Functionalized 2,5-disubstituted benzazepines: Stereoselective synthesis of 3-methyl-5-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-2-carbonitrile and related derivatives

Article abstract of DOI:10.1055/s-2004-825618

A stereoselective synthesis of 2-carbonitrile and 2-aminomethyl-substituted 5-phenylbenzazepine derivatives was developed starting from [4-hydroxy-3-(methyloxy)phenyl]acetic acid. The key step in the synthesis is a stereoselective addition of cyanide to 3-methyl-1-phenyl-2,3-dihydro-1H-3- benzazepine (4) to give a 15:1 trans/cis mixture of 2-carbonitrile-5-phenyl benzazepine diastereomers 5a/5b in 83% yield. The stereochemistry of the major product was deduced by ¹H NMR NOESY analysis. The carbonitrile diastereomers could be separated and further manipulated by reduction to the corresponding aminomethyl derivatives 3a and 3b in a stereoselective manner. The aminomethyl benzazepine template 3 has potential to serve as a handle for the synthesis of a variety of derivatives modified at the 2-position of the benzazepine scaffold, as illustrated by an acylation of the primary amine of 3 followed by mild deprotection of the 7-phenol functionality.

Full text of DOI:10.1055/s-2004-825618

1394
LETTER
Functionalized 2,5-Disubstituted Benzazepines: Stereoselective Synthesis of
3-Methyl-5-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-2-carbonitrile and
Related Derivatives
F
unctiona
e
lized 2,5-
D
f
isubstitu
f
ted
B
enzazepin
E
es . Cobb, Suganthini S. Nanthakumar,1 Randy Rutkowske, David E. Uehling*
GlaxoSmithKline, 5 Moore Dr., Research Triangle Park, NC 27709, USA
Fax +1(919)4836053; E-mail: david.e.uehling@gsk.com.
Received 26 March 2004
This paper is dedicated to the career of Clayton H. Heathcock for 40 years of scholarship and teaching at UC Berkeley
Abstract: A stereoselective synthesis of 2-carbonitrile and 2-ami-
nomethyl-substituted 5-phenylbenzazepine derivatives was devel-
oped starting from [4-hydroxy-3-(methyloxy)phenyl]acetic acid.
The key step in the synthesis is a stereoselective addition of cyanide
to 3-methyl-1-phenyl-2,3-dihydro-1H-3-benzazepine (4) to give a
15:1 trans/cis mixture of 2-carbonitrile-5-phenyl benzazepine dia-
stereomers 5a/5b in 83% yield. The stereochemistry of the major
1
product was deduced by H NMR NOESY analysis. The carboni-
trile diastereomers could be separated and further manipulated by
reduction to the corresponding aminomethyl derivatives 3a and 3b
in a stereoselective manner. The aminomethyl benzazepine tem-
plate 3 has potential to serve as a handle for the synthesis of a vari-
ety of derivatives modified at the 2-position of the benzazepine
scaffold, as illustrated by an acylation of the primary amine of 3
followed by mild deprotection of the 7-phenol functionality.
Key words: 2,5-trans-disubstituted 2-aminomethyl 3-benzazepine,
cyanide addition, stereoselective synthesis
Figure 1 Benzazepines derivatives of interest
2,3,4,5-Tetrahydro-1H-3-benzazepines (e.g. compound
1) are of significant interest due to their pharmacological
activity against dopamine and other biological receptors.2
Because nitrile addition to 1,2,3,4-tetrahydropyridine sys-
Nearly all examples that contain a 1-phenyl substituent
that have been disclosed are unsubstituted on methylene
groups adjacent to the nitrogen (positions 2 and 4) on the
benzazepine scaffold.3 A few years ago we reported the
synthesis of 2-alkyl-5-phenyl benzazepines 2 (Figure 1).
In one of the routes disclosed, high cis selectivity could be
obtained, particularly when R was benzyl.4 In order to
extend our understanding of the biological properties of 3-
benzazepines substituted within the 7-membered ring, we
sought to develop syntheses of the 1-phenyl-3-benz-
azepine scaffold substituted at the 2-position5 with func-
tionalized amine substituents as represented by structure
3. In addition, we sought to develop a route that would
generate a free phenol for possible further derivatization.
