Synthesis of 6H-indolo[2,3-b][1,6]naphthyridines and related compounds as the 5-aza analogues of ellipticine alkaloids

Article abstract of DOI:10.1021/jo000978e

Treatment of 2-(1-alkynyl)phenyl isocyanates 6 with the iminophosphorane 14 produced in situ the benzoenynyl carbodiimides 15. Thermolysis of 15 under refluxing p-xylene furnished the 6H-indolo[2,3-b][1,6]naphthyridines 5, which could be regarded as the 5-aza analogues of ellipticine alkaloids. Similarly, condensation of 6 with the iminophosphorane 20 led to the formation of the 6H-indolo[2,3-b][1,5]naphthyridines 25 as the major isomer and the 10H-indolo[2,3-b][1,7]naphthyridines 26 as the minor isomer. The indolonaphthyridines 32, 33, and 34 having a methoxyl substituent were likewise synthesized. Treatment of the diisocyanate 43 with 2 equiv of the iminophosphorane 7 furnished 45 having two indoloquinoline units incorporated in a seven-fused-ring system.

Full text of DOI:10.1021/jo000978e

J . Org. Chem. 2000, 65, 7977-7983
7977
Syn th esis of 6H-In d olo[2,3-b][1,6]n a p h th yr id in es a n d Rela ted
Com p ou n d s a s th e 5-Aza An a logu es of Ellip ticin e Alk a loid s
Quan Zhang, Chongsheng Shi, Hai-Ren Zhang, and Kung K. Wang*
Department of Chemistry, West Virginia University, Morgantown, West Virginia 26506-6045
kwang@wvu.edu
Received J une 28, 2000
Treatment of 2-(1-alkynyl)phenyl isocyanates 6 with the iminophosphorane 14 produced in situ
the benzoenynyl carbodiimides 15. Thermolysis of 15 under refluxing p-xylene furnished the 6H-
indolo[2,3-b][1,6]naphthyridines 5, which could be regarded as the 5-aza analogues of ellipticine
alkaloids. Similarly, condensation of 6 with the iminophosphorane 20 led to the formation of the
6H-indolo[2,3-b][1,5]naphthyridines 25 as the major isomer and the 10H- indolo[2,3-b][1,7]-
naphthyridines 26 as the minor isomer. The indolonaphthyridines 32, 33, and 34 having a methoxyl
substituent were likewise synthesized. Treatment of the diisocyanate 43 with 2 equiv of the
iminophosphorane 7 furnished 45 having two indoloquinoline units incorporated in a seven-fused-
ring system.
In tr od u ction
Ellipticine (1) and 9-methoxyellipticine (2) are two
naturally occurring 6H-pyrido[4,3-b]carbazole alkaloids
isolated from the leaves of Ochrosia elliptica Labill
(family Apocynaceae).1 The discovery of their antitumor
activities in 19672 has led to an explosion of synthetic,
biological, and pharmacological studies of ellipticine and
its derivatives.3 Several ellipticine derivatives have been
used in clinical trials.3a-c More recently, 5-methyl-5H-
indolo[2,3-b]quinoline (3a ), an indoloquinoline alkaloid
isolated from the West African plant Cryptolepis sanguino-
lenta,4 was reported to display a strong antiplasmodial
activity.5 Similarly, 3b having a methyl substituent at
by treatment with sodium hydroxide led to 3 directly (eq
the C11 position exhibited a strong antibacterial, anti-
mycotic, and cytotoxic activity in vitro as well as signifi-
cant antitumor properties in vivo.6 Methylation of 6H-
indolo[2,3-b]quinolines 4 with dimethyl sulfate followed
1).6,7 The interesting biological activities of ellipticines
* To whom correspondence should be addressed. Phone:
(304) 293-3068, ext 4441. Fax: (304) 293-4904. E-mail: kwang@wvu.edu.
(1) Goodwin S.; Smith, A. F.; Horning, E. C. J . Am. Chem. Soc. 1959,
81, 1903-1908.
(2) Dalton, L. K.; Demerac, S.; Elmes, B. C.; Loder, J . W.; Swan, J .
M.; Teitei, T. Aust. J . Chem. 1967, 20, 2715-2727.
and indoloquinolines prompted us to develop a new
synthetic route to the 6H-indolo[2,3-b][1,6]naphthyridines
5, which could be regarded as the 5-aza analogues of
ellipticines merging the heterocyclic frameworks of
both ellipticine and indoloquinoline. Only one synthetic
route involving a seven-step synthesis of 3-acetyl-4-
(methylamino)pyridine from 3-acetylpyridine followed by
condensation with oxindole to form 5,11-dimethyl-5H-
(3) (a) Gribble, G. W. In The Alkaloids; Brossi, A., Ed.; Academic
Press: New York, 1990; Vol. 39, p 239. (b) Suffness, M.; Cordell, G. A.
In The Alkaloids; Brossi, A., Ed.; Academic Press: New York,
1985; Vol. 25, pp 89, 304. (c) Kansal, V. K.; Potier, P. Tetrahedron 1986,
42, 2389-2408. (d) Gribble, G. W.; Saulnier, M. G.; Obaza-Nutaitis, J .
A.; Ketcha, D. M. J . Org. Chem. 1992, 57, 5891-5899. (e) Ishikura,
M.; Yaginuma, T.; Agata, I.; Miwa, Y.; Yanada, R.; Taga, T. Synlett
1997, 214-216. (f) D´ıaz, M. T.; Cobas, A.; Guitia´n, E.; Castedo, L.
Synlett 1998, 157-158. (g) Ergu¨n, Y.; Patir, S.; Okay, G. J . Heterocycl.
Chem. 1998, 35, 1445-1447. (h) Ishikura, M.; Hino, A.; Yaginuma,
T.; Agata, I.; Katagiri, N. Tetrahedron 2000, 56, 193-207. (i) Anderson,
W. K.; Gopalsamy, A.; Reddy, P. S. J . Med. Chem. 1994, 37, 1955-
1963.
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J . J . Med. Chem. 1994, 37, 3503-3510.
(7) (a) Molina, P.; Fresneda, P. M.; Delgado, S. Synthesis 1999, 326-
329. (b) Alajar´ın, M.; Molina, P.; Vidal, A. J . Nat. Prod. 1997, 60, 747-
748. (c) Kaczmarek, L.; Balicki, R.; Nantka-Namirski, P.; Peczyn´ska-
Czoch, W.; Mordarski, M. Arch. Pharm. (Weinheim) 1988, 321, 463-
467.
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H., J r.; Martin, G. E. J . Heterocycl. Chem. 1996, 33, 239-243. (b)
Cimanga, K.; De Bruyne, T.; Pieters, L.; Claeys, M.; Vlietinck, A.
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C. A. J . Nat. Prod. 1997, 60, 688-691.
