DD250452A5 - UNKRAUTBEKAEMPFUNGSMITTEL - Google Patents

Abstract

The invention relates to novel weedkillers which are characterized by a content of herbicidally active 3-aryluracils of the formula I in which R1, R2, R3, R4, R5, R6 and X have the meanings given in the description, and their use for weed control , The invention also relates to the preparation of these and other 3-aryluracils and their salts, other new weedkillers characterized by containing certain herbicidally active starting materials and the use of these weedkillers. Formula I

Description

25 C /

Weed killer

Field of application of the invention

The invention relates to a weed control agent containing new 3-aryluracils for agricultural use.

Characteristic of the known technical solutions

There is no information available which herbicidally active compounds have hitherto been used as active ingredient in weedkillers.

Object of the invention

The aim of the invention is the provision of new agents with a strong herbicidal action.

Explanation of the essence of the invention

The invention has for its object to find new compounds with strong herbicidal activity, which are suitable as active ingredient in herbicidal compositions.

-7.11.88- 3853-8 $

-Ia-

According to the invention are heterocyclic compounds, namely 3-aryluracils of the general formula as the active ingredient in the new weed control agent

COOR

applied, in which

Is hydrogen, C ^^ - alkyl, C ₂ _ ₄ -alkenyl, C ₄ - alkynyl, C ₀ --Alkoxyalkyl, formyl, C _n, alkanoyl or _C? c-alkoxycarbonyl,

Hydrogen, C. ' Alkyl, C _? _ ₄ alkenyl, C. · -Alkynyl or _C? , .- alkoxyalkyl,

Halogen or nitro, hydrogen or halogen,

R "

or

5 R and

and X

Hydrogen, halogen, C 1-4 alkyl, chloromethyl.

Bromomethyl, hydroxymethyl,

(C 1-4 alkoxy) methyl.

J - D

(C alkylthio) methyl, cyano. Nitro or thiocyanates hydrogen, C

-Alkyl or C-fluoroalkyl,

R which is substituted by C ₁ alkyl _- together tri- or tetramethylene, in which a methylene may be replaced by oxygen or sulfur, and optionally.

Oxygen or sulfur means, with the provisos that (i) if R is fluorine

6, R exclusively C _n -alkyl or

R for

C ₁ fluoroalkyl, and (ii) if

Cyano, R exclusively hydrogen or C-alkyl and X exclusively oxygen,

and salts of those compounds of the formula I. in which

12 R and / or R is hydrogen.

Those compounds of the formula I in which R and R 2 are different from hydrogen, ie the compounds

the general formula

COOR

η : ue-3335-iv

wherein

1 'is RC-alkyl, C-alkenyl, C _o -alkynyl,

C alkoxyalkyl, formyl, C alkanoyl or 2 - 6 2 - 6

C means alkoxycarbonyl,

2 ' ²

RC ₁ , .- alkyl. C_. Alkenyl. C ₀ -alkynyl or

1- fa <ί - 4 <s-4

C _{0th-alkoxyalkyl,} 2 - 6

and

3 4 5 6

R, R. R, R and X have the meanings given above, with the above statements (i) and (ii),

are herbicidally active and are useful as active ingredients of weedkillers. The remaining connections of the

1 2

Formula I, ie those in which R and R are hydrogen, and salts of these compounds are primarily suitable as starting materials for the preparation of the compounds of formula I ¹ , but also some of these residual compounds I have herbicidal properties.

The invention also includes weed control compositions which contain compounds of the formula I 'as active ingredients, processes for the preparation of the compounds according to the invention and the use of the compounds of the formula I' or compositions for controlling weeds.

In the above formula I or I ¹ , "halogen" includes fluorine, chlorine, bromine and iodine. The alkyl, alkenyl and alkynyl radicals may be straight-chain or branched, and this also applies to the or each alkyl part of the alkoxyalkyl, alkanoyl,

Alkoxycarbonyl, alkoxymethyl, alkylthiomethyl and 30

3.-86

_ 4 -

5 6

Fluoroalkyl groups applies. The fused rings formed by R and R are exemplified by the following substructures:

A C 1-4 fluoroalkyl group may be one or more 1-4

Have fluorine atoms, which may be mentioned as an example of a polyfluorinated alkyl group trifluoromethyl.

The salts of the compounds of formula I are, in particular, alkali metal salts, e.g. Sodium and potassium salts; Alkaline earth metal salts, e.g. Calcium and magnesium salts; Ammonium salts, i. unsubstituted ammonium salts

13 3 86- 33351-, ·

and mono- or poly-substituted ammonium salts, e.g. Triethylammonium and methylammonium salts, as well as salts with other organic bases, e.g. with pyridine.

The possible presence of at least one asymmetric carbon atom in the compounds of the formula I or I ¹ has the consequence that the compounds can occur in optically isomeric forms. The presence of a possible aliphatic C = C double bond can also geometric isomerism occur. In addition, in those compounds of formula I in which R is hydrogen, it is not excluded that keto-enol tautomerism (-NH-CX = -N = C (XH) -) occurs. Formula I or I ¹ is intended to include all of these possible isomeric forms as well as mixtures thereof.

1 1 '2 2' means R or R or R or R C ".-

L · * - * ±

Alkenyl or C-alkynyl, this radical is preferably allyl or propargyl. As C alkanoyl group comes

2 - 6

preferably C alkanoyl, while the

<£ ~~ fs

C-alkoxycarbonyl groups are the preferred C-alkoxy-2-4 2-6

carbonyl groups. In general, a halogen atom which may be present is preferably fluorine. Chlorine or bromine.

1 1 independently of one another, R and R are preferably straight-chain C ₁ -alkyl (in particular methyl); R

2 'or R preferably C _n ^ -alkyl or C_. -Alkoxy

3 ^λ ~ ^{6 2} ~ 8

alkyl; R is preferably chlorine or bromine; R is preferably fluorine; R is preferably hydrogen, fluorine, chlorine, bromine or straight-chain C 1 -C 4 alkyl (in particular methyl or ethyl); and R preferably straight-chain C-alkyl (especially methyl or ethyl) or C-fluoroalkyl

3.3.86-3335-U

(especially trifluoromethyl). Likewise preferred

5 6

R and R together are Tn or tetramethylene. X is preferably oxygen.

Particularly preferred compounds of the formula I or I 'are:

2-chloro-4- £ luor-5- (1.2.4,5,6,7-hexahydro-l-methyl-2,4-dioxo-SH-cyclopentatdjpyrimidin-S-YLJ-benzoic acid isopropyl ester.

2-chloro-4-fluoro-5- [1.4,5,6.7.8-hexahydro-l-methyl-2,4-dioxo-3 (2H) -quinazolinyl] -benzoic acid isopropyl ester,

2-Chloro-4-fluoro-5- [3,6-dihydro-3,4-dimethyl-2,6-dioxole (2H) -pyrimidinyl] -benzoic acid isopropyl ester, 2-chloro-4-fluoro-5- [ 5-bromo-3,6-dihydro-3,4-dimethy1-2,6-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester,

2-Chloro-4-fluoro-5- [3.6-dihydro-3,4-dimethyl-5-fluoro-2,6-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester, 2-chloro-4-fluoro-5 - [3,6-dihydro-3,4-dimethyl-5-iodo-2,6-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester,

2-chloro-4-fluoro-5- [3,6-dihydro-3,4-dimethyl-5-hydroxymethyl-2,6-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester,

2-chloro-4-fluoro-5- [4-äthy1-3,6-dihydro-3-methy1-2,6-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester,

2-chloro-4-fluoro-5- [3,6-dihydro-3-methyl-4-propyl-2,6-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester,

2-chloro-4-fluoro-5- [3,6-dihydro-3-methyl-4-trifluormethy1-2,6-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester.

2-bromo-4-fluoro-5- (1.2,4,5,6,7-hexahydro-l-methyl-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) -benzoic acid isopropyl ester,

3335'it

2-chloro-4-fluoro-5- [3,6-dihydro-5-fluoro-3-raethyl-4-trifluoromethyl-2,6-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester,

, 2-Chloro-4-fluoro-5- [3 _# 6-dihydro-3,4-dimethyl-5-nitro-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester,

2-chloro-4-fluoro-5- (1.2,4,5,6,7-hexahydro-l-methyl-2.4-dioxo-SH-cyclopenta [d] pyrimidin-3-yl) -benzoic acid- (2-methoxy 1-methylethyl) ester and

2-chloro-4-fluoro-5- (l, 2,4,5.6,7-hexahydro-l-methyl-2,4-dioxo-3H-cyclopentafd] pyrimidin-3-yl) -benzoic acid-tert-butyl ester.

Further representatives of compounds of the formula I are:

2-chloro-4-fluoro-5- (l, 2.4,5,6,7-hexahydro-l-methyl-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) -benzoic acid- (2 -methoxyäthyl) ester,

2-Chloro-4-fluoro-5- (1, 2,4,5,6,7-hexahydro-1-methyl-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) -benzoic acid ethyl ester and

2-chloro-4-fluoro-5- (l, 2.4.5,6,7-hexahydro-l-methyl-2,4-

13.3.86- 3335-U

dioxo-3H-cyclopenta [d] pyrimidiη-3-yl) -benzoic acid ρropy1 ester.

The inventive method for the preparation of the compounds of formula I and their salts is characterized in that

a) for the preparation of those compounds of the formula I,

1 2

in which R is hydrogen and R is C-alkyl. C_ .-

 ΙΟ-alkenyl. C 1-4 alkynyl or C 1-4 alkoxyalkyl mean 2-4 2-6

and R is different from chlorine, bromine, iodine. Chloromethyl. Bromomethyl, hydroxymethyl, (C., .- alkoxy) methyl, (C _n _-

1- b 1 -b

Alkylthio) methyl, cyano. Nitro or thiocyanato is. and metal salts of those compounds of the formula I in which R is hydrogen, a compound of the general formula

wherein

2 ¹ R

R "

and R ⁷

COOR

2 '

II

C _n , -alkyl. C, alkenyl,

Alkynyl or

C represents alkoxyalkyl. R and X have the meanings given above.

Hydrogen, fluorine, C-alkyl or together with

R optionally modified tri- or tetramethylene, as defined in more detail above. means.

lower alkyl, preferably C alkyl.

subjected to a base-catalyzed cyclization and

α ο o c.

if desired, a possibly obtained metal salt form of the uracil derivative is converted into the corresponding acid form (R = hydrogen) by treatment with an acid.

b) for the preparation of those compounds of formula I in which R is C-alkyl, C-alkenyl, C-alkynyl,

C alkoxyalkyl, formyl, C alkanoyl or C 2 - 6 2 - 6 2-6

Alkoxycarbonyl, a uracil derivative of the general formula

COOR '

Ia

wherein R, R. R, R, R and X have the meanings given above.

an alkylation or acylation with a corresponding C 1-6 alkyl, C 1-10 alkenyl, Q.- alkynyl,

C "alkoxyalkyl, formyl, C", alkanoyl or C 2-6 2-6 2-6

Alkoxycarbonyl group-containing alkylating or acylating agent,

c) for the preparation of those compounds of the formula I in which RC-alkyl »C-alkenyl, C ₄ ~ alkynyl or C" _fi -alkoxyalkyl, R is different from chlorine, bromine, iodine, chloromethyl, bromomethyl, hydroxymethyl, (C-alkoxy )methyl. (C ₁ _ ₅ alkylthio) methyl. Cyano. Nitro or thiocyanato, and X is sulfur, a compound of the general formula

 οο

2 5 C ..:

COOR

III

worm

R. R '

and R ⁸

C alkyl, C

X ~ "τ:

Alkenyl, C-alkynyl or

ο - TL

C represents alkoxyalkyl, .2 - 6 -

R and R have the meanings given above

Fluorine. C 1 -C 4 alkyl, (C 1 -C 4 alkoxy) carbonyl or

together with R as defined above tri- or

Tetramethylene means, wherein, in the case of R

Fluorine, RC ₁ _ ₄ -alkyl or C-fluoroalkyl is »

with N, N'-thiocarbonyldiimidazolide or thiophosgen

8 and, if R is (C, alkoxy) carbonyl, the 5-alkoxycarbonyl-2-thiouracil thus prepared of the general formula

CO'OR ²

IV

wherein

and

2 3 4 6

R, R, R and R have the meanings given above

U 3.86-

(C ₁ _ ₄ alkoxy) carbonyl group.

subjected to hydrolysis and decarboxylation.

d). for the purpose of preparing those compounds of the formula I in which R is chlorine. Bromine or iodine means a uracil derivative of the general formula

.- .. R ¹ .

COOR

wherein R, R. R. R. R and X have the meanings given above, chlorinated, brominated or iodinated,

e) for the preparation of those compounds of the formula I in which R is chlorine or bromomethyl, (i) a uracil derivative of the abovementioned formula Ib treated with chlorine or bromomethoxymethane or (ii) a 5-hydroxymethyluracil of the general formula

,1

HIGH

COOR '

2 3 4 6. worm R, R, R, R and X are those given above

35 meanings.

treated with thionyl chloride or bromide or (iii) a 5-methyluracil of the general formula

i a 3 ä ι;

'· Q ο ζ ·!

COOR

in which R, R, R, R, R and X have the abovementioned meanings, treated with N-chlorosuccinimide or N-bromosucciniride,

f) for the preparation of those compounds of formula I »in which R is hydroxymethyl, a 5-halomethyluracil of the general formula

.COOR

Ie

12 3 4 worm R, R, R, R, R and X are as defined above.

Possess 5 meanings and R chloro-,

Bromo- or iodomethyl means hydrolyzed.

g) for the preparation of those compounds of the formula I in which R is (C ₁ alkoxy) -ethyl or (C _n -C -alkylthio) -

L - D 1- D

methyl is a 5-halomethyluracil of the above-mentioned

5 '

given formula Ie, in which R is chlorine or bromomethyl, with an alkali metal alcoholate or thioalkoholat the general formula

R ⁹ M

wherein RC ₁ , .- alkoxy or C ₁ - alkylthio and M a

1-5 JL-b

Alkali metal, preferably sodium or potassium, mean, or treated with a C -alkanol or C-alkylmercaptan.

h) for the preparation of those compounds of formula I in which R is (C alkylthio) methyl, a 5-hydroxymethyluracil of the above formula Ic treated with a C alkyl mercaptan.

i) for the preparation of those compounds of the formula I,

1 5 6

in which R is hydrogen, R is cyano, R is hydrogen or

C. alkyl and X represents oxygen, a compound of

general formula

OOR

COOR '

VI

2 3 4 wherein R, R and R are as defined above.

6 'have obligations and R is hydrogen or C, _ ₄ alkyl

means subjected to an acid-catalyzed hydrolysis.

j) for the preparation of those compounds of the formula I in which R is nitro, a uracil derivative of the above-indicated formula Ib nitrated.

k) for the preparation of those compounds of the formula I,

in which R is thiocyanato, a uracil derivative of

treated above formula Ib with thiocyanogen

1) for the preparation of those compounds of the formula I,

in which R is hydrogen, a benzoic acid ester

the general formula

COOR

If

Wherein R, R, R, R, R, R and X are the above

have given meanings, hydrolyzed to the corresponding benzoic acid,

m) for the preparation of those compounds of formula I in which R is C alkyl, C "alkenyl, C» alkynyl

or C 1-4 alkoxyalkyl, a benzoic acid of all-2-6

common formula

COOH

13 4 5 6

worm R, R, R, R, R and X have the meanings given above,

or a reactive derivative thereof correspondingly esterified. or

18 385- 3335ΊΑ

η) in order to prepare those compounds of the formula I,

2 in which R is C-alkyl, C-alkenyl, C _ alkynyl or C-alkoxyalkyl, a benzoic acid ester of

2-6 above formula If a transesterification reaction with

an alkanol, alkenol or alkynol of the general formula

R ² "oH VII

2 "in which R is C ₂ _, -alkyl, C -.- alkenyl, C" -alkynyl or C -alkoxyalkyl, 2-6

subjecting the reagent of formula VII to higher boiling.

2 '

is as the alkanol. Alkenol or alkynol R OH,

and, if desired, a compound of the formula thus obtained

12

I, in which R and / or R is hydrogen, converted into a salt.

