Synthesis of 7-alkoxy/hydroxy-α-methyltryptamines

Article abstract of DOI:10.1081/SCC-120034160

A simple method for the preparation of 7-alkoxy/hydroxy-α -methyl-DL-tryptamines is reported. The key steps of the synthesis are the Japp-Klingemann coupling of 2-piperidone-3-carboxylic acid 3 with diazonium salts 4, the Fischer-type cyclization of hydrazones 5 to β-carboline derivatives 6 and their hydrolysis to title compounds 8.

Full text of DOI:10.1081/SCC-120034160

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Synthesis of 7‐Alkoxy/Hydroxy‐α‐methyltryptamines
Nauzer P. Dubash a , Naveen K. Mangu a & Apparao Satyam a b
a Discovery Chemistry Division, Glenmark Research Centre, Glenmark Pharmaceuticals
Ltd., Navi Mumbai, India
b Nicholas Piramal India Limited, Quest Institute of Life Sciences, 1A, 1B and 1C—Nirlon
Complex, Near NSE Complex, Goregaon (East), Mumbai, 400 063, India
Published online: 20 Aug 2006.
To cite this article: Nauzer P. Dubash , Naveen K. Mangu & Apparao Satyam (2004) Synthesis of 7‐Alkoxy/
Hydroxy‐α‐methyltryptamines, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 34:10, 1791-1799, DOI: 10.1081/SCC-120034160
To link to this article: http://dx.doi.org/10.1081/SCC-120034160
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 10, pp. 1791–1799, 2004
Synthesis of 7-Alkoxy/Hydroxy-
a-methyltryptamines
Nauzer P. Dubash, Naveen K. Mangu, and
*
Apparao Satyam
Discovery Chemistry Division, Glenmark Research Centre,
Glenmark Pharmaceuticals Ltd., Navi Mumbai, India
ABSTRACT
A simple method for the preparation of 7-alkoxy/hydroxy-a-methyl-
DL-tryptamines is reported. The key steps of the synthesis are the Japp–
Klingemann coupling of 2-piperidone-3-carboxylic acid 3 with diazonium
salts 4, the Fischer-type cyclization of hydrazones 5 to b-carboline deriva-
tives 6 and their hydrolysis to title compounds 8.
Key Words: 7-Methoxy-a-methyltryptamine; 7-Hydroxy-a-methyltrypt-
amine; 7-Benzyloxy-a-methyltryptamine; Japp–Klingemann coupling;
Reductive amination.
*
Correspondence: Apparao Satyam, Nicholas Piramal India Limited, Quest Institute of
Life Sciences, 1A, 1B and 1C—Nirlon Complex, Near NSE Complex, Goregaon (East),
Mumbai 400 063, India; Fax: 91-22-5679 7451; E-mail: apparaosvgk@hotmail.com.
1791
DOI: 10.1081/SCC-120034160
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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Dubash, Mangu, and Satyam
INTRODUCTION
b3-Adrenoceptor agonists[1] (IA and IB)[2] are promising agents for the
treatment of obesity and diabetes and the former is currently in Phase II
clinical trials as a potential candidate for these indications.
In the context of our research on 7-substituted indole derivatives as
potential b3-agonists, we needed an efficient method for the synthesis of
7-hydroxy-a-methyltryptamine 8b. Most of the reported methods[2,3] for
7-substituted a-methyltryptamines start from a preformed 7-substituted indole
nucleus and preparation of such appropriately substituted indoles[4] in itself is
cumbersome. Preparation of an enantiomerically pure a-methyltryptamine
from the corresponding tryptophan is known.[5] However, this method
requires prior synthesis of the corresponding optically pure 7-alkoxytrypto-
phan. This led us to devise a simple alternative synthetic method (a similar
approach was reported for the synthesis of 7-alkoxytryptamine[6]) for the
said compounds, and we wish to report those results in this communication.
As depicted in Sch. 1, the steps involved in the synthetic route include:
(1) reductive amination of diethyl (3-oxobutyl)malonate (1)[7] to yield
3-carboethoxy-6-methyl-2-piperidone (2) which is hydrolyzed to 6-methyl-
2-piperidone-3-carboxylic acid (3); (2) Japp–Klingemann coupling of
acid 3 with diazonium salt 4a or 4b (freshly prepared from o-anisidine or
2-benzyloxyaniline, respectively) to yield the corresponding hydrazone
derivative 5a or 5b, (3) Fischer-type cyclization of 5a or 5b to yield the
corresponding 3-methyl-1-oxo-1,2,3,4-tetrahydro-b-carboline derivative 6a or
6b; (4) Basic hydrolysis of 6a or 6b to give a presumed intermediate amino
acid 7a or 7b, which is subjected to decarboxylation conditions to yield the
desired a-methyltryptamine. Decarboxylation in refluxing 8% sulfuric acid,
as per the literature method,[6b] afforded tryptamine derivatives 8 in negligible
yields (11–15% of 8a and 0% of 8b), presumably due to poor solubility in
8% sulfuric acid. However, decarboxylation of 7a in refluxing 6 N hydro-
chloric acid afforded 8a[3b] in 81% yield, which was converted to its hydro-
chloride salt for characterization. In the case of the benzyloxy derivative