10.1021/jo000978e CCC: $19.00 © 2000 American Chemical Society
Published on Web 10/21/2000

7978 J . Org. Chem., Vol. 65, No. 23, 2000
Zhang et al.
Sch em e 1
Sch em e 2
indolo[2,3-b][1,6]naphthyridine as the 5-aza analogue of
ellipticine had been reported previously.8
We recently reported an efficient synthetic route to
the 6H-indolo[2,3-b]quinolines 4 via thermolysis of the
benzoenynyl carbodiimides 8, derived from the aza-Wittig
reaction between the 2-(1-alkynyl)phenyl isocyanates 6
and the iminophosphorane 7 (Scheme 1).9a Presumably
the reaction proceeds either through a two-step biradical
pathway involving an initial C2-C6 cyclization of 8 to
form the biradicals 9 followed by an intramolecular
radical-radical coupling or through a concerted intramo-
lecular Diels-Alder reaction to furnish 10. A subsequent
tautomerization then provided 4. We envisioned that by
replacing the phenyl group in the iminophosphorane 7
with a pyridyl group, the synthetic sequence outlined in
Scheme 1 could lead to a variety of indolonaphthyridines
as the 5-aza analogues of ellipticines and the much less
studied isoellipticines10 in which the pyridine nitrogen
is at a different ring D position.
cross-coupling reaction between 2-iodoaniline (18) and
propyne to afford 19 followed by treatment of 19 with
triphosgene (eq 2).12 The iminophosphorane 14 was a
known compound, and several synthetic procedures had
been reported.13 The procedure for the preparation of
iminophosphoranes by treatment of primary arylamines
with dibromotriphenylphosphorane (Ph3PBr2) appeared
to offer the most direct route to 14.13e,f,14 Indeed, the use
of 4-aminopyridine to react with Ph3PBr2 produced 14
(74% yield) in a single step (eq 3).
Resu lts a n d Discu ssion
The requisite 2-(1-alkynyl)phenyl isocyanates 6 were
prepared from methyl 2-iodobenzoate (11) according to
the reported procedure (Scheme 2).9a The Pd-catalyzed
cross-coupling reaction between 11 and 1-alkynes pro-
vided the methyl 2-(1-alkynyl)benzoates 12. Hydrolysis
of 12 gave the corresponding 2-(1-alkynyl)benzoic acids
13. Treatment of 13 with diphenyl phosphorazidate then
furnished 6 via a modified Curtius rearrangement.11
Alternatively, 6a was also obtained by the Pd-catalyzed
The aza-Wittig reaction between 6 and 14 produced
in situ the benzoenynyl carbodiimides 15. Thermolysis
of 15 under refluxing p-xylene then furnished the 6H-
indolo[2,3-b][1,6]naphthyridines 5 in a single operation
from 6. Again, the transformation from 15 to 17 could
(8) Kononova, V. V.; Semenov, A. A. Khim. Geterotsikl. Soedin. 1982,
1211-1214.
(9) (a) Shi, C.; Zhang, Q.; Wang, K. K. J . Org. Chem. 1999, 64, 925-
932. (b) For a similar study, see: Schmittel, M.; Steffen, J .-P.; Engels,
B.; Lennartz, C.; Hanrath, M. Angew. Chem., Int. Ed. 1998, 37, 2371-
2373. (c) For a photochemically induced reaction, see: Schmittel, M.;
Rodr´ıguez, D.; Steffen, J .-P. Angew. Chem., Int. Ed. 2000, 39, 2152-
2155.
(10) (a) Miyake, S.; Sasaki, A.; Ohta, T.; Shudo, K. Tetrahedron Lett.
1985, 26, 5815-5818. (b) Ketcha, D. M.; Gribble, G. W. J . Org. Chem.
1985, 50, 5451-5457. (c) Saulnier, M. G.; Gribble, G. W. J . Org. Chem.
1983, 48, 2690-2695. (d) May, C.; Moody, C. J . J . Chem. Soc., Perkin
Trans. 1 1988, 247-250. (e) Viossat, B.; Dung, N.-H.; Lancelot, J .-C.;
Benazeth, S.; Rault, S.; Robba, M. Chem. Pharm. Bull. 1987, 35, 1724-
1733.
(11) (a) Shioiri, T.; Ninomiya, K.; Yamada, S.-i. J . Am. Chem. Soc.
1972, 94, 6203-6205. (b) Ninomiya, K.; Shioiri, T.; Yamada, S.
Tetrahedron 1974, 30, 2151-2157. (c) Rigby, J . H.; Balasubramanian,
N. J . Org. Chem. 1989, 54, 224-228.
(12) Eckert, H.; Forster, B. Angew. Chem., Int. Ed. Engl. 1987, 26,
894-895.
(13) (a) Hill, P. L.; Yap, G. P. A.; Rheingold, A. L.; Maatta, E. A. J .
Chem. Soc., Chem. Commun. 1995, 737-738. (b)Matrosov, E. I.;
Amanov, R. U.; Antipin, M. Y.; Struchkov, Y. T.; Khodak, A. A.;
Matveeva, A. G.; Kabachnik, A. M. I. Dokl. Akad. Nauk SSSR 1991,
316, 161-164. (c) Anders, E.; Markus, F. Chem. Ber. 1989, 122, 119-
122. (d) Anders, E.; Markus, F. Tetrahedron Lett. 1987, 28, 2675-2676.
(e) Bo¨deker, J .; Ko¨ckritz, A.; Ko¨ckritz, P.; Radeglia, R. J . Prakt. Chem.
1985, 327, 723-730. (f) Kulpe, S.; Seidel, I.; Bo¨deker, J .; Ko¨ckritz, P.
Cryst. Res. Technol. 1984, 19, 649-654.

6H-Indolo[2,3-b][1,6]naphthyridines
J . Org. Chem., Vol. 65, No. 23, 2000 7979
Sch em e 3
Sch em e 4
proceed either through a two-step biradical pathway or
through a concerted intramolecular Diels-Alder reaction.
It is worth noting that the synthetic sequence outlined
in Scheme 2 allows easy introduction of an alkyl, an
alkenyl, or an aryl substituent as the R group at the C11
position of 5.
It was straightforward to introduce a methoxyl group at
the C9 position of 5 by starting from the readily available
methyl 4-methoxysalicylate (27). Treatment of 27 with
trifluoromethanesulfonic anhydride produced the corre-
sponding triflate 28 in 98% yield (Scheme 4). A Pd-
catalyzed cross-coupling reaction with propyne then
furnished 29.18 The remaining sequence of reactions
resembles those outlined in Scheme 2. The aza-Wittig
reaction between 31 and 14 followed by thermolysis
produced 32 having a 9-methoxyl substituent in 33%
yield. Similarly, 33 and 34 were obtained by treatment
of 31 with 20.
