CN-substituted 4-oxo-4h-pyrido[1,2-a]pyrazines and electrochemical method for their preparation

Abstract

FIELD: agriculture.SUBSTANCE: invention relates to new CN- substituted 4-oxo-4H-pyrido[1,2-a]pyrazines of general formula (I), which have fungicidal activity and can be used in agriculture as fungicidal agents. In formula (I) R1 =alkyl C1-C4, phenyl, 4-FC6H4, 4-OMEC6H4, 4-ClC6H4 or CH2COOEt.EFFECT: invention also relates to a method for producing the said compounds.3 cl, 2 tbl, 9 ex

Description

[0001] The proposed invention relates to the field of organic chemistry, to derivatives of pyrido[1,2-a]pyrazines, specifically to new, undescribed in the literature, CN-substituted 4-oxo-4H-pyrido[1,2-a]pyrazines of the general formula:

[0002] ,

[0003] where R 1 = alkyl C1-C4, phenyl, 4-FC6H4, 4-OMeC6H4, 4-ClC6H4 or CH2COOEt and to the electrochemical method for their preparation. Compounds of formula I have fungicidal activity.

[0004] The synthesized compounds can be used in agriculture as fungicides.

[0005] The literature describes derivatives of oxo-pyrido[1,2-a]pyrazines that have antibacterial (WO 2011031745 A1, 17.03.2011), antiviral (WO 2002004444 A2, 17.01.2002) activity, and are used as inhibitors in the treatment of cardiovascular diseases and cerebrovascular diseases (WO 2024078620 A1, 18.04.2024). In addition, oxo-pyrido[1,2-a]pyrazines are known to be isopropenyl transferase inhibitors (WO 1998050029 A1, 12.11.1998) and are also used to treat diseases or conditions associated with abnormal splicing processes (WO 2021207554 A1, 14.10.2021). However, none of the patents provide data on the fungicidal activity of 4-oxo-pyrido[1,2-a]pyrazine derivatives.

[0006] It was also reported that a saturated heterocyclic compound, 3-isopropylhexahydro-4H-pyrido[1,2-a]pyrazine-1,4(6H)-dione, was isolated from the Bacillus licheniformis QX928 strain of microorganisms. This compound may be one of the first compounds obtained from microorganisms that has antibacterial activity and is a quorum sensing inhibitor (H. Qiu, S. Chen, A. Yin, T. Miao, F. Shen, Y. Li, Y. Xiao, J. Hai, B. Xu, J. Integr. Agric., 2024, DOI: org / 10.1016 / j.jia.2024.04.021).

[0007] An analogue in structure to the claimed CN-substituted 4-oxo-4H-pyrido[1,2-a]pyrazines (I) is methyl 1-(ethoxycarbonyl)-4-oxo-4H-pyrido[1,2-a]pyrazine-3-acetate of formula (V), obtained by a two-stage sequential reaction from ethyl 2-amino-2-(pyridin-2-yl)acetate (II) and dimethyl acetylene diacetate (DMAD) (III). The intermediate enamine (IV) undergoes cyclization in a solution of sodium methoxide in methanol at room temperature, giving product (V) in 75% yield (P. Kolar, M. Tišler, A. Pizzioli, Transformations of the pyrido[1,2-a]pyrazine ring system into imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrimidines and 2-oxa-6a,10c-diazaaceanthrylenes, J. Heterocycl. Chem., 1996, 33, 639–642). The process proceeds according to Scheme 1:

[0008]

[0009] The fungicidal activity of the structural analogue has not been described in the literature. A highly effective systemic fungicide, 1-(4-chlorophenoxy)-3,3-dimethyl-1-(1,2,4-triazol-1-yl)butan-2-one (Triadimefon), is described in the literature for the protection of agricultural crops from powdery mildew and rust. The systemic fungicide Quadris (azoxytrobin)-methyl(2-E)-2-(2-{[6-(2-cyanophenoxy)pyrimidin-4-yl]oxy}phenyl)-3-methoxyprop-2-enoate is also known.

[0010] However, there is no information in the literature on fungicidal activity in the series of substituted 4-oxo-4H-pyrido[1,2-a]pyrazines.

[0011] The technical objective of the present invention is to expand the range of substituted 4-oxo-4H-pyrido[1,2-a]pyrazines, in particular those containing a cyano group at the C-1 atom, and to develop an efficient method for their preparation.

