- G (V) - CARBOXYARYL SUBSTITUTED DIPHENYL UREA AS RAF KINASE INHIBITORS

0001 : [Field of the present invention] The present invention, an aryl group of urea and used in medical treatment of disease raf intermediary such a chemical composition for use in the therapy. 0002 : [Background of the present invention] p21^ras oncogene and proceeding to the human solid hepatoma generating a major contribution by the user, of the 30% of all sudden changes in human hepatoma (Bolton et al. Ann. Rep. Med. Chem. 1994, 29,165-74; Bos. Cancer Res. 1989, 49, 4682-9). In the normal non-mutational, ras protein is almost all of the command signal by the growth factor in biotissue transformant in cascade of key elements (Avruch et al. Trends Biochem. Sci. 1994, 19,279-83). Physilogically guanine nucleotide ras the protein in the coupling, the coupling activation-GTP and GDP ras-coupled between the rest of the cycling of the other adjusting endogeneous GTP and ATPase activity is controlled strictly by the protein. In the cells in the hepatoma ras mutational protein, GTP endogeneous ATPase activity is relaxed, therefore the protein such as enzymatic raf serinekinase [...] constructive multiplication of the signal is transmitted to the downstream. These have the same mutational protein-guiding pharmacotherapy cell proliferation (Magnuson et al. Semin. Cencer Biol. 1994, 5,247-53). Due to the de-activation of the raf serinekinase raf serinekinase autoantibody administered by inhibiting signal path, or a negative or raf serinekinase raf immunodominant ~~~ immunodominant MEK serinekinase's substrate by expression of simultaneous activation of the negative effect of inhibiting the ras, representing the normal growth-transformed cells is shown leading to the reverse (Daum et al. Trenss Biochem. Sci. 1994, 19,474-80; Fridman et al. J. Biol. Chem. 1994,269, 30105-8 view). Kolch et al. A further (Nature 1991,349,426-28), by inhibiting the development of RNA raf sense antipass oncogene cytostatic related to block in which it is shown. Similarly, the inhibition of serinekinase raf (by fibrogenesis), various human tumor type in vivo and in vitro in inhibition of the propagation of the correlation (Monia et al. Nat. Med. 1996, 2,668-75). 0003 : [Outline of present invention] The present invention serinekinase ~~~ compd. raf enzyme. The enzyme p21^ras since the effector downstream of, for example, this inhibitor oncocyte raf serinekinase mediated and/or raf cytostatic hepatoma serinekinase path as in the treatment of human and animal is indicated for useful in chemical composition. In the particular example these human or animal compd. hepatoma raticidal hepatoma useful for the treatment of solid. Because these pharmacotherapy progress of the cascade transformant signal depending on ras protein, therefore this cascade through the interrupted, that is sensitive to raf serinekinase by inhibition of treatment. Therefore, the compound of the present invention, for example hepatoma retinoblastoma (for example, a pulmonary, biohybrid, Parathyroidal, Cystitis or colonal of), or adenoma osteomyelodysplasia abnormality (e.g. myelogenous leukemic) (for example, adenoma colonal microvillus-like) including a solid hepatoma hepatoma. 0004 : The present invention therefore, inhibiting raf serinekinase route, aryl and aryl containing urea and generally analog heteroaryloxazolidinone compd. described. The present invention, and in human periodontosis mammalia raf intermediary for treating condition. The present invention for inhibiting the leather compd. serinekinase raf enzyme, raf serinekinase hepatoma mediated by the growth of the cell for treating compound, composition and method directed to, in this case the formula I or compd. pharmaceutically acceptable salts thereof can be administered. 0005 : A-D-B (I) 0006 : In the formula I, The D-NH-C (O)-NH-and; The A--L-(M-L¹)_q substd. min. to carbon atoms 40 which, in this case, the direct coupling D L to 5 or 6 membered ring structure, L¹ substd. of at least 5 includes a circular base, at least 1 atom M having a base and a bridge, q is an integer of 1-3, L and then L¹ annular structure of the nitrogen, oxygen and sulfur containing 0-4 selected from the group consisting of an operator; The B or substituted aryl or until ticyclic unsubstd., or nitrogen, oxygen and sulfur containing 0-4 D operator selected from the group consisting of at least 6-membered ring structure directly to a carbon atom having 30 to the heteroaryl group; Here L¹ the-SO₂ R_x, -C (O) R_x and-C (NR_y) R_z is selected from the group consisting of substituted by at least one, and; R_y whether the hydrogen, or optionally N, S and O contains a hetero atom selected from until halopurine pefuse optionally substituted by a halogen group to carbon-carbon atom 24 ; R_z whether the hydrogen, or optionally a halogen, hydroxy, and optionally N, S and O contains a hetero atom selected from until halopurine pefuse optionally substituted with halogen to carbon-carbon atom 24 substituted substd. optionally N, S and O containing hetero-atom selected from a carbon atom 30 to carbon-based group; R_x the R_z whether, or NR_a R_b and, in this case R_a and R_b comprises, A) independently, or hydrogen, or optionally a halogen, hydroxy, and optionally N, S and O contains a hetero atom selected from halogen or optionally-OSi (R_f)₃ substituted to carbon-carbon atom 24 substituted substd. optionally N, S and O containing hetero-atom selected from a carbon atom 30 to carbon-based group, here R_f whether the hydrogen, or optionally a halogen, hydroxy and optionally N, S and O contains a hetero atom selected from optionally substituted with halogen to carbon-carbon atom 24 substituted substd. optionally N, S and O containing hetero-atom selected from a carbon atom 24 to carbon-based group, or b) R_a and R_b is transported by N, S and O of the hetero atom 1-3 selected from 5 to 7-membered heterocyclic ring formed, or halogen, hydroxy or optionally N, S and O contains a hetero atom selected from optionally substituted with halogen to carbon-carbon atom 24 substd. substituted N, S and O are selected from a hetero atom 1-3 substd. 5 to 7-membered heterocyclic ring formed of, or c) R_a or R_b 5 of at least one of the annular structure coupled to the base so as to form an L-C (O)-, C_1-5 2 divalent alkylene or substd. C_1-5 2 the divalent alkylene, substd. C_1-5 2 divalent alkylene substituents of halogen, hydroxy and optionally N, S and O contains a hetero atom selected from optionally substituted with halogen to carbon-carbon atom 24 substituent groups selected from the group consisting of; When B is substituted, or substituted or L L¹ is replaced by additional, the substituent is a halogen and until halopurine pefuse W_n (n the 0-3) is selected from the group consisting of, In this case intended for the independent W-CN, -CO₂ R⁷, -C (O) NR⁷ R⁷, -C (O) R⁷, -NO₂, -OR⁷, -SR⁷, -NR⁷ R⁷, -NR⁷ C (O) OR⁷, -NR⁷ C (O) R⁷, -Q-Ar, and optionally N, S and O contains a hetero atom selected from the-CN, -CO₂ R⁷, -C (O) R⁷, -C (O) NR⁷ R⁷, -OR⁷, -SR⁷, -NR⁷ R⁷, -NO₂, -NR⁷ C (O) R⁷, -NR⁷ C (O) O R⁷ pefuse halopurine and selected from the group consisting of halogen substituent of 1 or more carbon atoms 24 optionally substituted to carbon-based substrate is selected from the group consisting of independent, here each R⁷ is H or optionally N, S and O contains a hetero atom selected from optionally substituted with halogen to carbon-carbon atom 24 are independently selected from the group, Here, the Q-O-, -S-, -N (R⁷)-, -(CH₂)_m-, -C (O)-, -CH (OH)-, -(CH₂)_m O-, -(CH₂)_m S-, -(CH₂)_m N (R⁷)-, -O (CH₂)_m-, CHX^a-, -CX^a₂-, -S (CH₂)_m-, or-N (R⁷) ((CH₂)_m-and (1-3 and m the X^a is a halogen); then The nitrogen Ar, is selected from the group consisting of oxygen and sulfur containing hetero atom 0-2, optionally substituted with halogen pefuse until halopurine, optionally Z_n1 5 or 6-membered aromatic rings are substituted by the structure, n1 is 0 to 3, and in this case, the respective Z-CN, -CO₂ R⁷, -C (O) R⁷, -C (O) NR⁷ R⁷, -NO₂, -OR⁷, -SR⁷, -NR⁷ R⁷, -NR⁷ C (O) OR⁷, -NR⁷ C (O) R⁷ and optionally N, S and O contains a hetero atom selected from the arbitrarily-CN, -CO₂ R⁷, -C (O) R⁷, -C (O) NR⁷ R⁷, -OR⁷, -SR⁷, -NO₂, -NR⁷ R⁷, -NR⁷ C (O) R⁷ and-NR⁷ C (O) OR⁷ 1 or more selected from a group consisting of a carbon atom 24 substituted to carbon-based substrate is selected from the group consisting of independent, R⁷ above relationships. 0007 : In the formula I, is not suitable for limiting the heteroaryl group, a monocyclic 1-3 or aromatic ring containing a carbon atom 5-12 contg. ring system, in which an aromatic ring in at least one of the rings, one or more of the ring carbon atoms, for example less than 1 1-4 in oxygen, nitrogen or sulfur atoms are substituted b Each ring is typically 3-7 atom. For example, 2-or 3-B the Tetrahydrofurylcarbonyl, 2-or 3-tienyl, 2-or 4-triazinylurea, 1-, 2-or 3-pyrroyl, 1-, 2-, 4-or 5-imidazolylmethyl, 1-, 3-, 4-or 5-gyrazolyl, 2-, 4-or 5-oxazolile, 3-, 4-or 5-isoxazolyl, 2-, 4-or 5-Thiazoryl, 3-, 4-or 5-Isothiazolylbenzoxazine, 2-, 3-or 4-pyridyl, 2-, 4-, 5-or 6-Pirimidinyl, 1, 2, 3-triazole-1-, -4-or-5-yl, 1, 2, 4-triazole-1-, -3-or-5-yl, 5-bistetrazolyl, 1, 2, 3-Oxadiazol-4-or-5-yl, 1, 2, 4-Oxadiazol-3-5-ylacetic even the comb-, 1, 3, 4-thiadiazol-2-or-5-yl, 1, 2, 4, -thiadizole-3-or-5-yl, 1, 2, 3-thiadiazole-4-or-5-yl, 2-, 3-, 4-, 5-or 6-2H [...] -, 2-, 3-or 4-4H [...] -, 3-or 4-pyridazinyl, Heptanepyrazinyl, 2-, 3-, 4-, 5-, 6-or 7-Benzofranyl, 2-, 3-, 4-, 5-, 6-or 7- [...] , 1-, 2-, 3-, 4-, 5-, 6-or 7-indolylpiperidine, 1-, 2-, 4-or 5-dihydrobenzo imidazolylmethyl, 1-, 3-, 4-, 5-, 6-or 7-dihydrobenzo Pyrazolylacetic, 2-, 4-, 5-, 6-or 7-dihydrobenzo oxazolile, 3-, 4-, 5-, 6-or 7-dihydrobenzo isoxazolyl, 1-, 3-, 4-, 5-, 6-or 7-benzothiazolyloxazolidinone, 2-, 4-, 5-, 6-or 7-benzoisothiazolyl, 2-, 4-, 5-, 6-or 7-benzisothiazoles -1, 3-oxadiazolyl, 2-, 3-, 4-, 5-, 6-, 7-or 8-Quinolynylmethoxy, 1-, 3-, 4-, 5-, 6-, 7-or 8-isoquinolinyl, 1-, 2-, 3-, 4-or 9-carbosorylethyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, -8 or 9-acridinyl, or 2-, 4-, 5-, 6-, 7-or 8-quinazolinyl, additionally or optionally substituted phenyl, 2-or 3-tienyl, 1, 3, 4-thiazolylacetic, 3-pyrroyl, 3-gyrazolyl, or 5-2-thiazolylpyrrole Aminothiazolyl, or the l For example, the 4-dimethylpolysiloxaness B, 5-methyl-2-tienyl, 4-methyl-2-tienyl, 1-methyl-3-pyrroyl, 1-methyl-3-gyrazolyl, 5-methyl-2-thiazolylpyrrole can or 5-methyl -1, 2, 4-thiadiazole-2-yl. 0008 : As a whole, for example through a suitable substrate such as alkyl and alkoxy alkyl groups of all the straight-chain and a part hydroxyisopropyl, isobutyl, sec-butyl, tert-butyl photoisomerization branch including such as methyl, ethyl, propyl, butyl and the l 0009 : Suitable hetero atoms, for example the aryl group include phenyl, 1-and 2-naphthylacetic. 0010 : Here, the term "cycloalkylurea" is used having an alkyl substituent which does not have the meaning the annular structure, for instance C₄ cycloalkylurea fluorocyclopropyl groups are methyl and butyl group cyclometallized substd.. The term "cycloalkylurea" used herein includes an unsaturated heterocyclic group. 0011 : A suitable halogen group F, Cl, Br and/or I includes, from substd. pefuse 1 (that is, the base of which is substituted with a halogen atom H) is substituted by an alkyl group is a halogen capable when, based on the given type of mixing substd. halogen atom. 0012 : The present invention related to the compound of formula I in itself. The present invention of the compound of formula I pharmaceutically acceptable salts. The suitable pharmaceutically acceptable salts are well known to the skilled person, the hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methane sulfonic acid, trifluoromethane sulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, 1-naphthalenedicarboxylic acid, 2-naphthalene sulfonic acid, acetic acid, trifluoroacetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenyl acetic acid, and an inorganic acid, an organic acid such as mandellic and including a basic salt. In addition the pharmaceutically acceptable salts of alkali cation (e.g. Li⁺, Na⁺ or K⁺), alkaline earth metal cation (e.g. mg⁺², Ca⁺² or Ba⁺²), includes ammonium cation of basic and acid salt, an inorganic salt, the aliphatic and aromatic-substituted ammonium, and triethylamine, N, N-diethyl amine, N, N-dicyclohexyl amine, glabridin, pyridine, N, N-dimethyl amino pyridine (DMAP), 1, 4-diazabicyclo " 2. 2. 2 "Octane (DABCO), 1, 5-diazabicyclo" 4. 3. 0 "tricyclononene -5 (DBN) and 1, 8-diazabicyclo" 5. 4. 0" made of urethane or de-7-sensor (DBU) from protophilic peralkyl includes ammonium cation-containing organic bases. 0013 : Many of the compound of formula I has an asymmetric carbon atoms, and optically active racemizing therefore present in shape. The method of separating and neurotransmitter diastereomer mixture is well known to the skilled person. The present invention has an effect of inhibiting the compound of formula I isolated racemizing enclosing or optically active. 0014 : general preparation method The compound of formula I, there are known on the market and operation from starting materials prepared by using a chemical reaction. Nevertheless, those skilled in order to help synthesizable compd. prepd. generally b More detailed embodiment of the following experiments. 0015 : By using the standard method bisaniline substd. can be generated (March, Advanced Organic Chemistry 3rd Ed, John Willy, New York (1985); Larock, Comprehensive Organic Transformations; VCH Publishers, New York (1985)). As shown in the scheme 1, Ni hydroxytriarylamine in common, and a metal catalyst such as Pd or Pt H₂ is used, or fluoroformate, or borohydride Methylcyclohexa diene such as by using a hydrogen transfer agent synthesized by reduction of nitroarylated (Rylander, Hydrogenation Methods; Academic Press, London, UK (1985)). The nitroarylated LiAlH₄ using a strong hydrogen source such as a (Syden-Penne, Reduction by the Alumino-and Borohydrides in Organic Synthesis; VCH Publishers; New York (1991)), or Fe shapeoften acidic medium, such as using a dry air supplying device Sn or Ca (March, Advansed Organic Chemistry 3rd Ed; John Wiley, New York (1985); Larock, Comprehensive Organic Transformations; VCH Publishers; New York (1989)), can also be directly reduced. 0016 : [And 1] 0017 : I scheme. The reduction of nitroarylated hydroxytriarylamine Common nitroarylated HNO₃ instead of or NO₂⁺ electrophilic aromatic using a source produced by nitroalcohol. Before the reducing nitroarylated hand can be added. Therefore the nitroarylated, 0018 : [And 2] 0019 : By substituting, desorption that are possible (for example F, Cl, Br, etc.) based alkylthiolate (scheme illustrated in II) or the like in the processing of nucleophilic reagent [...] substd. reaction can be received. The type of coupling nitroarylated Ullmann reaction (II scheme) can be received. 0020 : [And 3] 0021 : II scheme. The selected use nitroarylated nucleophobic arom. substd. The transition metal intermediary nitroarylated can receive the cross coupling reaction. For example, camphorsulfonate nitroarylated, [...] reagent or the like trifurate nuclephilic nitroarylated, arylboronic acid (Suzuki reaction, illustrated below), zinc or tin (still reaction) aryl, aryl, aryl (negisi reaction) and tested as subjected to reaction nuclephilic palladium intermediary cloth, biaryl (5). 0022 : [And 4] 0023 : To obtain resorcinarene sulfonyl chloride (7) has a corresponding processing at either of polyanilin or nitroarylated chlorosulfonic acid. A source of fluoride and KF sulfonyl chloride as the reaction fluorosulfonyl sulfonylfluoride (8). (8) a source of fluoride fluorosulfonyl difluorobromoacetyl presence of trisphenols dimethylsulfonium difluorostilbene trimethylcyclo siliconate ([...]) (FASF) of the corresponding reaction [...] triphloro methyl sulfone (9) leading t Instead, for example, zinc amalgam sulfonyl chloride (7) being returned by resorcinarene Thiolcarboxylic (10). (10) the presence of a base CHClF₂ thiolcarboxylic difluorostilbene methyl mercaptan (11) is given, this CrO₃ acetic anhydride (Sedova et al. Zh. Org. Khim. 1970, 6,568) of an arbitrary kind including an oxidizing agent in the oxidizing to polysulfone (12). 0024 : [And 5] 0025 : III scheme. A method of selecting a synthetic fluorinated aryl sulfone As shown in the scheme IV, asymmetrical [...] hydroxytriarylamine (13) (14) and the urea generating reaction can be included. The [...] , phosgene, or trichloromethylpyrimidine Chloropyridin fluoroformate (diphosgene), bis (trichloromethyl) carbonate (triarylboron phosgene), or N, N '-diimidazole (CDI) by processing such as phosgene Heteroarylnaphthalene equivalent can be synthesized from amine. The isocyanate, ester, acid or anhydride heterorings sulfonylhalides carboxyl acid derivatives such as [...] dislocation. In this way, the acid derivative (16) and subsequently the hideout source of the reaction of the isocyanate dislocation. The corresponding carboxylic acid (17) or similar [...] (OPPA) [...] of reagent used can also be applied to dislocation. 0026 : [And 6] 0027 : IV scheme. The selected method of generating asymmetric urea Finally, the urea is well known to the skilled person, the method which can be used for further processing. 0028 : The present invention, and the compound of formula I Electrophysiologic acceptable carrier includes a chemical composition. 