Synthesis and rearrangements of 7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]-and 7h-pyrrolo[3,2-e][1,2,4]triazolo[4,3-c]pyrimidines

Article abstract of DOI:10.1007/s11172-006-0445-2

7H-Pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidines were synthesized by the reactions of 2-ethoxymethyleneamino-1H-pyrrole-3-carbonitriles with acid hydrazides and by the reactions of aminoiminopyrimidines (prepared based on the above-mentioned carbonitriles) with acid chlorides.

Full text of DOI:10.1007/s11172-006-0445-2

Russian Chemical Bulletin, International Edition, Vol. 55, No. 8, pp. 1492—1497, August, 2006
1492
Synthesis and rearrangements of 7Hꢀpyrrolo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]ꢀ
and 7Hꢀpyrrolo[3,2ꢀe][1,2,4]triazolo[4,3ꢀc]pyrimidines
E. V. Vorob´ev, E. S. Kurbatov, V. V. Krasnikov, V. V. Mezheritskii,ꢀ and E. V. Usova
Institute of Physical and Organic Chemistry, Rostov State University,
194/2 prosp. Stachki, 344090 RostovꢀonꢀDon, Russian Federation.
Fax: +7 (863) 243 4667. Eꢀmail: mezher@ipoc.rsu.ru
7HꢀPyrrolo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidines were synthesized by the reactions of
2ꢀethoxymethyleneaminoꢀ1Hꢀpyrroleꢀ3ꢀcarbonitriles with acid hydrazides and by the reacꢀ
tions of aminoiminopyrimidines (prepared based on the aboveꢀmentioned carbonitriles) with
acid chlorides.
Key words: 7Hꢀpyrrolo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidines, acid hydrazides, Dimroth
rearrangement.
Scheme 1
Triazolopyrimidines are of interest not only for the
synthesis of heterocyclic systems but also as compounds
having biological activity and exhibiting, in particular,
hypotensive,1 antiseptic,2 antiarrhythmic,3,4 and antiꢀ
asthmatic5 properties.
In the present study, we report a new preparative proꢀ
cedure for the synthesis of triazolo[1,5ꢀc]pyrimidines
(Scheme 1). The reactions of acyloins 1a,b with amines
afforded amino ketones 2a—c, which were transformed
into key starting 2ꢀaminoꢀ3ꢀcyanopyrroles 3a—c. Based
on the latter compounds, we developed a oneꢀpot proceꢀ
dure for the synthesis of 7Hꢀpyrrolo[3,2ꢀe][1,2,4]triꢀ
azolo[1,5ꢀc]pyrimidines.
Acyloins 1a,b are involved in the modified Voigt reacꢀ
tion with amines in the presence of trifluorocacetic acid
as a catalyst. The resulting amino ketones 2a—c are subꢀ
jected to Knoevenagel condensation with malononitrile
without isolation, and the resulting products undergo cyꢀ
clization to form aminonitriles 3a—c.
Aliphatic amines (except for tertꢀbutylamine) and aroꢀ
matic and heterocyclic amines (2ꢀ and 3ꢀaminopyridines,
2ꢀaminothiazoles, and aminobenzoxazole) can be inꢀ
volved in this reaction. The reactions of acyloins 1a,b
with mꢀanisidine (toluene, CF3COOH) do not stop at the
formation of amino ketones 2, and the latter undergo
cyclization to form 6ꢀmethoxyꢀ2,3ꢀdimethylindole 5 (the
synthesis of such systems has been described in detail in
the literature6).
R1
Me
Ph
R2
3ꢀpyridyl
Bn
a
b
c
Me
2ꢀfurfuryl
Refluxing of aminonitriles 3a—c with triethyl orthoꢀ
formate over a short period of time affords imidic esters
4a—c in nearly quantitative yields, and these esters are
subjected to cascade heterocyclization with acid hydrꢀ
azides (nucleophilic substitution of the ethoxy group to
give compounds 6a—r followed by the intramolecular
nucleophilic addition at the carbon—nitrogen bond to
form pyrrolopyrimidines 7a—r and, finally, cyclization
yielding pyrrolotriazolopyrimidines 8a—r) (Scheme 2).
The ease of bisꢀheterocyclization is attributed to the
following fact. Being ambident, the starting hydrazides
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1438—1443, August, 2006.
1066ꢀ5285/06/5508ꢀ1492 © 2006 Springer Science+Business Media, Inc.

7HꢀPyrrolo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidines Russ.Chem.Bull., Int.Ed., Vol. 55, No. 8, August, 2006
1493
Scheme 2
This transformation deserves attention because the forꢀ
mation of the pyrimidine and triazole rings occurs as a
oneꢀpot reaction and is, on the whole, a milder reaction
compared to procedures for the synthesis of related comꢀ
pounds described earlier.7,8 It should be noted that the
pathway from acyloins 1a,b to 2ꢀsubstituted 7Hꢀpyrꢀ
rolo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidines 8a—r inꢀ
volves only three preparative steps because the synthesis
of aminopyrroles 3 is performed without isolation of inꢀ
termediate amino ketones 2, and the reactions 4 → 8
proceed under reflux in chlorobenzene or acetic acid to
give the target products in 35—90% yields. The proceꢀ
dure for the synthesis of 7Hꢀpyrrolo[3,2ꢀe][1,2,4]triazoꢀ
lo[1,5ꢀc]pyrimidines 8 developed in the present study is
much simpler than the widely used methods for the
preparation of such tricyclic systems. For example, the
most wellꢀknown multistep procedure for the synthesis
(Scheme 3) involves the preparation of 3ꢀaminoꢀ4ꢀ
iminopyrimidines 9 followed by the reaction of the latter
with carboxylic acids or their derivatives (anhydrides, acid
chlorides, or esters).9—11
If desired acid hydrazides are preparatively inaccesꢀ
sible, the synthesis of target products 8 can be performed
in two steps. The reaction of ester 4 with hydrazine hyꢀ
drate produces 3ꢀaminoꢀ4ꢀiminopyrimidine 9 and acylaꢀ
tion of the latter with the corresponding acid chloride
affords compound 8 (see Scheme 3). Pyrimidine 9 can be
transformed into hydrazinopyrimidine 10 by the Dimroth
rearrangement and then into [1,2,4]triazolo[4,3ꢀc]pyriꢀ
midines 11 in the same manner.