[0012] The stated technical task is achieved by a new, CN-substituted 4-oxo-4H-pyrido[1,2-a]pyrazine of the general formula:

[0013] ,

[0014] where R 1= alkyl C1-C4, phenyl, 4-FC6H4, 4-OMeC6H4, 4-ClC6H4 or CH2COOEt and the method for their preparation.

[0015] The proposed compounds of general formula I are new and for the first time in the series of substituted 4-oxo-4H-pyrido[1,2-a]pyrazines fungicidal activity has been detected.

[0016] An electrochemical method for obtaining CN-substituted 4-oxo-4H-pyrido[1,2-a]pyrazine of general formula I is proposed:

[0017] ,

[0018] where R 1 = alkyl C1-C4, phenyl, 4-FC6H4, 4-OMeC6H4, 4-ClC6H4 or CH2COOEt; consisting in that, pyridine-2-carbaldehyde of the formula:

[0019]

[0020] is reacted with the corresponding α-amino ester of the general formula

[0021] ,

[0022] where R 1has the above values, and the process is carried out in an undivided electrolyzer equipped with a cathode and an anode, in galvanostatic mode in the presence of ammonium thiocyanate in a medium of an aqueous solution of DMSO and pyridine at a temperature of 50-100°C and a current density of 20-27 mA / cm 2 with subsequent isolation of the target product.

[0023] In the proposed method, ammonium thiocyanate is used as the cyanidating agent and electrolyte, and pyridine is used as the base. A glassy carbon plate serves as the anode, and a platinum plate serves as the cathode. The process proceeds according to the following Scheme 2:

[0024]

[0025] The claimed CN-substituted 4-oxo-4H-pyrido[1,2-a]pyrazines of general formula (I) differ from previously published compounds, including compound (V), by the presence of a cyano group at the C-1 atom of the pyrido[1,2-a]pyrazine ring, as well as a convenient one-step electrochemical method for obtaining them from pyridine-2-carbaldehyde, α-aminoesters, and ammonium thiocyanate.

[0026] The present invention provides access to CN-substituted 4-oxo-4H-pyrido[1,2-a]pyrazines in a single step from pyridine-2-carbaldehyde and α-amino esters using electric current for in situ generation of cyanide anions from ammonium thiocyanate and assembly of the heterocyclic framework through a cascade oxidation / cyclization process. The use of electric current and ammonium thiocyanate as a source of [CN] significantly improves the environmental friendliness of the proposed method, since there is no need for aggressive chemical oxidants and toxic cyanating agents such as hydrocyanic acid or its salts. As a result of the reaction, novel, previously undescribed in the literature, heterocycles of general formula I (ai) were obtained in yields ranging from 22 to 43%.

[0027] The obtained CN-substituted 4-oxo-4H-pyrido[1,2-a]pyrazines were tested for fungicidal activity against pathogenic fungi belonging to various taxonomic classes that cause great damage to agriculture and plant production: Venturia inaequalis (Vi); Rhizoctonia solani (Rs), Fusarium oxysporum (Fo), Fusarium moniliforme (Fm), Bipolaris sorokiniana (Bs), Sclerotinia sclerotiorum (Ss), Fusarium culmorum (Fc), Alternaria solani (As), Colletotrichum coccodes (Cc). The effect of the tested compounds on the radial mycelial growth in potato sucrose agar was measured at a concentration of 30 mg / L. Commercially available fungicides Triadimefon and Quadris (azoxytrobin) were used as control compounds (Tables 1, 2).

[0028]

[0029]

[0030]

[0031]

[0032] Among the tested compounds, 4-oxo-4H-pyrido[1,2-a]pyrazine-1-carbonitrile Ic demonstrated the best fungicidal activity, being most effective against four types of fungi (Vi, Rs, Fo, and Bs). Compound Ib showed greater activity than Triadimefon against Rs.

[0033] Based on the experimental data in Tables 1 and 2 obtained for 4-oxo-4H-pyrido[1,2-a]pyrazine-1-carbonitriles containing both alkyl and phenyl substituents, it can be concluded that CN-substituted 4-oxo-4H-pyrido[1,2-a]pyrazines of general formula I, where R 1 =4-FC6H4, 4-OMeC6H4, 4-ClC6H4 will also exhibit fungicidal activity against the studied phytopathogenic fungi.

