Synthesis and ring transformations of 1-amino-1,2,3,9a-tetrahydroimidazo[1, 2-a]indol-2(9H)-ones

Article abstract of DOI:10.1016/j.tet.2006.01.054

Heating 1-carbamoylmethyl-2,3,3-trimethyl-3H-indolinium chloride in the presence of hydrazine bishydrate produces regioselectively the five-membered heterocycle 1-amino-1,2,3,9a-tetrahydro-9,9,9a-trimethylimidazo[1,2-a]indol- 2(9H)-one. The assignment of

Full text of DOI:10.1016/j.tet.2006.01.054

Tetrahedron 62 (2006) 3309–3319
Synthesis and ring transformations of
1-amino-1,2,3,9a-tetrahydroimidazo[1,2-a]indol-2(9H)-ones
a
Joana Dumciu¯te, Vytas Martynaitis, Wolfgang Holzer, Sven Mangelinckx,
a
b
c
ˇ
˙
c
Norbert De Kimpe and Algirdas Sackus
a,
ˇ
*
ˇ
aDepartment of Organic Chemistry, Kaunas University of Technology, LT-50270 Kaunas, Lithuania
bDepartment of Drug Synthesis, Faculty of Life Sciences, University of Vienna, Pharmaziezentrum, A-1090 Vienna, Austria
cDepartment of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure links 653, B-9000 Gent, Belgium
Received 14 December 2005; revised 11 January 2006; accepted 17 January 2006
Available online 20 February 2006
Abstract—Heating 1-carbamoylmethyl-2,3,3-trimethyl-3H-indolinium chloride in the presence of hydrazine bishydrate produces
regioselectively the five-membered heterocycle 1-amino-1,2,3,9a-tetrahydro-9,9,9a-trimethylimidazo[1,2-a]indol-2(9H)-one. The assign-
ment of the structure is based on extensive 1H, 13C and 15N NMR spectroscopic studies. No ring-chain tautomerism of the 1-amino-1,2,3,9a-
tetrahydroimidazo[1,2-a]indol-2(9H)-one was observed to open-chain hydrazides or the corresponding six-membered 1,2,10,10a-
tetrahydro[1,2,4]triazino[4,3-a]indol-3(4H)-one. Further transformations of 1-amino-1,2,3,9a-tetrahydroimidazo[1,2-a]indol-2(9H)-one
were performed by treatment with aromatic aldehydes, acid chlorides and isocyanates giving access to 40 novel hydrazones, N,N0-
diacylhydrazines, N-acyl-N0-carbamoylhydrazines and 1,3,4-oxadiazoles.
q 2006 Elsevier Ltd. All rights reserved.
1. Introduction
introduced in some compounds to modify their physiologi-
cal activities such as cognition enhancing activity,2
nootropic activity,3 antimalarial activity,4 and analgesic
activity.5 Metabolic stable N-terminal imidazolidin-4-one
prodrugs of Leu-enkephalin have also been prepared.6
Compounds containing the indole-1-acetamide moiety also
exhibit interesting physiological activities such as central
muscle relaxation,7 anticonvulsive activity,8 and CNS
depressant activity.9
1-Carbamoylmethyl-3H-indolinium salts 1 are known to
cyclize to 1,2,3,9a-tetrahydroimidazo[1,2-a]indol-2(9H)-
ones upon treatment with base.1 If, however, the 1-carba-
moylmethyl-3H-indolinium salts 1 are transformed to the
corresponding hydrazides 2, further cyclization could either
lead to 1-amino-1,2,3,9a-tetrahydroimidazo[1,2-a]indol-
2(9H)-ones 3, similar as to ring closure of the amides, or
to the corresponding six-membered ring systems, that is,
1,2,10,10a-tetrahydro[1,2,4]triazino[4,3-a]indol-3(4H)-one
4, if the terminal NH2 group enters into reaction (Scheme 1).
The objective of this work is to investigate the reaction of
such hydrazides and, apart from the structural investi-
gations, to study the reactivity of the novel cyclic products
and route to novel heterocyclic compounds. The potential
biological activity of the unknown 1-amino-1,2,3,9a-
tetrahydroimidazo[1,2-a]indol-2(9H)-ones is also of inter-
est, as these tricyclic derivatives contain both the 2,3-
dihydro-1H-indole and imidazolidin-4-one nuclei. Via the
reaction of an a-amino amide with a carbonyl compound
followed by intramolecular cyclization, the conformation-
ally rigid imidazolidin-4-one scaffold has already been
2. Results and discussion
Heating 1-carbamoylmethyl-2,3,3-trimethyl-3H-indolinium
chloride 1 in the presence of hydrazine bishydrate, resulted
in the isolation of a cyclized compound identified as the
racemic five-membered heterocycle 1-amino-1,2,3,9a-tetra-
hydro-9,9,9a-trimethylimidazo[1,2-a]indol-2(9H)-one (3)
(Scheme 2).
The main evidence for the assignment of structure 3,
containing the 3-aminoimidazolidin-4-one ring, follows
from the 15N NMR data. The 15N,1H HMBC spectrum
shows three different N-atoms (d K317.6, K299.1 and
K224.6 ppm). In a 15N DEPT experiment (optimized for
1JNHZ70 Hz) only the N-atom with the smallest chemical
shift (d K317.6) emerges, namely as a triplet (1JZ68.9 Hz)
Keywords: Hydrazides; Structural identification; 1,2,3,9a-Tetrahydro-
imidazo[1,2-a]indol-2(9H)-ones; Hydrazines; Oxadiazoles.
*
Corresponding author.
e-mail: algirdas.sackus@ktu.lt
Tel./fax:
C370
37
451432;
0040–4020/$ - see front matter q 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.01.054

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3310
Scheme 1.
nucleophilic site and not the NH2-group.12 The exclusive
formation of the five-membered ring can be tentatively
rationalized on the basis of the E/Z rotamerism of hydrazide
2 with respect to the nitrogen–carbon hydrazide bond with
partial double bond character (Scheme 3). Studies concern-
ing this hindered rotation of hydrazine derivatives have
shown that steric effects of the substituents are driving the
equilibrium towards the (Z) forms, augmented by intra-
molecular hydrogen bonding in the (Z) form.13 It can be
assumed that the large steric effect of the indolylmethyl
carbonyl substituent of hydrazide 2 and the two possible
intramolecular hydrogen bonds between the hydrogen
atoms attached to the nitrogen and the oxygen atom, make
the (Z) form much more favored. This (Z)-hydrazide is
Scheme 2.
and thus proving to origin from an NH2 moiety what
definitely rules out structure 4. Moreover, the 15N, 1H
HMBC spectrum exhibits a correlation between the nitrogen
atom with the largest chemical shift (N-1, d K224.6) and
the protons of 9a-CH3 (d 1.40 ppm), what seems improbable
with structure 4 where the involved nuclei would be
separated by four bonds and thus no correlation is expected.
In addition, in the 1H NMR spectrum there is only one sharp
signal of relative intensity two for the NH-protons. For
structure 4, two different type of NH-signals have to be
expected (CONH, N–NH). The assignments presented in
Figure 1a are based on the combined application of standard
NMR techniques such as NOE-difference (Fig. 1b),
NOESY, APT, DEPT, HSQC, HMBC and long-range
INEPT spectra with selective excitation.10
Although the amino nitrogen atom of the hydrazide moiety
of 2 is more reactive11 than the amide one, the condensation
reaction involves the latter exclusively to give a five-
membered ring. This observed reactivity is similar to
addition reactions of phenylhydrazine in which it was
proven that the N-1 of phenylhydrazine reacts as the
1
Figure 1. (a) H (italics), 13C and 15N NMR (bold) chemical shifts [ppm;
ref. TMS (1H and 13C) and CH3NO2 (15N)] for 3 in DMSO-d6. (b) Relevant
NOE correlations.

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3311
heptan-5-ones.20 Moreover, reactions between a-amino acid
hydrazides and carbonyl functions like imidoyl chlorides,21
thioesters,22 orthocarboxylates,23 in which both five- and
six-membered compounds could be formed, seem to give
systematically the six-membered 1,2,4-triazin-6-ones.
Therefore, it seems acceptable to assume that 3-amino-
imidazolidin-4-ones are the preferred ring-chain tautomers
with respect to 1,2,4-triazin-6-ones if imidazolidinone C-2
and C-5 are sp3-hybridized, otherwise 1,2,4-triazin-6-ones
seem to be favored. The only exception observed so far
being the 1,3,4-triazabicyclo[4.1.0]heptan-5-ones,20 in
which, however, C-5 also has more double-bond character,
being part of a three-membered ring. Interesting to mention
also is the fact that acid-catalyzed rearrangement of
substituted N-aminoimidazolidinones to 3-imino-hexahy-
dro-1,2,4-triazine-6-ones has been reported.24
Further proof for the presence of the primary amino group in
the cyclized compound was given by reacting the
3-aminoimidazolidin-4-one 3 with different types of
electrophiles. Heating compound 3 with aromatic aldehydes
in ethanol in the presence of catalytic amounts of piperidine
afforded the corresponding hydrazones 6a–d as single
E-isomers in good to fair yield after crystallization
(Scheme 4).25 Further reduction of these 1-(arylidenamino)-
imidazo[1,2-a]indolones 6a–d with sodium borohydride in
ethanol at 70 8C resulted in ring cleavage of the annelated
imidazolidin-4-one ring,26 to give acylated hydrazones
7a–d. The lower yields can probably be explained by
partial reduction of the hydrazone moiety.