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7-Alkoxy/Hydroxy-a-methyltryptamines
1793
Scheme 1. Reagents and conditions: (a) 10% Pd/C, HCOONH4, MeOH–H2O (9 : 1),
rt, 16 hr; (b) 0.5N KOH–THF (2 : 1), rt, 1 hr; (c) CH3CO2NA. pH ꢀ4.5, 08C, 5 hr; (d)
CH3CO2H, reflux, 5–5.5 hr; (e) 2.3N KOH–EtOH (1 : 2), reflux, 18–40 hr; (f) i. 6N
HCl, reflux, 1–20 hr ii. basification to pH ꢀ8 with 10% NaOH; (g) (Boc)2O,
EtOAc–THF (5 : 1), rt, 2 hr; (h) BrCH2CO2Et, K2CO3, DMF, rt, 4 hr.

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Dubash, Mangu, and Satyam
7b, decarboxylation was accompanied by debenzylation when refluxed in 3 N
hydrochloric acid, affording 7-hydroxy-a-methyltryptamine (8b) in 55%
yield. 8b was converted in two steps to 3-(2-tert-butoxycarbonylamino-
propyl)-7-ethoxycarbonylmethoxyindole (10), an important starting material
for the synthesis of AD-9677 (IA).
In summary, a simple method for the synthesis of 7-alkoxy/hydroxy-a-
methyltryptamines has been developed from cheap or easily synthesizable
starting materials. Resolution of these tryptamine derivatives using standard
resolution techniques will afford optically pure building blocks for the
synthesis of derivatives of AD-9677 as potential b3-agonists. Studies in this
direction are currently underway.
EXPERIMENTAL
General
Melting points were recorded on LABINDIA MR-VIS apparatus and are
1
uncorrected. H-NMR spectra were recorded in CDCl3 on a Varian Mercury
300 (300 MHz) Instrument. Chemical shifts are given in parts per million
(ppm) relative to tetramethylsilane (TMS). Mass spectra (MS) were obtained
on Finnegan Navigator ESI instrument and the data reported as m/z (mass spec-
tral service was obtained from Ashco Labs, Mumbai). Microanalysis was done
on Perkin–Elmer CHN Analyzer 2400. Column chromatography was done on
silica gel, 100–200 mesh (SISCO Labs., India). Thin-layer chromatography
(TLC) was done on aluminum plates pre-coated with Merck silica gel
60 F254. If not otherwise indicated, commercially available chemicals were
used as received. All solvents were laboratory grade and anhydrous solvents
were prepared according to literature procedures and handled under nitrogen.
o-Benzyloxyaniline (4b). Step 1: To a stirred suspension of o-amino-
phenol (50 g, 0.458 mol) in dichloromethane (1 L) was added drop-wise a solution
of di-tert-butyl dicarbonate (160 g, 0.733 mol) in dichloromethane (500 mL).
The reaction mixture was stirred at room temperature under nitrogen for
24 h. The mixture was concentrated in vacuo, triturated with ice-cold petrol-
eum ether (500 mL) and filtered to afford o-[N-(tert-butoxycarbonyl)amino]
phenol (87 g, 91%) as a white solid, mp: 144–1478C. 1H-NMR: d 1.54 (s, 9H),
6.59 (bs, 1H), 6.80–6.86 (m, 1H), 6.93–7.05 (m, 3H), 7.96 (bs, 1H). The
compound was used in the next step without further purification.
Step 2: To a solution of o-[N-(tert-Butoxycarbonyl)amino]phenol (10 g,
47 mmol) in acetone (100 mL) was added anhydrous potassium carbonate
(10 g, 71 mmol) and benzyl bromide (8.99 g, 52 mmol) and the mixture was
stirred at room temperature under nitrogen for 12 hr. The mixture was filtered

