TW379217B - Process for the preparation of arylamides of heteroaromatic carboxylic acids - Google Patents

Description

V. Description of the invention (A7 B7 The present invention relates to a method for preparing an aryl ammonium amine of a heteroaromatic carboxylic acid, which is composed of a heteroaromatic compound, a catalyst and a base, and reacted with carbon monoxide and an aromatic amine. The present invention further relates to a method for preparing an aryl amidine of a heteroaromatic carboxylic acid, which comprises a tertiary substituent or a heteroaryloxy tertiary substituent on a heteroaromatic carboxylic acid. Heteroaryl hydroxy compounds react to produce (hetero) aryloxy serino-to-aromatic squamium compounds' These compounds are further reacted with carbon monoxide and arylamines in a catalyst and a base. The amidines prepared according to the present invention , Its general molecular structure is as follows 3〆, 5

AJ

R6 IN R7 (Please read the notes on the back before filling out this page) Order 0 Printed by the Consumers ’Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs: where A1 is nitrogen or CR1, A2 is nitrogen or CH2, and A3 is nitrogen or CR3, A4 is nitrogen or CR4, and A5 is nitrogen or CR5, the prerequisite is that at least one of the ring members of A1 to A5 is nitrogen, and any two nitrogen atoms are not directly bonded to each other; R to R 'If Among them, for independent hydrogen, one to four carbon papers are applicable to China_ 家 榡 准. (⑽) μ specifications (training 7 today Xian>) • Line-printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs

A7 ____B7 V. Description of the invention (2): --- Atomic alkyl or aryl groups, among the substituents from R1 to P5, there is a group of molecular formula _ OR, and the towel R is ㈣ to replace filaments or filaments. R6 is hydrogen or an alkyl group of one to four carbon atoms; and R7 is an aryl or heteroaryl group optionally substituted. The above-mentioned donkey amines specifically include this bite-, p-dense bite-, p-diazabenzene-, ^ -triazine-carboxylic acid arylamine. ^ Many of these compounds of molecular formula, especially one in which the R1 to R5 substituents are an aryloxy group (-OR) next to the nitrogen atom on a ring, are important herbicides (WO-A 94/27974 , EP-A 0 053 011 and EP-A 0 447 004). These conventional compounds have traditionally been synthesized from the relative acid or acid acid derivatives (acid chloride compounds, esters, and tenths), although these compounds are not readily available and are therefore expensive. Therefore, the object of the present invention is to Easy-to-obtain isolates provide alternative ... According to the present invention, this object can be achieved by the method of applying for patents in the first and the third paragraph of J3. Halogen compounds, the general molecular structure of which is A3 /, A5 Π,

X where A1 to A5 are as defined above and X is chlorine, bromine or iodine. It reacts directly with carbon monoxide and primary or secondary amines in a base. The general molecular structure of this paper applies Chinese National Standard (CNS) A4. Specifications (210X297 mm) (Please read the precautions on the back before filling this page), equipment. Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 __B7 V. Description of the invention (3) The formula is r6-nh-r7 m Among them, R6 and R7 are as defined above. If there is a compound of iridium and diphosphine, the general molecular structure is as follows: R8R9P- [CH2] „-PR10Ru! Y5 When it is used as a catalyst, 'the desired product is almost obtained ( I) in full yield. In the above formula IV, R8 to R11 are independently phenyl or substituted phenyl and are "3 or 4." Here and in the following, alkyl groups of one to four carbon atoms It should be understood that its meaning is a linear and branched first, second or third stage alkyl group containing up to four carbon atoms. Here and below, aryl or heteroaryl groups should be understood Especially monocyclic or polycyclic systems such as phenyl, naphthyl, biphenyl Group, 1 group, furyl group, azapentyl group, pyrazolyl group, phenylthio group, pyridyl group, indyl group, or lymophilic group. These may have one or more of the same or different substituents, such as Low alkyl groups such as methyl, alkylated groups such as trifluoromethyl, alkoxy groups with lower carbon number such as methoxy or alkylthio groups with lower carbon number or: Methylthio or ethylsulfate. Substituted phenyl should be understood and its meanings are in particular, for example, (Shou) phenyl, (Shou-) methoxyphenyl, (Shou) tolyl or (# /-) triphenyl Fluorofluorenylphenyl. Halogen compounds (Π) used as starting materials are conventional compounds or analogs are prepared as conventional compounds. A large number of such compounds have been published 'for example in US-A 4 254 125 and EP-A 0 001 187. I mount I order (please read the precautions on the back before filling this page)

-7- Description of the invention (The compound (II) can be advantageously prepared by 10,000 methods, in which the scale of the formula -OR is bonded to the carbon atom next to the nitrogen atom on the-ring, the halide in the method, which is generally The molecular structure is A4,

V, where A1 to A5 are as defined above, and its precursor is one of the substituents ⑷ to ^ on the carbon atom next to the upper atom: Z is chlorine, bromine or sulfone and X is with it Independent chlorine, bromine, and heteroaryl compounds are reacted. The general molecule and the conversion formula are as follows.

