TW387888B - Novel quinolone-or naphthylidone-carboxylic acid derivatives or their salts - Google Patents

Description

C; '!:' O'wi i. ^ -R victorius NIHJJ02! I 71 I mg T3 5 chamber mm D > 萏 0.012 0.025 0.006 0.012 03 4 Ling 0.0121 ρ mmk 0.012 0.05 00 > -Cf〇o § < 0.006 0.05 < 0.006 0.012 00 I \ \ < 0.006 ρ 0.012 0.025 00 s 1.56 〇p 00 fttVcooh ΗΝ〇Γϊί ^ M · CHjCHaF 0.05 0.39 0.05 0.05 00 0 Fy ^ A ^ COOH 0.025 ο r〇0.051 0.0251 CO o ^ xr $; #

: ¾ 腾 # 菌 NIHJJC ~ 2 I 1 1 w I T 1 1 T1 § Ό 1 fr Rong '0.003 0.025 0.006 0.006 00 BU Q. 0 0 0.012 < 0.006 < 0.006 < 0.006 00 i \ 0 § 1 0.05 < 0.012 < 0.012 < 0.012 CO ffv ^ Vcooh ΗΝ〇φτχ ^ F 0.05 〇 ho p p CO 々1. 1 < 0.006! 0.025 < 0.006 (0.012 00 OMe ^ 0.025 0.05 0.025 0.025 00 〇Me 0.051 0.051 0.051 0.051 CO 1 E. coli NIHJJ02 1 1 1 snow 71 莒% 1 τι g 1 m 缂 compound 1 3.13 1,56 ο fo '0.39: σ > fXjCVc〇〇h NH 丨 3.13 0.012 0.012 0.012 i § 0.006 ο fo 0.012 0.012 00 i § 0.025 0.78 0.025 0.05 CO k 0 丨 0.006 ο FO 0.025 0.012 00% o §. < 0.006 0.05 < 0,006 < 0.006 CO O § 99a Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7___ V. Description of the invention (,) TECHNICAL FIELD The present invention is not limited to Gram's clarity «and Gram-negative 别MRS A has neopentanone or erythridone-carboxylic acid derivative represented by the general formula [I] with selective anti- «activity. BACKGROUND ART As a synthetic antibacterial agent for linolinone, hitherto has been widely used on beds Norfloxacin, Ciprofloxacin, »Ofloxacin, etc., but MRSA does not have sufficient activity for the Rhododendron genus 0, especially MRSA, so I hope that this kind of details ® Synthetic Antibacterial Beta with Effective Pan-Anti-Glycemic Formula 91 Presentation of the invention In this case, the inventor carried out a bottom-out study and found that the folinone- or erythridone-carboxylic acid derivative or its salt represented by the general formula [I] has excellent antibacterial activity: 5

R

R 2 ο wherein R1 represents a hydrogen atom or a carboxyl carboxyl group; R2 represents a substituted or unsubstituted alkyl, alkenyl, alkylene, aryl, or heterocyclic group; R3 represents at least one of : Hydrogen atom, halogen atom, substituted or unsubstituted alkyl group, alkenyl group, alkenyl group, aryl group, alkane group or alkylthio group, nitro group, fluorenyl group, fluorenyl group, protected or unprotected The hydroxyl group of this paper is applicable to China National Standard (CNS) A4 specification (210X297 mm) according to this paper standard --------- * Packing ----- 1T--M ---- "line (please Please read the notes on the back before filling out this page) 5. Description of the invention (>) A7 B7 Protected or unprotected carbonylalkyl, protected or unreserved amine, protected or unreserved Alkylamino, dialkylamino, protected or unprotected amidyl, protected or unspectrumed alkylamine alkyl and dialkylamine alkyl; R4 represents at least one of the following: hydrogen Atoms, halogen atoms substituted or unsubstituted alkyl, alkenyl, cycloalkyl, aralkyl, aryl, alkanoyl or alkane bases, protected or unprotected hydroxyl groups, protected Unreserved hydroxyalkyl, protected or unprotected amine, protected or unprotected alkane, dialkylamino, protected or unprotected amine alkyl, protected or Unprotected alkylamine alkyl, dialkylamine alkyl, alkylene, oxy, imine and sulfonium atoms bonded to R4 to form a sane ring; Rs represents a hydrogen atom, substituted or unsubstituted Substituted alkyl, cycloalkyl, alkylsulfonyl, arylsulfonyl, fluorenyl or aryl, protected or unprotected amine alkyl, protected or unprotected alkylamine alkyl, dioxane Aminoalkyl or hydroxyalkyl protected or unprotected; Re means fluorene atom, halogen atom, substituted or unsubstituted alkyl, alkyl or alkyl group, protected or unprotected hydroxy group, Protected or unprotected amine or nitro

Or V, where Y represents a plutonium atom --------- (, — install ------ order-> ---- (line (please read the precautions on the back before filling this page) The Central Standards Bureau of the Ministry of Economic Affairs prints a rubidium atom, a substituted or unsubstituted alkyl group, an alkyl group or an alkyl group, or a protected or unprotected hydroxyl group or R2 to form a base represented by the following formula:丨 B where R7 represents at least one of the following: hydrogen atom, alkyl group, haloalkyl group, protected or unprotected hydroxyalkyl group, alkylene group and bond with 87

R7 This paper size applies Chinese National Standard (_CNS) A4 specification (210X297 mm) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (4) The base of the erbium atom generates a base of alkane, and B Represents a fluorene atom, a sulfur atom, or an imine group which may be substituted by an alkyl group; and X represents a fluorene atom or a halogen atom, and thus the invention is completed. The present invention is explained in detail in the following β. Explain that unless the S line is specified in the 軎, the term " halogen atom " means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom; the term " alkyl " Ci-10 alkyl such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, second butyl, third butyl, pentyl, hexyl, heptyl, octyl, etc. &Quot; Lower alkyl " means straight or branched "C 1-5 alkyl such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, second butyl , Third butyl, pentyl, etc .; "Alkyl" refers to a straight or branched chain, such as a methyl group, a methyl group, a methyl group, an n-propyl group, an isopropyl group , N-butylfluorenyl, isobutoxy, second butanyl, third butoxy, pentyl, hexyl, heptyl, octyl, etc .; " lower alkyl " Straight or branched (31-5 alkyl groups such as methylamino, ethyl «, n-propanyl, isopropoxy, n-butanyl, isobutanyl, second butoxy, third butane Gasoyl, pentyloxy, etc .; " Alkylthio > The term quot means a linear or branched «Ci-! 〇 alkylthio group such as methylthio, ethylthio, n-propylthio, isopropylthio, n-butyl«, isobutylthio, second butylthio Group, third butylthio group, pentylthio group, hexylthio group, heptyl group, octylthio group, etc .; the term "lowly alkanoyl" means a straight or branched Ci-5 alkylthio group such as methylthio , Hexylthio, n-propyl base, isopropylthio, n-butylfluorenyl, isobutylthio, second butylsulfanyl, third butylsulfanyl, pentylthio, etc .; " fluorenyl •• means a formyl group , Linear or branched c2-S alkyl fluorenyl group such as ethyl fluorenyl group, this paper size applies the Chinese National Standard (0NS) A4 specification (210X297 mm) ----------- ^ < pack- ----- Order —- ^ ---- f line (please read the notes on the back before filling this page) Printed by A7 __ B7_ of the Consumer Co-operation of the Central Standardization Bureau of the Ministry of Economic Affairs V. Description of the Invention (4) Ethylcarboxyl, etc. or arylfluorenyl, such as benzamyl, lysyl, etc .; " low-nitroalkane carbonyl " means a straight or branched Ci-salkanecarbonyl group, such as methylamino, ethoxy Yiji, n-propyl, carbonyl, isopropyl *, butyl, carbonyl, isobutyl Carbonyl, second butane carbonyl, third butane fluorenyl, pentane carbonyl, etc .; " alkylamino " means a straight or branched bond ^^-ω alkylamino such as methylamino, ethylamino , Propylamino, butylamino, pentamine, hexylamine, heptylamine, octylamine, etc .; "lower alkylamino" means a straight or branched Ci-s alkylamino group such as methylamine -Ethylamino, propylamino, etc .; the term "dialkylamino" means a dimer or branched Ci-1D alkylamino group such as dimethylamino, diethylamino, methylethylamino, dipropylamino , Dibutylamino, dipentylamino, dihexylamino, diheptylamino, dioctylamino, etc .; " Di-oligomeric alkylamino " means the two straight «or branched Ci-s alkane According to groups such as dimethylamino, diethylamino, methylethylamino, etc .; amine alkyl " one 谞 means straight or branched amine group Cl-30, such as methyl, limb ethyl, propyl , Aminebutyl, aminepentyl, aminehexyl, amineheptyl, amineoctyl, etc .; " amine lower alkyl " means an amine linear or branched Ci-5 alkyl group such as aminemethyl, Amine ethyl, amine propyl, etc .; " Alkyl alkyl H-feed means straight or branch C 1 -Alkylamino-straight or branched Cl-! O alkyl such as methylaminomethyl, methylaminoethyl, ethylaminomethyl, methylaminopropyl, propylaminoethyl, methylamine Butylbutyl, butylaminohexyl, pentaminomethyl, methylidylhexyl, heptylpropyl, butylaminooctyl, etc .; " lower alkylamino-low sulfoalkyl " Straight or branched Ci-5 alkylamino-straight or branched Ci-s alkyl such as methylaminomethyl, methylaminoethyl, ethylaminomethyl, methylaminopropyl, propylaminoethyl The term "dialkylaminoalkyl" means two linear or branch paper sizes, using China National Standard (CNS) A4 (210X297 mm) -------- AI equipment -(Please read the precautions on the back before filling out this page) Order A7 B7 Printed by the Ministry of Economic Affairs, China Standards Bureau, Consumer Affairs Cooperation, Du Printed 5. Description of the invention (, branched Cl-10 alkylamino straight chain or Branched Cl-10 alkyl groups such as dimethylaminomethyl, diethylaminomethyl, diethyllimylpropyl, dimethylaminobutylhexylaminomethyl, dipentylaminoheptyl, dioctylamine Hexyl, etc .; " Di-oligosulfanylamino-lower alkyl "; The term means di- or dibranched Ci-5 alkylamino- or straight-chain or branched Cl-s alkyl such as dimethylaminomethyl, diethylaminomethyl, diethylaminoethyl, di "Methylaminopropyl", etc .; "hydroxyalkyl" means hydroxy-ortho or branched Cl-omega alkyl such as hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, Hydroxyhexyl, hydroxypentyl, hydroxyoctyl, etc .; "hydroxy-lower alkyl" means hydroxy-straight or branched Ci-alkyl such as hydroxymethyl, hydroxyethyl, hydroxypropyl, etc .; The term "haloalkyl" means a halogen-straight or branched Ci-10 alkyl group such as fluoromethyl, cyanomethyl, bromomethyl, dioxanyl, trifluoromethyl, trichloromethyl, Aminoethyl, diaminoethyl, triaminoethyl, "propyl," butyl, pentyl, "hexyl, cyanoheptyl, octyl, etc .; " halo-lower alkyl " Represents halogen straight or branched Ci-s alkyl such as gas methyl, cyanomethyl, bromomethyl, di «methyl, trifluoromethyl, tricyanomethyl,« ethyl, dichloroethyl, tri Hydroethyl, chloropropyl, etc .; " alkenyl " means straight or branched C2-! 〇alkenyl such as Alkenyl, allyl, isopropenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, etc .; " lower alkenyl " means straight-chain or branched c2- s alkenyl such as vinyl, allyl, etc. " alkylene " represents a straight or branched chain Cl-10 alkylene such as methylene, ethylene, propylene, isopropylidene , Butylene, hexylene, octyl, etc .; "low master alkylene" means straight or branched Ci-S alkylene such as methylene, ethylene, this paper size applies Chinese national standards (CMS) A4 specification (21.0X297mm) -------- 《I Pack-(Please read the precautions on the back before filling this page) Order the central sample of the Ministry of Economic Affairs 扃 Printed by the consumer consumer cooperative A7 B7___ V. Description of the invention (fr) propylene, isopropylidene, etc .; " fluorinated alkyl " means β-alkynyl such as chenyl, cyclobutyl, chenpentyl, hexyl, etc .; " "Schenane ring" Yipu means C 3 -s sane ring such as fluorene propane, succinic butane, hexane, etc .; "Schenyl xiang" N — the word indicates a straight bond or branch Ci-10 alkyl coating Methylsulfonyl Ethylsulfonyl, n-propylsulfanyl, isopropylsulfosyl, n-butylphosphonium, isobutyl sulfonyl, second butylsulfonyl, third butylsulfonyl , Amyl androyl, hexyl, magnetic, heptylsulfonyl, octylsulfonyl, etc .; " lower alkylalkylglycosyl " means straight or branched Ci-s alkylsulfonyl Such as methylsulfonyl, ethylsulfanyl, n-propylsulfanyl, isopropylsulfanyl, n-butylsulfonyl • isobutylsulfonyl, second butylsulfonyl, Tributylisopropyl, pentylsulfenyl, etc .; Haryl "means phenyl or lycyl; etc .;" arylsulfonyl "means benzene-based glycosyl or lysylpyridinyl Etc .; "aralkyl" means benzyl or phenethyl, etc .; and "heteropyridyl" means that it contains at least one heteroatom selected from the group consisting of a gas atom, a cyan atom and a base atom. Heterocyclic atoms of 4-, 5-, or 6-Beschen strips or their coupling strips are, for example, a radical radical, a radical radical, a nitrogen radical, a furanyl radical, or a pyrrolyl radical. , Fluorenyl, oxazolyl, isoxazolyl, oxazolyl Group, oxazolyl, isoxazolyl, pyrrolidinyl, benzofuranyl, benzosulfanyl, pyrhexyl, pyrinyl, pyrimidinyl or morpholinyl. Substituted or unsubstituted low «alkyl, fluorenyl·low" alkyl, alkenyl, oxyalkyl, aryl or fluorenyl fluorenyl substituents in R2; substituted or unsubstituted low in R3 Alkyl, alkyl, alkalenyl, alkyl, cycloalkyl, aryl, alkane, alkane, alkanyl, alkanethio, or this paper is applicable to Chinese national rhenium (CNS> A4) Specifications (210X297mm) I ------ At Packing ------ Order --- ^ ---- Γ Line (Please read the precautions on the back before filling this page) Α7 Β7 V. Description of the invention ( 7) Substituents of alkylthio groups; substituted or unsubstituted lower alkyl groups, alkyl groups, lower alkylene groups, alkenyl groups, alkenyl groups, aralkyl groups, aryl groups, and low sulfonyl alkyl groups in R4 / Alkyl, sulfoalkylphosphino or alkylthio substituents; substituted or unsubstituted lower alkyl groups, alkyl groups, alkenyl groups, lower alkyl groups, alkyl groups in R 5 Alkyl, aryl-fluorenyl, fluorenyl or aryl substituents; substituted or unsubstituted lower sulfoalkyl, alkyl, lower alkane, alkoxy, lower alkanethio in Re Or a thiol substituent; and substituted or unsubstituted in Y Substituted lower alkyl, alkyl, lower alkane, alkane, sulfoalkylthio or alkylthio substituents containing halogen atoms, fluorenyl groups, protected or unprotected carboxyl groups, protected Or unprotected hydroxy, well-protected or unprotected amine, lower alkyl, lower sulfoalkoxy, lower sulfoalkane carbonyl, aryl, octyl, lower alkyl, halo-low Fluorenyl, protected or unprotected sulfoalkylamino and di-oligomeric amine, and may be substituted by at least one of these substituents β Central Bureau of Standards, Ministry of Economic Affairs w: printed by Industrial and Consumer Cooperatives (Please read the notes on the back before filling out this page.) The carboxy protecting group includes all the conventional carboxy protecting groups. It is worth mentioning that it is a low sulfoalkyl group such as methyl, ethyl, n-propyl, isopropyl, 1, dimethyl propyl, n-butyl, tertiary butyl, etc .; aryl groups such as phenyl, legyl, etc .; aryl-lower alkyl groups such as benzyl, benzyl, trityl , P-nitrobenzyl, p-methylbenzyl, fluoren (p-methoxyphenyl) methyl, etc .; g-lower alkyl such as ethenylmethyl, benzamylmethyl, p- Nifedipine Methyl, p-o-benzyl methyl, p-methanesulfonyl benzyl methyl, etc .; gas-containing heterobenzyl groups such as 2-tetrahydropiperanyl, 2-tetrahydrofuranyl, etc .; halogen -Lower alkyl groups such as 2,2,2-trichloroethyl, etc .; lower sulfoalkylsilyl groups such as 2- (trimethylsilyl) ethyl; etc. Paper size is applicable to China National Standard (bNS> A4 (210 × 297 mm)) Printed by Shellfish Consumer Cooperative of Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (s), propane gas methyl, tamyl gas methyl Etc .; fluorene-containing heterocyclic oligoalkyl groups such as fluorenediamidomethyl, succinimidomethyl, etc .; cycloalkyl groups such as oxohexyl, etc .; oligomeric alkoxy-lower alkyl groups such as methoxymethyl Methyl, methoxyethoxymethyl, 2- (fluorenylsilyl) ethoxymethyl and the like; aryl-lower alkylthio-lower alkyl such as benzylmethyl and the like; Lower alkyl groups such as methylmethyl, 2-methylthioethyl, etc .; arylthio-lower alkyl groups such as phenylthiomethyl, etc .; lower sulfenyl groups such as 1,1-dimethyl-2 -Propenyl, 3-methyl-3-butenyl, allyl, etc .; and substituted silyl groups Such as trimethylsilyl, triethylsilyl, tripropylsilyl, diethylisopropylsilyl, third-butyldimethylsilyl, third-butyldiphenylsilyl, Diphenylmethylsilyl, tert-butylmethoxyphenylsilyl, etc .; etc. Protected amines, oligosulphonylamino, alkylamino, amine-oligosulfanyl, aminealkyl, oligoalkylamino-oligosulfoalkyl or alkylaminoalkyl triprotective groups all Known amine protecting groups, especially worth mentioning are sugar groups such as trichloroethane carbonyl, tribromoethane carbonyl, benzyl carbonyl, p-nitrobenzyl carboxyl, o-bromobenzyl carbonyl, (monodi- Or tricyanoglycosyl, trifluoroethionyl, phenylethylglycosyl, methylosyl, acetamyl, benzoyl, third-pentylcarbonyl, third-butylene, p-methylene Benzylcarbonyl, 3,4-Dimethylbenzylcarbonyl, 4- (phenylmethyl «) benzylcarbonyl, 2-furyloxycarbonyl, diphenylmethoxycarbonyl, 1,1-dimethylpropanecarbonyl , Isopropylcarbonyl, phthalofluorenyl, succinimidyl, propylamine, leukoamino, 1-adaminyl carbonyl, 8-phosphinoyl carboxyl, etc .; aryl-lower alkyl such as benzyl, di Benzyl, trityl, etc .; arylthio groups such as 2-nitrophenylthio, 2,4-dinitrophenyl bases, etc .; alkyl- and aryl-alkyl groups such as methanesulfonyl-10 -This paper size applies to China National Standard (CNS > Α4 size (210X297mm) ( (Please read the note on the back before filling this page). ΛI Packing ------ Order | U ---- ^ Printed by the Industrial and Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 _B7_ V. Description of Invention (9 ) Group, p-tolyl fluorenyl and the like; bis-oligosulfanylamino-lower fluorenylene such as N, N-dimethylaminomethylene and the like; aryl-low sulfoalkylene such as benzylene, 2-Hydroxybenzylidene; 2-Hydroxy-5-cyanobenzylidene, 2-Hydroxy-1-lylmethylene, etc .; Cyanofluorene-containing ring alkylenes such as 3-hydroxy-4-pyridinylidene Methyl, etc .; aachen alkyl such as cyclohexylene, 2-ethyl «carbonylhexylene, 2-ethyl« carbonylcyclopentylene, 2-ethyl K-hexylene, 3,3-dimethyl-5 -Hexylene, etc .; diaryl and diaryl-lower W alkyl phosphorus S groups such as diphenylphosphonal, dibenzylpyridinyl and the like; oxalanyl alkyl groups such as 5-methyl- 2-Gas-2H-1,3-Digas-ene-Wu-4-ylmethyl, etc .; substituted silyl groups such as trimethylsilyl, etc .; etc. In addition, the hydroxyl groups protected by hydrazone, hydroxy-lower Alkyl or hydroxyalkyl protecting groups include all conventional hydroxy-protecting groups, especially notable are sugars such as benzyl carboxy, 4-nitrobenzyl, carbonyl, 3,4-dimethylbenzyloxy Methyl group, methyl group, ethyl carbonyl group, tert-butoxy glass group, 1, dimethyl dimethyl carbonyl group, isopropyl carbonyl group, isobutyl carbonyl group, diphenyl carbonyl group, 2,2 , 2-trichloroethoxycarbonyl, 2,2,2-tribromoethoxycarbonyl, 2- (trimethylsilyl) -ethoxycarbonyl, 2- (phenylsulfonyl) ethoxycarbonyl, 2- (Triphenylphosphinofluorenyl) ethane carbonyl, 2-fluorene carbonyl, 1-adamantane carbonyl, ethylene carbamoyl, allyl «carbonyl, S-benzylthiocarbonyl, 4-ethoxy-1-phenylene Carbonyl, 8-carboline oxycarbonyl, ethanoyl, formamyl, cyanoethanoyl, diethylethyl, trifluoroethyl, trifluoroethylethyl, methyl acetyl, ethylbenzene Group, pentamyloxy, benzamidine and the like; lower sulfoalkyl such as methyl, tertiary-butyl, 2,2,2-trifluoroethyl, 2-trimethylsilylethyl, etc .; Low sulfoalkenyl such as allyl; aralkylene such as benzyl, for -11- (Please read the precautions on the back before filling this page)

If the size of the paper wave is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) Printed by A7 B7 of the Zhengong Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the invention (,... -Dimethylbenzyl, diphenylmethyl, trityl, etc .; oxygen-containing and alkali-containing heterocyclic groups such as tetrahydrofuran, tetrahydropiperanyl, tetrahydrothiosulfa, etc .; Alkane- and oxane-sulfo-lower sulfoalkyl groups such as methyl methyl, methylthiomethyl, benzyl methyl, 2-methyl ethyl methyl, 2,2,2-triethoxymethyl , 2- (trimethylsilane 碁) > Acetylmethyl, 1-ethoxyethyl, etc .; Alkyl- and aryl-hexyl groups such as methanesulfonyl, p-toluenesulfonyl, etc .; substituted Silyl groups such as trimethylsilyl, triethylsilyl, triisopropylsilyl, diethylisopropylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilane Group, benzylsilyl group, tert-butylmethylphenylsilyl group, etc .; etc. The salt of the compound represented by the general formula [I] contains a known group usually having a basic group such as an amino group and an acid group. Such as hydroxy, carboxyl and other salts. Basic group salts include, for example, salts produced by amidine and inorganic 'acids such as hydrofluoric acid, ammonium bromide, sulfuric acid, and the like; and formed with carboxylic acids such as tartaric acid, formic acid, picolinic acid, trichloroacetic acid, and tricyanoacetic acid. Salts; and salts produced from maleic acids such as methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, 2,4,6-trimethylbenzene acid, lysenesulfonic acid, and the like; Salts produced by crocodile metals such as pins, potassium, etc .; with age soils such as calcium, magnesium, etc .; ammonium salts; nitrogen-containing organic sickles such as trimethylamine, triethylamine, tributylamine, pyridine, Ν, Ν- Dimethylaniline, N-methylhexahydropyridine, N-methyldiethylamine, dicyclohexylamine, procaine, dibenzylamine, N-benzyl-fluorene-phenylethylamine, 1-Evanamine (ephenamine), Ν, ΙΓ, dibenzyl ethylene diamine, etc .; etc. Among the salts represented by the general formula [1], the "acceptable salt of the drug table is preferred β 1-2"- Paper size: China National Standard (CNS > Α4 size (210X297mm) --------- ^ I pack ------ 1T-^ ---- "line (please first (Please read the notes on the back and fill in this page.) Printed by A7 B7 V. Description of the invention (d) Among the compounds of the present invention, the compounds of the following formula [1] are preferred, wherein R2 represents a substituted or unsubstituted lower alkylene group, a lower alkylene group, Cycloalkyl, aryl, or heterocarbo; R3 represents at least one group selected from the group consisting of fluorene, halogenated or unsubstituted lower alkyl, haloalkenyl, alkyl, aryl , Low alkyloxanyl or sulfoalkylthio, nitro, fluorenyl, fluorenyl, protected or unprotected hydroxy, protected or unprotected hydroxy-low sulfoalkyl, protected or unprotected Protected or unprotected oligoalkylamine, di-lower alkylamine, protected or unprotected amine-oligosulfonyl, protected or unprotected Sulfoalkylamino-lower alkyl and di-lower alkylamino-lower alkyl; R 4 represents at least one group selected from the group consisting of a halogen atom, a halogen atom, substituted or unsubstituted lower alkyl Group, oligoalkenyl, cycloalkyl, aralkyl, aryl, oligomeric alkyl or oligoalkylthio, protected or unprotected hydroxy, protected or unprotected Protected hydroxy-low sulfoalkyl, protected or unprotected amine, protected or unprotected lower alkylamine, di-lower alkylamine, protected or unprotected amine -Lower alkyl, protected or unprotected alkylamino-lower alkyl, di-lower alkylamino-lower alkyl ·, lower alkylene, oxy, fluorenyl and The sulfonic atom bonded to R4 forms a alkane ring group; RS represents an argon atom, a substituted or unsubstituted lower sulfoalkyl group, an octyl group, a lower alkylsulfonyl group, an arylfluorenyl group, and a ferment Or aryl, protected or unprotected amine-lower alkyl, protected or unprotected low sulfoalkylamino-lower alkyl, di-lower alkylamino-lower alkyl Or protected or unprotected hydroxy-lower alkyl; R6 represents a fluorene atom, a halogen atom, substituted or unsubstituted 1-3 3- This paper size applies to Chinese National Standard (CNS) M specifications (210X297 mm) ) --------- ^ I install ------ order 丨 ^ .---- f line (please read the precautions on the back before filling this page) Consumption cooperation Du printed A7 B7 V. Invention theory (Ι >) Wo lower alkyl, lower alkyl Wo "sulfo group or lower alkylthio group, a hydroxyl group protected with or without the security Jin, the nitro group or the protected or unprotected; Na / represents

Or / / where Y represents a hydrogen atom, Xie atom, substituted or unselected I

Y is substituted with lower alkyl, lower sulfoalkane or lower alkylthio, or protected or unprotected hydroxyl group or a group represented by the following formula with R2