The cyclization according to process variant a) can conveniently be carried out by reacting the compound of formula II in an inert protic organic solvent such as an alcohol, e.g. Methanol, ethanol or isopropanol; an inert aprotic organic solvent such as an aliphatic or cyclic ether, e.g. 1,2-dimethoxyethane, tetrahydrofuran or dioxane, or an aromatic, e.g. Benzene or toluene; an inert aprotic polar organic solvent, e.g. Dimethylformamide or dimethylsulfoxide, such solvents optionally in the two-phase mixture with a hydrocarbon. e.g. η-hexane, can be used; or water with a base at temperatures between room temperature and the reflux temperature of the reaction mixture. The bases used are preferably sodium alcoholates. Alkali metal hydroxides, especially sodium hydroxide and potassium hydroxide. Alkali metal carbonates, in particular sodium carbonate and potassium carbonate, and sodium hydride into consideration. If the solvent is an alkanol,

- 16 - *

.. Alkenol or alkynol is used, then this solvent conveniently corresponds to the respective hydroxy

2 '

bond R OH; This avoids undesirable competing transesterification reactions. When sodium hydride is used as the base, the solvent is preferably an aliphatic or cyclic ether. Dimethylformamide or dimethyl sulfoxide.

After completion of the cyclization, if one of the above-mentioned bases or the like is used, the product is in the form of the corresponding alkali metal salt. This can be isolated and purified in a manner known per se or the mixture can be acidified to isolate the particular compound of formula I per se. For this purpose, it is preferable to use a mineral acid such as hydrochloric acid or a strong organic acid such as acetic acid or p-toluenesulfonic acid.

In process variant b), the term "alkylation" stands for the introduction of a C-alkyl-, C-

J. - Q £ » - Ql

Alkenyl, C-alkynyl or C-alkoxyalkyl group on

Ct - Q £ * - O

unsubstituted nitrogen atom of the uracil nucleus. In addition, in this sense, the term "acylation" for the corresponding introduction of a formyl, C ₀ , -Alkanoyl- or

Δ - o

C alkoxycarbonyl group. The alkylating agent is 2-6

suitably a C-alkyl, C-alkenyl,

J_ ~ - fx & - * Ί

C-alkynyl or C-alkoxyalkyl halide. par-

it - 41 ά. - D

the corresponding chloride or bromide »or sulfate used. The acylating agent used is in particular an formic acid halide, a C ₀ -alkanecarboxylic acid halide

Δ - D

or anhydride or chloro or Bromameisensäure C-alkyl esters in question, wherein the respective chloride or bromide is the preferred halide.

The alkylation is conveniently carried out in the presence of an inert, protic organic solvent such as a lower alkanol. e.g. Ethanol, optionally in

• iQQQi

Mixture with water; an inert, aprotic organic solvent, such as an aliphatic or cyclic ether, for example 1,2-dimethoxyethane, tetrahydrofuran or dioxane; or an inert, aprotic, polar organic solvent, for example dimethylformamide or dimethylsulfoxide, and in the presence of a base, such as sodium hydride, of an alkali metal alcoholate. in particular sodium alkoxide, or an alkali metal carbonate, in particular sodium carbonate, at temperatures between 0 ^° C. and about 50 ^° C., preferably at room temperature. In a preferred embodiment, the uracil derivative of the formula Ia is first treated with the base, such as sodium hydride, ethanolate or carbonate, in the solvent and after a short reaction time with the halide in the same solvent. The reaction is usually completed depending on the solvent used within a relatively short time or after a few hours. The acylation with a halide can be carried out in a similar manner, but in this case, in particular in an aprotic solvent and in the presence of sodium hydride is used as a base. When using an alkanecarboxylic acid anhydride as the acylating agent, the acylation is conveniently carried out without base.

In the case of the alkylation of a uracil derivative of the formula yes in which X is sulfur, mixtures of the corresponding N- and S-alkylated products are generally produced.

The desired N-alkyl, N-alkenyl, N-alkynyl or N-alkoxyalkyluracil can be isolated in a conventional manner from such a mixture, but in these cases, the process variant c) is recommended.

The reaction according to process variant c) is conveniently carried out using N, N'-thiocarbonyldiimidazolide in the melt or using thiophosgene in the presence of an aprotic organic solvent, such as a chlorinated aliphatic hydrocarbon, e.g.

• i ο ο ο C

1,2-dichloroethane, or an aromatic, for example toluene, as well as in the presence of an organic tertiary base »such as triethylamine or pyridine. The reaction temperatures are generally in the range of about room temperature to 50 ⁰ C, wherein preferably operated at room temperature.

In the case of using a starting material of

Formula III in which R is (C-alkoxy) carbonyl, the thus prepared 5-alkoxycarbonyl-2-thiouracil of formula IV is hydrolyzed and then decarboxylated to give the compound of formula I in which R is hydrogen , This is conveniently done in one step by briefly warming the product IV in the presence of aqueous hydrochloric acid or trifluoroacetic acid. In this

8 ', R preferably denotes tert-butoxycarbonyl.

The chlorination or bromination according to process variant d) is expediently carried out by means of elemental chlorine or suiferofuryl chloride or elemental bromine or suidofryl bromide, in the presence of an inert organic solvent, such as acetic acid or a chlorinated aliphatic hydrocarbon, for example methylene chloride, chloroform or carbon tetrachloride, and a temperature range from 0 ^° C. to 60 ^° C., preferably at room temperature. In addition, the reaction can be carried out with the aid of an acid-binding agent, for which purpose sodium acetate and tertiary amines, such as triethylamine, dimethylaniline and pyridine, are particularly preferred acid-binding agents.

The iodination according to this process variant is expediently carried out using elemental iodine as the iodination agent and a low-boiling aliphatic carboxylic acid, such as. Acetic acid, as a solvent and at temperatures between about 0 ⁰ C and about 110 ⁰ C, preferably at room temperature. In addition, it proves to be expedient to carry out the reaction in the presence of an acid, such as fuming nitric acid. To eliminate surplus

8 3.86-3335. ^

After completion of the reaction, iodine can be added to saturated aqueous sodium hydrogen sulfite solution.

Process variant e) (i) involves the direct introduction of a chloromethyl or bromomethyl group in unsubstituted 5-position of the uracil nucleus, where the uracil derivative of formula Ib is advantageously reacted with chlorine or bromomethoxymethane in the absence of a diluent and at elevated temperature. preferably in the temperature range of about 80 ⁰ C to about 140 ⁰ C, in particular at about 100 ⁰ C, is reacted. The reaction can be carried out, for example, in a heated closed reaction vessel under self-pressure.

Process variant e) (ii) can also be carried out without a diluent. In the case of using a diluent, this is conveniently a chlorinated aliphatic hydrocarbon, such as methylene chloride, chloroform or carbon tetrachloride. In addition, the reaction is conveniently carried out at temperatures between 0 ⁰ C and 40 ⁰ C, preferably at room temperature.

As a further process for the preparation of the novel 5-chloromethyl- and 5-bromomethyluracils, process variant e) (iii) is suitable. This is conveniently carried out by reacting the 5-methyluracil of formula Id in the presence of a diluent, preferably a chlorinated hydrocarbon such as carbon tetrachloride, at elevated temperature, preferably at temperatures between 70 ⁰ C and 100 ⁰ C, with N-chloro or N -Bromosomuccinimide treated. It proves to be advantageous to carry out the reaction with the aid of a radical-forming catalyst, such as dibenzoyl peroxide, and / or under UV irradiation.

The reaction according to process variant f) can conveniently be carried out by reacting the 5-halogen

 i ο "ο

*> J I

methyluracil of the formula Ie with an aqueous solution of an inorganic base such as an alkali metal carbonate or bicarbonate, in particular sodium carbonate or bicarbonate, treated, at temperatures between 0 ⁰ C and 70 ⁰ C, preferably at room temperature.

In the process variant g), the alkali metal alcoholate or thioalkoholat is conveniently generated in situ, by reaction of the alkali metal with the

9 Alcohol or mercaptan R H. The treatment of the 5-chloromethyl or 5-bromomethyluracil of the formula Ie with the alcoholate or thioalcoholate is then carried out in excess

Alcohol or mercaptan RH as a diluent. If desired, however, the alcoholate or thioalcoholate can first be isolated and optionally purified. In any case, an auxiliary solvent may be used, such as an aliphatic or cyclic ether, especially 1,2-dimethoxyethane, tetrahydrofuran or dioxane. In the case of treatment with the C ₁ ^ -alkanol or C, ^ -alkylmercaptan

g X - b J.- b

RH does not require the reaction with an alkali metal. In both cases, the reaction is conveniently carried out at temperatures between 0 ° C and your boiling point of the reaction mixture, preferably between room temperature and 70 ⁰ C.

Alternatively, the 5 - [(C alkylthio) methyl] -

X - J

uracils according to process variant h) are prepared, wherein conveniently the corresponding 5-hydroxymethyluracil of the formula Ic is treated with the C, _ alkylmercaptan in the presence of a solvent and at elevated temperature. The preferred solvents are lower alkanols. and reaction temperatures of 100 ⁰ C to 150 ⁰ C. The

'Choice of alcoholic solvent may be by nature of

2 respective group R in the 5-hydroxymethyluracil Ic depend:

If the 5-hydroxymethyluracil of the formula Ic is a benzoin

2 säureester is (R is C ₁ _ ₆ alkyl, Q. alkenyl,

C-alkynyl or C-alkoxyalkyl) and as solution 2-4 2-6

18 3 ft R- 1 3 9 s-ί

an alkanol, alkenol or alkynol is used, then this solvent conveniently corresponds to the respective hydroxy compound R OH; This avoids undesirable competing transesterification reactions.

The hydrolysis according to process variant i) is conveniently carried out by means of a mineral acid, such as hydrochloric acid, in aqueous solution at temperatures between ^20.degree. C. and 100.degree. C., preferably at room temperature. It can

also water-miscible solvents, such as lower ones

Alcohols and aliphatic or cyclic ethers, e.g. 1,2-dimethoxyethane, tetrahydrofuran and dioxane, with the choice of any alcoholic solvent used for the reason given above

by the nature of the respective group R in the compound

VI can depend.

The nitration according to process variant j) is conveniently carried out by means of mixtures or solutions containing nitric acid or nitric acid, in particular mixtures of nitric acid, sulfuric acid and possibly also sulfur trioxide, solutions of nitric acid in glacial acetic acid and solutions of concentrated nitric acid in chlorinated hydrocarbons, for example methylene chloride, 1,2-nitric acid. Dichloroethane and carbon tetrachloride. In general, the compound of formula Ib is introduced in portions into the nitrating agent and the mixture at room temperature or slightly elevated temperature, ie up to about 50 ⁰ C, stirred.

The thiocyanogen required in process variant k) is expediently generated in situ, for example by reacting lead or ammonium thiocyanate with bromine in the presence of a diluent at relatively low temperatures, such as 0 ^° C. to 30 ^° C., preferably 0 ^° C. to 10 ° ⁰ C. Suitable diluents are halogenated aliphatic hydrocarbons, such as methylene chloride and tetra-

Zi-

chlorine-carbon. and aliphatic or cyclic ethers such as 1,2-dimethoxyethane, tetrahydrofuran and dioxane, and in the case of ammonium thiocyanate also lower alkanecarboxylic »such as acetic acid. The uracil derivative of the formula Ib may be present from the beginning in the thiocyanogen-generating reaction medium or may be introduced subsequently into this medium, possibly after removal. e.g. by filtration, the remaining solid portions of the medium. In any case, the temperature of the reaction mixture is conveniently kept relatively low, within the temperature range given above, until the reaction is complete.

The hydrolysis of the benzoic acid ester If according to process variant 1) can be carried out by methods known per se, in particular using an organic solvent in aqueous solution, such as aqueous alkanol, eg ethanol, or an aliphatic or cyclic ether, eg 1,2-direthoxyethane, tetrahydrofuran or dioxane, in aqueous solution, and an inorganic base, such as sodium or potassium hydroxide, at temperatures between 0 ⁰ C and 70 ° C, preferably at room temperature.

Process variant (m) is an esterification of a substituted benzoic acid or of a reactive derivative thereof, which can likewise be carried out by methods known per se. Thus, for example, a salt of an acid of the formula Ig with a C-. ^ Alkyl, C ". Alkenyl, C". Alkynyl or C, _c -

X-DΔ -4 ώ -'i A - b

Alkoxyalkyl chloride. bromide, iodide, sulfate, mesylate or tosylate in an inert diluent at temperatures of about room temperature to 100 ⁰ C, for example at the reflux temperature of the reaction mixture, preferably in the temperature range of 40 ⁰ C to 70 ⁰ C, implemented. The salts of the benzoic acid of the formula Ig are, in particular, alkali metal salts, for example the sodium, potassium or lithium salt, alkaline earth metal salts. for example, the magnesium, calcium or

^ ο ο ς ·; L

Barium salt, and salts with organic bases, such as tertiary amines, e.g. Triethylamine, 1,5-diazabicyclo [4,3,0] non-5-ene, 1,8-diazabicyclo [5,4,0] undec-7-ene and 1,4-diazabicyclo [2 , 2,2] octane, in question, wherein the alkali metal salts, in particular the sodium salt, are preferred. The diluents which can be used are preferably inert organic solvents, such as lower alkanols, for example ' Ethanol, aliphatic and cyclic ethers, e.g. Diethyl ether, tetrahydrofuran and dioxane. Ketones, e.g. Acetone and 2-butanone. Dimethylformamide, dimethyl sulfoxide and hexamethylphosphoric triamide. The salt can be prepared in situ by reacting the acid with a suitable inorganic base, e.g. an alkali metal or alkaline earth metal carbonate or bicarbonate, or organic base, to the salt and this then reacted in the same reaction medium with the second reactant.

In the case of using an acid halide of the benzoic acid of formula Ig as a reactive derivative of 'this is conveniently effected with a C. _ _fi alkanol, C "alkenol, C -alkynol or C. Alkoxyalkanol in an inert organic solvent, such as an aliphatic or cyclic ether, for example diethyl ether. Tetrahydrofuran or dioxane, an aliphatic or aromatic hydrocarbon, for example η-hexane, benzene or toluene, or a halogenated, in particular chlorinated. Hydrocarbon, for example methylene chloride «chloroform or carbon tetrachloride, at temperatures of about -20 ⁰ C to 100 ⁰ C, preferably from 0 ⁰ C to 50 ⁰ C, reacted. In addition, it is expedient to work in the presence of an acid-binding agent, such as an organic base. eg triethylamine, pyridine, 1,5-diazabicyclo [4,3,0] non-5-ene, 1,8-diazabicyclo [5,4,0] undec-7-ene or 1,4-diaza bicyclo [2.2,2] octane. The acid halide is preferably the acid chloride.

As further eligible reactive derivatives of benzoic acid of the formula Ig are the corresponding

3 feet

£ J

O-acyl-1,3-dicyclohexylisourea and the corresponding N-acylimidazole or acid anhydride. Such derivatives, like the acid halide with a C alkanol,

1 - 6

C-alkenol, C-alkynol or C-alkoxyalkanol 2-4 2-4 2-6

be reacted to obtain the desired benzoic acid esters. In these cases, however, the use of an acid-binding agent is unnecessary,

The reaction according to process variant n) can conveniently be carried out by heating the benzoic acid ester of the formula If in excess alkanol, alkenol or alkynol of the formula VII in the presence of a basic catalyst such as sodium cyanide, preferably at the reflux temperature of the reaction mixture. In the course of

2 'of the reaction, the radical R of the benzoic acid ester of

2 '

Formula If replaced by the radical R from the compound of formula VII, wherein the opposite to the compound VII lower-boiling alkanol, alkenol or alkynol of the formula

R OH is released.

The salts of the compounds of the formula I thus obtained,

12

in which R and / or R is hydrogen, can be prepared in a conventional manner, such as by dissolving the compound of formula I in a solution of a relevant inorganic or organic base. Salt formation usually takes place within a short time at room temperature. In one embodiment, the sodium salt is prepared by dissolving the uracil derivative I in aqueous sodium hydroxide solution at room temperature using equivalent amounts of the uracil derivative and sodium hydroxide. The solid salt can then be isolated by precipitation with a suitable inert solvent or by evaporation of the solvent. Another embodiment is to introduce an aqueous solution of an alkali metal salt of uracil derivative I into an aqueous solution of a salt having a metal cation other than an alkali metal cation, the second

"O

Metal salt of the uracil derivative is produced. This embodiment generally serves to prepare uracil metal salts which are insoluble in water.

