Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
  • C07C303/34—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfuric acids
• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
  • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
  • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
  • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C307/00—Amides of sulfuric acids, i.e. compounds having singly-bound oxygen atoms of sulfate groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
  • C07C307/04—Diamides of sulfuric acids
  • C07C307/06—Diamides of sulfuric acids having nitrogen atoms of the sulfamide groups bound to acyclic carbon atoms
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C381/00—Compounds containing carbon and sulfur and having functional groups not covered by groups C07C301/00 - C07C337/00
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
  • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
  • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
  • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
  • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
  • C07D239/52—Two oxygen atoms
  • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals

Definitions

• the present invention relates to a process for the preparation of sulfonic acid diamides of general formula I.
• R 1 and R 2 independently of one another are a primary alkyl radical having 1 to 8 C atoms, a secondary alkyl radical having 3 to 8 C atoms or a cycloalkyl radical having 5 to 8 C atoms or together with the nitrogen atom is a 5- to Form 8-membered, saturated nitrogen heterocycle, which may have, in addition to the nitrogen atom, a further selected from O and S heteroatom as a ring member, wherein the nitrogen heterocycle is unsubstituted or 1, 2, 3 or 4 alkyl groups each having 1 to 4 carbon atoms as substituents can have.
• Sulfonkladiamide of formula I are interesting intermediates for the preparation of active ingredients, eg. For the preparation of the herbicidal active ingredients described in WO01 / 83459.
• WO01 / 83459 describes the preparation of sulfonic acid diamides of the general formula I by reacting chlorosulfonamide with a primary or secondary amine.
• the chlorosulfonamide is prepared by hydrolysis of chlorosulfonyl isocyanate.
• chlorosulfonyl isocyanate is comparatively expensive.
• WO 03/097589 in turn describes the preparation of sulfonic acid diamides of the general formula I which comprises, in a first step, the chlorosulfonic acid amide of a primary or secondary amine by successive reaction of the primary or secondary amine with sulfur trioxide in the presence of a tertiary amine followed by the reaction of thereby obtained ammonium salt of the corresponding amidosulfonic acid with phosphorus halide manufactures. Subsequently, the obtained Chlorsulfonklamid, hereinafter also referred to as sulfamoyl chloride, with ammonia.
• the method is characterized by better yields, but is relatively expensive due to the large number of steps.
• the present invention is therefore based on the object to provide an easy to carry out process for the preparation of sulfonic acid diamides of the above-mentioned general formula I, which provides these compounds in good yields and which can be carried out with inexpensive starting materials.
• This object is surprisingly achieved by the method defined below.
• the present invention is a process for the preparation of sulfonic acid diamides of the abovementioned general formula I, comprising the following steps:
• R 1 and R 2 have the meanings given above, with sulfuryl chloride in an inert, especially an aromatic solvent in the presence of a tertiary amine, to a sulfamoyl chloride of the formula III
• R 1 and R 2 have the meanings given above, and
• step ii) wherein in step ii) the sulfamoyl chloride of the formula III is used in the form of the solution obtained in step i) in the inert, in particular the aromatic solvent.
• the process according to the invention has a number of advantages.
• the method according to the invention is comparatively easy to carry out.
• it provides the desired sulfonic acid diamides I in good yields, based both on the secondary amine used and on the sulfuryl chloride used.
• the release of hydrogen chloride is largely or completely avoided.
• the use of expensive starting materials such as chlorosulfonyl isocyanate is not required.
• the reaction can also be handled well on an industrial scale.
• the sulfonic acid diamides I are obtained in a sufficient purity for further use, so that it does not require any expensive purification process.
• step i) of the process according to the invention a secondary amine of the formula II, as defined above, is reacted with sulfuryl chloride in an inert, in particular an aromatic solvent in the presence of a tertiary amine.
• the tertiary amine serves as an auxiliary base for binding the liberated in the reaction hydrogen chloride and is usually in an amount of at least 0.9 equivalents, preferably in an amount of at least 1, 0 equivalents, for. B. in an amount of 1, 0 to 2 equivalents and in particular in an amount of 1, 05 to 1, 5 equivalents, based on the secondary amine used.
