CS291484A2 - Zpusob vyroby 1 l4 l4 lfluoralkylmethylthio nebo sulfonyl pfenoxy pfenyl p 1,3,5 triazin 2,4,6 l1h,3h,5h p trionu - Google Patents

Description

Author of the invention HABERKORN AXEL drWUPPERTAL (NSR) KUME TOIOHIKO, HIND (JAPAN)

Patent proprietor of BAYER AKTIENGESBLLSGHAPT, LEVERKUSEN (NSR) <RTI ID = 0.0> &lt; / RTI &gt; <RTI ID = 0.0> &quot; </RTI> Method of Production 1- (4-L4- (fluoroalkylmethylthio) or sulfonyl) phenoxy] phenyl-1,3,5-triazine. , 6 (1H, 3H, 5H) -triones Registered 18 04 «84Preferences from 23)» · 04 «83 #SS> 'PV 2914 * -84f (P 33 14 739.6)

The present invention relates to a process for producing 1- (4-L4- (fluoroalkylmethylthio- or sulfonyl) phenoxyphenyl) -1,3,5-triazine-2,4,6 (1H, 3H, 5H). ) -tri, which have valuable pharmacological properties and can be used in pharmacy as anti-coccidiosis for different animal species and possibly also in humans *

According to the invention, 1- [4- [4- (fluoro-alkylmethylthio- or sulfonyl) phenoxy] phenyl] -1,3,5-triazine-2,4,6 (1H, 3H, 5H) -triones are prepared. of Formula I

(I) wherein R 1 is C 1 -C 3 fluoroalkyl, for example trifluoromethyl and tetrafluoroethyl, X and Y are the same or different and are hydrogen, C 1-3 alkyl, C 1-3 alkoxy or halogen, R is C 1 -C 4 alkyl, for example methyl, ethyl or propyl and n is 0 or 2, and the pharmaceutically acceptable salts thereof;

These compounds are valuable for their efficacy against coccidiosis in humans and various animal species.

The compounds of the formula (I) and their salts according to the invention are prepared by the addition of a urea derivative of the formula II

(II)

Y 4 wherein f R, X, Ϊ, i and a are as defined above,

treated with a carbonyl isocyanate of formula III

O

M R 2 -G-NGO (ΙΙΓ) wherein R 2 is halogen, C 1 -C 6 alkoxy or C 6 -C 10 aryloxy, at temperatures between 0 and 120 G, preferably 20 to 100 gG, where appropriate Most of the substituted ureas of formula II, which are used as starting materials, are not yet known. However, these compounds can be readily prepared by methods known per se, ie. «Μ

A) reacting 4 * [4 '(fluoroalkylmethylthio- or -sulfonyl) -phenoxyjanilines with substituted isocyanates with a tartrate solvent at temperatures between 0 and 130 ° C; or B) reacting 4- [4- (fluoroalkylmethylthio- or sulfonyl) -phenoxy] phenylisocyanates with alkylamines in an inert solvent at temperatures between 0 and 100 ° C »

Alternative urea production is described in "Methoden der org. Chemistry *, (Houben-Weyl), 4th Edition, Volume III, pp. 157 and 158 #

As the diluent for the reaction of the urea derivatives II with the carbonyl isocyanates of the formula III, all organic solvents which are inert in the reaction are suitable. These include, in addition to pyridine, preferentially aromatic hydrocarbons, for example benzene, toluene and alkylene, halogenated hydrocarbons, for example dichloroethane and carbon tetrachloride, halogenated aromatic hydrocarbons, e.g. chlorobenzene and dichlorobenzene, and ethers such as tetrahydrofuran and dioxane ·

The reaction temperature of the reaction of the ureas of formula II with the carbonyl isocyanates of formula III can be varied over a wide range. Generally, this reaction is carried out at a temperature between 0 and 150 ° C, preferably between 20 and 100 ° C. In the above reaction step, the reaction can be carried out at atmospheric pressure or at elevated pressure. Generally, the reaction is performed at atmospheric pressure.

Possible oxidizing agents for converting the fluoroalkylmethylthioderivatives of formula (I) wherein n is zero to the corresponding oxidized compounds of formula (I) wherein n is 2 are, for example, hydrogen peroxide, for example, m-chloroperbenzoic acid, chromium acid, potassium permanganate and potassium periodate. The compound obtained can be converted, for example, by reacting the compound with an inorganic or organic base on the corresponding salt.