R-OH Printed by the Central Standard of the Ministry of Economic Affairs, Consumer Cooperatives, where R is the definition as read. The two-stage method comprising this reaction and the reaction of _ and (m), in the manner described above, will be described in more detail below for the "other-purpose", and the preferred practical side to which the same applies. The preparation method of the present invention is more suitable for preparing amidine (丨), wherein ¥ is nitrogen and the other ring members form the pyrimidine ring. Where R1 is a group of molecular formula '_〇r, R is amidamine (T) as defined above is acetophenone: preferably _⑴ is, those with: nitrogen and the other ¥ tg form this pyridine ring, those Where A1 and A5 are nitrogen and form a pyrimidine ring with the other ring members,

| _; ^ ----- I-^ ----- ^ ------- ^ (Please read the notes on the back before filling out this page) Printed by A7, Consumers Cooperative of the Central Standards Bureau, Ministry of Economic Affairs -----; _B7____ V. Description of the invention (5) ^ ~~ --- ~ Those in which A and A4 are nitrogen and the other ring members form a p-diazabenzene ring and those in which A1, A3 and A5 are nitrogen * And the rest of the ring-shaped elements, 3,5_ triazabenzene ring. Of the above four species, those in which R2 is a group of molecular formula _OR, and R is amidamine as defined above, are particularly preferred in that order. Other preferred amidines (I) are those of the phenyl group in which R is an optionally selected substituent. It is particularly suitable for the above-mentioned amidines containing peach, pyrimidine, diazabenzene or 1,3,5-triazabenzene ring, wherein R1 or R2 is a group of molecular formula _OR. Other preferred amidines are those of the phenyl group in which R6 is hydrogen and R7 is an optionally selected substituent. The preferred halogen compound (II) is a gaseous compound (χ = α). Catalytically active hydrogenated compounds in the form of a finely divided element (such as palladium on activated carbon), palladium (π) salts (such as chloride or acetate), or suitable palladium (II) complexes (For example, dichlorobis (triphenylphosphine) face (π), and the method of reaction with diphosphine is effectively formed in situ. The preferred amount of palladium used is 0.02 to 0.2 mole percentage of palladium (Π ) Or 0.5 to 2 mole percentage of the face (0) (such as pwc), based on _ compound (II) under each condition ^ It is best to use an excessive amount of diphosphorus lice (based on face), which is more than A preferred use amount is 0.02 to 5 mole percent, which is also based on the halogen compound (II). The solvent used may be relatively non-polar, such as toluene or xylene, or polar, such as etham, tetrahydrofuran or Long preparation of dimethyl ethyl donkey amine. The test used is preferably a relatively weak test. It does not need to be soluble in the quilt. -1. Line (Please read the precautions on the back before filling out this page) This paper ruler and the general T storehouse standard (CNS) A4 size (210x29 ^ in the Ministry of Economic Affairs Standard Bureau employee consumer cooperatives printed A7 B7 V. Description of the invention (6) The solvent used. Suitable bases are carbonates such as sodium carbonate or potassium carbonate, or acetates such as sodium acetate. Particularly good results are obtained with sodium acetate. The preferred reaction temperature is 80 to 250. (:. The preferred carbon monoxide pressure is 1 to 50 bar. The following examples are provided to illustrate how to make the method according to the present invention. Example 1 2-Chloro-6- [3- (trifluoromethyl) phenoxy] 17.45 g (690 mmol) of sodium hydride (95%) was suspended in 420 ml of crocetin-dimethylacetamide. 107 The gram (658 millimoles) of 3 · (trifluoromethyl) g was added dropwise at 2 hours over 15 hours. The resulting phenate solution was added dropwise at 2.5 hours under nitrogen containing 162.4 grams (1.097 Moore) 2,6-dichloro pillow was deposited in 330 ml of Dragon, Li-dimethylacetamide solution and heated to 90 ° C. After another 3 hours of reaction time the mixture was cooled to room temperature The precipitate of sodium chloride was filtered out, and the filtrate was concentrated. The residue was toluene and 0.1N hydrochloric acid. The organic layer was washed with a saturated sodium chloride solution and concentrated. The oily residue (about 200 grams) was evaporated under vacuum. Yield: 151.5 grams (84%) of a colorless oil, Analysis by phase chromatography) 99.8% refractive index ("d2C >) = 1.5267 mass spectrometer; mass-to-charge ratio (w / 〇: 273/275; 238; 39 hydrogen-nuclear magnetic resonance spectrometer (trichloromethane)): (5 = 6.84 (d, J = 7.8Hz, 1H); 7.07 (d, J = 7.8Hz, 1H); 7.35 (m, 1H); 7.42 (m, 1H); 7.45-7.52 The paper dimensions are applicable to Chinese national standards ( CNS) A4 specification (2 丨 οχ ”7mm) • 10- (Please read the precautions on the back before filling out this page). Installation.-Order and invention description ((m, 2H); 7.65 (t, · // = 7.8 Hz, 1H). C13-NMR spectrometer (trichloromethane): ^ = 109.88 (CH); 118.16 (CH); 119.24 (CH); 121.67 (CH); 123.74 (CF3); 124.50 (CH); 130.24 (GH) ); 132.21 (CCF3); 141.77 (CH); 149.12 (C); 153.89 (C); 162.28 (C) 〇 Example 2 [3- (trifluoromethyl) phenoxy] this pyridine 7.68 g of sodium hydride After the dispersion (approximately 50% in mineral oil) was purged with pentane under nitrogen, 100 ml of fan-fanyldimethanamine was added. 21.92 g (135 mmol) of 3 · (trifluoromethyl) phenol was added dropwise dropwise over 30 minutes in i · W. The obtained fermented salt solution was added dropwise dropwise under nitrogen for 2 hours to a solution containing 20.1 g (136 millimoles) of 2,3-dichloropyridine in 80 ml of agrosol dimethylformamide, And heated to 120. (: After a reaction time of 3 hours, the mixture was cooled to room temperature, the precipitate of sodium chloride was filtered out, and the filtrate was concentrated. After the residue was extracted with toluene and 0.1N hydrochloric acid, the organic liquid layer was The saturated sodium fluoride solution was washed and concentrated. The oily residue was distilled under vacuum. Yield: 24.75 g (67%) colorless oil, content (analyzed by gas chromatography) 99.7% boiling point is 145- 148 ° C refractive index (t? D2G) = 1.5282 (Please read the precautions on the back before filling this page).

