JPH0339510B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention relates to a novel pyridopyrimidine derivative useful as a herbicide or an intermediate thereof, and a method for producing the same. [Prior art] Compounds similar to the present substance having a pyridopyrimidine structure include Chemical Abstracts (Chem.Abstr.) Vol. 90, 54893 (1979), Vol. 97, 182350.
(1982) are known.
However, until now, the 7 of the pyridopyrimidine ring
No pyridopyrimidine derivatives substituted with carboxyl, alkoxycarbonyl, or hydroxyl groups have been synthesized at all. While conducting research on pyridopyrimidine derivatives, the present inventors developed a method for synthesizing novel pyridopyrimidine compounds substituted with a carboxyl group, an alkoxycarbonyl group, or a hydroxyl group at the 7-position. They discovered that it has excellent herbicidal activity and completed the present invention. [Summary of the invention] That is, the present invention has the general formula [] [In the formula, R ¹ is the general formula [] (Here, R ⁶ and R ⁷ are each hydrogen, a lower alkyl group, or R ⁶ and R ⁷ combine to represent an alkylene group having 4 to 6 carbon atoms.) or the general formula [] (Here, R ⁸ represents hydrogen or an aralkyl group,
n represents 2 or 3. ) indicates a group represented by
R ² , R ³ and R ⁵ each represent hydrogen or a lower alkyl group, and R ⁴ represents a lower alkoxylcarbonyl group, carboxyl group or hydroxyl group. below,
same. The present invention provides a pyridopyrimidine derivative represented by the following. In the present invention, as a method for producing the above-mentioned novel pyridopyrimidine derivative, the general formula [] A method characterized by intramolecular condensation of a pyrimidinecarboxylic acid amide derivative represented by the general formula [-] in the presence of a base. (In the formula, R ^8-1 represents an aralkyl group.Hereinafter,
same. ) is hydrogenolyzed to give the general formula [−] A method for producing the claimed substance represented by the general formula [−] (In the formula, R ⁹ represents a lower alkyl group.Hereinafter,
same. ) is hydrolyzed to form the general formula [−] The present invention provides a method for producing the substance of the present application represented by: [Description of the substance of the present application] The substance of the present application is represented by the general formula []. In the formula, R ¹ represents a group represented by the general formula [] or []. Examples of lower alkyl groups for R ⁶ to R ⁸ in general formulas [] and [] include methyl group, ethyl group, n
-propyl group, iso-propyl group, n-butyl group,
Examples include iso-butyl group, sec-butyl group, t-butyl group, etc., and the lower alkyl group for R ⁶ and R ⁷ is preferably a methyl group. R ⁶
Examples of the alkylene group to which and R ⁷ are bonded include a butylene group, a pentylene group, a hexylene group, and the like, with a pentylene group being preferred. Furthermore, as the aralkyl group for R ⁸ , benzyl group,
Examples include diphenylmethyl group and triphenylmethyl group. Particularly preferred among the above R ⁸ are hydrogen and a benzyl group. n in formula [] is 2 or 3, particularly preferably 2. Furthermore, the lower alkyl groups for R ² , R ³ and R ⁵ include those listed above. Preferred for R ² is hydrogen and R ³
The preferred one is ethyl group. Furthermore, R ⁵ is preferably a methyl group or hydrogen, and particularly preferably hydrogen. Furthermore, examples of the lower alkoxycarbonyl group for R ⁴ include a methoxycarbonyl group, an ethoxycarbonyl group, and a propoxycarbonyl group, among which an ethoxycarbonyl group is preferred. In addition, even if the substance of the present application is in a free state, it is in the form of a salt,
For example, it may be in the form of an acid addition salt. Such salts can also be used as herbicides. Examples of acid addition salts include mineral acids such as hydrochloric acid, sulfuric acid, and phosphoric acid, and organic acids such as acetic acid, maleic acid, and citric acid. Examples of the substances of the present application are shown in Table 1 below.