The corresponding anilines of general formula IV - 7 -

(IV) wherein f R, η, X and Y are as defined above,

may be prepared by reduction of the corresponding nitro derivatives of formula V

wherein • p R, η, X and Y have the meanings given above ♦ ** θ **

The nitro derivatives of general formula V can be prepared by condensation of a compound of formula VI

NO (VI) wherein X and Ί are as defined above and Z is a halogen atom, for example a chlorine atom or a bromine atom,

with 4 - (fluoroalkylmethylthio- or sulfonyl) phenol general formula VII

(VII) «in which f

Ran have the above-mentioned meanings *

The phenol derivatives of formula VII wherein n is zero can be produced by reacting 4-hydroxythiophenol with a fluoroalkylmethylsulfonate of formula VIII R2-SO2-OCH2Rf (VIII) wherein R is as defined above and R is a hydrocarbon radical such as a methyl radical, an ethyl radical , a phenyl radical or a tolyl radical, in an aprotic polar solvent, for example N, N-dimethylformamide or dimethylsulfoxide, the presence of an organic or inorganic base, for example potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide or hydride. - 10 -

The fluoroalkyl sulfonate of formula (VIII) may be prepared by procedures known from the published publications, for example from the Journal of the American

Skt,

Chemical Society, Vod., 75, p. 5978, and Journal of Organic Chemistry, 35, p. 3195, but each of the fluoroalkylsulfonate isolation methods described in these publications is rather complicated. fluoralkanol, for example β, β, β-trifluoroethanol, sulfonyl chloride, for example p-toluenesulfonyl chloride, a catalytic amount of a phase transfer catalyst, for example triethylbenzylammonium chloride, and an inert diluent, e.g.

The reaction temperature can be varied within wide limits, but preferably at temperatures between 20 and 70 ° C. The amount of each reactant may be stoichiometric, or the fluoroalkanol and / or sodium hydroxide may be used in excess of the stoichiometric amount.

The compounds of formula I as well as their pharmaceutically acceptable non-toxic salts according to the invention have a good effect on anti-diverse kokeidias in poultry, for example Eimeria tenella (cokeidiosa of chickens), Eimeria acervulina, Eimeria brunetti, Eimeria maxima, Eimeria mitis , Eimeria neeatrix and Eimeria praecox (small intestinal coccidiosis in chickens).

In addition, the compounds can be used for the prophylaxis and treatment of coccidiosis infections of other species in domestic poultry. In addition, the compounds of the present invention have potent activity in coccidiosis infections in mammals. Further, said compounds may be used for the treatment or prophylaxis of toxoplasmosis, both in the treatment of cats which are responsible for the ejection of infectious stages (oocysts) and for the treatment of infected humans; Coccidiosis infections can lead to considerable losses in domestic animals and represent a real problem in the cultivation of poultry and mammals such as bovine animals, sheep, rabbits and dogs. The effect of the known compositions against coccidiosis is in most cases limited by a few species of poultry. Treatment and prophylaxis of coccidiosis in mammals is still a major unresolved problem. 12 -

The pharmaceutical compositions containing the compounds of the present invention contain greater or lesser amounts, for example 0.1 to 99.5%, preferably 0.5 to 90%, of at least one 1- (fluoroalkylmethylthio- or sulfonyl) phenyl substituted 1,3,5- a triazine defined above in combination with a pharmaceutically acceptable, non-toxic, inert carrier or filler, the carrier comprising one or more solid, semi-solid or liquid diluents, extenders, and auxiliaries that are non-toxic, inert, and pharmaceutically acceptable. These pharmaceutical compositions are preferably used in the form of dosage units, i. special units which contain a predetermined amount of medicament that corresponds to the portion indicated by the dose or the multiple of the dose which, according to calculation, yields the desired therapeutic effect. The dosage units may contain one, two, three, four or more individual doses, or alternatively one half, one third, or one quarter of a single dose. The unit dose preferably contains an amount sufficient to achieve the desired therapeutic effect after administration of a single or non-single use. several dosage units according to a predetermined therapeutic regimen for dosing, usually whole, one-half, one-third, or one-quarter-one, two, three, or four times daily daily dosages »Other therapeutic agents may be used concurrently»

Oral administration may be by using solid and liquid unit dosage forms, for example, powders, tablets, dragees, capsules, granules, suspensions, solutions, and the like.