It should be emphasized that compounds 11 are genꢀ
erated only if R = H, Me, or Et. However, these comꢀ
pounds undergo the Dimroth rearrangement to give comꢀ
pounds 8 upon heating for several hours in an aqueousꢀ
ethanolic solution of an alkali. Under the reaction condiꢀ
tions, compounds 11 containing bulkier substituents R
were rearranged into isomers 8. The "steric pressure" of
6—8
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
R1
Me
Me
Me
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
R2
R3
4ꢀMeOC6H4CH2
PhOCH2
2ꢀHOC6H4
4ꢀpyridyl
3ꢀpyridyl
3ꢀpyridyl
3ꢀpyridyl
3ꢀpyridyl
3ꢀpyridyl
3ꢀpyridyl
Bn
(2ꢀbenzoxazolylthio)methyl
2ꢀBrC6H4
4ꢀMeOC6H4CH2
PhOCH2
2ꢀHOC6H4
Bn
Bn
Bn
Bn
4ꢀpyridyl
(2ꢀbenzoxazolylthio)methyl
2ꢀBrC6H4
Ph
Bn
Me
Me
Me
Me
Me
Me
2ꢀfurfuryl
2ꢀfurfuryl
2ꢀfurfuryl
2ꢀfurfuryl
2ꢀfurfuryl
2ꢀfurfuryl
4ꢀMeOC6H4CH2
PhOCH2
2ꢀHOC6H4
4ꢀpyridyl
(2ꢀbenzoxazolylthio)methyl
2ꢀBrC6H4
contain the active highly nucleophilic amino group, which
is favorable for condensation to form compounds 6a—r
followed by their cyclization to give iminopyrrolopyrimidiꢀ
nes 7a—r. In this case, the electrophilicity of the carbon
atom of the CO group increases because the N atom of
the hydrazide fragment is involved in the electronꢀwithꢀ
drawing fragment of compounds 7a—r. In addition, the
presence of the azole N atom in intermediates 7a—r adjaꢀ
cent to the imino group substantially increases the nucleoꢀ
philicity of the latter, which facilitates cyclization of comꢀ
pounds 7a—r to form pyrrolotriazolopyrimidines 8a—r.
Acid hydrazides involved in the reaction can contain
reactive groups (OH, NH2, etc.), due to which comꢀ
pounds 8 can serve as the starting compounds for funcꢀ
tionalization.
Fig. 1. Charges on atoms and interatomic distances in the
[1,2,4]triazolo[1,5ꢀc]ꢀ and [1,2,4]triazolo[4,3ꢀc]pyrimidine fragꢀ
ments calculated by the B3LYP/6ꢀ31G** method.

1494
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 8, August, 2006
Vorob´ev et al.
Scheme 3
R = H (s),Me (t), Et (u), Pr (v), Bu (w), (4ꢀmethylphenoxy)methyl (x), 1,3(2H)ꢀdioxoꢀ1Hꢀisoindolꢀ2ꢀylmethyl (y)
(17.6 g, 0.2 mol) in toluene (100 mL) in the presence of 5 mol.%
trichloroacetic acid was refluxed using a Dean—Stark trap until
an equimolar amount of water was eliminated. The mixture was
cooled to room temperature, and malononitrile (13.4 g, 0.2 mol)
was added. Then the reaction mixture was refluxed with the use
of a Dean—Stark trap until 0.2 mol of water was eliminated (the
total times t of the first and second steps for particular comꢀ
pounds are given below). Toluene was distilled off. The precipiꢀ
tate was filtered off and washed with a small amount of PriOH
and diethyl ether. 2ꢀAminopyrroleꢀ3ꢀcarbonitriles 3 are suitable
for use without additional purification. Analytically pure samples
were prepared by recrystallization from toluene.
bulky substituents is the main driving force for the rearꢀ
rangement 11 → 8.
The charges on atoms and interatomic distances in the
[1,2,4]triazolo[1,5ꢀc]ꢀ and [1,2,4]triazolo[4,3ꢀc]pyriꢀ
midine fragments calculated by the B3LYP/6ꢀ31G**
method (calculations were performed for compounds 8v
and 11v) are presented in Fig. 1. In our opinion, a more
uniform distribution of these parameters in the strucꢀ
ture of 8 compared to 11 is the second factor responꢀ
sible for higher thermodynamic stability of 7Hꢀpyrroꢀ
lo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidines 8.
2ꢀAminoꢀ4,5ꢀdimethylꢀ1ꢀ(pyridinꢀ3ꢀyl)ꢀ1Hꢀpyrroleꢀ3ꢀcarboꢀ
nitrile (3a), t = 4 h. The yield was 33 g (78%), colorless crystals,
m.p. 190—193 °C. Found (%): C, 67.85; H, 5.69; N, 26.37.
Experimental
C
12H12N4. Calculated (%): C, 67.92; H, 5.66; N, 26.42.
1
The H NMR spectra were recorded on Bruker DPXꢀ250
1H NMR, δ: 1.81 and 2.08 (both s, 3 H each, Me); 3.81 (s, 2 H,
NH2); 7.48 (t, 1 H, CH, J = 8.2 Hz); 7.64 (d, 1 H, CH, J =
8.5 Hz); 8.58 (s, 1 H, CH); 8.77 (d, 1 H, CH, J = 5.5 Hz).
2ꢀAminoꢀ1ꢀbenzylꢀ4,5ꢀdiphenylꢀ1Hꢀpyrroleꢀ3ꢀcarbonitrile
(3b), t = 1.5 h. The yield was 1.71 g (49%), paleꢀyellow crystals,
m.p. 120—121 °C. Found (%): C, 82.43; H, 5.49; N, 12.00.
C24H19N3. Calculated (%): C, 82.52; H, 5.44; N, 12.03.