[0034] Thus, a new class of fungicides, CN-substituted 4-oxo-4H-pyrido[1,2-a]pyrazines, was discovered.

[0035] The obtained results can serve as a basis for the development of fungicidal preparations in agriculture.

[0036] The technical result of the invention is the expansion of the range of substituted 4-oxo-4H-pyrido[1,2-a]pyrazines, the creation of new fungicidal agents based on new compounds of CN-substituted 4-oxo-4H-pyrido[1,2-a]pyrazines of general formula I, exhibiting high fungicidal activity, as well as the development of an electrochemical method for their production.

[0037] The invention can be illustrated by the following examples, which do not limit its scope.

[0038] Example 1. Preparation of 3-methyl-4-oxo-4H-pyrido[1,2-a]pyrazine-1-carbonitrile (Ia)

[0039] The undivided cell was equipped with a glassy carbon anode (3 cm 2 ) and a platinum cathode (3 cm 2) and connected to an adjustable DC power supply. A solution of pyridine-2-carbaldehyde VI (1.0 mmol, 107 mg, 1.0 equiv.), ethyl alaninate VII (2.0 mmol, 234 mg, 2.0 equiv.), NH4SCN (2.0 mmol, 152 mg, 2.0 equiv.), and pyridine (0.5 mmol, 39 mg, 40 μL, 0.5 equiv.) in 10 mL DMSO with H2O (1.0 mmol, 18 μL, 1.0 equiv.) was subjected to DC electrolysis at 50°C with stirring for 214 min at I=60 mA (j=20 mA / cm 2 ). The reaction mixture was then diluted with H2O (30 mL) and washed with a 1:1 mixture of PE and ethyl acetate (2×30 mL). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure using a rotary evaporator (15-20 mmHg) (bath temperature about 30-40°C). Product Ia was isolated by column chromatography on SiO2. 22% (40 mg, 0.22 mmol) solid was obtained, mp 163-164°C. PE / EtOAc = 5:1 to 2:1, R ƒ =0.45 (PE / EtOAc=2:1). 1H NMR (300.13 MHz, CDCl3, δ): δ 8.95 (d, J=7.2 Hz, 1H), 7.90 (d, J=9.0 Hz, 1H), 7.78-7.62 (m, 1H), 7.28 (t, J=7.2 Hz, 1H), 2.58 (s, 3H). 13 WITH{ 1 H} NMR (75.48 MHz, CDCl3, δ): 150.7, 145.3, 138.6, 133.8, 126.9, 122.2, 118.3, 116.3, 103.3, 20.7. High-resolution mass spectrum (ESI-TOF) m / z [M+H] + . Calculated for [C 10 H8N3O] + : 186.0662. Found: 186.0664.

[0040] Preparation of 4-oxo-3-propyl-4H-pyrido[1,2-a]pyrazine-1-carbonitrile (Ib)

[0041] The undivided cell was equipped with a glassy carbon anode (3 cm 2 ) and a platinum cathode (3 cm 2) and connected to an adjustable DC power supply. A solution of pyridine-2-carbaldehyde VI (1.0 mmol, 107 mg, 1.0 equiv.), ethyl 2-aminopentanoate VII (2.0 mmol, 290 mg, 2.0 equiv.), NH4SCN (2.0 mmol, 152 mg, 2.0 equiv.) and pyridine (0.5 mmol, 39 mg, 40 μL, 0.5 equiv.) in 10 mL DMSO with H2O (1.0 mmol, 18 μL, 1.0 equiv.) was subjected to DC electrolysis at 70°C with stirring for 214 min. at I=80 mA (j=27 mA / cm 2 ). The reaction mixture was then diluted with H2O (30 mL) and washed with a 1:1 mixture of PE and ethyl acetate (2×30 mL). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure using a rotary evaporator (15-20 mmHg) (bath temperature about 30-40°C). Product Ib was isolated by column chromatography on SiO2. 24% (52 mg, 0.24 mmol) solid was obtained, mp 112-113°C. PE / EtOAc = 5:1 to 1:1, R ƒ =0.27 (PE / EtOAc=1:1). 1H NMR (300.13 MHz, CDCl3, δ): 8.98 (d, J=7.3 Hz, 1H), 7.93 (d, J=9.0 Hz, 1H), 7.73-7.64 (m, 1H), 7.34-7.17 (m, 1H), 4.2 Hz (J=7.7). 2H), 1.80 (sext, J=7.4 Hz, 2H) 1.03 (t, J=7.4 Hz, 3H). 13 C{ 1 H} NMR (75.48 MHz, CDCl3, δ): 150.5, 148.7, 138.5, 133.7, 127.1, 122.3, 118.2, 116.5, 103.6, 35.6, 20.5, 14.1. High-resolution mass spectroscopy (ESI-TOF) m / z [M+H] + . Calculated for [C 12 H 12 N3] + : 214.0975. Found: 214.0977.