Wherein R7 represents at least one of the following groups: fluorene atom, lower sulfoalkyl group, halo-lower sulfoalkyl group, protected or unprotected hydroxy-lower alkyl group, lower fluorene group and R7 bond The resulting gardenia produces a alkane group, and B represents a gas atom, a sulfur atom, or an imine group, which may be substituted by a lower alkyl group and X represents a curved atom. More preferred are the above-mentioned compounds, but R3 represents at least one selected from the group consisting of: * atom, curved atom, substituted or unsubstituted lower alkyl group, lower sulfoalkyl group or lower alkyl group, nitrate Phenyl group, fluorenyl group, protected or unprotected hydroxyl group and protected or unprotected amine group. Particularly preferred are the aforementioned compounds, but R4 is at least one group of S from: fluorene atom, substituted or unprotected Substituted lower alkylene, lower alkylene and alkylene ring formed by the halogen atom bonded to R4. Desirable are the aforementioned compounds but R5 represents a hydrogen atom or a substituted or unsubstituted low sulfoalkyl or octyl group. "Among the compounds of the present invention, the representative compounds are as follows: Isoindin-kib 8-methyl_1,4_ mono «-4-oxysuccinol-3-carboxyl. 1-ethyl-6-fluoro-7- (isoindolino-porphyrin-boxy) _8 _Methyl_1,4_diaza-4-fluorenyl Holin-3-carboxylic acid " 14- This paper uses China National Standard (CNS > ΛΑ Specifications (210X297 mm) ---- ---- f -install ------ τίί ---- IΓ line (please read the notes on the back before filling this page) Printed by the Consumers Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7_ V. Description of the invention ( Μ) • 1- (2,4-difluorophenyl) -6-fluoro-7- (isoindolinolin-5-yl) -8-methyl-1,4-dihydro-4-amino group S Phenyl-3-carboxylic acid • 6-fluoro-1: (4-hydroxyphenyl) -7- (isoindololin-5-yl) -8-methyl-1,4-dihydro-4-gas Metholin-3-carboxylic acid6-fluoro-1- (4-fluorophenyl) -7- (isoindolinamidin-5-yl) -8-methyl-1,4-dihydro-4 -Gastoline-3-carboxylic acid • 6-fluoro- l-[(lR, 2S) -2-fluorosynyl] -7- (isoindolinolin-5-yl) -8-methyl- 1, 4-Difluorene-4-oxo 1¾line-3-carboxylic acid • 1-cyclopropyl-6-fluoro-8-methyl-7- (2-methyl-isoindo Idol_-5-yl) -1,4-bihan-4 -Aminomethyl-3-amino acid • 1-ethyl-6-fluoro-8-methyl-7- (2-methyliso1¾olinolin-5-yl) -1, 4-dihydro-4 -Aminopyridin-3-carboxylic acid • 1- (2,4-difluorophenyl) -6-fluoro-8-methyl-7- (2-methylisoindolinolin-5-yl)- 1,4-dihydro-4-amino-phenanthroline-3-carboxylic acid. 6-fluoro-bu (4-hydroxyphenyl) -8-methyl-7- (2-methylisoindolinline- 5-yl) -1,4-dihydro-4-aminopyridin-3-carboxylic acid • 6-fluoro-1- (4-fluorophenyl) -8-methyl-7- (2-formyl) Isoindolinline- 5-yl) -1,4-dihydro-4-yloxyline-3-carboxylic acid • 6-fluoro-l-[(lR, 2S) -2-fluorochenyl] -8-Methyl-7- (2-methylisoinolinolin-5-yl) -1,4-dihydro-4-aminoquinoline-3-carboxylic acid Fluoro-7- (isoindoline-5-yl) -1,4-dihydro-4-amino 1¾line-3-carboxylic acid_1-ethyl-6-gas-7- (isoindolin Porphyrin-5-yl) -1,4-dihydro-4-amino group »Quydroxy-3-3-carboxylic acid-1 5- This paper size applies to Chinese national standard (tNS) A4 specification (2 丨 OXW7 mm)- ------- f 1 pack-(Please read the notes on the back before filling this page) Order U1. • Printed by the Consumer Standards Cooperative of the Central Bureau of Standards of the Ministry of Economics A7 B7__ 5. Description of the invention (to) • 1- (2,4-difluorophenyl) -6-argon-7- (isoindolin- 5-yl > -1,4-diargon-4- «yl Ifline-3-carboxylic acid • 6-gas-1 (4-xiangphenyl) -7- (isochronous 丨 time #-5- Radical) -1,4-difi-4-4-amino radical R_-3-carboxylic acid • 6-fluoro-1- (4-fluorophenyl) -7- (isoindolinamidine-5-yl) -1 , 4-Dihydro-4 -aminoaminoline-3-carboxylic acid • 6-fluoro-1-[(1R.2S) -2-fluorocyclopropyl] -7- (isoindolinline-5-yl ) -1,4-dioxo-4-airyl if hydrolysate-3-dwarf acid • 1-chenpropyl-β-fluoro-7- (2-methyl-isoindolinolin-5-yl) -1 , 4-dihydro-4-oxyquinoline-3-carboxylic acid • ethyl-6-fluoro-7- (2-methylisoinolinolin-5-yl) -1, 4-dihydro-4- Pyroline-3-carboxylic acid • 1- (2, 4-difluorophenyl) -6-fluoro-7- (2-methylisoindoHdolin-5-yl) -1, 4-di氲 -4-Amino group> Phenyl-3-carboxylic acid • 6-fluoro-1- (4-hydroxyphenyl > -7- (2-methylisoindol Idololin-5-yl) -1,4 -Dipyridin-4-yloxyline-3-carboxylic acid • 6-fluorene-1- (4-fluorophenyl) -7- (2-methylisoindolin-5-yl) -1, 4 -Dihydro-4-oxyphospholine-3-carboxylic acid. 8-cyano-1-[( 1 R · 2 S)-2-cyanopropyl] -7-(2 -methylisoindole H dorolin-5-yl) -1,4-dihydro-4-amino ifolin-3-carboxy Acid 1-Ceryl-6-cyano-7- (isoindolinyl-5-yl) -8-methoxy-1,4-dihydro-4-amino-Bolin-3-carboxylic acid • 1-Ethyl-6-fluoro-7- (isoindolinylidolin-5-yl) -8-methylamino-1,4-difluoren-4-yloxy-3-carboxylic acid-1 6 The size of this paper is applicable to the national standard (& NS) A4 specification (210X297mm) -------- f installed .-------- visit r --- f line (please read the back first Please pay attention to this page, please fill in this page) Employees ’cooperation with the Central Bureau of Standards, Ministry of Economic Affairs, Du Yincha A 7 B7 Five 'Invention Description (κ) • 1- (2,4-difluorophenyl) -6-drug-7- (Isoindin_-5-yl) -8-methoxy-1,4-difluoren-4-yl-Hlyin-3-bagic acid. 6-fluoro-1,-(4-hydroxyphenyl) -7-(Isoindoline-5 -yl) -8 -methoxy-1,4-dihydro-4-aminoyl-3-carboxylic acid-6-fluoro-1- (4-fluorobenzene ) -7- (isoindolinylidolin-5-yl> -8-methylamino-1,4-difluorene-4 -oxybetaline-3 -carboxylic acid • 6-cyano-1- [ (1R, 2S) -2-fluorosynyl] -7- (isoindolinolin-5-yl) -8-methylamino-1,4-difluoren-4-yl PfW: -3-carboxy Acid • 1-chen Propyl-6-gang-8-methyl-7- (2-methyl-iso13 丨 hryn-5-yl) -1,4-diargon-4-yl group i-line-3-carboxylic acid • Ethyl-6-fluoro-8-methylamino- 7- (2-methylisoindolinolin-5-yl) -1,4-dihydro-4-aminoyl 3-caproic acid • 1 -(2,4-difluorophenyl) -6-fluoro-8-methylamino- 7- (2-methylisoindolinline-5 "yl) -1,4-dihydro-4-oxy W-3-carboxylic acid • 6-Homo-1- (4-hydroxyphenyl) -8-methylamino-7- (2-methylisoindolinline-5 -yl) -1,4- Dihydro-4-amino group f-line-3-carboxylic acid • 6-fluoro-bu (4-fluorophenyl) -8-methylamino group 7- (2-methylisoindolinyl-5- ) -1,4-Difluoren-4-oxy 丨 Quylen-3-carboxylic acid • 6-Fluoro-l-[(lR, 2S) -2-fluorosynyl] -8-methylamino- 7- (2-methylisoindololin-5-yl) -1,4-dihydro-4-amino-based morpholine-3-carboxylic acid • 8-Amino-Phenyl-6-fluoro-7 -(Isoindol_-5-yl) -1,4-bisfluoren-4-oxyβline-3-carboxylic acid • 8-fluoren-1-ethyl-6-gas-7- (iso_3丨 丨 $ -5--5-)-1,4 -dihydro- 4-gas-based folin-3 -carboxylic acid-1 7-This paper size applies to China National Standard Car (CNS) A4 specification (210X297 mm ) -------- ^, batch of clothing-(Please read the precautions on the back first (Fill in this page)

1T -f line '41 · Printed by A7 B7__ of the Central Laboratories of the Ministry of Economic Affairs and Consumer Cooperatives V. Description of the invention (' b) -7-(Isoin1 $ line-5-yl) -1,4-dihydro-4-airylline-3-carboxylic acid -7- (isoindioftft-5-yl) -1,4-dihydro-4-airyl BfW-3 -bagic acid • 8-chloro-6-fluoro-1- (4-fluorophenyl)- 7-(isoindolin_-5-yl) -1,4-dihydro-4- «yl If chloro-3-carboxylic acid • 8-cyano-6-fluoro-1-[(1R, 2S) -2 -Fluorocyclopropyl] -7- (isoindolinone-5-yl) -1,4-dihydro-4-oxyHW-3-carboxylic acid. 8-*-Buchenpropyl-6- Fluoro-7- (2-methyl-isoindolinolin-5-yl) -1,4-dihydro-4-aminoylpyridin-3-carboxylic acid • 8-cyano-1-ethyl-6- Fluoro-7- (2-methylisoindolinol-5-yl) -1,4-dihydro-4-aminopyroline-3-carboxylic acid • 8-cyano-1- (2,4- Difluorophenyl) -6-fluoro-7- (2-methylisoindin W-5 -yl) -1,4 -biphenyl-4-amino branched-leaching-3-carboxylic acid • 8-nitrogen- 6-Fluoro-1- (4-hydroxyphenyl) -7- (2-methylisoinolinolin-5-yl) -1,4-dihydro-4-amino ifolin-3-carboxylic acid • 8-chloro-6-fluoro-bu (4-fluorophenyl) -7- (2-methylisoinolinolin-5-yl) -1,4-dihydro-4 -Oxygen technology: -3-carboxylic acid • 8-chloro-6-fluoro-1-[(111,23) -2-fluorochenpropyl] -7- (2-methylisoindolinline-5 -Yl) -1,4-dihydro-4-oxoporphyrin-3-carboxylic acid • 1-cyclopropyl-6,8-dicyano-7- (isoindolinolin-5-yl) -1 1,4-Difluorene- 4-aminopyridin-3-carboxylic acid • 1-ethyl-6,8-difluoro-7- (isoindolinolin-5-yl)> -1,4-dihydro -4-Gastoline-3-carboxylic acid _ 1 8 _ This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) -------- ^ — 装 ----- -Order-„----" Line (Please read the precautions on the back before filling out this page) Printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (^) • 6,8 -difluoro 1- (2,4-difluorophenyl) -7- (isoindole <5-5-yl) -1,4-dihydro-4-oxycinolin-3-carboxylic acid • 6,8-di Pa- (4-hydroxyphenyl) -7- (isoindololin-5-yl) -1,4-dihydro-4-oxoporphyrin-3-carboxylic acid • 6,8-difluoro- 1- (4-fluorophenyl) -7- (isoindololin-5-yl) -1,4-difluoren-4-oxylaurin-3-carboxylic acid • 6, 8-difluoro-1 -[(1R, 2S) -2-fluorocyclopropyl] -7- (isoindolinline-5 -yl) -1,4 -two articles-4-amino group f #-3-bagic acid • 1 -Cyclopropyl-6, 8-difluoro-7- (2-methyl-isoinolinolin-5-yl) -1,4-dihydro-4-aminodenoline-3-carboxylic acid • ethyl -6,8-difluoro-7- (2-methylisoindiolidene-5-yl &gt; &gt; -1,4-difluoren-4-ylamino B1line-3-carboxylic acid Difluoro-1- (2,4-difluorophenyl) -7- (2-methylisoindolinolin-5-yl) -1,4-difluoren-4-amino IH phthaloline-3-carboxy Acid • 6,8-difluoro-1- (4-hydroxyphenyl) -7- (2-methylisoindolinline-5-yl> -1,4-dihydro-4- «yl (f咻 -3-carboxylic acid • 6, 8-difluoro1- (4-fluorophenyl) -7- (2-methyliso13 丨 inolin-5-yl) -1,4-dihydro-4- Oxyline-3-carboxylic acid • 6,8-difluoro-1-[(lR, 2S) -2-fluoroamidinopropyl] -7- (2-methylisoindinoline-5-yl) -1,4-dihydro-4-aminohydantoline-3-carboxylic acid • 1-chenpropyl-6-fluoro-7- (isoindolinline-5-yl) -1,4-dihydro- 4-oxy-1, 8-Ceridine-3-carboxylic acid • 1-ethyl-6-fluoro-7- (isoindohordolin-5-yl) -1,4-diargon-4-gas -1,8-Radiidine-3-carboxylic acid-1 9- This paper uses Chinese National Standard (CNS) A4 (210X297) for paper size --------- ^ Outfit --- --- Order ------- "Line (Please read the notes on the back before filling this page) Central of the Ministry of Economy A7 B7 printed by the Consumer Cooperatives of the quasi bureau 5. Description of the invention M) • 1- (2,4-difluorophenyl) -6-fluoro-7- (isoindolinolin-5-yl) -1,4- Difluoren-4-yl-1,8-eryridin-3-carboxylic acid • 6-fluoro-1: (4-hydroxyphenyl) -7- (isoindolinline-5-yl) -1,4 -Diamidine-4 -Gasyl-1,8-lyridin-3-carboxylic acid • 6-fluoro-1- (4-fluorophenyl) -7- (isoindolinyl-5-yl &gt; -1 , 4-Dihydro-4 -amino-1,8-radidine-3-carboxylic acid • 6-fluoro-1- [(1R, 2S) -2-fluorocyclopropyl] -7- (isoindole Phenyl-5-yl) -1,4-bisfluoren-4-oxy-1,8-eryridine-3-carboxylic acid. 1-Chloropropyl-6-fluoro-7- (2-methyl-iso Indolin W-5-yl) -1 · 4-Diargon-4-oxy-1,8-Radiidine-3-carboxylic acid • 1-Ethyl-6-fluoro-7- (2-methyliso Indoline-5-yl &gt; -1,4-difluorene-4- «yl-1,8-eryridin-3-carboxylic acid • 1- (2,4-difluorophenyl) -6-fluoro -7- (2-methylisoindole_-5-yl) -1,4-dihydro-4-carbyl-1,8-eryridine-3-carboxylic acid 6-fluoro-1- (4 -Hydroxyphenyl &gt; -7- (2-methylisoindolin-5-yl) -1,4-dihydro-4-amino-1,8-eryridine-3-carboxylic acid • 6- Fluoro-1- (4-fluorophenyl) -7- (2-methylisoindole I »-5-yl) -1,4-difluoren-4-yl-1,8-ceridine-3 -Carboxylic acid • 6-fluoro-bu [(1R, 2S) -2- Fluoropropyl] -7- (2-methylisoindololin-5-yl) -1,4-di'hydro-4-carbyl-1,8-Lyodo-3-unsaturated acid • -9 -Fluoro-10- (isoindolinolin-5-yl) -3-methyl # -7-oxy-2, 3-difluorene-7-pyridine [1,2,3-de] [1,4 ] Benzene 骈 丨 §Trap-6-carboxylic acid • (S) -9-Fluoro-10- (isoindiolidene-5-yl) -3-methyl-7-airyl-2,3-difluorene -7-pyridine hydrazine [1,2, 3-de] 〔1,4] Benzene 骈 §-6-carboxylic acid-20- --------- f —pack -------- -Order | _.---- (line (please read the precautions on the back before filling this page) This paper wave scale is applicable to China National Standard (CNS) A4 specifications (210X297 mm) Printing A7 _B7_ V. Explanation of the invention) • 9-fluoro-3-methyl-10- (2-methylisoindolinium-5-yl) -7-amino-2, 3-dihydro-7 -Pyridine hydrazine [1,2,3-de] [1,4] benzene sulfonium-6-carboxylic acid_ (S)-9 -th -3 -methyl-1 0-(2 -methylisoindole Indolin-5 -yl) -7-amino-2,3-dihydro-7-pyridine hydrazine [1,2,3- (16] [1,4] benzene hydrazone-6-carboxylic acid.1 -Cyclopropyl-5,6,8-trifluoro-7- (isoinolinolin-5-yl)-1,4-dihydro-4-oxyB-line-3-carboxylic acid Propyl-5,6,8-trifluoro-7 -(2-methylisoindionium_- 5-yl) -1,4-dihydro-4-aminopyroline-3-carboxylic acid • 1-cyclopropyl-5, 6, 8-trifluoro- 7- (isoindolinamidine-5-yl) -1,4-diamidino-4-amino-Bolinyl-3-carboxylic acid • 5-amino-1-cyclopropyl-6,8-digas- 7- (iso 丨 flin-5-yl) -1,4-dihydro-4-airyl β-line-5-carboxylic acid • 5-amino-1-carbopropyl-6,8-difluoro- 7- (2-methylisopropyl 1--5-yl) -1,4-dihydro-4-aminopyridin-3-carboxylic acid • 1-Chrysanyl S-6-fluoro-7- (7-Fluoroisoinolinolin-5-yl) -1,4-dihydro-4 -aminocyanoline-3-carboxylic acid • 1-chenpropyl-6-fluoro-7- (7-methyl Isoinline W-5-yl &gt; -1,4-diamidino-4-aminopyroline-3-carboxylic acid1-propylpropyl-6-gas-7- (4,6,7-tris覩 iso 丨 § 丨 Glycol-5-yl) -1,4-Difluorene-4-ylaminophenyl-3-carboxylic acid • 1-Homopropyl-6-fluoro-7- (3-methyliso Indole ¢ 1: -5-yl) -1,4-dihydro-4 -aminopyridine-3-carboxylic acid • 1-Cyclopropyl-7- (1,3-dimethylisoindolin_ -5-based) -6-fluoro-1,4- -2 1- This paper scale is applicable to Chinese National Standard (CNS) A4 (210X297 mm) T ^ nn ^ ii— · mi Kn 1 &quot; wv m vvn — N ^^^ 1 Μ Body i ^ Λ &amp;. (Please read the notes on the back before filling in this ) 〆 / V Out the five confessed - - Gold 3 7 B: [0, said sleeping surface I 3 6 I a see - propan 413 Mar Ϊ ϊ - gas * 1 I · 4 · two - carboxylic acid!.

7 7 AB based-5 I phthaloline «31 Isomethyldicarboxylic acid dicarboxylic acid _ _ 13 3 1 g 3 (W (7 B 7-£ -sEls UT * 集 戸 I Yin Chen-4 Chen 1- Hydrogen 1- • di · fluoro I 6 I group-5-phthaloline 2?, 3 1 0-6 Eosin I 5 I hydration Mr acid carboxyl-3 I morpholine 0 base gas I 4-hydrazone

Methyl Fluoride I 8 Sun 0-6 I Phenyl-1A I 5 Porphyrin 2 P3I Isoacid Carboxylic Acid 3-Vi Hydoxy Oxygen 4 Methionyl Dimethyl Fluoride 8-Cyanide 6 Phenyl Ethyl Carboxyl I 3- Isoline Ilf base gas I 4-氲 bis «Acid-5-啭 1¾» 3 | iso. ^^ ϋ. 1 --— ί mu ml ·--1 nn —i ml (Please read the precautions on the back first Fill in this page) Group 8 1-Pholine * ^ tB T group I) Oxy-benzene Tfluoro 1-Porphyrinyl hydrazone, l ·-* fluoro-48-hydrogen R-one-0-4 6, radical-5 I phosphono I, j {iso

