Reaction of 3-arylmethylidene-3h-furan- 2-ones with 3-amino-1,2,4-triazole as a convenient technique to synthesize condensed diazepinones

Article abstract of DOI:10.1080/00397911.2010.502989

The interaction of the arylmethylidene derivatives of 3H-furan-2-ones with 3-amino-1,2,4-triazole was studied. The structure of the final products depends on reaction conditions and reagent ratio. Copyright

Full text of DOI:10.1080/00397911.2010.502989

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Reaction of 3-Arylmethylidene-3H-
furan-2-ones with 3-Amino-1,2,4-
triazole as a Convenient Technique to
Synthesize Condensed Diazepinones
T. V. Anis'kova a , V. V. Chadina b & A. Y. Yegorova a
a Saratov State University, Saratov, Russian Federation
b Engels Technological Institute of Saratov State Polytechnical
University, Engels, Russian Federation
Published online: 25 May 2011.
To cite this article: T. V. Anis'kova , V. V. Chadina & A. Y. Yegorova (2011) Reaction of 3-
Arylmethylidene-3H-furan-2-ones with 3-Amino-1,2,4-triazole as a Convenient Technique
to Synthesize Condensed Diazepinones, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 41:15, 2315-2322, DOI:
10.1080/00397911.2010.502989
To link to this article: http://dx.doi.org/10.1080/00397911.2010.502989
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Synthetic Communications1, 41: 2315–2322, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.502989
REACTION OF 3-ARYLMETHYLIDENE-3H-FURAN-
2-ONES WITH 3-AMINO-1,2,4-TRIAZOLE AS A
CONVENIENT TECHNIQUE TO SYNTHESIZE
CONDENSED DIAZEPINONES
T. V. Anis’kova,1 V. V. Chadina,2 and A. Y. Yegorova1
1Saratov State University, Saratov, Russian Federation
2Engels Technological Institute of Saratov State Polytechnical University,
Engels, Russian Federation
GRAPHICAL ABSTRACT
Abstract The interaction of the arylmethylidene derivatives of 3H-furan-2-ones with
3-amino-1,2,4-triazole was studied. The structure of the final products depends on reaction
conditions and reagent ratio.
Keywords 3-Amino-1,2,4-triazole; diazepin-5-one; 3H-furan-2-ones
INTRODUCTION
The arylmethylidene derivatives of 3H-furan-2-ones are interesting mainly as
intermediate compounds combining the properties of internal esters and a,b-
unsaturated carbonylic compounds. They are capable of reacting with substances
having mobile hydrogen atoms.
The structure of the compounds determines the possibility of their interaction
with various binucleophilic reagents, which can proceed with opening of the lactonic
Received February 2, 2010.
Address correspondence to T. V. Anis’kova, Saratov State University, 83 Astrakhanskaya Str.,
410012 Saratov, Russian Federation. E-mail: aniskovatv@mail.ru
2315

