A mild one-pot synthesis of thieno[3,4-c]pyrazoles and their conversion into pyrazole analogs of o-quinodimethane

Article abstract of DOI:10.1055/s-1998-6095

The reaction of alkyl or aryl hydrazine hydrochlorides with 4-cyano-3-oxotetrahydrothiophene (1) in refluxing ethanol afforded, in a regioselective manner, the corresponding 2-alkyl- or 2-aryl-3-aminothieno[3,4-c]pyrazoles 3a-1 with good yields. As representative examples, the compounds 3a, 3e, and 3k, after standard acetylation procedure, have been efficiently converted into the corresponding sulfolenes 6a, 6e, and 6k which readily undergo sulfur dioxide extrusion upon heating and in the presence of dienophiles, such as N-phenylmaleimide and ethyl fumarate, give die corresponding [4+2] cycloadducts in good yields.

Full text of DOI:10.1055/s-1998-6095

SYNTHESIS
September 1998
1331
A Mild One-Pot Synthesis of Thieno[3,4-c]pyrazoles and Their Conversion into
Pyrazole Analogs of o-Quinodimethane
Pier Giovanni Baraldi,*a Hussein El-Kashef,b Stefano Manfredini,a Maria J. Pineda de las Infantas,c Romeo
Romagnoli,a Giampiero Spallutoa
a Dipartimento di Scienze Farmaceutiche, Via Fossato di Mortara 17/19, I-44100, Ferrara, Italy
Phone +39(532)291293; Fax +39(532)291296; E-mail: pgb@dns.unife.it
b Department of Chemistry, University of Assiut, Assiut, Egypt
c Departamento de Quìmica Orgànica y Farmacéutica, Facultad de Farmacia, Campus de Cartuja s/n, ES-18071 Granada, Spain.
Received 24 February 1998
Abstract: The reaction of alkyl or aryl hydrazine hydrochlorides
treatment with various substituted hydrazines and subse-
quent N-acetylation, is readily transformed into the corre-
sponding sulfolene by oxidation. The thermal extrusion of
sulfur dioxide generates the o-quinodimethane intermedi-
ate, which is readily trapped with dienophiles.
with 4-cyano-3-oxotetrahydrothiophene (1) in refluxing ethanol
afforded, in a regioselective manner, the corresponding 2-alkyl- or
2-aryl-3-aminothieno[3,4-c]pyrazoles 3a–l with good yields. As
representative examples, the compounds 3a, 3e, and 3k, after
standard acetylation procedure, have been efficiently converted
into the corresponding sulfolenes 6a, 6e, and 6k which readily
undergo sulfur dioxide extrusion upon heating and in the presence
of dienophiles, such as N-phenylmaleimide and ethyl fumarate,
give the corresponding [4+2] cycloadducts in good yields.
Starting from 4-cyano-3-oxotetrahydrothiophene (1),11
easily prepared by tandem Michael–Dieckmann reaction
between acrylonitrile and methyl thioglycolate, the reac-
tion with substituted hydrazine hydrochlorides 2a–l in re-
fluxing ethanol, gave, regioselectively, the thieno[3,4-
c]pyrazoles 3a–l in 82–96% yield. The regioselectivity of
this process has been confirmed by treatment of oxonitrile
1 with phenylhydrazine, to obtain a 1:1 mixture of the de-
rivatives 3a and 4 readily separated by column chroma-
tography. The formation of 4 indicates that the unsubsti-
tuted nitrogen of phenylhydrazine is the preferred site of
reaction with the carbonyl functionality of 1. Cyclization
of 4 to give the product 3a, was performed by heating the
ethanolic mixture with few drops of 5% HCl solution.