* 1T

Benzoic acid fluorocarboxyl-* 4 3 / IV | 1-Phenyl group ^ 0 Gas S towel-«Fluoro T 8-Hydrogen mV I 5 I morpholine, jl isoline 1 radical II Fluoro-5 6w •» * Economy Ministry of Work, Central Bureau, Work Bureau, Consumer Cooperatives, Indole 3, Pyridoxine * 111, Propionate ^ 0 Ring, R, Oxygen, 0, 4 2 I) -Hydrogen S -2, 2 * IR 4 枉 8, i- 2 Fluorine-I 6 4 II Argon diisocyanate 4-methyl0 morpholine-carboxy gas 3-acid oxymethanefluoric acid carboxyiso- 5 1 phosphonium hydrazone ?, iso-I-methyl-5-phosphonium hydrazone * isopropylmethyl-2/1-7 -Gas methyl fluoride I 8 Fluoride-6 I based ethyl-4 £ 2, Di- (phosphinoyloxybenzene 0 Dimethyl methofluoric acid? End Jm 2? HI isopropyl methyl This paper standard applies to Chinese national standards ( CNS &gt; A4 specification (210X297 mm) Consumer cooperation of the Central Standards Bureau of the Ministry of Economic Affairs Du Yin 袈 A7 B7_ V. Description of the invention -3-carboxylic acid • 6-fluoro-8-cyanomethyl-1- (4-hydroxyphenyl) -7- (2-methylisoinolinolin-5-yl) -l, 4-p hydrogen- 4-Gas P1 phthaloline-3-carboxylic acid • 6-fluoro-8-fluoromethoxy-1- (4-fluorophenyl) -7- (2-methylisoindolinline-5-yl) -1 , 4-Diargon-4-aminopyroline-3-carboxylic acid • 6-cyano-bu [(111,23) -2-fluorosine Group] -8-fluoromethyl gas-7- (2-methyliso 丨 3 丨 Lymph-5-yl) -1,4-dihydro-4-airyl 8-difluoromethane-6-fluoro-7- (isoindolinium-5-yl) -1,4-bisfluoren-4- «ylβline-3-carboxyl Methoxy-buethyl-6-fluoro-7- (isoindolinolin-5-yl) -1,4-difluoren-4-aminoquinoline-3-carboxylic acid • 8-difluoromethyl-1- (2,4-difluorophenyl) -β-fluoro-7- (isoindolyl-5-yl) -1,4-dihydro-4-aminozoline-3-carboxylic acid • 8-di Fluoromethyl-6-fluoro-1- (4-hydroxyphenyl) -7- (isoindolinline-5-yl) -1,4-dihydro-4-aminopyridin-3-carboxylic acid • 8-Difluoromethane "-6-fluoro-1- (4-fluorophenyl) -7- (isopropylimide rongolin-5-yl) -1,4-dihydro-4-oxoline- 3-carboxylic acid. 8-difluoromethane-6-fluoro-l-[(lR, 2S) -2-cyanopropyl] -7- (isoindolinolin-5-yl) -1,4- Dihydro-4-amino cinnamo-3-carboxylic acid • 1-cyclopropyl-8-difluoromethoxy-6-fluoro-7- (2-methyl-isoindolinyl-5-yl) -1,4 -dihydro-4-amino cyanoline-3-carboxylic acid8-difluoromethyl-1-ethyl-6-fluorene-7- (2-methylisoindolinoline-5- Group) -1,4-dihydro-4-amino-II-line-3-carboxylic acid • 8-difluoromethoxy-1- (2,4-difluorophenyl) -6-chip-7- (2 -Methyliso -23- The size of this paper is applicable to China National Standard (CNS) A4 (210X297 mm) I ------- ζ 1 etc .------ Order-: ---- (line (please Please read the notes on the back before filling this page) Consumption Cooperation by Employees of the Central Bureau of Standards, Ministry of Economic Affairs, Printed A7 B7_ V. Description of the Invention (0) Porphyrin-5-yl) -1,4-Difluorene-4-yl 11-Phenolin-3-carboxylic acid • 8-Difluoromethane-6-cyano-1- (4-hydroxyphenyl) -7- (2-methylisoindolinolin-5-yl) -1,4- Dihydro-4-amino β-line-3-carboxylic acid • 8-difluoromethane-6-fluoro-1- (4-fluorophenyl) -7- (2-methylisoindolinline-5- ) -1,4-Difluorene- 4- «yl 丨 folin-3-carboxylic acid • 8-difluoromethane-6-fluoro-bu [(11?, 28bu 2-fluorocyclopropyl]- 7- (2-methylisoinolinolin-5-yl) -1,4-dihydro-4-air-based lysine-3-carboxylic acid • Phenyl-6-fluoro-8-hydroxy-7 -(Isoindone) Doryl-5-kib 1,4-dihydro-4-aminopyridin-3-carboxylic acid • 1-ethyl-6-gas-8-xiang- 7- (iso丨 Duo IS-5-yl) -1,4-difluorene-4-oxoline-3-carboxylic acid. 1- (2,4-difluorophenyl) -6-fluoro-8-hydroxy-7 -(Isoinolinolin-5-yl &gt; -1,4-dihydro-4-amino group KuiLin-3-carboxylic acid • 6-Ga-8-Li-1- (4-Liphenyl) -7- (Different 丨 3 丨 Lin -5-yl) -1,4-difluoren-4-yl-guilin-3-carboxylic acid • 6-fluoro-1- (4-fluorophenyl) &gt; -8-hydroxy-7- (isoindole) Phenyl-5-yl) -1,4-dihydro-4-aminopyridin-3-carboxylic acid • 6-cyano-bu [(lR, 2S) -2-fluorosynyl] -8-hydroxy- 7- (Isoinolinolin-5-yl) -1,4-diamidino-4-amino ifolin-3-carboxylic acid • 6-fluoro-1- (2-cyanoethyl) -7- (iso Indolin 1 »-5-yl) -8-methyl-1,4-dihydro-4-oxy" Porphyrin-3-carboxylic acid • 6-fluoro-1- (2-fluoroethyl) -8- Methyl-7- (2-methylisoindolinol-5-yl) -1,4-dihydro-4-aminopyridin-3-carboxylic acid • 6-fluoro-bu (2-fluoroethyl Base] -7-(isoindolinline-5 -yl) -1,4 -difluorene-24- This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) -------- -f '—install ------ order „----“ line (please read the precautions on the back before filling this page) employee cooperation of the Central Bureau of Standards, Ministry of Economic Affairs, printed A7 £ 7__ V. Invention Explanation (") 4-Aminopyrimin-3-boxic acid • 6-fluoro-bu (2-fluoroethyl) -7- (2-methylisoindole D-do-5-yl) -1, 4 -dihydro-4-fluorenyl laurate W-3-carboxylic acid • 6-fluoro-1- (2-fluoroethyl] -7- (isoindioline-5-yl) -8-methyl-1 , 4-two -4-Gasyl β-line-3-carboxylic acid • 6-fluoro-1- (2-fluoroethyl) -7- (2-methylisoindoleH-rongolin-5-yl) -8-methyl- 1,4-dihydro-4-oxoline-3-carboxylic acid • 8-cyano-6-fluoro-1- (2-fluoroethyl] -7- (isoindololin-5-yl)- 1,4-dihydro-4-aminopyroline-3-carboxylic acid • 8-chloro 6-fluoro-1- (2-fluoroethyl) -7- (2-methylisoindolin I-doline-5 -Yl) -1,4-difluoren-4-oxypyridine-3-carboxylic acid • 6,8-digas-1- (2-daithyl) -7- (iso 丨 3 丨 hrhen-5- ) -1,4-Difluoren-4- «ylHolin-3-carboxylic acid • 6, 8-difluoro-1- (2-fluoroethyl] -7- (2-methylisoindolin ft -5-yl) -1,4-bisfluoren-4-ylidinoline-3-carboxylic acid • 6-fluoro-1- (2-fluoroethyl] -7- (isoindolinolin-5-yl ) -1,4-dihydro-4-airyl-1,8-eryridine-3-carboxylic acid • 6-fluoro-bu (2-fluoroethyl) -7-(2-methylisoindolinoline -5-yl) -1,4-dihydro-4-airyl-1,8-eryridin-3-carboxylic acid • 6-fluoro-7- (iso13 丨 Porinolin-5-yl> -8 -Methyl-1- (monooxo-3-yl) -1,4-dihydro-4-ylamino-4-line-3-carboxylic acid • 6-fluoro-7-(isoindoleline-5- Yl) -1- (monomethylsilanyl-3-yl) -1,4-dihydro-4-ylpyridin-3-carboxylic acid. 6-fluorene-7- (isoindolindol-5-yl ) -8-Mechanical-1- (Yiqi鼷 -3-based) -2 5 * The paper Λ degree applies to the Chinese National Standard (CNS) A4 specification (210X297 mm) -------- ^ — packing ------ ir ---- -"Line (Please read the notes on the back before filling this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A 7 B7_ V. Description of the Invention (4) -1,4-Difluorene-4-Gasyl-K -3-carboxylic acid • 8-chloro-6-fluoro-7- (isoindolinone-5-yl) -1- (monooxo-3-yl) -1,4-diargon-4- Gas-Based Technol-3-carboxylic Acid • 6,8-Difluoro-7- (Isoindolyl-5-yl) -1-(— Gasidine-3-yl) -1,4-Difluorene- 4-Gauryl cinolin-3-carboxylic acid • 6-fluoro-7- (isoindole_dorolin-5-yl) -1- (monomethylbenzo-3-yl) -1 · 4-dihydro- 4-Amino-1,8-eryridine-3-carboxylic acid • 6-fluoro-7-(isoindolinline-5 -yl) -1-(isoxazol-3 -yl) -8 -methyl -1,4-dihydro-4-yloxyline-3-carboxylic acid • 6-fluoro-7- (isoindolinodol-5-yl) -1- (isoxazol-3-yl)- 1,4-dihydro-4-aminopyridin-3-carboxylic acid • 6-fluoro-7-(iso-isopyridin-5 -yl) -1-(isoxazole-3 -yl) -8 -Methane-1,4-dihydro-4-oxy 丨 S-Phenyl-3-carboxylic acid • 8- «-6-Fluoro-7- (isoindole 丨 dololin-5-yl) -1- (iso丨 §azole-3-yl) -1,4- Hydroxy-4-oxoquinoline-3-carboxylic acid • 6, 8-difluoro-7- (isoindolinline-5-yl) -bu (isopropazol-3-yl) -1,4-di Hydrogen-4-amino dark phthaloline-3-carboxylic acid • 6-fluoro-7-(isoindolinline-5 -yl) -1-(isoxazol-3 -yl) -1,4 -dihydro- 4-amino-1,8-pyridin-3-carboxylic acid • 1-chenpropyl-6-fluoro-8-methylazine-7- (3-methylisoindolin-5-yl) -1 , 4-Dihydro-4-aminoyl phenanthroline-3-carboxylic acid_ 1-chenpropyl-7- (1,3-dimethylisoindolinolin-5-yl) -6-fluoro-8- Methane-1,4-bisfluoren-4-ylpyridin-3-carboxylic acid • Phenyl-6-fluoro-8-methane-6- (1-methylisoindolinol-5 -Base) -1 -2 6-This paper size is applicable to China National Standard (CNS) A4 specification (210X297mm) --------- f 1 pack -------- Order --―-- --f-line (Please read the notes on the back before filling this page) Printed by the Consumers Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the Invention (J), 4-Dihydro-4-fluorenyl-3 -Carboxylic acid · Phenyl-6-fluoro-8-methyl "-7- [spiro [isoindolinline-1,11-chenpropane] -5-yl,)-1,4-dihydro-4 -Oxy 丨 Poroline-3-carboxylic acid • 1-Ceryl-6-fluoro-7- (1-iminoisoinolinolin-5-yl) -8 -Methane-1,4 -dihydro-4-airyl BE _ -3-unsaturated acid • 1-gallyl-7-U, 7-difluoroisoindolinium-Idolline-5-yl) -6- Oxy-8-methyl-1, 4-dihydro-4-oxypyridine-3-carboxylic acid • 5-amino-1-cyclopropyl-6-fluoro-7- (isoindolinline-5 -Yl) -8-methyl-1,4-bisfluoren-4-yl-pyridin-3-carboxylic acid. 1-benzyl-6-fluoro-7 .- (4-cyanoindoline- 5-yl) -8-methoxy-1,4-dihydro-4-carbyl group If W -3-Canoic acid • Phenylpropyl-8-difluoromethane-6-fluoro-7- (3- Methyl isoindolino-5-yl) -1,4-dihydro-4-oxyfluoroline-3-carboxylic acid • Phenylpropyl-8-difluoromethane-7- (1,3- Dimethylisoindolin-5-yl) -6-cyano-1,4-dihydro-4-oxyHfline-3-carboxylic acid • Phenyl-8-digasmethyl-6- GAS- 7- (1-methylisoindolinol-5-yl) -1,4 -digas-4-oxy if hemp-3-dwarf acid • 1-chenpropyl-8-difluoromethoxy -6-Fluoro-7- [蠼 [Iso [IndoH-doline-1,1'-Chenpropane] -5-yl) -1,4-difluoren-4-aminopyridin-3-carboxylic acid Ethylpropyl-8-difluoromethane-6-daily 7- (1-iminoisoindolinyl-5 -yl) -1,4-difluoren-4-yl 丨 folin-3 -Carboxylic acid 1-chenpropyl-7- (4,7-dicyanoisoinolinolin-5-yl) -8-difluoromethoxy-6-fluoro-1,4- Hydroxy-4-oxy Kfline-3-carboxylic acid • 5-Amino-1-chenpropyl-8-difluoromethoxy-6-fluoro-7- (isoindolinoline 5- -2 7- This paper size applies to China National Standard (CNS) A4 specification (210X 297 mm) —------- ^ — packing * ------ Xu-^ "line (please read the precautions on the back first) Refill this page) Printed by A7 _B7_ of the Consumer Cooperatives of the Central Procurement Bureau of the Ministry of Economy Propyl-8-difluoromethoxy-6-fluoro-7- (4-fluoro-isoindolline-5-yl) -1,4-bisarthr-4-aminoylfluorin-3-carboxylic acid • 1-Ceryl-6-fluoro-7- (4-fluoroisoindolyl-5-yl) -1,4-dihydro-4-aminopyridin-3-carboxylic acid • 1-chenpropyl -7- (4, 7-difluoroisoindolinium $ -5-yl) -6-fluoro-1,4-difluoren-4-ylamino-3-phenylcarboxylic acid • Phenyl-6 -Fluoro-8-fluoromethyl-7- (isoindole I # line-5-yl) -1,4-dihydro-4-oxyifline-3-carboxylic acid • 1-cyclopropyl-6- Fluoro-8- «methyl-7- (2-methylisoinolinolin-5-yl) -1,4-difluoren-4-oxy 丨 folin-3-carboxylic acid -7- (1,3-dimethylisoindolin-1dolin-5-yl) -6-fluoro-8-fluoromethyl-1,4-dihydro-4-airyl β-line-3-carboxylic acid • 1-cyclopropyl-8-difluoromethyl-6-fluoro-7- (isoinolinolin-5-yl) -1,4-dihydro-4-oxy_fline-3-carboxylic acid • 1-Hydroxypropyl-8-difluoromethyl-6-fluoro-7- (2-methylisoindolinium Ironyl-5-yl) -1,4-dihydro-4-amino group _-3 -Dwarf acid • Phenyl-8-difluoromethyl-7- (1,3-dimethylisoindolin-5-yl) -6-fluoro-1,4-difluoren-4-oxo I-Porphyrin-3-carboxylic acid • 1-Ceryl-6-cyano-7- (isoindoleline-5-yl> -8-trimethyl-1,4-dihydro-4 -Amino cyanoline-3-carboxylic acid, • cyclopropyl-6-fluoro-7- (2-methylisoindinolin-5-yl) -8-trifluoromethyl-1,4-di Hydrogen-4-amino-iso-folin-3-carboxylic acid • 1-Ceryl-7- (1,3-dimethylisoindolinol_-5-yl) -6-fluoro-8-tri -2 8 ~ This paper size applies Chinese National Standard (CMS) A4 specification (210X297mm) --------- ^ Ί Equipment-(Please read the precautions on the back before filling this page) Order- 2 A7 B7 _ V. Description of the invention (&gt; 9) Fluoromethyl-1,4-dihydro-4-oxyfluoroline-3-carboxylic acid • Buchenpropyl-6-fluoro-7- (isoindole (Purinolin-5-yl) -5,8-dimethyl-1,4-dihydro-4-oxyβ phthaloline-3-carboxylic acid • Phenyl-6-fluoro-5,8-dimethyl -7- (2-methylisoindolinline-5 -Yl) -1,4-dihydro-4-oxypyrene-3-aranoic acid • Butoxypropyl-6-fluoro-5,8-dimethyl-7- (1,3-dimethyl Isoindole-5-rongolin-5-yl) -1,4-bisfluoren-4-oxyquinoline-3-carboxylic acid • 8-chloro-1-cyclopropyl-7- (isoindioline-5- Yl) -1,4-dihydro-4-ylaminopyridin-3-carboxylic acid • 1-chenpropyl-8-fluoro-7- (isoindololin-5-yl) -1,4-di Hydroxy-4-oxoline-3-carboxylic acid • cyclopropyl-7- (iso-I-tertrin W-5-yl) -8-methyl-1,4-dicyano-4-amino When the compound of general formula [I] or its salt has isomers (such as optical isomers, geometric isomers, tautomers, etc.), the present invention includes these isomers, and The compound or its salt may be in a solvate or hydrate or multiple crystalline forms. The production method of the compound of the present invention is explained below. The compound of the present invention can be synthesized according to, for example, the following method. --------- f -install, ------ IT—a r --- f line (please read the precautions on the back before filling this page) Employees' Cooperatives of Central Bureau of Standards, Ministry of Economic Affairs Printing -29- This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) A7 B7 V. Description of invention (4 [Manufacturing method 1] R6 0

R6 〇

[4] or a salt thereof [2] or a salt thereof

Sn (Alk) 3 catalyst R6 〇

CO2R1

[5] or its salt I ------- Λ I equipment -------- Order 丨 ----- f line (Please read the precautions on the back before filling this page) Central Bureau of Standards, Ministry of Economic Affairs The work-consumption cooperation is printed as the general formulas [1], [2], [3], [4] and [51 above, where R1, R2, R4, Rs, Rs, and X are defined as above; Gas atom, bromine atom or iodine atom; and Alfc represents a linear or branched alkyl group containing 1 to 6 値 atoms β -30- This paper size applies to the Chinese National Standard (CNS) A4 specification (2 丨 0X297 mm) DuPont A7 B7 printed by Shellfish Consumer Cooperation of the Central Bureau of Standards, Ministry of Economic Affairs 5. Description of the invention (0) Salts of compounds of the general formulas [2], [3], [4] and [5] contain the general formula [1] Compounds are the same salts. A compound of the general formula [1] or its "can be used to catalyze the adduct in the presence or absence of silver, or a compound of the general formula [2] or its salt and an organic tin compound or its salt or The general formula U] has an eaves compound or a salt thereof and a compound of the general formula [5] or a compound thereof to obtain β. The solvent used in this reaction may be any solvent, as long as the reaction does not produce a bad color. As for solvents, it is worth mentioning, for example, aromatic benzene, toluene, xylene, etc .; ethers such as dioxane, tetrahydrofuran, phenyl methyl ether, dioxane diethyl ether, dimethyl lysate Please wait, please wait, please wait; wake up, such as Ν, Ν-dimethyl mesitamine, Ν, Ν-dimethylacetamide, etc .; Yaming, such as dimethylarsine, etc., and these soluble "I They can be used alone or as a mixture of two or more. This reaction uses a complex SI that contains, for example, PdCl2 (PPh3) 2, Pd (PPh3) «,

PdCl2 [P (0-tolyl) 3] 2, PdCl2 + 2P (OEt) 3 and PdCl2 (PhCN) 2, where Pli represents a phenyl group. The use of the eaves tin compound or its salt of the general formula [3] is at least 1 mole, preferably 1.0 to 2.0 moles per mole of the compound [2] or its salt, and the compound of the general formula [5] The amount of M or its salt is at least 1 mole, preferably 1. G to 5.0 moles per mole of the organic tin compound of the general formula [4] or its salt. Such a coupling reaction is usually in an inert gas ( For example, argon, nitrogen) in the atmosphere at 50 to 17Q * C temperature for 1 minute to 24 hours to complete. The compound of the general formula [1] or a salt thereof thus obtained can be subjected to a known reaction such as gasification, primogenation, rearrangement, substitution, halogenation, dehydration, and water-3 by the former. CNS) A4 specification (210X297mm) -------- Λ-installation ------ order. 丨 -Γ, --- Γ line (please read the precautions on the back before filling this page) A7 _B7__ 5. Explanation of the invention (v) The solution or the appropriate combination of these anti- «will be converted into another compound of the general formula [1] or its salt. If the general formula 12 of the aforementioned production method], [31, [4] And the compound of [5] or its salt has isomers (such as optical isomers, geometric isomers, tautomers, etc.), then these equivalent structures may be substituted. Moreover, the aforementioned compound or its surface may be a solvent Hydrates or hydrates or various crystalline forms. When the compounds of the general formulas [1], [2], [3],. [4] and [5] or their 81 contains an amino group, a hydroxyl group or a carboxyl group can be used in advance The conventional spleen protects this group and removes the protecting group in a known manner after the reaction. Next, the compound of the general formula [21, [31, [4] and [5] or a salt thereof (starting from the production of the compound of the present invention) The method of cracking is described as follows: • Organic tin compounds of the general formulas [3] and [4] or their "is a new compound. First of all, the compounds of the general formula [21 or * and the organic tin compounds of the general formula [4] or their salts. It can be synthesized according to the following method. -------- Λ I Pack-(Please read the precautions on the back before filling out this page) * tr Central Ministry of Economic Affairs, Central Bureau of Standards, Another Industry Consumer Cooperative Cooperative Indigo -32 -This paper size applies to China National Standards (CNS) A4 ^ grid (210X297 mm) A7 B7 V. Description of the invention (~) R6 R6

nn ml ml &gt; n ^ — I ^ 1 · (Please read the precautions on the back before filling out this page),-'° .Γ line, printed by the staff consumer cooperative of the Central Bureau of Standards, Ministry of Economic Affairs

C02R1 The size of this paper is applicable to China National Standard (CNS) A4 (210X297 mm) • 33 · Printed by ABC Consumer Cooperatives, Central Standards Bureau of the Ministry of Economic Affairs 袈 Α7 Β7 V. Description of the invention (p) As the general formula [2] above, 4], [61, [7], [81, [9], [10], [11] \ / and [12], R1, R2, Re, A, X, X1 and Aik are defined as above; R14 · Represents a carboxyl protecting group as R1; R 24 represents a substituted or unsubstituted 焼 16, ** group, schenyl group, aryl group or heteroschenyl group as R2; 〆 is a group represented by the formula: 'N 〆 or 夂 C〆T a where Ya represents a hydrogen atom, a tooth atom, a substituted or unsubstituted alkyl group, an alkyl group or an alkylthio group, or a protected or unprotected hydroxyl group; and X2 represents a ® atom . The salts of the compounds of the general formulas [6], [7], [8], [9], [10], [1 II and [1 2] include the same compounds as those of the compounds of the general formula [1]. The steps are explained as follows: (U general formula [VII compound or its salt or general formula [1II compound or its hydrazine is generally known in the industry via the general formula [61 compound or its general formula [10] compound or its salt, respectively. (A) For example, according to the method described in Angewant C Henie, Internati na 1 Edition in English, vol. 18, page 72 (1 979), a compound of the general formula [6] or a salt thereof The carboxyl group of the compound of the general formula [10] or a salt thereof, such as N,! Γ-carbonyldiimidazole, converts the compound into an active acid amine, and then the active acid amine and malonate The magnesium salt can be converted to a compound of the general formula [7! Or a salt thereof or a compound of the general formula [11] or an active acid sulfonium amine and a malonic acid monoester magnesium sulfide.醮 can be any solvent and contains, for example, aromatic tobaccos such as benzene, toluene, xylene, etc .; ethers such as dioxane, tetrahydrofuran, diethyl ether, etc .; halogenated hydrocarbons such as dicyano-3 4-This paper is in accordance with China's national standards ( CNS) Α4 specification (2 丨 0 × 297 mm) -------- f -install -------- 訏 Ir --- f cable (please read the first Please note this page, please fill in this page) DuPont printed A7 B7 produced by the Central Bureau of Standards and Quarantine of the Ministry of Economic Affairs _ V. Description of the invention (") Methane, cyanoform, ethane, etc .; Methyl methyl B amine, Ν, Ν-dimethyl ethyl amine, etc. These solvols can be used alone or as a mixture of two or more. H, (T-carbonyldiazole and malonate The amount of the magnesium salt of the ester is at least 1 mole, preferably 1 to 2 moles, relative to the compound of the general formula [6] or [10] of the mole. The reaction is usually 僳 0-100 * 0, Preferably, the temperature is 10-80eC for 5 minutes to 30 hours. (B) As for another method, the compound of the general formula [6] or a carboxyl group of the * or the compound of the general U0] carboxyl group is modified. For example, the sulfur saccharyl group is converted into an acid halide and subsequently the acid halide is a metal salt of a malonic acid diester such as the malonate diester or the reaction of "magnesium", and the reaction mixture is then hydrated. In the dissolution, p-toluene acid or triacetic acid was used for partial removal and decarboxylation of the carboxyl protecting group, and thus the general formula [Ήcompound or its] or the general formula [Π] compound or its. The cocoon used in the reaction of the compound with the malonate diester gold osmium salt can be any solvent as long as it does not adversely affect the reaction, and it must additionally contain the same solvent as the aforementioned U) (a) _ βmalonate diester metal The amount of salt is at least 1 ear, preferably 1 to 3 ears, relative to the general formula [61 or [101] compound or its salt per ear. This reaction is usually carried out at a temperature of -50 to 10 (TC). 5 minutes to 30 hours. (2) (a &gt; A compound of the general formula [9] or a salt thereof or a compound of the general formula [12] or a salt thereof may be passed through the compound of the general formula [71 or a salt thereof or a general formula 丨 11], respectively. The compound or its hydrazone is reacted with an orthoester such as methyl orthoformate and ethyl orthoformate equal to acetic acid, and then reacted with a compound of the general formula [8] or its ". Solvents used in these reactions _ as long as there is no adverse effect on the reaction, it can be any solvent containing, for example, aromatic smoke such as benzene, toluene, xylene, etc .; such as -35- This paper is applicable to Chinese national standards ( CNS) A4 specification (210X297mm) I ------- 丨 installed, ----- ordered --i ---- A line (please read the precautions on the back before filling out this note) Printed A7 B7__ Printed by the Shellfish Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs V. Description of the Invention (4) Di-Isoane, Tetrahydrofuran, Phenylmethyl «, Dioxane Diethyl«, Dimethyl Solvent Fermentation, such as formazan, acetic fermentation, propionate, etc .; halogenated halogens such as di «methane, cyanoform, dicyanoethane, etc .; amines such as N, N-dimethylformamide, Ν, Ν -di Methyl ethylamine, etc .; such as dimethylene, etc .; etc. These solvents can be used alone or in combination of two or more. The amount of ortho-acid sugar is relative to the general formula [毎 or [11] The compound or its stupid is at least 1 ear, preferably 1 to 10 moles. The reaction is usually carried out at a temperature of 0-15 (TC, preferably 50-1 50 ° C for 20 minutes to 50 hours In the reaction with the compound of the general formula U] or its reaction after time ❶, the general formula [8] The use of the compound or its salt is at least 1 mole relative to the general formula [Ή or [11] of the compound or its salt. These reactions are usually inferior to O-iWC, preferably 10-60 · 0. (B) As for another method, the compound of the general formula (Ή compound or its 鼸 or the formula [11] or its "and acetal such as Ν, Ν-dimethylmethylose according to two Methyl acetals, η, N-dimethylformamide diethyl aldehydes, etc., are reacted in the presence or absence of acetic anhydride, such as acetic anhydride, etc., and then converted into the following general reactions [8] or their salts. The compound of the general formula [9] or a salt thereof, or the compound of the general formula [12 丨 or a salt thereof. The solvent used in the foregoing reaction can be any solvent as long as it does not cause an adverse color reaction, and further includes the above (2) & lt a) The same amount of the same solution is at least 1 mole relative to the compound of the general formula [7] or [11] or its salt, and about 1 to 5 deciles compared to 。. Reaction with S Usually you carry out the reaction for 20 minutes to 50 hours at a temperature of 0-100 eC, preferably 20-85 °. Afterwards, the compound of the general formula [81 or its compound], the compound of the general formula [8] or its The amount of tincture relative to tincture The compound of formula [7] or its color is at least 1 mole, and these reactions are usually carried out at a temperature of preferably 10-6 D eC for a period of 20 minutes to 30 hours. (3) General formula [ 21 The compound or its salt or the compound of the general formula [41] or its salt can be identified through the compound of the general formula [9] or its crocodile or the compound of the general formula [12] or its salt in the presence or absence of fluoride salt or age, respectively. It can be obtained by reaction. Soluble in reaction _ as long as it does not cause adverse color response to the reaction, it can be any solvent containing, for example, sugar amines such as Ν, Ν-dimethylformamide, Ν, Ν-dimethylacetamide Amines, etc .; ethers such as dioxane, phenylmethyl ether, dioxalyl dimethyl ether, dimethyl lysolysine, etc .; fluorene, such as dimethylarsine, etc .; etc. These solvents can be used alone or in combination of two or more. Visible Fluoride-3 to be used-6-This paper size is applicable to China National Standard (CNS) A4 (210 × 297 mm) --------- f 1 Packing -------- Order-- --f line (please read the note on the back before filling in this). Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 _ _ _B7___ V. Description of the invention (β) The surface contains such as sodium fluoride, potassium Etc., and the sickle to be used includes, for example, sodium oxalate, sulfonic acid, potassium third butoxide, argon pin and the like. The amount of fluoride or _ is equivalent to at least 1 mol, preferably 1.0 to 3.0 mol, of the compound of the general formula [9] or [12], respectively. The reaction is usually provided at a range of 0-180 ° F for 5 minutes to 30 hours. It is believed that the compound of the general formula [3] or [4] where // is the following formula:

Under the CIY basic expression, the generation 2 R is public, where the definitions of B and R7 can be prepared according to the methods described in Japanese Patent Laid-open No. 2-85,255 and the like. An aryl tin compound of the general formula [10] or a salt thereof, an aryl tin compound of the general formula [11] or a salt of the aryl tin compound of the general formula [4], or an aryl tin compound of the general formula [4] may be respectively halogenated through an aryl compound through the general formula I 6] Or a salt thereof, a compound of the general formula [71] or a halogenated aryl compound, or a halogenated aryl compound of the general formula [2] The method described in (1386) can be used as a solvent for the reaction of hexaalkyl diradane, and the catalyst can be used as the catalyst without any adverse effect on the reaction. The special case 傜 is the same as the aforementioned cracking method 1. The amount of hexaalkyldistannane is at least 1 mole, preferably 1.0 to 3.0 moles per mole of the general formula [6] [7] or [2] ® aryl compound or a salt thereof. The response is usually like 4 0-1 6 0 -C -37- ------- ii installation -------- order- t --- Γ line (please read the precautions on the back before filling in this (Page) This paper is in Chinese National Standard (CNS) A4g (210X297 mm). It is printed on A7 (_____; B7 ___) by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs. 5. The temperature of the description of invention (4) is 1-7 2 Hour time β When the general formula [2], [4], [6], [7], [8], [9], [10], [11] or [12] in the production route contains an amine In the case of a hydroxyl group, a hydroxyl group or a carboxyl group, the conventional protecting group can be used to protect the group in advance, and the protecting group can be removed in a known manner after the reaction is completed. When the general method [2], [4], [6], [ 7], [8], [9], [10], [11] or [12] or their salts have isomers (such as optical isomers, geometric isomers, tautomers, etc.), These isomers may be substituted. The aforementioned compounds or their salts may be used in solvates or hydrates or in the desired crystal form. After the reaction is complete, the reaction mixture may be used for this purpose in subsequent reactions without the need to isolate the compound. A compound of the general formula [6] or Salts and compounds of the general formula [2] or their salts (one of the starting materials for the production of the compounds of the present invention) can be synthesized from known compounds. The synthesis method can be converted by the method described in, for example, Japanese Patent Laid-Open No. 1-100,166 The method containing the pain X ', that is, using mulberry mel to reverse the reaction. Subsequently, the organotin compound or its salt of the general formula [3] can be synthesized according to, for example, the following synthesis method: R4 R4

[5] or a salt thereof [3] or a salt thereof wherein R 3, R 4, R s, X 1 and Aik are as defined above. The compound of the general formula [3] or its hydrazone can pass through the compound of the general formula [5] or its salt root_ 3 8-This paper size applies to the Chinese National Standard (CNS) A4 specification (210 × 297 mm) (please read the note on the back first) (Fill in this page again)-Pack ^

* 1T

X A7 B7 V. Description of the invention U! It is obtained by reacting hexaalkyldisilazane with rake complex catalyst according to the above method. In the above production method, when the compound of the general formula [3] or 丨 5] or its isomers (such as light isomers, geometric isomers, tautomers, etc.), these isomers may be replaced. . The above compounds or their salts can be used in a solvent or in a crystal form. When the compound of the general formula [3] or [5] has an amine group or a hydroxyl group, this group can be protected in advance with a conventional protecting group and the protecting group can be removed in a known manner after completion of the reaction. The isoindolinium halide represented by the general formula [5] or one of the starting materials used in the production of the compound of the present invention can be synthesized by the following synthetic methods, for example, according to Organic Synthesis Book 5, 1064-106 6 The method is described in Japanese Patent Publication No. 63-179,872, Japanese Patent Publication No. 2-62,8Ϊ5, or Japanese Patent Publication No. 3-52,888 or 4 ^ 1116111-? (^ 811./ Drug Res. 3〇 (ll), 1487-1493 (1980), etc. -------- ^ · Equipment ---- (Please read the precautions on the back before filling this page)

