TW388760B - Cyclohexane derivatives - Google Patents

Description

88 · 9- Ηϊ 壬 壬 J hi: Bu 7 B7 V. Description of the invention (μ) Example 47 2- (N-benzenesulfonyl asparagine alkoxy) -1- (oxazole hydrazone [l, 2- aj Pyridin-6-yl) -fT-methylcyclohexanemethanilamine 0.55 g 2- (fluorenyl-benzenesulfonyl- / 8-benzyl aspartame carbamoyl group) > -1- (oxazolyl) [1,2-alpyridin-6-yl> -N'-formamidine thiomethanamine (prepared in Example 3Θ) was dissolved in 5b1 Two Crocodile Farm, and 5 «1 IN NaOH was added. Stir at room temperature for 30 minutes After that, water and benzene were added. The aqueous phase was separated and adjusted to a pH of about 5 with dilute acid, and extracted with argon / ethanol. The organic phase was dried over anhydrous magnesium sulfate, the solvent was evaporated, dissolved in ethanol, added with active tritium, filtered and concentrated. , Crystallized from diethyl ether to obtain 0.31 g of the object, pale yellow powder (yield 66%). • mp CC): 153-157 ... • NMR (400MHz, 6, DMSO-d6): 1.26 (1H, m) , 1.34-1.44 (2H, m), 1.51-1,62 (2H, m), 2.06-2.28 (4H, m), 2.74 (1H, m), 2.90 (3H. D. J = 4.4Hz), 3.79 (1H, m), 5.95 (1H, m), 7.31 (1H, d, J = 9.5Hz). 7.44-7.63 (6H.m), 7.6G (1H, s), 8.03 (1H, s), 8.16 (1H, d, J = 8.6Hz), 8.52 (1H, s), 9.53 (1H. Br) -101- Chinese paper standard (CNS Μ4 regulations) (210X297 mm) (please read the note on the back before writing this page) .tr Central Sample Rate Bureau of the Ministry of Economy _B7_ V. Description of the invention (') The present invention is a hexane derivative of blue which can be used as a stork. In detail, a hexane derivative having W »pore activity. [Prior art] Gas" K is early A well-known disease, due to the reversible structure of the respiratory tract, it is difficult to breathe, and asthma is the main box, but the cause is still unclear. The rodent is generally divided into atopic aerobic chewing and contaminated air domain according to the disease type. And these two types of mixed gas, ". But some types of gas pancreas have little difference in symptoms and lung physiological changes during seizures, isochronous treatment, etc. The frequency of coexistence of respiratory sensitivities is too high to be considered incidental. Teacher B and research workers of asthma treatment generally believe that various types of asthma cause a disease. The above types of chewing therapies are currently divided into three, one is currently regarded as the best Yumin treatment, but there are "Generally ineffective lack of adhesion" s-a kind of non-specific treatment, its example is investment y- globulin and vaccine gold salt, but most of the therapies unknown organic order shortcomings. The third is symptomatic treatment. Although it includes various methods, it is mainly paeonia. Examples of drugs used for this purpose include and-stimulants, such as isoprotereno1 and Salbutanal; stability of mast cell membranes, such as dinacrotonate; baicalin preparations, such as tea age and amine tea sickle; and the like Sterilization but no-irritation causes side effects such as arrhythmia, high blood pressure, headache; scutellaria capsules cause side effects such as gastrointestinal diseases and neuropathy; steroids cause strong side effects such as diabetes and osteoporosis . Be careful when administering these drugs. Also, the stability of mast cell membrane has the disadvantage that it can only be administered as an inhalant. Therefore, it is difficult to administer to children and the elderly. * It is not effective and slow for heavy asthma. The paper size is applicable to China's a half size (CNS) A4 specification (210X297 mm) (please read the note f on the back before filling this page) [installation. VV 'line A7 B7 V. Description of the invention ( >). So in terms of ease of use, stabilizers still need to be changed. [The gist of the invention] In this case, it is still to be developed. The mechanism of action is novel, but it is safe to use and easy to prevent chewing. The inventors are committed to researching and developing the results of tincture, and pay attention to the ATP-sensitive potassium channel opening activity. Further research began to find compounds with a variety of activities. According to the research results, it was found that the following hexane derivatives can achieve the above-mentioned purpose. Based on this, the β-potassium channel opening activity-based asthma control agent of the present invention has never been marketed in Japan. Meipu Patent No. 4200640 shows hydroxyalkylpyrimidinamine «Ester, which is sold as an anti-angiopathic agent based on potassium channel opening effect, but the compound of the present invention is structurally different from the nitroester. In addition, compounds having potassium channel opening activity are shown in JP-B 5 9 1 5 0/1 9 9 0, JP-A 6 3 2 60/1 9 9 1, 2 8 9 5 4 3/1 9 9 0, 28 6 6 5 9/1 9 9 0, 2 1 1 566/1 989, 27 3/1 9 90, 3 0 82 7 5/1 989, 2 58760/1 9 9 0, etc. Structure is different. The compound of the present invention is the following formula < 1) Cyclohexane derivative or its permissible salt (please read the note on the back before filling in this page) * | 1 pack · .1T- Central Ministry of Economic Affairs Industrial and consumer cooperative seal «.

-N \ r: (I) [wherein R1 and R2 can be the same or different, each of which is hydrogen or low alkyl, and the paper standard uses China National Standard (CNS) A4 specification (210X297 mm) A7 B7 V. Description of the invention (i) R3 is an optionally substituted aryl or an optionally substituted heteroaryl, X is a gas or sulfur, and Y is a hydrazone of the formula: \ .CH4〇-)-p J (1) (P is 0 or 1, J is a fluorenyl group of the following formula: -W ^ NZ ^ R5 (2) (where R4 is hydrogen or lower alkyl, Rs is an optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, or optionally substituted Heteroaralkyl; Z1 (please read the note on the back before filling in this page) -installed as -S〇2-or -C0-, which is the following formula: (3) -COfCH2 ^ sf-N— V—fCOiy 'R10 J, line (where a and x are 0 or 1, s is zero or an integer from 1 to 6, and Rw is hydrogen or lower alkyl), as shown in the following formula: -COCH-

R 11 (4) M Central Japan Bureau of Standards, Shellfish Consumer Cooperation, Du Yincai (where R11 is hydrogen, lower alkyl, hydroxyalkyl, any substituted aralkyl or any protected carboxyalkyl), or the following formula Base: Substitute H2 ^ T (5) (where g is zero or an integer from 1 to 6))}, as shown in the following formula (6): \ (6) -5-This paper scale is applicable to China National Standards (CNS > A4 specifications (210X297 males) A7 B7 V. Description of the invention (4 {where q is 0 or 1, I {is the following formula: -W2-N-Z2-R7 (7) (where Reg hydrogen Or lower alkyl, R7 is any substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl or optionally substituted heteroaralkyl; Z2 is -S02-or -C0-, and W2 is a fluorenyl group of the formula:- COfCH2fTf-N—V—eco ^ yU12 Jk (8) (Please read the note f on the back 5th before filling in this I) Γ Install ·

(Where b and y are each 0 or 1, t is zero or an integer from 1 to 6, and R is 氲 or a lower alkyl group), as shown in the following formula: -COCH-

R 13 (9), ιτ (wherein R13 is lower alkyl, hydroxyalkyl, optionally substituted aralkyl or any protected carboxyalkyl group), or a fluorenyl group of the formula: fCH2 ^ T (1〇) (Formula Where h is zero or an integer from 1 to 6))}; or the following formula (11) basis: line carp central department # quasi-office labor charge co-operative printing \ / C = NWfL {L is the following formula (12) basis : -W3-N-Z3-R9 (11) (12) (where 1 to 8 are hydrogen or lower alkyl; R9 is an optionally substituted aryl, an optionally substituted aralkyl, an optionally substituted heteroaryl or an optionally substituted hetero Aralkyl; Z3 -6-This paper size is applicable to Chinese National Standard (CNS) A4 Washing (210X297 mm) 5. Description of the invention (,)

For -SO A7 B7 or-CO-, W 3 is the following formula (13 > basis: -COfCHg ^ nf-N V (CO ^ -IrW \ (13) Where c and z are each 0 or 1, u is zero or an integer from 1 to 6; R14 is hydrogen or lower alkyl), as shown in the following formula (14): -COCH- | (14) (where R 15 is low Alkyl, hydroxyalkyl, optionally substituted aralkyl, or protected carboxyalkyl), or a group of formula (15): fCH2fj (15) (wherein i is zero or an integer of 1 to 6>); r Is 0 or 1}] β. Suitable hexane compounds (I) are R1 is hydrogen, R2 is Ci_e alkyl, R3 is oxazolylpyridinyl, X is sulfur, Y is = CH-0-J And J is -COCH2 -NH-S02 -naphthyl. S-is suitably that in formula (I), R1 is fluorene, R2 is ethyl, R3 is oxazolylpyridyl, X is thio, and Y is = CH-0 -J and J is -COCH2-NH-S02-extracting group. The third one is suitably that in formula (I), R1 is hydrogen, R2 is ethyl, R3 is oxazolylpyridyl, X is sulfur, and Y is = CH-0-J and J is -C0CH2-NH-S02-naphthyl. Particularly preferred are compounds of formulae (Π) and (III). The present invention provides a pharmacological composition containing a pharmacologically effective amount of cyclohexane derivative Physical or pharmacological Xu salt and pharmacologically acceptable carrier, as well as prevention and treatment of diseases that are effective for potassium channel opening, are administered to patients with a pharmacologically effective amount of a cyclohexane derivative or a pharmacologically acceptable salt thereof. -7- (锖 Read the back first Note: Note: Please fill in this page again.) R. The size of the paper is set to the China National Standards (CNS) A4 (210X297 mm). The Central Car Rubbing Bureau of the Ministry of Economic Affairs β: Industrial and consumer cooperation printing A7 B7 5. Explanation of the invention (knowledge) In the above definition, the lower alkyl group of R1, R2, R4, Re, R8, RW ~ R15 is straight or branched Ci-β, such as methyl, ethyl, n-propyl, isopropyl , Butyl, isobutyl, second butyl, third butyl, pentyl, isopentyl, neopentyl, third pentyl, 1-methylbutyl, 2-methylbutyl, 3- Methylbutyl, 1,2-dimethylpropyl, hexyl, isohexyl, methylpentyl, 2-methylpentyl, 3-methylpentyl, 1, 1-dimethylbutyl, 1, 2-dimethylbutyl, 2, 2-methylbutyl, 1, 3-dimethylbutyl, 2, 3-dimethylbutyl, 3, 3-dimethylbutyl, 1-ethyl Butylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,1,2-tri Methylpropyl, ethyl-methylpropyl and ethyl-2-methylpropyl, especially methyl, ethyl, n-propyl and isopropyl. The hydroxyalkyl groups of R11, R13 and R15 are as described above. Alkyl, in which 1 to 3 hydroxy groups are each connected to any sulfonic atom. The aryl group constituting R3, R5, R7 and R9 optionally substituted aryl group is phenyl group, phenyl group, anthryl group, and the like. Its substituents are halogens such as fluorine, gas, bromine or iodine; lower alkyl groups; lower halogenated alkyl groups such as trifluoromethyl; hydroxyalkyl groups; nitro groups; hydroxyl groups; lower alkoxy groups; cyano groups; lower alkyl sulfur Β; amine group; amido group; alkylamino group, etc. β in which the lower alkyl group is the same as above, and the lower alkyl group is derived from the former lower alkyl group. Derivatives from aliphatic saturated monocarboxylic acids, such as formyl, ethyl, and propionyl; Derivatives from aliphatic saturated dicarboxylic acids, such as sulforyl, malonyl, succinyl, glutaric Aldehyde; Derived from aliphatic unsaturated carboxylic acid, such as acrolein, propynyl hydrazone; Derived from fluorene cyclic carboxylic acid, such as benzyl benzoyl, methyl benzyl hydrazone 8-This paper is applicable to China Standard (CNS) Λ4 specification (210X297 mm) I ------: -i -----.- order ------- line (please read the note f on the back of S first, then fill in (On this page) Printed by the Shell Cooperative Consumer Cooperative of the Central Bureau of Standard Vehicles of the Ministry of Economic Affairs *. A7 _B7_ V. Description of the Invention (7), Carboxymannyl, Cinnamonyl; and Derivatives from heterocyclic carboxylic acids, such as furanyl, Indigo Groups. The aryl group may have 1 to 5 of the aforementioned substituents ^ The heteroaryl group constituting R3, R 5, R7 and R9 optionally substituted heteroaryl is a 5- to 7-membered ring or a fused ring, and is selected from N, S and 1 to 3 heteroatoms of 0, such as benzoyl, furyl, pyranyl, pyrrolyl, 2H-pyrrolyl, oxazolyl, isoxazolyl, pyridyl, indino, blindyl, Late alkenyl, isomorpholinyl, and sulfonium groups, but not limited to this β. Among the substituents, the aralkyl group before β forms an optionally substituted aralkyl group Rs, R11, R7, R13, R9, and R15. The group is the same as described above, and the alkyl portion thereof is the same as that of the lower alkyl β, and the optionally substituted heteroaryl group R5, R7, and R9 is the same as described above, and the alkyl portion thereof is the same as that of the lower alkyl group. The carboxy protecting group constituting any of the protected carboxyalkyl groups R11, R13 and R 15 is preferably a lower alkyl group such as methyl or ethyl, an aralkyl group, a heteroaralkyl group, and the like. The alkyl portion is the same as that of the lower alkyl group. Any master atom of this alkyl group can be attached to any protected carboxyl group. Representative examples of aralkyl are benzyl, tolylmethyl, and lythyl, but not limited to this. Representative examples of heteroaralkyl are pyridylmethyl, furanethyl, and propyl, but not limited to this β The pharmacologically acceptable salts of the present invention include salts of inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, and phosphoric acid; salts of organic acids such as acetic acid, maleic acid, tartaric acid, methanesulfonic acid, benzenesulfonic acid, and toluenesulfonic acid; And such as arginine, asparagus-9- (Please read the note on the back before filling in this I) "Packing. ≫ 1r. The size of thread paper is applicable to China National Sample Rate (CNS) Λ4 specification (210X297 mm) )

• N \ r: ap p J A7 B7 V. Description of the invention (ί) Amino acids and salts of amino acids such as glutamic acid β The derivatives of the present invention can form gold salt, such as «, potassium, calcium or magnesium Salt "The rationale of the present invention includes some metal salts" The structure shows that the compounds of the present invention may exist in various optical isomers β or may exist as geometric isomers depending on the substituents. These are included in the present invention . In the compound of the present invention, it is preferable to use the following formula U '> Compound (I,) (please read the note on the back before filling in this buttercup) ", ιτ. In formula (I ·), R1, R2, R3 , X, J, and P are the same as above. Particularly preferably, R1, R2, R3, X, J, and P are as follows. One of R1 and R2 is hydrogen, and S is a lower alkyl group, particularly methyl, ethyl. Or propyl, preferably methyl. R3 is preferably an optionally substituted heteroaryl, more preferably imidazolylpyridyl, most preferably oxazolyl [1,2-alPttidine-6-yl. Although J is a fluorenyl group of the formula: -W ^ NZ ^ R5 (2) (where W1, R 4, Rs, and Z1 are the same as before), but W1 should be the following formula-1 0- This paper size applies the Chinese National Standard (CNS) Α4 specification (210X297 mm) ) Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs *. V. Description of the invention (9) Α7 Β7 ⑷: -COCH- where R 11 is particularly suitable for hydrogen or low alkyl, preferably hydrogen 〇 4 is suitable for hydrogen 》 R5 is preferably an optionally substituted aryl group or an optionally substituted heteroaryl group, particularly an aryl group, preferably a leaf group. Z 1 is preferably -SO 2 -β In the compound of formula (I), the best optical isomer is the following formula ( Π) (4)

• N: R1 (II) (wherein R1, R2, R3, X, and 同 are the same as before). Therefore, the best compound of the present invention is represented by the following formula (II): (Please read the "$" on the back side before filling out (This page) -JI. Τ equipment.

(Ill) The main preparation method of the compound according to the present invention is as follows: β Preparation method 1 Υ is the compound of the formula (16) (I) -1 1-This paper uses Chinese national kneading rate (CNS) A4 specifications (2 丨 0X297) (Mm) 5. Description of the invention (,.)

CH-0-J A7 B7 (16 where J is the same as above) can be manufactured according to the following method:

(IV) J-OH (V)

(VI) Ministry of Economic Affairs Central #quasi bureau wc industrial and consumer cooperation Du printed manufacturing According to this manufacturing method, the object (VI) can be produced by condensing compound (IV) with compound (V) or its reactive derivative according to the usual method. Reactive derivatives of the compound (V) are its cavities and symmetrical anhydrides. When the compound (V) is used in a free form, the condensation is generally carried out in the presence of a condensing agent. Although any conventional condensing agent can be used, its suitable examples are diphenylphosphamide, ethyl formate, methanesulfonium, 1, 3-dicyclohexylsulfonimide, 1, 1-carbonyldioxazole, and even Diethyl nitrogen dicarboxylate and dipyridyl disulfide. According to this production method, the reaction is sometimes carried out in the presence of a base. Although available for this purpose at any age, its suitable examples include organic, such as diisopropylethylamine, triethylamine, pyridine, methyl, Itidine, dimethylpyridine, N, N-dimethylaniline And 4-dimethylaminopyridine; and inorganic bases such as potassium sulfonate and NaOH. Suitable examples of the solvent include a yeast such as ethanol; an ether such as tetrahydrofuran; a hydrocarbon such as toluene; a halogen solvent such as digasmethane; a polar aprotic solvent such as ethyl acetate, N-dimethylmethylamine and acetonitrile; And pyridine. The reaction temperature can be about -20 ° C to the reflux temperature of the solvent. -1 2- (Please read the note f on the back before filling this page)-Packing. 11. This paper size applies to China National Standards (CNS > A4 size (210X297 mm) A7 B7 V. Description of the invention (,,) Method 2 in the compound (I) is Y:

CH-O-W ^ N (where W 1

• N: ZO1-!? 5 (17) R4 and Rs are the same as before) HO-W ^ NC ^ (VIII) (Process 1)

• N: (Please read the note on the back before writing this page) (IV) (IX) Unprotect (Process 2)

N (X) \ r; Printed by the Consumer Procurement Cooperative of the Central Procurement Bureau of the Ministry of Economic Affairs

-N; (XII) QZ »-Rs (XI) (Process 3) Rs-Z 丨 -NW 丨 -0 (where K1, k2, R3, R4, R5, wi zl, and X are the same as before) 3 is off And R20 is a protecting group). -13- The paper size is in accordance with Chinese National Standards (CNS > A4 size (210X297 mm)) 5. Description of the invention (a) A7 B7 How to reduce the nitrogen content of the printing method of the Shell Sample Consumer Cooperative of the Central Sample Rate Bureau of the Ministry of Economic Affairs Can be three, such as oxygen can be used. Next, let ’s talk about Yuling, hydrocarbons, Benzyl benzyl 0 S, use 0, IK " OH., IEX) M; {Gas removal is the only problem, but alkenyl --- and furan W-butane dehydrogenating agent I, ester di C propyl N potassium hydrogen Mfo triplet} halogenated and other ethyl groups are iso-N, acid tetra-non ”M acid acid 0 digestion W basic acid teaching one by one, such as sex i; w is such as adipic acid in the alkyl 1-, such as pyridine, birch-.rM variant fluorescein-like silica atmosphere, Presence, pyridine, ether; β-tri- or mono-containing group, 1. Total _ base age., Alkane by XOR, XOR), methyl chloride, strontium, mechanol, methyl srn, and acid (birthday ^ Ξ ^ 114 | with _ 乙 乙 «" 丨 0 Μ 0 物Derivatives T, phosphorus-based groups are included, and are protected, such as £ 0 ~~, so that the phenyl group b-pyridine is included in the benzene, such as ¥ 10 ° deprotection acidification IX) should be the second section of Mm have For example, W alcohol 'di-2 is used in addition to the salt and < instead, it is the base of Example 2 and the methyl-encapsulated N for the reaction of W-allyl sulfonylpyridinate / contracting agent. ί < Combined with VB) Isc is suitable for SEBg, but the amine example is ^ N, may be X) 丨 Physicalized R phthaloyl-S B method, pyrimidine suitable halogen, degree} (1 method and 1 combination (VI-based, protective agent _ Pyrodizide made by one and two; brewing temperature 2 material protection process and compound protection base protection 3 acid For this purpose, 4-agent phenylethyl should be combined with chemical protection order. Bao Bao Reduction of 1, carboxylic acid with this amine and dissolved formic acid to produce acid to decompose acid (condensation of benzyl, diamine for ethylamine such as ethyl). First read the note on the back of the paper and then fill in this X) The paper size is applicable to the Chinese national rubbing rate (CNS > Α4 size (210X297mm) A7 B7 Fei cooperation Du Yin «. 5. Description of the invention (* 〇1 1 carbonyl and benzyl can be removed under hydrogenation conditions 9 ethynyl 9 benzyl and 1 1 hydrazone can be used in hydrochloric acid f sulfuric acid or triacetic acid It can be removed under acidic conditions or under mild conditions such as Na OH 1 1 or hydrazine. 1 1 it 1 Protective groups and deprotection conditions are not limited to these examples. m select 0 back A 1 I 1 1 ί process 3) Note i 1 Let compound (X > and compound (XI > or its antisense derivative) be entangled according to common law and then 1 1 \ d to obtain a hundred F (XII). F This 1 (reactive derivative of compound (XI) includes its fermented halogen and symmetric anhydride. If the page 1 1 compound UI) is used in a free-form type, it is usually reduced by 1 in the presence of a condensing agent. 1 in 0 1 1 shrink A suitable example of m is diphenylphosphamide 9 ethyl formate > methanesulfonate 1 1 9 1, 3 -dicyclohexyl fluorinated diimine, 1 1 I-m-based difluorene 9 difluoro ' 1 Diethyl dicarboxylate and dipyridyl disulfide 0 1 I According to this production method 9 The reaction is sometimes performed under the coexistence of age 0 Although any age may be 1 1 1 for this purpose 9 but its suitable examples include organic age 9 such as Diisopropylethylamine > tri 1 1 ethylamine pyridine 9 methylpyridine 9 dimethylpyridine »N, N-dimethylbenzene line I amine and 4-dimethylaminopyridine; and inorganic bases For example, m-potassium acid and Na 0H 〇1 1 solvents include alcohols> such as acetic ether 9 such as tetrahydrofuran 9 \ I such as toluene rack solvent m 9 such as Erfang Jiayuan polar aprotic solvent t such as J 1 acetic acid Ethyl esters, N, N-dimethylformamide and acetonitrile and pyridine. 1 1 The reaction temperature can be about -2 0 ° C to the reflux temperature of the solvent. 1 I Preparation method 3. 1 1 Y in the compound (I) is based on the following formula (1 8) * 1 1 -1 5- 1 1 1 1 This paper is based on Chinese national standards (CNS > A4 size (210X297) Millimeters) Printed by the Central Sample Rate Bureau of the Ministry of Economic Affairs, Shellfish Consumer Cooperation, Du printed A7 B7 V. Description of Invention (β) \ Factory = 忖 冬 OiyL (18) (where L and a are the same as before) can also be manufactured according to the following method H2N-f 0-VL (XIV) R1 or its acid tank R2 base

(XIII)

0 <:

L-eo- ^ r-N (XV) Compound UIII) and compound (XIV) or an acid addition salt thereof are condensed in the presence of age to obtain the target compound (XV). This age is preferably pyridine or sodium acetate. The solvent used is preferably an alcohol such as methanol, pyridine or water, but any organic inert solvent may be used. The reaction temperature can be about 0 ° c to the reflux temperature of the solvent. Preparation method 4 Y in the compound (I) is the base of the following formula (18): \ C = _— jL (18) / (where L and a are the same as before) can also be manufactured according to the following preparation method: -16- This paper size Free use of Chinese national standards (CNS specifications (210X297 mm) (please read the "$" on the back side before filling in this card)) 5. Description of the invention ()

(XIII) A7 B7

HiN-^-O ^ i-L (XIV) R1 or its acid addition salt

(Please read "Note f on the back of the book before filling in the book") II Packing · Printing Order of Compound UIII by the Central Standards Bureau of the Ministry of Economic Affairs and the Industrial Cooperative Cooperative) and compound (XIV) or its acid addition salt A suitable example of the target substance uv) e-Isanoic acid that is condensed in the presence of it is aluminized aluminum and titanium tetrafluoride. The solvent used should be halogenated, such as dioxane, but any organic solvent that is inert to the reaction can also be used. The β reaction temperature can be about 0 ° C to the reflux temperature of the solvent. Preparation method 5 Y in the compound (I) is the base of the following formula (19): \ CH-NH-K (19) I (where κ is the same as above) can also be manufactured according to the following production method: -17 This paper is used in China Standard (CNS) Λ4 Specification (210X297mm) Order · Line V. Description of Invention (4)

(XV,) restore A7 B7

-N: (XVII)

K-NH Ministry of Economic Affairs Central Government Bureau of Japan ’s Industrial Cooperative Co., Ltd. printed the order compound (XV1) (prepared by manufacturing method 3 or 4) according to the usual method to obtain the target product (XVI I). The logic element can be carried out by conventional methods such as gold tritium hydrogen complex or catalyst tritium. Examples of Jinyang argon complexes include sodium sulfonium borohydride and sodium borohydride β. Suitable lysyl ether, such as tetrahydrofuran, or fermentation, such as methanol. The reaction temperature is about -20 ° C to the reflux temperature of the solvent. Catalysts can be hydrogenated using conventional catalysts, such as Pd-C, vaporized platinum, Raney nickel or rhodium-vaporized aluminum. The solvent used is preferably an alcohol, such as methanol; a hydrocarbon, such as toluene; an ether, such as tetrahydrofuran; H, N-dimethylformamide; or ethyl acetate. The reaction temperature should be 0 ° C to the reflux temperature of the solvent. Production method 6 Y in the compound (I) is a group of the following formula (20): \ / CH-W2-NH-Z2-R5 (20) (where W2, Z2, and R5 are the same as before) can be produced according to the following production method:- 18- This paper size applies to China National Standards (CNS) Λ4 specification (210X297 mm) (please read the note on the back before filling in this page)-IΓ binding. Order-line A7 B7 V. Description of the invention (" 7