0029 : The compound, peroral, local, non-peroral, suction or by spraying, a dosing unit can effectively Transvaginal preparation, or through the Sublingually proctocele manner. The administration by injection, intravenous, intramuscular, subcutaneous injection and non-Peroral, and including the use of injection technique. One or more compound and one or more pharmaceutically acceptable carrier and if desired and if the other active component can exist in combination. 0030 : The composition used is intended peroral, chemical composition for the manufacture of a suitable known who can be prepared according to the method. Such a composition comprises diluting agent, sweetener, flavor, and reuteri coloring agent is selected from the group consisting of one or more of a pharmaceutical agent in order to prepare a takable can be included. The tablet, the tablet which is suitable for the production of non-toxic pharmaceutically acceptable auxiliary agent containing the active component in the mixture. These auxiliary agent, such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or inert diluent such as sodium phosphate; and for example as alginate degranulation exoenzyme or disintegrating agent; and for example magnesium stearate, talc, stearic acid or the like can be used as a binder. Whether the non-coated tablets, and absorption in the collapsed or delaying gaster Enterically thereof, thereby to provide a lasting action for a long period of time can be covered by a known technique. As an example, glyceryl monostearate glyeryl distearate or time delay material can be used. These compounds are prepared in the form of solid rapid release. 0031 : Use of a preparation for Peroral, hardened gelatin capsule and inert diluent as an individual component, for example a mixture of calcium carbonate, calcium phosphate or kaolin, can provide a soft gelatin capsule or active ingredient is water or oil as the medium, for example oil siruko, or paraffin and soujutsu mixed flow. 0032 : Suitable for the production of an aqueous suspension of auxiliary agent in a mixture of an aqueous suspension containing the active components can be used. The suspending agent, such an auxiliary agent, for example, sodium carboxymethyl cellulose, methyl cellulose, hydroxy trifluoropropylmethylsiloxane cellulose, sodium alginate, polyvinyl pyrrolidone, gum tragacanth, gum acacia and, dispersed [...] natural or wetting agent, for example Lecithinized, long chain aliphatic alcohol or ethylene oxide condensate, e.g. perfluoroethylenoxy cetanol unreactants, polyoxyethylene sorbitol monooleate or a fatty acid and a partial ester obtained from a hexitol of the condensation product of ethylene oxide, or a partial ester and fatty acids obtained from a hexitol anhydride, for example the condensation product of ethylene oxide, polyoxyethylene sorbitan monooleate. One or more of the aqueous suspension reuteri, or n-propyl p-hydroxy benzoic acid, for example ethyl; one or more coloring agent; one or more flavors, and one or more of such as sucrose thiophenesaccharin sweetener can be included. 0033 : By addition of water is suitable for the preparation of an aqueous suspension and the dispersed powder degranulation, dispersion or wetting agent, and one or more suspension reuteri active component of the mixture. A suitable wetting agent and dispersing agent or dispersed by the already mentioned above are exemplary. Additional auxiliary agent, for example, sweetening agents, flavoring agent and a coloring agent can be present. 0034 : The shape of the non-aqueous liquid pharmaceutical compound, for example, an active component is a vegetable oil, for example [...] oil, peanut oil or soujutsu, mineral or dispersed in a liquid such as paraffin formulable by can be in the form of oil suspension. Oil suspension the thickening agent, for example, beeswax, paraffin or contg. cetyl alcohol hardness. In order to obtain takable peroral preparation, and the like can be applied for a flavoring agent. These compsn. by the addition of an antioxidant such as ascorbic acid can be preserved. 0035 : The chemical composition of the present invention in the form of an oil-in-water emulsion. The oil phase [...] oil or vegetable oil such as olive oil, or liquid, for example paraffin mineral oil, or a mixture of these. For example, gum acacia gum emulsifier is suitable for natural or gum tragacanth, natural example soybean Lecithinized [...] , and fatty acid or ester and derived from a hexitol anhydride partial esters such as sorbitan monooleate, and the condensation product of ethylene oxide, for example, an ester of the polyoxyethylene sorbitan monooleate. The emulsion sweetener can include and flavor. 0036 : For example, the syrup and [...][...] sweetening agents, propylene glycol, or sucrose tartaricum prescription. The reducing agent in the formulation, reuteri, flavoring agent and a coloring agent can be incorporated. 0037 : For dosage of medicine compd. proctocele phenylpyrazole agent can also be in the form o These compositions, however, is a solid at ordinary temperature and the liquids or proctocele vaginosis, then proctocele vaginosis drug or melting it in a proper non-irritating and auxiliary agent can be prepared by mixing. Such a material is polyethylene glycol and cocoa butter. 0038 : Because of the use of all pharmacotherapy here described is of a compound of formula I, preferably of the 0 pharmacotherapy Peroral per 1. All 01 to 200 mg/kg body weight. Intravenous, intramuscular, subcutaneous injection and non-Peroral, including the use of injection and injection technique for administration per dose is 1, preferably 0. All 01 to 200 mg/kg body weight. 1 0 is preferably per pharmacotherapy proctocele administration. All 01 to 200 mg/kg body weight. 1 1 to 4 per day for topical administration is doser pharmacotherapy is preferably 0. 1 to 200 mg. 1 0 is preferably sucked per pharmacotherapy administration. All 01 to 10 mg/kg body weight. 0039 : The skilled person, the specific method for dosing depends on various factors, that all the treatment is administered daily when it is considered that will be recognized. However, given a specific dose level to a patient, the specific activity of the compound administered, the age of the patient, the weight of the patient, the general health of the patient, the patient's sexuality, alimentary, dosing time, administration routes, excrement speed, drug combination, and medical symptoms including a critical degree, depending on a variety of factors which will be understood. Furthermore, the skilled person, the number of daily dosage of the salt or a pharmaceutically acceptable compd. about days of therapeutic course I type, in other words a limited optimum treatment mode and will be recognized by those who can retain the use of a test course idioms treatment. 0040 : However, for a particular patient dose level is specified, a specific activity of the compound is employed, age, weight, general health status, sexuality, meal, dosing time, administration routes, excrement speed, drug formulation, and severity of disease treatment depend on various factors including the will be understood. 0041 : 13 January 1999 inventor on a temporary application No. A non-provisional application No 60/115,877 and 25 February 1999 in application. 09/257,266 less than and including all of the cited patent application, and the entire disclosure of patent publication referred to here as a constant. 0042 : Type I from the compound of the known compound (or known from starting materials capable of producing compd.) preparing a general example on can be manufactured through the method. Inhibiting serinekinase raf the activity of a given compound, for example daily assay according to the operation disclosed b For the purpose of illustration and example only, and is not intended to limit the present invention may also be so, that the same must not be loosened. 0043 : The reaction is carried out in all of the flame in the oven drying or drying the glass fixture under a positive pressure of dry nitrogen or dry argon, note the stirred magnetically is not possible. The sensitive liquid and is transferred by a syringe or cannulization soln., then through the rubber plug is introduced into the reaction vessel. Unless special note, the term "concentrated under reduced pressure" of about 15mmHg rotary evaporator Buchi in use. Note as 0 and the "high vacuum". 4-1. 0mmHg chloronicotinamide. 0044 : All of the reported temperature of C. (°C) is not corrected. Unless SI, and the weight percent of all parts. 0045 : Reagent grade and solvent is used commercially for further purification. N-cyclohexyl-N '-the carbodiimide Calbiochem-Novabiochem Corp (methyl polystyrene). Purchased f 3-t-butylanilines, methoxyaniline 5-t-butyl-2-, 4-bromo-3-(trifluoromethyl) aniline, 4-t-butyl-2-nitro aniline, 3-amino-2-naphthol, ethyl 4-isocyanatophenyl Dihydroxybenzoate, N-acetyl-4-chloro-2-methoxy-5-(trifluoromethyl) 4-chloro-3-bisaniline and phenyl isocyanate (trifluoromethyl) by the purchaser, without further purification. 3-amino-2-methoxy Quinolin synthetic (E. Cho et al. WO98/00402; A. Cordi et al. EP542,609; IBID Bioorg. Med. Chem. 3, 1995, 129), 4-(3-aminophenoxy carbamoylalkanoic)-1-nitrobenzenesulfonamide (K. Ikawa, magazine pharmaeutically 79, 1950, 760; Chem. Abstr. 53, 1959, 12761b), 3-t- [...] (O. Rohr et al. , DE2,436,108) and 2-methoxy-5-(trifluoromethyl) phenyl isocyanate (K. Inukai et al. , JP42025067, IBID industrial magazine 70, 1967, 491) described b 0046 : The thin layer chromatography (TLC) 250 µm pre- coat glass back silica gel Whatman 60A F-254 implementation of plate is used. Visualization of the plate is carried out by one or more of the following techniques. (A) ultraviolet irradiation, (b) iodine vapor exposed to, (c) ethanol dephosphorizing moribdenum in 10% and then immersed in a solution of a heating plate, (d) cerium sulfate soln. plate during the immersion heating and subsequently, (e) 2, 4-dinitrophenylhydrazine immersed in solution of ethanol and subsequently heating the plate. The silica gel column chromatography (flash chromatography) EM 230-400 mesh is performed using a science. 0047 : The melting point (mp), automatic melting or Mettler FP66 Thomas-Hoover melting device is decided by using a device, which is not corrected. The Fourier transform infrared spectrum Mattson 4020 Galaxy series obtained by using a spectrophotometer. The protophilic (¹ H) nuclear magnetic resonance (NMR) spectrum, General Electric GN-Microfloral 300 (300MHz) spectrometer, as standard Me₄ Si (δ0. 00) or solvent protophilic (CHCl₃ δ 7. 26 ; MeOH δ3. 30 ; DMSO δ2. 49) is measured. Carbon (¹³ C) NMR spectrum and General Electric GN-Microfloral 300 (75MHz) spectrometer, as a standard solvent (CDCl₃ δ 77. 0 ; MeOD-d₃; δ49. 0 ; DMSO-d₆ δ 39. 5) is measured. Low resolution mass spectrum (MS) and the high resolution mass spectrum (HRMS), electron impact (EI) as a mass spectrum, or impact speed atoms (FAB) obtained as the mass spectrum. The sample introduction of electron impact mass spectrum (EI-MS) Vacumetric desorption chemical ionization probe for a fuse provided with knurling-packard 5989A mass spectrum obtained by the thermometer. The ion source is maintained at 250 °C. The electronic energy 70eV and electron impact ionization current trap 300 μ A is executed. Liquid cesium secondary ion mass spectrum (FAB-MS) that the impact speed of the latest type nuclear Kratos Concept 1-H spectrum obtained by using the flowmeter. As the reagent gas chemical ionization mass spectrum (CI-MS) (1×10^-4 100torr to 2. 5×10^-4 100torr) or methane and ammonia is used, hewlett-packard MS-engine (5989A) obtained by using. Direct insertion desorption chemical ionization (DCI) probe (Vacumetrics, Inc. ) Rising up from the 0-15A sec. at 10, all traces of sample to a (-1-2 min) 10A. The spectrum from the scanning 50-800amu 2 sec/in. The mass spectrum electrospray HPLC (HPLC ES-MS), obtained by using a fuse provided with knurling-packard 1100HPLC Finnigan LCQ quat. ion-trap mass spectrum having a pump, a variable wavelength detector, C-18 column, and electrospray ionization. The spectrum of ion source by using a time variable according to the number of ions from the scanning 120-800amu. The gas chromatography/mass spectrum of ion-selective (GC-MS), methyl silicone HP-1 column (0. A coating 33 mm; 25m×0. 2 mm) to a fuse provided with knurling-packard 5890 gas chromatograph, and selective detector hewlett-packard 5971 pts.mass obtained in (ionization energy 70eV). The analysis of the Robertson Microlit Labs. Madison NJ is implemented. 0048 : All of the compound, and structure belonging to the NMR spectrum coincides, or HRMS LRMS and a display element. 0049 : code list of AcOH acetate Anh anhyride BOC t butoxycarboxylic calbonyl CDI 1, 1' diimidazole- Conc concn. D day Dec decomposition DMAC N, N-dimethylacetamide DMPU 1, 3-dimethyl -3, 4, 5, 6-tetrahydropyrimidine-Z (1H) pyrimidinecarboxylic DMF dimethyl formamide Dimethyl sulfoxide DMSO [...] DPPA EDCI 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide EtOAc ethyl acetate EtOH ethanol (100%) Et₂ O diethyl ether Et₃ N triethylamineborane When h Epoxytriazole hydroxybenzo HOBT 1- Chloroperoxy benzoic acid m-CPBA 3- MeOH methanol Pet. Ether petroleum ether (boiling range 30-60°C) Temp temp. Hydroxytetrahydrofuran THF TFA trifluorolactic AcOH Tf trifluoromethanesulfonyl 0050 : A. The general method of polyanilin substd.. A1. Ester formation then saponificate ester, and via a dislocation vinylcarbamate [...] hydroxytriarylamine protection for the generation of a generic method. 2-amino-3-methoxy naphthalene synthetic. 0051 : [And 7] 0052 : Step 1 ; 3-methoxy-2-naphthoic acid methyl DMF in 3-hydroxynaphthoic acid methyl (10. 1g, 50. 1mmol) and K₂ CO₃ (7. 96g, 57. 6mmol) at room temperature for 15 minutes stirring a slurry, then iodofluoroalkyl methane (3. 43 ml, 55. 1mmol) in processing. At room temperature overnight stirring a mixture, is treated with a water (200 ml). The mixture is extracted in EtOAc (2×200ml), an organic layer synoecism unsatd. NaCl solution (100 ml) in washing, drying (MgSO₄) and, under reduced pressure (about 0. 4mmHg overnight) is concentrated, as saw foil color oil 3-methoxy-2-naphthoic acid methyl (10. 30g) is obtained.¹ H-NMR (DMSO-d₆) δ2. 70 (s, 3H), 2. 85 (s, 3H), 7. 38 (app t, J=8. 09Hz, 1H), 7. 44 (s, 1H), 7. 53 (app t, J=8. 09Hz, 1H), 7. 84 (d, J=8. 09Hz, 1H), 7. 90 (s, 1H), 8. 21 (s, 1H) 0053 : [And 8] 0054 : Step 2 ; 3-methoxy-2-naphthoic acid MeOH (100 ml) in a 3-methoxy-2-naphthoic acid methyl (6. 28g, 29. 10mmol) and water (10 ml) 1N NaOH solution (33 of solution at room temperature. 4 ml, 33. 4mmol) in processing. The mixture is heated at reflux temperature 3, 10% citric acid solution. The solution is obtained by extracting EtOAc (2×100ml). Washing, drying (MgSO₄) synoecism org. layer is in a saturated saline, then a vacuum concentrator. Phenylbicyclohexane residue and kneading, washing Phenylbicyclohexane several times, as a white solid 3-methoxy-2-naphthoic acid (5. 40g, 92%)is obtained.¹ H-NMR (DMSO-d₆) δ3. 88 (s, 3H), 7. 34-7. 41 (m, 2H), 7. 49-7. 54 (m, 1H), 7. 83 (d, J=8. 09Hz, 1H), 7. 91 (d, J=8. 09Hz, 1H), 8. 19 (s, 1H), 12. 83 (br s, 1H) 0055 : [And 9] 0056 : Step 3 ; 2-(N-(carbobenzyloxy) amino-3-methoxy naphthalene In toluene anhyride (70 ml) 3-methoxy-2-naphthoic acid (3. 36g, 16. 6mmol) and Et₃ N (2. 59 ml, 18. 6mmol) and Et₃ N (2. 59 ml, 18. 6mmol) 15 minutes stirring of the solution at room temperature, then in toluene (10 ml) DPPA (5. 12g, 18. 6mmol) by using a solution of a pipette. The mixture is heated at 80 °C 2. After cooling the mixture to room, benzyl alcohol (2. 06 ml, 20mmol) using a syringe. The mixture is then heated to 80 °C overnight. The mixture is cooled to room temperature, adding 10% citric acid solution, is extracted in EtOAc (2×100ml). Washing, drying (MgSO₄) synoecism org. layer is in a saturated saline, a vacuum concentrator. The residue is refined by column chromatography (14% EtOAc/86% ethanol), corallite oil, 2-(N-carbobenzyloxy) amino-3-methoxy naphthalene (5. 1g, 100%)is obtained.¹ H-NMR (DMSO-d₆) δ3. 89 (s, 3H), 5. 17 (s, 2H), 7. 27-7. 44 (m, 8H), 7. 72-7. 75 (m, 2H), 8. 20 (s, 1H), 8. 76 (s, 1H) 0057 : [And 10] 0058 : Step 4 ; 2-amino-3-methoxy naphthalene EtOAc (70 ml) in 2-(N-(carbobenzyloxy) amino-3-methoxy naphthalene (5. 0g, 16. 3mmol) and Pd/C (0. 5g) slurry H₂ atmosphere maintained at room temperature overnight (balloon). The mixture is filtered through the sedum light, pink powder as the vacuum concentrator 2-amino-3-methoxy naphthalene (2. 40g, 85%)is obtained.¹ H-NMR (DMSO-d₆) δ3. 86 (s, 3H), 6. 85 (s, 2H), 7. 04-7. 16 (m, 2H), 7. 43 (d, J=8. 0Hz, 1H), 7. 56 (d, J=8. 0Hz, 1H); EI-MS m/z 173 "M⁺" A2. For generation of a next hydroxytriarylamine polypyridine carbamylmethylenephosphoric Supernucleophilic bisaniline diperfluoroalkylcarbamyl via coupling of ω. 4 (carbamylmethylenephosphoric 2-N-methyl-4-pyridyloxy) of polyanilin synthesis. 0059 : [And 11] 0060 : A step 1a; Menisci transestrification 4-chloro-N-methyl-2- [...] synthetic Caution: this is highly dangerous potentially explosive reaction. In a room of N-methyl formamide (250 ml) 4-Chloropyridine (10. 0g) of soln. stirring, concentrated sulfuric acid (3. 