TW200413340A - Dibenzoxazepines - Google Patents

Abstract

The present invention relates to compounds, processes for their preparation, pharmaceutical compositions comprising them, and the use thereof for the treatment and/or prophylaxis of disorders in humans or animals, especially of cardiovascular disorders, e.g. of atherosclerosis.

Description

200413340 A7 __________ B7 V. Description of the invention (i) The technical field to which the invention belongs The invention relates to a compound, a preparation method thereof, a medical composition containing the compound, and its application for treating and / or preventing human or animal diseases , Especially for the treatment of cardiovascular disease, such as atherosclerosis. Prior art Dibenzoxazepines have been described in WO 00/48603 as αν; 53, αν ^ 5 and / or integrin receptor antagonists, especially for the treatment of arterial atherosclerosis. WO 99/11626 describes dibenzoxazepines as fibrinogen and / or vitronectin receptor antagonists, especially for the treatment of atherosclerosis. EP_A 419 861 describes the use of dibenzoxamine for the treatment and / or prevention of AIDS. 15 US 4,728,735 application of dibenzothiazepine 1 * ^-〇 anti-gastric ulcer dibenzothiazepine for the treatment of cardiovascular diseases is described in CiPLt / S 1982, 423831 (JP-A-57002278) and 1984, 191915 (JP-A-Printed by Employee Consumer Cooperatives, Bureau of Intellectual Property, Ministry of Economy, 58225073). 20 is now generally known as atherosclerosis, inflammation hardened parts of Pathology. These inflammatory vascular changes are characterized by (especially) migration of monocytes and increased release of cytokines in the pre-inflammatory phase. In particular, the monocytes that have migrated into the formation of foam cells and the altered metabolism of these foam cells are important for patch development and stability and are extremely important. It can be seen that the size of the jade paper conforms to the Chinese National Standard < CNS) A4 specification (210 x 297 Gongchu) 200413340 A7 B7 V. Description of the invention (2) The giant salamander cells significantly change their gene expression when loaded with lipid. In this case, the increase in the performance of the 'aminopeptidase N is particularly remarkable. Amino peptidase N is a transmembrane enzyme corresponding to the CD13 antigen (EC 3 · 4 · 11 · 12). Amino peptidase n catalyzes the elimination of the N • terminus of amino acids (5 are preferred with neutral amino acid residues). In synaptic membranes, aminopeptidase N thus deactivates neuropeptide hormones such as endorphin and cerebral myelin. Other substrates include kinin, chemotropic peptide (MCP-1) and extracellular matrix components. Numerous publications have shown that aminoamylase N is involved in angiogenesis and tumor spread. Membrane proteases can not only show their biological effects by cleaving proteins, but can also show them through signal conversion programs10. May prove amino peptidase and signal conversion Ν monocytes of about (Santos et al., Cellular Immunology 2000, 20/22 · 32) square in strong amine-like enzyme Ν performance under conditions similar to the forming and foam cells Bed The participation of aminoamylase N in lymphocytes and monocytes shows that inhibition of aminopeptidase can protect the blood vessel wall, and has a positive effect on the development of patch 15 and patch stability. The invention therefore relates to a compound having the following formula

This paper ruler does not use the middle threshold standard (C: NS) A4 specification (210 X 297 male) 200413340 A7 B7 V. Description of the invention (3) Y series contains one or more double or parameter keys as appropriate the stretch Ci-G alkyl chain wherein one or more carbon atoms based group optionally substituted with engaged, and wherein one or more carbon atoms based individual is optionally nitrogen, oxygen, or sulfur atom substitution in the Y, There must be at least one carbon atom between heteroatom and R3, and at least one carbon atom must exist between two heteroatoms in Y. R1 is halogen, trifluoromethyl, trifluoromethoxy, cyanide , nitro, amino, alkyl - amino, hydroxy, alkyl, alkoxy, carboxy, alkoxycarbonyl, aminocarbonyl, or alkylaminocarbonyl group, an alkoxycarbonyl group wherein 10 and alkylaminocarbonyl may be 〇, 1 or 2 substituents, wherein the substituents are individually selected from the group consisting of alkoxy, aryl, heteroaryl, cycloalkyl, heterocyclyl and trimethylsilyl, η is the number 0, 1, 2 or 3, 15 where if η is 2 or 3, the R1 groups may be the same or different, R2 is an alkyl group, member of the Intellectual Property Bureau of the Ministry of Economic Affairs Printed by Consumer Cooperatives where the alkyl group may be substituted with 0, 1 or 2 substituents, where the substituents are individually selected from the group consisting of i-prime, hydroxyl, alkoxy, alkoxy, carboxyl, alkoxycarbonyl, and aminocarbonyl , the group consisting of alkyl aminocarbonyl, aryl, 20 heteroaryl, cycloalkyl, heterocyclic group and heterocyclic carbonyl group, wherein the aryl, heteroaryl, cycloalkyl, and heterocyclyl may be 0, 1, 2, or 3 substituents, each of which is selected from the group consisting of halogen, trifluoromethyl, trifluoromethoxy, cyano, nitro, amine, and this paper is in accordance with the Chinese garden standard (CNS ) A4 size (210x297 male dark) 200413340 A7 B7 V. description of the invention (4) 51 015 intellectual property Office employee economic co-op 20 printed alkylamino, hydroxy, alkyl, alkoxy, carboxy, alkoxycarbonyl , an amine group, and the group proposed several burn-yl group consisting of 'R3 or an amine-based group by is, R4 is halogen-based, trifluoromethyl, trifluoromethoxy, cyano, bowls, amino, Alkyl-amino, hydroxyl, alkyl, alkoxy, carboxyl, oxycarbonyl, aminocarbonyl, or alkylaminocarbonyl 'm system Several billion, 1 or 2, wherein when m is 2 system, the R4 groups are the same or different Calls' and salts thereof which solvation of solvates and salts thereof. The compounds of the present invention are compounds of general formula (I) and their salts, solvates and salt solvates. The compounds of general formula (I) and the compounds and their salts, solvates and the compounds described in the following examples and the Salt solvates, wherein the compounds covered by the general formula (I) and described below are not salts, solvates, and solvates of the salts. The compounds of the present invention exist in stereoisomeric forms (mirror isomers, non-mirror isomers) depending on their structure. The present invention is therefore related to its isomers, and isomers and individual mixtures. The component having stereoisomeric purity can be isolated in a known manner from a mixture of enantiomers and / or non-enantiomers. The present invention also relates to the tautomers of the compound depending on the structure of the compound. Preferred compounds in the present invention are physiologically acceptable salts of the compounds of the present invention. Physiologically acceptable salts of the compounds encompassed ⑴ inorganic Suo, carboxylic acids and the acid addition salts, such as hydrochloric, hydrobromic, sulfuric, phosphoric, methanesulfonic -6- 200413340 A7 B7 V. Description of the Invention (5) Acid , Ethanesulfonic acid, toluenesulfonic acid, benzenesulfonic acid, naphthalenedicarboxylic acid, acetic acid, propionic acid, lactic acid, tartaric acid, malic acid, citric acid, fumaric acid, maleic acid and benzyl acid salts . The physiologically acceptable salts of compound (I) also cover the 5 types of salts of customary bases, such as the preferred alkali metal salts (such as sodium and potassium salts), alkaline earth metal salts (such as calcium salts and magnesium salts), and ammonia or Organic amines having 1 to 16 C atoms (e.g. preferred ethylamine, diethylamine, triethylamine, ethyldiisopropylamine, monoethanolamine, dihexanolamine, triethanolamine, dicyclohexylamine, dimethylamine Derived from methyl alcohol, procaine, diammonium amine, N-methylformal, di 10 rosinamine, spermine, lysine, ethylenediamine and methylpiperidine) Ammonium salt. A solvate in the present invention means a compound form that forms a complex in a solid state or a liquid state through coordination with a solvent molecule. Hydrate systems are specific solvate forms in which they coordinate with water. 15 In the present invention, unless otherwise stated, the substituents have the following meanings: • The printing of the alkyl group itself and in the alkoxy, alkylamino, alkylaminocarbonyl, and alkoxycarbonyl groups are performed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economy "Alkane I and" alkyl i "means straight or branched chain alkyl groups having 1 to 8 carbon atoms, usually 1 to 6 (preferably 1 to 4 and 20, especially 1 to 3) Carbon atoms, examples are methyl, ethyl, n-propyl, isopropyl, third butyl, n-pentyl, and n-hexyl. The alkylene group means a straight group containing one or more double bonds or reference bonds, as appropriate. Chain or branched chain alkylene, where one or more carbon atoms are optionally substituted with a oxy group, and one or more carbon atoms are optionally individually nitrogen and oxygen threshold of standards (CNS) A4 size (210 X 297 well-ao) 200413340 intellectual property Office employee economic co-op five printed A7 B7 described invention (6) substituted or a sulfur atom. examples which may be mentioned in the preferred alkylene methyl, ethyl stretching, stretch propyl, propoxy hospital-1,2-diyl, prop-burning -22--diyl, but-burning _13 • diyl, but- 2,4-diyl, pent heartburn, heart-diyl, 2-methyl-pentyl burning _2, heart-diyl, _ o-ch2 _, _ s_ch2_, ... · CH2_s, CIV〇CH2 ·, 4 5 CH2-CH2 *, burning -12- prop-1-oxa-diyl, but-3-oxa-4-burning _2-diyl, butane-3-thia-2,4-diyl, and was Α ο until Representative examples of preferred There are methoxy, ethoxy, n-propoxy, isopropoxy, tertiary butoxy, n-pentyloxy and n-hexyloxy. 10 groups so far have "one" or "two" The alkylamine group of the substituent (individually selected) is preferably a methylamine group, an ethylamine group, an n-propylamino group, an isopropylamino group, a third butylamino group, an n-amino group, 'n-hexylamino group, NN_di Methylamine, from diethylamino, wethyl ## methylamino, propylmethyl-n-propylamino, N-isopropyl-N-JL propylamino, N-tert-butylmethylamine N_ethyl_ 15 N-SL amine amino trans-JV-JL hexyl- 仏 ψ amine group. So far amine series represents an alkylamine carbonyl group with one or two alkyl substituents (individual choice). Good examples are methylamine carbonyl, ethylamine carbonyl, n-propylamine carbonyl, isopropylamine carbonyl, tertiary butylamine carbonyl, n-pentylamine carbonyl, and n-hexylamine. Group, ΛΓ with dimethylamine carbonyl, diethylamine carbonyl, all ethyl-ΛΓ · methylamine 20 carbonyl, # • methyl 4 n-propylamine carbonyl, qinisopropyl-ΛΓ · n-propylamine carbonyl, third butyl_ co-methylaminocarbonyl, # • ethyl - Qin n-pentyl aminocarbonyl and Qin n-hexyl _Ν-γ aminocarbonyl the preferred examples are methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, iso-propoxycarbonyl group, the Tributoxycarbonyl, n-fluorenyloxycarbonyl and n-hexyl-8- This paper standard applies the middle threshold standard (CNSH4 specification (2 丨 0 X 297mm *)

200413340 Α7

Oxycarbonyl. Here, it means that the cycloalkyl group usually has 3 to 8 (preferably 5 to 7) carbon atoms. Examples of preferred cycloalkyl groups are cyclopropyl, cyclobutyl, and cyclopentyl. , Cyclohexyl and cycloheptyl. 5 JL 棊. Means a mono- to tricyclic aromatic group usually having 6 to 14 carbon atoms; preferable examples can be mentioned phenyl, naphthyl and phenanthryl. The H group represents an aromatic monomer having usually 5 to 10 (preferably 5 to 6) ring atoms and up to 5 (preferably up to 4) heteroatoms selected from §, 0, and n. Cyclic or bicyclic groups, preferred examples are thienyl, furfuranyl, pyrrolyl, thiazolyl, humazolyl, hydradiazolyl, pyrazolyl, imidazolyl, pyridyl, pyrimidinyl, pyridyl , Pyridinyl, indolyl, and indazole are basically odorant, benzophenylthio, hydrazone, isoxazine. Turtle Blue 1 based shame having usually 4-10 (preferably to 5-8) ring atoms and with up to three (preferably at up to two) selected from N, square, s, 15 s〇, s 〇2 series of heteroatoms and / or heterocyclic monocyclic or polycyclic

Ring is preferred) heterocyclyl. The heterocyclic group may be a saturated or partially unsaturated 5- to 8-membered monocyclic saturated heterocyclic group having up to two heteroatoms selected from the 0, N, and S series, and preferred examples are such as tetrahydrofuran · 2-yl , Pyrrolidin-2-yl, printed by the consumer cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, pyrrolidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and perhydronitrogen. KenyaϋA is a heterocyclic group connected via a carbonyl group. Preferred examples include tetrahydrofuran-2 · ylcarbonyl, pyrrolidin-2-ylcarbonyl, pyrrolidin-3-ylquinyl, pyrrolinylcarbonyl, piperidinylcarbonyl, etc. Fushen carbonyl, perhydronitrogen. • 9- This paper size is subject to Chinese National Standard (CNS) A4 regulations (21 × X 297 mm) 200413340 A7 B7 V. Description of the invention (〇Electric rabbit means fluorine, gas, bromine and moth, and fluorine and gas are used If a group in a compound of the present invention is substituted, the group (unless otherwise stated) may have one or more identical or different substituents. Up to three identical or different substituents may be used. Substitution is preferred. Substitution by a substituent of 5 is particularly preferred. In another specific example, the present invention relates to a compound of general formula ⑴ wherein Y is Ci-Ce containing one or more double or reference bonds, as appropriate. stretch alkyl chain, wherein one or more carbon atoms based group optionally substituted with engaged, and 10 wherein one or more carbon atoms are substituted individually based optionally nitrogen, oxygen, or sulfur atoms, the hetero atom in Y, and R3 is necessary there between at least one carbon atom, and Y is between the two hetero atoms at least one of carbon atoms required there, Rl tooth-based pigment, a trifluoromethyl group, a trifluoromethoxy group, a nitrogen group, a nitro group , 15 amino, _ alkyl group, hydroxy, alkyl, alkoxy, carboxy, alkoxycarbonyl, Aminocarbonyl or alkylaminocarbonyl, η is a number of 0, 1, 2 or 3, where if η is 2 or 3, the R1 groups may be the same or different R2 is an alkyl group, 20 wherein the alkyl group may be substituted by 0, 1 or 2 substituents, wherein the substituents are individually selected from the group consisting of sulfanil, hydroxyl, alkoxy, carboxyl, alkoxycarbonyl, and aminocarbonyl. , Alkylaminocarbonyl, aryl, heteroaryl, cycloalkyl, and heterocyclyl groups, where aryl, heteroaryl, cycloalkyl, and heterocyclyl can pass 0, 1, 2 -10 - this applies China national standard paper scale (CNS) A4 size (210 X 297 mm) 200413340 A7 B7 V. invention is described in (9) or three substituents, wherein the substituents are individually selected from the group consisting of _ hormone, trifluoromethyl A group of methyl, trifluoromethoxy, cyano, nitro, amine, alkylamino, hydroxyl, alkyl, alkoxy, carboxyl, oxyalkyl, aminocarbonyl and alkylaminocarbonyl groups , 5 R3 is hydroxy or amine-based, R4 is i-based pigment, trifluoromethyl, trifluoromethoxy, cyano, nitro, amino, alkyl - amino, hydroxy, Group, alkoxy group, carboxyl group, alkoxy group, amine group or amine group, and 10 m is a number of 0, 1, or 2, wherein if m is 2, the R4 groups may be the same or similar In another specific example, the present invention relates to a compound of the general formula ⑴ wherein Y is -0_ch2c (= o)-or -o- (ch2) 2c (= o)-, 15 wherein γ is via oxygen Connected to dibenzoxanthine ring, R is _ prime, dimethyl, gas, amine, meridian, oxo, carboxyl, alkoxycarbonyl, aminocarbonyl or alkylaminocarbonyl, economic Printed by the Ministry of Intellectual Property Bureau, Shelley Consumer Cooperative, where the alkoxycarbonyl group may be substituted with 0 or 1 substituent, wherein the substituent is selected from the group consisting of alkoxy, aryl, cycloalkyl and trimethylmethyl 20 In the group formed, η is a number of 1 or 2, where if η is 2, the R1 groups may be the same or different, and R2 is a alkynyl group, where the aryl group may be substituted by 0 or 1 substituent, Where the substitution

200413340 Α7

V. Description of the invention (10) The group is selected from the group consisting of hydroxyl, alkoxy, carboxyl, alkoxycarbonyl, aryl and heteroaryl, wherein aryl and heteroaryl can be passed through G, b2 or 3 Substituted by a substituent, wherein the substituent is ㈣ selected from the group consisting of i-prime, amine, amine 5 group, meridian group, fluorene, thiol 1 group, thiol group, amine group, and alkylaminocarbonyl group. In group, R3 is the warp basis, and m is the number 0. 10 In the example of the ship, the present invention is related to a compound of general formula ⑴ in which Y is -o-ch2c (= o)-, wherein Y is connected to dibenzyloxynitrogen ring via oxygen, and R1 is _ prime , Amine, hydroxyl, alkoxy, carboxyl, alkoxycarbonyl, aminecarbonyl or alkylaminocarbonyl, η is a number of 0, 1, or 2, where if η is 2, the R1 group may be the same or Differently, R2 is an alkyl group, which is printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. The alkyl group may be substituted by 0 or 1 substituent, and the substituted 20 group is selected from the group consisting of hydroxyl, alkoxy, carboxy, and alkane A group consisting of oxycarbonyl, aryl, and heteroaryl, wherein aryl and heteroaryl may be substituted with 0, 1, 2 or 3 substituents, wherein the substituents are individually selected from halogen, amine, alkylamino, hydroxy, alkyl, alkoxy, carboxy, alkoxycarbonyl, carbonyl amine present paper -12- applies the Chinese national standard scale (CNS) A4 eligible regulations (210 X 297 well «) 200413340 A7

Fifth, the invention is described in group (a carbonyl group, and an alkoxy group composed of 'R3 is a hydroxyl group-based, and the number-based 0.5 m another example, (the I) For a compound of the general formula wherein Y system of the present invention is -0-CH2C (= 0)-, where Y is ortho to the amine group 1 of dibenzoxanthine via oxygen, 10 R1 is fluorine, gas, stream, trifluoromethyl, cyanide Radical, methoxy, methoxy or ethoxycarbonyl,

Wherein methoxycarbonyl and ethoxycarbonyl may be substituted by 0 or 1 substituent, wherein the substituent is selected from the group consisting of methoxy, phenyl, ring and trimethylsilyl, A 15 η The number is 1, and R2 is an alkyl group. It is printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. The alkyl group may be substituted by 1 substituent. The substituent is selected from the group consisting of hydroxyl, third butoxy, and third but In the group consisting of oxycarbonyl and 2,2-dimethylprop-1-oxycarbonyl, 20 R3 is a warp group, and m is a number of zero. A preferred compound of the general formula (I) of the present invention is wherein Y is -0-CH2C (= 0)-'where Y is connected to dibenzo-13 via oxygen. 13- CNS) A4 size (297 2 Shu 〇X well slime) 200413340 A7 B7 V. invention is described in (12) call oxynitride ring, R3 is a hydroxyl group-based, and R1, R2, R4, m and η lines are as defined above. The preferred compound is the invention of formula (I) in which 5 Υ line is -0-CH2C (= 0) -, wherein the oxygen is connected via a line to Upsilon dibenzo oxynitride call acyl amine functional group of the ring ortho, R3 is a hydroxyl group-based, and R1, R2, R4, m and η lines as defined hereinbefore. Preferred compounds of the general formula (I) of the present invention are those in which 10 R1 is an alkoxycarbonyl group, and R2 to R4, fluorene, m, and η are as defined above. Preferred compounds of the general formula (I) of the present invention are those in which R1 is trifluoromethyl, cyano, carboxyl or methoxycarbonyl, and R2 to R4, Y, m and η are as defined above. 15 Preferred compounds of the general formula (I) of the present invention are those in which R1 is trifluoromethyl or cyano, and R2 to R4, Y, m and η are as defined above. Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs

Compound. 4 I I I I I I I custom window face I I I of the present invention is preferably of the formula (I) wherein η also based number 1, 20 and R1 to R4, Υ-based and m are as defined hereinbefore. Preferably, the compound of the general formula (I) of the present invention also has R2 as an alkyl group, wherein the alkyl group may be substituted by a substituent, wherein the substituent is selected from the group consisting of a carboxyl group and an alkoxycarbonyl group, -14 -Wood paper ruler / 5 oil use SS furniture standard (CNS) A4 specification (2 丨 〇 X 297 mm) 200413340 A7 B7 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 5. Description of invention (13) and R1 R3, R4, Y, m and η are as defined above. Preferred compounds of the general formula (I) of the present invention are those wherein R2 is a third butoxycarbonylmethyl group, and R1, R3, R4, fluorene, m and η are as defined above. 5 Preferred compounds of the general formula (I) of the present invention are also those in which m is a number of 0, that is, the R4 substituent is absent, and R1 to R3, Y and η are as defined above. The present invention further relates to a method for preparing a compound of formula ⑴, wherein the 10 [[alpha]] with a compound of formula 1 15 20 pair of public

, R3 0 (Π), where R1, R3, R4, Y, m, and η have the aforementioned meaning and react with a compound having the formula R ^ X1 (III) where R2 has the aforementioned definition, and X1 is a halogen, and Gas or bromine is better, or [B] Compound with the following formula 15- This paper ruler / 5 is suitable for "China National Standard (CNS) A4 Specification (2 丨 0 X 297 mm)"; i oh IIIIII stupid I Order IIIII and II line III! 200413340 A7 B7 V. Description of the invention (14)

Among them, R1, R2, R4, m and η have the meanings shown above, and react with the compound of the following formula 1 R3 ^ " A, X2 (V) printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs, where R3 has the foregoing In the meaning shown, 15 X2 is halogen, preferably gas or bromine, and A is CVCV alkane chain of Y, which has been shortened by heavy atoms and optionally contains one or more double or reference bonds, one of which Or more than one carbon atom is optionally substituted with a oxy group, and one or more of them are individually replaced by nitrogen, oxygen or sulfur atoms, and at least one carbon must exist between the hetero atom 20 and R3 of A atoms, but there is necessary to break at least one atom, to produce a compound of the formula -16- present sheet having the proper dimensions and W Bin national standards (CNS) A4 eligible Regulation (2Uix297 mm) set in the line between the two hetero atoms a 200413340 Α7 B7 V. Description of the invention (15) 5

da), where R to R, A, m and η have the meanings shown above. The compounds of the general formula (la) are rarely compounds of the general formula VII where γ is equal. The reaction carried out by the method [A] and the method [B] is usually performed in an inert solvent in the presence of a base 10, and potassium iodide is optionally stored, and is performed at a temperature ranging from room temperature to 50 C under atmospheric pressure. Better. Examples of ordering are testing metal hydroxides, such as sodium hydroxide, lithium hydroxide, or potassium hydroxide, or osmium metal phosphonates, such as cesium carbonate, sodium carbonate, or potassium carbonate, using an aqueous solution as appropriate, and potassium carbonate as good. Line 15 Examples of inert solvents are ethers, such as 1,2-dimethoxyethane, dioxane, tetrahydrofuran, glycol dimethyl ether, or di (ethylene glycol) printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. ) Dimethyl ether, alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol or tertiary butanol, or dimethylformamide, or a mixture of solvents, and dimethylformamidine Amine or dioxane is preferred. 2 The groups R1, R2 and R3 in the compound of the general formula (I) may optionally contain a protective group, which is removed by a deprotection reaction after the reaction. This is done by standard methods of protective chemistry. Compounds of the general formulae (III) and (V) are known or can be synthesized from suitable precursors by known methods. -17- The size of this paper applies the Chinese National Standard (CNS) A4 (210x297 mm) 200413340 A7 B7 V. Description of the invention (16) The compound of general formula (II) is known, or a compound of the following formula can be used

(VI), \ 5 5 where 1 ^, 113, 114, y, 111, and 11 have the meanings described above, and R5 is an alkyl group, preferably methyl or ethyl, and 10 is an acidic organic catalyst Prepared by reaction. The reaction is usually carried out in an inert solvent, and it is preferably carried out at a temperature ranging from 50 ° C to the reflux of the solvent under atmospheric pressure. Examples of the acidic organic catalyst are p-toluenesulfonic acid, methanesulfonic acid, trifluoroacetic acid or camphorsulfonic acid, and p-toluenesulfonic acid is preferred. 15 Examples of inert solvents are ethers such as dioxane, glycol dimethyl ether or bis (ethylene glycol) dimethyl ether, hydrocarbons such as benzene, xylene, toluene or petroleum fractions, xylene or Toluene is preferred. Based compound formula (VI) or by the known compound of the formula Economy Intellectual Property Office employee printed consumer cooperatives 20