The iminophosphorane 20,13e prepared from 3-amino-
pyridine and Ph3PBr2 in 76% yield, was also used for
the aza-Wittig reaction with 6 to produce in situ the
benzoenynyl carbodiimides 21 (Scheme 3). Subsequent
thermolysis under refluxing p-xylene furnished the 6H-
indolo[2,3-b][1,5]naphthyridines 25 as the major isomer
and the 10H-indolo[2,3-b][1,7]naphthyridines 26 as the
minor isomer. Apparently, cyclization of 21 furnished the
formal Diels-Alder adducts 23 preferentially, leading to
25 as the major isomer. The reason for such a preference
is not clear at this time. The structures of 25 and 26
represent two rare heterocyclic systems that could be
regarded as the aza analogues of isoellipticines. There
was only one earlier report of a indolonaphthyridine
derivative having the heterocyclic structure of 25.15 The
indolonaphthyridine 26a was previously synthesized by
condensation of 4-acetyl-3-aminopyridine with oxindole.16
Several ellipticine derivatives having either a 9-hy-
droxyl or a 9-methoxyl substituent were found to possess
potent antitumor activities.3a-c Transformation of these
derivatives to the corresponding quinone imines to allow
subsequent attack by a nucleophilic substrate was re-
ported to be responsible for their antitumor activities.3a-c,17
We reported earlier the use of 1,4-phenylene diiso-
cyanate (35) for the aza-Wittig reaction with 2 equiv of
the iminophosphorane 36 to produce in situ 37 for
subsequent thermolysis to furnish 38 having two indolo-
quinoline units incorporated in a seven-fused-ring system
with a helical twist (Scheme 5).9a The strategy of using
a diisocyanate for the construction of the seven-fused-
ring systems was also adopted in the current study.
The commercially available diethyl 2,5-dihydroxytereph-
thalate (39) was readily transformed to 43 having two
benzoenynyl isocyanate units (Scheme 6). Unfortunately,
attempts to produce 44 by treatment of 43 with 2 equiv
of 14 for the aza-Wittig reaction followed by thermolysis
afforded a dark brown solid which was difficult to
characterize by spectroscopic methods because of its low
solubility in common organic solvents. On the other hand,
treatment of 43 with 2 equiv of 79a,14b led to the formation
of a slightly soluble solid to allow characterization by
(14) (a) Molina, P.; Alajar´ın, M.; Vidal, A. J . Chem. Soc., Chem.
Commun. 1990, 1277-1279. (b) Horner, L.; Oediger, H. J ustus Liebigs
Ann. Chem. 1959, 627, 142-162.
1
HRMS and H NMR. The spectroscopic data support the
(15) Plieninger, H.; von Wittenau, M. S.; Kiefer, B. Chem. Ber. 1958,
91, 2095-2103.
formation of 45 having two linearly fused indoloquinoline
units in its structure.
(16) Estel, L.; Linard, F.; Marsais, F.; Godard, A.; Que´guiner, G. J .
Heterocycl. Chem. 1989, 26, 105-112.
(17) (a) Meunier, G.; de Montauzon, D.; Bernadou, J .; Grassy, G.;
Bonnafous, M.; Cros, S.; Meunier, B. Mol. Pharmacol. 1988, 33, 93-
102. (b) Dugue, B.; Auclair, C.; Meunier, B. Cancer Res. 1986, 46,
3828-3833.
(18) (a) Chen, Q.-Y.; Yang, Z.-Y. Tetrahedron Lett. 1986, 27, 1171-
1174. (b) Alami, M.; Ferri, F.; Linstrumelle, G. Tetrahedron Lett. 1993,
34, 6403-6406.

7980 J . Org. Chem., Vol. 65, No. 23, 2000
Zhang et al.
Sch em e 5
Sch em e 6
Con clu sion s
A new and efficient synthetic pathway to indolonaph-
thyridines has been developed. The synthetic route is
convergent and allows easy placement of a variety of
substituents around the periphery of the heterocyclic ring
system. The structures of indolonaphthyridines resemble
those of ellipticine alkaloids, making them good candi-
dates as DNA intercalating agents with potentially
interesting biological activities.
1H δ 7.89 (1 H, dd, J ) 7.9 and 1.4 Hz), 7.52 (1 H, dd, J ) 7.7
and 1.3 Hz), 7.42 (1 H, td, J ) 7.6 and 1.4 Hz), 7.31 (1 H, td,
J ) 7.3 and 1.4 Hz), 3.92 (3 H, s), 2.13 (3 H, s); 13C δ 166.9,
134.3, 131.8, 131.6, 130.1, 127.1, 124.6, 91.5, 78.3, 52.1, 4.8;
MS m/z 174 (M+), 159, 143, 131, 115; HRMS calcd for C11H10O2
174.0681, found 174.0686.
Exp er im en ta l Section
Diethyl ether and tetrahydrofuran (THF) were distilled
from benzophenone ketyl prior to use. Triethylamine was
distilled from CaH2. 2-Iodoaniline was purchased from Oak-
wood Products, Inc. and was used as received. 1-Alkynes were
obtained from GFS Chemicals, Inc. and were used without
further purification. Dibromotriphenylphosphorane (Ph3PBr2),
diphenyl phosphorazidate (DPPA), Pd(PPh3)2Cl2, p-xylene
(anhydrous), N,N-dimethylformamide (DMF), N,N-diisopro-
pylethylamine, 1-ethynylcyclohexene, triphosgene, 3-amino-
pyridine, 4-aminopyridine, methyl 4-methoxysalicylate (27),
trifluoromethanesulfonic (triflic) anhydride, and diethyl 2,5-
dihydroxyterephthalate (39) were purchased from Aldrich
and were used as received. Methyl 2-iodobenzoate (11) was
purchased from Lancaster. Melting points are uncorrected. 1H
(270 MHZ) and 13C (67.9 MHZ) NMR spectra were recorded
in CDCl3 using CHCl3 (1H δ 7.26) or CDCl3 (13C δ 77.0) as
internal standard unless otherwise indicated.
2-(1-P r op yn yl)ben zoic Acid (13a ).20 The following pro-
cedure for the preparation of 13a is representative. A solution
of 3.934 g (22.61 mmol) of 12a in 100 mL of THF and 99 mL
of a 1 N NaOH solution was heated at 50 °C for 12 h. The
reaction mixture was cooled in an ice-water bath and acidified
with a dilute HCl solution. The organic layer was separated,
washed with water, dried over MgSO4, and concentrated. The
residue was purified by recrystallization from 50% of diethyl
ether in hexanes to afford 13a (2.20 g, 13.8 mmol, 61%) as a
light yellow solid: mp 87.5-88 °C (lit.20 87-90 °C); IR 3300-
2400 (br), 1675, 1284, 754 cm-1; 1H δ 11.82 (1 H, br OH), 8.05
(1 H, dd, J ) 8.0 and 1.3 Hz), 7.54 (1 H, dd, J ) 7.9 and 1.4
Hz), 7.48 (1 H, td, J ) 7.7 and 1.5 Hz), 7.35 (1 H, td, J ) 7.7
and 1.5 Hz), 2.14 (3 H, s); 13C δ 171.5, 134.4, 132.4, 131.0,
130.6, 127.3, 124.9, 92.7, 78.1, 4.8; MS m/z 160 (M+), 145, 131,
118, 89; HRMS calcd for C10H8O2 160.0524, found 160.0523.