55 ml) is heated. To this mixture H₂ O₂ (H₂ O in 30% wt, 17 ml) then FeSO₄ · 7H₂ O is applied, by heating. The mixture is 1 hour stirring at room temperature in a dark place, then slowly heated to 45 °C 4 times are required. When the foam is [...] , 60 °C reaction product is heated at 16. An opaque brown soln. obtd. H₂ O (700 ml) 10% NaOH then obtained by diluting the solution. The mixture is extracted by the EtOAc (3×500ml). The organic phase (3×150ml) saturated saline wash, separately, by synoecism, drying (MgSO₄) by, the silica gel with aid of EtOAc filtered through the pad. A purification column chromatography (Phenylbicyclohexane 50% EtOAc/50% until the gradient from Phenylbicyclohexane 80% EtOAc/20%)obtained by a brown oil. The oil 0 °C obtd. yellow crystallized 72 at the time is required, 4-chloro-N-methyl-2- [...] (0. 61g, 5. 3%)is obtained. TLC (Phenylbicyclohexane 50% EtOAc/50%)Rf0. 50 ;¹ H-NMR (CDCl₃) δ3. 04 (d, J=5. 1Hz, 3H), 7. 43 (dd, J=5. 4, 2. 4Hz, 1H), 7. 96 (br s, 1H), 8. 21 (s, 1H), 8. 44 (d, J=5. 1Hz, 1H), CI-Ms m/z 173 "(M+H)⁺" 0061 : [And 12] 0062 : Step 1b; dipicolinic acid 4-chloropyridine-2-through the synthesis of HCl carbonylchloride Anhydrous DMF (6. 0 ml) between a 40-50 ° C SOCl₂ (180 ml) to added. In this temperature range of 10 minutes stirring soln., next dipicolinic acid (60. 0g, 487mmol) in addition to a little at 30 minutes. 72 °C solution is obtained by heating time (violently SO₂ generation) 16 and a yellow solid precipitation occurs. The mixture is cooled to room temperature, diluted with toluene (500 ml), 200 ml to concd.. This added toluene/2 times the concentration process. The dried residue is hardly obtained by filtration, washed with toluene (2×200ml) solid, drying time under high vacuum 4, yellow orange solid as 4-chloropyridine-2-carbonylchloride HCl salt (92. 0g, 89%)is obtained. 0063 : [And 13] 0064 : Step 2 ; 4-chloropyridine-2-carboxylic acid methyl synthesis of HCl Anhydrous DMF (10. 0 ml) between a 40-48 ° C SOCl₂ (300 ml) to added. In this temperature range of 10 minutes stirring soln., next to 30 minutes dipicolinic acid (100g, 812mmol) in b 72 °C solution is obtained by heating time (violently SO₂ generation) 16 and generated by a yellow solid. The mixture is cooled to room temperature, diluted with toluene (500 ml), 200 ml to concd.. Toluene added/2 times the concentration process. The dried residue is hardly obtained by filtration, washed with toluene (50 ml) solid, drying time under high vacuum 4, gray solid as 4-chloropyridine-2-carbonylchloride HCl salt (27. 2g, 16%)is obtained. This material is placed in another. 0065 : In addition the MeOH (200 ml) at a speed to maintain a temperature of 55 °C diphosgene to red. 45 minutes stirring the contents at ambient temperature, is cooled to 5° C, Et₂ O (200 ml) is dropped. A solid obtained by filtering, Et₂ O (200 ml) washing, drying under reduced pressure 35 °C, 4-chloro-2-carboxylic acid methyl HCl and a white solid (110g, 65%)is obtained. mp108-112°C;¹ H-NMR (CDSO-d₆) δ3. 88 (s, 3H), 7. 82 (dd, J=5. 5, 2. 2Hz, 1H), 8. 08 (d, J=2. 2Hz, 1H), 8. 68 (d, J=5. 5Hz, 1H), 10. 68 (br s, 1H), ; HPLC ES-MS m/z 178 "(M+H)⁺" 0066 : [And 14] 0067 : Step 3a; 4-chloro-2-pyridinesulfonic-2-carboxylic acid methyl 4-chloro-N-methyl-2- [...] synthetic In the 0 °C MeOH (75 ml) of 4-chloro-2-methyl pyridine carboxylic acid HCl salt (89. 0g, 428mmol) in THF (lL) 2 of the suspension. 0M 5 °C Biphenylmethylamine soln. processing speed is kept lower than the inside temperature. The mixture is stored at 3 °C 5 time, then a vacuum concentrator. The obtained solid suspended in EtOAc (1L), and a filter. The filtrate is washed with saturated (500 ml), dried (MgSO₄), as corallite by 4-chloro-N-methyl-2- [...] (71. 2g, 97%)is obtained. mp 41-43°C;¹ H-NMR (DMSO-d₆) δ2. 81 (s, 3H), 7. 74 (dd, J=5. 1, 2. 2Hz, 1H), 8. 00 (d, J=2. 2, 1H), 8. 61 (d, J=5. 1Hz, 1H), 8. 85 (brd, 1H); CI-MS m/z "(M+H)⁺" 0068 : [And 15] 0069 : Step 3b; 4-chloropyridine-2-carbonylchloride from 4-chloro-N-methyl-2- [...] synthetic 4-chloro-2-carbonylchloride HCl salt (7. 0g, 32. 95mmol) 2 in a slightly THF (100 ml). A mixed solution of 0 °C to 0M of Biphenylmethylamine soln. and MeOH (20 ml). 3 °C mixture obtained at time 4, then a vacuum concentrator. The obtained solid suspended in EtOAc (100 ml) almost dry, filtered. Washing, drying (MgSO₄) diphosgene is in a saturated NaCl solution (2×100ml), 4-chloro-N-methyl-3- [...] (4 as by yellow crystals. 95g, 88%)is obtained. Mp37-40 ° C 0070 : [And 16] 0071 : Step 4 ; 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) of polyanilin synthetic 4-amino phenol (9 in the DMF (150 ml) anhyride. 60g, 88. Soln. 0mmol) of potassium t-butoxide (10. 29g, 91. 7mmol) by processing, reddish brown mixture of 2 hours at room temperature with stirring. The content of 4-chloro-N-methyl-2- [...] (15. 0g, 87. 9mmol) and K₂ CO₃ (6. 50g, 47. 0mmol) by processing, by heating at 80 °C 8. By cooling the mixture to room temperature, saturated saline EtOAc (500 ml) and between the distributor (500 ml). The water phase is extracted by EtOAc. Washing, drying (MgSO₄) org. layer is in a saturated saline synoecism (4×1000ml), a vacuum concentrator. In the solid 3 obtained by drying under reduced pressure 35 °C, bright brown solid matter as 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) bisaniline is obtained.¹ H-NMR (DMSO-d₆) δ2. 77 (d, J=4. 8Hz, 3H), 5. 17 (br s, 2H), 6. 64, 6. 86 (quartet 'BB' AA, J=8. 4Hz, 4H), 7. 06 (dd, J=5. 5, 2. 5Hz, 1H), 7. 33 (d, J=2. 5Hz, 1H), 8. 44 (d, J=5. 5Hz, 1H), 8. 73 (br d, 1H); HPLC ES-MS m/z "(M+H)⁺" 0072 : A3. The general method of synthesizing bisaniline resorcinarene nitroalcohol Supernucleophilic arom. added subsequently by reduction. 5-(4-aminophenoxy) isoindolin -1, 3-dione synthesis. 0073 : [And 17] 0074 : Step 1 ; 5-hydroxy isoindolin -1, 3-dione synthetic In the ammonium carbonate (5 concd. AcOH (25 ml). 28g, 54. 9mmol) 4-hydroxy acid (5 to the mixture. 0g, 27. 45mmol) is slowly added. The mixture is heated at 120 °C 45 minutes, then a bright yellow transparent 160 °C 2 by heating in the mixture. The mixture is kept at 160 °C, about 15 ml concentrated, and then cooled to room temperature, to adjust the pH10 1N NaOH solution. This mixture is cooled to 0 °C, acidic pH5 1N HCl solution is used to slowly. The obtained precipitate collected by filtering, drying the powder as a product as corallite 5 bisisoindoline hydroxyacid -1, 3-dione (3. 24g, 72%)is obtained.¹ H-NMR (DMSO-d₆) δ7. 00-7. 03 (m, 2H), 7. 56 (d, J=9. 3Hz, 1H) 0075 : [And 18] 0076 : Step 2 ; 5-(4-nitrophenoxy) isoindolin -1, 3-dione synthetic In the DMF (40 ml) of NaH room (1. 1g, 44. 9mmol) under agitation of the slurry, in DMF (40 ml) 5-hydroxy isoindolin -1, 3-dione (3. 2g, 19. 6mmol) solution. Bright yellowish green mixture is returned to the room, 1 hour stirring, then 1-fluoro-4-nitrobenzenesulfonamide (2. 67g, 18. 7mmol) 3-4 divided by using a syringe. The mixture is heated at night 70 °C, then cooled to room temperature, water (150 ml) diluted slowly, by extracting EtOAc (2×100ml). Drying (MgSO₄) synoecism org. layer by a, 5-(4-nitrophenoxy) isoindolin -1, 3-dione (3 as by yellow solid. 3g, 62%)is obtained. TLC (Phenylbicyclohexane 30% EtOAc/70%)Rf0. 28 ;¹ H-NMR (DMSO-d₆) δ7. 32 (d, J=12Hz, 2H), 7. 52-7. 57 (m, 2H), 7. 89 (d, J=7. 8Hz, 1H), 8. 29 (d, J=9Hz, 2H), 11. 43 (br s, 1H); CI-MS m/z "(M+H)⁺, 100%" 0077 : [And 19] 0078 : Step 3 ; 5-(4-aminophenoxy) isoindolin 1, 3-dione synthetic Concd. AcOH (12 ml) and water (0. 1 ml) in a 5-(4-nitrophenoxy) isoindolin -1, 3-dione (0. 6g, 2. 11mmol) down stirring soln. of argon, between iron powder (0. 59g, 55. 9mmol) is slowly added. This mixture 72 time stirring at room temperature, then diluted with water (25 ml), extracting the EtOAc (3×50ml). The layer is dried (MgSO₄) org. synoecism by, as brown solid matter by 5-(4-aminophenoxy) isoindolin -1, 3-dione (0. 4g, 75%)is obtained. TLC (Phenylbicyclohexane 50% EtOAc/50%)Rf0z27;¹ H-NMR (DMSO-d₆) δ5. 14 (br s, 2H), 6. 62 (d, J=8. 7Hz, 2H), 6. 84 (d, J=8. 7Hz, 2H), 7. 03 (d, J=2. 1Hz, 1H), 7. 23 (dd, 1H), 7. 75 (d, J=8. 4Hz, 1H), 11. 02 (s, 1H); HPLC ES-MS m/z 255 "(M+H)⁺, 100%" 0079 : A4. The general method of synthesizing bisaniline Pyrrolylbenzimidazole. 5-t-butyl-2-(2, 5- dimethyl pyro rill) of polyanilin synthesis. 0080 : [And 20] 0081 : Step 1 ; 1-(4-t-butyl-2-nitrophenyl)-2, 5-dimethylpyrrole synthetic In Fluoroalkylcyclohexane (10 ml) 2-nitro-4-t-butylanilines (0. 5g, 2. 57mmol) using a syringe AcOH under stirring to a solution of (0. 1 ml) and acetonylbenzamide hydroxyacetone (0. 299g, 2. 63mmol) is added. While removing the heated 72 120 °C volatile content of the reaction mixture at a time. The reaction mixture is cooled to room temperature, CH₂ Cl₂ (10 ml) diluted, and saturated saline (15 ml) 1N HCl (15 ml), 1N NaOH solution (15 ml) successively washing, drying (MgSO₄) by, a vacuum concentrator. An orange-brown solid column chromatography (60gSiO₂; 67EtOAc/94% obtained from a gradient Phenylbicyclohexane Phenylbicyclohexane 25% EtOAc/75%)by purifying, yellow photogenesis solid as 1-(4-t-butyl-2-nitrophenyl)-2, 5-dimethylpyrrole (0. 34g, 49%)is obtained. TLC (Phenylbicyclohexane 15% EtOAc/85%)Rf0. 67 ;¹ H-NMR (CDCl₃) δ1. 34 (s, 9H), 1. 89 (s, 6H), 5. 84 (s, 2H), 7. 19-7. 24 (m, 1H), 7. 62 (dd, 1H), 7. 88 (d, J=2. 4Hz, 1H); CI-MS m/z 273 "(M+H)⁺, 50%" 0082 : [And 21] 0083 : Step 2 ; 5-t-butyl-2-(2, 5- dimethyl pyro rill) of polyanilin synthetic H₂ atmosphere under (balloon) 1-(4-t-butyl-2-nitrophenyl)-2, 5-dimethylpyrrole (0. 341g, 1. 25mmol) and, 10% Pd/C (0. 056g) and, a slurry of stirring EtOAc (50 ml) 72 hours, then filtered through the pad sedum light. The filtrate is concentrated under a reduced pressure, as yellow solid 5-t-butyl-2-(2, 5- dimethyl pyro rill) bisaniline (0. 30g, 99%)is obtained. TLC (Phenylbicyclohexane 10% EtOAc/90%)Rf0. 43 ;¹ H-NMR (DMSO-d₆) δ1. 28 (s, 9H), 1. 87-1. 91 (m, 8H), 5. 85 (br s, 2H), 6. 73-6. 96 (m, 3H), 7. 28 (br s, 1H) 0084 : A5. From anilirie arom. substd. nuclephilic anilirie of general synthetic method. 4-(2-N-carbamoylalkanoic)-4-pyridyloxy)-2-methylaniline hydrocloride synthesis. 0085 : [And 22] 0086 : In drying dimethylacetamide (75 ml) 4-amino-3-methyl phenol (5. 45g, 44. Soln. 25mmol) of potassium t-butoxide (10. 86g, 96. 77mmol) by processing, black mixture until a stirring flask is at room temperature. Then squeezes 4-chloro-N-methyl-2- [...] (method A2, step 3b; 7. 52g, 44. 2mmol) by processing, by heating at 110 °C 8. The mixture is cooled to room temperature, (75 ml) and diluted with water. The organic layer is extracted by the EtOAc (5×100ml). Washing, drying (MgSO₄) organic layer (200 ml) in a saturated saline soln., vacuum concentration. The black oil residues Et₂ O (50 ml) by processing, by the ultrasonic treatment. Next soln. HCl (Et₂ O in 1M, 100 ml) in, 5 minutes stirring at room temperature. The dark pink solid (7. 04g, 24. 1mmol) is filtered from the solution, in storage before use 0 °C under anaerobic conditions.¹ H-NMR (DMSO-d₆) δ2. 41 (s, 3H), 2. 78 (d, J=4. 4Hz, 3H), 4. 93 (br s, 2H), 7. 19 (dd, J=8. 5, 2. 6Hz, 1H), 7. 23 (dd, J=5. 5, 2. 6Hz, 1H), 7. 26 (d, J=2. 6Hz, 1H), 7. 55 (d, J=2. 6Hz, 1H), 7. 64 (d, J=8. 8Hz, 1H), 8. 55 (d, J=5. 9Hz, 1H), 8. 99 (q, J=4. 8Hz, 1H) 0087 : A6. Hydroxyaniline from N-protection, and by removing nucleophobic arom. substd. anilirie of general synthetic method. 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-2-chloroaniline synthesis. 0088 : [And 23] 0089 : Step 1 ; 3-chloro-4-(2, 2, 2-trifluoroacetylamino) phenol synthetic Iron (3. 24g, 58. 00mmol) applied while stirring the TFA (200 ml). To this slurry, 2-chloro-4-nitro phenol (10. 0g, 58. (20 ml) monofluoroacetate triarylboron anhyride 0mmol) and is added. 6 stirring at room temperature in this gray slurry. Iron is filtered from the solution, the remaining concd. reduced pressure. The gray solid dissolved in water (20 ml). The yellow obtd. unsatd. NaHCO₃ soln. (50 ml) is added to the solution. The removed solid precipitated from solution. As can be seen from the separation product soln. (determined by using mini- bi- Al) until a diphosgene NaHCO₃ soln.. A slightly yellow solution extracted by a rearers EtOAc (3×125ml). Washing, drying (MgSO₄) synoecism org. layer is in a saturated NaCl solution (125 ml), the vacuum concentration.¹ H-NMR nitro phenol and starting material, the product desired 3-chloro-4-(2, 2, 2-trifluoroacetylamino) indicates that a ratio of 1:1. Without further purification of the crude material is used in the next step. 0090 : [And 24] 0091 : Step 2 ; 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-2-(2, 2, 2-trifluoroethane) chlorophenylcarbamic acetoacetamide synthetic In drying dimethylacetamide (50 ml) meleimide 3-chloro-4-(2, 2, 2-trifluoroacetylamino) phenol (5. 62g, 23. Soln. 46mmol) of potassium t-butoxide (5. 16g, 45. 98mmol) by processing, themosensitive [...] color mixture to mixing at room temperature until the room temperature of the flask. The mixture is 4-chloro-N-methyl-2- [...] (method A2, step 3b; 1. 99g, 11. 7mmol) by processing, by heating at 100 °C under argon 4 days. The reaction mixture is cooled to room temperature of black, cold water is poured in to the next (100 ml). The mixture is extracted in EtOAc (3×75ml), decompression concd. synoecism org. layer. A brown oil residue [...] (20% EtOAc/petroleum ether 40% EtOAc/petroleum ether from a gradient) is purified by, yellow solid matter as 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-2-chloropheml-(2, 2, 2-trifluoroethane) acetaminde (8. 59g, 23. 0mmol) is obtained. 0092 : [And 25] 0093 : Step 3 ; 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-2-chloroaniline synthetic In drying 4-benzodioxane (20 ml) meleimide 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-2-chloropheml-(2, 2, 2- torr fluoro) acetaminde (8. 59g, 23. 0mmol) solution is treated with 1N NaOH solution (20 ml). 8 hours and this brown soln., EtOAc (40 ml) is added to the solution. The organic layer is extracted with green EtOAc (3×40ml), then the solvent is concentrated, is left as a green oil 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-2-chloroaniline (2. 86g, 10. 30mmol) is obtained.¹ H-NMR (DMSO-d₆) δ2. 77 (d, J=4. 8Hz, 3H), 5. 51 (s, 2H), 6. 60 (dd, J=8. 5, 2. 6Hz, 1H), 6. 76 (d, J=2. 6, 1H), 7. 03 (d, J=8. 5Hz, 1H), 7. 07 (dd, J=5. 5, 2. 6Hz, 1H), 7. 27 (d, J=2. 6Hz, 1H), 8. 46 (d, J=5. 5Hz, 1H), 8. 75 (q, J=4. 8Hz, 1H) 0094 : A7. Because of the general method of polyanilin acylation. 4-chloro-2-methoxy-5-(trifluoromethyl) of polyanilin synthesis. 0095 : [And 26] 0096 : In 6M HCl solution (24 ml) 3-chloro-6-(N-acetyl)-4-(trifluoromethyl) trifluoroanisole (4. 00g, 14. 95mmol) 1 heated to the reflux temperature. A solution is cooled to room temperature obtained, slightly solidified therebetween. The mixture is diluted with water (20 ml), until it becomes solid basic soln. unsatd. NaHCO₃ NaOH and treated with a mixture of a solution. The organic layer CH₂ Cl₂ (3×50ml) extracts, drying (MgSO₄) synoecism org. layer is, by, brown oil as 4-chloro-2-methoxy-5-(trifluoromethyl) bisaniline (3. 20g, 14. 2mmol) is obtained.¹ H-NMR (DMSO-d₆) δ3. 84 (s, 3H), 5. 30 (s, 2H), 7. 01 (s, 2H) A8. Ω ω--alkoxyphenol-carboxyphenyl bisaniline general synthesis method. 4-(3-(N-methyl carbamoylalkanoic)-4-methoxy phenoxycarboxylic) of polyanilin synthesis. 0097 : [And 27] 0098 : Step 1 ; 4-(3-methoxycarbonyl-4-methoxy phenoxycarboxylic)-1-nitrobenzenesulfonamide 4-(3-4-hydroxy phenoxycarboxylic)-1-nitrobenzenesulfonamide (method A13, step 1 in the specification of and similar embodiment 2, 5-dihydroxy benzoic acid production; 12mmol) soln. hydroxyacetone (50 ml) of K₂ CO₃ (5g) and dimethyl sulfate (3. 5 ml) is added. The mixture is heated to the reflux temperature at night, to cool the room, filtered through the pad sedum light. The solution obtained by subjecting a, SiO₂ absorbed, by purifying column chromatography (Phenylbicyclohexane 50% EtOAc/50%), yellow powder as 4-(3-methoxycarbonyl-4-methoxy phenoxycarboxylic)-1-nitrobenzenesulfonamide (3g) is obtained. Mp115-118 ° C 0099 : [And 28] 0100 : Step 2 ; 4-(3-4-methoxy phenoxycarboxylic)-1-nitrobenzenesulfonamide MeOH (45 ml) in 4-(3-methoxycarbonyl-4-methoxy phenoxycarboxylic)-1-nitrobenzenesulfonamide (1. 2g) and KOH (0. A mixture of water (5 ml) 33g) and stirred overnight at room temperature, then heated at reflux temperature 4. The mixture is cooled to room temperature, the vacuum concentration. The residue is dissolved in water (50 ml), and a mixture of an acidic aqueous 1N HCl solution. The mixture is extracted by the EtOAc (50 ml). The layer is dried (MgSO₄) org. is, by 4-(3-4-methoxy phenoxycarboxylic)-1-nitrobenzenesulfonamide (1. 04g) is obtained. 0101 : [And 29] 0102 : Step 3 ; 4-(3-(N-methyl carbamoylalkanoic)-4-methoxy phenoxycarboxylic)-1-nitrobenzenesulfonamide CH₂ Cl₂ (12 ml) in 4-(3-4-methoxy phenoxycarboxylic)-1-nitrobenzenesulfonamide (0. 50g, 1. 75mmol) soln. SOCl₂ (0. 64 ml, 8. 77mmol) adding little by little. 18 circulates the solution obtained by heating at a temperature, cooled to room temperature, the vacuum concentration. A yellow solid matter obtd. CH₂ Cl₂ (3 ml) dissolved, soln. obtd. Biphenylmethylamine soln. (THF in 2. 0M, 3. 5 ml, 7. 03mmol) and then gradually processing (caution: gas generator), a stirring at room temperature for 4 hours. The mixture obtained 1N NaOH soln., CH₂ Cl₂ (23 ml) extraction. The organic layer is dried, 4-(3-N-carbamoylalkanoic)-4-methoxy phenoxycarboxylic)-1-nitrobenzenesulfonamide (0 by reduced pressure drying as yellow solid. 50g, 95%)is obtained. 0103 : [And 30] 0104 : Step 4 ; 4-(3-(N-methyl carbamoylalkanoic)-4-methoxy phenoxycarboxylic) bisaniline EtOH (55 ml) of 4-(3-(N-methyl carbamoylalkanoic)-4-methoxy phenoxycarboxylic)-1-nitrobenzenesulfonamide (0. 78g, 2. 