(RX

-18- The size of this paper applies to China National Standard (CNS) A4 (210 X 297 mm) 200413340 A7 B7 V. Description of the invention (17) where R1, R3, R4, R5, Y, m and η have In the meaning shown above, it is prepared by reacting with a reducing agent. The reaction is usually carried out in an inert solvent, preferably at a temperature ranging from room temperature to the reflux of the solvent at atmospheric pressure to 3 bar. 5 Examples of reducing agents are palladium on carbon in a hydrogen atmosphere, palladium on carbon in the presence of ammonium formate, iron in concentrated acetic acid, iron / gasified iron (III), tin (II) gasified or hydrochloric acid Of the tin, gasified tin (II) is preferred. Examples of inert solvents are ethers such as diethyl ether, methyl tert-butyl ether, 1,2 · dimethoxyethane, dioxane, tetrahydrofuran, diol dimethyl 10 ether, or bis (ethylene glycol) ) Dimethyl ethers, alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol or tertiary butanol, or mixtures of alcohols and water, hydrocarbons such as benzene, xylene, toluene, Alkane, cyclohexane or petroleum distillates, or other solvents such as dimethylformamide, dimethylacetamide, acetonitrile, ethyl acetate or pyridine. 15 In the case of palladium on carbon, ethanol, methanol, isopropanol, tetrahydrofuran or a mixture of ethyl acetate and ethanol is preferred, and in the case of iron / gasified iron (III), a mixture of water and ethanol is preferred In the case of vaporized tin (II), dimethylformamide, dioxane or methanol is preferred. Employees of the Intellectual Property Bureau of the Ministry of Economic Affairs, Consumer Cooperatives, Compounds of general formula (VII) are known or can be synthesized from known precursors by appropriate methods. The compound of the general formula (IV) is known or can be borrowed by the compound of the following formula: 19- This paper ruler is applicable to the specification of S. chinensis (CNS) A4 (2 丨 〇χ 297 公 鼙) 200413340 Α7 Β7 V. Description of the invention ( 18)

, (R) m (Rl) n ^ V. v ι〇Η y (vm), ο wherein R1, R4, m, and n have the meanings shown above and the compound of the following formula 10 -X3 (K), wherein R3 has the meaning shown above, and X3 is halogen, Gas or bromine is preferred, and 15 is prepared by reacting with one equivalent of a compound of general formula (IX). This reaction is carried out under the reaction conditions described in the methods [A] and [B]. Compounds of general formula (IX) are known or can be synthesized from suitable precursors by known methods. Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. Compounds of general formula (VIII) are known or can be borrowed. 20

-20- (X), not the paper size wooden house À À quasi lattice (CNS) A4 size (210x297 well slime) 200413340 A7 B7 V. invention is described in (19) wherein R ^ R4 applicable ,! ! 1 and η have the meanings indicated above 'and are prepared by reacting with a weak acid. The reaction is carried out under the reaction conditions described for the compound of the general formula (II). The compound of the general formula (X) is known or can be obtained by the compound of the formula 5

(XI), 15 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 10 where R1, R4, m and η have the meanings shown above 'and are prepared by reacting with a reducing agent. The reaction system for the reaction conditions a compound of formula (VI) described for the. Compounds of general formula (XI) are known or can be synthesized from known prior vehicles by known methods. In another method, the compound of formula (IV)

(ΧΠ), where R1, R2, R4, m, and η have the meanings indicated above. -21 · National Standard (CNS) A4 Specification (210 X 297 cm) for this paper size. 200413340 Α7 Β7 Five 2. Description of the invention (20) It is prepared by reacting with a reducing agent, preferably in a hydrogen atmosphere in ethanol, methanol isopropanol or tetrahydrofuran, at a temperature ranging from room temperature to the reflux temperature of the solvent at atmospheric pressure to 3 bar, using carbon. The reaction was performed on palladium. Compounds of general formula (XII) are known or can be borrowed from compounds of formula 5 10

〇 (xm), wherein R1, R4, m and η have the meanings shown above, and are prepared by reacting with a compound of the general formula (III) under the reaction conditions described in the method [A]. Compounds of general formula (XIII) are known or can be borrowed from compounds of formula 15

(XIV), printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs20 where η has the meaning shown above, and R6 is an alkyl group, preferably methyl or ethyl, for compounds of general formula (II) It is prepared by carrying out a reaction under the reaction conditions. -22- national standard threshold in this paper (CNS) A4 size ί 2 Shu 0 X 297 mm scale applicable) 200413340 A7 B7 Ministry of Economic Affairs Intellectual Property Office employees consumer cooperatives print run of five invention is described in (21) 5 of the general formula (XIV ) Compounds are known or can be obtained by

Among them, Chi 1, Hua 4, 6, 111, and 11 have the meanings shown above, and are prepared by reacting under the reaction conditions described for the compound of the general formula (VI). Compounds of the general formula (XV) are known or can be prepared by known methods from suitable precursors. When R2 is a third butoxycarbonylmethyl group, the reaction can be carried out by the following alternative method: 15!) A compound of the general formula (VIII) and two equivalents of third butyl bromoacetate are described in method [A] The reaction was performed under the reaction conditions (Comparative Example 55A). 2) Selectively eliminate the third butyl group on _Y_R3 by reacting it with trimethylsilyl silane and sodium iodide in three-gas methylbenzene. The preparation of the compounds of the present invention can be illustrated by the following synthetic scheme: -23- 4 Order 200413340 A7 B7 V. Description of the invention (22 scheme

h3 4 Order Ministry of Economic Affairs Intellectual Property Office employees consumer cooperatives printed

H3C

Line - · _ wood paper size is not handed Shu 3 Threshold family standard Falcon (CNS) A4 size (21CU297 public curly) 200413340 A7B7

Wooden paper ruler / 5 Applicable to China National Min Family Standard (CNS) A4 specification (210 x 297 g t) 200413340 A7 B7 V. Description of the invention (24) The present invention also relates to a kind of disease prevention and treatment (especially cardiovascular disease, such as Atherosclerosis) compounds of general formula ⑴, and related medicines containing compounds of general formula (I) and excipients, and related compounds of general formula ⑴ are used for the manufacture of cardiovascular disease (especially atherosclerosis) 5 applications of medicine. It can be used for the prevention and treatment of cardiovascular diseases (such as, for example, atherosclerosis, reperfusion tissue damage after stroke, myocardial infarction or terminal vascular occlusion) or inflammatory diseases and autoimmune diseases (such as, for example, arthritis, rheumatic joints) Inflammation, osteoporosis, Crohn's disease, chronic 10 inflammatory lung diseases such as adult dyspnea, ards, transplant rejection, chronic inflammatory fibrosis of organs, such as liver fibrosis, or systemic autoimmunity Diseases Systemic lupus erythematosus or other forms of lupus erythematosus or epidermal inflammatory diseases such as psoriasis or cancer (such as, for example, lung and prostate cancer) or chronic pain. 15 The active ingredient can act systemically and / or locally. In this regard, it may be administered in a manner suitable, such as, for example, by oral, parenteral, pulmonary, nasal, sublingual, translingual, buccal, rectal, transdermal, transmembrane, or transauricular Dosing by route, or as an implant. Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs This active ingredient can be administered in a dosage form suitable for these routes. Suitable for oral administration are known forms of administration which deliver the active ingredient quickly and / or in a modified form, such as, for example, (uncoated or coated keys such as keys with enteric coatings or membrane coatings) ), Capsules, sugar suspicions, granules, pellets, powders, emulsions, suspensions and -26- 200413340 A7 B7 Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 5. Description of invention (25) Parenteral administration can avoid the absorption step (Intravenous, intraarterial, intracardiac, spinal or lumbar) or including absorption (intramuscular, subcutaneous, intradermal, percutaneous or intraperitoneal). Suitable forms for parenteral administration include solutions, suspensions, emulsions, cold-dried products, and sterile powder 5 injection and infusion preparations. Oral administration is preferred. Suitable for other routes of administration are, for example, inhalation (including powder inhalers, sprayers), nasal drops / solutions, sprays; spinals or capsules for suppository, sublingual or buccal administration, suppositories, ears And eye preparations, vaginal 10 capsules, aqueous suspensions (lotions, shaking mixtures), lipophilic suspensions, ointments, creams, emulsions, powders, or implants for administration. The active ingredient can be converted into the stated administration form in a known manner. This is an inert, non-toxic, pharmaceutically acceptable excipient. Inter alia, carriers (for example microcrystalline cellulose), solvents (e.g. liquid polyethylene glycols Li), 15 emulsifiers (e.g. sodium dodecyl sulphate), dispersing agents (e.g. polyvinylpyrrolidone wide synthetic and natural biopolymers ( for example albumin), stabilizers (e.g. antioxidants such as ascorbic acid), colorants (e.g. inorganic pigments such as iron oxides) or masking the taste and / or odor. In case of a generally well-parenteral administration preferably administered every 24 hours based about 5 to 2050 mg / kg body weight 'to achieve the effect. Oral administration is about 5 to 100 mg / kg body weight every 24 hours. _ But it may be necessary to deviate from the stated dosage, especially depending on body weight, administration Depending on the route, the individual response to the active ingredient, the formulation mode, and the time or interval of administration. 4; η 4 ·:

200413340 Α7 Β7 V. Description of the invention (26 The percentage data in the tests and examples below are percentages by weight, unless otherwise stated; parts are parts by weight. Solvent ratio, dilution ratio and concentration data of liquid / liquid solution are each By volume. The statement "w / v" means "weight / volume". Therefore, for example, "10% w / v" means 100 ml of a solution or suspension containing 10 grams of substance. A) Example economy Printed by the Ministry of Intellectual Property Bureau's Consumer Cooperative

Reduction: Boc BSA 10 CDC13 cone. C02 DIEA DMAP third butoxycarbonyl base medium deuterium gas imitation concentrated carbon dioxide diisopropylethylamine 4-fandidimethylaminopyridine 15 20 DMF dimethylformamide DMSO di methylsulfinyl Sa EDCI dimethylaminopropyl ethylcarbodiimide stuffed imide X HC1 eq. ESI electrospray ionization (MS medium) h hour HATU square · hexafluorophosphate (7-aza-benzotriazole 1-yl) _ tetramethyluronium Qiang HPLC High pressure, high performance liquid chromatography 28 · 4 η 4 applies the present Chinese national standard paper size (CNS) A4 size (21ϋχ297 mm) 200413340 A7 B7 V. invention is described in (27 ) LC-MS coupled with liquid chromatography / mass spectrometry min minutes MPLC medium pressure liquid chromatography MS mass spectrometry 5 MW molecular weight [g / mole] NMR nuclear magnetic resonance spectrum Pd / C palladium / carbon Rf retention index (TLC) RP reverse phase 10 RP HPLC reverse phase HPLC RT room temperature Rt retention time (HPLC) sat. Saturated TFA trifluoroacetic acid 15 THF tetrahydrofuran Tris tris (hydroxymethyl) methylamine Tris-HCl tris (hydroxymethyl) methylamine HPLC and LC_MS method : Printing Method for Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs (HP LC): column C18, 2.1 x 150 mm, temperature 50 20 ° C, eluent A: acetonitrile, eluate B: 0.1% hydrochloric acid in water, gradient: 0 to 3 minutes A: B = 10: 90, flow rate 0.9 Ml / min; 3 to 6 minutes A: B = 90: 10, flow rate 1.2 ml / min. Method 2 (LC_MS): Equipment: Micromass Platform LCZ with HPLC Agilent 1100 series; Column: Grom-SIL120 ODS- jg- This paper standard is applicable to Chinese National Standard (CNS > A4 specification (210 \ 297 public «) — 200413340 A7 B7 V. invention is described (2〇4 HE, 50 mm χ2 · 0 mm, 3 [mu] m; eluting was a: 1 liter of water + 1 ml of 50% strength formic acid, eluting material B: 1 liter of acetonitrile + 1 ml of 50% strength formic acid ; Gradient: 0 · 0 minutes 100% A- > 0 · 2 minutes 100% A-2 · 9 minutes 30% A ~ > 3 · 1 minutes 10% A-^ 4 · 5 minutes 10% A; furnace: 5 55 ° C; flow rate: 2.8 square mL / min; UV detection: 208-400 nm method 3 (LC_MS): device: HPLC Agilent 1100 series having a Micromass Platform LCZ; column: Grom-SIL120 ODS-4 HE, 50 mm χ2 · 0 mm, 3 [mu] m; eluting material A: 1 liter of water 10 + 1 ml of 50% strength formic acid, eluting material B: 1 liter of acetonitrile + 1 ml of 50% strength formic acid; gradient: 0.0 minutes 100% A-0.2 min 100% A ~ > 2.9 min 30% Α-3 · 1 min 10% Α · ~ > 4 · 5 min 10% A; slope: 55 ° C; flow rate: 0.8 ml / min; UV detection 208 to 400 nanometers. 15 Method 4 (LC-MS >: Equipment: HPLC Micromass Quattro LCZ printed by Employee Consumer Cooperative of Agilent 1100 Department of Intellectual Property Bureau of the Ministry of Economic Affairs; column: Grom-SIL120 ODS-4 HE, 50 mm χ2 · 0 mm, 3 [mu] m; eluting material A: 1 liter of water + 1 ml of 50% strength formic acid, was eluting B ·· 1 liter of acetonitrile + 1 ml of 50% strength formic acid; gradient: billion billion · min 100ο / 〇Α -0.2 min 100% Α- > 2 · 9 20 min 30% Α-3 · 1 min 10% Α-4.5 min 10% Α; furnace ·· 55 ° C; flow rate of 0.8 ml · / min; UV detection : 208 to 400 nanometers. Method 5 (LC-MS): MS equipment type · Micromass ZQ; HPLC device type: Waters Alliance 2790; Column: Grom_Sil -30- This paper standard applies to Chinese National Standards (CNS > A4 specifications) (210x297 mm) 200413340 A7 B7 V. Description of the invention (29) 120 ODS-4 HE, 50x2 mm, 3.0 microns; Dissolve A: water +500 microliters 50% strength formic acid / liter, dissolve B: acetonitrile +500 [mu] l of 50% strength formic acid / l; gradient · 0.0 minutes 0% B ^ min square 〇.2% A- 2 · 9 minutes 80% B-3.1 min 90% B 4.5 minutes 90% B; oven: 45 5 ° C; flow rate: 0.8 ml / min; 210 nm UV detection ··. Method 6 (LC-MS): MS equipment type: Micromass ZQ; HPLC device type · HP 1100 series; column: Grom-Sil 120 ODS-4 HE, 50x2 mm, 3.0 micron; eluate A: water + 500 micron l of 50% strength formic acid / liter, eluting B ·· acetonitrile was +500 10 microliters of 50% strength acid Yue / liter; gradient: 0 · 0 minutes 70% B-4.5 minutes 90% B; oven: 50 ° C; Flow rate: 0.8 ml / min; UV detection: 210 nm. Print Method 7 (LC-MS) of Consumer Cooperatives of Intellectual Property Bureau of the Ministry of Economic Affairs: MS Equipment Type: Micromass ZQ; HPLC Device Type: HP 1100 Series; UV DAD; Column: Grom-15 Sil 120 ODS-4 HE, 50x2 mm, 3.0 [mu] m; eluting was A: water + 500 [mu] l of 50% strength formic acid / liter, eluting were B: acetonitrile + 500 [mu] l of 50% strength formic acid / liter; gradient: min square 〇.〇 min 70% B-2.9 % B—3 · 1 minute 90% B—4.5 minute 90% B; furnace: 50 ° C; flow rate: 0.8ml / min; ultraviolet detection · 210nm. 20 Method 8 (HPLC): Apparatus: DAD detector having the HP 1100; column: Kromasil RP-18,60 mm χ2 mm, 3.5 [mu] m; eluting material A: 5 mL HCKV liters of water, eluting Beta was: acetonitrile ; Gradient: 2% B for 0 minutes, 2% B for 0.5 minutes, 90% B for 4.5 minutes, 90% B for 6.5 minutes; Flow rate: 0.75 ml / min; Temperature · 30 ° C; UV detection -31- The size of this paper applies to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 200413340 A7 B7 V. Description of the invention (30) Measurement: 210 nm. Method 9 (HPLC equipment: HP 1100 with DAD detection; column: Kromasil RP-18, 60 mm X 2 mm, 3.5 microns; eluate A: 5 ml HCKV liters of water, eluate B: acetonitrile; Gradient: 0% 2% B, 0.5 minute 2% B, 4.5 minutes 90% B, 9 minutes 90% B; flow rate: 0.75 ml / min; temperature: 30 ° C; UV detection: 210 nm. Method 10 (LC-MS): MS apparatus type: Micromass ZQ; HPLC apparatus type: Waters Alliance 2795; column ·· Merck 10 Chromolith SpeedROD RP-18e, 50x4.6 mm; eluting was A: water + 500 [mu] l of 50% strength Formic acid / liter, eluate b ·· acetonitrile + 500 microliters of 50% strength formic acid / liter; gradient: 0.00min. 0min. 95.0 / 4.0B-4.0min. 95% B; furnace: 35 ° C; flow rate: 〇 . h〇 square min ml / min - 1.9 min 3.0 ml / min ~4.0 min 3.0 ml / min for 15 clock; UV detection: 210 nm method 11 (preparation HPLC): column material: YMC GEL ODS AQ S 5 / 15 micron; mobile phase: acetonitrile / water gradient 10: 90 > 90: 10. Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs

20 Starting compound f Example 1A 4-[(2,2-Dimethyl · 4-Hydoxy-4H-1,3-benzodioxane_5_yl) oxy] _3_nitro A vinegar -32- bitterness of this paper scale applicable Chinese national standard mound (CNS) A4 size (210x297 mm) - 200413340 Α7 Β7 V. invention is described in (31)

7.59 grams (35.2 millimoles) of methyl 4-gas-3-nitrobenzate and 6.84 grams (35.2 millimoles) of 5 · hydroxy_2,2_dimethyl-4Η-1,3-benzene and dioxane-4-one (see A. Hadfield, etc., Synth · Commun. 1994,24,1025) 10 in dimethylformamide in the solution was mixed with 5.35 g (38.8 mmol) of potassium carbonate mixture, Stir at 70 ° C for 8 hours. The mixture was poured into 400 ml of ice and 250 ml of ethyl acetate. The organic phase was extracted with 150 ml each of water and a saturated sodium gas solution. The organic phase was dried over magnesium sulfate, and then the solvent was removed under reduced pressure. The residue was silica gel column (cyclohexane: ethyl acetate 2: 1) 15 gave the 11.3 g (86% of theory) of product. MS (DCI): m / z = 391 (M + NH4) + printed by the Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs ^ -NMR (200 MHz, DMSO-d6): (5 = 1.67 (s, 9H), 3 · 88 (s, 3H), 7,04-7.1 (m, 3H), 7.81 (dd, 1H), 8.11 (dd, 20 1H), 8. 54 (d, 1H).

Example 2A 3- amino-4 - [(2,2-dimethyl-4-yloxy engagement -4H-1,3- benzo-dioxin 5--33- present paper size suitable order Wen Threshold Home Standard (CNS) A4 specification (210x297 male «) 200413340 A7 B7 V. Description of the invention (32) yl) oxy] methyl benzate

Economic Intellectual Property Office employee consumer cooperative printed 10.9 g (29.1 mmol) of the compound from Example 1A in the embodiment 116 ml of concentrated acetic acid (204 mmol) iron mixed and 6 ml of water and 11.4 g, 10 to 50 ° Stir at C for 3 hours. The mixture was poured into 580 ml of acetone and the solid was filtered off. The filtrate was purified on a silica gel column (digas methane: ethyl acetate 100: 5) to give 9.93 g (95% of theory) of the product. MS (DCI): m / z = 361 (M + NH4) + 15 h-NMR (300 MHz, DMSO-d6):. 5 = 1 · 71 (s, 9H), 3 · 81 (s, 3H), . 5.31 (s, 2H), 6.53 (d, 1H), 6.85 (dd, 2H), 7.16 (dd, 1H), 7.46 (d, 1H), 7.56 (dd, 1H) Example 3A 20 1 · hydroxy - 11_Hydroxy-1,10, ll-dihydrodibenzo [b, f] [l, 4] oxazepine-8-formic acid methyl ester-34- The paper size is applicable to the national threshold standard (CNS ) A4 size (210x297 well ») 200413340 A7 B7 prescribed line V. invention is described in (33)

The Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs printed 9.87 g (28.8 mmol) of the compound of Example 2A in 140 ml of xylene, mixed with 0.55 mg (2.9 mmol) of p-toluenesulfonic acid, and stirred under reflux. Overnight. Crystallized separated was washed with methanol, to produce 9.96 g (84% of theory processor 10 value) of product. MS (ESI):. M / z = 286 (M + H) + iH-NMR (300 MHz, DMSO-d6): 5 = 3 · 85 (s, 3H), 6,80-6.90 (m, 2H) , 7.45-7.54 (m, 2H), 7.77 (dd, 15 1H), 7.84 (d, 1H).