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[Manufacturing method invention, Part 1]

The substance of the present application represented by the general formula [] can be produced by intramolecular condensation of the pyrimidine carbonamide derivative represented by the general formula [] in the presence of a base. Such bases include sodium hydride, potassium hydride, potassium t-butoxide, n-butyllithium, etc. Among them, sodium hydride is preferred, and is used in an amount of 0.1 to 5 equivalents based on the compound []. As the reaction solvent, aprotic polar solvents such as dimethylformamide, diethylformamide, dimethylsulfoxide, etc. can be used. The reaction is completed in 1 to 24 hours at a temperature of 0°C to 200°C. After the reaction, the compound of general formula [] can be obtained by processing and purifying according to conventional methods. Specifically, it can be produced by the operations described in Examples (the following production methods are also similar). [Manufacturing method invention, Part 2] Among the substances of the present application, the compound represented by the general formula [-] can be obtained by hydrogenolyzing the pyridopyrimidine derivative represented by the general formula [-]. As a catalyst, Pd/C, Pd/Al ₂ O ₃ , Pd black,
Metal catalysts such as Raney nickel can be used, with Pd/C being preferred. The solvent used is water, an alcoholic solvent such as methanol or ethanol, or a lower fatty acid such as acetic acid or propionic acid, the hydrogen pressure is normal pressure to 20 Kg/cm ² -G, the reaction temperature is 0°C to 120°C, and the reaction time is 1 or more
The reaction can be completed in 24 hours. After separating the catalyst from the reaction mixture, the compound [-] can be obtained by processing according to a conventional method. [Manufacturing method invention, Part 3] Among the substances of the present application, the compound represented by the general formula [-] can be obtained by hydrolyzing the pyridopyrimidine derivative represented by the general formula [-]. Hydrolysis is carried out using a base. As a base,
Examples include sodium hydroxide, potassium hydroxide, etc., and the molar ratio to [-] is 1 to 20
It is. As the solvent, water, a lower alcohol such as methanol or ethanol, or a mixed solvent thereof can be used. The reaction temperature is 0°C to 100°C, and the reaction is completed in 1 to 24 hours.
After the reaction, the desired product can be obtained by neutralizing with an acid and then following a conventional method. [Usefulness of the claimed substance] The claimed substance has excellent activity as a herbicide.
That is, the substance of the present application can be used as a herbicide for paddy fields and upland fields. The herbicides are particularly effective against paddy field weeds such as Japanese grasshopper, Japanese cyperus, Japanese cypress, Japanese fireweed, and Japanese grasshopper, as well as upland weeds such as Japanese barnyard grass, Japanese grasshopper, Japanese staghorn grass, Japanese grasshopper, Japanese grasshopper, and white grass. In order to use the claimed substance as a herbicide, the claimed substance alone or together with a carrier, surfactant, dispersant,
It can be formulated into wettable powders, emulsions, microgranules, granules, etc. by adding adjuvants, diluted to an appropriate concentration, and sprayed or applied directly. The present invention will be specifically explained below using Examples, Experimental Examples, etc. [Example] Example 1 2-(4-benzyl-1-piperazinyl)-5,
Production of ethyl 6-dihydro-6-ethyl-5-oxopyrido[4,3-d]pyrimidine-7-carboxylate 2-(4-benzyl-1-piperazinyl)-N-
Ethyl-N-ethyloxaloyl-4-methylpyrimidine-5-carbonamide 0.3g (0.68m
mol), sodium hydride 0.027g (60% in oil,
0.68 mmol), and 5 ml of dimethylformamide
The mixture was reacted at 120°C for 2 hours. 50g ice water
was added and extracted with ethyl acetate. The oil layer was washed with saturated brine and dried over sodium sulfate. After evaporating ethyl acetate under reduced pressure, the residue was subjected to silica gel column chromatography (developing solvent: ethyl acetate).
to obtain 0.095 g of pale yellow oil (yield: 33
%). Infrared absorption spectrum (neat; cm ^-1 ) 1730, 1660, 1613, 1574 ¹ H-nuclear magnetic resonance spectrum (deuterated chloroform; ppm) 1.35 (3H, t, J = 7Hz), 1.42 (3H,
t, J=7Hz), 2.51 (4H, t, J=5.5Hz), 3.55
(2H, s), 3.98 (4H, t, J=5.5Hz) 4.26 (2H,
q, J=7Hz), 4.40 (2H, q, J=7Hz), 6.75
(1H, s), 7.37 (5H, s), 9.22 (1H, s) Mass spectrum 421 (molecular ion peak) Example 2 5,6-dihydro-6-ethyl-5-oxo-
2-(1-piperazinyl)pyrido[4,3-d]
Production of ethyl pyrimidine-7-carboxylate 2-(4-benzyl-1-piperazinyl)-5,
Ethyl 6-dihydro-6-ethyl-5-oxopyrido[4,3-d]pyrimidine-7-carboxylate 0.399 g (0.95 mmol), 10% Pd/c 0.04 g
(0.038 mmol), formic acid 0.044 g (0.96 mmol), and ethanol 20 ml while blowing hydrogen into the mixture.
