Synthesis of substituted pyrazolo[1,5- a ]quinoxalines using the reductive cyclization
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1965
Synthesis of substituted pyrazolo[1,5-a]quinoxalines using the reductive cyclization V. A. Panova,а S. A. Ivanovskii,a A. A. Shetnev,а Zh. V. Chirkova,b T. N. Sudzilovskaya,b and S. I. Filimonovb aK.
D. Ushinsky Yaroslavl State Pedagogical University, Pharmaceutical Technology Transfer Center, 108/1 ul. Respublikanskaya, 150000 Yaroslavl, Russian Federation. Fax: +7 (485 2) 30 5661. E-mail: [email protected] bYaroslavl State Technical University, 88 Moskovskii prosp., 150023 Yaroslavl, Russian Federation. Fax: +7 (485 2) 44 0729. E-mail: fi[email protected] New pyrazolo[1,5-a]quinoxalin-4-ones were obtained by reductive cyclization from the corresponding 1-(2-nitroaryl)pyrazole-5-carboxylates. Alternatively, pyrazolo[1,5-a]quinoxalines were prepared from N-hydroxypyrazolo[1,5-a]quinoxalines. Key words: reductive cyclization, N-dehydroxylation, palladium catalysis, pyrazolo[1,5-a]quinoxaline.
Derivatives of pyrazole1 and quinoxaline2—5 are among the most popular compounds in organic chemistry. This is due to the wide range of practical properties exhibited by compounds containing pyrazole6,7 and quinoxaline moieties.8 Less studied class of compounds are pyrazolo[1,5-a]quinoxalines, which exhibit various types of biological activity and are inhibitors of certain human enzymes.9,10 There are several approaches to the synthesis of substituted pyrazolo[1,5-a]quinoxalines;11,12 the simplest method seems to be the reduction of the corresponding 2-nitroarylpyrazole-5-carboxylates using metal catalysis.13 Earlier14 we described a method for the regioselective preparation of N-arylpyrazole-5-carboxylates,1 the reduc-
tion of which with Sn(II) led to substituted N-hydroxypyrazolo[1,5-a]quinoxalin-4-ones 2 (Scheme 1). We have developed a direct method for the synthesis of pyrazolo[1,5-a]quinoxalin-4-ones by reduction of compounds 1 using 10% palladium on carbon (method A). The best results have been achieved using methanol as a solvent at a temperature of 71—73 °C and a hydrogen pressure of 4—5 atm. However, target pyrazolo[1,5-a]quinoxaline 3, obtained by this method, was difficult to separate from the catalyst impurity due to extremely low solubility of the product in organic solvents (satisfactory solubility of compounds 3 was observed only in DMF or DMSO).
Scheme 1
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1965—1970, October, 2020. 1066-5285/20/6910-1965 © 2020 Springer Science+Business Media LLC
1966
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 10, October, 2020
Table 1. Synthesis of NH-pyrazolo[1,5-a]quinoxalines 3 Compound
R1
R2
Yield 3 (%) Method A Method B*
1a, 3a 1b, 3b 1c, 3c 1d, 3d 1e, 3e 1f, 3f 1g, 3g 1h 3h 1i 3i 1j 3j
Ph 4-MeC6H4 4-MeOC6H4 4-ClC6H4 Ph 4-MeC6H4 4-MeOC6H4 Ph Ph 4-MeC6H4 4-MeC6H4 4-MeOC6H4 4-MeOC6H4
COOEt COOEt COOEt COOEt CN CN CN NO2 NH2 NO2 NH2 NO2 NH2
66 69 — 64 — — — — — — 73 — 71
85 (72) 73 (63) 89 (72) 93 (79) 70 (45) 59 (33) 75 (65) — 69 (42) — 59 (39) — 67 (45)
* Yield in two steps is shown in parentheses.
We also carried out the r
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