1H NMR, δ: 3.81 (s, 2 H, NH2); 4.12 (m, 2 H, CH2); 5.11 (s,
2 H, CH2); 6.87—7.35 (m, 15 H, 15 CH).
(250 MHz) and Varian Unityꢀ300 (300 MHz) instruments in
CDCl3 with Me4Si as the internal standard. The IR spectra were
measured on a Specord IRꢀ75 spectrometer in Nujol mulls. The
electronꢀimpact mass spectra were obtained on a Finigan Mat
Incos 50 instrument at the ionizing voltage of 70 V using a direct
inlet system. Chromatographic purification of the compounds
was performed on aluminum oxide using chloroform as the
eluent.
Acetone (Acros Organics), benzoin (Fluka), malononitrile
(Alfa Alsar), benzylamine, 3ꢀaminopyridine, and furfurylamine
(Lancaster) were used in the synthesis.
Synthesis of compounds 3a—c (general procedure). A susꢀ
pension of the corresponding amine (0.2 mol) and acyloin 1
2ꢀAminoꢀ1ꢀ(2ꢀfurfuryl)ꢀ4,5ꢀdimethylꢀ1Hꢀpyrroleꢀ3ꢀcarboꢀ
nitrile (3c), t = 1 h. The yield was 34.8 g (81%), colorless crysꢀ
tals, m.p. 108—110 °C. Found (%): C, 66.87; H, 6.12; N, 19.56.
C12H13N3O. Calculated (%): C, 66.98; H, 6.05; N, 19.53.
1H NMR, δ: 2.06 and 2.16 (both s, 3 H each, Me); 3.85 (s, 2 H,

7HꢀPyrrolo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidines Russ.Chem.Bull., Int.Ed., Vol. 55, No. 8, August, 2006
1495
NH2); 4.84 (s, 2 H, CH2), 6.21 (d, 1 H, CH, J = 3.7 Hz); 6.31 (t,
1 H, CH, J = 3.2 Hz); 7.20 (s, 1 H, CH).
(t, 1 H, CH, J = 7.9 Hz); 7.80 (d, 1 H, CH, J = 8.8 Hz); 8.71 (d,
1 H, CH, J = 3.0 Hz); 8.80 (d, 1 H, CH, J = 5.3 Hz); 9.0
(s, 1 H, CH).
6ꢀMethoxyꢀ2,3ꢀdimethylꢀ1Hꢀindole (5). The yield was 13 g
(75%), colorless crystals, m.p. 130 °C. Found (%): C, 75.34;
H, 7.51; N, 8.73. C11H13NO. Calculated (%): C, 75.43; H, 7.43;
N, 8.00. 1H NMR, δ: 2.21, 2.35, and 3.85 (all s, 3 H each, Me);
6.74 (m, 2 H, CH2); 7.33 (d, 1 H, CH, J = 8.8 Hz); 7.52
(s, 1 H, CH).
Synthesis of compounds 4a—c (general procedure). Comꢀ
pound 3 (0.1 mol) in triethyl formate (40 mL, 0.5 mol) containꢀ
ing 10 mol.% acetic acid was refluxed for 1.5 h, poured onto a
Petri dish, and concentrated to dryness. The resulting imido
esters are suitable for use without additional purification. Anaꢀ
lytically pure samples were obtained by recrystallization from
toluene.
2ꢀ(2ꢀHydroxyphenyl)ꢀ8,9ꢀdimethylꢀ7ꢀ(pyridinꢀ3ꢀyl)ꢀ7Hꢀpyrꢀ
rolo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidine (8c). The yield was
2.53 g (71%), paleꢀyellow crystals, m.p. 250—252 °C. Found (%):
C, 67.32; H, 4.56; N, 23.52. C20H16N6O. Calculated (%):
C, 67.40; H, 4.53; N, 23.58. 1H NMR, δ: 2.33 and 2.65 (both s,
3 H each, Me); 7.01 (t, 1 H, CH, J = 7.9 Hz); 7.17 (d, 1 H, CH,
J = 8.5 Hz); 7.40 (t, 1 H, CH, J = 8.2 Hz); 7.57 (t, 1 H, CH, J =
8.7 Hz); 7.79 (d, 1 H, CH, J = 8.7 Hz); 8.21 (d, 1 H, CH, J =
7.6 Hz); 8.77 (d, 1 H, CH, J = 3.0 Hz); 8.81 (d, 1 H, CH, J =
5.0 Hz); 9.0 (s, 1 H, CH); 11.6 (s, 1 H, OH).
8 , 9 ꢀ D i m e t h y l ꢀ 2 , 7 ꢀ d i ( p y r i d i n ꢀ 3 ꢀ y l ) ꢀ 7 H ꢀ p y r r o ꢀ
lo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidine (8d). The yield was
2.53 g (66%), colorless crystals, m.p. 230—231 °C. Found (%):
C, 66.77; H, 4.50; N, 28.75. C19H15N7. Calculated (%): C, 66.85;
H, 4.43; N, 28.72. 1H NMR, δ: 2.32 and 2.65 (both s, 3 H each,
Me); 7.58 (t, 1 H, CH, J = 8.7 Hz); 7.81 (d, 1 H, CH, J =
8.4 Hz); 8.24 (d, 1 H, CH, J = 6.4 Hz); 8.30 (d, 1 H, CH, J =
7.9 Hz); 8.81 (m, 4 H, 4 CH); 9.00 (s, 1 H, CH).
2ꢀ(2ꢀBenzoxazolylthio)methylꢀ8,9ꢀdimethylꢀ7ꢀ(pyridinꢀ3ꢀyl)ꢀ
7Hꢀpyrrolo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidine (8e). The
yield was 2.47 g (58%), colorless crystals, m.p. 178—181 °C.
Found (%): C, 61.78; H, 4.12; N, 22.88; S, 7.52. C22H17N7OS.
Calculated (%): C, 61.81; H, 4.01; N, 22.94; S, 7.50. 1H NMR,
δ: 2.29 and 2.61 (both s, 3 H each, Me); 4.88 (s, 2 H, CH2); 7.25
(m, 2 H, 2 CH); 7.46 (d, 1 H, CH, J = 8.2 Hz); 7.60 (t, 1 H, CH,
J = 8.0 Hz); 7.67 (d, 1 H, CH, J = 8.2 Hz); 7.81 (d, 1 H, CH,
J = 8.3 Hz); 8.70 (d, 1 H, CH, J = 3.2 Hz); 8.79 (d, 1 H, CH,
J = 5.2 Hz); 9.00 (s, 1 H, CH).