Herein, we wish to report a general method for synthesis
of 2,5-disubstituted benzazepines with a nitrile group at
the 2-position. Because this route selectively delivers the
trans configuration between the 5-phenyl and 2-nitrile
substituents, this methodogy complements the previous
approach that delivers the cis stereochemistry as the
favored diastereomer.
tems to afford cyanamines is a well-known process
(Equation 1),6 we envisioned accessing compounds of
structure 3 via nitrile addition to the 1-phenyl-2,3-dihy-
dro-1H-3-benzazepine system, followed by reduction
(Scheme 1). However, in contrast to the 6-membered ring
system, little precedent exists for the analogous reaction
in benzazepine systems.7 In addition to testing the effi-
ciency of the nitrile addition reaction itself, we also sought
to understand if the features resident in the 3-benzazepine
ring system would govern a stereochemical preference for
cis vs trans addition.
Equation 1 Reaction of 1,2,3,4-tetrahydropyridine systems with
cyanide
In order to address the foregoing questions, we developed
the route to intermediate 4 shown in Scheme 2. This
sequence began with commercially available [4-hydroxy-
3-(methyloxy)phenyl]acetic acid (6) and racemic 2-
(methylamino)-1-phenylethanol (7), which were coupled
under standard conditions to afford hydroxy amide 8 in
SYNLETT 2004, No. 8, pp 1394–1398
0
1.
0
7.
2
0
0
4
Advanced online publication: 04.06.2004
DOI: 10.1055/s-2004-825618; Art ID: Y02604ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Functionalized 2,5-Disubstituted Benzazepines
1395
Scheme 1 Proposed route to benzazepine derivatives 3
high yield. Subjecting 8 to neat methanesulfonic acid for
3 hours provided the 1,3,4,5-tetrahydro-2H-3-benz-
azepin-2-one derivative 9 (Scheme 2),8 which was pro-
tected as its MOM ether. The lactam functionality was
then reduced with DIBALH in toluene to give, after silica
gel chromatography, the novel targeted intermediate 2,3-
dihydro-1H-3-benzazepine 4.9
With 4 in hand, we proceeded to investigate the nitrile
addition to obtain 5. After experimenting with various
conditions that gave sub-optimal yields, we found that
treatment of 4 with KCN in methanol in the presence of
pH 7.2 phosphate buffer provided the nitrile adduct isolat-
ed in 83% yield as a 15:1 mixture of trans/cis diastereo-
mers 5a/5b (Scheme 2).10 The structure of the major
isomer, which was easily purified via recrystallization or
column chromatography, was determined through
NOESY experiments (Figure 2). It was found that re-
exposure of the isolated minor isomer 5b to the reaction
conditions led to generation of 5a as the major product
(5a/5b = ca. 6:1), suggesting that the reaction is under a
significant degree of thermodynamic control. Although
conditions to preferentially generate 5b were not identi-
fied, a ca. 1:1 mixture of nitrile epimers could be obtained
by deprotonating the product 5a with KHMDS and
quenching with 2,6-di-tert-butyl-hydroxy toluene. The cis
isomer 5b could then be readily isolated by chromatogra-
phy (Equation 2).11 In this experiment, it is believed that
the ca. 1:1 product ratio is a result of unselective kinetic
protonation of the trigonal C-2 anionic center, given that
under the conditions employed it is unlikely that there is
an opportunity for subsequent equilibration following
protonation by the phenol.
Scheme 2 Synthesis of nitrile derivative 5
Equation 2 Epimerization to prepare cis nitrile 3b
sponding to that of the starting nitrile) was observed under
strictly anhydrous conditions. Interestingly, however, it
was found that deactivation of the LiAlH4 by slow addi-
tion of 0.5 molar equivalents H2O (relative to LiAlH4) pri-
or to addition of the nitrile afforded a good diasteomeric
excess of either 3a or 3b (Scheme 3).12 The explanation
for the suppression of stereochemical erosion with the
non-anhydrous conditions is not clear, but may be due to
formation of a reducing complex with decreased Lewis
acidity, which mitigates the tendency of the carbonitrile
substituent to epimerize prior to reduction.13 A variety of
alternative conditions were also attempted to affect reduc-
tion of the nitrile [e.g. Raney-Ni, LiAl(Ot-Bu)3H, LiBH4,
Subjecting either 5a or 5b to LiAlH4 in THF led in high
yield to the formation of primary amino methyl product 3.