2-(1-P r op yn yl)p h en yl Isocya n a te (6a ). The following
procedure for the preparation of 6a is representative. To a
solution of 2.163 g (13.52 mmol) of 13a in 30 mL of anhydrous
benzene were added 1.9 mL of triethylamine and 2.9 mL (13.5
mmol) of DPPA. After 3 h at room temperature, the reaction
mixture was heated under reflux for 2 h until the nitrogen
gas evolution had ceased. The reaction mixture was then
washed with a saturated NH4Cl solution and water, dried over
MgSO4, and concentrated. The reside was purified by flash
chromatography (silica gel/5% diethyl ether in hexanes) to
afford 6a (1.65 g, 10.5 mmol, 78%) as a light yellow liquid: IR
Meth yl 2-(1-P r op yn yl)ben zoa te (12a ).19 The following
procedure for the preparation of 12a is representative. To a
degassed solution of 1.53 g of Pd(PPh3)2Cl2 (2.18 mmol), 0.414
g of CuI (2.18 mmol), 6.55 g of methyl 2-iodobenzoate (11, 25.0
mmol), and 13.8 mL of N,N-diisopropylethylamine (79.0 mmol)
in 80 mL of DMF was added 1.0 L of gaseous propyne (41
mmol) introduced with a gastight syringe. After 24 h at room
temperature, the reaction mixture was poured into a flask
containing 100 mL of a saturated NH4Cl solution and 100 mL
of pentane. After filtration, the organic layer was separated,
washed with water, dried over MgSO4, and concentrated. The
residue was purified by flash chromatography (silica gel/5%
diethyl ether in hexanes) to afford 12a (4.26 g, 24.5 mmol, 98%)
1
(neat) 2241, 1723, 755 cm-1; H δ 7.37 (1 H, dd, J ) 7.5 and
as a light yellow liquid: IR (neat) 2244, 1731, 1250, 757 cm-1
;
1.6 Hz), 7.21 (1 H, td, J ) 7.7 and 1.7 Hz), 7.10 (1 H, td, J )
(19) (a) Pschirer, N. G.; Bunz, U. H. F. Tetrahedron Lett. 1999, 40,
2481-2484. (b) Fu¨rstner, A.; Seidel, G. Tetrahedron 1995, 51, 11165-
11176.
(20) Sashida, H.; Kawamukai, A. J . Heterocycl. Chem. 1998, 35,
165-167.

6H-Indolo[2,3-b][1,6]naphthyridines
J . Org. Chem., Vol. 65, No. 23, 2000 7981
7.5 and 1.3 Hz), 7.00 (1 H, dd, J ) 7.9 and 1.5 Hz), 2.13 (3 H,
s); 13C δ 135.4, 131.8, 128.6, 127.7, 125.2, 123.3, 121.5, 95.4,
75.7, 4.4; MS m/z 157 (M+), 129, 102; HRMS calcd for C10H7-
NO 157.0528, found 157.0525.
anhydrous benzene was heated under reflux for 5 h. The
reaction mixture was purified by flash chromatography (silica
gel/10% ethanol in hexanes) to furnish 20 (4.04 g, 11.4 mmol,
76%) as a brown solid: IR 713, 694 cm-1; 1H δ 8.11 (1 H, d, J
) 2.7 Hz), 7.87 (1 H, dd, J ) 4.6 and 1.4 Hz), 7.78-7.69 (6 H,
m), 7.57-7.41 (9 H, m), 7.05 (1 H, dm, J ) 8.2 and 1 Hz), 6.91
(1 H, ddm, J ) 8.2, 4.6, and 1 Hz); 13C δ 147.7 (d, J ) 2 Hz),
145.1 (d, J ) 17.6 Hz), 138.3, 132.4 (d, J ) 9.8 Hz), 131.9 (d,
J ) 2.6 Hz), 130.3 (d, J ) 99.4 Hz), 129.4 (d, J ) 18.1 Hz),
128.7 (d, J ) 11.9 Hz), 123.3; MS m/z 355 (MH+), 279, 201;
HRMS calcd for C23H20N2P (MH+) 355.1364, found 355.1368.
11-Meth yl-6H-in dolo[2,3-b][1,5]n aph th yr idin e (25a) an d
5-Meth yl-10H-in d olo[2,3-b][1,7]n a p h th yr id in e (26a ).16 To
a solution of 0.708 g of 20 (2.00 mmol) in 3 mL of anhydrous
benzene was added 0.314 g of 6a (2.00 mmol) in 7 mL of
anhydrous benzene via cannula under a nitrogen atmosphere
at room temperature. After 2 h at room temperature, the
reaction mixture was filtered through a short silica gel column
to remove triphenylphosphine oxide. The column was further
eluded with p-xylene. The combined benzene and p-xylene
solutions were concentrated in vacuo to remove benzene. The
remaining p-xylene solution was heated to reflux under a
nitrogen atmosphere for 12 h. The reaction mixture was
concentrated in vacuo, and the residue was purified by flash
chromatography (silica gel/12:7:1 of hexanes:diethyl ether:
methanol) followed by preparative thin-layer chromatography
to furnish 0.272 g (1.17 mmol, 58%) of 25a and 0.081 g (0.35
mmol, 17%) of 26a as pale yellow crystals. 25a : IR (KBr) 1610,
Alternatively, 6a was also prepared from triphosgene and
2-(1-propynyl)aniline (19), which was readily obtained in
essentially quantitative yield by using the Pd(PPh3)2Cl2-
catalyzed cross-coupling reaction between 2-iodoaniline and
propyne as described previously.9a To a solution of 1.089 g of
triphosgene (3.67 mmol) in 20 mL of anhydrous benzene was
added dropwise a mixture of 1.310 g of 19 (10.0 mmol) and
2.78 mL of anhydrous triethylamine (20.0 mmol) in 30 mL of
anhydrous benzene under a nitrogen atmosphere at room
temperature. After 2 h at 70 °C, the white precipitate of
triethylamine hydrochloride was removed by filtration, and
the filtrate was concentrated in vacuo. The residue was
purified by flash chromatography (silica gel/10-20% of diethyl
ether in hexanes) to give 1.507 g of 6a (9.60 mmol, 96%).