* 1T

Class S Printed by the Consumer Cooperatives of the Central Government Bureau of the Ministry of Economic Affairs [13]

14 1 or its salt

This paper size applies to Chinese national standards (CNS &gt; A4 size (210X297 mm)

Printed by the Employees' Cooperatives of the Central Government Bureau of the Ministry of Economic Affairs A7 B7 V. Invention Description

U5] or a salt thereof wherein R3, 1 ^ and ^ are as defined above, and γ represents a removing group. The salt of the compound of the general formula [13] '[141, [15] and [5a] includes the salt as described for the compound of the general formula [1]. The removing group of Y contains a halogen atom such as a gas atom, a bromine atom, etc. "The general formula [5] or a salt thereof can be reacted via a compound of the general formula [13] or a salt thereof via the rS (JH2 reaction, or via a compound of the general formula [14] or The salt is obtained by dehydration. On the other hand, the compound of the general formula [5aj or its salt, which contains an imine group, can be obtained by a closed reaction of the compound of the general formula [15] or its salt. In addition, the general formula [13 ], [14] or [15] compounds or their salts, and organotin compounds derived from compounds of the general formula [13], [14] or [15] or their salts can be combined with the compounds of the general formula [4] or [2] or The salt is subjected to a coupling reaction according to the same method as in Production Method 1 above, and the obtained compound is subjected to the isocyanate ring formation reaction according to the aforementioned method to obtain a compound of the general formula [1] or a salt thereof. In the aforementioned production method, when the general formula When [13], [14], [15] or [5a] compounds or their salts have isomers (such as optical isomers, geometric isomers, mutual isomers, etc.), these isomers may be Instead, the aforementioned compounds or their salts may be used in solvates or hydrates or in multiple crystal forms. When the compounds of the general formula [13], [14], [15] or [5a] or When the salt has an amine group or a hydroxyl group, this group can be protected in advance with a conventional protecting group, and the protecting group can be removed in a known manner after the reaction. The compound of the general formula [1] or a salt thereof can also be produced by any of the production methods shown below. -40- This paper size applies to China National Standard (CNS) A4 (210X297mm) (Please read the precautions on the back before filling this page)

A7 B7 V. Description of the invention (God [Method 2] R6 0

C02Rla 16] or its salt 1) orthoester or acetal 2) R 2¾ -JJH 2 [8] or its salt R6 0

ί ——--- I 1—--I — ^ n nn--: I · ---- -ΪΙ (锖 Please read the notes on the back before filling this page),? τ Central Bureau of Standards, Ministry of Economic Affairs Printed by Employee Consumer Cooperative R6 0

CO2R1 1] or its salt-41 This paper size applies to Chinese National Standards (CNS) A4 specifications (210 × 297 mm) A7 B7 V. Description of the invention (and) Among them R1, Ria, R2, R221, R3, R4, RS, R6 , A〆Λα1, X and X 2 are defined as above. The salt of the compound of the general formula [16] or [17] includes the same salt as previously described for the compound of the general formula [1]. A compound of the general formula [1] or a salt thereof can be prepared from a compound of the general formula [16] or a salt thereof according to the aforementioned method (a compound of the general formula [2] or [4] or a salt thereof from a compound of the general formula [7] or [Η] Synthesis). In other words, the compound of the general formula [1] or its salt can be reacted with the orthoester or acetal in the presence or absence of an acid anhydride such as acetic anhydride via the compound of the general formula U6] or its salt, and then reacted with the general formula [8] or its salt. The reaction is obtained by a compound of the general formula [17] or a thinner than a thin-walled reaction in the presence or absence of a fluoride salt or _. The compound of the general formula [1] or a salt thereof thus obtained can be converted to B via a known reaction such as gasification, passogen, rearrangement, substitution, toothing, dehydration, hydrolysis, etc. -A compound of the general formula [1]. In the aforementioned production method, when the compound of the general formula 丨 8], [16] or [17] or its salt has isomers (such as optical isomers, geometric isomers, tautomers, etc.), these isomers Things can be replaced. The aforementioned compounds or their salts can be used in the form of solvates or hydrates or the desired crystal form. The Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs prints -------- Γ-- (Please read the Note: Please fill in this page again) When the compound of the general formula [8], [161, [17] or [1] or its salt has an amine group, a hydroxyl group or a carboxyl group, a conventional protecting group may be used to protect the group in advance and complete the reaction. The protecting group is then removed in a conventional manner. After completion of the reaction, the reaction mixture may be used in the subsequent reaction without isolating the target compound. Next, the compound of the general formula [16] or a salt thereof, which is one of the starting materials for producing the compound of the present invention, will be described below. The compound of the general formula [16] or hydrazone is novel and can be synthesized according to, for example, the following production method. ___ _________- 4 _________ This paper size applies to Chinese National Standards (CNS) A4 specifications (2 丨 〇 X 297 mm) A7 B7 V. Description of the invention (4) Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs R6

[16] or a -43- I ------- Γ Pack 1 (· Please read the precautions on the back before filling this page)

、 1T This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X297mm). Du Yinshu A7 B7, employee cooperation of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (0) In the above formula [6], [7], [10], [11], [16] and [18],! {1,11 ^, K3, K4, R5, Re, X, X1, X2 and Uk are defined as above. The compounds of the general formula [18] include the same compounds as the general formula [1]. The compound of the general formula [16] or a salt thereof can be synthesized from a compound of the general formula [7] or [11] or a salt thereof according to the same method as described in the production method 1 above, or can also be prepared by subjecting a compound of the general formula [18] or a salt thereof according to the foregoing Methods Production was carried out by esterification. The compound of the general formula [7] or a salt thereof or the compound of the general formula [11] or a salt thereof can be respectively subjected to the ketone through the compound of the general formula [6] or a salt thereof or the compound of the general formula [1 Q] or a salt thereof according to the aforementioned method. Obtained from esterification. On the other hand, the compound of the general formula [18] or a salt thereof can be prepared from the compound of the general formula [6] or [10] or a salt thereof according to the same method as in the aforementioned production method 1. When the compound of the general formula [6], [7], [10], [11], [16] or [18] or a salt thereof has an amine group, a hydroxyl group or a carboxyl group, the conventional protecting group may be used to protect the group in advance, and This group is removed in a known manner after the reaction. In the foregoing preparation method, when the compound of the general formula U], [7], [10], 丨 11], [16] or [18] has a isomer (optical isomer, geometric isomer, mutual variation) Structures, etc.), these isomers may be used instead, and the aforementioned compounds or their salts may be used as solvates or hydrates or desired crystals. After the reaction is completed, the reaction mixture can be used for the post-reaction reaction without isolating the target compound. The compound of the general formula [I] or its salt thus obtained can be isolated and passivated according to conventional methods such as extraction, crystallization, formula analysis, etc. When the compound of the present invention is used as a mash, the compound can be formulated as Zorru-4 4 -This paper size applies Chinese National Standard (CNS) A4 specification (210X297mm) I -------- ^ -I (Please read the precautions on the back before filling this page), -'0 Central of the Ministry of Economic Affairs Standards Bureau's consumer cooperation Du printed A7 _ B7_ '__ 5. Description of the invention (G) Excipients, carriers or diluents used in conventional pharmaceutical preparations can be mixed and can be tablets, capsules, powders, thin syrups, granules Thin I, Jiujing, dispersing liquid, emulsion, solution thin I, suppository I, ointment, injection and other 剤 type oral or external administration. The route, dosage and frequency of administration can be appropriately changed according to the age, weight and symptoms of the patient. It is usually divided into a ratio of 0.1 to 100 aig / kg / day-one to several portions of the compound administered to the patient by oral or external gambling (for example, by injection, drip, intramucosal administration, etc.). Next, the pharmacological activities of the representative compounds of the present invention will be described. Antibacterial activity test method According to the method of the Japanese Chemotherapy Association [CHEMOTHERARY, V〇1.

'I 29, Νο · 1, page 7 6-7 9 (1 9 8 1)], a loop of bacterial solution of inoculation loop (via Miller's nutritional juice (manufactured by D if co) at 37 * C 20 hours and adjusted to a concentration of 1Q6 cells / plate (1Q8 cells / ml)) Inoculated on the Miller rowton agar culture base (Difco Di) containing the test compound, and cultured at 37 eC for 20 hours, and with Later, the growth of the larvae was observed to determine the minimum degree of growth inhibition. The concentration was expressed as MIM # 8 / · 1). The test results are shown in Table U. The asterisks in Table 1 are defined as follows: *: / 5-lactamase-productive MRSA (methicillin-resistant Staphylococcus aureus) Test compound A: 1-cyclopropyl- 6-fluoro-7- (isoindhenyl-5-yl) -8-methyl-1,4-dihydro-4-oxy! -3-carboxylic acid reference compound B: 1-Cyclopropyl-6-fluoro-7- (1-hexahydropyridyl) -1, -45 * This paper size is applicable to China National Standard (CNS 丨 8-4 specifications) (2ι.οχ297 mm) ---------- Installation «— (Please read the notes on the back before filling in this page ·) Order A7 B7 V. Description of the Invention (Private) 4-Dihydro-4 -Oxy H $ line-3-carboxylic acid (Cyproxaxin) Table 1 MIC (μ g / m 1) AB Staphylococcus aureus FDA 2 0 9 P 0. 0 5 0. 2 Staphylococcus aureus F-137 * S 0. 0 5 0.39 Staphylococcus aureus F- 5 9 7 ** 0.05 Pack-I (Please read the notes on the back before filling this page) From the previous results, we can know that the compound of the present invention has excellent antibacterial activity. The best mode for carrying out the present invention Hereinafter, further details of the present invention will be described with reference to reference examples and examples. However, the present invention is by no means limited to this. Unless otherwise specified, the mixing ratio of the dissolving agent is like the silica gel 60, 7 7 3 4 (HER 0 & Co., INC.). Also in reference examples and examples, &quot; di-TFA &quot; · ^ means triacetic acid -d! and "d 6-DMS 0" means dimethylarmine-de. Reference Example 1 3.04 §ethyl 3-bromo-2 was dissolved in 3,001 toluene. 4,5-trifluorobenzoate, and 5.11 g of tributylvinyltin and 0.25 g of tris (triphenylphosphonium) were added to the solution (0), and then the resulting mixture was heated under a nitrogen atmosphere for 2 hours-46 -This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) -11 K4 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economics A7 B7. ). The reaction mixture was concentrated under reduced pressure, and the obtained residue was purified by column chromatography (isocyanate: n-hexane: ethyl acetate = 100: 1) to obtain ethyl 2,4,5-trifluoro- as a colorless oil. 3-Vinyl benzoate. The oily product thus obtained was dissolved in a mixed solvent of 62b1 formazan and 12b1 dichloromethane, and then odor gas was added at -5CTC for 3 hours, and then nitrogen was blown in. After 30 minutes, the temperature of the solution was raised to -20eC and 0.881 g of sodium borosulfide was subsequently added, after which the resulting mixture was stirred at room temperature for 12 hours. Mixture and addition of a mixed solvent of ethyl acetate and 400b1 PH 600b1 of ice-water and adjusted to 1 to 6N-hydrochloric acid gas, and then the resulting organic layer was BU washed with saturated saline solution and then dried over anhydrous sulfate scribe dehydration. The solvent was then removed by distillation under reduced pressure. The residue thus obtained was purified by column chromatography (dissolved in thin I: n-hexane: ethyl acetate = 4: 1) to obtain 1.70 g of ethyl as a colorless oil) -hydroxymethyl-2,4,5-tri Fluorobenzoate. IR (net) cm-i: υ〇〇1720 NMR (CDC13) δ value: 1.38 (3Η, t, J = 6.8Hz), 2.60 (lH, t, J = 5.0Hz), 4.39 (2H, q, J = 6.8Hz), 4.65-4.95 (2Hf m), 7.40-8.00 (1H, m) Reference Example 2 (1> Dissolved 61.7 g of ethyl 2,4, 5-trifluoro-3-methylbenzoate To this solution was added in 3 08b1 dimethylarsine and 4 2.3 g of sodium azide, and the resulting mixture was then stirred at 55 ° C. for 14 hours. The reaction mixture was cooled to room temperature and then added to ethyl acetate 500ffll. And mixed with 1200B1 water. The generated organic tritium is separated. It is washed with water and then dehydrated with anhydrous magnesium sulfate. Then the solvent is distilled off under reduced pressure to obtain 65.3 g of ethyl 4- * deuterium in the form of light yellow oil. -47- The size of this paper is applicable to China National Standard (CNS) A4 specification (210 × 297 mm) --------- Γ Packing ::-(Please read the notes on the back before filling in this card)

* 1T K line Consumption cooperation by employees of the Central Bureau of Standards, Ministry of Economic Affairs, Du printed A7 B7 V. Description of the invention (4) 2, 5-difluoro-3-methyl stearic acid ester. (2) Suspend 14.2 g of stannous gas in 60b1 formazan and dropwise add 10.10 g of ethyl 4-azido-2,5-difluoro-3-form in this suspension at room temperature over 1 hour. A solution of benzoic acid in 20.1 formazan, and then the resulting mixture was stirred at the same temperature for 30 minutes β to remove the formazan under reduced pressure, and 30 ml of ether and 〇〇〇Β1 were added to the obtained residue. Water, and then the pH was adjusted to 12.5 with 2N 氲 gasified sodium water solution. The resulting organic layer was separated, washed with water and dehydrated with anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure to obtain 8.91 g of ethyl 4-amino-2,5-difluoro-3-methylbenzoate β as a yellow oil (3) 8.91 g of ethyl 4-azide was dissolved -2,5-difluoro-3-methylbenzoic acid_ In 50 ml of acetic acid and add 50b1 2N sodium hydrogenated aqueous solution to the solution, and then the resulting mixture was stirred at room temperature for 3 hours. 50 ml of 2NBI acid was added to the reaction mixture and the resulting crystals were collected by filtration to obtain 5.45 g of colorless crystalline 4-amino-2,5-difluoro-3-methylbenzoic acid. IR (KBr) cm-i: υ〇〇1701, 1636 NMR (άχ-TFA) δ value: 2.50 (3H, s), 7.86 (1H, dd, J = 5.4Hz, J = 9.3Hz) Reference example 3 ( 1) Dissolve 13.2g of ethyl 3-difluoromethane-2,4,5-trifluorobenzoate in 66b1 dimethyl iodide and add 7.3 g * sodium nitride to this solution, and then obtain the mixture Stir at room temperature for 5 hours. Add 150ml of ethyl acetate and 150b1 ice water to the reaction mixture. 11 is adjusted to 2 with 2NH acid, and the resulting organic layer is separated and then sequentially with water and saturated brine-4 8-This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) ----- --- C, install ^ — (Please read the precautions on the back before filling this page) Order

X Printed by A7 B7 of the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. V. Description of the invention (47) The solution was washed and then dehydrated with anhydrous sodium sulfate. Then the solvent was removed by evaporation under reduced pressure. The obtained residue was purified by column chromatography (dissolution: n-hexane: ethyl acetate = 10: 1) to obtain 13.9 g of ethyl-4-azido-2,5-difluoro-3-formaldehyde as a colorless oil. Gas benzoate β (2) Dissolve 13.8 g of ethyl 4-azido-2,5-difluoro-3-difluoromethaneformate in 210 ml of acetic acid and 70 nl of ethyl acetate, and add 138 g 5% rake-sulfur was added to the solution, and the resulting mixture was then stirred at 5fleC for 6 hours under a stream of hydrogen. The reaction mixture was filtered and the resulting filtrate was concentrated under reduced pressure to obtain 12.3 g of colorless crystalline ethyl 4-amino-2,5-difluoro-3-difluoromethanebenzoate. (3) Suspend 12.3 g of ethyl 4-amino-2,5-difluoro-3-difluoromethanebenzoate in 61 ml of ethanol, and add 31bI 2U argon sodium aqueous solution to the suspension. The resulting mixture was stirred at 40 · 0 for 1 hour. 35 Bl 2N nitrogen acid was added to the reaction mixture, and the resulting splatter was collected by filtration to obtain 10.6 g of colorless crystalline 4-amino-2,5-difluoro-3-digasmethylbenzoic acid. IR (KBr) cm-1: υ〇-〇1703, 1636 NMR {CDCI3-CD3OD) 6 value i 6.62 (1H, tf J = 74Hz) f 7.49 (1H, ddf J = 6.3Hz, J = 11.7Hz) to In the same manner, the following compound e. 4-amino-2,5-difluoro-3-fluorobenzoic acid IR (KBr) cm-1 was obtained: uc = 〇1705, 1637 NMR (d6-DMSO) δ value: 5.60 (1H , d, J = 54HZ), 6.05 (2H, brs), 7.32 (1H, dd, J = 6.lHz, J = 11.7Hz) -49- This paper size applies to China National Standard (CNS) A4 specification (21 OX297 (Public Director) (Please read the precautions on the back before filling this page). Install '7 printed by the Consumers' Cooperative of the Central Bureau of Standards of the Ministry of Online Economics Ⅴ. Description of the invention (〇) • 4-Amino-2,5- Difluoro-3-hydroxymethylbenzoic acid IR (KBr) cm-i: υ〇β〇1717, 1639 NMR (CDCI3-CD3OD) δ value: 4.72 (2Η, d, J = 2.0Hz), 7.48 (1H, dd, J = 6.8Hz, J = 11.7Hz) Reference Example 4 26.3 | 4-Amino-2,5-difluoro-3-methylbenzoic acid was suspended in 658 | «14.7% hydrobromic acid, and 161 g of bromine Add hydrazone to the suspension. A solution of 16.5 g of sodium nitrite in 165? 1 water was added dropwise to this suspension over 1 hour with ice cooling, and the resulting mixture was stirred at the same temperature for 1 hour and then at the same temperature for 2 hours. To the reaction mixture was added 700B1 toluene and the resulting organic layer was separated, washed with waterfall hydrochloric acid, and then dehydrated with anhydrous magnesium sulfate. The solvent was then removed by evaporation under reduced pressure. To the obtained residue was added n-hexane and the obtained crystals were collected by filtration to obtain 29.5 g of colorless crystalline 4-bromo-2,5-difluoro-3-methylbenzoic acid. IR (KBr) cm-i: υ〇 · ο 1699 NMR (CDC13) δ value: 2.41 (3H, d, J = 2.9Hz), 7.57 (1H, άά, J = 6.3Hzf J = 7.8Hz) In the same way The following compound 0.4-bromo-2,5-difluoro-3-difluoromethoxybenzoic acid IR (KBr) cm-1 was obtained: υ〇 = ο 1718, 1698 NMR (CDCI3-CD3OD) δ value: 6.65 ( 1Η, t, J = 74Hz), 7.66 (1H, dd, J = 5.9Hz, J = 8.3Hz) • 4-bromo-2, 5-didai-3-fluoromethanebenzoic acid Standard (CNS) A4 specification (210X297 male) --------- C Pack --- (Please read the precautions on the back before filling this page)

, 1T

X

A Consumption cooperation by employees of the Central Bureau of Standards, Ministry of Economic Affairs, printed A7 B7 V. Description of the invention (49) IR (KBr) cm-1: uc = 〇1703 NMR (CDCI3) δ value: 5.72 (2Η, d, J = 53Hz) , 6.33 (1Η, brs), 7.63 (1H, dd, J = 5.8Hzf J = 8.3Hz) • 4-bromo-2, 5-difluoro-3-hydroxymethylbenzoic acid IR (KBr) cm-1: υ〇 = 〇1718 NMR (CD3OD) δ value: 4.83 (2H, d, J = 2, 4Hz), 7.68 (lHf dd, J = 6.1 Hz, J = 8.5 Hz) Reference Example 5 Dissolved in 8 ml sulfuric acid 2. Og 4-bromo-2,5-diiso-3-methylbenzoic acid and 4 ml of 1 nitrate were added dropwise to the solution with ice cooling, and the resulting mixture was then stirred at room temperature for 1 hour. The reaction mixture was added with a mixed solvent of 5Db1 ether and 50b1 ice water, and the resulting organic layer was separated, washed with a saturated saline solution and then dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure. To the residue thus obtained was added n-hexane and the resulting crystals were collected by filtration to obtain 1.9 g of pale yellow crystalline 4-aque-2,5-difluoro-3-methyl-6-nitrobenzoic acid. IR (KBr) cm-1: υ〇 = 〇1718 NMR (CDC13) δ value: 4.16 (3H, d, J〒2.9Hz), 8.75 (1H, brs) Reference Example 6 Dissolved in 100 ml of anhydrous tetrahydrofuran 10 · Og Bromo-2,5-difluoro-3-methylbenzoic acid and 9.69 g of fi, N'-carbonyldioxazole were added to the solution with ice quenching, and the resulting mixture was then stirred at room temperature for 1 hour. Subsequently, 8.56g of magnesium acetylacetate was added to the mixture and the resulting mixture was at -5 1- This paper size is applicable to China National Standard (CNS) A4 (210X297 mm) -------- packing *- -(Please read the precautions on the back before filling this page) Order A7 B7 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs' V. Description of the invention (β) Stir for 20 hours β reaction mixture is added to 200βι1 ethyl acetate and 300B1 A mixture of water and pH was adjusted to 1 with 6 N hydrochloric acid. The resulting organic layer was then separated, followed by saturated aqueous sodium hydrogen acetate solution. It was washed with water and a saturated saline solution, and then dried over anhydrous magnesium sulfate. Then, the solvent β was distilled off under reduced pressure, and the residue thus obtained was purified by column chromatography (eluent = n-hexane: ethyl acetate = 10: 1) to obtain 8. 9.5 g of colorless crystalline ethyl 4-bromo-2,5 -Difluoro-3-methylbenzoyl acetate β IR (KBr) cm-1: v &gt; c = 0 1644 NMR (CDCI3) δ value: 1.00-1.70 (3H, m), 2.41 (3H, d, J = 2.9Hz), 3.70-4.70 (3.2Hf m), 5.84 (0.4H, s) f 7.30-7.75 (1H, m), 12.5 (0.4H, brs) The following compounds were obtained in the same manner. • Ethyl 4-bromo-2,5-difluoren-3-difluoromethanebenzyl acetate IR (KBr) cm-i: uc = 〇1670 NMR (CDCI3) δ value: 0.70-1.40 ( 3Η, m), 3.60-4.50 (3.2H, m), 5.85 (0.4H, s), 6.62 (1H, t, J = 73Hz), 7.30-7.70 (1H, m), 12.7 (0.4H, s) • Ethyl 4-bromo-2,5-difluoro-3-fluoromethylbenzaldehyde acetate IR (KBr) cra-1: υ〇 = 〇1654 NMR (CDCI3) 6 Value: 1.00-1.50 (3Η , m), 3.60-4.50 (3.2H, m) f 5.69 (2H, d, J = 53Hz), 5.83 (0.4Hr s), 7.20-7.70 (1H, m), 12.6 (0.4H, s) Reference examples 7 1.8084-bromo-2,5-difluoro-3-hydroxymethylbenzoic acid suspended in 181111 di-52- --------- Γ -pack *-(Please read the precautions on the back before (Fill in this page) '1T · K line paper size is applicable to Chinese National Standard (CNS) Α4 size (210 × 297 mm) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 ___ ^ _, B7__ 5. Description of the invention (β) 1.64 g of triethylamine and 0.84 g of acetic acid were added to the gaseous methane and in the suspension under ice cooling, and the suspension was stirred for 1 hour. The temperature of the suspension was then raised to room temperature, at which time the mixture was stirred for another 12 hours. The reverse mixture was added to a mixed solvent of 20 ml of digas methane and 50 · 1 water, and the pH was adjusted to 1 with 6N hydrochloric acid. The radon layer was subsequently separated, washed with a planer and a saline solution, and then dehydrated with anhydrous sulfuric acid. Remove the solvent by evaporating under reduced pressure. The obtained residue was purified by column chromatography (eluent: cyanoform: acetic acid = 9: 1) to obtain 3-ethylacetoxymethyl-4-bromo-2,5-diargonbenzoic acid as a colorless oil. The obtained oily product was dissolved in 42.1 anhydrous tetramethylfuran, and 1.64 g of N, N1-carbonyldioxazole was added under ice-cooling. The resulting mixture was stirred at room temperature for 1 hour. Subsequently, 1.45 g of magnesium acetylacetate was added thereto, and the resulting mixture was stirred at the same temperature for 2 hours (ϊ hours. The reaction mixture was added to a mixed solution of 80B1 ethyl acetate and 10 Nl water and the pH was adjusted to 1 with 6N hydrochloric acid. The organic layer was then separated, washed with a saturated saline solution and then dried over anhydrous magnesium sulfate. Then the solvent was removed by distillation under reduced pressure. The residue thus obtained was purified by column chromatography (eluent: n-hexane: ethyl acetate = 20 : 1) Obtained 1.3 2 g of colorless crystalline ethyl 3-ethoxymethyl-4-bromo-2,5-difluorobenzylidene acetate. IR (KBr) cm-i: uc = 〇1742, 1654 NMR (CDC13) δ value: 1.00-1.50 (3Η, m), 2.08 (3Η, s), 3.80-4.50 (3_2H, m), 5.32 (2H, d, J = 2.4Hz), 5.87 (0.4Hr s ) f 7.40-7.90 (lHr m) r 12.3 (0.4H, brs) -53- This paper size applies to China National Standard (CNS) Α4 size (2 丨 0 × 297 mm) --------- c pack -— (Please read the notes on the back before filling this page)

* 1T Κ4 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 V. Description of the invention () Reference Example 8 In 1.0 g of 4-bromo-2,5-difluoro-3-methane-6-nitrobenzoic acid 3 ml of vaporized thiosulfanyl group and 0.3β1 N, N-dimethylformamide were added thereto, and the resulting mixture was heated under reflux for 1 hour. The reaction mixture was concentrated under reduced pressure to obtain ammonia. Another 0.4 g of 60% sodium hydride was suspended in 30B1 tetrahydrofuran, and 1.8 g of ethyl tert-butyl malonate was added dropwise to the suspension under ice cooling. The suspension was then suspended. Stir at the same temperature for 2 hours. To the obtained reaction mixture was added dropwise a solution of the aforementioned aldehyde nitrogen in 10 l tetramethylenefuran at -20 eC, and the resulting mixture was stirred under ice-cooling for 30 minutes and then at room temperature for 1 hour. The reaction mixture was added to a mixed solution of 50nl of ethyl acetate and 50b1 of water, and the pH was adjusted to 1 with 6H hydrochloric acid. The resulting organic hydrazone was separated, washed successively with water and a saturated saline solution and then dried over anhydrous magnesium sulfate. Then, the solvent β was removed by distillation under reduced pressure, and the residue thus obtained was added with 10 »1 dichloromethane and trifluoroacetic acid, and the resulting mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and the obtained residue was purified by column chromatography (solvent: toluene) to obtain 0.9 g of colorless crystalline ethyl 4-bromo-2,5-difluoro-3-methane-6- Nitrobenzyl acetate. IR (KBr) cm-1: υ〇 = ο 1737r 1718 NMR (CDCI3) δ value: 1.25 (3H, t, J = 7.3Hz), 3.60-4.40 (7H, m) Refer to Example 9 (1) in 15〇1 «1 digas methane dissolved 30.08 ethyl 4-bromo-2,5-difluoro-3-methylbenzylidene acetate, and 19.1 g of acetic anhydride and 22.3 g of N, N-dimethyl Formaldehyde dimethyl acetal was added to the solution, and the resulting mixture was -54- This paper size applies to China National Standard (CNS) A4 (210X297 mm) — i —I. I l · — I (Please read first Note on the back, please fill in this page again.),? Τ Aye B7, B7, Consumer Cooperation of the Central Bureau of Standards of the Ministry of Economic Affairs, A7 B7 5. Description of Invention (β) Stir at room temperature for 1 hour. The solvent was then distilled off under reduced pressure. The obtained residue was dissolved in ethanol and 5.90 g of benzylamine was added thereto, and then the resulting mixture was stirred at room temperature for 30 minutes. Then, the solvent was distilled off under reduced pressure. To the resulting residue was added n-hexane and the resulting crystals were filtered to obtain 35.7 g of colorless crystalline ethyl 2- (4-bromo-2,5-difluoro-3-methyl). Benzamidine) -3-cyclopropylaminoacrylic acid. (2) Dissolve 35.0 g of ethyl 2- (4-bromo-2,5-dicyano-3-methylbenzyl) -3-gallylamino acrylate in 175 ml of dimethylidene 1¾, and 27.4 g of potassium osmate was added to the solution, and the resulting mixture was then stirred at 10 ° C for 3D minutes. The reaction mixture was cooled to room temperature, and 1DDOml water was added thereto, and the resulting crystals were collected by filtration to obtain 30.0 g of colorless crystalline ethyl 7-bromo-1-cyclopropyl-6-fluoro-8-methyl- 1,4-dihydro-4-oxetine Iffline-3-carboxylic acid ester "IR (KBr) cm-1: uc = 01731 NMR (CDC13) δ value: 0.70-1.70 (7Η, m), 2.91 ( 3Η, s), 3.70-4.10 (1H, m), 4.38 (2Hf qf J = 7.3Hz), 8.01 (1H, dr J = 8.3Hz) / 8.65 (1H, s) The following compounds were obtained in the same manner. • Ethyl 7-bromo-bupropion-8-difluoromethane-6-fluoro-1,4-difluoren-4-oxyIlfline-3-carboxylic acid ester IR (KBr) cm-1: υ〇 = 〇1723 NMR (CDCI3) 5 values: 0.90-1.60 (7Hr m), 3,80-4.15 (1H, m), 4.39 (2H, q, J = 7.3Hz) f 6.59 (1H, tr J = 74Hz), 8.16 (1H, d, J = 8.3Hz), 8.61 (1H, s) ~ 5 5-This paper size applies to China National Standard (CNS) A4 (21〇 ×: 297mm) ---- ----- C 、 装 — (Please read the notes on the back before filling this page) -1T.

