2-substituted pyrazolo(1,5-a)pyrimidine derivatives and herbicidal compositions containing them

82356/2 2 mnyn nmonw ) »τ>ο>~ΐ’ο[β-5,1]·ι5ι tic>3 nnbin ]din o>5>oon o’nviy »5oip trvran 2-Substituted pyrazolo[l,5-a]pyrimidine derivatives and herbicidal compositions containing them

SCHERING AGROCHEMICALS LIMITED C. 71872 82356/2

This invention concerns herbicidal 2-substituted pyrazolo[l,5-a]pyrimidine derivatives, processes for their preparation, and compositions containing them.

In one aspect, the invention provides the pyrazolopyrimidine derivatives of the formula:

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28.IV.1987 for underlined meanings and -salts thereof wherein R1 represents hydrogen, hydroxy, halo, alkyl or haloalkyl; 2 R represents hydrogen, hydroxy, halo, alkyl, iialoalkyl, phenyl or pyridyl, or together with R6 represents an alkylene chain of 3 or 4 carbon atoms; R6 represents hydrogen, halo or alkyl; R3 represents cyano. carboxy, alkoxycarbonyl in which the alkyl moiety may be further substituted by alkoxy, or carbamoyl which may be substituted by one or more alkyl, cycloalkyl or amino groups; X represents -SO2~O- or -SO2~NR- where R represents hydrogen, alkyl, alkenyl or alkynyl; and 2 82356/3 ί R4 represents phenyl or phenyl substituted by up to 4 26.IV. 1987 halogen, alkyl, haloalkyl, nitro, amino, alkoxycarbonyl or for underlined haloalkoxy groups; meanings any alkyl moiety present in the groups defined above being of 1 to 6 carbon atoms, and any alkenyl or alkynyl moiety being of 2 to 6 carbon atoms.

When r\ or R® represents halo, it is preferably chloro or bromo. 1 2

When R or R represents or. contains an alkyl group, that group is preferably of 1 to 6 carbon atoms, especially of 1 to 4 carbon atoms. Specific preferred unsubstituted alkyl or alkyl-containing groups which R* 1 and may represent include methyl, ethyl, n-propyl, isopropyl, n-butyl and t-butyl. The alkyl group may if desired be substituted, for example by one or more halogen atoms, e.g. fluorine, chlorine or bromine. Specific preferred substituted alkyl-containing groups which R1 and R^ may represent include chloromethyl, bromomethyl, dichloromethyl or trifluoromethyl.

When R represents an alkenyl or alkynyl group, that 28.TV. 1987 group is preferably of 2 to 6 carbon atoms, for example allyl, vinyl or propargyl. Any such alkenyl or alkynyl group is preferably unsubstituted. - 3 - 82356/3 28.IV.1987 for underlined meanings R and R independently preferably represent hydrogen, hydroxy, methyl, trifluoromethyl or chloro.

When R represents or contains an alkyl group, that group is preferably of 1 to 6 carbon atoms, especially of 1 to 4 carbon atoms. Specific preferred groups which R6 may represent include methyl, ethyl, n-propyl, isopropyl, n-butyl. t-butyl.. R6 preferably represents hydrogen, chloro or methyl, or together with R2 represents a trimethylene chain. q

When R contains an alkyl group, that group is preferably of 1 to 6 carbon atoms, especially of 1 to 4 carbon atoms. Specific preferred groups containing q unsubstituted alkyl moieties which R may represent include methoxycarbonyl, methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, ethoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, methylcarbamoyl and dimethylcarbamoyl. The alkyl group may if desired be substituted, for example by alkoxy groups of 1 to 4 carbon atoms, e.g. methoxy or ethoxy. A specific preferred group containing substituted q alkyl moieties which R may represent includes ethoxyethoxycarbonyl. R3 preferably represents carboxy, substituted or unsubstituted alkoxycarbonyl of 2 to 5 carbon atoms (for example methoxycarbonyl or ethoxycarbonyl), carbamoyl or substituted carbamoyl (for example hydrazinocarbonyl or alkyl-substituted hydrazinocarbonyl). - 4 -

X 1 82356/3 4 R preferably represents a phenyl group substituted by one or more chlorine atoms, methyl groups, 2b.IV. 1987 ^Ikoxycarbonyl groups (especially of 2 to 5 carbon atoms), 2o.IV.1987 28. IV.1987 nitro groups.

When R represents or contains alkyl, that moiety is preferably of 1 to 6 carbon atoms, especially of 1 to 4 carbon atoms. Specific preferred groups which R may represent include methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl.