Powders are produced by grinding the compound to a suitably fine particle size and blending with a similarly ground pharmaceutical carrier, for example, an edible carbohydrate, for example, starch, lactose, sucrose, glucose, or mannitol. preservatives, dispersants and dyes *

Capsules are prepared by first obtaining a powder blend as described above, which is then filled into gelatin shells adapted for this purpose. Glidants such as colloidal silicon dioxide, talc, magnesium stearate may be added to the powder blend prior to filling. Disintegrating or solubilizing agents such as agar-agar, calcium carbonate, or sodium carbonate may also be added to these formulations to improve the usability of the medicament when applied in capsule form. .

Tablets are made, for example, by preparation of powder mixtures, by granulating or processing pearl-shaped particles, by adding glidants and by disintegrating agents and compressing them into tablets. The powder mixture is prepared by mixing the comminuted compounds with a diluent or extender or base, as described above, and optionally a binder such as carboxymethylcellulose, alginate, gelatin or polyvinylpyrrolidone, a dissolution agent, for example, paraffin, a resorption accelerator, with, for example, a quaternary salt or an adsorbent such as bentonite, kaolin or dicalcium phosphate. The powder mixture can be granulated by wetting it with a binder such as a syrup, a starch paste, an gum arabic in a mucilaginous or a cellulose derivative solution or a polymeric compound, and passing the mixture through a sieve. Alternatively, instead of producing the granulate, the powder blend can be processed in a tabletting machine to obtain imperfectly formed beads which can then be comminuted. - 15

Glidant may be added to the granulate to prevent sticking to the nozzles of the tabletting machine, such as stearic acid, stearic acid salt, talc or mineral oil. The glidant mixture is then compressed into tablets. These medicaments can also be combined with loose inert carriers, then tablets are compressed directly from the blends without the need to prepare granules or beads. The tablets may be provided with a clear or opaque topcoat consisting of a shellac coating of sugar or polymeric material or a wax coating. For these coatings, a dye may be added to distinguish different unit doses.

Liquids for oral administration, for example, solutions, syrups, and elixirs, may be prepared in unit dosage form such that a given amount contains a predetermined amount of the active compound.

Syrups may be prepared by dissolving the active ingredient in an aqueous solution of sucrose which has been suitably flavored while the elixirs are prepared by incorporating a non-toxic alcoholic carrier. The suspensions may be prepared by dispersing the compound in a non-toxic carrier. Solubility-modifying agents and emulsifiers, such as, for example, 16-ethoxylated isostearyl alcohols and polyoxyethylene sorbitol esters, preservatives and flavor enhancers such as essential oil and saccharin may also be added.

Where appropriate or appropriate, oral dosage formulations may be formulated as microcapsules. Such a formulation can also be made so that the release of the active ingredient is prolonged or maintained for a period of time, for example by encapsulating or encapsulating the fine dispersed material into polymers, waxes and the like,

Parenteral administration may be by the use of liquid unit dosage forms, for example, sterile solutions and suspensions, which are intended for subcutaneous, intramuscular or intravenous injection. These preparations are made by suspending or dissolving a metered amount of a compound in a non-toxic liquid carrier suitable for injection purposes, e.g. environment, and sterilizing suspension or mite. Alternatively, the metered amounts of the active compound can be filled into the vial, the vial and its contents then sterilized and sealed. The respective vials or carrier may also be intended to be mixed prior to application. Non-toxic salts and salt solutions can also be added to these preparations to provide an isotonic injection solution. Stabilizers, preservatives and emulsifiers can also be added.

Applicable applications can be by using suppositories that contain a mixture of the active compounds with low melting, water-soluble or insoluble solids such as polyethylene glycol, cocoa butter, esters, for example, myristyl palmitate, or mixtures thereof. Localization can be accomplished using solid unit dosage forms, for example, powders, or liquid or semi-solid dosage forms, such as solutions, suspensions, ointments, pastes, creams, and gels. Powders are prepared using carrier materials such as talc, bentonite, silicic acid, powdered polyamide, and the like. In the case of liquid and liquid formulations, for example, polyethylene glycols, vegetable and mineral oils may be added to the carriers described above. alcohols such as isopropanol. Other auxiliaries may also be present, such as emulsifiers, preservatives, coloring agents, aqueous substances and the like. The compositions may also be applied in the form of aerosols using conventional propellants such as chlorofluorocarbons. A preferred daily dose is 25 mg to 25 active ingredients.

