TW548272B - Benzimidazole derivatives - Google Patents

Abstract

Novel benzimidazole derivatives represented by general formula (I) or pharmaceutically acceptable salts thereof wherein R3 represents carboxy, esterified carboxy, carboxamide, amino, amido or sulfonyl. Because of having hyopglycemic or PDE5 inhibitory effects, these compounds or salts thereof are useful as remedies for impaired glucose tolerance, diabetes, complications of diabetes, insulin resistant syndrome, hyperlipidemia, atherosclerosis, cardiovascular diseases, hyperglycemia, hypertension, angina pectoris, pulmonary hypertension, congestive heart failure, glomerular diseases, tubular interstitial diseases, renal failure, angiostenosis, peripheral vascular disease, apoplexy, chronic reversible obstructive diseases, allergic rhinitis, urticaria, glaucoma, diseases characterized by abnormality in intestinal motility, sexual impotence, nephritis, cancerous cachexia, or post-PCTA reconstriction.

Description

沪 i?: ^-^ M, t *; / i moxibustion combined with bamboo buckle 卬 548272 A7, description of the invention () :) The present invention relates to novel benzodiazepine derivatives, especially Concerning novel benzoic salivary or pharmaceutically acceptable salts having blood sugar lowering activity or PDE5 inhibitory effect. The present invention relates to the above-mentioned stupid microphone. Pharmaceuticals or their ingredients. Benmemin is a new type of salt that can be tolerated by the stupid sialo derivative; at the same time, it provides a medicinal preparation using the above-mentioned benzene bio or its salt as an active ingredient for prevention Treatment of glucose tolerance disorders, diabetes mellitus (type u diabetes), diabetic comorbidities (diabetic nephropathy, diabetic neurological disorder, diabetic omentum, etc.), membranin resistance syndrome (tonguelin receptor abnormalities, R? bS〇n_Mendenha11 Syndrome, Leprechaunism, K〇bberiing_Dunnigan Syndrome, Seip Syndrome, Syndrome, Cushing Syndrome, Acromegaly, etc.), Hyperlipidemia, Atherosclerosis, Cardiovascular Diseases (Asthma, Insufficiency, etc.), High Glycemia (for example, those with abnormal glucose metabolism and other characteristics of eating disorders), or hypertension, or asthma, high blood pressure, and high lung pressure also include congestive heart failure, glomerular disease (such as diabetic kidney Glomerular sclerosis, etc.), urinary tubulointerstitial diseases (for example, kidneys based on FK506, cyclosporine, etc .: renal insufficiency, arterial sclerosis, vascular stenosis ( Such as percutaneous arterial formation surgery), terminal vascular disease, cerebral hemorrhage, chronic reversible occlusive disease (such as bronchitis, asthma (chronic asthma, allergic asthma) ^ allergic rhinitis m Qingchun, ㈣ is a material abnormality disease (Such as allergic bowel syndrome), impotence, such as organs n = (Please read the precautions on the back before filling out this page), the paper size of the ax line applies Chinese National Standard (CNS) A4 specification (210X 297 male 4) 548272 A7 V. Description of the invention (2) — 1 · ~-(麴 Read the precautions on the back before filling out impotence on this page, etc.) Diabetes comorbidities (such as diabetic gangrene, diabetic joint disease, diabetic lumen sclerosis, diabetes Skin abnormalities, diabetic: neurological abnormalities, diabetic cataracts, diabetic omentosis, etc.), nephritis, malignant cancer, or restenosis after PCTA, etc. The present inventors and others provide a pharmaceutical preparation using the following formula ⑴ ~ The benzimidazole derivatives represented by (IV) and (VIII) to (XIV) or their pharmaceutically acceptable salts are used as effective ingredients for the prevention and treatment of glucose tolerance. Diabetes (Type 2 diabetes), Diabetes comorbidities (Diabetic nephropathy, Diabetic neurological disorder, Diabetic retinopathy, etc.), Insulin resistance syndrome (Insulin receptor abnormality, Robson-Mendenhall syndrome, Leprechaunism, Kobbeding-Dunnigan syndrome , Seip,-Mouth syndrome, LaWrence syndrome, Cushing syndrome, megacephaly, etc.), Hyperlipidemia, Atherosclerosis, Cardiovascular disease (stenosis, insufficiency, etc.), 鬲 Glycemia (for example, attached to Those who have abnormal glucose metabolism such as eating disorders), or hypertension, or angina, hypertension, pulmonary hypertension, congestion, insufficiency, glomerular disease (such as diabetic glomerulosclerosis, etc.) , Urinary tubulointerstitial disease (such as kidney disease caused by FK506, cyclosporine, etc.), renal insufficiency, atherosclerosis, vascular stenosis (such as the latter in percutaneous arterial surgery), terminal vascular disease, Cerebral hemorrhage, chronic reversible occlusive disease (eg bronchitis, asthma (chronic asthma, = allergic asthma)), allergic Rhinitis, measles, glaucoma, diseases characterized by abnormal bowel movements (such as allergic bowel syndrome), impotence (such as organ impotence, mental impotence, etc.), comorbidities of diabetes (such as diabetic necrosis, diabetes Arthritis, diabetic glomerulosclerosis, diabetic paper-sized coffee towel Etc.), nephritis, malignant cancer (R4), diabetic cataract, diabetes, restenosis after PCTA, etc.

0) Haohubu Zhongji ii: ^-而 乃 ν-, in the consumer cooperation formula (I), 'R! Is a hydrogen atom, arylsulfonyl-lower alkyl group, and a free_prime atom group can be used , Lower alkyl, lower alkoxy, succinyl, aryl lower alkyl, aryl lower alkoxy, arylsulfonyl lower alkyl, arylsulfonylamino, cyanoaryl, and heterocyclic One or two radicals in the group formed by the radical may be substituted with aryl or heterocyclic radical. R2 is a hydrogen atom, a lower cycloalkyl group, a hydroxyl group, a lower alkoxy group, a weyl group, a lower sulfur group, an amine group, a lower alkyl group, a carboxyl group, an aryl group, or a lower alkyl group; the lower alkyl group can be used_ Element atom, lower alkoxy, cyano, carbonyl, aryl, or heterocyclyl. R3 is a tertiary group, an acetate-retarded group, an amidated weanyl group, an amino group, an amidino group, or a sulfonyl group; the amine group and the amidino group may be replaced by a fluorenyl group or a lutein group; the The term hydrazone is a combination with a free atom, an amine group or an amino group. In addition, R * 3 may be combined with the mother nucleus via a low-level sintered base or a low-level dilute support. R4 is a neutral substituent. η represents an integer from 0 to 3. Or lower alkynyl; the haloaryl, lower amine, cyano, and arylhaloaryl lower alkoxy ----------- private clothing ^^ I (Please read the precautions on the back first Fill in this page; 1. ^ 1-Threaded Paper Size Applicable to China National Standard (CNS) Α4 Specification (210X297 mm) A7

548272 I ----- ~ ____________ __B7 Α, description of the invention (4) n (R :)

(In formula (II), 'R6 is an aryl lower alkyl group, and a free halogen atom, a halogen aryl group, a lower alkyl group, a halogen lower alkyl group, a lower alkoxy group, an azido group, an amine group, a cyano group, One or two of the groups consisting of aryl, cyanoaryl, aryl-lower alkoxy, arylsulfonyl-lower alkyl, arylsulfonylamino, aryl-lower alkyl and heterocyclic groups R7 is lower alkyl or lower cycloalkyl. R8 is aminofluorenyl; the aminofluorenyl is a lower alkyl, aryl, heterocyclyl, and 9 substituted with aryl or heterocyclic group. \ g〆〇 < '' Ο Ola) (In the formula (Ila), R9 is an alkyl group with a carbon number of up to 8, lower alkyl, aryl lower alkyl, hydroxy lower alkyl, tri-lower alkyl Silyl lower alkyl, lower alkoxy lower alkyl, lower alkylthio lower alkyl, heterocyclic group, or aryl group; the aryl group may use a halogen atom, lower alkyl group, lower alkyl group, lower alkyl group Or nitro.) R8 can be combined with the mother core through lower alkylene or lower alkenylene. It is a hydrocarbyl group which can be substituted with ii. η represents an integer from 0 to 3. ______ This paper size applies the Chinese National Standard (CNS) Α4 specification (210X 297 mm) '1 (Please read the precautions on the back before filling this page

, 1T

R

548272 Α7 — B7 Description of the invention (n (R4,) (Ml) In formula (III), R6 is an aryl lower alkyl group, and a halogen atom, a lower alkyl group, a lower alkyl group, a lower alkoxy group, Nitro, amine, cyano, aryl, iaryl, cyanaryl, aryl lower alkoxy, arylsulfonyl lower alkyl, arylsulfonylamino, aryl lower alkyl, and heterocyclic ring R7 is a lower alkyl group or a lower cycloalkyl group.

Ru is Ilia (Please read the notes on the back before filling this page)

R 2 \, y '° (Ilia) line · One (In formula (Ilia), R12 is an alkyl group having up to 8 carbon atoms, halogen lower alkyl group, aryl lower alkyl group, hydroxy lower alkyl group, triple lower alkyl group Methylsilyl lower alkyl, lower alkoxy lower alkyl, lower alkylthio lower alkyl, heterocyclic group, or aryl group; the aryl group can use a prime atom, a lower alkyl group, a halogenated lower alkyl group , Lower alkoxy or nitro.) And Ri! Can be combined with the mother core through lower alkylene or lower alkenylene. Chi 4 'is a hydrocarbyl group which may be substituted by a functional element. η represents an integer from 0 to 3. The size of this paper is suitable for China National Standard (CNS) A4 (210X297 mm) 548272 A7 B7 Invention 7; see Ming (FV)

(IV) In the formula (IV), Ri3 is an aryl lower alkyl group, and a halogen atom, a lower alkyl group, a ii lower alkyl group, a lower alkoxy group, a nitro group, an amine group, a cyano group, an aryl group, One or two of the groups consisting of a aryl group, a lacto square group, a square lower group, a lower aromatic group, a lower aromatic group, a arylamino group, and a heterocyclic group are substituted. Rl4 is lower alkyl. R15 is a substituent represented by the formula (IVa) (iVa) (where R16 in the formula (IVa) is a lower alkyl group or an aryl group) KV is a hydrocarbon group which may be substituted with a halogen. η represents an integer from 0 to 3.

R 2 6 n (R /) (Read the precautions on the back first for details, then check this page j-、 11

R (VIII) In the formula (VIII), I is a hydrogen atom, an arylsulfonyl group, or a lower alkyl group; the lower alkyl group may use a halogen atom, a aryl group, or a lower paper. Standard (CNS) A4 specification (210 × 297 mm) A7 548272 __________ B7 V. Description of the invention (7) Alkenyl, halogenated lower alkyl, lower alkoxy, nitro, amine, cyano, aryl, aryl One or two of the group consisting of lower alkyl, aryl lower alkyl, aryl lower alkyl, arylsulfonyl lower alkyl, arylsulfonylamino, cyanoaryl and heterocyclic group It may be substituted by an aryl group or an aryl group or a heterocyclic group. R2 is a hydrogen atom, a lower cyclic alkyl group, a mesityl group, a hydroxy lower alkyl group, a lower alkyl group, a weyl group, a lower alkyl group, an amine group, a lower alkyl group, a carboxyl group, an aryl group, or a lower alkyl group; The lower alkyl group may be substituted with a prime atom, a lower alkoxy group, a cyano group, a halocarbonyl group, an aryl group, or a heterocyclic group. R25 is alkyl, lower cycloalkyl, lower alkyl, tri-lower alkylsilyl lower alkyl, lower alkoxy lower alkyl, lower sulfur thio lower alkyl, aryl , Heterocyclyl, aryl lower alkyl, or hydroxy lower alkyl; the aryl may be substituted with a halogen atom, lower alkyl, halogen lower alkyl, lower alkoxy, or nitro. R26 is a hydrogen atom or a lower alkyl group; when both R25 and r26 are a lower alkyl group, they may be bonded to each other to form a ring. Y is a few bases or a lower elongation base. A represents a simple bond or a low-level sintered base or a low-level dilute support. Chi 4 'represents a hydrocarbyl group which may be substituted by dentin. η represents an integer of 0 to 3. (Review the notes on the back before filling out this page

1T line

The size of this paper is covered by the Chinese National Standard (CNS) A4 specification (210 × 297 mm) 548272 A7 B7 V. Description of the invention (¾Read the precautions on the back before filling this page} In formula (IX), 'R' is the carbon number Alkyl, halo-lower alkyl, arylsulfonyl, aryl-lower alkyl, heterocyclic-lower alkyl, and heterocyclic-lower alkyl groups up to 7; the aromatic ring of the aryl-lower alkyl can be selected from Halogen atom, lower alkyl, halogen lower alkyl, cyanoaryl, amine, lower alkoxy, nitro, cyano, aryl, dentaryl, arylsulfonyl lower alkyl, arylsulfonyl Arylamino, aryl lower alkoxy, aryl lower alkyl, heterocyclyl, aryloxy, arylcarbonyl, arylcarbonylamino, or aryl lower alkoxy substituted with one or two halogen atoms One or two of these groups are substituted. R28 is a hydrogen atom, an alkyl group having up to 7 carbon atoms, a halogen lower alkyl group, a lower alkoxy lower alkyl group, a lower cycloalkyl group, an aryl group, an aryl lower alkyl group , Lower alkylamino, lower alkoxy, lower alkylthio, hydroxyl, thiol, amine, or carboxyl. R25 is carbon Alkyl, halogen lower alkyl, tri-lower alkylsilyl lower alkyl, lower alkoxy lower alkyl, lower alkylthio lower alkyl, aryl, heterocyclic, aryl Lower alkyl, or hydroxy lower alkyl; the aryl may be substituted with a ii element atom, a lower alkyl, a halogen lower alkyl, a lower alkyloxy or a nitro group. R26 is a hydrogen atom or a lower alkyl; when the r25 When both r26 are lower alkyl groups, they can be combined with each other to form a ring. Y is a naphthyl group or a lower alkylene group. A represents a simple bond or a lower alkylene group or a lower alkenyl group. R29 is a hydrogen atom or a lower alkylene group The paper size is applicable to China National Standard (CNS) A4 (210X 297 mm) 548272 A7 B7 η (FV)

R 33 -A-

R 32 30 (X)

R In the formula (X), R30 is a hydrogen atom, a lower alkyl group, and can be represented by the formula (Xa) P31 ~ θ ^ (Xa) (in the formula (Xa), a hydrogen atom, a cyanoaryl group, and an amine group , Lower alkoxy, nitro, cyano, aryl, haloaryl, arylsulfonyl lower alkyl, arylsulfonylamino, aryl lower alkoxy, aryl lower alkyl, hetero Cyclic group, or aryloxy group.) Substituted aryl lower alkyl group, aryl lower alkyl group which may be substituted with one or one halogen atom, aryl group, heterocyclic lower alkyl group, arylcarbonylamino group , Arylcarbonyl, arylalkenyl, or lower alkylene dioxyaryl; the alkyl portion of the aryl lower alkyl may be replaced with a lower alkyl. R32 is a hydrogen atom, a lower alkyl group, a i-lower alkyl group, a lower cycloalkyl group, an aryl group, an aryl lower alkyl group, a lower alkylamino group, a lower alkoxy group, a lower sulfur group, a lower alkyl group, or a lower alkyl group. Or lower heterocyclic radical. Carboxyl, lower alkoxycarbonyl, (2-cyanoaryl) oxyweiyl, or formula (Xb) (read the precautions on the back before filling in this page), \ 呑

R 34 Υ 一 (Xb) (In formula (Xb), γ is a carbonyl group or a lower alkylene group, and Rw is a standard that can be used with appropriate standards. $ (CNS) A4 specification (21GX 297 Gong Chu 548272 A7) V. Description of the invention (丨 〇) —'— ~ '—— Substituted aryl or heterocyclic group substituted lower alkyl, aryl, or represented substituent.' Clay. --------- — (Read the precautions on the back before filling this page) A is a simple bond or a lower alkylene or a lower alkenyl group. R4 'is a hydrocarbon group that can be substituted with halogen. I, also includes alkyl and * alkyl groups , Fast-based, and the like substituted by halides. The square R4 'may be saturated or unsaturated, and may be chained or unchained. Depending on the situation, it may be branched. When it is substituted by halogen In this case, there are no restrictions on the type and number of teeth. N represents an integer from 0 to 3. Therefore, it can be combined! One, two, or three R4 can be combined without 仏, and it can be combined. The position system is ortho, meta, and para positions for other substituents. However, f R3. N = 0 at 4 hydrogen, that is, I is not bound. R ^ A < XfR35 (X〇 ^ Equation 37 (XI ) 'R35 is a hydrogen atom, an aryl group, a lower alkyloxy lower alkynyl group, a lower alkyl group, or an aryl lower alkyl group. Haohu Zhongzhong «. ^-XJh.T Consumption Hezhu Private Seal R36 is a carboxyl group , Lower alkoxycarbonyl, heterocyclic lower alkylamino, or heterocyclic lower alkylcarbamoyl. R37 and R38 are independent hydrogen, halogen, lower alkyl, halogen lower alkyl, and aryl, respectively. , Aryl lower alkyl, or aryl lower alkoxy. A represents simple bonding or lower alkylene or lower alkenyl; when R35 is lower alkyl, A represents lower alkylene or lower alkenyl The size of this paper is suitable for "China National Standard (CNS) A4 Specification (210X297mm) 548272 A7 B7

5. Description of the invention (1 1 R '4 0,

Γ ^ νΛI V-R (XII) 39

R 3 8 R- In formula (XII), 'R' and R38 are independent hydrogen atom, halogen atom, lower alkyl group, i-lower alkyl 'aryl group, aryl lower alkyl group, or aryl lower alkoxy group R39 is a lower alkyl group. Rule 40 is a hydrogen atom, a lower alkyloxy group, a lower alkyl group, a lower bond alkyl group, or an amino group.

3Θ (XIII) In the formula (XIII), R37 and R38 are each independently a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkyl group, an aryl group, an aryl lower alkyl group, or an aryl lower alkoxy group. R7 is lower alkyl or lower cycloalkyl R, '? 9

(Read the precautions on the back before filling this page), \ 二 口 548272 A7 V. Description of the invention (12) In formula (XIV), R 'and R38 are independent hydrogen atom, halogen atom, lower alkyl, Halo-lower alkyl, aryl, aryl-lower alkyl, or aryl-lower alkyl. R7 is lower-alkyl or lower-cycloalkyl. Rq is 2-methylpyridylcarbamoyl, carboxyl --- pyrrole Alkylcarbonyl, N-methyl-N- (2-pyridinylfluorenyl) carbamoyl, bpiperidinylcarbonyl, [2-N-oxy) -t-stilbylmethyl] carbamoyl, '(Dimethylamino) benzylaminofluorenyl, piperonylcarbamoyl, N-fluorenyl-N · (fluorenylpyridinyl) carbamoyl, thiomorphinylcarbonyl, halostone fluorenyl, Aminosulfonyl, sulfenylaminosulfonyl, lower alkoxycarbonyl, or carboxyl. R29 is a hydrogen atom or lower alkyl; when R41 is a lower alkylcarbonyl or carboxyl, R29 is a lower alkyl. 'The present invention provides novel benzimidazole derivatives and salts thereof represented by the above formulae (VIII) to (XIV). The benzimidazole derivatives provided according to the present invention may be It is manufactured by the following reaction formulas (a) to ⑴. (诮 Read the precautions on the back before filling in this page. The size of the 11-line paper is suitable / A China National Standard Car (CNS) A4 Specification (21〇χ (297 mm) A7 548272 B7 V. Description of the invention (丨 3) 3a wX ^^ NHCOR.a ⑴ D r ^ VN〇2 R3a ~ i T -1 ^^ NCOR2a Λ, Hta (2) D ^ VNH2 W_. ( 3) ^. -—R3a ^^, N) ~ 'N (4) R〗 a SO:'. 2 — ^ NHCOR2b (5) D r ^ VN〇2 3t7 ~ £] C ~~ " ^ ^ nh2 (6) 々N〇2-(7) ⑻ '-/ b y ---- --.------- ¾ Read the precautions on the back before filling in this page.

Rid NH ^ 3d

NO. NH,

, 1T line NHCOR ^ ^ 3d NHCOR ^ ^ 3d

NHCOR ^ (14) (15) (16) (d) R3 (17) Rld The size of this paper is suitable / 彳] Chinese National Standard (CNS) A4 specification (210X 297 mm) 548272 A7 V. Description of the invention (14 r -〇c no2 nh2 ο: νη7 ΝΗ, r3 (18) (19)

Ν ο: ^ (20) Η (e) (21) ~ R-〇C (22) NO · 2 NHCOR2f f ~ nh2 NHC〇R2f R3f (23) R3f " 〇C ^ f (25) 'Ru Rla ~ Rif is selected from Η (24) ⑴

R22 N R23 'R 23 27, Han 30, or the formula "RmR,

R 38 (Read the precautions on the back before filling in this page)

, 1T R. ^ ^ ^-^ ', Μ ν in the good sedimentary part; disappear in the combination ^ (where R37 and R38 represent the same as above), one of the representatives selected from the aforementioned R2, R7, Ri4, r :, = R35 or R39. The substituents Rh ~ R3f are optional from formula 32

R 2 5

RI 2 6 (where Rw, R26, γ, and A represent the same as the aforementioned). The paper size of the thread paper is suitable for the Chinese National Standard (CNS) A4 specification (210X 297 mm) 548272 A7 B7 5. Description of the invention (15) ~ Substituent, the aforementioned R3, R8, Rll, Ri5, Ri9, r24, Qian 33, AR%, NHR40, CN, or Rq. In addition, R3a to R3f can be interchanged with a predetermined substituent. For example, the ester compound (26) shown in the reaction formula (phantom or hydrazone) can be replaced with an acid compound (27) or a halogenated acid compound (28), and the dream can also be produced by the action of amines or sulfonamides. The object of interest is benzimidazole. Derivatives such as those shown in the reaction formulas ⑴ or ⑴ or (k) or ⑴ or (m) or (η) may also be performed. These transformations of R3a ~ R3f can be performed according to any of the reaction formulas (a) ~ ⑴, and depending on the stability of Rla ~ Rif and 4 ~ ^ in the formula, or which is easier to separate the product, etc., to determine What process is used.

Rg〇2〇-- I < 2a-f < x ---------- ΜΦΙ (诮 Please read the notes on the back before filling this page)

Ria ~ f (9) (26) (27) (In the reaction formula, 1 represents a lower alkyl group, and Ru ~ and Rhf represent the phase described above), then H〇2C- (27) \ Ria -1 -1 2a ~ f

Z 〇C — I (Z in the reaction formula, which represents a gas atom or a bromine atom, as described above) (28)

R (h), line 11

R la ^ and R ^ ~ f represent phases h2n 〇

(29) (R la ~ f < 2a ~ f NC-

-N

Ri (') 2a ~ f (30) represents the same as the previous one) a ~ f Paper size 剌 + _Home materials (CNS) A4 specifications (210X 297 Gongchu 548272 A7 --------- —----------- B7 V. Description of the invention (16) h〇2c

^ ~ R2a ~ f (27)

V-R23M Ria ~ f (j)

Ria ~ f

: 2a-f Ria ~ f

: 2a to f Ria to f (32) (33) (In the reaction formula, Rla to laf are the same as those described above.) In reaction formula (a), the compound of the formula (I) is aminated with sodium hydride and diisopropylhydrazone. Lithium, lithium bicarbonate, lithium carbonate, lithium hydroxide, sodium bicarbonate, sodium carbonate, sodium hydroxide, potassium bicarbonate, potassium carbonate, potassium hydroxide and other bases and R ^ z (z is a gas atom, bromine atom, toluene A compound represented by sulfonyloxy, methanesulfonyloxy) is reacted to produce a compound of formula (2). The compound of formula (2) is' reduced by 1) using reduced iron or zinc under acidic conditions, or 2) using a transition metal catalyst such as palladium, platinum, ruthenium, or nickel under a hydrogen atmosphere to perform reduction Or, 3) using a transition metal catalyst such as Krypton, Nitrogen, Ruthenium, Nickel in the presence of formic acid for reduction, or 4) using sodium bisulfite for reduction, etc., to transform into a compound of formula (3). Since the compound of formula (3) according to method 1) can be cyclized in the reaction and the compound of formula (4) is directly obtained, it is more commonly used. Under any of the conditions 1) to 4), a part of the compound of the formula (4) is formed. The compound of formula (3) is a compound of formula (4) produced by carboxylic acid, sulfonic acid or inorganic acid such as acetic acid, p-toluenesulfonic acid, hydrochloric acid, sulfuric acid, phosphoric acid and the like. In the reaction formula (b), the compound of the formula (5) passes the lithium bicarbonate and carbonic acid paper standard of China State Standard (CNS) A4 (210X297 mm) (翱 Please read the precautions on the back before filling this page ), -5 mouth 548272 A7 -______ B7 V. Description of the invention (17) Read the note f on the back JI before filling in this page j Ding, = 0 lithium, lithium hydroxide, sodium bicarbonate, sodium carbonate, hydroxide Sodium, bicarbonate, acid clock, hydroxide_special test 'or acetic acid, p-toluene acid, hydrochloric acid, sulfuric acid, phosphoric acid and other carboxylic acids, sulfonic acids or inorganic acids are hydrolyzed or hydrolyzed to produce the formula (6 ). Let the compound of formula (6) and sodium hydride, lithium diisopropylamidide, lithium bicarbonate, lithium carbonate, lithium hydroxide, sodium bicarbonate, sodium carbonate, sodium hydroxide, potassium bicarbonate, potassium carbonate, hydroxide A base such as potassium is reacted with a compound represented by RlbZ (Z is a chlorine atom, a bromine atom, a tosylsulfonyloxy group, a sulfonylsulfenyloxy group) to produce a compound of formula (7). The compound of formula (7) is reduced by using iron or zinc under acidic conditions, or 2) using a transition metal catalyst such as palladium, platinum, ruthenium, or nickel under a hydrogen atmosphere to Perform reduction, or 3) use transition metal catalysts such as Krypton, platinum, ruthenium, nickel in the presence of sacrificial acid for reduction, or 4) use sodium bisulfite for reduction, etc., and replace k with formula (8) Of compounds. A carboxylic acid or an acid chloride or an acid bromide or an acid anhydride corresponding to the compound of the formula (8) is used to produce a compound of the formula (9). In the reaction formula (c), a compound represented by the formula (10) and a compound represented by r1cnh2 are used to produce a compound represented by the formula (11). The conversion from the compound of the formula (11) to the compound of the formula (13) is the same as that in the reaction formula (..., the conversion of the compound from the formula (that is, the conversion of the compound into the compound of the formula (9). In the reaction formula (d), the formula (14) ) Compounds are reduced by 丨) using reduced iron or zinc under acidic conditions, or 2) using a transition metal catalyst such as palladium, platinum, ruthenium, or nickel under a nitrogen atmosphere to reduce To produce a compound of formula (15). Let the compound of formula (15) 548272 A7 3e B7 V. Description of the invention (18) hydrogen clock, carbonic acid M, lithium hydroxide, sodium bicarbonate, sodium carbonate, sodium hydroxide, potassium bicarbonate, potassium carbonate, potassium hydroxide, etc. A base and a compound represented by RidZ (z is a chlorine atom, a bromine atom, an xylbenzenesulfonyloxy group, an xylsulfonyloxy group) are reacted to produce a compound of formula (16). Compound of formula (6): A compound of formula (17) is produced by using a slow acid, a carboxylic acid or an inorganic acid such as acetic acid, p-toluenesulfonic acid, hydrochloric acid, sulfuric acid, or phosphoric acid. In the reaction formula (e), the compound of the formula (18) is reduced by using reduced iron or zinc under acidic conditions, or 2) using palladium, platinum, ruthenium, nickel, etc. under a hydrogen atmosphere. Transition metal catalyst for reduction, or 3) the use of palladium, platinum, ruthenium, nickel and other transition metal catalysts for reduction in the presence of formic acid, or 4) the use of sodium bisulfite for reduction and other methods to transform into the formula (19) The compound. The compound corresponding to the compound of formula (19) is used to produce a compound of formula or acid gas or acid desert or acid anhydride. Let the compound of formula (20) and sodium hydroxide, lithium diisopropylamidide, lithium bicarbonate, lithium carbonate, lithium hydroxide, sodium bicarbonate, sodium carbonate, sodium hydroxide, potassium bicarbonate, potassium carbonate, hydrogen A base such as potassium oxide and a compound represented by U (z is a gas atom, a bromine atom, a tosylsulfonyloxy group, a methanesulfonyloxy group) are reacted to produce a compound of the formula (21). Based on these methods, the compound of formula (21) obtained is generally a mixture of positions 5 and 6 at the substitution position of R, or a mixture of positions 4 and 7 and is separated by recrystallization, column chromatography, and thin layer chromatography. , High-speed liquid chromatography separation and other methods can be refined. In the reaction formula (f), the compound of the formula (22) is “reduced by using reduced iron or zinc under acidic conditions, or 2) under a hydrogen atmosphere (¾ read the precautions on the back before filling in this page)