\ r! ΟII ^ Rir 〇? 21〇), ten < (xvm) or \ CN R21, (Ph) 3-?-CH ^ -T (XIX) __ (process l)

(XX) Reduction (Process 2>

(Please read the note on the back before filling this page) • Packing. Order Q-Z2-R5 (XXII) (Process 3)

Printed by the Central Consumer Bureau of the Ministry of Online Economics and Consumer Goods Cooperatives (where R1, R2, R3, R5, Z2, W2 and X are the same as before, T is a radical, such as dentition or hydroxyl, and R21 is Low alkyl; R21 is hydrogen, low alkyl, etc .; S is dentin) β (Process 1)

The compound (XIII) was reacted with the compound (XVIII) or (XIX) through the conventional Wittig reaction to obtain the compound (XXK * 19- This paper size applies to the Chinese National Standard (CNS) A4 specification (210X297 mm)

• J— 1 ^ 1 IJ Printed by the Shellfish Consumer Cooperative of the Central Bureau of Quasi-Ministry of Economic Affairs «. A7 _._ B7_ V. The invention is clear (< 〇 The age of suitable examples are gold flooding hydrides, such as NaH; organic lithium compounds, Such as n-butyllithium; and gold oxane gaseous compounds, such as tert-butyrate. The solvents used should be tetrahydrofuran, etc., or polar aprotic solvents such as H, N-dimethylmethanamine, etc. The reverse temperature can be about -78 ° C of the reflux temperature of the solvent. (Process 2 > The compound (XX) obtained in Process 1 is transported to the compound (XXI) according to the usual method. Kryogen can be used as a metal argon complex or contact Solvent hydrogenation is carried out by conventional methods. Examples of gold complexes include sodium sulfonium borohydride, sodium borohydride, and aluminum hydride. Suitable solvents are ether, such as tetrahydrofuran, or fermentation, such as methanol. About -20eC ~ reflux temperature of the solvent β The hydrogenation of the catalyst can be used with conventional catalysts, such as Pd-C, platinum vaporized, Ruan Laixian or rhenium-aluminum gasified. The solvent used should be alcohol, such as methanol; hydrocarbons, such as Toluene; ether, such as tetramethylfuran; N, N-dimethylformamide; or ethyl acetate. The reaction temperature is preferably 0 ° C to the reflux temperature of the solvent. (Process 3) Let process 2 obtain Compound (XXI) is condensed with compound (XXII) or a reactive derivative thereof according to an ordinary method to obtain a target compound (XXIU). Reactive derivatives of compound (XXII) include halogen halides and symmetrical anhydrides. If compound UXII) is free When using it, it is often in the presence of a condensing agent. -20- This paper size is applicable to China · Fujian Standard (CNS M4 specification (210X297 mm) --------- ^-(please read " And note $ item *-fill in this page), ιτ M printed by the Ministry of Economic Affairs of the Ministry of Standards and Technology Bureau of the Bayer Consumer Cooperatives *. A7 B7_ 5. Description of the invention (Heart) Condensation. An example of a condensing agent is diphenylphosphatamine , Ethyl formate, methanesulfonium, 1,3-dichenhexyl triethylenedimine, 1,3-dibenzyl dizidazole, diethyl azodicarboxylate and dipyridyl difluorene. In the preparation method, the reaction is sometimes carried out under the coexistence of age. Although any _ can be used for this purpose, examples include organic age, such as diisopropylethylpyridine, triethylamine, pyrimidine, methylpyridine, and Methylpyridine, N, N-dimethylbenzene and 4-dimethylaminopyridine; and inorganic sickle, such as potassium osmate and UaOHe solvents, suitable examples include fermentation, such as ethanol; ether, such as tetra «furan; Hydrocarbons, such as toluene; Halogen solvents, such as dioxomethane; Alkaline, non-proton solvents, such as ethyl acetate, H, N-dimethylformamide and acetonitrile; and pyridine. The reaction temperature can be about -20 ° C to the reflux temperature of the solvent. Production method 7 Compound (I) can be obtained as an optical isomer by the following method. For example, the optically active compound (Iβ) can be optically dissociated from the raw materials or the intermediates of production methods 1 to 6 by conventional methods, and The obtained optically active raw material or intermediate amidine treatment is used to produce it. In addition, the desired optical isomer (I #) can also be produced by directly performing optical analysis of the product (I) according to a conventional method. Optical analysis can be performed by any conventional method, for example, using optically active acids such as tartaric acid, dibenzyl tartaric acid, amygdalic acid, and other methods, such as Rhenium Derivatives-20a- This paper is applicable to China National Standard (CNS) A4 (210X297 mm) --------- rl ^ .------ IT ----- ,. 1 Wei • · ψ (Please read the note f on the back first # -Fill this page ) V. Description of the invention) A7 B7

Methods such as cocoon cocoon, and HPLC with optical analytical column. The compound (IV) used as a raw material in this production method can be produced according to WO 93/08 1 68. Production method A

R *

• N; (IV) H0 R: (please read "Note f on the back and then 4 nests on this page"). Packing. Printed by the Ministry of Economic Affairs of the Bureau of Shellfish Consumer Cooperatives (where R1, R 2, R3 And X are the same as before). The compound (XIII) is obtained as a metal hydrogen complex or a metal hydrogen compound to obtain the compound (IV). This gold complex includes sodium borohydride and lithium aluminum hydride, and the gold flooding hydride is preferably diisobutyl aluminum hydride. The solvents used include, for example, alcohols such as methanol; W, such as tetrahydrofuran, and hydrocarbons, such as toluene, but any organic solvent inert to the reaction may be used. The reaction temperature can be about -78 ° C to about 5fl ° Ce. The compound (VI) can be obtained by vaporizing the compound (V) in an alcohol solvent by alkane gasification. In this case, isopropyl alcohol is preferably used as the solvent, and alkane aluminum oxide is used as the reducing agent. The reaction temperature can be from room temperature to the reflux temperature of the solvent. The effects of the present invention will be described below by way of experimental examples. Pharmacological experiment example: Relaxation effect on smooth muscles of trachea taken out of guinea pigs i) Experimental method-2 1-, TΓ · The size of the paper is applicable to China National Standards (CNS > A4 (210X297 mm)) Printed by the Industrial and Consumer Cooperatives • A7 B7 V. Description of the invention (w) Kill Hartley male guinea pigs weighing 3,000 to 500 grams, cut the neck to remove the trachea, cut the trachea on the opposite side of the trachea smooth muscle, and cut the cartilage Cut a piece of Chinese film between them and use it as a trachea sample. "This crop was hung vertically in a Magnus tube (1 0 1) filled with 37« C Krebs-Henseleit fluid, and the passable person contained 9 5 χ gas and 5 3; C The pressure of 0 2 is equal to the contraction change at a load of about 0.5 grams. After the specimen is stabilized, 10 · M potassium potassium is added to the Magnus tube to cause contraction. After the contraction is stabilized, the test compound is added to the Magnus tube. To determine the change in tension. The relaxation ratio (%) caused by the addition of various concentrations of the test compound is calculated based on the shrinkage caused by the addition of 10 · M potassium potassium to 1005! To determine the relaxation egg reaction curve based on this. Curve to calculate muscle relaxation Concentration (ECS0) at 50% of the large shrinkage. Ii) The test results are shown in Table 1, where the compound numbers are as follows: Compound 1: 2- (N-benzenesulfosylglycine fluorenyloxy) -1- (oxazole骈 [1,2-a] pyridine-6-yl) -N'-methylcyclohexanemethanilamine compound 2: 2- (M- (p-toluenesulfonyl) glycinefluorenyl) -1 -(Oxazolyl [l, 2-a] pyridine-6-yl) -N'-formamidine hexanemethanilamine compound 3: 2- (N- (4-fluorobenzenesulfonyl 1 glycinamine) Gas group> -1- (oxazolyl, 2-al »ftidine-6-yl} -N'-methylhexane thiomethanamine compound 4: -benzylsulfonyl) glycinyloxy ) -Bu (oxazolidine [l, 2-a] pyridin-6-yl > -N '-methylcan hexane-22- This paper size applies to Chinese National Standard (CNS M4 Specification (2 丨 〇 >) < 297 mm) -------: --- i -------- order · ------ 0 (please read the note $ on the back first and then write it down Ϊ Ministry of Economy Central Standards Bureau Zhengong. Consumption Cooperation Du printed A7 B7 V. Description of the Invention (d) Methionamide Compound 5: 2- (N- (4-Bromobenzenesulfonyl) Glycinoloxy) -1- (Oxazolidine [1,2-a] pyridin-6-yl) -N1-methylcyclohexanemethanilamine compound 6: 2- (N- (4-Tris-methylbenzenesulfonyl) glycine hydrazone > -Bu (oxazolyl [l, 2-a] pyridine-6-yl) -N'-methylhexyl Thiamin compound 7: 2- (N- (4-methylaminobenzenesulfonyl) glycine Samino) -1- (Deep sleep 骈 1,2-3] pyridine-6-yl) 1 ' -Methylcyclohexanemethanilamine compound 8: 2- (N- (2-methylaminobenzenesulfonyl) glycinaldehyde) -Bu （oxazolidine [l, 2-ajlft «-6- ) -N'-methylcyclohexanemethanilamine compound 9: 2- (N- (2,5-dichlorobenzenesulfonyl) glycine) -1- (imidazolium [1,2, -a] pyridine-6-yl) -N · -methylcyclohexanemethanilamine compound 10: 1- (imidazolium fl, 2-allftidine-6-yl) -N-methyl-2-(2 , 3,4,5,6-pentafluorobenzenesulfonylamino) acetonitrile cyclohexanemethanamine compound 11: 2- (N- (2- # sulfonyl} glycinylamino) -1- (oxazolidine [1,2-a 丨 pyrimidin-6-yl) -N'-methylcyclohexanemethanilamine compound 12: 2- (1 (8-1 ^ morpholinsulfonyl) Glycylpyridyl) -1- (oxazolyl [l, 2-a] pyridin-6-yl) -N'-methylcyclohexane-23- This paper is for Chinese National Standard (CNS) Α4 Specifications (210X297 mm) (please " Note 4 on the back is written in 4 copies. 筲) Order · A7 B7 printed by the Central Bureau of Standards, Ministry of Economic Affairs, Work and Consumption Cooperation. V. Description of the invention (">) Methionamine compound 13: 2- (N- ( 6-iso 丨 f-line sulfonyl) glycine fluorenyl) -bu (oxazolyl [l, 2-a] pyrimidin-6-yl) -N · -methylhexylmethanamine compound : 2- (N- (2--Sulfinyl) > Glycosylamino) -Bu (oxazolyl [l, 2-a] pyrimidin-6-yl) -ΙΓ-methanehexane Thioamidin compound 15: 2- (N- (2-methylpyrazol-3-ylsulfonyl) glycinyl) -1- (imidazolium [1,2-alpyridin-6-yl) -N'-formamidine thiomethoxamine compound 16: 2- (N-benzylfluorenylglyoxanyl) -1- (oxazolyl [1,2-a] pyridine-6-yl)- N′-methylcyclohexanemethionine compound 17: 2- (N- (N′-4-benzenesulfonylglycinamido) glycine 醯 amino) -b (-[l, 2 -al-pyridine-6-yl> -N " -methylcyclohexanemethanilamine compound 18: 2- (2-benzenesulfenylamine ethylamino) -pyrazoleazole fl, 2-a] pyridine -6-yl) cyclohexanemethanilamine compound 19: (-)-(lS, 2R) -2- (N-benzylsulfonylglycinal)-Bu ( Imidazolium [l, 2-a] pyridine-6-yl) -N · -methylcyclohexanemethanilamine, and compound 20: (-)-(lS, 2R) -2- (Ni-naphthalenesulfonium Glycine) Glycine 甘 Gasyl) -1- (oxazolyl 骈 1,2-a] pyridine-6-yl) -f) '-Methylcyclohexanemethionin 6 -2 4-Applicable to this paper standard China ’s poverty rate (CNS > A4 size (210X297 mm) ------ ΊΙΚ equipment -----; 1 order · ------! 1 final (please read "Notes on the back" ^ • Please fill in this item again Jr) A7 B7 Λ, description of the invention (4) [Table 1] Relaxation active compound 1 7.8 Compound 2 7.3 Compound 3 7.8 Compound 4 7.8 Compound 5 7.7 Compound 6 6.9 Compound 7 7, 4 Compound 8 7.4 Compound 9 7.3 Compound 10 6.1 Compound 11 7.4 Compound 12 7.3 Compound 13 7.3 Compound 14 7.8 Compound 15 7.3 Compound 16 7.3 Compound 17 6.8 Compound 18 7.8 Compound 19 8.1 Compound 20 7.5 (Please read the note on the back before filling in this page) -I installed · -Ordered-_ Threaded paper size Easy to use in poor countries (CNS > A4 size (210X297 public 4 A 7 B7 Printed by the Central Government Bureau of the Ministry of Economic Affairs, Shellfish Consumption Cooperation, Du printed 5. Description of the invention (^) 1 1 It is known from the results of the above physical experiment »The compound of the present invention has potassium channels 1 1 and can be used as potassium channels Prevention and treatment of diseases that are effective in opening up 1 1 m 〇 The disease cases include bronchial asthma, high blood pressure such as narrow, 1 1 and 1 heart disease and other hemorrhagic heart disease and cancer »But the compounds of the present invention have potassium channels. 1 1 Any disease that can be effectively controlled by the opening effect is effective. 1 | 1 and the compound of the present invention has low m-stability and Anjin »so it is valuable. 0 Note i The compound of the present invention can be administered by P or parenterally. F The amount depends on the patient's ▼ item 1 1 symptoms and degree »age» sex »the difference in the prestige of the drug 9 vote f this K method of administration» the period of administration 9 the interval of 9 administration Types and properties of the agent * There are female S— < 1 | The types of active ingredients and so on vary 9—Generally every adult M mouth is about 0. 1 ~] 000 1 1 9 is preferably 0.5 to 500 9 especially 1 ^ -1 0 1 g, divided into 1 several times 1 should be 1 or 2 times 1 | admin; at the time of injection > the dose is 0. 1 ~ 100 Ug / kg, if administered as an infusion, it is usually 9 when it is ordered 0 1 100, preferably about 0.05 to 5 fl, more preferably 0.1 1 10 I ng, divided into 1,-several times, preferably 1 or 2 times. The inhalant 1 I according to the present invention can be pulverized by a compound of the present invention using a jet mill or the like. 9 If necessary, interfacial activity 1 1 can be added. The inhalant can be prepared according to the conventional method. Manufactured with customary carriers. Detailed 9 line I when preparing α m solid preparations 9 Add the tincture to the main medicine 9 Add adhesive if necessary 1 1 Agent 9 Dispersant 9 Slipper > Colorant and / or flavoring agent 9 And made into tablets 1 | 9 coated tablets 9 granules 9 powder m or capsules 0 1 I Examples of excipients include lactose > corn starch > sucrose > glucose 9 flowers 1 1 楸 alcohol 9 crystalline m androgen 7Ϊ1Γ. Silicon dioxide, binders include polyvinyl alcohol 1 | polyvinyl ether * ethyl m vitamins »methyl cellulose Acacia gum» Scutellaria baicalensis 1 1 > gelatin 9 insect wax 9 hydroxypropyl m vitamins ♦ hydroxypropylmethyl m-vitamin > 1 1 -26- 1 1 1 1 This paper is suitable for China National ratio (CNS) Λ4 specification (210X297 mm) A7 __ B7 V. Description of the invention (^) Calcium betulinate, period sugar and pectin; smoothness _ includes magnesium stearate, talc, polyethylene glycol, Silica and hardened vegetable oil; colorants include κ drug add licensee; tinting agents include cocoa powder, menthol, aromatic powder, peppermint oil, pickled tincture and cinnamon powder. It is necessary that the cocoons and glumes can be coated with sugar, Mingzhi, etc. if necessary. When the injection is made, add PB stabilizers, buffers, stabilizers, and / or additives in the main capsule as needed. Dissolve thinly and make cocoon by subcutaneous, intramuscular or intravenous injection. The following examples illustrate the present invention, but are not limited thereto. Working example 1 2- (4-methyloxazole-I-yl) cyclohexanone (锖 Please read the note f on the back * 8 before filling in this page) 装 装 ·

-Order 1. 150 g (1.83 Gu 〇1) 4-After dissolving methyl amidazole in 1.5A ethyl acetate, add 314 g (2.27 BOU potassium potassium acetate and heat to 70-C, add 267 g over 1 hour) (2.02BO1) 2-gas hexanone and acetonitrile (0.70 ·) solution. After dripping, heat to reflux for 2 hours, add 31.8 g (0.230 HO1) potassium sulphate and 50.0 g (0.377 · 〇1) 2- Cyclohexanone / acetonitrile (O.lil > and heated to reflux for 5 hours. After cooling, filter and wash the cake with acetonitrile. Combine the filtrate and the washing solution and evaporate the solvent under vacuum. "420 g of the residue was obtained in a 3 kg silica gel column Chromatography [Dichloromethane / methanol = 200: 1 ~ 30: 1 (containing 0.2% concentrated ammonia)] -27- This paper size uses the Chinese national standard (CNS specification (210X297 mm) line · Central Eel Ministry) Rated shellfish consumer cooperation, Du Yangzhuang, Ministry of Economics, Central Bureau of the Ministry of Economic Affairs, Central Bureau, Gongyan Consumer Cooperative, printed A7 B7. 5. Description of the invention (4), 143 grams of brown oil were obtained. Crystallization from dichloromethane yielded 87.8 grams of the target. Colorless crystals (yield 27%). • NMR (400MHz, δ, CDC13): 1.76 (1H, m), 1.86 (1H, m) 2.03-2.13 (2H, m), 2.20 (1H, m), 2.24 ( 3H, s), 2.39-2.51 (2H, m), 2.64 (1H, m), 4.67 ( 1H, dd, J = 13.0, 5.5Hz), 6.59 (1H, s). 7.34 (1Η · s) Preparation Example 2 N-methyl-bu (4-methylimidazol-1-yl) -2- Gas cyclohexanemethanil

9.88 g (0.247βο1) of sodium sulfide (60% oil suspension) was suspended in 1A 1,4-dioxane, and 41.4 g (0.232 «〇1>) of the ketone obtained in Preparation Example 1 was added. The mixture was heated under reflux for 2 hours to obtain When the yellow suspension was cooled to 20 * C with ice, a solution of 17.Oil (0.249 · ο1) methyl isothiocarbamate and 1,4-dioxane 70 · 1 was added. 150β1 Ν, Ν-dimethyl was added next. After the methyl formamide was stirred at 50 eC for 1 hour, the resulting ochre-colored suspension was ice-cooled, 200 12 N hydrochloric acid was added, and the solution was neutralized with saturated sodium bisulfate, followed by methane (IX 2Q., 2X1 A). After extraction and washing with brine, it was dried over anhydrous sodium sulfate and concentrated in vacuo. The crystals were collected by filtration to obtain 39.2 g of the target product, light brown colored crystals (yield 67% >). CNS) Α4 specification (210X297 mm) -------: -IK equipment -----. 丨 Order ------- 〆 (Please read the note on the back before filling this page) Printed on A7 _B7 _ by the Sample Producing Bureau of the Ministry of Economic Affairs _B7 _ V. Description of the invention (> 7) • NMR (400MHz, δ, CDClj): 1.76 (1H, m). 1.88 (1H, m), 1.94 -2.06 (2H, m), 2.22 (3H, s). 2.48-2.58 (2H, m), 2.78 (1H, m), 3.14 (3H, d, J = 4.5Hz), 3.22 (1H, m), 6.64 (1H, s), 7.42 (1H, s), 8.04 (1H, bs) Preparation Example 3 2- (imidazolium (1 , 2-a] «tidine-6-yl) cyclohexanone

After adding 8.98 g of magnesium to 300 ml of tetrahydrofuran, add 22.07 g of 6-bromodiazepine [1,2-alBft # and 21.2b1, a small portion of 1, 2-dibromoethane / 200b1 tetrahydrofuran, and heat. When β started the reaction later, the rest of the solution was added dropwise while maintaining gentle reflux. After stirring for 1 hour, a solution of 15.8 g of 2-methylaminocyclohexanone and 20.1 tetrahydrofuran was added dropwise. After stirring at room temperature for 2.5 hours, add a saturated aqueous solution of ammonium, add hydrochloric acid and ethyl acetate β to recover the aqueous phase, age with concentrated ammonia, extract with dichloromethane, dry over anhydrous magnesium sulfate, and evaporate the solvent. To give 24.05 grams of brown oil. 19.0 g of this oil was dissolved in 40 · 1 digas methane and dripped into 60β1 concentrated sulfuric acid under ice cooling. After stirring for 1.5 hours, it was poured onto ice and alkalized with concentrated water. Extracted by atmospheric imitation, dried over anhydrous magnesium sulfate, and evaporated to remove the solvent. The column was subjected to silica gel column chromatography (digas methane / methanol = 40: 1 ~ 20: 1). The obtained oil was from B-29. Applicable to Chinese National Kneading (CNS) Α4 specification (210X297 mm) (Please read the note on the back and write this page first) r Pack. Order-· Thread ---- A7 _B7_ V. Description of the invention (d ) The ether crystallized to obtain 7.4 g of the desired product as a milky white powder (yield 39%). • mp (eC): 120-121.5 • NMR (400MHz, δ, CDClj): 1.76-2.12 (4H, m). 2.16-2.28 (1H, m), 2.29-2.38 (lH, m), 2.44-2.62 ( 2H, m), 3.59 (1H, dd, J = 5.5, 12.4Hz), 6.95 (1H, dd, J = 1.6, 9.3Hz), 7.52 (1H, dd, J = 0.5, 1.3Hz), 7.57 (1H , d, J = 9.3Hz). 7.60 (1H, d, J = 1.3Hz), 7.94 (1H, dd, J = 0.5, 1.3Hz) Preparation Example 4 2 -Hydroxy-bu (4-methylimidazole- 1-based) -N-methanyl methionamine (L-type) (please read "Note on the back" before writing this page)

Ordered by the Central Standards Bureau of the Ministry of Economic Affairs, printed by the Consumers Cooperative, 19.09 grams of the product of Preparation Example 2 was suspended in 290 B 1 methanol, and after stirring under ice-cold, 1.44 grams of sodium borohydride was added, and the silicone Thin sacral chromatography (ambient imitation: formazan = 10: 1), a mixture containing low-polar diastereomers (L-type) as the main and highly volatile (M-fluorene) was obtained. After 30 minutes, concentrate to about 70b1 and add about 200 IB 1 of water. The precipitate was collected by filtration and washed with water to obtain 1.1.85 g of the target substance, a white solid (62% yield). Β -30-line-ill --1 —4 · This paper uses China National Standard (CNS) A4 Specifications (210X297 mm) A7 B7 V. Description of the invention (> 9) .m, p. CC): 193-193 • NMR (400MHz, δ, CDC13): 1.28 (1Η, m), 1.46-1.84 (5Η , m), 1.92 (1Η, m), 2.24UH. d, J = 0.9Hz), 2.28 (1H. m), 2.58 (1Η, m). 3.08 (3Hf d, J = 4.8Hz), 3.47 (1H, br), 4.95 (1H, dd, J = 3.7, 11.2Hz). 7.1K1H, d, J = 0.9Hz). 7.26 (1H, br), 7.98 (1H, s) Preparation Example 5 2 -Hydroxy -N-methyl-bu (2-methyloxazolidine [1,2-alpyridin-6-yl) hexamethylene chloride (L-type) (Fill in this page)

, 1T_ 3.03 g (2-methylfluorene [1,2- &] pyridin-6-yl)-^ methyl-2-air cyclohexanemethanilamine suspended in 30b1 formazan and cold After that, add 0.15 grams of boron gas soda. After stirring for 1 hour, 50b1 of water was added, the insolubles were collected by filtration, and recrystallized sequentially from ethanol and acetonitrile to obtain 1.24 g of the target product (white powder) as a diastereomer (yield 41%). • mp (· 〇: 238-243 (dec.) • NMR (400MHz, δ, DMSO): 1.28-1 · 39 (2Η, m), 1.53-1.70 (2Η · m), 1.96 (1H, m), -3 1-This paper size is applicable to China National Standard (CNS) A4 (210X297mm), Central Bureau of Economic Affairs, Ministry of Economic Affairs, Shellfish Consumer Cooperatives, Du printed by the Ministry of Economic Affairs, Zhongfu Standard Bureau, Zhengong Consumer Cooperative «. A7 B7_ V. Description of the invention (w) 2.19 (1H, m), 2.30OH, d, J = 0.7Hz), 2.49 (1H, m), 2.9K3H, d, J = 4.2Hz), 3.32 (1H. M ), 4.61 (1H, br), 4.90UH, br), 7.26 (1H, dd, J = dd, J = 1.6, 9.5Hz), 7.30 (1H, d, J = 9.5Hz), 7.66 (1H, s ), 8.52 (1H, s). 9.22 (1H, br) Preparation Example 6 N-ethyl-2-hydroxy-1- (oxazolylfl, 2-a) pyridin-6-yl) hexane methylsulfide Amidine (a mixture of L- and M-diastereomers with a ratio of about 5: 1)