2ꢀ(2ꢀBromophenyl)ꢀ8,9ꢀdimethylꢀ7ꢀ(pyridinꢀ3ꢀyl)ꢀ7Hꢀ
pyrrolo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidine (8f). The yield
was 2.77 g (66%), colorless crystals, m.p. 193—195 °C. Found
(%): C, 57.17; H, 3.61; Br, 19.06; N, 20.04. C20H15BrN6. Calꢀ
culated (%): C, 57.29; H, 3.61; Br, 19.06; N, 20.04. 1H NMR, δ:
2.35 and 2.61 (both s, 3 H each, Me); 7.32 (t, 1 H, CH, J = 7.5
Hz); 7.41 (t, 1 H, CH, J = 8.0 Hz); 7.58 (t, 1 H, CH, J = 7.4
Hz); 7.80 (m, 2 H, 2 CH); 8.01 (d, 1 H, CH, J = 8.3 Hz); 8.75
(d, 1 H, CH, J = 3.3 Hz); 8.82 (d, 1 H, CH, J = 6.1 Hz); 9.04 (s,
1 H, CH).
2ꢀEthoxymethylideneaminoꢀ4,5ꢀdimethylꢀ1ꢀ(pyridinꢀ3ꢀ
yl)pyrroleꢀ3ꢀcarbonitrile (4a). The yield was 24.6 g (92%), colorꢀ
less crystals, m.p. 68—71 °C. Found (%): C, 67.07; H, 6.03;
N, 20.79. C15H16N4O. Calculated (%): C, 67.16; H, 5.97;
1
N, 20.90. H NMR, δ: 1.81 and 2.08 (both s, 3 H each, Me);
2.43 (t, 3 H, Me, J = 7.8 Hz); 4.42 (m, 2 H, CH2); 7.16 (t, 1 H,
CH, J = 8.3 Hz); 7.42 (d, 1 H, CH, J = 8.6 Hz); 8.41 and 8.58
(both s, 1 H each, CH); 8.77 (d, 1 H, CH, J = 5.5 Hz).
1ꢀBenzylꢀ2ꢀethoxymethylideneaminoꢀ4,5ꢀdiphenylpyrroleꢀ3ꢀ
carbonitrile (4b). The yield was 33 g (85%), colorless crystals,
m.p. 111—113 °C. Found (%): C, 79.93; H, 5.75; N, 10.29.
C
27H23N3O. Calculated (%): C, 80.00; H, 5.67; N, 10.37.
1H NMR, δ: 1.35 (t, 3 H, Me, J = 7.2 Hz); 4.11 (m, 2 H, CH2);
5.07 (s, 2 H, CH2); 6.92—7.44 (m, 15 H, 15 CH); 8.55
(s, 1 H, CH).
2ꢀEthoxymethylideneaminoꢀ1ꢀ(2ꢀfurfuryl)ꢀ4,5ꢀdimethylꢀ
pyrroleꢀ3ꢀcarbonitrile (4c). The yield was 23 g (85%), paleꢀyelꢀ
low crystals, m.p. 124—125 °C. Found (%): C, 66.35; H, 6.36;
N, 15.43. C15H17N3O2. Calculated (%): C, 66.42; H, 6.27;
1
N, 15.49. H NMR, δ: 2.42 (t, 3 H, Me, J = 7.8 Hz); 2.07 and
2.15 (both s, 3 H each, Me); 4.35 (m, 2 H, CH2); 5.01 (s, 2 H,
CH2); 6.05 (d, 1 H, CH, J = 3.8 Hz); 6.28 (t, 1 H, CH, J =
4.0 Hz); 7.33 and 8.40 (both s, 1 H each, CH).
Synthesis of compounds 8a—r (general procedure). A susꢀ
pension of imido ester 4 (0.01 mol) and the corresponding acid
hydrazide (0.01 mol) was refluxed in chlorobenzene (30 mL) for
4 h. The mixture was cooled and chlorobenzene was distilled off.
The reaction mixture was chromatographed (CHCl3/Al2O3),
filtered, and washed with ethyl ether.
7ꢀBenzylꢀ2ꢀ(4ꢀmethoxyphenyl)methylꢀ8,9ꢀdiphenylꢀ7Hꢀpyrꢀ
rolo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidine (8g). The yield was
3.75 g (72%), colorless crystals, m.p. 145—146 °C. Found (%):
C, 78.17; H, 5.29; N, 13.37. C34H27N5O. Calculated (%):
C, 78.29; H, 5.22; N, 13.43. 1H NMR, δ: 3.78 (s, 3 H,
Me); 5.49 (s, 2 H, CH2); 6.81 (d, 4 H, CH, J = 8.9 Hz);
7.11—7.43 (m, 13 H, CH); 7.62 (d, 2 H, CH, J = 9.9 Hz); 9.00
(s, 1 H, CH).
2ꢀ(4ꢀMethoxyphenyl)methylꢀ8,9ꢀdimethylꢀ7ꢀ(pyridinꢀ3ꢀyl)ꢀ
7Hꢀpyrrolo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidine (8a). The
yield was 2.95 g (77%), colorless crystals, m.p. 145—147 °C.