In both instances however, erosion of the stereochemistry
at the C-2 position with a ca. 1.5:1 mixture of product dia-
stereomers (with the predominant diastereomer corre-
Synlett 2004, No. 8, 1394–1398 © Thieme Stuttgart · New York

1396
J. E. Cobb et al.
LETTER
In summary, we have developed a synthetic route to the
novel 2-aminomethyl substituted benzazepine scaffold 3.
The synthesis of this class of derivatives is accomplished
via a nitrile addition reaction to the novel unsaturated
benzazepine derivative 4. In the process of developing
this reaction, we observed a high degree of selectivity to
preferentially generate the trans carbonitrile 5a. The
stereoselectivity of this reaction sequence complements
the cis-selective approach reported previously.4 In addi-
tion, through our ability to epimerize and readily purify
the cis derivative 5b, we are able to access in preparative
fashion analogues that are enriched in either diastereomer.
The versatility of this chemistry through the synthesis of
further analogues in a parallel chemistry format has been
explored and will be described in the future.
Scheme 3 Reduction of cis and trans nitriles 3a and 3b
DIBAL]. These conditions afforded either poor yields or
a high degree of scrambling at the C-2 stereocenter.
With the benzazepine 3 in hand, we exemplified its utility
as a scaffold for further derivatization through coupling it
with an amide and liberation of the phenol. In the repre-
sentative example, the cis diastereomer 3b was coupled
with 1-methyl-1H-indole-2-carboxylic acid to give the
corresponding amide derivative in high yield
(Equation 3).14 The MOM protecting group could then be
readily removed to give the corresponding phenol. Similar
reactions with the trans derivative as well as transforma-
tions to related derivatives using other electrophilic
moieties [e.g. (Boc)2O, Ac2O, etc.] have been successfully
carried out in good (>80%) yield.
Figure 2 NOE interactions observed for cis- and trans-5
Acknowledgment
The authors would like to thank Sam Gerritz, Darryl McDougal and
Michael Rabinowiz for helpful discussions.
References
(1) Current address: Vertex Pharmaceuticals, 130 Waverly
Street, Cambridge, MA 02139.
(2) Recent reviews of 3-benzazepines: (a) Bourne, J. A. CNS
Drug Reviews 2001, 7, 399. (b) Kawase, M.; Saito, S.;
Motohashi, N. Int. J. Antimicrob. Agents 2000, 14, 193.
(3) (a) Walter, L. A.; Chang, W. K. U.S. Patent 3393192, 1968.
(b) Kasparek, S. Adv. Heterocycl. Chem. 1974, 17, 45.
(c) Berger, J. G.; Chang, W. K.; Clader, J. W.; Hou, D.;
Chipkin, R. E.; McPhail, A. T. J. Med. Chem. 1989, 32,
1913. (d) Chumpradit, S.; Kung, M. P.; Billings, J. J.; Kung,
H. F. J. Med. Chem. 1991, 34, 877.
(4) Gerritz, S. W.; Smith, J. S.; Nanthakumar, S. S.; Uehling, D.
E.; Cobb, J. E. Org. Lett. 2000, 2, 4099.
(5) Because of the IUPAC priority system, the substituent on the
carbon adjacent to the benzazepine nitrogen results in the
phenyl substituent being at the 5-position rather than the 1-
position as in compounds described in ref.3
(6) For examples and further references see: (a) Heathcock, C.
H.; Norman, M. H.; Dickman, D. A. J. Org. Chem. 1990, 55,
798. (b) Mitch, C. H. Tetrahedron Lett. 1988, 29, 6831.
(c) Grierson, D. S.; Harris, M.; Husson, H.-P. J. Am. Chem.
Soc. 1980, 102, 1064.
Equation 3 Acylation and deprotection of amine derivative 3b
(7) A related reaction with a 1-benzazepine substrate has been
reported: Corbel, J. C.; Uriac, P.; Huet, J.; Martin, C. A. E.;
Advenier, C. J. Med. Chem. 1995, 30, 3.
Synlett 2004, No. 8, 1394–1398 © Thieme Stuttgart · New York

LETTER
Functionalized 2,5-Disubstituted Benzazepines
1397
(8) For an analogous route to a secondary, rather than tertiary
lactam, see: Berney, D.; Schuh, K. Helv. Chim. Acta 1981,
64, 373.