2316
T. V. ANIS’KOVA, V. V. CHADINA, AND A. Y. YEGOROVA
cycle, formation of amides and hydrazides of substituted 4-oxoalkane acids, their
cyclic amides, and other recyclization products.
Michael’s condensation,[1] and interactions with electrophilic[2] and nucleophi-
lic reagents[3] were studied in the 3-arylmethylene-3H-furan-2-on series earlier.
The compounds, which incorporate a triazole ring, have a wide range of prac-
tical applications.[4] Introduction of this fragment into the structure of synthesized
compounds considerably expands the application areas of the compounds for the
first time.
RESULTS AND DISCUSSION
The interaction of furanones with triazole was carried out at an equimolar
reagent ratio, while boiling in a solution of ethanol. Aminotriazole was introduced
into the reaction gradually.
The ratio of interaction reagents, by the use of the equimolar ratio of reagents,
led to the formation of structures, which, according to elementary analysis, infrared
(IR), and NMR spectroscopy, were identified as triazolodiazepinones 2a–e.
=
The absorption band of a multiple C C bond conjugated with a carbonylic
=
group within 1630–1590 cmꢀ1, the absorption band of a C C bond within
1668–1660 cmꢀ1, the absorption band of a C O bond within 1680–1670 cmꢀ1, valent
=
oscillation of the NH group located within 3100–3080 cmꢀ1, and oscillations of an
aromatic ring noted within 1525–1485 cmꢀ1 are observed in the IR spectra of com-
pounds 2a–e.
The 1H NMR spectra of compounds 2a–e contain a set of signals to completely
confirm the hypothesized structure; namely, the singlet of a proton at C6 of the
diazepinone ring is located within 6.74–6.86 ppm, the singlet of a proton of a
exocyclic sp2-hybridized carbon atom is noted within 7.31–7.54 ppm, the proton of
the NH group is observed within 8.46–8.86 ppm, and the protons of aromatic rings
lay within 6.92–8.24 ppm.
Additional evidence of the structure has been made on the basis of the 13C NMR
spectra. In the spectra of compounds 2a–e noted are the signal of the carbon atom of a
carbonylic group within 168.4–169.4 ppm, the signal of a sp2-hybridized carbon atom
of a diazepinone ring within 99.1–99.8 ppm, and the signal of a sp2-hybridized carbon
atom of the triazole ring within 159.1–161.6 ppm. The carbon atoms of the aromatic
fragments are shown by a series of signals within 105.7–149.7 ppm.
Probably at the first stage, the most basic center of aminotriazole is attacked by
the carbon atom of the carbonylic group, which results in opening of the lactone
ring. Stabilization of the intermediate formed is possible by several directions,
including by attacking the unshared electronic pair of the nitrogen atom by the car-
bon atom of the carbonylic group with subsequent heterocyclization, which led to
formation of diazepinone structures 2a–e. Other possible ways of heterocyclization
[(attacking the amide nitrogen atom by the carbonylic group to form substituted
pyrrol-2-ones (structure A) and attacking the nitrogen atom of the triazole ring by
=
the multiple C C bond to form structure B)] are not realized.
=
We did not exclude initial addition of the triazol ring by the multiple C C
bond and subsequent heterocyclization resulting in formation of structure C;
however, this direction of the reaction is not realized as well.

SYNTHESIS OF DIAZEPINONES
2317
Furanones were introduced into the reaction with excessive triazole. The inter-
action was carried out at room temperature by mixing the components in an alcohol
solution for 1 h.
1
As a result, the products obtained were characterized according to IR and H
NMR spectroscopy as butanamide 3a, f–i.
In the IR spectra of compounds 3a, f–i, the absorption bands within
3418–3318 cmꢀ1 characteristic of NH group oscillations, 3229–3226 cmꢀ1 of imino
group oscillations, 1655–1643 cmꢀ1 of C O group oscillations (‘‘amide I’’), and
=
1564–1539 cmꢀ1 (‘‘amide II’’) are noted.
The 1H NMR spectra of compounds 3a, f–i contain the singlet of the protons of
the methylene link located within 1.98–2.13 ppm, the singlet of the NH group of the
amide fragment noted within 8.53–8.97 ppm, two singlets of the NH groups of the tria-
zole rings within 7.85–8.31 ppm, the singlet of the arylmethylene fragment located
within 6.75–6.93 ppm, and a series of signals of aromatic protons within 6.92–7.54 ppm.
The 13C NMR spectra contain a signal of the sp3-hybridized carbon atom of
the CH2 group within 19.8–25.7 ppm, the sp2-hybridized carbon atom of the imino
group located within 167.1–168.4 ppm, an sp2-hybridized amide carbon atom noted
within 168.5–170.1 ppm, the signal of sp2-hybridized carbon atoms of triazole rings
within 159.3–163.5 ppm, and a series of signals of sp2-hybridized carbon atoms of
aromatic rings within 99.8–155.3 ppm.
Probably, opening of the lactone ring and addition of a second triazole mol-
ecule by the free keto group proceed simultaneously and led to formation of com-
pounds 3a, f–i.
The reaction stops at the stage of formation of compounds 3a, f–i, Owing to
the low reactivity of the functional groups and steric hindrances, none of the possible
cyclization directions is realized.
Thus, the interaction of furanones with triazole was studied. The structure of
the products depends on reaction conditions and reagent ratio.
EXPERIMENTAL
IR spectra were registered on a Specord (Germany) device, the spectral range
being 400–4000 cmꢀ1 (in a KBr tablet). 1H NMR spectra were recorded on a Varian
400 spectrometer (400 MHz) in CDCl3, with tetramethylsilane (TMS) as the internal
standard. 13C NMR spectra were recorded on a Varian 400 spectrometer (100 MHz)
in CDCl3, with TMS as the internal standard.
5-Aryl-3-arylmethylidene-3H-furan-2-ones were obtained according to the
known technique.[5]
Synthesis of 6-Arylmethylene-8-R-4H-[1,2,4]triazolo-
[1,5-a][1,3]diazepin-5(6H)-one (2)
5-Aryl-3-arylmethylidene-3H-furan-2-one (0.01 mol) in ethanol (15 mL) is
placed into a 50-mL flat-bottomed flask supplied with a dropping funnel. The reac-
tion mixture is mixed and heated at direct introduction (through the dropping
funnel) of an ethenol solution of 3-amino-1,2,4-triazol. The reaction is stopped when
5-aryl-3-arylmethylene-3H-furan-2-one stain on thin-layer chromatography (TLC)