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7-Alkoxy/Hydroxy-a-methyltryptamines
1795
and the filtrate was concentrated in vacuo. The residue was taken up in ethyl
acetate (100 mL), washed with water (2 ꢀ 50 mL), brine (2 ꢀ 50 mL) and
dried (Na2SO4). The crude product was purified by column chromatography
on silica gel using 4% ethyl acetate in petroleum ether as eluent to afford
N-Boc-(2-benzyloxy)-aniline (11 g, 77%) as a white solid, mp: 67–708C.
1H-NMR: d 1.51 (s, 9H), 5.09 (s, 2H), 6.86–6.95 (m, 3H), 7.06 (bs, 1H),
7.32–7.40 (m, 4H), 8.05–8.09 (m, 1H).
Step 3: To a solution of N-Boc-(2-benzyloxy)-aniline (10 g, 33 mmol) in
dichloromethane (50 mL) was added drop-wise a solution of trifluoroacetic
acid (20 mL) in dichloromethane (20 mL) and stirred at room temperature
under nitrogen for 1 hr. When TLC of the mixture indicated disappearance
of starting material, the reaction mixture was concentrated under vacuum.
The residue was partitioned between 1 N NaOH (50 mL) and ether (50 mL).
The ether layer was separated and the aq. layer was extracted with fresh
ether (50 mL). The combined ether extract was washed with brine (50 mL),
dried over anhydrous sodium sulfate, and concentrated in vacuo to give a
viscous oil, which solidified on standing in the refrigerator. The crude product
was obtained as a white solid, mp: 37–388C; 1H-NMR: d 5.09 (s, 2H), 6.06 (bs,
2H), 6.81–6.90 (m, 2H), 6.96–7.02 (m, 1H), 7.12–7.16 (m, 1H), 7.23–7.33
(m, 3H), 7.38–7.42 (m, 2H). The product was used in the next reaction
without further purification.
Ethyl 6-methyl-2-oxopiperidine-3-carboxylate (2). To a stirred sol-
ution of diethyl (3-oxobutyl)malonate (1)[7] (2 g, 8.68 mmol) in methanol
(20 mL) was added a solution of ammonium formate (5.46 g, 86.8 mmol) in
water (3 mL). When a clear solution was obtained, 10% Pd–C (1.14 g) was
added and the mixture was stirred at room temperature for 16 hr. The reaction
mixture was filtered through a celite pad and the pad was washed with hot
methanol (2 ꢀ 30 mL). The filtrate was concentrated in vacuo and taken up
in ethyl acetate (50 mL). The ethyl acetate solution was washed with water
(2 ꢀ 30 mL), dried over anhydrous sodium sulfate, and concentrated to afford
a yellow oil. The crude product was purified by column chromatography using
10% ethyl acetate in petroleum ether as eluent. Fractions containing the dia-
stereomeric mixture of products (Rf ¼ 0.38 and 0.48, EtOAc, iodine visualiza-
tion) were pooled and concentrated to afford 1.08 g (67%) of 2 as a white
1
crystalline solid, mp: 74–798C; H-NMR: d 1.19–1.32 (m, 6H), 1.91–2.21
(m, 4H), 3.26–3.37 (m, 1H), 3.49–3.60 (m, 1H), 4.14–4.24 (m, 2H), 6.19
(bs, 0.5 H), 6.29 (bs, 0.5 H). MS m/z: 186 [M þ H]þ ; Anal. Calcd. for
C19H15NO3: C, 58.36; H, 8.16; N, 7.56. Found: C, 58.08; H, 8.46; N, 7.47.
6-Methylpiperidine-2, 3-dione 3-[(2-methoxyphenyl)hydrazone] (5a). To
a solution of ethyl 6-methyl-2-oxopiperidine-3-carboxylate (2) (1g, 5.4mmol) in
THF (10 mL) was added 0.5 N potassium hydroxide (0.606 g KOH, 10.8 mmol)
and the mixture was stirred at room temperature for 1 hr. THF was evaporated