Im in op h osp h or a n e 14.13e,f A reaction mixture of 0.753 g
(8.0 mmol) of 4-aminopyridine, 3.72 g (8.8 mmol) of Ph3PBr2,
2.46 mL of anhydrous triethylamine, and 60 mL of anhydrous
benzene was heated under reflux for 5 h. Triethylammonium
bromide was removed by filtration, and the filtrate was
concentrated. The residue was purified by passing through a
short column (silica gel/20% ethanol in diethyl ether) to furnish
14 (2.096 g, 5.921 mmol, 74%) as a light brown solid: IR 1585,
1
1495, 1360, 1109, 719, 694 cm-1; H δ 8.04 (2 H, d, J ) 5.0
Hz), 7.77-7.67 (6 H, m), 7.55 (3 H, td, J ) 7.2 and 1.7 Hz),
7.5-7.4 (6 H, m), 6.59 (2 H, d, J ) 5.7 Hz); 13C δ 158.9 (d, J )
2 Hz), 149.4, 132.5 (d, J ) 9.8 Hz), 132.1 (d, J ) 2.6 Hz), 129.5
(d, J ) 99.4 Hz), 128.8 (d, J ) 11.9 Hz), 118.7 (d, J ) 19.2
Hz); MS m/z 355 (MH+), 279; HRMS calcd for C23H20N2P (MH+)
355.1364, found 355.1386.
1
1407, 734 cm-1; H δ 9.73 (1 H, br, s, NH), 8.95 (1 H, dd, J )
4.0 and 1.7 Hz), 8.33 (1 H, dd, J ) 8.6 and 1.7 Hz), 8.30 (1 H,
d, J ) 7.7 Hz), 7.62 (1 H, dd, J ) 8.5 and 4.1 Hz), 7.55 (1 H,
td, J ) 7.5 and 1.1 Hz), 7.50 (1 H, d, J ) 7.2 Hz), 7.35 (1 H,
ddd, J ) 7.5, 6.9, and 1.6 Hz), 3.37 (3 H, s); 13C δ (DMSO-d6)
152.1, 146.2, 141.7, 141.3, 140.0, 139.0, 135.0, 128.1, 124.0,
123.5, 121.0, 120.0, 118.6, 110.9, 13.4; MS m/z 233 (M+), 205,
152; HRMS calcd for C15H11N3 233.0953, found 233.0954. Anal.
Calcd for C15H11N3: C, 77.23; H, 4.75; N, 18.01. Found: C,
11-Meth yl-6H-in d olo[2,3-b][1,6]n a p h th yr id in e (5a ). The
following procedure for the preparation of 5a is representative.
To 0.354 g (1.00 mmol) of 14 in 40 mL of anhydrous p-xylene
was introduced via cannula a solution of 0.157 g (1.00 mmol)
of 6a in 10 mL of anhydrous p-xylene under a nitrogen
atmosphere at room temperature. After 1.5 h, the reaction
mixture was heated under reflux for 15 h. The reaction mixture
was then concentrated to yield a solid residue. After three
cycles of washing the residue with 40 mL of diethyl ether
followed by centrifugation and decanting the supernatant
liquid, the remaining solid was pumped to dryness in vacuo
to afford 5a (0.114 g, 0.49 mmol, 49%) as a brown solid:
compound turns black without melting at 290 °C; IR 1604,
1
76.95; H, 4.83; N, 17.76. 26a : IR (KBr) 1615, 742 cm-1; H δ
(DMSO-d6) 11.97 (1 H, s), 9.32 (1 H, s), 8.51 (1 H, d, J ) 5.7
Hz), 8.39 (1 H, d, J ) 7.7 Hz), 8.21 (1 H, d, J ) 5.7 Hz), 7.60
(1 H, t, J ) 7.5 Hz), 7.54 (1 H, d, J ) 7.2 Hz), 7.32 (1 H, t, J
) 7.3 Hz), 3.18 (3 H, s); 13C δ (DMSO-d6) 152.8, 151.7, 142.0,
139.6, 137.8, 128.7, 126.3, 124.5, 120.4, 120.1, 119.1, 117.0,
111.0, 14.4; MS m/z 233 (M+), 205, 151; HRMS calcd for
C
15H11N3 233.0953, found 233.0950.
11-P r opyl-6H-in dolo[2,3-b][1,5]n aph th yr idin e (25b) an d
1
1237, 740 cm-1; H δ 9.68 (1 H, s), 8.73 (1 H, d, J ) 5.9 Hz),
5-P r op yl-10H-in d olo[2,3-b][1,7]n a p h th yr id in e (26b). To
0.354 g (1.0 mmol) of 20 in 40 mL of anhydrous p-xylene was
introduced via cannula a solution of 0.185 g (1.0 mmol) of 6b9a
in 10 mL of anhydrous p-xylene under a nitrogen atmosphere
at room temperature. After 1.5 h, the reaction mixture was
heated under reflux for 15 h. The reaction mixture was then
concentrated, and the residue was purified by column chro-
matography (silica gel/10% ethanol and 20% diethyl ether in
hexanes) to afford 25b (0.174 g, 0.667 mmol, 67%) and 26b
(0.013 g, 0.050 mmol, 5%) as brown solids. 25b: mp 234-236
8.29 (1 H, d, J ) 7.9 Hz), 7.85 (1 H, d, J ) 5.9 Hz), 7.58 (1 H,
t, J ) 7 Hz), 7.53 (1 H, d, J ) 7 Hz), 7.38 (1 H, ddd, J ) 8, 6,
and 1.5 Hz), 3.31 (3 H, s); 13C δ (DMSO-d6) 155.0, 150.2, 149.4,
145.8, 141.8, 140.9, 128.7, 124.6, 121.5, 121.0, 120.8, 117.7,
111.7, 14.8; MS m/z 233 (M+), 205, 179; HRMS calcd for
C
15H11N3 233.0953, found 233.0963.