2318
T. V. ANIS’KOVA, V. V. CHADINA, AND A. Y. YEGOROVA
vanishes. The excessive solvent is evaporated. The crystals obtained are recrystallized
from isopropyl alcohol.
6-[(3,4-Dimethoxyphenyl)methylidene]-8-(4-methylphenyl)-4H-
[1,2,4]triazolo[1,5-a][1,3]diazepin-5(6H)-one (2a)
Yield: 83%, mp 158–160 ꢁC. Anal. calcd. for C22H20N4O3: C, 68.03; H, 5.19; N,
1
14.42. Found: C, 67.81; H, 5.59; N, 14.35. H NMR (400 MHz, CDCl3): d 2.38 (s,
3H), 3.86 (s, 6H), 6.74 (s, 1H), 6.95–7.26 (m, 7H), 7.31 (s, 1H), 8.64 (s, 1H). 13C
NMR (100 MHz, CDCl3,): d 26.0, 56.3, 56.4, 99.3, 105.7, 108.7, 114.9, 121.3,
121.4, 125.8, 125.9, 129.1, 131.5, 133.9, 134.8, 136.4, 148.6, 149.7, 161.6, 169.4.
6-(4-Methylphenyl)-8-[(2-nitrophenyl)methylidene]-4H-
[1,2,4]triazolo[1,5-a][1,3]diazepin-5(6H)-one (2b)
Yield: 76%, mp 143–145 ꢁC. Anal. calcd. for C20H15N5O3: C, 64.34; H, 4.05; N,
1
18.76. Found: C, 64.12; H, 4.44; N, 18.69. H NMR (400 MHz, CDCl3): d 2.41 (s,
3H), 6.86 (s, 1H), 7.26–8.24 (m, 8H), 7.36 (s, 1H), 8.46 (s, 1H). 13C NMR
(100 MHz, CDCl3): d 21.3, 99.8, 120.3, 121.8, 122.5, 123.7, 126.9, 127.2, 128.4,
129.1, 129.5, 131.7, 132.7, 138.4, 140.7, 148.7, 159.1, 168.8.
6-[(4-Hydroxy-3-methoxyphenyl)methylidene]-8-(4-methylphenyl)-
4H-[1,2,4]triazolo[1,5-a][1,3]diazepin-5(6H)-one (2c)
Yield: 86%, mp 149–151 ꢁC. Anal. calcd. for C21H18N4O3: C, 67.37; H, 4.85; N,
1
14.96. Found: C, 67.51; H, 4.59; N, 14.75. H NMR (400 MHz, CDCl3): d 2.38 (s,
3H), 3.89 (s, 3H), 5.12 (s, 1H), 6.83 (s, 1H), 6.96–7.34 (m, 8H), 7.40 (s, 1H), 8.54
(s, 1H). 13C NMR (100 MHz, CDCl3): d 34.0, 58.6, 99.1, 109.4, 115.5, 123.7,
125.8, 127.9, 129.3, 130.3, 132.6, 133.7, 135.7, 136,8, 138.9, 143.8, 148.7, 159.3, 168.4.
6-[(2-Nitrophenyl)methylidene]-8-phenyl-4H-[1,2,4]triazolo-
[1,5-a][1,3]diazepin-5(6H)-one (2d)
Yield: 84%, mp 143–145 ꢁC. Anal. calcd. for C19H13N5O3: C, 63.51; H, 3.65; N,
1
19.49. Found: C, 63.35; H, 3.43; N, 19.85. H NMR (400 MHz, CDCl3): d 6.78 (s,
1H), 6.92–7.24 (m, 9H), 7.52 (s, 1H), 8.68 (s, 1H). 13C NMR (100 MHz, CDCl3):
d 99.5, 108.6, 113.7, 113.8, 127.5, 127.6, 128.1, 128.9, 129.9, 131.6, 133.7, 134.8,
136.2, 138,9, 142.4, 145.8, 149.7, 160.7, 168.9.
6-[(2-Chlorophenyl)methylidene]-8-phenyl-4H-[1,2,4]triazolo-
[1,5-a][1,3]diazepin-5(6H)-one (2e)
Yield: 86%, mp 145–147 ꢁC. Anal. calcd. for C19H13ClN4O: C, 65.43; H, 3.76;
N, 16.06. Found: C, 65.74; H, 3.65; N, 15.95. 1H NMR (400 MHz, CDCl3): d 6.75 (s,
1H), 7.03–7.25 (m, 9H), 7.54 (s, 1H), 8.86 (s, 1H). 13C NMR (100 MHz, CDCl3): d
99.7, 107.5, 116.6, 116.7, 126.3, 126.4, 126.8, 127.6, 128.9, 131.5, 132.0, 134.4, 136.4,
136.9, 140.5, 142.3, 147.3, 161.5, 168.5.