[0042] Example 3. Preparation of 3-butyl-4-oxo-4H-pyrido[1,2-a]pyrazine-1-carbonitrile (Ic)

[0043] The non-split cell was equipped with a glass carbon anode (3 cm 2 ) and a platinum cathode (3 cm 2) and connected to an adjustable DC power supply. A solution of pyridine-2-carbaldehyde VI (1.0 mmol, 107 mg, 1.0 equiv.), ethyl 2-aminohexanoate VII (2.0 mmol, 318 mg, 2.0 equiv.), NH4SCN (2.0 mmol, 152 mg, 2.0 equiv.), and pyridine (0.5 mmol, 39 mg, 40 μL, 0.5 equiv.) in 10 mL DMSO with H2O (1.0 mmol, 18 μL, 1.0 equiv.) was subjected to DC electrolysis at 100°C with stirring for 214 min at I=60 mA (j=20 mA / cm 2 ). The reaction mixture was then diluted with H2O (30 mL) and washed with a 1:1 mixture of PE and ethyl acetate (2×30 mL). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure using a rotary evaporator (15-20 mmHg) (bath temperature about 30-40°C). Product Ic was isolated by column chromatography on SiO2. 34% (77 mg, 0.34 mmol) solid was obtained, mp 114-116°C. PE / EtOAc = 5:1 to 1:1, R ƒ =0.27 (PE / EtOAc=2:1). 1H NMR (300.13 MHz, CDCl3, δ): δ 8.96 (d, J=7.3 Hz, 1H), 7.91 (d, J=9.0 Hz, 1H), 7.76-7.62 (m, 1H), 7.26 (t, J=7.3 Hz, 1H), 2.93 (t, J=7.6 Hz, 2H), 1.72 (quint, J=7.6 Hz, 2H), 1.41 (sext, J=7.6 Hz, 2H), 0.93 (t, J=7.6 Hz, 3H). 13 WITH{ 1 H} NMR (75.48 MHz, CDCl3, δ): 141.2, 137.0, 124.2, 122.2, 117.5, 115.2, 114.6, 101.2, 28.7, 26.3, 22.6, 13.9. High-resolution mass spectrum (ESI-TOF) m / z [M+H] + . Calculated for [C 13 H 14 N3O] + : 228.1131. Found: 228.1125.

[0044] Example 4. Preparation of 3-isobutyl-4-oxo-4H-pyrido[1,2-a]pyrazine-1-carbonitrile (Id)

[0045] The undivided cell was equipped with a glassy carbon anode (3 cm 2 ) and a platinum cathode (3 cm 2) and connected to an adjustable DC power supply. A solution of pyridine-2-carbaldehyde VI (1.0 mmol, 107 mg, 1.0 equiv.), ethyl leucinate VII (2.0 mmol, 318 mg, 2.0 equiv.), NH4SCN (2.0 mmol, 152 mg, 2.0 equiv.), and pyridine (0.5 mmol, 39 mg, 40 μL, 0.5 equiv.) in 10 mL DMSO with H2O (2.0 mmol, 36 μL, 4.0 equiv.) was subjected to DC electrolysis at 70°C with stirring for 214 min at I=60 mA (j=20 mA / cm 2 ). The reaction mixture was then diluted with H2O (30 mL) and washed with a 1:1 mixture of PE and ethyl acetate (2×30 mL). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure using a rotary evaporator (15-20 mmHg) (bath temperature about 30-40°C). Product Id was isolated by column chromatography on SiO2. 28% (64 mg, 0.28 mmol) solids were obtained, mp 130-131°C. PE / EtOAc = 5:1 to 1:1, R ƒ =0.20 (PE / EtOAc=2:1). 1H NMR (300.13 MHz, CDCl3, δ): 8.98 (d, J=7.3 Hz, 1H), 7.93 (d, J=9.0 Hz, 1H), 7.76-7.60 (m, 1H), 7.27 (t, J=7.3 Hz, 1H), 2.84 (d, J=6.7 Hz, 2H), 2.28 (sept, J=6.7 Hz, 1H), 0.98 (d, J=6.7 Hz, 6H). 13 { 1 H} NMR (75.48 MHz, CDCl3, δ): 150.6, 148.1, 138.5, 133.7, 127.2, 122.3, 118.2, 116.5, 103.6, 42.3, 27.3, 22.7. High-resolution mass spectrum (ESI-TOF) m / z [M+H] + . Calculated for [C 13 H 14 N3O] + : 228.1131. Found: 228.1130.