H, J = 7.2 Hz), 7.35–7.39 (m, 2 H). 1H NMR NOESY
analysis indicated that 5b is the assigned cis diastereomer.
(12) Reduction of Nitrile 5a or 5b to Give Aminomethyl
Benzazepines 3a and 3b. Compound 3a as major
(9) Synthesis of 3-Methyl-7-(methyloxy)-8-
{[(methyloxy)methyl]oxy}-1-phenyl-2,3-dihydro-1H-3-
benzazepine (4): To a –78 °C solution of lactam 9 (2.63 g,
7.72 mmol) in anhyd THF (50 mL) under N2 was added via
syringe 1.5 M DIBALH in toluene (6.69 mmol, 10.04
mmol). The mixture was stirred at –78 °C for 2 h, allowed to
warm to ambient temperature and stirred for 16 h. The
mixture was quenched by slow addition of sat. aq NH4Cl (75
mL). The mixture was extracted with 1:1 hexane–EtOAc
(150 mL). The organic layer was separated and stirred
rapidly for 2 h with sat. aq sodium potassium tartrate. The
organic layer was separated, dried over Na2SO4, filtered and
concentrated to afford a yellow oil. Purification by silica gel
chromatography (2:1 hexanes–EtOAc as eluant) gave 1.29 g
(51%) of product. 1H NMR (400 MHz, CDCl3): d = 2.62 (s,
3 H), 3.43 (s, 3 H), 3.49–3.56 (m, 2 H), 3.85, (s, 3 H), 4.42
(d, 1 H, J = 5.2 Hz), 5.02 (d, 1 H, J = 11.2 Hz), 5.06 (d, 1 H,
J = 6.4 Hz), 5.10 (d, 1 H, J = 6.4 Hz), 5.88 (d, 1 H, J = 11.2
Hz), 6.63 (s, 1 H), 6.73 (s, 1 H), 7.08 (d, 2 H, J = 7.6 Hz),
7.16 (t, 1 H, J = 7.2 Hz), 7.25 (d, 2 H, J = 7.6 Hz).
diastereomer: To a solution of 50 mg of 5a (0.142 mmol) in
THF (2.0 mL) was added 4 mL H2O, followed by 15 mg
(0.395 mmol) LiAlH4. The mixture was stirred for 45 min
and an additional 17 mg (0.45 mmol) of LiAlH4 was added.
The mixture was stirred for 30 min and, after cooling to 0 °C
quenched by addition of 30 mL H2O, 30 mL 15% NaOH and
60 mL H2O. The mixture was filtered through a pad of Celite
and concentrated to afford a quantitative yield of product 3
judged by 1H NMR to be an 11:1 mixture of 3a and 3b. 1H
NMR (400 MHz, CDCl3): d = 2.42 (s, 3 H), 2.60–2.73 (m, 2
H), 2.75–2.84 (m, 2 H), 3.10 (dd, 1 H, J = 14.0, 10.0 Hz),
3.20–3.30 (m, 4 H), 3.38 (s, 3 H), 3.75 (t, 1 H, J = 4.5 Hz),
3.85 (s, 3 H), 4.40 (dd, 1 H, J = 8.0, 3.0 Hz), 4.98 (d, 1 H,
J = 6.4 Hz), 5.01 (d, 1 H, J = 6.4 Hz), 6.48 (s, 1 H), 6.67 (s,
1 H), 7.15 (d, 2 H, J = 7.0 Hz), 7.25 (t, 1 H, J = 7.0 Hz), 7.32
(t, 1 H, J = 7.0 Hz). Compound 3b as major diastereomer:
The same procedure as was employed above was carried out
on 5b (101.4 mg, 0.288 mmol) using 6 mL H2O (0.33 mmol)
and 27 mg (0.71 mmol) LiAlH4 in 4 mL THF to supply a
quantitative yield of 3 judged to be a 1:7 mixture of 3a:3b.