Scheme 3.
potentially capable of ring-chain tautomerism ðZÞK2%3,
while the unfavorable (E)-form would potentially be
capable of ring-chain tautomerism ðEÞK2%4. No other
ring-chain tautomeric forms of 1-amino-1,2,3,9a-tetra-
hydro-9,9,9a-trimethylimidazo[1,2-a]indol-2(9H)-one (3)
were, however, visible by H and 13C NMR in CDCl3 or
1
DMSO-d6, which can be explained by the annellation effect,
that is, due to higher substitution and thereby higher
conjugation the tricyclic compound 3 is expected to be more
favored than the open-chain hydrazide 2. These obser-
vations are in agreement with similar ring closures of
a-amino acid hydrazides with aldehydes or ketones, which
also resulted in 3-aminoimidazolidin-4-ones,14 or the open-
chain hydrazone tautomers in the case of low substituted
compounds.14c Similarly, glycine hydroxamic acid con-
denses with benzaldehyde15 and ketones,16 leading to the
formation of five-membered 3-hydroxyimidazolidin-4-ones.
To the best of our knowledge, only few reports have been
made on the synthesis of 1,2,4-triazin-6-ones from the
reaction of a-amino acid hydrazides with aldehyde or
ketone functions. Regarding a first report on the reaction of
a-amino acid phenylhydrazides with formaldehyde,17 it was
stated by the same group in a later disclosure,14a that the
proposed six-membered ring structures might be incorrect.
A second report involved the intramolecular reaction of
oxamic hydrazides with a ketone function giving 1,2,4-
triazin-5,6-diones.18 Also reported is the synthesis of
pyrazolotriazines by reaction of pyrazolecarboxylic acid
hydrazides and acetone.19 Another special case involved
reaction of aziridine-2-carboxylic acid hydrazides with
acetone or cyclohexanone giving 1,3,4-triazabicyclo[4.1.0]-
Acylation of 3-aminoimidazolidin-4-one 3 with acetyl
chloride or benzoyl chlorides afforded N,N0-diacylhydra-
zines 8a–f, which also could be reduced upon reaction with
sodium borohydride to give ring cleaved N,N0-diacyl-
hydrazines 9a–f (Scheme 5). Both N,N0-diacylhydrazines
8c,d,f and 9c,d,f were cyclized to 1,3,4-oxadiazoles 10c,d,f
and 11c,d,f under dehydration condition utilizing triphenyl-
phosphine in carbon tetrachloride in the presence of
triethylamine.27 Similarly, N-acyl-N0-carbamoylhydrazines
12a–d and 13a–d, prepared by reaction of imidazolidinone
3 with isocyanates and further reduction, respectively, were
cyclized to 2-amino-1,3,4-oxadiazoles 14a–c and 15a–c
(Scheme 6). Substituted 1,3,4-oxadiazoles exhibit numerous
pharmacological properties, including analgesic, antiin-
flammatory, anticonvulsive, diuretic, antiemetic, hypnotic
and sedative activities.28 More specific, 2-amino-1,3,4-
oxadiazoles act as muscle relaxants29 and possess anti-
mitotic activity.30
Scheme 4.

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3312
Scheme 5.
Scheme 6.
3. Conclusion
acid chlorides and isocyanates, respectively. Further
cyclizations to potentially active 1,3,4-oxadiazoles 10, 11,
14 and 15 were performed under dehydration conditions.
1-Carbamoylmethyl-3H-indolinium salt 1 is regioselec-
tively cyclized into a five-membered ring compound, that
is, 1-amino-1,2,3,9a-tetrahydroimidazo[1,2-a]indol-2(9H)-
one 3, via an intermediate hydrazide 2. No indication of the
presence of other ring chain tautomers was observed and
1-amino-1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-one
3 was readily transformed into novel hydrazones 6, N,N0-
diacylhydrazines 8 and 9 and N-acyl-N0-carbamoylhydra-
zines 12 and 13 upon treatment with aromatic aldehydes,
4. Experimental
4.1. General
The melting points were determined in open capillary tubes
on a Bu¨chi B-540 melting point apparatus and are

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3313
uncorrected. Infrared spectra were recorded on a Perkin
Elmer Spectrum One spectrometer using potassium bromide
pellets. H NMR spectra were recorded at 270 MHz on a
4.04 (1H, d, JZ16.6 Hz, CH(H)), 6.77–7.74 (8H, m, aromatic
protons), 8.96 (1H, s, N]CH). 13C NMR (75 MHz, CDCl3): d
19.4 (9a-CH3), 24.5 (9-CH3), 27.2 (9-CH3), 48.7 (9-C), 53.5
(CH2), 94.6 (9a-C), 111.9, 115.7 (d, JZ22.0 Hz, 2!CH),
122.2, 122.3, 127.9, 129.3 (d, JZ8.5 Hz, 2!CH), 130.8 (d,
JZ3.1 Hz, C), 139.2, 149.9 (Ar-C), 154.6 (C]N), 162.5 (d,
1
Jeol-270 spectrometer, at 300 MHz on a Varian Unity Inova
spectrometer and at 500 MHz on a Bruker Avance 500
spectrometer; 13C NMR spectra were registered at 67.5, 75
and 125 MHz, respectively. Chemical shifts, expressed in
parts per million, were relative to tetramethylsilane (TMS).
15N NMR spectra (50.69 MHz) were obtained on a Bruker
Avance 500 spectrometer using a ‘directly’ detecting
broadband observe probe and were referenced against
neat, external nitromethane (coaxial capillary). Mass
spectra were recorded on a Agilent 110 (series MS with
VL) instrument. For thin-layer chromatographic (TLC)
analyses, Merck precoated TLC plates (silica gel 60 F254)
were used.
JZ251.4 Hz, C–F), 168.9 (C]O). IR (KBr, cmK1): nC]O
Z
1703; nC]NZ1607. MS m/z (%): 338 (MCHC, 100). Anal.
Calcd for C20H20FN3O: C 71.20; H 5.97; N 12.45. Found: C
71.47; H 5.63; N 12.14.
4.3.2. 1-{[(1E)-(4-Chlorophenyl)methylene]amino}-
1,2,3,9a-tetrahydro-9,9,9a-trimethylimidazo[1,2-a]indol-
2(9H)-one 6b. Yield 44%. Mp 168–169 8C. 1H NMR
(270 MHz, CDCl3): d 1.30 (3H, s, 9-CH3), 1.31 (3H, s,
9-CH3), 1.73 (3H, s, 9a-CH3), 3.98 (1H, d, JZ16.2 Hz,
CH(H)), 3.99 (1H, d, JZ16.2 Hz, CH(H)), 6.74–7.65 (8H, m,
aromatic protons), 8.99 (1H, s, N]CH). 13C NMR
(67.5 MHz, CDCl3): d 19.5 (9a-CH3), 24.6 (9-CH3), 27.1 (9-
CH3), 48.7 (9-C), 53.5 (CH2), 94.6 (9a-C), 111.9, 122.19,
122.3, 127.9, 128.6(2!C), 128.9 (2!C), 133.2, 136.5, 139.3,
149.9 (Ar-C), 154.2 (C]N), 169.6 (C]O). IR (KBr, cmK1):
nC]OZ1700; nC]NZ1603. MS m/z (%): 356/54 (MCHC,
100). Anal. CalcdforC20H20ClN3O:C67.89;H5.70;N11.88.
Found: C 67.58; H 5.35; N 11.73.
4.2. Synthetic procedures
4.2.1. Synthesis of 1-amino-1,2,3,9a-tetrahydro-9,9,9a-
trimethylimidazo[1,2-a]indol-2(9H)-one 3. A mixture
of 1-carbamoylmethyl-2,3,3-trimethyl-3H-indolinium
chloride 1 (2.53 g, 10 mmol) and hydrazine hydrate (55%,
10 mL) was heated at 70 8C for 0.5 h. The reaction mixture
was cooled to room temperature, the liquid layer was poured
out from the resulting resinous substance, and the latter was
crystallized from diethyl ether. The obtained crystalline
material was recrystallized from ethanol to yield 1.85 g
4.3.3.
1-{[(1E)-(4-Bromophenyl)methylene]amino}-
1,2,3,9a-tetrahydro-9,9,9a-trimethylimidazo[1,2-a]indol-
2(9H)-one 6c. Yield 54%. Mp 170–171 8C. 1H NMR
(270 MHz, CDCl3): d 1.30 (3H, s, 9-CH3), 1.32 (3H, s, 9-
CH3), 1.74 (3H, s, 9a-CH3), 3.98 (1H, d, JZ16.5 Hz, CH(H)),
3.98 (1H, d, JZ16.5 Hz, CH(H)), 6.75–7.66 (8H, m, aromatic
protons), 8.98(1H, s, N]CH). 13C NMR (67.5 MHz, CDCl3):
d 19.5 (9a-CH3), 24.6 (9-CH3), 27.1 (9-CH3), 48.8 (9-C), 53.6
(CH2), 94.7 (9a-C), 112.0, 122.2, 122.3, 124.9, 127.9, 128.8
(2!C), 131.9 (2!C), 133.7, 139.3, 149.9 (Ar-C), 154.3
(C]N), 169.6 (C]O). IR (KBr, cmK1): nC]OZ1703;
nC]NZ1595. MS m/z (%): 400/398 (MCHC, 100). Anal.
Calcd for C20H20BrN3O: C 60.31; H 5.06; N 10.55. Found: C
59.98; H 5.35; N 10.78.