60mmol) and, 10% Pd/C (0. 20g) of slurry H₂ 1 (balloon) 2 under atmospheric pressure. 5 agitating, sedum light filtered through the pad. The resultant solution is concentrated under a reduced pressure, gray solid as 4-(3-(N-methyl carbamoylalkanoic)-4-methoxy phenoxycarboxylic) bisaniline (0. 68g, 96%)is obtained. TLC (0. 1% Et₃ N/99. 9% EtOAc) Rf0. 36 A9. Ω-alkyl contg. bisphthalimide bisaniline general synthetic method. 5-(4-aminophenoxy)-2-methyl isoindolin -1, 3-dione synthesis. 0105 : [And 31] Step 1 ; 5-(4-nitrophenoxy)-2-methyl isoindolin -1, 3-dione synthetic DMF (15 ml) in 5-(4-nitrophenoxy) isoindolin -1, 3-dione (A3 step 2 ; 1. 0g, 3. 52mmol) and NaH (0. 13g, 5. 27mmol) of the slurry is stirred at room temperature for 1 hour, gargal methylalkyl (0. 3 ml, 4. 57mmol) in processing. The mixture is stirred overnight at room temperature, is cooled to 0° C, is treated with water (10 ml). The solid is collected, vacuum drying, as bright yellow solid 5-(4-nitrophenoxy)-2-methyl isoindolin -1, 3-dione (0. 87g, 83%)is obtained. TLC (Phenylbicyclohexane 35% EtOAc/65%)Rf0. 61 0106 : [And 32] 0107 : Step 2 ; 5-(4-aminophenoxy)-2-methyl isoindolin -1, 3-dione synthetic MeOH nitro phenoxy-2-methyl isoindolin -1, 3-dione (0. 87g, 2. 78mmol) and 10% Pd/C (0. The slurry is stirred overnight 10g) of H₂ 1 under atmospheric pressure (balloon). The mixture is filtered through a pad of sedum, vacuum concentration. A yellow solid matter dissolved in EtOAc (3 ml) obtd., SiO₂ phnomenon of yellow solid matter is filtered through as (Phenylbicyclohexane 60% EtOAc/40%)5-(4-aminophenoxy)-2-methyl isoindolin -1, 3-dione (0. 67g, 86%)is obtained. TLC (Phenylbicyclohexane 40% EtOAc/60%)Rf0. 27 0108 : A10. Ω-alkoxycarboxylic calbonyl aryl amine transestrification a precursor ω-carbamoylarylurea anilirie general synthesis method. 4-(2-(N-(2-dimethylmorpholine-4-ylethyl) carbamoylalkanoic) pyridyloxy) of polyanilin synthesis. 0109 : [And 33] 0110 : Step 1 ; 4-chloro-2-(N-(2-dimethylmorpholine-4-ylethyl) carbamoylalkanoic) of synthetic polypyridine In THF (20 ml) 4-chloropyridine-2-carboxylic acid methyl HCl salt (method A2, step 2 ; 1. 01g, 4. Soln. 86mmol) (2-aminoethyl) dimethylmorpholine 4 (2. 55 ml, 19. 4mmol) is dropped, the solution obtained by heating the recirculating 20 at a time, by cooling to room temperature, is treated with water (50 ml). The mixture is extracted by the EtOAc (50 ml). The layer is dried (MgSO₄) org. is, by, a yellow oil as 4-chloro-2-(N-(2-dimethylmorpholine-4-ylethyl) polypyridine carbamoylalkanoic (1. 25g, 95%)is obtained. TLC (10% MeOH/90% EtOAc) Rf0. 50 0111 : [And 34] 0112 : Step 2 ; 4-(2-(N-2-dimethylmorpholine-4-ylethyl) carbamoylalkanoic) pin triatoma oxymeter) of polyanilin synthetic 4-amino phenol (0 in the DMF (8 ml). 49g, 4. Potassium t-butoxide (0 52mmol) a 53g, 4. 75mmol) 2 time stirring of the solution at room temperature, then the 4-chloro-2-(N-(2-dimethylmorpholine-4-ylethyl) carbamoylalkanoic) polypyridine (1. 22g, 4. 52mmol) and K₂ CO₃ (0. 31g, 2. 26mmol) sequentially. The mixture is heated overnight at 75 °C, cooled to room temperature, the separation between the EtOAc (25 ml) and saturated NaCl solution (25 ml). The water phase is extracted by EtOAc (25 ml), an organic layer synoecism wash unsatd. NaCl solution (3×25ml), a vacuum concentrator. Purification column chromatography (58g; 100% EtOAc 25% MeOH/75% EtOAc from a gradient) obtained by a brown solid matter, 4-(2-(N-dimethylmorpholine-4-ylethyl) carbamoylalkanoic) pyridyloxy) bisaniline (1. 0g, 65%)is obtained. TLC (10% MeOH/90% EtOAc) Rf0. 32 0113 : A11. A general method of reducing to hydroxytriarylamine resorcinarene nitroalcohol. 4-(3-aminophenoxy) of polyanilin synthesis. 0114 : [And 35] In the MeOH (120 ml) 4-(3-aminophenoxy)-1-nitrobenzenesulfonamide (5. 38g, 20. 7mmol) and 10% Pd/C (0. 50g) of the slurry is stirred H₂ atmosphere (balloon) 2 days. The mixture is filtered through a pad of sedum, by a 4-(3-aminophenoxy) bisaniline brown solid matter (2. 26g, 48%)obtained by a TLC (10% MeOH/90% CH₂ Cl₂) Rf0. 44 (stripes) 0115 : A12. The general method of polyanilin isoindolinone contg.. 4-(1-oxoisoindolines-5-carbonoyloxysilane) of polyanilin synthesis. 0116 : [And 36] 0117 : Step 1 ; 5-hydroxy isoindolin-1-one of synthetic 5-hydroxy tetrafluorophthalimide (19 in AcOH (500 ml). 8g, 121mmol) soln. zinc powder (47. 6g, 729mmol) separately and added slowly, then the mixture is heated at reflux temperature 40 minutes, when heated by filtration, the vacuum concentration. This reaction is repeated in the same scale, an oily residue synoecism column chromatography (1. 1 kg SiO₂; 60% EtOAc/40% 25% MeOH/75% EtOAc Phenylbicyclohexane from a gradient) is purified by, 5-hydroxy isoindolin-1-one (3. 77g) is obtained. TLC (100% EtOAc) Rf0. 17 ; HPLC ES-MS m/z "(M+H)⁺" 0118 : [And 37] 0119 : Step 2 ; 4-(1-isoindolin-5-carbonoyloxysilane)-1-nitrobenzenesulfonamide In DMF NaH (0. 39g, 16. 1mmol) to a slurry by 0 °C bisisoindoline 5-hydroxy-1-(2. 0g, 13. 4mmol) adding little by little. The obtained slurry is warmed to room temperature, the stirring to 45 minutes, then adding 4-fluoro-1-alkoxynitrobenzenes, 70 °C 3 at a heating time. The mixture is cooled to 0 °C, until the water is dripped precipitation is generated. The solid is collected, 4-(1-isoindolin-5-carbonoyloxysilane)-1-nitrobenzenesulfonamide (3 as dark yellow solid. 23g, 89%)is obtained. TLC (100% EtOAc) Rf0. 35 0120 : [And 38] 0121 : Step 3 ; 4-(1-oxoisoindolines-5-carbonoyloxysilane) bisaniline EtOH (50 ml) of 4-(1-isoindolino-5-carbonoyloxysilane)-1-(2. 12g, 7. 8mmol) and, 10% Pd/C (0. 20g) of the slurry is stirred H₂ atmosphere (balloon) 4, sedum light filtered through the pad. By filtering, 4-(1-oxoisoindolines-5-carbonoyloxysilane) obtained as a solid dark yellow polyaniline. TLC (100% EtOAc) Rf0. 15 0122 : A13. The general method of polyanilin resorcinarene nitroalcohol ω-carbamoylalkanoic EDCI reduction through intermediary amide produced subsequently. 4-(methyl carbamoylalkanoic Phenoxyalkanoic 3-N-) of polyanilin synthesis. 0123 : [And 39] 0124 : Step 1 ; 4-(3-aminophenoxy ethoxycarbonyl)-1-nitrobenzenesulfonamide synthetic In the DMF (125 ml) 4-fluoro-1-nitrobenzenesulfonamide (16 ml, 150mmol) and, 3-hydroxy benzoic acid ethyl (25g, 150mmol) and, K₂ CO₃ (41g, 300mmol) recirculating heated overnight at a temperature of the mixture, cooled to room temperature, water treatment (250 ml). The mixture is extracted in EtOAc (3×150ml), synoecism (3×100ml) and an organic layer sequentially unsatd. NaCl solution (2×100ml) washing with water, drying (MgSO₄) by, a vacuum concentrator. The residue is purified by column chromatography (Phenylbicyclohexane 10% EtOAc/90%), oil as 4-(3-ethoxypurine calbonyl phenoxycarboxylic)-1-nitrobenzenesulfonamide (38g) is obtained. 0125 : [And 40] 0126 : Step 2 ; 4-(3-aminophenoxy)-1-nitrobenzenesulfonamide synthetic 3:1 THF/aq. in (75 ml) 4-(3-aminophenoxy ethoxycarbonyl)-1-nitrobenzenesulfonamide (5. 14g, 17. 9mmol) (36 ml) of water to the mixture in a violent stirring LiOH·H₂ O (1. 50g, 35. 8mmol) solution is added. The mixture is heated to 50 °C at night, to cool the room, by, pH2 soln. to adjust the 1M HCl. A bright yellow solid obtained by filtration, washed with hydroxyhexanamide, 4-(3-aminophenoxy)-1-nitrobenzenesulfonamide (4. 40g, 95%)is obtained. 0127 : [And 41] 0128 : Step 3 ; 4-(3-(N-methyl carbamoylalkanoic) phenoxycarboxylic)-1-nitrobenzenesulfonamide CH₂ Cl₂ (45 ml) in 4-(3-aminophenoxy)-1-nitrobenzenesulfonamide (3. 72g, 14. 4mmol) and, EDCI·HCl (3. 63g, 18. 6mmol) and, N-methyl morpholine (1. 6 ml, 14. 5mmol) mixture is stirred at room temperature for 3, then the vacuum concentration. The residue is dissolved in EtOAc (50 ml), the mixture is extracted by the 1M HCl solution (50 ml). The water extracted in EtOAc layer (2×50ml), washing, drying (MgSO₄) synoecism org. layer is in a saturated NaCl solution (50 ml), by, oil as 4-(3-(N-methyl carbamoylalkanoic) phenoxycarboxylic)-1-nitrobenzenesulfonamide (1. 89g) is obtained. 0129 : [And 42] 0130 : Step 4 ; 4-(3-(N-methyl carbamoylalkanoic) phenoxycarboxylic) of polyanilin synthetic In EtOAc (20 ml) 4-(3-(N-methyl carbamoylalkanoic) phenoxycarboxylic)-1-nitrobenzenesulfonamide (1. 89g, 6. 95mmol) and 10% Pd/C (0. 24g) slurry H₂ atmosphere stirring overnight (balloon). The mixture is filtered through a pad of sedum, by, column chromatography (5% MeOH/95% CH₂ Cl₂) residue by refined. Oil under vacuum obtained by solidifying overnight, yellow solid matter as 4-(3-(N-methyl carbamoylalkanoic) phenoxycarboxylic) bisaniline (0. 95g, 56%). 0131 : A14. Ω-carbamoylalkanoic resorcinarene nitroalcohol synthetic through reduction of polyanilin EDCI intermediary amide produced subsequently. 4-(3-(5-methoxycarbonyl) pyridyloxy) of polyanilin synthesis. 0132 : [And 43] 0133 : Step 1 ; 4-(3-(5-methoxycarbonyl) pyridyloxy)-1-nitrobenzenesulfonamide synthetic In DMF (20 ml) of NaH (0. 63g, 26. 1mmol) of slurry in the DMF (10 ml) to 5-hydroxynicotinic (2. 0g, 13. 1mmol) is added. The mixture obtained in the DMF (10 ml) 4-fluoronitrobenzene (1. 4 ml, 13. 1mmol) is added to the solution, heated overnight at 70° C, cooled to room temperature, and then treated with water (50 ml) MeOH (5 ml). The mixture is extracted in EtOAc (100 ml), decompression concd. org. layer. The residue is purified by column chromatography (Phenylbicyclohexane 30% EtOAc/70%), 4-(3-(5-methoxycarbonyl) pyridyloxy)-1-nitrobenzenesulfonamide (0. 60g) is obtained. 0134 : [And 44] 0135 : Step 2 ; 4-(3-(5-methoxycarbonyl) pyridyloxy) of polyanilin synthetic MeOH/EtOAc during 4-(3-(5-methoxycarbonyl) pyridyloxy)-1-nitrobenzenesulfonamide (0. 60g, 2. The slurry of 20mmol) and 10% Pd/C H₂ atmosphere (balloon) 72 hours. The mixture is filtered, the decompression concd. diphosgene. The residue (Phenylbicyclohexane 30% EtOAc/70% gradient from 10% EtOAc/90%)column chromatography purified by, 4-(3-(5-methoxycarbonyl) pyridyloxy) bisaniline (0. 28g, 60%)is obtained.¹ H-NMR (CDCl₃) δ3. 92 (s, 3H), 6. 71 (d, 2H), 6. 89 (d, 2H), 7. 73 (d, 1H), 8. 51 (d, 1H), 8. 87 (d, 1H) 0136 : A15. Synthetic bisaniline electrophilic nitroalcohol by and then reduced. 4-(3-methyl Sulfamoylbenzoic phenoxycarboxylic) of polyanilin synthesis. 0137 : [And 45] Step 1 ; N-methyl-3-bromobenzene sulfoneamide synthetic 3-bromobenzenesulfonyl chloride (2 in THF (15 ml). 5g, 11. 2mmol) in ° C soln. Biphenylmethylamine (THF in 2. 0M; 28 ml, 56mmol) is added. The obtained solution is warmed to room temperature, the stirring overnight at room temperature. The mixture is separated between the EtOAc (25 ml) and 1M HCl solution (25 ml), water phase is extracted by EtOAc (2×25ml). Synoecism (2×25ml) and an organic layer sequentially unsatd. NaCl solution (25 ml) washing with water, drying (MgSO₄) and, by, white solid as N-methyl-3-bromobenzene sulfoneamide (2. 8g, 99%)is obtained. 0138 : [And 46] 0139 : Step 2 ; 4-(3-(N-methyl Sulfamoylbenzoic) Phenyloxyaniline) of synthetic hydroxybenzenesulfonic In the DMF (25 ml) phenol (1. 9g, 20mmol) and, K₂ CO₃ (6. 0g, 40mmol) and, CuI (4g, 20mmol) to a slurry of N-methyl-3-bromobenzene sulfoneamide (2. 5g, 10mmol) is added, the mixture is stirred overnight at a temperature recirculated, cooled to room temperature, the separation between the EtOAc (50 ml) and 1N HCl solution (50 ml). The water layer is extracted by EtOAc (2×50ml), an organic phase water synoecism (2×50ml) and successively washing unsatd. NaCl solution (50 ml), dried (MgSO₄) by, a vacuum concentrator. The residue of oil by purifying column chromatography (Phenylbicyclohexane 30% EtOAc/70%), 4-(3-(N-methyl Sulfamoylbenzoic) phenoxycarboxylic) benzene (0. 30g) is obtained. 0140 : [And 47] 0141 : Step 3 ; 4-(3-(N-methyl Sulfamoylbenzoic) Phenyloxyaniline)-1-nitrobenzenesulfonamide synthetic In the TFA (6 ml) 4-(3-(N-methyl Sulfamoylbenzoic) Phenyloxyaniline) benzene (0. 30g, 1. 14mmol) soln. NaNO₂ (0. 097g, 1. 14mmol) adding a little by little over 5 minutes. 1-10 ° C obtained by stirring time soln., warmed to room temperature, the vacuum concentration. EtOAc (10 ml) and water (10 ml) of residue is separated between, organic phase water (10 ml) and saturated NaCl solution (10 ml) sequentially by washing, drying (MgSO₄) and, by 4-(3-(N-methyl Sulfamoylbenzoic) Phenyloxyaniline)-1-nitrobenzenesulfonamide (0. 20g) is obtained. This material is used in the next step without further purification. 0142 : [And 48] 0143 : Step 4 ; 4-(3-(N-methyl Sulfamoylbenzoic) Phenyloxyaniline) of polyanilin synthetic In EtOAc (20 ml) 4-(3-(N-methyl Sulfamoylbenzoic) Phenyloxyaniline)-1-nitrobenzenesulfonamide (0. 30g) and 10% Pd/C (0. 030g) slurry H₂ atmosphere stirring overnight (balloon). The mixture is filtered through a pad of sedum, concd. diphosgene is reduced. The residue is purified by column chromatography (Phenylbicyclohexane 30% EtOAc170%), 4-(3-(N-methyl Sulfamoylbenzoic) Phenyloxyaniline) bisaniline (0. 070g) is obtained. 0144 : A16. Ω-ketone modification. 4-(4-(1-(N-methoxysalicylic) iminoethyl) bisaniline phenoxyphenol synthesis of HCl. 0145 : [And 49] 0146 : 4-(4-aminophenoxy) bisaniline HCl salt (method A13, step 4 in a similar mode of manufacture; 1. 0g, 3. 89mmol) of EtOH (10 ml) and polypyridine (1. 0 ml) in a slurry of O-methyl hydroxylamine HCl salt (0. 65g, 7. 78mmol, 2. 0 equiv.) is added. The mixture is heated to the reflux temperature and 30 minutes, cooled to room temperature, the vacuum concentration. The obtained solid materail (10 ml) and water, wash water, yellow solid matter as 4-(4-(1-(N-methoxysalicylic) iminoethyl) phenoxycarboxylic bisaniline HCl salt (0. 85g) is obtained. TLC (50% EtOAc/50% petroleum ether) Rf0. 78 ;¹ H-NMR (DMSO-d₆) δ3. 90 (s, 3H), 5. 70 (s, 3H); HPLC-MS m/z "(m+H)⁺" 0147 : A17. N-(ω-butyldiphenylsilyloxy alkyl) acid synthesis. 4-(4-(2-ethyl carbamoylalkanoic (N-2-triisopropylbenzene siloxymethanes)) pyridyloxy bisaniline synthesis. 0148 : [And 50] 0149 : Step 1 ; 4-chloro-N-(2-triisopropylsilyloxy) ethyl pyridine-2- [...] In the DMF (7 ml) anhyride 4-chloro-N-(2-hydroxyethyl)-2- [...] (method A2, similar to step 3b in a mode of manufacturing; 1. 5g, 7. 5mmol) diisopropylbenzene silyl chloride (1 soln.. 59g, 8. 2mmol), 1. 1 equiv.) and imidazolecarboxylic (1. 12g, 16. 4mmol, 2. 2 equiv.) is added. 3 obtd. yellow solution is stirred at room temperature, the vacuum concentration. The residue is separated between the water (10 ml) and EtOAc (10 ml), water extracted by the EtOAc phase. The layer is dried (MgSO₄) org. synoecism is, by, orange oil, 4-chloro-2-(N-(2-triisopropylsilyloxy) ethyl) [...] (2. 32g, 88%)is obtained. The device is used in the next step without further purification. 0150 : [And 51] 0151 : Step 2 ; 4-(4-(2-(N-(2-triisopropylsilyloxy) ethyl carbamoylalkanoic) pyridyloxy bisaniline 4-hydroxyaniline (0 in the DMF (8 ml) anhyride. 70g, 6. 0mmol) soln. potassium p-t-butoxide (0. 67g, 6. 0mmol, 1 equivalent) in addition to the (heated) temporarily. When the mixture is cooled to room temperature, in the DMF (4 ml) 4-chloro-2-(N-(2-triisopropylsilyloxy) ethyl) [...] (2. 32g, 6mmol, 1 equivalent) is added, then K₂ CO₃ (0. 42g, 3. 0mmol, 0. 50 equiv.) is added. The mixture is cooled in an ice water bath to 0 °C, slowly dripping water (about 1 ml). By extracting the EtOAc (3×10ml) an organic layer, washing, drying (MgSO₄) synoecism org. layer is in a saturated NaCl solution (20 ml), the vacuum concentration. Brown oily residue of column chromatography (SiO₂, 30% EtOAc/70% refined petroleum ether), brown oil as 4-(4-(2-(N-(2-triisopropylsilyloxy) ethyl carbamoylalkanoic) pyridyloxy bisaniline (0. 99g, 38%)is obtained. 0152 : A18. 2-2-ethyl pyridine polypyridine hydroxyphenylalkanecarboxylate through oxidation of a synthetic ester. 4-(5-(2-methoxy calbonyl) pyridyloxy) of polyanilin synthesis. 0153 : [And 52] 0154 : Step 1 ; 4-(5-(2-methyl) pyridyloxy-1-nitrobenzenesulfonamide DMF (100 ml) in 5-hydroxy-2-methyl pyridine (10. 0g, 91. 6mmol), 1-fluoro-4-nitrobenzenesulfonamide (9. 8 ml, 91. 6mmol, 1 equiv.), K₂ CO₃ (25g, 183mmol, 2. 0 equiv.) at a temperature of the recirculating mixture heated overnight. The mixture is cooled to room temperature, is treated with water (200 ml),. The extracted in EtOAc (3×100ml). Synoecism (2×100ml) and an organic layer sequentially unsatd. NaCl solution (100 ml) washing with water, drying (MgSO₄) and, by, brown solid matter as 4-(5-(2-methyl) pyridyloxy)-1-nitrobenzenesulfonamide (12. 3g) is obtained. 0155 : [And 53] 0156 : Step 2 ; 4-(5-(2-methoxy calbonyl) pyridyloxy)-1-nitrobenzenesulfonamide synthetic Polypyridine (20 ml) in 4-(5-(2-methyl) pyridyloxy)-1-nitrobenzenesulfonamide (1. 70g, 7. Selenium dioxide (2 39mmol) a 50g, 22. 2mmol, 3. 0 equiv.) a mixture of 5 hours at a temperature recirculated, cooled to room temperature. The obtained slurry is filtered, the vacuum concentration. The residue is dissolved in MeOH (100 ml), by treating the concd. soln. HCl solution (7 ml), then heated at reflux temperature 3, cooled to room temperature, the vacuum concentration. Between the separated residues of EtOAc (50 ml) and 1N NaOH (50 ml). The water layer is extracted in EtOAc (2×50ml), synoecism (2×50ml) and an organic layer sequentially washing water saturated NaCl solution (50 ml), dried (MgSO₄) by, a vacuum concentrator. Column chromatography (SiO₂, 50% EtOAc/50% residue Phenylbicyclohexane) by purifying, 4-(5-(2-methoxy calbonyl) pyridyloxy)-1-nitrobenzenesulfonamide (0. 70g) is obtained. 0157 : [And 54] 0158 : Step 3 ; 4-(5-(3-methoxycarbonyl) [...]) of polyanilin synthetic In EtOAc (20 ml) and MeOH (5 ml) of 4-(5-(2-methoxy calbonyl) pyridyloxy)-1-nitrobenzenesulfonamide (0. 