11-P r op yl-6H-in d olo[2,3-b][1,6]n a p h th yr id in e (5b). The
same procedure was repeated as described for 5a except that
to 0.354 g (1.00 mmol) of 14 in 40 mL of anhydrous p-xylene
was treated with a solution of 0.185 g (1.00 mmol) of 6b9a in
10 mL of anhydrous p-xylene. Purification by flash column
chromatography (silica gel/5% ethanol and 20% diethyl ether
in hexanes) afforded 5b (0.133 g, 0.51 mmol, 51%) as a brown
solid: compound turns black without melting at 249 °C; IR
1
°C (dec); IR 1613, 1457, 764, 720 cm-1; H δ 11.32 (1 H, br s,
NH), 8.91 (1 H, dd, J ) 4.1 and 1.6 Hz), 8.27 (1 H, dd, J ) 8.4
and 1.4 Hz), 8.12 (1 H, d, J ) 7.9 Hz), 7.55-7.45 (3 H, m),
7.30 (1 H, ddd, J ) 8.1, 5.7, and 2.7 Hz), 3.82 (2 H, t, J ) 8.0
Hz), 1.92 (2 H, sextet, J ) 7.6 Hz), 1.20 (3 H, t, J ) 7.4 Hz);
13C δ 152.7, 146.5, 146.4, 141.4, 141.2, 139.5, 134.6, 128.1,
124.1, 123.4, 121.5, 120.7, 119.1, 110.9, 29.6, 22.8, 14.7; MS
m/z 261 (M+), 246, 233, 219; HRMS calcd for C17H15N3
261.1266, found 261.1265. Anal. Calcd for C17H15N3: C, 78.13;
H, 5.79; N, 16.08. Found: C, 78.27; H, 5.79; N, 16.05. 26b: IR
1
1602, 1574, 1462, 817, 734 cm-1; H δ 12.09 (1 H, br s, NH),
9.59 (1 H, s), 8.60 (1 H, d, J ) 5.9 Hz), 8.06 (1 H, d, J ) 7.9
Hz), 7.77 (1 H, d, J ) 5.6 Hz), 7.42 (2 H, m), 7.31 (1 H, ddd, J
) 7.9, 5.2, and 2.7 Hz), 3.62 (2 H, t, J ) 8.0 Hz), 1.96 (2 H,
sextet, J ) 7.5 Hz), 1.23 (3 H, t, J ) 7.3 Hz); 13C δ (DMSO-d6)
155.1, 150.1, 149.5, 145.8, 145.2, 141.9, 128.7, 124.2, 121.1,
120.9, 119.4, 117.2, 111.8, 29.7, 23.7, 14.7; MS m/z 261 (M+),
244, 232, 205; HRMS calcd for C17H15N3 261.1266, found
261.1260; Anal. Calcd for C17H15N3: C, 78.13; H, 5.79; N, 16.08.
Found: C, 78.01; H, 5.78; N, 16.04.
1
1472, 797, 726 cm-1; H δ 9.72 (1 H, br s, NH), 9.56 (1 H, s),
8.60 (1 H, d, J ) 5.9 Hz), 8.22 (1 H, d, J ) 7.6 Hz), 8.06 (1 H,
d, J ) 5.9 Hz), 7.65-7.57 (2 H, m), 7.38 (1 H, ddd, J ) 8.1,
5.2, and 2.4 Hz), 3.64 (2 H, t, J ) 8.0 Hz), 1.96 (2 H, sextet, J
1
) 7.7 Hz), 1.22 (3 H, t, J ) 7.4 Hz); H δ (DMSO-d6) 12.02 (1
Im in op h osp h or a n e 20.13e The same procedure was re-
peated as described for 14 except that a mixture of 1.412 g
(15.0 mmol) of 3-aminopyridine, 7.281 g (17.2 mmol) of Ph3-
PBr2, 4.61 mL of anhydrous triethylamine, and 80 mL of
H, s), 9.36 (1 H, s), 8.51 (1 H, d, J ) 4.2 Hz), 8.28 (1 H, d, J )
7.9 Hz), 8.23 (1 H, d, J ) 5.9 Hz), 7.61 (1 H, t, J ) 7.4 Hz),
7.56 (1 H, d, J ) 7.3 Hz), 7.35 (1 H, t, J ) 7.3 Hz), 3.64 (2 H,
t, J ) 7.7 Hz), 1.83 (2 H, sextet, J ) 7.6 Hz), 1.12 (3 H, t, J )

7982 J . Org. Chem., Vol. 65, No. 23, 2000
Zhang et al.
7.4 Hz); 13C δ (DMSO-d6) 153.6, 152.3, 142.7, 140.1, 129.3,
126.3, 124.7, 120.9, 120.3, 119.3, 117.5, 111.8, 30.0, 23.1, 14.7;
MS m/z 261 (M+), 232, 205; HRMS calcd for C17H15N3 261.1266,
found 261.1261.
pumped to dryness in vacuo to afford 32 (0.035 g, 0.133 mmol,
33%) as a brown solid: compound turns black without melting
at 284 °C; IR 1603, 1481, 1298, 1212, 811 cm-1; 1H δ (DMSO-
d6) 11.92 (1 H br s, NH), 9.72 (1 H, s), 8.62 (1 H, d, J ) 6.2
Hz), 7.86 (1 H, d, J ) 2.2 Hz), 7.80 (1 H, d, J ) 5.9 Hz), 7.47
(1 H, d, J ) 8.7 Hz), 7.23 (1 H, dd, J ) 8.7 and 2.5 Hz), 3.91
(3 H, s), 3.29 (3 H, s); 13C δ (DMSO-d6) 155.8, 154.8, 150.2,
148.6, 142.1, 142.0, 136.1, 129.8, 121.8, 118.5, 116.8, 112.6,
108.9, 56.4, 15.0; MS m/z 263 (M+), 248, 220; HRMS calcd for
Tr ifla te 28. To a solution of 0.547 g (3.00 mmol) of methyl
4-methoxysalicylate (27) and 1.53 mL of pyridine (18.9 mmol)
at 0 °C was added dropwise 0.555 mL (3.34 mmol) of trifluo-
romethanesulfonic anhydride. After 5 min of stirring at 0 °C
followed by an additional 2 h of stirring at room temperature,
the reaction mixture was heated at 40 °C for 24 h. The reaction
mixture was then poured into a flask containing 20 mL of H2O
and 20 mL of Et2O. The organic layer was separated, washed
with water, a 10% aq HCl solution, water, and a saturated
NaCl solution, dried over MgSO4, and concentrated. The
residue was purified by flash chromatography (silica gel/20%
diethyl ether in hexanes) to furnish 28 (0.923 g, 2.94 mmol,
98%) as a pale yellow liquid: IR (neat) 1727, 1618, 1427, 1277,
C
16H13N3O 263.1059, found 263.1051.