1
(80%) of 3. Mp 100–101 8C. H NMR (500 MHz, DMSO-
d6): d 1.15 (3H, s, 9-CH3), 1.39 (3H, s, 9-CH3), 1.40 (3H, s,
2
9a-CH3), 3.75–3.90 (2H, AB-q, JZ16.5 Hz, NCH2), 4.44
(2H, s, NH2), 6.81–6.89 (2H, m, 5-H, 7-H), 7.01–7.12 (2H,
m, 6-H, 8-H). 13C NMR (125 MHz, DMSO-d6): d 17.1 (9a-
CH3), 23.6 (9-CH3), 26.9 (9-CH3), 47.5 (C-9), 52.0 (C-3),
93.0 (C-9a), 111.7 (C-5), 121.3 (C-7), 122.1 (C-8), 127.4
(C-6), 139.2 (C-8a), 150.5 (C-4a), 172.1 (C]O). 15N NMR
(50.69 MHz, DMSO-d6): d K224.6 (N-1), K299.1 (N-4),
Z
1
K317.6 (t, JZ68.9 Hz, NH2). IR (KBr, cmK1): nN–H
3330; nN–HZ3210; nC]OZ1705. MS m/z (%): 232 (MC
HC, 100). Anal. Calcd for C13H17N3O: C 67.51; H 7.41; N
18.17. Found: C 67.33; H 7.31; N 18.39.
4.3.4. 1-{[(1E)-(4-[Dimethylamino]phenyl)methylene]-
amino}-1,2,3,9a-tetrahydro-9,9,9a-trimethylimidazo[1,2-
a]indol-2(9H)-one 6d. Yield 86%. Mp 205–206 8C. 1H NMR
(270 MHz,CDCl3):d1.28(3H, s,9-CH3),1.31(3H, s,9-CH3),
1.73(3H, s, 9a-CH3), 2.99(6H, s, N(CH3)2), 3.96(2H, s, CH2),
6.66–7.60 (8H, m, aromatic protons), 8.78 (1H, s, N]CH).
13C NMR (67.5 MHz, CDCl3):d 19.6(9a-CH3), 24.9(9-CH3),
27.0 (9-CH3), 40.1 (N(CH3)2), 48.7 (9-C), 53.7 (CH2), 94.3
(9a-C), 111.6 (2!C), 111.9, 121.9, 122.2, 122.4, 127.8, 128.9
(2!C), 139.6, 150.1, 152.0 (Ar-C), 157.0 (C]N), 168.4
(C]O). IR (KBr, cmK1): nC]OZ1700; nC]NZ1602. MS m/
z (%): 363 (MCHC, 100). Anal. Calcd for C22H26N4O: C
72.90; H 7.23; N 15.46. Found: C 72.64; H 6.99; N 15.70.
4.3. General procedure for the condensation of 1-amino-
1,2,3,9a-tetrahydro-9,9,9a-trimethylimidazo[1,2-a]indol-
2(9H)-one (3) with aromatic aldehydes
To a solution of 3 (0.93 g, 4 mmol) and appropriate
benzaldehyde (4.4 mmol) in absolute ethanol (20 mL)
three drops of piperidine were added and the mixture was
refluxed for 2 h, after which the mixture was cooled to room
temperature. The reaction mixture was poured into water
(40 mL) and extracted with diethyl ether (3!20 mL). The
combined organic extracts were washed with water
(20 mL), dried over anhydrous sodium sulfate. Evaporation
of the solvent gave a residue, which was crystallized from
absolute ethanol to give the corresponding 1-arylidenamino-
imidazo[1,2-a]indolones (6a–d).
4.4. General procedure for the acylation of 1-amino-
1,2,3,9a-tetrahydro-9,9,9a-trimethylimidazo[1,2-a]indol-
2(9H)-one (3) with acetyl and benzoyl chlorides
4.3.1.
1-{[(1E)-(4-Fluorophenyl)methylene]amino}-
1,2,3,9a-tetrahydro-9,9,9a-trimethylimidazo[1,2-a]indol-
2(9H)-one 6a. Yield 60%. Mp 158–159 8C. 1H NMR
(300 MHz, CDCl3): d 1.31 (3H, s, 9-CH3), 1.34 (3H, s, 9-
CH3), 1.76 (3H, s, 9a-CH3), 3.98 (1H, d, JZ16.6 Hz, CH(H)),
To a stirred solution of 3 (1.16 g, 5 mmol) in dioxane
(7.5 mL), a solution of acetyl chloride or the appropriate
benzoyl chloride (6.5 mmol) in dioxane (10 mL) was added
dropwise at room temperature. The formed crystals (8a and

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3314
8e) were separated by filtration, or the formed resinous
substance (8b–d, 8f) was separated by decantation of the
solvent, and dissolved in water (25 mL). Solid NaHCO3 was
added in portions to basify the mixture to pH 8–9. The
mixture was extracted with diethyl ether (3!25 mL), the
combined extracts were washed with water (25 mL) and
dried over anhydrous sodium sulfate. The solvent was
evaporated in vacuo and the residue was crys0 tallized from
ethanol to give the corresponding 1-(N -acylamino)-
1,2,3,9a-tetrahydro-9,9,9a-trimethylimidazo[1,2-a]indol-
2(9H)-ones (8a–f).
CH3), 23.6 (9-CH3), 27.7 (9-CH3), 48.6 (9-C), 52.4 (CH2),
95.4 (9a-C), 112.2, 117.8, 118.8, 121.3, 121.4, 122.2, 125.8,
127.6, 138.4 (2!C), 149.8 (2!C) (Ar-C), 160.3 (C]O),
170.6 (C]O). IR (KBr, cmK1): nN–HZ3224; nC]OZ1737;
nC]OZ1717. MS m/z (%): 372 (MCHC, 100). Anal. Calcd
for C20H19F2N3O2: C 64.68; H 5.16; N 11.31. Found: C
64.33; H 5.37; N 11.52.
4.4.5. N-(9,9,9a-Trimethyl-2-oxo-2,3,9,9a-tetrahydro-
1H-imidazo[1,2-a]indol-1-yl)benzamide 8e. Yield 64%.
Mp 168–169 8C. 1H NMR (300 MHz, CDCl3): d 1.20 (3H, s,
9-CH3), 1.36 (3H, s, 9-CH3), 1.52 (3H, s, 9a-CH3), 3.70 (1H,
d, JZ16.5 Hz, CH(H)), 3.97 (1H, d, JZ16.5 Hz, CH(H)),
6.67–7.67 (9H, m, aromatic protons), 8.92 (1H, s, NH). 13C
NMR (75 MHz, CDCl3): d 17.9 (9a-CH3), 23.8 (9-CH3),
26.9 (9-CH3), 48.4 (9-C), 52.4 (CH2), 95.0 (9a-C), 112.1,
121.9, 122.3, 127.4 (2!C), 127.8, 128.3 (2!C), 130.8,
131.9, 138.9, 149.3 (Ar-C), 165.6 (C]O), 172.0 (C]O). IR
(KBr, cmK1): nN–HZ3266; nC]OZ1724; nC]OZ1687. MS
m/z (%): 336 (MCHC, 100). Anal. Calcd for C20H21N3O2:
C 71.62; H 6.31; N 12.53. Found: C 71.25; H 6.43; N 12.72.
4.4.1. N-(9,9,9a-Trimethyl-2-oxo-2,3,9,9a-tetrahydro-
1H-imidazo[1,2-a]indol-1-yl)acetamide 8a. Yield 85%.
Mp 201–202 8C. 1H NMR (270 MHz, CDCl3): d 1.10 (3H, s,
9-CH3), 1.28 (3H, s, 9-CH3), 1.41 (3H, s, 9a-CH3), 1.48 (3H,
s, CH3CO), 3.80 (1H, d, JZ16.5 Hz, CH(H)), 3.93 (1H, d,
JZ16.5 Hz, CH(H)), 6.67–7.30 (4H, m, aromatic protons),
8.22 (1H, s, NH). 13C NMR (67.5 MHz, CDCl3): d 16.9 (9a-
CH3), 20.0 (9-CH3), 23.4 (9-CH3), 27.4 (C]OCH3), 48.4
(9-C), 52.7 (CH2), 95.3 (9a-C), 112.0, 122.3, 122.5, 127.9,
138.7, 149.6 (Ar-C), 168.4 (C]O), 172.5 (C]O). IR (KBr,
cmK1): nN–HZ3250; nC]OZ1730; nC]OZ1680. MS m/z
(%): 274 (MCHC, 100). Anal. Calcd for C15H19N3O2: C
65.91; H 7.01; N 15.37. Found: C 65.54; H 7.39; N 15.12.
4.4.6. 2-Bromo-N-(9,9,9a-trimethyl-2-oxo-2,3,9,9a-tetra-
hydro-1H-imidazo[1,2-a]indol-1-yl)benzamide 8f. Yield
41%. Mp 173–174 8C. 1H NMR (300 MHz, CDCl3): d 1.25
(3H, s, 9-CH3), 1.49 (3H, s, 9-CH3), 1.70 (3H, s, 9a-CH3),
3.87 (1H, d, JZ16.6 Hz, CH(H)), 4.04 (1H, d, JZ16.6 Hz,
CH(H)), 6.73–7.59 (9H, m, aromatic protons and NH). 13C
NMR (75 MHz, CDCl3): d 17.8 (9a-CH3), 24.1 (9-CH3),
27.6 (9-CH3), 48.6 (9-C), 52.3 (CH2), 95.2 (9a-C), 112.1,
119.3, 122.2, 122.3, 127.6, 128.0, 129.9, 131.9, 133.3,
135.2, 138.5, 149.8 (Ar-C), 165.7 (C]O), 170.8 (C]O). IR
(KBr, cmK1): nN–HZ3257; nC]OZ1726; nC]OZ1684. MS
m/z (%): 416/14 (MCHC, 100). Anal. Calcd for
C20H20BrN3O2: C 57.98; H 4.87; N 10.14. Found: C
57.58; H 5.12; N 9.98.