5.0 g of N-ethyl-pyridine (oxazolyl [l, 2-a] pyridine-6-yl) -2-acyclohexylmethanamine was suspended in 55 μm of methanol and ice-cooled, and 0.25 g of sodium borohydride was added. ^ After stirring for 30 minutes, add about 1050 ml of water to collect the crystals and analyze them in a thin layer of silica. The crystals were obtained as a mixture containing low-polar diastereomeric (L-type) mainly and highly polar (M-type). Recrystallization from ethanol yielded 2.83 g of the target, a white powder (yield 56%). This is a ratio of L- and M diastereomers of about 5: 1, but without further purification for the next process. • NMR ( 400MHz, ύ, DMS〇-dg): 1.02, 1.19 (total 3H, t, J = 7.1Hz), 1.26-1.49 (2H, m), 1.52-1.70 (2H, m), 1.82. 2.00 (total 1H, m), 2.21, 2.74 (total 1H, m), 2.49, 3.75 (total 1H, m), -32- This paper size adopts China National Standard (CNS) A4 specification (210X297 mm) (please read " Note $ on the back, then fill in the book to buy): Binding · A7 B7 V. Description of the invention (w)-3.42-3.55 (lH, m), 3.55-3.70 (1 Γ, m), 4.28, 4.65 (total 1Η , m), 4.89, 6.14 (total 1H, br), 7.34, 7.37 (t〇tal 1H, dd, J = 1.8, 9.7Hz), 7.43, 7.47 (total, d, J = 9.7Hz), 7.51, 7.52 (t otal 1H, d, J = 1.3Hz), 7.93, 7.95 (total 1H, s), 8.45, -8.59 (total 1H, m), 9.34, 10.4 (total 1H, br) Preparation Example 7 2 -Hydroxy-N- The ratio of methyl-1- (2-trismethylmethyloxazolidine1,2-a] pyrimidin-6-yl) cyclohexanemethanilamine (L- and M-diastereomers is about 4 : 1 mixture) ---------- K Pack-(Please read the note on the back before filling this page)

Order, the Central Standards Bureau of the Ministry of Economic Affairs will print 1.86 grams of 1- (2-trifluoromethyloxazolyl [l, 2-alpyridin-6-yl) -N-methyl-2-gas After hexane methionamine was suspended in 17 nl of methanol and ice-cooled, 0.08 g of sodium borohydride was added. After stirring for 1 hour, water was added and the mixture was extracted with chloroform, dried over anhydrous magnesium sulfate, the solvent was distilled off, and recrystallized from ethyl acetate / n-hexane to obtain 1.53 g of an intended product as a white solid (yield 84%). This diastereomer-containing ratio is approximately 4: 1 and is no longer refined for the next reaction. -33- This paper size is applicable to China National Kneading Rate (CNS) Α4 specification (210X297mm), ί%.-^ N-—1 n —4 A7 __B7___ V. Description of the invention Uv) • NMR (400MHz, 6 , CDClj): 1.18-1.32 (1H. M), 1-44-1.98 (5H, m), 2.27, 2.04 (total 1H, m), 2.40, 3.01 (total 1H, m). 3.16, 3.34 (total 3H , d, J = 4.6Hz), 3.38, 5.51 (total 1H, ¢ 3.38: d, J = 3.8Hz. 65.51: br, disappeared in D2〇), 4.79, 4.32 (total 1H, m), 7.41, 7.01 ( total 1H, d, J * 9.7Hz). 7.54, 7.32 (total 1H, dd, J = 1.8, 9.7Hz), 7.76, 7.65 (total 1H. m), 8.78, 7.98 (total 1H, m), 8.03, 10.53 (total 1H, br) Preparation Example 8 (-)-(lS, 2R) -2-hydroxy-1- (oxazolyl [l, 2-a] pyridin-6-yl) -N-methylcyclohexyl Methylmethane (Please read "Note f on the back side before filling out this page")

Order, · 42.91 g (± >-Bu (oxazolyl [1,2-a] pyridin-6-yl) -N-methyl-2- After suspended in 50flml of formazan, aircannyl sulfanilamide was added at room temperature, and 1.70 g of sodium borohydride was added. After stirring for 30 minutes, 1JI water was added and filtered to obtain 36.32 g of light yellow powdery cake. This powder and 4 7.2 9 g (+ > -dibenzylfluorenyl-D-tartaric acid are hot dissolved in water and ethanol, 1: 5 mixed solution of acetic acid 1.8. After standing at room temperature for 12 hours, collect the precipitate, The obtained 21.56 grams of orange needle crystals were suspended in 200 · 1 water, and 50 · 1 concentrated ammonia water β was added and stirred at room temperature for 1 hour, and then the insoluble matter was collected by filtration to obtain 9.51 g (purity > 99ί) of the target substance-3 4 _ 本Paper size is in accordance with China National Standard (CNS) A4 (210X297 mm). Printed by A7 B7, Shellfish Consumer Cooperative, Central Standards Bureau, Ministry of Economic Affairs. 5. Description of invention (W), light orange powder (yield 26%). The optical purity was measured by high-speed liquid chromatography on a column. ≪ Conditions of liquid chromatography > Column: CHIRALCEL (registered trader) OJ (product of Daicel Chemical Industry Co., Ltd. (250 0 mn X 4. 6 * I. D.) : N-hexane / 2-propionase = 4/1 (v / v > mixed liquid column temperature: room temperature flow rate: 1 «ιΐ / min tide detection method: ultraviolet cotton absorption (2 5 4 η) retention time 1 3. 3 minutes (13.3 and 21.5 depending on racemic change) • mp (* 〇: 244-246 (dec.) • Specific rotation U] D28: -44. (C = 0.68, DMF) • NMR (400MHz, 6, DMSO-dg): 1.26-1.40 (3H, m). 1.52-1.72 (2H, m), 1.93-2.02 (1H, m), 2.15-2.25 (1H, m), 2.47-2 · 55 (1H, m), 2.92 (3H, d, J = 4.4Hz), 4.60-4.66 (lH, m), 4.88-4.94 (lH, m), 7.32 (1H, dd, J = 1.8, 9.5Hz) , 7.44 (1H, d, J = 9.5Hz), 7.51 (1H, d, J = 1.3Hz), 7.96 (1H, m), 8.63 (1H, m), 9.20-9.30 (lH, m) Preparation Example 9 2- (N-Third-Butanecarbonylglycine) -1,2-apanyl f 1,2-a] pyridin-6-yl)-methylcyclohexanemethionamine-35- The scale is applicable to China ’s national standard (0?) 8 4 specifications (2 丨 0 father 297 mm): ---;. Installed -------- I order -------- line (please first " Read the note f on the back and rewrite this page) 5. Description of the invention (μ)

H3C HiC H, C person A7 B7

The Central Government Bureau of the Ministry of Economic Affairs, Shellfish, Consumer Cooperation, and Du Printing will produce 2.00 g of 2-hydroxy-1- (oxazolyl [1,2- & 1pyridine-6-yl) -11-methanhexanemethane Amine (M-type), 2.42 g of N-tert-butoxycarbonylglycinic acid, 2.86 g of N, N · -dichenhexylphosphonium diimide and 0.84 g of 4-dimethylaminopyridine. 35.1 N, N-dimethylmethanamine. After stirring at room temperature for 16 hours, ethyl acetate and saturated sodium bicarbonate were added, and insoluble matters were filtered off. The organic phase was separated, washed with water and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography (methane / methanol = 30/1) and crystallized from methane / ether to obtain 2.66 g of the object, white powder (86% yield). • mp (β〇: 140-142 • NMR (400MHz, δ. CDC13): 1.37 (9Η, s), 1.32-1 · 47 (1Η, s), 1.48-1.69 (3Η, m). 1.72-1.85 ( 1H, m), 2.24-2.38 (2H, m), 2.53-2.66 (1H, m), 3.12 (3H, d, J = 3.6Hz), 3.59 (lH, dd, J = 4.8, 1.8Hz), 3.54 -3.70 (lH, m), 3.88 (1H, dd, J = 4.8, 18Hz), 4.96-5.08 (lH, m), 5.90-6.01 (1H, m), 7.13 (1H, dd, J = lHz, 9.4 Hz), 7.30 (1H, d, J = 9.4Hz), 7.57 (1H, s), 7.58 (1H, d, J = lHz), 8.07 (1H, brs), 8.43 (1H, s) 36-paper The dimensions are applicable to the Chinese National Ladder Half (CNS > A4 size (210X297 cm) (please read the note f on the back before writing this page on Qin)) -11 Pack. Order > Line V. Description of Invention (β A7 B7 Preparation Examples 10-20 The following compounds were obtained by following the preparation of Example 9. Preparation Example 10 2- (H-Third-Butanecarbonylglycinylase) ylazol-1-yl) cyclohexanemethanamine methyl-bu (4-A

H3CH »C

H3C

CH: (Please read the note f on the back of the S before you fill in this purchase) • Installed · Printed by the Wc Industrial and Consumer Cooperative of the Central Bureau of Vehicles of the Ministry of Economic Affairs • mp CC): 191-193 • NMR (400MHz, δ, CDC13): 1.27 (1H, m), 1.46 (& H, s), 1.48-1.78 (4H, m), 2.06 (1H, in), 2.29 (3H, d, J = 0.9Hz). 2.38 (1H, m) , 2.81 (1H, m), 3.04 (3H, d, J = 4.8Hz), 3.78 (1H, dd, J = 5.1Hz, 18.1Hz), 3.99 (1Η, dd, J = 6.4Hz · 18.1Hz ), 5.00 (1H, br) 6.0K1H, dd, J = 3.7Hz, 11.7Hz), 6.77 (1H, br), 7.26 (1H, s), 7.79 (1H, s) Preparation Example 11 2- (N- Tert-Butylcarbonylglyceryloxy) -N'-ethyl-1- (oxazolyl [l, 2-a] pyridin-6-yl) cyclohexanemethanilamine-37-for paper : Dimensions: Chinese National Standard (CNS) A4 (210X297 mm) Order · Line A7B7

H, C H.C V. Description of the invention (#)

H3C: Fire mp CC): 206-210 NMR (400MHz, δ, CDC13): 1.1K3H, t, J = 7.3Hz), 1.32-1.46 (1 «, m), 1.38 (9H, s), 1.51-1.68 (3H, m). 1.80 (1H, m), 2.23-2.38 (2H, m), 2.59 (1H, m), 3.53-3.75 (311, m), 3.91 (1H, dd, J = 6.2Hz, 17.9 Hz). 5.01 (1H, br). 5.99 (111, dd, J = 2.9, 8.6Hz), 7.2K1H, dd. J = 1.3, 9.5Hz). 7.4K1H. Br). 7.49 (1H, d, J = 9.5 Hz). 7.62 (1H, s). 7.63 (1H, s), 8.47 (111, s) Preparation Example 12 2- (H-Third-Butylcarbonylglycinylamino) -N'-methyl -(2-methyloxazolidine [1,2-a] pyrimidin-6-yl) cyclohexanemethanilamine -------- I-; -I-ΙΓpack ----- -I, π .------ (please read the note $ on the back before filling out this page) Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs

HjC HaC H, C Fire

CH, This paper size is applicable to China_Home Slope (CNS) A4 specification (210X297mm) A7 B7 V. Description of the invention (μ) • mp (" C): 229-233 (dec.) • NMR (400MHz , δ, CDClj): 1.34 (9H, s), 1.40 (1H, m), 1.50-1.85 (4H, m), 2.22 (1H, m), 2.35 (1H, m), 2.46 (3H, s), 2.58 (1H, m), 3.08 (3H, d, J = 4.8Hz), 3.62 (1H, dd, J = 5.Q, 17.9Hz), 3.91 (1H, dd, J = 6.0, 17.9Hz), 4.97 (1H, br), 5.95 (1H, dd, J = 3.5, 9.3Hz), 7.15 (1H, d, J = 9.7Hz), 7.37 (1H, s), 7.39 (1H, d. J = 9.7Hz) . 7.49 (1H, br), 8.40 (1H, s) Preparation Example 13 (Please read the note on the back and fill in this page first) r Binding · Binding-

H, C HaC H3C: Fire 2-(N-tertiary butane carbonyl glycamine aldehyde) -IT-methyl-1-(2 fluoromethyloxazolyl [l, 2-a] pyridine-6- Methyl) cyclohexane methylamine

CF: Seal of the Shellfish Consumer Cooperative of the Central Samples and Standards Bureau of the Ministry of Economic Affairs • mp (eC): 199-204 * NMR (400MHz, «, CDClj): 1.34 (9H, s), 1.37 (1H, m), 1.52- 1.95 (4H, m), 2.28 (1H, m), 2.37 (1H, m), 2.60 (1H, m), 3.13 (3H, d, J = 4.6Hz), 3.63 (1H, dd, J = 5.6, 18.0Hz). 33- The standard of this paper is t 阄 national standard rate (CNS) A4 specification (210X297mm) Printed by A7 __.____ B7_ Jade, invention description (cedar) 3.87 (1H, dd, J = 6.0, 18.0Hz). 5.00 (1H, m). 5.99 (1H. Dd, J = 2.8, 8.4Hz), 7.37UH, dd, J = 1.5, 9.5Hz), 7.43 ( 1H, d, J = 9.5Hz), 7.70 (1H, br), 7.88 (1H, s), 8.48 (1H, s) Preparation Example 14 2- (N-Third-butanecarbonylcarnitamine enzyme gas group)- 1-sleeper [1,2-al-pyridin-6-yl) -N'-formamidine methionine

H, C HaC

HiC: Fire

NMR (400MHz, 6, CDClj): 1.33, 1.41 (total 9H, s). 1.22-1.96 (5H, m), 2.17-2.4K2H, m) 2.53-2.66 (lH, m), 2.71, 2.77 (total 3H, s), 3.09, 3.11 (total 3H, d, J = 4.8Hz), 3.62, 3.67 (total 1H. D, J = 17.9Hz). 4.01, 4.05 (total 1H, d, J = 13.0Hz), 5.90, 6.14 (total 1H, dd, J = 3.5, 8.9Hz), 7.18. 7.23 (total 1H, dd, J = 1.3. 9.5Hz). 7.43 · 7.50 (total 1H, d, J = 9.5IIz), 7.54 -7.92 (ΠΙΙ, ra), 8.48 (1H, s) Preparation Example 15 2- (N-Third-butanecarbonyl-Ling-propylamine fluorenyl) -40- (oxazole hydrazone [1 ^ rci. / Ί. -------: --- 7 ^ ----- ^ — ιτ ------ ^ (please read the note f on the back before filling this page) Standard (CNS) A4 (210X297 mm) i. Description of the invention (Clever) A7 B7 a] Pyridin-6-yl >

H, Cn NaC

* mp CC): 183-185 'NMR (400MHz, b, CDClj): 1.30-1.46 (1H. m) · 1.4K9H, s), 1 · 52-1.82 (4H, m), 2.20 (1H, m) 2.30-2 · 39 (2Η, m), 2.47 (1H. M), 2.62 (1H, m). 3.09 (3H, d. J = 4.8Hz), 3.24 (1H, m), 3.39 (1H, m) , 4.89 (1 ^, br), 5.97 (1H, dd, J = 3.1, 8.8Hz), 7.22 (1H, dd, J = 1.3, 9.5Hz), 7.46 (1H, br), 7.52 (1H, d, J = 9.5Hz), 7.64 (1H, d, J = 1.3Hz), 7.68 (1H, s), 8.56 (1H, s) Preparation Example 162- (2- (U-Third Butane Carboxamido)) Butyrinyl-> (oxazolyl, 2-a] pyridin-6-yl) -N'-methane hexane methyl brick amine (please read the note $ on the back before writing 4) 贳) C line · .ΤΓ line ---- Printed by the Central Bureau of Standards of the Ministry of Economy

HaC

This paper size is applicable to China National Standard (CNS) A4 (210X297 mm) • V. Description of the invention (ρ) A7 B7 • mp (β〇: 176-178 • NMR (400MHz, δ, CDCljH 1.18-1.85 (19H , m). 2.23 (1H, m), 2.38 (1H, m), 2.65 (1H, m), 3.08 (3H, d, J = 4.8Hz), 4.98 (1H, br), 5.93 (1H, dd, J = 3.3, 9.5Hz), 7.24 (1H, m), 7.48-7.68 (4H, m), 8.56 (1H, br) Preparation Example 172- (N-Third butane carbonylpropylamine enzyme gas group)-Bu ( Oxazolidine [l, 2-a] pyridin-6-yl) -N'-methylhexylmethanamine (mixture of diastereomers about 3: 2)

H, C

(Please read the note on the back before filling in this X) Equipment · Printed by the Shellfish Consumer Cooperative of the Central Bureau of Economic Affairs of the Ministry of Economic Affairs «. NMR (400MHz, 6, CDClj): 1.14-1.88 (5H, m), 1.03, 1.27 (total 3H, d. J = 7.1Hz), 1.35, 1.38 (total 9H, s), 2.20-2.41 (211, m), 2.56-2.68 (lH, m), 3.09 (3H, d, J = 4.8 Hz), 4.05-4.26 (1H, m), 4.89, 5.00 (total 1H. D, J = 8.0Hz), 5.99 (1H, dd, J = 3.1, 8.8Hz), 7.19, 7.21 (total 1H. Dd, J = 1.8, 9.5Hz), 7.39-7.49 (1H, m), 7.43, 7.47 (total 1H, d, J * 9'.5Hz), 7.58-7.64 (2H.m), 7.67, 7.85 (total 1H, br), 8.47, 8.50 (total 1H, s) 42- The paper size is applicable »Country kneading rate (0?) &8; 4 specifications (2 丨 0 > < 297 mm) Central Kneading Bureau, Ministry of Economic Affairs Printed on A7 Consumer Cooperatives. B7. V. Description of the invention U *) Preparation Example 18 2- (N-Third butane carbonyl amphetamine hydrazone) -1- (眯 脞 骈 [1,2 -a] 丨 ft Pyridin-6-yl) -N · -methanyl methionamine (a mixture of diastereomers with a ratio of about 3: 2).

• NMR (400MHz, 6. CDC13): 1.18-1.82 (5H, m), 1.33, 1.35 (total 911, s), 2.01-2.77 (3H, m). 2.96-3.10 (5H, m), 4.37. 4.46 (total 1H, m), 4.86, 4.91 (total 1H, d, J = 8.6Hz), 5.83, 5.89 (total 1H, m). 6.98-7.33 (GH, m), 7.38-7.65 (4H, m), 8.23, 8.54 (total 1H, s) Preparation Example 13 2- (N-Third-butanecarbonylproline enzyme gas group) -1: (oxazolyl U, 2-al pyridin-6-yl) -N ' -Methylcyclohexanemethoxamine (mixture of diastereomeric f ratio of about 1: 1) -43- This paper size is in accordance with China National Standard (CNS) A4 (210 > < 297 mm) ( Please read the note on the back of the page before writing this page) 『Binding and ordering. A7 B7 Λ 、 Invention description (^)

• NMR (400MHz. Δ, CDClj): 1.20-1.94 (1811. M). 2.12-2.70 (311, m), 3.04. 3.09 (total 3H, d, J = 4.8Hz), 3.25-3.55 (2H, m ). 4.26-4.33 (lH, m), 6.07, 6.14 (total 1H, m), 7.09 (1H, m). 7.15-7.24 (1H, m), 7.55-7.70 (3H, m), 8.59, 8.67 ( total 1H, s) Preparation Example 20 2-iN-Third-butanylcarbonyl-fluorene-benzyl asparaginyloxy) -Bu (oxazolyl 骈 fl, 2-a) pyridine-6-yl) -H ' -Methylcyclohexanemethionin (a mixture of diastereomers with a ratio of about 1: 1) IIIIII —I —pack nnn. Order, 1 — ~ I 'line (please read the “$” on the back side before filling (This page) Printed by the Central Government Bureau of the Ministry of Economic Affairs

-4 4 This paper size applies to China's national kneading rate (CNS) A4 specification (210X297 mm) A7 B7 V. Description of the invention (o) • NMR (400MHz, δ, CDClj): 1.27-1.88 (8H, m), 1.30 , 1.35 (total 9H, s), 2.23-2.37 (2H, m), 2.52-2.76 (2H, m), 2.82-2.95 (lH, m), 3.08, 3.12 (total 3H, d, J = 4.6Hz) , 4.30-4.49 (lH, m), 4.91-5.04 (2H, m), 5.32, 5.54 (total 1H, m), 5.81, 5.93 (t〇tal 1H, m), 7.03-7.13 (lH, m), 7.21- 7.40 (6H, m). 7.55-7.65 (2H, m). 8.00-8.20 (lH, br), 8.46-8.52 (lH, m) Preparation example 21 2- (N-Third-butanecarbonyl isovalerate Oxamethoxan) -Bu (oxazosin [1,2-albipyridin-6-yl) -N'-methylcyclohexanemethanilamine (M-type) (Please read Note f on the back first Items on this page).

, 1T, 1.0 g of 2-hydroxy-bu (oxazolyl [1,2-a] pyridin-6-yl) -N-methylcyclohexanemethanilamine printed by the Central Working Group Consumer Cooperative of the Ministry of Economic Affairs , 1.32 g of N, fT -dicyclohexyl trifluoride diimide, 1.44 g of (L) -N -third butane carbonylisohumoxamic acid and 0.4 g of 4-dimethylaminopyridine were put into 20b1 N, N- Dimethyl methyl amine, and after stirring at room temperature for 17 hours, add ethyl acetate and saturated sodium bisulfate water, filter off the insoluble matter β, take the ethyl acetate phase, and wash with water and saturated brine. , Dried over anhydrous magnesium sulfate, distilled off the solvent, and subjected to silica gel column chromatography (digas methane / methyl-45- this paper size is applicable to the middle and low countries) (CNS specification (210X297 mm) A7 £ 7_ V. Description of the invention ( ") Fermentation = 40: 1), 0.41 g (253!) Of low-polar diastereomers (L-type), white powder, and 0.52 g (3 1! 〇 highly volatile (M-type) ), White powder 〇 mp (eC): 228-229 • NMR (400MHz, 6, CDC13): 0.55 (3H, br d, J = 6.2Hz), 0.78 (3H, d, J = 6.8Hz), 1.18 -1.38 (2H, m), 1.41 (9H, s), 1.48-1.88 (4H, m), 2.29 (1H, m), 2.37 (1H ', m), 2.65 (1H, m), 3. 08 (3H.d, J = 4.8Hz), 4.10 (1H, dd, J = 4.9Hz, 9.2Hz), 4.96 (1H, d, J = 9.2Hz), 5.95 (1H, m), 7.24 (1H, m), 7.39 (1H, br), 7.56 (1H, d, J = 9.7Hz), 7.66 (1H, s), 7.67 (1H, s) 8.58 (1H, br s) Preparation Examples 22 ~ 24 Similar Preparation Examples 2 1 each to obtain the following compounds. Preparation Example 22 2- (N-Third-butanecarbonylisohumapoxamylase > > -1- (oxazolidine [1,2-alpyrimidin-6-yl)- fT -Methylcyclohexanemethanilamine (L-type) > / v, —av IIIIII -y I Pack —— Order · I line (please read the note on the back before filling this page) Ministry of Economy Printed by the Central Sample Rates Cooperative Consumer Cooperative

_ 4 6 _ This paper size is applicable to the standard of Chinese households (CNS specifications < 210X297 mm). The Central Standards Bureau of the Ministry of Economic Affairs, β 消费, Consumer Cooperation, Du printed A7 _B7_ V. Description of the invention (w) • mp CC): 248-249 • NMR (400MHz, 6, CDClj): 0.79 (3H, d, J = 6.8Hz). 0.87 (3H, d, J = 6.8Hz), 1.20-1.34 (1H, m), 1.37 (9H, s), 1.51-1.69 (3H, m), 1.78 (1H, m), 2.00 (1H. m). 2.24-2.40 (2H, m), 2.59 (1H, m), 3.10 (3H, d, J = 4.4Hz), 3.98 (1H, dd, J * 5.5. 8.4Hz), 4.82 (1H, d, J = 8.4Hz), 6.00 (1H, dd, J = 3.5, 8.6Hz), 7.17 (1H, m) , 7.35 (1Η, br d, J = 9.9Hz), 7.56 (1H, s), 7.60 (1H, s). 7.94 (1H, br), 8.45 (1H, br s) Preparation Example 23 2- ( N-Third-butanecarbonyl--0-Third-butylserine fluorenyl group -1- (imidino [l, 2-a] pyridin-6-yl) -N'-methylcyclohexane Methamidamine (M-type)

• mp (· 〇: 201-205 • NMR (400MHz, δ, CDClg): 1.06 (9Η, S), 1.38 (9Η, s), 1.42 (1Η, m), 1.50-1.70 (3Η, m), 1.82 UH. M), 2.25-2.40 (2Η, m), -47- This paper size is applicable to China National Standards (CNS) Α4 size (210X297 mm) (please read the "$" on the back side before writing this page) ) · Ι. * 1Τ'—Printed A7 _._ B7_ Λ, _._ B7_ Λ, Invention Note (4〇2.59 (1H, m), 3.11 (3H, d, J = 4.4Hz) , 3.48 (1H, m), 3.65 (1Η · m), 4.16 (1H, m), 5.16 (1H, d, J = 8.2Hz), 5.93 (1H, m), 7.10-7.2K1H, m) , 7.29-7.36 (1H, m), 7.54-7.65 (2H · in). 7.79-8.10 (1H, m), 8.41-8.50 (1H, m) Preparation Example 2- 2- (N-Third butanecarbonyl- 0-Tertiary butyl serine zymoyl-imidazolium (imidazolium fl, 2-a] pyrimidin-6-yl) -N1-draxylmethanesulfonamide (L-type)