When R represents alkenyl or alkynyl, it is preferably of 2 to 6 carbon atoms, for example, vinyl, allyl or propargyl. X preferably represents -SO^-NH-. “ Preferred salts of the compounds of formula I are those of the compounds where X represents -SC^-NR-, particularly alkali-metal salts, e.g. sodium or potassium salts, ammonium salts, trialkyl-ammonium salts, and salts with heterocyclic bases, e.g. the pvridinium salts. - 5 - 82356/3 28.IV.1987 for underlined meanings

In a particularly preferred group of compounds of 1 2 formula I, one of R and R represents methyl and the other represents hydrogen or methyl, R6 is hydrogen, 3 . R is methoxycarbonyl, ethoxycarbonyl, carbamoyl, methylcarbamoyl or dimethylcarbamoyl. X is - S Ο 2 N H - , and 4 . R is phenyl substituted by one or more fluorine, chlorine or bromine atoms, alkoxycarbonyl groups of 2 to 5 carbon atoms, or methyl or nitro groups.

Especially preferred compounds according to the invention are those of the Examples provided hereinafter though particular mention may be made of methyl 2-(2,6-dichlorophenylsulphamoyl)-5,7-dimethylpyraz0lo-[1,5-a]pyrimidine-3-carboxylate and methyl 2-(2,6-dichlorophenylsulphamoyl )-5-methy1-7-trifluoromethylpyrazoloti, 5 -a ] pyrimidine-3 -car boxy late. 6 82356/3

The pyrazolopyrimidine derivatives of formula I are prepared by reacting an aminopyrazole of the formula:

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X - R4 (II) 3 4 where R , R , R and R' are as defined hereinbefore, in a suitable solvent medium, with a diketone of the formula: r1cochr6cor2 (III) 12 6 where R , R and R are as defined hereinbefore, to give the desired compound.

The solvent medium employed is preferably an alkanol such as ethanol, or acetic acid, and the reaction is desirably carried out with heating, e.g«,to reflux. 7 82356/2

Where a compound of formula III is used in 1 2 which R and/or R are protecting groups, e.g. alkoxy groups, these groups are subsequently hydrolysed off.

The compounds of formula I may also be prepared by a process in which.a pyrazolopyrimidine sulphonyl halide of the formula:

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8 82356/3 12 3 6 where R . R , R and R are as defined hereinbefore, and Hal represents halogen, is reacted in the presence of a base with a compound of the formula r4NHR or R4OH where R and R4 are as defined hereinbefore to give the desired compound. ..

The reaction is conveniently effected at room temperature or with heating, eg from 10 to 100°C, and in a suitable solvent medium, for example pyridine.

The base is preferably an organic base, especially a tertiary orgaic base, for example 4-dimethylaminopyridine.

The compounds of formula IV may themselves be prepared . 4 by reacting a compound of formula I wherein X-R represents benzylthio with the appropriate halogen or sulphuryl halide in a suitable solvent medium, to give the desired compound.

The reaction is desirably effected with cooling to less than ambient temperature, eg to a temperature of -10°C to 5°C. 9 82356/3 28 IV 1987 Salts of the compounds of formula I may be prepared by reaction thereof with a suitable base containing the desired cation, eg the appropriate trialkylamine.

The compounds of formula I may also be interconverted by methods known per se. For example, the compounds of formula I in which X represents a group -SO2NR where R is other than hydrogen, may in general be prepared from the corresponding compounds of formula I where R is hydrogen by reaction thereof in the presence of a strong base, for example sodium hydride, with a halide of formula RHal.

Carboxy groups present in the compounds of formula I may be esterified, ester groups present may be hydrolysed to give the corresponding acids, and cyano or ester groups 28.IV.1987 may be converted to carbamoyl or substituted carbamoyl groups Such transformations, as well as many others, may be effected by techniques well-known to those skilled in the art, and various examples of such transformations are provided hereinafter.

The compounds of formula I are herbicidally-active against a wide range of broad-leaved and grassy weeds, but 10

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are comparatively safe to certain crop species. They may thus be of use as selective herbicides, particularly in the control of a range of weeds in cereals or other crops, eg wheat, barley, maize, soya beans, oilseed rape, cotton or sugar beet.

In another aspect, the invention provides a herbicidal composition which comprises one or more compounds of the invention in association with a suitable carrier and/or surface active agent.

The compositions usually contain from 0.01 to 99% by weight of the present compounds, and are normally produced initially as concentrates containing from 0.5 to 99%, preferably from 0.5 to 85%. and especially from 10 to 50% by weight thereof. Such concentrates are diluted if necessary before application to the locus to be treated such that the active ingredient comprises from 0.01 to 5% by weight of the formulation applied.

The carrier may be water, in which case an organic solvent may also be present, though this is not usually employed. A flowable suspension concentrate may be formed by grinding the compound with water, a wetting agent and a suspending agent, e.g. xanthan gum.