Found (%): C, 68.54; H, 5.32; N, 21.82. C22H20N6O. Calcuꢀ
1
lated (%): C, 68.73; H, 5.24; N, 21.86. H NMR, δ: 2.31, 2.62,
and 3.78 (all s, 3 H each, Me); 4.27 (s, 2 H, CH2); 6.88 (d, 2 H,
CH, J = 9.0 Hz); 7.38 (d, 2 H, CH, J = 9.1 Hz); 7.55 (t, 2 H,
CH, J = 8.6 Hz); 7.61 (t, 1 H, CH, J = 7.4 Hz); 7.81 (d, 1 H,
CH, J = 8.4 Hz); 8.74 (s, 1 H, CH); 8.79 (d, 1 H, CH, J =
5.4 Hz); 8.9 (s, 1 H, CH).
8,9ꢀDimethylꢀ2ꢀphenoxymethylꢀ7ꢀ(pyridinꢀ3ꢀyl)ꢀ7Hꢀpyrꢀ
rolo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidine (8b). The yield was
2.49 g (65%), colorless crystals, m.p. 170—172 °C. Found (%):
C, 68.01; H, 4.95; N, 22.58. C21H18N6O. Calculated (%):
C, 68.09; H, 4.90; N, 22.69. 1H NMR, δ: 2.31 and 2.58 (both s,
3 H each, Me); 5.43 (s, 2 H, CH2); 7.01 (t, 1 H, CH, J =
7.5 Hz); 7.12 (d, 1 H, CH, J = 8.5 Hz); 7.32 (m, 3 H, CH); 7.64
7ꢀBenzylꢀ2ꢀphenoxymethylꢀ8,9ꢀdiphenylꢀ7Hꢀpyrroꢀ
lo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidine (8h). The yield was
3.54 g (68%), paleꢀyellow crystals, m.p. 141—143 °C. Found (%):
C, 77.95; H, 4.98; N, 13.76. C33H25N5O. Calculated (%):
C, 78.09; H, 4.96; N, 13.80. 1H NMR, δ: 5.38 and 5.50 (both s,
2 H each, CH2); 6.9 (m, 2 H, 2 CH); 7.10—7.44 (m, 17 H,
17 CH); 7.51 (d, 1 H, CH, J = 9.9 Hz); 9.11 (s, 1 H, CH).
7ꢀBenzylꢀ2ꢀ(2ꢀhydroxyphenyl)ꢀ8,9ꢀdiphenylꢀ7Hꢀpyrroꢀ
lo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidine (8i). The yield was
4.14 g (84%), colorless crystals, m.p. 205—207 °C. Found (%):
C, 77.78; H, 4.76; N, 14.06. C32H23N5O. Calculated (%):
1
C, 77.87; H, 4.70; N, 14.19. H NMR, δ: 5.61 (s, 2 H, CH2);

1496
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 8, August, 2006
Vorob´ev et al.
6.90 (m, 4 H, CH2); 7.22—7.48 (m, 14 H, CH); 8.11 (d, 1 H,
CH, J = 7.47 Hz); 9.49 (s, 1 H, CH); 11.45 (s, 1 H, OH).
7ꢀBenzylꢀ8,9ꢀdiphenylꢀ2ꢀ(pyridinꢀ4ꢀyl)ꢀ7Hꢀpyrroꢀ
lo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidine (8j). The yield was
3.25 g (68%), paleꢀyellow crystals, m.p. 207—209 °C. Found (%):
C, 77.71; H, 4.72; N, 17.49. C31H22N6. Calculated (%): C, 77.80;
H, 4.63; N, 17.56. 1H NMR, δ: 5.51 (s, 2 H, CH2); 6.92 (m, 2 H,
CH); 7.14—7.40 (m, 11 H, 11 CH); 7.62 (d, 2 H, CH, J =
7.8 Hz); 8.03 (d, 2 H, CH, J = 6.1 Hz); 8.75 (d, 2 H, CH, J =
6.8 Hz); 9.16 (s, 1 H, CH).
3.2 Hz); 8.21 (d, 2 H, 2 CH, J = 6.5 Hz); 8.79 (d, 2 H, 2 CH, J =
6.7 Hz); 9.02 (s, 1 H, CH).
2ꢀ(2ꢀBenzoxazolylthio)methylꢀ7ꢀ(2ꢀfurfuryl)ꢀ8,9ꢀdimethylꢀ
7Hꢀpyrrolo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidine (8q). The
yield was 2.58 g (75%), colorless crystals, m.p. 172—175 °C.
Found (%): C, 61.27; H, 4.27; N, 19.44; S, 7.49. C22H18N6O2S.
Calculated (%): C, 61.38; H, 4.21; N, 19.52; S, 7.45. 1H NMR,
δ: 2.41 and 2.48 (both s, 3 H each, Me); 4.88 and 5.47
(both s, 2 H each, CH2); 6.20 (d, 1 H, CH, J = 4.1 Hz); 6.28
(t, 1 H, CH, J = 5.0 Hz); 7.25—7.33 (m, 3 H, 3 CH); 7.45 (d,
1 H, CH, J = 8.1 Hz); 7.65 (d, 1 H, CH, J = 7.7 Hz); 8.98
(s, 1 H, CH).
2ꢀ(2ꢀBenzoxazolylthio)methylꢀ7ꢀbenzylꢀ8,9ꢀdiphenylꢀ7Hꢀ
pyrrolo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidine (8k). The yield
was 4.34 g (77%), colorless crystals, m.p. 165—167 °C.
Found (%): C, 72.26; H, 4.35; N, 14.79. C34H24N6OS. Calcuꢀ
2ꢀ(2ꢀBromophenyl)ꢀ7ꢀ(2ꢀfurfuryl)ꢀ8,9ꢀdimethylꢀ7Hꢀpyrroꢀ
lo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidine (8r). The yield was
3.50 g (83%), paleꢀyellow crystals, m.p. 159—161 °C. Found (%):
C, 56.81; H, 3.89; Br, 18.97; N, 16.47. C20H16BrN5O. Calcuꢀ
1
lated (%): C, 72.32; H, 4.28; N, 14.88. H NMR, δ: 4.92 and
5.53 (both s, 2 H each, CH2); 6.90 (d, 2 H, CH, J = 8.7 Hz);
7.12—7.50 (m, 17 H, CH); 9.11 (s, 1 H).
1
lated (%): C, 56.89; H, 3.82; Br, 18.92; N, 16.58. H NMR, δ:
7ꢀBenzylꢀ2ꢀ(2ꢀbromophenyl)ꢀ8,9ꢀdiphenylꢀ7Hꢀpyrroꢀ
lo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidine (8l). The yield was
4.61 g (83%), colorless crystals, m.p. 187—191 °C. Found (%):
C, 69.06; H, 4.06. Br, 14.39; N, 12.52. C32H22BrN5. Calꢀ
2.42 and 2.49 (both s, 3 H each, Me); 5.53 (s, 2 H, CH2); 6.21
(d, 1 H, J = 8.4 Hz); 6.30 (t, 1 H, CH); 7.28 (m, 3 H, 3 CH);
7.53 and 8.00 (both d, 1 H each, CH, J = 7.8 Hz); 9.03
(s, 1 H, CH).