• mp (· 〇: 219-223 (dec.) • NMR (400MHz, 4. CDClj): 1.07 (9H, s). 1.2K9H, s), 3.34 (1H, m), 1.50-1.62 (2H, m ). 1.68 (1H, m), 1.90 (1H, m), 2.18 (1H, m), 2.38 (1H, m), 2.65 (1H, m), 3.09 (3H, d, J = 4.6Hz), 3.45 (1H, dd, J = 3.5, 9.2Hz). 3.70 (1H, m), 4.2K1H, m), 5.33 (1H, d, J = 8.1Hz), 5.71 (1H, m), 7.12-7.19 (1H , m), 7.48-7.54 (1H, m), 7.62-7.74 (3H, m), 8.52-8.58 (lH, m) Preparation Examples 25 -48- This paper scale is applicable to China National Standard (CNS) A4 specifications ( 210X297 mm) (please read the notes on the back before writing this page) [installation, IT · line A7 B7 V. invention description (〇) (+)-(lS, 2R) -2- (N- Tert-butoxycarbonyl eucalyptyl) -1- (fluorene [1,2-a] pyridine-6-yl) -N'-methanehexylmethanamine

5.11 g of this (-)-(13,21〇-2-hydroxy-bu (oxazolyl [1,2-81pyridin-6-yl) -N-methylcyclohexanemethanilamide, 6.2 g of N- Dibutylaminoglycine, 7.3 g ff, Ν'-dicyclohexylsulfodiimide and 2.16 g 4-dimethylaminopyridine were injected into 60 · 1 Ν, Ν-dimethylformamide Enzyme was stirred at room temperature overnight. The solid was filtered off and concentrated in vacuo. Ethyl acetate was added, washed with water and saturated brine, dried over anhydrous magnesium sulfate, the solvent was evaporated, and the residue was subjected to silica gel column chromatography (dichloromethane). / Methanol = 30: 1), crystallized from n-hexane / ethyl acetate to obtain 6.89 g of the target, a white powder (yield 88%). (Please read the note $ on the back before filling in this I). ..— Line-to-work consumer cooperation with Central Standards Bureau of the Ministry of Economic Affairs Du printed mp (β〇: 172-173 • Specific rotation U] D28: +24.3. (C = 0.68, chloroform) • NMR (400MHz, β, CDClj ) 1.37 (9H, s), 1.32-1.47 (1H, s), 1.48-1.69 (2H. M), 1.72-1.85 (1H · m) · 2.24-2.38 (2H, m), 2.53-2.66 (1H, m), 3 · 12 (3Η, d, J = 3.6Hz), 3.59 (1H, dd, J = 4.8, -49- The standard of this paper is to use the Chinese national standard (CNS Μ4 specification (210X297 mm)

2 A7 B7 V. Description of the invention (W) 18Hz), 3.54-3.70 (lH, m), 3.88 (1H, dd, J = 4.8, 18Hz), 4.96-5.08 (lH, m), 5.90-6.01 (1H, m), 7.13 (1H, dd. J = l, 9.4Hz), 7.30 (1H, d, J = 9.4Hz), 7.57 (1H, s), 7.58 (1H, d, J = lHz), 8.07 (1H , br s), 8.43 (1H, S) Preparation Example 2 6 2- (2-Bu # sulfamoyl) ethoxy) -bu (oxazolyl [1,2-a! pyridine-6-yl) -1-((4-methylbenzylthio)-(methylimino) methyl) hexane

CH 1.31 g 2- (Deep sleep [1,2-aHft pyridin-6-yl) -2-((4-methylbenzyl) (methylimino) methyl) cyclohexanol suspended in 50 »1 After cooling to -60 T with tetrahydrofuran, 0.4 g of potassium tert-butoxide was added. After stirring for 2.5 hours, 0.82 g of N- (naphthosulfonyl) aziridine was added. The temperature was gradually raised to 0 ° C, and the mixture was stirred under ice cooling for 5.5 hours, and then a saturated aqueous ammonium solution was added. It was extracted with ammonium hydroxide and dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography (methane / methanol = 40: 1) to obtain 0.4 g of the target substance as white amorphous (yield 1). 9 % .). -50- This paper size is applicable to China National Standard (CNS) Α4 specification (210X297 mm) -------: -IK Pack -----: 丨 Order .------ Line (read Read the note on the back first and then fill in this purchase) Central Government Bureau of Standards, Ministry of Economic Affairs, Shellfish Consumer Cooperation Du printed A7 B7

V. Description of the invention (〇) • NMR (400MHz, 6, CDClg): 1.43 (1H, m), 1.68 (iH, m), 1.76-1.84 (2H, m), 2.04 (1H, m), 2.44 (1H , m), 2.74-2.90 (2H, m), 3.0K1H, m), 3.33 (1H, d, J = 12.3Hz), 3.50 (1H, m), 3.58 (1H, d, J = 12.3Hz), 3.60 (3H, s), 3.68-3.75 (5H, m), 4.22 (1H, br s), 4.54 (1H, br), 6.50-6.56 (2H, m), 6.61-6.67 (2H, m), 7.15 (1H, dd, J = 1.8, 9.5Hz), 7.38-7.6K7H, m), 7.65 (1H, d, J = l.lHz), 8.02 (1H, m) Preparation Example 27 2- (2 -Benzylsulfonate Enzyme ethoxy >-((oxazosin [l, 2-a] U | tidine-6-jib ((4-methylbenzylthio) (methylimino) methyl) cyclohexyl Alkanes 0CH: ------- ^ --- ^ -----. · 1 Order ------ 0 (Please read the note on the back before filling in this page) Central Standards of the Ministry of Economic Affairs Cooperating with local shellfish consumer cooperation, Du Yinxian imitation Preparation Example 26, but using zylidene. Acrylidine. Phenylsulfonyl aziridine instead of N- (1-Cesulfuron 5 1 This paper is applicable to Chinese national standard ( CNS) A4 specification (210X297 mm) A7 B7 V. Description of invention (β) • NMR (400MHz, b, CDC13): 1.12-1.40 (2H. M), 1.52-1.66C2H, m), 1.88 (1H, m ), 2.34 (1H, m), 2.68 (1H, m). 2.85 (1H, m), 2.93 (1H, m), 3.33 (1H, d, J = 12.3Hz), 3.38 (111, m), 3.59 (311, s), 3.68-3.74 (511, m). 4.13 (1H, br s). 4.81 (1H, br), 6.50-6.56 (2H, m), 6.61-6.67 (211, m), 7.06 (1H, dd, J = 1.8, 9.5Hz), 7.41-7.50 (3H, m), 7.56- 7.66 (3H, m), 7.90 (1H, m), 7.94 (1H, dd, J = 1.6, 7.9Hz), 8.04 (1H · d. J = 8.2Hz). 8.10 (1H, dd. J = ll 7.3 Hz), 8.42 (1H, d, J = 8.8Hz) Cleavage preparation example 28 2-Glycine oxo-imidazolium (imidazolium [1,2-a] pyrimidin-6-yl) -N-methylcyclohexyl Methanethioamide (please read the note on the back before filling this page) • Pack.

The Central Rubbing Bureau of the Ministry of Economic Affairs, ΛIndustry and Consumer Cooperation, Du printed 2.43 g of 2--third butyl gas carbonylglycine hydrazone-based) -bupropazole hydrazone [l, 2-a] 枇 巧- 6-yl) -N, -methylcyclohexanemethanilamine was dissolved in 5.1 dioxane, and after ice cooling, 5b1 trifluoroacetic acid was added. After stirring for 1 hour, it was basified with sodium sulfonate by adding ice water. It was extracted with dichloromethane and dried over anhydrous magnesium sulfate, and the solvent was distilled off. The obtained solid was washed with ether. -52- This paper is suitable for China Standards (CNS) M specifications (210X297 mm) B7 V. Description of the invention (M ) To obtain 1.71 g of the target product as a pale yellow powder (yield 92%). This was not refined any more for the next reaction. (Please read the note on the back before filling in this page.) Preparation Examples 29 to 31 The following compounds were obtained in the same manner as in Preparation Example 28. Preparation Example 2-Glycinylamino-N-methyl-1- (4-methylfluoren-1-yl) cyclohexanemethanilamine

2-Proline fluorenyl-1- (oxazolyl [l, 2-a] pyridin-6-yl) -N-methylcyclohexanemethanilamine (diastereomer ratio of about 1: 1 mixture)

Produced by Dumpling Cooperative of the Central Government Bureau of the Ministry of Economic Affairs of China. Preparation Example 3 1 1- (Azolo [l, 2-a] Pttidine-6-yl) -N-methyl- (2-carnitamine气 -53- This paper is scaled to the Chinese national kneading rate (CNS specification (210X297 mm) A7 B7 Printed by the Central Government Bureau of the Ministry of Economic Affairs, Shellfish Consumer Cooperative, Du printed 5. Description of the invention (h)) Zymamine

Preparation Example 32 2- (fluorenyl-benzyl asparagine gas group) -1- (oxazolidine [1,2-aIlttimidine-6-yl group] -N-methylcyclohexanemethanilamine (single Diastereomer)

1.10 g of 2- (N-tert-butanylcarbonyl-therapeutic-benzyl aspartame fluorenyl) -bu (oxazolyl [1,2-alpyridin-6-yl) -N'-methylcyclohexane Methionamine (prepared in Preparation Example 20) was dissolved in 5b1 dinitromethane, and 5nl of trifluoroacetic acid was added. After stirring under ice-cooling for 1 hour, water was added to soda with disulfonic acid. Extracted by gas imitation, dried with anhydrous magnesium sulfate, evaporated and dissolved in silica gel column chromatography (dichloromethane / methanol = 10 :, to obtain 0.67 grams of high pole -54-) This paper is suitable for Chinese families. (CNS > A4 size (210X297 mm) ------- „--- ^ -----, 1 order ------- 0 (Please read the note on the back before filling in This page} A7 ___ B7_ V. Description of the invention (^) Diastereomers, colorless oil (71% yield). • NMR (400MHz, δ, CDClj): 1.41-1.74 (7H, m), 2.21-2.33 (2H.m). 2.52-2.77 (3H, m), 3.11 (3H, d, J = 4.6Hz), 3.5.4 (1H, m). 5.05 (1H, d, J = 12.3Hz), 5.09 ( 1H, d, J = X2.3Hz), 6.03 (1H, dd, J = 2.9, 7.5Hz), 7.10-7.19 (1H, m), 7.28-7.38 (6H, m), 7.54-7.58 (2H, m ), 7.98-8.11 (1H, br), 8.41-8.45 (1H, m) Preparation Example 33 2 -Glycaminofluorenyl-1- (oxazolidine1,2-aHftidine-6-yl) -N -Methyl hexane methionamine dihydrochloride (please first read the note on the back and then write this page)-Pack.

Ding 'line Ministry of Economic Affairs Central Bureau of Quasi-Bureau Consumption Cooperation for Shellfish Du India Packing 6.0 g 2- (N-Third-Butane-Carboxyglycinamine-Gasyl) -1- (Sleep Cake [l, 2-a] pyrimidine -6-yl) -N'-formamidine thiomethanamine (Preparation Example 9 Preparation) After dissolving in 120β1 aerosol, add 30β1 4N HC1 / ethyl acetate. After stirring at room temperature for 4 hours, evaporate to dryness. 5.8 g of the target substance was obtained, and the white powder was no longer refined for the next reaction. Preparation Example 34 (IS, 2IU-2 -Glycine hydrazone-bu (oxazolyl [1, 2-a] pyridin- 6- -55- This paper size is in accordance with Chinese national standard (CNS > A4 size (210X297mm))

A7 B7 V. Description of the invention (β) -N-methylcyclohexanemethanamine dihydrochloride

12.0 g (+)-(lS, 2R) -2- (N-Third-butanecarbonylglyceryl sulfanyl group)-Bu (imidazo [1,2-a] pyridin-6-yl)- Ν'-methyl rose hexane methylthiopyramine (prepared in Preparation Example 25) was dissolved in 250 · 1, and 60 · 1 10 3: HC1 / ethyl acetate was added. After stirring at room temperature for 12 hours, it was concentrated and Add in ethyl acetate to filter the insolubles to obtain 11.3 g of the target product, a pale orange powder (yield 100 ×) ^ no longer refined for the next reaction. Preparation Example 35 The third butane carbonylglycinyl group) glycine fermentation gas group) -1- (oxazolidine [1,2-alBftidine-6-yl > -N " -formamidine

0.5 g of 2-glycerofluorenyl-pyridine (oxazolyl. [1,2-alffttidine-6-yl) N-methylcyclohexanemethanilamine (prepared in Preparation Example 33) 0.3 g of N-third Ding-56- This paper size is free to use Chinese National Standard Half (CNS) A4 specification (210X297 mm) -------: -IK Pack ------- Order, ------ (Please (Please read the note on the back before filling in this page) Printed by the Central Ministry of Economic Affairs

A7 B7 V. Description of the invention (beating) Gas carbonyl glycine, 0.35 g of N, N'-dicyclohexyl sulfodiimide and 0.23 g of N-hydroxybenzotriazole are put into 10.1 acetonitrile. After stirring at room temperature for 14 hours, add formic acid, remove insoluble matter by filtration, add dichloromethane and remove insoluble matter, and then use silica gel column chromatography (dichloromethane / methanol = 30: 1 ~ 20: 1) β The oil obtained was crystallized from acetonitrile to obtain 0.67 g of the target substance, a white powder (yield 95%). β • mp (eC): 177-180 • NMR (400MHz, δ · CDC13): 1.31-1.49 (1H, m), 1.44 (9H, s), 1.50-1.69 (3H, m), 1.84 (1H, m), 2.25 (1H, m), 2.34 (1H, m). 2.61 (1H. M), 3.10 (3H, d, J = 4.6Hz), 3.64-3.84 (3H.m), 4.04 (1H, dd, J = 5.7, 17.6Hz), 5.18 (1H, br), 5.98 (lH, m), 6.77 (1H, br ), 7.19 (1H, d, J = 9.5Hz), 7.43 (1H, d, J = 9.5Hz), 7.6〇 (lH, s), 7.67 (1H, s), 7.84 (1H, br), 8.47 ( 1H, s) Preparation Example 36 2-(N-(N '-Third-butanecarbonylcarbonylglycinamido) carnitine 81 amino>-bulfazolidine [l, 2-a] pyridine-6- Based) -N " -Methylcyclohexanemethanilamine S ΗοΟΠ I H3C 0 H # C (please read the note f on the back before filling in this page) —Packing. Order 'line

This paper size is applicable to China's Standards for Standards (CNS) A4 (210X297 mm). The central government's bureau of the Ministry of Economic Affairs, Shellfish Consumer Cooperation Du Yin *. A7 _B7_ V. Description of the Invention (A) The product of Preparation Example 31 is The starting material was prepared in the same manner as in Preparation Example 35. • NMR (400MHz, 6, CDClj): 1.21, 1.39 (total 9H, s), 1.18-1.85 (5H, m). 2.12-2.40 (2H, m), 2.51-2.74 (1H, m), 2.78, 2.88 (total 3H, s), 3.04, 3.10 (total 3H, d, J = 4.6Hz), 3.71-4.1S (4H, m), 5.12, 5.25 (total 1H, br), 6.02, 6.10 (total 1H, dd , J = 3.5, 9.3Hz), 7.15, 7.25 (total 1H, dd, J = 1.8, 9.5Hz). 7.36. 7.77 (total 1H, br), 7.56, 7.59 (total 1H, d, J = 9.5Hz) , 7.63, 7.66 (total 1H, d, J = 1.8Hz), 7.72, 7.77 (total 1H. S). »; 36, 8.49 (total 1H, s) Example 1 2- (N-benzenesulfonylglycine Fluorenyl) _ -6 -yl) -N "-methylcyclohexanemethanilamine X / 〇 * fΗ0 0.5 g 2 -glycinamine fluorenyl-1- (oxazolyl [1,2-a] Pyridin-6-yl) -methylcyclohexanemethylthio-amine (prepared in Preparation Example 28) was suspended in 3 ml of digas methane, 0.13 · 1 pyridine was added, stirred under ice cooling, and 0.2β1benzenesulfonyl-58- was added dropwise. (Please read "Note $ on the back side before filling out this page) -pack.-(Oxazole 眯 [l, 2-a 丨 pyridine

Order-· This paper size uses China National Standard (CNS) A4 specification (210X297 mm) A7 B7

V. Description of the invention (P Fermentation / 2β1 Dilute methane β 40 minutes, add concentrated atmosphere water and add water, followed by extraction with ammonium followed by drying with anhydrous sodium sulfate, evaporate the solvent, and use silica gel column chromatography (diazomethane / Formazan = 40: 1), crystallized from dichloromethane / ethyl acetate, and recrystallized from ethyl acetate to obtain 0.49 g of the target substance, white needles (yield 72%. • mp CC): 226- 227 • NMR (400MHz, 6, CDClj): 1.38 (1H, m), 1.51-1.8K4H, m), 2.18 (1H, m), 2.37 (1H. M), 2.57 (1H, m). 3.06 (3H , d, J = 4.8Hz), 3.6K1H, d, J = 17.8Hz), 3.72 (1H, d, J = 17.8Hz), 5.42 (1H, br), 5.94 (1H, dd, J = 3.5, 9.3 Hz), 7.18 (lHf dd, J = 1.8, 9.5Hz), 7.45-7.54 (3H, m), 7.54-7.63 (3H, m), 7.70 < lH, s >, 7.77-7.81 (2H, m) , 8.59 (1H, m) Example 2 2- (N- (2-furansulfonyl) glycine fluorenyl group> -1- (oxazole fluorenyl fl, 2-a) pyridin-6-yl}- Ν '-Methylcyclohexane-Methionamide ------- ^ ---- Meal -----,-Order, ------ 0 (Please read "Note $ on the back" first (4 more pages on this page) Printed by the Central Government of the Ministry of Economic Affairs

0.2 g of 2-glycine hydrazone (oxazolyl [1,2-a] pyridin-6-yl) -59- This paper size applies to China National Kneading (CNS) A4 size (210X297 mm) } A7 B7 V. Description of the invention (W) -H-Methylamine thiomethoxamine (prepared in Preparation Example 28) was suspended in 2nl Hitidine, and fl. 11 g of 2-furansulfonamide was added dropwise under ice-cooling β After stirring for 2 hours, add dilute water. Extract with dichloromethane and dry over anhydrous magnesium sulfate, evaporate the solvent, and use silica gel column chromatography (dicyanomethane / formaldehyde = 40/1) to crystallize from ether to obtain 0.15. Gram target, light yellow powder (54% yield). • NMR (400MHz, 6, CDC13): 1.38 (1H, m), 1.49-1.84 (4H, m), 2.21 (1H, m), 2.37 (1H , m), 2.58 (1H, m), 3.07 (3H, d, J = 4.6Hz), 3.72 (1H, d, J = 17.9Hz), 3.81 (1H, d, J = 17.9Hz), 5.97 (1H , dd, J = 3.7, 9.5Hz). 6.47 (1H, dd, J = 1.8, 3.5HZ), 6.97 (1H. dd, J = 0.9, 3.5Hz), 7.15-7.27 (2H, m), 2.46 ( 1H, d, J = 9.5Hz), 7.54 (1H, dd, J = 0.9, 1.8Hz), 7.57 (1H, d, J = l.lHz), 7.59 (1H, br), 7.68 (1H, m) , 8.57 (1H, m) Example 3 2- (N- (2-Blannylsulfonyl) glycinylamino) -1- (oxazolyl [1,2-a] pyridin-6-yl) -Ν '-甲 环 己Methylthio leaven amine (please, "read the back of the note and then fill in item f of this page) - loaded 1T 'line Ministry of Economic Affairs Bureau of the Central rub quasi HIGHLAND consumer cooperatives printing equipment

0.3 g 2 -Glycine hydrazone-1- (oxazolyl [1,2-a] pyridine-6-yl) *** 6 0- This paper is standard for Chinese national standards (CNS M4 specification ( 210X297mm) Shellfish Consumer Cooperation Duyinhu A7 B7, Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the Invention (") -N -Methylcyclohexane Methionine (prepared in Preparation Example 28) suspended in 3.1 atmosphere Methane, add 0.08 · 1 pyridine, add 0.17 g of 2-sulfanylsulfonium under ice cooling, stir for 1 hour, stir at room temperature for 15 minutes and add dilute water. Extract with chloroform and dry over anhydrous magnesium sulfate. The solvent was distilled off, and the residue was subjected to silica gel column chromatography (methane / methanol = 40: 1), and the obtained oil was crystallized from chloroform / acetamidine, 0.31 g of the target substance, and a white powder (yield 72%). Mp ( β〇: 143-145 • NMR (400MHz, δ, CDClj): 1.40 (1H, m), 1.52-1.68 (3H, m), 1.76 (1H, m), 2.2K1H, m), 2.38 (1H, m ), 2.56 (1H, m), 3.07 (3H, d, J = 4.6Hz), 3.67 (1H, d, J = 17.8Hz), 3.80 (1H, d. J = 17.8Hz), 5.37 (1H, br ), 5.98 (1H, dd, J = 3.5, 9.4Hz), 7.08 (1H, m), 7.21 (1H, dd, J = 1.8, 9.5Hz), 7.40 (1H, br), 7.50-7.56 (2H, m), 7.59 (1H, ra), 7.64 (1H, m), 7.70 (1H, br s), 8.56 (1H, m ) Examples 4 to 27 The following compounds were prepared as in Example 3. Example 4 2- (4- (o-methylbenzylsulfonyl) glycine)-1- (oxazolyl [l, 2-a] pyridine -6-based) -fT -Methylcyclohexanemethanilamine-61- This paper size is applicable to China National Standard (CNS) A4 (210X297 mm) ZIV ———————————— — II (Please read the note on the back before writing this page) Threading --- r. A7 B7

5. Description of the invention (b.)

• NMR (400MHz, δ, CDC13): 1.30-1.42 (1H, m). 1.50-1.80 (4 ». M), 2.14-2.22 (11 !, m), 2.32-2.40 (lH, m). 2.42, 2.61 (total 3H, s). 2.54-2.63 (lH, m), 3.05, 3.06 (total 3H, d, J = 4.6Hz), 3.58, 3.6〇 (total 1H, d. J = 17.4Hz), 3.68, 3.69 (total 1H, d, J = 17.4Hzl, 5.52-5.66 (111. Br), 5.92, 5.93 (total 1H, dd, J = 3.8, 9.3Hz), 7.13-7.18 (1H. M). 7.25-7.87 (811. m), 8.58-8.63 (1H, m) Example 5 2- (N- (m-toluenesulfonyl) glycine hydrazone> -Bu (Pyridin-6-yl) -N '-methyl hexane methionamine Γ--i-- (please read the note on the back and fill in the book to buy it) The Ministry of Economic Affairs Ministry of Economic Affairs Bureau Shellfish Consumption Cooperation Du printed

H »C

-62- This paper size applies to Chinese National Standard (CNS) A4 (210X297mm) A7 B7

V. Description of the invention (W • mp (e C): 206-209 • NMR (400MHz, δ, CDC13): 1.36 (1H. M). 1.52-1.69 (3H, m), 1.76UH, m), 2.18 ( 1H, m), 2.37 (1H, m), 2.41 (3H.s), 2.58 (1H, m), 3.06 (3H, d, J = 4.6Hz), 3.6K1H, dd, J = 4.6, 17.9Hz) . 3.71 (1H, dd. J = 5.3, 17.9Hz), 5.48 (1H, br), 5.94 (1H, dd, J = 3.5, 9.7Hz), 7.18 (1H, dd, J * 1.6, 9.5Hz), 7.36-J.42 (2H, m), 7.49 (1H, d, J = 9.5Hz), 7.54-7.64 (4H, m), 7.72 (1H, m), 8.63 (1H, m) (Please read the " Note on the back of the page, please fill in this page) Example 6 2- (N- (p-toluenesulfonyl) glycine hydrazone) -1- (眯 脞 骈 [1,2-a] pyridine-6-yl ) -TT -Methylcyclohexanemethanine

mp (· 〇: 216-218 NMR (400MHz, CDClj): 1.36 (1H, m), 1.50-1.69 (3H, m), 1.T4 (1H, m), 2.16UH, m), 2.37 (1H, m), 2.43 (3H, S), 2.58 (1H, Wc Industrial and Consumer Cooperatives' Seal, Central Bureau of Standards, Ministry of Economic Affairs -63 This paper uses Chinese National Standard (CNS) A4 specifications (210X: 297 mm)

A7 ____B7_ V. Description of the invention (A) m >, 3.06 (3Η · d. J = 4.8Hz), 3.60 (1H, dd, J = 5.1, 17.6Hz), 3.70 (1H, dd. J = 5.7, 17.6Hz) 5.18 (1H, br), 5.93 (1H, dd. J: 3.7, 9.7Hz), 7.19 (1H, dd, J = 1.8, 9.5Hz), 7.28-7.32 (2H. M). 7.45 ( 1H, br), 7.54 (1H, d, J * 9.5Hz), 7.64 (1H, s), 7.65-7.69 (2H, m), 7.73 (1H, s), 8.63 (1H, s) Example 7 2- (N- (2-methylaminobenzenesulfonyl) glycinase) -Bu (oxazolyl [1,2-a] pyridine-6-yl} -N · -methylcyclohexane methylthiolase amine