The carrier may alternatively be a water immiscible organic solvent, e.g. a hydrocarbon which boils within the range 130-270°C. e.g. xylene, in which the compound is 11 dissolved or suspended. An emulsifiable concentrate containing a water immiscible solvent may be formed with a surface active agent so that the concentrate acts as a self-emulsifiable oil on admixture with water.

The carrier may alternatively be a water-miscible organic solvent e.g. 2-methoxy ethanol, methanol, propylene glycol, diethylene glycol, diethylene glycol monoethyl ether, methylformamide or dimethylformamide.

The carrier may alternatively be a solid, which may be finely divided or granular. Examples of suitable solids are limestone, clays, sand, mica, chalk, attapulgite, diatomite, perlite, sepiolite. silicas, silicates, lignosulphonates and solid fertilizers. The carrier can be of natural or synthetic origin or can be modified natural material.

Hettable powders soluble or dispersible in water may be formed by admixing the compound in particulate form with a particulate carrier or spraying molten compound on to the particulate carrier, admixing a wetting agent and a dispersing agent and finely grinding the whole powder mixture.

An aerosol composition may be formed by admixing the compound with a propellant, e.g. a polyhalogenated alkane such as dichlorofluoromethane, and suitably also with a solvent. 12

The term 'surface active agent* is used in the broad sense to include materials variously called emulsifying agents, dispersing agents and wetting agents. Such agents are well known in the art.

The surface active agents used may comprise anionic surface active agents, for example mono- or di-esters of phosphoric acid with a fatty alcohol ethoxylate, or salts of such esters, fatty alcohol sulphates such as sodium dodecyl sulphate, ethoxylated fatty alcohol sulphates, ethoxylated alkylphenol sulphates, lignin sulphates, petroleum sulphonates, alkylaryl sulphonates such as alkyl-benzene sulphonates or lower alkylnaphthalene sulphonates, salts of sulphonated naphthaleneformaldehyde condensates, salts of sulphonated phenolformaldehyde condensates, or more complex sulphonates such as the amide sulphonates, e.g. the sulphonated condensation product of oleic acid and N-methyl taurine or the dialkyl sulphosuccinates e.g. the sodium sulphonate of dioctyl succinate.

The surface active agents may also comprise non-ionic agents, for example condensation products or fatty acid esters, fatty alcohols, fatty acid amides or alkyl-substituted phenols with ethylene oxide, fatty esters of polyhydric alcohol ethers e.g. sorbitan fatty acid esters, condensation products of such esters with 13 ethylene oxide e.g. polyoxyethylene sorbitan fatty acid esters, block copolymers of ethylene oxide and propylene oxide, acetylenic glycols such as 2,4,7,9-tetramethyl-5-decyn-4,7-diol, or ethoxylated acetylenic glycols.

The surface active agents may also comprise cationic agents, for example alkyl- and/or aryl-substituted quaternary ammonium compounds such as cetyl trimethylammonium bromide, or ethoxylated tertiary fatty amines.

Preferred surface active agents include ethoxylated fatty alcohol sulphates, lignin sulphonates, alkyl-aryl sulphonates, salts of sulphonated naphthaleneformaldehyde condensates, salts of sulphonated phenolformaldehyde condensates, sodium oleoyl N-methyltauride, dialkyl sulphosuccinates, alkyl phenol ethoxylates, and fatty alkyl ethoxylates.

The present active compounds, especially those of the Examples provided hereinafter, and particularly methyl 2-(2.6-dichlorophenylsulphamoyl)-5,7-dimethylpyrazoloti, 5-a]pyrimidine-3-carboxylate and methyl 2-(2,6-dichlorophenylsulphamoyl ) -5 -me thy 1-7 -tri fluor omethy lpyr a zolo-[1,5-a]pyrimidine-3-carboxylate, may be admixed with another pesticide, eg a herbicide, fungicide or insecticide, or a plant growth regulator, particularly another herbicide. Suitable further herbicides include 14 82356/2 trietazine, linuron, MCPA, dichlorprop, isoxaben, diflufenican, metolachlor, fluometuron, oxyfluorfen. fomesafen, bentazone, prometryne, norflurazon, chlomazone, EPTC, imazaquin, and especially isoproturon, methabenzthiazuron, trifluralin, ioxynil, bromoxynil, benazolin, mecoprop, fluroxypyr, alachlor, acifluorfen, lactofen. metribuzin and pendimethalin.

The present compounds may be applied to plants, the soil, land or aquatic areas, and particularly to a locus at which a crop is growing or is about to grow. The compounds are active both pre- and post-emergence.

The invention is illustrated by the following Examples, in which Me = methyl, Et = ethyl. Ph = phenyl and cyhex = cyclohexyl.