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1796
Dubash, Mangu, and Satyam
and the resulting aqueous solution was cooled to 08C and acidified to pH 2–3
using 1 N hydrochloric acid and the mixture was kept at 08C (Flask 1). In a sep-
arate flask (Flask 2), a solution of o-anisidine (0.665 g, 5.4 mmol) in 3 N HCl
(9 mL) was cooled to 08C and diazotized by drop-wise addition of a solution of
sodium nitrite (0.38 g, 5.5 mmol) in water (1.5 mL) and the mixture was stirred
at 08C for 30 min. The mixture from Flask 1 was added in one lot to the diazotized
solution in Flask 2. Then, a solution of sodium acetate (2.5 g, 30 mmol) in water
(3 mL) was added and the mixture was stirred at 08C for 5 hr. The mixture was
filtered and the yellow precipitate was washed with cold water (4 ꢀ 25 mL)
and dried in a vacuum desiccator to afford the corresponding hydrazone 5a
(1.04 g, 78%) as a yellow solid, mp: 202–2058C. 1H-NMR: d 1.26
(d, J ¼ 6.6 Hz, 3H), 1.56–1.69 (m, 1H), 2.00–2.08 (m, 1H), 2.58–2.82
(m, 2H), 3.58–3.86 (m, 1H), 3.87 (s, 3H), 5.88 (bs, 1H), 6.80–7.24 (m, 3H),
7.47 (d, J ¼ 8.4 Hz, 1H), 12.91 (bs, 1H). MS m/z: 248 [M þ H]. The compound
was used in the next step without further purification.
8-Methoxy-3-methyl-2,3,4,9-tetrahydro-1H-b-carbolin-1-one (6a). A
turbid solution of the hydrazone 5a (13 g, 52 mmol) in glacial acetic acid
(125 mL) was refluxed for 5 hr (Note: the turbidity clears within a few minutes
of heating). Acetic acid was removed in vacuo, the residue was triturated with
water (ꢀ125 mL) and basified with conc. NH4OH (pH ꢀ 8.0). The resulting
precipitate was filtered, washed with cold water (4 ꢀ 50 mL), and dried in a
vacuum desiccator. The crude product was purified by column chromato-
graphy (1 : 1 ethyl acetate/petroleum ether) to afford the corresponding
b-carboline derivative 6a (7.21 g, 59%) as a yellow solid, mp: 166–1728C.
1
Purity: 98.73% by HPLC. H-NMR: d 1.41 (d, J ¼ 6.3 Hz, 3H), 2.73–2.82
(dd, J ¼ 11.4 Hz, 16 Hz, 1H), 3.03–3.10 (dd, J ¼ 5.4 Hz, 16 Hz, 1H), 3.95
(s, 3H), 4.01–4.09 (h, 1H), 5.70 (bs, 1H), 6.70 (d, J ¼ 7.8 Hz, 1H), 7.04
(t, J ¼ 7.8 Hz, 1H), 7.15 (d, J ¼ 8.1 Hz, 1H), 9.16 (bs, 1H). MS m/z: 461
[2M þ H]þ; Anal. Calcd. for C13H14N2O2 0.6 HCO2H: C, 66.97; H, 6.28;
.
N, 11.49. Found: C, 66.62; H, 6.66; N, 11.96.
7-Methoxy-a-methyltryptamine (8a). To a solution of the carboline
derivative 6a (0.23 g, 1 mmol) in EtOH : H2O (5 L : 2.5 mL) was added
potassium hydroxide (0.561g, 10mmol) and the solution was refluxed for 18hr.
Ethanol was removed in vacuo, the residue was dissolved in 6 N HCl (5mL)
and the mixture was refluxed for 1 hr. The reaction mixture was cooled and
neutralized by the addition of 1 N NaOH. The reaction mixture was extracted
with dichloromethane (3 ꢀ 20mL), washed with water (20 mL), dried over
anhydrous sodium sulfate and concentrated to afford 7-methoxy-a-methyltrypt-
amine (8a) (0.167g, 81%) as a reddish gum. The free base was dissolved in
ether and the resulting solution was treated with 1 M solution of hydrogen
chloride in ether. The product, 7-methoxy-a-methyltryptamine hydrochloride,
separated in crystalline form and it was collected and dried, mp: 245–2468C