• mp CC): 145-148 • NMR (400MHz, i, CDClj): 1.28-1.42 (1H, m), 1.46-1.62 (3Η · m). 1.64-1.76 (1Η · m), 2.04-2.13 (lH m), 2.13-2.23 (111, in), 2.27-2.36 (1H, m), 2.55-2.65 (lH, m), 3.04 (3H, d, J = 4.8Hz), 3.52 (1H, d, J = 18.〇Hz) r 3.68 (1H, d, J = 18.0Hz), 3.98 (3H, s), 5.85 (br s), 5.89 (dd, J = 3.4, 8.9Hz), 6.98-7.04 (2 » , in), 7.10 (dd, J = 1.7, 9.7Hz), 7.284 (1H, s) ^ 7.50 (1H, d, J = 1.3Hz), 7.51-7.59 (1H, m), 7.64 (1H, s) , 7.75 (1H, dd, J = 1.7, 8.1Hz), 8.20 (1H, br s) -64- The standard of this paper is B country standard (CNS) A4 specification (210X297 cm) J / 1%. ; ^ Install. 丨 order line (please read the note iWH *. On the back before filling out this page) Central Government Bureau of Ministry of Economic Affairs and Consumer Cooperation Du Yinli Central Government Bureau of Economic Affairs Ministry of Economic Affairs Shellfish Consumer Cooperative , B7 V. Description of the invention (^) Example 8 2-(H-(4-methylaminobenzenesulfonyl) glycinepyronyl) -1-(oxazolyl [l, 2-a] pyridine-6 -Yl) -JT-formamidine

• NMR (400MHz, δ, CDC13): 1.35 (1H, m) · 1.52-1.82 (4H. M), 2.18 (1Η · m), 2.37 (1H, m), 2.60 (1H, m), 3.07 (3H , d, J = 4.8Hz), 3.59 (1H, d, J = 17.8Hz), 3.69 (1H, d. J = 17.8Hz). 3.86 (3H, s), 5.78 (111, dd, J = 3. T, 9.7Hz), 6.94-6.99 (2H, m), 7.2K1H, dd, J = 1.8, 9.7Hz), 7.5K1H, d, J = 9.7Hz), 7.57 (1H, br). 7.61 (111, d, J = 1.3Hz), 7.70-7.75 (3H.m), 8.65 (1H, m) Example 9 2- (N- (4-fluorobenzenesulfonyl) glycinyloxy) -1- (眯Pyrazonium [1,2-a] pyridine-6-yl) -N'-methylcyclohexanemethanilamine-65- This paper is based on China National Standard (CNS > A4 size (210X297)) ------- M .-- ^ install -----, 1 order, ------ line (please read the note f on the back before filling this page) A7 B7

V. Description of the invention (with) mp (· 〇: 207-210 NMR (400MHz, », CDC13): 1.40 (1H, m). 1.51-1.80 (4H. 2.19 (1H, m), 2.37 (1H m), 2.56 (111, m), 3.07 (3H, d. J = 4.8Hz), 3.61 (1 », d, J = 17.8Hz), 3.72 (111, d, J = 17.8Hz). 5.55 (1H, br) , 5.96 (1H, dd, J = 3.5, 9.2Hz). 7.15-7.21 (2H, m), 7.22 (1H, dd. J = 1.8. 9.7Hz), 7.49 (1H, d, J = 9.7Hz), 7.55 (1H, br), 7.60 (1H, d, J = 1.3Hz). 7.70 (1H. M), 7.78-7.84 (2H, m), 8.58 (1H, m) ^^^ 1 ^^^ 1 ^ ^^ 1 ^^^ 1 ^^^ 1 nn (Please read the note on the back and read this page before writing this page), -ιτ, Example 10 2- (N- (4-Gabenzenesulfonyl) group醯 Gasyl) -1,2-a] pyridin-6-yl) -IT-methylcyclohexanemethionin This paper size applies to China National Standard (CNS) Α4 specification (210X297 mm)

Du Yinzheng, A7 B7, Shellfish Consumption Cooperation of the Central Sample Bureau of the Ministry of Economic Affairs V. Description of Invention (W)

Cl • m.p. CC): 205-206 (dec.) • NMR (400MHz, δ, DMS0-d6):

1.21-1.34 (1H, m), 1.38-1.49 (211, m), 1.49-1.66 (2H m), 2.08-2.20 (2H, m), 2.64-2.74 (211, m), 2.90 (3 », s ), 3.27 (1H. D, J = 18.0Hz), 3.60 (1H, d. J = 18.0Hz) 5.95 (1H, m), 7.22 (Ilf, dd, J = 1.8, 9.5Hz), 7.30C1H d, J = 9.5Hz), 7.55 (1H.d, J = l.lHz), 7.57-7.65 (4H, m), 7.96 (1H, d, J = 0.7Hz), 8.21 (1H, br s), 8.5K1H , s), 9.46 (1H, br s) Example 1 1 2- (N- (4-Bromobenzenesulfonyl) Glycine 瞌 Gasyl) -Buxazole 眯 [1,2-a] pyridine-6 -Base) -N'-Methylcyclohexanemethanilamine 67 This paper size applies to the Chinese national kneading rate (CNS > Λ4 size (210X297 mm) (please read the note f on the back before writing this page) )

A7 B7 V. Description of the invention (A)

Br mp Co: 208-210 (dec.) NMR (400MHz, h, DMSO-dg): 1.21-1.34 (1H, in), 1.38-1.49 (2H.m), 1.49-1.65 (2H. In), 2.07-2.20 (2H, m), 2.65-2.74 (1H, m), 2.90 (3 ». D, J = 3.8Hz), 3.28 (111, d. J = 18.0Hz), 3.60 (111, d. J = 18.0Hz), 5.95 (1H, br s), 7.22 (111, dd, J = 2.0, 9.7Hz), 7.43 (1H. D, J = 9.5Hz). 7.52-7.57 (3H, m). 7.72- 7.77 (2H, m). 7.96 (1H, s), 8.22 (111, s), 8.50 (1H, s), 9.46 (111. Br s) 2 1 Example ----- ^^ ----- ^ 丨 Order · ------ ^ (Please read and read the note f on the back before filling in this page) Thiamethanamine hexyl ring). Methyl '醯' T sulfo} Phenyl 6- II 啶 I I batch 4X n oxazole 眯 this paper standard uses China National Sample Rate (CNS) Λ4 specifications ( 2 丨 0X297 mm) 5. Description of the invention (W) ja A7 B7

• mp CC): 215-217 • NMR (400MHz, δ, CDC13): 1.43 (1H, m). 1.52-1.78 (4H. M). 2.19 (1H. M), 2.38 (1H. M), 2.54 ( 111, m), 3.07 (3H, d. J = 4.6Hz), 3.67 (1H, d. J = 17.8Hz), 3.77 (1H, d, J = 17.8Hz). 5.99 (1H, dd, J = 3.7 , 9.3Hz), 7.23-7.30 (2H. M), 7.47 (1H, br), 7.50 (1H. D, J = 9.7Hz), 7.60 (111, d, J = 1.3Hz), 7.69 (1H, s ), 7.78-7.82 (2H.m), 7.89-7.94 (2H, m), 8.55 (1H, m) Example 13 2- (N- (4-trifluoromethylbenzylsulfonyl 1glycine) ) -Bu (oxazolyl [1,2-a] pyridine-6-yl) -N'-methylcyclohexanemethanilamine (please read the note on the back—item before filling out this page). Γ. Ordered by the Central Bureau of Standards, Ministry of Economic Affairs, Shellfish Consumer Cooperation Du-69- This paper size is applicable to the Chinese national standard (CNS > Λ4 size (210X297 mm) A7 _ · '' B7 V. Description of the invention (W)

Printed by Shelley Consumer Cooperative, Bureau of Standards Loss in the Ministry of Economic Affairs • mp (eC): 214-215 (dec.) • NMR (400MHz, δ. DMSO): 1.20-1.34 (1H, m) · 1.38-1.48 (2H , m), 1.50-1.63 (2H, in). 2.06-2.19 (2H.m), 2.64-2.73 (1H. in), 2.90 (311. d, J = 4.0Hz), 3.33 (111, d, J = 18.1Hz), 3.65 (111, d, J = 18.1Hz), 5.95 (1H, b'r s), 7.22 (1H, dd, J = 1.8, 9.7HZ), 7.43 (1H, d, J = 9.7 Hz), 7.55 (1H, dJ = l.lHz), 7.84 (2H, d, J = 8.3IIz), 7.93 (2H, d, J = 8.3Hz), 7.96 (1H. S). 8.40 (1H. Br s), 8.50 (1H. s), 9.46 (1H, br s) Example 14 2- (N- (4-Ethylaminobenzenesulfonyl) glycine_oxy) -1- (amizolam , 2-a] pyrimidin-6-yl) -N'-methylcyclohexanemethanamine -------- M--i-- (Please read the note on the back before filling in this page ) Order I ml < ^ 1 ml The paper size is applicable to China Standards for Households (CNS) A4 specification (210X297 mm) A7 B7 V. Description of invention (w)

AcNH NMR (400MHz, δ. DMSO-dg): 1.20-1.32 (1H, m), 1.35-1.64 (411, m), 2.06 (311, s) t 2.02-2.18 (2H, m), 2.65-2.70 ( lH.m). 2.88 (3H, d, J = 3.5Hz), 3.19 (1H, d, J = 18.0Hz), 3.49 (1H, d, J = 18.0Hz), 5.92 (1H. bs), 7.18 ( 1H, dd, J = 9.5, 2.0Hz), 7.40 (1H, d, J = 9.5Hz), 7.52 (1H, d, J = 2.0Hz), 7.53 (1H, d, J = 9.0Hz), 7.67 (1H, d, J = 9.0Hz), 7.92 (1H, m), 7.93 (1H, s), 8.49 (1H, s), 9.42 (1H, bs), 10.23 (1H, s > Example 15 2- (N- (2, 3-Digas benzenesulfonyl) glycine fluorenyl) -1- (The work of the Central Bureau of Standards and Technology of the Ministry of Economic Affairs and Consumer Cooperation for Du Printing (please read the note f on the back first) Write another page on this page) 骈 [l, 2-a] 丨 Tyridin-6-yl)-『-Methylmethane thiomethanamine-7 1 This paper is based on China National Standard (CNS) Α4 specifications (210X297 mm) A7 B7

• 5. Description of the invention (M)

• mp ('〇: 224-226 • NMR (400MHz, 6, DMS0-d6): 1.28 (1H, m), 1.38-1.48 (2H, in), 1.50-1.66 (2H, m), 2.1K1H, m ). 2.69 (1H, m). 2.90 (3H, d. J = 4.4Hz), 3.4K1H. D, J = 18.1Hz), 3.69 (111, d, J = 18.1Hz), 5.95 < 1H, br ), 7.19 (1 », dd, J = 1.6, 9.7Hz), 7.4K1H, d, J = 9.7Hz). 7.48 (1H, t, J = 8.1Hz), 7.55 (1H, s), 7.69UH, dd, J = 1.5, 8.1Hz), 7.89 (111, dd, J = 1.5, 8.1Hz), 7.96 (1H, s), 8.47 (2H, s), 9.46 (1H, br) Example 16 2- (N -(4-Ethylaminosulfonyl) glycinaldehyde >-[(oxazolyl [l, 2-a] pyridin-6-yl) '-N'-methylcyclohexanemethyl Thiamin -------: ---: packing ------- order ------- line (please read the "$" in the back * before filling this page) Ministry of Economic Affairs Printed by the Central Government Bureau of Industry and Consumer Cooperatives 7 2- This paper is scaled to the standard of China National Association (CNS) A4 (210 × 297 mm) V. Description of the invention (A7 B7

• NMR (400MHz, 6, CDClj): 1.30-1.43 (1H. M), 1.50-1.66 (2Η · m). 1.67-1 · 82 (2Η, m), 2.15-2.23 (1H, m), 2.33 ( 3H, s), 2.34-2.40 (1H, m), 2.54-2.63 (lH, m), 3.05 (3H, d. J = 4.5Hz), 3.62 (1H, d. J = 18.0Hz), 3.70 (1 », D, J = 18.0Hz), 5.95 (1H, dd, J = 8.0, 3.5Hz), 7.19 (1H, dd, J = 9.5, 2.0Hz), 7.12-7.34 (2H, m). 7.44 (1H , d, J = 9.5Hz), 7.56 (1H, d, J = 1.0Hz), 7.64-7.72 (2H, m), 7.73-7.89 (2H, m). 8.59 (1H, s) Example " 2- (N- (4-methylthiobenzenesulfonyl) glycinase) -1- (oxazolyl [1,2-a] pyridine-6-yl) -N'-methylcyclohexanemethylsulfide Enzyme (Please read the note on the back before filling in this page)

* tT Printed by the Shellfish Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs nn m · Il ^ i -73 This paper size is applicable to China's Standards (CNS) A4 (210X297 mm >) V. Description of Invention (V)

MeS A7 B7

NMR (400MHz. Ft, CD3〇D): 1.37-1.48 (1H.m), 1.53-1.62 (211.m), 1.72-1.81 (2H.m), 2.36-2.5K2H, m), 2.5K3H, s ), 2.75-2.82 (111, m), 3.00 (3H, s), 3.37 (1H, d, J = 18.0Hz), 3.43 (111, d, J = 18.0Hz), 6.27-6.31 (1H. M) , 7.30-7.34 (2 », in), 7.47-7.53 (2H, m), 7.79 (1H, d, J = 9.5Hz), 7.98 (1H, d. J = 2.0Hz), 8.23 (1H, br s ), 8.24 (111, dd, J = 9.5, 1.5Hz), 8.9K1H, br s) Example 18 2- (H- (4-nitrophenylsulfonyl) glycinase) -1- (oxazole骈 [1,2-a] lttidine-6-yl) -N'-methylcyclohexanemethanilamine (please read the note f on the back before filling in this Jr): Packing. Order. —Line Economy Ministry of the Central Government, Prospective Bureau, Industrial and Consumer Cooperation, Du Print 02NR

-7 4-This paper size is applicable to China Standards (CNS) A4 specification (210X25 > 7mm) A7 B7 V. Description of the invention (rotary) NMR (400MHz, 6. CDgOD): 1.35-1.46 (1H, m), 1.46-1.7 (4H, m), 2.26-2.36 (2H, m), 2.59-2.67 (lH, m), 2.98 (3H, s), 3.43 (1H, d, J = 18.0Hz), 3.70 (1H.d, J = 18.0Hz), 4.87 (2H, s), 6.09 (1H, m), 7.40 (1H, d, J = 9.5Hz). 7.45 (1H, dd, J = 9.5, 2.0Hz) , 7.52 (1H, d, J = 1.0Hz), 7.83 (1H, bs), 7.87-7.9K2H, m), 8.28-8.32 (2H, m), 8.55 (1H, bs) (Please read the note on the back first f), fill in this page again) Example 19 '2- (N- (3-Nitrobenzenesulfonylglycine)> τΐ- (oxazolidine [1,2-aHftidine-6-yl) -fT -Methylcyclohexanemethionin

Economic Central Bureau of Work, Consumption of Work, Cooperatives • NMR (400MHZ, δ, CDC13): 1.40-1.64 (4H, m). 1.65-1.76 (1H, m), 2.18-2.27 (1H, m), 2.32-2.39 (lH, m), 2.50-2.59 (1H, m), 3.04 (3H, d, J = 5.0Hz), 3.6611H, d, J = 18.0Hz), 3.86 (1H, d, J = 18.0Hz), 6.00 (1H · dd, J = 8.0, 3.0Hz), 7.24 (1H, -7 5 This paper size is in accordance with China National Standard (CNS) A4 size (210X297 mm)

Printed by the Central Standards Bureau of the Ministry of Economic Affairs and Consumer Cooperatives A7 B7 V. Description of Invention (74) dd, J = 9.5, 2.0Hz), 7.29 (1H, d. J = 9.5Hz), 7.44 (1H, d, J = 1.0Hz), 7.60 (1H.s), 7.70 (1H. Dd. J = 8.0, 8.0Hz), 7.86-7.92UHm), 8.10 (1H, ddd, J = 8.0, 1.5, l.OHz) 8.37 (1H, ddd. J = 8.0, 2.0, 1.0Hz). 8.48 (1H, bs >, 8.51-8.53 (1H, m) Example 20 2- (N- (2-Kbenzenesulfonyl S) glycine) Hydrazone > -1- (HuiShui-Ai- > -N'-methylcyclohexanemethanine

• NMR (400MHz · 4 · CD3〇D): 1.34_1 · 46 (1Η · in) · 1.46-1.76 (4Η · π〇, 2.27_2.38 (211, m), 2.60-2.68 (1Η, m) , 2.97 (3Η, s), 3.57 (1Η.d, J = 18.5Hz), 3.78 (1Η, d, J = 18.5Hz), 4.87 (2Η. S), 6.1〇 (1Η, m), 7.38 (1Η , d, J = 9.5Hz), 7.44 (1Η, dd. J = 9.5, 2.0Hz), 7.53 (1H, d, J = 1.0Hz), 7.70-7.85 (4H, ra), 8.51-8.55 (1H, m), 8.54 (1H, bs) Example 21 2- (N- (2 Benzenesulfonyl) glycine hydrazone > -1- (imidazolium [1,2 -7 6-for paper size China National Standards (CNS M4 Specification U 丨 0X297mm) (Read the notes on the back ^^ before reading the script 萸)

B7

Example 22

V. Description of the Invention (V a) 丨 ftidine-6-yl) -N'-Methylamine

• mp (eC): 199-200 (dec.) • NMR (400MHz, 6. DMS0-dG): 1.20-1.32 (1H, Πΐ) Λ1. * 37-1.48 (2Η, m), 1.48-1.66 (211 , m). 2.07-2.20 (2H.m), 2.65-2.75 (111, m), 2.89 (311, d, J = 4.2Hz), 3.40 (1H, d, J = 18.3Hz), 3.T6 { 1I1, d, J = 18.3Hz). 5.94 (1H, br s), 7.20 (1H, dd, J = 1.6, 9.5Hz), T.28-7.46 (3H, in), 7.55 (1H, s), 7.59 (1H, dt, J = 1.5, 7.7Hz), 7.63-7.70 (1 », m), 7.96 (111, s), 8.38 (1H, br s), 8.56 (1H, s), 9.47 (1H, br s) (Please read the note on the back before writing this page)

N (2, 5-Diphenylbenzenesulfonyl) glycinaldehydeoxy) (printed by [1,2-a] pyridin-6-yl) in the Consumers Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs '-Cyclohexidine-Methionamine-77- The standard of this paper is Chinese National Standard (CNS) A4 (210X297 mm) 5. Description of the invention (A)

Cl A7 B7

Seal of Consumers' Cooperatives, Central Bureau of Standards, Ministry of Economic Affairs • mp (eC): 200-202 (dec.) • NMR (400MHz, δ, CDClj): 1.34-1.46 (1H. M), 1.46-1.64 (3H. m), 1.68-1.79 (1H, m), 1.98 (1H, br), 2.17-2.2G (1H, m). 2.30-2.38 (1 », m), 2.55-2.64 (lH.m), 3.06 ( 3H, d, J = 4.6Hz), 3.65 (1H, d, J = 17.9Hz). 3.77 (1H, J = 17.9Hz), 5.97 (1H. Dd, J = 3.1, 5.97Hz). 7.16 (1H, dd, J = 1.8, 9.7Hz). 7.30 (1H, d. J = 9.5Hz), 7.43-7.50 (3H, m), 7.62 (1H, s), 7.95 (1H, d, J = 2.2IIz), 8.07 (1 », br), 8.54 (1H, s) Example 23 2- (H- (4-Amo-3-nitrobenzylsulfonyl) glycine hydrazone) -bu (oxazolyl [1,2 -aHftidine-6-yl) -N_-methylcyclohexanemethanil 78- This paper size applies to China National Standard (CMS > A4 size (210X297 mm > • vr '— I — III yp pack) — Ϋ Γ Order-IIII ——line (please read the note on the back before filling in this page) 5. Description of the invention (17

A7 B7

NMR (400MHz, δ, CDClj): 1.40-1.55 (2H, m), 1.55-1.65 (211, m). 1.67-1.77 (111, m), 2.18-2.27 (1H, m). 2.31-2.39 (1H m). 2.50-2.58 (1H, m), 3.04 (3H, d, J = 5.0Hz), 3.65 (1H, d, J = 18.0Hz), 3.82 (1H, d, * J = 18.0Hz), 6.03 (1H, dd, J = 8.0, 3.0Hz), 7.26 (2H, m), 7.4K1H, d, J = 1.0Hz). 7.58 (1H, s), 7.67 (1H, d, J = 8.0Hz) , 7.88 (1H, bs). 7.89 (1H, dd. J = 8.0, 2.0Hz), 8.17 (1H, d, J = 2.0Hz), 8.46 (1H, s) Example 24 2- (Ν- (2- Methylpyrazole-3-ylsulfonyl) Glycosylamino) -Bu (oxazolyl [1,2-a] pyridin-6-yl) -N'-methylcyclohexanemethanilamine Please First M face note

I page 1T line Printed by the Central Bureau of Standards of the Ministry of Economic Affairs >

This paper size is applicable to the national beam ratio of China (CNS M4 specification (210X297 mm). Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. A7 _B7_ V. Description of the invention (7〇 mp (eC): 193-194 • NMR (400MHz , δ, CDClg): 1.43 (1H, m), 1.50-1.79 (4H, m), 2.2K1H, m), 2.36 (1H, m), 2.54 (1H, m), 3.06 (3H, d, J = 4.6Hz), 3.64 (1H, d, J = 17.9Hz), 3.77 (1H, d, J = 17.9Hz), 4.07 (3H, s), 6.0K1H, dd, J = 3.5, 8.9Hz), 6.66 (1H, d, J = 2.2Hz), 7.25 (1H, dd, J = l: 8, 9.5Hz), 7.27 (1H. D, J = 2.2Hz), 7.44-7.54 (2H, m), 7.58 { 1H, d, J = l.lHz), 7.67 (1H, m), 8.52 (1H, m) Example 25 2- (N- (2-leafylsulfonyl) glycosaminoloxy) -1- (眯[1,2-a] pyrimidin-6-yl) -N'-methylcyclohexanemethionin

• NMR (400MHz, δ, CDClj): 1.33UH, m), 1.48-1.70 (4H, m), 2.08 (1H. M). 2.35 (1H, m), 2.55 (1H, m), 3.03 (3H, d, J = 4.8Hz), 3.64 (1H, dd, J = 3.7, 17.8Hz). 3.75 (1H, dd, J = 5.3, -8 0-This paper size applies to China's national kneading rate (CNS) Λ4 specifications ( 210X297 mm) (please read the note on the back before writing this page)-binding. V. Invention Description (Bamboo) A7 B7 17.8Hz), 5.38 (1H, br), 5.91 (1H, dd. J = 3.7, 9.5Hz), 7.17 (1H, dd, J = 1.8, 9.7Hz). 7.43 (1H, br), 7.52 (1H, d, J = 9.7Hz), 7.59-7.65 (2H, m), 7.67 (1H, dd. J = 1.5, 7.0Hz), 7.72 (1H, s), 7.76 (1H, dd, J = 1.8, 8.6Hz), 7.90-7.98 (3H, m), 8.37 (1H, d, J = 1.8Hz), 8.6K1H, s) Example 26 2- (N- (Busyl) glycinylamino) -1- (oxazolyl [1,2 -a 丨 pyridine-6- ) -N'-methylcyclohexanemethanilamine

(Please read the note f on the back before filling this page) • Installed · Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs I • mp (eC): 158-160 • NMR (400MHz, δ, DMSO-dg ): 1.20-1.27 (1Ηm), 1.34-1.40 (2H.m), 1.46-1.56 (211, m), 2.00-2.08 (2H, m). 2.61-2.68 (1H, m), 2.89 (1H , d, J = 4.0Hz), 3.29 (1H, d, J = 18.0Hz), 3.58 (1H, d. J = 18.0Hz), 5.90 (1H. br s), 7.16 (111, dd, J = 9.5 , 2.0Hz), 7.4K1H, d, J = 9.5Hz) f 7.53-7.57 (2H, m), 7.63-7.70 (2H, m), 7.85-7.89 (1H, m), 7.96 (1H, s), 8.06-8.09 (lH, m), 8.19 (1H, d, J = 8.0Hz), 8.44-8.49 (2H, m), 8.53-8.56 (lH, m) 9.44 (1H, br s) 8 1- present Paper scale Chinese national kneading rate (CNS) Λ4 size (210X297 mm) n In n I —L · B7 V. Description of the invention (S.) Example 27 2- (N-Benzylsulfonylglycine base ) -Bupropazolium [1,2-alpyridine 6-yl) -N'-methylcyclohexanemethanine

NMR (400MZ, δ, CDClj): 1.25-1.38 (1H.m), 1.50-1.67 (2H, m), 1.77-1.84 (111.in), 1.9-2.K1H.bs), 2.18-2.23 (111 , m), 2.31-2.40 (1H, ra), 2.56-2.63 (lH, m), 3.01 (3H, d, J = 4.5Hz) f 3.46 (1H, d, J = 18.0He). 3.52 (111, d, J = 18.0Hz). 4.18 (1H, d, J = 14.0Hz). 4.23 (1 ». d, (Please read the note on the back and write this page) Cooperative printed J = 14.0Hz), 5.80 (1H, bs), 5.92 (111, dd, J = 9.0, 3.5Hz), 7.13 (1H, dd, J = 10.0. 2.0Hz), 7,33 (1 » , d, J = 10.0Hz), 7.35 (511, m). 7.46 (111, d, J = 1.0Hz), 7.62 (1H, s), 7.95 (1H, bs), 8.55 (1H, s) Example 28 2- (N-benzenesulfonylthiocarbamidine) -1- (4-methylimidazole-butyl) -N'-methylcyclohexanemethanilamine-82 This paper is in accordance with Chinese national standards ( CNS) A4 specification (210X297 mm) B7 V. Description of invention (/ 1)