Example 4A 10 (2-Third-butoxy-2-synoxyethyl) -1-hydroxy-11-synthoxy-10,11-dihydrodibenzo [b, f] [l, 4] Oxynitrogen-8-methyl formate-35- This paper is in accordance with China National Standard (CNS) A4 (210 X 297 mm) 200413340 A7 B7 V. Description of the invention (34)

300 mg (1.05 mmol) of the compound of Example 3A in 3 ml of dimethylformamide with 205 mg (1.05 mmol) of tert-butyl bromoacetate and 145 mg (1.05 mmol) potassium carbonate was mixed and stirred overnight at room temperature. 10 The mixture was poured into 20 ml of water and 20 ml of ethyl acetate. The organic phase was extracted with 20 ml of water and saturated sodium gas solution. The organic phase was dried over magnesium sulfate. The solvent was removed under reduced pressure to give a residue, which was purified (ii methane gas) on silica column to produce 213 mg (51% of theory) of product. 15 MS (ESI): m / z = 422 (M + Na) +.] H-NMR (300 MHz, DMSO-d6): 1.44 (s, 9H), 3.85 (s, 3H), 4.70 (s, 2H), 6 · 82 (d, 1H), 6.90 (d, 1H), 7 · 43 (dd, lH), 7.53 (d, 1H), 7 · 85 (d, lH), 7.91 (s , LH), 10 · 44 (s, lH) · 20

Example 5A 1- (2 · Third-butoxy-2-synoxyethoxy) -10- (2-Third-butoxy-2-synoxyethyl) _11_Hydroxy tomb-10, 11-Dihydrodibenzo [b, f] [l, 4] oxazepine-8-methyl formate-36- This paper is sized to the Chinese National Standard (CNS) A4 (2⑴X 297 mm) 200413340 A7 B7 V. Description of Invention (35)

ch3 Printed 95 mg (0.24 mmol) of Example 4A compound in 3 ml of dimethylformamide with 46 mg (0.24 mmol) of tert-butyl bromoacetate and 49 Mix 10 mg (0.35 mmol) potassium carbonate and stir overnight at room temperature. The mixture was poured into 20 ml of water and 20 ml of ethyl acetate. The organic phase was extracted with 20 ml of water and saturated sodium gas solution. The organic phase was dried over magnesium sulfate. Removal of the solvent under reduced pressure gave 0.12 g (99% of theory) of product. 15 MS (DCI): m / z = 531 (M + NH4) + ^ -NMR (200 MHz, DMSO-d6):.. Δ = L 34 (s, 9H), 1 39 (s, 9H), 3 · 84 (s, 3H), 4 · 64-4 · 72 (m, 4H), 6 · 82 (d, 1H), 7 · 01 (d, lH), 7 · 40-7 · 54 (m, 2H ), 7.81 (dd, lH), 7.96 (d, 1H). 20

Example 6A (R, S) -1 (H2-Third-butoxy-1-fluorenyl-2-hexyloxyethyl) -1-hydroxy-11-hexyloxy-10,11-diargon diphenyl and [1), £] [1,4] -37- 8-carboxylate call oxynitride of the present paper is suitable China national standard scale (CNS) A4 size (210 X 297 mm) 200413340 A7 B7 V. invention described (36)

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs as in Example 4A, from 400 mg (1.4 mmol) of the compound of Example 3A and 293 mg (1.4 mmol) of (R, S) -bromopropionic acid tert-butyl ester Perform 10 preparations. Purification on a silica gel column (ethyl acetate: cyclohexane 5: 1) yielded 37 mg (7% of theory) of the product. LC-MS (Method 2): Rt = 4.2 minutes MS (ESI): m / z = 436 (M + Na) + 15

Example 7A (R, S) -l- [2- (Benzyloxy) -2-hexyloxyethoxy) -10- (third butoxy-1-methyl-2-hexyloxyethyl ) -11_Hydroxy_10,11_difluorene dibenzo [b, f] [l, 4] oxazepine-8-formic acid methyl ester-38- This paper size applies to Chinese National Standard (CNS) A4 specifications (210x297 mm) 200413340 A7 B7 V. Description of invention (π

5 37 mg (0.089 mmol) of the compound of Example 6A was dissolved in 1 ml of DMF with 18.5 mg (0.13 mmol) of potassium carbonate and 20.5 mg of 10 (0.089 mmol) benzyl bromoacetate. The mixture was stirred at room temperature for 4 hours, and after adding 5 ml of water, it was extracted with ethyl acetate. The combined organic phases were dried over magnesium sulfate and concentrated in vacuo. To give 18 mg (36% of theory) of product which was reacted without purification. 15 Example 8A 1- [2- (Ethyloxy) -2-hexyloxyethoxy] -10- (2-third butoxy-2-hexyloxyethyl) -11-hexyl- l〇, ll-dihydrodibenzo [b, f] [l, 4] oxazepine-8-methyl formate Printed by the Employees ’Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs 20

H3CT

-39 · This paper size applies the Chinese National Standard iCNS) A4 specification (210 X 297 mm) 200413340 A7 B7 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 5. Description of the invention (38) According to the method of Example 7A from 2 g (5.0 mmol) of Example 4A compound and 1.15 g (5.0 mmol) of benzyl bromoacetate embodiment prepared. Purification by chromatography on a silica gel column (digas methane: methanol 1: 0 to 3: 1) yielded 2.47 5 g (90% of theory) of the product. LC-MS (Method 3): Rt = 4.22 minutes MS (ESI): m / z = 548 (M + H) +. ^ -NMR (300 MHz, DMSO-d6): δ = L 38 (s, 9H) , 3 · 81 10 (s, 3H), 4.68 (d, 2H), 4.90 (d, 2H), 5.15 (s, 2H), 6.88 (d, lH), 7.03 (d, 1H), 7 · 30 ( s, 5H), 7 · 45 (dd, lH), 7.52 (d, lH), 7.82 (d, lH), 7.95 (s, lH).

f Example 9A 15 [1J2_ (benzyloxy) -2-ethoxy engagement oxy] -8 · (methoxycarbonyl) -11-bonded group dibenz l: b, f] [l, 4] Oxynitrol-10 (11H) _yl] acetic acid 20

This paper specifically applicable scale Chinese National Standard (CNS) A4 size (210 X 297 mm) 200413340 A7 B7 Ministry of Economic Affairs Intellectual Property Office employees consumer cooperatives printed five or description of the invention (39) 500 mg (0.91 mmol) Example A solution of the 8A compound in 4 ml of difluoromethane was mixed with 0.35 ml (4.6 mmol) of trifluoroacetic acid. The mixture was stirred at RT for 16 hours, after which 0.35 ml (4.6 mmol) of trifluoroacetic acid was added. The mixture was stirred for an additional 5 hours at RT, diluted with 5 ethyl acetate, and washed several times with dilute hydrochloric acid. After drying over magnesium sulfate, the volatile components were condensed out in vacuo. The residue was purified by preparative HPLC (Method 11). This gave 240 mg (53% of theory) of the desired product. 10 LC-MS (Method 3): Rt = 3.49 minutes MS (ESI): m / z = 492 (M + H) + ^ -NMR (300 MHz, DMSO-d6):. (5 = 3.83 (s, 3H ), 4.62 (d, 1H), 4.76 (d, 1H), 4.91 (s, 2H), 5.15 (s, 2H), 6.87 (d, 1H), 7.03 (d , 1H), 7.30 (s, 5H), 7 · 46 15 (dd, lH), 7 · 50 (d, lH), 7.82 (d, lH), 7 · 97 (s, lH) ·

Example 10A 1- [2- (benzyloxy) -2-hexyloxyethoxy] -10- {2- [Third-butyl (methyl) amine 20-yl] -2-hexyloxyethyl Bu 11-Hydroxy-10,11-dihydrodibenzo [b, f] [l, 4] oxazepine-8-methyl formate-41- This paper is in accordance with Chinese National Standard (CNS) A4 eligible (210 X 297 mm)

200413340 A7 B7 V. Description of the invention (40)

50 mg (0.1 mmol) of the compound of Example 9A, 10.6 mg (0.12 mmol) of N-methyl-N-tert-butylamine and 77 mg (0.2 mmol) printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 10 ear) A solution of HATU in 2 ml of DMF was mixed with 0.04 ml (0.2 mmol) of N, N-diisopropylethylamine. The mixture was mixed at RT for 16 hours, diluted with ethyl acetate, and successively washed with 0.1 M hydrochloric acid and a saturated aqueous sodium hydrogen carbonate solution. After drying over magnesium sulfate, the volatile components were removed in vacuo. The product was obtained, which was reacted further without further purification. 15 LC-MS < (Method 3): Rt = 3.88 minutes MS (ESI): m / z = 461 (M + H) +.

20 Example 11A 1- (2-benzyloxy-2-hexyloxyethoxy) -10- (2- (2,2-dimethylpropoxy) 2-hexyloxyethyl)- 11-Hydroxy-10,11-dihydrodibenzo [1], phantom [1,4] oxazepine-8-methyl formate '-42- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 200413340 A7 B7 V. Description of the invention (41)

A solution of 50 mg (0.1 mmol) of the compound of Example 9A, 6.2 mg of 10 DMAP and 29 mg (0.15 mmol) of EDCI in 6 ml of digas methane and 10.7 mg ( 0.12 mmol) neopentyl alcohol. The mixture was stirred at RT for 16 hours, diluted with ethyl acetate, and washed successively with 0.1 M hydrochloric acid and a saturated aqueous sodium hydrogen carbonate solution. After drying with magnesium sulfate, the volatile components were removed in the air. 55 mg (98% of theory) were obtained. LC_MS (Method 3): Rt = 4.06 minutes MS (ESI): m / z = 562 (M + H) +. B-NMR (200 MHz, DMSO-d6): 6 = 1.38 (s, 9H), 3 · 52 20 (s, 2H), 3.83 (s, 3H), 4.70 (d, 2H), 4.90 (s, 2H), 5.16 (s, 2H), 6.86 (d, 1H), 7.02 (d, 1H), 7.31 (s, 5H), 7.42 (dd, 1H), 7.52 (d, 1H), 7.82 (d, 1H), 8.00 (s, 1H). / -43- applies the present paper China national standard scale (CNS) A4 Regulations (2iOX297 mm) 200413340 A7 B7 V. Description of the Invention (42)

Example 12A 10- (4,4-Difluorenyl-2-hexyloxypentyl) -1-hydroxy-11-hexyloxy-10,11-dihydrodibenzo [b, f] [l, 4] Oxylomethyl-8-formate

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 5 According to the method of Example 4A from 500 mg (1.75 mmol) of the compound of Example 3A and 338 mg (1.75 mmol) of 1-bromo-4,4-dimethyl- 2-pentanone was prepared. Purification (ethyl acetate: cyclohexane 5: 1) on silica column to produce 290 mg (41% of theory) of product. 10 LC-MS (Method 3): Rt = 4.60 minutes MS (ESI): m / z = 398 (M + H) +. ^ -NMR (200 MHz, DMSO-d6): δ = 1.03 (s, 9H) , 1.40 (s, 2H), 3.83 (s, 3H), 4.91 (s, 2H), 6.82 (d, 1H), 15 6.90 (d, 1H), 7.45 (dd, 1H), 7.51 (d, 1H) , 7.68 (s, 1H), 7.83 (d, 1H). -44- This paper size applies to China National Standard (CNS) A4 (210x297 mm) 200413340 A7 B7

V. Description of the invention (43) f Example 13A 1- (2-benzyloxy-2-hexyloxyethoxy) -10- (4,4-dimethyl-2_hexylpentyl)- 11-Hydroxy-1,10, ll-diargydibenzo [b, f] [l, 4] oxazepine-8-formic acid methyl ester

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. Example 7A was prepared from 230 mg (0.58 mmol) of the compound of Example 12A and 133 mg (0.58 mmol) of benzyl bromoacetate. Purification on a silica gel column (digas methane: methanol 1: 0 to 3: 1) yielded 0.02 mg (91% of theory) of the product. 10 LC-MS (Method 3): Rt = 4.04 minutes MS (ESI): m / z = 546 (M + H) +.! H-NMR (300 MHz, DMSO-d6): 1.02 (s, 9H), 2 · 37 (d, 1H), 2.52 (d, 1H), 3.81 (s, 3H), 4.76 (d, 1H), 15 4.89 (s, 2H), 4.99 (d, 1H), 5.16 (s, 2H ), 6.87 (d, 1H), 7.03 (d, 1H), 7.30 (s, 5H), 7.45 (dd, 1H), 7.51 (d, lH), 7.77 (s, lH), 7. · 79 (d, lH) · -45- applies the present paper China national standard scale (CNS) A4 eligible Regulation (210x297 mm) 200413340 A7 B7 V. invention is described in (44)

Example 14A Methyl 2-benzyloxy-6-hydroxybenzoate

HO

Printed on M 5 4.8 ml (40.4 mmol) benzyl bromide and 7.97 g (57.7 mmol) of potassium carbonate are continuously added to 10 g (57.7 mmol) of 2,6-di A solution of methyl hydroxybenzoate in 100 ml of acetone. The mixture was stirred at RT overnight. After adding 500 ml of ethyl acetate, it was washed with water and dried over magnesium sulfate, and the volatile components were removed in vacuo. The residue was dissolved in 50 ml of acetone and mixed again with 2.4 ml of benzyl bromide and 4 g of potassium carbonate. Stirring was repeated overnight and the mixture was treated as before. The resulting mixture was separated on a silica gel column (ethyl acetate: cyclohexane 1: 5). This gave 3.93 g (26% of theory) of the desired product. 15 LC-MS (Method 3): Rt = 3.47 minutes MS (ESI): m / z = 259 (M + H) + ^ -NMR (200 MHz, DMSO-d6):. 5 = 3 · 75 (s, 3H), 5 · 12 -46- This paper size is applicable to Chinese National Standard iCNS) A4 (210x297 mm) 200413340 A7 B7 V. Description of the invention (45) (s, 2H), 6.50 (d, lH), 6 58 (d, 1H), 7.17 (dd, 1H), 7.35 (m, 5H), 9.98 (s, 1H). Example 15A 5 2-hydroxy-6- (2 · methoxy -2-Hydroxyethoxy) methyl benzate

HO

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs from Example 14A from 15 g (89.2 mmol) methyl 2,6-dihydroxybenzoate, 12.3 g (80.3 mmol) methyl bromoacetate, 12.3 g (89.2 10 mmol) potassium carbonate was prepared in 120 ml of acetone. The resulting mixture was separated on a #gel column (ethyl acetate: cyclohexane 1: 5). This gave 3.38 g (16% of theory) of the desired product. LC-MS (Method 4): Rt = 3.73 minutes 15 MS (ESI): m / z = 241 (M + H) +. ^ -NMR (200 MHz, DMSO-d6): δ = 3.68 (s, 3H) , 3 · 76 (s, 3H), 4.75 (s, 2H), 6.38 (d, 1H), 6.52 (d, 1H), 7. 15 (dd, 1H), 10.00 (s, 1H). -47- this paper scale applicable Chinese national standard (CNS) A4 size (210 X297 mm) 200413340 A7 B7 V. invention is described in (46)

Example 16A Methyl 2- (benzyloxy) -6-hydroxy-4-methylbenzoate

HO

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 5 according to Example 14A from 11 g (58.6 mmol) of methyl 2,6-dihydroxy-4-methylbenzylate and 9.02 g (52.7 mmol) Benzyl bromide was prepared. The resulting mixture was separated on a silica gel column (ethyl acetate: cyclohexane 1: 5). 4.4 g (28% of theory) of the desired product are obtained. 10 LC-MS (Method 5): Rt = 3.72 minutes MS (ESI): m / z = 273 (M + H) + ^ -NMR (400 MHz, DMSO-d6):. Δ = 2.22 (s, 3H) , 3,73 (s, 3H), 5.09 (s, 2H), 6.33 (s, 1H), 6.44 (s, 1H), 15 7. 31 (m, 1H), 7.39 (m, 4H), 9.98 ( s, 1H). -48- this paper applies the Chinese national standard scale (CNS) A4 size (210x297 mm) 200413340 A7 B7 V. invention is described in (47)

Example 17A 4- [3- (Benzyloxy) -2- (methoxycarbonyl) phenoxy] -3-nitrobenzoic acid methyl ester

CH3, '\ 5 2.96 g (13.7 mmol) of methyl 4-nitro-3-nitrobenzate and 1.90 g (13.7 mmol) of potassium carbonate were continuously added to 3.22 g (12.5 mmol) of the compound of Example 14A In 30 ml of DMF. The mixture was stirred at 70 ° C oil bath temperature for 5 hours. After cooling to RT, it was diluted with 200 ml of ethyl acetate. After washing with water and drying over magnesium sulfate, move in a vacuum for 10 minutes to remove rabbit-like ingredients. The residue was chromatographed on silica gel (ethyl acetate: cyclohexane 1: 5). 4.3 g (79% of theory) of the desired product are obtained. Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs (Method 3): Rt = 3.67 minutes MS (ESI): m / z = 438 (M + H) +. 15 ^ -NMR (200 MHz, DMSO-d6): 5 = 3.68 (s, 3H), 3.90 (s, 3H), 5.23 (s, 2H), 6.89 (d, lH), 7.12 (d, lH), 7.20 (d, lH ), 7.40 (m, 5H), 7.54 (dd, 1H), 8. 19 (d, 1H), 8.51 (d, 1H). -49- This paper size applies to China National Standard (CNS) A4 specifications ( 210x297 mm) 200413340 A7 B7 V. Description of the invention (4〇

Example 18A 2- (4- cyano-2-nitrophenoxy) -6- (2-methoxy ethoxy group -2- co) benzylic acid methyl ester

According to the method of Example 17A, 1.52 g (6.33 mmol) of the compound of Example 15A, 1.27 g (6.96 mmol) of 4-gas-2-nitrobenzonitrile and 960 mg (6.96 mmol) potassium carbonate was prepared in 15 ml DMF. The crude product was chromatographed on silica gel (ethyl acetate: cyclohexane 1: 5). The desired product was obtained before 10 2.21 (90% of theory). LC-MS (Method 2): Rt = 3.40 minutes MS (ESI): m / z = 409 (M + Na) +. ^ -NMR (200 MHz5 DMSO-d6): 6 = 3.68 (s, 3H) , 3.72 15 (s, 3H), 4.95 (s, 2H), 6.93 (d, lH), 7.04 (d, lH), 7.11 (d, H), 7.52 (dd , LH), 8 · 10 (d, 1H), 8 · 68 (s, 1H) · f -50- This paper size applies to China National Standard (CNS) A4 (210x297 mm) 200413340 A7 B7 V. Description of the invention (49)

Example 19A 2- (Benzyloxy) -6- [4- (methoxycarbonyl) -2-nitrophenoxy] -4-methylbenzyl methyl ester

. 0CH was prepared in the same manner as in Example 17A from 2.20 g (8.1 mmol) of the compound of Example 16A and 1.92 g (8.9 mmol) of methyl 4-nitro-3-nitrobenzate. The crude product was chromatographed on silica gel (ethyl acetate: cyclohexane 1: 5). L0 g (27% of theory) of the desired product was obtained. 10 LC-MS (Method 4): Rt = 3.33 minutes MS (ESI): m / z = 452 (M + H) +. Printed by the Consumer Cooperative of Intellectual Property Bureau, Ministry of Economic Affairs] H-NMR (200 MHz, DMSO- d6) :, 6 = 2.33 (s, 3H), 3.64 (s, 3H), 3.88 (s, 3H), 5.23 (s, 2H), 6.75 (s, 1H), 15 7 · 04 ( s, lH), 7.11 (d, lH), 7.37-7 · 48 (m, 5H), 7.54 (dd, 1H), 8.19 (d, lH), 8.51 (d, lH) · -51- This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 200413340 A7 B7 V. Description of the invention (50)

Example 20A 4-[(2,2-Dimethyl · 4 · Hydroxy-4H-1,3-benzodicyclohexylcyclo_5-yl) oxy] -3-acyl + wax

Employees' Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs printed 3.0 grams (16.43 millimoles) of 4-gas-3-nitrobenzonitrile and 3.2 grams (16.43 millimoles) of 5-hydroxy-2,2-dimethyl-411 -1,3-Benzodicyclohexan-4-one was dissolved in 25 ml of DMF, and after adding 2.498 g (18.08 mol) of potassium carbonate, it was stirred overnight at 70 ° C. The mixture was worked up by pouring into 250 ml of water and extracting three times with ethyl acetate. The organic phase was dried over sodium sulfate and concentrated. To give 4.89 g (78% of theory) of product, without further purification. LC_MS (Method 4): Rt = 3.60 minutes 15 MS (ESIpos): m / z = 341 (M + H) +.

Example 21A 4-Gas 3-nitrobenzoic acid 2- (trimethylsilyl) ethyl ester-52- This paper is in accordance with Chinese National Standard (CNS) A4 Regulation (210 X 297 mm) 200413340 A7 B7 V. Description of the Invention

3.00 g (13.64 mmol) of 4-acyl-3-nitrobenzyl gas gas dissolved in 8 ml of pyridine, under ice-cooling, was added 1.93 g (16.36 mmol) methyl 5 three silicon alkyl alcohol, The mixture was stirred at room temperature for 3 hours. The reaction mixture was diluted by toluene and washed with 1N hydrochloric acid and a saturated sodium gas solution. The organic phase was dried over sodium sulfate and concentrated in vacuo. To give 3.99 g (87% of theory) of product, without further purification. MS (EI): m / z = 319 (M + NH4) +

10 Example 22A 4 · [(2, & dimethyl-4-hexyloxy-4H_1,3_benzodioxane-5_yl) oxy] -3_nitrobenzoic acid 2- ( Trimethylsilyl) ethyl ester printed by the Consumers ’Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs 4Ν Cic3 ο

This applies China National Standard Paper Scale (CNS) A4 size (2U) X 297 mm) 200413340 A7 B7 V. invention is described in (52) 3.9 g (12.92 mmol) of 4-benzyloxy-3-nitrobenzoic acid 2 gas · (Trimethylsilyl) ethyl ester and 2.51 g (12.92 mmol) of 5-hydroxy-2,2-dimethyl-4H-1,3-benzodioxane-4-one were dissolved in 25 After adding 1.96 g (14.21 mmol) of potassium carbonate to ml of DMF, it was stirred overnight at 70 ° C. 5 The mixture was worked up by pouring into 250 ml of water and extracting three times with ethyl acetate. The organic phase was dried over sodium sulfate and concentrated. 5.91 g (84% of theory) of the product were obtained without further purification. LC-MS (Method 6): Rt = 1.30 minutes 10 MS (ESIpos): m / z = 460 (M + H) +

Example 23A 2,2-Dimethyl-5- [2-nitro-4- (trifluoromethyl) phenoxy] -4fluorene-1,3-benzodioxane-4-one F c

Economic Intellectual Property Office employee consumer cooperative printed 3.7 g (13.7 'mmol) of 1-bromo-2-nitro-4- (trifluoromethyl) benzene and 2.66 g (13.70 mmol) of 5 hydroxy _2,2_ -4Η-1,3- dimethyl-benzodioxin -54- applies the present paper China national standard scale (CNS) A4 eligible regulations (210 X 297 mm) 200413340 A7 B7 V. DESCRIPTION OF THE iNVENTION (53) Hexyl-4-hole system was dissolved in 25 ml of DMF. After adding 2.08 g (15.07 mmol) of potassium carbonate, it was stirred at 70 ° C. overnight. The mixture was worked up by pouring into 250 ml of water and extracting three times with ethyl acetate. The organic phase was dried over sodium sulfate and concentrated. 5.16 g (5 95% of theory) of the product were obtained. LC-MS (Method 7): Rt = 3.95 minutes MS (ESIpos): m / z = 384 (M + H) +

Example 10. 24A 2- (2- methoxy-ethoxy -2- engagement yloxy) -6- [2-nitro-4- (trifluoromethyl) phenoxy] benzyl methyl

〇H3

F Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economy, 2000 mg (8.33 mmol) of 2-hydroxy-6- (2-methoxy_2_oxyoxyethoxy) benzyl methyl ester and 2066 mg (9.16 mmol) mole) -2-nitro-1- gas -4_ (trifluoromethyl) benzene was dissolved in 30 ml of N, N- dimethylformamide, in a suitable scale paper Tim -55- present China national standard (CNS ) A4 specification (210 X 297) 200413340 A7 B7 V. Description of the invention (54)-After adding 1266 mg (9.16 mmol) of potassium oxalate, stir for 4 hours under 7 generations. After cooling, the mixture was diluted with water and extracted three times with ethyl acetate. The organic phase was washed with sodium chloride solution and dried over sulfuric acid. Remove the volatile constituents in true ^. The crude product was purified on silica gel (mobile phase: 25 mL / ethyl acetate 20: 1). 2965 mg (82% of theory) of product 0 LC-MS (Method 4): Rt = 2.94 minutes MS (ESIpos): m / z = 430 (M + H) + 10

Example 25A 5- (4-Fluoro-2-nitrophenoxy) -2,2 · dimethyl-4H-1,3-benzodioxane-4_one

15 2.0 g (10.3 mmol) of 5-Hydroxy-2,2-dimethyl_43--1,3-benzodioxanil-4-¾ printed under the mouse by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs Dissolved in 20 ml of anhydrous water, add -56- Zhang scale applicable to China National Standard (CNS) A4 specifications (210 x 297 public love ^ ------ 200413340 A7 B7 V. Description of the invention (55) 1.64 g (10.3 millimeters) Mol) 2,5-difluoronitrobenzene and 1.42 g (10.3 mmol) of anhydrous potassium carbonate. The mixture was stirred overnight at 70 ° C. During processing, DMF was removed in vacuo and the residue was dissolved in acetic acid ethyl, washed twice with water, washed with a saturated solution of sodium gas, dried over magnesium sulfate and finally purified by 5 column chromatography. (silica gel: cyclohexane / diethyl methane gas 3: 1). 2 grams produced (52% of theory) Product. HPLC (Method 8): Rt = 4.74 minutes MS (DCI): m / z = 334 (M + H) + 10

Example 26A 5- (4- Gas 2-nitrophenoxy) -2,2-dimethyl-benzo _4H-1,3- dioxane-4-one embodiment

Printed 2.0 g (10.3 mmol) of 5-Hydroxy-2,2-dimethyl_4H-1,3-benzodioxane-4-one dissolved in argon by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economy In 34 ml of anhydrous DMF, add -57- This paper size applies the Chinese National Standard (CNS) A4 regulations (210 x 297 male; *) 200413340 A7 B7 V. Description of the invention (56) 1.81 g (10.3 mmol) 5-Gas-2-fluoronitrobenzene and 1.42 g (10.3 mmol) of anhydrous potassium carbonate. The mixture was stirred at 70 ° C. overnight. During the treatment, it was diluted with ethyl acetate and washed several times with water and a saturated sodium gas solution. After drying over magnesium sulfate, purification was performed by column chromatography (silica gel · cyclohexane / ethyl acetate 5: 1 to 2: 1). This gave 2.79 g (76% of theory) of the product. HPLC (Method 8): Rt = 4.81 minutes MS (DCI): m / z = 350 (M + H) +

10 Example 27A 5- (4- bromo-2-nitrophenoxy) -2,2_ -4H-1,3- dimethyl-benzo-dioxane-4-one

Ο Ο

Printed 2.0 grams (10.3 mmol) of 5-hydroxy-2,2-dimethyl-4H-1,3_benzodi 15-oxanecyclo-4-one under argon by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs Dissolved in 20 ml of anhydrous DMF, 2.27 g (10.3 mmol) of 5-bromo-2-fluoronitrobenzene and 1.42 g (10.3 mmol) of anhydrous potassium carbonate were added. The mixture was stirred at 70 ° C. overnight. When processed, removal of DMF in vacuo, the residue was dissolved in ethyl acetate, and the scale applied to the sheet -58- present China National Standard (CNS) A4 size (210 X 297 mm) 200413340 A7 B7 V. invention Instructions (57) Wash three times with water. After drying over magnesium sulfate, it was purified by column chromatography (silica gel: cyclohexane / ethyl acetate 4: 1). 3.0 g (75% of theory) of the product are obtained. HPLC (Method 8): Rt = 4.86 minutes 5 MS (DCI): m / z = 441 (M + NH4) +

Example 28A 3-Amino · 4- [3- (benzyloxy) _2_ (methoxycarbonyl) phenoxy] benzyl methyl ester

CH3

Economic portion wise property Office employee consumption cooperatives 10 4.30 g (9.8 mmol) of Example 17A Compound 120 methanol the solution was mixed with 11.1 g (49.2 mmol) gasification of tin (11) chloride dihydrate mixed. The mixture was stirred at 70 ° C for 4 hours, and then concentrated in vacuo. The residue 15 was stirred with 200 ml of water and ethyl acetate, and the aqueous phase was adjusted to pH 8 by adding sodium carbonate. The resulting suspension was filtered through a calcium ore. The phases were then separated and the aqueous phase was extracted with ethyl acetate. The combined extracts were washed with water, dried over sulfuric acid, and concentrated in vacuo. The residue was chromatographed (6S purpose acetate: cyclohexane 1: 3) on silica. To obtain 2.2 grams (55% of the theoretical value) -59- Zhang scale required by China National Standard (CNS) A4 specifications (210 X 297 Gongchu) 200413340 A7 B7 V. Description of invention (50 objects. LC-MS (method 4): Rt = 3.02 minutes MS (ESI): m / z = 408 (m + H) + 5 ^ -NMR (200 MHz, DMSO-d6):. δ = 3. 76 (s, 3H), 3.81 (s, 3H), 5.20 (s, 2H), 5.25 (s, 2H), 6.48 (d, lH), 6.81 (d, lH), 6.98 (d, lH), 7 · 15 (d, lH), 7.38 (m, 7H) ·

Example 10. 29A 2- (2-methyl-4-cyanophenoxy) -6- (2-methoxy-ethoxy -2- engagement yloxy) benzyl acid methyl ester

The Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs printed 1.20 g (3.11 mmol) of the compound of Example 18A and 3.50 g (15.5 mmol) of tin (II) in 50 ml of methanol according to the method of Example 28A. Dihydrate / prepared. To give 1.02 g (92% of theory) of the desired product. -60- This paper size applies Chinese National Standard (CNS) A4 (210x297 mm) 200413340 A7 B7 V. Description of Invention (59) LC-MS (Method 2): Rt = 3.30 minutes MS (ESI): m / z = 457 (M + H) + 5 h-NMR (300 MHz, DMSO-d6): (5 = 3 · 70 (s, 3H), 3.77 (s, 3H), 4.89 (s, 2H), 5.43 ( s, br, 2H), 6.55 (d, 1H), 6.80 (d, 1H), 6.83 (dd, 1H), 6.94 (dd, 1H), 7.10 (s, lH), 7.37 (dd, lH).