9-Meth oxy-11-m eth yl-6H-in d olo[2,3-b][1,5]n a p h th yr i-
d in e (33) a n d 7-Meth oxy-5-m eth yl-10H-in d olo[2,3-b][1,7]-
n a p h th yr id in e (34). The same procedure was repeated as
described for 25b and 26b except that 0.056 g (0.299 mmol)
of 31 was treated with 0.117 g (0.329 mmol) of 20. Purification
by washing the crude residual three times with 30 mL of
diethyl ether afforded 33 (0.034 g, 0.128 mmol, 43%) as a
yellow solid. The combined diethyl ether solutions were
pumped to dryness in vacuo, and the residue was further
purified by flash chromatography (silica gel/10% ethanol
and 20% diethyl ether in hexanes) to afford 34 (0.0031 g,
0.012 mmol, 4%) as a yellow solid. 33: compound turns black
without melting at 285 °C; IR 1490, 1463, 831, 788 cm-1; 1H δ
8.95 (1 H, d, J ) 3.1 Hz), 8.34 (1 H, d, J ) 8.1 Hz), 7.78 (1 H,
d, J ) 2.0 Hz), 7.63 (1 H, dd, J ) 8.6 and 4.1 Hz), 7.44 (1 H,
d, J ) 8.7 Hz), 7.18 (1 H, dd, J ) 8.7 and 2.2 Hz), 3.96 (3 H,
s), 3.35 (3 H, s); 1H δ (DMSO-d6) 11.78 (1 H, s), 8.91 (1 H, dd,
J ) 1.5 and 2.5 Hz), 8.34 (1 H, dd, J ) 1.3 and 7.3 Hz),
7.80 (1 H, d, J ) 2.5 Hz), 7.74 (1 H, dd, J ) 3.9 and 8.4 Hz),
7.46 (1 H, d, J ) 8.7 Hz), 7.22 (1 H, dd, J ) 2.4 and 7.6 Hz),
3.91 (3 H, s), 3.28 (3 H, s); 13C δ (DMSO-d6) 154.3, 152.6, 146.5,
141.3, 141.0, 138.8, 136.6, 135.4, 124.2, 121.8, 119.5, 116.8,
112.3, 108.5, 56.3, 14.0; MS m/z 263 (M+), 248, 220; HRMS
calcd for C16H13N3O 263.1059, found 263.1052. 34: 1H δ
(DMSO-d6) 12.23 (1 H, s), 9.69 (1 H, s), 8.69 (2 H, br s), 7.96
(1 H, d, J ) 2.2 Hz), 7.56 (1 H, d, J ) 8.7 Hz), 7.36 (1 H, dd,
J ) 8.7 and 2.2 Hz), 3.94 (3 H, s), 3.28 (3 H, s); MS m/z
263 (M+), 248, 220; HRMS calcd for C16H13N3O 263.1059,
found 263.1057.
1
1210, 1142, 832 cm-1; H δ 8.04 (1 H, d, J ) 9.0 Hz), 6.94 (1
H, dd, J ) 8.8 and 2.4 Hz), 6.76 (1 H, d, J ) 2.2 Hz), 3.92 (3
H, s), 3.87 (3 H, s); 13C δ 163.94, 163.90, 149.6, 134.1, 118.7
(q, J ) 320.5 Hz), 116.2, 113.4, 108.8, 56.0, 52.3; MS m/z 314
(M+), 283, 219, 153; HRMS calcd for C10H9F3O6S 314.0072,
found 314.0086.
Meth yl 4-Meth oxyl-2-(1-p r op yn yl)ben zoa te (29). The
same procedure was repeated as described for 12a except that
a mixture of 2.10 g of Pd(PPh3)2Cl2 (3.0 mmol), 0.57 g of CuI
(3.0 mmol), 9.08 g of 28 (29.0 mmol), and 16.5 mL of N,N-
diisopropylethylamine (95 mmol) in 120 mL of DMF was
treated with 1.3 L of gaseous propyne (53 mmol) to afford 29
(4.983 g, 24.4 mmol, 84%) as a light yellow liquid: IR (neat)
1
2235, 1727, 1598, 779, 699 cm-1; H δ 7.88 (1 H, d, J ) 8.7
Hz), 6.99 (1 H, d, J ) 2.5 Hz), 6.82 (1 H, dd, J ) 8.8 and 2.7
Hz), 3.87 (3 H, s), 3.82 (3 H, s), 2.13 (3 H, s); 13C δ 166.0, 161.8,
132.1, 126.5, 123.6, 118.5, 113.4, 91.3, 78.4, 55.2, 51.6, 4.5; MS
m/z 204 (M+), 189, 173, 161, 145; HRMS calcd for C12H12O3
204.0786, found 204.0796.
4-Meth oxy-2-(1-p r op yn yl)ben zoic Acid (30). To a flask
containing 0.214 g of LiOH monohydrate (5.1 mmol) in 20 mL
of methanol and 10 mL of water was added a solution of 0.208
g (1.02 mmol) of 29 in 10 mL of methanol. The resulting
mixture was heated at 35 °C for 24 h before it was allowed to
cool to room temperature. The flask was then placed in an ice-
water bath. A dilute NH4Cl solution at 0 °C was added until
the pH of the solution became ca. 8. The solution was then
treated dropwise with a dilute aqueous acetic acid solution
until the pH reached ca. 5. At this point a white solid appeared.
The solution was further acidified with a dilute HCl solution
until the pH reached ca. 4. The white solid precipitate was
collected by filtration followed by washing with water and
pumping to dryness to afford 0.137 g of 30 (0.721 mmol, 70%)
as a white solid: mp 171-173 °C; IR 1671, 1594, 1210, 849,
778 cm-1; 1H δ 8.05 (1 H, d, J ) 9.0 Hz), 7.02 (1 H, d, J ) 2.5
Hz), 6.88 (1 H, dd, J ) 8.8 and 2.7 Hz), 3.86 (3 H, s), 2.15 (3
H, s); 13C δ 169.6, 162.6, 133.6, 126.5, 122.8, 118.8, 114.0, 93.2,
78.3, 55.5, 4.8; MS m/z 190 (M+), 173, 161, 147, 135; HRMS
calcd for C11H10O3 190.0630, found 190.0625.
Tr ifla te 40. The same reaction procedure was repeated as
described for 28 except that 3.76 g of diethyl 2,5-dihydroxy-
terephthalate (39, 14.8 mmol) in 15 mL of pyridine was treated
with 10.05 g (35.6 mmol) of triflic anhydride to afford 40 (7.41
g, 14.3 mmol, 97%) as white crystalline needles: mp 109-111
°C; IR (KBr) 1732, 796, 713 cm-1 1H NMR δ 7.98 (2 H, s),
;
4.49 (4 H, q, J ) 7.2 Hz); 1.44 (6 H, t, J ) 7.2 Hz); 13C δ
NMR 161.4, 146.4, 129.8, 127.2, 118.6 (q, J ) 320.6 Hz), 63.4,
13.9; MS m/z 519 (MH+), 518, 490, 473; HRMS calcd for
C
14H12F6O10S2 517.9776, found 517.9754.