[0046] Example 5. Preparation of 4-oxo-3-phenyl-4H-pyrido[1,2-a]pyrazine-1-carbonitrile (Ie)

[0047] The undivided cell was equipped with a glassy carbon anode (3 cm 2 ) and a platinum cathode (3 cm 2) and connected to an adjustable DC power supply. A solution of pyridine-2-carbaldehyde VI (1.0 mmol, 107 mg, 1.0 equiv.), ethyl 2-amino-2-phenylacetate VII (2.0 mmol, 358 mg, 2.0 equiv.), NH4SCN (2.0 mmol, 152 mg, 2.0 equiv.) and pyridine (0.5 mmol, 39 mg, 40 μL, 0.5 equiv.) in 10 mL DMSO with H2O (1.0 mmol, 18 μL, 1.0 equiv.) was subjected to DC electrolysis at 70°C with stirring for 214 min. at I=60 mA (j=20 mA / cm 2 ). The reaction mixture was then diluted with H2O (30 mL) and washed with a 1:1 mixture of PE and ethyl acetate (2×30 mL). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure using a rotary evaporator (15-20 mmHg) (bath temperature about 30-40°C). Product Ie was isolated by column chromatography on SiO2. 42% (104 mg, 0.42 mmol) solid was obtained, mp 207-208°C. PE / EtOAc = 5:1 to 1:1, R ƒ =0.40 (PE / EtOAc=2:1). 1H NMR (300.13 MHz, CDCl3, δ): δ 9.20 (d, J=7.3 Hz, 1H), 8.41 (dd, J=8.1, 1.7 Hz, 2H), 8.03 (d, J=8.9 Hz, 1H), 7.86-7.70 (m, 1H), 7.55-7.42 (m, 3H), 7.41-7.30 (m, 1H). 13 { 1 H} NMR (75.48 MHz, CDCl3, δ): 149.6, 140.1, 138.8, 135.5, 134.7, 129.9, 128.8, 128.4, 128.1, 122.6, 118.9, 116.3, 104.7. High-resolution mass spectrum (ESI-TOF) m / z [M+H] + . Calculated for [C 15 H 10 N3O] + : 248.0818. Found: 248.0821.

[0048] Example 6. Preparation of 3-(4-fluorophenyl)-4-oxo-4H-pyrido[1,2-a]pyrazine-1-carbonitrile (If)

[0049] The undivided cell was equipped with a glassy carbon anode (3 cm 2 ) and a platinum cathode (3 cm 2) and connected to an adjustable DC power supply. A solution of pyridine-2-carbaldehyde VI (1.0 mmol, 107 mg, 1.0 equiv.), ethyl 2-amino-2-(4-fluorophenyl)acetate VII (2.0 mmol, 394 mg, 2.0 equiv.), NH4SCN (2.0 mmol, 152 mg, 2.0 equiv.), and pyridine (0.5 mmol, 39 mg, 40 μL, 0.5 equiv.) in 10 mL DMSO with H2O (1.0 mmol, 18 μL, 1.0 equiv.) was subjected to DC electrolysis at 70°C with stirring for 214 min at I=60 mA (j=20 mA / cm 2 ). After this, the reaction mixture was diluted with H2O (30 mL) and washed with a mixture of PE and ethyl acetate (1:1) (2×30 mL). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure using a rotary evaporator (15-20 mmHg) (bath temperature about 30-40°C). The product If was isolated by column chromatography on SiO2. Obtained 25% (66 mg, 0.25 mmol), solid, mp 192-193°C. PE / EtOAc = 5:1 to 1:1, R ƒ =0.31 (PE / EtOAc=2:1). 1H NMR (300.13 MHz, DMSO-d6) δ 9.18 (d, J=7.2 Hz, 1H), 8.57-8.25 (m, 2H), 8.18-7.96 (m, 2H), 7.69-7.60 (m, 1H), 7-7.1 (m, 1H). 13 C{ 1 H} NMR (75.48 MHz, DMSO-d6) δ 162.5 (d, J=247.2 Hz), 149.6, 139.2, 136.9, 136.2, 132.2 (d, J=3.3 Hz), 121.9, 120.1, 116.7, 115.0 (d, J=22.2 Hz), 19 F NMR (282.5 MHz, DMSO-d6) δ-112.6. High-resolution mass spectroscopy (ESI-TOF) m / z [M+H] + . Calculated for [C 15 H9FN3O] + : 266.0724. Found: 266.0720.