Example 10 30A 2_ [2- amino-4- (methoxycarbonyl) phenoxy] -6- (benzyloxy) -4_ methylbenzyl acid methyl ester

CH,. ^ 〇 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 15 According to the method of Example 28A, 1.9 g (2.22 mmol) of the compound of Example 19 A was prepared. The crude product was chromatographed on line (ethyl acetate: hexane 1: 3) on the rubber pieces. To obtain 700 mg (75% of the theoretical value) -61 · This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 200413340 A7 B7 V. Description of the invention (60) LC-MS ( method 7): Rt = 3.61 minutes MS (ESI): m / z = 422 (m + H) + 5 ^ -NMR (200 MHz, DMSO-d6):. δ ^ 9 oa r square ", (s, 3H ), 3.72 (s, 3H), 3.81 (s, 3H), 5.19 (s, 2H), 5 25 (s 2h) 6.30 (s, 1H), 6.80 (d, 1H), 6 · 84 (S, 1H), 715 '(d 1h' 7.38 (m, 6H). ''

10 Example 31A 3- amino-owned -4 _ [(2,2-dimethyl-4-yloxy engagement _4H-1,3_-benzo-dioxane 5-yl) oxy] _ _ Order one thousand carbonitrile

Line I 1 I _ Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 15 20 = 7 grams (14.31 millimoles), resembling dimethyl icyloxyl 1,3_benzodioxane_5 _-yl) oxy] -3-nitrobenzonitrile was dissolved in a mixture of acetic acid and 3 ml 6〇 ml of water, the addition of 5 595 g (loo.18 mmol) of iron powder. The suspension was stirred at RT for 1 hour, and sampled at 5 ° C for 3 hours. After cooling, it was diluted with 300 ml of propidium I and pumped through calcium stone breaking -62- This paper applies the national standard (CNS) A4 specifications (210 × 297 male ^ 7 200413340 A7 B7 V. Description of the invention (61) Filtration, washing with a large amount of acetone. The filtrate was concentrated and suspended in digas methane / ethyl acetate 5: 1. The precipitate was filtered by suction and dried It produced 1.46 g (32% of theory) of product, which was used without further purification 5 LC-MS (method 2):. Rt = 3.50 minutes MS (ESIpos): m / z = 311 (m + H) +

Example 32A 10 3-Amino-4 _ [(2,2-dimethyl-4-hexyloxy-4H-1,3-benzodioxane-5-yl) oxy] benzoic acid 2- (Trimethylsilyl) ethyl ester

15 5.9 g (12.84 mmol) printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 4-[(2,2-dimethyl-4-hexyloxy_4H-1,3-benzodioxane- 5-yl) oxy] -3-nitrobenzoic acid 2- (trimethylsilyl) ethyl ester was dissolved in 60 ml (1 048 09 mmol) of acetic acid and 3 ml of water, and 5.019 g was added (89.88 mmol) Iron powder. Suspension at -63- This paper size is in accordance with Chinese National Standard (CNS) A4 (210x297 mm) 200413340 A7 B7 V. Description of the invention (62) Stir for 1 hour at RT and 3 hours at 50 ° C. After cooling, diluted with 300 ml of acetone, suction filtered through a calcium mineral, a large amount of acetone wash. The filtrate was concentrated, suspended in methane / ethyl acetate 5: 1 and concentrated again, and the residue was purified on silica gel (mobile phase: methane / ethyl acetate 30: 1). 3.52 g (63% of theory) of the product were obtained. LC-MS (Method 6): Rt = 1.06 minutes MS (ESIpos): m / z = 430 (M + H) +

10 Example 33A 5- [2_ -4_ amine (trifluoromethyl) phenoxy] -2,2-dimethyl -4H-1,3- benzodioxin-oxohexanoic cyclic ketone F ΙΓ _4-

5.15 g (13.44 mmol) of 2,2-dimethyl-5- [2-nitro-4- (trifluoromethyl) phenoxy] -4H-1 printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs The 3-benzodioxan-4-one was dissolved in 100 ml of a 1: 1 ethyl acetate / ethanol mixture at RT. Add 1.43 grams (1.34 millimoles) of 10% palladium on carbon and 5.084 grams (80.62 millimoles) of ammonium formate, mixture -64- This paper size applies to China National Standard (CNS) A4 (210 X 297 cm) 200413340 A7 B7 V. Description of the invention (63) Stir overnight at 80 ° C. After the mixture was cooled, the crystals were filtered off through calcium ore and washed with ethanol. The crude product was purified on silica (mobile phase: two gas methane / ethyl acetate 30: 1). 3.54 g (65% of theory) of the product were obtained. 5 LC-MS (Method 2): Rt = 3.70 minutes MS (ESIpos): m / z = 354 (M + H) +

Example 34A {[11- co-8- (trifluoromethyl) -10,11-dihydro-dibenzo [b, f] [l, 4] 10 call oxynitride-yl] oxy } Methyl acetate

Economic Intellectual Property Office employee consumer cooperative print 2 940.0 mg (6.85 mmol) of 2- (2-methoxy ethoxy group bonded _2_ 15-yl) -6- [2-nitro _4- (C Fluoromethyl) phenoxy] benzyl methyl ester was dissolved in a 1: 1 (10 ml total) mixture of ethyl acetate and ethanol. Was added 729 mg (0.68 mmol) Pd / C (10%) and 2591 mg (41.4 mmol) of ammonium formate, followed by stirring at 80 ° C 2 hours. After the reaction mixture was cooled, it was filtered through a silica glass frit. Washed with ethanol and the volatiles removed in vacuo -65- applies the present paper China National Standard Scale (CNS) A4 size (2U) X 297 mm) 200413340 A7 B7 V. Description of the Invention (64) of the component. This gave 2 477 mg (86% of theory) of the product without further purification. LC-MS (method 5) Rt = 3.42 minutes 5 MS (ESIpos):. M / z = 400 (M + H) +

Example 35A 5- (2-Amino-4-aminophenoxy) -2,2-dimethyl-4H-1,3-phenylhydrazone dioxane_ 0 0

1.9 grams (5.70 mmol) of 5- (4-fluoro-2-nitrophenoxy) -2,2-dimethyl-4H-1,3-benzo Dioxane-4-one was dissolved in 15 ml of ethanol, and 300 mg of palladium hydroxide (20%) on carbon was added. The mixture was stirred under an argon atmosphere for 15 minutes until the reaction was complete. It was processed by filtering calcium ore and washing with ethanol. Because the filtrate contains additional traces of carbon, it is filtered through a calcium ore (with a thin layer of silica gel) and washed with ethanol. Concentrated and dried in vacuo to produce 1.5 g (87% of theory) of product. This scale sheet -66- applies the Chinese national standard (CNSVU size (210x297 mm) 200413340 A7 B7 V. Description of the Invention (65) HPLC (Method 8): Rt = 4.48 minutes MS (DCI): m / z = 304 (M + H) +

5 paste of Example 36A 5- (2- amino -4-gas phenoxy) -2,2-dimethyl -4H-1,3- benzodioxin-gas portion 10 wise economic property Bureau membered consumption cooperatives PRINTED 15

(G) (2.80 mmol) 5- (4-Ga · 2-nitrophenoxy) 2,2,4,4Η-1,3-benzodioxan-4-one with 10 ml of acetic acid, and 5 millibases. Then, 1.12 g (20 millimoles) of iron was added, and the mixture was added to ° C. Stir at this temperature until the reaction is complete. After cooling to room temperature, 'dilute with C =, filter through calcium ore. The filtrate concentrated in vacuo. 〒 benzene was added and evaporated to dryness twice = the residue was suspended in ethyl acetate, filtered through silica gel. the filtrate was concentrated and dried in vacuo. to give 〇92 g (99% of theory), _ without further purification HPLC (method 8):. Rt = 4.62 minutes -67 · 200413340 A7 B7 V. invention is described in (66) MS (DCI): m / z = 320 (m + H) +

Example 37A 5- (2-Amino-4-bromophenoxy) -2,2-dimethyl · 4Η-1,3-benzodioxane-5 Ό Ο

1 g (2.554 mmol) 5- (4-bromo · 2-nitrophenoxy) _2,2_difluorenyl-4Η-1,3-benzene printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs Dioxane-4-one was mixed with 10 ml of acetic acid and 0.5 ml of water. Then 992 mg (17.8 mmol) of iron was added and the mixture was heated to 50 15 ° C. Stir at this temperature until the reaction is complete. Cool to RT, dilute with acetone and filter through calcium ore. The filtrate was concentrated in vacuo. Toluene was added and subsequently evaporated to dryness twice. The residue was suspended in ethyl acetate and filtered through silica gel. The filtrate was concentrated and dried in vacuo. 0.89 g (95% of theory) of crude product was obtained without further purification. 20 HPLC (Method 8): Rt = 4.60 minutes MS (DCI): m / z = 364 (M + H) +

Examples 38A -68- This paper size applies Chinese National Standard (CNS) A4 regulations (210 X 297 mm) 200413340 A7 B7 V. Description of the invention (67) 1-benzyloxy-11-hexyloxy-10, 11-Dihydrodibenzo [b, f] [l, 4] oxazepine-8-formic acid methyl ester

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economy 10 2.20 g (5.1 mmol) of the solution of the compound of Example 28A in 200 ml of toluene was mixed with 193 mg (1.0 mmol) of p-toluenesulfonic acid hydrate and reflux Stir overnight at temperature. After cooling to RT, it was concentrated in vacuo. The residue was chromatographed on silica gel (cyclohexane: ethyl acetate 3: 1). This gave 1.49 g (78% of theory) of the desired compound. 15 LC-Μέ (Method 3): Rt = 3.35 minutes MS (ESI): m / z = 376 (M + H) +. H-NMR (200 MHz, DMSO-d6): 6 = 3.81 (s, 3H) , 5. 17 (s, 2H), 6.95 (d, 1H), 7.05 (d, 1H), 7.28-7.55 20 (m, 7H), 7.69 (m, 2H).

Example 39A

[(8-cyano-11-synthoxy-10,11-dihydrodibenzo [b, f] [l, 4] oxazepine) oxy] methyl acetate-69- Paper size Applicable to China National Standard (CNS) A4 specification (210x297 mm) 200413340 A7 B7 V. Description of invention (68 5

〇-10 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs \ CH, 791 mg (2.22 mmol) of the compound of Example 29A in 250 ml of toluene and 76 mg (0.44 mmol) of p-toluenesulfonate Acid hydrate mixed. The mixture was heated at reflux temperature overnight. After cooling to RT, it was washed once with a saturated aqueous sodium bicarbonate solution, dried over magnesium sulfate, and concentrated in vacuo. The formed product was used without further purification. LC-MS (Method 2): Rt = 3.02 minutes 15 MS (ESI): m / z = 325 (M + H) +. Ο This paper size applies Chinese National Standard (CNS) A4 specifications (2i0x297 public funding;) 200413340 A7 B7 V. Description of Invention (69)

Example 40A Methyl 1- (benzyloxy) -3-methyl-11-hexyloxy-10,11-dihydrodibenzo [b, f] [l, 4]

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 10 According to the method of Example 38A, it was prepared from 700 mg (1.66 mmol) of the compound of Example 30A. The crude product was chromatographed on silica gel (cyclohexane: ethyl acetate 3: 1). This gave 448 mg (67% of theory) of the desired compound. 15 LC-MS (Method 3): Rt = 3.41 minutes MS (ESI): m / z = 390 (M + H) + ^ -NMR (400 MHz, DMSO-d6):. (5 = 2.32 (s, 3H ), 3.83 (s, 3H), 5.16 (s, 2H), 6.82 (s, 1H), 6.92 (s, 1H), 20 7.31 (dd, 1H), 7.40 (m, 3H), 7.49 (m , 2H), 7.71 (m, 2H), 10.47 (s, 1H). -71- this paper applies the Chinese national standard scale (CNS) A4 size (210 X 297 mm) 200413340 A7 B7 V. invention is described in (70 )

Example 41A 1-Hydroxy-11-synthoxy-10,11-dihydrodibenzo [1], p- [1,4] oxazepine nitrile

2.9 g (7.29 mmol) of 3-amino-4-[(2,2-dimethyl-10yl-4-hexyloxy-4H_1,3-benzodioxane) with a purity of 78% -5-yl) oxy] benzonitrile at RT was dissolved in 50.0 ml of xylene was added 〇139 g (0.73 mmol) 4_-toluenesulfonic acid monohydrate. The suspension was at 14 ° C. (: Stir overnight. After the reaction mixture is cooled, the precipitate is filtered off with suction and washed with cyclohexane. The precipitate is then suspended in methanol, filtered with suction for several times, and then dried under a high vacuum. 2.33 g (95% of theory) of the product was obtained without purification. The LC-MS was printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs (Method 2): Rt = 3.40 min. MS (ESIpos): m / z = 253 ( M + H) + -72- This € standard applies to China National Standard (CNS) A4 specifications (210 X 297 Gongchu__y 200413340 A7

Example 42A 1-Hydroxy-1benzooxy-10, Π-dihydrodibenzo [b, f] [l, 4] oxazepine-8-formic acid 2. · (trimethylsilyl) ethyl Ester 10 15 HX h3c ^ \ .. CH,. Gg Η 、 〇

3.5 grams (8.15 millimoles) of 3-amino-4-[(2,2-dimethyl-4_oxo-4_-1,3-benzodioxan-5-yl) Oxy] 2- (trimethylmetazone) ethyl benzate was dissolved in 50.0 ml of xylene at RT, and 0 (0.82 mmol) 4-toluene acid monohydrate was added. The suspension was dropped overnight at URC. After the reaction mixture was cooled, the precipitate was filtered off with suction, the precipitate was washed with cyclohexane and suspended in methanol, and filtered with suction for several times. The residue was dissolved in iN sodium hydroxide in vinegar extracted with ethyl acetate. the organic phase was dried over sodium sulfate and concentrated. G.734 give g (24% of theory) of product, without further purification. order

Line 1 I • I economic Intellectual Property Office employee consumer cooperative printed 20 LC-MS (Method 2): Rt = 3 · 20 minutes MS (ESIpos): m / z = 372 (M + H) + -73- 200413340 A7 B7 V. Description of Invention (72)

Example 43A {[11-Hydroxy-8- (trifluoromethyl) -10,11-dihydrodibenzo [b, f] [l, 4] oxazepine-1-yl] oxy} Methyl acetate

Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 10 2.45 g (5.83 mmol) 2 · [2-amino-4- (trifluoromethyl) phenoxy]-6- (2-methoxy-2- co-methoxyethoxy) benzyl acetate was dissolved at RT in a 400.0 ml of xylene was added 0.221 g (1.17 mmol) of 4-toluenesulfonic acid monohydrate. The suspension was stirred at 140 ° C overnight. After the reaction mixture was cooled, the precipitate was filtered off with suction and washed with cyclohexane. The precipitate was suspended in methyl alcohol 15, suction filtration several times. It is dried under high vacuum. 0.583% (27% of theory) of the product was obtained without further purification. LC-MS (Method 4). Rt = 2.65 minutes MS (ESIpos): m / z = 368 (M + H) + -74- This paper size applies to China National Standard (CNS) A4 (210x297 mm) 200413340 A7 B7 V. Description of Invention (73)

Example 44A 8-fluoro small hydroxydibenzo [b, f] [l, 4] oxazepine-11 (10H) -one

10 1.5 g (4.95 mmol) 5_ (2_-amino-4-fluorophenoxy) -2,2-dimethyl-cyclohexyl -4H-1,3- benzodioxin-4-one and 20 Mix xylene with 94 mg (0.49 mmol) of p-toluenesulfonic acid monohydrate. The reaction mixture was stirred at 120 ° C overnight and then concentrated in vacuo. The formed residue was stirred in methanol and the formed solid was filtered off and dried in vacuo. To give 94,815 mg (78% of theory) of product. HPLC (Method 9): Rt = 4.47 minutes MS (DCI): m / z = 246 (M + H) + Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs -75- This paper standard applies to China National Standard (CNS) A4 Specifications (210 X 297 mm) 200413340 A7 B7 V. Description of the invention (μ) f Example 8-Ga-1-hydroxydibenzo [b, f] [l, 4]

919 mg (2.87 mmol) 5_ (2-Amine-4-Gaphenoxy) -2,2-di10methyl_4H-1,3-benzodioxane with 12 ml of xylene and 55 mg (0.29 mmol) p-toluenesulfonic acid monohydrate was mixed. The reaction mixture was stirred at reflux overnight and then concentrated in vacuo. The formed residue was stirred 'in methanol to decant the formed solid and dried in vacuo. This gave 671 mg (88% of theory) of the product. 15 HPLC (Method 8): Rt = 4.74 minutes MS (DCI): m / z = 262 (M + H) + Intellectual Property Office employee Economic Co-op printed

Example 46A 20 8-bromo · 1 · Cylendibenzo 1 >, £] [1,4] oxazepine-11 (1〇11) -one

The standard of this series applies to China National Standard (CNS) A4 specification (21〇χ 297 200413340 A7 B7 V. Description of the invention (75) 892 mg (2.45 mmol) 5- (2 • amino-4-bromophenoxy) ) -2,2-Dimethyl-4fluorene-1,3-benzodioxane-4-one was mixed with 10 ml of xylene and 47 mg (0.24 mmol) of p-toluenesulfonic acid monohydrate. The reaction mixture 5 was stirred under reflux overnight. Because the reaction was not complete, an additional 47 mg (0.24 mmol) of p-toluenesulfonic acid monohydrate was added, and the mixture was stirred under reflux for another 24 hours. It was concentrated in vacuo to form The residue was stirred in methanol. The solid formed was filtered off and dried in vacuo. 581 mg (78% of theory) of the product were obtained. 10 HPLC (Method 8): Rt = 4.71 min MS (DCI): m / z = 306 (M + H) +

Example 47A 15 1-Hydroxy-11-synthoxy-10,11-dihydrodibenzo [b, f] [l, 4] oxazepine-8-formic acid

Economic Intellectual Property Office employee printed consumer cooperative 4.32 g (15.14 mmol) of 1-hydroxy-10,11-dihydro-bonded _11_ dibenzo [b, f] [l, 4] - Oxyazepine-8-formic acid methyl ester is dissolved in 33 ml of THF, and 0.798 g (33.32 mmol) of oxyhydrogen-77- added to 33 ml of water. This paper is in accordance with China National Standard (CNS) A4 (210 X 297 mm) 200413340 A7 B7 V. Description of the invention (76) After lithium sulfide, stir overnight at RT. The mixture was acidified by 1N hydrochloric acid and most of the solvent was removed in vacuo. The precipitate was filtered off under suction and dried under high vacuum. 4.443 g (quantitative) of the product were obtained without further purification. 5 LC-MS (Method 7): Rt = 2.96 minutes MS (ESIpos): m / z = 272 (M + H) +

Sinus Example 48A 10 1- hydroxy-11 co-10,11-dihydro-dibenzo [b, f] [l, 4] oxynitride call 2.8.4 formic acid benzyl ester

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, 220 mg (0.81 mmol) of 1-Hydroxy-11-Hydroxy-10,11-Dihydro20 Dibenzo [1], £] [1,4] oxygen Nitrogen-8-formic acid and 5.0 ml (49.18 mmol) of benzyl alcohol were mixed with 16 mg (0.16 mmol) of sulfuric acid and stirred at 150 ° C for 3 hours. The mixture was diluted with ethyl acetate and treated with a saturated sodium carbonate solution and washing the bismuth with a sodium gas solution. The organic phase was dried over sodium sulfate and concentrated. Purified by preparative HPLC (method 11), and then purified on silica gel (Mobile-78- This paper size applies to Chinese National Standard (CNS) A4 specifications (210 X 297 mm) 200413340 A7 B7 V. Description of invention (Τ7) phase : two gas / methanol 20: 1). This gave 122 mg (41% of theory) of the product. LC-MS (Method 3): Rt = 3.92 minutes 5 MS (ESIpos): m / z = 362 (M + H) +

Example 49A 1-Hydroxy-11-synthoxy-10,11-diargondibenzo [b, f] [l, 4] oxazepine-8-formate cyclopentylmethyl acetate

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, 220 mg (0.81 mmol of molybdenyl-11-hoxy-1-10, ι_dihydrodibenzo [b, f] [l, 4] oxazepine- 8-formic acid and 5.0 ml (49.18 mmol) of cyclopentylmethanol were mixed with 16 mg (0.16 mmol) of sulfuric acid, and stirred at 16 (Tc 20 for 3 hours. The reaction mixture was diluted with ethyl acetate and saturated with Sodium carbonate solution and washing with sodium vaporized solution for processing. The organic phase was dried over sodium sulfate and concentrated. Drying in vacuum for 3 hours gave 270 mg (94% of theory) of the product, no further purification. -79- This paper The scale is applicable to Chinese National Standard (CNS) A4 regulations. Bio 200413340 A7 B7 V. Description of the invention (78) LC-MS (Method 3): Rt = 4.49 minutes MS (ESIpos): m / z = 354 (M + H) +

Example 50A 5 1-Hydroxy-11-synthoxy-lO, ll-dihydrodibenzo [b, f] [l, 4] oxazepine-8-fluorenic acid methoxyethyl acetate

300 mg (1.11 mmol) of CH3 printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs call nitrogen and oxygen 8-carboxylic acid 5.0 ml (63.41 mmol) of 2-methoxyethanol and 22 mg (0.22 mmol) mixture of sulfuric acid, was stirred at reflux for 3 hours. The reaction mixture was treated by slightly concentrating, diluting with ethyl acetate, and washing with a saturated sodium carbonate solution and washing with a sodium gas solution. The organic phase was dried over sodium sulfate and concentrated. This gave 243 mg (ο% of theory) of the 20 product without further purification. LC-MS (Method 2): Rt = 3.60 minutes MS (ESIpos): m / z = 330 (M + H) + -80- 200413340 A7 B7 V. Description of the invention (79)

Example 51A Hydroxy-N- (2-methoxyethyl) -N_methyl-11-synthoxy-ΐο ,; ^ dihydrodibenzo [b, f] [l, 4] oxazepine Tetamine