50g) and 10% Pd/C (0. 050g) mending H₂ slurry of F (balloon) placed in the atmosphere. The mixture is filtered through a pad of sedum, concd. diphosgene is reduced. Column chromatography (SiO₂, 70% EtOAc/30% residue Phenylbicyclohexane) by purifying, 4-(5-(2-methoxy calbonyl) pyridyloxy) bisaniline (0. 40g) is obtained. A19. Ω-sulfonylated bisaniline synthesis. 4-(4-methylsulfonylbenzoylguanidine Phenyloxyaniline) of polyanilin synthesis. 0159 : [And 55] 0160 : Step 1 ; 4-(4-methylsulfonylbenzoylguanidine phenoxycarboxylic)-1-nitrobenzenesulfonamide CH₂ Cl₂ (75 ml) of 4-(4- methyl thio phenoxy)-1-(2. 0g, 7. 7mmol) at 0 °C soln. m-CPBA (57-86%, 4. 0g) is slowly added, the reaction mixture is stirred at room temperature for 5 hours. The reaction mixture is treated with 1N NaOH solution (25 ml). The organic layer 1N NaOH solution (25 ml), water (25 ml) and saturated NaCl solution (25 ml) sequentially by washing, drying (MgSO₄) to, vacuum drying, solid as 4-(4-methylsulfonylbenzoylguanidine oxymeter)-1-nitrobenzenesulfonamide is obtained. 0161 : Step 2 ; 4-(4-methylsulfonylbenzoylguanidine phenoxycarboxylic)-1-bisaniline 4-(4-methylsulfonylbenzoylguanidine phenoxycarboxylic)-1-alkoxynitrobenzenes method A18, described in step 3 and of similar form to the polyaniline. 0162 : B. The synthesis of urea precursors. B1. The isocyanate synthesis using the CDI polyanilin. 4-bromo-3-(trifluoromethyl) phenyl isocyanate synthesis. 0163 : [And 56] 0164 : Step 1 ; 4-bromo-3-(trifluoromethyl) synthesis of HCl bisaniline Et₂ O (500 ml) in 4-bromo-3-(trifluoromethyl) bisaniline (64g, 267mmol) soln. HCl soln. (Et₂ O in 1M, 300 ml) is dropped, the mixture is stirred at room temperature for 16 hours. A white precipitate obtained by filtration to remove pinkring, Et₂ O (50 ml) wash, 5-bromo-3-(trifluoromethyl) bisaniline HCl salt (73g, 98%)is obtained. 0165 : [And 57] 0166 : Step 2 ; 4-bromo-3-(trifluoromethyl) phenyl isocyanate synthesis In toluene (278 ml) 4-bromo-3-(trifluoromethyl) bisaniline HCl salt (36. 8g, 133mmol) suspensionlike fluoroformate Chloropyridin trichloromethylpyrimidine dropping into the liquid, the mixture is heated at reflux temperature 18. A mixture obtained by, a residue CH₂ Cl₂ (500 ml) treated with, a vacuum concentrator. CH₂ Cl₂ processing/concn. protocol is repeated, 16 the oil storing time obtained at 20° C-succinylated color, yellow brown solid as 4-bromo-3-(trifluoromethyl) phenyl isocyanate (35. 1g, 86%)is obtained. GC-MS m/z 265 (M⁺) 0167 : C. A method for the production of urea. C1a. Due to the reaction of the isocyanate and general bisaniline of urea synthesis process. N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) phenyl) the synthesis of urea. 0168 : [And 58] 0169 : CH₂ Cl₂ (35 ml) during 4-chloro-3-phenyl isocyanate (trimethylcyclo) (14. 60g, 65. 90mmol) of soln. CH₂ Cl₂ (35 ml) in 4-(2-(N-alkoxycarbonylmethylcarbonylpyrazine)-4-pyridyloxy) bisaniline (method A2, step 4 ; 16. 0g, 65. 77mmol) to 0 °C dripped in suspension. The mixture is stirred at room 22. Yellow solid matter is filtered by obtd., CH₂ Cl₂ (2×30ml) washing, drying under reduced pressure (about 1mmHg), gray solid as N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) phenyl) urea (28. 5g, 93%)is obtained. mp207-209°C;¹ H-NMR (DMSO-d₆) δ2. 77 (d, J=4. 8Hz, 3H), 7. 16 (m, 3H), 7. 37 (d, J=2. 5Hz, 1H), 7. 62 (m, 4H), 8. 11 (d, J=2. 5Hz, 1H), 8. 49 (d, J=5. 5Hz, 1H), 8. 77 (br d, 1H), 8. 99 (s, 1H), 9. 21 (s, 1H); HPLC ES-MS m/z 465 "(M+H)⁺" 0170 : C1b. Due to the reaction of the isocyanate and general bisaniline of urea synthesis process. N-(4-bromo-3-(trifluoromethyl) phenyl)-N '-(4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) phenyl) the synthesis of urea. 0171 : [And 59] 0172 : CH₂ Cl₂ (80 ml) in 4-bromo-3-(trifluoromethyl) phenyl isocyanate (method B1, step 2 ; 8. 0g, 30. 1mmol) soln. CH₂ Cl₂ (40 ml) in 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) bisaniline (method A2, step 4 ; 7. 0g, 28. 8mmol) 0 °C soln. by dripping. The mixture is stirred at room temperature for 16 hours. Yellow solid matter is filtered by obtd., CH₂ Cl₂ (2×50ml) washing, drying under reduced pressure (about 1mmHg) 40 °C, N-(4-bromo-3-(trimethylcyclo fluoro) phenyl)-N '-(4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) phenyl) urea corallite solid (13. 2g, 90%)obtained by a mp203-205°C;¹ H-NMR (DMSO-d₆) δ2. 77 (d, J=4. 8Hz, 3H), 7. 16 (m, 3H), 7. 37 (d, J=2. 5Hz, 1H), 7. 58 (m, 3H), 7. 77 (d, J=8. 8Hz, 1H), 8. 11 (d, J=2. 5Hz, 1H), 8. 49 (d, J=5. 5Hz, 1H), 8. 77 (br d, 1H), 8. 99 (s, 1H), 9. 21 (s, 1H); HPLC ES-MS m/z 509 "(M+H)⁺" 0173 : C1c. Due to the reaction of the isocyanate and general bisaniline of urea synthesis process. N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(2-methyl-4-(methyl carbamoylalkanoic 2-N-)-4-pyridyloxy) phenyl) the synthesis of urea. 0174 : [And 60] 0175 : CH₂ Cl₂ (1 ml) of 2-methyl-4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) bisaniline (method A5; 0. 11g, 0. 45mmol) soln. Et₃ N (0. 16 ml) and 4-chloro-3-(trifluoromethyl) phenyl isocyanate (0. 10g, 0. 45mmol) in processing. 6 obtained by stirring a brown solution at room temperature, then treated with water (3 ml). The water layer is extracted by EtOAc (3×5ml), organic layer is dried (MgSO₄) it, by a brown oil as N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(2-methyl-4-(2-methyl carbamoylalkanoic)-4-pyridyloxy) phenyl) urea (0. 11g, 0. 22mmol) is obtained.¹ H-NMR (DMSO-d₆) δ2. 27 (s, 3H), 2. 77 (d, J=4. 8Hz, 3H), 7. 03 (dd, J=8. 5, 2. 6Hz, 1H), 7. 11 (d, J=2. 9Hz, 1H), 7. 15 (dd, J=5. 5, 2. 6Hz, 1H), 7. 38 (d, J=2. 6Hz, 1H), 7. 62 (app d, J=2. 6Hz, 2H), 7. 84 (d, J=8. 8Hz, 1H), 8. 12 (s, 1H), 8. 17 (s, 1H), 8. 50 (d, J=5. 5Hz, 1H), 8. 78 (q, J=5. 2Hz, 1H), 9. 52 (s, 1H); HPLC ES-MS m/z 479 "(M+H)⁺" 0176 : C1d. Due to the reaction of the isocyanate and general bisaniline of urea synthesis process. N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(4-aminophenyl) the synthesis of urea. 0177 : [And 61] 0178 : CH₂ Cl₂ (308 ml) in 4-chloro-3-(trifluoromethyl) phenyl isocyanate (2. 77g, 10. 3mmol) p-phenylene diamine (3 to the solution. 32g, 30. 7mmol) in addition to temporarily. The mixture is stirred at room temperature for 1 hour, CH₂ Cl₂ (100 ml) treated with, a vacuum concentrator. The mixture obtained is dissolved to pink EtOAc (110 ml) and MeOH (15 ml) of a solid, transparent soln. 0. Washed in 05N HCl solution. By an organic layer, impure N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(4-aminophenyl) urea (3. 3g) is obtained. TLC (100% EtOAc) Rf0. 72 0179 : C1e. Due to the reaction of the isocyanate and general bisaniline of urea synthesis process. N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(4-ethoxypurine carbonylphenyl) the synthesis of urea. 0180 : [And 62] 0181 : CH₂ Cl₂ (30 ml) in 4-ethyl alkylbenzonic isocyanated (3. 14g, 16. 4mmol) soln. 4-chloro-3-(trifluoromethyl) bisaniline (3. 31g, 16. 4mmol) is added, with stirring overnight solution at room temperature. The obtained slurry is CH₂ Cl₂ (50 ml) diluted with water, filtered, white solid as N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(4-ethoxypurine carbonylphenyl) urea (5. 93g, 97%)is obtained. TLC (Phenylbicyclohexane 40% EtOAc/60%)Rf0. 44 0182 : C1f. Due to the reaction of the isocyanate and general bisaniline of urea synthesis process. N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(3-carboxyphenyl) the synthesis of urea. 0183 : [And 63] 0184 : CH₂ Cl₂ (8 ml) in 4-chloro-3-(trifluoromethyl) phenyl isocyanate (1. 21g, 5. 46mmol) soln. 4-(3-aminophenoxy) bisaniline (method A11; 0. 81g, 5. 76mmol) is added, the mixture is stirred overnight at room temperature, by treating the MeOH (8 ml), and further stirred for 2 hours. The resultant mixture is subjected to a reduced pressure. Brown solid materail obtd. 1:1 EtOAc/Phenylbicyclohexane soln., gray solid as N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(3-carboxyphenyl) urea (1. 21g, 76%)is obtained. 0185 : C2a. Bisaniline and N, N '-diimidazole reaction 2 then bisaniline of general method for the synthesis of the addition of urea. N-(2-methoxy-5-(trifluoromethyl) phenyl)-N '-(4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) phenyl) the synthesis of urea. 0186 : [And 64] 0187 : Anhyride CH₂ Cl₂ (15 ml) in 2-methoxy-5-(trifluoromethyl) bisaniline (0. 15g) 0 °C soln. in a CDI (0. 13g) is added. 1 time obtd. warmed to room temperature in a solution, 16 hours at room temperature, then the 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) bisaniline (0. 18g) and processing. The yellow solution is stirred at room temperature for 72, H₂ O (125 ml) in processing. A mixture obtained by extracting the EtOAc (2×150ml) in water, washing, drying (MgSO₄) synoecism org. layer is in a saturated NaCl solution (100 ml), the vacuum concentration. The residue is wrenched (Phenylbicyclohexane 90% EtOAc/10%), and the obtained white solid collected by filtration, washed in EtOAc. The filtrate is concentrated under a reduced pressure, a residue of oil column chromatography (Phenylbicyclohexane 33% EtOAc/67% Phenylbicyclohexane 50% EtOAc/50% from a gradient) is purified by, bright yellow solid as N-(2-methoxy-5-(trifluoromethyl) phenyl)-N '-(4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) phenylureas (0. 098g, 30%)is obtained. TLC (100% EtOAc) Rf0. 62 ;¹ H-NMR (DMSO-d₆) δ2. 76 (d, J=4. 8Hz, 3H), 3. 96 (s, 3H), 7. 1-7. 6 (m, 11H), 8. 4-8. 6 (m, 11H), 8. 75 (d, J=4. 8Hz, 1H), 9. 55 (s, 1H); FAB-MS m/z 461 "(M+H)⁺" 0188 : C2b. Bisaniline and N, N '-diimidazole reaction 2 due to the addition of a second for the synthesis of urea bisaniline of general method. N, N ' as a by-product of the reaction operation diimidazole-symmetry of urea. Bis (4-(2-(N-methyl carbamoylalkanoic)-4- [...]) phenyl) urea. 0189 : [And 65] 0190 : Anhyride CH₂ Cl₂ (15 ml) in 3-amino-2-methoxy Quinolin (0. 14g) while stirring to a solution of a CDI (0. 13g) in addition to 0 °C. 1 warmed to room temperature over time obtd. soln., 16 hours at room temperature. The mixture is 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) bisaniline (0. 18g) by processing, yellow soln. obtd. 72 hours at room temperature, then treated with water (125 ml). A mixture obtained by extracting an.aq. EtOAc (2×150ml), an organic layer is saturated NaCl solution (100 ml) synoecism wash, a vacuum concentrator. The residue is wrenched (Phenylbicyclohexane 90% EtOAc/10%), obtained by white solid is filtered, washed with EtOAc, bis (4-(N-methyl carbamoylalkanoic)-4-pyridyloxy) phenyl) urea (0. 081g, 44% is obtained. TLC (100% EtOAc) Rf0. 50 ;¹ H-NMR (DMSO-d₆) δ2. 76 (d, J=5. 1Hz, 6H), 7. 1-7. 6 (m, 12H), 8. 48 (d, J=5. 4Hz, 1H), 8. 75 (d, J=4. 8Hz, 2H), 8. 86 (s, 2H); HPLC ES-MS m/z 513 "(M+H)⁺" 0191 : C2c. Due to the reaction of the isocyanate and general bisaniline of urea synthesis process. N-(2-methoxy-5-(trifluoromethyl) phenyl)-N '-(4-(1, 3-dioxo methoxyindoline-5-carbonoyloxysilane) phenylureas synthesis. 0192 : [And 66] 0193 : CH₂ Cl (1. 5 ml) in 2-methoxy-5-(trifluoromethyl) phenyl isocyanate (0. 10g, 0. 47mmol) into a soln. under stirring 5-(4-aminophenoxy) methoxyindoline -1, 3-dione (method A3, step 3 ; 0. 12g, 0. 47mmol) in addition to temporarily. The mixture is stirred 12, next CH₂ Cl₂ (10 ml) in processing and MeOH (5 ml). The mixture is successively soln. 1N HCl (15 ml) and saturated NaCl solution (15 ml) washing, drying (MgSO₄) and, by, white solid as N-(2-methoxy-5-(trifluoromethyl) phenyl)-N '-(4-(1, 3-dioxo isoindolin-5-carbonoyloxysilane) phenyl) urea (0. 2g, 96%)is obtained. TLC (Phenylbicyclohexane 70% EtOAc/30%)Rf0. 50 ;¹ H-NMR (DMSO-d₆) δ3. 95 (s, 3H), 7. 31-7. 10 (m, 6H), 7. 37 (d, J=9. 3Hz, 2H), 7. 80 (d, J=8. 7Hz, 1H), 8. 53 (br s, 2H), 9. 57 (s, 1H), 11. 27 (br s, 1H); HPLC ES-MS m/z 472. 0 "(M+H)⁺, 100%" 0194 : C2d. Bisaniline and N, N ' diimidazole -2 by the addition of a second reaction of urea synthesis general method of polyaniline. N-(5-(t-butyl)-2-(2, 5- dimethyl pyro rill) phenyl)-N '-(4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) phenyl) the synthesis of urea. 0195 : [And 67] 0196 : CH₂ Cl₂ (2 ml) in a CDI (0. 21g, 1. 30mmol) soln. under stirring 5-(t-butyl)-2-(2. 5- dimethyl pyro rill) bisaniline (method A4, step 2 ; 0. 30g, 1. 24mmol) in addition to temporarily. The mixture is stirred at room temperature for 4 hours, then, 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) bisaniline (0. 065g, 0. 267mmol) in addition to temporarily. The mixture is heated at night 36 °C, cooled to room temperature, by diluting EtOAc (5 ml). The mixture with the water (15 ml) and 1N HCl (15 ml) soln. successively washed, dried, and filtered through the silica gel pad (50g), yellow solid matter as N-(5-(t-butyl)-2-(2, 5- dimethyl pyro rill) phenyl)-N '-(4-(2-methyl carbamoylalkanoic)-4-pyridyloxy) urea (0. 033g, 24%)is obtained. TLC (Phenylbicyclohexane 40% EtOAc/60%)Rf0. 24 ;¹ H-NMR (hydroxyacetone-d₆) δ1. 37 (s, 9H), 1. 89 (s, 6H), 2. 89 (d, J=4. 8Hz, 3H), 5. 83 (s, 2H), 6. 87-7. 20 (m, 6H), 7. 17 (dd, 1H), 7. 51-7. 58 (m, 3H), 8. 43 (d, J=5. 4Hz, 1H), 8. 57 (d, J=2. 1Hz, 1H), 8. 80 (br s, 1H); HPLC ES-MS 512 "(M+H)⁺, 100%" 0197 : C3. The method uses a combination of urea synthesis diphenylmethyl triarylboron phosgene. One of the to be connected into a dichloroethaneand bisaniline (0. 10M). 8 ml vial (0 to the soln. contg. dichloroethaneand (1 ml). 5 ml) is added to the system. Into this bis (trichloromethyl) carbonate solution (in dichloroethaneand 0. 12M, 0. 2 ml, 0. 4 equiv.) is added, then diisopropylnaphthalene phenoxyethylamine (during dichloroethaneand 0. 35M, 0. 2 ml, 1. 2 equiv.) is added. The vial is a cap, 5 hours at 80° C, cooled to room temperature in about 10 hours. 2 bisaniline of adding the first, (during dichloroethaneand 0. 10M, 0. 5 ml, 1. 0 equiv.), then diisopropylnaphthalene phenoxyethylamine (during dichloroethaneand 0. 35M, 0. 2 ml, 1. 2 equiv.) is added. The mixture is heated at 80 °C 4, cooled to room temperature, MeOH (0. 5 ml) in processing. The mixture is concentrated to a reduced pressure, is purified by a reverse phase HPLC. 0198 : C4. 2 of phosgene reaction then bisaniline bisaniline and due to the addition of a general method of synthesizing urea. N-(2-methoxy-5-(trifluoromethyl) phenyl)-N '-(4-2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-phenyl) the synthesis of urea. 0199 : [And 68] 0200 : CH₂ Cl₂ (20 ml) of phosgene (toluene and 1. 9M, 2. 07 ml, 0. 21g, 1. 30mmol) 0 °C polypyridine anhyride under agitation to the solution of (0. Next, 2-methoxy-5-(trifluoromethyl) bisaniline (0 . 32 ml) 75g) is added. A mixture of stirred yellow 1, then a vacuum concentrator. Applied to a solid obtained toluene (20 ml), then 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) bisaniline (method A2 in preparation of, 0. 30g) is applied, in a suspension obtained 80 °C 20 hours, and cooled to room temperature. The mixture is diluted with water (100 ml), and basic unsatd. NaHCO₃ soln. (2-3ml). This basic solution is extracted in EtOAc (2×250ml), organic layer separately washed with saturated NaCl solution, soln., drying (MgSO₄) by, a vacuum concentrator. The resultant residue is dissolved in brown pinkring MeOH, SiO₂ (100g) absorbed. Column chromatography (300g SiO₂; 1% Et₃ N/33% EtOAc/66% Phenylbicyclohexane from 1% Et₃ N/99% EtOAc to 1% Et₃ N/20% MeOH/79% EtOAc gradient), then the concentration of the strong solution in EtOAc under reduced pressure 45 °C. This processing Phenylbicyclohexane (10 ml) and N-(2-methoxy-5-(trifluoromethyl) phenyl)-N '-(4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) phenyl) urea is slowly crystal (0. 44g) is formed. TLC (1% Et₃ N/99% EtOAc) Rf0. 40 0201 : D. Crossconversion of urea. N-(4-chloro-3-( (trifluoromethyl) phenyl)-N '-(4-(3-methoxysalicylic carbonylphenyl) Carboxyamino aminophenylacetylene) the synthesis of urea. D1a. Ω ω of urea-aminophenylacetylene [...] -conversion of urea. N-(4-chloro-3-( (trifluoromethyl) phenyl)-N '-(4-(3-methyl carbamoylalkanoic) phenyl) Carboxyamino aminophenylacetylene) the synthesis of urea. 0202 : [And 69] 0203 : In DMF (8 ml), N-(4-chloro-3-( (trifluoromethyl) phenyl)-N '-(4-aminophenyl) urea (method C1d; 0. 050g, 1. 52mmol), monomethylation isophthalate (0. 25g, 1. 38mmol), HOBT·H₂ O (0. 41g, 3. 03mmol) and N-methyl morpholine (0. 33 ml, 3. 03mmol) into a soln. EDCI·HCl (0. 29g, 1. 52mmol) is added. The mixture is stirred overnight at room temperature, is diluted with EtOAc (25 ml), water (25 ml) and sequentially washed unsatd. NaHCO₃ soln. (25 ml). The layer is dried (MgSO₄) org. by, a vacuum concentrator. A solid obtained by kneading EtOAc soln. (Phenylbicyclohexane 80% EtOAc/20%), N-(4-chloro-3-( (trifluoromethyl) phenyl)-N '-(4-(3-methoxysalicylic carbonylphenyl) Carboxyamino aminophenylacetylene) urea (0. 27g, 43%)is obtained. Mp121-122°C; TLC (Phenylbicyclohexane 80% EtOAc/20%)Rf0. 75 0204 : D1b. Ω ω-phenylureas-Carboxyamino phenylureas of conversion (aryl carbamoylalkanoic). N-(4-chloro-3-( (trifluoromethyl) phenyl)-N '-(4-(3-methyl carbamoylalkanoic phenylpropionic) carbamoylphenyl) the synthesis of urea. 0205 : [And 70] 0206 : In DMF (3 ml) of N-(4-chloro-3-( (trifluoromethyl) phenyl)-N '-(4-(3-methyl carbamoylalkanoic phenylpropionic) Carboxyamino aminophenylacetylene) urea (0. 14g, 0. 48mmol), 3-methyl carbamoylalkanoic bisaniline (0. 080g, 0. 55mmol), HOBT·H₂ O (0. 14g, 1. 07mmol) and N-methyl morpholine (0. 5 ml, 1. 07mmol) in a 0 °C soln. EDCI·HCl (0. 10g, 0. 