Key words: 2-alkyl/aryl-3-aminothieno[3,4-c]pyrazoles, regio-
specificity, 3,4-dimethylenepyrazoles, Diels–Alder adduct, anti-
hypertensive agents
The thieno[3,4-c]pyrazoles are a class of active com-
pounds currently employed in the field of medicinal
chemistry for their remarkable antiinflammatory,1 analge-
sic and antithrombotic activities, and for the treatment of
cardiovascular or cerebrovascular diseases, hyperglycae-
mia and hyperlipoemia.2
The reported syntheses of thieno[3,4-c]pyrazoles usually
proceed from thiophene derivatives, treatment with alkyl-
or arylhydrazines gives the corresponding hydrazones
which are then cyclized to give a mixture of the two pyra-
zoles, albeit with good regioselectivity.3–5
Moreover, the corresponding pyrazolo-sulfolenes, as
stable precursors for pyrazole analogs of o-quin-
odimethanes,4, 5 are prepared either by constructing the
sulfolene ring by oxidation of the thieno[3,4-c]pyrazole,3
or building the N-unsubstituted pyrazole ring on a pre-ex-
isting cyclic sulfone system. The latter route is more at-
tractive if suitably functionalized 3-sulfolenes are readily
available. Storr et al.6, 7 have reported the generation of a
pyrazole-fused sulfone following base-induced aromati-
zation of the intermediate derived by addition of di-
azomethane to 3-(phenylsulfonyl)-2,5-dihydrothiophene
S,S-dioxide. Subsequent N-protection gave an inseparable
mixture of N1 and N2 substituted derivatives. Finally, the
synthesis of pyrazolo-3-sulfolenes has been recently re-
ported in the literature8–10 by treatment of 4-acyl-3-
chloro-3-sulfolenes with hydrazine in refluxing ethanol.
Scheme 1
All attempts to oxidize the 2-substituted 3-ami-
nothieno[3,4-c]pyrazole 3a, 3e, and 3k gave poor yields
(23–30%) of the corresponding sulfolenes, and this was
presumably due to the concomitant formation of oxidized
products on the 3-amino group. The use of the N-acetylat-
ed derivatives 5a, 5e, and 5k, instead of the parents 3a, 3e,
and 3k, avoided the above described occurrence and re-
markably improved the oxidation step. In fact, the
Our interest in the development of a mild synthetic
procedure for the preparation of 2-alkyl/aryl-3-ami-
nothieno[3,4-c]pyrazoles, prompted us develop a new
one-pot synthesis that takes advantage of our previous
studies on 4-cyano-3-oxotetrahydrothiophene (1).11
Moreover, 4-cyano-3-oxotetrahydrothiophene (1), after

SYNTHESIS
Papers
Table. 2-Substituted 3-Aminothieno [3,4-c]pyrazoles Prepared
1332
Com-
pound
R
Yielda mp
Molecular
Formulab
1H NMR (CDCl3)
δ, J (Hz)
MS (70 eV)
m/z (%)
(%)
(°C)
3a
3b
Ph
90
165–168 C11H11N3S
3.78 (s, 2H), 3.91 (s, 2H), 4.61 (bs, 2H),
7.32–7.74 (m, 5H)
217 (M+, 45), 93 (25),
81 (43), 79 (36), 77 (100)
o-CH3O–C6H4 83
155–156 C12H13N3OS 3.80 (s, 2H), 3.88 (s, 2H) 3.96 (s, 1H), 4.64
(bs, 2H), 7.02 (dd, 2H, J = 2 and 6.8), 7.92
(dd, 2H, J = 2 and 6.8)
3b
3d
3e
3f
o-Cl–C6H4
m-Cl–C6H4
p-Cl–C6H4
87
85
81
150–152 C11H10ClN3S 3.82 (s, 2H), 3.90 (s, 2H), 4.64 (bs, 2H),
7.22–7.68 (m, 4H)
251 (M+, 62), 216 (21),
127 (60), 111 (54), 75 (100)
251 (M+, 80), 153 (20), 111
(100), 108 (30)
251 (M+, 100), 206 (13),
127 (22), 75 (53)
285 (M+, 13), 207 (20), 161
(14), 81 (100)
286 (M+, trace), 232 (22),
207 (42), 81 (68), 44 (100)
285 (M+, 100), 250 (40),
145 (26), 109 (30)
155 (M+, 100), 122 (53),
110 (38), 66 (37)
145–147 C11H10ClN3S 3.80 (s, 2H), 3.86 (s, 2H), 4.66 (bs, 2H), 7.13
(s, 1H), 7.20–7.58 (m, 3H)
172–174 C11H10ClN3S 3.77 (s, 2H), 3.84 (s, 2H), 4.60 (bs, 2H), 7.21