1H NMR (400 MHz, CDCl3): d = 2.60 (s, 3 H), 2.63–2.81 (m,
4 H), 2.99 (dd, 1 H, J = 14.4, 3.2 Hz), 3.21 (d, 1 H, J = 14.1
Hz), 3.32 (s, 3 H), 3.47 (dd, 1 H, J = 14.4, 10.0 Hz), 3.71–
3.74 (m, 2 H), 3.83 (s, 3 H), 4.46 (dd, 1 H, J = 10.0, 2.8 Hz),
4.91 (d, 1 H, J = 6.4 Hz), 4.93 (d, 1 H, J = 6.4 Hz), 6.38 (s,
1 H), 6.62 (s, 1 H), 7.11 (d, 2 H, J = 6.8 Hz), 7.23 (t, 1 H,
J = 6.8 Hz), 7.31 (t, 2 H, J = 7.2 Hz).
(10) Synthesis of trans-3-Methyl-8-(methyloxy)-7-
{[(methyloxy)methyl]oxy}-5-phenyl-2,3,4,5-tetrahydro-
1H-3-benzazepine-2-carbonitrile (5a): To a solution of
enamine 4 (1.29 g, 3.96 mmol) in MeOH (70 mL) was added
KCN (1.29 g, 19.8 mmol) followed by pH 7.2 phosphate
buffer (15 mL). The mixture was stirred at ambient
temperature for 3 d. The solvent was removed and the
mixture was partitioned between H2O (50 mL) and 2:1
hexane–EtOAc (75 mL). The organic layer was separated,
dried over Na2SO4, filtered and concentrated to afford 1.16 g
(83%) of product as a pale yellow solid judged to be a >15:1
mixture of 5a:5b by 1H NMR. Anal. Calcd for C21H24N2O3:
C, 71.56; H, 6.86; N, 7.95. Found: C, 71.29; H, 7.09; N, 7.55.
A sample of diastereomerically pure 5a (0.63 g) was
obtained by recrystallization from Et2O as a white solid, mp
157–158 °C. 1H NMR (400 MHz, CDCl3): d = 2.47 (s, 3 H),
2.71 (dd, 1 H, J = 15.0, 6.1 Hz), 3.02 (t, 2 H, J = 6.7 Hz),
3.48 (m, 1 H), 3.50 (s, 3 H), 3.87 (m, 1 H), 3.88 (s, 3 H), 4.15
(d, 1 H, J = 4.8 Hz), 5.18 (d, 1 H, J = 6.9 Hz), 5.21 (d, 1 H,
J = 6.9 Hz), 6.69 (s, 1 H), 6.98 (s, 1 H), 7.08 (d, 2 H, J = 7.5
Hz), 7.17 (t, 1 H, J = 7.6 Hz), 7.24–7.28 (m, 2 H). 1H NMR
NOESY analysis indicated that 5a is the trans diastereomer
as assigned.
(13) A possible explanation for the difference in the high
diastereoselectivity of the cyanide addition to 4 (Scheme 2)
compared to poor selectivity of the LiAlH4 reduction under
anhydrous conditions may be the fact that both are under
thermodynamic control but involve distinct amine
protonation states. At pH 7.2 there may be a strong
thermodynamic preference for the protonated form of 5a
relative to the protonated form of 5b, while under the
conditions of the reduction there may be little
thermodynamic bias between free base 5a and 5b.
Experiments to further examine this question by attempting
the epimerization of 5a or 5b under more basic conditions in
the presence of a proton source have not been carried out.
(14) N-{[(2R*,5R*)-7-Hydroxy-3-methyl-8-(methyloxy)-5-
phenyl-2,3,4,5-tetrahydro-1H-3-benzazepin-2-
(11) cis-3-Methyl-8-(methyloxy)-7-
yl]methyl}-1-methyl-1H-indole-2-carboxamide
{[(methyloxy)methyl]oxy}-5-phenyl-2,3,4,5-tetrahydro-
1H-3-benzazepine-2-carbonitrile (5b): The foregoing 15:1
mixture of trans/cis benzazepines 5a and 5b (1.40 g, 3.97
mmol) was dissolved in anhyd THF (60 mL) and the solution
was cooled under N2 to –78 °C. A solution of KHMDS in
toluene (11.9 mL of 0.5 M solution, 5.96 mmol) was added
and the mixture was stirred for 20 min. A solution of 2,6-
tert-butylhydroxytoluene (1.54 g, 7.0 mmol) in THF (10
mL) was added slowly via syringe. The mixture was stirred
for 1 h at –78 °C, allowed to warm to 0 °C, and partitioned
between sat. aq NaHCO3 and 1:1 hexane–EtOAc. The
organic layer was separated and dried over Na2SO4, filtered
and concentrated. Purification by silica gel chromatography
(2:1 hexane–EtOAc) afforded in order of mobility 5a (0.76
g, 2.15 mmol) and 5b (mp 137–138 °C) (0.44 g, 1.25 mmol).