The reaction was carried out at 100°C for 2 hours. After cooling, the catalyst was separated and washed with ethanol. The solvent was distilled off from the mother liquor to obtain 0.314 g of pale yellow oil (yield 100%). ^1H -nuclear magnetic resonance spectrum (deuterium chloroform; ppm) 1.36 (3H, t, J = 7Hz), 1.44 (3H,
t, J=7Hz), 3.27 (4H, bs), 4.0~4.6 (9H,
m) 6.77 (1H, s), 9.27 (1H, s) Example 3 5,6-dihydro-6-ethyl-2-(1-piperidinyl)-5-oxopyrido [4,3-d]
Preparation of ethyl pyrimidine-7-carboxylate According to Example 1, 2-[4-benzyl-1-
piperazinyl)-N-ethyl N-ethyloxaloyl-4-methylpyrimidine-5-carbonamide instead of N-ethyl-N-ethyloxaloyl-4-methyl-2-(1-piperidinyl)pyrimidine-5-carbonamide. Obtained in 25% yield using amide. Colorless crystal mp105-108℃ IR (KBr tablet) 1740, 1665, 1615 1H-NMR ( _CDCl3 ) ^1.34 (3H, t, J = 7.0), 1.42 (3H, t, J =
7.0), 1.70 (6H, m), 3.92 (4H, m), 4.18 (2H,
q, J = 7.0), 4.41 (2H, q, J = 7.0) 6.75 (1H,
d, J=0.9), 9.20 (1H, d, J=0.9) Example 4 5,6-dihydro-2-dimethylamino-6-
Preparation of ethyl-5-oxopyrido[4,3-d]pyrimidine-7-carboxylate 2-(4-benzyl-1-piperazinyl)-N-ethyl-N-ethyloxaloyl-4 according to Example 1 -methylpyrimidine-2-dimethylamino-N-ethyl- instead of 5-carbonamide
It was obtained using N-ethyloxaloyl-4-methylpyrimidine-5-carbonamide in a yield of 21%. Colorless crystal mp94-96℃ IR (KBr tablet) 1740, 1665, 1615 ¹ H-NMR (CDCl ₃ ) 1.35 (3H, t, J = 7.0) 1.43 (3H, t, J = 7.0),
3.28 (6H, s), 4.26 (2H, q, J=7.0), 4.41
(2H, q, J=7.0), 6.78 (1H, s), 9.23 (1H,
s) Example 5 5,6-dihydro-2-dimethylamino-6-
Process for producing ethyl-5-oxopyrido[4,3-d]pyrimidine-7-carboxylic acid 5,6-dihydro-6-ethyl-2-dimethylamino-6-ethyl-5-oxopyride[4,3
-d] Ethyl pyrimidine-7-carboxylate 120 mg
(0.41 mmol) were added with 3 ml of ethanol and 10 ml of a 2% aqueous sodium hydroxide solution, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was neutralized with 2N hydrochloric acid and dried under reduced pressure. The dried product was extracted with ethanol, and the resulting ethanol solution was concentrated under reduced pressure to obtain 95 mg (yield: 88%) of colorless crystals. Melting point 242-245℃ ¹ H-NMR (DMSO-d ₆ ) 1.20 (3H, t, J=7.0), 3.19 (6H, s), 4.07
(2H, q, J=7.0), 5.96 (1H, s), 8.96 (1H,
s) Example 6 2-(4-benzyl-1-piperazinyl)-5,
Production of 6-dihydro-6-ethyl-5-oxopyrido[4,3-d]pyrimidin-7-ol Sodium hydride (60% in oil) 0.3g (7.5m
mol) with hexane and dimethylformamide.
It was suspended in 10ml. 15 ml of a solution of 2.0 g (4.6 mmol) of 2-(4-benzyl-1-piperazinyl)-N-ethoxycarbonyl-N-ethyl-4-methylpyrimidine-5-carbonamide in dimethylformamide was added thereto, and the mixture was heated at 100°C. The reaction was allowed to proceed for 15 minutes. After the reaction is complete, cool and add 0.4g of ammonium chloride.
(75 mmol) was added. Dimethylformamide was distilled off under reduced pressure, and 100 ml of chloroform and 100 ml of water were added to the residue.