The resulting compounds of the formula I and salts thereof can be isolated and purified by methods known per se. Furthermore, it is familiar to the person skilled in the art in which order certain reactions under process variants b) and d) to n) are to be carried out expediently in order to avoid possible undesired competing reactions.

If no specific synthesis is carried out to isolate pure isomers, the product can be obtained as a mixture of two or more isomers. The isomers can be separated by methods known per se. If desired, for example, pure optically active isomers can also be prepared by synthesis from corresponding optically active starting materials.

The starting materials of formula II being new,

can be prepared in a known manner, e.g. according to the following Reaction Schemes 1 [Methods aa). bb) and cc)]: 25

ι ü. 0. UU O ο ο ~ ι

;) ί ~ π ' ^r , i, -j L /' -. · · ·

Reaction Schemes 1

aa)

R "

C-OR

H-N

; σ

COOR R ³

HN R "" C-OR ⁷

COOR R ³

νπΐ

IX

Ha

bb) R "

2 XCN

-OR

JCOOR

XI

H-N

C-OR

Il

COOR R ³

hb

R \ ^ OR

cc)

10

C-OR

Il

H-N

R ~

COOR ² 'R'

H-N

C-OR ¹ Il

ro;

• COOR

XII

hc

13.3.8 δ - 3335-U

2 '3 In _{1 of} the above reaction schemes, R, R.

R, R, R, R and X are as defined above.

5 "'6"

services; R is hydrogen or C ₁ alkyl; R is C-alkyl, C-fluoroalkyl or together with R optionally modified tri- or tetramethylene,

10 as defined in more detail above; and R is lower alkyl, preferably C alkyl.

The method aa) is expediently carried out by allowing the compounds of the formulas VIII and IX to react with one another in an essentially anhydrous diluent and in the presence of an acidic catalyst at elevated temperature. Suitable diluents are, in particular with water, azeotropic organic solvents, such as aromatics, for example benzene, toluene and xylenes; halogenated hydrocarbons, such as methylene chloride, chloroform, carbon tetrachloride and chlorobenzene; and aliphatic and cyclic ethers, such as 1,2-dimethoxyethane, tetrahydrofuran and dioxane, and, as acidic catalysts, especially strong mineral acids, such as sulfuric acid and hydrochloric acid; organic acids such as p-toluenesulfonic acid; Phosphorus-containing acids such as orthophosphoric acid and polyphosphoric acid; and acidic cation exchangers such as "Amberlyst 15" (Fluka). It generally works in a temperature range of about 70 ⁰ C to 120 ⁰ C, preferably at the reflux temperature of the reaction mixture. Under these reaction conditions, the desired rapid removal of the water formed in the reaction is achieved.

The reaction according to the method bb) is conveniently carried out in the presence of a substantially anhydrous aprotic organic solvent, such as an aliphatic or cyclic ether, e.g. Diethyl ether, 1,2-dimethoxyethane, tetrahydrofuran or dioxane, an aliphatic or aromatic hydrocarbon, e.g. n-hexane. Benzene, toluene or a xylene; or a halogenated aliphatic hydrocarbon, e.g. Methylene chloride,

η η r "· OO κ -:. '

f <

Chloroform. Carbon tetrachloride or 1,2-dichloroethane, and optionally in the presence of an organic tertiary base, such as triethylamine or pyridine, the latter can serve as both a solvent and as a base, or a Metallhydridbase, such as sodium or potassium. The reaction temperatures are preferably in the range of about room temperature to 50 ^° C., and it is particularly preferred to operate at room temperature.

The reaction according to the method cc) is conveniently carried out in an inert, water-miscible, organic solvent, such as an aliphatic or cyclic ether. for example, 1,2-dimethoxyethane, tetrahydrofuran or dioxane, or a lower alkanol. as ethanol, at temperatures between 50 ⁰ C and 100 ⁰ C, preferably at the reflux temperature of the reaction mixture, or in an aromatic solvent such as benzene, toluene or xylene in the presence of an acidic catalyst such as hydrochloric acid or p-toluenesulfonic acid, at temperatures between 50 ⁰ C and 100 ⁰ C. preferably 60 ⁰ C to 80 ⁰ C performed.

The compounds of the formulas Ia-Ig which are used as starting materials in process variants b), d) -h) and j) -n) are subgroups of compounds of the formula I.

The starting materials of the formula III required in process variant c) can be prepared in a manner known per se, specifically in accordance with reaction scheme 2 below:

13 3 8R- "i3? H-i

scheme

... 's L

^R \ / ^{NH 0C}

R H XIII

COOR

XIV

III

1 "2 In the above reaction scheme R, R, R,

6 R and R are as defined above, wherein

R is (C, .alpha.-alkoxy) carbonyl, preferably tert-butoxycarbonyl. The reaction of the compounds of the formulas XIII and XIV is conveniently carried out in an aprotic organic solvent, such as an aliphatic or cyclic ether. For example, diethyl ether or tetrahydrofuran, at temperatures between 0 ⁰ C and 50 ⁰ C, preferably at room temperature. As a rule, the reactants react spontaneously and exothermically.

The starting materials of the formula VI required in process variant i) can also be prepared in a manner known per se, specifically according to reaction scheme 3 below:

Reaction scheme 3

OCN

COOR

CN

XIV

XV

R ² OOC

NHCONH CN 4 r6 'CN

NH

00R 3

COOR '

2 3 4

In the above reaction scheme, R, R, R

6 'and R have the meanings given above.

The reaction of the compounds of the formulas XIV and XV with one another can conveniently be carried out in the presence of a diluent, in particular an aprotic. polar organic diluent, such as dimethylformamide or dimethyl sulfoxide, as well as in the presence of a base, such as sodium hydride, take place. It is preferably worked at temperatures between 20 ⁰ C and 50 ⁰ C. To isolate the product of formula VI is acidified, the free 5-cyanocytosine of formula VI is released, for example, from the corresponding sodium salt.

The remaining in process variants a) - n) and methods aa) - cc) and the starting materials or reagents involved in reaction schemes 2 and 3 are either known or can be prepared by methods known per se.

The novel compounds of the formula I ¹ have herbicidal properties and are suitable for controlling weeds, including grass weeds, in particular Setaria fa berii, Digitaria sanguinalis, Poa annua, Chenopodium album, Amaranthus retroflexus, Abutilon theopharasti, Sinapsis alba and Datura stramonium, in various Crop crops, especially in cotton and soybean cultures. In addition, the compounds are both pre-emergence and post-emergence herbicides.

Certain compounds of the formula II also have herbicidal properties and can be used in a manner similar to the compounds I ¹ for controlling grass weeds and weeds, in particular those mentioned above. The new compounds II form a further subject of the present invention. Due to their particularly pronounced herbicidal activity, 2-chloro-4-fluoro-5- {3- [2-

- (ethoxycarbonyl) -1-cyclohexen -1-yl] ureido} benzoic acid isopropyl ester and the 2-chloro-4-fluoro-5- {3- [2- (ethoxycarbonyl) -l-methylpropenyljureidoj-benzoic acid isopropyl ester Compounds of the formula II

In practice, a concentration usually suffices

from 0.01-6.0 kg of active ingredient of the formula I ¹ or II / ha, preferably 0.05-2.0 kg of active ingredient of the formula I ¹ or II / ha, in order to achieve the desired herbicidal effect, wherein im In general, the compounds of formula I ^{1 are} significantly more effective than the herbicidally active compounds of formula II. Particularly preferred is the concentration series 0.05-1.5 kg of active ingredient of formula I ¹ or II / ha.

The weed control composition according to the invention is characterized in that it contains an effective amount of at least one compound of the formula I ¹ or II, as defined above, as well as formulation auxiliaries. The agent conveniently contains at least one of the following formulation auxiliaries: solid carriers; Solvent or dispersant; Surfactants (wetting and emulsifying agents); Dispersants (without surfactant action); and stabilizers. Using such and other auxiliaries, these compounds, ie the herbicidal active compounds, can be converted into the customary formulations, such as dusts, powders, granules, solutions, emulsions. Suspensions, emulsifiable concentrates, pastes and the like.

The compounds of the formula I ¹ and II are generally water-insoluble and can be formulated according to the methods customary for water-insoluble compounds using the relevant formulation auxiliaries. The preparation of the agents can be carried out in a conventional manner, for example by mixing the respective active substance with solid Trägerstöffen. by dissolving or suspending in suitable solvents or dispersants, possibly using surfactants as wetting agents.

HQ? Q fi -

or emulsifiers and / or dispersants, by diluting already prepared emulsifiable concentrates with solvents or dispersants, etc.

Suitable solid carriers are essentially: natural minerals, such as chalk, dolomite, limestone, clays and silica and their salts (for example kieselguhr, kaolin, bentonite, talc, attapulgite and montmorillonite); synthetic minerals, such as fumed silica, alumina and silicates; organic substances such as cellulose, starch, urea and synthetic resins; and fertilizers such as phosphates and nitrates, such carriers being e.g. may be present as a powder or as granules.

Suitable solvents or dispersants are essentially: aromatics, such as benzene, toluene, xylenes and alkylnaphthalenes, chlorinated aromatics and chlorinated aliphatic hydrocarbons, such as chlorobenzenes, chloroethylenes and methylene chloride, aliphatic hydrocarbons, such as cyclohexane and paraffins, for example Alcohols, such as butanol and glycol, and their ethers and esters; ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone and cyclohexanone, and strongly polar solvents or dispersants, such as dimethylformamide, N-methylpyrrolidone and dimethyl sulfoxide, such solvents preferably having flash points of At least 30 ^° C. and boiling points of at least 50 ^° C. and water The solvents or dispersants also include what are known as liquefied gaseous extenders or carriers which are products which are gaseous at room temperature and under atmospheric pressure Products are in particular Aerosol propellants, such as halogenated hydrocarbons. eg dichlorodifluoromethane. If the weed control composition according to the invention is in the form of a pressurized gas packing, it is expedient to use a solvent in addition to the propellant gas.

• ι ο ο 0 r ,.

2 5

The surfactants (wetting and emulsifying agents) may be non-ionic compounds, such as condensation products of fatty acids, fatty alcohols or fatty-substituted phenols with ethylene oxide; Fatty acid esters and ethers of sugars or polyhydric alcohols; the products obtained from sugars or polyhydric alcohols by condensation with ethylene oxide; Block polymers of ethylene oxide and propylene oxide; or alkyldimethylamine oxides.

The surfactants may also be anionic compounds such as soaps, fatty sulfate esters, e.g., dodecyl sodium sulfate, octadecyl sodium sulfate, and cetyl sodium sulfate; alkyl sulfonates, aryl sulfonates, and fatty aromatic sulfonates such as alkylbenzenesulfonates, e.g., calcium dodecylbenzenesulfonate.

15 and butylnaphthalenesulfonates; and more complex fatty sulfonates, e.g., the amide condensation products of oleic acid and N-methyl taurine and the sodium sulfonate of dioctyl succinate.

Finally, the surfactants may be cationic compounds such as alkyl dimethyl benzyl ammonium chlorides, dialkyl dimethyl ammonium chlorides, alkyl trimethyl ammonium chlorides and ethoxylated quaternary ammonium chlorides.

Suitable dispersants (without surfactant action) are essentially lignin, sodium and ammonium salts of ligninsulfonic acids, sodium salts of maleic anhydride-diisobutylene copolymers, sodium and ammonium salts of sulfonated polycondensation products of naphthalene and formaldehyde, and sulfite waste liquors

 30

As dispersants, which in particular as Verdickungsbzw. Anti-settling agents are suitable, e.g. Methyl cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, polyvinyl alcohol. Alginates. Caseinate and blood albumin are used.

Examples of suitable stabilizers are acid-binding agents, e.g. Epichlorohydrin, phenyl glycidyl ether and soybean epoxides; Antioxidants, e.g. Gallic acid ester and butylhydroxytoluene; UV absorbers. e.g. substituted benzophenones, diphenylacrylonitrile acid esters and cinnamic acid esters; and deactivators, e.g. Salts of Aethylendiaminotetraessigsäure and polyglycols.

The weed control agents according to the invention may contain, in addition to the active compounds according to the invention, synergists and other active substances, e.g. Insecticides, acaricides, fungicides, plant growth regulators and fertilizers. Such combination agents are suitable for enhancing the activity or broadening the activity spectrum.

The weed control compositions according to the invention generally contain between 0.01 and 95% by weight, preferably between 0.5 and 75% by weight, of one or more compounds of the formula I ¹ or II as active ingredient (e). For example, they may be in a form suitable for storage and transportation. In such formulations, eg emulsifiable concentrates, the active ingredient concentration is normally in the higher range, preferably between 1 and 50% by weight, in particular between 10 and 20% by weight. These formulations can then be diluted, for example with the same or different inert substances, to concentrations of active compound which are suitable for practical use, ie preferably about 0.01 to 10 percent by weight, in particular about 0.5 to 5 percent by weight. However, the active substance concentrations can also be smaller or larger.

As mentioned above, the preparation of the weed control compositions according to the invention can be carried out in a manner known per se.

i i!

ϊ ..

For the preparation of powdered preparations of the active ingredient, ie at least one compound of formula I ¹ or II, are mixed with solid carrier, for example by co-milling; or you can impregnate the solid carrier with a solution or suspension of the drug and then remove the solvent or dispersant by evaporation, heating or suction under reduced pressure. By adding surfactants or dispersants, it is possible to make such pulverulent agents readily wettable with water so that they can be converted into aqueous suspensions which are suitable, for example, as sprays.

The compound of formula I ¹ or II may also be mixed with a surfactant and a solid carrier to form a wettable powder which is dispersible in water, or it may be mixed with a solid pre-granulated carrier to form a granular product.

If desired, the compound of formula I ¹ or II can be dissolved in a water-immiscible solvent, such as a high boiling hydrocarbon »conveniently containing dissolved emulsifier, so that the solution acts self-emulsifying upon addition to water. Otherwise, the active ingredient may be mixed with an emulsifying agent and the mixture then diluted with water to the desired concentration. In addition, the active ingredient can be dissolved in a solvent and then mixed with an emulsifier. Such a mixture can also be diluted with water to the desired concentration. In this way, emulsifiable concentrates or ready-to-use emulsions are obtained.

The use of the weed control compositions according to the invention, which forms a further subject of the present invention, can be carried out by customary application methods such as spraying, spraying, dusts. Pouring or

Sprinkle., Done. The method according to the invention for controlling weeds is characterized in that the product to be protected against weeds and / or the weeds is treated with a compound of the formula I ¹ or II according to the invention or with a weed control composition according to the invention.

From management example

The following examples serve to illustrate the invention.

I. Preparation of the compounds of the formula I;

example 1

A solution of 118.0 g of 2-chloro-5- (3- (2- (ethoxycarbonyl) -1-cyclopenten-1-yl) ureido) benzoic acid ethyl ester in 800 ml of absolute 1,2-dimethoxyethane is added with stirring C. for 10 minutes to a suspension of 7.7 g of sodium hydride in 800 ml of absolute 1,2-dimethoxyethane. The reaction mixture is then stirred for 1 hour, treated with 20 ml of acetic acid and evaporated to dryness under reduced pressure. The residue is dissolved in 2 l of methylene chloride and washed twice with 1 1 of water. The organic phase is dried over anhydrous sodium sulfate and evaporated to crystallization. The residue is treated with 1 l of n-hexane, and the crystals are filtered off with suction and washed with η-hexane. To obtain the 2-chloro-5- (1,2,4, -5,6,7-hexahydro-2,4-dioxo-3H-cyclopenta (d) pyrimidin-3-yl) · benzoic acid ethyl ester, m.p. «178-180 ⁰ C.

- 37a -

In analogous fashion, one obtains when using:

2-Chloro-5- (3- (2- (ethoxycarbonyl) -l-cyclohexen-1-yl) -ureido) -benzoic acid ethyl ester gives the 2-chloro-5- (1,4,5,6,7,8 hexahydro-2,4-dioxo-3 (2H) -quinazolinyl) benzoic acid ethyl

- 38 esters. Mp. 196-198 ° C.

2-Chloro-4-fluoro-5- {3- [2- (ethoxycarbonyl) -1-cyclopenten-1-yljureido} -benzoic acid isopropyl ester, the 2-chloro-4-fluoro-5- (1: 2, 4, 5, 5) , 6,7-hexahydro-2,4-dioxo-3H-cyclopenta [dj pyrimidin-3-yl) -benzoic acid isopropyl ester, mp. 204-207 ⁰ C.