• Equivalents is synonymous with the term moles per mole or mole equivalents.
• Suitable tertiary amines include trialkylamines, in particular those having 1 to 6 C atoms in the alkyl radicals, N-cycloalkyl-N, N-dialkylamines, in particular N-cyclohexyl-N, N-dialkylamines having 1 to 6 C atoms in the alkyl radicals, N, N-dialkylanilines having preferably 1 to 6 C atoms in the alkyl radicals and pyridine and quinoline bases.
• Suitable tertiary amines are: from the group of trialkylamines: trimethylamine, triethylamine, tri-n-propylamine, tri-n-butylamine, dimethylethylamine, dimethyl-n-propylamine, dimethyl-n-butylamine, dimethyl-isopropylamine, dimethyl 2-butylamine, diethyl-n-propylamine, diethylisopropylamine, diethyl-n-butylamine, tri-n-hexylamine and the like; from the group of N-cycloalkyl-N, N-dialkylamines: dimethylcyclohexylamine and diethylcyclohexylamine; from the group of N, N-dialkylanilines: dimethylaniline and diethylaniline; from the group of pyridine and quinoline bases: pyridine, ⁇ -, ⁇ - and ⁇ -picoline,
• Preferred tertiary amines are trialkylamines and N-cycloalkyl-N, N-dialkylamines, in particular tri-C 1 -C 6 -alkylamines and N-cyclohexyl-N, N-di-C 1 -C 6 -alkylamines.
• a tri-Ci-C ⁇ -alkylamine is used as the tertiary amine, a tri-Ci-C ⁇ -alkylamine and in particular trimethylamine or triethylamine.
• the process of the invention is basically suitable for the preparation of sulfonic acid amides of any secondary aliphatic or cyclic amines.
• R 1 and R 2 may be primary or secondary alkyl radicals having preferably 1 to 6 or 3 to 6 C atoms or may be a cycloalkyl radical having preferably 5 or 6 C atoms. In this case, R 1 and R 2 may be the same or different.
• R 1 and R 2 can also together with the nitrogen atom to which they are attached form a 5-, 6-, 7- or 8-membered, saturated nitrogen heterocycle which, in addition to the nitrogen atom, forms another, lower O- and one nitrogen atom S may have selected heteroatom as ring member and which is optionally substituted, but the ⁇ -carbon atoms (the ring carbon atoms bound to the nitrogen atom) are preferably unsubstituted or have a substituent.
• primary alkyl radical having 1 to 8 C atoms denotes a saturated, linear or branched hydrocarbon radical having 1 to 8 and in particular 1 to 6 C atoms, which is bonded to the nitrogen atom via a CH 2 group.
• primary alkyl radicals are methyl, ethyl, n-propyl, n-butyl, 2-methylpropyl (isobutyl), n-pentyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 4- Methylpentyl, 2-ethylbutyl, etc.
• secondary alkyl radical having 3 to 8 C atoms stands for a saturated acyclic hydrocarbon radical having 3 to 8 C atoms, which is bonded to the nitrogen atom via a secondary carbon atom.
• Examples of secondary alkyl radicals are 2-propyl (1-methylethyl), 2-butyl, 2-pentyl, 3-pentyl, 2-hexyl, 3-hexyl, 3-methyl-2-butyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl etc.
• a secondary amine II is used in which the two radicals R 1 and R 2 are different alkyl radicals from one another.
• the radical R 1 in the formulas I, II and III is a primary alkyl radical having 1 to 8, in particular 1 to 6 and especially having 1 or 2 C atoms or a secondary alkyl radical having 3 to 8, in particular 3 to 6 and especially with 3 or 4 C atoms.
• the radical R 2 is in particular a secondary alkyl radical having 3 to 8, in particular 3 to 6 and especially 3 or 4 C atoms.