Added ml. The chloroform layer was separated, and the aqueous layer was extracted twice with 100 ml of chloroform. The chloroform layers were combined, dried over sodium sulfate, and concentrated under reduced pressure. The yellow oil obtained was purified by silica gel column chromatography (developing solvent: ethyl acetate) to obtain 0.6 g of yellow crystals (yield: 36%). Melting point 147-150℃ Infrared absorption spectrum (KBr tablet; cm ^-1 ) 1668, 1630, 1598, 1578 ¹ H-nuclear magnetic resonance spectrum (deuterium chloroform; ppm) 1.20 (3H, t, J = 7.2), 2.51 (4H ,
m), 3.58 (2H, s), 3.95 (8H, m), 7.35 (5H,
s), 8.95 (1H, s) [Herbicide formulation example] Next, formulation examples will be explained. Note that the numbers indicate weight percentages. Formulation example (wettable powder) The compound of the present invention 10% Higher alcohol sulfate ester sodium salt 3% Kaolin 87% or more are uniformly mixed and ground to prepare a wettable powder. Test Example 1 (Paddy rice test) A porcelain pot with an inner diameter of 9 cm was filled with loose paddy soil, water was added, plowing was performed, and various paddy weed seeds were sown. Rice seedlings at the two-leaf stage were transplanted to a depth of 1 cm and submerged in water to a depth of 2 cm. The next day, a predetermined amount of the wettable powder prepared according to the above formulation example was diluted with water and dripped into water (spraying amount: 300 g/10 a).
On the 20th day after chemical treatment, the chemical damage to rice and herbicidal efficacy against weeds were investigated. The results are shown in Table 1. Test Example 2 (Field soil treatment test) A porcelain pot with an inner diameter of 9 cm was filled with field soil, various plant seeds were sown, and the pot was covered with 1 cm of soil. Immediately, disperse a predetermined amount (300 g) of the hydrating agent prepared according to the formulation example in an amount of water of 200 g per 10 a,
The entire surface of the soil was sprayed with a small sprayer. The herbicidal effect was investigated 20 days after chemical treatment. The results are shown in Table 2. Weeding effect 5 Complete death 4 Weeding effect large 3 Weeding effect medium 2 Weeding effect small 1 Weeding effect slight 0 Ineffective (normal)

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Claims (1)

[Claims] 1. General formula [] [In the formula, R ¹ is the general formula [] (Here, R ⁶ and R ⁷ are each hydrogen, a lower alkyl group, or R ⁶ and R ⁷ combine to represent an alkylene group having 4 to 6 carbon atoms.) or the general formula [] (Here, R ⁸ represents hydrogen, a lower alkyl group or an aralkyl group, and n represents 2 or 3.) R ² , R ³ and R ⁵ each represent hydrogen or a lower alkyl group. , R ⁴ represents a lower alkoxycarbonyl group, carboxyl group or hydroxyl group. ]
A pyridopyrimidine derivative represented by 2 General formula [] [In the formula, R ¹ is the general formula [] (Here, R ⁶ and R ⁷ are each hydrogen, a lower alkyl group, or R ⁶ and R ⁷ combine to represent an alkylene group having 4 to 6 carbon atoms.) or the general formula [] (Here, R ⁸ represents hydrogen or an aralkyl group, and n
indicates 2 or 3. ) indicates a group represented by
R ² , R ³ and R ⁵ each represent hydrogen or a lower alkyl group, and R ⁴ represents a lower alkoxycarbonyl group, carboxyl group or hydroxyl group. A general formula characterized by intramolecular condensation of a pyrimidinecarboxylic acid amide derivative represented by ] in the presence of a base [] A method for producing a pyridopyrimidine derivative represented by the formula (wherein R ¹ to R ⁵ are the same as above). 3 General formula [-] (In the formula, R ^8-1 represents an aralkyl group, R ² , R ³ and R ⁵ each represent hydrogen or a lower alkyl group,
R ⁴ represents a lower alkoxycarbonyl group, carboxyl group or hydroxyl group, and n represents 2 or 3. ]
General formula [−] characterized by hydrogenolyzing a pyridopyrimidine derivative represented by A method for producing a pyridopyrimidine derivative represented by the formula (wherein R ² to R ⁵ and n are the same as above). 4 General formula [-] [In the formula, R ¹ is the general formula [] (Here, R ⁶ and R ⁷ are each hydrogen, a lower alkyl group, or R ⁶ and R ⁷ combine to represent an alkylene group having 4 to 6 carbon atoms.) or the general formula [] (Here, R ⁸ represents hydrogen or an aralkyl group, and n
indicates 2 or 3. ) indicates a group represented by
R ² , R ³ and R ⁵ each represent hydrogen or a lower alkyl group, and R ⁹ represents a lower alkyl group. General formula [−] characterized by hydrolyzing a pyridopyrimidine derivative represented by ] (In the formula, R ¹ , R ² , R ³ and R ⁵ are the same as above.)
A method for producing a pyridopyrimidine derivative represented by