Preparative Example A

Methyl 2-benzylthio-5, 7-dimethylpyrazolo[1,5-alpyrimidine- -3-carboxylate (Compound Al) (intermediates) (a) Methyl 3,3-di (benzylthio)-2-cyanoacrylate

Sodium (51.8g) was dissolved in methanol (820 ml), and 375 ml of this solution were treated with methyl cyanoacetate (123.8g). The temperature fell from 20°C to about 15°C during the addition. Carbon disulphide (37.5 ml) was added, the temperature rising to about 40°C. The mixture was cooled to 20°C and was treated with a further 188 ml of the methoxide solution followed by carbon 15 disulphide (19 ml). After cooling again to 20°C, the remaining methoxide solution was added, followed by carbon disulphide (9 ml) at 2O°C. The total of carbon disulphide added was 65.5 ml. When the additions were complete, the mixture was stirred at room temperature for 3 hours. Potassium iodide (3g) was added followed dropwise by benzyl chloride (275.8g). The temperature rose to about 55°C during the addition. The mixture was then boiled under reflux for 1 hour. After cooling, the mixture was poured into 5 1 of iced water, and the solid material was filtered off, washed thoroughly with water and dried, to give 320.2g of desired product. (b) Methyl 3-amino-5-benzylthiopyrazole-4-carboxylate A stirred mixture of the product of stage (a) (87.Og) and hydrazine hydrate (12.3g) in methanol (340 ml) was boiled under reflux for 5 hours. After cooling, the mixture was evaporated to dryness. The residue was stirred with sodium carbonate solution for 15 minutes. The solid was filtered off, washed with water and recrystallised from acetonitrile to give 28.9g of desired product, mp 1O3-1O6°C. (c) Methyl 2-benzylthio-5,7-dimethylpyrazolo[1,5-a] -pyrimidine-3-carboxylate A stirred mixture of the product of stage (b) (54.7g) and pentane-2,4-dione (20.8g) in glacial acetic acid (425 16 82356/3 ml) was boiled under reflux for 3 hours. After standing at room temperature overnight, the solid was filtered off and recrystallised from acetonitrile to give 54.4g of desired product, mp 161.-164°C.

Examples A2-A28 (intermediates)

The following compounds of formula I where R6 is hydrogen, and X represents -SCH2- were prepared by methods analogous to that of Example A, but using appropriately protected ketones of formula III where necessary: 28.IV.1987 28,IV.1987

No . Rl R2 R3 R4 (Ph subst:) M Pt (°C) A2 Me Me COOEt - 156-159 A3 Me Me CN 2-C1 165-168 A4 Me Me CN 2,6-diCl 206-208 A5 Me Me CN 2.5-diMe 177-179 A6 cf3. CF3 CN - 137-139 A7 H > Me CN - 112-114. A8 OH OH COOMe - 192-194 A9 Me OH COOMe - 256-258 A10 Me Cl COOMe - 188-190 All Me Me COOH 198-199 A12 H H COOMe - 169-171 ’ A13 Cl Cl COOMe - 208-210 A14 H Me COOMe - 180-182 [A15 H Ph COOMe — 162-164 17 82356/3 NO . RI R2 R3 R4 (Ph subst:) M Pt (OC1 28.IV.1987 j A16 Me Ph COOMe - 175-177 A17 Me CF3 COOMe - 162-164 28.IV.1987 Γ A18 Me Me CONMe2 - 148-150 A19 cf3 cf3 COOMe - 118-120 A20 H Me CN - 142-144 A21 Me Me CN - 138-140 A22 Me Me conh2 4-C1 230-232 A23 Me Me conh2 - 242-244 A24 Me GF 3 CN 131-133 The following ' 4 intermediates where R - represents phenyl and X represents -SCH2~ were also prepared by methods analogous to that of Example A: No . RI R2 R6 R3 M Pt (°C) A2 5 Me Me Cl COOMe 183-185 A26 Me Me Me COOMe 183-185 [A27 Me -(CH. ),- COOMe 201-203 .IV.1987 2 3 A2 8 Me -(ch2 ^3- CN 135-137 Preparative Examples B and C deleted - 18 - (82356/3