2-Chloro-4-fluoro-5- {3- [2- (ethoxycarbonyl) -1-eye-lohexen-1-yl-jureido} -benzoic acid isopropyl ester, the 2-chloro-4-fluoro-5- [1, 4, 5,6,7,8-hexahydro-2,4-dioxo-3 (2H) -quinazolinyl] -benzoic acid isopropyl ester, mp. 203-205 ⁰ C.

2-Chloro-5- {3- [2- (ethoxycarbonyl) vinyl jureido} benzoic acid ethyl ester with sodium ethylate in ethanol, the 2-chloro-5- [3,6-dihydro-2,6-dioxo-l (2H ) -pyrimidinylj-benzoic acid ethyl ester. Mp. 170-172 ⁰ C.

2-Chloro-5- {3- [2- (ethoxycarbonyl) -1-methyl-vinyl] -ureido} -benzoic acid ethyl ester den2-chloro-5- [3,6-dihydro-4-methyl-2,6-dioxo -l (2H) -pyrimidinyl] -benzoic acid ethyl ester, m.p. 220-223 ⁰ C.

2-chloro-4-fluoro-5- {3- [2- (ethoxycarbonyl) -l-methylvinyl jureido} -benzoic acid isopropyl ester with sodium isopropylate in isopropanol, the 2-chloro-4-fluoro-5- [3,6-dihydro -4-methyl-2,6-dioxo-1 (2H) -pyrimidinyl-1-benzoic acid isopropyl ester. Mp 134-136 ° C.

2-Chloro-4-fluoro-5- iso-5- {3- (2-methoxycarbonyl) propenyljureido} -benzoic acid with sodium isopropylate in isopropanol / dimethylformamide mixture containing 2-chloro-4-fluoro-5- [3.6-dihydro- 5-methyl-2,6-dioxo-1 (2H) -pyrimidiny1 j-benzoic acid isopropyl ester, mp. 170-173 ⁰ C.

Ethyl 2-chloro-5- {3- [2- (ethoxycarbonyl) -l-methyl-propenyl-jureido} -benzoate gives 2-chloro-5- [3,6-dihydroxy]

η P _ 1. Q Ί. S "ί

5 '

- 39 -

-4,5-dimethyl-2,6-dioxo-l (2H) -pyrimidinyl] -benzoic acid ethyl ester. Mp 202-204 ⁰ C.

2-Chloro-4-fluoro-5- {3- [2- (ethoxycarbonyl) -1-methyl-propenyl] ureido} -benzoic acid isopropyl ester with sodium isopropylate in isopropanol / dimethylformamide mixture containing 2-chloro-4-fluoro-5- [ 3.6-dihydro-4,5-dimethy1-2,6-dioxo-l (2H) -pyrimididinyl] -benzoic acid isopropyl ester, Snip. 155-157 ° C.

5- {3- [2- (Aethoxycarbonyl) -1-cyclopenten-1-yl] ureido} -2-nitrobenzoic acid ethyl ester with sodium ethylate in ethanol, the 2-nitro-5- (1,2,4,5,6, 7-hexahydro-2,4-dioxo -3H-cyclopentaCdJpyrimidin-S-YLJ-benzoic acid ethyl ester, mp. 205-208 ⁰ C.

2-chloro-4-fluoro-5- {3- [4- (methoxycarbonyl) -2,5-dihy-

drothien-3-yl] ureido} -benzoic acid isopropyl ester with sodium isopropylate in isopropanol / dimethylformamide mixture containing 2-chloro-4-fluoro-5- {.1. 2,5,7-tetrahydro-2,4-dioxothieno [3 »4-d] pyrimidine-3 (4H) -yl} -benzoic acid isopropyl ester, Srap. 18O-183 ° C.

2-Chloro-5- {3- [4- (methoxycarbonyl) -2,5-dihydro-thien-3-yl] ureido} -benzoic acid ethyl ester with sodium ethylate in AeChanol the 2-chloro-5- {1,2, Ethyl 5,7-tetrahydro-2,4-dioxo-thieno [3,4-d] pyrimidine-3 (4H) -yl} -benzoate, m.p. 194-196 ° C.

2-Chloro-4-fluoro-5- {3- [2- (methoxycarbonyl) -4,5-dihydro-thien-3-yljureido} -benzoic acid isopropyl ester with sodium isopropylate in isopropanol / dimethylformamide mixture containing 2-chloro-4 fluoro-5- {1,4,6,7-tetrahydro-2,4-dioxo-thieno [3,2-d] pyrimidine-3 (2H) -yl} -benzoic acid isopropyl ester, m.p. 252-254 ° C

 35

2-Chloro-4-fluoro-5- {3- [2- (ethoxycarbonyl) -2-fluoro-1-methylvinyl] ureido} -benzoic acid isopropyl ester with

_Λ .λ Λ Γ-

- 40 -

Sodium isopropylate in isopropanol / dimethylformamide mixture isopropyl 2-chloro-4-fluoro-5- [3,6-dihydro-5-fluoro-4-methyl-2,6-dioxo-l (2H) -pyrimidinyl] benzoate,

H-NMR _(CDCl3. 400 MHz) 9.99 ppm (s, lH). 7.84 ppm (d.hl), 7.37 ppm (d.hl). 5.26 ppm (m.lH), 2.18 ppm (d, 3H), 1.38 ppm (d, 3H). 1.36 ppm (d, 3H).

2-Chloro-4-fluoro-5- {3- [2- (ethoxycarbonyl) -1-propylvinyl] ureido} -benzoic acid isopropyl ester with sodium isopropylate in isopropanol, the 2-chloro-4-fluoro-5- [3,6- dihydro-4-propyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester. Mp 192-193 ° C.

2-Chloro-4-fluoro-5- {3- [2- (ethoxycarbonyl) -l-ethyl-vinyl-ureido} -benzoic acid isopropyl ester with sodium isopropylate in isopropanol, the 2-chloro-4-fluoro-5- [4-ethyl-3, 6- dihydro-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester, m.p. 121-124 ° C.

2-Chloro-4-fluoro-5- {3- [2- (ethoxycarbonyl) -l-methyl-1-butenyl] ureido} -benzoic acid isopropyl ester with sodium isopropylate in isopropanol / dimethylformamide mixture containing the 2-chloro-4- 176-178 ° C fluoro-5- [5-ethoxy-1,3,6-dihydro-4-methyl-2,6-dioxo-1 (2H) -pyrimidinyl] benzoate, m.p.

2-Chloro-4-fluoro-5- {3- [2- (ethoxycarbonyl) -l-ethyl-l-propenyl] ureido} -benzoic acid isopropyl ester with sodium isopropylate in isopropanol / dimethylformamide mixture containing the 2-chloro-4- 192- -194 ° C fluoro-5- [4-ethyl-3,6-dihydro-5-methyl-2,6-dioxo-1 (2H) -pyrimidinyl] benzoate, m.p.

2,4-Difluoro-5- {3- [2- (ethoxycarbonyl) -l-cyclopenten-1-yl] ureido} -benzoic acid isopropyl ester with sodium isopropylate in isopropanol, the 2,4-difluoro-5- (1.2 , 4,5,6,7-hexahydro-2,4-dioxo-3H-cyclopenta [dj-pyrimidin-3-yl] -benzoic acid

- ο ο ".

- 41 acid isopropyl ester, mp 231-234 ° C.

2,4-Dichloro-5- {3- [2- (ethoxycarbonyl) -1-eye-lopenten-1-yl] -ureido} -benzoic acid isopropyl ester with sodium isopropylate in isopropanol the 2,4-dichloro-5- (1, 2,4,5,6,7-hexahydro-2,4-dioxo-SH-cyclopenta [d] pyrimidin-3-yl] -benzoic acid isopropyl ester, m.p. 186-189 ° C.

2-Bromo-4-chloro-5- {3- [2- (ethoxycarbonyl) -l-cyclopenten-1-yl] ureido} -benzoic acid isopropyl ester with sodium isopropylate in isopropanol, the 2-bromo-4-chloro-5- (1,2,4.5,6 "7- hexahydro-2,4-dioxo-SH-cyclopentafd] pyrimidin-3-yl) - benzoic acid isopropyl ester, mp 208-210 ⁰ C..

, 15 2-Bromo-4-fluoro-5- {3- [2- (ethoxycarbonyl) -1-cyclopenten-1-yl] ureido} -benzoic acid isopropyl ester with sodium isopropylate in isopropanol, the 2-bromo-4-fluoro. or-5- (1, 2, 4, 5, 6, 7-hexahydro-2,4-dioxo-SH-cyclopenta [d] pyrimidin-3-yl) -benzoic acid isopropyl ester. Mp 214-216 ° C.

2, 4-dibromo-5- {3- [2- (ethoxycarbonyl) -l-cyclopentene-1-one

-yljureido} -benzoic acid isopropyl ester (with sodium isopropoxide in isopropanol to 2.4-dibromo-5- 1,2,4,5. 6,7-hexahydro-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl ) -benzoic acid isopropyl ester, m.p. 223-226 ° C.

2-Chloro-4-fluoro-5- {3- [3- (ethoxycarbonyl) -4,5-dihydro-furan-2-yl] ureido} -benzoic acid isopropyl ester with sodium isopropylate in isopropanol / dimethylformamide mixture 2- Chloro-4-fluoro-5- {1,2,5 »6-tetrahydro-2,4-dioxo-furo [2,3-d] pyrimidin-3 (4H) -yl} -benzoic acid isopropyl ester, m.p. 213-215 ° C.

2-Chloro-5- {3- [2- (ethoxycarbonyl) -1-methylvinyl] thioureido} -benzoic acid isopropyl ester with sodium isopropylate in isopropanol / dimethylformamide mixture containing 2-chloro-5- [3,6-dihydro-4- methyl-6-oxo-2-thioxo-1 (2H) -

- 42 -pyrimidinyl] benzoic acid isopropyl ester.

2-chloro-5- {3- [2- (ethoxycarbonyl) -1-trifluoromethylvinyl] thioureido} -benzoic acid isopropyl ester with sodium isopropylate in isopropanol / dimethylformamide mixture containing 2-chloro-5- [3,6-dihydro-4 - trifluoromethyl-6-oxo-2-thioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester.

2-Chloro-5- {3- [2- (ethoxycarbonyl) -1-cyclopenten-1-yl] thioureido} -benzoic acid isopropyl ester with sodium isopropylate in isopropanol / dimethylformamide mixture containing 2-chloro-5- (1.2,4, 5,6,7-hexahydro-4-oxo-2-thioxo-3H-cyclopenta [d] pyrimidin-3-yl) -benzoic acid isopropyl ester. ·

Example 2

A solution of 3.55 g of ethyl 3-amino-4,4,4-trifluorcrotonsäure in 50 ml of η-hexane is added with stirring at 0-3 ⁰ C for 15 .Minuten to 0.85 g of a 55% sodium hydride dispersion in 50 ml Dimethylformamide is added dropwise, and the mixture is stirred for 30 minutes. Subsequently, a solution of 5.0 g of isopropyl 2-chloro-4-fluoro-5-isocyanatobenzoate in 100 ml of η-hexane is added dropwise with stirring and cooling for 5 minutes. The temperature of the reaction mixture rises to 10 ⁰ C, and the mixture is then stirred for one hour at room temperature. The resulting intermediate 2-chloro-4-fluoro-5- {3- [2- (ethoxycarbonyl) -1-trifluoromethyl-vinyljureidoj-benzoic acid isopropyl ester is not isolated.

By addition of concentrated acetic acid, the mixture is brought to pH 4, poured into 750 ml of water and the aqueous mixture is extracted with 300 ml of ethyl acetate. The 35th

HO QQC- A?,?> H- \

- 43 -

organic phase is dried over anhydrous sodium sulfate and then evaporated to dryness under reduced pressure and the residue recrystallized from diethyl ether / η-hexane. This gives 2-chloro-4-fluoro-5- [3,6-dihydro-4-trifluoromethyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester, m.p. -129 ° C.

Example 3

In a solution of 7.5 g of 3-0x0-2,4,4,4-tetrafluorobutyrate in 20 ml of toluene is introduced at 75 ° C with stirring ammonia to saturation. Subsequently, the reaction mixture is heated to reflux temperature using a water separator for 5 hours to form the intermediate 3-amino-2,4,4,4-tetrafluorcrotonic acid ethyl ester.

The reaction mixture is added dropwise at ^{0 0} C with stirring for 20 minutes to a suspension of 1.62 g of a 55% sodium hydride dispersion in 80 ml of absolute dimethylformamide and the whole stirred for 15 minutes at 0 ⁰ C and then to -5 ° C. cooled. A solution of 9.56 g of 2-chloro-4-fluoro-5-isocyanatobenzoic acid isopropyl ester in 40 ml of η-hexane is added. The temperature of the reaction mixture rises to 10 ⁰ C, and the mixture is then stirred for 3 hours at room temperature. The resulting intermediate 2-chloro-4-fluoro-5- {3- [2- (ethoxycarbonyl) -2-fluoro-1-trifluoromethyl-vinyljureido} - benzoic acid isopropyl ester is not isolated.

The reaction mixture is poured into 1.5 1 of water containing 20 ml of 2N hydrochloric acid, and the aqueous mixture extracted twice with 200 ml of ethyl acetate. The organic phase is washed with water, dried over anhydrous sodium sulfate and evaporated under reduced pressure

_ 44 -

Dry one. The residue was stirred briefly with 100 ml of diethyl ether and a solution of 5 g Natrlumhydrogencarbonat in 300 ml of water at 50 ⁰ C and cooled. After separating the aqueous phase, the organic phase with three times

a solution of 2.5 g of sodium bicarbonate in 100 ml of water, and then the combined aqueous solutions are adjusted to pH 1 with 15 ml of concentrated hydrochloric acid and extracted with diethyl ether. Then the organic phase is washed with water, over

dried anhydrous sodium sulfate and evaporated to dryness under reduced pressure. Finally, the residue is recrystallized from diethyl ether / n-hexane.

This gives the isopropyl 2-chloro-4-fluoro-5- [3,6-dihydro-5-fluoro-4-trifluoromethyl-2,6-dioxo-1 (2H) -pyrimidinyl] benzoate, M.p. 102-106 ⁰ C.

Example 4

A solution of 1.80 g of 3-amino-2,4-difluorcrotonsäure- ethyl ester in 20 ml of absolute dimethylformamide is added dropwise with stirring at room temperature for 10 minutes to 0.48 g of a 55% sodium hydride dispersion in 25 ml of absolute dimethylformamide , and the mixture is 15 minutes

stirred. Subsequently, 2.81 g of isopropyl 2-chloro-4-fluoro-5-isocyanatobenzoate are added, the temperature of the reaction mixture rising to 35 ° C. Thereafter, the mixture is stirred for 2 hours at room temperature. The resulting intermediate 2-chloro-4-fluoro-5- {3- [2- (ethoxycarbonyl) -2-fluoro-1-fluoromethyl-vinyl] ureido} - benzoic acid isopropyl ester is not isolated.

The mixture is poured into 300 ml of water containing 5.5 ml of 2N hydrochloric acid, the aqueous mixture is extracted three times with 50 ml of ethyl acetate each time, and the combined organics are washed.

No

~ ¹ ^ ° i h'i - <

- 45 -

with water, dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The residue is purified by chromatography on a silica gel column using ethyl acetate / n-hexane (1: 1) as the eluent and recrystallized from diethyl ether / η-hexane. The isopropyl 2-chloro-4-fluoro-5- [3,6-dihydro-5-fluoro-4-fluoromethyl-2,6-dioxo-1 (2H) -pyrimidinyl] benzoate, m.p. 171, is obtained -173 ° C.

Example 5

A solution of 50.2 g of ethyl 2-chloro-5- (1,2,4,5,6,7-hexahydro-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) benzoate in 300 ml of absolute 1,2-dimethoxyethane

Stirred with stirring at 20 ⁰ C for 10 minutes to a suspension of 3.6 g of sodium hydride in 100 ml of absolute 1,2-dimethoxyethane. The reaction mixture is stirred for 1 hour, treated with 21.3 g of methyl iodide and stirred for a further 2 hours. It is then made neutral with 0.5 ml of acetic acid and evaporated to dryness under reduced pressure. The residue is dissolved in 500 ml of ethyl acetate, the solution is extracted by shaking three times with 250 ml of water and the organic phase is dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The residue is dissolved in 50 ml of hot methylene chloride, seeded and treated with diethyl ether. The ethyl 2-chloro-5- (1,2,4,5,6,7-hexahydro-1-methy1-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) benzoate is obtained. Mp 141-143 ° C.