. • IT-Printed by the Consumers' Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs, this paper is approved to comply with the Chinese National Standard _ (CNS) A4 Specification (21 () &gt; &lt; 297 public i! A7 B7 V. Description of the invention (8) Mass spectrometer; Mass-to-charge ratio (speaking ^): 2 3/275 hydrogen-nuclear magnetic resonance spectrometer (trichloromethane): ^-6.99 (m, 1H); 7.36 (d , 1H); 7.45-7.53 (m, 3H); 7.77 (Mountain 1H); 8.02 (d, 1H). Carbon thirteen nuclear magnetic resonance spectrometer (trichloromethane): ^ ^ 118.66 (CH) &gt; 119.44 (CH); 119.98 (CH); 12175 (CH); 123.78 (CF3); 124.94 (CH); 130.13 (CH); 132.16 (CCF3); 139.65 (CH); 145.20 (CH); 153.88 (C) 158.51 (C) 〇 Example 3 Preparation of (4-fluorophenyl) -6- [3- (trifluoromethyl) phenoxy] benzyl-2-hydrocarbyloxamine 6.84 g (25 mmol) ) 2-Ga-6- [3- (trifluoromethyl) .phenoxy] pillow (content: 99.5%, prepared according to Example 1), 4.17 g (37.5 mmol) of 4-fluoro Aniline, 2.92 g (27.5 mmol) sodium carbonate, 0.27 g (27 g) 0.25 mol) face / activity barrier (10 and 0.32 g (0.75 mol) of ι, 4-bis (diphenylphosphino) butane (IV, << = 4, R8 = R9 = r1 = R11 = phenyl) was placed in an autoclave in 25 ml of xylene at room temperature. This autoclave was filled with an inert gas, and after adding carbon monoxide at a pressure of 5 bar, the temperature was raised. To 200 ° C. The pressure of carbon monoxide was increased to 14.5 bar, and the mixture was stirred for 16 hours at 200 ° C. After cooling to room temperature and reduced pressure, the reaction mixture was mixed with 50 ml of xylene and 50 ml of This paper size is applicable to China National Standard (CNS) A4 specification (210X297mm) -12- ---------- ^! (Please read the precautions on the back before filling this page) Order-Line Economy Printed by A7 B7 in the Consumer Cooperatives of the Ministry of Standards of the People's Republic of China 5. Description of the invention (9) ~ Water treatment and filtration. The aqueous layer is extracted with 25 ml of xylene, and all organic liquid layers are washed with 30 ha; the water is washed. Dissolved The composition of the product was determined by gas chromatography analysis. The title compound (donkey amine) was found to have a content of 921% '1.9% isolated And 6.0% of by-products (3.1% of secondary amines' are formed by direct substitution of aniline with chlorine, and 2.9% of 2- [3 · (trifluoromethyl) phenoxy] is pyridine and is hydrolyzed by Formed). After the solvent was distilled off, the obtained crude product (8,63 g) was obtained as a yellow solid. This crude product was purified by recrystallization from methylcyclohexane. Yield: 6.3 g (67%) of colorless crystals. Melting point: 104-105 mass spectrometer; mass-to-charge ratio (m / 2): 376 (JVT), 238 hydrogen-nuclear magnetic resonance spectrometer (trichloromethane): δ = 6.99-7.04 (m, 2Η); 7.17 (d, J = 8.4 Hz, 1H); 7.40 (m, 1H); 7.46-7.51 (m, 2H); 7,55-7.63 (m, 3H); 7.93 ( t, J = 7.8 Hz, 1H); 8.03 (d5 «/ = 7.8 Hz, 1H); 9.24 (br. m, 1H). Example 4 (4-Fluorophenyl) -6- [3- (trifluoromethyl) phenoxy] is required to bite_2-hydrocarbylamine except 17.5 mg (25 mmol) of palladium / activated carbon Ear) of digas bis (triphenylphosphine) palladium (Π) substitution, the experimental procedure is as described in Example 3. The carbon monoxide pressure was 12.8 bar, the temperature was 150 ° C and the reaction time was 17.7 hours. The composition of the product dissolved in xylene was determined by gas chromatography. It was found that the title compound (ammonium amine) with a content of 96.0% and 4.0% of this paper standard is applicable to the Chinese National Standard (CNS) A4 specification (210X297) ---------- ά —-----, 耵------ Silk please read the notes on the back before filling in this page} A7 B7 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (10) By-products (2.3% secondary amine , 17% of the product of hydrogenolysis). Example 5 Preparation of (4-fluorophenyl) -6- [3- (trifluoromethyl) phenoxy] This disease _2_nicotinylamine except 1,4 -Bis (diphenylphosphino) butane was substituted with n bis (diphenylphosphino) propane (IV, << = 3, R8 = R9 = R10 = R-fluorenyl) with the same molar amount, experimental procedure As described in Example 4. The pressure of carbon monoxide was 16 bar and the reaction time was 21.6 hours. The composition of the product dissolved in xylene was determined by gas chromatography analysis. The title compound (amimine) was found to be 98.9% by 0.1% The educts and 1.0% by-products (0.3% of secondary secondary amines and 0.7% of chlorolysis products). Example 6 Preparation of (2,4-difluorophenyl) -2- [3_ (tri Fluoromethyl) phenoxy] this lake_ Dihydrofenicam (Diflufenicam) Similar to Example 4 '6.84 g (25 mol) of 3-chloro-2_ (3-trifluoromethyl) phenoxy lake (prepared according to Example 2 ), 4.84 grams (37.5 millimoles) of 2,4-difluoroaniline, 2.92 grams (27.5 millimoles) of sodium obstruction, 17.5 mg (25 millimoles) of dichlorobis (triphenylphosphine) Hydrogen) palladium (II) and 0.32 g (0.75 mmol) of 1,4-bis (diphenylphosphino) butane in 25 ml of xylene at 190-195 ° C and 15 bar of carbon monoxide It was reacted under pressure for 19 hours. The conversion rate was about 80%. »Same as in Example 3. This mixture was extracted to obtain 6 g of crude product, which was a yellow crystalline solid. Applicable to China National Standard (CNS) A4 (210X297mm) • 14- ^ 9 (Please read the notes on the back before filling this page)