Administration may be by oral, parenteral, i.e. intramuscularly, intraperitoneally and intravenously), rectally and locally. 2 of these dosage forms are particularly preferred for oral administration. In connection with the use of the compounds of the present invention, the present invention also relates to feed and food containing from about 25 to about 5,000%, preferably from about 50 to about 250 ppm, of a compound of the present invention in combination with a suitable feed formulation. As an example, feed © for chickens the following composition ^ z * 52,000% kernel feed kale17,995% kernel soya beans 5,000% kernel wheat flour3,000% fish meal3,000% tapioca meal 3,000 $ kernel green lucerne2,000% ground wheat germ - 19 - 2,000% soybean oil1,600% fish bone meal1,500% whey powder 1,400% calcium carbonate for feed and food1,000% calcium phosphate for feed and food1,000% molasses 0.500% beer yeast 0.005% l-L3,5-dichloro ~ 4- (4- (3,0,0-trifluoroethylthio) phenoxy) phenyl] -3-methyl-1,3,5-triazine-2,4,4 (1H, 3H, 5H) - trion 100,000%

Such feeds or foodstuffs may serve both for medical purposes and for professional purposes. lactic.

By using the compounds of the invention, concentrates or pre-formulations containing from 1 to 30, preferably from 10 to 20,% by weight of the compound produced according to the invention can be prepared with an edible organic or inorganic carrier, for example maize flour or corn from corn and soybean or mineral salts, which preferably they contain a small amount of edible oil to prevent dusting, such as corn oil or soybean oil. The premix thus obtained can be added to the full poultry feed prior to feeding the animals.

The compounds of the present invention can also be added to drinking water for animals treated with bulk or prophylaxis of kokeidiosis.

Feeds can be used both for medical purposes and for prophylactic purposes »

For the treatment and prophylaxis of kokeidiosis in poultry, especially in chickens, ducks, geese and turkeys, 25 to 100 ppm, preferably 50 to 100 ppa, of a compound of the invention are mixed with a suitable edible material, for example a nutritional feed composition. If desired, these amounts may be increased, particularly when the recipient is well tolerated by the recipient. In the treatment of individual animals, for example in the treatment of kokeidiosis in mammals or in the treatment of oxoplasmosis, amounts of 5 to 250 mg per kg of body weight per day are preferably administered, to achieve the desired effective results. Nevertheless, it may be necessary to deviate from the amounts given, in particular depending on the body weight of the test animal, depending on the type of application method, but also with regard to the species and its individual drug reaction or the type of formulation and the time or interval in which it is applied. Thus, in certain cases, less than the minimum quantity mentioned may be sufficient, while in other cases the upper limit provided above may be exceeded. When larger amounts are applied, it may be advantageous to divide the amount throughout the day into smaller individual doses.

The coccidiostatic efficacy of the compounds of formula (I) according to the invention is illustrated in Table 1, where Eimeria tenella (coccidiosis of caecum / acacia), Eimeria acervalina and Eimeria maxima (coccidiosis of small intestine and chickens) are reported as examples of coccidiosis efficacy and poultry, while Eimeria falci-formas (mouse coccidiosis) is exemplified by coccidiosis in mammals.

For example, when chickens aged 9-11 days are infected with 4000 spore oocysts of the intolerantly virulent strains of Eimeria acervalina, Eimeria maximaa Eimeria tenella, i.e., the causative agents of intestinal coccidiosis, the untreated comparator excreted at least 300,000 to 500,000 oocysts / g of spore from day 5 on day 9 post infection. During the disease, weight gain decreases substantially, and serious, macro-scopically detectable changes occur mainly in the intestines, which may lead to severe haemerrhagic diarrhea and may die. When testing the efficacy of anti-aceria acervulina, Eimeria maxima and Eimeria tenellase, the compounds of the invention apply pre-infections 3 days up to 8 days post-infection (end of the experiment).