(d, 2H, J = 8.2), 7.45 (d, 2H, J = 8.2)
m,p-Cl2–C6H4 86
o,p-Cl2–C6H4 93
o,m'-Cl2–C6H4 87
190–192 C11H9Cl2N3S 3.82 (s, 2H), 3.90 (s, 2H), 4.12 (bs, 2H), 7.48
(d, 1H, J = 7.2), 7.65 (d, 1H, J = 7.2), 7.86 (s, 1H)
3g
3h
3i
211–213 C11H9Cl2N3S 3.83 (s, 2H), 3.91 (s, 2H), 5.32 (bs, 2H), 7.58
(d, 1H, J = 7), 7.70 (d, 1H, J = 7), 7.83 (s, 1H)
152–153 C11H9Cl2N3S 3.81 (s, 2H), 3.94 (s, 2H), 4.15 (bs, 2H), 7.55
(d, 1H, J = 7), 7.67 (d, 1H, J = 7), 7.84 (s, 1H)
CH3
83
89
82
175–176 C6H9N3S
140–142 C7H11N3S
3.77 (s, 3H), 3.80 (s, 2H), 3.89 (s, 2H), 4.77
(bs, 2H)
3j
CH2CH3
(CH2)3CH3
1.12 (t, 3H, J = 7.1), 3.79 (s, 2H), 3.84 (q, 2H,
J = 7.1), 3.88 (s, 2H), 4.78 (bs, 2H)
168 (M+, 100), 140 (39),
97 (40)
197 (M+, 95), 154 (100),
3k
81–82
C9H15N3S
1.01 (t, 3H, J = 7.2), 1.40 (m, 2H), 1.81 (m, 2H),
3.40 (bs, 2H), 3.79 (s, 2H), 3.90 (t, 2H, J = 7.4), 141 (46), 98 (38)
3.96 (s, 2H)
3l
(CH3)3C
86
154–155 C9H15N3S
1.2 (s, 9H), 3.79 (s, 2H), 3.88 (s, 2H), 4.78 (bs, 2H) 197 (M+, 100), 140 (94),
124 (88), 112 (77)
a Yield of isolated, purified products after crystallization
b Satisfactory analyses obtained: C ± 0.25, H ± 0.22, N ± 0.10, Cl ± 0.12.
zole analogs of o-quinodimethanes 7a, 7e, and 7k which
could be efficiently trapped by means of Diels–Alder re-
actions.
N-acetylation of 3a, 3e, and 3k with acetyl chloride and
triethylamine (TEA) at room temperature afforded the
products 5a, 5e, and 5k in almost quantitative yield, which
after subsequent oxidation with excess of 3-chloroperox-
ybenzoic acid (m-CPBA) proceeded smoothly to give the
sulfones 6a, 6e, and 6k, respectively, in 76–86% yield.
These 2-substituted 3-(acetylamino)thieno[3,4-c]pyrazole
S,S-dioxides 6a, 6e, and 6k are precursors of pyrazole an-
alogs of o-xylylenes (o-quinodimethanes) 7a, 7e, and 7k,
and can be trapped in Diels–Alder reactions by several
commercially available dienophiles.
Finally, in view of the known biological activity of this
class of compounds, they were also subjected to prelimi-
nary evaluation as antihypertensive agents. It is remark-
able that compounds 3d–f were very active with a proba-
ble mechanism of potassium channel openers.12
All reactions were carried out under argon, unless otherwise de-
scribed. Standard syringe techniques were applied for transferring an-
hydrous solvents. Reaction progress and product mixtures were rou-
tinely monitored by TLC on silica gel (precoated F254 Merk plates)
To trap the transient 3,4-dimethylenepyrazole intermedi-
ates 7a, 7e, and 7k, a solution of ethyl fumarate (2 equiv)
and sulfolenes 6a, 6e, and 6k in 1,2,4-trichlorobenzene
was heated at 200°C under an inert atmosphere for one
hour. In all cases, the tetrahydroindazoles 8a, 8e, and 8k
were recovered in good yields. By a similar strategy, with
the use of N-phenylmaleimide (2 equiv) as dienophile, the
Diels–Alder cycloadducts 9a, 9e, and 9k have been isolat-
ed in good yield.
1
and visualized with aq KMnO4. H NMR spectra were obtained in
CDCl3 with a Bruker AC 200 spectrometer. Chemical shifts (δ) are
given in ppm downfield from TMS. MS were obtained on a Fisons
MD 800. Mps were determined on a Buchi–Tottoli apparatus and are
uncorrected. Chromatography was performed with Merck 60–200
1
mesh silica gel. All products reported showed H NMR spectra in
agreement with the assigned structures. Organic solutions were dried
over anhyd MgSO4. Anhyd CH2Cl2 was distilled from CaH2 prior to
use. Elemental analyses were effected by the microanalytical labora-
tory of Dipartimento di Chimica, University of Ferrara.