Printed by the Employees' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. 5. A description of the invention (11) of Jiaji has been re-purified. Yield: 3.25 g (33%) of a white solid. Melting point: 157-159. (: Mass spectrometer; mass-to-charge ratio (_): 394 (] \ 〇, 266 (100%) nitrogen-nuclear magnetic resonance optical display (trichloromethane: ^ = 6.89-6.96 (m, 2H); 7 26 (^ lH); 7.46 (m5 1H) '7.54-7 · 63 (m, 3H); 8 28 (dd, 1H); 8.52 (m, 1H); 8 71 (this 1H); 9 97 (chemical s, m) ° Comparative Example 1 except that Z 1,4-bis (diphenylpentyl) butyl green has the same molar amount of triphenylphosphine substitution '. The experimental procedure is as described in Example 4. After passing through A reaction time of 15 5 hours and a pressure of 15 bar-carbon oxide, the composition of the product dissolved in xylene was determined by gas chromatography analysis. Only 43 2% of the desired product and 56.8% of unconverted eluates were found. Control implementation Example 2 Except that 1,4-bis (diphenylphosphino) butane was replaced with the same molar amount of tri-tri-butylphosphine. The experiment is exactly as shown on the side 4. The reaction time is too small and the 14 bar Carbon monoxide pressure, the composition of the product dissolved in xylene was determined by gas chromatography analysis. Only a trace amount (04%) of the desired product and 96.8% of the unconverted isolates were found. Comparative Example 3 Diphenylphosphine ) Butane was replaced by the same molar amount of bis (diphenylphosphino) ethane, and the experimental procedure was as described in Example 4. This paper size is applicable to China National Standard (CNS) A4 specification (210X297 male body --- ------ i-Seeds .. Thread (please read the precautions on the back before filling this page) A7 B7 V. Description of the invention (l2) After a reaction time of 20.2 hours and a carbon monoxide pressure of 147 bar, = The product composition of xylene was determined by gas chromatography analysis. Only a small amount (2.2%) of the desired product and %% of unconverted isolates were found. (Please read the precautions on the back before filling this page)- Packing · -Ordering, painting, sr silk 丨 Printed in paper size applicable towels by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs!) Home Turn (CNS) A4 size (21Qx297 male thin) -16-