Compound 5b: 1H NMR (400 MHz, CDCl3): d = 2.49 (s, 3
H), 2.92 (dd, 1 H, J = 12.4, 9.6 Hz), 2.99–3.08 (m, 2 H), 3.28
(s, 3 H), 3.48 (d, 1 H, J = 14.8 Hz), 3.84 (s, 3 H), 4.06 (d, 1
H, J = 4.8 Hz), 4.18 (d, 1 H, J = 9.6 Hz), 4.89 (s, 2 H), 6.27
(s, 1 H), 6.73 (s, 1 H), 7.17 (s, 1 H), 7.19 (s, 1 H), 7.29 (t, 1
Hydrochloride (11): To a solution of 7:1 cis/trans
benzazepines 3b:3a obtained from the foregoing procedure
(27.3 mg, 0.077 mmol) and N,N-diisopropylethylamine (27
mL, 0.154 mmol) was added 1-(3-dimethylaminopropyl)-3-
ethylcarbodiimide hydrochloride (21.5 mg, 0.112 mmol),
and N-methyl indole-2-carboxylate (21 mg, 0.12 mmol)
followed by 1-hydroxybenzotriazole monohydrate (3 mg,
0.02 mmol). The solution was stirred at ambient temperature
for 15 h. The mixture was partitioned between H2O and
EtOAc. The organic layer was separated, washed with sat. aq
NaCl, filtered and concentrated to afford the crude product,
which was purified by silica gel chromatography to give
26.0 mg (66% yield) of the pure MOM protected ether amide
product as a 7:1 mixture of diastereomers by 1H NMR. 1H
NMR (major, cis diastereomer) resonances include: d = 2.67
(s, 3 H), 2.78 (dd, 1 H, J = 15.0, 7.2 Hz), 2.97 (br s, 1 H),
3.03 (d, 1 H, J = 14.4 Hz), 3.19 (dt, 1 H, J = 7.7, 3.6 Hz),
3.33 (s, 3 H), 3.53–3.61 (m, 2 H), 3.84 (s, 3 H), 4.04 (s, 2 H),
4.50 (d, 1 H, J = 8.4 Hz), 4.94 (s, 2 H), 6.41 (s, 1 H), 6.66 (s,
1 H), 6.74 (s, 1 H), 7.11–7.15 (m, 3 H), 7.24–7.38 (m, 5 H),
Synlett 2004, No. 8, 1394–1398 © Thieme Stuttgart · New York

1398
J. E. Cobb et al.
LETTER
7.61 (d, 1 H, J = 7.9 Hz). This material was dissolved in
MeOH (1.0 mL) and 1.0 N aq HCl was added (1.0 mL). The
mixture was stirred at ambient temperature for 1.5 h. The
solvent was removed and the mixture was resubjected to the
above conditions and lyophilized to 24.6 mg of the product
phenol hydrochloride salt 11 as a cream colored powder
judged to be a 7:1 mixture of cis/trans diastereomers. Low
res. MS = 470.2 [M + H]. 1H NMR (400 MHz, DMSO-d6):
d = 2.96 (s, 1.5 H), 3.00–3.10 (m, 3 H), 3.15 (s, 1.5 H), 3.40–
3.60 (s, 1.5 H), 3.63 (s, 1.5 H), 3.63–3.80 (m, 1 H), 4.00 (s,
3 H), 4.00–4.10 (m, 1 H), 4.60 (d, 0.5 H, J = 8.0 Hz), 5.85 (s,
0.5 H), 5.95 (s, 0.5 H), 6.80–6.95 (m, 1 H), 7.05–7.70 (m, 11
H), 8.62–8.80 (m, 1 H), 8.80–8.81 (s, 0.5 H), 10.06 (br s, 1
H). Anal. Calcd. for C29H31N3O3·1.9HCl: C, 64.64; H, 6.15;
N. 7.80. Found: C, 64.70; H, 6.10; N, 7.66.
Synlett 2004, No. 8, 1394–1398 © Thieme Stuttgart · New York