1T male A7 548272 V. Explanation of the invention (丨 9) Use of transition metal catalysts such as palladium, platinum, ruthenium, nickel for reduction, or 3) Use of transition metals such as barium, ruthenium, ruthenium, nickel in the presence of sacrificial acid A catalyst is used for reduction, or 4) sodium bisulfite is used for reduction to convert the compound into a compound of formula (23). Because the compound according to the method 丨 formula "will be cyclized in the reaction and the compound of formula (24) is directly obtained, it is more commonly used. It will be partially generated under any of the conditions 1) ~ 4). A compound of formula (24). A compound of formula (23) is a compound of formula (24) produced by carboxylic acid, sulfonic acid, or inorganic acid such as acetic acid, p-toluenesulfonic acid, hydrochloric acid, sulfuric acid, phosphoric acid, or the like. The compound of 24) is converted into the benzimidazole compound of formula (25) according to the method of converting formula (20) to formula (21) in reaction formula (e). Based on this method, the formula (from The compound of 25) is generally a mixture of the 5th and 6th positions of the RSf substitution position, or a mixture of the 4th and 7th positions. It can be separated by recrystallization, column chromatography, thin layer chromatography, high-speed liquid chromatography and other methods. Purified. In the reaction formula (g), the compound of the formula (26) can be hydrolyzed by the base of lithium hydroxide, sodium hydroxide, potassium hydroxide and the like to produce a compound of the formula (27). Let the formula (27) After reacting with carbonyldiimidazole, it can react with amines or amines in the presence of In order to produce a benzimid sigma derivative. In the reaction formula (h), the compound of the formula (27) is obtained by vaporizing thionine, thionine bromide, trichloride, pentagasine scale or The basic chloride is converted into an acid dentate represented by the formula (28). The compound of the formula (28) is reacted with amines or sulfonamides to produce a benzimidazole derivative. In the reaction formula, The compound of formula (29) is reacted with titanium tetraoxide to make -----____ This paper size is in accordance with China National Standard (CNS) A4 specification (210X297 mm) (Read the precautions on the back before filling in this paper Page j P.,-= t > 548272 A7 B7 V. Description of the invention (20) The compound represented by formula (30) is produced. In the reaction formula ⑴, in the presence of an alcohol represented by a third butanol, let A compound of formula (27) is reacted with azides represented by dibenzylphosphonium azide to produce a compound of formula (31). An acid is used to decompose the compound of formula (31) to give formula (32) A compound of formula (32) is reacted with a compound represented by R40Z (Z represents a gas atom or a bromine atom) to produce formula (33) Compound &

Rg〇2C ~

(26) < 2a to f

Park ~ f (邡 Please read the notes on the back before filling in this page) zH2COcn > < 2a ~ f (35)

Ria ~ f (Rg Ru ~ f, R2a ~ f in the reaction formula are the same as those mentioned above, and Z represents a chlorine atom, a bromine atom, a benzenesulfonyloxy group or a methanesulfonyloxy group) " Γ ^ ν ^ Ν zh2c (35) H〇2C-

R

-N < 2a-f, but nch2c4 i》 (36) line (I) (37)

Ria-f (Ru ~ f, f, z in the reaction formula are the same as those mentioned above) 24 paper size over / fl towel _ Jia 榡 quan (CNS) 8 4 gauge plus / tear public hair) 548272 A7 B7 5 And invention description 6i h〇h2c

RgCK ^^ 〇

Cl3 < 2a-f

Ria ~ f

Ria ~ f (38)

2d -f Ria- f (40) (m) (39) (In the reaction formula, R 1 a ~ f ^^ 2 a ~ f Rg represents the same as the above)

N ^ -RN Ria ~ f 2a -f (π) 阅读 Read the precautions on the back before filling in this page. In (k), the compound of formula (26) is converted into a compound of formula (34) after reduction. Next, it is converted into thionyl chloride, thionyl bromide, phosphorus hydroxychloride, phosphorus hydroxybromide, phosphorus trichloride, phosphorus pentachloride, sulfonylsulfonyl gas, or tosylsulfonium, etc. A compound represented by formula (35). In the reaction formula (λ), a compound of the formula (35) is reacted with sodium cyanide or cyanamide to produce a compound of the formula (36). The compound of the formula (36) is hydrolyzed by hydrogenation, sodium hydroxide, or potassium hydroxide to produce a carboxylic acid of the formula (37). In the reaction formula (m), the compound of the formula (38) obtained by oxidizing the formula (34) is reacted with an alkyl group (tribenzylphosphonium benzidine) to obtain a compound of the formula (39). The compound of formula (39) can be hydrolyzed by lithium hydroxide, sodium hydroxide, or potassium hydroxide to produce a carboxylic acid of formula (40). Order the compound of formula (35), (37) or this paper to fit the Chinese National Standard (CNS) A4 size (210X 297 mm) 548272 A7 B7 5. Description of the invention) (40) The compound reacts with amines and amines To make benzene yarn sitting compounds. In the reaction formula (I), the compound of the formula (39) is produced by reducing a transition metal catalyst such as, tumbling, or Shu in a hydrogen atmosphere or in the presence of formic acid to produce a compound of the formula (41). In addition, the compound represented by formula (1,) (n (where Ru ~ f, Rh ~ f, R3a ~ f represents the same as above; represents one selected from the description of R4, FU, and R29), By using each as a starting material in the reaction formulae (a) to (f),

R3a ~ ^ X n〇2 NHCOR13 (2,) (where Rla, Rn, are the same as those mentioned above; on behalf of the one selected from the aforementioned R4, R4 ’, R29) 4b tr

NO 2

R (3,) NHCOR2b (where Rlb, Ra, and ruler are the same as those mentioned above; R4b represents the one selected from the aforementioned R4, R4 ’, and R29) R3

NO F 2 (4,) JJl. The size of this paper is / 1] Chinese national standard (CNS) A4 size (210x297 mm) 548272 V. Description of the invention Dagger 3; representative selected from (where Rlc, R2c And R3c are the same as those of R4, RV, and R29)

Md ^ 3d

NO, (5,) NHCOR. (Where Rid, R2d, R3d represents the phase of the aforementioned R4, R4 ', R29) is the same as the above;

N〇2 (6Ί nh2 (where Rle, R2e, and R3e are the same as those mentioned above, and R4, R4 ’, and R29) are representative of choice (read the precautions on the back before filling in this page.

The compound represented by R 4f \ ^ NHC〇R2f cn (^ 中 ^^ represents the same as the former represents R4, R4 ', and R29) is manufactured. Any intermediate system of each of the above reactions can be purified by the refining method commonly used in synthesis, that is, recrystallization, column chromatography separation, thin color separation, high-speed liquid chromatography separation, etc. if necessary. The compound system of the present invention, which is the final product of the reaction, can be purified by ordinary organic compound purification methods, that is, recrystallization, column chromatography separation, thin layer chromatography separation, high-speed liquid chromatography separation, etc., if necessary. And the compound / the paper size 4 / species ® national counties (CNS) Λ4 specifications (21 () > < 297 issued) — order ------ line W --- A7 548272 V. Description of the invention (24) The ^-system can be performed by methods such as NMR spectrum analysis, mass spectrum analysis, IR spectrum analysis, elemental analysis, and melting point determination. Various definitions within the scope of the present invention described above and below in this specification are explained in detail by the following preferred examples. The term "lower level" means that the number of carbon atoms is from 1 to 6 when it is not particularly limited. Suitable examples of lower alkyl include fluorenyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, second butyl, third butyl, n-pentyl, isofluorenyl, and 2-pentyl, 3rd-pentyl, fluorenylbutyl, n-hexyl, methylpentyl, 2-methylpentyl, 3-methylpentyl, 'fluorenylmethyl, ethylethyl, Linear or branched, such as 2-ethylbutyl, dimethylbutyl, 2, fluorenedifluorenylbutyl, 3,3-dimethylbutyl, 1-ethyl_1βmethylpropyl As an example, it is preferable to use a carbon number of 1 to 3. The alkyl group having 7 carbon atoms may be methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, second butyl, third butyl, n-pentyl, isopentyl, or 2-pentyl, 3-pentyl, 2-methylbutyl, n-hexyl, ^ methylpentyl, 2-fluorenylpentyl, 3-fluorenylpentyl, 4-methylpentyl, 1-ethyl Butyl, 2-ethylbutyl, 3-ethylbutyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 1-ethyl -丨 -methylpropyl, n-heptyl, 1-methylhexyl, 2-fluorenylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl '1-ethylpentyl, 2 -Ethylpentyl, 3-ethylpentyl, 4-ethylpentyl, 1,1-dimethylpentyl, 2,2-diamidylpentyl, 3,3-diamidylpentyl, 4 As an example, a linear or branched alkynyl group such as 4,4-fluorenylpentyl and 1-propylbutyl. Alkyl groups up to 8 carbons can be methyl, ethyl, n-propyl, isopropyl ________ Μ _ This paper is a standard of Yaozhou China National Standard (CNS) A4 (210X297 mm) ------- --- M9! (Read the precautions on the back and then fill out this page} 、 11 line A7 548272 V. Description of the invention (25), n-butyl, isobutyl, second butyl, third butyl, N-pentyl, iso-pentyl, second-pentyl, third-pentyl, 2-methylbutyl, n-hexyl, ^ fluorenylpentyl, 2-methylpentyl, 3-fluorenylfluorenyl, 4 -Fluorenylpentyl, 1-ethylbutyl, 2-ethylbutyl, 3-ethylbutyl, 1,1-difluorenylbutyl, 2,2-monofluorenylbutyl, 3,3- Dimethylbutyl, 1-ethyl-1-methylpropyl, n-heptyl, 1-methylhexyl, 2-fluorenylhexyl, 3-fluorenylhexyl, 4-fluorenylhexyl, 5-methyl Hexyl, 1-ethylpentyl, 2-ethylpentyl, 3-ethylfluorenyl, 4-ethylpentyl, 1,1-difluorenylfluorenyl, 2,2-difluorenylpentyl, 3 , 3-Difluorenylpentyl, 4,4-dimethylpentyl, 1-propylbutyl, n-octyl, fluorenylheptyl, 2-methylheptyl, 3-methylheptyl, 4-fluorenylheptyl, 5-fluorenylheptyl, 6- Fluorenylheptyl, 1-ethylhexyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 5-ethylhexyl, 1,1-dimethylhexyl, 2,2 • dimethyl Hexyl, 3,3-dimethylhexyl, 4,4-diamidylhexyl, 5,5-dimethylhexyl, 1-propylpentyl, 2-propylpentyl, etc. Examples of lower alkyl groups are lower alkylenes such as methyl, ethylene, propylene, butylene, pentyl, and hexamethylene, and alkylenes having a carbon number of 6 or less; those with a carbon number of 3 are preferred: lower alkylenes Vinyl, propylene, 2-propylene, butylene, 2-butylene, 3-butylene, μpentene, 2-marine, 3.pentene ', 4-pentene Supporting, 1-hexene, 2 · hexene, 3_hexene, 4_hexene, etc. ^ Thin carbons with a carbon number of 6 or less; and those with a carbon number M ^ are more examples .: =: Take the fluorine atom, gas atom, desert atom, and atom atom as Η, and the preferred ones are fluorine atom, gas atom, bromine atom. This paper size is 210x3 ^ (诮 Please read the precautions on the back before filling in this Page) Order 548272 A7 -------------— V. Description of the invention (26) ~ ^ — ---— ~ — i Lower alkyl can be via fluorine atom, gas Straight-chain or branched alkynyl radicals of carbon number U substituted with ions, molybdenum atoms, or atoms; compared with the two, which are replaced by random atoms 'chlorine and bromine atoms with carbon number 8 up to' Linear or branched alkyl groups having 1 to 3 carbon atoms. Examples include methylated, difluorinated, trimethylated, vaporized methyl, methyl chloride & _chlorinated Methyl, methyl bromide, methyl dibromide, methyl tribromide, b-fluorinated ethyl, i-gasified ethyl, 1-brominated ethyl, 2-fluorinated ethyl, 2-gas Ethyl, 2-bromoethyl, a difluorinated ethyl, 1,2-dichlorinated ethyl, ethyl dibromide, 2,2,2-trifluoroethyl, ethyl heptafluoride Base, 1 · gasified propyl, chloropropyl, propylamine propyl, 2-methylated propyl, 2-chloropropyl, 2-methylated propyl, 3-methylated propyl, 3 -Chloropropyl, 3-bromopropyl, 1,2,2-difluoropropyl, 丨, ^ monochloropropyl, 1,2-dibromopropyl, 2,3-difluoropropyl Group, 2,3-monochloropropyl, 2,3-dibromopropyl, 3,3,3-trifluoropropyl, 2,2,3,3,3-pentafluoropropyl, 2 -Fluorinated butyl, 2-gasified butyl, 2-bromobutyl, 4-fluorinated butyl Methyl, 4-chlorobutyl, 4-bromobutyl, 4,4,4-difluorobutyl, 2,2,3,3,4,4,4-heptafluorobutyl, perfluorinated Butyl, 2-fluorinated pentyl, 2-gasified pentyl, 2-desertified pentyl, 5-fluorinated pentyl, 5-gasified pentyl, 5-bromopentyl, perfluorinated pentyl , 2-hexyl fluoride, 2-hexyl hexyl, 2-bromohexyl, 6-hexyl fluoride, 6-hexyl hexyl, 6-hexyl bromide, perfluorohexyl, 2-fluoroheptyl, Examples include 2-gasified heptyl, 2- > odorized heptyl, 7-fluorinated heptyl, 7-chlorinated heptyl, 7-desertified heptyl, perfluorinated heptyl, and the like. Low-grade oxyhydroxide is a straight-bonded or branched system up to the number of isthmuses up to 6 --- This paper size is suitable for China National Standard (CNS) A4 size (21 OX 29 * 7 mm) (read first read (Notes on the back then fill out this page)

, 1T line A7 548272 V. Description of the invention (27) " ~ 'oxy can be methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, fluorene 2 Butoxy, third butoxy, n-pentyloxy, isopentyloxy, second pentyloxy, third pentyloxy, methylbutoxy, n-hexyloxy, isohexyloxy, third hexyloxy Methyl, 2hexyloxy, methylpentyloxy, 3-methylpentyloxy, _ethylbutoxy, 2-ethylbutoxy, ι, ι-dimethylbutoxy, 2 As examples, 2-dimethylbutoxy, monomethylbutoxy, 1-ethylmethylpropoxy and the like. Preferred are methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy 1 2 butoxy, third butoxy; and carbon number 3 is Better. The lower% alkyl group is a cycloalkyl group having 3 to 7 carbon atoms; the preferred ones include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl as examples; more preferred is 1 to 4 carbon atoms Examples include cyclopropyl and cyclobutyl. The lower alkoxy lower alkyl group is a straight or branched alkyl group having a carbon number of 8 to 8 substituted by a linear or branched alkoxy group. Examples include methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, methoxyhexyl, methoxyheptyl, methoxyoctyl, and ethyl. Oxymethyl, ethoxyethyl, ethoxybutyl, ethoxypentyl, ethoxyhexyl, ethoxyheptyl, ethoxyoctyl, propoxymethyl, propoxyethyl Group, propoxypropyl, propoxybutyl, propoxypentyl, isopropoxymethyl, isopropoxyethyl, isopropoxypropyl, isopropoxybutyl, isopropyl Oxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, isobutoxymethyl, isobutoxyethyl, isobutoxypropyl, Isobutoxybutyl and butyl paper sizes Applicable to China National Standard (CNS) Α4 size (υ〇χ 297mm) (诮 Please read the notes on the back before filling in this page)

1T line 548272 A7 B7 V. Description of the invention (28) oxyfluorenyl group, 2butoxyethyl group, 2butoxypropyl group, 2butoxybutyl group, 3butoxyoxy group, Third butoxyethyl, third butoxypropyl, third butoxybutyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, hexyloxy Examples are fluorenyl, hexyloxyethyl, hexyloxypropyl, and the like; preferably, an alkoxy group having 1 to 2 carbon atoms and a calcining group having 1 to 2 carbon atoms are combined. The tri-lower alkylsilyl lower alkyl group may be a combination of a trimethyl vermiculyl group, a diethyl vermiculyl group, a tripropylmethacyl group, or the like with the aforementioned lower alkyl group. The lower alkylamino group is a linear or branched alkylamino group having up to 6 carbon atoms. Examples include amido, ethylamine, n-propylamine, isopropylamine, n-butylamine, isobutylamine, second butylamine, third butylamine, n-pentylamine, isoamylamine, 2-pentylamino, 3-pentylamino, 2-fluorenylbutylamino, n-hexylamino, 1-fluorenylpentamine, 2-fluorenylpentamine, 3-fluorenylpentamine, 4- Methylpentylamino, 1-ethylbutylamino, 2-ethylbutylamino, 3-ethylbutylamino, 1,1-diamidinobutylamine, 2,2-diamidinobutylamine As an example, a methyl group, a 3,3-dimethylbutylamino group, a 1-ethyl-1-amidinopropylamino group, and the like. Preferred are those having 1 to 4 carbon atoms, and examples thereof include amido, ethylamine, n-propylamine, isopropylamine, n-butylamine, isobutylamine, second butylamino, and third butylamino As an example. The lower sulfur burning group is a linear or branched sulfur burning group having up to 6 carbon atoms. Examples include methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, di-2-butylthio, third butylthio, n-pentylthio, isopentylthio , 2th pentylthio, 3th pentylthio, 2-methylbutylthio This paper is compliant with China National Standard (CNS) A4 (210X 297 mm) (掮 Please read the notes on the back before filling in this page )%!

1T 548272 A7 B7 V. Description of the invention (29) group, n-hexylthio group, isohexylthio group, third hexylthio group, second hexylthio group, 2-methylpentylthio group, 3-methylpentylthio group, 1-ethylbutylthio, 2-ethylbutylthio, 1,1-dimethylbutylthio, 2,2-diamidinobutylthio, 3,3-dimethylbutylthio, 1 -Ethyl-1-amidinopropylthio and the like. The preferred number is 1 to 4 carbon atoms, and examples include methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, second butylthio, and third butyl. An example is sulfur. The lower alkylthio-lower alkyl group is a straight-chain or branched alkynyl group substituted by the aforementioned linear or branched alkylthio group having a carbon number of 6 or less. The lower alkoxycarbonyl group is a linear or branched lower alkoxycarbonyl group having 6 to 6 carbon atoms in the alkyl portion. Examples include fluorenyloxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, second butoxycarbonyl, third butoxycarbonyl, N-pentyloxycarbonyl, iso-pentyloxycarbonyl, 2nd-pentyloxycarbonyl, 3rd-pentyloxycarbonyl, 2-fluorenylbutoxycarbonyl, n-hexyloxycarbonyl, iso-hexyloxycarbonyl, 3hexyloxy Carbonyl, 2hexyloxycarbonyl, 2-methylpentyloxycarbonyl, 3-methylfluorenyloxy, 1-ethylbutoxyhexyl, 2-ethylbutoxycarbonyl, 1,1 Dioxobutoxycarbonyl, 2,2-dimethylbutoxycarbonyl, 3,3-dimethylbutoxycarbonyl, 1-ethyl-1-methylpropoxycarbonyl, and the like are exemplified. More preferably, it is a carbonyl group combined with an alkoxy group having 1 to 4 carbon atoms, and examples thereof include a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an isopropoxycarbonyl group, an n-butoxycarbonyl group, and an isopropyl group. Paper size China National Standard (CNS) A4 size (210X 297 mm) (Read the precautions on the back before filling this page)