Dieth yl 2,5-Di(1-d ecyn yl)ter ep h th a la te (41). The same
procedure was repeated as described for 29 except that a
solution of 0.340 g of Pd(PPh3)2Cl2 (0.484 mmol), 0.092 g of
CuI (0.48 mmol), 1.794 g of 40 (3.46 mmol), and 3.6 mL of N,N-
diisopropylethylamine (20.8 mmol) in 10 mL of DMF and 11
mL of THF was treated with 1.87 mL (1.435 g) of 1-decyne
(10.4 mmol) to afford 41 (1.656 g, 3.35 mmol, 97%) as a wax:
1
4-Meth oxy-2-(1-p r op yn yl)p h en yl Isocya n a te (31). The
same procedure was repeated as described for 6a except that
0.785 g (4.13 mmol) of 30 was treated with 0.58 mL of
triethylamine and 0.89 mL (4.13 mmol) of DPPA to afford 31
(0.596 g, 3.19 mmol, 77%) as a white solid: IR (neat) 1513,
mp 45-47 °C; IR 2229, 1735 cm-1; H δ 7.96 (2 H, s), 4.38 (4
H, q, J ) 7.1 Hz); 2.46 (4 H, t, J ) 7.0 Hz), 1.67-1.57 (4 H,
m), 1.5-1.2 (20 H, m), 1.40 (6 H, t, J ) 7.1 Hz), 0.87 (6 H, t,
J ) 6.9 Hz); 13C δ 165.4, 135.7, 134.4, 122.9, 98.1, 78.5, 61.4,
31.8, 29.2, 29.1, 29.0, 28.5, 22.6, 19.9, 14.2, 14.1; MS m/z 494
(M+), 465, 396, 367, 341; HRMS calcd for C32H46O4 494.3396,
found 494.3406.
1
1204, 1032 cm-1; H δ 6.92 (1 H, d, J ) 9.0 Hz), 6.89 (1 H, d,
J ) 3.9 Hz), 6.75 (1 H, dd, J ) 8.7 and 3.1 Hz), 3.77 (3 H, s),
2.12 (3 H, s); 13C δ 156.8, 128.2, 127.3, 124.2, 122.1, 116.3,
114.9, 95.1, 75.7, 55.5, 4.5; MS m/z 187 (M+), 172, 159, 144;
HRMS calcd for C11H9NO2 187.0633, found 187.0640.
2,5-Di(1-d ecyn yl)ter ep h th a lic Acid (42). The same pro-
cedure was repeated as described for 30 except that a solution
of 2.048 g of 41 (4.15 mmol) in 40 mL of THF was treated with
a solution of 1.52 g of LiOH monohydrate (36.2 mmol) in 70
mL of methanol and 70 mL of water to afford 1.526 g (3.48
mmol, 84%) of 42 as a white solid: mp 147-153 °C; IR 3300-
9-Meth oxy-11-m eth yl-6H-in d olo[2,3-b][1,6]n a p h th yr i-
d in e (32). The same procedure was repeated as described for
5a except that 0.076 g (0.404 mmol) of 31 was treated with
0.157 g (0.445 mmol) of 14. After three cycles of washing the
concentrated residue with diethyl ether, centrifugation, and
decanting the supernatant liquid, the residual solid was heated
under reflux in 40 mL of benzene for 1 h. The mixture was
allowed to cool to room temperature followed by centrifugation
and decanting the supernatant liquid. The remaining solid was
1
2300 (br, OH), 2229, 1704 cm-1; H δ (DMSO-d6) 13.35 (2 H,
br s), 7.79 (2 H, s), 2.42 (4 H, t, J ) 6.7 Hz), 1.57-1.35 (8 H,
m), 1.23 (16 H, br), 0.83 (6 H, t, J ) 6.4 Hz); 13C δ (DMSO-d6)
166.3, 135.6, 134.7, 122.0, 98.0, 78.6, 31.4, 28.7, 28.6, 28.3, 28.0,
22.2, 19.1, 14.0; MS m/z 438 (M+), 421, 393, 363, 340; HRMS
calcd for C28H38O4 438.2770, found 438.2756.

6H-Indolo[2,3-b][1,6]naphthyridines
J . Org. Chem., Vol. 65, No. 23, 2000 7983
Diisocya n a te 43. The same procedure was repeated as
described for 31 except that 1.086 g (2.48 mmol) of 42 was
treated with 0.70 mL of triethylamine and 1.07 mL (4.96
mmol) of DPPA to afford 43 (0.755 g, 1.75 mmol, 71%) as a
(DMSO-d6) 11.46 (2 H, s), 8.34 (2 H, d, J ) 7.9 Hz), 8.27 (2 H,
s), 7.97 (2 H, d, J ) 8.4 Hz), 7.71 (2 H, td, J ) 7.6 and 1 Hz),
7.50 (2 H, td, J ) 7.5 and 1 Hz), 3.74 (4 H, t, J ) 7.9 Hz), 1.92
(4 H, quintet, J ) 7.3 Hz), 1.69 (4 H, quintet, J ) 7.5 Hz),
1.44 (4 H, quintet, J ) 7.1 Hz), 1.38-1.22 (12 H, m), 0.84 (6
H, t, J ) 6.9 Hz); MS m/z 583 (MH+), 483, 385; HRMS calcd
for C40H47N4 583.3801 (MH+), found 583.3820.
white solid: mp (sealed tube) 64-66 °C; IR 2261, 2222 cm-1
;
1H δ 6.99 (2 H, s), 2.46 (4 H, t, J ) 7.2 Hz), 1.62 (4 H, quintet,
J ) 7.2 Hz), 1.48-1.23 (20 H, m), 0.88 (6 H, t, J ) 6.5 Hz); 13
C
δ 132.3, 127.6, 126.4, 121.7, 102.0, 75.5, 31.8, 29.2, 29.1, 29.0,
28.0, 22.6, 19.7, 14.1; MS m/z 432 (M+), 406, 205; HRMS calcd
for C28H36N2O2 432.2777, found 432.2771.
Ack n ow led gm en t. The financial support of the
National Science Foundation (CHE-9618676) is grate-
fully acknowledged.
In d oloqu in olin e 45. To a solution of 0.455 g of the
iminophosphorane 79a,14b (1.288 mmol) in 40 mL of anhydrous
p-xylene was introduced via cannula a solution of 0.278 g of
43 (0.644 mmol) in 10 mL of p-xylene under a nitrogen
atmosphere. After 1.5 h at room temperature, the reaction
mixture was heated under reflux for 6 h before it was allowed
to cool to room temperature and concentrated. After three
cycles of washing the residue with ethanol, centrifugation, and
decanting the supernatant liquid, the remaining solid was
washed with diethyl ether and then pumped to dryness in
vacuo to afford 0.140 g of 45 (0.241 mmol, 37%) as a yellow
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures, spectroscopic and analytical data for 5c,d , 6c, 12c,
13c, 25c,d , and 26c,d , and 1H and/or 13C NMR spectra for
compounds 5a -d , 6a ,c, 12a ,c, 13a ,c, 14, 20, 25a -d , 26a -d ,
28-34, 40-43, and 45. This material is available free of charge
via the Internet at http://pubs.acs.org.
solid: mp >360 °C; IR (KBr) 1626, 1609, 1586 cm-1
;
1H δ
J O000978E