Preparative Example D

Methyl 2-(2,6-dichlorophenylsulphamoyi)-5,7-dimethyl -pyrazoIori,5-alpyrimidine-3-carboxylate (Compound DI) (a) Methyl 2-(chlorosulphonyl)-5,7-dimethylpyrazolo Γ1,5-a 1 -pyrimidine-3-carboxylate A vigorously stirred suspension of the product of Example A(c) (20g) in a 50/50 mixture of glacial acetic acid and water (116 ml) was cooled to below 0°C and was treated over 2 hours with chlorine whilst maintaining the temperature at 0-2°C. The solid material was then filtered off, washed with water followed by petroleum ether (60-80) and dried in vacuo to give 17.6g of desired product. 19 82356/2 (b) Methyl 2-(2,6-dichlorophenylsulphamoyl)-5,7-dimethyl -pyrazolof1,5-a 1pyrimidine-3-carboxylate A stirred solution of 2,6-dichloroaniline (10.66g) and 4-(dimethylamino)pyridine (0.4g) in dry pyridine (100 ml) was treated portionwise with the crude product of stage (a) (10.Og). A yellow precipitate appeared - 20 - 82356/2 immediately following the addition. The suspension was stirred overnight at room temperature, and the precipitate redissolved. The mixture was then evaporated to dryness. the with residue being dissolved of dilute in dichloromethane, hydrochloric acid. washed and dried two portions over magnesium sulphate. Fil tration and evapora tion gave a residue which was triturated with methanol. The solid product was filtered off and recrystallised from acetonitrile to give 5.5g of the desired compound, mp 250- 252° C. Examples D2-D54 The following compounds of formula I where R6 represents hydrogen, and X represents -SO2NH- were prepared by methods analogous to that of Example D: No. Rl R2 R3 R4 (Ph subst:) M Pt (°C) D2 Me Me COOMe 2.6-diCl,3-Me 218-220 D3 Me Me COOMe 2-C1,6-Me 234-236 D4 Me Me COOMe 2-CF3 188-190 D5 Me Me COOMe 2.6-diF 196-198 D6 Me Me COOMe 2-NO2 138-140 D7 Me Me COOH 2,6-diCl 263-265 D8 Me Me CN 2-C1 176-179 D9 Me Me CN 2.6-diCl 262-265 DIO cf3 CF3 CN 2-C1 153-156 Dll Me H COOMe 2,6-diCl,3-Me 286-289 21 82356/3 .IV.1987 .IV.1987 D12 Me H COOMe 2,6-diCl 244-246 D13 Me H COOMe 2.6-diF 197-199 D14 Me Me COOEt 2,6-diCl 206-208 D15 Me Me COOiPr 2,6-diCl 190-192 D16 Me Me COOMe 2-C1.6-F 182-184 D17 Me H COOH 2.6-diCl 244-246 D18 H Me COOMe 2,6-diCl 225-227 D19 Me H COOEt 2,6-diCl 194-196 D20 Me Me COOnBu 2,6-diCl 191-193 D21 H Me COOMe 2,6-diBr 209-210 D22 H Me COOMe 2-C1.6-Me 187-189 D23 H Me COOMe 2,6-diF 195-197 D24 H Me COOMe 2.6-diCl, 3-Me 229-231 D25 Me Me COOMe 2-Me.6-NO2 218-220 D2 6 H Ph COOMe 2,6-diCl 254-256 D27 H Ph COOMe 2.6-diCl,3-Me 250-252 D28 Me Ph COOMe 2.6-diCl 258-261 D29 Me cf3 COOMe 2,6-diCl 227-229 D30 Me cf3 COOMe 2,6-diCl,3-Me 269-271 D31 Me Me CONMe2 2,6-diCl 233-235 D32 Me Me COOMe 2.6-diBr 185-187 [D3 3 Me Me COOMe 2-Me .6-COOEt 175-177 D34 H &lt;c-- Me CN 2,6-diCl 244-246 D35 Me Me CN 2,6-diF 249-252 D3 6 Me Me CN 2,6-diCl,3-Me 287-290 22 82356/2 D37 D3 8 Me Me Me Me COOMe CN 2.6-diCl-3.5-diNO2 2-Cl,6-Me 250-252 255-257 28. IV. 1987 [d39 Me Me COOMe 2-CHF2O 196-198 D4G CF3 CF3 COOMe 2,6-diCl 172-174 28. IV. 1987 [^41 H 2-Py COOMe 2,6-diCl 268-270 D4 2 Me Me COOMe 4-C1 195-198 D4 3 Me Me COOMe 2-C1 152-154 28,IV.1987 Me Me COOMe 2-Me ,6-COOMe 195-198 D4 5 Me Me CN 2-C1,6-F 268-270 The following compounds where X represents -SO2NH - were also prepared by methods analogous to that of Example D: No. Rl R2 R6 R3 R4 (Ph subst: ) M.Pt °C D4 6 Me Me Me COOMe 2,6-diCl 221-223 D 47 Me Me Cl COOMe 2,6-diCl,3-Me 158-160 D 48 Me Me Cl COOMe 2,6-diCl 168-171 D 49 Me Me Me COOH 2,6-diCl 280-282 , „ D 50 Me -(CH_ ).- COOMe 2,6-diCl 201-203 28.IV.1987 2 ' 3 D 51 Me -(ch2 ^3" CN 2,6-diCl 235-237 - 23 - 82356/2 28.IV.1987

Preparative Example e

Methyl 5!,7-dimethyl-2-(2-methylphenoxysulphonyl)- pyrazolo[l,5-a)pyrimidine-3-carboxylate