(Please read the note on the back before writing # on this page) CH, 0.3 g of 2-glycinylamino-N-methyl-1- (4-methyloxazole-butyl) methane Tetramine (prepared in Preparation Example 29) was dissolved in 5.1 dichloromethane, and 0.13 «1 triethylamine was added. After ice-cooling, 0.12B1 benzenesulfonate / 21 methylene chloride was added dropwise, and after 1 hour, 5.1 concentrated water was added to add water. It was extracted with chloroform, dried over anhydrous sodium sulfate, the solvent was distilled off, and then subjected to silica gel column chromatography (diazomethane / methanol = 40: 1). The obtained oil was crystallized from ethyl acetate / n-hexane to obtain 0.24 g of the target substance as a white powder (yield 55%). • mp (β〇: 201-202 • NMR (400MHz, 6, CDClj): Ministry of Economic Affairs * Standard Rate Bureau, Office of Consumers and Consumers Cooperation Du printed 1.28 (1H, m), 1.46 (1H, m), 1.53-1.75 (3H, m), 1.90 (1H, m), 2.29 (3H, d, J = 0.7Hz), 2.36 (1H, m), 2.73 (1H, m), 3.00 (3H, d, J = 4.8Hz) , 3.73 (1H, dd, J = 4.0, 18.1Hz), 3.83 (1H, dd, J = 5.1, 18.1Hz), 5.22 (1H. Br), 5.95 (1H, dd, J = 3.8, 11.9Hz), 6.77 (XH, br), 6.93 (1H, s), 7.51-7.56 (2 », m), 7.60 (1H, m), 7.78 (1H, s), 7.82-7.87 (2H, m) Example 29 2- (N -benzenesulfonyl gas base) -bu (oxazolyl [1,2-a] pyridine-6-yl) -8 3-This paper size applies to China's national ratio (CNS > A4 size (210X297 mm) ) A7 B7 Du Yin, ec industrial and consumer cooperation of the Central Standards Bureau of the Ministry of Economic Affairs «. V. Description of the invention (/ >) -N'-methylcyclohexanemethanamine

Using the product of Preparation Example 30 as a raw material, the target product was prepared as in Example 3. • NMR (400MHz, h, CDC13); 1.22 (1H. M), 1.53-2.05 (811, m), 2.10, 2.30 (total 1H. M), 2.41-2.52 (111, m), 2.63-2.78 (111 , m). 3.02, 3.21 (total 1H, m), 3.08, 3.09 (total 3H, d, J = 4.8Hz), 3.29, 3.56 (t〇tal 1H, m), 4.19, 4.24 (total 1H, dd, 64.19 peak, J = 3.3, 8.8Hz), 64.24 peak, J = 2.6, 8.2Hz), 5.80, 5.91 (total 1H, dd, J = 3.7, 11.0Hz), 7.17, 7.20 (total 1H, dd, J = 1.8, 9.7 Hz), 7.39, 7.73 (total 1H, br), 7.51- 7.68 (4H, m), 7.76-8.04 (3H, m), 8.87, 9.14 (tot: al 1H, s) Example 30 2- ( N-benzenesulfenyl-therapeutic-benzyl asparagine) -B (oxazolyl [1,2-a] pyridin-6-yl) -N'-formamidine hexane mesylate- 84- The size of this paper is applicable to the national standard (CNS) Λ4 specification (210X297 mm) ------- „--- ^ -----, —ir ------- lacquer ( Please read the note on the back before filling in this page) A7 B7 Printed by the Shellfish Consumer Cooperative of the Central Rubbing Bureau of the Ministry of Economic Affairs 5. Description of the Invention (Η)

• mp CC): 109-114 • NMR (400MHz, δ, CDC13): 1.33 (1H. In), 1.48-1.65 (3H, m), 1.78 (111, m). 2.22 (1H, m), 2.38 ( 1 », m), 2.58 (111.dd, J = 5.3, 17.0Hz). 2.65 (1H, m), 2.78 (1H, dd, J = 4.8, 17.0Hz), 3.08 (3H, d, J = 4.8 Hz), 4.2K1H, br). 4.92 (1H, d. J = 12.3Hz), 4.99 (1H. D, J = 12.3Hz), 5.90 (1H, dd. J = 3.1, 9.0Hz), 6.14 (111 , br), 7.12 (1H, ddd. J = 2.0, '4.8 · 9.6Hz). 7.22-7.26 (2H, m), 7.30-7.37 (3H, m), 7.40 (1H, m), 7.43-7.49 ( 211, m), 7.53-7.60 (2H, m). 7.71-7.79 (3H, m). 7.82 (1H, br), 8.74UH. Br s) Example 31 2- (N-benzenesulfonylpropylamine ) -Bu (oxazolyl [1,2-a] pyridin-6-yl) -N'-methylcyclohexanemethanilamine (about 3: 1 mixture-8 5-Applicable to this paper size B national standard (CNS > A4 specification (210X297 mm) ------- „---;-installation ------ I order. ----- (read the first (Note $ items and then fill out this page)

A7 _._ B7 V. Description of the invention (private) r ^ Vs, 0.7 ° 0.73 g 2- ίΝ-third butane carbonylpropylamine hydrazone) -1- (眯 畦 骈 [l, 2-al pyridin-6 -Yl) -N'-methanyl methionamine (prepared in Preparation Example 17) was dissolved in 10 · 1 azoform, and 10Bl 93 was added; HC1 / ethyl acetate. After stirring at room temperature for 12 hours, the solvent was distilled off, and the obtained white amorphous substance was dissolved in 4b1 pyridine, and 0.41B1 benzenesulfonic acid was added. After stirring at room temperature for 2 hours, saturated replay acid water was added. It was extracted with dichloromethane and dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue was crystallized from silica gel column chromatography (dichloromethane / methanol = 30: 1) and crystallized from dichloromethane / ether to obtain 0.33 g of the target substance, white. Powder (41% yield). • NMR (400MHz, δ, CDClj): 0.89, 1.18 (t〇tal 3H, d, J = 7.1Hz), 1.29-1.84 (5H, m), 2.04-2.41 (2H, m), 2.53-2.65 (1H , m), 3.05, 3.07 (total 3H, d, J = 4.8Hz), 3.82-3.93 (1H, m), 5.53-5.70 (lH, m), 5.88-5.94 (1 », m), 7.17, 7.19 (total 1H, dd, J = 1.8, 9.5Hz), 7.43-7.52 (3H, m), 7.54-7.82 (6H, m), 8.44, 8.73 (total 1H, s) Example 32 '-86- This paper The scale applies to China's national standard (CNS > Λ4 specification (210X297 mm) ------- installation -----, --ir .------ (please read the "$" on the back side first) (Fill in this part again.) Manufactured by the Central Government Bureau of the Ministry of Economic Affairs, Shellfish Consumer Cooperation, Du printed. Ⅴ. Description of the Invention (Κ) 2- (N- (1-leafylsulfonyl)-> 8-propylamine hydrazone > -1- (oxazolidine [1,2-a] pyridine-6-yl)-(Γ-methylcyclohexanemethanilamine

Example 31, except that the product of Preparation Example 15 was used as the raw material, and 1-sulfonyl nitrogen was used instead of benzenesulfonium to obtain the target substance. • mp CC): 136-141 • NMR (400MHz, 6, CDC13): 1.4K1H, m), 1.53-1.7K4H, m), 2.13 (111, m), 2.29-2.48 (3Η · m), 2.55 ( 1Ηm), 3.08 (2H, m). 3.009 (3Η, d, J = 4.6Hz), 5.46 (1H, t, J = 6.6Hz), 6.0K1H, dd, J = 3.1, 9.0Hz) , 7.24 (1H, dd, J = 1.8, 9.5Hz), printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the note on the back to get this page) 7.46 (1H, br). 7.50-7.56 (211, m), 7.59-7.72 (4H. M), 7.95 (1H, dd, J = 0.9, 8.2Hz). 8.08 (1H, d, J = 8.2Hz), 8.20 (1H, dd, J = 1.3 , 7.3Hz), 8.50 (1H, m), 8.58 (1H, d, J = 8.8Hz) Example 33 2- (N-benzenesulfonyl benzylpropylamine hydrazone) -1- (oxazole hydrazone [l, 2-a] pyridine-6-yl > -N'-methylcyclohexane_methionanamine (L-type) -87- This paper uses Chinese national standard (CNS > A4 size (210X297) (Centi) _B7 V. Description of the Invention (M)

1.88 g of 2- (N-tertiary butanecarbonylphenylalaninylamino) -1- (imidazolidine [1,2-alpyridin-6-yl) -tT-methylcyclohexanemethanilamine Preparation Example 18) Dissolved in 10βΙ dichloromethane, added 10βΙ trifluoroacetic acid, and stirred under ice-cooling for 30 minutes, then added ice water to age with sodium acetate. Extracted by gas imitation, dried over anhydrous magnesium sulfate, and distilled off the solvent. The pale yellow amorphous obtained was dissolved in 15 · 1 digas methane and 0.54 · 1 triethylamine was added, and then cooled to -30 ° C and added dropwise. 0.5β1 benzene sulfonase / 2bI digas methane. Gradually raise to 0 ° C and stir for 7 hours, add dilute ammonia water, extract with aerobic extraction and dry with anhydrous magnesium sulfate, evaporate the solvent, and use silica gel column chromatography (dichloromethane / methanol = 50: 1 ~ 40: Π, 0.06 g (3X) of low-polar diastereomer (L-type), white powder, and 0.10 g (553;) of highly polar (M-type) white powder were obtained. Mp (eC ): 139-144 Printed by Shellfish Consumer Cooperative of the Ministry of Economic Affairs of the Ministry of Economic Affairs (please read the note on the back before filling this page) • NMR (400MHz, δ, CDClj): 1.28 (1H, m), 1.56 -1.72 (4H, m), 2.00 (1H, m), 2.39 (1H.ra), 2.60-2.82 (3H, m). 3.04 (3H, d, J = 4.8Hz), 4.07 (1H, m), 4.92 (1H, d, J = 9.2Hz), 5.84 (1H. Dd, J = 3.5. 9.3Hz), 6.84-6.89 (2H, m), ~ 8 8 ~ This paper size applies to China «Home Standard (CNS) A4 specification (210X297 mm) Printed by A. Shell, Consumer Cooperation, Central Standards Bureau, Ministry of Economic Affairs A7 ___B7 _ ^ _ V. Description of the invention (p) 7.13-7.22 (4H, m), 7.39-7.48 (3H, m), 7.51-7.66 (5H, m), 7.7K1H, s), 8.58 (1H, m) Example 34 2- (N-benzenesulfonyl phenylpropylamine hydrazone) -bu (oxazole hydrazone U, 2_a) pyridine

OB (202: 205-NMR) (400MHz, δ, CDC13): 1.25 (1Η · m), 1.53-1.89 (4Η · m), 2.24 (1H, m), 2.39 (1H, m), 2.63 (1H, m), 2.71 (1H, dd, J = 8.8, 15.2Hz), 3.01 (1H, dd, J = 6.4, 15.2Hz), 3.02 (3H, d, J = 4.8 Hz), 4.04 (1H, m), 4.74 (1H, m), 5.86 (1H, dd, J = 4.0, 10.6Hz), 6.86-6.91 (2H. M), 7.12-7.23 (4H. M), 7.30 (1H, m), 7.38-7.44 (211, m), 7.52-7.62 (4H, m), 7.64 (1H, d, J = l.lHz), 7.83 (1H, s), 8.83 (1H, m) Example 35 2-. (N-((T-benzenesulfonylglycinamido) glycine 醯 gasoline) -1- (眯 -89- This paper is based on the Chinese National Standard (CNS M4 Specification (2 丨0X297mm} I — — II; 7 pack. Order. Thread (please read the note on the back before filling in this page) B7 V. Description of the invention (Immortal) azole [1, 2-a] pyridine-6- ) -N "-methylcyclohexanemethanine

S

(Please read the note on the back before filling out this page) 〇2 0.56 g of 2- (N- (fT-Third-Butylcarbonylglycinyl) glycinaldehyde) -B (imidazolium [l, 2-aHttidine-6-yl) -N " -methylcyclohexanemethanamine (prepared in Preparation Example 35) was dissolved in 5.1 dinitromethane, and 5b1 trifluoroacetic acid was added. After stirring under ice-cooling for 1 hour, ice water was added to scoop it with sodium acetate. It was extracted with a gas imitation / methanol and dried over anhydrous magnesium sulfate, and the solvent was distilled off to obtain a pale yellow amorphous substance. This was suspended in 4 ml of digas methane, and after adding 0.97 * 1 pyridine to ice-cooling, 0.15 · 1 benzene sulfonase / lml di-methane β was added dropwise for 1 hour, and then dilute water was added. It was extracted with chloroform, dried over anhydrous magnesium sulfate, the solvent was distilled off, and then subjected to silica gel column chromatography (methane / methanol = 30: 1). The obtained oil was crystallized from digas methane / diethyl ether and recrystallized from ethanol / water to obtain 0.19 g of the target substance as a white powder. Printed by Shellfish Consumer Cooperative, Central Bureau of Standards, Ministry of Economic Affairs • mp (eC): 140-142 • NMR (400MHz, δ, CDClg): 1.25 (1H, m), 1.50-1.72 (3H, m), 1.88 (1H, m), 2.23-2.39 (2H, m), 2.72 (1H, in), 3.10 (3H, d, J = 4.7Hz), -90- This paper size is applicable to China National Liang Zhun (CNS > A4 specification (210X297 Mm)

A7 B7 V. Description of the invention (M) 3.48 (2H, br), 3.82 (1H, dd, J = 5.3, 17.9Hz), 4.09 (1H, dd, J = 6.2, 17.9Hz), 5.92 (1H, dd, J = 3.3, 9.3Hz), 6.13 (1H, br), 7.06 (1H, t, J = 6.8Hz), 7.18 (1H, dd, J = 1.5, 9.7Hz), 7.45-7.64 (7H, m), 7.69-7.76 (2H, m), 8.56 (1H, m) Example 36 2- (N- (N'-benzylsulfonylglycosaminomethyl) carnitine hydrazone) -1- (amizoazole [1 , 2-allfftidine-6-yl) -N "-methylhexylmethanamine

0.68 g of 2- (N- (M'-Third-Butylcarbonylglycinylase) carnitine hydrazone > -1- (imidazolium [l, 2-alpyridine-6-yl) -N "- Methylcyclohexanemethanilamine (prepared in Preparation Example 36) was dissolved in 10 ml of aerosol, 30 ml of 72 HC1 / ethyl acetate was added, and after stirring at room temperature for 3.5 hours, diethyl ether was added to collect insoluble matter by filtration and a pale yellow powder. This powder was suspended in 4 ml of dichloromethane, and 0.6% of triethylamine was added. After cooling to -15 ° C, 0.18 ml of benzenesulfuric gas / 1) 111 digasmethane was added dropwise. After stirring for 15 minutes, dilute ammonia was added. Extraction by gas-formation and drying with anhydrous magnesium sulfate, evaporation of the solvent, chromatography on a silica gel column (digas methane / methanol = 30: 1), and crystallization from diaminomethane / ether, 0.53 g of the target substance, white powder ( Total Yield 73%}. -9 1-This paper is standard for Chinese countries (CNS M4 specification (210X297 mm) I .------ 1--Pack --------- Order · ------ line (please note the $ item on the back of S # first and then fill out this page).

V. Description of the invention (91) NMR (400MHz, δ, CDC13): 1.38-1 · 86 (5Η, m), 2.23-2.36 (2Η · m), 2.48-2.59 (1H, m), 2.64, 2.69 (total 3H.s), 3.09 (311, d, J = 4.6IIz), 3.60, 3.66 (total 1H, d, J = 16.1IIz), 3.62, 3.71 (total 1H, d, J = 16.1Hz), 3.75, 3.88 (total 1H, d, J = 16.8Hz), 3.81, 3.94 (total 1H, d, J = 16.8Hz), 5.60, 5.76 (total 1H, br), 6.07, 6.19 (total 1H, dd, J = 3.1, 8.1Hz), 7.21-7.26 (111, m), 7.40-7.62 (5H, m), 7.65, 7.69 (total 1H.s). 7.77-7.90 (3H, m), 8.29, 8.38 (t〇tal 1H, s) Example 37 2- (N-benzenesulfenylglycine 蜷 amino) (imidazolium [l, 2-a] pyridin-6-yl) -N'-acetamidohexanethiolamine

0.4 8 g of 2- (N-third butanecarbonylcarbonylglycinyloxy) -S'-ethyl-1- (oxazolyl [1,2-alpyrimidin-6-methyl] cyclohexanemethyl Thiamin (prepared in Preparation Example 11) was dissolved in 5W digas methane, and 5 ml of trifluoroacetic acid was added. After ice-cooling for 30 minutes, ice wood was added to sulfonate with sodium sulfonate. Extracted with helium-formaldehyde, dried over anhydrous magnesium sulfate, and evaporated. Remove the solvent to obtain a pale yellow amorphous. This suspension is at -9 Z ~ This paper size is applicable to China National Standards (CNS) Λ4 specifications (210X297 mm) ---------- ^ pack- ---- 丨 Order; ------ line (please read "Note f on the back side and then fill out this page) Printed by the Central Ministry of Economic Affairs of the Central Bureau of the Kneading Bureau, Shellfish Consumer Cooperative, printed A7 B7 V. Description of the invention (P) 5. · 1 Dichloromethane, add 0.15 house 1 triethylamine, cool to -30 ° C, add 0.14 · 1 benzenesulfonazine nitrogen / 1 1 1 dichloromethane. After stirring for 1 hour, add dilute ammonia water, times Extraction with atmospheric imitation, drying over anhydrous magnesium sulfate, evaporation of the solvent, and crystallization from diazomethane / ether, 0.26 g of the target substance was obtained as a white powder (52% yield) β • mp (β〇: 206-208 • NMR (400MHz, 6, CDClg): 1.07 (311, t. J = 7.3Hz). 1.38 (111. Tn). 1. DG 1. HO (- 111, m), 2.18 (1H, m), 2.35 (111, m), 2.55 (111, m), 3.47-3.71 (3H, m), 3.73 (1 ».d, J = 17.8Hz), 5.32 ( 111, br), 5.96 (1H, dd, J = 3.5, 9.2Hz), 7.18 (111, br), 7.21 (1H, dd, J = 1.8, 9.5Hz), 7.47-7.62 (411, m), 7.63 (1H, m), 7.71 (1H, m), 7.76-7.82 (2H, m). 8.57 (111, m) Examples 38 to 46 The following compounds were obtained as in Example 37. Example 38 2- (N-benzenesulfonic acid) Fluorenylglycine hydrazone > -Bu (2-methyloxazolyl) 1,2-a] pyridin-6-yl) -N'-methylcyclohexanemethanamine I 11111 _ ;. 1 — ^ 装 — III I-order, I-line (please read the note f on the back before filling in this card)) The policy of the Central Standards Bureau of the Ministry of Economic Affairs, Shellfish Consumer Cooperatives, India-93- This paper size applies to China's National Slope (CNS) A mayi grid (210X297 mm) A7 B7

V. Description of the invention (^) CH: Guang-·· · / mp (eC): 205-207 NMR (400MHz, δ, CDClj): 1.36 (1H. M), 1.49-1.77 (4H, m). 2.15 ( 111, m), 2.34 (1H.m), 2.44 (311, d, J = 0.5Hz), 2.54 (1H, m). 3.04 (3H.d, J = 4.6Hz), 3.60 (1H, d. J = 17.9Hz), 3.72 (1H, d, J = 17.9Hz), 5.33 (111, bf), 5.94 (111, dd. J = 3.7, 9.5Hz), T.13 (1H, dd, J = 1.8, 9.5Hz), 7.39 (1H, d, J = 9.5Hz), 7.43-7.54 (411, m), 7.59 (1 ». M), 7.77-7.82 (2», m), 8.49 (1H, m) 39 2- (N-benzenesulfonylglycine 醯 amino) -1- (2-trifluoromethyloxazolyl [l, 2-a] pyridin-6-yl) -N'-methylcyclohexane Methionine I -------- Ι-^ pack ----- 1 order, ------ 0 (please read the note on the back before filling in this page) Economy Du Yinye

CF: This paper is suitable for Chinese and national standards (CNS > Α4 size (210X297mm)

A7 _ ^ _ B7_ V. Description of the Invention (W) «mp CC): 223-224 • NMR (400MHz, i, CDCI3): 1.32 (1H, m), 1.46-1.70 (3H, m), 1.78 (1H, m), 2.19 (1H.m), 2.40 (1H.m), 2.60 (111.m), 3.08 (311, d, J = 4.6Hz), 3.63 (1H, dd, J = 5.8, 17.9Hz), 3.75 (1H. Dd, J = 6.0, 17.9Hz), 5.05 (1H, dd, J = 5.8. 6.0Hz) t 5.95 (1H, dd, J = 3.7, 9.5Hz), 7.35 (1H, dd, J = 1.8, 9.9Hz), 7.45 (1H, br). 7.49-7.64 (4H..m), 7.76-7.7K2H, m), 8.02 (1H, s), 8.67 (111, s) Example 40 2- (N -Sulfosyl-Glycosyl-Cytosyl) -Bu (oxazosin [1,2-a] pyridine-6-yl) -ίΤ "ethanecyclohexanemethyl'thiomamine

S 0, ^ · ϋ • NMR (400MHz, β, CDCI3): 0.97 (3H, t, J = 7.0Hz), 1.18-1.28 (1H. M), 1.32-1.40 (2H, m), 1.44-1.56 ( 2H, m), 1.98-2.14 (2H, m), 2.62-2.70 (lH, m), 3.24-3.50 (2H, m), 3.54-3.60 (2 », m), 5.88 (lH, m), 7.17 (111, dd, J = 10.0, 2.0Hz), -95- This paper size is applicable to China National Standard (CNS) A4 (210X297 mm) ^ / m \ fr, \ I ------- ^ --- Installation ------ 丨 Order .--; -------- Line (Please read "Note f on the back side before filling out this page") Printed by Zhengong Consumer Cooperative, Central Bureau of the Ministry of Economic Affairs

A7 B7 V. Description of the invention (material) 7.4K1H, d, J * 10.0HZ), 7.53-7.57 (2H, m), 7.63-7.69 {2H, m), 7.8β (1Η, dd, J = 7.5-l .〇Hz), 7.96 (1H, s). 8.06-8.08 (lH, m), 8.19 (1H, d, J = 8.0Hz), 8.44-8.47 (2H, in), 8.54 (1H, m), 9.42 (1H, m) Example 4 1 2- (N-Sulfosulphinylglycine) -B (2-methylimidazolium [1,2 -a] pyridin-6-yl> -N ' -Methylcyclohexanemethanamine

• NMR (400MHz, δ, DMSO-dg): 1.17-1.26 (1H, m), 1.32-1.39 (211, m), 1.44-1.54 (2 ». M), 1.96-2.10 (2», m), 2.31 (3H, s), 2.60-2.68 (1H, m) t 2.88 (3H, d. J = 3.5Hz). 3.27 (1H. D, J = 18.0Hz), 3.56 (1H, d, J = 18.0Hz ), 5.89 (111, m), 7.10 (111, dd, J = 10.0, 2.0Hz), 7.26 (1H. D, J = 10.0Hz), 7.55 (111, dd, J = 8.0, 7.5Hz ), 7.63-7.70 (3H, m), 7.89 (111, dd, J = 7.5, 1.0Hz), 8.06-8., 08 (111, m). 8.19 (1 », d, J = 8.0Hz), 8.32 (1H, s), 8.35-8.45 (1H, bs), 8.54-8.56 (1H, m), 9.42 (1H, bs) This paper size is applicable to China National Standard (CNS) A4 (210X297 mm) ------- M--: installed ------ 1 order, ------ line (please read the note $ on the back before filling this page) Printed by Consumer Cooperatives B7 V. Description of the Invention (Hot) 2- (H- (8-Technolinylsulfonyl) glycinase gas group > -Bu (oxazolam [1,2 -a] pyridine-6- ) -N'-Methylcyclohexane Methionamine

(Please read the note f on the back before reading this page) • mp CC): 149-152 • NMR (400MHz, δ, CDC13): 1.28 (1H, m), 1.52-1.73 (3H, m). 1.82 (1H, m), 2.14UH, m), 2.4K1H, m), 2.63 (1 », m), 3.08 (311, d, J = 4.8Hz), 3.63-3.77 (2H, m), 5.80 (111 , dd, J = 3.8, 10.4Hz), 6.86 (1H.t, J = 6.2Hz), 7.14 (1H, dd, J = 1.8, 9.5Hz), 7.53 (111, br), 7.54 (111, d, J = 9.5Hz), 7.59 (1H, dd, J = 4.4, 8.4IIz), 7.63 (111, m), 7.66 (1H, m), 7.83 (111. S). 8.08 (111, dd, J = 1.5 , 8.4Hz), 8.28-8.35 (211, m), 8.83 (111, s), 9.01 (111. Dd, J = 1.5, 4.4Hz) Printed Example of Offset Consumer Cooperatives, Central Standards Bureau, Ministry of Economic Affairs 43 2- ( 2- (N-benzenesulfonylamino) isobutyrylamino) -bu (oxazolidine [1,2-a 丨 pyridine-6-yl) -N'-methylachen hexanemethanamine-97 -This paper XJt applies the Chinese National Standard (CNS) A4 «UM 210X297 mm) A7 B7 5. Description of the invention