In an analogous manner, the use of:

ο ο ο c. ^ 3 3 5 " \ τ

- 4 6 -

2-Chloro-5- [l, 4,5,6,7,8-hexahydro-2,4-dioxo-3 (2H) -quinazolinyl] -benzoic acid ethyl ester, the 2-chloro-5- [1,4,5,6, 7,8 -hexahydrö-l-methyl-2,4-dioxo-3 (2H) -quinazolinyl] -benzoic acid ethyl ester, mp. 108-112 ⁰ C.

2-chloro-4-fluoro-5- (l, 2.4,5,6,7-hexahydro-2,4-dioxo-3H

-cyclopenta [dj-pyrimidin-3-yl] -benzoic acid isopropyl ester, the 2-chloro-4-fluoro-5- (l, 2,4,5,6,7-hexahydro-l-methyl-2,4-dioxo-3H -cyclopenta [d] pyrimidin-3-yl) -benzoic acid isopropyl ester, m.p. 111-113 ° C.

2-Chloro-4-fluoro-5- [1,4,5,6,7,8-hexahydr0-2,4-dioxo-3 (2H) -quinazolinyl] -benzoic acid isopropyl ester 2-chloro-4- fluoro-5- [l, 4,5,6,7,8-hexahydro-l-methyl-2,4-dioxo-3 (2H) - - (5-quinazolinyl] -benzoic acid isopropyl ester, m.p. 113-115 ° C ,

2-Chloro-5- (l, 2,4,5,6,7-hexahydro-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) -benzoic acid ethyl ester and chlorodimethyl ether in dimethylformamide den 2 -Chloro-5- (1,2,4,5,6,7-hexahydro-l-methoxymethyl-2,4-dioxo-SH-cyclopenta [d] -pyrimidin-3-yl) -benzoic acid ethyl ester. Mp. 103-106 ⁰ C.

2-Chloro-5- (1, 2,4,5,6,7-hexahydro-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) -benzoic acid ethyl ester and 3-bromo-1-propyne 2-Chloro-5- {1,2,4,5,6,7-hexahydro-1- (2-propynyl) -2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl} -benzoic acid ethyl ester, m.p. 123 ° C.

2-Chloro-5- [3,6-dihydro-2,6-dioxo-l (2H) -pyrimidinyl] - benzoic acid ethyl ester in dimethylformamide, the 2-chloro-5- - [3.6-dihydro-3-methyl- Ethyl 2,6-dioxo-l (2H) -pyrimidinyl] benzoate, mp 147-148 ° C.

Ethyl 2-chloro-5- [3,6-dihydro-4-methyl-2,6-dioxo-l (2H) -pyrimidinyl] benzoate gives 2-chloro-5- [3,6-dihydro-3, 4-dimethy1-2,6-dioxo-1 (2H) -pyrimidinyl-benzoic acid

O V- 'v7 ~'

i 5

- 47-ethyl ester, m.p. 120-122 ⁰ C.

2-Chloro-4-fluoro-5- [3,6-dihydro-4-methyl-2,6-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester with sodium isopropylate in isopropanol, the 2-chloro-4-fluoro -5- [3,6-dihydro-3,4-dimethyl-2,6-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester, ¹ H NMR (CDCl 3 60MHz) 7.88 ppm (of IH ), 7.38 ppm (d, IH), 5.77 ppm (s, IH), 5.30 ppm (mH), 3.50 ppm (s, 3H), 2.36 ppm (s, 3H), 1, 40 ppm (d, 6H).

2-chloro-4-fluoro-5- [3,6-dihydro-5-methyl-2.6-dioxo-l (2H)

-pyrimidinyl] -benzoic acid isopropyl ester in dimethylformamide, the 2-chloro-4-fluoro-5- [3,6-dihydro-3,5-dimethyl-2,6-dioxo-1 (2FI) pyrimidinyl] benzoic acid isopropyl ester, mp. 177- -180 ⁰ C.

2-Chloro-5- [3,6-dihydro-4,5-dimethy1-2,6-dioxo-l (2H) -pyrimidinyl] -benzoic acid ethyl ester, the 2-chloro-5- [3,6-dihydro-3,4, Ethyl 5-trimethyl-2,6-dioxo-1 (2H) -pyrimidinyl] benzoate, mp 159-161 ° C.

2-Chloro-4-fluoro-5- [3.6-dihydro-4,5-dimethy1-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester in dimethylformamide, the 2-chloro-4-fluoro-5 -. [3,6-dihydro-3,4,5-trimethyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester, mp 119-120 ⁰ C.

Ethyl 2-nitro-5- (1,2,4,6,6-hexahydro-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) benzoate with sodium ethylate in ethanol Ethyl 5-nitro-5- (1,2,4,5,6,7-hexahydro-1-methyl-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) -benzoate, mp 188-190 ° C.

2-Chloro-4-fluoro-5- {1,2,5,7-tetrahydro-2,4-dioxo-thieno [3,4-d] pyrimidine-3 (4H) -yl} -benzoic acid isopropyl ester in dimethylformamide 2- Chloro-4-fluoro-5- {1,2,5,7-tetrahydro-1-methyl-2,4-dioxothieno [3,4-d] pyrimidine

C O

- 48 -

• · -3 (4H) .- yl} -benzoic acid isopropyl ester. H NMR (CDCl 4 400 MHz) 7.82 ppm (d, IH), 7.35 ppm (d, IH). 5.23 ppm (m, IH). 4.24 ppm (m, 2H), 4.09 ppm (m, 2H), 3.45 ppm (s, 3H), 1.36 ppm (d, 6H).

2-chloro-S- {1,2,5,7-tetrahydro-2,4-dioxothieno

[3,4-d] pyrimidine-3 (4H) -yl} -benzoic acid ethyl ester in dimethylformamide the 2-chloro-5- {1,2,5,7-tetrahydro-l-methyl-2,4-dioxo -thieno [3,4-d] pyrimidine-3 (4H) -yl} - benzoic acid ethyl ester, m.p. 2O3-2O6 ° C.

2-Chloro-4-fluoro-5- {i, 4,6,7-tetrahydro-2,4-dioxo-thieno [3,2-d] pyrimidin-3 (2H) -yl} -benzoic acid isopropyl ester 2-Chloro-4-fluoro-5- {1,4,6,7-tetrahydro-1-methyl-2,4-dioxothieno [3.2-d] pyrimidin-3 (2H) -yl} -benzoic acid - isopropyl ester, mp. 156-158 ° C.

2-Chloro-4-fluoro-5- [3,6-dihydro-5-fluoro-4-methyl-2,6-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester and dimethylsulfate in dimethylformamide 2- Chloro-4-fluoro-5 - [3,6-dihydro-3,4-dimethyl-5-fluoro-2,6-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester, m.p. 112-115 ° C ,

2-Chloro-4-fluoro-5- [3,6-dihydro-4-propyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester and dimethyl sulfate with sodium isopropylate in isopropanol, the 2-chloro 4-fluoro-5- [3.6-dihydro-3-methyl-4-propyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester, 1 H NMR (CDCl ₃ , 400 MHz) 7, 83 ppm (d.hl), 7.34 ppm (d.hl), 5.73 ppm (s.IH), 5.23 ppm (m.lH), 3.45 ppm (s, 3H), 2.53 ppm (t, 2H), 1.72ppm (m.2H), 1.36ppm (d, 6H), 1.10ppm (t.3H).

2-Chloro-4-fluoro-5- [3,6-dihydro-4-ethyl-2. 6-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester and dimethyl sulfate with sodium isopropylate in isopropanol, the 2-chloro-4-fluoro-5- [4-ethyl-3,6-dihydro-3-methyl-2, 6-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester, H-NMR (CDCl, 400

I d 0. ο υ

JJ K

- 49 -

MHz) .7.84 ppm (d.lH). 7.34 ppm (d.lH). 5.75 ppm (s.lH), 5.25 ppm (m.lH), 3.45 ppm (s, 3H). 2.61 ppm (m, 2H), 1.36 ppm id. 6H). 1.31 DDm it .. 3H).

(D.6H). 1.31 ppm (t.3H).

2-Chloro-4-fluoro-5- [5-ethyl-3,6-dihydro-4-methyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester and dimethylsulfate in dimethylformamide 2- Chloro-4-fluoro-5- [5-ethyl-3,6-dihydro-3,4-dimethyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester, by NMR (CDCl3) 400 MHz) 7.83 ppm (d.lH). 7.33 ppm (d.hl), 5.23 ppm (m.lH), 3.48 ppm (s, 3H), 2.51 ppm (m, 2H), 2.34 ppm (s, 3H), 1.35 ppm (2xd.6H), 1.09 ppm (t, 3H).

2-Chloro-4-fluoro-5- [4-ethyl-3,3-dihydro-5-methyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester and dimethyl sulfate in dimethylformamide, the 2-chloro 4-fluoro-5- [4-ethyl-3,6-dihydro-3,5-dimethyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester, 1 H NMR (CDCl 2, 400 MHz ) 7.82 ppm (d.lH). 7.33 ppm (d, 1H), 5.23 ppm (m, IH), 3.51 ppm (s, 3H). 2.71 ppm (m.2H), 2.04 ppm (s.3H), 1.35 ppm (d, 6H), 1.28 ppm (t, 3H).

2-Chloro-4-fluoro-5- [3,6-dihydro-2,6-dioxo-4-trifluoromethy1-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester and dimethylsulfate in dimethylformamide, the 2-chloro-4-fluoro -5- - [3.6-dihydro-3-methyl-4-trifluoromethyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester, 1 H-NMR (CDCl 2, 400 MHz) 7.84 ppm (i.e. 1H), 7.37 ppm (d.lH), 6.38 ppm (s.lH). 5.25 ppm (m.lH), 3.57 ppm (d, 3H), 1.36 ppm (d, 6H).

2-Chloro-4-fluoro-5- [5-cyano-3,6-dihydro-2,6-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester and dimethylsulfate in dimethylformamide, the 2-chloro-4- fluoro-5- [5-cyano-3,6-dihydro-3-methyl-2,6-dioxo-l (2H) -pyrimidinyl] -benzoic acid

isopropyl ester, ¹ H-NMR _(CDCl3, 400 MHz) 8.00 ppm

(S, IH). 7.83 ppm (d.lH), 7.38 ppm (d.lH). 5.25 ppm (m.lH).

HO 'TOC- "; X ^.

2 5: '

- 50 -

3.55 ppm (s.3H), 1.37 ppm (2xd, 6H).

2-Chloro-4-fluoro-5- [5-cyano-3,6-dihydro-4-methyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester and dimethylsulfate in dimethylformamide 2- Chloro-4-fluoro-5- [5-cyano-3,6-dihydro-3,4-dimethyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester, m.p. 171-173 ° C.

2-chloro-4-fluoro-5- [3,6-dihydro-5-fluoro-4-trifluoromethyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester and dimethylsulfate in dimethylformamide 2- Chloro-4-fluoro-5- [3,6-dihydro-5-fluoro-3-methyl-4-trifluoromethyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester, m.p. 66 -68 ° C.

2,4-difluoro-5- (l, 2,4.5,6.7-hexahydro-2,4-dioxo-3H-

-cyclopenta [d] pyrimidin-3-yl) -benzoic acid isopropyl ester and dimethylsulfate with sodium isopropylate in isopropanol, 2,4-difluoro-5- (1,2,4,5,6,7-hexahydro-1-methyl-2,4-dioxo-3H - cyclopentet-pyrimidin-S-yl) -benzoic acid isopropyl ester, m.p. 112-115 ° C.

2,4-Dichloro-5- (1, 2,4,5,6,7-hexahydrio-2,4-dioxo-3H-cyclopenta-cydipyrimidine-S-yl) -benzoic acid isopropyl ester and dimethylsulfate with sodium isopropylate in isopropanol, 2 , 4-dichloro-5- (l, 2,4,5,6,7-hexahydrο-1-methy1 -2,4-dioxo-3H-cyclopenta [djpyrimidin-3-yl) -benzoic acid isopropyl ester ¹ H NMR _(CDCl3, 400 MHz) 7.78 ppm (s.lH). 7.65 ppm (S.IH). 5.23 ppm (m.lH). 3.42 ppm (s, 3H), 2.96 ppm (m.2H). 2.82 ppm (m, 2H). 2.17 ppm (m, 2H). 1.35 ppm (d.6H).

2-Bromo-4-chloro-5- (1, 2,4,5,6,7-hexahydro-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) -benzoic acid isopropyl ester and dimethylsulfate with sodium isopropylate in isopropanol, the 2-bromo-4-chloro-5- (1,2,4,5,6,7-hexahydro-1-methyl-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) - benzoic acid isopropyl ester. ¹ H-NMR _(CDCl3, 400 MHz) 7.86 ppm (s.lH), 7.74 ppm

- 51 -

.. (S.IH). 5.23 ppm (m, IH). 3.42 ppm (s, 3H), 2.96 ppm (m, 2H). 2.82 ppm (m 2H), 2.18 ppm (m, 2H), 1.35 ppm (d, 6H).

Isopropyl 2-bromo-4-fluoro-5- (1,2,4,5,6,7-hexahydro-2,4-dioxo-3H-cyclopentadd) pyrimidine-5-yl-benzoate and dimethylsulfate containing 2-bromo- 4-fluoro-5- (l, 2,4,5,6,7-hexahydro -l-methyl-2,4- dioxo-SH-cyclopentatdJpyrimidin-S-YLJ-benzoic acid isopropyl ester, mp. 116-120 ⁰ C.

2,4-dibromo-5- (1, 2,4,5,6,7-hexahydro-2,4-dioxo-SH-cyclo)

penta [d] pyrimidin-3-yl) -benzoic acid isopropyl ester and dimethyl sulfate with sodium isopropylate in isopropanol, the 2,4-dibromo-5- (l, 2,4,5,6,7-hexahydro-1-methyl-2, 4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) -benzoic acid isopropyl ester ¹ H-NMR _(CDCl3, 400 MHz) 8.03 ppm (s.lH). 4.72 ppm (s, IH), 5.23 ppm (m.lH), 2.96 ppm (m, 2H). 2.83 ppm (m, 2H), 2.17 ppm (m.2H). 1.35 ppm (d.6H).

2-Chloro-4-fluoro-5- [3,6-dihydro-5-fluoro-4-fluoromethyl-2,6-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester and dimethylsulfate in dimethylformamide 2- Chloro-4-fluoro-5- [3,6-dihydro-5-fluoro-4-fluoro-methyl-3-methyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester. Mp. 85-89 ° C.

2-chloro-4-fluoro-5- (1,2,5,6-tetrahydro-2,4-dioxo-furo)

[2,3-d] pyrimidine-3 (4H) -yl) -benzoic acid isopropyl ester, the 2-chloro-4-fluoro-5- {1,2,5,6-tetrahydro-1-methyl-2,4- dioxo-furo [2.3-d] pyrimidin-3 (4H) -yl} -benzoic acid isopropyl ester, mp. 170-173 ⁰ C.

U 3.86

- 52 ..;. Example 6

A solution of 3.6 g of 2-chloro-4-fluoro-5- (1, 2, 4, 5, 6, 7, -hexahydro-2,4-dioxo-SH-cyclopenta [d] pyrimidine-3-one. yl) -benzoic acid isopropyl ester in 50 ml of absolute dimethylformamide is stirred with 0.43 g of a 55% sodium hydride dispersion for 2 hours at room temperature; Subsequently, a solution of 0.93 g of acetyl chloride in 10 ml of absolute dimethylformamide is added dropwise over 10 minutes and the mixture stirred for 2 hours. The reaction mixture is dissolved in 100 ml of ethyl acetate and the solution washed thoroughly with water. The organic phase is dried over anhydrous sodium sulfate and evaporated to dryness. The residue is purified by chromatography on a silica gel column while using methylene chloride / ethyl acetate (3: 1) as the eluent. The 2-chloro-4-fluoro-5- (1,2,4,5,6,7-hexahydro-1-acetyl-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) is obtained ) -benzoic acid isopropyl ester. H-NMR _(CDCl3, 400 MHz) 7.86 ppm (d, IH). 7.37 ppm (dH), 5.24 ppm (mH), 3.13 ppm (m, 2H), 2.75 ppm (m, 2H). 2.68 ppm (see 3H). 2.12 ppm (m, 2H), 1.36 ppm (d, 6H).