4.4.2. 2-Chloro-N-(9,9,9a-trimethyl-2-oxo-2,3,9,9a-tetra-
hydro-1H-imidazo[1,2-a]indol-1-yl)benzamide 8b. Yield
45%. Mp 177–178 8C. 1H NMR (270 MHz, CDCl3): d 1.24
(3H, s, 9-CH3), 1.48 (3H, s, 9-CH3), 1.67 (3H, s, 9a-CH3),
3.85 (1H, d, JZ16.7 Hz, CH(H)), 4.02 (1H, d, JZ16.7 Hz,
CH(H)), 6.72–7.73 (9H, m, aromatic protons and NH). 13C
NMR (67.5 MHz, CDCl3): d 17.7 (9a-CH3), 24.0 (9-CH3),
27.6 (9-CH3), 48.5 (9-C), 52.4 (CH2), 95.2 (9a-C), 112.1,
122.2, 122.3, 127.3, 128.0, 130.1, 130.5, 130.8, 132.0,
132.6, 138.5, 149.8 (Ar-C), 164.7 (C]O), 170.8 (C]O). IR
(KBr, cmK1): nN–HZ3290; nC]OZ1730; nC]OZ1690. MS
m/z (%): 372/70 (MCHC, 100). Anal. Calcd for
C20H20ClN3O2: C 64.95; H 5.45; N 11.36. Found: C
65.20; H 5.11; N 11.17.
4.5. General procedure for the reaction of 1-amino-
1,2,3,9a-tetrahydro-9,9,9a-trimethylimidazo[1,2-a]indol-
2(9H)-one (3) with isocyanates
4.4.3. 4-Chloro-N-(9,9,9a-trimethyl-2-oxo-2,3,9,9a-tetra-
hydro-1H-imidazo[1,2-a]indol-1-yl)benzamide 8c. Yield
47%. Mp 202–203 8C. 1H NMR (270 MHz, CDCl3): d 1.17
(3H, s, 9-CH3), 1.29 (3H, s, 9-CH3), 1.47 (3H, s, 9a-CH3),
3.66 (1H, d, JZ16.6 Hz, CH(H)), 3.91 (1H, d, JZ16.6 Hz,
CH(H)), 6.64–7.26 (8H, m, aromatic protons), 8.93 (1H, s,
NH). 13C NMR (67.5 MHz, CDCl3): d 18.0 (9a-CH3), 23.8
(9-CH3), 26.9 (9-CH3), 48.4 (9-C), 52.5 (CH2), 95.2 (9a-C),
112.2, 121.9, 122.4, 127.9, 128.6, 128.8 (2!C), 128.9
(2!C), 138.6, 138.9, 149.2 (Ar-C), 164.4 (C]O), 172.3
(C]O). IR (KBr, cmK1): nN–HZ3250; nC]OZ1730;
nC]OZ1695. MS m/z (%): 372/70 (MCHC, 100). Anal.
Calcd for C20H20ClN3O2: C 64.95; H 5.45; N 11.36. Found:
C 65.33; H 5.09; N 11.21.
To a solution of 3 (1.0 g, 4.32 mmol) in dry toluene
(10 mL), the appropriate phenylisocyanate (4.32 mmol) was
added and the mixture was heated at 80 8C for 2 h. Then the
reaction mixture was cooled to room temperature, the
precipitated solid was filtered off and recrystallized from
ethanol to give the corresponding 1-(1,2,3,9a-tetrahydro-
9,9,9a-trimethylimidazo[1,2-a]indol-2(9H)-on-1-yl)-3-phe-
nylureas (12a–d).
4.5.1. 1-Phenyl-3-(9,9,9a-trimethyl-2-oxo-2,3,9,9a-tetra-
hydro-1H-imidazo[1,2-a]indol-1-yl)urea 12a. Yield 38%.
1
Mp 182–183 8C. H NMR (270 MHz, DMSO-d6): d 1.15
(3H, s, 9-CH3), 1.42 (3H, s, 9-CH3), 1.51 (3H, s, 9a-CH3),
3.92 (2H, s, NCH2CO), 6.88–7.41 (9H, m, aromatic
protons), 8.26 (1H, br s, NH), 8.79 (1H, br s, NH). 13C
NMR (67.5 MHz, DMSO-d6): d 17.3 (9a-CH3), 23.0 (9-
CH3), 27.3 (9-CH3), 47.8 (9-C), 51.7 (CH2), 93.0 (9a-C),
112.0, 118.0 (2!C), 121.7, 121.9, 122.2, 127.6, 128.7
(2!C), 138.9, 139.3, 150.1 (Ar-C), 153.7 (C]O), 171.4
(C]O). IR (KBr, cmK1): nN–HZ3312; nC]OZ1711;
nC]OZ1687. MS m/z (%): 351 (MCHC, 100). Anal.
4.4.4. 2,5-Difluoro-N-(9,9,9a-trimethyl-2-oxo-2,3,9,9a-
tetrahydro-1H-imidazo[1,2-a]indol-1-yl)benzamide 8d.
Yield 40%. Mp 203–204 8C. H NMR (270 MHz, CDCl3):
1
d 1.24 (3H, s, 9-CH3), 1.52 (3H, s, 9-CH3), 1.64 (3H, s, 9a-
CH3), 3.92 (1H, d, JZ16.3 Hz, CH(H)), 4.05 (1H, d,
JZ16.3 Hz, CH(H)), 6.73–7.77 (7H, m, aromatic protons),
8.16 (1H, s, NH). 13C NMR (67.5 MHz, CDCl3): d 17.4 (9a-

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J. Dumciu¯te et al. / Tetrahedron 62 (2006) 3309–3319
3315
Calcd for C20H22N4O2: C 68.55; H 6.33; N 15.99. Found: C
68.32; H 6.65; N 15.97.
crystallized from ethanol to obtain the various N0-
substituted 2,3-dihydro-2,3,3-trimethyl-1H-indole-1-acetic
acid N0-substituted hydrazides (7a–d, 9a–f, 13a–d).
4.5.2. 1-(2-Fluorophenyl)-3-(9,9,9a-trimethyl-2-oxo-
2,3,9,9a-tetrahydro-1H-imidazo[1,2-a]indol-1-yl)urea
12b. Yield 69%. Mp 194–196 8C. 1H NMR (270 MHz,
DMSO-d6): d 1.15 (3H, s, 9-CH3), 1.43 (3H, s, 9-CH3), 1.51
(3H, s, 9a-CH3), 3.94 (2H, s, NCH2CO), 6.89–7.43 (8H, m,
aromatic protons), 8.24 (1H, br s, NH), 8.79 (1H, br s, NH).
13C NMR (67.5 MHz, DMSO-d6): d 17.8 (9a-CH3), 25.6
(9-CH3), 27.8 (9-CH3), 48.8 (9-C), 52.2 (CH2), 93.7 (9a-C),
112.7, 115.5, 115.7, 120.8, 122.4, 122.8, 123.2, 125.1,
127.8, 128.3, 139.5, 150.7 (Ar-C), 153.8 (C]O), 171.9
(C]O). IR (KBr, cmK1): nN–HZ3325; nC]OZ1712;
nC]OZ1690. MS m/z (%): 369 (MCHC, 100). Anal.
Calcd for C20H21FN4O2: C 65.20; H 5.75; N 15.21. Found:
C 65.03; H 5.92; N 15.52.
4.6.1. N0-[(1E)-(4-Fluorophenyl)methylene]-2-(2,3,3-tri-
methyl-2,3-dihydro-1H-indol-1-yl)acetohydrazide 7a.
Yield 45%. Mp 148–150 8C. H NMR (300 MHz, CDCl3):
1
d 1.13 (3H, s, 3-CH3), 1.25 (3H, d, JZ6.6 Hz, 2-CH3), 1.34
(3H, s, 3-CH3), 3.17 (1H, q, JZ6.6 Hz, 2-CH), 3.77 (2H, s,
CH2), 6.50–7.75 (8H, m, aromatic protons), 8.06 (1H, s,
NH), 9.73 (1H, s, N]CH). 13C NMR (75 MHz, CDCl3): d
12.9 (2-CH3), 23.6 (3-CH3), 25.8 (3-CH3), 43.1 (3-C), 53.1
(CH2), 72.3 (CH), 108.7, 116.1 (d, JZ22.1 Hz, 2!CH),
120.9, 122.5, 128.0, 129.8 (d, JZ3.0 Hz, C), 129.9 (d, JZ
8.6 Hz, 2!CH), 139.5, 148.0 (Ar-C), 150.3 (C]N), 164.4
(d, JZ251.4 Hz, C–F), 167.1 (C]O). IR (KBr, cmK1):
nN–HZ3190; nC]OZ1685; nC]NZ1606. MS m/z (%): 340
(MCHC, 100). Anal. Calcd for C20H22FN3O: C 70.77; H
6.53; N 12.38. Found: C 70.43; H 6.67; N 12.01.
4.5.3. 1-(2-Chlorophenyl)-3-(9,9,9a-trimethyl-2-oxo-
2,3,9,9a-tetrahydro-1H-imidazo[1,2-a]indol-1-yl)urea
12c. Yield 52%. Mp 199–200 8C. 1H NMR (270 MHz,
DMSO-d6): d 1.17 (3H, s, 9-CH3), 1.44 (3H, s, 9-CH3), 1.55
(3H, s, 9a-CH3), 3.98 (2H, s, NCH2CO), 6.90–8.16 (8H, m,
aromatic protons), 8.34 (1H, br s, NH), 8.93 (1H, br s, NH).