• mp CC): 211-214 • NMR (400MHz, 6, CDC13): 1.23 (3H. S), 1.24 (3H, s), 1.28 (1H, m), 1.52-1.7T (3H, m), 1.98 (1H, m), 2.3K1H, m), 2.39 (1 », m), 2.70 (1H, m). 3.05 (3H, d, J = 4.8Hz), 5.08 (1H, s), 5.96 (1H. dd. J = 3.7, 9.9Hz), 7.16 (1H, dd, J = 1.8, 9.7Hz), 7.36 (111, br), 7.47-7.53 (211. in), 7.57 (1H, m), 7.61 (111 , d, J = 9.7Hz), 7.64 (1H, d, J = 1.3Hz), 7.81-7.88 (2H, m), 7.89 (1H. s), 8.83 (1H, m) Example 44 2- (N- Benzenesulfonylsilylamine aldehydeoxy) -1- (oxazolyl [l, 2-a 丨 pyridin-6-yl > -N'-shenyl hexanemethanamine (please read the (Note $ item and write this page again) Printed by the Central Ministry of Economic Affairs

The size of this paper is in accordance with China National Standard (CNS) A4 (2 丨 0 × 7mm) B7 V. Description of the invention (97) • mp (eC): 203-205 (dec.) • NMR (400MHz · δ, CDC13 ): 1.45-1.78 (4H, m), 1.85 (111, m), 2.22 (111, m), 2.40UH, m). 2.58 (1H, m), 3.07 (311, d. J = 4.8Hz), 3.50 (1H · dd · J = 4.0, 11.5Hz), 3.89 (1H, m), 3.95 (1H, dd, J = 2.2, 11.5Hz), 5.55 (1H. Br), 6.00 (1H, dd, J = 3.8, 11.2Hz), 7.19 (1H, dd, J = 1.6, 9.5Hz), 7.48-7.56 (3H, m). 7.58-7.65 (3H, m), 7.82-7.86 (2H, m), 7.93 (1H , s), 8.98 (1H, br) Example 45 2- (N-benzenesulfenyl isovalerinase gas group) -bu (oxazolyl [l, 2 = a] pyridin-6-yl) -N '-Methanine Methionamine (L-type)

• mp (eC): 207-208 Printed by the Shellfish Consumer Cooperative of the Central Board of Governors of the Ministry of Economic Affairs (please read the “$” on the back before filling out this page) • NMR (400MHz, β, CDC13): 0.20 (3H. br d, J = 6.8Hz). 0.70 (3H, d, J = 6.8Hz), 1.20-1.54 (6H, m). 2.20 (1H. m), 2.26 (1 », m), -99- This paper Standards use the Chinese National Kneading Rate (CNS) A4 specification (210X2 to 7 mm today) Printed on the A7 _; __ B7_ of the Central Standards Bureau of the Ministry of Economic Affairs _; __ B7_ V. Description of the invention (shirt) 2.50 (1H, m), 3.07 (3H, d, J = 4.8Hz). 3.57 (1H, dd. J = 4.0, 9.9Hz). 5.34 (1H. D, J = 9.9Hz), 5.88 (1H, dd. J = 3.1, 7.0Hz) , 7.16 (1H, dd, J = 1.8, 9.7Hz), 7.37 (111, d, J = 9.7Hz), 7.44-7.50 (211, m), 7.52-7.58 (2H, m), 7.60 (1H. D , J = 1.8Hz). 7.75-7.82 (311. M), 8.32 (1H, s) Example 46 2- (N-benzenesulfonylisovalerylpyridyl) -1- (oxazolyl [l , 2-a] pyrimidin-6-yl) -N'-methylcyclohexanemethionin (M-type)

• mp (* 〇: 204-207 • NMR (400MHz, b, CDClj): 0.67 (3H, d. J = 6.4Hzi, 0.68 (3 », d. J = 6.4Hz), 1.33 (1H, m), 1.48-1.64 (3H, m), 1.77 (111, m), 1.96 (1H, m), 2.24-2.37 (2H, m), 2.62 (1H, m), 3.04 (3H, d, J = 4.6Hz) , 3.58 (111. M), 5.27 (1H, d, J = 9.0Hz), 5.89 (1H, dd, J = 3.3, 9.0Hz), 7.12 (1H, m), 7.38-7.49 (3H, m), 7.53-7.60 (2 », m), 7.72-7.84 (4H. M), 8.67 (11 s) -100- The paper Λ degree is free to use the national rate of China (CNS > A4 * l grid (210X297 mm) -------- ^ ---- Install ----- 11 Order, ------ 0 (Please read Note f on the back before filling this page)

88 · 9- Ηϊ 壬 壬 J hi: Bu 7 B7 V. Description of the invention (μ) Example 47 2- (N-benzenesulfonyl asparagine alkoxy) -1- (oxazole hydrazone [l, 2- aj Pyridin-6-yl) -fT-methylcyclohexanemethanilamine 0.55 g 2- (fluorenyl-benzenesulfonyl- / 8-benzyl aspartame carbamoyl group) > -1- (oxazolyl) [1,2-alpyridin-6-yl> -N'-formamidine thiomethanamine (prepared in Example 3Θ) was dissolved in 5b1 Two Crocodile Farm, and 5 «1 IN NaOH was added. Stir at room temperature for 30 minutes After that, water and benzene were added. The aqueous phase was separated and adjusted to a pH of about 5 with dilute acid, and extracted with argon / ethanol. The organic phase was dried over anhydrous magnesium sulfate, the solvent was evaporated, dissolved in ethanol, added with active tritium, filtered and concentrated. , Crystallized from diethyl ether to obtain 0.31 g of the object, pale yellow powder (yield 66%). • mp CC): 153-157 ... • NMR (400MHz, 6, DMSO-d6): 1.26 (1H, m) , 1.34-1.44 (2H, m), 1.51-1,62 (2H, m), 2.06-2.28 (4H, m), 2.74 (1H, m), 2.90 (3H. D. J = 4.4Hz), 3.79 (1H, m), 5.95 (1H, m), 7.31 (1H, d, J = 9.5Hz). 7.44-7.63 (6H.m), 7.6G (1H, s), 8.03 (1H, s), 8.16 (1H, d, J = 8.6Hz), 8.52 (1H, s), 9.53 (1H. Br) -101- Chinese paper standard (CNS Μ4 regulations) (210X297mm) (please read the note on the back before writing this page) .tr Printed by the Central Sample Rate Bureau of the Ministry of Economic Affairs, Industrial and Commercial Cooperation, Ⅴ. Description of the Invention) A7 B7 Example 48 (-)-( lS, 2R) -2- (H-benzenesulfonylglycine aspirating group) -oxazolidine [l, 2-a] pyridin-6-yl) -N · -methylcyclohexanemethanilamine

Production of 0.5g (IS, 2R) -2 -glycine aerosol-1- (眯 畦 骈 丨 1,2-alpyridine-6-yl) -N -Methylcyclohexanemethionamine dihydrochloride (prepared in Preparation Example 34) was dissolved in 3 ml of pyridine, and 0.33B1 benzenesulfonic acid was added. After stirring at room temperature for 50 minutes, saturated sodium persulfate water was added. It was extracted with a gas-like solution and dried over anhydrous magnesium acetate, and the solvent was distilled off. The residue was crystallized from silica gel column chromatography (diazomethane / methanol = 30: 1) and crystallized from digasmethane / ether to obtain 0.38 g of the target substance. Powder (65% yield). • mp (β〇: 202-205 • Specific rotation U] D28: -68.2. (C = 1.01, DMF) • NMR (400MHz, δ, CDClg): 1.38 (1H, m), 1.51-1.8K4H, m) , 2.18 (1H, m), 2.37 (1H, m), 2.57 (1H, m), 3.06 (3H, d, J = 4.8Hz), 3.61 (1H, d, J = 17.8Hz), 3.72 (1H, d, J = 17.8Hz), 5.42 (1H, br), 5.94 (1H, dd, J = 3.5, 9.3Hz), -10 2- This paper's flt scale is applicable to China National Standards (CNS M4 specification (210X297 mm) II n I ϋ ϋ iM I —y II —-H Ί— nn II n ^ (Please read “Note f on the back side before filling in this note”)

A7 _B7 _ V. Description of the invention (W) 7.18 (1H, dd, J = 1.8, 9.5Hz). 7.45-7.54 (3H, m), 7.54-7.63 (3H, m), 7.70 (1H, s), 7.77 -7.81 (2H, m), 8.59 (1H, m) Example 4 9 ~ 5 3 Following Example 4 8 gives the following compound e Example 49 (+)-(lS, 2R) -2- (N- (8-Ufline Sulfonyl) Glycine 醯 Gasyl) -1- (oxazolyl [1,2-allftidine-6-yl) -N'-methylcyclohexane formamidine

r ^ N (• mp (eC): 155-159 specific rotation [α I 28: + 5 2 · 2 ° (c = 1 · 0 1, CHC 1 3) Example 50 (IS, 2R) -2- (E -(6 -Isocyanolinesulfonyl) glycinylamino) -1-(oxazolidine [l, 2-a] fftidine-6-yl) -N'-methylcyclohexanemethanilamine 103- The size of this paper is applicable to the Chinese national standard (CNS M4 specification (210X297 mm) ------- Γ--: installed ----- order; ------ 〆 (please first Read the note on the back of the page and fill in this page} Du Yinye A7 B7, Shellfish Consumption Cooperation between China and Husband Bureau of the Ministry of Economic Affairs 5. Description of the invention (,. ≫)

(Please read the note on the back before writing this page) • mp CC): 209-210 (dec.) • NMR (400MHz, 4. CDClj): 1.33-1.6K4H, m), 1.65-1.76 ( lH, m), 2.12-2.65 (511, m). 3.02 (3H, d, J = 4.6Hz), 3.58 (1H, d, J = 17.9Hz), 3.72 (1H, d, J = 17.9Hz); 5.96 (1H, dd, J = 2.9, 7.9Hz). 7.12-7.22 (2LIIf m), 7.39 (111. D, J = l.lHz), 7.60-7.69 (2H, m), 8.17 (1H, d, J = 8.2Hz), 8.28 (1H, br s), 8.30-8.36 (2H, m), 8.42 (111, d, J = 6.2Hz), 8.57 (111, br s), 9.27 (111, s) 51 (-Bu (IS, 2R)-(fi-i2 -methylpyrazole-3-ylsulfonyl) glycinase gas group > -1- (triazolil, 2-a) pyridine- 6-based)-ΓΓ-Methionine Methionamine Printed by the Central Bureau of Specimen of the Ministry of Economic Affairs, Shellfish Consumer Cooperatives -10 4 This paper is scaled to the Chinese National Standard (CNS Μ4 Specification (2 丨 〇 > <; 297 mm) A7 B7

V. Description of the invention (.y)

mp (· 〇: 199-202 specific rotation 丨 e) D28: -81.8 · (c = 1.00. DMF) NMR (400MHz, i, CDC13): 1.43 (1H, m), 1.50-1.79 (4H, m), 2.21 (111, m), 2.36 (1H, m), 2.54 (111, m), 3.06 (3 », d, J = 4.6Hz), 3.64 (1H, d, J = 17.9Hz), 3.77 (111, d, J = 17.9Hz), 4,07 (3 «,. S), 6.QU1H, dd, 5 * 8.9Hz), 6.66 (111.d, J = 2.2Hz), 7.25 (1H. dd. J = 1.8, 9.5Hz), 7.2 ^ (111, d. J = 2.2Hz), 7.44-7.54 (2H, m), 7.58 (1 », d, J = l.lHz), 7.67 (1H, m), 8.52 (1H, m) Μ ---- (Please read the note in the back on the back and fill in this page first) Print and repair 5. "(Bubu (1 S, 2 R) -2-ί N-i-p-toluene: see group> Glycine 醯 Gasyl) -Bu 卜 azole 眯 丨 1,2-3 丨 Pyridin-6-yl) -N, -formyl Methanamine

Hac This paper uses the Chinese National Standard (CNS) Λ4 specification (210X297 mm) B7 V. Description of the invention (· ~) • m.p. (eC): 189-202 • Specific rotation [et] D28: +16.6. (C = 0.51, CHC13) • NMR (400MHz, h, CDC13): 1.36 (1H, m), 1.50-1.69 (311, m), 1.74 (111, m). 2.16 (1H, m) · 2.37 (1H M), 2.43 (3H, s), 2.58 (1Hm), 3.06 (3H, d, J = 4.8Hz). 3.60 (1H, dd, J = 5.1, 17.6HZ), 3.70 (1H, dd, J = 5.7, 17.6Hz). 5.18 (111, br). 5.93 (111. Dd, J = 3.7, 9.7Hz), 7.19 (1H, dd. J = 1.8, 9.5Hz), 7.28-7.32 (2H. M ), 7.45 (111, br), 7.54 (1H, d, J = 9.5Hz), 7.64 (1H, s), 7.65-7.69 (2H, m), 7.73 (1H, s), 8.63 (1H, s) Example 53 (-)-(lS, 2R) -2- (Ji- (2-l $ pansulfonyl) glycine-gas-producing group) -1- (oxazolyl [1,2-a] pyridine-6 -Yl) -N'-methylcyclohexanemethanine

Work cooperation and consumption cooperation of the Central Bureau of Standards of the Ministry of Economic Affairs

m.p. (eC): 134-138 (please read the note on the back and fill in the WT page first) Specific rotation [a] D28: -6.6. (C = 1.00, CHC13) NMR (400MHz, b, CDC13): -1 0 6-National standard for papers that are not suitable for use (CNS > A4 specification (210X297)) A7 B7 (-)-(lS, 2R) -2- (N- (N- (Sulfuryl) Glycine 醯 Gasyl) -1-(Adifloxacin fl, 2-a 丨 pyridin-6-yl) -fi_ -Methylsane Hexane Zymamine

V. Description of the invention (^) 1.40 (1H, m), 1.52-1.68 (3H, m). 1.76 (1H, m), 2.21 (1H, m), 2.38 (1H, m), 2.56 (1H, m) , 3.07 (3H, d, J = 4.6Hz), 3.67 (1H, d, J = 17.8Hz), 3.80 (1H. D. J = 17.8Hz), 5.37 (111, br), 5.98 (111, dd, J = 3.5, 9.4Hz), 7.08 (1H, m), 7.21 (1H, dd, J = 1.8, 9.5Hz), 7.40 (1H, br), 7.50-7.56 (2H, m), 7.59 (1H, m ), 7.64 (1H, m), 7.70 (1H, br s), 8.56 (1H, m) Example 54 6.9g (+)-(13,21?)-2- (BU third butane carboxyglycinamine (Gasyl) -oxazolone [1,2-alpyridin-6-yl> -N'-methylcyclohexanemethylthiotyramine (prepared in Preparation Example 25) dissolved in 130B1 aerosol and added 30ml 4N HC1 / Ethyl acetate. After stirring overnight at room temperature, it was evaporated to dryness in vacuo to obtain a white powder. This powder was dissolved in 10Offll pyridine and stirred under ice-cooling. After adding 6.4 g of 1-lysulfonium, it was poured into a saturated solution. Sodium osmium water. Extracted by atmospheric imitation without -107- This paper size is used by the Chinese family (CNS > M size (210X297 mm) ----- ^ ---;-pack ----- Ί 定 ------- line (please read "Note f on the back side before filling out this page) Printed Economy Printed by the Central Bureau of Standards Shellfish Consumer Cooperative A7 __B7_ V. Description of the invention (Ά) Water magnesium sulfate was dried, the solvent was distilled off, and crystallized from dichloromethane to obtain pale yellow crystals. The filtrate was subjected to silica gel column chromatography (dichloromethane). / Methanol = 30: 1), and combined with the above pale yellow crystals, a total of 6.1 g (yield 74%) of the target was obtained. • mp CC): 158-160 • Specific rotation / U] D28: -66.7 * (c = 1.0, DMF) • NMR (400MHz, δ, DMS0-dfi): 1.20-1.27 (1H, m), 1.34-1.40 (211, m), 1,46-1.56 (2H, m), 2.00-2.08 ( 2H, m), 2.61-2.68 (111. M), 2.89 (111, d, J = 4.0Hz), 3.29 (1H, d, J = 18.0Hz), 3.58 (111, d, J = 18.0Hz), 5.90 (111, br s), 7.16 (111, dd. J = 9.5, 2.0Hz), 7.4K1H, d, J = 9.5Hz), 7.53-7.57 (2H, m), 7.63-7.70 (2H, m) , 7.85-7.89 (1H, m), 7.96 (111, s). 8.06-8.09 (lH, m), 8.19 (111, d, J = 8.0Hz), 8.44-8.49 (2H, m), 8.53-8.56 (lH, m), 9.44 (1H, br s) Example 55 2- (H-benzylfluorenylglycinyl) -1- (oxazolylU, 2-ajpyridin-6-yl) -N ' -Methylcyclohexanemethanilamine-108- This paper size is applicable to China National Standard (CNS) A4 (210X297 mm) I I I I I I J. I I I — order 1 — I I I line (please read the note f on the back before filling out this page) A7 B7 Printed by the Central Government's Bureau of the Ministry of Economic Affairs on the consumer cooperation of Du Du V. Invention Description (^ 7)

0.2 g of 2-glycosylamino-1- (oxazolyl [1,2-aliitidine-6-yl) -N-methylhexylmethanilamine (prepared in Preparation Example 28) suspended in 2b1 diamine Methane was added with 0.05 · 1.1% of pyridine and 0.15 g of benzoic anhydride. After stirring at room temperature for 18 hours, saturated sodium bicarbonate was added. Extracted by atmospheric imitation, dried over anhydrous magnesium sulfate, evaporated the solvent, and then subjected to silica gel column chromatography (dichloromethane / methanol = 30: i >, adding ether and filtering the insoluble matter to obtain 0.15 g of the target substance, white powder. (Yield 57%). • mp (* 〇: 226-229 • NMR (400MHz, 6, CDClj): 1.33 (1H. M), 1.51-1.87 (4H, ra). 2.22 (1H, m), 2.35 (1H, m), 2.61 (1H, m). 3.04 (3H, d. J = 4.6Hz), 4.00 (1H. Dd, J = 4.9, 17.9Hz), 4.25 (1H, dd, J = 5.7, 17.9 Hz), 6.00 (1H, dd. J = 3.7, 9.7Hz), 6.71 (1H, br t, J = 6Hz), 7.18-7.27 (2H, m), 7.38-7.58 (6H, ra), 7.69-7.74 (2H, m), 8.45 (1H, m) Example 56 2- (N-((2-Methanesulfonic acid.amino) benzyl) glycinyloxy) -1- (oxazolyl [1, 2-a] pyridine-6-yl) -N'-methylcyclohexanemethanilamine-109- This paper uses the two standards of China (CNS) A4 specification (210X297 mm); 7 ^ -11T I ^ (Please read the note on the back before filling in this page) B7 V. Description of the invention (* .〇

(Please read the note f on the back before filling this page) 0.2 g 2 -Glycine hydrazone-1- (oxazolyl [1,2-a] pyrimidin-6-yl > -N-methyl Methanesulfanilamide, 0.15 g of 2-methanesulfonamidobenzylcarboxylic acid, 0.14 g of N, N'-dicyclohexylfluorinated diimide and 0.09 g of N-hydroxybenzotriazole are placed in 2b1 acetonitrile, After stirring at room temperature for 14 hours, acetonitrile was added to remove insoluble matters, and cystic acid was added to saturated sodium bisulfate. The extract was extracted with chloroform, dried over anhydrous magnesium sulfate, and the solvent was distilled off. ; Methane / methanol = 20: 1), crystallized from dimethane / ether to obtain 0.23 g of the target, white. Powder (yield 73%). • mp (eC): 156-160 • NMR (400MHz, δ , CDC13): 1.42-1.88 (5H, m), 2.25-2.40 (2 », m), 2.58 (1H, m), 3.00 (3H, s), 3.09 (3H, d, J = 4.8Hz), 3.88 (1H, dd, J = 4.8, 18.1Hz), 4.17 (111, dd, J = 5.5, 18.1Hz), printed by the Shellfish Consumer Cooperative of the Central Bureau of the Ministry of Economic Affairs, 6.14 (1H, dd, J = 3.3, 8.4Hz), 6.95 (1 », br t, J = 4Hz), 7.13 (1H, m), 7.25 (1H, br), 7.30 (1H, dd. J = 1.8, 9.5Hz). 7.44-7.61 (6H , m), 7.69 (111, m), 8.43 (1H, m) Example 5 7 ~ 59 -1 10- Zhang Jiuyong used in the standard »CNS 4 specification (210X297 mm) Printed by the Central Government Bureau of Standards of the Ministry of Economic Affairs, Shellfish Consumer Cooperative, printed A7 B7 5. Description of the invention (W) Example 5 6 The following compounds were obtained ^ Example 57 2- (N- (2-Benzylbenzyl) glycinol) -1-(oxazolidine fl, 2-a] pyrimidin-6-yl) -IT-methylcyclohexanemethylsulfide Zymamine

• mp- CC): 209-211 • NMR (400MHz, 6. CDClj): 1.45-1.88 (5H, m), 2.17-2.26 (2H, m), 2.64 (1H, m), 3.05 (3H, d, J = 4.8Hz), 4.30 (111, d. J = 17.2Hz), 4.36 (1H, d, J = 17.2Hz), 5.95 (111, dd, J-3.5, 9.2Hz), 7.09 (1H, dd, J = 1.6, 9.5Hz). 7.21-7.39 (4H, m), 7.59 (1H, d, J = l.lHz), 7.72-7.82 (3 », m). 8.26 (1H, m) Example 58 2- (H- (2-methylbenzylfluorenyl) glycinylamino) -1- (oxazolyl [1,2-a] pyridin-6-yl) -IT -methylcyclohexanemethylthiosulfanyl Amine-111- This paper size is applicable to the rate of poor countries (CNS > A4 size (210X297mm)) ------- Γ-u equipment ----- Order: ------ i (Please read the note $ on the back before filling in this page) A7 B7

V. Description of the invention (π)

H, CO

• mp (.C): 222-224 • NMR (400MHz, 2, CDC13): 1.50-1.90 (5H, ra), 2 / 2KIH, m), 2.36 (111, m), 2.65 (1H, m). 3.06 (3H, d, J = 4.6Hz), 3.99 (3H, s), 4.00 (1H, dd, J = 4.9, 17.9Hz). 4.29 (111, dd. J = 5.9, J5.89. (LHt d (J. a = 3. &, 9.9Hz). «.96t. 7.03 (2H. M)? Dd. J = 1.8, 9.5Hz), 7.33 (1H, s), 7.40-7.53 (3H, m) , 7.69 (1H, br), 7.99 (1H, dd, J = 1.6, 7.9Hz), 8.42 (1H, br t, J = 7Hz), 8.44 (1H. M)

Example M 2- (N- (1, # carbonyl> Glycinaloxy) -bu (oxazolyl [1,2-ajpyridin-6-yl >-) -112- The standard of this paper is Chinese National Standard (CNS) A4 (210X297 mm) ------- τ--: installed ----- 1 order ------- line ( Please read the note f on the back before filling in this I) Printed by Bei Gong Xiao F Cooperative, Central Bureau of Standards, Ministry of Economic Affairs

B7 V. Description of Invention ("·)

• mp CC): 164-168 • NMR (400MHz, h, CDC13): 1.40 (1H, m), 1.51-1.73 (3H, m), 1.85 (1H, ra), 2.28-2.39 (2H, m), 2.58 (1H, m), 3.00 (3H, d, J = 4.6Hz), 4.04 (1H, dd, J = 4.9, 17.9Hz), 4.32 (1H, dd, J = 5.7, 17.9Hz). 6.07 (1H , dd. J = 3.5, 9.0Hz), 6.64 (1 », t, J = 5.5Hz). 7.19 (111, dd, J = 1.8, 9.5Hz), 7.38 (1H, d. J = 9.5Hz), 7.41-7.54 (5H, m), 7.61 (1H, dd, J = ll, 7.0Hz), 7., 76 (1H, br), 7.87 (1 », d, J = 8.1Hz), 7.94 (1H, d, J = 8.4Hz), 8.28 (111, dd, J = 0.7, 8.6Hz), 8.47 (1H, m) Example 60 2- (N-Phenethylfluorenylglycinoloxy) -Bu (imidazolium [l, 2-a] pyridine-6-yl) -N'-methylcyclohexanemethanilamine-113- -------:- ---- Line (Please read the note on the back of the page before filling in this page) The Central Kneading Bureau of the Ministry of Economic Affairs βζindustrial consumption cooperation Du printed This paper is applicable to China National Standards (CNS) Α4 specifications (2 丨 0 > < 297 mm)

V. Description of the invention (,, M A7 B7

Printed by the Ministry of Economic Affairs, Central Bureau of Standards and Labor, Cooperative Consumers' Cooperative 0.2 g of 2-glycine, carbamoyl-1- (oxazolyl [l, 2-a] pyridin-6-yl) -N-formen Hexanemethionamine < Preparation Example 28 Preparation} Suspended in 2b1 dioxane, 0.05B1 pyridine was added, and 0.09B1 phenethylhydrazone gas was added dropwise under ice cooling. After stirring under cooling for 30 minutes, after stirring at room temperature for 30 minutes, stirring at room temperature for 40 minutes, adding saturated aqueous sodium bisulfate for extraction with chloroform, drying over anhydrous magnesium sulfate, evaporating the solvent, Chromatography (dichloromethane / methanol = 30: 1 to 20: 1) and crystallization from dichloromethane / ether to obtain 0.17 g of the target product as a white powder (yield 63%). • mp CC): 131-136 • NMR (400MHz, δ, CDC13): 1.40UH, m), 1,48-1.64 (2Η, m), 1.71-1.82 (2Η. M). 2.21-2.33 (2H, m), 2.56 (1H, m), 3.07 (3H, cl, J = 4.6Hz), 3.53 (1H, d, J = 13.7Hz), 3.58 (1H, d, J = 13.7Hz), 3.66 (111, dd, J = 4.6, 18.1Hz), 4.01 (111, dd, J = 5.9, 18.1Hz), 5.91 (1H, br t, J = 6Hz), 6.00 (1H, dd, J = 3.5, 8.8Hz), 7.20 (111, dd, J = 2.0, 9.7Hz), 7.21-7.37 (5H, m), 7.45 (111, d, J = 9.7Hz), T.58-7.65 (3H, tn), 8.41 (1H, m) -1 14 This paper size is in accordance with Chinese National Standard (CNS) Α4 size (210X297 mm) (Please read the note f on the back before filling this page)