In an analogous manner, the use of: 25

13.3.8l · 3335

- 53 -

2-Chloro-4-fluoro-5- (1,2,4,5,6,7-hexahydro-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) -benzoic acid isopropyl ester and methyl chloro-racemate 2-Chloro-4-fluoro-5- {1,2,4,5,6,7-hexahydrio-1-methoxycarbonyl-2,4-dioxo-3H-cyclopenta-difjpyrimidine-S-yl} -benzoic acid isopropyl ester, ¹ H-NMR _(CDCl3, 400 MHz) 7.84 ppm (d, IH), 7.35 ppm (d, IH), 5.24 ppm (m, IH), 4.03 ppm (s, 3H) , 3.02 ppm (m.sup.2H). 2.79 ppm (m, 2H), 2.16 ppm (m, 2H). 1.36 ppm (d, 6H).

| 0 2-Chloro-4-fluoro-5- [3,6-dihydro-4-methyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester, the 2-chloro-4-one fluoro-5- [3-acetyl-3.6-dihydro-4-methyl -2,6-dioxo-l (2H) - pyrimidinyl]. -benzoic acid isopropyl ester, mp 168-170 ⁰ C.

Example 7

To a solution of 15.0 g of isopropyl 2-chloro-4-fluoro-5- [3,6-dihydro-3,4-dimethy1-2,6-dioxo-l (2H) -pyrimidinyl] benzoate in 100 ml of acetic acid are added dropwise at room temperature 6.3 g of sulfuryl chloride for 1 minute while stirring, during which the temperature rises to about 30 ⁰ C. The mixture is subsequently stirred at room temperature for 15 minutes and the reaction mixture is evaporated to dryness under reduced pressure. The residue is dissolved in ethyl acetate and the solution washed successively with aqueous sodium bicarbonate solution and water. The organic phase is dried over anhydrous sodium sulfate and evaporated to dryness. The residue is recrystallized from methylene chloride / diethyl ether. The 2-chloro-4-fluoro-5- [5-chloro-3,6-dihydro-3,4-dimethy1-2.6-dioxo-l (2H) -pyrimidinyl] - benzoic acid isopropyl ester, mp. 15O- 153 ° C.

In an analogous manner, the use of: 35

2-Chloro-4-fluoro-5- [3.6-dihydro-4-methyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester is the 2-chloro

i 0 0 0 Q - "OO

- 54 -

4-fluoro-5- [5-chloro-3.6-dihydro-4-methyl-2,6-dioxo-1 (2H) -pyrimidinyl] benzoic acid isopropyl ester. M.p. 198-201 ⁰ C.

Example 8

To a solution of 3.4 g of 2-chloro-4-fluoro-5- [3.6-

-dihydro-4-methyl-2,6-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester in 20 ml of acetic acid with stirring at 25 ° C for 25 minutes, a solution of 1.7 g of bromine in 20 ml of acetic acid was added dropwise. The reaction mixture is stirred for 1 hour and evaporated to dryness under reduced pressure. The residue is dissolved in diethyl ether and washed with aqueous sodium bicarbonate solution, then with water. The organic phase is dried over anhydrous sodium sulfate and evaporated to dryness. The residue is recrystallized from diethyl ether / n-hexane. The 2-chloro-4-fluoro-5- [5- bromo-3,6-dihydro-4-methyl-2,6-dioxo-1 (2H) -pyrimidinyl] - benzoic acid isopropyl ester, m.p. 187-189 ° C.

In an analogous manner, using:

2-chloro-4-fluoro-5- [3,6-dihydro-3,4-dimethy1-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester is the 2-chloro-4-fluoro-5- [5-bromo-3,6-dihydro-3,4-dimethy1-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester. Mp 127-129 ° C.

Example 9 30

1.50 g of isopropyl 2-chloro-4-fluoro-5- [3,6-dihydro-3,4-dimethyl-2,6-dioxo-1 (2H) -pyrimidinyl] benzoate in 10 ml of acetic acid are charged with 0 , Added 70 g of iodine and stirred for 1 hour at room temperature. Subsequently, the reaction mixture is treated with 0.67 g of 100% nitric acid and stirred for 3 hours at room temperature. The reaction mixture is poured onto 150 ml of ice-water and extracted with 100 ml of ethyl acetate.

.13.3.86- 333 5 1 -η-

- 55 -

, extracted acetate. The organic phase is washed with 150 ml of water, then with 150 ml of aqueous sodium bicarbonate solution and finally with 150 ml of saturated, aqueous sodium hydrogen sulfite solution. The upper phase is dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The residue is recrystallized from methylene chloride / n-hexane. The 2-chloro-4-fluoro-5- [3,6-dihydro-3,4-dimethyl-5-iodo-2,6-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester, m.p. ,

'147-150 ⁰ C.

In an analogous manner, the use of:

2-Chloro-4-fluoro-5- [3,6-dihydro-4-methyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester, the 2-chloro-4-fluoro-5 [3,6-Dihydro-5-iodo-4-methyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester, m.p. 211-213 ° C.

Example 10

5.0 g of 2-chloro-4-fluoro-5- [3.6-dihydro-3,4-dimethyl-2,6-

-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester and 5.7 g of chlorodimethyl ether are heated in an autoclave for 24 hours (about 8-9 atm.) At 100 ⁰ C. After cooling the reaction mixture, this is mixed with methylene chloride and evaporated under reduced pressure at 50 ⁰ C to dryness. There is thus obtained the 2-chloro-4-fluoro-5- [5-chloromethyl-3,6-dihydro-3,4-dimethyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester which for any further reactions do not need to be cleaned. H-NMR (CDCl, 400 MHz) 7.83 ppm (d.lH). 7.34 ppm (d.lH). 5.24 ppm (rn.lH), 4.64 ppm (d, IH), 4.54 ppm (d.hl), 3.52 ppm (s, 3H), 2.48 ppm (s, 3H), 1.37 ppm (i.e. , 3H). 1.35 ppm (d.3H).

Example 11

A solution of 3.5 g of 2-chloro-4-fluoro-5- [3,6-dihydro-

-7

- 56 -

-3,5-dimethyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester in 100 ml carbon tetrachloride is heated with 1.8 g of N-bromosuccinimide and some dibenzoyl peroxide with stirring for 1 hour at reflux temperature. The reaction mixture is illuminated with a 150W bulb. The succinimide is filtered off with suction and the filtrate is evaporated to dryness under reduced pressure. The residue is purified by chromatography on a silica gel column using methylene chloride / ethyl acetate (7: 1) as the eluent. The 2-chloro-4-fluoro-5- [5-bromomethyl-3,6-dihydro-3-methyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester, 1 H-NMR, is obtained (CDC1_, 400 MHz) 7.84 ppm (d, IH). 7.58 ppm (s, IH), 7.36 ppm (ie IH). 5.24 ppm (m, IH), 4.35 ppm (d, IH), 4.29 ppm (d, IH), 3.48 ppm (s, 3H), .15 1.37 ppm (2d, 6H).

Example 12

A solution of 1.14 g of 2-chloro-4-fluoro-5- [5-chloromethyl-3,6-dihydro-3,4-dimethyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid. isopropyl ester in 20 ml of 1,2-dimethoxyethane is stirred with a solution of 0.47 g of sodium bicarbonate in 10 ml of water for 3 hours at room temperature. The solvent is distilled off under reduced pressure and the residue is extracted with ethyl acetate. The organic phase is dried over anhydrous sodium sulfate and evaporated to dryness. The residue is purified by chromatography on a silica gel column using methylene chloride / ethyl acetate (2: 1) as the eluent. The isopropyl 2-chloro-4-fluoro-5- [3,6-dihydro-3,4-dimethyl-5-hydroxymethyl-2, 6-dioxo-1 (2H) -pyrimidinyl] benzoate is obtained. H-NMR _(CDCl3), 400 MHz) 7.83 ppm (d.lH). 7.35 ppm (d.lH). 5.24 ppm (m.lH), 4.59 ppm (d.lH). 4.54 ppm (d.lH), 3.50 ppm (s.3H), 2.44 ppm (s.3H), 2.34 ppm (s, ca.

IH. very broad), 1.36 ppm (d, 6H).

- 57 Example 13

1.14 g of 2-chloro-4-fluoro-5- [5-chloromethyl-3,6-dihydro-3,4-dimethyl-2,6-dioxo-1 (2H) -pyriraidinyl] benzoic acid '- isopropyl esters are dissolved in 10 ml of methanol and the solution is heated at 60 ^° C. for 45 minutes. The reaction mixture is evaporated to dryness under reduced pressure and the residue is dissolved in ethyl acetate and extracted by shaking with aqueous sodium bicarbonate solution. The organic phase is dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure and the residue is purified by chromatography on a silica gel column using diethyl ether / ethyl acetate (15: 1) as the eluent. The 2-chloro

-) 5 -4-fluoro-5- [3,6-dihydro-3,4-dimethyl-5-methoxymethyl-2, 6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester, ¹ H- NMR (CDCl, 400 MHz) 7.82 ppm (d.lH). 7.33 ppm (d.lH), 5.23 ppm (m.lH). 4.40 ppm (d.lH). 4.33 ppm (d.lH). 3.49 ppm (s, 3H). 3.39 ppm (s, 3H), 2.43 ppm (s, 3H), 1.35 ppm (d.6H).

In an analogous manner, the use of:

2-Chloro-4-fluoro-5- [5-chloro-methyl-3,6-dihydro-3,4-dimethy1-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester with isopropanol 2- Chloro-4-fluoro-5- [3,6-dihydro-3,4-dimethyl-5-isopropoxymethyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester. H-NMR (CDCl. ₃ 400 MHz) 7.82 ppm (d, lH), 7:32 ppm (d, lH), 5.22 ppm (m.lH), 4.45 ppm (d, IH), 4.34 ppm (d .lH), 3.69 ppm (m.lH). 3.48 ppm (s.3H), 2.44 ppm (s.3H), 1.35 ppm (d, 6H). 1.21 ppm (d, 6H).

Example 14 35

1.14 g of 2-chloro-4-fluoro-5- [5-chloromethyl-3,6-dihydro-3,4-dimethyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid

- 58 -

, , , isopropyl ester and 0.21 g of sodium methanethiolate are stirred in 5 ml of dimethylformamide for 16 hours at room temperature. The reaction mixture is poured into 100 ml of water and the aqueous mixture extracted with 50 ml of ethyl acetate. The organic phase is washed with water, dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The residue is purified by chromatography on a silica gel column using diethyl ether / n-hexane (7: 1) as the eluent. ¹ is obtained the 2-chloro-4-fluoro-5- [3,6-dihydro-3,4-dimethyl -5-methylthiomethyl-2, 6-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester, H NMR (CDCl _3, 400 MHz) 7.83 ppm (d.hl), 7.33 ppm (d, 1H), 5.23 ppm (in, IH). 3.67 ppm (d.hl), 3.62 ppm (d.hl), 3.50 ppm (s, 3H). 2.43 ppm (p.3H). 2.17 ppm (s.3H).

1.36 ppm (2xd, 6H).

Example 15

3.40 g of isopropyl 5- [6-amino-5-cyano-2-oxo-l (2H) -pyrimidinyl] -2-chloro-4-fluorobenzoate are dissolved in a solution of 100 ml of isopropanol and 10 ml of 2N hydrochloric acid Stirred for 1 hour at room temperature. The reaction mixture is largely concentrated under reduced pressure and extracted with ethyl acetate. The organic phase is washed with aqueous sodium bicarbonate solution, then with water and dried over anhydrous sodium sulfate. It is then evaporated to dryness under reduced pressure, and the residue is dissolved in diethyl ether, treated with charcoal and evaporated to dryness. The residue is recrystallized from diethyl ether / n-hexane. The product is 2-chloro-4-fluoro-5- [5-cyano-3,6-dihydro-2,6-dioxo-1 (2H) -pyrimidinyl] benzoate, m.p. 143-145 ° C.

In an analogous manner, the use of: 35

5- [6-Amino-5-cyano-4-methyl-2-oxo-1 (2H) -pyrimidinyl] -2-chloro-4-fluorobenzoic acid isopropyl ester, the 2-chloro-4-

- 59 - '

^ -fluoro- 5- [5-cyano-3,6-dihydro-4-methyl-2,6-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester. Mp. 189-193 ° C.

Example 16

A solution of 1.50 g of 2-chloro-4-fluoro-5- [3,6-dihydro-

2.0 ml of 100% nitric acid is added at room temperature with stirring to 4-methyl -2,6-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester in 30 ml of methylene chloride.

The solution is then mixed with 5 drops of concentrated sulfuric acid and stirred for 48 hours at room temperature. The reaction mixture is poured onto 150 ml of ice-water, diluted with 100 ml of ethyl acetate and washed four times with 150 ml of water. The organic phase is dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The residue is recrystallized from diethyl ether. 2-Chloro-4-fluoro-5- [3,6-dihydro-4-ethyl-5-nitro-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester, m.p. 205 ⁰ C.

In an analogous manner, the use of:

2-Chloro-4-fluoro-5- [3,6-dihydro-3,4-dimethyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester is the 2-chloro-4-fluoro -5- [3,6-dihydro-3 _# 4-dimethyl-5-nitro-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester. Mp 129-131 ° C.

Example 17 30

1.8 g of bromine in 10 ml of acetic acid are added dropwise with stirring at 10-15 ^° C. to 2.1 g of ammonium thiamide in 80 ml of acetic acid over a period of 15 minutes. Subsequently, 1.5 g of isopropyl 2-chloro-4-fluoro-5- [3.6-dihydro-4-methyl-2,6-dioxo-l (2H) -pyrimidinyl] benzoate in 15 ml of acetic acid for 5 minutes at 10 -15 ⁰ C was added dropwise, and the Reaktionsge.raisch is 1 hour at room temperature downstream

- 60 -

 ο

stirred and then largely evaporated under reduced pressure. The residue is dissolved in ethyl acetate, the insoluble matter is filtered off with suction and the filtrate is washed with aqueous sodium bicarbonate solution, then with water. The organic phase is dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The residue is purified by chromatography on a silica gel column using methylene chloride / ethyl acetate (3: 1) as the eluent. The product is recrystallized from methylene chloride / diethyl ether. The isopropyl 2-chloro-4-fluoro-5- [3,6-dihydro-4-methyl-5-thiocyanato-2,6-dioxo-1 (2H) -pyrimidinyl] benzoate is obtained. Mp 159-161 ° C.

-) 5 Analogously, the use of:

2-Chloro-4-fluoro-5- [3,6-dihydro-3,4-dimethyl-2,6-dioxo-1 (2H) -pyrimidinyl] -benzoic acid isopropyl ester is the 2-chloro-4-fluoro -5- [3,6-dihydro-3,4-dimethyl-5-thiocyanato-2,6-dioxo-l (2H) -pyrimidinyl] -benzoic acid isopropyl ester, ¹ H-NMR (CDCl. ₃ 400 MHz) 7.83 ppm (d, lH), 7.36 ppm (d.lH). 5.25 ppm (m, 1H). 3.59 ppm (s, 3H), 2.80 ppm (s, 3H), 1.38 ppm (d, 3H), 1.36 ppm (d, 3H).

Example 18

3.2 g of finely pulverized 2-chloro-5- (1,2,4,5,6,7-hexahydro-1-methyl-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) -benzoic acid and 3.5 g of freshly distilled thionyl chloride in 60 ml of absolute benzene are heated with stirring for 5 to 6 hours at reflux temperature until a clear solution is formed. The reaction mixture is evaporated to dryness, the acid chloride dissolved in 40 ml of absolute methylene chloride, 1.0 g of 1-methoxy-2-propanol and 0.9 g of pyridine added and the whole stirred at 23 ° C for 1 hour. Subsequently, the reaction mixture is evaporated to dryness, the residue dissolved in ethyl acetate and the solution

n? p.r- ^ 335 K

- 61 -

thoroughly washed with water. The organic phase is dried over anhydrous sodium sulfate and evaporated to dryness. The residue is purified by chromatography on 300 g of silica gel using ethyl acetate / methylene chloride (1: 3) as the eluent. The 2-chloro-5- (1, 2,4,5,6,7-hexahydro-1-methyl-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) -benzoic acid (2-chloro) is obtained. methoxy-l -methyläthyl) ester, ¹ H-NMR _(CDCl3, 400 MHz) 7.72 ppm (d, IH), 7:55 ppm (d, IH), 7.27 ppm (q, IH), 5.32 ppm (with IH).