13C NMR (67.5 MHz, DMSO-d6): d 17.1 (9a-CH3), 23.7 (9-
CH3), 27.3 (9-CH3), 47.7 (9-C), 51.5 (CH2), 93.2 (9a-C),
112.0, 120.4, 121.4, 121.8, 122.2, 123.4, 127.6 (2!C),
129.2, 135.5, 138.8, 150.1 (Ar-C), 153.4 (C]O), 172.1
(C]O). IR (KBr, cmK1): nN–HZ3365; nC]OZ1749;
nC]OZ1697. MS m/z (%): 387/85 (MCHC, 100). Anal.
Calcd for C20H21ClN4O2: C 62.42; H 5.50; N 14.56. Found:
C 62.13; H 5.72; N 14.78.
4.6.2. N0-[(1E)-(4-Chlorophenyl)methylene]-2-(2,3,3-tri-
methyl-2,3-dihydro-1H-indol-1-yl)acetohydrazide 7b.
Yield 26%. Mp 147–148 8C. H NMR (300 MHz, CDCl3):
1
d 1.14 (3H, s, 3-CH3), 1.25 (3H, d, JZ6.6 Hz, 2-CH3), 1.34
(3H, s, 3-CH3), 3.18 (1H, q, JZ6.6 Hz, 2-CH), 3.77 (2H, s,
CH2), 6.50–7.66 (8H, m, aromatic protons), 8.06 (1H, s,
NH), 9.80 (1H, s, N]CH). 13C NMR (75 MHz, CDCl3): d
12.6 (2-CH3), 23.2 (3-CH3), 25.4 (3-CH3), 42.8 (3-C), 52.7
(CH2), 71.9 (CH), 108.3, 120.6, 122.1, 127.7, 128.8 (2!C),
128.9 (2!C), 131.7, 136.5, 139.2, 147.6 (Ar-C), 149.9
(C]N), 166.9 (C]O). IR (KBr, cmK1): nN–HZ3190;
nC]OZ1680; nC]NZ1607. MS m/z (%): 358/56 (MCHC,
100). Anal. Calcd for C20H22ClN3O: C 67.50; H 6.23; N
11.81. Found: C 67.32; H 6.65; N 11.41.
4.5.4. 1-(4-Chlorophenyl)-3-(9,9,9a-trimethyl-2-oxo-
2,3,9,9a-tetrahydro-1H-imidazo[1,2-a]indol-1-yl)urea
12d. Yield 67%. Mp 211–212 8C. 1H NMR (270 MHz,
DMSO-d6): d 1.14 (3H, s, 9-CH3), 1.41 (3H, s, 9-CH3), 1.50
(3H, s, 9a-CH3), 3.92 (2H, s, CH2), 6.88–7.46 (8H, m,
aromatic protons), 8.32 (1H, br s, NH), 8.96 (1H, br s, NH).
13C NMR (67.5 MHz, DMSO-d6): d 17.3 (9a-CH3), 22.8 (9-
CH3), 27.3 (9-CH3), 47.8 (9-C), 51.6 (CH2), 93.0 (9a-C),
112.0, 119.5, 119.6, 121.7, 121.8, 125.5, 127.6, 128.5 (2!
C), 138.4, 138.9, 151.1 (Ar-C), 153.6 (C]O), 171.4
(C]O). IR (KBr, cmK1): nN–HZ3362; nC]OZ1723;
nC]OZ1681. MS m/z (%): 387/85 (MCHC, 100). Anal.
Calcd for C20H21ClN4O2: C 62.42; H 5.50; N 14.56. Found:
C 62.11; H 5.89; N 14.34.
4.6.3. N0-[(1E)-(4-Bromophenyl)methylene]-2-(2,3,3-tri-
methyl-2,3-dihydro-1H-indol-1-yl)acetohydrazide 7c.
Yield 37%. Mp 143–144 8C. H NMR (300 MHz, CDCl3):
1
d 1.13 (3H, s, 3-CH3), 1.25 (3H, d, JZ6.6 Hz, 2-CH3), 1.34
(3H, s, 3-CH3), 3.17 (1H, q, JZ6.6 Hz, 2-CH), 3.78 (2H, s,
CH2), 6.51–8.05 (9H, m, aromatic protons and NH), 9.76
(1H, s, N]CH). 13C NMR (75 MHz, CDCl3): d 12.6 (2-
CH3), 23.3 (3-CH3), 25.5 (3-CH3), 42.8 (3-C), 52.8 (CH2),
71.9 (CH), 108.3, 120.7, 122.2, 124.9, 127.7, 129.1 (2!C),
131.9 (2!C), 132.2, 139.2, 147.6 (Ar-C), 149.9 (C]N),
166.9 (C]O). IR (KBr, cmK1): nN–HZ3204; nC]OZ1677;
nC]NZ1605. MS m/z (%): 402/00 (MCHC, 100). Anal.
Calcd for C20H22BrN3O: C 60.01; H 5.54; N 10.50. Found:
C 60.33; H 5.72; N 10.37.
4.6. General procedure for the reduction of 1-(N-
substituted amino)-1,2,3,9a-tetrahydro-9,9,9a-trimethyli-
midazo[1,2-a]indol-2(9H)-ones (6a–d, 8a–f, 12a–d) with
sodium borohydride
4.6.4. N0-[(1E)-(4-[Dimethylamino]phenyl)methylene]-2-
(2,3,3-trimethyl-2,3-dihydro-1H-indol-1-yl)acetohydra-
zide 7d. Yield 64%. Mp 153–154 8C. H NMR (270 MHz,
1
To a solution of an appropriate N0-substituted 1-amino-
1,2,3,9a-tetrahydroimidazo[1,2-a]indol-2(9H)-one (6a–d,
8a–f, 12a–d) (1.35 mmol) in 20 mL of ethanol (6a–d,
8a–f) or 20 mL of tetrahydrofuran (12a–d), sodium
borohydride (0.153 g, 4.05 mmol) was added. The mixture
was heated at 70 8C for the indicated period, then cooled to
room temperature, poured into water (30 mL) and extracted
with ether (3!20 mL). The combined extracts were washed
with water (20 mL), dried over sodium sulfate, the solvent
removed under reduced pressure, and the residue
CDCl3): d 1.14 (3H, s, 3-CH3), 1.25 (3H, d, JZ6.6 Hz, 2-
CH3), 1.34 (3H, s, 3-CH3), 3.00 (6H, s, N(CH3)2), 3.17 (1H,
q, JZ6.6 Hz, 2-CH), 3.76 (2H, s, CH2), 6.52–7.86 (9H, m,
aromatic protons and NH), 9.53 (1H, s, N]CH). 13C NMR
(67.5 MHz, CDCl3): d 12.6 (2-CH3), 23.3 (3-CH3), 25.4 (3-
CH3), 40.1 (N(CH3)2), 42.8 (3-C), 52.7 (CH2), 71.9
(CH), 106.5, 111.5 (2!C), 120.4, 120.6, 122.0, 127.7,
129.3 (2!C), 139.2, 149.5, 150.0, 151.9, 166.0 (C]O). IR
(KBr, cmK1): nN–HZ3195; nC]OZ1690; nC]NZ1609. MS

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J. Dumciu¯te et al. / Tetrahedron 62 (2006) 3309–3319
3316
m/z (%): 365 (MCHC, 100). Anal. Calcd for C22H28N4O: C
72.50; H 7.74; N 15.37. Found: C 72.84; H 7.91; N 15.12.
(C]O), 167.2 (C]O). IR (KBr, cmK1): nN–HZ3205;
nC]OZ1700; nC]OZ1684. MS m/z (%): 374 (MCHC,
100). Anal. Calcd for C20H21F2N3O2: C 64.33; H 5.67; N
11.25. Found: C 64.05; H 5.81; N 11.42.
4.6.5. N0-Acetyl-2-(2,3,3-trimethyl-2,3-dihydro-1H-
indol-1-yl)acetohydrazide 9a. Yield 65%. Mp 172–
173 8C. H NMR (270 MHz, CDCl3): d 1.09 (3H, s, CH3),
1
4.6.9. N0-[(2,3,3-Trimethyl-2,3-dihydro-1H-indol-1-yl)a-
cetyl]benzohydrazide 9e. Yield 66%. Mp 125–126 8C. H
1
1.24 (3H, d, JZ6.6 Hz, CH3), 1.31 (3H, s, CH3), 2.03 (3H, s,
COCH3), 3.16 (1H, q, JZ6.6 Hz, CH), 3.72 (1H, d,
JZ17.8 Hz, CH(H)CO), 3.76 (1H, d, JZ17.8 Hz,
CH(H)CO), 6.48–7.25 (4H, m, aromatic protons), 9.35
(1H, s, NH), 9.62 (1H, s, NH). 13C NMR (67.5 MHz,
CDCl3): d 12.5 (2-CH3), 20.4 (3-CH3), 23.0 (3-CH3), 25.4
(CH3CO), 42.8 (3-C), 51.7 (CH2), 71.9 (CH), 107.9, 120.2,
122.0, 127.5, 139.1, 149.8 (Ar-C), 167.2 (C]O), 167.6
(C]O). IR (KBr, cmK1): nN–HZ3280; nC]OZ1710;
nC]OZ1675. MS m/z (%): 276 (MCHC, 100). Anal.
Calcd for C15H21N3O2: C 65.43; H 7.69; N 15.26. Found: C
65.11; H 7.82; N 15.54.