In summary, we have developed a very efficient route for
the preparation of 2-substituted 3-aminothieno[3,4-
c]pyrazoles 3a–l. As representative examples, the com-
pounds 3a, 3e, and 3k were transformed in good yields
into precursors 6a, 6e, and 6k of the corresponding pyra-
2-Substituted 3-Aminothieno[3,4-c]pyrazoles 3a–l; General Pro-
cedure:
A solution of the appropriate hydrazine hydrochloride (11 mmol) and
4-cyano-3-oxotetrahydrothiophene (1) (10 mmol) in EtOH (40 mL) was

SYNTHESIS
September 1998
1333
Scheme 2
refluxed for 1 h, concentrated under reduced pressure and the residue sol-
ubilized in water. The cooled solution (0°C) was basified to pH 10 with
5% NaOH, the precipitate filtered and recrystallized (EtOH/water).
2-Substituted 3-(Acetylamino)-2,6-dihydro-4H-thieno[3,4-
c]pyrazoles 5a, 5e, and 5k; General Procedure:
Acetyl chloride (0.5 mL, 6 mmol) was added dropwise to a solution
of 3a, 3e, or 3k (5 mmol) and triethylamine (0.84 mL, 6 mmol) in
anhyd CH2Cl2 (5 mL). The solution was stirred for 1 h at r.t., diluted
with CH2Cl2 (5 mL), washed with 5% HCl (5 mL) and then with sat.
NaHCO3 (5 mL). The organic layer was dried (Na2SO4) and evapo-
rated to give a solid which was purified by crystallization (EtOAc/
petroleum ether).
4-(2-Phenylhydrazino)-2,5-dihydrothiophene-3-carbonitrile (4):
To 4-cyano-3-oxotetrahydrothiophene (1) (1.27 g, 10 mmol) in
EtOH (10 mL) was added phenylhydrazine (1.08 g, 10 mmol) and
the resulting solution refluxed for 6 h. Then, EtOH was removed
under reduced pressure and the residue, after dilution with 5%
NaOH (10 mL) was extracted with EtOAc (3 × 20 mL). The recom-
bined organic layers were dried (Na2SO4) and concentrated in vac-
uo. The residue was purified by column chromatography (silica gel,
Et2O/petroleum ether 1:2) to give 4 (930 mg, 43%); mp 130–131°C;
and 3-amino-2-phenylthieno[3,4-c]pyrazole (3a) (930 mg, 43%) as
a yellow solid.
3-(Acetylamino)-2-phenyl-2,6-dihydro-4H-thieno[3,4-c]pyrazole
(5a): white solid; yield: 92%; mp 229–230°C.
1H NMR (CDCl3): δ = 2.00 (s, 3H), 3.85 (s, 2H), 3.90 (s, 2H), 7.24–
7.41 (m, 5H), 9.13 (s, 1H).
IR (KBr): ν = 3176, 2977, 1661, 1540, 1504, 1452, 1370, 1278 cm–1.
1H NMR (CDCl3): δ = 3.2–3.6 (m, 4H), 6.1 (bs, 1H), 6.8 (bs, 1H),
7.2–7.6 (m, 5H).
3-(Acetylamino)-2-(4-chlorophenyl)-2,6-dihydro-4H-thieno[3,4-
c]pyrazole (5e): brown solid; yield: 84%; mp 170–171°C.
1H NMR (CDCl3): δ = 2.24 (s, 3H), 3.82 (s, 2H), 4.09 (s, 2H), 7.25 (d,
2H, J = 8.8 Hz), 7.42 (d, 2H, J = 8.8 Hz), 9.21 (s, 1H).
IR: ν = 3100, 2200, 1650, 1610 cm–1.
IR (KBr): ν = 1726, 1498, 1410, 1368, 1248, 1210, 1000 cm–1.
3-Amino-2,6-dihydro-2-phenyl-4H-thieno[3,4-c]pyrazole (3a)
From 4:
3-(Acetylamino)-2-butyl-2,6-dihydro-4H-thieno[3,4-c]pyrazole (5k):
yellow solid; yield: 78%; mp 65–66°C.
To a stirred solution of 4 (651 mg, 3 mmol) in EtOH (10 mL) was
added 5% HCl (0.5 mL) and the system refluxed for 1 h. Then, the
solvent was removed in vacuo and the residue poured into water
(10 mL), the resulting solution was carefully basified at 0°C with 5%
aq NaOH. The solid which separated was collected and recrystallized
(EtOH/water) to provide 596 mg (90%) of 3a.