53mmol) is added. The mixture is warmed to room temperature, the stirring overnight. The mixture is treated with water (10 ml), extracting the EtOAc (25 ml). By an organic layer, a yellow solid matter dissolved in obtd. EtOAc (3 ml), silica gel is filtered through the pad (17g, 10% MeOH/90% EtOAc Phenylbicyclohexane 70% EtOAc/30% from a gradient), white solid as N-(4-chloro-3-( (trifluoromethyl) phenyl)-N '-(4-(3-methyl carbamoylalkanoic phenylpropionic) carbamoylphenyl) urea (0. 097g, 41%)is obtained. Mp225-229 °C; TLC (100% EtOAc) Rf0. 23 0207 : D1c. Ω ω-phenylureas-Carboxyamino phenylureas (aryl carbamoylalkanoic) of the conversion to a combination approach. N-(4-chloro-3-( (trifluoromethyl) phenyl)-N '-(4-(N-(3-pyridyl) carbamoylalkanoic) phenyl) carbamoylalkanoic) phenyl) the synthesis of urea. 0208 : [And 71] 0209 : 1, 2-dichloroethane (1 ml) of N-(4-chloro-3-( (trifluoromethyl) phenyl)-N '-(3-carboxyphenyl) urea (method C1f; 0. 030g, 0. 067mmol) and N-cyclohexyl-N-(methyl polystyrene) carbocation imide (55 mg) mixture of CH₂ Cl₂ in 3-aminopyrin soln. (1M; 0. 074 ml, 0. 074mmol) in processing. (In the case of a small amount of insoluble or suspensionlike DMSO is added. ) 36 °C mixture obtained by heating at night, treated with a reaction mixture rearers THF (1 ml), heating continues to 18 hours. The mixture is stirred at 72 36 °C, cooled to room temperature, filter. A solution of silica gel (1g) phnomenon filtering. Under the pressure of concentrated N-(4-chloro-3-( (trifluoromethyl) phenyl)-N '-(4-(N-(3-(N-(3-pyridyl) carbamoylalkanoic) phenyl) carbamoylalkanoic) phenyl) urea (0. 024g, 59%). TLC (Phenylbicyclohexane 70% EtOAc/30%)Rf0. 12 0210 : D2. Ω ω-aryl-carboalkoxypyrimidine carbamoylarylurea conversion of urea. N-(4-chloro-3-( (trifluoromethyl) phenyl)-N '-(4-(3-methyl carbamoylalkanoic phenylpropionic) Carboxyamino aminophenylacetylene) the synthesis of urea. 0211 : [And 72] 0212 : N-(4-chloro-3-( (trifluoromethyl) phenyl)-N '-(4-(3-carbocation Trifluoromethoxyphenyl) Carboxyamino aminophenylacetylene) urea of sample (0. 17g, 0. 34mmol) during Biphenylmethylamine (THF 2M; 1 ml, 1 t 7mmol) is added. The mixture is stirred overnight at room temperature, by, white solid as N-(4-chloro-3-( (trifluoromethyl) phenyl)-N '-(4-(3-methyl carbamoylalkanoic phenylpropionic) Carboxyamino aminophenylacetylene) urea is obtained. Mp247 °C; TLC (100% EtOAc) Rf0. 35 0213 : D3. Ω ω of urea-carboxy aryl, aryl-carboalkoxypyrimidine conversion of urea. N-(4-chloro-3-( (trifluoromethyl) phenyl)-N '-(4-carboxyphenyl) the synthesis of urea. 0214 : [And 73] 0215 : MeOH (75 ml) of N-(4-chloro-3-( (trifluoromethyl) phenyl)-N '-(4-ethoxypurine carbonylphenyl) urea (method C1e; 5. 93g, 15. 3mmol) KOH aqueous slurry (2. 5N, 10 ml, 23mmol) is added. The mixture is heated to the reflux temperature in 12 hours, cooled to room temperature, the vacuum concentration. The residue (50 ml) and diluted with water, the soln. pH2-3 and 1N HCl. The solid is collected, by drying under reduced pressure, white solid as N-(4-chloro-3-( (trifluoromethyl) phenyl)-N '-(4-carboxyphenyl) urea (5. 05g, 92%)is obtained. 0216 : D4. Ω ω-alkylamidoalkanol of conversion to-alkoxyphenol ester. N-(4-chloro-3-( (trifluoromethyl) phenyl)-N '-( (4-(3-(5-(2-diethylaminoethylmethacrylate) carbamoylalkanoic) Pyridylalkyl) oxyphenyl) the synthesis of urea. 0217 : [And 74] 0218 : Step 1 ; N-(4-chloro-3-( (trifluoromethyl) phenyl)-N '-( (4-(3-(5-Carboxyamino Pyridylalkyl) of synthetic phenylureas oxystyrene N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(4-(3-(5-methoxycarbonyl Pyridylalkyl) oxyphenyl) the urea, Cla method similar to the method of 4-chloro-3-(trifluoromethyl) and phenyl isocyanate, 4-(3-(5- [...]) Oxyaniline (method A14, step 2) and synthesis. MeOH (10 ml) of N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-( (4-(3-(5-methoxycarbonyl Pyridylalkyl) oxyphenyl) urea (0. 26g, 0. 56mmol) suspensionlike KOH (1 ml) of water (0. 14g, 2. 5mmol) soln., stirred at room temperature for 1 hour. The mixture obtained pH3 adjusted 1N HCl soln., produced by precipitation is filtered, washed with water. EtOH (10 ml) dissolved in a solid obtained, the concentrated solution is reduced. This EtOH/2 times repeatedly concn. operation, N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(4-(3-(5-Carboxyamino polypyridine) oxyphenyl) urea (0. 18g, 71%)is obtained. 0219 : [And 75] 0220 : Step 2 ; N-(4-chloro-3-(trifluoromethyl) phenyl-N '-( (4-(3-(5-(2-diethylaminoethylmethacrylate) carbamoylalkanoic) Pyridylalkyl) oxyphenyl) the synthesis of urea. DMF (2. 5 ml) in, N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-( (4-(3-(5-Carboxyamino Pyridylalkyl) oxyphenyl) urea (0. 050g, 0. 011mmol), N, N- dimethyl ethylene diamine (0. 22 mg, 0. 17mmol), HOBT (0. 028g, 0. 17mmol), N-methyl morpholine (0. 035g, 0. 28mmol) and EDCI·HCl (0. 032g, 0. The mixture is stirred overnight 17mmol) at room temperature. The resultant solution is separated between the EtOAc (50 ml) and water (50 ml), water (35 ml) org. layer by washing, drying (MgSO₄) by, a vacuum concentrator. A minimum amount of residue CH₂ Cl₂ (about 2 ml) dissolved in, this soln. Et₂ O is dropped, white precipitate as N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-( (4-(3-(5-(2-diethylaminoethylmethacrylate) carbamoylalkanoic) Pyridylalkyl) oxyphenyl) urea (0. 48g, 84%)is obtained.¹ H-NMR (DMSO-d₆) δ2. 10 (s, 6H), 3. 26 (s, H), 7. 03 (d, 2H), 7. 52 (d, 2H), 7. 60 (m, 3H), 8. 05 (s, 1H), 8. 43 (s, 1H), 8. 58 (t, 1H), 8. 69 (s, 1H) 8. 90 (s, 1H), 9. 14 (s, 1H); HPLC ES-MS m/z 522 "(M+H)⁺" 0221 : D5. Ω-N-(butyldiphenylsilyloxy alkyl) for protection of the general method for degassing. N-(4-chloro-3-( (trifluoromethyl) phenyl)-N '-(4-(4-(2-(N-(2-hydroxy) ethyl carbamoylalkanoic) pyridyloxy phenylpropionic) the synthesis of urea. 0222 : [And 76] 0223 : In anhydrous THF (2 ml) N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(4-(4-(2-(N-(2-triisopropylsilyloxy) ethyl carbamoylalkanoic) pyridyloxy phenylureas (method C1a is similar to the method of manufacture; 0. 25g, 0. 37mmol) soln., tetrabutyl ammonium sulfonylfluoride soln. (THF in 1. 0M, 2 ml) is added. The mixture is stirred at room temperature for 50 minutes, treated with water (10 ml). By extracting an.aq. mixture EtOAc (3×10ml), organic layer is dried (MgSO₄) by, a vacuum concentrator. Column chromatography (SiO₂; 100% residue from a gradient Phenylbicyclohexane Phenylbicyclohexane 40% EtOAc/60%)by purifying, white solid as N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(4-(4-(2-(N-(2-hydroxy) ethyl carbamoylalkanoic) pyridyloxy phenylpropionic) urea (0. 019g, 10%)is obtained. 0224 : According to the detailed experimental operation on less then the table in the list of compounds. Illustrative compounds (front view for the characterization of the compound) 0225 : Enteries 1 : 4-the synthesized polyaniline (3-N-carbamoylalkanoic phenoxycarboxylic) according to method A13. According to the method of C3, 4-bis (trichloromethyl) carbonate subsequently (3-N-carbamoylalkanoic phenoxycarboxylic) and reacting to 3-t-butylanilines bisaniline, urea is obtained. 0226 : Enteries 2 : Method A13, according to step 1 and p-4-fluoro-1-by reacting [...] hydroxyacetophenones, 4-(4-aminophenoxy)-1-nitrobenzenesulfonamide is obtained. The method A13, is reduced in accordance with step 4, 4-(4-aminophenoxy) bisaniline is obtained. According to a method C3 3-t-butylanilines 4-bis (trichloromethyl) carbonate (4-acetylthiophenes phenoxycarboxylic) then bisaniline and reaction of urea is obtained. 0227 : Enteries 3 : According to the method C2d, a CDI 3-t-butylanilines, then according to the manufacturing method A8 4-(methyl carbamoylalkanoic 3-N-)-4-methoxy phenoxycarboxylic) and reacting bisaniline, urea is obtained. 0228 : Enteries 4 : According to the method B1, a 5-t-butyl-2-5-t-butyl-2- [...] methoxyaniline converted. This 4-and reacting the isocyanate (3-N-carbamoylalkanoic phenoxycarboxylic) manufactured according to a method A13 bisaniline, urea is obtained. 0229 : Enteries 5 : According to the method C2d, CDI, then 4-(methyl carbamoylalkanoic 3-N-)-4-methoxy phenoxycarboxylic) (manufactured in accordance with the method A8) bisaniline 5-t-butyl-2-and reaction-methoxyaniline, urea is obtained. 0230 : Enteries 6 : The 5-(4-aminophenoxy) isoindolin -1, 3-dione according to method A3. According to the method C2d, 5-t-butyl-2-a CDI and methoxyaniline, then 5-(4-aminophenoxy) isoindolin -1, 3-dione and reacted, urea is obtained. 0231 : Enteries 7 : 4-according to the method A2 (1-oxoisoindolines-5-carbonoyloxysilane) bisaniline synthesized. According to the method C2d, and CDI and 5-t-butyl-2-methoxyaniline, then 4-(1-oxoisoindolines-5-carbonoyloxysilane) and reacting bisaniline, urea is obtained. 0232 : Enteries 8 : 4-according to the method A13 bisaniline synthesis (3-N-carbamoylalkanoic phenoxycarboxylic). According to the method C2a, 2-methoxy-5-(trifluoromethyl) CDI and aniline, then 4-(methyl carbamoylalkanoic Phenoxyalkanoic 3-N-) and reacting bisaniline, urea is obtained. 0233 : Enteries 9 : Method A3, according to step 2, a 4-2-chloro-5-nitropyridine hydroxyacetophenones polypyridine and reacted, 4-(4-aminophenoxy)-5-nitropyridine is obtained. Method A8, according to step 4, 4-(4-aminophenoxy)-5-nitropyridine to 4-(4-acetylthiophenes phenoxycarboxylic-5-is reduced to aminopyrin. According to the method B1, 2-methoxy-5-(trifluoromethyl) 2-methoxy-5-aniline (trifluoromethyl) phenyl isocyanate to conversion. 4-(4-aminophenoxy)-5-aminopyrin by reacting the isocyanate and according to a method C1a, urea is obtained. 0234 : Enteries 10 : Method A13, according to step 1 and p-4-fluoro-1-nitrobenzenesulfonamide reacting hydroxyacetophenones, 4-(4-aminophenoxy)-1-nitrobenzenesulfonamide is obtained. The method A13, step 4 4-(4-aminophenoxy) bisaniline according to the reduction. According to the method of C3, 5-(trifluoromethyl)-2-methoxybutyl bisaniline and screws (trichloromethylpyrimidine) carbonate, 4-(4-aminophenoxy) the adhesivility bisaniline and reacted, urea is obtained. 0235 : Enteries 11 : 4-chloro-N-methyl-2- [...] synthesizing method A2, according to step 3a method A2, according to step 4, 3-amino phenol and used instead of reacting a DMAC DMF, 3-(2-(N-methyl carbamoylalkanoic phenoxycarboxylic)-4-pyridyloxy) bisaniline is obtained. According to the method of C4, 2-methoxy-5-(trifluoromethyl) bisaniline and phosgene, then 3-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) and reacting bisaniline, urea is obtained. 0236 : Enteries 12 : Method A2, according to step 3b, 4-chloro-2-HCl and reacting the ammonia and carbonyl chloride, 4-chloro-2- [...] is generated. The method A2, according to step 4, instead of using a DMAC DMF 3-amino phenol and reacted, 3-(2-Carbamoylpiperidine-4-pyridyloxy) bisaniline is obtained. According to the method C2a, 2-methoxy-5-(trifluoromethyl) bisaniline and phosgene, then 3-(2-Carbamoylpiperidine-4-pyridyloxy) and reacting bisaniline, urea is obtained. 0237 : Enteries 13 : Method A2, according to step 3b 4-chloro-N-methyl-2- [...] synthesized. The method A2, according to step 4, instead of using a DMAC DMF aminosilicone and 4-by reacting phenol, 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) bisaniline is obtained. According to the method C2a, 2-methoxy-5-(trifluoromethyl) CDI and aniline, then 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) and reacting bisaniline, urea is obtained. 0238 : Enteries 14 : Method A2, according to step 3b, 4-chloro-2-HCl and reacting the ammonia carbonylchloride, 4-chloro-2- [...] is generated. The method A2, according to step 4, instead of using the DMAC DMF aminosilicone and 4-by reacting phenol, 4-(2-Carbamoylpiperidine-4-pyridyloxy) bisaniline is obtained. According to the method of C4, 2-methoxy-5-(trifluoromethyl) bisaniline phosgene, then 4-(2-Carbamoylpiperidine-4-pyridyloxy) and reacting bisaniline, urea is obtained. 0239 : Enteries 15 : According to the method C2d, 5-(trifluoromethyl)-2-a CDI and methoxyaniline, then according to the manufacturing method A8 4-(methyl carbamoylalkanoic 3-N-)-4-methoxy phenoxycarboxylic) and reacting bisaniline, urea is obtained. 0240 : Enteries 16 : According to the method A5, 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-2-methylaniline synthesized. Converting methoxyaniline 5-(trifluoromethyl)-2-5-(trifluoromethyl)-2-to [...] according to method B1. 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-2-methylaniline by reacting an isocyanate and according to this method C1, urea is obtained. 0241 : Enteries 17 : According to the method A6 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy-2-chloroaniline synthesized. Method B1 5-(trifluoromethyl)-2-according to methoxyaniline [...] 5-(trifluoromethyl)-2-to the converter. 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy-2-chloroaniline and reacting the isocyanate according to this method C1a, urea is obtained. 0242 : Enteries 18 : Method A2, according to step 4, 5-amino-2-methyl phenol method A2, step 3b according to the 4-chloro-N-methyl-2-and reacting [...] , 3-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-4-methylaniline is obtained. Converting methoxyaniline 5-(trifluoromethyl)-2-5-(trifluoromethyl)-2-to [...] according to method B1. The isocyanate to 3-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-4-methylaniline and reaction according the method C1a, urea is obtained. 0243 : Enteries 19 : Method A2, 4-chloro-2-step 3b according to react and phenoxyethylamine carbonylchloride. 4-amino phenol and reaction method A2, according to step 4 4-chloro-N-ethyl-2-to obtd. [...] , 4-(2-(N-ethyl carbamoylalkanoic)-4-pyridyloxy) bisaniline is obtained. Converting methoxyaniline 5-(trifluoromethyl)-2-5-(trifluoromethyl)-2-to [...] according to method B1. 4-(2-(N-ethyl carbamoylalkanoic)-4-pyridyloxy) by reacting the isocyanate and bisaniline according to method C1a, urea is obtained. 0244 : Enteries 20 : Method A2, according to step 4, the 4-chloro-N-methyl-2- [...] method A2 and reacted, 4-amino-2-Chloropyridin according to step 3b to phenol, 4-(2-(N-methyl carbamoylalkanoic) 3-chloro-4-(pyridyloxy)-aniline is obtained. The converted 5-(trifluoromethyl)-2-5-(trifluoromethyl-2-to methoxyaniline [...] according to method B1. 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-3-Chloropyridin bisaniline and reacting the isocyanate according to method C1a, urea is obtained. 0245 : Enteries 21 : Oxidation of 4-(4- methyl thio phenoxy)-1-alkoxynitrobenzenes method A19, according to step 1, 4-(4-methylsulfonylbenzoylguanidine phenoxycarboxylic)-1-nitrobenzenesulfonamide is obtained. This method A19 alkoxynitrobenzenes, reduced according to step 2, 4-(4-methylsulfonylbenzoylguanidine phenoxycarboxylic)-1-bisaniline is obtained. 4-(4-methylsulfonylbenzoylguanidine phenoxycarboxylic)-1-and reacting bisaniline 5-(trifluoromethyl)-2- [...] according to method C1a, urea is obtained. 0246 : Enteries 22 : Method A15, according to step 4 4-(3-aminophenoxy carbamoylalkanoic)-1-4-(3-aminophenoxy carbamoylalkanoic) alkoxynitrobenzenes bisaniline reduced t 4-(3-aminophenoxy carbamoylalkanoic) by reacting bisaniline and 5-(trifluoromethyl)-2- [...] according to method C1a, urea is obtained. 0247 : Enteries 23 : The 5-(4-aminophenoxy) isoindolin -1, 3-dione according to method A3. Method B1 5-(trifluoromethyl)-2-according to methoxyaniline [...] 5-(trifluoromethyl)-2-to the converter. 5-(4-aminophenoxy) isoindolin -1, 3-dione according to method C1a and reacting the isocyanate, urea is obtained. 0248 : Enteries 24 : Method A2, 4-chloro-2-step 3b according to react and dimethylaminoborane carbonylchloride. 4-amino phenol and reaction method A2, according to step 4 4-chloro-N, N-dimethyl-2-to obtd. [...] , 4-(2-(N, N-dimethylcarbamoyl)-4-Pyridylalkyl bisaniline is obtained. Method B1 5-(trifluoromethyl)-2-according to methoxyaniline [...] 5-(trifluoromethyl)-2-to the converter. 4-(2-(N, N-dimethylcarbamoyl)-4-pyridyloxy) by reacting the isocyanate and bisaniline according to method C1a, urea is obtained. 0249 : Enteries 25 : The 4-(1-oxoisoindolines-5-carbonoyloxysilane) according to method A12 bisaniline. 5-(trifluoromethyl)-2-CDI according to method C2d methoxyaniline, then 4-(1-oxoisoindolines-5-carbonoyloxysilane) treated with bisaniline, urea is obtained. 0250 : Enteries 26 : 4-4-and fluoronitrobenzene hydroxyacetophenones by reacting a method A13, according to step 1, 4-(4-aminophenoxy) obtd. alkoxynitrobenzenes. This alkoxynitrobenzenes method A13, is reduced in accordance with step 4, and 4-(4-aminophenoxy) by bisaniline, according to this method A16 compd. 4-(4-(1-(N-methoxysalicylic) iminoethyl) converted to salt bisaniline phenoxyphenol HCl. Converting methoxyaniline 5-(trifluoromethyl)-2-5-(trifluoromethyl)-2-to [...] according to method B1. 4-(4-(1-(N-methoxysalicylic) iminoethyl) phenoxycarboxylic bisaniline HCl and salt by reacting the isocyanate according to method C1a, urea is obtained. 0251 : Enteries 27 : 4-chloro-N- [...] a method A2, as described in step 3b synthesized. 4-amino phenol and reaction method A2, according to this Chloropyridine step 4, 4-(4-(2-(N-methyl carbamoylalkanoic) and obtd. phenyl thio aniline. Conversion to 5-(trifluoromethyl)-2-5-(trifluoromethyl-2-to methoxyaniline [...] according to method B1, is reacted with 4-(4-(2-(N-methyl carbamoylalkanoic) phenylthioacetic) and according to the same method C1a bisaniline, urea is obtained. 0252 : Enteries 28 : The 5-(4-aminophenoxy)-2-methyl isoindolin -1, 3-dione according to method A9. 