NMR (270 MHz, CDCl3): d 1.11 (3H, s, CH3), 1.25 (3H, d,
JZ6.8 Hz, CH3), 1.31 (3H, s, CH3), 3.16 (1H, q, JZ6.8 Hz,
CH), 3.76 (1H, d, JZ17.8 Hz, CH(H)), 3.83 (1H, d, JZ
17.8 Hz, CH(H)), 6.45–7.85 (9H, m, aromatic protons), 9.43
(1H, d, JZ6.0 Hz, NH), 9.73 (1H, d, JZ6.0 Hz, NH). 13C
NMR (67.5 MHz, CDCl3): d 12.6 (2-CH3), 23.2 (3-CH3),
25.5 (3-CH3), 42.9 (3-C), 52.1 (CH2), 72.1 (CH), 108.1,
120.4, 122.1, 127.3 (2!C), 127.6, 128.6 (2!C), 131.2,
132.3, 139.2, 149.9 (Ar-C), 164.3 (C]O), 167.9 (C]O). IR
(KBr, cmK1): nN–HZ3257; nC]OZ1697; nC]OZ1684. MS
m/z (%): 338 (MCHC, 100). Anal. Calcd for C20H23N3O2:
C 71.19; H 6.87; N 12.45. Found: C 71.01; H 7.19; N 12.17.
4.6.6. 2-Chloro-N0-[(2,3,3-trimethyl-2,3-dihydro-1H-
indol-1-yl)acetyl]benzohydrazide 9b. Yield 75%. Mp
169–170 8C. H NMR (270 MHz, CDCl3): d 1.14 (3H, s,
4.6.10. 2-Bromo-N0-[(2,3,3-trimethyl-2,3-dihydro-1H-
indol-1-yl)acetyl]benzohydrazide 9f. Yield 70%. Mp
167–168 8C. H NMR (300 MHz, CDCl3): d 1.13 (3H, s,
1
1
CH3), 1.30 (3H, d, JZ6.6 Hz, CH3), 1.34 (3H, s, CH3), 3.18
(1H, q, JZ6.6 Hz, CH), 3.76 (1H, d, JZ17.0 Hz,
CH(H)CO), 3.80 (1H, d, JZ17.0 Hz, CH(H)CO), 6.53–
7.78 (8H, m, aromatic protons), 9.23 (1H, d, JZ6.12 Hz,
NH), 9.46 (1H, d, JZ6.12 Hz, NH). 13C NMR (67.5 MHz,
CDCl3): d 12.7 (2-CH3), 23.2 (3-CH3), 25.5 (3-CH3), 42.9
(3-C), 52.1 (CH2), 72.1 (CH), 108.2, 120.4, 122.1, 127.1,
127.7, 130.5, 130.8, 131.3, 131.5, 132.3, 139.2, 149.9 (Ar-
CH3), 1.28 (3H, d, JZ6.6 Hz, CH3), 1.33 (3H, s, CH3), 3.18
(1H, q, JZ6.6 Hz, CH), 3.71 (1H, d, JZ17.8 Hz, CH(H)),
3.79 (1H, d, JZ17.8 Hz, CH(H)), 6.52–7.62 (8H, m,
aromatic protons), 9.14 (1H, br s, NH), 9.43 (1H, br s,
NH). 13C NMR (75 MHz, CDCl3): d 12.6 (2-CH3), 23.2 (3-
CH3), 25.5 (3-CH3), 42.8 (3-C), 52.0 (CH2), 72.1 (CH),
108.2, 119.9, 120.4, 122.1, 127.5, 127.6, 130.2, 132.1,
133.6, 134.2, 139.2, 149.9 (Ar-C), 163.6 (C]O), 167.4
(C]O). IR (KBr, cmK1): nN–HZ3355; nN–HZ3213;
nC]OZ1711; nC]OZ1671. MS m/z (%): 418/16 (MC
HC, 100). Anal. Calcd for C20H22BrN3O2: C 57.70; H 5.33;
N 10.09. Found: C 57.42; H 5.70; N 9.98.
C), 162.4 (C]O), 167.3 (C]O). IR (KBr, cmK1): nN–H
Z
3350; nN–HZ3220; nC]OZ1703; nC]OZ1671. MS m/z
(%): 374/72 (MCHC, 100). Anal. Calcd for
C20H22ClN3O2: C 64.60; H 5.96; N 11.30. Found: C
64.91; H 6.13; N 11.05.
4.6.7. 4-Chloro-N0-[(2,3,3-trimethyl-2,3-dihydro-1H-
indol-1-yl)acetyl]benzohydrazide 9c. Yield 62%. Mp
174–175 8C. H NMR (270 MHz, CDCl3): d 1.13 (3H, s,
4.6.11. N-Phenyl-2-[(2,3,3-trimethyl-2,3-dihydro-1H-
indol-1-yl)acetyl]hydrazinecarboxamide 13a. Yield
71%. Mp 189–190 8C. H NMR (270 MHz, DMSO-d6): d
1
1
CH3), 1.27 (3H, d, JZ6.4 Hz, CH3), 1.34 (3H, s, CH3), 3.19
(1H, q, JZ6.4 Hz, CH), 3.78 (1H, d, JZ18.0 Hz,
CH(H)CO), 3.81 (1H, d, JZ18.0 Hz, CH(H)CO), 6.52–
7.75 (8H, m, aromatic protons), 9.35 (1H, d, JZ4.8 Hz,
NH), 9.89 (1H, d, JZ4.8 Hz, NH). 13C NMR (67.5 MHz,
CDCl3): d 12.6 (2-CH3), 23.2 (3-CH3), 25.5 (3-CH3), 42.9
(3-C), 52.2 (CH2), 72.1 (CH), 108.0, 120.5, 122.5, 127.6,
128.7 (2!C), 128.9 (2!C), 129.5, 138.6, 139.2, 149.8 (Ar-
0.98 (3H, s, 3-CH3), 1.17 (3H, d, JZ6.3 Hz, 2-CH3), 1.24
(3H, s, 3-CH3), 3.32 (1H, q, JZ6.3 Hz, CH), 3.68 (1H, d,
JZ16.8 Hz, CH(H)), 3.88 (1H, d, JZ16.8 Hz, CH(H)),
6.53–7.52 (9H, m, aromatic protons), 8.07 (1H, br s, NH),
8.66 (1H, br s, NH), 9.76 (1H, br s, NH). 13C NMR
(67.5 MHz, DMSO-d6): d 12.0 (2-CH3), 22.9 (3-CH3), 25.6
(3-CH3), 42.1 (3-C), 47.8 (CH2), 69.3 (CH), 107.3, 117.9,
118.3 (2!C), 121.4, 121.8, 126.9, 128.6 (2!C), 138.4,
139.5, 150.3 (Ar-C), 155.2 (C]O), 169.4 (C]O). IR (KBr,
cmK1): nN–HZ3288; nC]OZ1725; nC]OZ1652. MS m/z
(%): 353 (MCHC, 100). Anal. Calcd for C20H24N4O2: C
68.16; H 6.86; N 15.90. Found: C 68.45; H 7.11; N 15.56.
C), 163.6 (C]O), 168.7 (C]O). IR (KBr, cmK1): nN–H
Z
3220; nC]OZ1696; nC]OZ1684. MS m/z (%): 374/72
(MCHC, 73), 160 (100). Anal. Calcd for C20H22ClN3O2: C
64.60; H 5.96; N 11.30. Found: C 64.93; H 5.79; N 11.12.
4.6.8. 2,5-Difluoro-N0-[(2,3,3-trimethyl-2,3-dihydro-1H-
indol-1-yl)acetyl]benzohydrazide 9d. Yield 64%. Mp
114–115 8C. H NMR (270 MHz, CDCl3): d 1.14 (3H, s,
4.6.12. N-(2-Fluorophenyl)-2-[(2,3,3-trimethyl-2,3-dihy-
dro-1H-indol-1-yl)acetyl]hydrazinecarboxamide 13b.
Yield 60%. Mp 178–179 8C. H NMR (270 MHz, DMSO-
1
1
CH3), 1.27 (3H, d, JZ6.8 Hz, CH3), 1.34 (3H, s, CH3), 3.19
(1H, q, JZ6.8 Hz, CH), 3.80 (1H, d, JZ17.8 Hz, CH(H)),
3.83 (1H, d, JZ17.8 Hz, CH(H)), 6.54–7.79 (7H, m,
aromatic protons), 9.28 (1H, d, JZ6.0 Hz, NH), 9.44 (1H,
d, JZ6.0 Hz, NH). 13C NMR (67.5 MHz, CDCl3): d 12.6
(2-CH3), 23.2 (3-CH3), 25.4 (3-CH3), 42.9 (3-C), 52.0
(CH2), 72.1 (CH), 108.0, 117.5, 117.8, 118.2, 120.4, 120.9,
122.2, 127.6, 139.2, 149.9, 156.4, 158.4 (Ar-C), 160.8
d6): d 0.98 (3H, s, 3-CH3), 1.17 (3H, d, JZ6.6 Hz, 2-CH3),
1.24 (3H, s, 3-CH3), 3.29 (1H, q, JZ6.6 Hz, CH), 3.67 (1H,
d, JZ16.9 Hz, CH(H)), 3.87 (1H, d, JZ16.9 Hz, CH(H)),
6.36–7.99 (8H, m, aromatic protons), 8.04 (1H, br s, NH),
8.51 (1H, br s, NH), 9.87 (1H, br s, NH). 13C NMR
(67.5 MHz, DMSO-d6): d 11.9 (2-CH3), 22.9 (3-CH3), 25.6
(3-CH3), 42.1 (3-C), 47.9 (CH2), 69.4 (CH), 107.2, 114.8,
115.1, 117.9, 120.9, 121.4, 124.4, 127.6, 129.1, 135.4,

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J. Dumciu¯te et al. / Tetrahedron 62 (2006) 3309–3319
3317
138.7, 150.0 (Ar-C), 154.7 (C]O), 169.3 (C]O). IR (KBr,
cmK1): nN–HZ3305; nC]OZ1727; nC]OZ1646. MS m/z
(%): 371 (MCHC, 100). Anal. Calcd for C20H23FN4O2: C
64.85; H 6.26; N 15.13. Found: C 64.79; H 6.41; N 15.43.