[0050] Example 7. Preparation of 3-(4-chlorophenyl)-4-oxo-4H-pyrido[1,2-a]pyrazine-1-carbonitrile (Ig)

[0051] The non-split cell was equipped with a glass carbon anode (3 cm 2 ) and a platinum cathode (3 cm 2) and connected to an adjustable DC power supply. A solution of pyridine-2-carbaldehyde VI (1.0 mmol, 107 mg, 1.0 equiv.), ethyl 2-amino-2-(4-chlorophenyl)acetate VII (2.0 mmol, 427 mg, 2.0 equiv.), NH4SCN (2.0 mmol, 152 mg, 2.0 equiv.), and pyridine (0.5 mmol, 39 mg, 40 μL, 0.5 equiv.) in 10 mL DMSO with H2O (1.0 mmol, 18 μL, 1.0 equiv.) was subjected to DC electrolysis at 70°C with stirring for 214 min at I=60 mA (j=20 mA / cm 2 ). The reaction mixture was then diluted with H2O (30 mL) and washed with a 1:1 mixture of PE and ethyl acetate (2×30 mL). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure using a rotary evaporator (15-20 mmHg) (bath temperature about 30-40°C). The product Ig was isolated by column chromatography on SiO2. 23% (65 mg, 0.23 mmol) solid was obtained, mp 168-169°C. PE / EtOAc = 5:1 to 1:1, R ƒ =0.24 (PE / EtOAc=2:1). 1H NMR (300.13 MHz, DMSO-d6, δ): 9.19 (d, J=7.2 Hz, 1H), 8.36 (d, J=8.7 Hz, 2H), 8.17-7.99 (m, 2H), 7.73-7.62 (m, 1H), 7.7.7 Hz (7.8 Hz). 2H). 13 C{ 1 H} NMR (75.48 MHz, DMSO-d6, δ): 149.6, 139.3, 137.3, 135.5, 134.5, 133.6, 129.6, 128.5, 128.2, 122.0, 120.3, 16.7. 103.44.

[0052] High-resolution mass spectrum (ESI-TOF) m / z [M+H] + . Calculated for [C 15 H9ClN3O] + : 282.0429. Found: 282.0431.

[0053] Example 8. Preparation of 3-(4-methoxyphenyl)-4-oxo-4H-pyrido[1,2-a]pyrazine-1-carbonitrile (Ih)

[0054] The non-split cell was equipped with a glass carbon anode (3 cm 2 ) and a platinum cathode (3 cm 2) and connected to an adjustable DC power supply. A solution of pyridine-2-carbaldehyde VI (1.0 mmol, 107 mg, 1.0 equiv.), ethyl 2-amino-2-(4-methoxyphenyl)acetate VII (2.0 mmol, 419 mg, 2.0 equiv.), NH4SCN (2.0 mmol, 152 mg, 2.0 equiv.), and pyridine (0.5 mmol, 39 mg, 40 μL, 0.5 equiv.) in 10 mL DMSO with H2O (1.0 mmol, 18 μL, 1.0 equiv.) was subjected to DC electrolysis at 70°C with stirring for 214 min at I=60 mA (j=20 mA / cm 2 ). The reaction mixture was then diluted with H2O (30 mL) and washed with a 1:1 mixture of PE and ethyl acetate (2×30 mL). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure using a rotary evaporator (15-20 mmHg) (bath temperature about 30-40°C). Product Ih was isolated by column chromatography on SiO2. 36% (100 mg, 0.36 mmol) solids were obtained, mp 228-230°C. PE / EtOAc = 5:1 to 1:1, R ƒ =0.22 (PE / EtOAc=2:1). 1H NMR (300.13 MHz, DMSO-d6, δ): 9.14 (d, J=6.9 Hz, 1H), 8.34 (d, J=8.4 Hz, 2H), 8.04-7.94 (m, 2H), 7.66-7.52 (m, 1H), 7.52 (m, J=6.8 Hz, 2H). 2H), 3.83 (s, 3H). 13 C{ 1 H} NMR (75.48 MHz, DMSO-d6, δ): 160.1, 149.6, 138.7, 137.6, 136.0, 129.6, 128.2, 128.0, 121.8, 119.7, 16.9, 13.0, 13.6. 55.2. High-resolution mass spectroscopy (ESI-TOF) m / z [M+H] + . Calculated for [C 16 H 12 N3O2] + : 278.0924 Found: 278.0916.