5-(trifluoromethyl)-2-methoxyaniline according to method B1 5-(trifluoromethyl)-2-converted into [...] , according to this method C1a 5-(4-aminophenoxy)-2-methyl isoindolin -1, 3-dione and reacted, urea is obtained. 0253 : Enteries 29 : Method A2, 4-chloro-N- [...] according to step 3b synthesized. 3-aminothiophenols reaction method A2 and, according to this Chloropyridine step 4, 3-(4-(2-(N-methyl carbamoylalkanoic) phenylthioacetic) bisaniline is obtained. 5-(trifluoromethyl)-2-methoxyaniline according to method B1 5-(trifluoromethyl)-2-converted into [...] , according to this method C1a 3-(4-(2-(N-methyl carbamoylalkanoic) phenylthioacetic) and reacting bisaniline, urea is obtained. 0254 : Enteries 30 : Method A2, according to step 3b 4-chloropyridine-2-and reactive carbonyl chloride hydroxyisopropyl amine. 4-amino phenol and reaction method A2, according to step 4 4-chloro-N-isopropyl-2-to obtd. [...] , 4-(2-(N-isopropylcarbamoyl)-4-pyridyloxy) bisaniline is obtained. Conversion to 5-(trifluoromethyl)-2-methoxyaniline to 5-(trifluoromethyl)-2- [...] according to method B1, 4-(2-(N-isopropylcarbamoyl)-4-pyridyloxy) by reacting the isocyanate and bisaniline according to method C1a, urea is obtained. 0255 : Enteries 31 : According to the method A14, 4-(3-(5-methoxycarbonyl) bisaniline synthesized. Conversion to 5-(trifluoromethyl)-2-methoxyaniline to 5-(trifluoromethyl)-2- [...] according to method B1, 4-(3-(5-methoxycarbonyl) pyridyloxy) by reacting the isocyanate and bisaniline according to method C1a, urea is obtained. Method D saponificate, according to step 1 N-(5-(trifluoromethyl)-2-methoxyphenyl)-N '-(4-(3-(5-methoxysalicylic sulfonamidecarbonylpyridine) oxymeter) phenyl) urea, 4-(2-aminoethyl) coupling and method D4 dimethylmorpholine, step 2 according to the corresponding acid, amide is obtained. 0256 : Enteries 32 : The 4-(3-(5-methoxycarbonyl) pyridyloxy) according to method A14 bisaniline. 5-(trifluoromethyl)-2-methoxyaniline according to method B1 5-(trifluoromethyl)-2- [...] into, the isocyanate according to method C1a 4-(3-(5-methoxycarbonyl) pyridyloxy) and reacting aniline, and urea. Method D4 saponificate, according to step 1 N-(5-(trifluoromethyl) phenyl)-N '-(4-(3-(5-methoxycarbonyl Pyridylalkyl) oxymeter) phenyl) urea, and coupling method D4 Biphenylmethylamine, step 2 according to the corresponding acid, amide is obtained. 0257 : Enteries 33 : According to the method A14, 4-(3-(5-methoxycarbonyl) pyridyloxy) bisaniline synthesized. Conversion to 5-(trifluoromethyl)-2-methoxyaniline according to method B1 5-(trifluoromethyl)-2- [...] to, 4-(3-(5-methoxycarbonyl) pyridyloxy) by reacting the isocyanate and bisaniline according to method C1a, urea is obtained. Method D4 saponificate, according to step 1 N-(5-(trifluoromethyl)-2-methoxyphenyl)-N '-(4-(3-(5-methoxycarbonyl Pyridylalkyl) oxymeter) phenyl) urea, N, N- dimethyl ethylene diamine and coupling method D4, step 2 according to the corresponding acid, amide is obtained. 0258 : Enteries 34 : According to the method A11, 4-(3-aminophenoxy) bisaniline synthesized. 5-(trifluoromethyl)-2-methoxyaniline according to method B1 5-(trifluoromethyl)-2- [...] into, the isocyanate according to method C1f and 4-(3-aminophenoxy) by reacting bisaniline, N-(5-(trifluoromethyl)-2-methoxyphenyl)-N '-(3-phenoxyphenyl Carboxyamino) and the urea, and according to the same method D1c 3-aminopyrin. 0259 : Enteries 35 : The 4-(3-aminophenoxy) according to method A11 bisaniline. Conversion to 5-(trifluoromethyl)-2-methoxyaniline to 5-(trifluoromethyl)-2- [...] according to method B1, and 4-(3-aminophenoxy) by reacting the isocyanate bisaniline according to method C1f, N-(5-(trifluoromethyl)-2-methoxyphenyl)-N '-(3-carboxyphenyl) urea is obtained. N-(4-fluorophenyl) according to a method D1c and piperazinamide this compound. 0260 : Enteries 36 : The 4-(3-aminophenoxy) according to method A11 bisaniline. 5-(trifluoromethyl)-2-methoxyaniline according to method B1 5-(trifluoromethyl)-2- [...] into, the isocyanate according to method C1f and 4-(3-aminophenoxy) by reacting bisaniline, N-(5-(trifluoromethyl)-2-methoxyphenyl)-N '-(3-carboxyphenyl) and the urea, and according to the same method D1c 4-fluoroaniline. 0261 : Enteries 37 : The 4-(3-aminophenoxy) according to method A11 bisaniline. 5-(trifluoromethyl)-2-methoxyaniline according to method B1 5-(trifluoromethyl)-2- [...] into, the isocyanate according to method C1f and 4-(3-aminophenoxy) by reacting bisaniline, N-(5-(trifluoromethyl)-2-methoxyphenyl)-N '-(3-carboxyphenyl) and the urea, 4-(dimethylamino) according to the same method D1c bisaniline and connected. 0262 : Enteries 38 : The 4-(3-aminophenoxy) according to method A11 bisaniline. Conversion to 5-(trifluoromethyl)-2-methoxyaniline to 5-(trifluoromethyl)-2- [...] according to method B1, and 4-(3-aminophenoxy) by reacting the isocyanate bisaniline according to method C1f, N-(5-(trifluoromethyl)-2-methoxyphenyl)-N '-(3-carboxyphenyl) and the urea, 5-amino-2-and according to the same method D1c methoxypyridine connected. 0263 : Enteries 39 : The 4-(3-aminophenoxy) according to method A11 bisaniline. 5-(trifluoromethyl)-2-methoxyaniline according to method B1 5-(trifluoromethyl)-2- [...] into, the isocyanate according to method C1f and 4-(3-aminophenoxy) by reacting bisaniline, N-(5-(trifluoromethyl)-2-methoxyphenyl)-N '-(3-carboxyphenyl) and the urea, and according to the same method D1c bisaniline morpholmno -4. 0264 : Enteries 40 : The 4-(3-aminophenoxy) according to method A11 bisaniline. Conversion to 5-(trifluoromethyl)-2-methoxyaniline to 5-(trifluoromethyl)-2- [...] according to method B1, and 4-(3-aminophenoxy) by reacting the isocyanate bisaniline according to method C1f, N-(5-(trifluoromethyl)-2-methoxyphenyl)-N '-(3-carboxyphenyl) and the urea, N-(2-Pyridylalkyl) and according to the same method D1c phenylpiperazin connected. 0265 : Enteries 41 : The 4-(3-(N-methyl carbamoylalkanoic) phenoxycarboxylic) according to method A13 bisaniline. According to the method of C3, 4-chloro-3-(trifluoromethyl) is converted to an isocyanate bisaniline, then (3-(N-methyl carbamoylalkanoic) phenoxycarboxylic) and reacting bisaniline, urea is obtained. 0266 : Enteries 42 : 4-according to the method A2 (sulfonylcarbamoyltriazole 2-N-methyl-4-pyridyloxy) bisaniline synthesized. 4-chloro-3-(trifluoromethyl) 4-phenyl isocyanate according to method C1a (sulfonylcarbamoyltriazole 2-N-methyl-4-pyridyloxy) and reacting bisaniline, urea is obtained. 0267 : Enteries 43 : Method A2, according to step 3b, 4-chloro-2-carbonylchloride HCl and reacting the ammonia salt, 4-chloro-2- [...] is generated. 4-amino phenol and reaction method A2, according to this step 4, 4-(2-Carbamoylpiperidine-4-pyridyloxy) bisaniline is generated. According to the method C1a, 4-chloro-3-(trifluoromethyl)-phenyl isocyanate to 4 (2-Carbamoylpiperidine-4-pyridyloxy) and reacting bisaniline, urea is obtained. 0268 : Enteries 44 : Method A2, according to step 3b, 4-chloro-2-carbonylchloride HCl and reacting the ammonia salt, 4-chloro-2- [...] is generated. 3-amino phenol and reaction method A2, according to this step 4, 3-(2-Carbamoylpiperidine-4-pyridyloxy) bisaniline is generated. According to the method C1a, 4-chloro-3-(trifluoromethyl) phenyl isocyanate to 3-(2-Carbamoylpiperidine-4-pyridyloxy) and reacting bisaniline, urea is obtained. 0269 : Enteries 45 : Method A2, according to step 3a, 3-amino phenol and reaction method A2, according to step 4 4-chloro-N-methyl-2- [...] to, 3-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) bisaniline is generated. According to the method C1a, 4-chloro-3-(trifluoromethyl) phenyl isocyanate to 3-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) and reacting bisaniline, urea is obtained. 0270 : Enteries 46 : The 5-(4-aminophenoxy) isoindolin -1, 3-dione according to method A3. According to the method C1a, 4-chloro-3-(trifluoromethyl) phenyl isocyanate to 5-(4-aminophenoxy) isoindolin -1, 3-dione and reacted, urea is obtained. 0271 : Enteries 47 : According to the method A5, 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-2-methylaniline synthesized. According to the method C1e, 4-chloro-3-(trifluoromethyl) phenyl isocyanate to 5-(4-aminophenoxy) isoindolin -1, 3-dione and reacted, urea is obtained. 0272 : Enteries 48 : According to the method of 15, 4-(3-N-methylsulfonylbenzoylguanidine) Phenyloxyaniline) bisaniline synthesized. According to the method C1a, 4-chloro-3-4-(trifluoromethyl) to (3-N-methylsulfonylbenzoylguanidine) phenyl isocyanate Hydroxyphenyloxymethyl) and reacting bisaniline, urea is obtained. 0273 : Enteries 49 : According to the method A6, 4-(2-(N-methyl carbamoylalkanoic) 2-chloro-4-(pyridyloxy)-bisaniline synthesized. According to the method C1a, 4-chloro-3-(trifluoromethyl) phenyl isocyanate to 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-2-chloroaniline and reacted, urea is obtained. 0274 : Enteries 50 : Method A2, according to step 4, 5-amino-2-methyl phenol is 4-chloro-N-methyl-2- [...] (method A2, according [...] 3b) and reacted, 3-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy-4-methylaniline is obtained. According to the method C1a, 4-chloro-3-(trifluoromethyl) phenyl isocyanate to 3-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-4-methylaniline and reacted, urea is obtained. 0275 : Enteries 51 : Method A2, according to step 3b, 4-chloro-2-and reaction phenoxyethylamine calbonyl chloride. 4-amino phenol and reaction method A2, according to step 4 4-chloro-N-ethyl-2-to obtd. [...] , 4-(2-(N-ethyl carbamoylalkanoic)-4-pyridyloxy) and bisaniline. According to the method C1a, 4-chloro-3-(trifluoromethyl)-phenyl isocyanate to 4 (and 2-(N-ethyl carbamoylalkanoic) by reacting bisaniline, urea is obtained. 0276 : Enteries 52 : Method A2, according to step 4, 4-amino-2-chloro-phenol, 4-chloro-N-methyl-2- [...] (method A2, according to step 3b synthetic) and reacted, 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy-3-Chloropyridin bisaniline is obtained. According to the method C1a, 4-chloro-3-(trifluoromethyl) phenyl isocyanate to 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-3-and reacting bisaniline Chloropyridin, urea is obtained. 0277 : Enteries 53 : Method A19, according to step 1, 4-(4- methyl thio phenoxy)-1-alkoxynitrobenzenes oxidized, 4-(4-methylsulfonylbenzoylguanidine phenoxycarboxylic)-1-nitrobenzenesulfonamide is obtained. This method A19 alkoxynitrobenzenes, reduced according to step 2, 4-(4-methylsulfonylbenzoylguanidine phenoxycarboxylic)-1-bisaniline is obtained. According to the method C1a, 4-chloro-3-(trifluoromethyl) phenyl isocyanate to 4-(4-methylsulfonylbenzoylguanidine phenoxycarboxylic)-1-and reacting bisaniline, urea is obtained. 0278 : Enteries 54 : Method A15, according to step 1, and 4-bromobenzenesulfonyl Biphenylmethylamine chloride by reaction, N-methyl-4-bromobenzene sulfoneamide is obtained. Method A15, according to step 2, N-methyl-4-bromobenzene Sulfonamidocarbonylpyridine and coupled with a phenol, 4-(4-(N-methylsulfonylbenzoylguanidine) phenoxycarboxylic) benzene. This compound is converted to 4-(4-(N-methyl Sulfamoylbenzoic) phenoxycarboxylic)-1-nitrobenzenesulfonamide to method 15, according to step 3, 4 is reduced (hydroxypropylsulfamoil 4-N-methyl)-same Hydroxyphenyloxymethyl) bisaniline to method A15, according to step 4. According to the method C1a, 4-chloro-3-4-(trifluoromethyl) to (3-N-Sulfamoylbenzoic) phenyl isocyanate Hydroxyphenyloxymethyl) and reacting bisaniline, urea is obtained. 0279 : Enteries 55 : Method A18, according to step 1, 5-hydroxy-2-methyl pyridine, 1-fluoro-4-and a connecting fluoronitrobenzene, 4-(5-(2-methyl) pyridyloxy)-1-nitrobenzenesulfonamide is obtained. This method A18 to oxidize a carboxylic methyl pyridine, according to step 2, a 4-(5-(2-methoxy carbamoylalkanoic) pyridyloxy)-1-alkoxynitrobenzenes ester in the n This alkoxynitrobenzenes method A18, according to step 3, 4-(5-(2-methoxy calbonyl) pyridyloxy) reduced to bisaniline. 4-chloro-3-by reaction (trifluoromethyl) and according to this method C1a bisaniline phenyl isocyanate, urea is obtained. 0280 : Enteries 56 : Method A18, according to step 1, 5-hydroxy-2-methyl pyridine, 1-fluoro-4-and a connecting fluoronitrobenzene, 4-(5-(2-methyl) pyridyloxy)-1-nitrobenzenesulfonamide is obtained. This oxide to a carboxylic methyl pyridine, method A18, wherein according to the step 2, 4-(5-(2-methoxy calbonyl) pyridyloxy)-1-nitrobenzenesulfonamide is obtained. This alkoxynitrobenzenes method A18, according to step 3, 4-(5-(2-methoxy calbonyl) pyridyloxy) reduced to bisaniline. 4-chloro-3-(trifluoromethyl) phenyl isocyanate bisaniline according to this method C1a and reacted, N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(4-(2-methoxy calbonyl)-5-pyridyloxy) phenyl) urea is obtained. According to this method D2 and reacting Biphenylmethylamine eicosapentaenoate, N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(2-(N-methyl carbamoylalkanoic)-5-pyridyloxy) phenyl) urea is obtained. 0281 : Enteries 57 : According to the method C1d N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(4-aminophenyl) urea is produced. The compound according to monomethylation isophthalate and connecting method D1a, urea is obtained. 0282 : Enteries 58 : According to the method C1d, N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(4-aminophenyl) urea is produced. According to the method D1a, N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(4-aminophenyl) connected to monomethylation isophthalate and urea, N-(4-chloro-3-(trifluoromethyl) phenyl)-N' -(4-(3-methoxysalicylic carbonylphenyl) Carboxyamino aminophenylacetylene) urea is obtained. According to the method of D2, treated with this Biphenylmethylamine urea, corresponding methylamide is obtained. 0283 : Enteries 59 : Method A, according to a step 3b, 4-chloro-2-and reaction dimethylaminoborane calbonyl chloride. 4-amino phenol and reaction method A2, according to step 4 4-chloro-N, N-dimethyl-2-to obtd. [...] , 4-(2-N, N-dimethylcarbamoyl)-4-pyridyloxy) bisaniline is obtained. According to the method C1a, 4-chloro-3-(trifluoromethyl) phenyl isocyanate and reacting on a bisaniline obtd., urea is obtained. 0284 : Enteries 60 : Method A13, according to step 1, and 4-4-fluoronitrobenzene hydroxyacetophenones reacting to, 4-(4-aminophenoxy) obtd. alkoxynitrobenzenes. This reduction of 4-(4-aminophenoxy) alkoxynitrobenzenes bisaniline to method 13, according to step 4, where it is converted to 4-(4-(1-(N-methoxysalicylic) iminoethyl) according to the method A16 bisaniline phenoxyphenol HCl. According to the method C1a, 4-chloro-3-(trifluoromethyl)-4-(4-aminophenoxy) phenyl isocyanate to react and bisaniline, urea is obtained. 0285 : Enteries 61 : Method A13, according to step 2, 4-(3-aminophenoxy)-1-nitrobenzenesulfonamide synthesized. This alkoxynitrobenzenes method A13, 4-(2-aminoethyl) according to step 3 and connected dimethylmorpholine, 4-(3-(N-(2-ethyl morphorinyl) carbamoylalkanoic) phenoxycarboxylic-1-nitrobenzenesulfonamide is obtained. Method A13, according to step 4, this alkoxynitrobenzenes 4-(3-(N-(2-ethyl morphorinyl) carbamoylalkanoic) phenoxycarboxylic) reduced to bisaniline. According to the method C1a, 4-chloro-3-(trifluoromethyl) phenyl isocyanate and react to this bisaniline, urea is obtained. 0286 : Enteries 62 : The 4-(3-aminophenoxy)-1-alkoxynitrobenzenes method A13, according to step 2. This alkoxynitrobenzenes method A13, according to step 3, and 1-(2-aminoethyl) connected aminopiperidine, 4-(2-ethyl piperidylamine) carbamoylalkanoic) phenoxycarboxylic-1-nitrobenzenesulfonamide is obtained. Method 13, according to step 4, a 4-(3-(N-(2- [...]) carbamoylalkanoic) phenoxycarboxylic) reduced to bisaniline. According to the method C1a, 4-chloro-3-(trifluoromethyl)-phenyl isocyanate to 4 (3-(N-(2-ethyl piperidylamine) carbamoylalkanoic) phenoxycarboxylic) and reacting bisaniline, urea is obtained. 0287 : Enteries 63 : The 4-(3-aminophenoxy)-1-alkoxynitrobenzenes method A13, according to step 2. This alkoxynitrobenzenes method A13, according to step 3, and connecting the tetrahydrofolic furfuryl amine , 4-(3-(N-Tetrahydroanthracene propagylfurylmethyl) carbamoylalkanoic) phenoxycarboxylic)-1-nitrobenzenesulfonamide is obtained. A 4-(3-(N-(Tetrahydroanthracene propagylfurylmethyl) carbamoylalkanoic) phenoxycarboxylic) reduced to bisaniline. According to the method C1a, 4-chloro-3-(trifluoromethyl)-phenyl isocyanate to 4 (3-(N-(Tetrahydroanthracene propagylfurylmethyl) carbamoylalkanoic) phenoxycarboxylic) and reacting bisaniline, urea is obtained. 0288 : Enteries 64 : The 4-(3-aminophenoxy)-1-alkoxynitrobenzenes method A13, according to step 2. 2-Methyl-1-ethylascorbic method A13 aminopyrrolidine and connected, this alkoxynitrobenzenes according to step 3, 4-(3-(N-(1-methyl pyrrolidinylquinoline) methyl) carbamoylalkanoic) phenoxycarboxylic)-1-nitrobenzenesulfonamide is obtained. A 4-(3-(N-(1-methyl pyrrolidinylquinoline) methyl) carbamoylalkanoic) phenoxycarboxylic) reduced to bisaniline. According to the method C1a, 4-chloro-3-(trifluoromethyl)-phenyl isocyanate to 4 (3-(N-(1-methyl pyrrolidinylquinoline) methyl) phenoxycarboxylic) and reacting bisaniline, urea is obtained. 0289 : Enteries 65 : Method 2, 4-chloro-N as in the step 3b [...] -synthesized. 4-aminothiophenols and processing method A2, according to this Chloropyridine step 4, 4-(4-(2-(N-methyl carbamoylalkanoic) phenylthioacetic) bisaniline is obtained. According to the method C1a, 4-chloro-3-trifluoromethyl) phenyl isocyanate to 4-(4-(2-(N-methyl carbamoylalkanoic) phenylthioacetic) and reacting bisaniline, urea is obtained. 