X Consumption cooperation by employees of the Central Bureau of Standards of the Ministry of Economic Affairs, Du printed A 7: B7 V. Description of invention (β). Ethyl 7-bromo-bupropion-6-fluoro-8-fluoromethyl-1,4-di Hydrogen-4-amino IFfline-3-carboxylic acid ester IR (KBr) cm-i: υ〇 = 〇1684, 1644 NMR (CDC13) 6 Value: 0.90-1.60 (7Η, m), 3.80-4.60 (3H , m), 5.69 (2H, df J = 54Hz), 8.11 (1H, d, J = 8.3Hz), 8.61 (1H, s) • Ethyl 8-acetamidine methyl-7-bromo-1-ring Propyl-6-fluoro-1,4-dihydro-4 -oxoline-3-carboxylic acid ester IR (KBr) cm-i: υ〇 = 〇1745, 1728, 1692 NMR {CDCI3) δ value: 〇.70-1 · 55 (7Η, m), 2.07 (3Η, s), 3.70-4.60 (3Η, m), 5.88 (2Η, s), 8.18 (1Η, d, J = 7.8Hz), 8.64 ( 1H, s) Reference Example 1 1.46 g of ethyl 8-acetamidomethyl-7-bromo-1-cyclopropyl-6-fluoro-1,4-dihydro-4-carbamoline-3- The carboxylic acid ester was suspended in 58b1 ethanol, and 19 ng of sodium formazan was added to the suspension, and the resulting mixture was then stirred at room temperature for 7 hours. 60 ml of water was added to the reaction mixture and the pH was adjusted to 7 with 1N hydrochloric acid, and the resulting crystal mold was collected by filtration to obtain 1.28 g of colorless crystalline ethyl 7-bromo-1-cyclopropyl-6-fluoro-8-hydroxymethyl -1,4-dihydro-4-oxydacryline-3-carboxylic acid ester IR (KBr) cm-i: υ〇 = 〇1718 NMR (di-TFA) δ value: 1.0S-1.90 (7H, m ), 4.45-5.30 (3Hr m) f 5.99 (2H, s), 8.38 (1H, d, J = 6.8Hz), 9.52 (1H, s) -56- (Please read the precautions on the back before filling this page ) Loading-

、 1T .K4 The size of this paper is applicable to China National Standard (CNS) A4 (210 X297 mm) Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 V. Description of the invention (") Reference example Π 1.27g ethyl 7 -Ao-1-cyclopropyl-6-fluoro-8- via methyl-1,4-dihydro-4-oxyl® phthaloline-3-phosphonate suspended in 127 ml of digas methane, and 1.3 3 g of diethylaminosulfur trifluoride was added dropwise to the suspension at -4 Q ° C, and the resulting mixture was then stirred at -2 ° C for 1 hour and then at 0 ° C for 3 hours. The reaction mixture was added to ice water And adjust the pH to 8 with a saturated diacid soda water. The organic layer was then separated, the strips were washed with saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was then evaporated under reduced pressure to remove the solvent. The residue thus obtained Purification by column chromatography (eluent: azoform; ethanol 2 100: 1) to obtain 1.05 g of colorless crystalline ethylbenzene bromide-1 -cyclopropyl-6 -fluoro-8-fluoromethyl -1,4-dihydro-4-aminopyroline-3-carboxylic acid ester IR (KBr) cm-li υ〇 = 〇1723, 1694 NMR (CDCI3) δ value: 0.60-1.75 (7Η, m) , 3.65-4.65 (3Hf m), 6.11 (2H, d, J = 47Hz), 8.21 (1H, ddr J = 2.2Hzr J = 8.1 Hz) f 8.64 (1H, s) Reference Example 1 2 5.00 g of ethyl 7-bromo-1-cyclopropyl "6-fluoro-8-methyl-1,4-dihydro-4 -oxoline- The 3-carboxylic acid ester was suspended in 50 ml of toluene, and 15.8 g of rhenium (tributyltin) and 95 Bg of rhenium (triphenylsulfonium) rake (II) were added to the suspension, and the resulting mixture was then heated under reflux for 24 hours. The reaction mixture was decompressed Concentrated, and the thus-obtained residue was purified by column chromatography (eluent: toluene: ethyl acetate = 10 ·· 1) to obtain 5.10 g of colorless crystalline ethyl 1-benzyl-6-fluoro-8-methyl -7_Tributylstannyl-14-dioxo-4-oxy1¾line-3-carboxylic acid. -57- This paper is suitable for Guanjia County (CNS) A4 · (21GX297 public envy) --- ------ C equipment— (Please read the precautions on the back before filling this page) Order KK Consumer Cooperation with the Central Bureau of the Ministry of Economic Affairs Du printed equipment A7 B7 V. Description of the invention (A) IR (KBr) cm -l: uc = 〇17 24 NHR (CDC13) 6 Value: 0.30-2.30 (34H, m), 2.79 (3H, s), 3.60-4.10 (1H, m) f 4.38 (2H, q, J = 6.8Hz ), 7.83 (1H, df J = 6.3Hz) r 8.63 (1H, s) The following compounds were obtained in the same manner. • Ethyl 1-cyclopropyl-6-fluoro-7-tributylstannyl-1,4-diargon-4-amino dark morpholine-3 -carboxylic acid ester IR (KBr) cm-1: Vq-o 1725 NMR (CDCI3) 6 Value: 0.50-1.80. (34Η, m), 3.10-3,70 (1H, m), 4.40 (2H, q, J = 6.8Hz) f 7.96 (1H, d, J = 2.0 Hz), 8.03 (1H, df J = 6.3H7.), 8.56 (1H, s) • Ethyl (S) -9-fluoro-3-methyl-7-oxy-10-tributyltin alkyl-2 , 3 -dihydro-7H-pyridine hydrazine [1,2,3-de] [1,4] benzene sulfonium trap-6-carboxylic acid ester IR (KBr) cm-1: υ〇 = 〇1718 NMR (CDC13 ) δ value: 0.30-2.30 (33H, m), 4.00-4.60 (5H, m), 7.60 (1H, d, J = 6.8Hz), 8.30 (1H, s) • Ethyl 1-cyclopropyl-6 -Fluoro-7-tributyltinyl-1,4-dihydro-4-airyl-1,8-eryridine-3-carboxylic acid ester IR (KBr) cm-1: uc = o 1729 NMR (CDCI3) θ value: 0 · 60-1 · 90 (34Η, in), 3.40-3 · 95 (1H, m), 4.40 (2Hf q, J = 6.8Hz), 8.16 (1H, d, J = 5.9Hz), 8.66 (1H, s) -58- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) —--------- C -Packing * — (Please read the note on the back first Please fill in this page for further information) tr- line 1. Description of invention (〇) A7 B7 Ministry of Economic Affairs榡 Associate Bureau MembersΗConsumer Cooperation Du Yincai * Ethyl 8-ml-cyclopropyl-6-fluoro-7-tributyltin alkyl-1,4-difluoren-4-amino 1¾line-3-carboxylate NMR (CDCI3) δ value: 0.60-1.90 (34Η, Π1), 3.90-4.60 (3Η, m), 7.93 (1H, d, J = 6.3Hz) f 8.63 (1H, s) Methyl-6-fluoro-8-methyl-7-tributylstannyl-1,4-difluoren-4-ylamino-methyl-3-carboxylic acid_ IR (KBr) cm-i: υ〇〇1731 NMR (CDC13) δ value. 〇 * ° · 4.0-2.0 (34Hf m) f 3.50-4.05 (4Η, m), 4.27 (2Η, q, J = 7.〇Hz), 7.84 (1Η, d, J = 6.4Hz), 8.57 (XHf S) Reference Example 1 3 (1) Dissolve 19.Dg 1-bromo-3,4-bis (hydroxymethyl) benzene in 38〇1 | 1 ether and add 112g of tribromo Phosphorus was cooled to this solution with ice, and then any resulting mixture was left for 3 days. The reaction mixture was added with SioooBi ice water and the pH was adjusted to 7 with sodium hydrogen sulfate, and then the mixture was extracted with 100 ul of ethyl acetate. The obtained organic layer was washed with saturated brine and then dried over anhydrous magnesium sulfate. Then, the solvent was removed by distillation under reduced pressure to obtain 28.5 g of colorless crystalline bromo-3,4-bis (bromomethyl) benzene. (2) 3.97g sodium sulfonamide (purity: 60% suspended in 70Bl N, N-dimethylformamide and 50ml of dimethylformamide solution containing 8.49g p-toluidinesulfonamide Then, the resulting mixture was stirred at 60 ° C for 3D scooping. The reaction mixture was added with 17.0 g of bromo 3,4-bis (bromomethyl ') benzene in 50ul of N, N-dimethylformamidine at 6 (TC). Amine solution, and the resulting mixture was stirred at 60 ec for 1 hour. The obtained reaction mixture was added to 500 ml of ice water and borrowed -59- (please read the precautions on the back before filling this page) Loading, 1Τ Κ Ministry of Economy Printed by the Consumer Standards Cooperative of the Central Bureau of Standards A7; B7 V. Description of the invention (Η) Collect the precipitate and purify it by column chromatography (eluent: aerosol) to obtain 15.2 g of crystalline 5-bromo-2- (pair Tosylsulfonyl) isoindolin. IR (KBr) cm-1: us〇2 1347, 1164 NMR (CDCI3) δ value: 2.39 (3Η, s), 4.56 (4Η, brs), 6.75 -7.90 (7Η, m) The following compounds were obtained in the same manner.. 5-Bromo-1 -methyl-2-(p-toluenesulfonyl) isoindolinoline IR (net) cnrl: us〇2 1347, 1164 NMR (CDCI3) δ value: 1.60, 1.66 (3Η, each, d, J = 6.0Hz), 2.34, 2. 39 (3H, each, s), 4.50-5.15 (3H, m), 6.70-7.95 (7H, m) • 5-bromo-3-methyl-2- (p-toluenesulfonyl) isoindinoline IR (net) cm-i: us〇2 1346, 1165 NMR (CDCI3) θ value: 1.62 (3Η, d, J = 6.3Hz), 2.38 (3H, s), 4.35-5.15 (3H, m), 6.65 -7.90 (7H, m). 5-Bromo-4,7-difluoro-2- (p-toluenesulfonyl) isoindioline IR (KBr) cm-1: us〇2 1348, 1163 'NMR ( CDC13) δ value 2.42 (3H, s), 4,66 (4H, s) r 6.88 (lHf tf J = 6.0Hz), 7.33 (2H, d, J = 8.0Hz), 7.78 (2Hf d, J = 8.0Hz) Reference Example 14 (1) To 1.50 g of 1- (1-aminocyclopropyl) -4-bromo-2-hydroxymethylbenzene and 8.5 ml of methanol was added 1.24 g of trifluoroacetic acid. The ethyl ester and the resulting mixture were stirred at room temperature for 24 hours. Remove the solvent and the remaining residue under reduced pressure -6 0-(Please read the precautions on the back before filling this page)-Packing. Order K4 This paper size is applicable to China National Standard (CNS) A4 size (210 X 297 mm) Duty-printing and consumer cooperation of the Central Bureau of Standards, Ministry of Economic Affairs, Du printed A7 _; B7 _ V. The description of the invention (β) was purified by column chromatography (eluent: fluoroform: ethyl fermentation = 30: 1) to obtain 1.02 g Colorless crystalline 4-bromo-2-hydroxymethyl-1- (1-trifluoroethoxyaminocyclopropyl) benzene. IR (KBr) cm small υ〇〇1717, 1702 NMR (CDC13) 5 value: 1.05-1.60 (4Η, 2.50 &lt; 1Η, brs) f 4.95 (2Η, s), 7.15-7.70 (3H, m) f 8.06 (1H, brs) (2) 9 50ng (l) of 4-bromo-2-hydroxymethyl-1- (1-trifluoroethylBaminomethylpropyl) benzene suspended in 2GB1benzene, and 68Geg three -N-butyrazine and 850Bg 1, plant-azodicarbonyl-bis (hexahydropyridine) were added in this order to the suspension and cooled with ice, and then the resulting mixture was raised to room temperature, The mixture was stirred at this time for 3 hours. The insoluble matter is removed by filtration, and then K is removed to remove the solvent. The obtained residue was purified by column chromatography (dissociation rain: n-hexane: ethyl acetate = 15 ·· 1) to obtain 720b g of colorless crystalline 5-o-2-trifluoroethylidene-fluorene [isoindoleline- 1,1 夂 cyclopropane] p IR (KBr) cm-1: υ〇 = 〇1697 NMfi (CDCI3) δ value: 0.75-1.20 (2Η, m), 2.30-2.75 (2H, m), 5.08 (2H, s), 6.56 (1H, d, J = 9.0Hz), 7.15-7.65 ^ 2H71n) Reference Example 15 5.Og 2- (p-toluenesulfonyl) -5- in 25 · 47% osmium bromide-5- Bromoisoindin was leached and suspended, and 4.0 g of phenol and 15.1 propionic acid were added to the suspension, and the resulting mixture was then heated under reflux for 4 hours. The reaction mixture was capsulated under reduced pressure, and ethanol was added to the obtained residue, and the obtained crystals were collected by filtration. 6 1 _ This paper size is applicable to China National Standard (CNS) A4 (210 × 297 mm) (please read the back first) Note for this page, please fill out this page) • installed ', 1Τ Κ

Consumption cooperation with employees of the Central Bureau of Standards, Ministry of Economic Affairs, Du printed A7 B7 V. Description of the invention (w) Obtained 3.5 g of 5-bromoisoindane bromate. The "bromide" obtained in suspension was suspended in 50 ml of digas methane, and 2.8 g of three were added. Ethylamine was added to the suspension, and then 2.4 g of benzyl chloride were added dropwise thereto under ice-cooling. The resulting mixture was then stirred at room temperature for 1 hour. After the reaction mixture was added to 50 · 1 water and the pH was adjusted to 6 with hydrochloric acid 6N, the resulting organic layer was separated, washed with a saturated saline solution and then dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure. To the residue thus obtained was added n-hexane, and the obtained crystals were collected by filtration to obtain 3.8 g of colorless crystalline 2-benzylgasoyl-5-bromoisoindole-P-doline. IR (KBr) cm-i: uc = 〇1705 NMR (CDC13) δ value: 4.69 Μ, s), 5.20 (2Η, s), 6.70-7.40 (8H, m) Reference example 16 1.20g 2- (pair- Tosylsulfonyl-5-bromoisoindololine was suspended in 24b1 toluene, and 3.95 g of hexabutyldibrane and 39 4 mg of triphenylhydrazone were added (0) to the suspension, and the resulting mixture was then obtained. The mixture was heated at reflux under a cyanide atmosphere for 24 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by column 1 chromatography (eluent: hexane: ethyl acetate = 10: 1) to obtain 0.92 g of an oil. The shape of 2- (p-toluenesulfonyl) -5-tributylstannane isoindole and wingline IR {Net J cm-1: us〇2 1349 f 1166 NMR (CDCI3) δ value: 0 · 20-2_00 (27Η , m), 2.40 (3Hr s), 4.61 (4H, brs), 6.50-8 · 00 {7H, m) The following compounds were obtained in the same manner. • 1-Methyl-2- (p-toluenesulfonyl) -5-trifluorobutylstannyl-iso-11-62- This paper size applies to China National Standard (CNS) Α size (210X297 mm)- -------- 「Approve ^ -I (Please read the precautions on the back before filling this page)

* tT A7 _ B7_ V. Description of the invention (Η) Timeline IR (net) cm-ι: υ5〇2 1349, 1165 NMR (CDC13) δ Value: 0.70-1.80 (30Η, m), 2.38 (3Η, s) , 4.55-5.15 (3H, τη), 6.90-7.90 (7Η, m) • 3-methyl-2- (p-toluenesulfonyl) -5-tributyltinalkyl-isoindolinoline IR (net) cm_1: uS〇2 1349, 1165 NMR (CDCI3) δ value: '0.60-1.90 (30H, Π〇, 2.37 (3H, s) r 4.30-5.20 (3Η, m), 6.80-7.90 (7H, m ) .5-Tributyltinalkyl-2-trifluoroacetamidino-spiro [isoindolin-1,1'-cyclopropane] IR (net.) Cirri: Dc = 0 1694 NMR (CDCI3) δ value: 0.70-2.10 (29Η, m), 2.35-2.75 (2H, m) r 5.16 (2H, s), 6.60-7.70 (3H, m) • Benzyloxycarbonyl-5-tributyltin alkyl isoindioline IR ( Net) cm-i: vjc = 〇1718, 1709 NMR (CDCI3) δ value: 0.30-1.70 (27Η, m), 4.73 (4Η, s), 5.15 (2H, s), 6.80-7.40 (8H, in) Reference Example 17 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs -------- {^ Pack-(Please read the precautions on the back before filling out this page) K4 in 27 »1 toluene, dissolve 3.55g 2- (p-toluenesulfonyl) -5-tributyltin alkyl isoindolinoline, and addition 1. 35 g of ethyl 4-bromo-2, 5-difluoro-3-methylbenzidine acetate and 0.29 g of gaseous thallium (triphenylhydrazone) were raked (II) to the solution, and the resulting mixture was then The mixture was heated under reflux in a nitrogen atmosphere for 8 hours. The reaction mixture was concentrated under reduced pressure, and the obtained residue was purified by column chromatography.-63- This paper is in accordance with Chinese National Standard (CNS) A4 (2 丨 0X297 mm). Printed by A7 B7, Consumer Cooperatives of the Bureau of Standards V. Description of the invention () (Dissolving agent: benzene: ethyl acetate = 70: 1) Obtain 1.25 g of colorless crystalline ethyl 2,5-difluoro-3-methyl-4 -[2- (p-toluenesulfonyl) isoamidinepyridin-5-yl] benzylideneacetate. IR (KBr) cnr !: i &gt; c = 〇1746 NMR (CDC13) δ value: 1.10-1.70 (3Η, m), 2.07 (3Η, d, J-2_9Hz), 2.41 (3H, Sr m), 3.80_4 · 50 (3 · 4π, m), 4.67 (4H, s), 5.88 (0.3H, s), 6.80-8.00 (8H, m), 12.6 (0.3Hr brs) The following compounds were obtained in the same manner. • Ethyl 2,5-difluoro-4- [2- (p-toluenesulfonyl) -isoindoline-2-yl] benzaldehyde acetate IR (KBr) cm-i: υ〇 = 〇17 47 NMR (CDCI3) δ value: 1.10-1.70 (3Η, m), 2.40 (3Η, s), 3.90-4.50 (3.2H, m), 4.66 (4H, s), 5.89 (0.4H, s ), 7.00- 8.00 {9H, m), 12.7 (0.4H, brs) • Ethyl 4- [2- (benzylcarbonyl) -isoindinoline-5-yl] -2, 5-difluorene-3 -Methane-6-nitrobenzylideneacetic acid IR (KBr) cm-1: uc = 〇1751, 1707 NMR (CDC13) δ value: 1.00-1.60 (3H, m), 3.60-4, .50 (6.2H, m), 4.81 (4H, s), 5.22 (2H, s), 5.50 (0.4H, s), 7.10-7.40 (8H, m), 12.2 (0.4H, brs) Reference example 1 8- 64- The size of this paper is applicable to Chinese National Standard (CNS) A4 (210X297 mm) --------- ^ pack --- (Please read the precautions on the back before filling this page) 丁-* ° Consumption cooperation between employees of the Central Bureau of Standards of the Ministry of Economic Affairs, printed A7 B7 'V. Description of the invention (Η) 700mg ethyl 7-bromo-cyclopropyl-6-fluoro-8-methyl-1,4-dihydro-4 -Oxy IH phthaloline-3-carboxylic acid ester, 889 mg of 1-cyano-2-methyl-4-tributyltin alkylbenzene and 13 {Ug gaseous scandium (triphenylhydrazone) scandium (II) Floating in 21ml of xylene, and the resulting suspension was heated at reflux for 2 hours. The reaction mixture was cooled to room temperature, and the precipitated crystals were collected by filtration. The obtained crude crystals were purified by column chromatography (eluent: aerosol) to obtain 49Gmg of colorless crystalline ethyl 7- (4-cyano-3-methyl) phenyl-1-cyclopropyl-6-fluoro-8. -Methane-1,4_dihydro-4-airyl molybdenyl-3-phosphonate. IR (KBr) cm-1: υ〇 = 〇1726 NMR (CDC13) δ value: 0.90-1.70 (7Η, m), 2.64 (3Η, s), 3.37 (3H, s), 3.65-4.15 (1H, m ), 4.40 (2Hf q, J = 7.0 Hz), 7.20-7.90 (3H, m), 8.03 (1H, d, J = 9.5Hz), 8.64 (1H, s) Example 1 in 25ml Ν, Ν- Dimethylformamide dissolves 2.30g of 2- (p-toluenesulfonyl) -5-bromoisoindioline, and adds 1.51 g of silver (I) oxide and 0.75 g of triphenylphosphine ) Palladium (0) into the solution, and the resulting mixture was stirred under a 1D (TC nitrogen atmosphere for 5 minutes. Then 1.54 g of ethyl 1-cyclopropyl-6-fluoro-8-methyl-7- was added to the reaction mixture. Tributylstannyl-1,4-dihydro-4-oxoroline-3-carboxylic acid ester was dissolved in 5 ml of Ν, Ν-dimethylformamide, and the resulting mixture was stirred at 100 ° C for 15 minutes The reaction mixture was added to a mixed solvent of 50 ml of ethyl acetate and 100 ml of water and the pH was adjusted to 2 with 2 N hydrochloric acid, and then the insoluble matter was removed by filtration. The resulting organic layer was separated by -6 5- (Please (Please read the notes on the back before filling out this page)