, 1T line 548272 Μ B7 oxycarbonyl group, 3th butoxycarbonyl group, etc. are five, description of the invention (3〇) butoxyl group, the second example 0 lower alkylcarbonyl group as the carbon number of the alkyl part to 6 A linear or branched alkylcarbonyl group. Examples include methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl, n-butylcarbonyl, isobutyl substrate, second butylcarbonyl, third butylcarbonyl, n-pentyl carbon, and isopentyl. Carbonyl, 2nd pentylcarbonyl, 3rd pentylcarbonyl, 2-methylbutylcarbonyl, n-hexylcarbonyl, isohexylcarbonyl, 3hexylcarbonyl, 2hexylcarbonyl, 2-methylpentylcarbonyl, 3 _Methylpentylcarbonyl, 丨 _ethylbutylcarbonyl, 2-ethylbutylcarbonyl, dimethylbutylcarbonyl, 2,2-dimethylbutylcarbonyl, 3,3-dimethylbutyl Examples are carbonyl, 1-ethyl-methylpropylcarbonyl, and the like. More preferably, it is a carbonyl group combined with an alkyl group having 1 to 4 carbon atoms. Examples of the carbonyl group include methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl, n-butylcarbonyl, isobutylcarbonyl, and Examples are butylcarbonyl, third butylcarbonyl, and the like. The lower alkanesulfonyl group is a linear or branched alkanesulfonyl group having up to 6 carbon atoms in the alkyl portion. Examples include methylsulfenyl, ethylsulfenyl, 1-propanesulfenyl, 2-propanesulfenyl, 1-butanesulfonyl, 2-butanesulfenyl, acetomethylsulfanyl, 1- ( 2-methylpropanylsulfanyl, arsenite, 2-pentylsulfanyl, 3-pentylsulfanyl, 1- (3-methylbutyl) sulfonyl, monomethylpropanyl Base, 1-hexylsulfenyl, 2-hexylsulfenyl, 3-hexylsulfenyl, 1- (2-methylpentyl) sulfonyl, 1- (3-methylpentyl) sulfonyl, 1- (4 -Phenylpentyl) chitosan, 2-ethylbutanite yellow, 3-ethylbutanite __________ Μ ____ This paper is suitable size 丨 彳] China National Standards (CNS) Α4 Specification ( 210X 297 mm) 548272 Λ7 B7 V. Description of the invention (31) group, 1,1-dimethylbutanesulfonyl, 2,2-dimethylbutanesulfonyl, 3,3-dimethylbutanesulfonyl Examples are fluorenyl, 1-ethyl-1 -fluorenylpropanthanthenyl, and the like. An alkylsulfonyl group having 1 to 4 carbon atoms is more preferred. The aryl group is 6 to 10 carbon atoms in this specification, and includes, for example, a phenyl group, a naphthyl group, and the like; when it is a simple naphthyl group, it includes a naphthyl group and a naphthyl group. The benzene ring or naphthalene ring may have the aforementioned substituents such as a halogen atom, a lower alkyl group, a cyano group, a nitro group, and a trifluoromethyl group. The arylsulfonyl group includes those in which the aforementioned aryl group is bonded to a sulfonyl group such as a benzylsulfonyl group, a benzylsulfonyl group, a naphthalenesulfonyl group, and the like. Lower aryl radicals include benzyl, phenyl, 2-phenylethyl, phenylpropyl, phenylbutyl, phenpentyl, phenylhexyl, naphthylmethyl, naphthylethyl, naphthylpropyl, naphthalene Butyl, naphthylpentyl and naphthylhexyl; φ represents those having an aryl group bonded to the aforementioned lower alkyl group. The aryl lower alkoxy system includes benzyloxy, Benzeneoxy, 2-Benzethoxy, phenylpropoxy, phenylbutoxy, pentyloxy, phenylhexyloxy, and naphthyloxy , Naphthylethoxy, naphthylpropoxy, naphthylbutoxy, and teapentyloxy; those with substituents on the stupid ring and on the naphthalene ring may also be used. Aromatic sulfonyl fluorenyl lower alkyl is benzylsulfonyl fluorenyl, fluorenylsulfonyl fluorenyl fluorenyl, naphthalenesulfonyl fluorenyl fluorenyl, and the like; that is, those in which the aforementioned arylsulfonyl group is bonded to the aforementioned lower alkyl. The aryl% fluorenylamino group includes a sulfonylamino group, a benzylsulfonylamino group, a naphthalenesulfonylamino group, and the like, and the arylfluorene is bonded to the amine group. , And aryloxy groups include oxygen atoms such as phenoxy, i • naphthyloxy, and 2-naphthyloxy. This paper is the national standard for making paper towels (CNSO A4 specification (2? 〇 ^ 97 ^ 7) (Notes on this page, please fill in this page again),-548272 A7 V. The description of the invention (32) has the aforementioned aryl group. The square carbonyl group includes a benzyl carbonyl group, a naphthalene carbonyl group, etc., and the aforementioned aryl group is combined. The amine group includes those having an arylcarbonyl group bonded to an amine group such as a carbamoylamine group and a naphthylcarbamidine group. The aryl lower alkenyl group includes a styryl group, a naphthylvinyl group and the like having a carbon number of 6 or less substituted by the aryl group. The heterocyclic group may be exemplified as described below, and specifically includes pyridyl, fluorenyl, isofluorenyl, thiazolyl, thiadiazolyl, benzofuryl, and dibenzo Furyl, thianaphthyl, 1H-1,2,3-triazolyl, ι, 2,4-trisyltetrawalyl, ° furanyl, thienyl ... Bilyl, odorant alpha, Methylpyridyl, indolyl, benzimidazolyl, etc .; these also include _isofluorinyl, methylisoquinolyl, and the like, which are substituted by the aforementioned halogen atom and lower alkyl heterocyclic ring Represents, for example, the aforementioned lower alkyl group substituted with the aforementioned heterocyclic group, such as fluorenyl, or the like; and the lower heterocyclic alkyl group represents the heterocyclic lower alkyl group substituted with dentin. Heterocyclic lower amine The group represents, for example, an amine group substituted by the aforementioned heterocyclic lower alkyl group such as α-methylamino; the heterocyclic lower alkylaminomethyl group represents the lower heterocyclic group such as pyridylaminomethylamino group Carbyl-substituted carbamoyl groups. Also, simple pyridyl groups include 2-pyridyl, 3-pyridyl, and 4-leafyl groups, and the bonding positions are not limited. Similarly, the bonding positions of other heterocyclic groups are also Unlimited. This paper is compliant with the China National Standard (CNS) A4 size (210X29 * 7mm) (read the precautions on the back before copying this page). 548272 A7 — -------- ------ B7 V. Description of the invention (33) ~~~~~ -A low-grade acryloxy group includes methylenedioxy group, ethynyl group, propylene dioxybenzyl group, etc. A suitable `` heterocyclyl '' represents a saturated or unsaturated atom having at least " solid oxygen atom, sulfur atom, rat atom and other heteroatoms A monocyclic or polycyclic heterocyclic group. A more preferred example is the following heterocyclic group. An unsaturation of 7 to 12 rings, preferably 9 or 10 rings, having 1 to 5 nitrogen atoms. Condensed heterocyclic group (preferably bicyclic group); for example, indolyl, isoindolyl, 2-indolyl, benzimidazolyl'fluorinyl, isofluorinyl, isoxazolyl, benzylidene An oxazolyl group, a tetrazolidine group, a tetrazolidine group (such as a tetrazol [l, 5-b] pyridyl group, etc.), a dihydroxytriazolidine group, etc .; one having 7 to 3 sulfur atoms 12-ring, preferably 9 or 10-ring unsaturated sigma condensing hetero% group (preferably bicyclic group) or 8, §_dioxide ·, such as dinaphthyl (such as 4Η-1, 3 Diphenyl, naphthyl, etc.), Benzobenzyl or its S, S-dioxide (eg benzo [a] pyrene or its s, s-dioxide, Benzo [b] thio Phenyl or its s, s-dioxide, etc.), etc .; unsaturated monocyclic heterocyclic groups having 3 to 8 rings, preferably 5 or 6 rings, having 1 to 4 nitrogen atoms, such as Billowy base, sialyl, sigma tr base, sigma base and its N-epoxide, feed group, sigma salyl group, sigma sigma base, three ° Sitting group (eg 4Η-1,2,4 · triazole, 1Η-1,2,3-triazole, 2Η-1,2,3-triazole, etc.), tetrazole (eg 1Η-tetrazole, 2Η Tetrazole, etc.), dihydroxytrimethyl (for example, 4'5-privyl-1,2,4-triplet, 2,5-diaphthyl-fluorene, 2,4-triplet, etc.); Saturated single-scale over 1 to 4 nitrogen atoms with 3 to 8 rings, preferably 5 or 6 rings. Medium 隼 (CNS) Λ4 specification (21〇χ 2 mm) (Read the precautions on the back before filling in this. Page ^ vi., -Port 548272 A7 _____________________ B7 V. Description of the invention (34) " Heterocyclic group, such as propyleneimino, pyrrolidinyl, imidazolidinyl, pyridinyl, pyrazinyl, piperidine Alkyl groups, etc.-Unsaturated condensed heterocyclic groups (preferably bicyclic groups) having 7 to 12 rings, preferably 9 or 10 rings, having 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, such as benzene Oxazolyl, benzoxadiazolyl, etc .;-unsaturated monocyclic heterocyclic groups having 3 to 8 rings, preferably 5 or 6 rings, having 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, such as嗔 σ sitting group, iso-0 oxa sitting group, 0 oxadiazo group (such as 1,2,4-oxadiazole, H4-oxadiazole, ι 2,5-oxadiazole, etc.) etc .;-saturated monocyclic heterocyclic groups having 3 to 8 rings, preferably 5 or 6 rings, having 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, such as morpholinyl Etc .;-An unsaturated condensed heterocyclic group (preferably a bicyclic group) having 7 to 12 rings, preferably 9 or 10 rings, having 1 to 2 sulfur atoms and ^ nitrogen atoms, such as benzoquinone. Sitting on the base, benzo noisy. Groups, etc .;-Unsaturated monocyclic groups having 3 to 8 rings, preferably 5 or 6 rings, having 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, such as thiazolyl, i, 2-thiazolyl , Thiasalyl'thiadiazolyl (eg 1,2,4-thiadiazole, 1,3,4-thiadiazole, 1,2,5 · thiadiazole, 1,2,3-thiadiazole Etc.);-saturated monocyclic heterocyclic groups having 3 to 8 rings, preferably 5 or 6 rings, having 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, such as thiazolidinyl, etc .; one having 1 sulfur An unsaturated monocyclic heterocyclic group having 3 to 8 rings, preferably 5 or 6 rings, such as thionyl and the like. The appropriate "esterified carboxyl group" may be exemplified by the following. A suitable example of the esterified part of the esterified fluorene group is low-grade ceryl ester ------- ______ This paper size is applicable to China National Standard (CNS) A4 (210X 297 mm) For the matters needing attention, fill in this page again, -0 Α7 548272 V. Description of the invention (35) (such as fluorenyl ester, ethyl ester, propyl ester, isopropyl ester, butyl ester, isobutyl ester, third butyl ester Esters, pentyl esters, hexyl esters, etc.), this lower alkyl group may have at least one suitable substituent, examples of which are, for example, lower alkyloxy (lower) alkyl esters [such as ethoxymethyl Esters, propionyloxymethyl esters, butyryloxymethyl esters, pentyloxymethyl esters, trimethylethylacetoxymethyl esters, hexamethylethoxymethyl esters, (or 2-) Acetyloxyethyl ester, or 2-, or 3) Acetyloxypropyl ester, 1- (or 2 ... or 3, or 4) Acetyloxybutyl ester, 1- (or 2_) propyl Ethyloxyethyl ester, Ethyl (or 2-, or 3-) Propyloxypropyl ester, Ethyl or Butyloxyethyl ester, ^ (or 2-) Isobutylethoxyethyl ester丨 _ (or 2-) trimethylacetoxyethyl ester, 1- (or 2-) hexyloxyethyl ester Isobutyl fluorenyl ethoxylate, 2-ethyl butyl fluorenyl ethoxylate, 3,3-dimethyl butyl fluorenyl ethoxylate, 1- (or 2_) pentyl oxyethyl ester, etc.] , Lower chain burned sulfonyl (lower) alkyl esters (such as 2- fluorenyl ethyl ester, etc.), mono (or di or tri) _ lower alkyl esters (such as 2- moth ethyl ester, 2, 2, 2 · Three gas ethyl ester, etc.); Lower alkoxycarbamyloxy (lower) alkyl groups [eg, alkoxycarbamyloxymethyl g, ethoxycarbamyloxybenzyl ester, propyl Oxycarbamyloxymethyl ester, 3rd butoxycarbamyloxymethyl δ 1- (or 2-) methoxycarbyloxyethyl g, b (or 2_) ethoxy Carbofluorenyl ethyl ester, 1- (or 2-) propoxy carbofluorenyl ethyl ester, etc.], fluorenyl (lower) alkyl, or (5-lower alkyloxy di. (Cyclo-4-yl) (lower) alkyl esters [e.g. (5-fluorenyl-fluorenyl 4,3_bisσoxocenyl-4-yl) methyl ester, 1,3-dioxocenyl-4-yl) methyl ester, (5-propyl-2-oxy-1,3-diomarocenyl-4-yl) ethyl vinegar, etc.]; lower alkenyl esters (Eg vinyl ester, allyl ester, etc.); low This paper scale suitable ΪΪΓΐ 'Kwan material (CNS) A4 size (210 X297 public Chu) (read to read the back of the precautions to fill out this page) .¾ Lou

1T line 548272 A7 V. Description of the invention (36) Alkynyl esters (such as ethynyl esters, propynyl esters, etc.); aryl (lower) alkyl esters (such as benzyl) which may have at least one suitable substituent Esters, 'methoxybenzyl vinegar, 4-nitrobenzyl motif, phenethyl vinegar, tribenzyl methyl vinegar, phenyl dixylyl ester, bis (methoxybenzyl) fluorenyl ester, 3, 'Dimethoxybenzyl, 4-hydroxy-3,5-di-3rd-butylbenzyl ester, etc.); aryl esters (e.g., phenyl esters,' chloro Phenyl ester, tolyl vinegar, tributyl butyl vinegar, trimethylbenzyl vinegar, tricresyl vinegar, cumyl ester, etc.); keto esters, etc. are examples. Preferred examples of the esterified carboxyl group protected by the esterification moiety so defined are the lower alkoxy and phenyl (or nitrobenzyl) (C1_C4) alkoxycarboxyl groups; the best are Examples are methoxycarboxyl, ethoxycarboxyl, and benzyloxycarboxyl. Examples of suitable "fluorenated carboxyl groups" include the following. Aminoamido, mono- or mono-lower alkylcarbamoyl (lower alkyl may be exemplified by the foregoing) [e.g. amidocarbamoyl, dimethylaminocarbamoyl, isopropylcarbamoyl , N-butylcarbamoyl, 3rd butylcarbamoyl, N-fluorenyl-N- (pyridinyl) aminofluorenyl, etc.], aryl lower alkylcarbamoyl (aryl and Lower alkyl can be exemplified by the foregoing) [e.g. benzylaminomethylamino, 3,4-methyldioxybenzylaminomethylamino, diaminobenzylaminomethyl, phenylethylamino Formamyl], cyclic lower alkylaminoformamyl having 3 to 7 carbon atoms (cyclic lower alkyl can be exemplified as the former) [eg, cyclopropylaminofluorenyl, cyclobutylaminofluorenyl , Cyclopentylcarbamyl, cyclohexylcarbamyl, etc.], " · 4 η This paper has a medium size national standard (CNS) A4 specification (210X297 ^ cent) '-(Read the first read on the back Note: Please fill in this page again), * = < »line 548272 Α7 Β7 V. Description of the invention (37) Arylaminofluorenyl (Aryl can use the former as an example) [eg phenylamino Fluorenyl, naphthylcarbamoyl, etc.], heterocyclic aminocarbamoyl (the heterocycle may be exemplified by the former [for example, thiazolylaminocarbamoyl, thiadiazolylaminofluorenyl, pyridyl Carbamate, triazolylacarbamoyl, tetrazolylamidoamino, N-methyl-N-α than pyridylaminoamidino, morpholinylcarbamoyl, etc.], heterocyclic lower Alkylaminocarbamyl (heterocyclic lower alkyl can be exemplified as the foregoing) [for example, morpholinylethylaminomethylamidino, pyridylmethylaminomethylamidino, fluorenyldioxybenzylcarbamoyl Etc.] N-disubstituted carbamoyl groups (such as morpholine carbonyl, thiamorpholine carbonyl, 1-perhydroazepine carbonyl, 1,1-dioxythiazole) that are members of a nitrogen-containing heterocyclic ring composed of a nitrogen atom Phenylcarbonyl, 1-piperidinylcarbonyl, 1-piperidinylcarbonyl, 4- (2-hydroxyethyl) -1-piperidinylcarbonyl, 4-methyl-1-piperidinylcarbonyl, carboxypyrrolidinyl Carbonyl, etc.), substituted sulfocarbamoylamino, etc. The substituents of the substituted sulfocarbamoylamino can be exemplified by the aforementioned alkynyl groups up to 8 carbons, lower alkynyl, and aryl alkynyl. Basic, Economic Basic Alkyl, tri-lower alkyl, lower alkyl, lower alkoxy lower alkyl, lower alkylthio lower alkyl, heterocyclyl, or aryl are examples; the aryl system can use the aforementioned i prime atom, Lower alkyl, i-lower alkyl, lower alkoxy or nitro, etc. Specifically, naphthylsulfonylaminofluorenyl, benzenesulfonylcarbamoyl, nitrobenzenesulfonyl Aminofluorenyl, triphenylsulfonylaminocarbamyl, lower alkoxybenzenesulfonylaminofluorenyl, halobenzenesulfonylaminofluorenyl, single or double lower alkyl This paper is suitable for China National Standard Rate (CNS) Λ4 specification (210X29 * 7 mm) -------------- IT ------ ^ wew— (Read the precautions on the back before filling in this Page) 548272 A7 B7 Description of the invention (38) benzenesulfonylaminocarbamyl group, alkylsulfonylcarbamylamino group with 1 to 8 carbon atoms (third butylsulfonylaminocarbamyl group, butylsulfonyl Fluorenylcarbamyl, propylsulfonylcarbamyl, isopropylsulfonylaminocarbamyl, methylsulfonylaminocarbamyl, octylsulfonylaminocarbamyl, pentyl Sulfonamide Fluorenyl, isopentylsulfonylaminofluorenyl, hexylsulfonylaminofluorenyl, etc.), trihalo (lower) alkylsulfonylaminofluorenyl, phenyl (lower) alkylsulfonium Aminocarbamoyl, tri-lower alkylsulfonylaminocarbamyl, lower alkylthio lower alkylsulfonylaminocarbamyl, lower alkoxy (lower) alkylsulfonylaminocarbamyl, An example is a fluorinylsulfonylcarbamoyl group. Suitable "fluorenyl" are aliphatic fluorenyl, aromatic fluorenyl, heterocyclic fluorenyl, and aliphatic fluorenyl substituted with aromatic or heterocyclic groups; for example, derived from carboxylic acid, carbonic acid, sulfonic acid, An example is a fluorenyl group such as urethane. The aliphatic fluorenyl group is a saturated or unsaturated non-cyclic or cyclic, for example, a lower alkyl fluorenyl group (for example, fluorenyl, ethyl fluorenyl, propyl fluorenyl, butyl fluorenyl, isobutyl fluorenyl, pentamyl, isopropyl Alkyl, lower alkylsulfonyl (such as methylamyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, etc.) Fluorenyl, butylsulfonyl, isobutylsulfonyl, pentylsulfonyl, hexylsulfonyl, etc.), alkyl, aminofluorenyl, N-carbylcarbamoyl ( (Such as methylaminomethyl, ethylaminomethyl, etc.), lower alkoxycarbonyl (such as methoxyhexyl, ethoxyquinyl, propoxyquinyl, butoxycarbonyl, third butyl) Alkoxycarbonyl, etc.), such as alkoxycarbonyl, lower alkenyloxycarbonyl (such as ethyleneoxycarbonyl, propyleneoxycarbonyl, etc.), etc. Paper size suitable for China National Standard Apple (CNS) A4 specifications (210X29 * 7 (Mm) -------------- IT ------ ^ 1 # — (Read the precautions on the back before filling this page) 548272 A7 __________ B7 V. Description of the invention ( 39) Alkyl carbonyl, lower alkenyl (such as propenyl, methacryl, methyl, etc.), alkenyl, cyclic (lower) alkylcarbonyl (eg, cyclopropanyl,% pentanecarbonyl, ring Hexanecarbonyl, etc.) are examples. Examples of aromatic private groups include C6-C10 aromatic groups (such as phenylfluorenyl, benzophenone, monophenylphenyl, etc.), N- (C6-C 丨 〇) arylcarbamoyl, ( For example, N-benzylcarbamoyl, N-benzylaminofluorenyl, N-naphthylcarbamoyl, etc.), C6-C10 aromatic hydrocarbon sulfonyl (such as benzylsulfonyl, p-toluenesulfonyl) Etc.) as an example. Hetero bad fluorenyl may be heterocyclic carbonyl; heterocyclic (lower) alkyl fluorenyl (such as heterocyclic fluorenyl, heterocyclic fluorenyl, heterocyclopentyl, heterocyclopentyl, etc.) ; Heterocyclic (lower) alkenyl (such as heterocyclopropenyl, heterocyclobutenyl, heterocyclopentenyl, heterocyclohexenyl, etc.); heterocyclic acetaldehyde, sulfenyl As examples. Examples of the aliphatic alcohol group substituted with an aromatic group include aralkyloxycarbonyl groups such as phenyl (lower) alkoxycarbonyl groups (such as phenoxycarbonyl, phenethoxycarbonyl, etc.). These fluorenyl groups can be further substituted with one or more appropriate substituents, such as nitro, and the like. A preferred fluorenyl group having such a substituent is nitroaralkoxycarbonyl (for example Nitrobenzyloxycarbonyl, etc.) as an example. The preferred salts of the benzimidazole derivatives of the present invention are non-toxic commonly used salts such as alkali metal salts such as sodium and sodium, alkaline earth metal salts such as calcium and magnesium, Salts of inorganic bases such as ammonium salts, and three paper sizes Chase China National Standard (CMS) A4 specification (210X 297 mm) (Please read the precautions on the back before filling this page)

1T line 548272 A7 B7 V. Description of the invention (40) Organics such as mono-ethylamine, pyridine, methylpyridine, ethanolamine, triethanolamine, dicyclohexylamine, N, N, -diethylene glycol, etc. Amine salts, and inorganic acid salts of hydrochloric acid, hydrogenated acid, sulfuric acid, phosphoric acid, etc., and organic carbonates of formic acid, acetic acid, trifluoroacetic acid ', maleic acid, tartaric acid, etc. Examples include paratoluene acids and other acid addition salts, and experimental or acidic amino acids such as arginine, aspartic acid, and glutamic acid. The compounds of the present invention are those having one or more asymmetric centers, and therefore exist as mirror images or diastereomers. In addition, some compounds containing an alkenyl group in the chemical formula have positive and negative isomers. In each case, the present invention includes mixtures thereof and each isomer. The compounds of the present invention may also be in the form of tautomers. The present invention includes mixtures thereof and each isomer. The compounds of the present invention and their salts can form a solvent, and this is also included in the scope β of the present invention. The formed solvents are: hydrate and ethanolate. In the specific compound system of the present invention, the benzimidazole derivative represented by the formula (IX) may be 6-benzenesulfonylaminocarbamyl_ 丨 ((chlorochlorobenzyl 2-methylbenzimidazole, Benzenesulfonylaminocarbamyl _ 丨 _ (biphenyl-'methyl) -2-ethylbenzimidazole, 5-benzenesulfonylaminocarbamyl chlorobenzyl) -2 ^ methylbenzyl Imidazole, 5_ (4-chlorobenzenesulfonylcarbamoylmethyl) 丨-^ chlorobenzyl) -2-methylbenzimidazole, 丨 ((chlorochlorobenzyl) _2_methyl_5_ (2_ Naphthylsulfonylamino ψ 醯 yl) benzimidazole, 1_ (2_chlorobenzyl basic paper ruler M / time off 0X29 ^ 7-- ~~ ----— (Read the precautions on the back before filling in this page)

'IT 548272 A7 B7 V. Description of the invention (41) Vermiculite, fluorenylamino, ammonium-2-fluorenylbenzimidazole, 6- (1-butanylaminocarbamyl) -1- (2_qi Benzyl) _2_fluorenylbenzimidazole, bu 2-oxobenzyl) -2-methyl-6- (1-octanesulfonylaminofluorenyl) benzimidazole, -oxobenzyl ) -2-methyl-6- (2-propanesulfonylcarbamoamido) benzimidazole, ^ (biphenyl-4-methyl) -6- (1-butanesulfonylcarbamoamido) -2_methylbenzimidazole, 6- (1-butanesulfonylaminofluorenyl) > 1- (2,4 • digasobenzyl) _fluorenylbenzimidazole, 1- (bibenzyl -4-methyl) -6- (1-butanesulfonylaminocarbamyl) -2-ethylbenzimidazole, 6-benzenesulfonylaminocarbamyl_; [_ (联 笨 -4_ 甲Group) -2-trifluoromethylbenzimidazole, 5-benzenesulfenylaminofluorenyl (biben-4-methyl) -2-trifluoromethylbenzimidazole, 6_benzenesulfonylamino Fluorenyl-2-cyclopropyl-1- (2-fluorobenzyl) benzimidazole, n-benzylsulfenyl-3_ [1_ (2_fluorobenzyl) -2-methylbenzimidazole Propyl] acrylamidonium, N-benzenesulfonamido-2- [l- (2-gaso-benzyl) _2_methylbenzimidazole_6_yl] acetamidoamine, 1- (2_ Benzyl) _2_fluorenyl_6_ (2-naphthalenesulfonylaminofluorenyl) benzimidazole, 1- (2-chlorobenzyl) _2_fluorenylnaphthalenesulfonylaminocarbamyl) benzene Benzalane, 6- (4-chlorobenzite, fluorenylcarbamoylcarbamoyl, carbamoyl benzyl) -2-fluorenylbenzimidazole, 6- (3-fluorobenzenesulfonylcarbamoylmethyl) -1 -(2-chlorobenzyl) -2-methylbenzimidazole, 5-benzenesulfonylcarbamoamidinyl_ 2-benzyl-1- (2-fluorobenzyl) benzimidazole, 6_ Phenylsulfonylcarbamoyl-2-benzyl-1- (2-chlorobenzyl) benzimidazole, 6-benzenesulfonylcarbamoyl Si & yl-1- (biben-4-methyl ) -2-Amidinobenzyl, ι_ (2-Azobenzyl) -2-amidino-6-trifluoroarsenoxanthenylaminomethyl benzobenzine, 6-benzylsulfonylamino Fluorenyl_b (2,4-dioxobenzyl) _2-fluorenylbenzo. Misal, chlorobenzyl) -6- (4-Hydroxybenzylsulfonylamino) This paper is suitable for Chinese National Standard (CNS) A4 (210X297 mm) (诮 Please read the notes on the back before filling This page • Ding, Ding, \\ " A7 548272 V. Description of the invention (42) Formamyl) -2_methylbenzyl miso, Bu (2-Azoyl) -2-methyl Winter (α-Toluene "methylcarbamyl" benzimidazolam, ^ chlorinated ¥ 4) A · -methylbenzite yellow Si-methylcarbamyl) 々 · methylbenzene, (read First read the > 1 notice on the back and then fill out this page. Benzyl yellow yellow carbamoyl) benzo. Sit, W2-chlorofluorenyl peak methyl winter [4_ (trifluoromethyl) benzylcarbamyl] benzopyrene, 6. (2 · chlorochlorobenzylcarbamate) + (2: Chloroyl group) -2-methylbenzyl, benzobenzylcarbamoyl, 2benzyl small (2,4-monokistilbyl) benzyl. Benzene, sulfonylaminocarbamoyl-2-benzyl-W2,4-dichlorobenzyl) benzobenzyl, benzobenzylcarbamoylmethylbenzylmethyl) _2, phenylbenzene Side-by-side, 6 · benzenesulfonylaminocarbamyl small (biphenyl-4-methyl) benzylbenzimidyl sigma, 6 • benzenesulfonylaminocarbamyl-1- (biben-4_ (Methyl) -2_methoxybenzimidazole, benzylsulfenylcarbamoyl- 丨-(biphenyl-4_methyl) _2_carboxybenzimidazole, benzsulfenylcarbamoyl- ; U (biphenyl_4_methyl) _2-fluorenylaminobenzimidazole, 2-amino-6-benzenesulfonylcarbamoylamino —— 丨 (biben_4_methyl) benzimidyl Wow, 6_benzylxanthenylcarbamyl (biphenyl_4_methyl) _2_n-propylbenzimidazole, 6-benzenesulfonylcarbamoyl (biben_4_methyl) _2_ Butyl benzimidazole, 6-benzylsulfonylaminocarbamyl (biphenyl_'methyl) -2-oxomethylbenzimidazole, 6_benzylsulfonylcarbamoyl_ 丨 _ (bi Benzyl-4-methyl) -2-methoxymethyl benzimidazole, Benzylcarbamoyl & L-based-1- (bibenzyl-4-methyl) -2-isopropylbenzimidazole Benzylsulfonylcarbamoamidin-1- (biphenyl-4-methyl) -2- Methylthiobenzimidazole, 6-benzenesulfonylaminocarbamyl-1- (bibenzyl-4_methyl) _2_ethylthiobenzimidazole, 6_benzenesulfonylaminocarbamyl-1- (Methylbenzyl) N-propyl sulfide basic paper size Tongzhou Chinese National Standard (CNS) A4 specification (210X 297mm) Μ 548272 s__________________B7_ V. Description of the invention (43) Benzowa, 6-benzylamino Benzyl group _ 1 _ (bibenzylidene)-2 n-hexylthiobenzimidazole, 6-benzenesulfenylaminofluorenyl (benzylidene) benzimidazole, 6-benzenesulfonylaminofluorene Hydrazine, 2-diphenyl benzyl) -2-fluorenylbenzimidazole, 6-benzenesulfonylcarbamoylbibenzylmethyl) -2-benzylbenzimidazole, 6-benzenesulfonyl Aminocarbamoyl fluorenyl — 1- (2-nitrobenzyl) benzimidazole, 6-benzenesulfonylaminocarbamylfluorenyl-1-benzylbenzimidazole, 6-benzenesulfonylamino Formamidine_2_methyl-; u ('nitrobenzyl) benzimidazole, 6-benzenesulfonamidoaminofluorenyl-"(' benzyloxybenzyl) -2-fluorenylbenzimidazole, 6_benzenesulfonamidomethyl-1- (2-chlorobenzyl) -2-fluorenylbenzimidazole, N_benzylsulfenylbenzyl) _ Fluorenylbenzimidazole-6-yl] propanamide, 6-benzylsulfonylcarbamoamidinyl_2_fluorenyl-l- [4- (l, 2,3-thiadiazol-4-yl) benzyl Yl] benzimidazole, chlorobenzyl) -2-fluorenyl-6- (8-fluorinylsulfonamidocarbamoyl) benzimidazole, 6- (4- 3rd-butylbenzoxanthenylaminofluorene Fluorenyl group ^^ Benzyl benzyl) _fluorenyl benzimidazole, 6-benzoxanthan fluorenylaminofluorenyl_2_fluorenyl-fluorenyl_ [4 · (trifluorofluorenyl) benzyl] benzo Imidazole, 5-sulfoamidomethylamidomethyl benzimidazole, 1- (biphenyl_4-methyl) -6- (1-butanesulfonylaminoamido) _ 2_oxofluorenyl Benzimidazole, 1- (4-benzyloxybenzyl) butanesulfonylaminofluorenyl) -2-benzyloxybenzylbenzimidazole, butansulfonylaminofluorenyl) -1- (2,4- Bicyclobenzyl) _2_oxofluorenylbenzimidazole), ι_ (fluorenyl link group) -2-fluorenyl-6- (1_propanesulfonylaminofluorenyl) benzimidazole, 6_ethylstone Yellow si-aminoaminofluorenyl_1- (2-cyclobenzylfluorenylbenzimidazole, 6_ (propanesulfonyl- 丨 -carbonyl) -1- (2-chlorobenzyl) _2_fluorenylbenzimidazole 6-benzylsulfonylaminofluorenyl-1- (bibenz-4-methyl) -2-cyclopropylbenzimidazole 、; [_ --- ~ —____ 47 _ This paper is suitable for ffl Chinese National Standard (CNS) A4 specification (210X 297 mm) (邡 Please read the precautions on the back before filling this page] .Private ^ ·. Order- Line 548272 A7 B7 V. Description of the invention (44) (2-chlorobenzyl) -2-methyl-6- (1-pentylsulfonylaminomethylamidino) benzimidazole, 1- (2-chloro Benzyl) -2-methyl-6-[(3-methylbutyl) sulfonamidocarbamoyl] benzimidazole, 1- (2-fluorobenzylhexylsulfonylcarbamoamido)- 2-methylbenzimidazole, 7- (1-butanxanthenylcarbamoyl) di-gaso-benzyl) _2_methylbenzimidazole, 1_ (2-_o-benzyl) _2_methyl_ 6 -[1- [3- (Dicarboxylate) propyl] carbamylcarbamyl] benzyl, wow, '(1-butanesulfonylaminocarbamyl', dioxobenzylmethylbenzimidazole , 1- (4-benzyloxybenzylbutanylaminocarbamyl) _fluorenylmethylbenzimidazole, 6- (1-butanesulfonylaminocarbamyl) -1-[(2, _cyanohydrazine Phenyl-4-yl) methyl] -2-methylbenzimidazole, 6-X-Ethylsulfonylaminofluorenyl) _1-[(2'-fluorobibenzyl-4-yl) methyl] 2-methylbenzimidazole, 6_ (1-butacil Formic acid group) -l-[(3-Gaminated biphenyl) methyl] methylbenzyl miso, 1- (2-gasofluorenyl) _6_ [(2-methoxyethyl) stone yellow Carbamidyl] -2-fluorenylbenzimidazole, chlorobenzyl) -6- (1-hexylfluorenylmethylformyl) -2-methylbenzo. Meter. Sit, ι_ (2,4_ dikisordinyl) -2-benzoyl (1-pentanylpyridylaminomethyl) benzo. Mi 0, ι_ (bibenzyl-4-fluorenyl) -2-ethyl-6 [1- [3- (methylthio) propyl] sulfonylaminofluorenyl] benzimidazole, 1- (4- Bibenzylidene) -2-ethyl-6- (1-pentylsulfonylaminocarbamyl) benzimidazole, 6- (1-butanesulfonylaminofluorenyl) -1- (2,4 _Dichlorobenzyl) -2-ethylbenzimidazole, 1- (4-biphenylfluorenyl) _2-ethylfluorenyl) butyl stilbene base gas-based sulfonyl group] stupid flavor σ sitting, 5- (1-Butane yellow fermented sulfonyl group S & yl) -1- (2,4-monogasofluorenyl) -2-fluorenylbenzimid alpha all, (4 · bibenzyl)- 5- (1-Butylsulfonylaminofluorenylethylbenzimidazole, ^ (4-bibenzylfluorenyl) -2-ethyl-6- (2-fluorenylethoxysulfonylaminofluorenyl) ) (Read the precautions on the back before filling in this page,-mouth