0290 : Enteries 66 : Method A2, according to step 3b, 4-chloro-2-and reaction calbonyl isopropylchroride with isopropyl amine. 4-amino phenol and reaction method A2, according to step 4 4-chloro-N-isopropyl-2-to obtd. [...] , 4-(2-(N-isopropylcarbamoyl)-4-pyridyloxy) bisaniline is obtained. According to the method C1a, 4-chloro-3-(trifluoromethyl)-phenyl isocyanate to 4 (2-(N-isopropylcarbamoyl)-4-pyridyloxy) and reacting bisaniline, urea is obtained. 0291 : Enteries 67 : According to the method C1e, N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(4-ethoxypurine carbonylphenyl) obtained by synthesizing urea. According to this method D3 saponificate urea, N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(4-carboxyphenyl) urea is obtained. 3-methyl carbamoylalkanoic and connected according to this method D1b bisaniline, N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(4-(3-methyl carbamoylalkanoic phenylpropionic) carbamoylphenyl) urea is obtained. 0292 : Enteries 68 : The 5-(4-aminophenoxy)-2-methyl isoindolin -1, 3-dione according to method A9. According to the method C1a, 4-chloro-3-phenyl isocyanate (trifluorolactic) to 5-(4-aminophenoxy)-2-methyl isoindolin -1, 3-dione and reacted, urea is obtained. 0293 : Enteries 69 : Method A2, according to step 3b, 4-chloro-N- [...] synthesized. 3-aminothiophenols reaction method A2 and, according to this chloropyridine step 4, 3-(4-(2-(N-methyl carbamoylalkanoic) phenylthioacetic) bisaniline is obtained. According to the method C1a, 4-chloro-3-(trifluoromethyl) phenyl isocyanate to 3-(4-(2-(N-methyl carbamoylalkanoic) phenylthioacetic) and reacting bisaniline, urea is obtained. 0294 : Enteries 70 : According to the method A10, 4-(2-(N-(2-dimethylmorpholine-4-ylethyl) carbamoylalkanoic) pyridyloxy) bisaniline synthesized. According to the method C1a, 4-chloro-3-(trifluoromethyl)-phenyl isocyanate to 4 (2-(N-(2-dimethylmorpholine-4-ylethyl) carbamoylalkanoic) pyridyloxy) and reacting bisaniline, urea is obtained. 0295 : Enteries 71 : According to the method A14, 4-(3-(5-methoxycarbonyl) pyridyloxy) bisaniline synthesized. According to the method C1a, 4-chloro-3-same (trifluoromethyl) by reacting and phenyl isocyanate, N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(4-(3-(5-methoxycarbonyl Pyridylalkyl) oxymeter) phenyl) urea is obtained. This method D4 saponificate, according to step 1, 4-(2-aminoethyl) and connected to the corresponding acid dimethylmorpholine, amide is obtained. 0296 : Enteries 72 : According to the method A14, 4-(3-(5-methoxycarbonyl) pyridyloxy) bisaniline synthesized. According to the method C1a, 4-chloro-3-same (trifluoromethyl) by reacting and phenyl isocyanate, N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(4-(3-(5-methoxycarbonyl pyridyloxy) phenylureas is obtained. This method D4 saponificate, according to step 1, and connected to the corresponding acid Biphenylmethylamine, amide is obtained. 0297 : Enteries 73 : According to the method A14, 4-(3-(5-methoxycarbonyl) pyridyloxy) bisaniline synthesized. According to the method C1a, 4-chloro-3-same (trifluoromethyl) by reacting and phenyl isocyanate, N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(4-(3-(5-methoxycarbonyl pyridyloxy) phenyl) urea is obtained. Method D4, according to step 1, it is saponificate, N, N- dimethyl ethylene diamine and connected to the corresponding acid, amide is obtained. 0298 : Enteries 74 : Method A2, according to step 3b, 4-chloro-2-2-hydroxyethyl carbonylchloride HCl and reacted with an amine salt, 4-chloro-N-(2-N-(2-triisopropylbenzene siloxymethanes) ethyl pyridine-2- [...] is generated. According to the method A17, 4-amino phenol and, by reaction, 4-(4-(2-(N-(2-triisopropylbenzene siloxymethanes) ethyl carbamoylalkanoic) pyridyloxy bisaniline is obtained. According to the method C1a, 4-chloro-3-same (trifluoromethyl) by reacting and phenyl isocyanate, N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(4-(4-(2-(N-(2-triisopropylbenzene siloxymethanes) ethyl carbamoylalkanoic) pyridyloxy phenylpropionic) urea is obtained. 0299 : Enteries 75 : 4-chloro-the synthesized polyaniline (3-carboxyphenoxy) according to method A11. According to this method C1f 4-chloro-3-(trifluoromethyl) and phenyl isocyanate and the reaction of urea, and according to the connecting method D1c 3-aminopyrin. 0300 : Enteries 76 : 4-chloro-the synthesized polyaniline (3-carboxyphenoxy) according to method A11. According to this method C1f 4-chloro-3-(trifluoromethyl) phenyl isocyanate and by reaction of urea and, according to the method D1c and N-(4-acetylphenylmethane) piperazine. 0301 : Enteries 77 : 4-chloro-the synthesized polyaniline (3-carboxyphenoxy) according to method A11. According to this method C1f 4-chloro-3-(trifluoromethyl) and phenyl isocyanate and the reaction of urea, and according to the connecting method D1c 4-fluoroaniline. 0302 : Enteries 78 : 4-chloro-the synthesized polyaniline (3-carboxyphenoxy) according to method A11. According to this method C1f 4-chloro-3-(trifluoromethyl) and by reaction of urea and phenyl isocyanate, 4-(dimethylamino) according to the method D1c bisaniline and connected. 0303 : Enteries 79 : 4-chloro-according to the method A11 (3-carboxyphenoxy)-bisaniline synthesized. According to this method C1f 4-chloro-3-(trifluoromethyl) phenyl isocyanate and by reaction of urea and, according to the connecting method D1c and N-phenyl diamine. 0304 : Enteries 80 : 4-chloro-according to the method A11 (3-carboxyphenoxy)-bisaniline synthesized. 4-chloro-3-(trifluoromethyl) and reaction of urea and phenyl isocyanate according to method C1f, and 2-according to the connecting method D1c methoxyethylamine. 0305 : Enteries 81 : 4-chloro-3-the synthesized polyaniline according to method A11 (Carboxyamino phenoxycarboxylic). According to this method C1f 4-chloro-3-(trifluoromethyl) and by reaction of urea and phenyl isocyanate, 5-amino-2-methoxypyridine according to method D1c and connected. 0306 : Enteries 82 : 4-chloro-3-the synthesized polyaniline according to method A11 (Carboxyamino phenoxycarboxylic). According to this method C1f 4-chloro-3-(trifluoromethyl) and phenyl isocyanate and the reaction of urea, and according to the connecting method D1c bisaniline morpholinoandrostane -4. 0307 : Enteries 83 : 4-chloro-3-the synthesized polyaniline according to method A11 (Carboxyamino phenoxycarboxylic). According to this method C1f 4-chloro-3-(trifluoromethyl) and by reaction of urea and phenyl isocyanate, N-(2-Pyridylalkyl) according to the method D1c phenylpiperazine and connected. 0308 : Enteries 84 : Method A2, according to step 3b, 4-chloro-2-2-hydroxyethyl aniline carbonylchloride HCl and reacting salt, 4-chloro-N-(2-triisopropylbenzene siloxymethanes) ethyl pyridine-2- [...] is obtained. According to the method A17, 4-diisopropylbenzene the silyl chloride and then reacting the amino phenol, 4-(4-(2-(N-(2-triisopropylbenzene siloxymethanes) ethyl carbamoylalkanoic) pyridyloxy bisaniline is obtained. According to this method C1a, 4-chloro-3-(trifluoromethyl) by reacting and phenyl isocyanate, N-(4-chloro-3-(trifluoromethyl) phenyl)-N '-(4-(4-(2-(N-2-triisopropylbenzene siloxymethanes) ethyl carbamoylalkanoic) pyridyloxy) phenylureas is obtained. 0309 : Enteries 85 : According to the method A2, 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) bisaniline synthesized. 4-bromo-3-(trifluoromethyl) according to method B1 bisaniline 4-bromo-3-(trifluoromethyl) is converted into a phenyl isocyanate. According to the method C1a, 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) 4-bromo-3-aniline (trifluoromethyl) by reacting and phenyl isocyanate, urea is obtained. 0310 : Enteries 86 : According to the method A6, 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-2-chloroaniline synthesized. 4-bromo-3-(trifluoromethyl) according to method B1 bisaniline 4-bromo-3-(trifluoromethyl) is converted into a phenyl isocyanate. According to the method C1a, 4-bromo-3-(trifluoromethyl) phenyl isocyanate to 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-2-chloroaniline and reacted, urea is obtained. 0311 : Enteries 87 : Method A2, according to step 4, the 4-chloro-N-methyl-2- [...] method A2 and reacted, 4-amino-2-Chloropyridin according to step 3b to phenol, 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-3-Chloropyridin bisaniline is obtained. According to the method B1, 4-bromo-3-(trifluoromethyl) 4-bromo-3-aniline (trifluoromethyl) is converted into a phenyl isocyanate. According to the method C1a, 4-bromo-3-(trifluoromethyl) phenyl isocyanate to 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-3-and reacting bisaniline Chloropyridin, urea is obtained. 0312 : Enteries 88 : Method A2, according to step 3b, 4-chloro-2-and reaction phenoxyethylamine calbonyl chloride. 4-amino phenol and reaction method A2, according to step 4 4-chloro-N-ethyl-2-to obtd. [...] , 4-(2-(N-ethyl carbamoylalkanoic)-4-pyridyloxy) bisaniline is obtained. According to the method B1, 4-bromo-3-(trifluoromethyl) 4-bromo-3-aniline (trifluoromethyl) phenyl isocyanate to conversion. According to the method C1a, 4-bromo-3-(trifluoromethyl)-phenyl isocyanate to 4 (2-(N-ethyl carbamoylalkanoic)-4-pyridyloxy) and reacting bisaniline, urea is obtained. 0313 : Enteries 89 : 3-amino phenol and reaction method A2, according to step 4 4-chloro-N-methyl-2- [...] synthesizing method A2, according to step 3a, 3-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) bisaniline is obtained. According to the method B1, 4-bromo-3-(trifluoromethyl) 4-bromo-3-aniline (trifluoromethyl) is converted into a phenyl isocyanate. According to the method C1a, 4-bromo-3-(trifluoromethyl) phenyl isocyanate to 3-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) and reacting bisaniline, urea is obtained. 0314 : Enteries 90 : Method A2, according to step 4, 5-amino-2-methyl phenol method A2, step 3b according to the 4-chloro-N-methyl-2-and reacting [...] , 3-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-4-methylaniline is obtained. According to the method B1, 4-bromo-3-(trifluoromethyl) 4-bromo-3-aniline (trifluoromethyl) phenyl isocyanate to conversion. According to the method C1a, 4-bromo-3-(trifluoromethyl) phenyl isocyanate to 3-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-4-methylaniline and reacted, urea is obtained. 0315 : Enteries 91 : Method A2, according to step 3b, 4-chloro-2-and reaction dimethylaminoborane calbonyl chloride. 4-amino phenol and reaction method A2, according to step 4 4-chloro-N, N-dimethyl-2-to obtd. [...] , 4-(2-(N, N-dimethylcarbamoyl)-4-pyridyloxy) bisaniline is obtained. According to the method B1, 4-bromo-3-(trifluoromethyl) 4-bromo-3-aniline (trifluoromethyl) phenyl isocyanate to conversion. According to the method C1a, 4-bromo-3-(trifluoromethyl)-phenyl isocyanate to 4 (2-(N, N-dimethylcarbamoyl)-4-pyridyloxy) and reacting bisaniline, urea is obtained. 0316 : Enteries 92 : Method A2, according to step 3b, 4-chloro-N- [...] synthesized. 4-aminothiophenols reaction method A2 and, according to this Chloropyridine step 4, 4-(4-(2-(N-methyl carbamoylalkanoic) phenylthioacetic) bisaniline is obtained. 4-bromo-3-(trifluoromethyl) according to method B1 bisaniline 4-bromo-3-(trifluoromethyl) phenyl isocyanate to conversion. According to the method C1a, 4-bromo-3-(trifluoromethyl)-phenyl isocyanate to 4 (4-(2-(N-methyl carbamoylalkanoic) phenylthioacetic) and reacting bisaniline, urea is obtained. 0317 : Enteries 93 : Method A2, according to step 3b, 4-chloro-N- [...] synthesized. 3-aminothiophenols reaction method A2 and, according to this Chloropyridine step 4, 3-(4-(2-(N-methyl carbamoylalkanoic) phenylthioacetic) bisaniline is obtained. 4-bromo-3-(trifluoromethyl) according to method B1 bisaniline 4-bromo-3-(trifluoromethyl) phenyl isocyanate to conversion. According to the method C1a, 4-bromo-3-(trifluoromethyl) phenyl isocyanate to 3-(4-(2-(N-methyl carbamoylalkanoic) phenylthioacetic) and reacting bisaniline, urea is obtained. 0318 : Enteries 94 : According to the method A10, 4-(2-(N-(2-dimethylmorpholine-4-ylethyl) carbamoylalkanoic) pyridyloxy) bisaniline synthesized. 4-bromo-3-converted (trifluoromethyl) according to method B1 bisaniline 4-bromo-3-(trifluoromethyl) to phenyl isocyanate. According to the method C1a, 4-bromo-3-(trifluoromethyl)-phenyl isocyanate to 4 (2-(N-(2-dimethylmorpholine-4-ylethyl) carbamoylalkanoic) and reacting polypyridine Oxyaniline, urea is obtained. 0319 : Enteries 95 : The 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) according to method A2 bisaniline. According to the method A7, 4-chloro-2-methoxy-5-(trifluoromethyl) synthesized polyaniline, converting the 4-chloro-2-methoxy-5-(trifluoromethyl) phenyl isocyanate according to method B1. According to the method C1a, 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) by reacting the isocyanate and a polyaniline, urea is obtained. 0320 : Enteries 96 : According to the method A6 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-2-chloroaniline synthesized. According to the method A7, 4-chloro-2-methoxy-5-(trifluoromethyl) synthesizing [...] , converting the 4-chloro-2-methoxy-5-(trifluoromethyl) phenyl isocyanate according the method B1. According to the method C1a, 4-(2-N-carbamoylalkanoic)-4-pyridyloxy)-2-chloroaniline and reacting to the isocyanate, urea is obtained. 0321 : Enteries 97 : Method A2, according to step 4, the 4-chloro-N-methyl-2- [...] method A2 and reacted, 4-amino-2-Chloropyridin according to step 3b to phenol, 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-3-Chloropyridin bisaniline is obtained. According to the method A7, 4-chloro-2-methoxy-5-(trifluoromethyl) synthesized polyaniline, converting the 4-chloro-2-methoxy-5-(trifluoromethyl) phenyl isocyanate according to method B1. According to the method C1a, 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy)-3-Chloropyridin by reacting the isocyanate and a polyaniline, urea is obtained. 0322 : Enteries 98 : Method A2, according to step 3a, 3-amino phenol and reaction method A2, according to step 4 4-chloro-N-methyl-2- [...] combined, 3-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) bisaniline is obtained. According to the method A7, 4-chloro-2-methoxy-5-(trifluoromethyl) synthesized polyaniline, converting the 4-chloro-2-methoxy-5-(trifluoromethyl) phenyl isocyanate according the method B1. According to the method C1a, 3-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) by reacting the isocyanate and a polyaniline, urea is obtained. 0323 : Enteries 99 : Method A2, according to step 3b, 4-chloro-2-and reaction phenoxyethylamine calbonyl chloride. 4-amino phenol and reaction method A2, according to step 4 4-chloro-N-ethyl-2-to obtd. [...] , 4-(2-(N-ethyl carbamoylalkanoic)-4-pyridyloxy) bisaniline is obtained. According to the method A7, 4-chloro-2-methoxy-5-(trifluoromethyl) synthesized polyaniline, converting the 4-chloro-2-methoxy-5-(trifluoromethyl) phenyl isocyanate according to method B1. According to the method C1a, 4-(2-(N-ethyl carbamoylalkanoic)-4-pyridyloxy) by reacting the isocyanate and a [...] , urea is obtained. 0324 : Enteries 100 : Method A2, 4-chloro-2-step 3b according to react and dimethylaminoborane carbonylchloride. 4-amino phenol and reaction method A2, according to step 4 4-chloro-N, N-dimethyl-2-to obtd. [...] , 4-(2-(N, N-dimethylcarbamoyl)-4-pyridyloxy) bisaniline is obtained. By 4-chloro-2-methoxy-5-(trifluoromethyl) according to method 7 bisaniline, converting the 4-chloro-2-methoxy-5-(trifluoromethyl) phenyl isocyanate according to method B1. According to the method C1a, 4-(2-(N, N-dimethylcarbamoyl-4-pyridyloxy) by reacting the isocyanate and a polyaniline, urea is obtained. 0325 : Enteries 101 : 3-amino phenol and reaction method A2, according to step 4 4-chloro-N-methyl-2- [...] synthesizing method A2, according to step 3a, 3-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) bisaniline is obtained. Method A1 as described in 2-amino-3-methoxy naphthalene synthesized. 3-bis (trichloromethyl) carbonate then (2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) bisaniline and 2-amino-3-methoxysalicylic reacting naphthalene according to method C3, urea is obtained. 0326 : Enteries 102 : The 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) according to method A2 bisaniline. According to the method A5 5-t-butyl-2-(2, 5- dimethyl pyro rill) synthesized polyaniline, then according to the same method C2d CDI 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) and reacting bisaniline, urea is obtained. 0327 : Enteries 103 : Method A2, according to step 3b 4-chloro-N-methyl-2- [...] synthesized. This method A2, according to step 4, instead of using the DMAC DMF aminosilicone and 4-by reacting phenol, 4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) bisaniline is obtained. According to the method C2b, 3-amino-2-4-and CDI then methoxyacetic Quinolin (2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) bisaniline reaction of bis (4-(2-(N-methyl carbamoylalkanoic)-4-pyridyloxy) phenyl) urea. 0328 : Below a detailed experimental operation of the compound is described. [Table 1] 0329 : [Table 2] 0330 : [Table 3] 0331 : [Table 4] 0332 : [Table 5] 0333 : [Table 6] 0334 : [Table 7] 0335 : In the following table 1-6 on the compound is synthesized by a general method, then a more detailed list of enteries and on experimental operation, is shown in the table, the characterization.