1
culated (%): C, 69.07; H, 3.98; Br, 14.36; N, 12.59. H NMR,
7ꢀBenzylꢀ4ꢀiminoꢀ5,6ꢀdimethylꢀ4,7ꢀdihydroꢀ3Hꢀpyrroꢀ
lo[2,3ꢀd]pyrimidineꢀ3ꢀamine (9). A suspension of imido ester
(0.1 mol) and hydrazine hydrate (6 mL, 0.12 mol) in benzene
was refluxed for 1 h. Then sodium methoxide (20 mg) was added
and the mixture was refluxed for 2 h. Then benzene was evapoꢀ
rated. The resulting solution was washed with a small amount of
PriOH and ethyl ether and recrystallized from toluene. The
yield was 21.6 g (81%), paleꢀyellow crystals, m.p. 145—147 °C.
Found (%): C, 67.34; H, 6.32; N, 26.19. C15H17N5. Calcuꢀ
δ: 5.51 (s, 2 H, CH2); 6.89 (m, 4 H, CH); 7.24—7.46 (m,
13 H, CH); 7.61 (d, 2 H, CH, J = 8.7 Hz); 7.72 (d, 1 H,
CH, J = 8.0 Hz); 8.00 (d, 1 H, CH, J = 7.7 Hz); 9.20
(s, 1 H, CH).
7ꢀ(2ꢀFurfuryl)ꢀ2ꢀ(4ꢀmethoxyphenyl)methylꢀ8,9ꢀdimethylꢀ
7Hꢀpyrrolo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidine (8m). The
yield was 2.67 g (69%), paleꢀyellow crystals, m.p. 123—125 °C.
Found (%): C, 68.13; H, 5.52; N, 17.93. C22H21N5O2. Calcuꢀ
1
1
lated (%): C, 68.20; H, 5.46; N, 18.08. H NMR, δ: 2.41, 2.55,
lated (%): C, 67.41; H, 6.37; N, 26.22. H NMR, δ: 2.13 and
and 3.79 (all s, 3 H each, Me); 4.25 and 5.42 (both s, 2 H each,
CH2); 6.21 (d, 1 H, CH, J = 4.1 Hz); 6.32 (t, 1 H, CH, J =
6.2 Hz); 6.86 (d, 2 H, 2 CH, J = 9.1 Hz); 7.21—7.38 (m, 3 H,
3 CH); 8.95 (s, 1 H, CH).
7ꢀ(2ꢀFurfuryl)ꢀ8,9ꢀdimethylꢀ2ꢀphenoxymethylꢀ7Hꢀpyrꢀ
rolo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidine (8n). The yield was
3.06 g (82%), colorless crystals, m.p. 157—160 °C. Found (%):
C, 67.46; H, 5.19; N, 18.67. C21H19N5O2. Calculated (%):
C, 67.55; H, 5.13; N, 18.76. 1H NMR, δ: 2.41 and 2.48 (both s,
3 H each, Me); 5.42 and 5.51 (both s, 2 H each, CH2); 6.20 (d,
1 H, CH, J = 3.7 Hz); 6.33 (t, 1 H, CH, J = 3.3 Hz); 6.95 (t,
2 H, 2 CH, J = 7.5 Hz); 7.15 (d, 2 H, 2 CH, J = 8.7 Hz); 7.32
(m, 3 H, 3 CH); 9.00 (s, 1 H, CH).
7ꢀ(2ꢀFurfuryl)ꢀ2ꢀ(2ꢀhydroxyphenyl)ꢀ8,9ꢀdimethylꢀ7Hꢀpyrꢀ
rolo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidine (8o). The yield was
2.66 g (74%), paleꢀyellow crystals, m.p. 178—180 °C. Found (%):
C, 66.77; H, 4.84; N, 19.41. C20H17N5O2. Calculated (%):
C, 66.84; H, 4.77; N, 19.49. 1H NMR, δ: 2.44 and 2.53 (both s,
3 H each, Me); 5.49 (s, 2 H, CH2); 6.22 (d, 1 H, CH, J =
7.3 Hz); 6.30 (t, 1 H, CH, J = 7.0 Hz); 6.95 (t, 1 H, CH, J =
8.5 Hz); 7.11 (d, 2 H, 2 CH, J = 9.0 Hz); 7.41 (m, 2 H, 2 CH);
8.22 (d, 1 H, CH, J = 9.0 Hz); 9.04 (s, 1 H, CH); 11.74
(s, 1 H, OH).
2.37 (both s, 3 H each, Me); 4.79 (s, 2 H, CH2); 5.25 (s, 2 H,
NH2); 6.20—6.80 (br.s, 1 H, NH); 7.02 (d, 2 H, CH, J =
8.5 Hz); 7.27 (m, 3 H, CH); 7.88 (s, 1 H, CH).
7ꢀBenzylꢀ4ꢀhydrazinoꢀ5,6ꢀdimethylꢀ7Hꢀpyrrolo[2,3ꢀd]pyriꢀ
midine (10). Amino imine 9 (22 g, 0.1 mol) was refluxed in an
aqueousꢀethanolic solution (75 mL of water and 75 mL of ethaꢀ
nol) in the presence of NaOH (20 mg) for 48 h. The reaction
mixture was concentrated to dryness, and ethanol (25 mL) was
added. After 12 h, the precipitate was filtered off and washed
with petroleum ether. The yield was 15.75 g (59%), colorless
crystals, m.p. 145—147 °C. Found (%): C, 67.28; H, 6.35;
N, 26.31. C15H17N5. Calculated (%): C, 67.41; H, 6.37; N, 26.22.