A stirred solution of the product of Example D(a) (2.0 g) and o-cresol (0.71 g) in dry pyridine (30 ml) was heated at about 60°C for 3 hours. After standing at room temperature for 2 days, the mixture was poured into water and extracted with 3 portions of dichloromethane which were combined, washed twice with dilute hydrochloric acidand dried over magnesium sulphate. Filtration and evaporation gave a residue which was recrystallised from methanol to give 1.1 g of desired product, mp 112-114°C. Preparative Example F

Methyl 2-(2,6-dichlorophenyl-N-proparqylsulphamoyl) - 5,7-dimethy1-pyrazolo[l,5-a 1pyrimidine-3-carboxylate (Compound FI)

Sodium hydride (0.3g) was added to a solution of the product of Example D (Compound DI) (4.3g) in dimethylformamide (50 ml), and the mixture was stirred at room temperature for 10 minutes. Propargyl bromide (1.1ml) was then added, and the mixture was refluxed for 24 82356/2 28.IV.1987 28.IV.1987 5½ hours, then left to cool. It was then poured into 750ml of distilled water, and the precipitate which formed was filtered off and dried. On recrystallisation from ethyl methyl ketone and then from acetonitrile. 1.3g of desired product, mp 225-229°C, was obtained..

Examples F2-F3

The N-allyl derivative (Compound F2), mp 157-160°C, and the N-methyl derivative (Compound F3), mp 202-204°C, corresponding to that of Example E were prepared by methods analogous to those described therein.

Preparative Example G-" 2-(2,6-Dichlorophenylsulphamoyl)-5,7-dimethylpyrazolo- Γ1,5-a1pyrimidine-3-carboxamide (Compound Gl)

The product of Example D9 (4.6g) was treated with concentrated sulphuric acid and was stirred at room temperature overnight. It was then poured into ice-water, and the precipitated solid was filtered off. washed with water and dried. It was then purified by dissolving it in dimethylformamide, filtering whilst hot, and reprecipitating the product from the filtrate by the addition of water, to give 3.0g of desired product, mp>320°C.

Examples G2-G7

The following compounds of formula I where R6 represents hydrogen were prepared by methods analogous to that of Example G: 25 82356/3'

No . SI R2 R3 R4 (Ph subst:) MiPt (° G 2 H --½ Me CONH2 2,6-diCl 238-240 G.3 Me Me conh2 2,6-diCl,3-Me >320 G 4 Me Me conh2 2,6-diF 233-235 G.5 Me Me conh2 2-C1.6-Me 255-257 G; 6 Me Me conh2 2-C1,6-F 320 The following compound of formula I where R2 and 28,1V. 1987 R together represent -(CH2)3- was prepared by-methods analogous to that of Example G.:

No . Rl R3 R4 (Ph subst:) M.Pt (° G7 Me conh2 2.6-diCl 242-244

Preparative Example H / 2-(2,6-Dichlorophenylsulphamoyl)-N,5,7-trimethylpyrazolo-

Γ1,5-a1pyrimidine-3-carboxamide (Compound hD A suspension of the product of Example DI (4g) in 33% methylamine solution in industrial methylated spirits (65 ml) was heated in a small autoclave at about 100°C overnight. After cooling, the resultant mixture was filtered, the filtered solid being washed with methanol, dried and recrystallised from glacial acetic acid, to give 1.6g of desired product, mp 284-286°C.

Example H2

The following compound of formula I where R6 represents hydrogen was prepared by a method analogous to that of Example h: - 26 - 82356/3 28.IV.1987 NO. Rl R2 R3 R4 (Ph subst:) M.Pt (°C) H2 Me Me CONHcyhex 2,6-diCl 236-238 Preparative Example X 2-Ethoxyethyl 2-(2,6-dichlorophenylsulphamoyl) - 5,7-dimethylpyrazolo[1,5-a 1 pyrimidine-3-carboxylate A suspension of the product of Example DI (l.Og) in 2-ethoxyethanol (25ml) was treated with titanium (IV)- butoxide (0.34g) and was refluxed overnight. After cooling, the mixture was poured into dilute hydrochloric acid and extracted with three portions of dichloromethane. These were combined, washed with sodium hydrogen carbonate solution and dried over magnesium sulphate. Filtration and evaporation gave a residue to which toluene was added. The solid material was filtered off, washed with toluene and dried to give 0.8g of desired product, mp 198-200°C. Preparative Example J 2-(2,6-Dichiorophenylsulphamoyl)-5,7-dimethylpyrazolo- Γ1,5-a 1pyrimidine-3-carbohydrazide Hydrazine hydrate (0.56ml) was added to a suspension of the product of Example DI in ethanol (50ml). The mixture was refluxed for 5 days, left to cool to room temperature, and then evaporated to give 4.0g,of desired product as a yellow solid, m,p 285-287°C. 27 82356/4 28.IV.1987

Preparative Example K ·

Isopropyl 2-(2,6-dichlorophenylsulphamoyl)-5,7-dimethyl -pyrazolo[1,5-a 1pyrimidine-3-carboxylate

The product of Example D7 (O.8g) in trifluoroacetic anhydride.;'(4ml) was treated with trif luoroacetic acid (2ml), and the resultant solution was treated carefully with ipropan-2-ol (20ml) and refluxed for 1 hour. The mixture was then evaporated to dryness, the residue was mixed with water, and the solid material was filtered off and recrystallised from propan-2-ol to give 0.6g of the desired product, mp 190-192°C, identical to that of Example D15.