1H NMR (CDCl3): δ = 0.92 (t, 3H, J = 7.2 Hz), 1.36 (m, 2H), 1.80 (m,
2H), 2.33 (s, 3H), 3.75 (s, 2H), 3.75 (t, 2H, J = 7.2 Hz), 4.01 (s, 2H),
9.15 (s, 1H).
IR (KBr): ν = 2960, 1729, 1706, 1596, 1465, 1397, 1371, 1314, 1220,
1015 cm–1.

SYNTHESIS
Papers
1334
2-Substituted 3-(Acetylamino)-2,6-dihydro-4H-thieno[3,4-
c]pyrazole 5,5-Dioxides 6a, 6e, and 6k; General Procedure:
To a solution of the sulfide 5a, 5e, or 5k (1 mmol) in CH2Cl2 (10 mL)
at 0 ˚C was added 55% m-CPBA (616 mg, 2.5 mmol) and the mixture
stirred at r.t. for 1 h. The mixture was diluted with CH2Cl2 (10 mL)
and washed with sat. aq NaHCO3 (3 × 10 mL) and sat. aq Na2S2O3
(3 × 10 mL). The organic layer was dried (MgSO4) and concentrated
under reduced pressure to give 6a, 6e, or 6k, respectively.
3-(Acetylamino)-2-alkyl/aryl-6-phenyl-2,4a,7a,8-tetrahydropyr-
azolo[3,4-f]isoindoles-5,7(4H,6H)-dione 9a, 9e, and 9k; General
Procedure:
Following the general procedure used for the synthesis of the com-
pound 8a, 8e, and 8k, starting from a solution of 6a, 6e, and 6k
(1 mmol), N-phenylmaleimide (346 mg, 2 mmol) in 1,2,4-trichlo-
robenzene (10 mL) which was refluxed for 1 h, after workup, the res-
idue was purified by column chromatography (silica gel, EtOAc) to
give the products 9a, 9e, and 9k, respectively.
3-(Acetylamino)-2-phenyl-2,6-dihydro-4H-thieno[3,4-c]pyrazole
5,5-Dioxide (6a): yellow solid; yield: 86%; mp 220–225°C.
1H NMR (CDCl3): δ = 2.00 (s, 3H), 4.25 (s, 2H), 4.47 (s, 2H), 7.44–
7.53 (m, 5H), 10.3 (s, 1H).
3-(Acetylamino)-2,6-diphenyl-2,4a,7a,8-tetrahydropyrazolo[3,4-f]-
isoindoles-5,7(4H,6H)-dione (9a): yellow solid; yield: 71%; mp 137–
140°C.
IR (KBr): ν = 3185, 1666, 1508, 1376, 1323, 1273, 1217, 1132 cm–1.
1H NMR (DMSO-d6): δ = 1.99 (s, 3H), 2.81 (2 overlapping dd, 2H, J
= 14.6 Hz), 3.00 (2 overlapping dd, 2H, J = 14.6 and 6 Hz), 3.47 (m,
1H), 3.60 (m, 1H), 7.11 (d, 2H, J = 7.4 Hz), 7.33–7.46 (m, 8H), 9.87
(s, 1H).
3-(Acetylamino)-2-(4-chlorophenyl)-2,6-dihydro-4H-thieno[3,4-
c]pyrazole 5,5-Dioxide (6e): yellow solid; yield: 76%; mp 205–
207°C.
IR (KBr): ν = 3248, 1709, 1597, 1503, 1381, 1177 cm–1.
1H NMR (CDCl3): δ = 2.28 (s, 3H), 4.18 (s, 2H), 4.40 (s, 2H), 7.26 (d,
2H, J = 8.1 Hz), 7.45 (d, 2H, J = 8 Hz), 9.15 (s, 1H).
IR (KBr): ν = 1732, 1497, 1373, 1326, 1210, 1196, 1125 cm–1.
3-(Acetylamino)-2-(4-chlorophenyl)-6-phenyl-2,4a,7a,8-tetrahydro-
pyrazolo[3,4-f]isoindoles-5,7(4H,6H)-dione (9e): white solid; yield:
58%; mp 95°C.
3-(Acetylamino)-2-butyl-2,6-dihydro-4H-thieno[3,4-c]pyrazole 5,5-
Dioxide (6k): white solid; yield: 84%; mp 122–125°C.
1H NMR (CDCl3): δ = 0.93 (t, 3H, J = 7.2 Hz), 1.36 (m, 2H), 1.80 (m,
2H), 2.31 (s, 3H), 3.84 (t, 2H, J = 7.4 Hz), 4.09 (s, 2H), 4.31 (s, 2H),
9.23 (s, 1H).