1H NMR, δ: 2.14 and 2.29 (both s, 3 H each, Me); 4.22—4.48
(br.d, 2 H, NH2, J = 16.8 Hz); 5.34 (s, 2 H, CH2); 7.01 (d, 2 H,
CH, J = 8.6 Hz); 7.22 (m, 3 H, CH); 7.61 (br.d, 1 H, NH, J =
16.2 Hz); 8.07 (s, 1 H, CH).
Synthesis of compounds 8s and 11s (general procedure). A soꢀ
lution of 4ꢀiminoꢀ3Hꢀpyrrolo[2,3ꢀd]pyrimidineꢀ3ꢀamine 9 or
hydrazine 10 (0.01 mol) in orthoformic ester (4 mL, 0.05 mol)
containing 10 mol.% acetic acid was refluxed for 2 h and puriꢀ
fied by column chromatography (CHCl3/Al2O3). Product 8s
or 11s was recrystallized from ethanol, filtered off, and washed
with ethanol.
7ꢀ(2ꢀFurfuryl)ꢀ8,9ꢀdimethylꢀ2ꢀ(pyridinꢀ4ꢀyl)ꢀ7Hꢀpyrroꢀ
lo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidine (8p). The yield was
2.68 g (78%), colorless crystals, m.p. 195—198 °C. Found (%):
C, 66.20; H, 4.75; N, 24.33. C19H16N6O. Calculated (%):
C, 66.27; H, 4.68; N, 24.40. 1H NMR, δ: 2.47 and 2.57 (both s,
3 H each, Me); 5.49 (s, 2 H, CH2); 6.25 (d, 1 H, CH, J =
4.3 Hz); 6.30 (t, 1 H, CH, J = 5.1 Hz); 7.35 (d, 1 H, CH, J =
7ꢀBenzylꢀ8,9ꢀdimethylꢀ7Hꢀpyrrolo[3,2ꢀe][1,2,4]triazoꢀ
lo[1,5ꢀc]pyrimidine (8s). The yield was 2.24 g (81%), colorless
crystals, m.p. 145—147 °C. Found (%): C, 69.24; H, 5.37;
N, 27.36. C16H15N5. Calculated (%): C, 69.31; H, 5.42; N, 27.27.
1H NMR, δ: 2.27 and 2.60 (both s, 3 H each, Me); 5.52 (s, 2 H,
CH2), 7.04 (d, 2 H, 2 CH, J = 8.5 Hz); 7.29 (m, 3 H, CH); 8.37
and 9.0 (both s, 1 H each, CH).

7HꢀPyrrolo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidines Russ.Chem.Bull., Int.Ed., Vol. 55, No. 8, August, 2006
1497
1
7ꢀBenzylꢀ8,9ꢀdimethylꢀ7Hꢀpyrrolo[3,2ꢀe][1,2,4]triazoꢀ
lo[4,3ꢀc]pyrimidine (11s). The yield was 1.88 g (68%), colorless
crystals, m.p. 145—147 °C. Found (%): C, 69.26; H, 5.36;
N, 27.32. C16H15N5. Calculated (%): C, 69.31; H, 5.42; N, 27.27.
1H NMR, δ: 2.28 and 2.58 (both s, 3 H each, Me); 5.51 (s, 2 H,
CH2); 7.05 (d, 2 H, 2 CH, J = 8.5 Hz); 7.27 (m, 3 H, CH); 8.61
and 8.86 (both s, 1 H each, CH).
Synthesis of compounds 8t—y and 11t,u (general procedure).
A suspension of the starting acid (0.01 mol) in chlorobenzene
(20 mL) and SOCl2 (0.72 mL, 0.01 mol) in the presence of
10 mol.% DMF was refluxed until elimination of HCl ceased.
Then amino imine 9 (method А) or hydrazine 10 (method B)
was added. The reaction mixture was refluxed for 4 h, extracted
three times with chloroform (20 mL) and an aqueous ammonia
solution (15% solution, 20 mL), purified by column chromatoꢀ
graphy (CHCl3/Al2O3), recrystallized from ethanol, filtered off,
and washed with ethanol.
7ꢀBenzylꢀ2,8,9ꢀtrimethylꢀ7Hꢀpyrrolo[3,2ꢀe][1,2,4]triazoꢀ
lo[1,5ꢀc]pyrimidine (8t). The yield was 1.42 g (49%), colorless
crystals, m.p. 138—141 °C. Found (%): C, 70.10; H, 5.84;
N, 24.05. C17H17N5. Calculated (%): C, 70.10; H, 5.84; N, 24.05.
1H NMR, δ: 2.29, 2.50, and 2.66 (all s, 3 H each, Me); 5.51 (s,
2 H, CH2); 7.0 (d, 2 H, 2 CH, J = 8.5 Hz); 7.30 (m, 3 H, CH);
8.90 (s, 1 H, CH).
N, 17.60. H NMR, δ: 2.27 and 2.59 (both s, 3 H each, Me);
5.39 and 5.52 (both s, 2 H each, CH2); 7.02 (m, 6 H, 6 CH);
7.30 (m, 3 H, CH); 8.98 (s, 1 H, CH).
7ꢀBenzylꢀ8,9ꢀdimethylꢀ2ꢀ[1,3(2H)ꢀdioxoꢀ1Hꢀisoindolꢀ2ꢀ
ylmethyl]ꢀ7Hꢀpyrrolo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidine
(8y). The yield was 1.93 g (43%) (method А), 1.88 g (42%)
(method B), colorless crystals, m.p. 202—205 °C. Found (%):
C, 69.24; H, 5.49; N, 27.19. C25H20N6O2. Calculated (%):
C, 69.31; H, 5.42; N, 27.27. 1H NMR, δ: 2.28 and 2.51 (both s,
3 H each, Me); 5.25 and 5.51 (both s, 2 H each, CH2); 6.97 (d,
2 H, 2 CH, J = 8.5 Hz); 7.26 (m, 3 H, CH); 7.82 and 7.95
(both m, 2 H each, 2 CH each); 8.84 (s, 1 H, CH).