The number of oocysts was determined by McMaster's (see Engelbrecht and co-workers of X $ X, "Parasitologische Arbeitsmethodea in Medizin und Veterinirmedizin", p. 172, Akademie-Verlag, Berlin (1965)) · Treatment for Eimeriafalciformis infection in mice, referred to as examples of coccidiosis and mammals are performed on the first, second, third, sixth, seventh and eighth days after infection. The infection is performed using 10,000 sporulated oocysts per mouse (weight 15 g). In the case of untreated comparator animals, there is massive oocyst excretion, bloody diarrhea, and 30% of the deaths of the infected animals, from day 7 post-infection.

The effective dose is that which completely or to a large extent avoids excretion of oocysts and / or removes the clinical signs of co-mortality including mortality. - 23 -

The lowest effective doses found under the experimental conditions are lower than those of the anticoccidiostat drugs that are commonly used to prevent coccidiosis in poultry. Further, the droppings are compounds of the invention - in addition to beneficial in terms of residues in the body - very effective against coccidiosis in mammals (Table 1).

The widespread resistance of coccidiosis to coccidiostats requires more effective compounds derived from new classes of chemical compounds. Also from this point of view, the enriching compounds of the present invention extend the diversity of these drugs.

I • t

CM

AND

i — IOS $ a • s E4 as o • rl <33 * 3 1 »MS CS MS 4 r4 r • rl as • 3 0 M 3 <<3 as as 3 3 • rl r 1 1 P 3 3 Φ Φ 3 • 3 Θ 3 3 3 3 j 3 j + J as 3 l l 3 3 3 Φ Φ Φ 3 1 1 1 PM PM PM PM PM PM PM PM PM PM PM 3 N • 3 P Φ 3 · ► r-1 ø> Φ 3 MS Ή 0 φ 3> N • 3 OP pej as 3 r3 O Λ Φ * 0 <3 O f? 3 l l))) MS MS MS MS t)) MS MS MS MS t t MS MS MS MS t O O O O • • • • • • • • • rl P 0 O &amp; 'b P • • Λ Λ KS KS KS KS KS>>>>>>>>>>>>>>>>' '' '' '' ' r4 i P <M f> P s o O • 3 3 KS 03 Ό 'gj 00 P. P. P. 8 P «P <« 3

T

CM

CM

i if

CM

I »· Continuation of Table 1 (0 <a o • rl ao (4 • rl Φ O 1” 1 tto <0 a (0

• H • 3

CO • rl a .a a) rl 14 i «0 r4 r-l Φ fi Φ +»

CS

I <0 and a. Rl r-l

ÉS o (0

v ©

CM »« continuation of table 1 r • rl

O 2 • rl <a • rl

O rl a

o O 00 IA IA «IA IA IA IA IA r r IA IA IA IA 1 1 1 l l l l l l l l

O § rl (9 • rl and Φ • rl <9 Q. IA OCM IArl 3

OJ rl

OJ • rl

X j * and g r-1 d

IA

CM rl

IA and M3

1 of - »r — 1 &amp; +3 Φ h> · ri i Φ 0 «O a Ό and P • rl Ό 4 F4 O s P 1 1—4 00 A 1 Λ OM> CM o 1 wa ι ř ř * bo a a 1 <Thu 1 r • rl fr a 1 oo VQ A r4 1 PAO φ O a 0 i Ό 1 3 • rl i Ť a • rl and HH p OO φ and Λ4 p Ό • rl Oi v «» 1 '1 1 IA CM 1 qs 1 il 1 r — i / · ri r rl 3 b> p A φ and r4 33 3 <a Φ r 0 r 0 T 1 CM z rl o 1 a srt <í? * 9 rH 3 • rl * &amp; r4 Ό and Φ • rl O 3 m and <a OS • H P 1 and φ CM? P 1 C ~ Ol ^ ~ z z-> 9 1 1 rl ca IA ip 1 I A rl O CM Φ a 1 a Ol «α a 1 O>» CO Z ~ and A and IA O | «3 >> ·» 1 and Gi • OiJ * CM P H z 1 O Φ P § 1 o a r-l 33 a • rl cÉ X? i • rl 0 | • P • H co 1 Φ <rt ta M-: 1 1 «- - - IA: IA O t_1 i M • rl 1 1 CO A r-l CM 1 1 II N - 27 Examples illustrate! Process for the Production of Active Substances: Example 1