、 1T Κ4 The size of this paper is applicable to Chinese National Standard (CNS) A4 specification (210 X 297 mm) Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 5. Description of the invention (〆) Saturated saline solution and then washed with anhydrous Dry over magnesium sulfate. The solvent was then distilled off under reduced pressure. The obtained residue was purified by column chromatography (eluent: toluene: ethyl acetate = 3: 1), and then ether was added, and the resulting crystals were collected by filtration to obtain 0.5 5 g of colorless crystalline ethyl 1- Cyclopropyl-6-fluoro-8-methyl-7- [2- (p-toluenesulfonyl) isoindolinolin-5-yl] -1,4-dihydro-4-aminopyridin- 3-carboxylic acid ester. IR (KBr) cm-i: υ〇〇1733, 1693 NME (CDC13) δ value: 0.70-1.60 (7Η, m,), 2.42 (3ΗΓ s), 2.50 (3H, s), 3.70-4.10 (1H, m), 4.40 (2Hf q, J = 7.3Hz), 4.69 (4H, s), 6.90-8.20 (8H, m), 8.70 (1H, s) The following compounds were obtained in the same manner. • Ethyl 1-cyclopropyl-6-fluoro-7- [2- (p-toluenesulfonyl) isoindolin Itorolin-5-yl] -1,4 -dihydro-4-amino azolin 3-carboxylic acid ester IR (KBr) cm-1: υ〇 = ο 1728, 1693 NMR (CDCI3) δ value: 0.90-1.55 (7Η, m), 2.41 (3Η, s), 3.20-3.70 (1H, m), 4.40 (2H, q, J = 6.8Hz), 4.69 (4H, s), 7.00-8.25 (9H, m), 8.57 (1H, s). Ethyl (S) -9-fluoro-3- Methyl-7-amino-10- [2- (p-toluenesulfonyl) isoindololin-5-yl] -2,3-dihydro-7H-pyridinium [1,2,3-de ]-[1,4] Benzene-6-carboxylic acid ester IR (KBr) cm-i: uc = 〇1721 NMR (CDCI3) δ value: 1.00-1 · 55 (6Η, in), 2 · 41 (3Η, s), 4.00-4.80 (9H, m), 6.90-7.90 (8H, m), 8.32 (1H, s) This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm)- ------- r Pack I — (Please read the notes on the back before filling this page) Order. K4 Consumption Cooperation with Employees of the Central Standards Bureau of the Ministry of Economic Affairs Du A7 B7 5. Invention Description (β). Ethyl -1-cyclopropyl-6-fluoro-7- [2- (p-toluenesulfonyl) -isoindiodoline-5-yl] -1,4-dihydro-4-amino-1, 8-naphthalenepyrene-3-carboxylic acid ester IR (KBr) cm-i: υ〇 = 〇1719, 1679, 1651 NMR (di-TFA) δ values: 1.10-1.90 (7H, m), 2.47 (3H, s), 4.10-5.10 (7Hf m), 7.20-8.80 (8Hf m), 9.45 ( 1H, s) • Ethyl 8-chloro-1-cyclopropyl-6-fluoro-7- [2- (p-s-benzenesulfenyl) isoindioline-5-yl] -1, 4-di Hydrogen-4-oxoline-3-carboxylate IR (KBr) cm-i: υ〇 = 〇1726 NMR (CDCI3) δ value: 0.70-1.70 (7H, m), 2.41 (3H, s ), 3.80-4.80 (7H, m), 6.90-8.25 (8Hf m), 8.69 (1H, S) Ethyl 1-cyclopropyl-7- [4, 7-difluoro-2- (p-toluene Sulfonyl) isoindolinolin-5-yl] -fluorene-fluoro-1,4-dihydro-4-oxyl-iline-3-carboxylic acid ester IR (KBr) cm-i: υ〇 = 〇 1728, 1690 NMR (CDCI3) δ value: 1.00-1.60 (7Η, m), 2.42 (3Η, s), 3.15-3.65 (1H, m), 4.39 (2H, q, J = 6.8Hz) f 4.74 (4H , s), 6.90-8.00 (6H, m), 8.20 (1H, d, J = 10.0Hz), 8.57 (1H, s). Ethyl 1-cyclopropyl-7- [4,7-difluoro- 2- (p-toluenesulfonyl) isoindoline-5 -yl] -6 -fluoro-8 -methane-1,4-dihydro-4 -aminoifolin-3 -carboxylic acid ester IR ( KBr) cm-i: uc = 0 1729, 1691 NMR (CDC13) S values: lu {7H, m), 2.44 (3H, s), 3.43 (3H, s), 3.70-4.95 (7H, m) , 6.80-8.15 (6H, m) f 8.57 (1H, s) __- 67-_ This paper size is applicable to China National Standard (CNS) A4 (210X297 mm) --------- Γ Installation l · — (Please read the back first Please note this page, please fill in this page) Order A7 B7 printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the Invention (讣) Example 2 47mg ethyl 7-bromo-1-fluorenyl-6-fluoro-8-methyl -1,4-dihydro-4-airyl-line-3-carboxylic acid ester was suspended in 1 ml of toluene, and 74 ng of 2- (p-toluenesulfonyl) -5-tributyltin was added to the suspension. Alkyl isoindoxaline and 1.5 mg of tris- (triphenylene) rake (0), and the resulting mixture was then heated under reflux under a nitrogen atmosphere for 18 hours. The reaction mixture was concentrated under reduced pressure, and the obtained residue was purified by column chromatography (eluent: n-hexane: ethyl acetate = 1: 1), then ether was added, and the resulting crystals were collected by filtration to obtain 27 m. g colorless crystalline ethylbucyclopropyl-6-fluoro-8-methyl-7- [2- (p-tolylaldehyde) isoindoline-5-yl] -1,4-dihydro- 4-Gauryl cyanoline-3-carboxylic acid ester. The physical properties of this compound are the same as those obtained in Example 1; The following compounds were obtained in the same manner. • Ethyl 1-cyclopropyl-6,8-difluoro-7- [2- (p-toluenesulfonyl) isoinolinolin-5-yl] -1,4-dihydro-4-yl Periline-3-carboxylic acid ester IR (KBr) cm-1: uc = 〇1731, 1696 NMR (CDC13) 6 Value: 0.90-1.80 (7H, m), 2.41 (3H, s), 3.60-4.10 (lHr m) f 4.10-4.90 (6H, m) f 6.80-8.30 (8H, m), 8.59 (1H, s) • Ethyl 1- (2,4-difluorophenyl) -6-fluoro-7- [ 2- (p-toluenesulfonyl) isoindololin-5-yl] -1,4-dihydro-4-amino-1,8-eryridine-3-carboxylic acid ester 6 8-This paper Standards are applicable to China National Standard (CNS) A4 specifications (210X297 mm) (read the precautions on the back before filling this page) Binding Printed by the Central Standards Bureau of the Ministry of Economic Affairs and Consumer Cooperatives A_B7__ 5. Description of the invention (K) IR (KBr) cra-1: uc = 〇1675, 1655 NMR (CDC13) 6 value: 1.40 (3H, t, J = 6.8Hz), 2.39 (3H, s), 4.41 (2H, q, J = 6.8Hz) , 4.63 (4H, s), 6.80-7.90 (10H, m), 8.48 (1H, d, J = 10.〇Hz) r 8.58 (1H, s). Ethyl 7- [2- (benzyl gas Number group) Isoinline_5 ~ yl] -bucyclopropyl-6-fluoro-8-fluoromethyl-1,4-difluoren-4-ylamino-3-carboxylate IR (KBr ) cm-ι: υ〇 = 〇1732, 1718 NMR (CDC13) δ value: 0.85-1.75 (7H, m), 3.85-4.65 (3H, m) f 4.81 (4H, s), 5.21 (2H, s) r 5.61 (2H, d, J = 48Hz), 7.05-7.55 (8H, m), 8.23 (1H, dd, J = 2.0Hz, 8.8Hz), 8.66 (1H, s) Example 3 0.25g ethyl 7-i Wu-1-chenpropylpropyl fluoride -8-Methane-1,4-dihydro-4 -amino ifolin-3-carboxylic acid ester was suspended in 5ml of toluene, and D.55g of 2- (p-methylbenzylsulfonyl) was added to the suspension. (B) 5-Tributyltin alkyl isoindane ramie and 0.09 g of trifluoride (triphenyl R) halide (II), and the resulting mixture was then heated under reflux for 8 hours under a hydrogen stream. The reaction mixture was concentrated under reduced stress, and The obtained residue was purified by column chromatography (thinning: aerosol), and then filtered by adding B to collect the resulting crystals to obtain 0.19 g of colorless crystalline ethylethyl 1-methylpropyl-6-fluoro-8-methyl gas. -7- [2- (p-toluene stilbyl) isoindolinolin-5-yl] -1,4-dihydro-4-oxyβ-lyl-3. -69- This paper size applies to Chinese National Standard (CNS) A4g (210 x 297 mm) (Please read the precautions on the back before filling this page) f

、 1T Consumption cooperation between employees of the Central Bureau of Standards of the Ministry of Economic Affairs, Du printed A7 B7 ′ 5. Description of invention uo IR (KBr) cm-1: Uc = 〇1731 NMR (CDC13) 5 Value: 0.80-1.70 (7H, m), 2.41 (3H, s), 3.32 (3H, s), 3.60-4.20 (1H, m), 4.40 (2H, q, J = 6.8Hz), 4.68 (4H, s), 7.10-7.50 (5H, m) r 7.60-8.15 (3H, m), 8.61 (1H, s) In the same manner, the following compound e is obtained: ethyl: l-cyclopropyl-6-fluoro-8-methyl-7- [1-methyl- 2- (p-toluenesulfonyl) isoindioline-5-yl] -1,4-difluoren-4-yl group fline-3-carboxylic acid ester IR (KBr) cm-1: υ〇 〇1732 NMR (CDCI3) δ value: 0.80-2.00 (10Η, m), 2.40 (3Η, s), 3.30 (3H, s), 3.75-5.30 (6H, m), 7.10-8.15 (8H, m) f 8.65 (1H, s). Ethyl 1-cyclopropyl-6-fluorene-8-methyl gas-7- [3-methyl-2- (p-toluenesulfonyl) isoindioline-5-yl ] -1,4-dihydro-4-amino group f-line-3-carboxylic acid ester IR (KBr) cm-1: \ Jc = 〇1729 NMR (CDCI3) S value: 0.90-1.80 (10H, m) , 2.39 (3H, s), 3.31 (3H, s) f 3.75-5.10 (6H, ro), 7.05-8.10 (8Hf m), 8.61 (1H, s) Ethyl 1-cyclopropyl-6-fluoro -8-methoxy-7- [2-trifluoroethionyl] -spiro [isoindine -1, 1 '-cyclopropane] -5 -yl] -1, 4 -dihydro-4 -amino-based phosphino-3 -carboxylate-70 &quot; This paper size applies to China National Standard (CNS) A4 specifications ( 210X297 mm) --------- C Pack l · — (Please read the notes on the back before filling this page) Order A7 B7 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs W) IR (KBr) cm-1: υ〇〇1731, 1697 NMR (CDCI3) δ values: 0.70-1.90 (9Η, in), 2.20-2.90 (2Hf m), 3.38 (3Hf s), 3.60-4.70 ( 3H, m) r 5.21 (2H, s), 6.55-8.20 (4H, m), 8.59 (1H, s) Ethylbucyclopropyl-8-difluoromethane-6-fluoro-7- 〔2 -(P-toluene aldehyde) isoinolinolin-5-yl] -1,4-bisfluoren-4-oxy If chloro-3-carboxylate IR (KBr) cm-1: υ〇 = 〇 1730 NMR (CDCI3) δ value: 0.90-1.70 (7Η, m), 2.40 (3Hr s), 3.70-4.85 (7H, m), 5.8.3 (1H, t, J = 75Hz), 7.00-8.30 (8H , m), 8.62 (1H, s) • Ethylbucyclopropyl-8-difluoromethane-6-fluoro-7- [3-methyl-2- (p-toluenesulfonyl) isoindolin Porphyrin-5-yl] -1,4-dihydro-4-pyridyl-3-carboxylate IR (KBr) cm-i: υ〇 = 〇1732 NMR (CDCI3) δ value: 0.70- 1.80 (10Η, m), 2.39 (3Η, s), 3.60-5.30 (6H, m), 5.80 (1H, t, J = 75Hz), 6.80-8.30 (8H, m), 8.64 (1H, s) • Ethylbucyclopropyl-8-difluoromethane-6-fluoro-7- [2-trimethylacetino-spiro [isoindolin-1,1, cyclopropyl-5-yl] -1 , 4-dihydro-4-aminopyridin-3-carboxylic acid ester IR (KBr) cm-i: υ〇〇〇1729, 1701 NMR (CDCI3) δ value: 0.80-1.65 (9Η, m), 2.40- 2.80 (2Η, m), 3.80-4.70 (3Η, m), 5.20 (2H, n) r 5.BB (1H, t, J = 74Hz), 6.70-7.60 (3Hf m) f 8.15 (1H, d, J = 9.0Hz), 8.61 (1H, s) -7 1-(Please read the precautions on the back before filling in this page) Binding K4 This paper size is applicable to China National Standard (CNS) A4 size (210X297 mm) Economy Ministry of Central Standards Bureau Consumers' Cooperative Printing Poly A7 V. Description of Invention (W) • Ethyl 1-cyclopropyl-6-fluoro-8-fluoromethane-7- [2- (p-toluenesulfonyl) iso Indolinolin-5-yl] -1,4-dihydro-4-oxyifline-3-carboxylic acid ester IR (KBr) cm-ι: υ〇 = 〇1727 NMR (CDCI3) δ value: 0.90- 1.60 (7Η, m), 2.41 (3Η, s), 3.75-4.80 (7H, m), 5.02 (2Hr d, J = 54Hz), 7.00- 7.85 (7H, m), 8.10 {1H, d, J = 9.3Hz), 8.62 (1H, s) • Ethylbucyclopropyl-6-fluoro-7- [1-methyl-2- (p-toluenesulfonyl) isoindolinolin-5-yl] -1, 4-dihydro-4 -Gas ifyl-3-carboxylate IR (KBr) cm-1: Uc = 〇1727 NMR (CDCI3) 6 Value: 1.00-1.90 (10Η, m), 2.38 (3Hr s), 3.20-3.70 (1H , m), 3.90-5.20 (5H, m), 7.00- 8.25 (9Hf m), 8.54 (lHf s) Ethyl 1-cyclopropyl-6-fluoro-7- [3-methyl-2- 2- ( P-toluenesulfonyl) isoinolinolin-5-yl] -1,4-dihydro-4-aminomethylphosphino-3-carboxylic acid ester IR (KBr) cm-i: uc = 〇1727, 1708 , 1695 NMR (CDCI3) δ values 0.80-1.90 (10Η, m), 2.39 (3H, s), 3.10-3.70 (1H, m), 3.90-5.20 (5H, m), 6.80-8.25 (9Hf m ), 8.55 (1H, s) • Ethyl 7- [2-(benzyloxycarbonyl) isoindioline-5-yl] -8-gas-6-fluoro-1-[(lR, 2S) -2- Fluorocyclopropyl] -1,4-dihydro-4-amino-based hydrochloride-3-carboxylic acid ester-72- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) (please first Read the notes on the back and fill in this page.) 1 、 Printed A7 B7 by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. 5. Description of Invention (W) IR (KBr) cm-i: υ〇 = 〇1726, 1709 NM R (CDCI3) δ value: 0.80-1.70 (5Η, ra), 3.80-4.90 (7.5H, m), 5.00-5.50 (2.5H, m), 6.90-7.90 (8H, m), 8.18 (1H, d , J = 8.8Hz), 8.59 (1H, d, J = 2.4Hz) Example 4 Dissolved in 21 »1 digas methane 20〇1» £ ethyl 2,5-difluoro-3-methyl-4- [ 2- (p-toluenesulfonyl) isoinducline-5-yl] benzylidene acetate, and in this solution were added 76ing acetic anhydride and 90Bg-dimethylformamide dimethyl acetal Then, the resulting mixture was stirred at room temperature for 2 hours. The solvent was then distilled off under reduced pressure. The obtained residue was dissolved in 1 ml of acetic acid, and a solution of 58 mg of 2-fluoroethylamine hydrochloride and 27 mg of sodium methoxide in 1b1 ethanol was added to the solution, and then the resulting mixture was stirred at room temperature for 20 minutes. The reaction mixture was concentrated under reduced pressure and the resulting mixture was dissolved in 2b1 N, N-dimethylformamide, followed by the addition of 65bg of potassium persulfate to the solution. The resulting mixture was stirred at 100 ° C for 1 hour. The reaction mixture was cooled to room temperature and then water was added to the mixture. The resulting precipitate was collected by filtration, and the resulting pale yellow solid was purified by column chromatography (isocyanate: n-hexane: ethyl acetate = 2: 1). Thereafter, diisopropyl ether was added thereto, and the resulting crystals were collected by filtration to obtain 126 mg of colorless crystalline ethyl-1-(2-fluoroethyl) -8-methyl-7- [2- (P-toluenesulfonyl) isoinolinolin-5-yl] -1,4-dihydro-4-oxoline-3-carboxylic acid ester. -7 3 ~ This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) S1 · --------- (install l ·-(Please read the precautions on the back before filling this page) Ordered the central standard of the Ministry of Economic Affairs of the Ministry of Economic Affairs, and printed by the employees of the quasi bureau A7: B7 V. Description of the invention (p) IR (KBr) cm-1: υ〇〇1724, 1696 NMR (CDCI3) δ value: 1.40 {3Η, t, J = 7.3H7 :), 2.2η (3H, s), 2.41 (3H, s), 4.00-5.10 (10H, m) f 6.90-7.90 (7H, m), 8.10 (1H, d, J = 9.3Hz), 8.48 (1H, s) The following compounds were obtained in the same manner. .Ethyl 1-ethyl-G-fluoro-8-methyl-7- [2-(. P-methylbenzylsulfonyl) isoindoline-5 -yl] -1,4-dihydro-4 -Gas-based HS phthaloline-3 -carboxylic acid ester IR (KBr) cm-i: i &gt; c = 〇1725, 1686 NMR (CDCI3) 6 values: 1.10-1.80 (6Η, m), 2.30 (3Η, s), 2.39 (3H, s), 4.10-4.90 (8Hr m), 7.00-8.00 (7H, m), 8.10 (1H, d, J = 9.3Hz), 8.46 (lHf s) (LR, 2S) -2-fluorocyclopropyl] -8-methyl-7- [2- (p-toluenesulfonyl) isoinP-Pinolin-5-yl] -1,4-difluorenyl- 4-Gaurinoline-3 -carboxylic acid ester IR (KBr) cm-i: υ〇 = 〇1725, 1690 NHR (CDCI3) δ value: 1.00-1.90 (5Η, m), 2.42 (6Η, s), 3.30-4.80 (7.5H, m), 5.10-5.5U (0.5! If m), 6.80-8.20 (8H, m), 8.57 (1H, d, J = 2.9Hz) Ethyl 1- (2,4 -Difluorophenyl) -6-fluoro-8-methyl-7- [2- (p-tosylsulfonyl) isoindololin-5-yl] -1,4-diargon-4 -amino丨 f-line-3-carboxylic acid ester IR (KBr) cm-l: υ〇 = 〇1734, 1700 This paper size is applicable to Chinese national standard (CNS> A4 specification (210X297 mm))-=-I (Please read first Note on the back then fill out this page) -Γ V. Description of the invention (w. Ethyl 1- (4- (Oxyphenyl) -6-fluoro-8-methyl-7- [2- (p-toluenesulfonyl) isoindololin-5-yl] -1,4-dihydro-4-carbamoline- 3-carboxylic acid ester IR (KBr) cm-i: uc = 〇1728, 1694 NMR (CDC13) δ value 1.10-1.80 (6H, m) r 2.36 (3H, S), 4.35 (2H, q, J = 7.3Hz), 4.60 (4Hr s) r 5.08 (2H, s), 6.80-7.90 (16H, m), 8.11 (1H, d, J = 9.3Hz), 8.43 (1H, s) Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs and Economics • Ethyl 6-fluoro-1- (2-fluoroethyl) -7- [2- (p-toluenesulfonyl) isoindioline-5-yl ] -1,4-dihydro-4-oxyfluoroline-3-carboxylic acid ester IR (KBr) cm-i: υ〇 = 〇1724 MHR (CDCI3) δ. Value: 1.40 (3Η, t, J = 7.3Hz), 2.41 (3H, s), 4.10-5.35 (10H, m), 7.00-7.90 (8Hf id), 8.20 (1H, df J-10.3Hz), 8.46 (1H, s) 1- (2, 4-difluorophenyl) -6-fluoro-7- [2- (p-tosylsulfonyl) isoinolinolin-5-yl] -1,4-dihydro-4-oxo Fluoroline-3-carboxylate IR (KBr) cm-1: uc = 〇1725 NMR (CDC13) δ value: 1.40 (3H, t, J = 7.3Hz), 2.39 (3H, s), 4.10-4.70 (6H, m), 6.90-7.90 (11H, m) f 8.23 (1H, d, J = 10.3Hz) r 8.38 (1H, s) 7 5 This paper size is in accordance with Chinese National Standard (CNS) A4 (210X297 mm). Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs. And 0.49 g of acetic anhydride were dissolved in 0.66 g of ethyl 4- [2- (benzylcarbonyl) isoindole II dorolin-5-yl] -2,5-difluoro-3-methane-6-nitrobenzene Formamyl acetate, and dissolved in reflux and heated for 30 minutes. The reaction mixture was concentrated under reduced pressure, and the resulting residue was dissolved in 3.3al ethanol and 2b1 dichloromethane. To the solution was added 0.08 g of benzylamine, and the resulting mixture was stirred at room temperature for 30 minutes. The reaction mixture was shrunk under reduced pressure, and the obtained residue was dissolved in 10 Bl of tetrahydrofuran. 0.05 g of 60% sodium hydride was added to the solution, and the resulting mixture was stirred at room temperature for 30 minutes. The reaction mixture was added with 10 inl 1N hydrochloric acid and the precipitated crystals were collected by filtration to obtain 0.33 g of colorless crystalline ethyl 7- [2- (benzylcarbonyl) isoindolinolin-5-yl] -1-cyclopropyl-6 -Fluoro-8-methyl-5-nitro-1,4-dihydro-4-amino-tetraline-3-carboxylic acid ester. IR (KBr) cm-i: uc = 〇1728, 1709 tJMR (CDC13) δ value: 0.90-1.60 (7H, m), 3.42 ΠΗ, s), 3.70-4.10 (1H, m), 4.34 (2H , q, J = 6.8H7,), 4.84 (4Hr s), 5.23 (2H, s), 7.05-7.55 (8H, m) f 8.61 (1H, s) Example 6 (1) 470mg ethyl 7- (4 -Cyano-3-methyl) phenyl-l-cyclopropyl-6-fluoro-8-methoxy-1,4-difluoren-4-ylsulfonium-3-phosphonate, 230 ng N -Bromobutyriminium and 50 mg of perbenzoic acid were suspended in 20b1 thorium helium helium, and the suspension was heated by interflow for 2 hours. Add llOagfi-bromo-76- to the reaction mixture (please read the precautions on the back before filling this page) Γ. Packing. The size of the paper is applicable to China National Standard (CNS) A4 (2 丨 0X297 mm) Central Ministry of Economy Printed by the Consumer Bureau of Standards Bureau A7 _l_B7_ V. Description of the invention (#) Succinimide and 20aig perbenzoic acid and the resulting mixture were heated under reflux for 2 hours. Repeat the operation. The solvent was distilled off under reduced pressure and the resulting 20β1 aeroform and 10B1 water were added to the residue to separate into two layers. The resulting organic layer was separated and dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure to obtain 37.0Bg ethyl 7- (3- Crude crystals of bromomethyl-4- «yl) phenyl 1-propenyl-6-fluoro-8-methyl-1,4-dihydro-4-oxyfluoroline-3-carboxylic acid ester. 2) The compound (76 mg) of sodium azide and 13 mg of tetra-n-butylammonium bromide obtained in (1) above were dissolved in a mixture of 2 ml of water and 2hi1 dichloromethane, and the solution was stirred at room temperature for 15 hours under reduced pressure. The solvent was removed by evaporation and 2G ml of ethyl acetate and 10βΙ water were added to the resulting residue to separate into two layers of β. The organic layer was separated, washed successively with water and a saturated saline solution, and then dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure, and diethyl ether was added to the obtained residue. The resulting crystals were collected by filtration to obtain 270 mg. Colorless crystalline ethyl 7- (3-azidomethyl-4-cyano) phenyl-bucyclopropyl-6-fluoro-8-methyl-1,4-dihydro-4-aminoquinoline 3-carboxylic acid ester. IR (KBr) cm-1: -N3 2103, υ〇 = ο 1728 HMR (CDCI3) 6 Value: 0.80-1.70 (7Η, m}, 3.3.7 (3Η, s), 3.70 -4.10 (1H, m) f 4.40 (2Hr q, J = 7.0Hz), 4.70 (2H, s) f 7.15-8.20 (4H, m) f 8.64 (1H, s) (3) at room temperature, about 1 After 3 hours, 3 ml of 210ieg of the compound obtained in (2) above was added dropwise in a methanol solution of 302 »g of stannous vaporized in 2» 1 methanol, and the resulting mixture was stirred at the same temperature for 30 minutes. Under reduced pressure Remove the solvent from steamed plums and add 10ml of chloroform and lQal saturated nitric acid to the residue. -77- This paper applies the Chinese National Standard (CNS) A4 specification (210X297 mm) --------- 1 pack- -(Please read the notes on the back before filling out this page)-&quot; Employees of Central Bureau of Standards, Ministry of Economic Affairs Means cooperative printing fee A7 _ ^ __ B7_ V. invention is described (# Γ aqueous potassium to Unexamined West subsequently (of Celite) insolubles were removed by filtration. The resulting filtrate was allowed to separate into two layers and the resulting organic layer was washed successively with a saturated potassium nitrate aqueous solution and a saturated saline solution and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by column chromatography [eluent: (chloroform: ethanol: concentrated water = 150: 25: 1) organic layer] to obtain 100 mg of cyclopropyl Methyl ester of 6-fluoro-7- (1-iminoisoinolinolin-5-yl) -8-methoxy-1,4-dihydro-4-airyl Pfline-3-carboxy And ethyl ester mixture. (4) In 100ing as above (3> Resulting mixture | Into a suspension of 2 ml of ethanol and 2 ml of dioxane and the like, add 1b1 1N aqueous sodium hydride solution and stir the resulting mixture at room temperature for 2 hours. Remove under reduced pressure The solvent and the obtained residue were added with 2 il of water, and then the insoluble matter was removed by filtration. The digasified gas was blown into the obtained filtrate and the crystals precipitated from the precipitate were collected by filtration to obtain 56 μm of colorless crystalline 1-propylpropyl-6. -Fluoro-7- (1-iminoisoindioline-5-yl) -8-methoxy-1,4-dihydro-4-oxyifolin-3-carboxylic acid IR (KBr) cm -l: uc = 〇1617

NfdR (di-TFA) δ value: 1.20-1.80 (4H, m), 3.61 {3ί1, s), 4.35-5.20 (3H, m), 7.70-8.5Q (4H, m), 9.53 (1H, s) Example 7 0.30 g of ethylbucyclopropyl-6-fluoro-8-methyl-7- [2- (p-toluenesulfonyl) isoindioline-5-yl] -1,4-dihydro -4-Oxylan-3-carboxylic acid ester was suspended in 3 ml of ethanol, and 3 ml of a 1 N aqueous sodium hydrogen solution and 3 μm of dioxane were added to the suspension, and the resulting mixture was then stirred at room temperature for 2 hours. 7 8- This paper size is applicable to China National Standard (CNS) Α4 size (210 X 297 mm) -------- V Pack— (Please read the notes on the back before filling this page) Γ Central Standards Bureau of the Ministry of Economic Affairs A7 B7 printed by employee consumer cooperatives V. Invention description (^). 3al 1HS acid and the crystals thus formed were added to the reaction mixture, and 0.27 g of colorless crystalline buchenpropyl-6-fluoro-8-methyl-7- [2- (p-toluenesulfonyl) was collected and collected by filtration. ) Isoinolinolin-5-yl] -1,4-dihydro * -4-aminopyridin-3-carboxylic acid. IR (KBr) cm-l: υ〇 = 〇1726 ilMR (t-TFA) δ value: 1.10-1.90 (4Η, m), 2.48 (3Η, s), 2.89 (3H, s), 4.50-5.00 (5H , m), 6.90-8.00 (7H, m), 8.30 (1H, df J = 7.8Hz), 9.62 (lHr s) In the same manner, the following compound e was obtained: -(P-toluenesulfonyl) isoindololin-5-yl] -1,4-dihydro-4-oxyfluorolin-3-carboxylic acid IR (KBr) cm-1: u〇〇1724 NMR (di-TFA) 6 values: 1.X0-1.90 (4Hf m), 2.47 (3H, s) f 3.80-4.45 (1H, m), 4.87 (4H, s), 7.10-8.00 (7H, m), 8.44 (1H, d, J = 9.3Hz) f 8.74 {1H, df J = 5.9Hz), 9.46 (1H, s) • (S) -9-fluoro-3-methyl-7-oxy-10- [2- (p-toluenesulfonyl) isoindololin-5-yl] -2,3-di «-7H-pyridinium [1,2,3-de] [1,4] benzene -6-Carboxylic acid IR (KBr) cm-1: uc = 〇1723 NMR (dx-TFA) δ value: 1.83 (3H, d, J = 6.8Hz), 2.47 (3H, s), 4.40-5.50 (7H , m), 7.00-8.30 (8H, m), 9.35 (1H, s) -79- This paper size uses China National Standard (_'CNS) A4 size (210X297 mm) (Please read the note on the back first Matters refill this page) Pack 'Order-