SYNTHESIS OF DIAZEPINONES
2319
Synthesis of 2-Arylmethylene-N-1H-1,2,4-triazol-5-yl-4-R-4-(1H-
1,2,4-triazol-5-ylimino)butanamide (3)
5-Aryl-3-arylmethylidene-3H-furan-2-one (0.01 mol) and 3-amino-1,2,4-
triazole (0.02 mol) are placed into a 50-mL flat-bottomed flask. The reaction mixture
is mixed in 15 mL of ethanol at room temperature for 2 h. The precipitated crystals
are filtered and recrystallized from ethanol.
2-[(3,4-Dimethoxyphenyl)methylidene]-N-1H-1,2,4-triazol-5-yl-
4-(4-methylphenyl)-4-(1H-1,2,4-triazol-5-ylimino)butanamide (3a)
Yield: 89%, mp 138–140 ꢁC. Anal. calcd. for C24H24N8O3: C, 61.01; H, 5.12; N,
1
23.72. Found: C, 61.24; H, 4.89; N, 24.0 5. H NMR (400 MHz, CDCl3): d 2.02 (s,
2H), 2.35 (s, 3H), 3.76 (s, 6H), 6.83 (s, 1H), 6.92–7.54 (m, 9H), 8.17 (s, 1H), 8.30 (s,
1H), 8.31 (s, 1H), 8.94 (s, 1H). 13C NMR (100 MHz, CDCl3): d 19.8, 24.3, 50.4, 50.5,
105.8, 106.1, 115.8, 118.5, 119.5, 120.9, 122.4, 123.8, 128.5, 132.1, 135.6, 138.1, 146.0,
146.8, 155.3, 159.3, 167.1, 168.5.
2-[(2-Nitrophenyl)methylidene]-N-1H-1,2,4-triazol-5-yl-
4-[(4-methoxyphenyl)-4-(1H-1,2,4-triazol-5-ylimino)butanamide (3f)
Yield: 93%, mp 178–180 ꢁC. Anal. calcd. for C22H19N9O4: C, 55.81; H, 4.05; N,
1
26.63. Found: C, 56.12; H, 4.50; N, 26.15. H NMR (400 MHz, CDCl3): d 1.98 (s,
2H), 3.82 (s, 3H), 6.93 (s, 1H), 7.02–7.34 (m, 10H), 7.62 (s, 1H), 7.85 (s, 1H), 7.86
(s, 1H), 8.53 (s, 1H). 13C NMR (100 MHz, CDCl3): d 20.3, 53.4, 102.3, 104.5,
105.6, 114.1, 115.3, 117.5, 122.1, 125.3, 127.5, 131.2, 134.5, 138.5, 144.9, 145.3,
153.5, 162.3, 168.4, 170.1.
2-[(3,4-Dimethoxyphenyl)methylidene]-N-1H-1,2,4-triazol-5-yl-
4-phenyl-4-(1H-1,2,4-triazol-5-ylimino)butanamide (3g)
Yield: 79%, mp 152–154 ꢁC. Anal. calcd. for C23H22N8O3: C, 60.25; H, 4.84; N,
1
24.44. Found: C, 60.49; H, 4.56; N, 24.65. H NMR (400 MHz, CDCl3): d 2.12 (s,
2H), 3.76 (s, 6H), 6.86 (s, 1H), 6.97–7.50 (m, 10H), 8.06 (s, 1H), 8.23 (s, 1H), 8.24
(s, 1H), 8.95 (s, 1H). 13C NMR (100 MHz, CDCl3): d 21.1, 55.1, 55.2, 99.8, 101.3,
101.4, 105.3, 110.7, 110.8, 113.9, 116.8, 120.9, 122.3, 125.7, 128.3, 132.2, 135.5,
142.9, 143.7, 153.7, 163.5, 167.3, 169.9.
2-[(2-Nitrophenyl)methylidene]-N-1H-1,2,4-triazol-5-yl-4-phenyl-4-
(1H-1,2,4-triazol-5-ylimino)butanamide (3h)
Yield: 91%, mp 164–166 ꢁC. Anal. calcd. for C21H17N9O3: C, 56.88; H, 3.86; N,
1
28.43. Found: C, 56.44; H, 3.25; N, 28.57. H NMR (400 MHz, CDCl3): d 2.05 (s,
2H), 6.75 (s, 1H), 6.98–7.48 (m, 11H), 8.13 (s, 1H), 8.15 (s, 1H), 8.28 (s, 1H), 8.90
(s, 1H). 13C NMR (100 MHz, CDCl3,): d 25.7, 102.7, 102.8, 104.6, 105.7, 107.3,
111.7, 112.6, 115.3, 118.4, 126.9, 130.5, 131.4, 138.6, 140.5, 143.8, 147.5, 156.3,
160.5, 167.4, 168.6.