• R 1 is a primary alkyl radical having 1 to 4 C atoms and especially methyl or ethyl and R 2 is a secondary alkyl radical having 3 to 8, in particular 3 to 6 and especially 3 or 4 C atoms and especially Isopropyl or 2-butyl.
• a secondary amine of the formula II is used in which R 1 is methyl and R 2 is a secondary alkyl radical having 3 to 8, in particular 3 to 6 and especially 3 or 4 C atoms.
• the secondary amine of the formula II and the sulfuryl chloride are preferably employed in a molar ratio suitable for the stoichiometry of the reaction, preferably in the range from 1: 1, 1 to 1, 1: 1, in particular in the range 1: 1, 05 to 1, 05: 1 and especially in the range of 1: 1, 02 to 1, 02: 1.
• step i) takes place in an inert, in particular an aromatic solvent.
• An inert solvent is understood as meaning an organic solvent which does not undergo any chemical reaction with the reagents, in particular with sulfuryl chloride, under the reaction conditions. These include in particular aromatic, aliphatic, araliphatic and cycloaliphatic hydrocarbons and also chlorinated and fluorinated hydrocarbons. Nitrogen-containing and / or oxygen-containing solvents are generally not inert, in particular if they have OH or NH groups (so-called protic solvents). The proportion of non-inert solvents in the inert solvent is usually not more than 10% by volume based on the total amount of the solvent. The inert solvent preferably contains no oxygen-containing and / or nitrogen-containing, aprotic solvents ( ⁇ 1% by volume).
• aromatic solvent those solvents whose main ingredient is aromatic room temperature liquid benzene derived compounds.
• aromatic solvent examples include benzene, alkylbenzenes such as toluene, xylene, trimethylbenzene and ethylbenzene, and also chlorinated and / or fluorinated benzenes such as chlorobenzene, fluorobenzene and dichlorobenzenes.
• the aromatic solvent may also contain up to 50% by volume, in particular not more than 30% by volume and especially not more than 10% by volume, of various inert solvents, for example aliphatic halogenated hydrocarbons, eg. For example, dichloromethane, trichloromethane and / or dichloroethane, aliphatic or cycloaliphatic hydrocarbons such as n-hexane, n-heptane, octane, cyclohexane, cycloheptane, cyclooctane and mixtures thereof.
• various inert solvents for example, dichloromethane, trichloromethane and / or dichloroethane, aliphatic or cycloaliphatic hydrocarbons such as n-hexane, n-heptane, octane, cyclohexane, cycloheptane, cyclooctane and mixtures thereof.
• the aromatic solvent may also comprise small amounts of non-inert, aprotic oxygen-containing and / or nitrogen-containing solvents, their proportion preferably not exceeding 10% by volume, based on the total amount of the solvent. agent.
• the aromatic solvent preferably contains no oxygen-containing and / or nitrogen-containing, aprotic solvents ( ⁇ 1% by volume).
• the reaction of the secondary amine II with sulfuryl chloride is carried out in the substantial or complete absence of protic solvents such as water or alcohols.
• protic solvents such as water or alcohols.
• the proportion of water and protic organic solvents will usually constitute not more than 0.1% (1000 ppm) and in particular not more than 500 ppm, especially not more than 300 ppm, based on the total amount of solvent used.
• aromatic compounds which are suitable as aromatic solvents are, in addition to benzene, alkylbenzenes such as toluene, xylene, trimethylbenzene and ethylbenzene and also chlorinated and / or fluorinated benzenes such as chlorobenzene, fluorobenzene and dichlorobenzenes.
• the aromatic solvent comprises chlorobenzene.
• chlorobenzene forms the major constituent, especially at least 80%, more preferably at least 90, or at least 95% by volume of the aromatic constituents of the aromatic solvent.
• chlorobenzene is the sole constituent and constitutes at least 95 and especially at least 98% by volume, based on the total amount of solvent.
• the reaction of the secondary amine of formula II with sulfuryl chloride is preferably carried out under temperature control and preferably at temperatures of not more than 50 0 C, in particular not more than 30 0 C and especially not more than 20 0 C.