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 10 250 mg (0,92 mmol) 1-Hydroxy-11-Hydroxy-1〇11-dihydrodibenzo [b, f] [l, 4] Oxyazepam-8-formic acid, 246 mg (2.777 mol) of N_ (2-methoxyethyl) methylamine and U mg (〇09 亳 mol) of 4-dimethylaminopyridine were dissolved in 6 ml DMF. The mixture was cooled i_3 (rc. At this temperature, 212 mg (1.11 mmol) of N-ethyl-N, _3 < dimethylamine 15-propylpropyl) was added to break down the diimine, and the mixture was returned to rt again. . Roll for 4 hours at RT. The mixture was worked up by diluting with water, adding in hydrochloric acid and extracting with ethyl acetate. The organic phase was washed with saturated sodium carbonate solution and sodium chloride solution, dried over sulfuric acid and concentrated. The crude product was purified on crushed gel (mobile phase: ethyl acetate). 100 mg (30% of theory) of the product were obtained. LC-MS (Method 4): Rt = 4.00 minutes MS (ESIpos): m / z = 343 (M + H) + -81- This paper size applies to China National Standard (CNS) A4 (210x297 mm) 200413340 A7 B7 V. Description of Invention (80)

Example 52A 1_ (2_Third butoxy-2-oxyoxyethoxy) -1〇_ (2_Third butoxy_2_oxyoxyethyl) -11-Hydroxy-1 〇, ll-dihydrodibenzo [b, f] [i, 4] oxazepine_8_formic acid 5

tl Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, 110 mg (0.18 mmol) _2_Hydroxyethyl) -11_Hydroxydihydrodibenzo [b, f] [l, 4] oxazepine-8-carboxylic acid 2- (trimethylsilyl) ethyl ester soluble Dissolve in 5 ml of tetrahydrosmell, add 0.2 ml (0.20 mmol) of 1N tetra-n-butylammonium fluoride solution at RT, and stir the mixture overnight at RT. Mix with a little water, add 1 ml of 1N hydrochloric acid, and concentrate at RT. The residue was purified by preparative HPLC (Method 11). This gave 95 mg (100% of theory) of the product. 20 HPLC (Method 7): Rt = 3.60 minutes MS (ESIpos): m / z = 500 (M + H) + ^ -NMR (300 MHz, DMS0-d6): 5 = 1.34 (s, 9H), l · 39 (s, 9H), 4.52-4.81 (m, 4H), 6.82 (d, 1H), 7.00 -82- Moderate rule paper on paper α ^ (labeled 97 97 2 X ο 200413340 81) five Description of the invention: 7.93 (d, 1H), 7.39-7.50 (m, 2H), 7.77 (dd, 1H), (s, lH). Example [1- (2-third butoxy-2-hyd) (Oxyethoxy) -8-cyano-11-synthoxydibenzo [b, f] [l, 4] oxazepine_110 (1111) -yl] tributylacetate 10 N = N-I ^ CHZ H3C 3 λ CH, HZC CH3 Order 15 20 &> fcr Green g (6.74 mmol) l-hydroxy-11-Hydroxydioxy · benzo [b, f] [l, 4 ] Nitrohalonitrile was dissolved in 20 liters of D] Vif 'at 5.45 ml (26.96 mmol) of tert-butyl bromoacetate and 2.794 g (20.22 mmol) of potassium carbonate were added. The mixture was stirred at RT for 1 minute, at 50 ° C. for 1 hour, and at 7 ° C. for 5 hours. The mixture was treated with a large amount of water and extracted three times with ethyl acetate. The organic phase was treated with a vaporized sodium solution Washed, dried with magnesium sulfate, and shrunk. 3.76 g (quantitative) of the product was obtained. / LC-MS (Method 7): Rt = 3.95 minutes-83- $ Zhang scale applicable in n ^^ "CNS) A4 Specifications (21〇χ 297 mm) 200413340 A7 B7 V. Description of the invention (82)

MS (ESIpos): m / z = 481 (M + H) + Example 54A 1- (2-Third-butoxy-2-hoxyoxyethoxy) -10- (2-Third-butoxy-2 _ co-oxyethyl) -11 co-10,11-dihydro-dibenzo [1), £] [1,4] oxynitride call 8-carboxylic acid 2- (trimethylsilyl silicon group ) ethyl

10 15 0.70 g (1.88 mmol) of 1-Hydroxy-11-Hydroxy-10,11 · dihydrodibenzo [b, f] [l, 4] oxygen 2- (trimethylsilyl) ethyl azahu-8-formate was dissolved in 8 ml 0%? With 11 butyl, and 0.84 ml (4.15 mmol) of tert-butyl bromoacetate and 0.521 g ( 3.77 mmol) of potassium carbonate. The mixture 20 was stirred for 10 minutes at RT and overnight at 50 ° C. The mixture was treated with a large amount of water and extracted three times with ethyl acetate. The organic phase was washed with a sodium gas solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by preparative HPLC (Method 11). This gave 209 mg (15% of theory) of the product. -84- This paper size is in accordance with Chinese National Standard (CNS) A4 (210x297 mm) 200413340 Α7 Β7 V. Description of the invention (83) LC-MS (Method 4): Rt = 4.90 minutes MS (ESIpos): m / z = 600 (M + H) +

Example 55A

[1 · (2-Third-butoxy · 2-Hydoxyethoxy) -11-Hydoxy-8- (trifluoromethyl) dibenzo [b, f] [l, 4] oxy nitrogen H-IO (IIH) -yl] tributyl acetate 10

" ° > ° Α, H3C 15 Printed 20 670 mg (2.27 mmol) of 1-hydroxy-8- (trifluoromethyl) -dibenzo [b, f] [l, 4] Oxaquinone-11 (10H) -one was dissolved in 20 ml of DMF at RT, and 1.835 ml (9.08 mmol) of tert-butyl bromoacetate and 627 mg (4.54 mmol) of carbonic acid were added. Potassium. The mixture was stirred at RT for 10 minutes, followed by stirring at 70 ° C overnight. The mixture was diluted with a large amount of water and extracted three times with ethyl acetate. The organic phase was washed with a vaporized sodium solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was borrowed from a material on silica gel (mobile phase: dichloromethane / ethyl acetate 20 ·· 1). Yield 1.185 g (99% of theory) of the product. 85- This paper size is in accordance with China National Standard (CNS) A4 (210 X 297 mm) 200413340 A7 B7 V. Description of the invention (84) LC-MS (Method 4): Rt = 4.00 minutes MS (ESIpos): m / z = 524 (M + H) +

5 耆 例 56A Example

[1- (2-Second butoxy-2-oxoethoxy) -8-deca-11-oxo dibenzo [b, f] [l, 4] oxazeptyl] acetic acid Ester 10

Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 20 15 938 mg (3.83 mmol) 8-fluoro-1-quinyldibenzopyrene dissolved in 6 liters of hydrazine-11 (10H) -one To anhydrous DMF, 59 g (11.48 mmol) of anhydrous potassium carbonate was added. With stirring at RT, 187 g (9.56 mmol) of tert-butyl bromoacetate was added. The mixture was stirred at rt overnight. Treatment was performed by diluting with ethyl acetate and washing twice with water and once with a saturated sodium gas solution. The organic phase was dried over magnesium sulfate, filtered and concentrated. To give 2 g (quantitative) of crude product, without further purification. HPLC (Method 9): Rt = 5.17 minutes-86- This paper size is applicable to Chinese National Standard (CNS) A4 specifications (210_X 297 public «) 200413340 A7 B7 V. Description of the invention (85) MS (ESIpos): m / z = 474 (M + H) +

Example 57A

[1- (2-Second butoxy_2-oxyethoxy) gas] 丨 _Hydroxydibenzo 5 [b, f] [l, 4] oxazepine-11 (1〇Η) · yl] acetate butyrate third purpose g

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, 660 mg (2.52 mmol) of 8-gas-i_hydroxydibenzooxy 15 azulone dissolved in 6 ml of anhydrous DMF, and 1.05 g (7.55 mmol) (Ear) anhydrous potassium carbonate. With stirring at rt, 23 g (6.31 mmol) of tert-butyl bromoacetate was added. The mixture was stirred overnight at rt. Treatment was performed by diluting with ethyl acetate and washing twice with water and once with a saturated sodium gas solution. The organic phase was dried over magnesium sulfate, filtered and filtered. 1.25 g (quantitative) of crude product were obtained without further purification. HPLC (Method 9): Rt = 5.24 minutes MS (DCI): m / z = 490 (M + H) + -87- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 200413340 A7 B7 V. invention is described in (86) -

Example 58A

[8-bromo-1- (2-oxo-2-butoxy third engagement ethoxy group bonded dibenzo [b, f] [l, 4] oxynitride call _10 (11η) _ yl] Tert-butyl acetate

566 mg (1.85 millimolar) -bromo- 丨 · hydroxydibenzopyroxynitrazol-11 (10H) __ is dissolved in 10 ml of anhydrous dmf and added to the '766 Milligrams (5.55 mmol) of anhydrous potassium carbonate. 901 mmol of 15 g (4 mmol) of tert-butyl bromoacetate was added under stirring at RT. The mixture was stirred overnight and removed by vacuum. The solvent, the residue was suspended in ethyl acetate and treated with water three times. The organic phase was dried over sulphuric acid, filtered and concentrated. 1.02 g (quantitative) of the crude product were obtained without further purification. 20 HPLC (Method 8): Rt = 5.34 MS (ESIpos): m / z = 534 (M + H) +

Example 59A 1- (2-Third-butoxy-2-oxyoxyethoxy) -10- (2-Third-butoxyoxy-88- This paper size applies to Chinese National Standard (CNS) A4 regulations Pyrene (210 X 297 mm) ----- " 一 "-200413340 A7 B7 V. Description of the Invention (87 Ethyl) -11-Heroxy-10,11-dihydrodibenzo [b, f ] [l, 4] oxazepine-8 · benzyl gallate 5 10

^ -ch3 H3C 15 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 20 105 mg (0.291 mmol) 1-Cyclo-11-Hydroxy · 10, ιi-dichlorodibenzo [b, f] [l, 4] winter oxynitride call at RT acid benzyl ester was dissolved in 3 ml of DMF was added 0.129 ml (0.64 mmol) acetic acid tertiary butyl acetate and desert 8〇 mg (0.58 mmol ) Carbonic acid unloading. The mixture was stirred at RT for 10 minutes and then / over night at 50 ° C. The reaction mixture was diluted with a large amount of water and extracted three times with ethyl acetate. The organic phase was washed with a vaporized sodium solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was borrowed from a silica gel material (mobile phase: methane / ethyl acetate 10: 1). This gave 123 g (71% of theory) of the product. LC-MS (Method 7): Rt = 4.21 minutes MS (ESIpos): m / z = 590 (M + H) + -89- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 200413340 A7 B7 V. Description of the invention (88)

Example 60A 1 · (2-Third-butoxy-2-synoxyethoxy) _10- (2-Third-butoxy-2-synoxyethyl) -11_synoxy · 10, 11-dihydrodibenzo | >, £] [1,4] oxazepine-8-formic acid cyclopentyl methyl ester

Economic Intellectual Property Office employee consumer cooperative printed 265 mg (0.75 mmol) of 1-hydroxy-11 co-10,11-dihydro-dibenzo [b, f] [l, 4] oxynitride call Cyclopentyl methyl-8-formate was dissolved in 15 3 liters of DMF at RT, and 0.333 ml (1.65 mmol) of tert-butyl bromoacetate and 207 mg (1.50 mmol) of potassium carbonate were added. The mixture was stirred at RT for 10 minutes, followed by stirring at 50 ° C overnight. The reaction mixture was diluted with a large amount of water and extracted three times with ethyl acetate. The organic phase was washed with a vaporized sodium solution, dried over magnesium sulfate, and concentrated in vacuo. Residue was taken on a silicone material (mobile phase: methane / ethyl acetate 10: 1). This gave 260.0 mg (59% of theory) of the product. LC-MS (Method 3): Rt = 4.93 minutes MS (ESIpos): m / z = 582 (M + H) + -90- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 200413340 A7 B7 V. Description of the invention (89) f Example 61A 1_ (2_Third butoxy-2-oxoethoxy) -10_ (2_Third butoxy_2_oxoethyl) -11-Hydroxy-1O, 11-dihydrodibenzo [1], phantom [154] oxazepine-8-formic acid 2-methoxyethyl 10

L〇 ° ° Ύ ° ρ〇 ^ X h3c 15 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 20 225 mg (0.68 mmol) 1_hydroxy_11_hexy-10, ^ -dihydro Dibenzo [b, f] [M] oxazepine-8-carboxylic acid 2-methoxyethyl ester was dissolved in 3 ml of DMF at RT, and 0.28 ml (I · 37 mmol) of acetic acid was added. dibutyl and 189 mg (1.37 mmol) of potassium carbonate. The mixture was dropped at RT for 10 minutes, followed by incubation overnight at 5 ° C. The reaction mixture was diluted with water and extracted with ethyl acetate three times for processing. Washed with 9-cavity sodium solution, dried over magnesium sulfate, and vacuumed. Zhongzengmu was gasified on silicon material (mobile phase: 248 mg (61% of theory) of methane / ethyl acetate) a) ° LC-MS (Method 2): Rt = 4.00 minutes • 91 · This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) line 200413340 A7 B7 V. Description of the invention (90MS (ESIpos): m / z = 558 (M + H) +

Example 62A

[1- (2-Third-butoxy-2-oxoethoxy) -8-{[(2-methoxyethyl) (methyl) amino] -carbonyl} -11-oxodi Benzo [b, f] [l, 4] oxazepine-ΙΟ (ΙΙΗ) -yl] tert-butyl acetate 10

1, CH3, CH, CH,

i Custom Line 1585 mg (0.25 mmol) of 1-hydroxy -N- (2- methoxyethyl) -N- methyl - Intellectual Property Office employee Economic Co-op group bonded printed 11- - 10,11-dihydrodibenzo [1], £] [1,4] oxazepine-8-carboxamide was dissolved in 6 ml of DMF at RT, and 0.11 ml (0.55 mmol) of bromine was added acid tert-butyl ester and 69 mg (0.50 mmol) of potassium carbonate. The mixture was stirred at RT for 10 minutes, and then stirred at 5 ° C overnight. The reaction mixture was diluted with a large amount of water and extracted three times with ethyl acetate and washed with sodium chloride solution. The organic phase was treated with sulfuric acid Dry with sodium, remove the solvent by evaporation, and dry the residue. 136.0 mg (94% of theory) of the product is obtained. 0 -92- This paper size applies the Chinese National Standard (CNS) A4 regulations (2i0 X 297 mm) 200413340 kl B7 V. Description of the invention (91) LC-MS (Method 4): Rt = 4.30 minutes MS (ESIpos): m / z = 571 (M + H) +

Example 63A

[1- (2-oxo-2-butoxy third engagement methoxyethoxy) -8 - [(diethylamino) - carbonyl] oxy -11- combined dibenzo [b, f] [l, 4] oxynitride call -IO (IIH) - yl] acetic acid tert-butyl ester 10

i Order 15 71 mg (0.150 millimolar) printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 2-Hydroxyethyl) -11-Hydroxy-10,11-diazadibenzo [b, f] [l, 4] oxazepine-8-carboxylic acid at RT, used in 4 ml DMF 28 mg (0.23 mmol) of DMAP and 114 mg (0.30 20 mmol) of hexafluorophosphate 0 (7-azabenzotriazol-1-yl) -N, N, N ', N '_ra Methylureazone was dissolved and 0.031 ml (0.30 mmol) of diethylamine was added. The mixture was stirred overnight at at RT. The reaction solution was diluted with water and extracted with ethyl acetate. Each organic was washed once with a sodium carbonate solution and a gasified sodium solution. The organic phase was dried over magnesium sulfate and concentrated in vacuo. Residual -93- line This paper is sized for China National Standard (CNS) A4 (210 X 297 mm) 200413340 A7 B7

The material was filtered with suction through a silica gel frit (mobile phase: ethyl acetate) and concentrated in vacuo. This gave 74 mg (85% of theory) of the product. LC-MS (Method 3): Rt == 4.24 minutes 5 MS (ESIpos): m / z-555 (M + H) +

Example 64A 1-Benzyloxy-10- (2-tert-butoxyethyl) _u-synthoxy_1〇11_dihydrodibenzo [b, f] [l, 4] oxazepine- 8- carboxylate 10

15 Printed by 255 mg (1.2 mmol) 2-tert-butoxyethyl bromide, 276 mg (2.0 mmol) potassium carbonate and 26.5 mg (0.16 mmol) ear) of potassium iodide in 300 continuously added 20 mg (0.8 mmol) Example 38 compound eight to 〇〇6 mL DMF / 1,4 · the two Zhi dioxane solution 12 ml. The mixture was stirred at an oil bath temperature of 60 ° C for 1 hour, and then stirred at a reflux temperature for 30 hours. After cooling to RT, it was diluted with 100 ml of dichloromethane and washed with water. The organics were dried over magnesium sulfate and concentrated in vacuo. Obtained 411 millimeters -94- This paper size is applicable to China g ^ (CNS) A4 gauge ⑽χ tear public hair) 200413340 A7 B7 V. Description of the invention (93) grams (95% of theoretical value) required product. LC-MS (Method 4): Rt = 3.37 minutes MS (ESI): m / z = 476 (M + H) + 5] H-NMR (200 MHz, DMSO-d6): (5 = 1.07 (s, 9H ), 3,58 (m, 2H), 3.79 (m, 1H), 3.81 (s, 3H), 4.35 (m, 1H), 5.10 (d, 1H), 5.19 (d, 1H), 6.96 (d, 1H), 7,04 (d, 1H), 7.28- 7.49 (m, 7H), 7.77 (d, 1H) 8.59 (s, 1H).

10 Example 65A {[10- (2-Third-butoxyethyl) -8-cyano-11-synoxy-10,11-dihydrodibenzo [b, f] [l, 4] oxy nitrogen call _1_ yl] oxy} acetate

5 IX Ministry of Economic Affairs Intellectual Property Office employees consumer cooperatives printed 20

ο- embodiment as in Example 64A from 125 mg (0.39 mmol) compound of Example 39A and 123 mg (0.58 mmol) bromo-butoxyethyl third embodiment was prepared. The crude product was chromatographed on silica (cyclohexane: ethyl acetate 3: 1). 68 mg (41% of theory) of the desired product were obtained. -95- This paper size is in accordance with China National Standard (CNS) A4 specifications (210 X 297 issued) 200413340 Α7 Β7 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 5. Description of the invention (94) LC-MS (Method 5): Rt = 3.38 minutes MS (ESI): m / z = 425 (M + H) + ^ -NMR (200 MHz, DMSO-d6): (5 = 1. 05 (s, 9H), 3. 42 5 (m , 1H), 3.58 (m, 1H), 3.68 (s, 3H), 4.13 (m, 2H), 6.85 (d, 1H), 7.01 (d, 1H), 7.42 (dd, lH), 7. 53 (d, 1H), 7.70 (d, 1H), 8.36 (s, 1H).

10 Example 66A 1_ (benzyloxy) _10_ (2-tert-butoxyethyl) -3-methyl_11-synoxy-10,11-dihydrodibenzo [b, f] [ l, 4] oxazepine-8-methyl formate

As in Example 64A, it was prepared from 428 mg (1.10 mmol) of the compound from Example 40A and 398 mg (1.65 mmol) of tert-butoxyethyl bromide. To give 295 g of a difference (55% of theory) of the desired product. -96-

This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 200413340 A7 B7 V. Description of the invention (95) LC-MS (Method 2): Rt = 4.33 minutes MS (ESI): m / z = 490 (M + H) + ^ -NMR (200 MHz, DMSO-d6): (5 = 1.05 (s, 9H), 2. 31 (s, 3H), 3.58 (m, 2H), 3.62 (m, 2H ), 3.81 (s, 3H), 5 3.82 (m, lH), 4.33 (m, lH), 5.08 (d, lH), 5.14 (d, lH), 6.81 ( s, lH), 6.90 (s, 1H), 7.27-7.48 (in, 6H), 7.76 (d, 1H), 8.58 (s, 1H).

Example 67A 10 ({10 - [(5- sec-butyl -1,2,4-σ Deficit two Han 3-yl) methyl] -8-- gas yl -11-bonded group 10,11 - dihydro-dibenzo [b, f] [l, 4] -l- yl} oxynitride call yloxoacetate

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 20 According to the method of Example 64A, from 186 mg (0.57 mmol) of the compound of Example 39A and 120 mg (0.69 mmol) of 5-tert-butyl-3- ( Gas methyl) -1,2,4-pyridadiazole was prepared. The crude product was isolated by preparative HPLC (Method 11). This gave 28 mg (10% of theory) of the desired product. -97- This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 200413340 Α7 Β7 V. Description of the invention (96) LC-MS (Method 4): Rt = 3.01 minutes MS (ESI): m / z = 463 (M + H) +. ^ -NMR (400 MHz, DMSO-d6): 5 = 1.35 (s, 9H), 3.63 (s, 3H), 4.82 (d, 1H), 4.87 (d, 1H) 5.31 (d, 1H) 5.49 (d, 1H), 6.87 (d, 1H), 7,04 (d, 1H), 7.45 (dd, 1H), 7.60 (d, 1H), 7.73 (d , 1H), 8.31 (s, 1H). 4

Example 68A 10 {[8- cyano-10- (4,4-dimethyl-2-yloxy bonded pentyl) -11-bonded group 10,11. Dihydro-dibenzo [b, f ] [l, 4] oxazepine-1-yl] oxy} methyl acetate 15

〇 \ CH, Thread I 1 I • Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economy 20 As in Example 64A, from 224 mg (0.69 mmol) of the compound of Example 39A and 171 mg (0.83 mmol) 1- Bromo-4,4-dimethyl-2-pentanone was prepared. The crude product was chromatographed on silica gel (cyclohexane: ethyl acetate 5.1). This gave 111 mg (37% of theory) of the desired product. -98- This paper size is in accordance with Chinese National Standard (CNS) A4 (210x297 mm) 200413340 A7 B7 V. Description of the invention (90 LC-MS (Method 10): Rt = 2.37 minutes MS (ESI): m / z = 437 (M + H) +. 4-NMR (200 MHz, DMSO-d6): 5 = 0.998 (s, 9H), 2.36 (d, 1H), 2.43 (d, 1H), 3.67 ( s, 3H), 4.81 (s, 2H), 5 4.91 (s, 2H), 6.87 (d, 1H), 7.04 (d, 1H), 7.45 (dd, 1H), 7. 57 (d, 1H), 7.71 (s, 1H), 7.87 (d, 1H).

Example 69A (R, S) -2- [8-cyano-1- (2-methoxy-2-hexyloxyethoxy) -11-hexyloxy 10 benzo [b, f] [ 1,4] oxazepine-IO (IIH) -yl] tributyl propionate

CH3 Printed solution of 267 mg (0.82 mmol) of the compound of Example 39A and 206 mg of 20 (0.99 mmol) of methyl 2-bromopropionate in 20 ml of DMF and 227 mg (1.65 mmol) potassium carbonate was mixed and stirred overnight at RT. An additional 3 equivalents of potassium carbonate and methyl 2-bromopropionate were each added, and the mixture was stirred at RT. 20 ml of 1M hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The combined extraction solution was dried with magnesium sulfate and concentrated in a vacuum. -99- This paper size is in accordance with Chinese National Standard (CNS) A4 (210x297 mm) 200413340 A7 B7 V. Description of the invention (98). The crude product was chromatographed on silica (cyclohexane: ethyl acetate 3: 1). This gave 250 mg (67% of theory) of the product. LC-MS (Method 10): Rt = 2.32 minutes 5 MS (ESI): m / z = 475 (M + Na) +.! H-NMR (300 MHz? CDC13): (5 = 1.35 (s, 9H) , 1.63 + 1.67 (2xd, 3H), 3.66 (s, 3H), 4.62 + 4.89 (2xq, 1H), 4.82 (s, 2H), 6.88 (d, 1H), 7.03 (d, 1H), 7.45 (dd , 1H), 7.59 (m, 1H), 7.75 (m, 1H), 7.90 + 10 7.95 (2xs, 1H).