3.57 ppm (q, IH). 3.48 ppm (q, IH). 3.39ppm (p.3H), 3.37ppm (s, 3H), 2.93ppm (m, 2H), 2.80ppm (m, 2H), 2.15ppm (m, 2H), 1.35ppm (ie 3H).

In an analogous manner, the use of:

2-chloro-5- (l, 2.4,5.6.7-hexahydro-l-methyl-2,4-dioxo-3H

-cyclopenta [d]) pyrimidin-3-yl) -benzoic acid over the corresponding acid chloride and tert-butanol the 2-chloro-5- (l, 2,4,5,6,7-hexahydro-l-methyl -2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) -benzoic acid tert -butyl ester, m.p.

2-Chloro-4-fluoro-5- (1,2,4,5,6,7-hexahydro-1-methyl-2,4-dioxo-SH-cyclopenta [d] pyrimidin-3-yl) -benzoic acid over the corresponding acid chloride and 1 -Methoxy-2-propanol, the 2-chloro-4-fluoro-5- (1,2,4,5,6,7-hexahydro-1-methyl-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) - benzoic acid (2-methoxy-1-methylethyl) ester. ¹ H-NMR _(CDCl3, 400 MHz) 7.84 ppm (d.lH), 7:34 ppm (d, lH), 5.30 ppm (m.lH). 3.56 ppm (q.lH). 3.47 ppm (q.lH). 3.40 ppm (s, 3H). 3.37 ppm (p.3H). 2.94 ppm (m, 2H). 2.80 ppm (m.2H). 2.16 ppm (m, 2H), 1.34 ppm (d.3H).

2-Chloro-4-fluoro-5- (1,2,4,5,6,7-hexahydro-1-methyl-2,4-dioxo-SH-cyclopentatdipyrimidine-S-yD-benzoic acid over the corresponding acid chloride and tert. Butanol the 2-chloro-4-fluoro-5- (l, 2.4.5.6, 7-hexahydro-l-methyl-2,4- <3-o-3-yl)

- 62 -

, -cyclopenta [d] pyrimidin-3-yl) -benzoic acid tert-butyl ester, 1 H-NMR (CDCl ₃ , 400 MHz) 7.76 ppm (d, 1H), 7.31 ppm (d, 1H), 3.41 ppm (s, 3H), 2.94 ppm (m, 2H), 2.81 ppm (m.2H), 2.17 ppm (m, 2H). 1.57 ppm (p.9H).

Example 19

A solution of 3.6 g of 2-chloro-5- [1,4,5,6,7,8-hexahydro-1-methyl-1,2,4-dioxo-3 (2H) -quinazolinyl] benzoic acid ethyl ether. ester in 70 ml of ethanol is maintained with 0.6 g of sodium hydroxide in 70 ml water for 10 minutes at 6O ⁰ C and then stirred for 1 hour. The solution is largely evaporated under reduced pressure and the residue is brought to pH 1 with 2N hydrochloric acid. The precipitate is shaken out five times with 50 ml of diethyl ether, and the organic phases are dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The 2-chloro-5- [1,4,5,6,7,8-hexahydro-1-methyl-2,4-dioxo-3 (2H) -quinazolinyl] benzoic acid is obtained.

The free acid is mixed with 0.84 g of sodium bicarbonate.

The mixture was stirred in 50 ml of water and the solution was evaporated to dryness under reduced pressure. The residue was evaporated three times with 50 ml of absolute ethanol to dryness, and triturated with a little diethyl ether, and the crystals are filtered off with suction and dried under reduced pressure at 70 ⁰ C. The 2-chloro-5- [1,4,5,6,7,8-hexahydro-1-methyl-2,4-dioxo-3 (2H) -quinazolinyl] -benzoic acid sodium salt is obtained.

1.78 g of the sodium salt are dissolved in 30 ml of absolute dimethylformamide, and the solution is heated to 100 ^° C. with 1.2 g of isopropyl bromide for 1 hour. The solvent is then removed under reduced pressure, the residue is dissolved in 100 ml of ethyl acetate, the solution is extracted by shaking with water and the organic phase is dried over anhydrous sodium sulfate. After removal of the

- 63 -

Solvent, the residue is crystallized from diethyl ether / n-hexane. The 2-chloro-5- [1,4,5,6,7,8-hexahydro-1-methyl-2,4-dioxo-3 (2H) -quinazolinyl] benzoic acid isopropyl ester, m.p. 138 ° C.

In an analogous manner, the use of:

2-Chloro-5- [1,4,5,6,7,8-hexahydro-2,4-dioxo-3 (2H) -quinazolinyl] -benzoic acid ethyl ester, the 2-chloro-5- [1,4,5, 6,7,8-hexahydro-2,4-dioxo-3 (2H) -quinazolinyl] -benzoic acid isopropyl ester. M.p. 205-207 ⁰ C.

Ethyl 2-chloro-5- (1,2,4,5,6,7-hexahydro-1-methyl-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) benzoate over the sodium salt the corresponding carboxylic acid and methyl iodide, the 2-chloro-5- (1,2,4,5,6,7-hexahydro-1-methyl-2, 4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) - benzoic acid methylester. Mp 164-166 ° C.

2-Chloro-S- (I.2,4,5,6,7-hexahydro-1-methyl-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) -benzoic acid ethyl ester via the sodium salt of the corresponding carboxylic acid and isopropyl bromide 2-Chloro-5- (1,2,4,5,6,7-hexahydro-1-methyl-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) -benzoic acid isopropyl ester, m.p. -150 ⁰ C.

Example 20

A solution of 26.6 g of 2-chloro-4-fluoro-5- (1,2,4,5,6,7-hexahydro-1-methyl-2,4-dioxo-3H-cyclopenta [d] pyrimidine - 3-yl) -benzoic acid isopropyl ester in 1.7 1 of methanol is added to a solution of 3.08 g of sodium hydroxide in 700 ml of water. The reaction mixture is stirred for 15 hours at room temperature during which 2.1 liters of water are continuously added dropwise. Stirring is continued for a further 15 hours, the pH of the mixture reaching 9-10. The mixture is acidified with concentrated hydrochloric acid and concentrated,

ο r »ftp- 3335'ι"

"t

- 64 -

, It is under reduced pressure at about 20 ° C to a volume of about 300 ml. The crystals are filtered off, washed with a little water and dried at 40-5O ⁰ C under reduced pressure. The 2-chloro-4-fluoro-5- (1,2,4,6,6,6-hexahydro-1-methyl-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) is obtained. benzoic acid, mp. 270-273 ⁰ C.

18.85 g of the acid are stirred with 4.67 g of sodium bicarbonate in 300 ml of water at 50 ^° C. for 30 minutes. The insoluble fraction is filtered off and the filtrate was evaporated under reduced pressure at 40-50 ⁰ C to dryness. The residue is dissolved in 50 ml of methanol and the solution is treated with 100 ml of benzene and evaporated to dryness under reduced pressure. Subsequently, with another 100 ml

- | 5 Benzene evaporated to dryness. The 2-chloro-4-fluoro-5- (1, 2,4,5 »6,7-hexahydro-1-methyl-2,4-dioxo-3H-cyclopenta [d] pyrimidija-3 yl) benzoic acid sodium salt.

1.9 g of the sodium salt are dissolved in 15 ml of absolute dimethylformamide and stirred at 70 ^° C. with 0.6 g of 3-bromo-1-propene for 2 hours. The solvent is distilled off under reduced pressure and the residue is dissolved in ethyl acetate / diethyl ether and extracted by shaking with water. The organic phase is dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The 2-chloro-4-fluoro-5- (1,2,4,5,6 ·, 7-hexahydro-l-methyl ^^ [d] pyrimidin-3-yl) -benzoic acid 2-propenyl ester, H NMR _(CDCl3, 400 MHz) 7.90 ppm (d.lH). 7.35 ppm (d.IH), 6.05-5.94 ppm (m, IH). 5.40 ppm (m.lH), 5.29 ppm (m.lH). 4.79 ppm '(m.2H), 3.41 ppm (s.3H). 2.94 ppm '(m, 2H), 2.81 ppm (m.2H). 2.16 ppm (m, 2H).

In an analogous manner, the use of: 35

Sodium salt of 2-chloro-4-fluoro-5- (1,2,4,5,6,7-hexahydro-1-methyl-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) -

250-

- 65 -

benzoic acid and chlorodimethyl ether give the 2-chloro-4-fluoro-5- (1,2,4,5,6,7-hexahydro-1-methyl-2,4-dioxo-3H-cyclopenta- [d] pyrimidine-3- yl) -benzoesäui: e-methoxymethyl, H-NMR _(CDCl3, 400 MHz) 7.93 ppm (d, lH), 7.36 ppm (d, lH), 5.45 ppm (S.2H), 3.54 ppm (s, 3H), 3.41 ppm (s, 3H). 2.95 ppm (m, 2H), 2.81 ppm (m, 2H). 2.17 ppm (m, 2H).

Sodium salt of 2-chloro-4-fluoro-5- (1,2,4,5,6,7-hexahydro-1-methyl-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) -benzoic acid and 3-bromo-l-propyne the 2-chloro-4-fluoro-5- (1,2,4,5,6,7-hexahydro-1-methyl-2,4-dioxo-3H-cyclopenta- [ d] pyrimidin-3-yl) benzoic acid -2-propynyl ester, mp 193-195 ° C.

Sodium salt of 2-chloro-4-fluoro-5- (1,2,4,5,6,7-hexahydro-1-methyl-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) - benzoic acid and methyl iodide, the 2-chloro-4-fluoro-5- (1,2,4,6,6,6-hexahydro-1-methyl-2,4-dioxo-3H-cyclopenta [d] pyrimidin-3-yl) benzoic acid methyl ester, mp 138-141 ° C.

II. Preparation of the compounds of the formula II:

Example 21

48.4 g of 2-chloro-5-ureido-benzoic acid ethyl ester and 31.2 g of cyclopentanone-2-carboxylic acid ethyl ester are heated in 500 ml of benzene and 2 g of toluene-4-sulfonic acid monohydrate for 6 hours at reflux. The water forming is removed by means of a water separator. Subsequently, the reaction mixture is evaporated to dryness, the residue dissolved in 700 ml of diethyl ether and the solution filtered. The filtrate is evaporated to dryness and the residue is chromatographed on 1.5 kg of silica gel using diethyl ether / n-hexane (1: 2) as the eluent. The 2-chloro-5- {3- [2- (ethoxycarbonyl) -1 -cyclopenten-1-yl] -ureido} -benzoic acid ethyl ester is obtained as colorless crystals. The

- 66 -

..Product is recrystallized from diethyl ether / n-hexane, mp 110-112 ⁰ C.

In an analogous manner, the use of:

Ethyl 2-chloro-5-ureidobenzoate and cyclohexanone

2-carboxylic acid ethyl ester 2-chloro-5- {3- [2- (ethoxycarbonyl) -1-cyclohexen-1-yljureidoj-benzoic acid ethyl ester, mp. 119-122 ° C.

2-Chloro-4-fluoro-5-ureidobenzoic acid isopropyl ester and

Cyclopentanone-2-carboxylic acid ethyl ester 2-chloro-4-fluoro-5- {3- [2- (ethoxycarbonyl) -l-cyclopenten-1-yl] ureido} - benzoic acid isopropyl ester, m.p. 146-149 ° C.

2-Chloro-4-fluoro-5-ureidobenzoic acid isopropyl ester and

Ethyl 2-chloro-4-fluoro-5- {3- [2- (ethoxycarbonyl) -l-cyclohexene-1-yl] ureido} - benzoic acid isopropyl ester, mp 129-130 ⁰ C.

Ethyl 2-nitro-5-ureidobenzoate and cyclopentanone-2-carboxylic acid ethyl ester give ethyl 5- {3- [2- (ethoxycarbonyl) -l-cyclopenten-1-yl] ureido} -2-nitrobenzoate, m.p. 152-155 ° C.

, ,

2-Chloro-4-fluoro-5-ureidobenzoic acid isopropyl ester and 3-oxo-tetrahydrothiophene-2-carboxylic acid methyl ester 2-chloro-4-fluoro-5- {3- [2- (methoxycarbonyl) -4,5-dihydro-thiene - 3-yl] ureido} -benzoic acid isopropyl ester, mp 161-163 ° C.

2-Chloro-4-fluoro-5-ureidobenzoic acid isopropyl ester and 3-oxo-tetrahydro-thiophene-4-carboxylic acid, ethyl ester, the 2-chloro-4-fluoro-5- {3- [4- (methoxycarbony1) -2,5-dihydro- thien-3-yl] ureido} -benzoic acid isopropyl ester.

Ethyl 2-chloro-5-ureidobenzoate and methyl 3-oxotetrahydrothiophene-4-carboxylate 2-chloro-5- {3-

U 3.86- 333Si.

- 67 -

[4- (methoxycarbonyl) -2,5-dihydro-thien-3-yl] ureido} - benzoic acid ethyl ester.

2-Chloro-4-fluoro-5-ureidobenzoic acid isopropyl ester and 3-oxo-caproic acid ethyl ester 2-chloro-4-fluoro-5- {3-r [2- (ethoxycarbonyl) -1-propylvinyl] ureido } benzoic acid isopropyl ester.

2-Chloro-4-fluoro-5-ureidobenzoic acid isopropyl ester and 3-oxo-n-valeric acid ethyl ester using finely pulverized Amberlyst®-15 (a free sulfongruppen, organic, polymeric resin) as a catalyst, the 2-chloro-4 -fluoro-5- {3- [2- (ethoxycarbonyl) -1-ethylvinyl-jureido} -benzoic acid isopropyl ester, m.p. 123-126 ° C.

2,4-Difluoro-5-ureidobenzoic acid isopropyleste ₄ r and

Cyclopentanone-2-carboxylic acid ethyl ester in toluene, the 2,4-difluoro-5- {3- [2- (ethoxycarbonyl) -1-cyclopenten-1-yl] -ureidoj-benzoic acid isopropyl ester, mp. 149-151 ° C. ,

2,4-dichloro-5-ureidobenzoic acid isopropyl ester and

Cyclopentanone-2-carboxylic acid ethyl ester using finely pulverized Amberlyst®-15 as a catalyst, the 2,4-dichloro-5- {3- [2- (ethoxycarbonyl) -l-cyclopenten-1-yl] -ureido} -benzoesäure- isopropyl ester. Mp 140-142 ⁰ C.

2-Bromo-4-chloro-5-ureidobenzoic acid isopropyl ester and cyclopentanone-2-carboxylic acid ethyl ester in toluene, the 2-bromo-4-chloro-5- {3- [2- (ethoxycarbonyl) -1-cyclopenten-l yl] ureido} benzoic acid isopropyl ester. Mp 131-132 ° C.

2,4-Dibromo-5-ureidobenzoic acid isopropyl ester and cyclopentanone-2-carboxylic acid ethyl ester in toluene, the 2,4-dibromo-5- {3- [2- (ethoxycarbonyl) -1-cyclopenten-1-yl-ureido} - benzoic acid isopropyl ester , Mp 157-158 ° C.

• i α }

- 68 -

2-Bromo-4-fluoro-5-ureidobenzoic acid isopropyl ester and cyclopentanone-2-carboxylic acid ethyl ester in toluene, the 2-bromo-4-fluoro-5- {3- [2- (ethoxycarbonyl) -l-cyclopenten-l -yl] ureido} -benzoic acid isopropyl ester, m.p. 15O-154 ° C.

4-Bromo-2-fluoro-5-ureidobenzoic acid isopropyl ester and

Cyclopentanone-2-carboxylic acid ethyl ester in toluene, the isopropyl 4-bromo-2-fluoro-5- {3- [2- (ethoxycarbonyl) -l-cyclopenten-1-yl] -ureido} benzoate. Mp 166-168 ° C.

Example 22

4.7 g of ethyl 3-amino-2-raetliylcrotonsäure, dissolved in 15 ml of absolute diethyl ether, is added at 23 ° C with stirring with a solution of 6.7 g of 2-chloro-5-isocyanatobenzoesäure- ethyl ester and 2 hours stirred. The reaction mixture is evaporated to dryness under reduced pressure and the residue is chromatographed on 400 g of silica gel using diethyl ether / n-hexane (1: 1) as the eluent. This gives the 2-chloro-5- - {3- [2- (ethoxycarbonyl) -l -methylpropenyl] ureido} - benzoic acid ethyl ester, mp. 88-91 ° C.