i -1!-II-1-· The size of the paper is suitable for China National Standard (CNS) A4 size (210X29 * 7mm) 48272 A7 B7 Μ 合 M ·· ;; 卬 卬 水水 ^^ 元 元 明 (I and taste / ^ — ^ 6- (i, butanesulfonylcarbamoyl) -2-ethyl-l- [4- (4 -1 down gas) benzyl] benzimidazole, 6- (1-butanesulfonylcarbamoyl) _ [4 (3,4 · dichlorobenzyloxy) benzyl] _2-ethylbenzimidazole , 6- (1-Butylsulfonium ,, ethoxymethylmethyl} hi [[2 (2,4_digasophenethyl)] _ 2-methylbenzene JE. Υή ^ 〇4λ \ ί: r λ Butylsulfonylaminocarbamyl) -1- [4- (2-pyridyl) benzyl: methylbenzimidazole, 6- (1-butylsulfonylaminocarbamyl) -Bu (2,4- Chloro ¥ yl) -2, cardiac dimethyl benzimidazole, 6- (1-butanesulfonylcarbamyl SE.: ¾ ^ w glycinyl-1- (4-phenoxybenzyl) benzimidazole, 6- (Butylpyridinylaminocarbamyl) -2-methyl ^-(2-pyridylmethyl) benzimidazole, 1-[(4-phenylamidine) T group)]-6- (1-butyl Sulfofluorenylaminomethylsulfonyl) _2_methylbenzimidyl = 2-heart ο-butanesulfonylaminofluorenyl) _2-fluorenyl- [4_ (2_phenylethyl) benzyl] benzimidazole , Stupid) benzyl] _6_ (1_ butylsulfonylaminomethylfluorenyl) _fluorenylmethylbenzimidazole, 6_ (丨 _butylsulfonylaminoaminofluorenyl) _2_methyl [(2benethandro) Fluorenyl] benzimidazoline, 1- (dibenzyl-2-methyl) -6_ (butylκamidocarbamoyl) _2_methylbenzimidazole, 6_ (bubusulfenylamino) (Methylamidino) -1_ (2,4-dioxobenzyl) -2-hydroxybenzimidazole, 6_ (1-butanesulfonylaminomethylamidino) _2_methyl-W2-pyridinomethyl) Examples are benzimidazole and 6- (1-butanesulfonylcarbamoyl) -2-methyl-1_ [3- (4-bromoisofluorinyl) methyl] benzimidazole. The formula (X) represents, specifically, 1- (2-cyanobenzyl) 6_ethoxycarbonyl-2-n-propylbenzimidazole, 6_ethoxycarbonyl_2_n-propyl_ 1 -(2-pyridylmethyl) benzimidazole, cardioethoxycarbonylmethyl_2-n-propylbenzimidazole, 1-n-butylethoxycarbonyl_2_n-propylbenzimidazole, 1- (bi Benthyl-4-methyl) _6_ethoxycarbonyl-2 • methylbenzyl, paper size Shizhou China National Winter Standard (CNS) A4 specification (210X 29 * 7 mm) ------- -Xu first read the notes on the back before filling out this page)

1T line 548272 A7 B7 V. Description of the invention (46) Ethoxycarbonyl-1- (2-methoxybenzyl) _2_methylbenzimidazole, cardioethoxycarbonylmethoxybenzyl) -2-methylbenzene Benzimidazole, 1β [2- (benzenesulfonylmethyl) benzyl] -6-ethoxycarbonyl-2-methylbenzimidazole, 1- (2_cyanobenzyl) _6_ (2_cyanocarboxycarbonyl) 2-methylbenzimidazole, N (biphenyl_fluorenylmethyl) _6_ethoxycarbonylmethylbenzimidazole, 6-ethoxycarbonyl-2-methylnaphthylmethyl) benzimidazole: W Benzene-4-methyl) _6_ethoxycarbonyl_2_ethylτbenzo1mazole, 6-ethoxycarbonyl-2-n-propyl-1-isopropylbenzimidazole, 2-benzyl— 6-ethoxycarbonyl-1-methylbenzimidazole, 6-carboxymethyl_2_n-propylbenzimidazole, 6-carboxy-2-n-propyl-1-isopropylbenzimidazole, "n Butyl-6-carboxy-2-n-propylbenzimidazole, 6-carboxymethylnitrobenzyl) benzimidazole, b (biphenyl_'methyl) _6_carboxy_2_methylbenzimidazole 6-Weiji-1- (2 • methoxybenzyl) · 2-methylbenzyl. Sit, slow — 1- (4-methoxybenzyl) -2-fluorenylbenzimidazole, 6_ Carboxy_2-methyl- (benzenesulfonylmethyl) benzyl] benzimidazole, 6-carboxy-i- (2-cyanobenzyl -2_ methylbenzimidazole, 6-carboxy-1- (bibenzylmethyl) _fluorenylmethylbenzimidazole, 6-carboxy-2-methyl-1- (2-naphthylmethyl) benzimidazole, ^ (Biphenyl_4_methyl) -6-carboxy-2-ethylbenzimidazole, 5-carboxy-2_methyl-: [_ (2_nitrobenzyl) benzimidazole, 1_ (biben_ 4_methyl) _6_carboxy_2_trifluoromethylbenzimidazole, 1- (biphenyl_4-fluorenyl) _5_carboxytrifluoromethylbenzimidazole, 5-ethoxycarbonyl-2 _Methylbenzimidazole, 2-benzyl_5_ethoxycarbonylbenzimidazole, 6-ethoxycarbonyl_2_methyl "-(I-nitrobenzyl) benzimidazole, 5-ethoxycarbonyl-2 -Fluorenyl-1- (2-nitrobenzyl) benzimidazole, ethoxycarbonyl-2-trifluoromethylbenzimidazole, ι_ (biphenyl-4-methyl) ethoxycarbonyl-2-tris Fluoromethyl benzimidazole, 1 gas dibenzyl ^ This paper is a standard Shizhou China national standard (0, 5) 8 4 specifications (210 \ 297 mm) 1 (Please read the precautions on the back before filling This page), 1T -line 548272 A7 ___________________ ___B7 V. Description of the invention (47) 5-ethoxycarbonyl-2-difluorofluorenylbenzimidazole, ι_fluorenyl_2_n-propyl_ 6- [( 2-pyridylmethyl) aminofluorene Yl] benzimidazole, 2-n-propylisopropyl-6-[(2-pyridinyl) aminofluorenyl] benzimidazole, n-butyl-2-n-propyl-6-[(2-pyridinyl) Yl) aminofluorenyl] benzimidazole, 2-benzyl_ 1-methyl-6-[(2-pyridinyl) aminofluorenyl] benzimidazole, 1- (2-fluorenyloxybenzyl) 2-methyl-6-[(2-pyridinyl) aminofluorenyl] benzimidazole, 1β (4-fluorenylbenzyl) -2-fluorenyl-6-[(2-pyridylmethyl) Carbamidyl] benzimidazole, 1- [2- (benzenesulfonyl) benzyl] _2_methyl_6 _ [(2_pyridylmethyl) carbamoyl] benzimidazole, Oxybenzyl 2-hexyl-6-[(2_pyridinyl) aminoamino]], and ^ (bibenzylidene-6-[(2-. Than bitenyl) aminoamino]]. Meter. Perylene, 2-Methenylnaphthyl) -6-[(2-cumidinyl) carbamoyl] benzimidazole, 丨 _ (biben_4_fluorenyl) -2_ethyl-6- [ (2-Pyridinyl) carbamoyl] benzimidazole, 2-fluorenyl-1- (2-nitrobenzyl) -6-[(2-pyridinyl) aminopyridyl] benzimidazole, 2 -Fluorenyl-1- (2-nitrobenzyl) -5 _ [(2-pyridylfluorenyl) aminofluorenyl] benzoxyl, 1- (bibenzyl_4_methyl) · 2-methyl- 6-[(2 "pyridinyl) carbamoyl] benzimidazole, 1- (4-benzyloxybenzyl) -2-fluorenyl-6-[(2-pyridylmethyl) aminomethyl] Benzimidazole, 2-methyl-1- (3,4-methyldioxybenzyl) -6-[(2-methylpyridinyl) aminoamido] Benzimidazole, 2_amido-6_ [ (2--pyridylmethyl) carbamoyl] -l- [4- (l, 2,3-thiadiazol-4-yl) benzyl] benzimidyl, 2-fluorenyl-5- [(2-Pyridinylmethyl) carbamoyl] benzimidazole, benzenesulfonyl-2-methyl-6-[(2-pyridinyl) carbamoyl] benzimidazole, ^ benzene Sulfonyl-2-fluorenyl-5-[(2-pyridinyl) carbamoyl] benzimidazole, 2-methyl-1- (4-nitrobenzyl) -6-[(2-pyridine Methyl) aminofluorenyl] benzimidyl paper ruler Fitness States (CNS) (210X 297 / > 4) '(Please read the notes and then fill in the back of this page)

1T line 548272 A7 B7 V. Description of the invention (48) Saliva, 2-fluorenyl small (4-nitrobenzyl) -5-[(2-pyridylmethyl) carbamoyl] benzo. Perylene, 2-fluorenyl-1- (2-benzylmethylpyridinylmethyl) aminofluorenyl] benzimidazole, 2-fluorenyl-1- (2-benzylmethyl) · 5-[(2- α-pyridylmethyl) carbamoyl] benzimidazole, 1- (4-aminobenzyl) _2_methyl-6 _ [(2-pyridylmethyl) carbamoyl] benzimidazole, 1- ( 4-aminobenzyl) -2-methyl-5-[(2-pyridinyl) carbamoyl] benzimidazole, 1- [4- (benzoxanthinylamino) benzyl] _2_methyl -6-[(2 ^ pyridinylmethyl) carbamoyl] benzimidazole, κ (biphenyl_4-methyl) _2 · fluorenyl-6-[(2-pyridylmethyl) carbamoyl] Benzimidazole, 2-benzyl-6-carboxy-1-methylbenzimidazole, 4-ethoxycarbonyl_2_fluorenylbenzimidazine, 1- (4-fluorenyloxy) -6- Ethoxy-2-yl is fluorenyl. Miwa, ι_ (4_benzyloxybenzyl) _6_carboxyfluorenylbenzimidazole, 6_ethoxycarbonyl_1-[(2, _cyanobiphenyl-4-yl) methyl] -2-methyl Benzo saliva, 6-carboxy-1-[(2, _cyanobiphenyl-4-yl) methyl] -2-methylbenzimidazole, 6_ethoxycarbonyl_1-[(2, _ Fluorobibenzyl-4-yl) methyl] -2-methylbenzylidene, 6-branyl-i-[(2, _fluorobibenzyl-4-yl) fluorenyl] -2- 曱Benzyl benzimidazolam, 6-ethoxyquinyl _; [_ [(% Fluorobiben-4-yl) fluorenyl] -2-fluorenylbenzo sigma, 6-tertyl "_1 _ [( 3-Fluorobiphenyl-4-yl) methyl] -2-fluorenylbentamethine, 1- (4-bibenzylmethyl) -5_ethoxyquinyl-2-ethylbenzoxyl , 1- (4-biphenylfluorenyl) sulfanyl_2_ethylbenzimidazole, 6-ethoxycarbonyl-2-ethyl-l- [4- (4-l-octyloxy) benzyl] benzyl Benzimidazole, 6-carboxyethylfluorobenzyloxy) benzyl] benzimidazole, 1- [4- (3,4-dichlorobenzyloxy) benzylethoxycarbonyl-2_ethylbenzyl Thallium, 6-tetyl_1_ [4_ (3,4 · di-aminobenzyloxy) benzyl] -2-ethylbenzimidazole, biphenylfluorenyl) _6_ (n-butylaminofluorenyl)- 2 -Ethyl Benzo and Miso, 1_ (4_ 联 笨 甲 奕) (¾Read the back first Please pay attention to writing this page again} The national standard of the paper size (CNS) A4 (210X29 * 7 mm) 548272 Α7 Β7 V. Description of the invention (49) 2 ethyl-6- (provincial saliva-2 -Carbamoyl) benzoyl saliva, 1_ (4_biphenylmethyl) -2-ethyl-6- (2-turidineaminomethylamidino) benzimidazole, azine 2 (2,4_ Digas phenethyl)]-6-ethoxycarbonyl-2-methylbenzimidazole, 6-carboxy "_ [2 (2,4-monogas ethyl)]-2-methylbenzo 17 m Saliva, 1- (4-bibenzylidene) 2 ethyl 6 (benzylmethyl) benzo. Sit, ι_ (4-bibenzylidene) -2-ethyl-6- (l, 3,4-thiadiazolyl-2-aminocarbamyl) benzimidazole, 1- (4-biphenylmethyl) -2-ethyl-6- (tetrazol-5-aminomethylfluorenyl) benzene Benzimidazole, 1- (4-biphenylmethyl) _2_ethyl_6_〇, 3, Dongtriazolecarbamoyl) benzimidazole, 1- (4-biphenylmethyl) _2-ethyl -6- (1,3,4_triazole_2_aminomethylfluorenyl) benzimidazole, iG-biphenylmethyl) ethyl-6- (3_σbipyridylcarbamoyl) benzimidazole, 丨Xing biphenylmethyl) _ ethyl ('pyridylaminomethyl) benzimidazole, 丨-^ dichlorobenzyl)- 2,4_difluorenyl_6_fluorenyloxybenzimidazole, 6-carboxy-1- (2,4-dichlorobenzyl) -2,4-dimethylbenzimidazole, 6-ethoxycarbonyl Methyl "-(benzophenoxybenzyl) benzimidazole, 6-carboxy-2-methyl-1- (4-phenoxybenzyl) benzimidazole, cardioethoxycarbonyl-2-fluorenyl-1- (2-. Bipyridylmethyl) benzimidazole, 6-carboxymethyl-1- (2-.pyridyl) benzimidazole, 6-ethoxycarbonyl_2_methyl_1_ (4-nitrobenzyl) Benzimidazole, 1- (4-aminobenzylethoxycarbonyl_2_fluorenylbenzimidazole, 1-[(4-benzylamino) benzyl] _6_ethoxycarbonyl-2-methylbenzimidazole , 1-[(4-benzylamino) benzyl 6-carboxy-2_methylbenzimidazole, 6-ethoxycarbonyl-2-fluorenyl_1- [4- (2-benzylvinyl) Benzyl] benzimidazole, 6-ethoxycarbonyl-2-methyl_1- [4- (2-benzylethyl) benzyl] benzimidazole, 6-carboxy-2-fluorenyl-1- [4 -(2-benzylethyl) benzyl] benzobenzyl, 1-[(4_benzyl) pentyl] -6-ethoxyquinyl-benzylbenzyl, paper scale suitable / 1 ] Chinese National Standard (CNS) Λ4 specification (210X 297 mm) I t. I! I HI II-i- = I 548272 V. Description of the invention (50) '~-salivary, W (4-benzylyl), winter slow _2_methylbenzyl, and _2_methyl- [4- (2-styryl) ) Benzyl] stupid ^ 〇 ^ ^ Bu (a sub-sigma sigma _ soil) -6-ethoxyquinyl-2-fluorenyl stupid and scented ^ Renopican. 2-methyl) -2-methylbenzoacetone, 6 • ethoxyquinyl_2_methylpyridinylmethyl) benzozazole, 6_stilbyl_2_ Fluorenyl small (2-βchalinelinemethyl) benzimidazole, 1- (2,4-di-oxobenzyl) -2_ meridyl_6_ethoxyquinylbenzimidazole, 6-ethoxyquinyl -2-methyl-small [3_ (4_mo-isoisopyrene) methyl] benzoyl salivate, and 6 provinces_2 • methyl_ [3 · (4_mo-isoisocyline) methyl] benzene A specific example of a benzimidazole derivative of the compound represented by the formula (XI) is 1 · (2-Azobenzyl) _6-ethoxyquinyl, benzyl, and 2_ Benzyl carboxyl gas benzyl) benzimidazole, h benzyl_6_carboxyl 1- (2-chlorobenzyl) benzimidazole, 2_benzylcarboxyl] _ (2,4_dichloro ^ ¥ Group) benzimidazole, 24 groups, 6-membered group small (2,4 dichloro substituted group) benzimidazole, 2-benzyl azobenzyl) _6_ethoxycarbonylbenzimidazole, 1 benzyl chloride Benzyl) -5-ethoxycarbonylbenzimidazole, fluorenylbenzyl (2,4-dichlorobenzyl) _6_ethoxycarbonylbenzimidazole, fluorenylbenzyl_1_ (2, each dioxobenzyl ) -5-ethoxycarbonylbenzimidazole, 1_ (2-chlorobenzyl) _2_methylbenzimidazole-6-acetate Acid, gas, benzyl group > fluorenylmethyl benzimidazole-6-methacrylic acid, 丨-(2-gaso benzylmethylbenzimidazole-6-acrylic acid, 1- (2-chloro Benzyl) _6- [2_ (σ than pyridylmethyl) carbamoyl] benzimidazole, 1- (biphenyl-4-methyl) _6_ethoxycarbonyl-2-methoxymethylbenzimidazole, 1- (biphenyl-4-methyl) _6_carboxymethoxymethylbenzimidazole, 1- (4-benzyloxybenzyl) -6-ethoxycarbonyl_2_methoxymethylbenzimidazole, ^ This paper is suitable for China National Standard (CNS) A4 size (210X297 public housing) (may read the precautions on the back before filling in this page, \: 口 54 548272 A7 B7 V. Description of the invention (51 (4 this oxybenzyl ) Lingji-2_methoxymethylbenzyl Mixin II # benzyl) -6-ethoxycarbonyl_2 · methoxymethylbenzimidazole, and qi (翱 Please read the notes on the back before filling (This page) 1-(2,4-Dichlorobenzyl) -2-methoxyf-based benzo miso, etc. as an example. Specific examples of the benzo-M derivative represented by the soil formula (χΠ) can be mentioned as follows: 6th butyl milk carbon-based small (2- oxobenzyl) -2 n-phenyl benzoyl saliva, 1 oxo. " The result is called 2 · n-propylbenzyl, w_6 ethyl ethyl amine small (2-benzylidene) -2-n-propylbenzimidazole, amine chlorobenzyl f n-propylbenzimidazole , 丨 ^ chlorobenzyl) -2-n-propyl · 6-ureidobenzimidyl °, 6 · 3rd T oxoylamino-1- (2-chlorobenzyl) · 2-form US benzimidazole, 6-amino-fluorenyl 2-azabenzyl) _2_methylbenzimidazoline, and 6- (1-butanesulfonylamino) -1- (2-chlorobenzyl) _Methylbenzimidazole and the like. Specific examples of the benzoyl salivary derivative represented by the formula (XIII) include 1- (2-chlorobenzyl) -6-cyano-2-cyclopropylbenzimidazole, and 1- (2-chloro Benzyl) -6-cyano-2-n-propylbenzimidazole and the like. Specific examples of the benzimidazole derivative represented by the formula (VI) include 1- (2-chlorobenzyl) (4-diamidinobenzylcarbonyl) _2-n-propylbenzimidazole, and 2 • chlorobenzyl) -2-n-propyl-6-thiomorpholine carbonyl benzimidazole, 丨 ((chlorochlorobenzyl) -2-cyclopropyl-6- (2-pyridylcarbonyl) benzyl Benzimidazole, 6- (2-carboxy-1 * -pyridyl carbonyl) -1- (2-gaso-benzyl) -2-n-propylbenzimidazole, di (2-gaso-benzyl) -6- [N-fluorenyl-N- (pyridinyl) carbonylcarbonyl 2-n-propylbenzazole, 1- (2-chlorobenzyl) _6_piperidylcarbonyl-2-n-propylbenzyl miso, 1- (2-Azobenzyl) -6- (Hypiperidinylcarbonyl) _2-n-propylbenzyl, 1- (2-Azobenzyl) -6- [N-fluorenyl-N -(2 "Bipyridine) Weiji] -2-The original paper size selection claw SI national standard (CNS) A4 specification (210X29 ^ 7 mm) ----- 548272 A7 ^ ^ ------- -B7 V. Explanation of the invention (52) — '--propylbenzimidazole, 2-n-butyl-1- (2-fluorobenzyl) _6_ [n_methyl_ (2 than fluorenylmethyl) Phenyl] benzimidazole, 2-cyclopropyl_ι_ (2-fluorobenzyl) > 6- (piperidylcarbonyl) benzimidazole, 2-[[1- (2-chlorobenzylethyl) Benzimidazole-6-yl] carbamidomethyl] pyridine oxide, and (2,4-monogaso benzylmethyl-6- (2 • pyridylcarbonyl) benzimidazole, etc. are exemplified. Also listed below The novel benzimidazole derivative is also included in the present invention, and the material is W2-bromobenzyl) ethoxycarbonyl-2-n-propylbenzo. M, ze, 6_ethoxy Small groups (2 · Azobenzyl n- = benzimidazole, 6-ethoxycarbonylfluorobenzyl) _2-n-propylbenzimidazole, 6_ethoxycarbonyl-1- (3-fluorobenzyl ) -2-n-propylbenzimidazole, 1- (2,6-dichlorobenzyl) -6-ethoxycarbonyl-n-propylbenzimidazole, 1- (3-methylbenzyl) _6_ethoxycarbonyl _2_n-propylbenzimidazole, 2_fluorenyl6ethoxy ^ yl_1_ (2_fluorobenzyl) benzimid., Ι_ (2_fluorobenzyl) _2-cyclobutyl- 6-ethoxycarbonyl benzimidazole, 丨 _ (2_oxobenzyl) -6-ethoxycarbonyl_2_n-pentylbenzimidazole, 5_carboxy_ 丨 _ (2 • oxobenzyl) _2 _N-propylbenzimidazole, 6_carboxy_ 丨 _ (3_methylbenzyl) _2_n-propylbenzimidazole, 2-n-butyl-7 · carboxy-1 · (2-air benzyl) Benzimidazole, 6-carboxyl- 丨 _ (2-fluorobenzyl) _2_cyclopropane Benzimidazole, 1-n-butyl-6-carboxy- 丨 pneumidofluorobenzyl) benzimidazole, 丨 fluorenylchlorobenzyl) _6_ chlorocarbonyl-2-cyclopropylbenzimidazole, gas孓 Gas benzyl) _6_morpholinecarbamidinyl-2-n-propylbenzimidazole, 2-n-butyl-1- (2-chlorobenzyl) dong [(2 "pyridylmethyl) Aminofluorenyl] benzazole, 2-n-butyl-5aminocarbamyl-1- (2_fluorobenzyl) benzimidazole, 1- (2_chlorobenzyl) _ This paper Standards apply Chinese National Standards (CNS) (21〇 > < 297 public envy)