• the lower limit is usually by the fixed point of the reaction mixture and the miscibility the reaction mixture determined. Frequently, the lower limit of the reaction temperature -10 0 C is not below.
• the secondary amine of formula II For the reaction of the secondary amine of formula II with sulfuryl chloride, it will be preferable to initially or partially add the total amount of the solvent and sulfuryl chloride in the reaction vessel, bring the template to the desired reaction temperature and to this end add the secondary amine II and the tertiary amine.
• the secondary amine and the tertiary amine can be diluted with the solvent used for the reaction.
• the addition of the secondary amine II and the tertiary amine is preferably carried out simultaneously, in particular as a mixture, so that the preferred molar ratios of secondary amine II and tertiary amine are maintained in the reaction mixture.
• the addition of secondary amine and tertiary amine is preferably under temperature control for an extended period of time, typically at least 20 minutes, more preferably at least 30 minutes and especially at least 60 minutes.
• the maximum duration of addi- is based on economic considerations and will usually not exceed 15 hours, and in particular 8 hours.
• the addition of secondary amine II and tertiary amine occurs within a period of one hour to 10 hours, and especially over a period of 2 hours to 8 hours.
• the reaction mixture may be subjected to an after-reaction after completion of the addition of secondary amine II and tertiary amine, which is typically in the range of 10 minutes to 8 hours and more preferably in the range of 30 minutes to 6 hours.
• an after-reaction after completion of the addition of secondary amine II and tertiary amine which is typically in the range of 10 minutes to 8 hours and more preferably in the range of 30 minutes to 6 hours.
• the total duration of addition and post-reaction phase will not exceed a period of 15 hours and especially 10 hours.
• the concentration of reactants, d. H. the total amount of sulfuryl chloride, secondary amine II and tertiary amine is preferably 10 to 50 wt .-% and in particular 20 to 40 wt .-%, based on the total weight of the reaction mixture.
• reaction mixture containing the sulfamoyl chloride III dissolved in the solvent.
• reaction mixture still contains the salts formed in the reaction, d. H. the hydrochloric acid addition salts of the tertiary amine.
• the reaction mixture obtained in this way can be reacted with ammonia directly in step ii) of the process according to the invention.
• the salts formed in the reaction are removed by extraction, before carrying out the reaction with ammonia in step ii).
• the extraction is usually carried out under acidic conditions, ie at pH ⁇ 7, in particular pH ⁇ 5 and especially pH ⁇ 3.
• a dilute acid in particular dilute hydrochloric acid.
• a dilute hydrochloric acid having a hydrogen chloride content in the range from 2 to 20% by weight and in particular in the range from 5 to 15% by weight.
• the extraction can be carried out by single or multiple treatment with the dilute aqueous acid.
• the extraction is carried out at temperatures below 30 0 C and in particular below 20 0 C, z. B. in the range of 0 to 30 ° C and especially in the range of 0 to 20 0 C.
• the containing the hydrochloride of the tertiary amine aqueous phase is separated. Any water can be removed by distillation. The distillative removal can be carried out at atmospheric pressure and is preferably carried out at reduced pressure. Optionally, it will replace distilled aromatic solvent.
• the resulting solution of the sulfamoyl chloride of the formula III in the inert solvent is reacted with ammonia in step ii).
• the concentration of sulfamoyl chloride is adjusted by adding further inert, in particular aromatic solvents.
• the concentration of sulfamoyl chloride is in the inert solvent in step ii) are in the range from 5 to 50% by weight, in particular 10 to 40% by weight and especially 20 to 30% by weight.
• the ammonia required for the reaction can be supplied in gaseous form or in the form of a solution, usually a non-aqueous solution.
• the solvent usually contains less than 1% protic components such as water.
• the ammonia is supplied in gaseous form.
• the reaction is then preferably carried out in an ammonia atmosphere.