Preparative Example L:

Methyl 2-(2,6-dichlorophenylsulphamoyl)-5-hydroxy-7-methyl -pyrazolo[1,5-a1pyrimidine-3-carboxylate (Compound Ml) (a) Methyl 3-acetamido-5-benzylthiopyrazole-4 - carboxylate

The product of Example A(b) (50g), acetic anhydride (2Og) and acetic acid (lOOg) were refluxed with stirring for 6 hours. The solvent was then removed, and the residue was recrystallised from toluene to give 49.5g of desired product. (b) Methyl 5-acetamido-3-chiorosulphonyl-lH-pyrazole-4- carboxylate

The product of stage (a) (20g) was suspended in 28 82356/3 28.IV.1987 concentrated hydrochloric acid and was cooled to' -5°C. Acetic acid (15ml) was then added, and chlorine gas was bubbled through with stirring and cooling to maintain the temperature between -5°C and 0°C. A further 10ml of concentrated hydrochloric acid was then added, and after 70 minutes, the solid was filtered off and washed with water/petroleum ether (60—80) towgive 15g of desired product. (c) Methyl 5-acetamido-3-(2,6-dichlorophenylsulphamoyl)-ΙΗ-pyrazole-4-carboxylate 2,6-dichloroaniline (5g) and N,N-dimethyl-4-amino-pyridine (0.3g) were dissolved in pyridine (50ml), and the product of stage (a) (5g) was added in portions. The mixture was then stirred at room temperature for 24 hours, after which the pyridine was removed, and the mixture was taken into dichloromethane. It was then washed with water, dried, and the solvent was removed. The residue was recrystallised from acetonitrile to give 3.6g of desired product. (d) Methyl 5-amino-3-(2,6-dichlorophenylsulphamoyl) -lH-pyrazole-4-carboxylate

The product of stage (c) (lOg) was dissolved in methanol (50ml) and potassium carbonate (2g) was added.

The reaction mixture was then refluxed for 6 hours, allowed to cool, and was poured into 1500ml water. The mixture was acidified with hydrochloric acid to precipitate the desired product in a yield of 5.4g. 29 82356/3 28.IV. 1987 (e-) Methyl 2-( 2.,.6-di chi or ophanylsulphamoyl )-5-...... hydroxy-7-methyl-pyrazolo(1,5-a1pyrimidine-3-carboxylate

The product of stage (d) (7g) was refluxed overnight with methyl acetoacetate (3g) in trifluoroacetic acid (25ml). The solvent was then removed and the residue was recrystallised from acetonitrile to give 5.6g of desired product, mp 31O-312°C.

Example M2

The compound corresponding to that of Example L where the substituent at the 7-position is hydroxy was prepared by an analogous method, mp 264-267°C.

"Preparative Example M

Methyl 2-(2,6-dichlorophenylsulphamoyl)-5-chloro-7-methyl- pyrazolof1,5-a1pyrimidine-3-carboxylate

The product of Example L (4g) was dissolved in pyridine (5ml), and thionyl chloride (25ml) was added.

The reaction mixture was then heated to reflux for 4 hours, the solvent was removed, and the residue was purified by chromatography to give 3.6g of the desired product, mp 256-257°C.

Formulation Example A 10¾ suspension concentrate of compound DI was prepared from the following ingredients: 30 82356/3 28.IV.1987 for β4· end underlined

Examples

Compound DI

Pluronic P75

Polyfon H

Propylene glycol

Anti-foam 1520

Veegum R

Kelzan (xanthan gum)

Formaldehyde (40% aq

Water

Analogous suspension prepared containing 0.5, of the compounds of Exam S/i 100 30 20 105 0.5 7.5 1.0 solution) l.o to 1 litre concentrate formulations 5, 10. 25, 50 and 85% by les D1-D51, Ξ, F, F1-F3, were weight G1-G7, K1-H2, I, F and K. HERBICIDAL EXAMPLE A (Pre-Emergence)

Seeds of the weed species listed below were sown in anodised aluminium pans 19 cm long x 9.5 cm wide x 6 cm deep, containing sterilized sandy loam. They were watered and then sprayed with the compounds of the Examples listed below formulated as a solution/suspension in 1:1 by volume of acetone and the wetting agent polyoxyethylene (20 mols) monolaurate solution (2 g per litre).