Order A7 548272 _________B7 _ V. Description of the invention (53) (Please read the precautions on the back before filling out this page} After the central sample of the M department, 工 only eliminates the cooperation and stamps the dream 2-cyclopropyl-6-? Lymphylbenzimidazole, 1_ (2-chlorobenzyl) -2-cyclopropyl-6-[(2-β specific sulfanyl) carbamoyl] benzyl alpha, ι_ (2 -Chlorobenzyl) -2-cyclobutyl-6-[(2-ton fluorenylmethyl) aminomethylfluorenyl] benzoumisaline, 1- (2-fluorobenzyl) -2-n-propyl 5--5-((2-pyridinyl) carbamoyl) benzimidazole, 1- (2-airobenzyl) -6-benzaminofluorenyl-2-n-propylbenzimidazole, 1 -(2-Aminobenzyl) -2-n-propyl-6-[(4-pyridinyl) carbamoyl] benzimidazole, 1- (2-chlorobenzyl) -2-n-propyl -6-[(3- ° specific fluorenyl) aminofluorenyl] benzimidyl. 1- (3_fluorenylbenzyl) -2-n-propyl-6-[(2- ° specific fluorenyl Carbamoyl) benzoyl sigma, 1_ (2-chlorobenzyl) -2-ethyl · 6-[(2-Qiudinyl) aminoamido] benzimidazole, 2 -N-butyl-1 · (2-chlorobenzyl) -7-[(2-pyridinyl) carbamoyl] benzimidene 4,1- (2-fluorobenzyl) -6-ethyl Oxycarbonyl_2 _Methylbenzimidyl salivate, 1- (3 -airofluorenyl) -6-ethoxyquinyl-2-n-propylbenzoxyl, 1-amyl-6-ethoxyn-n-propyl Stupid and scented α, 1 _ ('Azobenzyl) _ 6-ethoxyquinyl-2-n-propylbenzo. Scent, 6-ethoxyquinyl_2_fluorenyl_ 1- [2- (Dioxofluorenyl) fluorenyl] benzimidyl, 6_ethoxyweiyl_2_fluorenyl-1- [4_ (trifluorofluorenyl) benzyl] benzimidazole, 1_ (3, 4 · Dichlorobenzyl) -6-ethoxycarbonyl-2-methylbenzimidazole, 6-ethoxyquinyl-2-methyl-1- (2-fluorenylbenzyl) benzimidazole, K4- 3rd Benzyl ethoxyl group 2_methylbenzimidazole, 1_ (2-chlorobenzyl) quinone_ethoxycarbonylmethylbenzimidazole, i_ (2,6-dichlorobenzyl) _6 _Ethoxycarbonyl_2_fluorenylbenzimidazole, 1- (2,4-dioxobenzyl) -6-ethoxycarbonyl_2-methylbenzimidazole, 6-carboxy-K4-oxobenzyl Group) _2-n-propylbenzimidazole, 6 • carboxy-l- (2,6-digaso-benzyl) -2-methylbenzimidazole, 6-carboxy_2_ 曱 Basic paper scale Home Standard (CNS) A4 Specification (21G X297 ^) '-------_ 548272 A7 B7 V. Description of the Invention (54) [2- (trifluoromethyl) benzyl] benzimidium , Heart carboxy_2_methyl- 丨-^^ difluoromethyl) benzyl] benzimidal, 6_weiyl-1_ (3,4_digasobenzyl) _2_methylbenzamizineσ Sat, 1-fluorenyl-6-weiyl-2-n-propylbenzyl sigma miwa, 6-Ichizyl-1- (3-oxobenzyl) -2-n-propylbenzo sial, & Branyl_ι_ (24-dichlorobenzyl) _2_methylbenzimidazole, 1_ (4_th; 3 butylbenzyl) _6_carboxy-2-methylbenzimidazole, 6-carboxy-2-methyl 1- (2-methylbenzyl) benzimidazole, 1-benzyl-6-carboxy-2-methylbenzimidazole, 5-carboxy air-benzyl) -2-methylbenzimidazole, 6 _Carboxylchlorobenzyl) _2_methylbenzyl, 1- (2,4-monochlorofluorenyl) -2-methyl-6-[(2-. Specific sulfonyl) aminofluorenyl] benzimidazole, 1- (2-chlorobenzyl) -2-fluorenyl-6 _ [(fluorenylpyridinyl) aminofluorenyl] benzimidazole, 1- ( 3-Aromatic benzyl) _2_n-propyl_ 6-[(2 · -pyridinyl) aminopyridyl] benzimidazole, 丨 _pyridyl_2_n-propyl-6-[(2 -. Than stilbene) amino stilbyl] stupid β-single, 1- (4- azabenzyl) -2-propyl-6-[(2-. Pyridylmethyl) carbamoyl] Benzimidazole, ^ (2,6-dichlorobenzyl) -2-methyl-6-[(2-pyridylmethyl) carbamoyl] benzimidazole, 2-fluorenyl-6-[( 2- [alpha] pyridinyl) aminoamino (trifluoromethyl) fluorenyl] benzo sigma, 2-fluorenyl-6-[(2-position fluorenyl) aminofluorenyl] _1 -[4- (trifluoromethyl) benzyl] benzimidazole, 1- (3,4-dioxobenzyl) -2-methyl-6-[(2-tetramethylpyridyl) carbamate Brewing group] Stupid glutamate rice sigma, 2-fluorenyl small (2-fluorenylbenzyl) -6-[(2-Quet fluorenyl) aminophosphonic acid group] benzo flavor wow, 1_septyl_ 2 · fluorenyl-6-[(2- ° specific fluorenyl) aminofluorenyl] benzimidazole, 1- (4-third butylbenzyl) -2-fluorenyl-6-[(2-pyridylmethyl ) Aminopyrene] Benzimidazole, 6-Ammonia Fluorenyl-1- (2,4-difluorobenzyl) _2_ fluorenylbenzimidazole, 1- (2,4-difluorobenzyl) -2-methyl-6-[(2-pyridine Methyl) This paper has passed the Chinese National Standard (CNS) standard Λ4 specification (210X 297 mm) (诮 Please read the notes on the back before filling in this page ^^ 1. \ 、 线 一 548272 ΚΊ Β7 V. Description of the invention (55) —carbamoyl] benzimidazole, 1- (2,4-difluorobenzylfluorenyl_5_ [(2-α than fluorenyl) aminofluorenyl]] benzoσmidine, Difluorobenzyl > 7-ethoxycarbonyl-2-fluorenylbenzimidazole, 7_carbonyl q_ (2,4_digaso benzyl) _2_fluorenylbenzimidazole, 1_ (2,4_ Dioxobenzyl) _ 'ethoxycarbonyl-2-fluorenylbenzimidazole, 4-carboxyl-1- (2,4_dioxobenzyl) _2_methylbenzimidazole, 1- (2, 4-dioxobenzyl > 5-ethoxycarbonylmethylbenzoxazole, 5-carboxy- ^ 2,4-dichlorobenzyl) -2-methylbenzimidazole, and & (n-butyl Aminofluorenyl) -1- (2,4-dichlorobenzylfluorenylbenzyl) Benzoimidazole derivatives of the present invention as described above and their pharmaceutically acceptable salts are based on It is also sugar effect active, for example Impaired glucose tolerance, diarrhea (n-type diabetes), diabetic comorbidities (urinary nephropathy, diabetic dysmenorrhea, diabetic omentum), insulin resistance syndrome (insulin receptor abnormalities, Robs) 〇 Heart

Mendenhall ^ #, leprechaunism ^ Kobberling-Dunnigan Syndrome =, Seip Syndrome, Lawrence Syndrome, "Second-end megacephaly syndrome, etc.), Hyperlipidemia, Atherosclerosis, Heart = Duct Disease (Arrhythmia, Arrhythmia) Etc.), high ▲ glycemia (such as those with abnormal glucose metabolism characteristics such as ⑤ imbalance), or hypertension and other preventive and therapeutic functions; based on its cGMP-PDE (especially PDE_ P production level , Bone tendon relaxation, tracheal dilation, vasodilation, π tendon cell inhibition, allergic inhibition, etc., for stenosis, hypertension, pulmonary hypertension, congestive heart failure, glomerular disease: (such as diabetic Globular sclerosis, etc.), Urinary tubulointerstitial disease (Read the precautions on the back before filling out this page ... 1T

π (RJ

(In the formula (I), 'Ri is a hydrogen atom, arylsulfonyl group, or a lower alkyl-based alkyl group, 548272. V. Description of the invention (56) Disease (such as based on FK506, insufficiency such as cyclosporine, atherosclerosis , Kidney disease caused by vascular stenosis), those after renal surgery), is it too wide? Such as 'percutaneous arterial formation, the latter) terminal hemorrhagic disease, cerebral hemorrhage, chronic diseases (such as bronchitis, asthma (chronic asthma'), soil rhinitis, ramie therapy, glaucoma, characterized by intestinal motility "Yu Er"), allergies (such as allergic intestinal material), impotence (eg 疾病 7 disease: = urine :; and as fine as diabetes: diabetes: diabetes mellitus omental disease, etc.),: two f; cancer, It is quite effective in the prevention and treatment of various diseases such as restenosis after PCTA and the like. The inventors have found that the inventors cannot disclose it as a c_GMp phosphodiesterase in Unexamined Japanese Patent Publication No. 5-22000. Inhibitory benzobenzazole derivatives also exhibit the aforementioned activity, that is, these benzoimidazole derivatives can be used as effective therapeutic or preventive agents as the aforementioned compounds. That is, the present invention also includes the following formula: The representative benzimidazole derivative or a pharmaceutically acceptable medicament with the salts thereof as an active ingredient, (I) The low paper size is suitable for cutting, and the family standard (CNS) M specification (21〇 > < 297 mm (诮 Read the precautions on the back before (Write this page), -port 548272 A7 ------------------- B7 ^ V. Description of the invention (57) — ~ — ---- You can use optional free _ prime Atom, haloaryl, lower alkynyl, i-lower alkynyl 'lower alkynyl, schottyl, amine, cyano, aryl, aryl lower alkynyl, arylloweroxy, fluorenylloweroxy , One or two groups in the group consisting of lower aromatic group, lower alkynyl group, arylheteroamino group, cyanoaryl group and heterocyclic group may be substituted by 4, or aryl & or heterocyclic group may be substituted. Is a hydrogen atom, a lower cycloalkyl group, a hydroxyl group, a lower alkoxy group, a fluorenyl group, a lower alkylthio group, an amine group, a lower alkylamino group, a carboxyl group, an aryl group, or a lower alkyl group; a halogen atom may be used for the lower academic group , Lower dioxy, cyano, carbonyl, aryl, or heterocyclyl. R3 is carboxyl, esterified carboxyl, amidated carboxyl, amine, amidino, or sulfonyl; The amine group and the sulfonyl group may be substituted with a fluorenyl group or a sulfonyl group; the sulfonyl group is a combination with a hydrogen atom, an amine group, or a sulfonyl group. Also, I may be through a lower alkylene group or Lower alkenyl group Binding. R # is a neutral substituent. R4 may be a halogen atom, or a phenyl group, an aralkyl group, an alkynyl group, a lower alkoxy group, or the like. When R4 is an L group, it It can be saturated or unsaturated, chain or cyclic, and it can also be branched. When it is a prime atom or substituted with a prime, any kind of halogen can be used, and the number is not limited. Η represents 0 An integer of ~ 3. Therefore, one, two, or three R4 can be combined without &. The binding position is ortho, meta, and para for other substituents. Both can be.); It can be used as glucose tolerance disorders, diabetes (type II diabetes), diabetes comorbidities (diabetes% scale remote wealth ¥ 国 ^ 7 ^ 7 ^ specifications (2ι〇χ297 | ^ '~ --- --- ------ Pull, 丨 (谙 Please read the notes on the back before filling in this page j 、 = 口 口 548548 6JL. A7 V. Description of the invention (58) Sick nephropathy, diabetic insulin resistance syndrome w = ㈣ Diseased omentum, etc.),

Me H, n, group (insulin receptor abnormality, Robson-

Mendenhall syndrome nLePrechaumsm > Kobberling-

Dunnigan Syndrome, sg P Syndrome, Lawrence Syndrome, Cushing Syndrome, Anterior Meridian ^ 石 # 介 ， 广 ，， 1-； 正 寺), Hyperlipidemia, Atherosclerosis (Arrhythmia, Arrhythmia, etc.) 'High Glycemic disease (for example, those with the characteristics of glucose metabolism in the form of ingestion 矣 矣, Tiao Temple), or high blood pressure '+5, disease, hypertension, #hypertension, congestive heart failure (such as diabetic glomerulopathy) Bulbar sclerosis, etc.), urinary tubulointerstitial diseases "such as renal disease due to FK506, cyclosporine, etc.), renal insufficiency, atherosclerosis, vascular stenosis (e.g., percutaneous arterial surgery ), Peripheral vascular disease, cerebral hemorrhage, chronic reversible occlusive disease (such as bronchitis, asthma (chronic asthma, allergic asthma), allergic rhinitis, measles, glaucoma, diseases characterized by abnormal bowel movements (such as Allergic bowel syndrome), impotence (such as organic impotence, mental impotence, etc.), diabetic comorbidities (such as diabetic gangrene, diabetic joint disease, diabetic glomerular stiffness Disease, diabetic skin abnormalities, diabetic neurological abnormalities, diabetic cataracts, diabetic retinopathy, etc.), nephritis, malignant cancer, or restenosis after PCA, etc., pharmaceutical preparations for use as a therapeutic agent. Formula (I The specific examples of benzimide represented by) are butyl-1- (2-gaso-benzyl) -6-ethoxycarbonylbenzimidazole, 1-gas 4-bromo_2_fluorobenzyl ) -2-butyl-6-ethoxycarbonylbenzimidyl. Sat, 2-butyl-1_ (2 'monochlorobenzyl) -6-ethoxycarbonylbenzimidazole, 2-butyl-6-ethoxycarbon brewing paper scale Shizhou China National Standard (CNS ) A4 specification (210X 297mm) (read the precautions on the back before filling this page), = 口 • 丨 line 48272 A7 B7 invention description (59) — 1- (4-methoxycarbon-based base) Stupid sigma, butyl winter ethoxyl-W2'fluorobenzyl) benzo-sigma sigma, 2-butyl · buthoxyxyl small & trifluorofluorenyl (benzyl) benzimidyl Salivary, W2-Atomyl radicals) Ethoxybenzyl ethylbenzimidazole, i- (2-Atomylbenzyl) _6_ethoxycarbonylpropylbenzimidazole, 1- (2-chloro Benzyl) -2-cyclopropyl-6-ethoxycarbonylbenzimidazole, 1- (2-Gasoxybenzyl) -6_ethoxycarbonyl-2-isopropylbenzimidazole, 2-butyl 4 -(2-Atomylbenzyl) -5-ethoxycarbonylbenzimidazole, 2 ... butyl- 丨 Azobenzylchlorobenzyl) -7-Ethoxycarbonylbenzimidazole, 丨 Atomobiumbenzyl) _5_ethoxycarbonyl-2-propylbenzimidazole, 2-butyl_1- (2-chlorobenzyl) _6_carboxybenzimidazole, 2-butyl-6-carboxy-1- (4- Carboxybenzyl) benzimidazole, 6_carboxy-1- (2-chlorobenzyl) -2-ethylbenzimidazole, 6-carboxy-1β (2-chlorofluorenyl) -2-propylbenzimidazole, 6-carboxybenzyl) _2_ ring Propyl benzimidazole, 2-butyl-5-carboxy-1- (2-fluorobenzyl) imidazole, 2-butyl-1- (2-fluorobenzyl) -6 · dimethylaminofluorene Fluorenylbenzimidazole, 6- (benzylaminofluorenyl) -2-butyl-i ^ 2-chlorobenzyl) benzimidazole, 2-butyl 1 (2-oxofluorenyl) -6-? Pour a few bases of benzo. Perylene, 2-Butyl-6 · aminofluorenyl- (2-fluorobenzyl) benzimidazole, 2-butylchlorofluorenyl) -6- (4-fluorenyl group) Weidylbenzo ^ Αα, 2-butylamino substituted fluorenyl) -6- (fluorenylaminofluorenyl) benzo, σα, ^ aminopyridinyl (2-aminobenzyl) -2-ethylbenzyl Benzimidazole, 6-aminofluorenylaminobenzyl) _2-propylbenzimidazole, 6-aminobenzylaminobenzyl) _ 2-cyclopropylbenzimidazole, 2-butylaminobenzyl -κ (2-chlorobenzyl) benzimidazole, 2-butyl-1- (2-gaso-benzyl) -6_ (isopropylcarbonyl) benzimidazole, 1- (2-gaso-benzyl) -6-Chloroformyl-2_propylbenzyl (Please read the precautions on the back before filling in this page j

1. The paper size of the 1T line paper has passed the Chinese National Standard (CNS) A4 specification (210X 297 Gongchu) 548272 Α7 Β7 5. Invention Description (60) (Please read the precautions on the back before filling in this page and imidazole, (2-chlorobenzyl) -6- (methylaminomethylmethyl) -2-propylbenzimidazole, 1- (2-aminobenzyl) _6- (ethylaminomethylmethyl) _2_ Propyl benzimidazole, 1- (2-gaso-benzyl) _6_ (isopropylcarbamoylpropylbenzimidazole, 1-gaso 2-benzyl) _6_ (piperidinecarbonyl) _2_propyl Benzimidazole, oxobenzyl) -bu (morpholinecarbonyl) -2-propylbenzimidazole, 1- (2-chlorochloro) -6- (2-morpholineethylcarbamoyl) b 2 -Propylbenzimidazole, 1- (2-fluorobenzyl) _6- [4_ (2-hydroxyethyl) piperidinyl] carbonyl-2-propylbenzimidazole, 1- (2-chlorobenzyl ) -2-propyl-6- (2-pyridylmethyl) carbamoylbenzimidazole and 1- (2-chlorobenzyl) -2-propyl-6- [4- (4- Phenyl-1,2,3,6-tetrahydrotantidine 4-yl) butyl] carbamoylbenzimidazole and the like are taken as examples.

1T line ^ ^ ^ ^ the original and sigma sigma derivative when used in therapy, can make it suitable for oral or external use of organic, inorganic solids or liquid excipients as pharmaceutically acceptable A carrier, thereby forming a commonly used pharmaceutical preparation containing the aforementioned derivative as an active ingredient. The pharmaceutical preparations can be solids such as tablets, granules, powders, or capsules, and can also be liquids such as solutions, cornice's solution, syrup, emulsion, lemonade, and the like. If necessary, the above preparations may also contain auxiliaries, stabilizers, wetting agents and other commonly used additives such as lactose, citric acid, tartaric acid, stearic acid, magnesium stearate, white clay, sucrose, temple powder, talc, Gelatin, cold weather, pectin, groundnut oil, olive oil, cocoa butter, vinyl alcohol, etc. Although the amount of the aforementioned derivative varies with the patient's age, conditions, and the type and state of the disease, as well as the type of the aforementioned derivative, the amount of the derivative used is generally daily when taken orally- ———————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————— for the scales for injection is 0.1 to 10 mg / kg once a day. [Brief Description of Drawings] FIG. 1 is a diagram showing chemical formulas of compound (42) to compound (47). FIG. 2 is a diagram showing chemical formulas of compound (48) to compound (53). FIG. 3 is a diagram showing chemical formulas of compound (54) to compound (59). FIG. 4 is a diagram showing chemical formulas of compound (60) to compound (65). FIG. 5 is a diagram showing chemical formulas of compound (66) to compound (71). FIG. 6 is a diagram showing chemical formulas of compound (72) to compound (77). FIG. 7 is a diagram showing chemical formulas of compound (78) to compound (83). FIG. 8 is a diagram showing chemical formulas of compound (84) to compound (89). FIG. 9 is a diagram showing chemical formulas of compound (90) to compound (95). FIG. 10 is a diagram showing chemical formulas of compound (96) to compound (101). FIG. 11 is a diagram showing chemical formulas of compound (102) to compound (107). FIG. 12 is a diagram showing chemical formulas of compound (108) to compound (113). FIG. 13 is a diagram showing chemical formulas of compound (114) to compound (119). FIG. 14 is a diagram showing chemical formulas of compound (120) to compound (125). FIG. 15 is a diagram showing chemical formulas of compound (126) to compound (131). FIG. 16 is a diagram showing chemical formulas of compound (132) to compound (137). FIG. 17 is a diagram showing chemical formulas of compound (138) to compound (143). FIG. 18 is a diagram showing a chemical formula of a compound (144) to a compound (149). FIG. 19 is a diagram showing chemical formulas of compound (150) to compound (155). FIG. 20 is a diagram showing chemical formulas of compound (156) to compound (161). FIG. 21 is a diagram showing chemical formulas of compound (162) to compound (167). FIG. 22 is a diagram showing chemical formulas of compound (168) to compound (173). _65_ The size of this paper is China State Standard (CNS) A4 (210X 297 mm) (read the precautions on the back before filling out this page), order 548272 A7 B7 5. Description of the invention (62) Figure 23 shows the compounds (174) ~ Chemical formula of compound (179). FIG. 24 is a diagram showing chemical formulas of compound (180) to compound (185). FIG. 25 is a diagram showing chemical formulas of compound (186) to compound (191). FIG. 26 is a diagram showing chemical formulas of compound (192) to compound (197). FIG. 27 is a diagram showing chemical formulas of compound (198) to compound (203). FIG. 28 is a diagram showing chemical formulas of compound (204) to compound (209). FIG. 29 is a diagram showing chemical formulas of compound (210) to compound (215). FIG. 30 is a diagram showing chemical formulas of compound (216) to compound (221). FIG. 31 is a diagram showing chemical formulas of compound (222) to compound (227). FIG. 32 is a diagram showing chemical formulas of compound (228) to compound (233). FIG. 33 is a diagram showing chemical formulas of compound (234) to compound (239). FIG. 34 is a diagram showing chemical formulas of compound (240) to compound (245). FIG. 35 is a diagram showing chemical formulas of compound (246) to compound (251). FIG. 36 is a diagram showing chemical formulas of compound (252) to compound (257). FIG. 37 is a diagram showing chemical formulas of compound (258) to compound (263). FIG. 38 is a diagram showing chemical formulas of compound (264) to compound (269). FIG. 39 is a diagram showing chemical formulas of compound (270) to compound (275). FIG. 40 is a diagram showing chemical formulas of compound (276) to compound (281). FIG. 41 is a diagram showing chemical formulas of compound (282) to compound (287). FIG. 42 is a diagram showing chemical formulas of compound (288) to compound (293). FIG. 43 is a diagram showing chemical formulas of compound (294) to compound (299). FIG. 44 is a diagram showing chemical formulas of compound (300) to compound (305). FIG. 45 is a diagram showing chemical formulas of compound (306) to compound (311). Fig. 46 is a diagram showing chemical formulae of compound (312) to compound (316). _66 This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) (read the precautions on the back before reading this page), 1T Φ. 548272 A7 B7 V. Description of the invention (63) (Read the back on read (Please fill in this page again for precautions) Figure 47 shows the chemical formulas of compound (317) to compound (322). FIG. 48 is a diagram showing the chemical formula of compound (323) to compound (328). FIG. 49 is a diagram showing chemical formulas of compound (329) to compound (334). FIG. 50 is a diagram showing chemical formulas of compound (335) to compound (340). FIG. 51 is a diagram showing chemical formulas of compound (341) to compound (346). FIG. 52 is a diagram showing chemical formulas of compound (347) to compound (352). Fig. 53 is a diagram showing chemical formulas of compound (353) to compound (358). Fig. 54 is a diagram showing chemical formulas of compound (359) to compound (364). Fig. 55 is a diagram showing chemical formulas of compound (365) to compound (370). FIG. 56 is a diagram showing chemical formulas of compound (371) to compound (376). FIG. 57 is a diagram showing chemical formulas of compound (377) to compound (382). FIG. 58 is a diagram showing chemical formulas of compound (383) to compound (386). [Best Mode for Carrying Out the Invention] The present invention will be specifically described below with reference to the examples, but the present invention is not limited to these examples. < Production Example 1; Production of 3- [N- (2-bromobenzyl) butylamidino] -4-nitrobenzoate ethyl ester > Sodium hydride (100 mg, 60% suspension in oil) was added to a solution of ethyl 3-butylamido-4-nitrobenzoate (247 mg) in N, N-dimethylformamide (10 ml) . The reaction suspension was stirred at room temperature for 1 hour, and a solution of 2-bromobenzyl bromide (244 mg) in N, N-diamidinofluorene (2 ml) was slowly added dropwise over 10 minutes. After the aforementioned reaction mixture was stirred at room temperature for 1 hour, it was poured into ice water. Extraction of the oily substance with dioxane, __67_ This paper is in accordance with the Chinese National Standard (CNS) A4 specification (210X 297 mm) 548272 A7 B7_____ V. Description of the invention (64) (Read the precautions on the back before reading Fill out this page again) After washing with water and drying the organic solvent layer, it was concentrated under reduced pressure. The residue was developed by gel permeation chromatography, and was extracted with 25% ethyl acetate / n-hexane to give 3- [N- (2-bromobenzyl) butylamido] -4- as a yellow oil. Ethyl nitrobenzoate (540 mg). [Physical properties of compounds] ^ -NMR (CDCh, δ): 0.87 (3Η, t5 J = 8Hz) 3 1.48 (3H5 t3 J = 8Hz), 1.68 (2 H, sextet, J 2 8Hz) 3 2.03 (2H3 t, J2 8Hz), 4.30-4.46 (2H, melons), 4.70 (1H, d, J = 15Hz), 5.40 (1H, d, J2 15Hz), 7.08_7 · 34 (2H, in), 7.43 (1H, dd3 J = 1, 8 Hz), 7.58 (1H, dd, J2 1, 8Hz), 7.66 (1H, d, J2 1Hz), 7.96 (1H, d, J2 8Hz 8 • 16 (1H , Dd, J = 1, 8 Hz). ≪ Production Example 2; Production of 3- [N- (2-chlorobenzyl) phenylamidino] -4-nitrobenzoate > Using 3- Ethyl benzamino-4-nitrobenzoate (450 mg) and 2-chlorobenzyl bromide (243 mg) and 3- [N- ( 2-Chlorobenzyl) phenylamino] -4-nitrobenzoate (480g). [Physical properties of the compound] lH-NMR (CDCla, δ): 1.35 (335, t3 J = 8Hz) 5 4.35 (2H, q3 J-8Hz), 4.76 (1 H, bd, J = 15Hz), 5.82 (1H, bd, J = 15Hz), 7.10-8.00 (12H, m). That is: 111-113 ° C. ; Production Example 3; Preparation of 3- [N- (2-fluorobenzyl) butanamido] -4-nitrobenzoate Production> Ethyl 3-butylamido-4-nitrobenzoate (300 mg) and 2-fluorobenzyl bromide (243 mg) were used in the same manner as in Production Example 1 with ____ —-Ω ----- This paper size applies the middle-paid family standard ([Milk) 8 4 size (21 (^ 297 mm) 548272 Α7 Β7 V. Description of the invention (65) The yellow oily 3- [ N- (2-Fluorobenzyl) butylammonium l-4-nitrobenzoate (394g). [Physical properties of the compound] Ή-NMR (CDC13, 6): 0.85 (3H, t, J ^ SHz), 1.40 (3H, t, J = 8Hz), 1.65 (2H, sextet, J = 8Hz), 1.98 (2H, t, J = 8Hz), 4.30-4.45 (2H, m) 3 4.60 (1H, d5 J = 10Hz), 5.25 (1H, d, J = 10Hz), 6.88 (2H, t, J = 8Hz), 7.08 (2H, dd, J = 5, 8Hz), 7.24 (1H, dt, J = 1, 8Hz), 7.41 (1H, dt, J = 1, 8Hz), 7.69 (1H, d, J = 1Hz), 7.96 (1H, d, J: 8Hz), 8 · 15 ( 1H, dd, J = 1, 8Hz). < Production Example 4; Production of 3- [N- (4-fluorobenzyl) butylamidino] -4-nitrobenzoate ethyl ester > Using 3-butylamido-4-nitrobenzoate Acid ethyl ester (300 mg) and 4-fluorobenzyl bromide (243 mg) and 3- [N- (4-fluorobenzyl) benzene hydrazone as a yellow oil was obtained by the same method as in Production Example 1. Amino] -4-nitrobenzoate (400 g). [Physical properties of compound]! H-NMR (CDCh, δ): 0.86 (3Η, t, J-8Hz), 1.37 (3H, t, J-8Hz), 1.56-1.76 (2H, m), 1.96-2.04 ( 2H, m), 4 · 32-4 · 46 (2H, m), 4.40 (1H, d, J = MHz), 5.23 (1H, d, J = 14Hz), 6.95 (2H, t, J2 8Hz), 7.10 (2H, dd, J2 5, 8Hz), 7.47 (1 H, d3 J = lHz), 7.95 (1H, d, J = 8Hz), 8.16 (1H, dd, J = l, 8Hz) < Production Example 5; Production of 3- [N- (2-cyanobenzyl) butyramidinyl] -4-nitrobenzoate ethyl ester > Calcium carbonate (296 mg) was added to 3- In a solution of butylammonio-4-nitrobenzoate ethyl ester (200 mg) and 2-cyanobenzyl bromide (154 mg) in N, N-diamidinofluorenylamine, stir at 20 ° C for 3 hours . Use of ethyl acetate and ________ μ- This paper size applies to China National Standards (CNS) Α4 size (210X 297 mm) (read the precautions on the back before filling this page)