Claims (1)

rnimm: S? ^ 2j, 7 A8 B8 C8 D8 IMMjgZ patent application for a special brake sacrifice original A method for the production of amidine, its general molecular structure is as follows: AV 0 R6 IN R7 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs where A1 is nitrogen or CR1, A2 is nitrogen or CR2, A3 is nitrogen or CR3, A4 is nitrogen or CR4, and A5 is nitrogen or CR5. The prerequisites are: , At least one of the ring members of A1 to A5 is nitrogen and any two nitrogen atoms are not directly bonded to each other; if R1 to and 5 'are present, they are independent hydrogens, and an alkane of one to four carbon atoms Or aryl, one of the substituents of R1 to R5 is a group of the formula -OR, wherein r is an aryl or heteroaryl group of optionally selected substituents; R6 is hydrogen or an alkyl group of one to four carbon atoms; and R7 is an aryl or heteroaryl group with optional substituents. It is characterized as a monodentate compound. Its general molecular structure is as follows: (Please read the precautions on the back before filling out this page} 1C. Guan Jia Standard (November) from the threat (21 () &gt; &lt; 297 public 3 rnimm: S? ^ 2j, 7 A8 B8 C8 D8 IMMjgZ patent application for a special brake sacrifice original A method for the production of amidine, its general molecular structure is as follows: AV 0 R6 IN R7 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs where A1 is nitrogen or CR1, A2 is nitrogen or CR2, A3 is nitrogen or CR3, A4 is nitrogen or CR4, and A5 is nitrogen or CR5. The prerequisites are: , At least one of the ring members of A1 to A5 is nitrogen and any two nitrogen atoms are not directly bonded to each other; if R1 to and 5 'are present, they are independent hydrogens, and an alkane of one to four carbon atoms Or aryl, one of the substituents of R1 to R5 is a group of the formula -OR, wherein r is an aryl or heteroaryl group of optionally selected substituents; R6 is hydrogen or an alkyl group of one to four carbon atoms; and R7 is an aryl or heteroaryl group with optional substituents. It is characterized as a monodentate compound. Its general molecular structure is as follows: (Please read the precautions on the back before filling out this page} 1C. Guan Jia Standard (November) Congxue (21 () &gt; &297; 3 3-· ~ -__ VI. Patent Application Park A8 Β8 C8 D8 // K, A5A ^ a- Π, X Intellectual Property Office, Ministry of Economy Printed by the Employee Consumption Cooperative where A1 to A5 are as defined above and x is chlorine, bromine or iodine, directly with monooxygen Carbon and amine, its general molecular structure is as follows: R6-NH-R7 πΐ, where R6 and R7 are as defined above, in the complex compound of palladium and europium diphosphide, its general molecular structure is as follows: Rs ^ -m2 ] n ~ m10R11 iv, where R8 and R9 are independent phenyl or substituted phenyl and η is 3 or 4, and the reaction is checked. 2. According to the production method described in item 1 of the scope of patent application, where , A2 is nitrogen and is a bite of a bite than the Yodo ring. 3: According to the manufacturing method described in item 2 of the scope of patent application, wherein R1 is a group with a formula of -OR, and R is as item 1 of the scope of patent application 4. According to the manufacturing method described in item 1 of the scope of the patent application, wherein A1 is nitrogen and is a portion of a bito ring. '5. According to the manufacturing method described in item 1 of the scope of patent application, wherein A1 and A5 is the part of the ring that is seen and shouted. 