(]CH2), 106.8, 120.1, 122.7, 122.8, 128.3, 128.9 (2!C),
129.0, 130.4 (2!C), 137.5, 145.4 (Ar-C), 160.8 (2-C),
163.9, 164.3 (C–O–C). IR (KBr, cmK1): nC]NZ1655. MS
m/z (%): 354/52 (MCHC, 100). Anal. Calcd for
C20H18N3ClO: C 68.28; H 5.16; N 11.94. Found: C 68.08;
H 5.10; N 11.80.
4.6.13. N-(2-Chlorophenyl)-2-[(2,3,3-trimethyl-2,3-dihy-
dro-1H-indol-1-yl)acetyl]hydrazinecarboxamide 13c.
Yield 86%. Mp 180–181 8C. H NMR (270 MHz, DMSO-
1
4.7.2. 1-{[5-(2,5-Difluorophenyl)-1,3,4-oxadiazol-2-yl]-
methyl}-3,3-dimethyl-2-methyleneindoline 10d. Yield
d6): d 0.98 (3H, s, 3-CH3), 1.17 (3H, d, JZ6.6 Hz, 2-CH3),
1.24 (3H, s, 3-CH3), 3.30 (1H, q, JZ6.6 Hz, CH), 3.67 (1H,
d, JZ16.6 Hz, CH(H)), 3.89 (1H, d, JZ16.6 Hz, CH(H)),
6.51–8.11 (8H, m, aromatic protons), 8.19 (1H, br s, NH),
9.14 (1H, br s, NH), 9.63 (1H, br s, NH). 13C NMR
(67.5 MHz, DMSO-d6): d 12.0 (2-CH3), 23.0 (3-CH3), 25.6
(3-CH3), 42.1 (3-C), 48.0 (CH2), 69.3 (CH), 107.3, 117.9,
120.9, 121.4, 121.8, 123.2, 126.9, 127.6, 129.1, 135.8,
138.4, 150.3 (Ar-C), 154.5 (C]O), 168.9 (C]O). IR (KBr,
cmK1): nN–HZ3314; nC]OZ1724; nC]OZ1659. MS m/z
(%): 389/87 (MCHC, 100). Anal. Calcd for
C20H23ClN4O2: C 62.09; H 5.99; N 14.48. Found: C
61.78; H 5.75; N 14.59.
1
81%. Oil. H NMR (270 MHz, DMSO-d6): d 1.31 (6H, s,
2!3-CH3), 4.00 (1H, d, JZ2.2 Hz, ]CH(H)), 4.13 (1H, d,
JZ2.2 Hz, ]CH(H)), 5.21 (2H, s, CH2), 6.78–7.75 (7H, m,
aromatic protons). 13C NMR (67.5 MHz, DMSO-d6): d 29.7
(2!3-CH3), 36.9 (CH2), 43.8 (3-C), 76.1 (]CH2), 106.1,
112.8, 115.3, 115.7, 119.1, 119.4, 120.9, 122.1, 127.5,
136.8, 142.1, 144.7 (Ar-C), 160.1 (2-C), 163.6, 163.7 (C–O–
C). IR (KBr, cmK1): nC]NZ1655. MS m/z (%): 354 (MC
HC, 100). Anal. Calcd for C20H17N3F2O: C 67.98; H 4.85;
N 11.89. Found: C 67.53; H 4.56; N 11.53.
4.7.3. 1-{[5-(2-Bromophenyl)-1,3,4-oxadiazol-2-yl]-
methyl}-3,3-dimethyl-2-methyleneindoline 10f. Yield
1
80%. Oil. H NMR (270 MHz, DMSO-d6): d 1.31 (6H, s,
4.6.14. N-(4-Chlorophenyl)-2-[(2,3,3-trimethyl-2,3-dihy-
dro-1H-indol-1-yl)acetyl]hydrazinecarboxamide 13d.
Yield 20%. Mp 172–173 8C. H NMR (270 MHz, DMSO-
2!3-CH3), 4.01 (1H, d, JZ2.2 Hz, ]CH(H)), 4.15 (1H, d,
JZ2.2 Hz, ]CH(H)), 5.22 (2H, s, CH2), 6.77–7.85 (8H, m,
aromatic protons). 13C NMR (67.5 MHz, DMSO-d6): d 29.7
(2!3-CH3), 36.9 (CH2), 43.7 (3-C), 76.2 (]CH2), 106.2,
119.3, 120.7, 122.0, 124.5, 127.5, 128.3, 131.6, 133.4,
134.3, 136.8, 144.7 (Ar-C), 160.0 (2-C), 163.2, 163.4 (C–O–
C). IR (KBr, cmK1): nC]NZ1652. MS m/z (%): 398/96
(MCHC, 50). Anal. Calcd for C20H18N3BrO: C 60.62; H
4.58; N 10.60. Found: C 60.31; H 4.75; N 10.29.
1
d6): d 0.97 (3H, s, 3-CH3), 1.16 (3H, d, JZ6.6 Hz, 2-CH3),
1.23 (3H, s, 3-CH3), 3.29 (1H, q, JZ6.6 Hz, CH), 3.68 (1H,
d, JZ16.8 Hz, CH(H)), 3.87 (1H, d, JZ16.8 Hz, CH(H)),
6.52–7.54 (8H, m, aromatic protons), 8.15 (1H, br s, NH),
8.84 (1H, br s, NH), 9.75 (1H, br s, NH). 13C NMR
(67.5 MHz, DMSO-d6): d 11.9 (2-CH3), 22.9 (3-CH3), 25.6
(3-CH3), 47.8 (3-C), 64.9 (CH2), 69.3 (CH), 107.3, 117.9,
119.8, 121.4, 125.3, 126.9, 128.2, 128.4 (2!C), 138.3,
138.6, 150.3 (Ar-C), 155.1 (C]O), 169.4 (C]O). IR (KBr,
cmK1): nN–HZ3293; nC]OZ1700; nC]OZ1655. MS m/z
(%): 389/87 (MCHC, 100). Anal. Calcd for
C20H23ClN4O2: C 62.09; H 5.99; N 14.48. Found: C
62.13; H 6.18; N 14.72.
4.7.4.
1-{[5-(4-Chlorophenyl)-1,3,4-oxadiazol-2-
yl]methyl}-2,3,3-trimethylindoline 11c. Yield 99%. Mp
121–122 8C. 1H NMR (270 MHz, DMSO-d6): d 0.96 (3H, s,
3-CH3), 1.24 (6H, m, 2-CH3, 3-CH3), 3.28 (1H, q, JZ
6.5 Hz, CH), 4.59 (1H, d, JZ16.8 Hz, CH(H)), 4.87 (1H, d,
JZ16.8 Hz, CH(H)), 6.67–7.93 (8H, m, aromatic protons).
13C NMR (67.5 MHz, DMSO-d6): d 11.8 (2-CH3), 22.9 (3-
CH3), 25.3 (3-CH3), 42.2 (3-C, CH2), 68.5 (CH), 107.6,
118.7, 121.8, 122.1, 127.0, 128.2 (2!C), 129.7 (2!C),
136.7, 138.5, 148.9 (Ar-C), 163.4, 163.8 (C–O–C). IR (KBr,
cmK1): nC]NZ1606. MS m/z (%): 356/54 (MCHC, 50).
Anal. Calcd for C20H20N3ClO: C 67.89; H 5.70; N 11.88.
Found: C 67.55; H 5.35; N 11.69.
4.7. General procedure for the synthesis of 1-(1,3,4-
oxadiazol-2-yl)methylindole derivatives (10c,d,f, 11c,d,f,
14a–c, 15a–c)
To a stirred suspension of appropriate hydrazide (8c,d,f,
9c,d,f, 12a–c, 13a–c) (1 mmol) in dichloromethane (12 mL)
were added triphenylphosphine (1.57 mmol), carbon tetra-
chloride (5 mmol), triethylamine (1.57 mmol), and the
mixture was heated to reflux for 3 h. Then the mixture
was cooled to room temperature, poured into water (15 mL)
and extracted with dichloromethane (3!15 mL). Combined
organic layers were dried over sodium sulfate, the solvent
evaporated under reduced pressure. The residue was
chromatographed on a silica gel column with hexane/ethyl
acetate 2:1 as eluent to yield 1,3,4-oxadiazoles (10c,d,f,
11c,d,f, 14a–c, 15a–c).
4.7.5. 1-{[5-(2,5-Difluorophenyl)-1,3,4-oxadiazol-2-yl]-
methyl}-2,3,3-trimethylindoline 11d. Yield 80%. Mp
1
104–105 8C. H NMR (270 MHz, DMSO-d6): d 0.96 (3H,
s, 3-CH3), 1.25 (6H, m, 2-CH3, 3-CH3), 3.29 (1H, q, JZ
6.5 Hz, CH), 4.61 (1H, d, JZ16.8 Hz, CH(H)), 4.90 (1H, d,
JZ16.8 Hz, CH(H)), 6.66–7.76 (7H, m, aromatic protons).
13C NMR (67.5 MHz, DMSO-d6): d 11.7 (3-CH3), 22.8 (2-
CH3), 25.3 (3-CH3), 39.3 (3-C), 42.1 (CH2), 68.4 (CH),
107.5, 112.5, 115.5, 118.6, 119.0, 120.7, 121.7, 126.9,
138.4, 148.7, 156.9, 159.4 (Ar-C), 160.0, 164.1 (C–O–C).