1T 548272 A7 ---------------- B7__ 5. Description of the invention (66) Water is used to separate the aforementioned reaction mixture, and the organic layer is washed with water and brine. Dry over magnesium sulfate. After distilling off the solvent, you can get yellow (please read the precautions on the back before filling in this page) 3- [N- (2-cyanobenzyl) butylamidino] -4-nitro Acetyl Benzoate (330mg). [Physical properties of compound] Η Earn (CDCh, (5): 0.86 (3H, t, J: 8Hz), 1.49 (3H, t, J: 8Hz), 1.67 (2H, sextet, J2 8Hz), 2.02 (2H, t, J 8Hz), 4.28-4.52 (2H, m), 4.90 (1H, d, J: 15Hz), 5.28 (1H, d, J 2 15Hz), 7.40 (1H, t, J = 8Hz), 7.61 (1H, dt, J = 1, 8Hz), 7.70 (1H, d, J: 1Hz), 7.74 (1H, dd, J: 1, 8Hz), 8.02 (1H, d, J: 10Hz), 8 • 22 (1H, dd, J = 1, 10Hz). ≪ Manufacturing example 6 > ≪ Production Example 6-1; 3 · [N- (3-I-generation benzyl) butyramido] -4 · nitronitrobenzoate > [physical properties of the compound] yellow oil. LH-NMR (CDCh, 6): 0.86 (3Η, t, J: 7.5Hz), L35 (3Η, t, J = 7.5Hz) 1 68 (2H, ffl), 2.00 (2H, t, J = 7.5Hz), 4.36 (1H, d, J = 15Hz), 4.40 (2H m) 5 31 (1H, d, J: 15Hz), 6.85-7 · 28 (4H, m), 7.60 (1H, d , 7.97 (1H d J = 10Hz), 8.16 (1H, dd, J = 10, 1.5Hz). ≪ Production Example 6-2; 4-nitro-3- [N- (2-pyridylmethyl) >; N-butylamine [Base] -Ethyl Benzoate > This compound is used directly in the process described below. ________ 74 —_-__ _ This paper rule is a Chinese national standard ((: milk) 8 4 size (21〇'297 mm) ^ 548272 In the Ministry of Economics, the jujube and the jujube are replaced by 5 and combined with bamboo ii. A7 -------------------- E___ V. Description of the invention (67) [Compound of Physical properties] Yellow oil. ≪ Production Example 6_3; 3_ [N_2,6_dichlorobenzyl) butanamido] _4-nitrobenzoate ethyl ester > [Physical properties of compound] Old-dirty (CDCh, 6 ) 〇 89 (3H, t, J: 7.5 Hz), 1.38 (3H, t, J 2 7. 5Ηζ), 1.70 (2Η, m), 2.03 (2Η, t, J: 7.5Hz), 4.36 (2Η, m), 4.96 (1Η, d, J = 13.5Hz), 5.70 (1H, d, J = 13.5Hz), 7.10-7.28 (3H, m), 7.49 ( 1H, d, J = 1.5Hz), 8.03 (1H, d, J = 7_5Hz), 8.14 (1H, dd, J =: 7.5 and 1.5Hz) c mp: 85 —89 ° C. < Production Example 6-4; 3- [N- (3-methylbenzyl) propanamido] -4-nitrobenzoate ethyl ester > This compound was used directly in the production process described below. [Physical properties of the compound] Yellow oil. < Production Example 6-5; 3- [N- (2-fluorobenzyl) cyclopropanefluorenylamino] -4-nitrobenzoate ethyl ester > [Physical properties of compound] A yellow oily substance. W-NMR (CDCh, 6): 0.60-0.71 (2H, m), 0.91-1.14 (3H, m), 1.38 (3H, t, J = 7.5Hz) 3 4.37 (2H, m), 4.62 ( 1H, d, J = 12Hz), 5.30 (1H, d, J = 12Hz), 6.92 (1H, t, J: 7.5Hz), 7.10 (1H, t, J: 7.5Hz), 7.26 (1H, m) , 7.42 (1H, t. J = 7 • 5Hz), 7.80 (1H, s), 7.99 (1H, d, J: 7.5Hz), 8.14 (1H, dd, J: 7.5 and 2Hz) State Chinese National Standard (CNS) A4 Specification (2 丨 0X 297 mm) (Please read the precautions on the back before filling this page)

、 1T ΛΨ. 548272 A7 __________________B7 V. Description of the invention (68) " < Production example 6-6; 3- [N- (2-Chlorobenzyl) cyclobutanefluorenylamino] _4_ Nitrobenzoic acid Ethyl esters> [Physical properties of compounds] (Read the precautions on the back before filling this page) ^ -NMR (CDCh, d); K37 (3H, t3 J = 7.5Hz), L68-L87 (4H3 m), 2.Z2-2.58 (2H, m), 2.75-2.94 (1H, m), 4.23-4.46 (2H, m), 4.63 UH, d, J: 15Hz), 5.

45 (1H5 d5 J = 15Hz), 7.14-7.24 (3H5 m) 5 7.35-7.45 (1H) m) 3 7.56 (1H3 d, J 2 2Hz), 7.97 (1H3 d, J: 9Hz), 8 · 13 (1H, dd, J: 9, 2Hz). < Production Example 6-7; 3-cyclobutanefluorenylamino-4_nitrobenzoate ethyl ester > [Physical properties of compound] (cdci3,6): 143 (3H, t, j: 7.5Hz ), 186-219 ⑽, melon), (4H, m), 3.20-3.41 (1H, m), 4.43 (2H, q, J: 7.5Hz), 7.80 (1H, dd, J = 10 , 2Hz) 3 8.26 (1H5 d5 J-10Hz), 9.45 (1H5 d5 J-2Hz) 〇 That is: 94-960C < Preparation 1 ^ Example 7; 3-acetamido-4-nitro'ylbenzo Production of hydrazine > The gaseous ethylenedioxane (3.9lml) was dripped into a gas of 3-acetamido-4-nitrobenzoic acid (7.00g) in a nitrogen atmosphere under an ice bath In a simmered (50 ml) solution, stir in an ice bath! For 2 hours, stir at room temperature for 2 and a half hours. After distilling off the reaction solvent, it was dissolved in tetrahydropyran (50 ml), and dropped into ammonia water (28/0) in a nitrogen bath under an ice atmosphere. After the reaction solution was stirred for 1 hour, water and acetic acid were added, and the precipitated solid (ca. 8 g) was filtered off. After the filtrate was separated into layers, the organic layer was washed with water, and the solvent was removed under reduced pressure by using the stone 'IL & L after drying', so as to obtain a residue. By using hot ethyl acetate, the purpose is to wash and filter the precipitated solids and residues. The size of this paper applies Chinese National Standard (CNS) A4 specifications (210X 297 mm) 548272 A7 ___________B7 V. Description of Invention (69) 3-Ethylamido-4-nitrobenzofluorenamine (4.94 g) was obtained. [Physical properties of the compound] 4-wake (DMS0-d6, ά): 2.08 (3H, s), 7.68 (1H, br s) 3 7.78 (1H, dd, J 2: 9, 2Hz), 7.94-8.05 (2H, m), 8.23 (1H, brs).

Mass (FAB): Z24〇 < Production Example 8; Production of 3- [N- (2-chlorobenzyl) acetamidinyl] _4-nitrobenzopyramine > This method is used to produce 3- [N- (2-chlorobenzyl) acetamidinyl] -4 · nitrobenzopyramine. [Physical properties of compound] W-dirty (DMS0-d6, (5): 1.86 (3H, s), 4.64 (1H, d, J = 15Hz), 5.06 (1H, d, J-2 15Hz) ), 7.22-7 · 40 (4H, m), 7.73 (1H, br s) 5 7.84 (1H, d, J = 2Hz), 8.03 (1H, dd, J: 9, 2Hz) , 8.14 (1H, d, J: 9Hz), 8.22 (1H, br s) 〇 < Production Example 9; 3- [N_ (2-Azobenzyl) acetamidinyl] -4-nitrobenzo Production of nitrate> In a nitrogen atmosphere, 1,4-dioxane (30 ml) was dropped into a dichloromethane solution (4 ml) of titanium tetragas (1.70 ml), and then A solution of 3- [N- (2-chlorobenzyl) acetamidinyl] _4-nitrobenzopyramine (2.70 g) was added dropwise to a solution of 4-bisσ oxalate (65 ml). After 15 minutes, triethylamine (3.14 g) was added, and the mixture was stirred in an ice bath for 2 hours. After the reaction was completed, the pressure was reduced to remove > cereals'. Water and acetic acid were added to the residue. After layering, the organic The layer was washed with water and dried with sulfuric acid, and then the pressure was reduced to remove the solvent. The column chromatography [200 ml, n-hexane-ethyl acetate (4-1)] was used to purify the residue to obtain 3- [N- (2-Atomylbenzyl) acetamidinyl] -4-nitro This ^ rule 'Guanjia County 1 CNS) A4 specifications (21Qx 297 = attack) ~ " (Read the precautions on the back before filling in this page), 11 Φ. 548272 Α7 Β7 V. Description of the invention (70) Tritium (1.21g). [Physical properties of compound] (Xu first read the precautions on the back and then fill out this page) 1 orbital (CDC13, 6): 1.92 (3H, s), 4.61 (1H, d, J 2 15Ηζ), 5. · 40 (1H, d, J = 15Hz), 7 · 18_7 · 50 (5H, m), 7 · 80 (1H, dd, J = 9, 2Hz) 3 801 (1H, d, J = 9Hz). Mass (FAB): 300.

IR (Nujol): 2250cm lQ < Production Example 10; Production of 3- [N- (2-Gas-benzyl) amino] -4-nitrobenzonitrazine > 35% hydrochloric acid (lml) A solution of benzyl) acetamido] -4-nitrobenzofluorenamine (850.11 M in dioxane (10 ml) was added and heated under reflux for 4 days. After the reaction liquid was distilled off, The layers were separated in a mixed solution of water and chloroform. The organic layer was washed with water, dried over magnesium sulfate, and then depressurized to remove the solvent. Column chromatography [50 ml, chloroform] The residue was purified to obtain 3- [N- (2-chlorobenzyl) amino] 4-nitrobenzopyrene (230 mg). [Physical properties of the compound]! -NMR (CDCh, (5): 4.65 (2H, d, J: 6Hz), 6.93 (1H, dd, J: 9, 2Hz), 7.10 (1H, d, J = 2Hz), 7.25-7.40 (3H, m), 7.40-7.54 (1H , M), 8.30 (1H, d, J: 9Hz), 8.45 (1H, br s), Mass (FAB): 258. IR (Nujol): 2220cm'l0 < Production Example 11; 4-amine Of 3-methyl-3- [N- (2-chlorobenzyl) amino] benzonitrazine> 10% palladium carbide (50 mg) was added to 3_ [N · (2-chlorobenzyl) amino] _4_ This paper size applies Chinese National Standard (CNS) Α4 regulations (210 × 297 mm) 548272 In the Ministry of Economic Affairs ^-^ h T, Consumption Hezhuzhuan $ A7 B7 V. Description of the invention (71) Nitrobenzonitrate (261mg), methanol (15ml), 1 In a mixed solution of 4,4-dioxane (3 ml), contact reduction was performed in a hydrogen atmosphere at 3 atmospheres. After the reaction was completed, the reaction solution was filtered through celite and the pressure was reduced to remove the filtrate. Ether was used. The obtained solid was washed and filtered to obtain 4-amino_3- [N- (2-chlorofluorenyl) amino] benzophenone (196 mg). [Physical properties of the compound] ^ -NMR (DMS0 -d6, δ): 4.39 (2H5 d3 J = 5Hz), 5.57 (1H, t5 J-5Hz), 5.69 (2 H, s), 6.46 (1H, d, J = 2Hz), 6.61 (1H, d, J: 9Hz), 6.88 (1H, dd, J = 9, 2Hz), 7.25-7.41 (3H, m), 7.44-7.54 (1H, m) 〇 < Example 1; Synthesis of 1- (2-bromobenzyl) _6-ethoxycarbonyl_2-n-propylbenzimidazole (42) > 3 · [N- (2-bromobenzyl) butanamido] Ethyl-4-nitrobenzoate (390 mg) and reduced iron (21 mg) were added to a mixed solution of acetic acid (iml) and ethanol (2mi) to form a suspension. The suspension was refluxed for 1 hour. Stir it vigorously. After the reaction was completed, it was cooled, filtered through celite, and then subjected to reduced pressure to concentrate the filtrate. Ethyl acetate and an aqueous solution of sodium bicarbonate were added to the residue to form a layer. After the organic solvent layer was dried, the solution was distilled under reduced pressure to obtain a brown residue. This residue was purified by column chromatography to give 1- (2-bromobenzyl) _6 ″ ethoxycarbonyl-2-n-propylbenzimidazole (42) (160mg) ° [Physical properties of compound (42)] H- NMR (CDCla, δ): 1.04 (3H, t, J-8Hz), 1.40 (3H, t, J = 8Hz), 1.78-1.98 (2H, m), 2.34 (2H, t, J = 8Hz) , 4.38 (2H, q, J: 8Hz), 5.45 (2H, s), 6.65 (1H, t, J-8Hz), 7.00 (in, tj J = 8Hz), 7.13 (1H, t5 J = 8Hz), 7.28 (1H3 t, J, (诮 Please read the precautions on the back before filling in this page),-口 Φ.

The decision of the Ministry of Economic Affairs and the elimination of the combination of bamboo fir and India 548272 A7 ----------------------., __ ____B7 V. Description of the invention (72) 8Ηζ), 7 · 78 (1H, d, J Ι 10Ηζ), 7.99 (1H, d, J = 10 Hz), 80 (1H, s). mp: 134-135 ° C. < Example 2 Synthesis of 1,1- (2-cyanobenzyl) -6-ethoxycarbonyl-2-n-propylbenzimidazole (43) > Use 3- [ N- (2-cyanobenzyl) butyramidinyl] -4-nitrobenzoate (390mg). Substantially the same method as in the example to give 1- (2-cyanobenzyl) as colorless crystals. ) _6_Ethoxycarbonyl_2_n-propylbenzimidazole (43) (160mg) 〇 [Physical properties of compound (43)] INMβ (CDC13, (5): 1, 4 (3H, t5 J: 8Hz) , 1.40 (3H, t, J: 8Hz), 1.88 (2 H, sextet, J: 8Hz), 2.80 (2H, t, J: 8Hz), 4.38 (2H, q, J 2 8Hz), 5. · 62 (2H, s) 5 6.57-6.63 (1H3 m) 3 7.38-7.50 (ZH5 m) 3 7.78 (1H, dd3 Jl, 8Hz) 3 7.79 (1H, d, J: 8Hz), 7.94 (1H, d, J: 1 Hz) 3 8,03 (1H, dd5 J: 13 8 Hz). mp: 132-134 ° C < Example 3; 1- (2-Azobenzyl) -6-ethoxycarbonyl Synthesis of 2-phenylbenzimidazole (44) > Using 3- [N- (2-chlorobenzyl) phenylamidino] -4-nitrobenzoate ethyl ester (460 mg) The method used in the examples to give 1- (2-chlorobenzyl) -6-ethoxycarbonyl-2-benzylbenzimid as yellow crystals (44) (220mg) ° [Physical properties of compound (44)] 'H-NMR (CDCh, δ): 1.40 (3Η, t, J-8Hz), 4.38 (2H, q, J = 8Hz), 5.56 (2H , s), 6.72 (H, dd, J = 1, 8Hz), 7.18 (1H, dt, J: 1, 8Hz), 7.30 (1H, dt, J = 1, 8Hz), 7.45-7.55 (4H , m), 7.64 (1H, d3 J ^ lHz), 7.68 (1H, d, J ^ lHz), 7.9 ---------------- This paper size applies to Chinese national standards ( CNS) A4 specification (210X 297mm) (诮 Please read the notes on the back before filling this page), \ 呑%! 548272 A7 B7 V. Description of the invention (73) ◦ (1H, d, J: 10Hz), 7 · 95 (1H, s), 8.08 (1H, dd, J: 13 8Hz). mp: 140-142 ° C. < Example 4; Synthesis of 6-ethoxycarbonyl-1- (2-fluorobenzyl) -2-n-propylbenzimidazole (45) > Using 3- [ N- (2-Fluorofluorenyl) butyramine] -4-Ethylshinoyl ethyl benzoate (390 mg) and the same method as in the example to give 6-ethoxyquinyl-1- (2-Fluorobenzyl) -2-n-propylbenzoxyl salivary (45) (160mg) 〇 [Physical properties of compound (45)] 1 (CDC13, 6): 1.04 (3H, t, J: 8Hz ), 1.40 (3H, t3 J: 8HZ), u-u (2H, m), 2.34 (2H, t, J = 8Hz), 4.38 (2H3 q, ιϋΗζ), 5.45 (2H, s) 6 65 (1H, t, J = 8Hz), 7.00 1H, t, J = 8Hz), 7.13 (1H, t, J = 8Hz), 7.28 (1H, t, J = 8Hz), 7.78 (1H , D, J = 10Hz), 7.99 (1H, d, J = 10Hz), 8.02 (1H, s). mp: 134-1350C. < Example 5; Synthesis of 6-ethoxycarbonyl-1-(4-fluorobenzyl) _2-n-propylbenzimidazole (46) > Use 3- [N- ( 4-Fluorobenzyl) butylammonio] -4-nitrobenzoate (400 mg) and the same method as in the example was used to give 6-ethoxyl-1-(4 as colorless crystals) -Fluorobenzyl) -2-n-propylbenzimidazole (45) (160mg) 〇 [Physical properties of compound (46)] 1 (CDCU d): 1.04 (3H, t, J: 8Hz), 1.40 (3H, t3 J: 8Hz) 5 i 88 (2H sextet, J-8Hz), 2.82 (2H, t, J-8Hz), 4.38 (2H, q, J ~ 8Hz) 5 3§ s)

· 00 (4H, d, J: 7Hz), 7.77 (1H, d, J = 8Hz), 7.98 (1H, d, J: 1HZ), 8 00 (1H) Standard (CNS) A4 specification (210X 297 mm) (诮 Please read the precautions on the back before filling this page)

1T 548272 A7 ____________________ B7 V. Description of the invention (74) 1, dd, J = 1, 8 Hz) mp: 134-1350C0 < Example 6 > The same method as in Example i was used to synthesize the following compounds. < Example 6-1; 6-ethoxycarbonyl-2-n-propylpyridylmethyl) benzimidazole (47) > [physical properties of compound (47)] Ή-NM (CDCls, 6): 1 · 03 (3H, t, ^ 7 · 5Ηζ), h39 (3H, seven, ㈣shu), ι 89 (2H5 m) 3 Z.86 (2H5 t5 J, 7.5Hz) 3 4.38 (2H3 q3 J, 7.5Hz ), 5.50 (2H, s), 6.7 2 (1H, d, J: 7.5Hz), 7.24 (1H, m), 7.58 (1H, dt, J: 7.5, 1.5Hz), 7.79 (1H, d, J : 7.5Hz), 7.96-8 · 02 (2H, m), 8.60 (1H, d, J: 4Hz). inp: 84 —85 ° C. < Example 6-2; 6-ethoxycarbonyl-1- (3-fluorobenzyl) _2-n-propylbenzothiazol (48) > [physical properties of compound (4 8)] INMR (CDCh , D): 1.04 (3H, t, J 2 7. 5Ηζ), 1.39 (3H, t, 1.90 (2H, m), 2.81 (2H, t, J: 7.5Hz) 54.39 (2H, q, J = 7.5HZ), 5.39 (2H, s), 6.7 0-6.84 (2H, m), 7.00 (m, dt, J: 8.5 and 1.5Hz), 7.78 (1H) d, J = 8.5Hz) , 7.96 (1H, s), 8.00 (1H, d, J: 8.5Hz). Mp: M2-146 ° C. ≪ Executive Example 6_3; l- (2,6_ two gas generation card Group) _6 · ethoxysulfanyl-2-n-propylbenzobenzo salivary (49) > [physical properties of compound (49)] This paper is in accordance with China National Standard (CNS) A4 size (210X297 mm) ( Please read the precautions on the back before filling this page), -5 '< > 548272 A7 ____________________ B7 V. Invention Description (75) (CDCla, ά): 1.03 (3Η, t5 J = 7.5Hz), 1.38 (3H5 t3 h88 (2H, m), 2.93 (2H, t, J: 7.5Hz), 4.34 (2H, q, j: 7.5Hz), 5 61 (2H, s) w 6 (1H, d, J = 7.5Hz), 7.39 (2H, d, J = 7.5Hz), 7 68 (ih, d, > 7.5Ηζ), 7 ^ · 1H, d, J-1.5Hz), 7.91 (2H5 d, J = 7.5Hz) mp: 153-156 ° C. < Example 6-4; 1- (3-methylbenzyl) + ethoxyquinyl_2_n-propyl (诮 Please read the precautions on the back before filling this page) Basic And taste saliva (50) [physical properties of compound (50)] colorless solid. 1 side (CDCl3, ㈨: (3H, t, ㈣ · 5Ηζ), 141 (3H, seven, ㈣ · 5Hz) [2H, m), 2.29 (3H, s), 2.82 (2H, t, J = 7.5Hz) 3 4.38 (2H, q, J = 7.5Hz) 5 3 5 (2H, s), 6.79-6.86 (2H, ffi) , 7.09 (1H, d5 J = 7.5Hz), 7.20 (1H, t, J = 7.5HZ), 7.76 (1H, d, J: 7.5Hz) 3 7.95-8 · 02 (2H, m) . < Example 6-5; 2-cyclopropyl-6-ethoxycarbonyl_H2_fluorobenzyl) benzimidazole (51) > [physical properties of compound (51)] H-NME (CDCh, δ): 1.1〇 (2Η, m) 3 1.27 (2H, m), 1.40 (3H, t5 J = 7.5Hz), 1.95 (1H, m), 4.37 (2H, q, J 2 7 · 5Ηζ), 5.56 (2H, s), 6.77 (1H, t, J, 7.5Hz), 7.03 (1H, t, J: 7.5Hz), 7.13 (1H, t, J: 7.5Hz), 7.29 ( 1H, ιη), 7.69 (1H, d, J: 7.5Hz), 7.96 (1H, d, J = 7.5Hz), 8.02 (1H, d, J = 2Hz). mp: 122-126 ° C < Example 6-6; 1- (2-Gas benzyl) -6-cyano-2-cyclopropylbenzimidazole (52) > [Compound (52) Physical properties] > 79 This paper is sized to China National Standard (CNS) A4 (210X297 mm),-= " 548272 A7 B7 V. Description of the invention (76) 'H-NKR (CDCh5 δ): 1.04- 1.24 (ZH, m) 3 1.24-1.39 (2H5 m) 5 1.83-2.01 (1H, m), 5.58 (2H, s) 5 6.54 (1H, d5 J to 2Hz), 7.16 (1H, td, J : 9, 2Hz), 7.22-7 (Please read the precautions on the back before filling this page) • 38 (1H, m), 7.43-7 · 56 (3H, m), 7.74 (1H, dd, J : 9, 2Hz).