、 TT • Central Liangzhun Bureau of Ministry of Economic Affairs, Industrial and Consumer Cooperation Du Yin *. A7 _._ B7_ V. Description of the Invention (^) Example 61 (+ >-( lS, 2R) -2- (N-Benzylbenzylgan) Aminase > -1- (oxazolidine [1,2-aHftpyridin-6-yl) -N'-Houchen hexanemethanil _

0.5 g of (18,2! 〇-2-Glycinepyridinyl-1- (oxazolyl [1,21] pyridin-6-yl) -N-methylcyclohexanemethanilamine dihydrochloride ( Preparation Example 34 Preparation) 0.16 g of benzoic acid, 0.27 g of N, N-dicyclohexylfluorinated diimine, 0.18 g of N-hydroxybenzyltriazole, and 0.35 Π1 triethylamine were added to 10 Bl of acetonitrile. Stir at room temperature After 60 hours, evaporate the solvent, concentrate and add saturated sodium bisulfate. Extract with chloroform and dry over anhydrous magnesium sulfate, evaporate the solvent, and perform column chromatography on silica gel (methane / methanol = 40: 1) , Crystallized from dichloromethane / diethyl ether to obtain 0.28 g of the target substance, a white powder (52% yield). • mp (.C): 141-145 • specific optical rotation U] D28: +65.3. (C = 1.03, CHC13 ) • NMR (400MHz, δ, CDClg): 1.33 (1H, m), 1.51-1.87 (4H, m), 2.22 (1H, m), -1 15- The A degree of this paper is applicable to the Chinese household furniture rate (CNS) > A4 size (210X297mm) -------:-: installed ----- ordered ^ ------ line (please read the note $ on the back first and then the floor copy) page)

A7 __B7_ V. Description of the invention () 2.35 (1H, m), 2.6K1H.m), 3.04 (3H, d, J = 4.6Hz), 4.00 (1H, dd, J = 4.9, 17.9Hz), 4.25 (1H , dd, J = 5.7, 17.9Hz), 6.00 (1H, dd, J = 3.7, 9.7Hz), 6.71 (1H, br t, J = 6Hz), 7.18-7.27 (2H, m), 7.38-7.58 ( 6H, m), 7.69-7.74 (2H, m), 8.45 (1H, m) Example 62 (+ >-( lS, 2R) -2- (N- (2-methylbenzyl) glycine) Gas group) -1- (triazolidine [1,2-alpyridin-6-yl) -N'-methylcyclohexanemethanilamine

Example 6 1 except that 2-methylamino.benzoic acid was used instead of benzoic acid to obtain the target product. • mp (eC): 126-129 • Specific rotation U] D28: + 117 · 9β (c = 0.99, CHC13) • NMR (400MHz, 6, CDClg): 1.50-1.90 (5H, m), 2.21 (1H, m), 2.36 (1H, m), 2.65 (1H, m), 3.06 (3H, d, J = 4.6Hz), 3.99 (3H, s), 4.00 (1H, dd, J = 4.9, 17.9Hz), 4.29 (1H, dd, J = 5.9, 17.9Hz), 5.89 (1H, dd, J = 3.8, 9.9Hz), 6.96- -116- This paper size applies to China's 81 standards (CNS) M specifications (210X297) ）) 4 \ ------- Γ--: equipment ----- order: ------ line (please read the note on the back before filling in this page) A7 B7 printed by DuPont Consumer Cooperatives. 5. Description of the invention (" 〇7.03 (2H, m), 7.17 (lH, dd, J = 1.8, 9.5Hz), 7.33C1H. S), 7.40-7.53 (3H , m), 7.69 (1H, br), 7.99 (1H, dd, J = 1.6, 7.9Hz), 8.42 (1H, br t, J = 7Hz), 8.44 (1H, m)

(Please read "Notes on the back" before writing this page). I Pack and order 0.25 g of 2-hydroxy-bu (oxazolyl [l, 2-aHftidine-6-yl) -N-methylcyclohexyl Methanethione, 0.4 g of N-benzenesulfonyl carnitine, 0.36 g of N, Ν'-dicyclohexylphosphonium diimide and 0.1 g of 4-dimethylaminopyridine, 4 ml of Ν, H- Dimethylformamide. After stirring at room temperature for 13 hours, add ethyl acetate and saturated heavy acid water, and remove insoluble matter by filtration. The organic layer was separated, washed with water and saturated brine, dried over anhydrous magnesium sulfate, and evaporated. The solvent was removed, and the product was crystallized from silica gel column chromatography (dichloromethane / formase = 40/1) and crystallized from dichloromethane / ether. To obtain 0.42 g of the target, white powder (yield 97%). -117- This paper size is suitable for Chinese families (CNS M4 specification (2 丨 〇 > < 297 mm) Central Ministry of Economic Affairs) Printed by the Zhuhai Bureau Shellfish Consumer Cooperative A7 B7 V. Description of Invention (" fc) • mp (β〇: 208-209 • NMR (400MHZ, ¢, CDClj): 1.29 (1H. In). 1.55-1.89 (4H , m), 2.22 (1 », m). 2.45 (1H, m), 2.62-2.71 (4H, m). 3.08 (3H. d, J = 4.8Hz), 3.67 (111, d, J = 17.0Ilz ), 4.04 (111, d. J = 17.0Hz), 5.97 (1H. Dd, J = 3.7, 10.4Hz), 7.18-7.27 (2H, m). 7.45-7.56 (3 », m), 7.57-7.65 (311.m), 7.71-7.76 (2H, m), 7.85 (1H, m), 8.90 (111, m) Example 64 2-((2, 3 -dihydro-1, budioxophenylene (a 1 Isotriazole-2 -yl) ethoxyl) -1- (imidazolidine [1,2-a] pyridine-6-yl) -N -methylcyclohexanemethanilamine (please read the back first (Note $ items, then fill out this page)

Order line Printed by the Central Bureau of Standards, Ministry of Economic Affairs, Shellfish Consumer Cooperative, and printed with -2-yl) acetic acid instead of benzylcarnitine to obtain the target product. • mp (eC): 223-224. NMR (400MHz, 5, CDClj): 1.31 (1H, m), 1.51-1.84 (4H, m), 2.24 (1H, m), 2.38 (1H, m), 2.57 (1H, m), 2.93 (3H, d, J = 4.8Hz), -1 18- This paper size adopts China National Standard (CNS) A4 size (210X297 mm) Staff consumption of the Central Government Bureau of the Ministry of Economic Affairs Cooperative prints A7 _; _B7_ 5. Description of the invention (" 7) 3.92 (1H. D, J = 17.4Hz), 4.11 (1H, d. J = 17.4Hz), 4.27 (1H, d, J = 13.9Hz ), 4.38 (1H, d, J = 13.9Hz), 6.04 (1H. Dd, J = 3.7, 9.9Hz), 7.20 (1H, dd, J = 1.8, 9.7Hz), 7.31-7.39 (2H. M) 7.45-7.58 (411. M). 7.63 (1H, dt, J = ll, 7.5Hz), 7.78 (1 », d, J = 7.5Hz). 8.63 (1H, m) Example 65 2- (Benzene sleep (Acetylidene) (1,2-oxapyridine-6-yl) -N-methylcyclohexane

Example 63, except that benzylfluorenylacetic acid was used in place of N-benzenesulfonylcarnitine to obtain the target compound. • mp (eC): 225-226 • NMR (400MHz, δ, CDC13): 1.23 (1H, m), 1.48-1.72 (3H, m), 1.85 (1H, m), 2.17-2.33 (2H, m) , 2.64 (1H, m), 3.05 (3H, d, J = 4.8Hz), 4.74 (1H, d, J = 15.7Hz), 4.86 (1H, d, J = 15.7Hz), 5.97 (1H, dd, J = 3.7, 9.9Hz), 7.11-7.18 (3H, m), 7.41-7.48 (3H. M), 7.56 (1H. D, J = l.lHz), 7.62 (1H, m), 7.95-7.99 ( 2H, m), 8.31 (1H, m) -1 1 9- The size of this paper is applicable to «Stay Home Standard (CNS) A4 Specification (210X297 mm); · Installation ----- T—Order-- ----- line (please read the note $ on the back before filling this page) Printed by A7 _; ._B7 _ of the Ministry of Economic Affairs Central Government Bureau Zhengong Consumer Cooperative Fifth, the invention description (,, ϊ) Example 66 6-((1-naphthalenecarboxyl) acetanyl group> -1- (oxazolidine [1,2-a] 丨 ftidine-6-yl} -N'-methylcyclohexanemethanilamine

Example 63, except that (1-naphthylcarboxy) acetic acid was used in place of sulfenylcarnitine to obtain the target compound. • mp (eC): 216-218 • NMR (400MHz, δ, CDClj): 1.27 (1H, m), 1.47-1.73 (3H, m), 1.88 (1H, m), 2.24-2.35 (2H, m) , 2.59 (1H, m), 3.02 (3H, d, J = 4.8Hz), 4.79 (1H, d, J = 15.7Hz), 4.90 (1H, d, J = 15.7Hz), 6.05 (1H, dd, J = 3.5. 9.3Hz), 6.97 (1H, s), T.10 (1H, dd, J = 1.8, 9.5Hz), 7.30 (1H, d, J = 9.9Hz), 7.39 (1H, d, J = 0.9Hz), 7.42-7.57 (4H, m), 7.91 (1H, m), 8.08 (1H, d, J = 8.2Hz), 8.23 (1H, dd, J = l .: 5, 7.1Hz), 8.27 (1H, m), 8.77 (1H, m) Example 67. 2- (2- (1-Cesulfenimido) ethenyl) -bu (imidazolium [l, 2-a] pyrimidin-6 -Base) -N -Methylhexylmethanamine-1 20- This paper is used in China at a high standard (CNS) Λ4 size (210X297 mm) (please read the "$" on the back side first) (Fill in this page)

B7 V. Description of the invention (M)

N: / (Please read "Notes on the back of the book and then fill in the book") Mix 0.4 g of 2- ί2-naphthylsulfonylamino) ethoxy) -1- (Deep sleep [1,2-a丨 Pyrimidin-6-yl) -Bu ((4-methylbenzyl) (methylidene) methyl) cyclohexane, 0.5el toluene, 5b1 trifluoroacetic acid and 5.1 dioxane After methane was stirred under ice-cooling for 1.5 hours, ice-water was added to make it salty with sulfonic acid. Extracted by atmospheric imitation, dried over anhydrous magnesium sulfate, evaporated the solvent quotient I, and purified by silica gel column chromatography (methane / methanol = 30: 1), and crystallized from ethyl acetate / n-hexane to obtain 0.21 g of the target substance. White powder (65% yield). Mp (eC): 128-132 • NMR (400MHz, 6, CDClj): 1.06 (1H, m), 1.39 (1H, m). 1.54 (1H, m ). 1.66 (1H, m), 1.91 (1H, m), 2.29UH, m), 2.56 (1H, m), printed by the Central Consumers Bureau of the Ministry of Carp Ministry of Work and Labor Cooperatives 3.05 (1H, m), 3.13 (3H, d, J = 4.8Hz), 3.15 (1H, m), 3.36 (1H, m), 3.72 (1H, m), 4.29 (1H, dd, J-3.9, II. 5Hz), 5.52 (1H , t, J = 5.7Hz), 7.16 (1H, dd, J = 1.8, 9.5Hz), 7.50-7.65 (7H, m), 7.95 (1H, dd, J = 1.8, 7.7Hz), 8.22 (1H, dd, 3 = 1.1, 7.3Hz), 8.66 (1H, d, J = 8.6Hz), 8.77 (1H s) -1 2 1-Λ degree of this paper is applicable to China National Standard (CNS M MM 210X297 mm) ) V. Description of the invention (^) A7 B7 Example 68 2- (2-benzenesulfonylamine ethoxy > -1- (眯 畦 骈 [1, group > -N-methylcyclohexanemethanilamine) a Hit pyridine-6-

The central government of the Ministry of Economic Affairs, Zhunyang Beigong Cooperative Co., Ltd. printed a copy of Example 67, but using the product of Preparation Example 27 as the raw material, the target β was obtained. • mp (eC): 109-112 • NMR (400MHz, 6, CDClg): 1.08 (1H, m), 1.37-1.79 (4H, m). 1.99 (1H, m), 1H, m), 2.57 (1H. M), 3.05-3.25 (2H, m), 3.14 (3H, d, J = 4.6Hz), 3.40 (1H, m), 3.78 (1H, m), 4.32 (1H, dd, J = 3.8, 11.7Hz), 5.29 (1H, br), 7.18 (1H, dd, J = 1.8, 9.5Hz), 7.47-7.66 (7H, m), 7.83-7.89 (2H, ra), 8.80 (1H, S) Example 69, 2- (2- ibuzesulfonylamino) ethoxyimino) -Bu (imidazolium [1 2-a] pyridin-6-yl) -N -methylcyclohexanemethanamine 122- This paper size applies to China National Standard (CNS) A4 (2 丨 OX25 »7mm (%) (Please read the note on the back before filling in this page) Order A7 B7

5. Description of the invention (...)

0.5 g of N-methyl-2-Ga-1- '(oxazolyl [1,2-a 丨 pyrimidin-6-yl) methane thiomethanamine, 1.02 g of 0-(2- (Bonaphthalenesulfonylamino) ethyl) hydroxylamine and 0.96 g of pyridinium p-toluenesulfonate were put into 5nl of pyridine, and after stirring at 80 π for 16 hours, saturated sodium bisulfate was added, followed by gas imitation. Extract and dry with anhydrous sulfuric acid, evaporate the solvent, and crystallize on silica gel column chromatography (ethyl acetate / methanol = 30/1) and crystallize from dichloromethane / acetamidine to obtain 0.67 g of the target substance as a white solid (yield 74%). • mp (.C): 127-131 • NMR (400MHz, δ, CDC13): 1.48-ί-.80 (3Η, m), 1.86 (1H, m), 2.12-2.36 (2H, m), 2.88 ( 1H, m), 3.03-3.14 (2H, m), 3.24 (1H, m), 3.26 (3H, d, J = 4.8Hz), 3.96-4.08 (2H, m), 5.29 (1H, t, J = 5.7Hz), 6.94 (1H, dd, J = 1.8, 9.5Hz), 7.38 (1H, d, J = 9.5Hz), 7.52-7, 68 (5H, m), 7.94 (111, m), 7.97 ( 1H, m), 8.09 (1H, d, J = 8.2Hz), 8.16 (III, br d, J = 5Hz), 8.20 (1H, dd, J = 1.3, 7.3Hz), 8.56 (111, m) 7fl 2- (2_ (1-sulfenylamino) ethylamine > -1- (Drowsiness [1,2-a] -12 3- This paper size is applicable to Chinese national standards (CNS > A4 Specifications (210/297 mm) 111 111 II: Order JIIII line (please read first! ^ Read the note on the back and fill in this page) Printed by the Central Ministry of Economic Affairs, Shellfish Consumer Cooperative, Printed by the Central Ministry of Economic Affairs Printing of industrial and consumer cooperatives A7 B7 V. Description of the invention l · ») Pyridin-6-yl) -N-methylcyclohexanemethanilamine (L-type)

/ V S

600ng 1- (Sleep Cake 丨 1,2-a] Bftfli-6-yl) -N-methyl-2-oxomethylhexanethioamide and 2.09 g of 1-naphthalenesulfonamidoethylamine were dissolved in 20nl of di-aerated methane, and add 1M tetra-aqueous ammonium / di-aerated methane 2nl at room temperature for 30 minutes and stir at night, then add 1 ml of concentrated water. The filtrate was concentrated in vacuo and 10 Bl of methanol was added. After adding 200 mg of m-based sodium borohydride at room temperature and stirred for 1 hour, the solution was concentrated in vacuo and saturated sodium bicarbonate was added. It was extracted with chloroform, dried over anhydrous sulfuric acid, concentrated in vacuo, and then subjected to silica gel chromatography (methane / ethyl acetate / methanol = 10: 10: 1) to obtain 280 mg of a low-polar diastereomer (L -Plastic) and 350ng of highly diastereomers (M-type), each of which is pale yellow crystal. • mp (eC): 185-186 • NMR (400MHz, δ, CDClg): 1.30-1.50 (2H, m), 1.56-1.89 (5H, m), 1.01-2.07 (1H, m), 2.42-2.52 (lH, m), 2.68-2.80 (lH, m), 2.81-2.9K1H, m) .2.91-3.04 (2H, m), 3.33 (3H, d, J = 4.8Hz), 3.35-3.42 (1H, m), 6.67-6.76 (1H, ra), -124- This paper is based on Chinese national standards (CNS ) A4 size (210X297mm) -------:-: installed ----- order ^ ------ line (please read the note $ on the back before filling this page) Printed by the Bayong Consumer Cooperative of the Central Ministry of Economic Affairs of the People's Republic of China. 38S760 ^ V. Description of the invention () 7.22 (1H, dd. J = 2. 9.6Hz), 7.31 (111, d. J = 1.2Hz), 7.37-7.56 (5H.m). 7.90 (1H, d. J = 8.4Hz), 8.02 (1H.d, J = 7.2Hz), 8.03 (1H, s), 8.13 (1H, dd, J = 1.2, 7.2Hz) , 8.47 (111, d, J = 8.8Hz) Example 7 1 2- (2- (naphthosulfonylamino) ethylamino group)-> ((U, 2_ajpyridin-6-yl group) ) -N-methylhexylmethanamine (M-type)

.mp (β〇: 137-138 • NMR (400MHz, δ, CDClj): 1.10-1.22 (1H, m), 1.33-1.70 (5H, in), 1.79-1.86 (1H, m), 2.28-2.35 ( lH, m), 2.44-2.62 (2H, m), 2.78-2.86 (1H, in), 2.95-3.ΌΚ2Η, m), 3.16 (3H, d, J = 3.6Hz), 3.49-3.54 (lH, m), 5.44-5.52 (1H, m), 7.17 (1H, dd, J = 2, 9.6Hz), 7.52-7.68 (6H, m), 7'.96 (1H, dd, J = 1.2, 8Hz) , 7.98-8.04 (1H, m), 8.08 (1H, d, J = 8Hz), 8.65 (1H, d, J = 8Hz), 9.10 (1H, s) -1 25- This paper size is suitable for Chinese countries Standard (CNS > A4 size (210X297mm) ------- r--: installed -----! Order J ------ line (please read the note on the back first) (Fill in this page again) V. Explanation of the invention (, β) Example 72 Heat and dissolve 4.06 g of the product of Example 25 in 30 «175% acetic acid water, add 0.52 · 1 methanesulfonic acid, stir under ice-cold for 30 minutes, and filter The precipitate was collected, washed with water, and dried at 100 * C in air overnight to obtain 4.27 g of the mesylate salt of the starting compound, white crystals, melting point 217-218 eC. 1H-NMR (DMSO-d6. Ppm) 1.22 * 1 J4 ( 1H, m), 1.38Ί.46 (2Η, m), 1.56 * 1.64 (2H. Mi. 2.10 * 2.22 (2H, m), 2.33 (3H, $). 2.74 * 2.80 (1H, m), 2.9l (3H. D. J = 4.5Hz). 3.39 (1H, dd, J «18.0.6.0H ?.), 3.53 (1H, dd. J = 18.0, 6.5Hz). 6.07 (1 H. s) · 7.58 (l H, dd, JsS.0.7.5Hz). 7.64 ~ 7.72 (2H ? N >. 7.80 (1 H. d, J = 7.5Hz). 7.90 (1 H. dJ = 9.5Hz), 7.97 (1H, dd, J «9.5f 1.5Hz), 8.08 (1H, dd. J = 8.0, 1.5Hz), 8.22-8.40 (3H, m), 8.89 (IH.s), 9 62ΠΗ brs) 14.3 (lH.brs), ^^ 1 · He ^^^ 1 i ^^ 1 ϋ ( Please read the note on the back of the page first and then #write this page) ijn ^ --- Printed by the Consumers ’Cooperatives of the Central Bureau of the Ministry of Economic Affairs-12 6- This paper is in use • National Standard (CNS) A4 specifications (210X297 mm)

Claims (1)

% tii month added A8 B8 C8 D8 6. Scope of patent application Λ3BS7S0 No. 83 1 08472 "Cyclohexane derivative" patent case (as amended on January 11, 1989) Λ Application patent scope: 1. A cyclohexane derivative of the formula (I) Pharmacologically acceptable salt (I) [wherein R1 and R2 may be the same or different, each is hydrogen or alkyl, R3 is 4 alkyl or halogen C !. 4 alkyl optionally substituted imidazolium pyridyl, X is sulfur * Y is as follows Formula: CH ^ OfyJ (1) (Please read the notes on the back before filling in this page) p is 1, J is based on the following formula: -W ^ -NZ ^ R5 Employee Consumer Cooperatives, Central Bureau of Standards, Ministry of Economic Affairs Printing bag (2) (where R4 is hydrogen or Ci_4 alkyl, R5 is Ci.4 alkyl, Ci.4 alkoxy, halogen, cyano, halogenated (^ .4 alkyl, C! .4 醯Amine Ci. # Alkoxy, Cb4 alkylthio, nitro or (^ .4 alkylsulfonamido to any substituted phenyl or unsubstituted naphthyl, or Ci.4 alkyl paper size applicable China National Standard (CNS) A4 specification (210X297 mm)% tii A8 B8 C8 D8 6. Scope of patent application Λ3BS7S0 No. 83 1 08472 "Cyclohexane derivative" patent case (as amended on January 11, 1989) Λ Application patent scope: 1. A cyclohexane derivative of the formula (I) Pharmacologically acceptable salt (I) [wherein R1 and R2 may be the same or different, each is hydrogen or alkyl, R3 is 4 alkyl or halogen C !. 4 alkyl optionally substituted imidazolium pyridyl, X is sulfur * Y is as follows Formula: CH ^ OfyJ (1) (Please read the notes on the back before filling in this page) p is 1, J is based on the following formula: -W ^ -NZ ^ R5 Employee Consumer Cooperatives, Central Bureau of Standards, Ministry of Economic Affairs Printing bag (2) (where R4 is hydrogen or Ci_4 alkyl, R5 is Ci.4 alkyl, Ci.4 alkoxy, halogen, cyano, halogenated (^ .4 alkyl, C! .4 醯Amine Ci. # Alkoxy, Cb4 alkylthio, nitro or (^ .4 alkylsulfonamido to any substituted phenyl or unsubstituted naphthyl, or Ci.4 alkyl paper size applicable Chinese National Standard (CNS) A4 specification (210X297 mm) A8 388760 1 Patent application scope of any substituted pyryl 'unsubstituted furyl, thienyl, quinolinyl or isoquinolinyl; Z1 is-S02-or -CO ·, W1 is a ⑶ group of the following formula: • CO-fCHoH ^ N-V-, II R10) (3) (where a and x are each 0, s is an integer from 1 to 4, and R10 is hydrogen as follows Formula base: -COCH- R 11 (4) --Γ —————— lull ___ c ( (Please read the notes on the back before filling this page) (where R11 is hydrogen, Ci.4 alkyl, hydroxy Ci.4 alkyl, benzene Cn alkyl, or any carboxy protected by benzene Ci.4 alkyl q.4 Alkyl), or hydrazone of the following formula: (5) (wherein g is an integer of 1 to 4)}]. 2. If the cyclohexane derivative of item 1 of the scope of patent application, or its molecular capacity Atf Ministry of Economic Affairs Department of Printing, Department of Work, Consumer Cooperatives, Central Bureau of Standards, Yanxu N 1 2 RR This paper size applies to Chinese National Standard (CNS) A4 size (21 OX297 g). Printed by the Bayer Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. 58 | __ D8. Patent application scope (where RhR ^ R ^ X and γ are each as defined in item 1 of the scope of patent application). 3_ If the cyclohexane derivative or the pharmacologically acceptable salt 'of item 1 of the scope of patent application is of the formula (I 11): (Ill) (where R1, R2, R3, X, j and p are each as defined in item 1 of the scope of patent application). 4. If the cyclohexane derivative or the pharmacological allowance of item 1 in the scope of the patent application allows Q 'in formula (I), R1 is hydrogen, 1-2 is Ci.4 alkyl, R3 is imidazolidine, and X is sulfur. , Y is = CH-0-J and J is -COCH2-NH-S02 · naphthyl. 5. For example, the cyclohexane derivative or pharmacologically acceptable salt thereof according to item 4 of the application, wherein R2 is ethyl. 6. —A kind of medicinal composition for the effective diseases of potassium channel opening, containing a medicinal effective amount such as the cyclohexane derivative or the pharmacologically acceptable salt and pharmacologically acceptable carrier of the first patent application scope. 7. The composition according to item 6 of the patent application, wherein bronchodilation, vasodilation or bladder smooth muscle relaxation are effective for the disease. 8. If the composition of the scope of patent application item 6, where the disease is asthma, blood pressure, frequent urinary incontinence, this paper size applies to the Chinese National Standard (CNS) M specifications (210 X 297 mm) (Please read first (Notes on the back are filled in on this page) • LT · C Order