To a solution of 4.25 g of N- (3,5-dichloro-4- [4- (β, β, β-trifluoromethyl thio) phenoxy] phenyl] -B-methyl-urea in 100 ml of toluene 1.16 g of chlorocarbonyl isocyanate in 2 ml of toluene are added dropwise with stirring. The mixture is stirred for 1 hour at 20-30 ° C and then boiled for 3 hours. After cooling, the reaction mixture was evaporated in vacuo. The solid obtained is recrystallized from ethanol to give 3.8 g of 1- [3,5-bis-4- [4- (β, β, β-trifluoromethylthio) phenoxy] phenyl] -3-methylthio. 1,3,5-triazine-2,4,6- (1H, 3H, 5H) -trione, m.p. 212-213 ° C. - 28

In the same manner as described in Example 1, the following compounds of formula I are prepared:

1b)

Melting point i 175 to 177 GC * · 29 * lc)

Melting point 167-178 ° C;

Mp 187-189 ° C.

Melting point: 183-185 GC.

If)

Temperatures to ° C. 31 · 1 <)

Melting point: 105-112 ° C 1h) hcf2f2ch2s

Melting point: 150-157 ° C »

32 Example 2

10 g of 30% aqueous hydrogen peroxide solution are added dropwise at about 20 DEG C. to a solution of 3.8 g of the compound 1 prepared above in 100 ml of glacial acetic acid as described above, and the mixture is stirred for 1 hour at 20 DEG to 30 DEG C. then a solution of 10 g of sodium thiosulfate in 100 ml of water is added to the cooled reaction mixture, and the mixture is stirred at room temperature for 0.5 hour, then evaporated under reduced pressure and then mixed with 20 ml of water for the remainder. The solid thus obtained is filtered off, washed with water, dried and recrystallized from ethanol. 2.5 g of 1- [3,5-dichloro-4- [4- (β, g, β-trifluoroethylsulfonyl) phenoxy] phenyl] β-methyl-1,3,5-triazine are obtained * 2.4.6 (1H, 3H, 5) * trione, mp 269-272 ° C *

Example 3

CHCl3 To a suspension of 1.9 g of N- [4- [4- (p, 3,0-trifluoro-ethylsulfonyl) phenoxy] phenyl] -N &apos; -methylurea in 10 ml of 1,2-dichloroethane was added with stirring a solution. 0.6 g of carbonocarbonyl isocyanate in 2 ml of 1,2-dichloroethane. The reaction mixture is then boiled for 5 hours and then cooled to room temperature. The solid obtained after evaporation of the reaction mixture was recrystallized from ethanol to give 1.6 g of 1- [4- [4- (0,0,0-trifluoroethylsulfonyl) phenoxy] phenyl] -3-methyl- 1,3,5-triazine-2,4,6 (1H, 3H, 5H) -trione, m.p.

Claims (2)

- 34 - OBJECT OF THE VIRUS 1. Process for the production of 1- (4-L4) (fluoroalkylmethylthio- or sulfonyl) phenoxy] phenyl / 1,3,5 &apos; (I) wherein R is a C 1 -C 3 fluoroalkyl group and X and Y are the same or different and are hydrogen, C 1 -C 3 alkyl, C 1 -C 3 alkoxy or halogen, 35 - R is an alkyl group having from 1 to 4 carbon atoms and n is an integer of 0 or 2, as well as their physiologically acceptable salts, characterized in that the urea derivative of formula (II) (II) wherein f * R, X, T, R and n are as defined above, acting with a carbonyl isocyanate of formula IIIO w R2 - G - KCO (III) wherein - 36 - 2 B represents halogen, alkoxy with 1 to about 6 carbon atoms or aryloxy of 6 to 10 carbon atoms, at temperatures between 0 and 120 ° C, preferably at 20 to 100 ° C, whereupon the optionally obtained compound of formula I is converted to a salt by treatment with a salt-forming component. from 2. The process of claim 1 wherein the reaction is carried out at atmospheric pressure. 3. The process of claim 1 wherein the corresponding compounds of formula (II) and (III) are used as the starting material to form a compound of formula (CF3) CH2S-. 3. A process according to claim 1 wherein the corresponding compounds of formula (II) and (III) are used as the starting material to form a compound of formula (II). 3. The process of claim 1 wherein the corresponding compounds of formula (II) and (III) are used as starting materials to form a compound of formula (II). "iiyd * 54 / 6OO / Nn