Mass (FAB): 308 (M + 1) 〇IR (Nujol): 2210 cm 10 < Example 6-7; 1- (2-chlorobenzyl) -2-cyclobutyl-6-ethoxycarbonyl Benzimidazole (53) > [Physical properties of compound (53)] ^ -NMR (CDCh, δ): 1.38 (3Η, t3 J = 7.5Hz), 1.90-2.21 (2H5 m) 5 2.Z1-2.24 ( 2H3 m) 5 2.46-2.70 (2H3 m) 3 3.52-3,73 (1H, m), 4.37 (2H3 q3 J = 7.5Hz) 3 5 • 39 (2H, s), 6.34 (1H, dd3 J = 9 , 2Hz), 7.06 (1H, td, J = 9, 2Hz), 7.23 (1H, td, J = 9, 2Hz), 7.46 (1H, dd, J = 9, 2Hz), 7.83 (1H, d, J = 9Hz), 7,92 (1H, d, J = 2Hz), 8.01 (1H, dd, J = 9, 2Hz). mp: 111-113 ° C < Examples 6-8; 1- (2-chlorobenzyl) -6-ethoxycarbonyl-2-n-pentylbenzimidazole (54) > [Compound (54 Physical properties) ^ -NMR (CDCla, δ): 0.87 (3H5 t, J-7.5Hz), 1.22-L47 (7H5 m) 3 1.74 ^ 1.93 (2H, m), 2.80 (2H, t, J = 7.5Hz), 4.37 (2H, q, J = 7.5Hz), 5.47 (2H, s), 6 39 (1H, dd, J2, 9, 2Hz), 7.08 (1H, td, J2 9, 2Hz), 7.19-7.33 (1H5 m), 7.48 (1H, dd, J = 9, 2IL), 7.79 (1H, d, J = 9Hz), 7,94 (1H, d3 J = 2Hz), 8.00 (iH dd, J 9.2, 2 Hz) < Example 7; 5-carboxy-1-(2-chlorobenzyl) -2-n-propylbenzimidazole (55) > The paper scale speed Use Chinese National Standard (CNS) A4 specification (210X297 mm) 5 you 272 A7 ________________B7 V. Description of the invention (77) Combine ethanol (20ml) with 10%. /. Aqueous sodium hydroxide solution (104 g) is added with 1- (2-gaso-benzyl) -5-ethoxycarbonyl j n-propylbenzimidazole (2.8 g) (read the precautions on the back before filling this page) Middle 'reflux for 4 hours. After the reaction solution was cooled, 0% hydrochloric acid was used to adjust the pH to 6. The crystals were collected, washed with water and dried under reduced pressure to give 5-carboxy-1 gas 2-chlorobenzyl) -2-n-propylbenzimidazole (55) (2.46 g) as a colorless solid. [Physical properties of compound (55)] 4-NMR (DMS0-d6, (5): 0.93 (3H, t, J: 7.5Hz), 1.75 (2H, m), 2.79 (2H, t , J = 7.5Hz), 5.61 (2H, s), 6.49 (1H, d, J: 7.5Hz), 7.21 (1H, t, J: 7.5Hz), 7.33 (1H, t, J = 7.5Hz), 7.46 (1H, d, J = 7.5Hz), 7.56 (1H, d, J = 7.5Hz), 7.8 〇 (1H, d, J = 7.5Hz) 3 8.20 (1H, s) 〇 < Example 8> The following compound was synthesized using the same method as in Example 7. < Example 8-1; 6-carboxy-1- (3-methylbenzyl) -n-propylbenzimidazole (56 ) > [Physical properties of compound (56)] A colorless solid. w-⑽⑽ so-d6, cnu⑽, t, J = 7.5Hz), L78 (2H, m), 2.23 (3h, s)

, 3.86 (2H, q, J = 7.5Hz), 5.53 (2H, s), 6.80 (1H, d, J: 7.5Hz), 6.91 (1H, S), 7.07 ( 1H, d, J: 7, 5Hz), 7.21 (1H3 t, J = 7.5Hz), 7′5 (1H, d, j: 7.5Hz), 7 • 79 (1H, d, J: 7.5Hz), 8.04 (1H, s) 0 '< Example 8-2; 2 · n-butylcarboxychlorobenzyl) benzimidazole (57) > This paper is suitable for the national standard (CNS) A4 specification of F1 ( 210X297 mm) 548272 A7 __________ _B7 V. Description of the invention (78) [Physical properties of compound (57)] INMR (DMS0-d6, 6): 0.84 (3H, t, J: 7.5Hz), 1.34 (2H, id) , [Π ⑽, m), 2.80 (2H, t, J: 7.5Hz), 5.89 (2H, s), 6.03 (1H, d5 J: 7.5Hz), 7.13 (1Η, t, J: 7.5Hz), 7.27 (2H, t5 7.48 (1H, d, J: 7.5Hz), 7.63 (1H, d, J-7.5Hz) 3 7.87 (1H3 d3 J-7.5Hz). Example 8-3; 6-Weiyl-2-cyclopropyl-1- (2-fluorobenzyl) benzimidazole C58) > [physical properties of compound (58)] 4-ugly (DMS〇- d6, d): 1.04-1.19 (4H, m), 2.37 (1H, m), 5.79 (2H, s), 7.0MlH, t, J: 7.5Hz), 7.15 (1H , T, Jt 7.5 Hz), 7.27 (1H, t, J: 10.5 Hz) 7.37 (1H, m), 7 · 60 (1H, d, J = 7.5Hz), 7 · 82 (1H, d, J: 7.5Hz), 8 · 11 (1H, s). That is: 224-229 ° C < Example 8-4; 2-n-butyl-6-carboxy-1- (2-fluorobenzyl) benzimidazole (59) > [Compound (59) Physical properties]-Ship (DMS0-d6, ά): 〇 87 (3H, t, J: 7.5Hz), 1.26-1.48 (2H, m), 1.60-1. 80 (2H, m), 2.90 ( 2H, t3 J: 7.5Hz), 5.63 (2H, s) 3 6.89 (1H, td, J: 9, 2Hz), 7.13 (1H, td, J2 9, 2Hz), 7.20-7 · 44 (2H, m), 7.64 (1H, d, J = 9Hz), 7.80 (1H, dd, J: 9, 2Hz), 8.08 (1H, d, J: 2Hz). mp: 216-219 ° C. < Example 9; Synthesis of 1- (2-gaso benzyl) -6-gasocarbonyl-2-cyclopropylbenzimidazole hydrochloride (60) > 6-Carboxy-1- (2-chlorobenzyl) -6-chlorocarbonyl-2-cyclopropylbenzimidone (390 g) was added with the second one containing N, N-difluorenimidine (1 drop) Chloroprene This paper is suitable for standard / fll7 standard (CNS) A4 (21GX 297 ^ cent) (Please read the precautions on the back before filling this page) Order-ΦΙ. 548272 A7 B7 V. Description of the invention (79) -(诮 Please read the precautions on the back before filling this page) 〇㈣ to prepare the suspension. At room temperature, vaporized ethyl acetate (0.208 ml) was dropped into the suspension over several minutes. After stirring at room temperature for 2 hours, the mixture was concentrated under reduced pressure. Diisocyanate is added to the residue and ^ finished to obtain a white powder! ♦ Chlorobenzyl X chlorochixyl cyclopropylbenzimidazole hydrochloride (60) (45 mg). Due to its unstable nature, it does not need to be refined and can be directly used as the raw material for the next step. 〆 < Example 10; Synthesis of 1- (2-chlorobenzyl) > 6_ (4-dimethylaminobenzylaminomethylamidino) -2-n-propylbenzimidazole (61) >; 6-Chloro-1- (2-chlorobenzyl) _2-n-propylbenzimidazole (40 mg) was dissolved in methylene chloride added with j drops of n, n_dimethylformamide (3 ml). Ethylene dichloride (28 mg) was added to the aforementioned solution at 5 C. The resulting solution was stirred at room temperature for 1 hour and then concentrated under reduced pressure. The residue was dissolved in dichloromethane ( 3mi), was added at room temperature to a mixed solution consisting of monomethylaminobenzidine hydrochloride (27 lmg) and dichloromethane (iomi) added with triethylamine (1ml). The obtained reaction mixture was stirred at room temperature for 丨 hours, washed with water and dried, and then concentrated under reduced pressure. The residue was developed and purified using thin-layer chromatography to obtain 丨 _ (2_chlorobenzyl) -6- (4- Difluorenylaminobenzylaminofluorenyl) _2-n-propylbenzimidazole (61) (215mg). [Physical properties of compound (61)] Colorless crystal. (CDCl3, ά): (3H, t, J: 7Hz), 1.88 (2H, sextet, J: 7Hz), 2. (2H, t, J: 7Hz), 2.95 (6H, s), 4.50 (2H, d, J: 5Hz), 5.45 (2H, s), 6.32 1H3 d, J: 5Hz), 6.36 UH, d, J: 7Hz), 6.72 (2H, d, J: calendar z) 3 7 · 07 (1H, dt This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X 297 mm) 548272 A7 __________________B7_ V. Description of the invention (8〇) 'Q , 8Hz), 7.20-7.25 (3H, m), 7.46 (1H, dd, J 2 1,8Hz) 3 7.58 (1H, dd, J: i, 8Hz), 7.76 (1H, d, J : 8Hz), 7.82 (1H, d, J: lHz). That is: 155-156 ° C. ≪ Example 1 l; (l- (2-chlorobenzyl) -6-morpholinaminomethylfluorenyl-2-n-propylbenzobenzoic acid (62) synthesis >; Using 6-Weiyi-1- (2-chlorobenzyl) -2-n-propylbenzo miso (200mg) and 4-aminomorphine (I24mg) and by the same method as in the examples In order to obtain 1- (2- oxobenzyl) -6-morphine aminopyrene-2-n-propylbenzoxaline (62) (205 mg). [Physical properties of compound (62)] Colorless crystals. lH-NMR (CDCh, δ): 1.03 (3H5 t5 J = 8Hz) 3 1.88 (2H, sextet, J = 8Hz) 5 2.62 (4H, bs), 2.72 (2H, t, J: 8Hz), 3 85 (4H, bs), 5.42 (2H, s), 6.42 (1H, dd, J: 1, 8Hz), 7.08 (1H, dt, J: 1, 8Hz), 7.20-7.28 ( 3H, m), 7.47 (1H, dd, Jl, 8Hz), 7.78 (1H3 dd, J = 113 8Hz). That is: 195-197 ° C. ≪ Example 12; 1- (2-chloro Synthesis of benzyl) -2-n-propyl-6-thiomorpholinecarbamoyl-benzimidazole (63) > Use of 6-retyl-1- (2-oxobenzyl) -2- N-propyl is stupid. Sit (200 mg) with thiomorpholine (125 mg) and use the same method as in Example 10 to give 1- (2-chlorobenzyl) -2-n-propyl-6 · thiomorpholine aminofluorene Fluorenyl-benzimidazole (63) (160 mg). [Physical properties of compound (63)]--; --μ—— This paper is suitable for China National Standard (CNS) A4 size (210X 297 mm) (please read the precautions on the back before filling in this page) 11 548272 A7-* ---------------------- B7____ 5. Description of the invention (81) A-colorless crystal. (Please read the precautions on the back first Fill in this page) H-plane (CDCh, (5): 1.03 (3H, t, J: 8Hz), 1.88 (2H, sextet, J: 8Hz), 2.78 (2H, t, J: 8Hz ), 2.96 (4H, bt, J: 5Hz), 3.88 (4H, bt, J: 5Hz), 5.46 (2H, s), 6.34 (1H, dd, J = 1, 8Hz ), 7.08 (1H, dt, J-2 1, 8Hz), 7.26 (2H, dt, J-2 1, 8Hz), 7.47 UH, dd, J: 15-8Hz), 7.58 (1H, bd , J = 8Hz), 7.76 (1H, s), 7.78 (1H5 d, J 2 8Hz), mp: 160-162 ° C, 〈Example 13; 2-n-butyl-1- (2-gas generation) Synthesis of benzyl) -6-[(2-pyridylmethyl) carbamoyl] benzilide (64) > using 6-carboxy-2-n-butyl-1- (2-chlorobenzyl ) Benzimidazole (200 mg) and 2-aminomethyl. Bipyridine (126 mg) and by the same method as in Example 10 to obtain 2- Butyl-1- (2-chlorobenzyl) -6-[(2-pyridylmethyl) aminomethyl] benzocarbamidine (64) (2 3 Omg). [Compound (64) 's Physical properties] Colorless crystal. 4- Xinjiang (CDC13, (S): 0.92 (3H, t, J: 8Hz), 1.42 (2H, sextet, J: 8Hz), 1.82 (2H, quintet, J: 8Hz), 2.82 (2H, t, J: 8Hz), 4.76 (1H, d, J: 5Hz), 5.46 (2 H, s), 6.38 (1H, dd, J: 1, 8Hz), 7.08 (1H3 dt, J = 1, 8Hz), 7.18-7.26 (2H, m), 7.32 (1H, d, J: 8Hz), 7.46 (1H, dd, J: l, 8Hz), 7.62 (1H, dt, J: 1, 8Hz), 7.72 (1H, dt, J2, 1,8Hz), 7.82 (1H, d, J2, 8Hz) 3 7.88 (1H, d, J2, 1Hz), 8.56 ( 1H, dd, J: l, 8Hz). mp: 175-176 ° C. < Example 14; Synthesis of 2-n-butyl-5-aminomethylamidin-1- (2-chlorobenzyl) benzimidazole (65) > Paper size Shizhou Chinese National Standard (CNS) A4 specification (210X 297 mm) 548272 A7 _________________ __B7 V. Description of the invention (82) '~~ Use 2-n-butylchlorobenzyl) _5_aminofluorenylbenzimidazole (100 mg) and by the same method as in Example 10 to give fluorene n-butyl-5-aminofluorenyl-1- (2-chlorobenzyl) benzimidazole (65) (i70 mg) . [Physical properties of compound (65)] Colorless crystals. ^ -NMR (DMS0-d6, d): 0.84 (3H5 t3 J ^ 8Hz) 5 1.35 (2H, sextet, J = 8Hz), 1. 68 (2H3 quints J 2 8Hz), 2.78 (2H, t, J: 8Hz), 5.58 (2H, s), 6.50 (1h3 dd, J: 13 8Hz), 7.25 (1H, dt3 J = 13 8Hz), 7.28 (1H, bs), 7.35 (1H , Dt, J: l, 8Hz) 5 7.42 (1H, d3 J ^ lOHz), 7.56 (1H3 dd5 J, l3 8Hz), 7.74 (1H, dd5 J = l5 10Hz), 7.96 (1H3 bs), 8.20 (1H , D, J: lHz). mp: 195-198 ° C. < Example 15; Synthesis of 1_ (2-chlorobenzyl) _2_cyclopropyl_6-morpholinecarbonylbenzimidazole (66) > Morpholine (298mg, 30% methanol solution) was added Dioxane (10 ml) was prepared as a solution. Chlorobenzyl) -6-fluorocarbonyl-2-cyclopropylbenzimidazole hydrochloride (14 mg) was added to the aforementioned solution at room temperature. After stirring the descriptive reaction mixture at room temperature for 1 hour, it was washed with water and passed through the Shanghai Department ^ it ^-^ h Concentrated under reduced pressure. Ether was used to recrystallize the residue to give i- (2-fluorobenzyl) -2-cyclopropyl-6-morpholinylbenzimidazole (66) (20 mg). [Physical properties of compound (66)] Colorless crystals. Old-leg (CDCh, ά) · 1.04-1.12 (2H3 m), 1.25-1.32 (2H, m) 3 1.82-1 · 96 (1H, m), 3.68 (8H, bs), 5.56 UH, s), 6.55 (1H, dd, J = 1, 8Hz), 7.13 (1H3 dt, J = 1, 8Hz), 7.22-7 · 29 (2H, m), 7.30 (1η, d, J = 1Hz), 7.46 (m, dd, J = 1, the paper size is in accordance with China National Standard (CNS) A4 specification (21〇'x 297)) 548272 A7 B7 V. Description of the invention (83 ) 8Hz), 7.77 (1H, d3 J-8Hz) N mp: 193-1950C0 < Example 16; l- (2-chlorobenzyl) -2-cyclopropyl-6-[(2-pyridine Synthesis of methyl) carbamoyl] benzo1 ^ sal (67) > using 1- (2-chlorobenzyl) -6-chlorocarbonyl-2-cyclopropylbenzimidazole hydrochloride (150 mg), 2-aminomethylpyridine (85 mg) and the same method as in Example 15 was used to obtain 1- (2-fluorobenzyl) -2-cyclopropyl-6-[(2- Acetidylmethyl) carbamoyl] benzimidazole (67) (95 mg). [Physical properties of compound (67)] Colorless crystals. IMR (CDC13, 6): 1.02-1.13 (2H, m), 1.24-1.32 (2H, melon), 1.82_1.95 (1H, m), 4.76 (2H3 d3 J 2 5Hz), 5.59 (2Η, s ), 7 · 11 (1H, dt3 with 1,8Ηζ), 7 · 20_7 • 26 (2Η3 m) 3 7.34 (1Η3 d, J 2 8Ηζ) 3 7 · 46 (1Η, dd3 J: 15 5ΗΗ), 7 · 60 (1Η, t, J = 5Ηζ), 7.66 (1Η, dd, J = 1, 8Ηζ), 7.73 (1Η, s), 7.88 (1Η, s). mp: 134-1350C. < Example 17 > Following the same method as in Example 15, the following compounds were obtained. < Example 17-1; 1- (2-Azobenzyl) _2_cyclopropyl_6- (2 • pyridylaminomethylamidino) benzimidazole (68) > [Physical properties of compound (68) ]! H-orbit (CDC13, 6): 1.16 (2H, m), 1.32 (2H, π〇, ^ (1H, "), 5.61 (2H, s), 6.57 (1H, d, J 2 7.5 and 1.5Ηζ), 7.15 (1H, dt, J = 7.5 and 1.55Ηζ), 7.22-7 · 31 (2H, π), 7.48 (1H, dd, J = 7.5 and 1.55 ζ) , Γ.77 (iH, Mountain J: 9Hz), 8.05 (2H, m), mp: 206 —209 ° C. ____ & JZ-_ This paper standard applies to China National Standard (CNS) A4 specification (210X297 (Mm) (Read the notes on the back before filling in this page)

, 1T A7 B7 methyl) carbamyl] benzoflavor (71) > 548272 &, Description of the invention (84) < 贝 ^ 例 17_2; 6- (2-branched + ground slightly burned several bases ) -1- (2-chlorofluorenyl) -2-n-propylbenzimidazole (69) > [physical properties of compound (69)]

'H'-NMR (DMS0-d6, (5) · 0 Q9 (QU f T). 92 · (3H, t, j: 7.5Hz), j (catch 2 丨 "), 2.77 (2H, t, J: 7.5Hz), 3% r9w (2H, m), 4.40 (1H, ID), 5.52 (2H, s) • 53 (1H, d, J: 7.5Hz) 5 7 · 2 · 7 · 71 ( 6H, phantom. 邺: 96 ° C0: Examples are called chloro chlorobenzyl) _2 · cyclobutyl «A. Specific methyl) carbamoylmethyl] benzimidal (70 [Compound (70 )] 1 dirty coffee 3, < n: 1 | 2.21 (2H, E), 2.25_2 37 (2H, E) 24 > 3.64 (1H, m), 4.76 (2H, d, J = 5Hz) , 5.39 (2H, s), 6.33 ΠΗ,! 5Hz) '7.05 (1H, t, J = 7.5Hz), 7.16-7.26 (2H, m), 7 33 (1H ,, J-7. ⑽, d , J: 7.5Hz), 7.69_7.76 (3H, n), 7 7 · 3 ⑽, mountain village _5Hz), 7

> s), 8.55 (1H, d, J = 5Hz), J-7'5Hz, 7.86 (1H flip: 183-1850C)

LV ^ -UPC

[Physical properties of compound (71)] H-wake (CDCh, d): 1.03 (3H, t, J: 7.5Hz), 1 90 (2H, 9 ◦ UH, vomit 2.80 (2H, tj 2 7. 5Ηζ ), 4.80 (2H, d, J: 5Hz), 5.44 (2H, s), 6 40 (1Η η. '' Νιπ5 α, J = ^. 5Hz) 3 7.09 (1Η, t, J = 7.5Hz), 7 · 2, 7.27 (3Η, m), 7 · 34 (1Η d, 7 υυ \ 5 U, j ~ 7-5Hz), 7.47 (1Η5 d J, 2 · 7 · 5Ηζ) 3 7.64-7.72 ( 2Η, m), 7.83 (1Η, dd, J: 7.5 and 2Hz) 8 30, J: 2Hz), 8.56 (1H, d3 J: 5Hz). ’· (Condition d mp: 115—116 ° C 〇 This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) (Read the precautions on the back before writing this page)

548272 A7 V. Description of the invention (85) < Beta Example 17-5; 1- (2-chlorobenzyl) _6_ [N-methyl-N- (2.pyridylmethyl) aminomethylmethyl] -2-N-propylbenzo sial (72) > [Physical properties of compound (72)] (It is necessary to read the precautions on the back before filling in this page) H NKR (DMS0-d6, δ): 1.03 (3Η, t3 J = 7.5Hz), 1.87 (2H, m), 2.79 (2H, t, J-7.5Hz), 3.05 (3H) brs), 4.60 (1H, brs), 4.87 (1H, brs), 5.40 (2H, d, J ~ Unknown), 6.38 (1H3 d, J is unknown), 7.05 (1H, brs) 3 7.2.2 (3H, id), 7.35-7.49 (3H, m) 3 7.60 -7.81 (2H3 m), 8.54 (1H3 brs) 0: 990C < Example 17-6; l- (2-chlorobenzyl; piperonylcarbamoyl-2-n-propylbenzimidazole) (73) > [physical properties of compound (73)]

tNMR (CDC13,6): 1.01 (3H3 t, J: 7.5Hz), 1.88 (2H, m), 2.78 (2H, t, J 々 • 5Hz), 4.54 (2H, d, J = 5Hz), 5.45 (2H, s) 5 5.95 (2H3 s), 6.36 (1H, d, J

: 7 · 5Ηζ), 6.44 (1H, t, J: 5Hz), 6.75-6.85 (3H, in), 7.08 (1H, t, J = 7.5 · 5Ηζ), 7.23 (1H, t, J : 7.5Hz), 7.45 (1H, d, J = 7.5Hz), 7.67 (1H, dd,, 2H z), 7.78 (1H, d, J = 7.5Hz), 7.83 (1H, s). mp: 13l-134 ° C. &lt; Example 17-7; l- (2-chlorobenzyl) -6-phenylaminofluorenyl_2-n-propyl benzoyl salivary (74) &gt; [Compound (Physical properties of (74)] 'H-NMR (CDCh, (5); L03 (3H5 t, J = 7.5Hz), 1.90 (2H, m), 2.81 (2H, t5 J = 7.5Hz), 5.47 (2H, s), 6.40 (1H, d5 J-7.5Hz), 7.06-7.18 (2H, m), 7.26 (1 H, t, J: 7.5Hz), 7.35 (2H3 t, J 2 7.5 · ζ), 7.48 (1H, d, J 7.5Hz), 7.64 (2H, d, J-7.5Hz), 7.72 (1H, dd, J: 7.5 and 2Hz), 7.85-7.95 (3H, m). Mp: 168〇C〇 The paper size is 548272 A7 B7 V. Description of the invention (86) &lt; Guan Example 17_8; 1- (2-Chlorobenzyl) -2-n-propyl-6-[(4-σι ^ σ-Determined methyl) aminofluorenyl] benzimidazole (75) &gt; (Please read the precautions on the back before filling in this page) [Physical properties of compound (75)] Ή-NMR (DMS0-d6, δ): 0.93 (3Η, t, J = 7.5Hz) 5 1.76 (2H, m), 2.78 (2H, t, J = 7.5Hz), 4.49 (2H, d, J = 5Hz), 6.42 (1H, d5 J = 7.5 Hz), 7.22 (1H, t. J 2: 7. 5Hz), 7.27 (2H, d, J: 7.5Ηζ), 7.34 (1H, t, J: 7.5Ηζ), 7.57 ( 1H, d, J = 7.5Hz), 7 · 6 9 (1H, d, J2 7, 5Hz), 7.80 (1H, d, J2 7.5Hz), 7.97 (1H, s), 8.48 (2H, d, J = 7.5Hz), 9.03 (1H, t, J 2 5Hz). Mp: 170-173 ° C. &Lt; Example 17-7; l- (2-chlorobenzyl) · 2-n-propyl-6-[(3-. Ratio. Fixed methyl) Carbamidyl] benzimidazole (76) &gt; [physical properties of compound (76)] 4-pyrene (DMS0-d6, ά): 0.95 (3H, t, J = 7.5Hz), 1.76 (2H, m), 2.80 (2H, t5 J = 7.5Hz), 4.50 (2H, d, J: 5Hz), 5.60 (2H, s), 6.42 (lH, d, J = 7.5Hz), 7.2 3 (1H, t , J2 7.5Hz), 7.30-7.58 (2H, in), 7.57 (1H, d, J2 7.5Hz), 7.67-7.74 (2H3 m) 5 7.75 (1H, d5 J = 7.5Hz), 7.97 (1H , s), 8.46 (1H, d, J = 5Hz), 8.56 (1H, s), 9.0 (1H, t, J = 5Hz). mp: 193-195 ° C. &lt; Examples 17-lO; l- (2.chlorobenzyl) -6- [N-fluorenyl-N- (2-pyridine) aminofluorenyl] -2 -N-propylbenzimidazole (77) &gt; [physical properties of compound (77)] ^ -NMR (DMS0-d6, δ): 0.90 (3Η, t, J = 7.5Hz), 1.70 (2H, m), 2.73 (2H? T, J = 7.5Hz), 3.40 (3H, s), 5.42 (2H, s), 6.23 (1H, d, J = 7.5Hz), 6.91 (1H, d, J = 7.5Hz) 3 6.98 (1H, m), 7.15-7.25 (3H3 m) 5 7.36 (1H, t, J = 7.5Hz), 7.4 This paper size applies to China National Standard (CNS) A4 specification (210X 297 mm) 548272 A7 B7 5 、 Explanation of the invention (87) —7.57 (3H, melon), 8.23 '(ι3m) (nip: 143 — 146oC0 &lt; (Please read the precautions on the back before filling out this page) 贝 施 例 Π_1 1; 1_ (2 · Chlorobenzyl) _ό_ (piperidinylcarbonyl) _ 2-n-propylbenzimidazole (78) &gt; [Physical properties of compound (78)] 'H-NMR (CDCla, (5) · 1 〇〇, t J-75Hz) w /,), M6 丄 94 (rigid, m), 2.80 ⑽ UH, ^, W, 3 64 (2H, t, ㈣ _, 5 A (muscle recognition 6.like, z 5 7 ° 7 (1H, t, J-7.5Hz), 7.19-7.29 (3H, m), 7 45 (1H d &gt; 7.76 (1H, d, J = 7.5Hz)) UH) d mp: 136 -137 ° C〇 &lt; Example Π-12; W3_methylbenzyl) _2-n-propyl-6 _ [(2-pyridylmethyl) aminomethylamidino] benzimidazole (79) &gt; [Physical properties of compound (79) ] iHiMR (CDCh, Magic · 1.02 (3H, t5 J = 7.5Hz), 1.88 (2H3 m), 2.26 (3H5 s), 2.81 (2H, t, J: 7.5Hz), 4.76 (2H, d, J: 5Hz), 5.36 (2H, s), 6.78-6.84 (2h3 m), 7.07 (1H, d, J: 7.5Hz), 7.13- 7.22 (2H, id), 7.33 (1H, d, J: 7.5Hz), 7.57-7.72 (2H, m), 7.78 (1H, d, J: 7.5Hz), 7.94 (1H, s) ， 8,55 (1H, d5 J 2 5Hz) 〇mp: 129-1310C 〇 The middle part ?: Digestion fc Hexylidine t <Example 17_13; 2-n-butylfluorobenzyl) _6- [N -Methyl-N (2-. Pyridinyl) carbamoyl] benzimidazole (80) &gt; [physical properties of compound (80)] 1 leg (CDCh, d): 0.92 (3H, t, J: 7.5Ηζ), 1 · 45 (2H, melon), 1.83 (2H, m), 2.86 (2H, t3 J = 7.5Hz), 3.06 (3H, brs), 4.61 (1H, brs), 4.86 ( 1H, brs), 5.37 (2H, brd) 3 6.62 (1H, brd) 3 6.97 (1H, brs), 7.07-7.85 (8H, m) 3 8.57 This paper is compliant with China National Standard (CNS) A4 specifications ( (210X 297mm) 548272 M 浐 Department Zhong Rong playing season and: only _T eliminates the need to print A7 B7 V. Description of the invention (88) (1H, d, J: 5Hz). mp: 97-100 ° C. <Example 17] 4; 1- (2-chlorobenzyl) _2-ethyl winter [(2-pyridyl) carbamoyl] benzimidazole (81) &gt; [Physical properties of compound (8 1)] ^ -NMR (CDCh, δ): 1.43 (3H5 t5 J = 7.5Hz), Z.84 (2H5 q5 J-7.5Hz), 4.76 (2H, d, J: 5Hz), 5.45 (2H, s), 6.37 (1H, d, J: 7.5Hz), 7.07 (1H, t, J: 7.5H z), 7.19-7.28 (2H, ffl), 7. · 33 (1H, d5 J: 7.5Hz), 7.45 (1H, dd, J = 7.5 and Sha 2 Hz), 7.62-7 · 75 (3H, m), 7.82 (1H, d, J: 7.5 Hz), 7.89 (1H3 d, J: 2Hz), 8.55 (1H, d, J = 5Hz). mp: 167-168 ° C &lt; Example 1Ή; 2. n-butylchlorobenzyl) -7 _ [(2-pyridylmethyl) carbamoyl] benzimidazole (82) &gt; [Compound (82 ) Properties] NMR (CDCh3 (5): 0.93 (3H, t, J = 7.5Hz), 1.42 (2H, m), 1.83 (2H, m) 2.81 (2H, t, J = 7.5Hz ), 4.44 (2H, d, J 2 5Hz), 5.70 (2H, s), 6.13 (m '' ddl J = 7.5 and 2Hz), 6.85-6.97 (3H, m), 7.12- 7.28 (4H, m), 7.34 (1H, d, J 2 7 5Hz), 7.62 (1H, dt, J: 7.5 and 2Hz), 7.88 (1H, d, J = 7.5Hz), 8.40 (ih, (j J = 5Hz) ^ mp: U2-1140C ^ &lt; Example 17 · 16; 2-cyclopropyl-1- (2-fluorobenzyl) -M piperonylcarbamyl) is unpleasant. (83) &gt; [Physical properties of compound (8 3)] 'H-NMR (DMSO-dfi 5.71 (2Η, 3), 5598 Π), 2 27 UH, Π), 4.38 (2Η &gt; &quot; J = 5H ^ · 98 (2Η, S), 6.73-6.91 (4Η, m), 7.14 (lHj t, j = 7.5Hz)) 7 (诮 Please read the precautions on the back before filling this page)