7ꢀBenzylꢀ3,8,9ꢀtrimethylꢀ7Hꢀpyrrolo[3,2ꢀe][1,2,4]triazoꢀ
lo[4,3ꢀc]pyrimidine (11t). The yield was 1.92 g (66%) (method B),
paleꢀyellow crystals, m.p. 189—191 °C. Found (%): C, 70.01;
H, 5.90; N, 23.98. C17H17N5. Calculated (%): C, 70.10; H, 5.84;
N, 24.05. 1H NMR, δ: 2.30, 2.48, and 2.87 (all s, 3 H each, Me);
5.51 (s, 2 H, CH2); 7.01 (d, 2 H, 2 CH, J = 8.5 Hz); 7.25 (m,
3 H, CH); 8.38 (s, 1 H, CH).
7ꢀBenzylꢀ3ꢀethylꢀ8,9ꢀdimethylꢀ7Hꢀpyrrolo[3,2ꢀe][1,2,4]triꢀ
azolo[4,3ꢀc]pyrimidine (11u). The yield was 2.17 g (71%)
(method B), colorless crystals, m.p. 170—173 °C. Found (%):
C, 70.76; H, 6.30; N, 22.94. C18H19N5. Calculated (%): C, 70.82;
1
H, 6.23; N, 22.95. H NMR, δ: 1.56 (t, 3 H, Me, J = 7.7 Hz);
7ꢀBenzylꢀ2ꢀethylꢀ8,9ꢀdimethylꢀ7Hꢀpyrrolo[3,2ꢀe][1,2,4]triꢀ
azolo[1,5ꢀc]pyrimidine (8u). The yield was 2.07 g (68%), colorꢀ
less crystals, m.p. 125—128 °C. Found (%): C, 70.67; H, 6.26;
N, 22.85. C18H19N5. Calculated (%): C, 70.82; H, 6.23; N, 22.95.
1H NMR, δ: 1.43 (t, 3 H, Me, J = 7.6 Hz); 2.28 and 2.54 (both s,
3 H each, Me); 3.01 (m, 2 H, CH2); 5.51 (s, 2 H, CH2); 7.00 (d,
2 H, 2 CH, J = 8.6 Hz); 7.26 (m, 3 H, CH); 8.92 (s, 1 H, CH).
8,9ꢀDimethylꢀ2ꢀpropylꢀ7Hꢀpyrrolo[3,2ꢀe][1,2,4]triazoꢀ
lo[1,5ꢀc]pyrimidine (8v). The yield was 1.75 g (55%) (method А),
1.85 g (58%) (method B), colorless crystals, m.p. 99—101 °C.
Found (%): C, 71.36; H, 6.62; N, 21.88. C19H21N5. Calcuꢀ
lated (%): C, 71.47; H, 6.58; N, 21.95. 1H NMR, δ: 1.22 (t, 3 H,
Me, J = 7.6 Hz); 1.90 (m, 2 H, CH2); 2.32 and 2.51 (both s,
3 H each, Me); 3.00 (t, 2 H, CH2, J = 8.1 Hz); 5.49 (s, 2 H,
CH2); 7.03 (d, 2 H, 2 CH, J = 8.5 Hz); 7.25 (m, 3 H, CH); 8.91
(s, 1 H, CH).
7ꢀBenzylꢀ2ꢀbutylꢀ8,9ꢀdimethylꢀ7Hꢀpyrrolo[3,2ꢀe][1,2,4]triꢀ
azolo[1,5ꢀc]pyrimidine (8w). The yield was 1.63 g (49%)
(method А), 1.43 g (43%) (method B), paleꢀyellow crystals,
m.p. 85—87 °C. Found (%): C, 71.89; H, 6.87; N, 21.00.
C20H23N5. Calculated (%): C, 72.07; H, 6.91; N, 21.02.
1H NMR, δ: 1.01 (t, 3 H, Me, J = 7.5 Hz); 1.48 and 1.87
(both m, 2 H each, CH2); 2.27 and 2.52 (both s, 3 H each, Me);
2.95 (t, 2 H, CH2, J = 8.2 Hz); 5.50 (s, 2 H, CH2); 7.02 (d, 2 H,
2 CH, J = 7.7 Hz); 7.27 (m, 3 H, CH); 8.91 (s, 1 H, CH).
7ꢀBenzylꢀ8,9ꢀdimethylꢀ2ꢀ(4ꢀmethylphenoxy)methylꢀ7Hꢀpyrꢀ
rolo[3,2ꢀe][1,2,4]triazolo[1,5ꢀc]pyrimidine (8x). The yield was
2.86 g (72%) (method А), 2.46 g (62%) (method B), colorless
crystals, m.p. 162—163 °C. Found (%): C, 72.44; H, 6.87;
N, 17.56. C24H23N5O. Calculated (%): C, 72.59; H, 6.80;
2.29 and 2.58 (both s, 3 H each, Me); 3.21 (m, 2 H, CH2); 5.51
(s, 2 H, CH2); 7.0 (d, 2 H, 2 CH, J = 8.5 Hz); 7.25 (m, 3 H,
CH); 8.40 (s, 1 H, CH).
References
1. B. Camerino, G. Palamidessi, and R. Sciaky, Gazz. Chim.
Ital., 1960, 90, 1821.
2. D. J. Brown, G. W. Grigg, Y. Iwai, K. N. McAndrew,
T. Nagamatsu, and R. Van Heeswyck, Aust. J. Chem., 1979,
32, 2713.
3. A. Dlugosz, Pol. J. Chem., 1992, 66, 131.
4. US Pat. 5358950, 1994; Chem. Abstrs, 1995, 122, 314561.
5. Ger. Pat. Offen. 2018550, 1970; Chem. Abstrs, 1971,
74, 22873.
6. E. Sondheimer and R. W. Holley, J. Am. Chem. Soc., 1954,
76, 2463.
7. H. Wamhoff, E. Kroth, and C. Strauch, Synthesis, 1993,
11, 1129.
8. M. R. Del Giudice, A. Borioni, C. Mustazza, and F. Gatta,
J. Heterocycl. Chem., 1994, 31, 1503.
9. C. G. Dave and R. D. Shah, Molecules, 2002, 7, 554.
10. C. G. Dave and R. D. Shah, J. Heterocycl. Chem., 2000,
37, 757.
11. A. E. Rashad, M. E. A. Zaki, S. S. Fatahala, and M. S.
Mohamed, Acta Pharm., 2005, 55, 237.
Received April 25, 2006;
in revised form July 28, 2006