Example 70A 10- (2-Third-butoxyethyl) -1-meryl-11-synthoxy-10,11-diazadibenzo 15 [b, f] [l, 4] oxazepine 8-carboxylate

The Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs printed 394 mg (0.83 mmol) of the compound of Example 64A in 15 ml-100-This paper size applies to China National Standard (CNS) A4 (210x 297 mm) 200413340 Α7 Β7 5 2. Description of the invention (99) The solution in ethanol is mixed with 66 mg of 10% palladium on activated carbon. The suspension was stirred at atmospheric pressure under a hydrogen atmosphere for 20 hours. Filter through diatomaceous earth, wash with 20 ml of ethanol, and concentrate in vacuo. This gave 227 mg (68% of theory) of the desired product. LC-MS (Method 7): Rt = 3.69 minutes MS (ESI): m / z-386 (M + H) +. (S, 9H), 3.71 ^ -NMR (200 MHz, DMSO-d6): δ = 1.] (m, 2H), 3.85 (s, 3H), 4.07 (m, 2H), 6.75 (d, 1H), 10 6.82 (d, 1H), 7.35 (dd, 1H), 7.46 (d , LH), 7.80 (d, 1H), 8.51 (s, 1H), 10.3 (s, br, 1H). Order

Embodiment Example 71A 15 10- (2 - Second butoxyethyl) -1-by-3-methyl-10,11-dihydro-bonded _11- dibenzo [b, f] [l, 4] 8-carboxylate oxygen and nitrogen line call economic intellectual property Office employee consumer cooperative printed 20 h ^ ° y〇C ° Ο N-

-101- This paper size is in accordance with China National Standard (CNS) A4 (210 x 297 mm) 200413340 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (100) 265 mg (0.54 millimolar) Example 66A compound 1 in 24 ml of ethanol and ethyl acetate: 1 mixture of the solution was mixed with 58 mg of 10% palladium on activated carbon and 205 mg (3.3 mmol) ammonium formate. The mixture was stirred at reflux temperature for 2 hours. After cooling to RT, it was filtered through calcium ore and washed with ethanol. After condensing the volatile components, it was dissolved in ethyl acetate and washed several times with water. The organic phase was dried over magnesium sulfate and concentrated in vacuo. This gave 222 g (99% of theory) of the desired product. LC-MS (Method 4): Rt = 3.38 minutes 10 MS (ESI): m / z = 400 (M + H) +. ^ -NMR (200 MHz, DMSO-d6): 5: 1.08 (s, 9H) , 2. 23 (s, 3H), 3.71 (m, 2H), 3.83 (s, 3H), 4.10 (m, 2H), 6.61 (s, 1H), 6.68 (s, 1H), 7.43 (d , 1H), 7.82 (d, 1H), 8.49 (s, 1H), 10.3 (s, br, 1H). -102- This paper size applies to China National Standard (CNS) A4 (210x297 mm) 200413340 A7 B7 Fifth, the invention is described (i〇l)

Example 72A 1- [2- (fluorenyloxy) -2-hexylethylethenyl] -10- (2-second butoxyethyl) -11_hexyl-10,11-dihydrodiphenyl And [1), £] [1,4] oxazepine-8-formate

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs As in Example 7A, it was prepared from 211 mg (0.55 mmol) of the compound of Example 70A and 125 mg (0.55 mmol) of benzyl bromoacetate. Purification by chromatography on silica gel (dichloromethane: methanol 1: 0 to 3: 1) gave 15 279 mg (85% of theory) of the product. LC-MS (Method 2): Rt = 4.08 minutes MS (ESI): m / z = 534 (M + H) +. WNMR (200 MHz, DMSO-d6): 5 = 1.07 (s, 9H), 3. · 53 20 (m, 2H), 3.75 (m, 1H), 3.82 (s, 3H), 4.37 (m, 1H), 4.86 (d, 1H), 4.91 (d, 1H), 5 · 12 (s, 2H), 6.86 (d, 1H), 7.0 (d, 1H), 7.27 (s, 5H), 7.38 (dd, 1H), 7.46 (d, 1H) ， 7.76 (d, 1H), 8.52 (s, 1H) · -103- The standard of the paper is applicable to the Chinese National Standard (CNS) A4 (210x297 mm) 200413340 A7 B7 V. Description of the invention (1〇2) Implementation Example 73A 1- [2- (Benzyloxy) -2-synthoxyethoxy] _10- (2-tert-butoxyethyl) -3-methyl-11-synthoxy-1〇, 11 -Dihydrodibenzo [1], £] [1,4] oxazepine_8-formic acid methyl ester 5 ο 1

C

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs As in Example 7A, it was prepared from 93 g (0.48 mmol) of the compound of Example 71A and 140 mg (0.58 mmol) of benzyl bromoacetate. Purified by chromatography on silica (: methanol 1: 0 to 3: 1, two gas methane) to produce 241 ml 15 g (92% of theory) of product. LC_MS (Method 7): Rt = 3.72 minutes MS (ESI): m / z = 548 (M + H) +.! H-NMR (200 MHz, DMSO-d6): 1.07 (s, 9H), 2. 23 20 (s, 3H), 3.55 (m, 2H), 3.75 (m, 1H), 3.83 (s, 3H), 4.25 (m, 1H), 4.87 (s, 2H), 5.12 (s, 2H), 6.65 (s, 1H), 6.83 (s, 1H), 7.29 (s, 5H), 7.39 (dd, 1H), 7.41 (d, 1H), 7: 76 (d, 1H), 8.52 (s, 1H). -104- This paper size is applicable to TD National Standard (CNS) A4 (210 X 297 mm)

200413340 A7 B7 V. Description of the invention (103)

Example 74A 1-Cycloyl-11-synyloxy-10- [2-synyl-2- (1-11 hexamethyl) ethyl] -10,11-diargondibenzo [b, f] [l, 4] oxazepine-8-carboxylic acid 2-methoxyethyl ester

10 15 150 mg (0.46 mol) 1-hydroxy-11-synthoxy-10,11-dihydrodibenzo [b, f] [l, 4] oxazepine-8-carboxylic acid 2-methoxy Ethyl acetate was dissolved in 6 ml of DMF at RT, and 0.097 ml (0.46 mmol) of 1- (bromoacetamido) piperidine and 126 mg (0.91 mmol) of potassium carbonate were added. The mixture was stirred at RT for 10 minutes and then at 50 ° C overnight. The reaction solution was diluted with 1 ml of water and worked up by preparative HPLC (Method 11). This gave 66 mg (27% of theory) of the product. Order! 1 I • LC-MS printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economy (Method 7): Rt = 3.59 minutes 20 MS (ESIpos): m / z = 455 (M + H) + 105- This paper size Applicable to China National Standard (CNS) A4 specification (210 X 297 mm) 200413340 A7 B7 V. Description of invention (104)

Example 75A 1- [2- (Benzyloxy) -2-hexyloxyethoxy] -π-hexyloxy-HK2-hexyloxy 2- (1-piperidinyl) -ethyl] -1 〇, ii • dihydrodibenzo [b, f] [l, 4] oxy nitrogen f8 formic acid 2-oxoethyl

62 mg (0.12 mmol; 87% purity) of the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 1-Hydroxy-1P containing a gas group — 1〇_ [2_ 合 oxy-2- (1-piperidinyl) Ethyl] _1〇, 11_dihydrodibenzo 15 0, [1,4] oxazepine-8-carboxylic acid 2-methoxyethyl ester was dissolved in 6 ml of DMF at 10, and 0 · was added. 42 ml (o.is mmol) of benzyl bromoacetate and 33 mg (0.24 mmol) of carbonate were removed. The mixture was allowed to stir for 15 minutes at rt and then stirred overnight at 50 ° C. The reaction solution was diluted with 1 ml of water and purified by preparative HPLC (Method 11). 0 mg (71% of theory) of the product was obtained. LC_MS (Method 4): Rt = 4.30 minutes MS (ESIpos): m / z = 603 (M + H) + -106-

200413340 A7 B7 V. Description of the invention (105)

Example 76A {[10-[(5-Third-butyl-1,2,4-oxadiazol-3-yl) methyl] -11-hexyloxy-8- (trifluoromethyl) -10, 11-dihydrodibenzo [b, f] [l, 4] oxazepine] oxy} methyl acetate

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, 94 亳 g (0.26 mmol) {[11-Hydroxy-8- (trifluoromethyl) -10,11-dihydrodibenzo [1] [1,4] oxazepine-1-yl] oxy} methyl acetate was dissolved in 5 ml of DMF at RT, and 89 亳 g (0.51 mmol 15 ears) was added. gas meth) Zhi-1,2,4-oxadiazole and 71 mg (0.51 mmol) of potassium carbonate. The mixture was stirred at RT for 10 minutes and at 50 ° C for 2 hours. The mixture was diluted with water / acetonitrile and purified by preparative HPLC (Method 11). This gave 103 mg (79% of theory) of the product. 20 LC-MS (Method 4): Rt = 3.90 minutes MS (ESIpos): m / z = 506 (M + H) + -107- This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs, 200413340 Α7 Β7 V. Description of Invention (106)

Example 77A {[10- (2_Third-butoxyethyl) _11βHydroxy_8- (trifluoromethyl> 10, n_dihydrodibenzo [b, f] [l, 4 ] Oxoazepine_1βyl] oxy 丨 methyl acetate

OIC 94 mg (0.26 millimolar dong (trifluoromethyl 10, π-dihydrodibenzo [b, f] [l, 4] oxazepine] oxy) methyl acetate at RT Dissolve in a mixture of 0.2 ml of DMF and 40 ml of dioxane 15 and add 71 mg (0.51 mmol) of potassium carbonate and 85 mg (0.05 mmol) of potassium iodide. The mixture is stirred at 6 (rc). After 1 hour, 孓 (2-bromoethoxy) -2-methylpropane was added. The mixture was stirred at 100 ° C overnight, and another 93 mg (0.51 mmol) of 2 · (2-acetone) was added. ) _2_Mesyl propionate mixture and then stirred overnight at 100t. The reaction solution was purified by preparation = '20 method Η) and purified. 33.0 mg (theoretical value of 27 / / cube. 〇) produced LC- MS (Method 4): Rt = 4.00 minutes MS (ESIpos): m / z = 468 (M + H) + -108-

1¾ scale is applicable to Chinese national standard (CNSU4 specification (210x297). 200413340 A7 B7 V. Description of invention (l07

Example 78A {[1〇- [2- (Third-butylamino) -2-hexyloxyethyl] 8- (methoxy) -n-hexyloxy-HU-dihydrodibenzo M [1, 4] oxazepine] oxy} acetic acid

° ^ 〇HX CH, 10 mg (0.14 mmol) of tertiary butylamine and 4 4 10 畑: 14 mg (0.05 mmol) of dimethylamino 20 mg ((U1 mmol) ) According to 3 dimethylaminopropyl) ethylcarbodiimide was added to the compound of 3 mM, gram (continued mol) to 9A, after overnight in the room, the pressure was reduced. The solvent was removed, and the residue was purified by preparative HPLC (Method 11) to produce 14 mg (π% of theory). LC-MS (Method 2) printed by the Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs: Rt = 3.9 minutes 20 MS (ESI): m / z = 547 (M + H) +.] H-NMR (400 MHz, DMSO-d6): 1.27 (s (s, 3H), 4.65 (AB signal, 2H), 4 · 09〇9H), 3.85 (AB signal,

2H), 5.17 (s, 2H), 6.89 (s, 1H), 7.05 (s ^ j) 7.32 (s, 4H), 7.44 (dd, 1H), 7.50 (d, 1H) '7 77L, 109- A7 B7 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs, 200413340 V. Description of the invention (108 7 · 82 (m, 2H), 7.96 (d, 1H). Example: Example 1 5 {[1〇- (2-Third-butoxy-2-synoxyethyl) -8- (methoxycarbonylb ^ -synoxy 1 10,11-monolactodibenzo [6, 1,4] oxazepine-1-yl] oxy} ethene

15 2. ^ 1 mg of trimethylsilyl gas (0.020 mmol) and 29 g of sodium iodide (0.020 mmol) were added to 0.10 g (0.19 mmol) of 3 ml of gas imitation Mol) The compound of Example 5A, and the mixture was heated under reflux overnight. The mixture was diluted with 20 ml of ethyl acetate and extracted three times with 20 ml of 1N hydrochloric acid each time. The organic phase was dried over magnesium sulfate. Pressure to eliminate the solvent removed to give residue 20, which by preparative HPLC (Method 11) gave 75 mg (84% of theory) of product. MS (ESI): m / z = 458 (M + H) +. 'H-NMR (400 MHz, DMSO-d6): δ-L 38 (s, 9H), 3.84 -110- Applicable to this paper size Chinese National Standard (CNS) A4 Regulations (210 X 297 mm)

200413340 A7 B7 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs V. Invention Description (109) (s, 3H), 4.56 (s, 2H), 4.68 (s, 2H), 6.80 (d, 1H) , 6.97 (d, 1H), 7.42 (t, 1H), 7.50 (d, 1H), 7.80 (dd, 1H), 7.96 (d, 1H). 5 Example 2 10- (2-third butoxy-2-oxoethyl) -1- (carboxymethoxy) -11-synoxy-10,11-dihydrodibenzo | >, £] [1 , 4] oxynitride call 8-carboxylic acid

ch3 15 0 ^ 27 g (0.53 mmol) of the compound of Example 5A in 2.5 ml of methanol was mixed with 30 mg (0.53 mmol) of potassium hydroxide and stirred at room temperature for 4 hours. The mixture was poured into 15 ml of ethyl acetate and extracted three times with 20 ml of a 1 N sodium hydroxide solution each time. The aqueous phase was acidified with concentrated hydrochloric acid and extracted three times with 20 ml of ethyl acetate. The organic phase was dried over magnesium sulfate. Removal of the solvent under reduced pressure yielded 0.17 g (65% of theory) of product. MS (ESI): m / z = 444 (M + H) +. ^ -NMR (200 MHz, DMSO-d6): δ = L 38 (2, 9H), -111- This paper scale is applicable to Chinese national standards ( CNS) A4 觇 袼 (210 X 297 mm)

200413340 A7 B7 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economy ), 7.79 (dd, 1H), 7.95 (d, 1H), 13.0 (br. S, 2H). 5 Example 3 [1- (carboxymethoxy) -8- (methoxycarbonyl) -11- Oxydibenzo [b, f] [l, 4] oxazepine-1O (11Η) -yl] acetic acid

0.10 g (0.19 mmol) of the compound of Example 5A in 3 ml of dioxane was mixed with 60 µl (88 mg, 0.78 mmol) of trifluoroacetic acid and stirred at room temperature for two days. The mixture was poured into 15 ml of ethyl acetate and extracted three times with 20 each of 20 ml of 1N hydrochloric acid. The organic phase was dried over magnesium sulfate. Removal of the solvent under reduced pressure gave a residue, which was purified by preparative HPLC (Method 11) to yield 26 mg (32% of theory) of the product. MS (ESI): m / z = 402 (M + H) +. -112- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm)

200413340 A7 B7 V. Description of the invention (111) ^ -NMR (200 MHz, DMSO-d6): δ = 3.84 (s, 3H), 4.55-4.85 (m, 4H), 6.83 (d, 1H), 7.01 (d, 1H), 7.45 (dd, 1H), 7.50 (d, 1H), 7.81 (dd, 1H), 7.98 (d, 1H), 13.0 (br.s, 2H). Example 4 1- (carboxyl (Methoxy) -10- (carboxymethyl) -11-synthoxy-10, ll-dihydrodibenzo [b, f] [l, 4] oxazepine-8-formic acid 10 15

〇

OH order

Line II Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economy 20 50 mg (0.10 mmol) of the compound of Example 5A in 1 ml of dioxane and 300 μl of water mixed with η mg (0J9 mmol) potassium hydroxide ' and stirred overnight at room temperature. The mixture was poured into 10 ml of ethyl acetate 'and extracted three times with 10 ml of 1N hydrochloric acid each time. The organic phase was dried over magnesium sulfate. The solvent was removed under reduced pressure. The residue was purified 'by preparative HPLC (Method 11) to give 12 milligrams (29% of theory) of the product. -113- This paper size is in accordance with China National Standard (CNS) A4 specification (21 × 297 Gongchu) 200413340 A7 B7 V. Description of the invention (ll2) MS (ESI): m / z = 388 (M + H) +. ! H-NMR (300 MHz, DMSO-d6): (5 = 4.5-4,8 (m, 4H), 6.83 (d, 1H), 7.00 (d, 1H), 7.41-7.49 (m, 2H), 7.78 (dd, 1H), 7.95 (d, 1H), 13.1 (br · s, 3H) · Example 5 (R, S)-{[10_ (2-thirdbutoxy-1-methyl- 2-Hydroxyethyl) -8- (methoxyquinyl) -11-Hydroxy-i〇, ii-dihydrodibenzo [b, f] [i, 4] oxazepine-1- Yl] oxy 10 yl} acetic acid

Member of the Intellectual Property Bureau of the Ministry of Economic Affairs, Consumer Cooperation, printed t 16 g (0.03 mmol) of a solution of the compound of Example 7A in 1 ml of THF 20 under argon was mixed with 5 mg of 10% activated carbon on palladium And stir in a hydrogen atmosphere for 2 hours. The mixture was filtered through calcium ore, washed with ethyl acetate 'and concentrated in vacuo. 1〇 mg of product was obtained (theoretical value 71〇 / square). LC-MS (Method 2) H7 minutes-114- scales are applicable to China Standards (CNS) A4 ^ T210729T ¥¥ 1 ---- 200413340 A7 B7 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs ) MS (ESI): m / z = 472 (M + H) +. ^ -NMR (400 MHz, DMSO-d6): δ = L 36, 1.40 (2xs, 9H), 1.48, 1.52 (2xd, 3H) , 3.83 (s, 3H), 4.70 (s, 2H), 4.89 (m, 1H), 6.82 (dd, 1H), 7.00 (d, 1H), 5 7.42 (dd, 1H), 7.51 (d, 1H) , 7.82 (d, 1H), 7.85 (s, 1H), 13.05 (sbr, 1H). Example 6 {[10- {2- [Third-butyl (methyl) amino] _2-Hydroxyethyl Gab 8- (methoxy M 10 group) -Π-synthoxy-lO, ll-dihydrodibenzo [b, f] [l, 4] oxazepine-1-yl] oxy} acetic acid

20 By the method described in Example 5, 75 mg (0.13 mmol) of the compound of Example 10A was used to obtain 75 mg (0.13 mmol) of a solid, which was crystallized from digas methane / diethyl ether to obtain 28 mg (45% of theory). %)product. LC-MS (Method 3): Rt = 3.47 minutes -115- This paper size applies to China National Standard (CNS) A4 (210 x 297 mm)

200413340 A7 B7 V. Description of the invention (1H) MS (ESI): m / z = 471 (M + H) +. Example 7 5 ((8- (methoxycarbonyl) -10- [2- (neopentyloxy) yl) -2-oxoethyl bonded] -11-bonded group 1〇, 11-dihydro-dibenzo [b, f] [l, 4] oxynitride call small-yl} oxy) acetic acid

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 15 Using the method described in Example 5 to obtain a solid from 60 mg (0.11 mmol) of the compound of Example 11A and crystallize from diethyl ether to obtain 30 mg (60% of theory) product. LC-MS (Method 3): Rt = 3.70 min. 20 MS (ESI): m / z = 472 (M + H) +. Example 8 {(10- (4,4-dimethyl-2-oxo (Pentyl) -8- (methoxycarbonyl) -11-hexyloxy- -116- This paper size applies to China National Standard (CNS) A4 (210 x 297 mm) 200413340 A7 B7 Employees ’Intellectual Property Bureau of the Ministry of Economic Affairs Printed by the cooperative V. Description of the invention (115) 10,11-dihydrodibenzo [1], phantom [1,4] oxazepine-1-yl] oxy} acetic acid

10 284 mg (0.52 mmol) of the compound of Example 13A in 26 ml of ethyl acetate: ethanol 1: 1 under argon with 197 mg (3.1 mmol) of ammonium formate and 111 mg of 10% activated carbon on palladium mixing. The mixture was stirred at an oil bath temperature of 80 ° C for 3 hours, cooled to RT and filtered through a calcium ore. The filtrate was diluted with ethyl acetate and washed with 0.1 M hydrochloric acid. The combined organic phases were dried over 15 magnesium sulfate and concentrated in vacuo. This gave 222 mg (80% of theory) of the desired product. LC-MS (Method 3): Rt = 3.59 minutes MS (ESI): m / z = 456 (M + H) +. 20 ^ -NMR (200 MHz, DMSO-d6): 1.02 (s, 9H), 2 38 (d, 1H), 2.52 (d, 1H), 3.82 (s, 3H), 4.69 (s, 2H), 4.78 (d, 1H), 4.99 (d, 1H), 6.81 (d, 1H), 7.01 (d, 1H), 7.45 (dd, 1H), 7.50 (d, 1H), 7.79 (m, 2H), 12.97 (s, br, 1H). -117- This paper size applies to the Chinese National Standard (CNS) A4 size (210x 297 mm)

200413340 A7 B7 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 5. Description of the Invention (116) Example 9 (11,3) -1-{[10- (2- (4,4-dimethyl-2-hydroxyl Amyl) -2-Hydroxyethyl) -8- (fluorenyloxycarbonyl) -11-hexyloxy-10,11-dihydrodibenzo [1], phantom [1,4] oxy nitrogen 5 H-1-yl] oxy} acetic acid

35 mg of sodium borohydride was added in portions over a period of 24 hours to a solution of 50 mg (0.11 15 mmol) of the compound of Example 8 in 2 ml of methanol. After the reaction was completed, 20 ml of ethyl acetate was added, the solution was washed with water, and the combined organic extract was dried over magnesium sulfate. The volatile components were removed in vacuo and the residue was chromatographed on silica gel (ethyl acetate: cyclohexane 1: 1). This gave 18 mg (35% of theory) of the desired product. 20 LC-MS (Method 3): Rt = 3.25 minutes MS (ESI): m / z = 458 (M + H) +. -118- This paper size applies to China National Standard (CNS) A4 (210 x 297) Mm)

A7 B7 V. Description of the invention (117) Example 10 {[10_ (2-Third butoxy gas ethanedibenzo [b, f] [i, 4] oxazepine_11_hexydi Breathadenyl] fluorenyl} acetic acid

Yi milligram (0.21 millimolar): group) _8 • cyano_11-Hydroxy-2 cage-butoxy-2-butoxyethoxy 15 20 The third butyl vinegar is soluble at RT '$, 4] Oxygen _10 (_ g acetate (0.21 mmol) acetic acid trimethylsuppressor and di 3 = medium 'add 22 mmol' ^ siloxanes and 31 mg (0.21 mmol) iodine, compound in Under reflux _ overnight. After cooling, dilute with dichloromethane and add 1 ml of 1N hydrochloric acid. The reaction mixture was in vacuo. The residue was dissolved in DMSO and purified by preparative HPLC (Method u). 36 mg (theoretical value) 40%) product. LC-MS (Method 7): Rt = 3.41 minutes MS (ESIpos): m / z = 425 (M + H) + ^ -NMR (300 MHz, DMS0-d6): 1.34 ( s, 9H), 4.49-4.88 (m, 4H), 6.86 (d, lH), 7.02 (d, lH), -119- scale applicable Zhang China national standard (CNS) A4 size (2 male hair 〖0 x 297 ) 200413340 A7 B7 V. Description of the invention (118) 7.46 (t, 1H), 7.58 (d, 1H), 7.73 (d, 1H), 8.01 (s, 1H), 13. 00 (sbr, 1H). Example 11 4 [(10- (2 • Third-butoxy-2-synyloxyethyl) -11-synthoxy-8-{[2- (trimethylsilyl) ethyl] carbonyl 10, ll-dihydrodibenzo [b, fl [l, 4] oxazepine-l-yl) oxy] acetic acid 10 15 Η3α

OH Order I! I • Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, 70 mg (0.12 mmol) 1- (2-Third-Butoxy-2_Hydroxyethoxy) -10- ( 2 -Third-butoxy-2-synoxyethyl) 11-synoxy-10,11-diazadibenzo [b, f] [l, 4] oxazepine-8-carboxylic acid 2- (Trimethylsilyl) ethyl ester was dissolved in 3 ml of trifluoromethane at 20 RT. 13 mg (0.12 mmol) of trimethylsilane and 17 mg (0.12 mmol) of iodide were added. sodium. The mixture was stirred at reflux for 3 hours. After cooling, it was diluted with digas methane and 1 ml of 1N hydrochloric acid was added. The reaction mixture was concentrated in vacuo. The residue was dissolved in DMSO and purified by preparative HPLC (Method 11). 36 mg-120- This paper is in accordance with the Chinese national standard (CNSU4 regulation (210 X 297 mm) 200413340 A7 B7 V. Product description (119) (56% of theory). LC-MS (Method 7) ): Rt = 4.26 minutes MS (ESIpos): m / z = 544 (M + H) + ^ -NMR (300 MHz, DMS0-d6): 5 = 0 · 01 (s, 9H), 1 · 01 (t , 2H), 1 · 35 (s, 9H), 4 · 31 (t, 2H), 4.49-4.71 (m, 4H), 6 · 80 (d, 1H), 6.96 (d, 1H), 7 · 36 -7 · 48 (m, 2H), 7 · 74 (dd, 1H), 7 · 89 (s, 1H), 12 · 94 (sbr, 1H) · 10 Example 12 {[10- (2 • third (Butoxy-2-oxoethyl) -11-oxo-8- (trifluoromethyl) -1〇, 11-dihydrodibenzo [b, f] [l, 4] oxazepine Xiaoji] oxy} acetic acid 15 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 20