2320
T. V. ANIS’KOVA, V. V. CHADINA, AND A. Y. YEGOROVA
Scheme 1. (a) R ¼ C6H4-CH3-4, Ar ¼ C6H3-OCH3-3,4; (b) R ¼ C6H4-CH3-4, Ar ¼ C6H4-NO2-2;
(c) R ¼ C6H4-CH3-4, Ar ¼ C6H3-OH,OCH3-3,4; (d) R ¼ C6H5, Ar ¼ C6H-NO2-2; (i) R ¼ C6H5,
Ar ¼ C6H4-Cl-2.
2-[(2-Chlorophenyl)methylidene]-N-1H-1,2,4-triazol-5-yl-4-phenyl-4-
(1H-1,2,4-triazol-5-ylimino)butanamide (3i)
Yield: 87%, mp 169–171 ꢁC. Anal. calcd. for C21H17ClN8O3: C, 58.27; H, 3.96;
N, 25.89. Found: C, 58.38; H, 3.54; N, 25.62. 1H NMR (400 MHz, CDCl3): d 2.13 (s,
2H), 6.82 (s, 1H), 6.94–7.53 (m, 11H), 8.24 (s, 1H), 8.25 (s, 1H), 8.31 (s, 1H), 8.97 (s,
1H). 13C NMR (100 MHz, CDCl3,): d 23.6, 100.3, 102.6, 104.8, 104.9, 106.5, 108.5,
Scheme 2. The possible directions of the heterocyclization.

