-C), 153.5 (3a-C), 138.4 (7a-C), 137.7
(3-CR1), 131.5 (1-CR1), 126.3 (4-CR1), 124.7 (5-CR1), 123.6
(2-CR1), 123.4 (6-CR1), 118.8 (CN), 94.2 (10c-C), 92.2
(10a-C), 67.5 (1-C), 67.4 (5-C), 61.9 (OCH2), 49.2 (NCH2),
40.4 (20,60-C), 37.2 (10-C), 25.7 (30,50-C), 18.4 (40-C).
Found: 63.0% C, 5.0% H, 6.7% Cl, 18.9% N; C27H26ClN7O2
requires 62.9% C, 5.1% H, 6.9% Cl, 19.0% N.
3.3. Spiro{pyrimido[4,5,6-ij]pyrrolo[2,3-c]2,7-naph-
thyridine-5,10-cyclohexanes} 14a–d. General procedure
A solution of pyrrolonaphthyridine 8a,b, 9e, 10f (2 mmol)

A. V. Tverdokhlebov et al. / Tetrahedron 60 (2004) 5777–5783
5783
¨ ¨
19. Bjork, P.; Hornfeldt, A. B.; Gronowitz, S. J. Heterocycl.
Chem. 1994, 31, 1161–1169.
¨ ¨
20. Bjork, P.; Aakermann, T.; Hornfeldt, A. B.; Gronowitz, S.
3.3.4. 8-(4-Chlorophenyl)-2-diethylamino-4,5,6,8,9,10-
hexahydro-9-oxosprio{pyrimido[4,5,6-ij]pyrrolo[2,3-c]-
2,7-naphthyridine-5,10-cyclohexane}-1-carbonitrile
(14d). Yield 71%. White powder. Mp 164 8C (from DMF–
EtOH mixture); nmax (KBr tablets) 3340, 2955, 2210, 1745,
1625, 1515, 1445, 1335, 1105, 810, 715 cm21. dH 7.53 (1H,
s, NH), 7.48 (3H, m, NH, HR1), 7.42 (2H, d, J¼8.4 Hz, HR1),
3.86 (2H, s, 10-CH2), 3.70 (4H, q, J¼7.2 Hz, NR2), 1.77
(4H, m, 20,60-CH2), 1.62 (4H, m, 30,50-CH2), 1.40 (2H, m,
40-CH2), 1.27 (6H, t, J¼7.2 Hz, NR2). dC 174.9 (9-CO),
165.2 (10b-C), 158.1 (3a-C), 155.6 (6a-C), 151.5 (2-C),
145.2 (7a-C), 137.5 (4-CR1), 133.3 (1-CR1), 126.7 (2,6-CR1),
124.4 (3,5-CR1), 116.8 (CN), 95.5 (10c-C), 87.4 (10a-C),
70.1 (5-C), 69.9 (1-C), 40.6 (CNR2), 39.7 (20,60-C), 38.8
(10-C), 25.3 (40-C), 21.1 (30,50-C), 10.5(CNR2). Found:
64.8% C, 5.7% H, 7.2% Cl, 19.5% N; C27H28ClN7O
requires 64.6% C, 5.6% H, 7.1% Cl, 19.5% N.
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