1H NMR (DMSO-d6): δ = 2.01 (s, 3H), 2.83 (dd, 2H, J = 15.8 and
7.6 Hz), 3.10 (dd, 2H, J = 15.6 and 7.6 Hz), 3.35 (m, 1H), 3.56 (m,
1H), 7.10 (d, 2H, J = 7.6 Hz), 7.34 (d, 2H, J = 8.6 Hz), 7.42 (d, 2H, J
= 8.4 Hz), 7.54 (m, 3H), 10.30 (s, 1H).
IR (KBr): ν = 3417, 1726, 1534, 1410, 1332, 1210 cm–1.
IR (KBr): ν = 2968, 1736, 1701, 1605, 1372, 1307, 1216, 1129 cm–1.
3-(Acetylamino)-2-butyl-6-phenyl-2,4a,7a,8-tetrahydropyrazo-
lo[3,4-f]isoindoles-5,7(4H,6H)-dione (9k): colorless oil; yield: 52%.
1H NMR (DMSO-d6): δ = 0.88 (t, 3H, J = 7.2 Hz), 1.10 (m, 2H), 1.69
(m, 2H), 2.07 (s, 3H), 2.83 (dd, 2H, J = 15.8 and 7.6 Hz), 3.10 (dd,
2H, J = 15.6 and 7.6 Hz), 3.35 (m, 1H), 3.56 (m, 1H), 4.04 (t, 2H, J =
7 Hz), 7.23 (m, 5H), 10.30 (s, 1H).
Diethyl 3-(Acetylamino)-2-alkyl/aryl-4,5,6,7-tetrahydro-2H-ind-
azole-5,6-dicarboxylates 8a, 8e, and 8k; General Procedure:
A mixture of 6a, 6e, and 6k (1 mmol) and diethyl fumarate (344 mg,
2 mmol) in 1,2,4-trichlorobenzene (5 mL) was heated to reflux for
1 h. Then, the cooled mixture was concentrated in vacuo and the res-
idue purified by column chromatography (silica gel, EtOAc) to give
the products 8a, 8e, and 8k, respectively.
IR (neat): ν = 3426, 1715, 1598, 1500, 1393, 1311, 1211, 1116 cm–1.
We wish to thank Ministero Università e Ricerca Scientifica
(MURST) (40 and 60%) for the financial support of this work.
Diethyl trans-3-(Acetylamino)-2-phenyl-4,5,6,7-tetrahydro-2H-inda-
zole-5,6-dicarboxylate (8a): yellow solid; yield: 68%; mp 174–
175°C.
1H NMR (DMSO-d6): δ = 1.20 (dt, 6H, J = 7 Hz), 1.97 (s, 3H), 2.5–
2.8 (m, 2H), 2.90–3.20 (m, 4H), 4.11 (dq, 4H), 7.46–7.60 (m, 5H),
9.86 (s, 1H).
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IR (KBr): ν = 3259, 1671, 1505, 1378, 1183, 1151 cm–1.
Diethyl trans-3-(Acetylamino)-2-(4-chlorophenyl)-4,5,6,7-tetrahy-
dro-2H-indazole-5,6-dicarboxylate (8e): white solid; yield: 62%; mp
252°C.
1H NMR (DMSO-d6): δ = 1.18 (dt, 6H, J = 7 Hz), 2.00 (s, 3H), 2.70–
3.20 (m, 6H), 7.22 (d, 2H, J = 7.2 Hz), 7.38 (d, 2H, J = 7.4 Hz), 10.3
(s, 1H).
IR (KBr): ν = 3267, 1657, 1485, 1367, 1212, 1145 cm–1.
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569.
(11) Baraldi, P. G.; Cacciari, B.; Manfredini, S.; Pollini, G. P.; Simo-
ni, D.; Spalluto, G.; Zanitato, V. J. Org. Chem. 1995, 60, 1461.
(12) Unpublished results.
Diethyl trans-3-(Acetylamino)-2-butyl-4,5,6,7-tetrahydro-2H-inda-
zole-5,6-dicarboxylate (8k): yellow oil; yield: 48%.
1H NMR (DMSO-d6): δ = 0.87 (t, 3H, J = 7.2 Hz), 1.13 (m, 8H), 1.66
(m, 2H), 2.07 (s, 3H), 2.7–3.3 (m, 6H), 4.00–4.20 (m, 6H), 10.15 (s,
1H).
IR (neat): ν = 3234, 1732, 1673, 1538, 1392, 1323, 1211, 1132 cm–1.