The concentration of each test compound and volume of application were calculated to give the desired rate of application of the compound in 450 litres per hectare. 31 82356/3

After 3 to 4 weeks growth in the controlled environment room (20°C; 75-95% relative humidity; 14 hours per day artificial illumination) the plants were visually assessed for any herbicidal response.

All differences from an untreated control were scored accordingly to an index where 0 = no effect, 1 = 1-24% effect. 2 = 25-69% effect. 3 = 70-89% effect and 4 = 90-100% effect. In the table below, the following letters are used to denote the plant species: a - Polygonum lapathifolium (Pale persicaria) b - Galium aparine (cleavers) c - Chrysanthemum segetum (corn marigold) d - Alopecurus myosuroides (blackgrass) e - Elymus repens (Couchgrass) f - Avena fatua (wild oat) g - Abutilon theophrasti (velvetleaf) h - Cyperus rotundus (purple nutsedge) i - Pharbitis purpurea (morningglory) j - Echinochloa crus-galli (barnyardgrass) k - Setaria viridis (green foxtail) 1 - Solanum nigrum (black nightshade)

The results obtained were as follows:

Ex Kg/ha a_b£de.f_ghi_j_k.X DI 2.5 4 4 444 3 4 4444 32 82356/3 28.IV.1987

Ex Kg/ha a b C d e. f a h i i k D3 1.0 4 4 4 3 4 . 3 1 2 3 4 4 D4 2.5 4 4 2 2 2 4 3 4 3 3 D5 1.0 3 4 2 3 3 3 0 2 2 2 D8 2.5 4 2 0 0 3 0 0 2 0 0 D9 2.5 4 4 3 2 3 0 2 2 0 2 DIO 1.0 3 4 4 3 3 0 3 4 4 3 4 D14 1.0 3 4 4 0 0 0 1 0 2 2 3 D16 1.0 4 4 4 2 3 2 4 0 3 2 3 D18 1.0 4 4 4 4 4 3 4 3 4 3 4 D21 0.5 4 4 4 2 3 3 4 4 4 4 4 D2 3 0.5 4 4 4 4 4 3 3 2 3 2 4 D24 0.5 4 4 4 2 2 2 3 3 3 2 3 D25 0.5 4 4 4 0 3 1 3 4 2 0 0 D2 9 0.5 3 4 4 4 4 2 3 3 3 4 4 D30 0.5 3 4 4 2 2 4 2 2 3 0 0 D31 0.5 3 4 4 0 0 2 2 0 2 0 0 D32 0.5 4 4 4 2 2 3 4 2 4 3 2 D34 0.5 3 4 4 2 2 4 2 4 2 0 0 F3 0.5 4 3 3 0 0 0 1 0 0 2 3 G1 0.5 4 4 4 3 4 3 4 4 4 4 4 1. 4 3 4 4 4 4 4 4 4 4 4 4 4 4 HERBICIDAL EXAMPLE B (Post-Emergence)

Seeds of the plant species listed below were sown in anodised aluminium pans, 19 cm long x 9.5 cm x 6 cm deep, containing sterilised sandy loam. They were then watered 33 82356/2 and placed in a controlled environment room (20°C; 75-95% relative humidity; 14 hours per day artificial illumination). Fourteen or twenty one days after sowing (depending on the species but when most plants had 2 to 3 true leaves) the seedlings received a foliar spray of the compounds of the Examples listed below, formulated as a solution/suspension in 1:1 by volume of acetone and the wetting agent polyoxyethylene (20 mols) monolaurate solution (2 g per litre). compound was of application of the

After 2 to 3 weeks room the plants were response.

All differences from an untreated control were

The concentration of each test calculated to give the desired rate compound in 450 litres per hectare, growth in the controlled environment visually assessed for any herbicidal scored according to an index where 0 = no effect, 1 = 1-24% , effect, 2 = 25-69% effect. 3 = 70-89% effect and 4 = 90- •100% effect In the table below. the letters used denote the same plant species as in Herbicidal Example A: The results obtained were a s follows: Ex Kq/ha a bed e f 9. h i i k 1 DI 2.5 4 4 3 3 3 4 4 4 3 4 D16 1.0 3 4 3 3 2 3 4 2 1 2 2 3 D18 1.0 2 4 4 3 3 3 2 2 2 2 3 3 D21 0.5 2 4 3 2 2 3 . 2 2 2 2 2 4 34 82356/2

Ex Kq/ha D23 0.5 D29 0.5

Gl 0.5 a b c 2 3 2 2 4 2 3 4 3 d e f 3 2 3 3 4 2 3 3 3 3. h i_ 2 11 0 0 2 12 2

1 X I 0 14 2 0 2 2 2 2 35