A Printed by A7 B7_, a consumer cooperative of the Central Bureau of Quasi-Economic Bureau of the Ministry of Economic Affairs V. Description of the invention (%) • Buchen Propyl-6-cyano-7- [2- (p-toluenesulfonyl) isoindole B-doline- 5-yl] -1,4-dihydro-4-oxy-1., 8-leso-3-saccharic acid IR (KBr *) cm-i: uc = 〇1718 NMR (di-TFA) δ value ： 1 · 20-1 · 90 (4H, m), 2.47 (3H, s), 4.20-4.70 (1H, m), 4.89 (4H, s), 7.20-8.90 (8Hr m) f 9.53 (1H, s ) • 1-Cyclopropyl-6,8-difluoro-7- [2- (p-tosylsulfonyl) isoindolinolin-5-yl] -1,4-dihydro-4-amino S Porphyrin-3-carboxylic acid IR (KBr) cm-1: υ〇 = 〇1729 NMR (CDC13) δ value: 0.90-1.80 (4H, m), 2.38 (3H, s), 3.60-4.30 (1H, m) , 4.67 (4H, s) f 7.00-8.30 (8H, m), 8.83 (1H, s), 14.0 (lHr brs) • 8-cyano-1-cyclopropyl-6-fluoro-7- [2-( P-toluenesulfonyl) isoindolinylidolin-5-yl] -1,4-difluoren-4-ylpyridin-3-carboxylic acid IR (KBr) cm-i; υ〇 = 〇1728 NMR (CDCI3) δ value: 0.70-1.50 (4Η, m) r 2.39 (3Η, s) f 4.00-4.50 (1H, m) f 4.67 (4H, s), 6.80-7.90 (7H, m), 8.13 (1H , d, J = 8.8Hz), 8.93 (1H, 5), 14.0 (1H, brs) • 1-cyclopropyl-7- [4,7-difluoro-2-(p-A Isopropyl) Isoindole "Dorin-5-yl] -6-gingival-1,4 -two-piece-4-oxysporin-3-conjugic acid _ 8 0 _ This paper size applies to China National Standards ( tNS &gt; A4 specification (210X297 mm) ---------- f. equipment, -------- II -------- (k (Please read the precautions on the back before (Fill in this page) Printed by the Central Ministry of Economic Affairs and Consumer Cooperatives A 7 B7 _ V. Description of the invention (w) IR (KBr) cm-1: υ〇 = 〇1734 NMR (di-TFA) 6 Value: 1.10 -1.85 (4H, m), 2.49 (3H, s), 4.00-4.45 (1H, m), 4.92 (4H, s), 7.10-8.10 (5H, m), 8.47 (1H, d, J = 8.5Hz ), 8.77 (1H, d, J = 5.5Hz), 9.49 (1H, s) • 1-cyclopropyl-7- [4, 7 -difluoro-2- (p-toluene} isopropyl) Phenolin-5-yl] -6-fluoro-8-methyl-1,4-dihydro-4-oxoline-3-carboxylic acid IR (KBr) cm-1: uc = 〇1730 NMR (CDCI3 ) δ value: 0.90-1.70 (4Η, m), 2.40 (3H, s), 3.47 (3H, s), 3.80-4.30 (1H, m), 4.81 (4H, s) f 6.80-8.20 (6H, m ), 8.85 (1H, s), 14.2 (1H, brs) • 1- (2, 4-dicyanophenyl) -6-fluoro-7- [2- (p-toluenesulfonyl) isoindolinium -5-yl] -1,4-dihydro-4-airyl-1,8-naphthyridin-3-carboxylic acid IR (KBr) cm-1 uc * 〇1724 NMR (di-TFA) 6 values: 2.46 (3H, s), 4.78 (4H, s), 7.05-8.15 (10H, m), 8.71 (lHf d, J = l〇.〇Hz ) f 9.50 (1H, s) • 7- [2- (benzylcarbonyl) isoindolinline-5-yl] -1-chenpropyl-6-cyano-8-fluoromethyl-1,4-di Argon-4-oxylaurin-3-carboxylic acid IR (KBr) cra-i: υ〇 = 〇1713 NMR (CDC13) δ value: 0.75-1.60 (4H, m), 4.00-4.50 (1H, m) , 4.85 (4H, s), 5.23 (2H, s), 5.70 (2H, d, J = 47Hz) f 6.80-7.75 (8H, m), 8.28 (1H, d, J = 7.5Hz), 8.95 (1H , s), 14.1 (1H, brs) _ 8 1-This paper uses the national standard ('CNS) A4 specification (210X297 mm) ---------' installation τ ----- -Order-· ---- Γ i (Please read the notes on the back before filling this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the Invention (0) • 1-cyclopropyl- 6-fluoro-8-methane-7- [2- (p-toluenesulfonyl) isoindole W-5 -yl] -1,4-dihelium-4 -gasyl β β-3- Pouch acid IR (KBr) cm-i: υ〇〇1727 NMR (CDCI3) 5 values 1.00-1.50 (4Η, m), 2.40 (3Η, s), 3.34 (3H, s), 3.80-4.40 (1H , m), 4.69 (4Hf brs), 6.90-8.20 (8Hf m), 8.86 (1H, s), 14.3 (1H, brs) • 1-Hydroxypropyl-6-«-8-methyl <<-7- [1-methyl-2-((p-toluenethio) isoindolinol-5-yl] -1,4-dihydro-4-aminobromoline-3-carboxylic acid IR (KBr) cm-1: υ〇 = 〇1734 NMR (di-TFA) δ value: 1.20-2 · 00 (7H, m ), 2.45 (3H, s), 3.54 (3H, s), 4.35-5.45 (4H, m), 7.00-7.95 (7H, m), 8.20 (1H, d, J = 8.5Hz), 9.49 (1H, s) • 1-Cyclopropyl-6-co-8-methoxy-7- [3-methyl-2- (p-, tosyl) isoindolinolin-5-yl] -1,4 -Dihydro-4-air cyline-3-carboxylic acid IR (KBr) cnr1: υοο 1728 NMR (CDCI3-D2O) δ value: 0.90-1.45 (4Η, m), 1.68 (3H, d, J = 6.5Hz), 2.39 (3H, s), 3.34 (3H, s), 3.80-4.30 (1H, m) f 4.55-5.25 (3H, m), 7.05-8.10 (8H, m), 8.85 (1H, s) • Bucyclopropyl-8-difluoromethoxy-6-fluoro-7- [2- (p-toluenesulfonyl) isoinolinolin-5-yl] -1,4 -difluorene-4 -Gas-based IFfline-3-carboxylic acid-82- This paper is suitable for China National Standard (_CNS) A4C4M 210X297 mm) --------- C · Install ·· — (Please read the back first Please note this page before filling in this page) ΐχ • S---imtw 泸 B7__ 5. Description of the invention (heart) IR (KBr) cm-l: υς = 〇1732 NMR (CDCI3 + CD3OD) 6 Values: 0.90-1.50 (4 horses, m), 2.42 (3H, s), 3.90-4.35 (1H, m), 4.70 (4H, s), 5.91 (1H, t, J = 75Hz), 7.15-7.95. (7H, m), 8.18 (1H, d, J = 9.0Hz), 8.92 (1H, s) • 1-chenpropyl-8-difluoromethane-6 -Fluoro-7- [3-methyl-2- (p-toluenesulfonyl) isoindolyl-5-yl] -1,4-diargon-4-oxy 丨 fline-3-carboxylic acid IR (KBr) cm-1: υ〇 = 〇1732 NMR (CDCI3) 6 value · 0.80-1.95 (7Η, m), 2.39 (3Η, S), 3.85-4.35 (1H, m), 4.45-5.25 ( 3H, m), 5.82 (1H, t, J = 74Hz), 7.10-7.50 (5Hf m), 7.55-7.90 (2H, m) f 8.18 (1H, d, J = 8.8Hz), 8.91 (1H, s ) f 14.0 (1H, brs) • 1-Ceryl-6-fluoro-8-fluoromethyl "-7- [2- (p-methylamidosulfonyl) isoindoline-5-yl]- 1,4-dihydro-4-amino cyanoline-3-carboxylic acid IR (KBr) cm-l: υ〇 * 〇1732 Printed by the Ministry of Economic Affairs Central Standards Bureau Bureau of Work Consumer Cooperatives (please read the note on the back first) Please fill in this page again) NMR (CDC13) δ value: 0.80-1.50 (4H, m), 2.42 (3H, s), 3.90-4.40 (1H, m), 4.69 &lt; 4H, s), 5.06 (2H, d, J = 53Hz) f 7.00-7.80 (7H, m) f 8.12 (1H, d, J = 8.8Hz), 8.91 (1H, s), 14 .2 (1H, brs) • 1-Ceryl-6-fluoro-7-[[Bromyl-2- (p-toluenesulfonyl) isoindole] 8 3 _ This paper is in accordance with China National Standard (fcNS) A4 Specifications (210X297 mm) B7 _ 5. Description of the invention (P) P-Colinolin-5-yl] -1,4-dihydro-4-airyl β-line-3-carboxylic acid IR (KBr) cm-i: υ〇 = 〇1751, 1734 NMR (di-TFA) δ value: 1.20-2 · 10 (7H, m), 2.45 (3H, s), 3.90-4.50 (1H, m), 4.60-5.50 (3H , m), 7.10-8.05 (7H, m), 8.42 (1H, d, J = 9.5Hz), 8.74 (1H, d, J = 6.0Hz), 9.46 (1H, s) • 1-chenpropyl- 6-fluoro-7- [3-methyl-2- (p-toluenesulfonyl) isoinolinolin-5-yl] -1,4-difluoren-4-yloxyquinolin-3-carboxylic acid IR (KBr) cm-i: υ〇 * 〇1754, 1736 NMR (di-TFA) 6 Value: 1.25-2.00 (7H, m), 2.46 (3H, s), 3.95-4.45 {1H, m) r 4.65 -5.50 (3H, m), 7.20-8.10 (7H, m), 8.44 (1H, d, J = 9.5Hz) f 8.74 (1H, d, J = 6.0Hz), 9.46 (1H, s) • 7- [2- (benzylcarbonyl) isoinolinolin-5-yl] -8-ammonia-6-fluoro-1-[(lR, 2S) -2-fluoropropyl] -1,4-dihydro-4 -Gas-based i-line-3-carboxylic acid IR (KBr) cm-1 ·: υ〇 = ο 1708 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs ( Please read the notes on the back and fill in this page first) NMR (CDC13) δ value: 0.90-2.20 (2Η, σι), 3.80-5.00 (5 · 5Η, m), 5.00-5.50 (2.5Η, m), 6.90 -7.50 (8Η, n〇, 8.20 (1H, d, J = 7.8Hz), 8.88 (1H, brs), 13.7 (1H, brs) -8 4 _ This paper size applies to the Chinese National Standard (tNS) A4 specifications ( 210 X 297 mm) A7 B7 V. Description of the invention (shirt) _ 6-fluoro-1- (2-fluoroethyl) -8-methoxy-7- [2- (p-toluenesulfonyl) isoindole丨 Porphyrin-5-yl] -1,4-difluoren-4-oxoline-3-carboxylic acid IR (κΒζ) cm-i: υς = 〇1718 NMR (di-TFA) δ value: 2.47 ( 3H, s}, 2.65 (3H, s), 3.70-6.00 (8H, m), 7.00-8.10 (7H, m), 8.36 (1H, d, J = 8.0Hz), 9.46 (1H, s) • 1 -Ethyl-6-fluorene-8-methyl-7- [2- (p-toluenesulfonyl) isoindolinolin-5-yl] -1,4-diargon-4-oxylaurin- 3-carboxylic acid IR (KBr) cm-1: uc = 〇1720 NMR (CDC13) δ value: 1.46 (3H, t, J = 7.3 Hz), 2.41 (6H, s), 4.15-4.90 (6H, m) , 6.90-7.90 (7Hf m), 8.14 (1H, d, J = 9.3Hz), 8.74 (1H, s), 14.4 (1H, brs) • 6-ore-1-[(111,23) -2- «Ceryl] -8-methyl-7- [2- (p-toluenesulfonyl) Indolinolin-5-yl] -1,4-dihydro-4-oxoline-3-carboxylic acid IR (KBr) cm-1: υ〇 = 〇1726 NMR (CDC13) δ value .: 0.80- 2.30 (2Hf m), 2.42 (3Hf * Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) s) f 2.51 (3H, s), 3.70-4.90 (5.5Hf m), 5.10-5.60 (0.5H, .m), 6.80-8.15 (8Hf m), 8.83 (1H, d, J = 2.9Hz) • 1- (2,4-difluorophenyl) -6-fluoro -8-methyl-7- [2- (p-toluenesulfonyl) isoindololin-5-yl] -1,4-difluorene-4 -oxyfluorin-3-carboxylic acid-85- / 'This paper size applies to Chinese national standard (' Seven Milk ') 4 specifications (210'; &lt; 297 mm) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 _B7__ V. Description of the invention (correction) IR (KBr ) cm-i: υ〇 = 〇1734 .1- (4-benzyloxyphenyl) -6-fluoro-8-methyl-7- [2- (p-toluenesulfonyl) isoindoline-5 -Yl] -1,4_diargon_4_amino group fline_3_carboxylic acid IR (KBr) cra-1: υ〇 »〇1728 NMR (di-TFA) δ value: 1.81 (3Η, s ), 2.46 (3Η, s), 4.60-5.70 (6H, m), 6.90-8.20 (16Hf m), 8.41 (1H, d, J = 8.3Hz) f 9.32 (lHr S) • 6-fluoro -1- (2-fluoroethyl-7- [2-(p-methylbenzylphosphonium) isoindololin-5-yl] -1,4-bisfluoren-4- «yl bismorpholine-3- Carboxylic acid IR (KBr) cm-i: υ〇 = 〇1719 NMR (di-TFA) δ value: 2.47 (3Hf s), 4.40-5.60 (8H, m), 7.10-8.60 (9H, m), 9 · 45 (1H, s) • 1- (2, 4-dicyanophenyl) -6-cyano-7- [2- (p-toluenesulfonyl) isoindolin >> $ line-5-yl] -1, 4-Difluoren-4-ylamino-2-line-3-carboxylic acid IR (KBr) cm-i: υ〇 = 〇 × 719 • 7- [2- (benzylcarbonyl) isoindolinline-5-yl] b Cannyl-6-fluoro-8-methyl-5-nitro-1,4-dihydro-4-aminoquinoline-3-carboxylic acid IR (KBr) cm-1: uc * 〇1736, 1702 NMR (CDCI3) δ values: 0.80-1.80 (4H, m), 3.45 (3H, s), 3.80-4.30 (1H, m), 4.86 (4H, s), 5.23 (2Hf S), 7.10-7.50 (8H , m), 8.92 (1H, s), 13.3 (1H, brs) -86- This paper size adopts China National Standard (CNS) A4 specification (210X297 mm) ---------- install '— (Please read the precautions on the back before filling in this page),-° -ο Printed by the Central Ministry of Economic Affairs of the Central Working Group Consumer Cooperative A7 B7 _ 5. Description of the invention (type) Example 8 0.53g 1-zhuo Propyl-6-dai-8-methyl-7- 〔2- (p-toluene Pyridyl) iso-indolyl-5-yl] -1,4-dihydro-4-oxyH-line-3-carboxylic acid suspended in 5.3.1 47% hydrobromic acid, and 0.28 g of phenol and 3.2 -1 propionic acid to suspension and the resulting mixture was heated under reflux for 1 hour. The reaction mixture was added to the residue under reduced pressure, and acetic acid, and the resulting crystals were collected by filtration to obtain 0.38 g of colorless crystalline 1-propenyl-6-fluoro-8-methyl-7- ( Isoindolyl-5-yl) -1,4-diamidino-4-aminobimorpholine-3-carboxylic acid phosphonium bromate. The obtained osmium bromide 91 was floated in 3.8.1 acetic acid and then dissolved in 7.6.1 0.5N argon-oxidized pin aqueous solution, and then osmium dioxide was blown into the solution. The resulting crystals were collected by filtration to obtain 0.2 7 g of colorless crystalline 1-cyclopropyl-6-fluoro-8-methyl-7- (isoindololin-5-yl) • 1,4-dihydro-4 -Oxygen Ift-3-complete acid. IR (KBr) cm-i: uc = 〇1643 NMR (di-TPA) 6 Value: 0.90-2.00 (4Hf m), 2.94 (3H, s), 4.40-5.30 (5H, m), 7.10-7.85 (3H , m) f 8.35 (lHf d, J = 7.8Hz) r 9.63 (1H, s) The following compounds were obtained in the same manner "• 1-fluorenyl- δ-fluorene-7- (isoindolyl-5-yl ) -1,4-Dihydro-4-amino-Bolin-3-carboxylic acid IR (KBr) cm-i: υ〇〇1615 NMR (di-TFA) δ Value: 1.20-2.10 (4Hf m) r 4.00 -4.60 (1H, m), 5.04 (4H, s), 7.40-8.10 (3H, m), 8.49 (1H, d, J = 9.3Hz), 8.74 (1H, d, J = 5.9Hz), 9.49 ( 1H, s) -87- &gt; 1 Paper size, using China National Standard (_CNS) A4 size (210X297 mm) --------- {&quot; 装 -------- Order ' --.---- Γ i (Please read the notes on the back before filling this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Invention Description (S &quot;. (S> -9-Fluoro- 3-methyl-10- (isoindolinolin-5-yl) -7-oxy-2, 3-difluorene-7H-pyridine [1,2,3-de] [1,4] benzene Beer trap-6-carboxylic acid IR (KBr) cm-i: υ〇 = 〇1717 NMR (di-TFA) 6 value 1.85 (lHld, J = 6.8Hz), 4.10-5.50 (7H, m), 7.64 (3H, s), 8.12 (1H, d, J = 8.8Hz), 9.37 (1H, s) • 1-Cannyl-6-fluoro-7- (isoindone W-5-yl) -1,4-dihydro-4-amino-1,8-eryridine-3-carboxylic acid IR (KBr) cm-i: υ〇 = 0〇1717 NMR (di-TFA) δ value: 1.00-2.00 (4H, m), 4.10-4.70 (1H, m), 5.03 (4H, s), 7.30-9.00 (4H, m), 9.53 (1H, s). 1-cyclopropyl-6,8-difluoro-7- (isoinolinolin-5-yl) -1,4-dihydro-4-oxyl f-line-3-carboxylic acid IR (KBr) cm-1: υ〇 = 〇1616 NMR (di-TFA) δ value: 1.30-2.00 (4H, m), 4.30-5.30 (5H, m), 7.71 ( 3Hf s) f 8.37 (1H, d, J = 7.8Hz), 9.52 (1H, s) • 8-cyano-1-chenpropyl-6-fluoro-7- (isoindolin crisp-5-yl)- 1,4-DiM-4-aminobromoline-3-carboxylic acid IR (KBr) cm-i: υ〇〇1636 NMR (di-TFA) δ value: 1.10-1.90 (4H, m), 4.60- 5.20 (5H, m), 7.30-7.80 (3H, m), 8.43 (1H, d, J = 6.8Hz), 9.63 (1H, s) -8 8 _ (Please read the precautions on the back before filling this page ) Installed.,-°

A This paper is again applicable to China National Standard (_CNS) A4 specification (210X297 mm) A7 B7___ V. Description of the invention (type) .1-chenpropyl-7- (4,7-difluoroisoindolinoline 5- (6-fluoro-1,4-dihydro-4-aminopyroline-3-carboxylic acid) IR (KBr) cm-i: υ〇 »〇1720 NMR (di-TFA) δ value": 1.15 -1.95 (4H, m) f 3.95-4.60 (1H, m), 5.13 (4H, s), 7.15-7.65 (1H, m), 8.51 (1H, d, J = 8.8Hz), 8.84 (1H , d, J = 5.4Hz), 9.51 (1H, s) • 1-Ceryl-7- (4,7-difluoroisoindole I-Ran-5-yl) -6-fluoro-8-methoxy -1,4-Difluoren-4-yl group quinoline-3-carboxylic acid IR (KBr) cm-1: υ〇 = 〇1734 NMR (di-TFA) δ value: 1.20-1.80 (4H, m) , 3.75 (3H, s), 4.45-4.95 (1H, m), 5.15 (4Hf s) f 7.20-7.55 (1H, m), 8.24 (1H, d, J = 8.5Hz), 9.50 (1H, s) • 1- (2, 4-difluorophenyl) -6-fluoro-7- (isoinolinolin-5-yl) -1, 4-difluoren-4-yl-1,8-叶 萌- 3-bag acid IR (KBr) cm-1: uc = 〇1654 NMR (di-TFA) δ value: 4.99 (4H, brs &gt;, 6.90-8.40 (6H, m), 8.78 (1H, d, J = 9.5Hz), 9.50 (1H, s) --------- ^ Installation ------- Order '--_---- C .i (Please read the precautions on the back before Fill out this ) Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 0 6-6 I-propylpropanylpyridine oxygen collection β »3 | isoS (acid 7-carboxymethylformaldehyde IR (KBr) cm-ι: u〇 = 〇 1637 NMR (di-TFA) 6 values: 1.20-1.80 (4H, m), 3.62 (3H, s), 4.40-5.20 (5Hf m), 7.73 (3H, brs) f 8.26 (lHf d, J = 8.3Hz ), 9.50 (1H, s) -89- This paper size is applicable to the Chinese national standard fr'dNS) A4 size (210X297 mm) Employees of the Central Standards Bureau of the Ministry of Economic Affairs and Consumer Cooperation Du printed A7-B7 V. Description of the invention (shirt) • 1-Ceryl-6-fluoro-8-methane- 7- (1-methylisoindolin-5-yl)-1.4-bispyridin-4-ylsulfonyl-3-carboxylic acid IR (KBr.) Cm-1: uc = 〇1726 NMR (di-TFA) 6 Values: 1.30-2.20 (7H, m), 3.60 (3H, s), 4.50-5.60 (4H, m), 7.30-8.00 ( 3H, m), 8.26 (lHf dr J = 8.3Hz) r 9.51 (1H, s) • 1-Chloropropyl-δ-dai-8-methyl gas-7- (3-methyliso 丨 丨 3 丨Phenyl-5-yl) -1.4-Diargon-4-aminobromoline-3-carboxylic acid IR (KBr) cm-1: uc = 〇1629 NMR (di-TFA) δ value: 1 · 10-2 · 10 (7H, m), 3.62 (3H, s), 4.30-5.65 (4H, m), 7.20-7.80 (3H, m), 8.29 (1H, d, J = 8.3Hz), 9.50 (1H, s) • 1-chen Propyl-8-difluoromethoxy-6-fluoro-7- (iso-isopyridin-5-yl) -1,4-bisfluoren-4-yloxyline-3-carboxylic acid IR (KBr) cm-l: υ〇 = 〇1636 NMR (di-TFA) δ value: 1.00-2.00 (4Hf m), 4.30-5.20 (5H, m), 6.20 (lHf t, J = 72Hz) f 7.72 (3Hf brs) f 8.46 (1H, df J = 8.3Hz) f 9.58 (1H, s) • 1-fluorenyl-8-dicyanomethoxy-6-cyano-7- (3-methyliso13 丨 fluorin-5 -Group) -1,4-dihydro-4-amino group f-line-3-carboxylic acid IR (KBr) cm-1: uc = 〇1638 NMR (di-TFA) δ value: 1.15-2.15 (7H, m), 4.45-5.15 (3H, m), 5.15-5.70 (1H, m), 6.20 (1H, t, J = 72Hz), 7.30-7.95 (3H, m), 8.46 {1H, d, J = 8.3 Hz), 9.59 (1H, s) -9 0-— i______ This paper size applies Chinese National Standard (CNS) A4 (210X29? Mm) --------- C Pack— (Please read the back first (Notes to fill out this page)

M A7 _B7___ V. Description of the invention (throw) • 1-Ceryl-6-fluoro-8-fluoromethyl-7- (isoindolin W-5-yl) -1, 4-difluoren-4-ox Benzylline-3-carboxylic acid IR (KBr) cm-i: υ〇 = 〇1732 NMR (di-TFA) δ value: 1.00-2.00 (4H, m), 4.50-5.25 (5Hf m), 5.28 (2H , d, J = 52Hz), 7.20-7.90 (3Hr m) f 8.39 (1H, dr J = 8.3Hz), 9.56 (1H, s) • 1-chenpropyl-6-fluoro-7- (1-form Iso-13-pyridin-5-yl) -1,4-difluoren-4-ylamino-3-carboxylic acid