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7-Alkoxy/Hydroxy-a-methyltryptamines
1797
(reported mp:[3b] 247–2488C). 1H-NMR: d 1.15 (d, J ¼ 6.3 Hz, 3H), 1.47 (bs,
2H), 2.59–2.66 (dd, J ¼ 8.1 Hz, 14Hz, 1H), 2.82–2.88 (dd, J ¼ 4.8 Hz, 14Hz,
1H), 3.23–3.30 (m, 1H), 3.93 (s, 3H), 6.62 (d, J ¼ 7.5 Hz, 1H), 6.97–7.03
(m, 2H), 7.18–7.23 (m, 1H), 8.34 (bs, 1H). MS m/z: 205 [M þ H]þ.
6-Methylpiperidine-2, 3-dione 3-[(2-benzyloxyphenyl)hydrazone] (5b).
The procedure followed was identical to that for 5a. The product was obtained
as a solid, mp: 160–1658C; yield: 62%; purity: 99.79% by HPLC [column:
ThermoHypersil Keystone 250 ꢀ 4.6 mm ꢀ 0.5 m; mobile phase: (isocratic
elution) A : B (35 : 65); A ¼ 0.05 M ammonium acetate buffer, B ¼
acetonitrile; flow rate: 1.0 mL/min; detection: 240 nm; RT ¼ 10.3 min].
1H-NMR: d 1.21 (d, J ¼ 6.6 Hz, 3H), 1.56–1.67 (m, 1H), 1.99–2.05
(m, 1H), 2.58–2.82 (m, 2H), 3.54–3.60 (m, 1H), 5.15 (s, 2H), 5.79 (bs,
1H), 6.76–6.94 (m, 3H), 7.26–7.38 (m, 3H), 7.47–7.52 (m, 3H), 13.10 (bs,
1H). MS m/z: 324 [M þ H]þ; Anal. Calcd. for C19H21N3O2: C, 70.55; H,
6.55; N, 12.99. Found: C, 70.46; H, 7.17; N, 13.13.
8-Benzyloxy-3-methyl-2,3,4,9-tetrahydro-1H-b-carbolin-1-one (6b). A
solution of the hydrazone 5b (3g, 9.29mmol) in glacial acetic acid (30mL)
was refluxed under nitrogen for 5.5 hr. Acetic acid was stripped off and the
residue was triturated with water (50 mL) and basified with conc. ammonium
hydroxide (pH ꢀ 8.0). The resulting precipitate was filtered, washed with
cold water (150mL), and dried in a vacuum desiccator. The crude brown solid
was purified by column chromatography on silica gel using 25–50% ethyl ace-
tate in petroleum ether as eluent to afford the corresponding b-carboline 6b
(1.60 g, 56%) as a yellow solid, mp: 169–1708C. 1H-NMR: d 1.41
(d, J ¼ 6.3 Hz, 3H), 2.74–2.83 (dd, J ¼ 11.4Hz, 15.9 Hz, 1H), 3.04–3.11
(dd, J ¼ 5 Hz, 15.4Hz, 1H), 4.01–4.12 (m, 1H), 5.20 (s, 2H), 5.45 (bs, 1H),
6.79 (d, J ¼ 7.5Hz, 1H), 7.04 (t, J ¼ 8.1 Hz, 1H), 7.17 (d, J ¼ 8.1 Hz, 1H),
7.33–7.47 (m, 5H), 9.08 (bs, 1H). MS m/z: 307 [M þ H]þ: Anal. Calcd. For
C19H18N2O2: C, 74.47; H, 5.93; N, 9.14. Found: C, 74.12; H, 6.54; N, 9.30.
7-Hydroxy-a-methyltryptamine (8b). To a solution of the b-carboline
derivative 6b (2.5 g, 8.17 mmol) in EtOH/H2O (83 mL : 42 mL) was added
potassium hydroxide (4.58 g, 81.7 mmol) and the solution was refluxed for
40 hr. EtOH was distilled off and the residue (supposed to contain the inter-
mediate 7b) was dissolved in 3 N hydrochloric acid (40 mL) and the mixture
was heated to 110–1208C and stirred at that temperature for 20 hr. (Note:
initially, a copious amount of white precipitate separated within a few
minutes of heating. However, the precipitate slowly dissolved over 1 hr period
to form a clear brown colored solution.) The mixture was cooled and extracted
with ether (100 mL). The aqueous layer was cooled and basified with 10%
solution of sodium hydroxide (30 mL) and was extracted with ethyl acetate
(3 ꢀ 100 mL). Combined organic extracts were washed with brine (100 mL),
dried over anhydrous sodium sulfate and concentrated in vacuo to afford