0

• 0H 200 mg (0.38 mmol) [1_ (2_Third-butoxy-2-ynoxyethoxy) -11_ynoxy_8- (trifluoromethyl) -10,11_di Hydrodibenzo [b, f] [l, 4] oxazepine-10 (11H) -yl] -triacetic acid is dissolved at 5 mmol under RT under argon. 121- This paper size applies Chinese national standards (CNS} A4 size (210 X 297 mm) 200413340 A7 B7 economic intellectual property Office employee consumer cooperative printed V. invention is described in (120) liter three-methane gas, was added 42 mg (0.38 mmol) gas Generation three Methylsilane and 57 mg (0.38 mmol) sodium iodide. The mixture was stirred overnight under reflux. After cooling, it was diluted with digas methane and 1 ml of an ammonium gasified solution was added. The reaction mixture was concentrated in vacuo. The residue was dissolved in Purified from acetonitrile by preparative HPLC (method 11). 130 mg (72% of theory) of the product were obtained. LC-MS (method 4): Rt = 4.20 min. MS (ESIpos): m / z = 468 (M + H) + 10 h-NMR (300 MHz, DMS0-d6): 5 = 1.35 (s, 9H), 4.59-4.84 (m, 4H), 6.86 (d, 1H), 7.03 (d, 1H), 7.45 (t, 2H), 7.60 (s, 2H), 7.84 (s, 1H), 13.00 (Sbr, 1H). 15 Example 13 {(10- (2- 第Butoxy-2-ynoxyethyl) -8-Ga-11-Hydroxy-10,11-dihydrodibenzo [b, f] [l, 4] oxazepine-1-yl] oxy Acetyl

This paper size is applicable to China Standard (CNS) A4 (210 X 297 mm)

200413340 A7 B7 V. Description of the invention (121) 150 mg (0.32 mmol) [1- (2-third butoxy-2-oxoethoxy) _8_fluoro-11 · hexoxy dibenzo [b, f] [l, 4] oxazepine-10 (11H) · yl] -t-acetic acid tert-butyl acetate was dissolved in 5 ml of anhydrous aerosol, and 10.3 mg of 5 (0.1 mmol) After methylsilane and 14.3 mg (0.1 mmol) of sodium iodide, the mixture was stirred overnight under reflux. The mixture was diluted with digas methane and washed once with 1N hydrochloric acid. The organic phase was dried over magnesium sulfate, filtered and concentrated. Purification was performed by preparative HPLC (Method 11). This gave 57.8 mg (43% of theory) of the product. 10 HPLC (Method 8): Rt = 4.52 minutes MS (DCI): m / z = 418 (M + H) + ^ -NMR (400 MHz, CDC13): δ = 1 · 52 (s, 9H), 4 · 31 (d, 1H), 4.79 (s, 2H), 4.81 (d, 1H), 6.86 (d, 1H), 15 6.89-7.00 (m, 3H), 7.23 (m, 1H), 7.45 (t, 1H), 12. 62, sbr, 1H). intellectual property Office employee economic co-op printed Example 1420 {[10- (2-oxo-2- butoxy second group bonded (Ethyl) -8-Ga-11-Hydroxy-10,11-dihydrodibenzo [b, f] [l, 4] oxazepine-1-yl] oxy} acetic acid-123- scale applicable Chinese national standard iCNS) A4 size (210 X 297 mm) 200413340 A7 B7 V. invention is described in (m)

Economic Intellectual Property Office employee consumer cooperative printed 200 mg (0.41 mmol) [1- (2-oxo-2-butoxy third engagement methoxyethoxy) -11- combined gas _8_ group dibenz [b, f] [l, 4] oxazepine_10 (11H) _yl] -acetic acid third butyl ester was dissolved in 5 ml of anhydrous aerosol, and 22.2 mg (0.2 mmol) was added to the gas After trimethylsilane and 30.6 mg (0.2 mmol) of sodium iodide, the mixture was stirred under reflux for 7 hours. The mixture was diluted with digas methane and washed once with 1N hydrochloric acid. The organic phase was dried over magnesium sulfate, filtered and concentrated. Purification was performed by preparative HPLC (Method 11). 90 mg (51% of theory 15) of product was produced. HPLC (Method 8). Rt = 4.62 minutes MS (DCI): m / z = 434 (M + H) + 'H-NMR (300 MHz, CDC13): 5- 1.51 (s, 9H), 4.34 (d, 20 1H), 4.76-4.78 (m, 3H), 6 · 84 (d, 1H), 6 · 95 (dd, 1H), 7 · 18-7.23 (m, 3H), 7 · 44 (t, 1H) ， 12.6 (sbr, 1H). -124- This paper size applies the Chinese National Standard (CNS) A4 Regulation (210 X 297 mm) 200413340 A7 B7 V. Description of the Invention (123) Example 15 [8-Bromo-1 -(2-Third-butoxy_2_oxoethoxy) -11-oxo dibenzo [b, f] [l, 4] oxazepine_10_ (11H) _yl] acetic acid

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 10 100 mg (0.19 mmol) [8-bromo-1- (2-tertiary butoxy-2-oxyoxyethoxy) _11_ 合 oxy Dibenzo [b, f] [l, 4] oxazepine-IO- (IIH) -yl] acetic acid tert-butyl acetate was dissolved in 2 ml of anhydrous aerosol, and 2.1 mg (0.02 mmol) of gas was added. After trimethylsilane generation and 28 mg (0.19 mmol) of 15 sodium iodide, the mixture was stirred under reflux for 7 hours. The mixture was diluted with digas methane and washed once with 1N hydrochloric acid. The organic phase was dried over magnesium sulfate, filtered and concentrated. Purification was performed by preparative HPLC (Method 11). This produced 48 mg (53% of theory) of the product. 20 HPLC (Method 9): Rt = 4.74 minutes MS (DCI): m / z = 478 (M + H) +! H-NMR (300 MHz, CDC13): (5 = 1.37 (s, 9H), 4.59 ( d, 1H), 4. 71-4.79 (m, 3H), 6.83 (d, 1H), 6.98 (d, 1H), 7.31-7.48 (m, 3H), 7.69 (d, 1H), 13.06 (sbr, 1H). -125- This paper size is in accordance with Chinese National Standard (CNS) A4 specification (2ί0 X 297 mm) 200413340 A7 B7 Printed by the Intellectual Property Bureau of the Ministry of Economic Affairs, Consumer Consumption Cooperatives. V. Invention Description (124) 10 15 20 Paste Example {[8-[(Benzyloxy) carbonyl] _10_ (2_thirdbutoxy_2_synthoxyethyl) _U_synthoxydihydrodibenzo [b, f] [l, 4 ] Oxyazepine 4 • yl] oxy} acetic acid

H3Cv / 100 mg (0.17 mmol) 1- (2-third butoxy-2-oxoethoxy) -10- (2-second butoxy-2-oxoethyl oxy Benzyl on · dihydrodibenzo [b, f] [l, 4] oxazepine-8-carboxylic acid benzyl ester was dissolved in 3 ml of three gas methane at rt, and mg (0.17 mmol) of gas was added Substituted trimethylsilane and 25 mg (0.17 mmol) sodium elixiride. The mixture was stirred under reflux for 4 hours. After cooling, it was diluted with dichloromethane and 1 ml of 1N hydrochloric acid was added. The reaction mixture was concentrated in vacuo The residue was dissolved in acetonitrile and purified by preparative HPLC (Method 11). 36 mg (56% of theory) of the product was produced. LC-MS (Method 3): Rt = 4.17 min MS (ESIpos): m / z = 534 (M + H) + -126- This paper size is applicable to China National Standard (CNS) A4 (2ί0 X 297)

Line II 200413340 Α7 Β7 V. Description of the invention (125) ^-NMR (200 MHz, DMSO-d6): 5 = 1.35 (s, 19H), 4.50-4.76 (m, 4H), 5.33 (dd, 2H) , 6.83 (d, 1H), 7.01 (d, 1H), 7.31-7.54 (m, 7H), 7.85 (dd, 1H), 7.98 (d'lH), 13.08 (sbr, 1H) · 5 Example 17 ( {10- (2-Third-butoxy-2-synoxyethyl) -8 _ [(cyclopentylmethoxy) carbonyl] -11-synoxy-1O, Π-dihydrodibenzo [ b, f] [l, 4] oxazepine-1-yl] oxy} acetic acid

10 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, 150 mg (0.26 mmol) 1- (2-Third-butoxy-2-oxyoxyethoxy) -10- (2-Third-butoxy -2-Hydroxyethyl) -11 · Hydroxy-10,11_dihydrodibenzo [b, f] [l, 4] oxazepine-8-carboxylic acid cyclopentyl methyl ester dissolved at RT To 3 15 ml of trigas methane, add 28 mg (0.26 mmol) of trimethylsilane and 39 mg (0.26 mmol) of sodium iodide. The mixture was stirred under reflux for 2 hours. After cooling, diluted with diethyl methane gas, was added 1 ml of this paper 1Ν salt -127- applicable China National Standard Scale (CNS) A4 size (2 mm 〖0 X 297) 200413340 A7 B7 V. Description of the Invention (I26) acid. The reaction mixture was concentrated in vacuo. The residue was dissolved in acetonitrile and purified by preparative HPLC (Method 11). This gave 104 mg (76% of theory) of the product. 5 LC-MS (Method 7) · Rt = 4.13 minutes MS (ESIpos): m / z = 526 (M + H) + h-NMR (300 MHz, DMSO-d6): 5 = L 12-1. 81 (m, 17H), 2.19-2.43 (m, 1H), 4.15 (t, 2H), 4.52-4.79 (m, 4H), 4.52-4.74 (m, 4H), 6.84 (d, 1H), 7.01 (d , 1H), 10 7.42-7.52 (m, 2H), 7.79 (dd, 1H), 7.82 (d, 1H), 12.98 (sbr, 1H). 15 Example 18 ((10- (2-third butoxy 2-Hydroxyethyl) -8-[(methoxyethoxy) carbonyl] -11-Hydroyl-10,11 · dihydrodibenzo [b, f] [l, 4] oxy Nitrophosphine] oxy} acetic acid binding surface I 1 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 20

> 〇H 0 100 mg (0.18 millimolar) 1- (2-tertiary butoxy_2_synthoxyethoxy-128- This paper size applies to China National Standard (CNS) A4 specifications (2 丨 0 X 297 mm) 200413340 A7 B7 V. Description of the invention (127) radicals) -10- (2-third butoxy-2-oxoethyl) -11_hexy-10,11-dihydrodibenzene And [b, f] [l, 4] oxazepine-8-carboxylic acid 2-methoxyethyl ester was dissolved in 3 ml of trigas methane at RT, and 19 mg (0.18 mmol) of trimethyl trimethyl Silane and 27 mg (0.18 mmol) sodium iodide. The mixture was stirred at reflux for 5 overnight. After cooling, it was diluted with digas methane and 1 ml of 1N hydrochloric acid was added. The reaction mixture was concentrated in vacuo. The residue was dissolved in acetonitrile and purified by preparative HPLC (Method 11). 80 mg (88% of theory) of the product were obtained. 0 10 LC-MS (Method 7): Rt = 3.47 minutes MS (ESIpos): m / z = 502 (M + H) + H! NMR (300 MHz, DMS0-d6): 5 = 1.40 (s, 9H), 3. 34 (s, 3H), 3.63 (t, 3H), 4.31-4.45 (m, 2H), 4.52- 4.74 (m, 4H), 6.85 ( d, 1H), 7.01 (d, 1H), 7.42- line I 1 I • 15 7.53 (m, 2H), 7.80 (dd, 1H), 7.95 (s, 01), 12.97 (Sbr, ΪΗ). Ministry of Economic Affairs Printed by the Intellectual Property Bureau's Consumer Cooperatives 20 Example 19 [(10- (2-Third-Butoxy_2-Hydroxyethyl) -8 · {[(2_methoxyethyl) (methyl) amine Group] carbonyl} -11-synthoxy-10, ll-dihydrodibenzo [b, f] [l, 4] oxazepine-1.yl) oxy] acetic acid. 129- Applicable to this paper standard Chinese national standard (CNS) A4 size (210 X 297 mm) 200413340 A7 B7 V. invention is described in (⑵

Ο

OH 10 Consumption cooperation among employees of the Intellectual Property Bureau of the Ministry of Economic Affairs, social media, U.O.O mg (0.263 mmol), u-th third butoxy · 2, certain ethoxy H-{[(2-methoxyethyl X methyl ) Amine group] _Mι and [b · oxazonium, phenyl] acetic acid tert-butyl acetic acid; dissolved in 6 ml of Sanqi Jiayuan 'added 29 mg (G26 mmol trimethyl hydrazone and 39 mmol gland 26 millimolar ice_n was cooled under reflux with a gas stirrer, diluted with two gas M, added J] ml of water. The reaction mixture was concentrated in vacuo. The residue was dissolved in acetonitrile by HPLC (Method 11). Purification (column material: YMC GEL 〇DS AQ S 5/15 micron; mobile phase: acetonitrile · water gradient 10: 90-90: 10; water + 0.1% hydrochloric acid). The final purification is based on silica gel frit (Mobile phase: methane / methanol 5: 1). 50 mg (36% of theory) of the product were obtained. 15 LC-MS (Method 7). Rt = 3.19 minutes MS (ESIpos): m / z = 515 (M + H) + iH-NMR (300 MHz, DMSO-d6): 5 1.35 (s, 9H),

-130- < ^ standard applies to China National Standard (CNS) A4 specifications (2 [0 X 297 mm 200413340 A7 B7

200413340 A7 B7 V. Description of the invention (130) Digas methane / methanol 5: 1). This gave 30 mg (56% of theory) of the product. LC_MS (Method 7): Rt = 3.40 minutes MS (ESIpos): m / z = 499 (M + H) + 5 ^ -NMR (300 MHz, DMS0-d6): L 07 (Sbr, 6H), 1.34 (s , 9H), 3.21-3.52 (m, 4H), 4.33 (s, 2H), 4.60 (d, 1H), 4.84 (d, 1H), 6.72 (d, 1H), 6,90 (d, 1H ), 7.18 (dd, 1H), 7.30-7.47 (m, 3H). 10 Example 21 {[10- (2 · Third butoxy · ethyl) _8- (methoxycarbonyl)-: 11 · Hydroxy -l〇 group, ll- dihydro-dibenzo [b, f] [l, 4] · ι · oxynitride call-yl] oxy} acetic acid

As in Example 8, it was prepared from 72 mg (0.13 mmol) of the compound of Example 72A. This gave 59 mg (99% of theory) of the desired product. Printed by the Employees' Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs. 丨 丨 竦 --------- tr ...... 丨 丨 4 丨-· -132- This paper uses the national standard of China 200413340 A7 B7 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. 5. Description of the invention (131) LC-MS (Method 2): Rt = 3.60 minutes MS (ESI): m / z = 444 (M + H) + ^ -NMR ( 400 MHz, DMSO-d6): 5 = 1.08 (s, 9H), 3. 58 5 (m, 1H), 3.77 (m, 1H), 3.82 (s, 3H), 3.85 (m , 1H), 4.20 (m, 1H), 4.62 (s, 2H), 6.68 (d, 1H), 6.88 (d, 1H), 7.35 (dd, 1H), 7.45 (d, 1H), 7.77 (d, 1H), 8.49 (s, 1H) · 10 Example 22 10- (2-Third-butoxy, ethyl) -1- (carboxymethoxy) -11-hexyloxy-10,11-di Hydrodibenzo [b, f] [l, 4] oxazepine-8-carboxylic acid

15 As in Example 2, the method was performed from 28 mg (0.06 mmol) -133-

This paper is in accordance with Chinese National Standard (CNS) A4 (2iO X 297 mm) 200413340 A7 B7 V. Description of the invention (132) The compound of Example 21 and 0.09 ml (0.18 mmol) of 2M lithium hydroxide solution were used for preparation. To give 23 mg (84% of theory) of the desired product. LC-MS (Method 7): Rt = 2.69 minutes 5 MS (ESI): m / z = 430 (M + H) +. 4-NMR (400 MHz, DMSO-d6): δ = 1. 08 (s, 9H), 3.55 (m, 1H), 3,72 (m, 1H), 3.88 (m, 1H), 4.21 (m, 1H), 4.71 (s, 2H), 6.83 (d, 1H), 6.99 (d, 1H), 7.41 (dd, 1H), 7.43 (d, 1H), 7.76 (d, 1H), 8.45 (s, 1H), 10 13.03 (s, br, lH). Example 23 {(10 -(2_Third-butoxyethyl) _8-cyano-11 · synoxy-10,11-dihydrodiphenyl 15 benzo [b, f] [l, 4] oxazepine-1-yl] Oxy} Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs

h3c ch3 -134- This paper size applies Chinese National Standard (CNS) A4 (2iO X 297 mm) 200413340 A7 B7 V. Description of the invention (133) 49 mg (0.12 mmol) Example 65A compound in 1 ml A 1: 1 solution in THF: methanol was mixed with 0.06 ml (0.12 mmol) of 2M lithium hydroxide in water. The mixture at 60 ° C under oil bath temperature for 30 minutes, and diluted with 10 ml of ethyl acetate, and the organic phase washed with dilute hydrochloric acid scrubber 5. Dried over magnesium sulfate, and the volatile components condensed in vacuo. This gave 46 mg (98% of theory) of the desired product. LC_MS (Method 7): Rt = 3.06 minutes MS (ESI): m / z = 411 (M + H) + 10 Example 24 ([10- (2-Third-butoxyethyl) -8- (A (Oxycarbonyl) -3-methyl-11-synthoxy-10,11-dihydrodibenzo [b, f] [l, 4] oxazepine] oxy} acetic acid 15 Intellectual property of the Ministry of Economic Affairs Printed by the Bureau's Consumer Cooperative

-135- This paper size is in accordance with China National Standard (CNS) A4 (210 X 297 mm) 200413340 Printed by the Consumers ’Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Description of Invention (134) Same as Example 8, since 270 Milligrams (0.13 millimoles) of the compound of Example 73A was prepared. This gave 220 mg (95% of theory) of the desired product. 5 LC_MS (Method 2): Rt = 3.77 minutes MS (ESI): m / z = 458 (M + H) +. B-NMR (200 MHz, DMSO-d6): 5 = 1,10 (s, 9H) , 2.28 (s, 3H), 3.57 (m, 1H), 3.75 (m, 1H), 3.81 (m, 1H), 3.83 (s, 3H), 4.22 (m, 1H), 4.68 (s, 2H ), 6.66 (s, 10 1H), 6.81 (s, 1H), 7.42 (d, 1H), 7.68 (d, 1H), 8.53 (s, 1H) Example 25 ((10-[(5- 第Tributyl-l, 2,4-4diazol-3-yl) methyl] -8-cyano · n-he 15oxy-1O, 11-dihydrodibenzo [1, £] [1,4] oxynitride call _1- yl} oxy) acetic acid :: 々

This paper size applies the Chinese National Standard (CNS) A4 specification (210x297 mm) 200413340 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (135) 23 mg (0.05 mmol) Example 67A compound in 1 ml of methylene chloride solution was mixed with 8.5 mg (0.06 mmol) potassium trimethyl silicon alkoxide. The mixture was stirred at RT for 1 hour, diluted with 5 ml of dichloromethane, and the organic phase was washed with dilute hydrochloric acid and water. Dry over magnesium sulfate and condense volatile constituents in vacuo. This gave 20 mg (90% of theory) of the desired product. LC-MS (Method 10): Rt = 2.12 minutes MS (ESI): m / z = 411 (M + H) +. 10 ^ -NMR (200 MHz, DMSO-d6): 5 = 1.33 (s, 9H), 4.72 (s, 2H), 5.30 (d, 1H), 5.50 (d, 1H), 6.84 (d, 1H), 7.02 (d, 1H), 7. · 45 (dd, 1H), 7.59 (d, 1H), 7 · 73 (d, 1H), 8.23 (s, 1H). 15 Example 26 {[8- cyano k-10- (4,4- dimethyl Yl_2 · oxopentyl) -11-oxo · 10,11-dihydrodibenzo [b, f] [l, 4] oxazepine-1-yl] oxy} acetic acid

-137- This paper size is in accordance with Chinese National Standard (CNS) A4 (210x297 mm) 200413340 Intellectual Property Bureau, Ministry of Economic Affairs, Consumer Co-operation, Printed by the Society A7 B7 V. Description of Invention (136) 'As in Example 25, since 1〇7 mg (〇25 mmol) of Example 68A compound prepared. 81 g (77% of theory) of the desired product were obtained. 5 LC-MS (Method 10): Rt = 2.18 minutes MS (ESIpos): m / z = 423 (M + H) +, ^ -NMR (200 MHz, DMSO-d6): 0,98 (s, 9H) , 2.37 (d, 1H), 2.46 (d, 1H), 4.58 (s, 2H), 4.87 (d, 1H), 4.97 (d, 1H), 6.79 (d, 1H), 6.97 (d, 1H), 7.42 (dd, 10 1H), 7.57 (d, 1H), 7.72 (s, 1H), 7.89 (d, 1H). Example 27 (R, S)-{[8 · cyano-10- (2 -Hydroxy_4,4-dimethylpentyl) -11-Hydroxy-15 10,11-; ^ Hydrodibenzoxazol-1-yl] oxy} acetic acid

138-200413340 A7 B7 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs. 5. Description of the invention (137) As in Example 9, the compound from Example 26 was prepared from 74 mg (0.18 mmol). The crude product was purified by preparative HPLC (Method 11). 5 mg (7% of theory) of the desired product were obtained. 5 LC-MS (Method 4): Rt = 2.82 minutes MS (ESI): m / z = 425 (Μ + Η) + ·! H-NMR (200 MHz, CDC13): 5 = 0.93, 1.03 (2xs, 9H), L46 (m, 2H), 3.70 (m, 1H), 4.18 (m, 1H), 4.48 (m, 10 1H), 4.83 (s, 2H), 6.88 (d, 1H), 6.98 (d, 1H), 7. 30-7. 65 (m, 3H), 8.42 (s, 1H). Example 28 15 (R, S)-{[10- (2- 三 Butoxy-1- methyl 2- engagement oxoethyl) -8 • cyano group bonded -11- -l1), ll- dihydro-dibenzo [b, f] [l, 4] oxynitride call-1-yl] oxy} acetic acid

-139- This paper size applies to China National Standard (CNS) A4 (210 x 297 mm)

200413340 A7 B7 V. Description of the invention (138) As Example 25, 40 mg (0.09 mmol) of the compound of Example 69A was prepared. The crude product was chromatographed on silica gel (cyclohexane: ethyl acetate 1 ·· 1). This gave 35 mg (88% of theory) of the product. 5 LOMS (Method 7): Rt = 2.99 minutes MS (ESI): m / z = 439 (Μ + Η) + · i ^ -NMR (300 MHz, CDC13): 5 = 1 · 36 (s, 9H), 1.67 (d, 3H), 4. 52 (s, 2H), 4.62, 4.90 (2xq, 1H), 6.75 (d, 10 1H), 6.96 (d, 1H), 7.40 (dd, 1H), 7.58 (m , 1H), 7.74 (m, 1H), 7.88, 7.93 (2xs, 1H). Modified Example 29 15 ((8-[(2-methoxyethoxy) carbonyl] -11-hexyl-10- [2-Hydroxy-2- (1-piperidinyl) ethyl] -10,11-dihydrodibenzo [b, f] [l, 4] oxazepine_1-yl} oxy ) Acetic acid line II 1 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs

140- This paper size is in accordance with China National Standard (CNS) A4 (210 x 297 mm) 200413340 A7 B7 V. Description of invention (l39 40.0 mg (0.066 millimolar) printed by the Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs 1- [2- (benzyloxy) -2-oxoethoxy] -11-hexyloxy-10- [2-hexyloxy-2- (1-piperidinyl) ethyl] -10,11- Dihydrodibenzo [b, f] [l, 4] oxazepine-8-carboxylic acid 2-methoxyethyl ester was dissolved in 4 milliliter 5 1: 1 ethyl acetate / ethanol mixture. 14 mg (0.01 Millimolar) 10% palladium on carbon and 25mg (0.40 mmol) ammonium formate, the mixture was stirred at 80 ° C for 3 hours. After the mixture was cooled, the catalyst was filtered out through calcium ore, and washed with ethanol. The solvent was removed in vacuo, and the residue was dissolved in 5 ml of trigas methane, and 1 ml of 1N hydrochloric acid was added. The mixture was evacuated through a sodium sulfate box, filtered through 10, and concentrated in vacuo. 34 mg (99% of theory) of the product LC-MS (Method 7): Rt = 3.22 minutes MS (ESIpos): m / z-513 (M + H) + 15 ^ -NMR (300 MHz, DMSO-d6): Occupy = 1.38-1 · 72 (m, 6H), 3.11-3.71 (m, 6H), 4.37 (d, 2H), 4.58-5.12 (m, 4H), 6.79 (d, 1 H), 6.98 (d, 1H), 7.20 (dd, 1H), 7.31-7.54 (m, 2H), 7.78 (dd, 1H), 7.91 (s, 1H), 13.02 (Sbr, 1H). 20 Implementation Example 30 {[10 _ [(5_Third-butyl-1,2,4-pyridadiazol-3-yl) methyl] -ll_synoxy-8- (trifluoromethyl) -1O, 11 ″ dihydrodibenzo [b, f] [l, 4] oxazepine] oxy} acetic acid-141- This paper size applies to China National Standard (CNS) A4 (21.0x297 mm) Order Line 200413340 A7 B7 V. Description of the invention (140)