In an analogous manner, using: 25

2-Chloro-4-fluoro-S-isocyanatobenzoic acid isopropyl ester and 3-amino-2-methylcrotonic acid ethyl ester give 2-chloro-4-fluoro-5- {3- [2- (ethoxycarbonyl) -1-methyl-propenyl] - ureido} -benzoic acid isopropyl ester, mp. 145-147 ° C.

2-Chloro-5-isocyanatobenzoic acid ethyl ester and 3-aminocrotonic acid ethyl ester 2-chloro-5- {3- [2- (ethoxycarbonyl) -1-methylvinyl] ureido} benzoic acid ethyl ester.

2-Chloro-4-fluoro-5-isocyanatobenzoic acid isopropyl ester and 3-aminocrotonic acid ethyl ester give 2-chloro-4-fluoro-5- {3- [2- (ethoxycarbonyl) -1-methylvinyl] ureido} benzoic acid

-; oo c. "ο ο

^ S O 4 7: i

- 69 acid isopropyl ester, mp. 147-150 ⁰ C.

Isopropyl 2-chloro-4-fluoro-S-isocyanatobenzoate and ethyl 3-amino-2-fluoro-crotonic acid, the 2-chloro-4-fluoro-5- {3- [2- (ethoxycarbonyl) -2-fluoro-1 -ethyl vinyl] -ureidoj-benzoic acid isopropyl ester, m.p. 15O-152 ° C.

2-Chloro-4-fluoro-5-isocyanatobenzoic acid isopropyl ester and 3-amino-2-ethylcrotonic acid ethyl ester in diraethylforraamide the 2-chloro-4-fluoro-5- {3- [2- (ethoxycarbonyl) -1-methyl -l-butenyl] ureido} -benzoic acid isopropyl ester, m.p. 112-115 ° C.

2-Chloro-4-fluoro-5-isocyanatobenzoic acid isopropyl ester and 3-amino-2-methyl-2-pentenoic acid ethyl ester 2-chloro-4-fluoro-5- {3- [2- (ethoxycarbonyl) -l ethyl-1-propenyl] -ureido} -benzoic acid isopropyl ester, m.p. 132-133 ° C.

2-Chloro-4-fluoro-5-isocyanatobenzoic acid isopropyl ester and 2-amino-4, S-dihydro-S-carboxylic acid ethyl ester, the 2-chloro-4-fluoro-5- {3- [3- (ethoxycarbonyl) - 4,5-dihydro-furan-2-yl] ureido} -benzoic acid isopropyl ester.

Example 23

6.0 g of ethyl 2-chloro-5-ureidobenzoate and 6.4 g of ethyl 3-ethoxyacrylate are heated to reflux temperature in 100 ml of 1,2-dimethoxyethane and then heated at this temperature for 5 minutes with 12 ml of 2N hydrochloric acid. The reaction mixture is evaporated to dryness under reduced pressure and the residue is purified by chromatography on 300 g of silica gel using ethyl acetate / n-hexane (1: 3) as the eluent. The ethyl 2-chloro-5- {3- [2- (ethoxycarbonyl) vinyl] -ureido} benzoate, mp 116-117 ° C., is obtained.

333b i τ

- 70 -

Example 24

27.4 g of isopropyl 2-chloro-4-fluoro-5-ureidobenzoate and 13.0 g of methyl 3-methoxy-2-methyl-acrylate are dissolved in 250 ml of benzene with 1.9 g of toluene-4-sulfonic acid monohydrate 2 Heated to reflux temperature for hours. The reaction mixture is evaporated to dryness under reduced pressure and the residue is stirred with 400 ml of diethyl ether. The insoluble part is filtered off with suction and the filtrate is evaporated to dryness under reduced pressure. The residue is purified by chromatography on 1 kg of silica gel using ethyl acetate / n-hexane (1: 3) as the eluent. The 2-chloro-4-fluoro-5- {3- [2- (methoxycarbonyl) -propenyl-jureido} -benzoic acid isopropyl ester, mp. 189-190 ° C., is obtained.

III. Preparation of the compounds of the formula VI :

Example 25

To 0.71 g of a 55% sodium hydride dispersion in

25 ml of dimethylformamide 1.52 g of 3-amino-2-cyanacrylsäurenitril added, and the mixture is stirred at 30 ⁰ C for 30 minutes. After completion of the evolution of hydrogen, the mixture is mixed with 4.20 g of 2-chloro-4-fluoro-5-isocyanatobenzoic acid isopropyl ester, during which the temperature rises to 30 ⁰ C. The mixture is then stirred for 2 hours at room temperature, poured the reaction mixture into water, and the aqueous mixture acidified with acetic acid and extracted twice with 100 ml of ethyl acetate. The organic phase is washed with water, dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The residue is dissolved in 50 ml of methylene chloride and brought to 0 ⁰ C by addition of diethyl ether and cooling to crystallize. The 5- [6-amino-5-cyano-2-oxo-1 (2H) -pyrimidinyl] -2-chloro-4- is obtained.

^1O

- 71 -

-fluorbenzoesäure isopropyl ester. Mp 212-213 ° C. In an analogous manner, the use of:

3-amino-2-cyanatocrotononitrile and 2-chloro-4-fluoro-5-isocyanatobenzoic acid isopropyl ester give 5- [6-amino-5-cyano-4-methyl-2-oxo-1 (2H) -pyrimidinyl] -2-chloro-4-fluorobenzoic acid isopropyl ester, m.p. 255-257 ° C.

IV. Formulation Examples :

Example 26

To prepare a 50% wettable powder, the ingredients listed below are mixed together:

Compound of formula I ¹ or II silicic acid, sodium hydrated lauryl sulfate 20 sodium lignosulfonate kaolin

This mixture is finely ground in a suitable mill.

0 o

0. 0.

Claims (18)

- 72 - Claim for invention 1'
in that R of the formula I * denotes methyl. 1. weed control agent, characterized in that it contains an effective amount of at least one compound of the general formula COOR 2-Chloro-4-fluoro-5- (1,2,4,5,5,7-hexahydro-1-yme 1-2,4-dioxo-3H-cyclopenta (d) pyrimidin-3-yl ) -benzoesauremethylester, contains selected compound and formulation auxiliaries. - 78 - 2-chloro-4-fluoro-5- (l, 2,4,5,6,7-hexahydro-l-methyl-2,4-dioxo-3H-cyclopenta (d) pyrimidin-3-yl) -benzoic acid 2-propynyl ester and 2-chloro-4-fluoro-5- (1,2,4,5,6,7-hexahydro-l-methy1-2,4-dioxo-3H-cyclopenta (d) pyrimidin-3-yl) -benzoic acid 2-propenyl ester, 2-chloro-5- (1,4,5,6,7,8-hexahydro-l-methy1-2,4-dxoxo-3 (2H) -quinazolinyl) -benzoic acid isopropyl ester, 2-chloro-5- (l, 2,4,5,6,7-hexahydro-l-methy1-2,4-d1OXO-3H-cycIopenta (d) pyrimidin-3-yl) -benzoic acid tert-butyl ester, 2,6-dioxo-1 (2H) -pyrimidinyl) -benzoic acid isopropyl ester, 2-chloro-4-f 2-chloro-4-fluoro-5- (1,2,4,5,6,7-hexahydro-1-methoxycarbony 1-2, 4-dioxo-3H-cyclopenta (d) pyrimidin-3-yl) benzoic acid acid isopropyl, 2-chloro-4-fluoro-5- {1,2,4,5,6,7-hexahydro-l-acetyl-2,4-dioxo-3H-cyclopenta (d) pyrimidin-3-yl) -benzoesäureisopropylester, 2 ~ bromo-4-chloro-5- (1,2,4,5,6,7-hexahydro-l-methy1-2,4-dioxo-3H-cyclopenta (d) pyrimidin-3-yl) -benzoesäureisopropylester, 2,4-dichloro-5- (l, 2,4,5,6,7-hexahydro-l-methyl-2,4-dioxo-3H-cyclopenta (d) pyrimidin-3-yl) -benzoic acid isopropyl esters, - 77 - 2-chloro-4-fluoro-5- (S-cy
2,6 ~ dioxo-l (2H) -pyrimidinyl) -benzoic acid isopropyl ester, 2-chloro ~ 4-f luor-5- (4-ethyl-3, 6-dihydro-3 ₁ 5-dirπethyl-2, 5 ~ dioxo-l (2H) -pyrimidinyl) -benzoic acid isopropyl ester, 2-Chloro-4-fluoro-5- (1,2,5,7-tetrahydro-1-methyl-2 , A -dioxothieno (3,4-d) pyrimidine-3 (4H) -yI) -banoic acid οpropylester, 2-chloro-4-fluoro-5- (3,6-dihydro-3,4,5-trimethyl-2 _< 6-dioxo-1 (2H) -pyrimidinyl) -benzoic acid isopropyl ester, 2-chloro-5- (3,5-dihydro-3,4,5-trimethyl-2,6-dioxo-l (2H) -pyrimidinyl) -benzoic acid ethyl ester, 2-Chloro-5- (3,6-dihydro-3,4-dirr>, ethyl ~ 2 _# 6-c! Ioxo-i (2H) -pyrimidinyl) -benzoic acid ethyl ester, 2-chloro-5- (! ^^, ö ^ .S-3 (2H) -quinazolinyl) -benzoic acid ethyl ester, 2-Chloro-5- (1,2,4,5,6,7-hexahydro-1-methyl-2,4-dioxo-3H-cyclopenta (d) pyrimidin-3-yl) -benzoic acid ethyl ester, 2-chloro-4-fluoro-5- (3,6-dihydro-5-fluoro-3-methyl-4-trifluoromethyl-2,5-dioxo-l (2H) -pyrimidinyl) -benzoesaureisopropy! Ester - 76 - selected compound and formulation adjuvants. , 2-Chloro-4-fluoro-5- (3,6-dihydro-3-methyl-4-propyl-2, 6α-oxo-1 (2H) -pyrimidinyl) -benzoic acid isopropyl ester and 2-chloro-4-fluoro-5- (3,6-dihydro-3,4-dimethyl-5-fluoro-2,6-dioxo-1 (2H) -pyrimidinyl) -benzoic acid isopropyl ester, Tert-Butyl 2-chloro-4-fluoro-5- (1,2,4,5,6,7-hexahydro-1-methyl-2,4-dioxo-SH-cyclopentadyl) pyrimidine-S-ylJ-benzoate selected compound and formulation adjuvants. 2-chloro-4-fluoro-5- (1,2,4,5,5i7-hexahydro-l-methyl-2,4-dioxo-3H-cyclopenta (d) pyrimidin-3-yl) -benzoic acid- (2 -methoxy-1-methylethyl) ester and 2-Chloro-4-fluoro-5- (3 ₁ 6-dihydro-3,4-dimethyl-5-nitro-2 _, 6-dioxo-1 (2H) -pyrimidinyl) -benzoic acid isopropyl ester, 2-bromo-4-fluoro-5- (l, 2,4,5,6,7-hexahydro-l-methyl-2,4-dioxo-3H-cyclopenta (d) pyrimidin-3-yl) -benzoesäureisopropylester, 2-chloro-4-fluoro-5- (3,6-dihydro-3-methyl-4-trifluorm6thy1-2,6-dioxo-l (2H) -pyrimidinyl) -benzoesaure isopropyl ester, 2-chloro-4-fluoro-5- (4-äthy1-3,6-dihydro-3-methy1-2,6-dioxo-l (2H) -pyrimidinyl) -benzoic acid isopropyl ester, f Γ ¹ * ΓΓ "/ ^ j ν / ⁴ ^ \, ^ ^: - ¹ C-? - 75 - 2-chloro-4-fluoro-5- (3,6-dihydro-3,4-dimethy1-5-hydroxymethyl-2,6-dioxo-l (2H) -pyrimidinyl) -benzoic acid isopropyl ester, 2-chloro-4-fluoro-5- (3,6-dihydro-3,4-dimethyl-5-iodo-2,6-dioxo-l (2H) -pyrimidinyl) -benzoesaure isopropyl ester, 2-chloro-4-fluoro-5- (5-bromo-3,6-dihydro ~ 3,4-dimethyl-2,6-dioxo-l (2H) -pyrimidinyl) -benzoic acid isopropyl ester, 2-chloro-4-fluoro-5- (3,6-dihydro-3,4-dimethyl-2,6-dioxole (2H) -pyrimidinyl) -benzoic acid isopropyl ester, 2-chloro-4-fluoro-5- {1,4,5,6,7,8-hexahydro-1-methyl-2 , a- dioxo-3 (2H) -quinazolinyl) -benzoic acid isopropyl ester, 2-chloro-4-fluoro-5- (1,2,4,5,6,7-hexahydro ~ l-methyl ~ 2 »4-dioxo-3H-cyclopenta (d) pyrimidin-3-yl) -benzoesäureisopropylester, 2 ' characterized in that R d or C ~ _fi represents alkoxyalkyl. 2. weed control agent according to item I ₁ marked 2 ' I ¹ wherein or
R and C ₂ _ ₄ alkenyl, C ₂ _ ₄ alkynyl, C_ --Alkoxyalkyl, Formylj Cp _r alkanoyl or C, -Älkoxycarbonyl, C 1 -C ₄ alkyl, C ₄ alkenyl, C 1 -C ₄ alkynyl or C 1 -C 4 alkoxyalkyl,
Halogen or nitro ·
Hydrogen or halogen Hydrogen, halogen, C ₄ -alkyl, chloromethyl, bromomethyl, hydroxymethyl, (C ₁ -C -alloxy) methyl, (C ₅ -alkylthio) methyl, cyano, nitro or thiocyanato,
Hydrogen, C _1-4 -alkyl or C-fluoroalkyl, R together tri- or tetramethylene, in which a methylene may be replaced by oxygen or sulfur, and which is optionally substituted by C-alkyl. - 73 - X is oxygen or sulfur, with the provisos that (i) when R is fluoro, R is C ₁ alkyl alone 3. weed control composition according to claim 1 or 2, 4. weed control agent according to one of the items 1 to 3, characterized in that R of the formula I 'is chlorine or bromine. 5. weed control agent according to one of the items 1 to 4, characterized in that R of the formula I 'is fluorine. 5 is C ₁ -fluoroalkyl, and- (ii) if R is for Cyano, R is exclusively hydrogen or C _1-4 -alkyl and X is exclusively oxygen,
and formulation adjuvants. 6. weed control agent according to one of the items 1 to 5, characterized in that R of the formula I 'is hydrogen, chlorine, bromine, methyl or ethyl. 7. weed control agent according to any one of items 1 to 6, characterized means characterized in that R of the formula I "fluorine -7a 8. weed control agent according to one of the items 1 to 6, characterized in that R of the formula I ^{1 is} methyl, ethyl or trifluoromethyl. 9. weed control agent according to one of the items 1 to 5, characterized in that together R and R of the formula I 'tri or tetramethylene mean. 10. weed control agent according to item 1, characterized in that it contains an effective amount of at least one of the group 11. weed control agent according to item 1, characterized in that it contains an effective amount of at least one of the group 12, weed control composition according to item 1, characterized in that it contains an effective amount of at least one of the group Weed control composition according to item 1, characterized in that it contains an effective amount of 2-chloro-4-fluoro-5- (3,6-dihydro-3,4-dimethyl-5-methoxy-methyl-2,6-dioxo) Contains 1 (2H) -pyrimidinyl) -benzoic acid isopropyl ester and formulation auxiliaries. 14. A process for the preparation of a weed control agent, characterized in that at least one of the compounds mentioned in point 1. mixed with formulation excipients. 15. A method for controlling weeds, characterized in that treating the weed to be protected and / or the weeds with an effective amount of an agent according to any one of items 1 to 6, 8 to 10 and 12, 16. A method of controlling weeds, characterized by treating the weeds to be protected against weeds and / or the weeds with an effective amount of an agent according to any of items 7, 11 and 13. 17 "Use of a jet" according to any one of items 1 to 6, 8 to 10 and 12, characterized by 'i / in. 49 5 5 3 'i C Ό κ. · ' - 79 - that it is used to control weeds. 18. Use of an agent according to one of the .Punkte 7, 11 and 13, characterized in that it is used for controlling weeds.