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Dubash, Mangu, and Satyam
7-hydroxy-a-methyltryptamine (8b) (0.812 g, 53%) as a brown solid, mp: 54–
1
558C (softening); H-NMR: d 1.19 (d, J ¼ 6.3 Hz, 3H), 2.51–2.62 (m, 4H),
2.84–2.90 (m, 1H), 3.25–3.31 (m, 1H), 6.51 (d, J ¼ 7.2 Hz, 1H), 6.84–
6.90 (m, 2H), 7.11 (d, J ¼ 7.8 Hz, 1H), 8.28 (bs, 1H). The compound was
used in the next step without further purification.
3-(2-Boc-aminopropyl)-7-hydroxy-indole (9). To a solution of 7-hydroxy-
a-methyltryptamine (8b) (0.3 g, 1.57 mmol) in THF (3 mL) was added a solution
of di-tert-butyl dicarbonate (0.396 g, 0.30 mmol) in THF (3 mL) and the mixture
was stirred at room temperature under nitrogen for 2 hr. The reaction mixture was
impregnated on silica gel and purified by column chromatography on silica
gel using 15–20% EtOAc in petroleum ether as eluent to afford 3-(2-Boc-amino-
propyl)-7-hydroxy-indole (9) (0.159 g, 34%) as a yellow oil, which solidified on
1
standing to an off-white solid, mp: 40–508C (softening); H-NMR: d 1.15
(d, J ¼ 6.9 Hz, 3H), 1.39 (s, 9H), 2.84–2.87 (m, 2H), 3.98 (m, 1H), 4.57
(bs, 1H), 6.61 (d, J ¼ 7.8 Hz, 1H), 6.80 (bs, 1H), 6.91 (t, J ¼ 7.8 Hz, 1H),
7.06–7.21 (m, 2H), 8.53 (bs, 1H). MS m/z: 291 [M þ H]þ.
3-(2-Boc-aminopropyl)-7-ethoxycarbonylmethoxy-indole (10). To
a
stirred solution of 3-(2-Boc-aminopropyl)-7-hydroxy-indole (9) (124mg,
0.427 mmol) in anhydrous DMF (4 mL) were added dry powdered potassium
carbonate (106mg, 0.768 mmol), potassium iodide (a pinch), and ethyl bromo-
acetate (82 mg, 0.487 mmol). The mixture was stirred at ambient temperature
under nitrogen for 4 hr when TLC analysis of the mixture indicated completion
of the reaction. The mixture was filtered, the filtrate was concentrated in
vacuo and the residue was impregnated on silica gel and purified by column
chromatography using 20% ethyl acetate in petroleum ether as eluent to afford
116 mg (72%) of 3-(2-Boc-aminopropyl)-7-ethoxycarbonylmethoxy-indole
(10) as a yellow oil, which upon scratching in pentane yielded a white solid,
mp: 99–1028C. 1H-NMR: d 1.11 (d, 3H, J ¼ 6.9 Hz, CH3), 1.29 (t, 3H,
J ¼ 7.2 Hz, CO2CH2CH3) 1.42 (s, 9HBoc), 2.79–2.96 (m, 2Hmethylene), 4.00
(m, 1Hmethine), 4.26 (q, 2H, J ¼ 7 Hz, CO2CH2CH3), 4.72 (s, 2H, OCH2CO2Et),
6.56 (d, 1H, J ¼ 7.8 Hz, H-6), 6.94–6.99 (m, 2H, H-2 þ H-5), 7.27 (d, 1H,
J ¼ 8.1 Hz, H-4), 8.57 (bs, 1H, NHindole). MS m/z: 377 [M þ H]þ and 277
[(M-Boc) þ H]þ; Anal. Calcd. for C20H28N2O5: C, 63.81; H, 7.50; N, 7.44.
Found: C, 64.23; H, 7.10; N, 7.59.
ACKNOWLEDGMENTS
The authors gratefully acknowledge the support from Glenmark Research
Centre. The authors thank Dr. B. Gopalan for his suggestions on the subject.
The authors also wish to thank Dr. Vinod R. Uchil and Mr. Machhindra Gund
for their technical help.

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Received in India December 3, 2003

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