IR (KBr) cm-i: υ〇 »〇1618 I NMR (di-TFA) δ value: 1.30-2.20 (7H, m), 4.00-4.50 (1H, m) f 4.80-5.70 (3H, m), 7.40-8.00 (3H, m) fl 8.49 (1H, d, J = 9.0Hz), 8.79 (lHf d, J = 6.0Hz), 9.49 (1H, s) (3-methylisoindyl) -1,4-diargon-4-amino bisphospholine-3-carboxylic acid IR (KBr) cm-i: υ〇 = 〇1618 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the notes on the back before filling this page) NMR (djL-TFA) δ value: 1.20-2.15 (7H, m), 3.95-4.50 (1H, m) f 4.70-5.70 (3ΗΛ m), 7.40 -8.05 (3H, m) f 8.15-9.00 (2H, m), 9.44 (1H, s) • 6-fluoro-1- (2-fluoroethyl) -7- (isoindolinolin-5-yl) -8-Methyl-1 / 4-difluoren-4-aminobimorpholine-3-carboxylic acid IR (KBr) cm-i: υ〇 = 〇1628 NMR (di-TFA) δ value: 2.73 {3H, s), 4.00-6.00 (8H, m), 7.00-7.90 (3H, m), 8.44 (1H, d, J = 7.3Hz), 9.53 (1H, s) -91-This paper size applies to Chinese national standards ( tNS) A4 size (210X297 mm) A7 B7___ printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (9.) • 1-Ethyl-6-fluoro-7- (isoindole II dorolin-5- base -8-Methyl-1,4-dihydro-4-ylamino-3-carboxylate IR {KBr) cm-i: υ〇 »〇1633 NMR (d! -TFA) δ value: 1 · 76 (3H, t, J = 7.3Hz), 2.78 (3Hf s), 4.80-5.50 (6H, m) f 7.30-7.70 (3H, m), 8.41 (1H, d, J = 7.8Hz), 9.45 ( 1H, s) • 6-Fluoro-bu [(1R, 2S) -2-Fluoropropyl] -7- (isoindololin-5-yl) -8-methyl-1,4-dihydro- 4-Gas-H-L-3--3-carboxylic acid IR (KBr) cm-i: υ〇 * 〇1634 NMR (di-TFA) δ value: 1.20-2.40 (2H, m), 2.88 (3H, s), 4.30 -5.90 (6H, m) f 7.10-7.90 (3H, m), 8.35 (1H, d, J = 7.3Hz), 9.53 (1H, s) .1- (2,4-difluorophenyl) -6 -Fluoro-7- (isoindioline-5-yl) -8-methyl1,4-difluoren-4-ylaminoβline-3-carboxylic acid IR (KBr) cm-i: uc = 〇1636 NMR (di-TFA) δ value: 1.90 (3H, s), 4.50-5 · 20 (4H, m), 6.80-8.00 (6H, m) f 8.45 (1H, d, J = 7.8Hz ), 9.35 (1H, s). 6-fluoren-1- (4-triphenyl) -7- (isoS3 丨 fluorid-5-yl) -8-methyl-1,4-difluorene- 4-oxylfline-3-carboxylic acid IR (KBr) cm-1: υ〇 = 〇1622 NMR (drTFA) δ value: 1.95 (3Η, s), 4.98 (4Η, brs), 6.50-7.80 ( 7H, m), 8.48 (1H, d, J = 7.7Hz), 9.32 (lHr s). -92- Paper size Use Chinese National Standard (fcNS) A4 specification (210X297 mm) --------- r Install f ------ ¾ --_---- (Dream (Please read the notes on the back first (Fill in this page again) Printed A7 B7 printed by the Shellfish Consumer Cooperative of the Central Bureau of Quasi-Ministry of Economic Affairs V. Description of the invention (V) • 6-fluoro-1- (2-fluoroethyl) -7- (isoindiodoline- 5-yl) -1,4-bisfluorene-4-fluorenyl Kfline-3-carboxylic acid IR (KBr) cm-i: uc-〇1618 NMR (di-TFA). Δ value: 4.40-5 · 80 (8H, m) r 7.50-8 · 10 (3H, m), 8.20-8.80 (2H, m), 9.48 (lHf s) • 1- (2,4-difluorophenyl) -6 -Fluoro-7- (isoindolinolin-5-yl) -1,4-bisS-4-oxoline-3-carboxylic acid IR (KBr) cm-i: uc.〇1622 NMR (di- TFA) δ value 4.96 (4H, brs), 7.00-8.00 (7Hr m), 8.56 (1H, d, J = 9.3Hz), 9.38 (1H, s) Example 9 50ag 1-cyclopropyl-6-cyano- 8-methyl «-7- [2- (p-toluenesulfonyl) isoindolin-5-yl] -1,4-difluoren-4-ylaminoβ-line-3-carboxylic acid suspended in 0.5b1 47¾ 氲 bromic acid, and 26M phenol and 0.3 · 1 propionic acid were added to the suspension, and the resulting mixture was then stirred at 13JTC for 6 hours. The reaction mixture was concentrated under reduced pressure, and 0.3 * 1 ethanol, 0.3 · 1 1 Torr argon sodium aqueous solution and 0.3 · 1 water were added to the obtained residue to dissolve the residue. Then the digassed tritium was blown into the solution, and the precipitated crystals were collected by filtration to obtain 12eg of pale yellow crystalline 1-canyl-6-fluoro-8-hydroxy-7- (isoindole_-5 -Yl) -1,4-difluoren-4-ylaminopyridin-3-carboxylic acid. IR (KBr) cm-1: uc * 〇1613 NMR (di-TFA) δ value: 1.00-1.80 (4H, m) f 4.50-5.20 (5H, m), 7.66 (3H, brs), 8.00 (1H, d, J = 8.6Hz} f 9.44 (1H, s) -93- This paper size is applicable to the Chinese National Standard (CNS) Λ4B (210X297 mm) (Please read the precautions on the back before filling this page) -pack- 1T- A7 B7 V. Description of the invention (9 &gt;) Example 10 / In 210 · «ethyl 1-fluorenyl-6-fluoro-8-methoxy-7- [2-trifluoroethylfluorenylfluorene [, Isoindinolinylpropan-5-yl] -1.4-dihydro-4- «ylpyroline carboxylate was added to the suspension of 4.2el acetic acid with 2.1al 1N fluorinated pin solution and 4.2.1 Alkane, and the resulting mixture was stirred and heated at 40 * C for 3 hours. The β reaction mixture was cooled to room temperature, and then insoluble matter was removed by filtration, and then radon dioxide was blown into the obtained filtrate. The crystals were collected by filtration to obtain 14 Oig pale yellow crystalline 1-benzyl-6-fluoro-8-methyl gas-7- [spiro [isoindolin-1,1 · -propylpropyl] -5-yl ] -1,4 -Dihydro-4-air-based technology leaching-3-bag acid β IR (KBr) cm-i: υ〇 = 〇1618 NMR (d6-DMSO) δ value: 0.80-1.50 (6Η, m ), 2.40-2.80 (2Η, m), 3. 43 (3Hf s), 4.00-4.40 (3H, m) f 6.90-7.60 (3Hf m) f 7.90 (1H, df J = 9.0Hz), 8.85 (1H, s) In the same manner, the following compound e is obtained:珲 propyl-8-difluoromethane-6-fluoro-7-[[[Isoinolino-pyrene, ι · -chenpropyl] -5 -yl] -1,4 -difluorene-4 -qi Printed by the Male Worker Consumer Cooperative of the Central Bureau of Quasi-Economy Bureau of the Ministry of Economic Affairs of Jijilin 3-Pack Acid (please read the precautions on the back before filling this page) IR (KBr) cm-i: υ〇 = 〇1636 NMR (d6- DMSO) δ value: 0.90-1.40 (6H, m), 2.40-2.60 (2H, m), 3.50-4.40 (3H, m), 6.67 (1H, t, J = 73Hz), 6.80-7.50 (3H, m ), 8.11 (1H, d, J = 9.0Hz), 8.88 (1H, s) -94- This & Zhang applies to China National Standards (fcNS) (21GX297 public address) &quot; Shellfish Consumer Cooperatives, Central Standards Bureau, Ministry of Economic Affairs Printing A7 B7 V. Description of the invention (90 Example 11 1 50 0 bg 7-[2-(benzyloxycarbonyl) isoindolino-doline-5 -yl] -8 -gas-6-fluoro-1-[( lR, 2S) -2-fluorosynyl] -1,4-dihydro-4-amino-Kolinolin-3-carboxylic acid was suspended in 25.1 acetic acid and 50ig 556 amidines, and the suspension was under a stream of hydrogen Stir at room temperature for 2 hours. The reaction mixture was filtered and then 2 μl of 6 N hydrochloric acid was added to the obtained filtrate, and then the mixture was concentrated under reduced pressure. The obtained residue was added with ethyl acetate, and the resulting crystals were collected by filtration. Add 0.7 * 1 acetic acid, 0.7 · 1 1N hydration sodium hydroxide solution and 0.7ml water to dissolve the crystals, and then add dilute acetic acid to adjust the solution P to the box-pass filter to collect the precipitated crystals to obtain 45ag Colorless crystallinity 8-«-6-Da-bu [(11?, 23 &gt; -2-Fluoropropyl] -7- (isoindololin-5-yl) -1,4-difluorene-4- Gasoline phthaloline-3-carboxylic acid. IR (KBr) cm-i: υ〇 = 〇1641 NMR (di-TFA) δ value: 1.30-2.30 (2H, ra), 4.30-5 · 90 (6Hr m), 7.20-7.80 (3H, m), 8.46 (1H, d, J = 7.3Hz), 9.56 (1H, S) Selling Example 12 Suspended in 10 · 1 acetic acid and 60ng 5% rake 85 * g 7 -[2- (benzyloxycarbonyl) isoindololin-5-yl] _Phenyl-6-fluoro-8-methoxy-5-nitro-1,4-difluoren-4-yl Porphyrin-3-carboxylic acid, and the suspension were stirred under a turbulent stream for 2 hours. The reaction mixture was filtered, and then 2.16 N hydrochloric acid was added to the resulting filtrate, after which the resulting mixture was shrunk under reduced pressure. The product is added with acetic acid, and the resulting crystals are collected by filtration. The obtained crystals are added with 0.55β1 ethanol, 0.5nl 1N sodium hydrogenated aqueous solution and 0.5 * 1 water-95- This paper size applies Chinese national standards (Death NS) A4:% # (210X297 mm) (Please read the precautions on the back before filling out this page)-Install !. Printed by A7 B7, Consumer Cooperatives of the Central Procurement Bureau of the Ministry of Economic Affairs 5. Description of Invention (μ) To dissolve the crystals. «After that, sulphur dioxide gas is blown into the solvent, and the crystals precipitated by collecting $ to obtain Hng light yellow crystalline 5-amino_1_ propyl-6-fluoro-7- (Isoinolinolin-5-yl) -8-methyl-1,4-dihydro-4-oxyquinoline-3-carboxylic acid IR (KBr) cm-i: υ〇 = 〇1716 NMR (h -TFA) δ value: 0.70-1.70 (4H, m), 3.58 (3Η, s), 4.00-4.70 (lHf m), 5.02 (4Hr brs), 7.70 (3H, brs), 9.29 (1H, s) 13 0.16 g of 7- [2- (benzylcarbonyl) isoindolin W: -5-yl] -1-chloropropyl-6-fluoro-8-fluoromethane-1,4-dihydro-4-oxo Gyroline-3-carboxylic acid was suspended in a 3.2 mil 130% bromide-acetic acid solution, and the suspension was coarsely seeded in the chamber for 40 minutes. The reaction mixture was decomposed under reduced pressure and ethyl acetate was added to the residue The resulting crystals were collected by filtration. The resulting crystals were dissolved in dilute aqueous sodium oxide solution and diluted with dilute hydrochloric acid to 7. The precipitated crystals were collected by filtration to obtain 68 mg of colorless crystals. Cyclopropyl-6-fluoro-1- cut --8- * methyl --7- (isoindole _ --5-yl) -1,4-Yun --4- «manifold yl-3-carboxylic acid. IR (KBr) cm ~ l: 〇c = o 1638 NMR (di-TFA) δ value: 1.10-2.05 (4Hf m), 4.65-5.25 (5H, m), 5.96 (2H, &lt; 3, J = 47Hz ), 7.25-7.85 (3H, m), 8.52 (1H, d, J = 7.8Hz), 9.65 (1H, s) Example 14 5 0 g 1 -Ceryl-6-fluoro-7-(iso Indoline-5-yl) -1,4-dihydro-4-fluorenyl-3-carboxylic acid hydrogen aluminate suspended in 0.50.1 formic acid, -96- This paper uses China National Standard (0NS) Α4 Specification (210X297 mm) --------- Γ -Installation * ------ IX --.---- (, (Please read the precautions on the back before (Fill in this page) A7 B7 printed by the Consumer Cooperatives of the Central Procurement Bureau of the Ministry of Economic Affairs 5. Description of the invention (π)

And 27ag of fentholine was added to the suspension, and then the mixture was drawn for 2 hours. The solvent was removed by evaporation under reduced pressure. The obtained residue was added with 5 · 1 water and pH to saturate the water and dissolved in water. The whole mixture was then scaled to 7 and then the obtained mixture was extracted with 5 parts of 5 through 1 «imitation extraction β. The imitation layer was dried over anhydrous magnesium sulfate and then reduced under S. Steaming »Remove the lysocyanine and add ethyl acetate to the obtained residue and collect the crystals collected by filtration to obtain 23ig pale yellow crystalline 1-benzyl-6-fluoro-7- (2-methylisoindolinline-5- Radical) -1,4-diargon-4-aminopyridin-3-carboxylic acid IR (KBr) cm-1: υ〇 = 〇1730 NMR (di-TFA) 6 Value: 1.20-2.05 (4H, m ), 3.39 (3H, s), 4.00-5.60 (5Hf m), 7.45-8.05 (3H, m), 8.50 (1H, d, J = 9.2Hz), 8.80 (1H, d, J = 5.9Hz) f 9.50 (1H, S) in the same way «to the following compounds" • 1-cyclopropyl-6-fluoro-8-methyl-7- (2-methylisoinolinolin-5-yl) -1,4 -Two articles: 4-Aminopyridin-3-carboxylic acid IR (KBr) cm-i: υ〇 = ο 1725 NMR (di-TFA) δ value: 1.05-2.00 (4H, m), 2.93 (3H , s), 3.38 (3Hf s), 4.30-5.50 (5H, .m), 7.20-7.80 (3H, in), 8.34 (1H, d 'J = 7.3Hz), 9.63 (1H, s) • (S )-9-fluoro-3-methyl-10-(2-methylisoindin_-5-yl) -7-amino-2,3-dihydro-7H-pyridinium [1,2,3 -de] [1, 4-]骈 Beer trap-6-bagic acid IR (KBr) cm-1: υ〇 = 〇1716 NMR (di-TFA) 6 value: 1.50-2.20 (3H, m) r 3.35 (3H, brs), 4.10-5.80 ( 7Hf m) f 6.90-8.30 (4H, m), 9.35 (1H, brs) -97_ This paper size is applicable to the Chinese national standard (NS NS) A4 size (210x297 mm) --------- f -Equipment * ------ 1T --- ^-1 ^ ^ (Please read the notes on the back before filling out this page) The Central Consumers' Bureau of the Ministry of Economic Affairs, Consumer Cooperatives, India A7 B7_. V. Description of the invention () • 1-Cyclopropyl-6-fluoro-7- (2-methylisoinolinolin-5-yl) -1,4-dihydro-4-amino-1,8-eryridine-3 -Carboxylic acid IR (KBr,) cm-i: υ〇〇1727 NMR (CDC13) δ value ': 0.90-1.55 (4Η, m &gt;, 2.63 (3Η, s), 3.50-4.20 (5H, m), 7.36 (1H, d, J = 8.3Hz), 7.80-8.20 (2H, m), 8.44 (1H, d, J = 10.7Hz) r 8.93 (1H, s) • 1-chenpropyl-6,8-two瓤 -7- (2-methylisoindole ramie-5-yl &gt; -1,4-diamidino-4-carbyl it _-3-box acid IR (KBr) cm-1: uc = 0 1648 NMR (CDCI3) δ: 0.90-1.50 (4Hf m) f 2.60 (3H, brs), 3.50-4.40 (5H, m), 7.25 (3H, s), 8.07 (1H, d, J = 8_5Hz), 8.87 { 1H, s) • 1-chenpropyl-6-gas-8-methylgas-7- (2-methyl-isoindole (Dorolin-5-yl) -1,4-dihydro-4-airyl If leaching-3-carboxylic acid IR (KBr) cm-1: uc = 〇1732 NMR (drTFA) δ value: 1.20-1.80 (4H , m), 3.39 (3H, s), 3.63 (3H, s) f 4.30-5.60 (5Hf m) f 7.73 (3Hf brs), 8.26 (1H, d, J = 8.5Hz), 9.52 (1H, s) '• Berchen propyl-8-difluoromethane-6-fluorene-7- (2-methylisoindolinline-5-yl) -1, 4-dihydro-4-amino group 丨-3- Carboxylic acid IR (KBr) cm-i: υ〇-〇1723 NMR (di-TFA) δ value: 1.00-2.00 (4H, m), 3.34 (3H, s), 4.30-5.50 (5H, ra), 6.23 (1H, t, J = 72Hz), 7.73 (3H, brs) f 8.47 (1H, d, J = 8.3Hz), 9.60 (1H, S) _l___ 9 8 -___ This paper is applicable to China ^ 橾 standard (_CNS ) A4 size (210X297mm) I ------- 1 pack .------, tT-^ ---- c · ^ (Please read the precautions on the back before filling this page) Printed A7 _B7_ by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs V. Description of the Invention (97) • 6-Ga-1- (2-fluoroethyl> -8-methyl-7- (2-methylisopropyl) Porphyrin- 5-yl) -1,4-dihydro-4-oxoline-3-carboxylic acid IR (KBr) cm-1; oc = o 1718 Industrial use The compound of the present invention is isoindoline硪 atom is bonded to linolinone- or eryridone- 7- position of the acid are useful as anti trunk Sonogashira agent. -99- This paper size is applicable to China National Standard ('CNS) A4 (210X297mm) I ------- C' Packing * ------ IX-; ---- (Please Read the precautions on the back before filling this page) C; '!:' O'wi i. ^ -R victorius NIHJJ02! I 71 I mg T3 5 chamber mm D &gt; 萏 0.012 0.025 0.006 0.012 03 4 Ling 0.0121 ρ mmk 0.012 0.05 00 &gt; -Cf〇o § &lt; 0.006 0.05 &lt; 0.006 0.012 00 I \ \ &lt; 0.006 ρ 0.012 0.025 00 s 1.56 〇p 00 fttVcooh ΗΝ〇Γϊί ^ M · CHjCHaF 0.05 0.39 0.05 0.05 00 0 Fy ^ A ^ COOH 0.025 ο r〇0.051 0.0251 CO o ^ xr $; #

: ¾ 腾 # 菌 NIHJJC ~ 2 I 1 1 w I T 1 1 T1 § Ό 1 fr Rong '0.003 0.025 0.006 0.006 00 BU Q. 0 0 0.012 &lt; 0.006 &lt; 0.006 &lt; 0.006 00 i \ 0 § 1 0.05 &lt; 0.012 &lt; 0.012 &lt; 0.012 CO ffv ^ Vcooh ΗΝ〇φτχ ^ F 0.05 〇 ho p p CO 々1. 1 &lt; 0.006! 0.025 &lt; 0.006 (0.012 00 OMe ^ 0.025 0.05 0.025 0.025 00 〇Me 0.051 0.051 0.051 0.051 CO 1 E. coli NIHJJ02 1 1 1 snow 71 莒% 1 τι g 1 m 缂 compound 1 3.13 1,56 ο fo '0.39: σ &gt; fXjCVc〇〇h NH 丨 3.13 0.012 0.012 0.012 i § 0.006 ο fo 0.012 0.012 00 i § 0.025 0.78 0.025 0.05 CO k 0 丨 0.006 ο FO 0.025 0.012 00% o §. &lt; 0.006 0.05 &lt; 0,006 &lt; 0.006 CO O § 99a 387838

^ M # aNIHJJC-2 1 1 1 1 -π gn〇g compound m ppp 0.05 1 \ ι I I E. coli NIHJJ02 wi 1 II -ng DI 1 compound 0.006 0.05 0.025 0.0251 i § 0.025 0.025 0.012 0.0251 f § 0.025 0.05 0.05 0.0251 § I 0.05 0.05 0.05 0.05 0 c〇〇H -ccrx / 0.012 0.05 0.025 0.025 i &amp; n § I 0.012 0.025 0.012 0.012 0 § p 0.05 0.025 0.051 s: ¾ 1 bacteria NIHJJ02! | IT 裒 1 1 1 * O Plug: 鼷. Compound p 3.13 o ho '0.39 CO ^ / XtVcooh CHjCHaF &lt; 0.006 -0.39 0.05 0.05 00 \ 0Ό12 0.012 0.003 omz ο § X 0.025 &lt; 0.006 &lt; 0.006 &lt; 0.006 ο% § X 0.012 p mm * . &lt; 0.006 0.0121 / ¾0 § &lt; 0.006 0.012 &lt; 0.006 0.012 ro 0 § &lt; 0.006 0.05 &lt; 0.006 | &lt; 0.006 | 05 0 F ^ YKrCOOH -a〇y / f

99b

Claims (1)

Α8 Bg C8 387838 D8 VI. Application scope of patent No. 84108286 "Novel ketone- or pyridone- acetic acid derivative or its salt j Patent application (1882 of 1998) Patent application scope: I month_ 〇1 | n-I 1 穸 n-II A new quinolinone- or pyridinecarboxylic acid derivative represented by the following formula or its permissive salt: R6 〇 C02R1 Printed by the Central Associated Bureau of the Ministry of Economic Affairs βζIndustrial Cooperative Cooperative, Tonghua Cl-4, C3, β3, and C3, β cycloalkyl or optionally halogen, hydroxyl, or benzyl Substituted phenyl; R3 represents at least one of the following: hydrogen atom and tooth atom: R4 represents at least one of the following: fluorene atom, halogen atom, Ci-4 alkyl group, imino group and R * The bonded iodine atom forms a C3-β sulphonium group; M represents a fluorene atom, "-4 alkyl, tosyl, halogenated Ci.4 fluorenyl or benzyloxycarbonyl: R6 represents a hydrogen atom, an amine or Nitro :, A ^ represents, / or, ./ I Υ, where Υ represents a fluorene atom, a halogen atom, CU-4 alkyl group, a halogenated Ci-4 alkyl group, an alkane group, and a dentified Ci- * alkane group Or hydroxyl -------- ^ Loading ------ order ------ f ice (Please read the precautions on the back before filling this page) CNS U4 Specification (210X297) 嫠 A8 Bg C8 387838 D8 6. Application for Patent Range No. 84108286 "Novel ketone_ or pyridone- acetic acid derivative or its salt j Patent application (1¾ in 1998) Patent application : I _ month | 〇1 | n n I I a representation of the formula I 1 Xi novelty quinolinone - or Juan piperidine carboxylic acid derivative or its salt fog lotus allowable: R6 billion C02R1 Printed by the Central Associated Bureau of the Ministry of Economic Affairs βζIndustrial Cooperative Cooperative, Tonghua Cl-4, C3, β3, and C3, β cycloalkyl or optionally halogen, hydroxyl, or benzyl Substituted phenyl; R3 represents at least one of the following: hydrogen atom and tooth atom: R4 represents at least one of the following: fluorene atom, halogen atom, Ci-4 alkyl group, imino group and R * The bonded iodine atom forms a C3-β sulphonium group; M represents a fluorene atom, "-4 alkyl, tosyl, halogenated Ci.4 fluorenyl or benzyloxycarbonyl: R6 represents a hydrogen atom, an amine or Nitro :, A ^ represents, / or, ./ I Υ, where Υ represents a fluorene atom, a halogen atom, CU-4 alkyl group, a halogenated Ci-4 alkyl group, an alkane group, and a dentified Ci- * alkane group Or hydroxyl -------- ^ Loading ------ order ------ f ice (Please read the precautions on the back before filling this page) CNS U4 specification (210X297 public money) Sealed by the Bayer Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 387888 I • D8 6. The scope of patent application, or the basis of the following formula with R2: Wherein RT represents at least one selected from the group consisting of a hydrogen atom, a Ci-4 alkyl group, and B represents an oxygen atom; and X represents a fluorene atom. a As described in the first paragraph of the patent claim, the peak ketone- or pyridone-carboxylic acid derivative or its pharmaceutically acceptable s, wherein R4 is at least one selected from the group consisting of a hydrogen atom, a Ci-4 alkyl group, And the c3 -β-cycloalkane group formed by the pyrene atom bonded to R4. 3. The dark ketone- or pyridinone-carboxylic acid derivative or its permissible salt, such as item 1 or 2 of the patent application park, wherein R5 represents a hydrogen atom or a Ci-4 fluorenyl group. 4. The quinine of item 1 or item 2 of the patent application park> A ketone- or pyridone-carboxylic acid derivative or a medically acceptable salt thereof, wherein Re represents an amine group. 5. For example, if the humulone · carboxylic acid derivative or the pharmaceutically acceptable salt thereof is the first or the second in the scope of patent application, the percentage is%, and the Y I γ is fixed as in the first item. 6. For example, # 1 or 2 # pyridone-carboxycarboxylic acid derivative or its permissible salt in the scope of Shenmei patent, where / is. 7. If the __face- or pyridone-carboxylic acid derivative or its peony allowable salt of item 1 of the applied patent garden is selected from the group consisting of: I 1-chenpropyl-6-fluoro-7-( Isoindio-5-yl) -8-methyl-1,4-dihydro-2 * This paper size is based on China Gujiazheng (CNS) M specifications (210X297 mm) ------- -f i ------ ir ----- * 〇 (please read the notes on the back before filling this page) 387888 8888 ABCD VI. Application scope of patent Acid, (S) -9-fluoro-3-methyl-10- (2-methylisoindion ¢ 8 呦 -5-yl) -7-amino-2,3-diamine: -7H-pyridine骈 [l, 2,3-de] [l, 4] Benzene-6-carboxylic acid, buchenpropyl-6-fluoro-7- (isoindolyl-5-yl) -8-formaldehyde Gas-1, 4-diargon-4-ylhydrazone_-3-carboxylic acid, buchenpropyl-8-difluoromethane-6-fluorene-7- (isoindolyl-5-yl)- 1,4-Diargon-4-aminoquino-3-carboxylic acid, and 5-amino-1-cyclopropyl-6-gas-7- (isoin1 «呦 -5-yl) -8 -Methyl-1,4-diamidino-4-aminoquino-3-carboxylic acid. 8. —Organic tin compounds or their salts represented by the formula: Sn (Alk); printed by Zhengong Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs, where R3, R * and 1 {8 are as defined in item 1 of the patent application garden, and Aik represents a linear or rifle h-4 alkyl group β 9. A quinolinium fluorene-or pyridone-carboxylic acid derivative represented by the following formula or its peony permissible salt R6 〇C02R1 This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) -------- d ------ IT ------ f ¥ (Please read the notes on the back first Write this page again) 387838 b8 D8 6. Scope of patent application Among them, R1, R2, Re, X and A are as defined in the first scope of patent application, and Aik represents a linear or branched C! * Alkyl group. 10—A derivative or a salt thereof represented by the formula: R6 Ο CO2R1 R3 where R1, R3,, Rs, Re, X and A are as defined in the first scope of the patent application. 11 A composition for use as an anti-drug, which comprises a peony, and is effective as described in the "Patentone- or Piridone-Carboxylic Acid Derivatives or their Peony Drugs" It is allowed to prepare Zoam. -------- ^ i ------ tr ----- 〇 (Please read the precautions on the back before filling out this page) Printed Paper Size by the Employees' Cooperatives of the Central Procurement Bureau of the Ministry of Economic Affairs Applicable to China National Standard (CNS) A4 (210X297 mm)