• the partial pressure of the ammonia in this ammonia atmosphere is typically in the range of 0.5 to 50 bar, in particular in the range of 1 to 30 bar and especially in the range of 2 to 20 bar.
• the gaseous ammonia may be diluted with a gaseous inert, such as air, nitrogen or argon or a mixture of these gases.
• the ratio of the ammonia partial pressure to the total partial pressure of all the inerts is preferably at least 1: 1, in particular at least 5: 1 and especially at least 10: 1.
• the total pressure of all gaseous components will usually not exceed 50 bar, in particular 30 bar and especially 20 bar.
• the partial pressure of the ammonia in the reaction vessel is preferably maintained in the abovementioned ranges.
• the reaction of the sulfamoyl chloride III with the ammonia is typically carried out at temperatures in the range of 10 to 100 0 C, in particular in the range of 30 to 80 0 C.
• the reaction time required for the reaction is usually 2 to 24 hours, in particular 4 to 16 hours.
• a reaction mixture which contains the sulfonic acid diamide of the general formula I together with the ammonium chloride formed by-product in the reaction in the inert, in particular the aromatic solvent.
• the ammonium chloride is usually removed. Since the ammonium chloride is present in the inert solvent as a suspended solid, it can basically be removed by filtration. Preferably, the ammonium chloride is removed by an aqueous extraction.
• the aqueous extraction is carried out at a pH ⁇ 7, in particular pH ⁇ 5 and especially pH ⁇ 3.
• a dilute aqueous acid in particular dilute aqueous hydrochloric acid and especially an aqueous hydrochloric acid having a hydrochloric acid concentration of 2 to 20 Wt .-% and in particular 5 to 15 wt .-%.
• the aqueous extraction of the reaction mixture can be carried out once or several times.
• the combined aqueous extracts are re-extracted one or more times with a suitable organic solvent in which the sulfonic acid I is soluble, in particular an aromatic solvent and especially with the inert used for the reaction, especially the aromatic solvent used for the reaction in order to avoid yield losses .
• a suitable organic solvent in which the sulfonic acid I is soluble in particular an aromatic solvent and especially with the inert used for the reaction, especially the aromatic solvent used for the reaction in order to avoid yield losses
• the extracted reaction mixture optionally after combination with the re-extracts, contains the sulfonic acid I in dissolved form with sufficient purity for further reactions.
• the solution can therefore be supplied as such or after isolation of the sulfonic acid I further reactions.
• the solution of sulfonic acid I will be concentrated by distillation, with any water and / or acid present in the solvent also being removed. It is also possible to isolate the sulfonamide in the usual way from the solution thus obtained, for example by concentration to dryness or by
• the sulfonic acid diamides of general formula I thus obtained can be used in particular for the preparation of herbicidal active compounds of general formula IV.
• R 1 and R 2 have the meanings given above.
• R a is hydrogen or C 1 -C 4 -alkyl
• R b is hydrogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl
• X and Y are hydrogen or halogen, where one of the radicals X or Y also CN can mean.
• a further aspect of the present invention relates to the use of the process according to the invention for the preparation of sulfonic acid diimides of the formula I for the preparation of herbicidal active compounds of the general formula IV.
• Another object of the present invention is a process for the preparation of herbicidal active compounds of the general formula IV, as described herein, comprising the following steps: a) Preparation of a sulphonic acid diimide of the formula I by the process described here and in the claims,
• reaction of the sulfonic acid diimide of the formula I with a nitrobenzoic acid chloride of the formula V can be carried out, for example, according to Scheme 2 on page 15 of WO 2004/039768 and according to the information given on pages 16 to 19 or example 1 on page 56 of WO 2004/039768 or be carried out according to the examples given here.
• the relevant disclosure of WO 2004/039768 is hereby incorporated by reference in its entirety.
• step b) 3-Nitrobenzoeklads of formula VI to the corresponding 3-Aminobenzoeklad of formula VII can also according to the information in WO 2004/039768 in Scheme 2 on page 15 and according to the information on pages 19 to 22 and 58 to 60 of WO 2004/039768, the disclosure of which is hereby fully incorporated by reference.