80 mg (0.158 mmol) printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs {[10-[(5-Third-Butyl-1,2,4-Zodiazol-3-yl) methyl]- 11-Hydroxy-8 · (trifluoromethyl) -10,11-dihydrodibenzo [b, f] [l, 4] oxazepine_1_yl] oxy} methyl acetate at RT Dissolve in 8 ml of THF and add 5 mg (0.19 mmol) of lithium hydroxide dissolved in 1 ml of water. The reaction mixture was stirred at RT for 3 hours and then purified by preparative HPLC (Method 11). This gave 60 mg (77% of theory) of the product. 10 LC-MS (Method 2): Rt = 3.80 minutes MS (ESIpos): m / z = 492 (M + H) +! H-NMR (300 MHz, DMS0-d6): 5 = 1.32 (s, 9H), 4 · 70 (d, 2H), 5.40 (dd, 2H), 6 · 84 (d, 1H), 7 · 02 (d, 1H), 15 7 · 45 (t, 1H), 7 · 60 (s, 2H), 8 · 10 (s, 1H), 12 · 98 (Sbr, 1H). -142- This paper size applies to China National Standard (CNS) A4 (210 x 297 mm) 200413340 A7 B7 5 2. Description of the invention (Ml) Example 31 {[10- (2-Third-butoxyethyl) -11-Hydroxy-8- (trifluoromethyl) -10,11-dihydrodibenzo [b , F] [l, 4] oxazepine-1-yl] oxy} acetic acid

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 5 32 mg (0.07 mmol) {[10- (2-Third-butoxyethyl) -11 · Hydroxy-8- (trifluoromethyl) -10 , 11-Dihydrodibenzo [b, f] [l, 4] oxazepine] oxy} hexanoate methyl ester was dissolved in 5 ml of THF at RT, and dissolved in 10 ml of 1 liter of water. 2 mg (0.08 mmol) of lithium hydroxide. The reaction mixture was stirred at RT for 1 hour and then purified by preparative HPLC (Method 11). To obtain 26 milligrams (83% of theory) of product. LC-MS (Method 7): Rt = 3.50 minutes 15 MS (ESIpos): m / z = 454 (M + H) + ^ H-NMR (200 MHz, DMS0-d6): (5 = 1.06 (s , 9H), 3.39-3.99 (m, 3H), 4.15-4.35 (m, 1H), 4.71 (s, 1H), -143- This paper size applies to China National Standard (CNS) A4 (23U) x 297 male (%) 200413340 A7 B7 V. Description of the invention (U2) 6.84 (d, 1H), 6.98 (d, 1H), 7.37-7.57 (m, 3H) 5 8,33 (s, 1H), 13.02 (sbr, 1H). 5 Example 32 {[10- (2-Third-butoxy-2-oxoethyl) _11-oxo-10,11-dihydrodibenzo [b, f] [l, 4 ] Oxazepine-1-yl] oxy} acetic acid 10

-0 Ο h3c ch3 Order I I I • Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 15 As in Example 1, 1-fluoro-2-nitrobenzene was used as the starting material for the preparation. MS (ESI): m / z = 400.0 (M + H) +. ^ -NMR (300 MHz, DMSO-d6): 5 = 1.37 (s, 9H), 4.54-4.72 (m, 4H), 6.81 (d , 1H), 6.97 (d, 1H), 7.17-7.30 (m, 2H), 7.33-7.45 (m, 3H). 144- This paper size applies to China National Standard (CNS) A4 (210x297 mm) 200413340 A7 B7 V. Description of the invention (143) Example 33 ({10- (2-Third-butoxy-2-oxoethyl) -8-[(isopropylamino) carbonyl] -11-oxo-10, 11-dihydrodibenzo | >, £] [1,4] oxazepine} oxy) acetic acid 5

i As in Example 1, a 4-gas-N-isopropyl-3-nitrobenzidine was prepared as a starting material. 10 MS (ESI): m / z = 458.2 (M + H) +. ^ -NMR (300 MHz, DMSO-d6): (5 = 1. 11-1. 17 (m, 6H), 1.37 (s, 9H), 4.04 (mc, 1H), 4.21 (s, 2H), 4.69 (AB signal, 2H), 6.70 (d, 1H), 6.86 (d, 1H), 7.34 15 (dd, 1H), 7.40 (d , 1H), 7.63 (dd, 1H), 7.78 (d, 1H), 8.20 (d, 1H). 145-line III t Printed on paper scales of the Intellectual Property Bureau Staff Consumer Cooperatives of the Ministry of Economic Affairs, China Paper Standards (CNS) A4 size (2i () X 297 mm) 200413340 A7 B7 economic intellectual property Office employee consumer cooperative printed V. Description of the invention (144) Example 34 3 - {[10- (2 • third butoxy-oxo-2- Oxyoxyethyl) -8- (methoxycarbonyl) -11-oxyl-10,11-dihydrodibenzo [b, f] [l, 4] oxazepine-1-yl] oxy } Propionic acid

0.10 g (0.25 mmol) Compound of Example 3A 20 mg (0.28 mmol) of cold-propiolactone and 0.038 mg (0.28 mmol) of potassium carbonate were mixed in 3 ml of dimethylformamide minced amines, in Heat at 60 ° C for 1 hour, then stir at room temperature overnight. Add another 20 mg (0.28 mmol) of stone-propiolactone and stir at room temperature with stirring overnight. After adding another 10 ml of ethyl acetate and 5 ml of water, the organic phase was extracted with 10 ml of a saturated solution. The organic phase was dried over magnesium sulfate and the solvent was removed under reduced pressure. The residue was purified by preparative HPLC (Method 11) to give 3 mg (3% of theory) of the product. 15 LC-MS (Method 3): Rt = 3.6 minutes MS (ESI): m / z = 472.2 (M + H) + -146- This paper size applies Chinese National Standard (CNS) A4 Regulation (2U) X 297 Mm)

200413340 A7 B7 Ministry of Economic Affairs Intellectual Property Office employees consumer cooperatives printed

V. Description of the Invention (I45) Example 35 {[10- [2- (Third-butylamino) -2-oxoethyl] -8- (methoxycarbonyl: hi 1-oxyl-10, ll-dihydrodibenzo [b, f] [l, 4] oxazepine-1-yl] oxy} acetic acid h3C CH3 5 1.4 mg palladium on carbon (0.013 mmol) was added to 10 ml of tetrahydrofuran 14 mg of the compound of Example 78A (0.026 mmol) embodiment, the mixture was hydrogenated at atmospheric pressure overnight. evacuated to diatomaceous earth catalyst was filtered off, leaving 10.5 mg (77% of theory) of product. 10 LC-MS ( Method 3): Rt = 3.29 minutes MS (ESI): m / z = 457 [M + H] +. 4-NMR (300 MHz, DMSO-d6): 5: 1 · 35 (s, 9H), 3 · 82 (s, 3H), 4.52 (AB signal, 2H), 4.66 (s, 2H), 6.83 15 (d, 1H), 6.87 (s, 1H), 7.00 (d, 1H), 7.40- 7.49 (m, 2H), 7.96 (s, 1H). B) Evaluation of physiological activity -147-

This paper scale applicable Chinese National Standard (CNS) A4 size (210 X 297 mm) 200413340 A7 B7 Ministry of Economic Affairs Intellectual Property Office employees consumer cooperatives printed V. invention indicates that the compounds of the invention Ο46 suitable for the treatment of cardiovascular diseases by The following evaluation systems are indicated: The human plasma polysaccharides (Sigma, St. Louis, USA) were separated by sodium sulfate precipitation. It was found that more than 80% of the total aminopeptidase activity was present in the 50 to 70% saturation fraction. After centrifugation at 10 〇〇〇g small platelets resuspended in buffer T (20 mM Tris-HCl, pH 7.5, 2 mM magnesium sulfate, edetate · 1Μ square and 200 mM sodium gas). The resulting protein solution was centrifuged at 10,000 g and desalted on a Sephadex G-25 column (Pharmacia Biotech, Uppsala, Sweden). The column is equilibrated with a buffer T. The desalted fraction was placed on an affinity chromatography column. The latter system by the murine monoclonal anti CD_13 antibody (Acris SM1070P, Bad Nauheim, Germany) was coupled to the N- (PEI) activated HiTrap column (Pharmacia Biotech, Uppsala, Sweden) was prepared hydroxysuccinimide. The column was equilibrated with buffer T. After inserting the sample, the column was washed 5 times with the column volume of buffer. The bound aminopeptidase N was eluted with a dissolution buffer (100 mM glycine and 0.5 M sodium carbonate, pH 2.5). The eluate was neutralized with Tris-HCl pH 9.0 20, aliquoted and frozen in liquid nitrogen. 10 15 Ala-7- i amine-4-methylcoumarin (Bachem, Heidelberg, Germany) was selected as the fluorescein receptor for aminopeptidase N. 148-Paper Standards are applicable to the Chinese National Standard (CNS) A4 specifications (210x 297 mm). Line 200413340 A7 B7 V. Description of the invention (147) (fluorogenic substrate) 〇 Enzymatic activity is based on containing 20mM MOPS pH 7.0, 100 mM chloride Measured in sodium, 5 mM calcium carbonate, 0.1% BSA, 25 # M substrate and 1 to 5 nanograms / ml aminopeptidase N buffer. The reaction was incubated at 37 ° C for 5 to 5 hours in a 384 or 1536 microtiter dish. Fluorescence was measured in a Spectra Fluor fluorescence reader (Tecan, Crailsheim, Germany). Table A shows the IC50 values of the selected compounds. Table A:

Ex. No. IC50 [/ zM] 1 0.015 2 0.034 3 2.2 4 3.9 10 0.001 12 0.045 28 0.002 10 Wandering test for human arterial vascular smooth muscle cells (hCAVSMC, 1.5 X 105 cells / Printed by the Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs Well-holes (TEBU, Offenbach, Germany) were inoculated into 6 well-hole culture dishes, and cultured in M 231 medium (growing body) 15 (TEBU, Offenbach, Germany) at 37 ° C / 5% carbon dioxide. 48 hours. Pull tombs, pre-coated Vitronectin (50 ng / cm 2 (Gibco / Invitrogen, Karlsruhe, Germany)). After half the culture time, remove half of the clustered cell monolayer. About 50 % ^ Plectin broken glass layer -149-

200413340 A7 B7 V. Description of the invention (l48) Retained in the cell-free area of the hole. The test medium MCDB-131 / 0.2% BSA (Molecular Cell Development Biology (MCDB); Basal Medium (BSA)) (Gibco / Invitrogen, Karlsruhe, Germany) was used instead of the growth medium, and 0.1 U Amino Peptide 5 Enzyme N (Pig or human) (Sigma, Taufkirchen, Germany) stimulates the cells. The test substance is then added at the stated concentration. After 24 and 48 hours of incubation, the distance traveled by cells in the free-well cave area was measured with a microscope. Each measurement point is represented as the average of four different 10 zones selected at time 0 hours. PDGF (platelet-derived growth factor), a potent chemokine for smooth muscle, was used as a positive control group (10 nM) (R & D systems, Wiesbaden-Nordenstadt, Germany). Within Beirut verification: mouse model 15 test substance dissolved in 5% Transcutol®, 10% Cremophor and the Ministry of Economic Affairs Intellectual Property Office staff consumer cooperation, social printed physiological mixture of 85% salt water. Female mice (line: 0Fl) (Iffa Credo, L'Arbresle Cedex, France) were treated with the test substance solution orally or intravenously. Control mice were treated with solvent only. 30 minutes after intravenous treatment and 45 minutes after oral treatment, all animals were injected with 2 mg / kg lipopolysaccharide by intraperitoneal injection (strain: Salmonella minnesota, manufacturer: Sigmg, Steinheim, Germany). Blood samples were taken 90 minutes after the intraperitoneal injection. A commercially available ELISA (manufacturer: R & D, Wiesbaden-Nordenstadt, Germany) was used to determine the tumor necrosis factor (TNF) a concentration in the corporate clear. -150- t scale applicable to China National Standard (CNS) A4 specification (210 X 297 mm) — 200413340 A7 B7 Printed by the Consumers ’Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 5. Description of the invention (I49) C) Drug composition Specific examples The substance of the present invention can be converted into a pharmaceutical preparation in the following manner: Lozenges: 5 Composition: 100 mg of the compound of Example 1, 50 mg of lactose (monohydrate), 50 mg of corn flour, 10 mg of polyethylene Pyrrolidone (pvp 25) (available from BASF, Germany) and 2 mg of stearate. The weight of the spinner was 212 mg, the diameter was 8 mm, and the meandering diameter was 12 mm. 10 Production: The mixture of the compound of Example 1, lactose and starch was granulated using a 5% strength PVP solution (m / m) in water. The granules were dried and then mixed with magnesium stearate for 5 minutes. This mixture is compressed using a conventional tablet press (see previous tablet mode). 15. Gas: Oral suspension liquid: Composition: 1,000 mg of the compound of Example 1, 1,000 mg of ethanol (96%), 400 mg of Rhodigd (Hansheng Gum), and 99 g of water. 20 A single 100 mg dose of a compound of this invention corresponds to 10 ml of an oral suspension. Manufacturing:

Rhodigel was suspended in ethanol, and the compound of Example was added to the suspension. Add water while searching. Keep stirring for about 6 hours until

-151-

200413340 A7 B7 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs V. Description of Invention (150)

Rhodigel is completely swollen. Solution for intravenous administration: Composition: 51 mg of the compound of Example 1, 15 g of polyethylene glycol 400 and 250 g of water for injection. Production: The compound of Example 1 and polyethylene glycol 400 were dissolved in water with stirring. The solution is sterilized by filtration (pore size 0.22 micron), and is divided into 10 heat-sterilized infusion bottles under sterilization conditions. The latter is sealed with an infusion stopper and a crimp cap. -152- This paper size applies to China National Standard (CNS) A4 (2U) x 297 mm)

Claims (1)

A8B8C8D8 200413340 VI. Application for Patent Scope 1. A compound (I) with the following formula, 5 where Y is a Q-C6 elongation chain containing one or more double bonds or reference bonds as appropriate, one or more carbon atoms It is optionally substituted with a synthoxy group, and one or more of the carbon atoms are individually replaced by nitrogen, oxygen, or sulfur atoms, and there must be at least one carbon atom between the hetero atom in Y and R3, There must be at least one carbon atom between the two heteroatoms in Y. R1 is halogen, trifluoromethyl, trifluoromethoxy, cyano, nitro, amine, alkyl-amine, hydroxyl , Alkyl, alkoxy, carboxyl, oxycarbonyl, aminocarbonyl, or alkylaminocarbonyl, 15 wherein alkoxycarbonyl and alkylaminocarbonyl can be substituted with 0, 1 or 2 substituents, wherein the substituent Are individually selected from the group consisting of alkoxy, aryl, heteroaryl, cycloalkyl, heterocyclyl, and trimethylsilyl, η is a number of 0, Γ, 2 or 3, 20 where if η If it is 2 or 3, the R1 groups can be the same or different. -153 This paper size applies the Chinese National Standard (CNS) A4 regulations. Grid (210 x 297 mm) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs, 200413340 A8 B8 C8 _D8_ VI. The scope of patent application R2 is an alkyl group, where the alkyl group may be substituted by 0, 1 or 2 substituents, wherein the substituents are selected from Group consisting of halogen, hydroxy, alkoxy, alkoxy, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, aryl, 5 heteroaryl, cycloalkyl, heterocyclyl, and heterocyclic carbonyl Group, wherein the aryl, heteroaryl, cycloalkyl, and heterocyclic group may be substituted with 0, 1, 2, or 3 substituents, wherein the substituents are individually selected from the group consisting of halogen, trifluoromethyl, and trifluoromethoxy Group consisting of amino, cyano, nitro, amine, 10 alkylamino, hydroxy, alkyl, alkoxy, carboxyl, alkoxycarbonyl, amine and amine, R3 is R4 is halogen, trifluorofluorenyl, trifluoromethoxy, cyano, nitro, amine, alkylamino, hydroxy, alkyl, alkoxy, carboxyl, alkyl 15 oxycarbonyl , Aminocarbonyl or alkylaminocarbonyl, m is 0, 1, or 2, where m is 2, the R4 group Are the same or different, and salts thereof, solvates thereof, and one salt of the fusion. Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 2. A compound of general formula (I) 20 This paper size applies to China National Standard (CNS) A4 specification (210 X 297 mm) 200413340 A8B8C8D8 6. Application for patent scope where Y is a CrG extended alkyl chain containing one or more double bonds or participation bonds as appropriate, one of which Or more carbon atoms are optionally substituted with a oxy group, and one or more of the carbon atoms are optionally replaced by nitrogen, oxygen, or 5 sulfur atoms, and there must be a hetero atom between Y and R3 At least one carbon atom, and there must be at least one carbon atom between the two heteroatoms in Y. R1 is a functional element, trifluoromethyl, trifluoromethoxy, cyano, nitro, amine, Amine group, mesityl group, alkyl group, alkyl group, alkyl group, alkyl group, oxycarbonyl, aminocarbonyl or alkylaminocarbonyl group, η is a number of 0, 1, 2 or 3, where η is 2 or 3 , Then the R1 groups may be the same or different, and R2 is an alkyl group, wherein the alkyl group may be substituted by 0, 1 or 2 substituents, wherein the 15-generation group is selected from halogen, hydroxyl, and alkoxy, respectively. , Carboxyl, alkylcarbonyl, aminocarbonyl, alkylaminocarbonyl, aryl, heteroaryl, cycloalkyl, and heterocyclic The group consisting of basic groups is printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs. Among them, aryl, heteroaryl, cycloalkyl and heterocyclic groups can be replaced by 0, 1, 2 or 3 substituents. The groups are each selected from the group consisting of halogen, trifluoromethyl, trifluoromethoxy, cyano, nitro, amine, alkylamino, hydroxyl, alkyl, alkoxy, carboxyl, alkoxycarbonyl, aminecarbonyl, and A group consisting of alkylaminocarbonyl groups, R3 is hydroxyl or bismuth, and R4 is i-prime, trifluoromethyl, trifluoromethoxy, cyano, nitro, -155 This paper is applicable to China Standard (CNS) A4 specification (210 X 297 male: f) 200413340 A8 B8 C8 D8 VI. Patent application scope and m3, Y R1 ί η 15 R2 Printed by a member of the Intellectual Property Bureau of the Ministry of Economic Affairs and Consumer Cooperatives 20 R3 Amine and alkyl -Amine, hydroxyl, alkyl, alkoxy, carboxyl, alkoxycarbonyl, aminecarbonyl or alkaminocarbonyl, the number is 0, 1 or 2, wherein if m is 2, the R4 groups may be the same Or different. For example, the compounds in the scope of patent application No. 1 or 2 are characterized as -0-CH2C (= 0)-or -〇- (CH2) 2C (= 0)-, where Y is connected to dibenzo via oxygen. The ring of oxygen and nitrogen is a halide, a trifluoromethyl group, a cyano group, an amine group, a thiol group, a thiol group, a carboxyl group, an alkoxycarbonyl group, an amine carbonyl group, or an alkaminocarbonyl group. Or a substituent, wherein the substituent is selected from the group consisting of alkoxy, aryl, cycloalkyl, and trimethylsilyl, and the number is 1 or 2, where η is 2 Then, the R1 groups may be the same or different, and is an alkyl group, wherein the alkyl group may be substituted by 0 or 1 substituent, wherein the substituent is selected from the group consisting of a hydroxyl group, an alkoxy group, a carboxyl group, an alkoxycarbonyl group, and an aromatic group. A group consisting of a aryl group and a heteroaryl group, wherein the aryl group and the heteroaryl group may be substituted with 0, 1, 2 or 3 substituents, wherein the substituents are individually selected from the group consisting of halide, amine, and alkylamino The group consisting of hydroxy, alkyl, alkoxy, carboxyl, alkoxycarbonyl, aminecarbonyl, and amine-based dietary groups is a warp-based group. 156 copies-applicable to dimensions (210x297 cm) 2 00413340 A8 B8 C8 D8 6. The scope of patent application and m is 0. 4. The compound according to any one of claims 1 to 3, characterized in that 5 Y is -0-CH2C (= 0)-, wherein Y is connected to the dibenzoxanthol ring via oxygen. In the adjacent positions of the amidine functional group, R1 is fluorine, gas, bromine, trifluoromethyl, cyano, carboxyl, methoxyquinyl, or ethoxycarbonyl. 10 Among them, methoxycarbonyl and ethoxycarbonyl can pass through. Or 1 substituent, wherein the substituent is selected from the group consisting of methoxy, phenyl, cyclopentyl, and trimethylsilyl, η is a number 1, R2 is an alkyl group, 15 The alkyl group may be substituted by 1 substituent, wherein the substituent is composed of a free hydroxyl group, a third butoxy group, a third butoxycarbonyl group, and 2,2-dimethylprop-1-oxoyl Group, R3 is hydroxyl, printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs, and 20m is 0. 5. The compound according to any one of items 1 to 4 of the scope of patent application, characterized in that Y is -0-CH2C (= 0)-, wherein Y is connected to the dibenzoxazole ring via oxygen, and k3 is a hydroxyl group. 6. A formula -157 for the preparation of the compound of general formula (I) as described in the first patent application scope. The paper size is applicable to the Chinese National Standard (CNS) A4 specification (210 x 297 mm) 200413340 A8 B8 C8 D8 6. Application Patent scope method, characterized in that [A] a compound having the formula Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, where R1, R3, R4, Y, m, and η have the meanings shown in item 1 of the scope of patent application, and react with compounds having the formula 10 R ^ X1 ( III) where R2 has the meaning as shown in item 1 of the scope of patent application, and X1 is halogen, preferably gas or bromine, or [B] a compound having the formula (IV), R〆〇158 The size of this paper is applicable to Chinese National Standard (CNS) A4 (210x297 mm) 200413340 6. Scope of patent application Among which R1, R2, R4, m and η have the same as the scope of patent application item 1 The meaning shown is that it reacts with a compound of the formula R3 ", X2 (V), where R3 has the meaning as shown in item 1 of the patent application range, X2 is halogen, preferably gas or bromine, and A is The Ci-Cr alkane chain of Y has been shortened by heavy atoms and optionally contains one or more double or reference bonds, where one or more carbon atoms are optionally substituted with a oxy group, and one or Multiple carbon atoms are individually replaced by nitrogen, oxygen or sulfur atoms, at least one carbon atom must exist between the trans atom in A and R3, and at least one must exist between two heteroatoms in A. Carbon atom, 15 produces compounds with the following formula: Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs , R3 (la), -159 This paper size is applicable to Chinese National Standard (CNS) A4 specification (210 X 297 mm) 200413340 A8 B8 C8 D8 VI. Application for patent scope where R1 to R4, A, m and η are as follows The meaning shown in item 1 of the scope of patent application. 7. A compound according to any one of claims 1 to 5, which is used to treat and / or prevent a disease. 58. A medicine containing at least one compound as described in any one of claims 1 to 5 of the scope of patent application, which also contains at least one pharmaceutically acceptable or pharmaceutically acceptable carrier or other excipient. 9. A compound as claimed in any one of claims 1 to 5 for use in the manufacture of medicine. 10 10. The medicine according to item 8 of the scope of patent application is for the treatment and / or prevention of cardiovascular diseases, inflammatory diseases, autoimmune diseases, cancer or chronic pain. 11. A method for preventing and treating atherosclerosis in a human or an animal, which comprises administering an effective amount of at least one compound such as any one of items 1 to 5 of the patent application scope. Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs -160 The paper size is in accordance with the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 200413340 (1) The designated representative of the case is: Figure _ (None) ( 2.) Brief description of the representative symbols of the components in this representative diagram: None If there is a chemical formula in this case, please disclose the discussion that allows the characteristics of the invention to be discussed _______ Discussion and discussion:;: _ 议 _ | 议 _ Chemical formula: (I), page 2-1