6. According to the manufacturing method described in item 1 of the scope of the patent application, where A1 and A4 are nitrogen and are a pair of diazabenzene rings. This paper X 渡 逋Use Chinese national standard (c secret) eight-view ^ (2ι〇χ297 mm) (Please read the precautions on the back before filling this page) I— I. Yu m II I 11— · -18-B7 &amp; 217 A8 B8 C8 D8 6. Scope of patent application 7. According to the manufacturing method described in item 1 of the scope of patent application, where A1, A3, and A5 are nitrogen. 8. According to the patent application park The manufacturing method according to item 4, 5, 6 or 7, wherein R2 is a group with a molecular formula of -OR, and R is as defined in item 1 in the scope of patent application. 9. According to the method in item 3 of the scope of patent application Wherein, R is a phenyl group of optionally selected substituents. 10. The production method according to item 1 of the scope of the patent application, wherein R6 is fluorene and R7 is a phenyl group of an optional substituent. 11. The method according to item 1 of the scope of patent application, wherein X is chlorine. 12. The method according to item 1 of the scope of patent application, wherein the phosphonium (IV) diphosphonium used is 1,3-bis (diphenylphosphino) propane or 1,4-bis (diphenylphosphine) A) butane. 13. According to the method for preparing amidine as described in item 1 of the scope of patent application, its general molecular structure is as follows: A. R6 N --C --------, Elephant-(Please read the note on the back first Please fill in the matter again for the matter.), -Β · Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 0 R7 Among them, in the first reaction, the general molecular structure of the dihalide is as follows: The paper scale is applicable to Chinese national standards (CNS) Λ4 specification (210X297 mm) -19- ^ 702x7 ----- Patent application scope A8 B8 C8 D8 z XA5 V, X where A1 to A5 are as defined in item 1 of the Chinese Patent Application Park, which is prerequisite. Niu 1 is one of the substituents on the carbon atom next to the milk atom on the ring = to R, substituted by Z , Z is chloro, o or ox, and x is independent of chloro, mo, or squatting, and reacts with aryl or heteroaryl light compounds. Its general molecular structure is as follows: .. R-OH VI. = 中R is as defined in item 1 of the scope of the patent application, and a (hetero) aryloxy compound is obtained. Its general molecular structure is as follows: Pi / y XA5 Wherein A1 to A5, R and x are as defined above, and the general molecular structure of the above products and carbon monoxide and amine in the second step reaction is as follows: ΙΓ, printed by the Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs r6-nh- r7 ΠΙ, where R6 and R7 are as defined above, in the complex compound of palladium and diphosphine, its general molecular structure is as follows: R8R9P- [CH2] M-PR10Rn rv, (Please read the precautions on the back first (Fill in this page again) CNS} A4 ~ ^ (210x29_7 ^) A8 B8 C8 D8 Patent application range Among them, R8 to R11 and η are as defined in item 1 of the patent application range, and they react with the first test. (Please read the precautions of the West before filling out this page.) Packing-&lt; 11 Printed by the Employees' Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs This paper uses the Chinese National Standard (CNS) Α4 specification (210 ×