• the reduction of compound VI is Bond VII was carried out by catalytic hydrogenation, as described on pages 21 f. and 60 of WO 2004/039768, or according to the example of the present application.
• R 1 , R ; ? , ⁇ and Y have the meanings given for formula IV and R 3 is C 1 -C 4 -alkyl, d 2) reaction of compound VIII with a 3-aminoacrylic acid ester of
• R a ' is hydrogen or Ci-C 4 alkyl
• R b is hydrogen
• Ci-C 4 - alkyl is 4 haloalkyl or Ci-C 4 alkyl
• R 4 is is C-C. d3
• R ' C 1 -C 4 -alkyl
• the alkylation can be carried out according to the methods described in WO 2006/010474 and WO 06/125746. Reacting the compound VII with phosgene or diphosgene according to the method described in WO 2004/039768, to obtain the corresponding isocyanate of the formula X,
• the phases were separated at 10 0 C and the organic phase was washed again with 250 g of 10% aqueous hydrochloric acid at 10 0 C.
• the organic phase was separated and concentrated at reduced pressure (30 mbar, 22 to 41 0 C) to remove water. In this way, 570 g of a solution of N-isopropyl-N-methylsulfamoyl chloride in chlorobenzene (about 25% by weight) were obtained. This corresponds to a yield of 84%.
• step i 343.4 g of the solution of N-isopropyl-N-methylsulfamoyl chloride in chlorobenzene (25% strength by weight) obtained in step i) were introduced into a pressure vessel which was flooded with nitrogen and ammonia. Subsequently, the partial pressure of the ammonia was increased to 5 bar. Then, the reactor contents were heated to 50 ° C, this temperature was maintained for 8 hours, maintaining an ammonia pressure of 6 bar was maintained. The suspension obtained in this case was added to 210 g of aqueous hydrochloric acid (8% strength), the solids present in the reaction mixture being dissolved. The pH of the aqueous phase was about 2.
• the reaction mixture was then stirred at 20 0 C for 1 h and diluted by adding 424 g of water and 138 g of isohexane.
• the aqueous phase was acidified to pH 4.5 with concentrated hydrochloric acid and then separated at 68-70 ° C.
• the organic phase was admixed with 430 g of water and 60 g of isohexane and the phases were separated again hot at pH 4.5.
• the resulting organic phase was treated with a further 280 g of isohexane and then cooled to 5 ° C.
• Step d1) N- [2-Chloro-4-fluoro-5 - ⁇ (ethoxycarbonyl) -amino ⁇ -benzoyl] -N'-isopropyl-N'-methylsulfamide (variant 1)
• N- (2-chloro-4-fluoro-5-aminobenzoyl) -N'-isopropyl-N'-methylsulfamide in 225 g of toluene was added 105 -1 10 0 C 22.7 g (0.207 mol) of ethyl chloroformate, followed by stirring for 6.5 hours at research 108-1 10 0 C.
• Step d1) N- [2-Chloro-4-fluoro-5 - ⁇ (ethoxycarbonyl) -amino ⁇ -benzoyl] -N'-isopropyl-N'-methylsulfamide (Variant 2)
• reaction mixture was metered into dilute sulfuric acid with cooling, the reaction mixture having a pH ⁇ 2 after completion of the addition and the title compound being obtained as a solid.
• the precipitated product was filtered off, washed with water and dried. 433 g (89% of theory) of the title compound [m.p. 238 ° C (decomposition)].
• Example 4 Preparation of 2-chloro-5- [3,6-dihydro-3-methyl-2,6-dioxo-4- (trifluoromethyl) -1- (2H) -pyrimidinyl] -4-fluoro-N- [ [methyl (1-methylethyl) amino] sulfonyl] benzamide (variant with crystallization of the product obtained in step d1))
• the preparation was carried out analogously to the procedure for Example 2 with the difference that step d 1) were carried out as follows:

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