IR (KBr, cmK1): nC]NZ1604. MS m/z (%): 356 (MCHC,
100). Anal. Calcd for C20H19N3F2O: C 67.59; H 5.39; N
11.82. Found: C 67.15; H 5.26; N 11.45.
4.7.1. 1-{[5-(4-Chlorophenyl)-1,3,4-oxadiazol-2-yl]-
methyl}-3,3-dimethyl-2-methyleneindoline 10c. Yield
1
90%. Mp 125–126 8C. H NMR (270 MHz, DMSO-d6): d
1.21 (6H, s, 2!3-CH3), 4.01 (1H, d, JZ2.2 Hz, ]CH(H)),
4.15 (1H, d, JZ2.2 Hz, ]CH(H)), 5.18 (2H, s, CH2), 6.78–
7.92 (8H, m, aromatic protons). 13C NMR (67.5 MHz,
DMSO-d6): d 30.4 (2!3-CH3), 37.8 (CH2), 44.5 (3-C), 76.8
4.7.6. 1-{[5-(2-Bromophenyl)-1,3,4-oxadiazol-2-yl]-
methyl}-2,3,3-trimethylindoline 11f. Yield 74%. Mp

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J. Dumciu¯te et al. / Tetrahedron 62 (2006) 3309–3319
3318
124–125 8C. 1H NMR (270 MHz, DMSO-d6): d 0.95 (3H, s,
3-CH3), 1.23 (6H, m, 2-CH3, 3-CH3), 3.34 (1H, q, JZ
6.5 Hz, CH), 4.61 (1H, d, JZ16.8 Hz, CH(H)), 4.92 (1H, d,
JZ16.8 Hz, CH(H)), 6.66–7.84 (8H, m, aromatic protons).
13C NMR (67.5 MHz, DMSO-d6): d 11.8 (2-CH3), 22.9 (3-
CH3), 25.3 (3-CH3), 42.2 (CH2, 3-C), 68.3 (CH), 107.8,
118.7, 120.7, 121.7, 124.7, 127.1, 128.3, 131.7, 133.4,
134.2, 138.5, 148.2 (Ar-C), 163.2, 164.1 (C–O–C). IR (KBr,
cmK1): nC]NZ1602. MS m/z (%): 400/98 (MCHC, 50).
Anal. Calcd for C20H20N3BrO: C 60.31; H 5.06; N 10.55.
Found: C 60.80; H 5.51; N 10.35.
(2-CH3), 22.9 (3-CH3), 25.3 (3-CH3), 30.2 (CH2), 42.2 (3-
C), 68.5 (CH), 107.7, 116.8 (2!C), 118.6, 121.7, 121.8,
127.1, 128.9 (2!C), 138.5, 138.7, 149.1 (Ar-C), 156.8,
160.0 (C–O–C). IR (KBr, cmK1): nN–HZ3201; nC]N
Z
1627. MS m/z (%): 335 (MCHC, 30). Anal. Calcd for
C20H22N4O: C 71.83; H 6.63; N 16.75. Found: C 72.16; H
7.03; N 16.25.
4.7.11. N-(2-Fluorophenyl)-5-[(2,3,3-trimethyl-2,3-dihy-
dro-1H-indol-1-yl)methyl]-1,3,4-oxadiazol-2-amine 15b.
Yield 85%. Mp 144–145 8C. H NMR (270 MHz, DMSO-
1
d6): d 0.95 (3H, s, 3-CH3), 1.21 (3H, d, JZ6.5 Hz, 2-CH3),
1.24 (3H, s, 3-CH3), 3.23 (1H, q, JZ6.5 Hz, CH), 4.39 (1H,
d, JZ16.5 Hz, CH(H)), 4.65 (1H, d, JZ16.5 Hz, CH(H)),
6.66–7.97 (8H, m, aromatic protons), 10.26 (1H, s, NH). 13C
NMR (67.5 MHz, DMSO-d6): d 11.8 (2-CH3), 22.9 (3-CH3)
25.3 (3-CH3), 30.2 (CH2), 42.2 (3-C), 68.5 (CH), 107.7,
115.3, 115.6, 118.6, 120.5, 121.7, 124.6, 126.4, 126.6,
127.0, 138.5, 149.0 (Ar-C), 157.4, 160.3 (C–O–C). IR (KBr,
cmK1): nN–HZ3165; nC]NZ1655. MS m/z (%): 353 (MC
HC, 100). Anal. Calcd for C20H21N4FO: C 68.16; H 6.01; N
15.90. Found: C 68.58; H 5.99; N 15.53.
4.7.7. 5-[(3,3-Dimethyl-2-methylene-2,3-dihydro-1H-
indol-1-yl)methyl]-N-phenyl-1,3,4-oxadiazol-2-amine
14a. Yield 30%. Oil. H NMR (270 MHz, DMSO-d6): d
1
1.29 (6H, s, 2!3-CH3), 3.98 (1H, d, JZ2.0 Hz, ]CH(H)),
4.11 (1H, d, JZ2.0 Hz, ]CH(H)), 4.99 (2H, s, CH2), 6.77–
7.53 (9H, m, aromatic protons), 10.46 (1H, s, NH). 13C
NMR (67.5 MHz, DMSO-d6): d 29.7 (2!3-CH3), 36.9
(CH2), 43.7 (3-C), 76.0 (]CH2), 106.0, 116.9 (2!C),
119.2, 121.8, 122.1, 127.6, 129.0 (2!C), 136.8, 138.6,
144.8 (Ar-C), 156.0 (2-C), 160.0, 160.1 (C–O–C). IR (KBr,
cmK1): nN–HZ3189; nC]NZ1655. MS m/z (%): 333 (MC
HC, 100). Anal. Calcd for C20H20N4O: C 72.27; H 6.06; N
16.86. Found: C 71.93; H 5.87; N 16.59.
4.7.12. N-(2-Chlorophenyl)-5-[(2,3,3-trimethyl-2,3-dihy-
dro-1H-indol-1-yl)methyl]-1,3,4-oxadiazol-2-amine 15c.
Yield 78%. Mp 94–95 8C. H NMR (270 MHz, CDCl3): d
1
4.7.8. 5-[(3,3-Dimethyl-2-methylene-2,3-dihydro-1H-
indol-1-yl)methyl]-N-(2-fluorophenyl)-1,3,4-oxadiazol-2-
amine 14b. Yield 65%. Mp 141–142 8C. 1H NMR
(270 MHz, DMSO-d6): d 1.30 (6H, s, 2!3-CH3), 3.98
(1H, d, JZ2.1 Hz, ]CH(H)), 4.11 (1H, d, JZ2.1 Hz,
]CH(H)), 4.98 (2H, s, CH2), 6.66–7.84 (8H, m, aromatic
protons), 10.31 (1H, s, NH). 13C NMR (67.5 MHz, DMSO-
d6): d 29.7 (2!3-CH3), 37.0 (CH2), 43.7 (3-C), 75.9
(]CH2), 106.0, 115.4, 115.6, 119.2, 120.6, 122.1, 123.6,
124.6, 126.5, 127.5, 136.8, 144.8 (Ar-C), 156.6 (2-C),
160.0, 160.4 (C–O–C). IR (KBr, cmK1): nN–HZ3160;
nC]NZ1654. MS m/z (%): 351 (MCHC, 100). Anal.
Calcd for C20H19N4FO: C 68.56; H 5.47; N 15.99. Found: C
68.09; H 5.90; N 15.59.
0.99 (3H, s, 3-CH3), 1.25 (6H, m, 2-CH3, 3-CH3), 3.19 (1H,
q, JZ6.5 Hz, CH), 4.37 (1H, d, JZ16.4 Hz, CH(H)), 4.55
(1H, d, JZ16.4 Hz, CH(H)), 6.69–8.12 (9H, m, aromatic
protons and NH). 13C NMR (67.5 MHz, DMSO-d6): d 12.1
(2-CH3), 22.9 (3-CH3), 25.4 (3-CH3), 40.1 (CH2), 42.6 (3-
C), 69.1 (CH), 107.6, 118.3, 119.2, 121.0, 121.9, 123.3,
127.3, 128.0, 129.1, 134.0, 138.8, 148.9 (Ar-C), 157.9,
171.0 (C–O–C). IR (KBr, cmK1): nN–HZ3208; nC]N
Z
1621. MS m/z (%): 371/69 (MCHC, 50). Anal. Calcd for
C20H21N4ClO: C 65.12; H 5.74; N 15.19. Found: C 64.77; H
6.21; N 15.04.
4.7.9. 5-[(3,3-Dimethyl-2-methylene-2,3-dihydro-1H-
indol-1-yl)methyl]-N-(2-chlorophenyl)-1,3,4-oxadiazol-
2-amine 14c. Yield 95%. Mp 125–126 8C. 1H NMR
(270 MHz, DMSO-d6): d 1.29 (6H, s, 2!3-CH3), 3.98
(1H, d, JZ2.1 Hz, ]CH(H)), 4.11 (1H, d, JZ2.1 Hz,
]CH(H)), 4.97 (2H, s, CH2), 6.77–7.91 (8H, m, aromatic
protons), 9.89 (1H, s, NH). 13C NMR (67.5 MHz, DMSO-
d6): d 29.7 (2!3-CH3), 37.1 (CH2), 43.7 (3-C), 75.9
(]CH2), 106.0, 119.2, 122.1, 122.2, 124.1, 124.8, 127.5,
127.8, 129.8, 135.3, 136.8, 144.8 (Ar-C), 156.8 (2-C),
160.0, 160.7 (C–O–C). IR (KBr, cmK1): nN–HZ3201;
nC]NZ1627. MS m/z (%): 369/67 (MCHC, 100). Anal.
Calcd for C20H19N4ClO: C 65.48; H 5.22; N 15.27. Found:
C 65.22; H 5.66; N 15.03.
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