SYNTHESIS OF DIAZEPINONES
2321
=
=
Scheme 3. (a) R C6H4-CH3-4, Ar ¼ C6H3-OCH3-3,4; (f) R C6H4-OCH3-4, Ar ¼ C6H4-NO2-2; (g)
=
=
=
R
C6H5, Ar ¼ C6H3-OCH3-3,4; (h) R C6H5, Ar ¼ C6H4-NO2-2; (i) R C6H5, Ar ¼ C6H4-Cl-2.
111.3, 114.4, 117.1, 122.6, 129.4, 130.6, 136.3, 139.5, 144.7, 148.8, 154.7,162.9,
167.4, 169.6.
ACKNOWLEDGMENT
The work was supported by grants of the President of Russian Federation for
governmental support of young Russian scientists, No. MK-2054.2011.3 and RFBR
No. 10-03-00640a.
REFERENCES
1. (a) Yegorova, A. Y.; Timofeeva, Z. Y. Common and specific features of the Michael con-
densation in the series of 3-R-3H-furan-2-ones. Russ. J. Gen. Chem. 2003, 73, 655–658; (b)
Yegorova, A. Y.; Chadina, V. V. Arylmethylene derivatives of 5-R-3H-furan-2-ones and
N-aryl-5-R-3H-pyrrol-2-ones in reaction with acetylacetone. Chem. Heterocycl. Comp.
2007, 43, 1233–1238; (c) Timofeeva, Z. Y.; Yegorova, A. Y. Michael condensation of
3-arylidene-3H-pyrrol-2-ones and 3-arylidene-3H-furan-2-ones with cyclohexanone. Chem.
Heterocycl. Comp. 2007, 43, 690–694; (d) Anis’kova, T. V.; Yegorova, A. Y.; Chadina, V.
V. Reaction of 5-aryl-3-arylmethylene substituted 3H-furan-2-ones and 3H-pyrrol-2-ones
with acetoacetic ester. Mend. Commun. 2008, 18, 167–168.
2. Yegorova, A. Y.; Sedavkina, V. A. Bromination of 5-substituted 3H-furan-2-ones and
3H-pyrrol-2-ones. Chem. Heterocycl. Comp. 2002, 38, 1319–1323.
3. Kamneva, I. E.; Burukhina, O. V.; Yegorova, A. Y. Ring expansion in 5-aryl-3-arylmethy-
lidenefuran-2-ones by the reaction with ethyl diazoacetate. Russ. Chem. Bull. 2007, 56,
2121–2122.
4. (a) Guile, S. D.; Alcaraz, L.; Birkinshaw, T. N.; Bowers, K. C.; Ebden, M. R.; Furber, M.;
Stocks, M. J. Antagonists of the P2 ꢂ 7 receptor: From lead identification to drug develop-
ment. J. Med. Chem. 2009, 52, 3123–3141; (b) Perez-Medrano, A.; Buckner, S. A.;
Coghlan, M. J.; Gregg, R. J.; Gopalakrishnan, M.; Kort, M. E.; Lynch, J. K.; Scott, V.
E.; Sullivan, J. P.; Whiteaker, K. L.; Carroll, W. A. Design and synthesis of novel cyano-
guanidine ATP-sensitive potassium channel openers for the treatment of overactive blad-
der. Bioorg. Med. Chem. Lett. 2004, 14, 397–400; (c) Zeng, Z.; Hyer, W. S.; Twamley,
B.; Shreeve, J. M. Cyclization of bifunctional 3,5-diamino-1H-1,2,4-triazole-1-carboximi-
damide, 5-amino-3-hydrazinotriazole, and 3,6-diguanidino-1,2,4,5-tetrazine: A one-step
route to fluorinated heteropolycycles. Synthesis 2008, 1775–1782; (d) Baraldi, P. G.;
Cacciari, B.; Spalluto, G.; Bergonzoni, M.; Dionisotti, S.; Ongini, E.; Varani, K.; Borea,
P. A.; Design, P. A. Synthesis, and biological evaluation of a second generation of

2322
T. V. ANIS’KOVA, V. V. CHADINA, AND A. Y. YEGOROVA
pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as potent and selective A2A adenosine
receptor antagonists. J. Med. Chem., 1998, 41, 2126; (e) Marino, J. P.; Fisher, P. W.;
Hofmann, G. A.; Kirkpatrick, R. B.; Janson, C. A.; Johnson, R. K.; Ma, C.; Mattern,
C. M. M.; Meek, T. D.; Ryan, M. D.; Schulz, X. C.; Smith, W. W.; Tew, D. G.; Tomazek,
T. A.; Veber, D. F.; Xiong, W. C.; Yamamoto, Y.; Yamashita, K.; Yang, G.; Thompson, S.
K. Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole phar-
macophore. J. Med. Chem., 2007, 50, 3777–3785.
5. Sedavkina, V. A.; Morozova, N. A.; Yegorova, A. Y.; Ostroumov, I. G. Synthesis of
5-alkyl-3H-thiolen-2-ones and 5-alkyl-3H-furan-2-ones and condensation reactions at the
heterocyclic methylene group. Chem. Heterocycl. Comp., 1987, 23, 377–380.