[0055] Example 9. Preparation of Ethyl 2-(1-cyano-4-oxo-4H-pyrido[1,2-a]pyrazine-3-yl)acetate (Ii)

[0056] The non-split cell was equipped with a glass carbon anode (3 cm 2 ) and a platinum cathode (3 cm 2) and connected to an adjustable DC power supply. A solution of pyridine-2-carbaldehyde VI (1.0 mmol, 107 mg, 1.0 equiv.), diethyl aspartate VII (2.0 mmol, 378 mg, 2.0 equiv.), NH4SCN (2.0 mmol, 152 mg, 2.0 equiv.), and pyridine (0.5 mmol, 39 mg, 40 μL, 0.5 equiv.) in 10 mL DMSO with H2O (1.0 mmol, 18 μL, 1.0 equiv.) was subjected to DC electrolysis at 70°C with stirring for 214 min at I=60 mA (j=20 mA / cm 2 ). The reaction mixture was then diluted with H2O (30 mL) and washed with a 1:1 mixture of PE and ethyl acetate (2×30 mL). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure using a rotary evaporator (15-20 mmHg) (bath temperature about 30-40°C). Product Ii was isolated by column chromatography on SiO2. 43% (111 mg, 0.43 mmol) solid was obtained, mp 150-151°C. PE / EtOAc = 3:1 to 1:1, R ƒ =0.30 (PE / EtOAc=2:1). 1H NMR (300.13 MHz, CDCl3, δ): δ 9.04 (d, J=7.2 Hz, 1H), 8.01 (d, J=9.0 Hz, 1H), 7.87-7.77 (m, 1H), 7.43-7.33 (m, 1H), 4.22 (k, 7.1 Hz, 2H), 3.99 (s, 2H), 1.29 (t, J=7.1 Hz, 3H). 13 { 1 H} NMR (75.48 MHz, CDCl3, δ): 169.5, 163.1, 150.4, 140.6, 139.3, 135.0, 127.4, 122.4, 118.9, 116.0, 103.9, 61.4, 39.8, 14.3. High-resolution mass spectrum (ESI-TOF) m / z [M+H] + . Calculated for [C 13 H 13 N3O3] + : 258.0873. Found: 258.0879.

Claims

1. CN-substituted 4-oxo-4H-pyrido[1,2-a]pyrazine of the general formula , where R 1 =alkyl C1-C4, phenyl, 4-FC6H4, 4-OMeC6H4, 4-ClC6H4 or CH2COOEt.

2. The compound according to claim 1 of the general formula , where R 1 =methyl, propyl, butyl, isobutyl, phenyl or CH2COOEt, which has fungicidal activity.

3. A method for obtaining CN-substituted 4-oxo-4H-pyrido[1,2-a]pyrazine according to paragraphs 1, 2 of the general formula , where R 1 =alkyl C1-C4, phenyl, 4-FC6H4, 4-OMeC6H4, 4-ClC6H4 or CH2COOEt, consisting in the fact that pyridine-2-carbaldehyde of the formula react with the corresponding α-amino ester of the general formula , where R 1has the above values, and the process is carried out in an undivided electrolyzer equipped with a platinum cathode and a glassy carbon anode, in galvanostatic mode in the presence of ammonium thiocyanate in a medium of an aqueous solution of DMSO and pyridine at a temperature of 50-100°C and a current density of 20-27 mA / cm 2 with subsequent isolation of the target product.

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