、 1T ^ _wl. 548272 A7 _____—_____ B7 __ V. Description of the invention (8 9) 27 (1H, t, J 2 7.5Ηζ), 7.36 (1H, m), 7.55 (1H, d, J: 7.5 Hz), 7.73 (1H, dd, J = 7, 5 and 2Hz), 8 · 04 (1H, s) 3 8 · 87 (1H, t, J = 5Hz). mP: 170-173 ° C. &lt; Examples 17-17; 2-[[l- (2-chlorobenzyl) -2-ethylbenzimidazole-6-yl] daiylaminomethyl] ratio. Determination of 1_oxide (84) &gt; [physical properties of compound (84)] ^ -NMR (CDCla, 6): 1.42 (3Η, t3 J-7.5Hz) 3 2.82 (2H, q5 J = 7.5Hz), 4.81 (2H, d, J: 7.5Hz), 5.43 (2H3 s), 6.31 (1H, d, J: 7.5Hz), 7.06 UH, t, J-27.5Hz) 3 7.20-7.31 (3H, in), 7.44 (1H, d, J 2 7.5Ηζ), 7.52 (1H, dd, J: 7, 5 and 2Hz) 3 7 · 65 (1H, dd, J = 7.5 and 2Hz) 3 7.77-7.83 (2H, m), 7.96 (1H, t, J = 7.5Ηζ), 8.23 (lH, dd, J = 7.5 and 2Hz). mp: 204-207 ° C. &lt; Example Π-18; 2-n-butyl-1 · (2-fluorobenzyl) -6_ (2-pyridylmethylaminomethyl) benzimidazole (85) &gt; [Compound (85) Physical properties] 1 surface (CDCL, 6): 0.92 (3H, t, J: 7.5Hz), 1.38-1.49 (2H, m) 5 1.77-1.88 (2H, in), 2.86 (2H, t, J = 7.5Hz), 4.78 (2H, d, J = 5Hz), 5.46 (2H, s), 6.67 (1H, t, J = 9Hz), 7.00 (1H, t, J = 9Hz), 7.13 (1H, t, J = 9Hz), 7.19-7.31 (2H, m), 7.33 (1H, d, J = 9Hz), 7.60 (1H, br maximum 値), 7.65-7.74 (2H, m), 7.79 (1H, d , J = 9Hz), 7.97 (1H, d, J = 2Hz), 8.58 PH, d, J = 5Hz) c mp: 154-155 ° C. &Lt; Example 18; 6th butoxycarbonyl group 3 Synthesis of Amino-1- (2-Azobenzyl) -2-n-propylbenzimidazole (86) &gt; This paper is standard / fl China National Standard (CNS) A4 specification (210X 297 mm) (Read the precautions on the back before you fill out this page), 11 548272 Α7 _______________B7 V. Description of the invention (9〇) '(翱 Read the precautions on the back before filling out this page) 6-pont-1- (2 -Air substituted fluorenyl) -2-n-propylbenzimidal (200 claws suspended in 3 butanol (5 ml) and Diphenylphosphonium phosphate (0.19 ml) and diisopropylethylamine (0.2 μm) were added below. After the reaction mixture was refluxed for 4 hours, ethyl acetate and water were used to separate the layers. The layer was washed with water, dried, and concentrated under reduced pressure. Ethyl acetate / hexane (丨 ·: 3) was used to develop and refine the residue by column chromatography, followed by recrystallization using ethyl acetate / hexane. 6_ 3rd Butoxycarbonylamino-1- (2 • Azobenzyl) -2-n-propylbenzimidal (86) (16511 ^;). [Physical Properties of Compound (86)] Colorless crystal. 1 hidden (CDC13, d): 0 · 98 (3H, t, J: 8Hz) 3 1.50 (9H, s), 1.86 (2H, sextet, J = 8Hz), 2.72 (2H3 t, J: 8Hz), 5.38 (2H, s), 6.40 (1H, dd, J: 13 8Hz), 6.95 (1H, dd, J = 1, 10Hz), 7.08 (1H, dt, J2 1 , 8Hz), 7.24 (1H, dt, J: l, 8Hz), 7.28 (1H, d, J = lHz), 7.45 (1H, dd, J = 13 8Hz), 7.66 (1H, d, J: 10 Hz). mp: 166-168 ° C. &lt; Example 19; Synthesis of 1- (2-chlorobenzyl) -6-cyano-2-n-propylbenzo sigma (87) &gt; under OC Add 1 mole of dioxan solution (0.14ml) and triethylamine (0.36ml) of titanium tetragas to 6-aminofluorenyl-1- (2-fluorobenzyl) -2-n In a tetrahydropyran solution (4 ml) of propyl benzimidazole (200 mg), stir at 20 ° C for 2 hours. The reaction mixture was separated using ethyl acetate and water, and the organic layer was washed with water, dried, and concentrated under reduced pressure. Ethyl acetate / hexane (1: 10 ~ 1: 3) was used to develop and refine the residue by column chromatography, and then ethyl acetate / hexane was used for recrystallization to obtain ___________ This paper is a Chinese national standard (CNS) A4 specification (210X 297 mm) 548272 A7 B7 V. Description of the invention (91) 1- (2-chlorobenzyl) -6-cyano-n-propylbenzimidazole (87) (140mg) 〇 [Physical properties of compound (87)] (诮 Please read the precautions on the back before filling in this page) Colorless crystal. lH-NMR (CDCls, (5): 1 05 t 1 nn, • (3H, t, J-8Hz), 1.90 (2H, sextet, J = 8Hz), 2.85 (2H, t, J 8Hz), 5.45 (2H s) 6 4? ΠΗ w τ 1., S; 3 b.4Z (lH, dd, J = 15 8Hz) 5 7.15 (1H, dt, J- U 8Hz), 7 · 28 (1H, dt, J 2i 8Hz) 7 AR (\ η ri, deleted), · 48 (1H, s), 7.50 (1H, d, J: 10Hz), 7. 54 (1H, dd, J-l5 8Hz), 7.85 (1H3 d, J-10Hz), mp: 124-126 ° C, &lt; Example 20; 1- (2-Gas benzyl) _6_methylamino group_2_ Synthesis of n-propylbenzimidazole (88) &gt; Dissolving 1- (2-chlorobenzyl) -2-n-propylbenzimidazole (150 mg) and triethylamine (61 mg) in two gases In methane (3 ml), sulfonium sulfonium chloride (70 mg) was added at room temperature and stirred for 1 hour, then washed with dilute hydrochloric acid, washed with water, dried and distilled under reduced pressure. The residue solid was filtered using ether to obtain 1- (2-chlorobenzyl) -6-methylaminos-n-propylbenzimidazole (88) (124 mg). [Physical Properties of Compound (88)] W-Certificate (CDCl3-CD3〇D ， ά) : 0.94 (3H, t, J 2 7.5Ηζ), 1.76 (2H, m), 2.71 (2H, t, J 2 7 · 5Ηζ), 2.81 (3H, s), 5.36 (2H s), 6.40 (1H, d, J: 7.5Hz), 6,98-7 • 22 (4H, m), 7,40 (1H, d, J: 7.5Hz), 7.5Q (1H3 d, J: 7.5Hz). Mp: 191-1930C0 &lt; Example 21; Synthesis of 6-acetamidinyl-1- (2-chlorobenzyl) -2-n-propylbenzimidazole (89) &gt; 95 copies Paper size China State Standard (CNS) A4 (210X297 mm) 548272 A7 I — __________________ B7 V. Description of the invention (92) (Read the precautions on the back before filling this page) At room temperature, mix acetic anhydride (62mg) A solution of 6-amino-1- (2-chlorobenzyl) -2-n-propylbenzimidazole (150mg) and triethylamine (61mg) in dichloromethane (3ml) was added. After stirring for 1 hour, it was washed with water, dried, and decompressed Luohe. 6_Ethylamine benzyl) was obtained by crystallization of the residue) _2-n-propylbenzimidazole (89) (143mg) . [Physical properties of compound (8 9)] Η face (CDCh ,: i · 00 (3H, t, J: 7.5Hz), 1.86 (2H, m), 2.17 (3H, s), 2.73 (2H , T, J-7 · 5Ηζ), 5.39 (2H, s), 6.43 (1H, d, J 2 7.5Ηζ), 6.98-7 · 11 (2 H, m), 7.22 ( 1H, t, J: 7.5Hz), 7.45 (1H, d3 J: 7.5Hz), 7.59 (1H, brs) 3 7 · 6 8 (1H, d, J: 7.5Hz), 7.84 (1H, d , J: 1.5Hz). Mp: 180-182 ° C0 &lt; Example of palladium palladium 22; Synthesis of 6-amino-1- (2-chlorobenzyl) _2-n-propylbenzimidazole (90) &gt;; Dissolve 6- 3rd butoxycarbonylamino (fluorenyl chlorobenzyl) _2-n-propylbenzimidal (700 mg) in dichloromethane (00 ml) and trigas hydrazone acetate) In the vehicle, the mixture was stirred at room temperature for 5 hours. A small amount of methylene chloride was added to the reaction solution, washed with an aqueous sodium carbonate solution, and then dried and evaporated under reduced pressure. A mixed solvent of n-hexane and _ was used to recrystallize the residue to obtain 6-amino] _ (2-chlorobenzyl) ^ n-propyl = azole (90) (455 mg). [Physical properties of compound (90)]! H-m (CDCla, d) · 1 π ημ + r. 丨. G1 ⑽, t, J: 7.5Hz), h86 (2Η

= 7.5HZ), 5.30 (2H, S), 6 41 (IH h.,, J (2H 'J • 4i (Roll d, J 2 1.5 μΗζ), 6.48 (1H, d 7 π, r 66 ( 1H, dd, J: 7.5 and 5Hz) 7 Mu, ^ 7 · 5Ηζ), 6. · Z), 7.1〇 (ίΗ, υ-7._, 7.25 (1Η, υ: 75 paper size 548272) A7 B7 Description of the invention (93) Ηζ) 3 7 · 46 (1H, d, j: 7.5Hz), 7.57 (11), d, j = 7 5Hz). Mp: 121-122 ° C. &Lt; Example 23; Synthesis of 1- (2-chlorobenzyl) -2-n-propyl-6-ureidobenzimidazole (91) &gt; The same method as in Example 21 was used to produce 1- ( 2-chlorobenzyl) -2-n-propyl-6-ureidobenzimidazole (91). [Physical properties of compound (91)] NMR (DMS0-d63,): 0.93 (3H3 t3 J. 7.5Hz) 3 L7Z (ZH,.), 2.73 (2H, t5 J-7.5Hz) 3 5.43 (2H3 s) 3 5.73 (2H5 s), 6.42 (1H3 dd5 J-7.5 R 1.5.5Hz) 3?, 〇 5 (1H, dd, J: 7, 5 and h5Hz) 3 7 · 22 (1H, shape, Q · 5 and 15Hz), 7.33 (1H, dt, J—7.5 and 1,5Hz), 7.45 (1H, d, J: 7.5Hz), 7.50 (1H, s), 7.57 (1H, dd, J: 7.5 and 1.5Ηζ), 8.50 (1H3 s). Mp: 198 ° C &lt; Production Example 12 ; 3-Acetylamine_4_nitrobenzoic acid Production of esters> Acetamidine (9 ml) was added to a mixture of ethyl 3-amino-4-nitrobenzoate (18.4 g) and N, N-dimethylaniline (200 ml) in an ice bath. The mixture was stirred at room temperature for 2 hours, and then at 50 ° C for 2 hours. The reaction solution was poured into cooled 1N hydrochloric acid, and ethyl acetate was used for extraction twice. The organic layer was subjected to 1N hydrochloric acid. , Washing with water, drying and distilling off the solvent. The residue was purified by silica gel column chromatography (eluent ·· ethyl acetate / hexane = 1/10 ~ 1/4) to obtain 3_acetamidine Ethyl nitrobenzoate (19.6g). [Physical properties of compound] ^ -NMRiCDCh, 6): L42 (3H, t5 J = 7.1Hz), 2.3Z (3H, s), 4.43 (2H, q, J- 7.1 This paper size applies the Chinese National Standard (CNS) A4 specification (210x297 mm (read the precautions on the back before filling this page). Order 548272 A7 B7 V. Description of the invention (94) Ηζ), 7.82 (1Η, dd, J = 1.8 and 8.7Hz), 8.25 (1H, d, J = 8.7Hz), 9.35 (1H, d, J = 1.8Hz) 3 10.19 (1H, s). (诮 Please read the precautions on the reverse side before filling in this page) &lt; Production Example 13; Production of 4-Tyrol-3-phenylethylamine benzoate ethyl ester &gt; Use 3-amine according to the method of Production Example 12 Ethyl-4-nitrobenzoate (2.02g) and vaporized phenylacetamidine (187g) to give 4-nitro-3-phenylethylamine benzoate ethyl acetate (3.30g). [Physical properties of compound] iH-NMIUCDCh, 6): 1.41 (3Η, t, J: 7.2Hz), 3.85 (muscle s), 4.42 (2Η, q, J 2 7 · 2 Ηζ) 3 7 · 34-7 · 49 (5Η3 m) 3 7.79 (1Η3 m) 3 8.19 (1Η, d, J: 8.7Hz), 9 · 39 (1Η, d, deduction of 1.6Ηζ ^ 1G.15 (1H &Lt; Production Example 14; Production of 3- [N- (2-chlorobenzyl) acetamidamine] -4-nitrobenzoate ethyl ester &gt; 60% sodium hydride ( (0.406 g) was added to a solution of ethyl 3-ethylamido-4-nitrobenzoate (1.706 g) in N, N-diamidinofluorenamine (12 ml), and stirred at room temperature for 40 minutes. Added 2 -A solution of chlorobenzyl bromide (1.806 g) in N, N-dimethylformamidine (10 ml) and stirred at room temperature for 3 hours. Pour the reaction mixture into cooled 1N hydrochloric acid and use Ethyl acetate was extracted twice. The organic layer was washed with hydrochloric acid, washed with water, dried, and distilled off the solvent. By silica gel column chromatography (eluent: ethyl acetate / hexane = 1/10 ~ 1 / 4) The residue was purified to obtain ethyl 3- [N- (2-chlorobenzyl) acetamidin] -4-nitrobenzoate (2.08 g). [Physical properties of the compound] 1H -NMR (CDCl3, δ): 1.38 (3H, t, J = 7.1Hz), 1.92 (3H5 s), 4.Z8-4.45 (2H, m) 5 4.72 (1H, d, J = 14.5Hz), 5.34 (1H, d, J 2 14.5Ηζ), 7 · 16_7 · 44 (4Η3 m), 7 · 69 (1Η _____ ω ___ This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) 548272 A7 B7 V. Description of the invention (95), d, J: 1.7Hz) 7.94 (1H, d, J: 8. he), 8.13 (1Η, dd, J = 1.7 and 8.4Ηζ) 〇 (Please read the precautions on the back before filling this page) &lt; Manufacturing example 15; 4 Production of -nitro-3- [N- [2- (trifluoromethyl) benzyl] acetamido] ethyl benzoate &gt; According to the method of Production Example 14, 3-acetamidine-4- Ethyl nitrobenzoate (1.49g) and 2- (trifluoromethyl) benzyl bromide (1.69g) to give 4-nitro-3- [N- [2- (trifluoromethyl) benzyl ] Acetylamino] Ethyl Benzoate (1.82g). [Physical Properties of Compound] lH-NMR (CDCl3, δ): 1.37 (3H, t3 J = 7.1Hz) 5 1.96 (3H, s) 3 4.29-4.42 (2H, m), 4.78 (1Η, d, J = 15.4Hz), 5.40 (1Η, d, J = 15.4Hz), 7.38 (1Η, t, J = 7.6Hz), 7.5 1 -7.58 (2H, m), 7.61 (1Η, d, J 2 1.7Ηζ), 7.67 (1Η, d, J 2 7.8Hz), 7,92 (1H, d3 J = 8 · 4Ηζ), 8 · 13 (1Η, dd, J = 1.7 and 8 · 4Ηζ). mp: 153.5-158.0 ° C. &lt; Production Example 16; Production of 4-nitro-3- [N- [4- (trifluoromethyl) benzyl] acetamido] ethyl benzoate &gt; According to the method of Production Example 14, ethyl 3-acetamidin-4-nitrobenzoate (1.5 g) and 4- (trifluoromethyl) benzyl bromide (1.71 g) were used to obtain 4- Nitro-3- [N- [4- (trifluorofluorenyl) benzyl] acetamido] ethyl benzoate (1.52 g). [Physical properties of compound] ^ -NMRiCDCh, δ): 1.36 (3H3 t, J = 7.1Hz), 1.91 (3H, s), 4.32-4.43 (2H, m), 4.42 (1Η, d, J 2:14 · 6Ηζ), 5.33 (1H, d, J = 14.6Hz), 7.30 (2H, d, J = 8.1Hz), 7.5 4 (2H5 d, J-8.1Hz) 3 7.6K1H, d, J = 1.8Hz) , 7.96 (1H3 d5 J-8.4Hz), 8.1Z (1H, dd, J2 1.8 and 8.4Hz). __________qq_____________. This paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) 548272 A7 B7 V. Description of the invention (96) &lt; Manufacturing example 17; 3. [Ν- (2-cyanobenzyl) ethyl醯 Amino group] Manufacture of 4-nitrobenzoic acid 2-cyanobenzyl ester &gt; (Read the precautions on the back before filling in this page) At room temperature, ' A solution of nitrobenzoic acid (1.50 g) in N, N-diamidinofluorenamine (10 mi) was dropped into 600 /. A slurry of sodium hydride (0.82 g) and N, N-dimethylformamide (iomi) was stirred for 30 minutes. Then, a solution of 2-cyanobenzyl bromide (3.93 g) in N, N-dimethylformamide (10 ml) was added dropwise, followed by stirring for 30 minutes. The reaction solution was poured into ethyl acetate, and the precipitated crystals were filtered out. The obtained crystals were washed with ethyl acetate, and then dissolved in three gas methane. The solid-removed filtrate was concentrated to obtain 1.96 g of 3- [N- (2-cyanobenzyl) acetamidinyl] -4-nitrobenzoic acid 2-cyanobenzyl ester as yellow crystals. [Physical properties of compound]-lH-NMR (CDCl3, δ): 1.92 (3H3 s), 4.92 (1H, d3 J = 4.8Hz) 3 5,24 (2H, d3 J = 4.9 Hz), 5.44 (2H, dd, J 2 7.9 and 2.9Ηζ), 7 · 36 (1Η, t, J: 7.5Hz), 7.47 (1Η, d, J 2 7 · 7Ηζ), 7.52 (1H, t, J = 7.7Hz), 7.56-7 · 62 (2Η, m), 7.63-7 · 71 (2Η, m), 7.76 (1H, d, J 2 7.8Ηζ), 7.80 (1Η, d , J = 1.7Hz), 7.99 (1Η, d, J = 8.4Hz), 8.25 (1H, dd, 11 = 8.4, and 1.8Ηζ). Cooperative private printing of the Ministry of Economic Affairs and Industry & Co., Ltd. & private printing &lt; Manufacturing Example 18; Production of 4-Amino-3- (N-Isopropylbutylamino) Ethyl Benzoate &gt; At Room Temperature Next, a solution of ethyl 3-butanamine-4-nitrobenzoate (2.00 g) in N, N-dimethylformamide (10 ml) was dropped into 60% sodium hydride (0.428 g) and N, N. -In a slurry of dimethylformamide (10 ml), stir for 30 minutes. Next, a solution of isopropyl iodide (1.46 g) in N, N-dimethylformamide (10 ml) was added dropwise, and the mixture was stirred at 100 ° C for 5 days. The reaction solution is injected with dilute hydrochloric acid (80g) and ethyl acetate. The paper size is in accordance with Chinese National Standard (CNS) A4 (210X297 mm) 548272. The goods and workers are co-operated with private label A7 B7 according to the central standard of the Ministry. (97) ^ ester (80 g) was mixed to separate the layers, and the obtained organic layer was washed with water (50 g) and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent · butane / ethyl acetate = 4Π) to obtain a crude product of 4_amino group_3_ (n_isopropyl 1 butanylamino) benzoate ethyl ester. (〇26〇g). Next, at room temperature, ethanol (3 ml) and acetic acid (2 ml) were added to 4-amino_3_ (n • isopropylbutylamidino) ethyl benzoate (〇26〇§), and then reduced. Iron (0.519 g), which was heated to reflux for 4 hours. A filtration aid was used to remove solids, and the filtrate was concentrated. The residue was added to ethyl acetate (30 ml) and dilute hydrochloric acid (30 ml) to separate the layers, and the organic layer was washed with water (30 mi) and concentrated under reduced pressure. Purification by thin-layer silica gel chromatography for separation (developing solvent: hexane / ethyl acetate = 1/1) to obtain 'amino_3_ (iceisopropylbutyrylamido) ethyl benzoate (0.06 g). [Physical properties of the compound] iH-NMMCDCh, ά): 〇 82 (3Η, t, J: 7.4 Hz), 1.01 (3Η, d, ㈣ 9Ηζ), 1.24 (3Η, d, J: 6.6 Hz), 1.38 (3Η, t, J: 7.0Hz), 1.54-1 · 62 (2Η, m), 1.87_2 · 04 (2Η, m), 4.34 (2Η, q, J = 7.0 Hz), 4.45 (2Η, s), 4.88-4.96 (1Η, ιη), 6.78 (1Η, d, &lt; 1: 1: 8 · 4Ηζ), 7.64 (1Η5 d, J : 1.9 Hz), 7.87 (1Η3 dd, J = 8.4 and 1.9Ηζ). &lt; Example 19; Production of 3-nitro-4_phenylacetamidinyl benzoate ethyl acetate &gt; According to the method of Production Example 12, ethyl 4-amino-3-nitrobenzoate ( 4.04 g) and phenylacetamidine (3 74 g) to give ethyl nitro-4-phenylethylaminobenzoate (600 g). &lt; Manufacturing Example 20; Manufacturing of N-benzenesulfonamido_3_amino_4_nitrobenzopyrene &gt; This paper size applies Chinese National Standard (CNS) A4 (210X297), (please first Read the notes on the back and fill out this page} Order--% ». 548272 A7 B7 V. Description of the invention (98) Add N, N-imidazole (28.9g) to 3 -acetamido-4-nitrobenzoin Acid (20.0g) in a solution of N, N-dimethylformamide (300ml), stir at room temperature for 1 hour (read the precautions on the back before reading this page). Add benzenesulfon Amidine (2800 g) and diazabicycloundecene (27.16 g) were stirred at 100 t for 4 days. After distilling off the solvent, dichloromethane and 10% aqueous sodium oxide solution were added to the residue. The mixture was stirred vigorously. The obtained aqueous layer was added with 10% hydrochloric acid for neutralization, and then chloroform was added and stirred vigorously. The precipitated crystals were filtered and dried to obtain N-benzenesulfonyl-3. -Amino-4-nitrobenzopyramine (I4.4g) 〇 [Physical properties of compound] INMIUDMSO-d6,): 6.93 (1Η, dd, J: 1.8 and 9.0Ηζ), 7.43 (1Η, d, J: 1.8H z) 5 7.52 (2H, br s), 7. 65 (2H, t, J = 7.5Hz), 7.74 (1H, t, J = 7.5Hz), 7.98-7.8 2 (3H, m) 5 12.74 (1H, s) 〇 &lt; Manufacture example 21; N-benzene Sulfonyl-3- (benzylamino) _Production of each nitrobenzylamine potassium salt &gt; Add 20% hydrogen carbonate solution (56_5g) and 4-bromomethylbiphenyl (11.5g) In a methanol solution (150 ml) of N-benzofluorenyl-3-amino-4-nitrobenzofluorenamine (iog) was stirred at 70 ° C for 3 hours. The crystals precipitated after filtration and cooling were dried to obtain N-benzenesulfonyl-3- (biphenyl-4-methylamino) -4-stoneshozylbenzoate salt (4.27 g). [Physical properties of compounds] W-NMR (DMS0-d6, ά): 4.65 (2Η, d, J: 5.8Hz), 7.19 (1Η3 d, J = 8.9Hz), 7.33-7 • 42 (4H , M), 7.57-7.71 (4Η, m) 3 7.75-7 · 81 (2Η, m), 8.02 (1Η, d, J 2 8.9Ηζ), 8.61 (1H , br t) 〇IR (Nujol): 1598cm1〇 -__—- _1 (1? ______ This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) 548272 A7 _____________________ B7 V. Description of invention (99) &lt; Production Example 22; Production of N-benzenesulfonamido-4-amino-3- (biphenyl-4-methylamino) benzamidine potassium salt &gt; (诮 Please read the precautions on the back before filling this page ) 5% palladium / carbon (0.64 g) was added to N-benzylsulfonyl-3- (biphenyl-4-methylamino) -4-nitrobenzofluorenamine potassium salt (4.27 g), 20% In a mixture of potassium bicarbonate aqueous solution (10.7 g) and methanol (200 ml), stir under a hydrogen ambient gas at 35 C for 14 hours. Add a mixed solution of acetone and water (acetone / water = 5/2, 400 ml) ) To dissolve the precipitated crystals and filter out the solids. The mash is concentrated and the precipitated filtrate is filtered and dried to give N-benzenesulfonyl-4-amino-3- (biben-4-methyl) Amine) Potassium salt of benzopyrene (3.15g). [Physical properties of compound] ^ -NMRCDMSO-dG, δ): 4.31 (2H, d, J = 5.7Hz), 4.85 (2H, s), 4.91 ( 1H3 br t5 J2 5.7Ηζ) 3 6.45 (1H, d, J = 7.9Hz), 7.07 (lH, s), 7.13 (lH, d, J: 7.9Hz), 7.29-7.36 (4H, m), 7.43-7.47 (4H, m), 7.60 (ZH, d, J = 8.1Hz), 7.65 (2H, d, J = 7.6Hz), 7.73-7 · 76 (2Η, m). IR (Nujol): 1574cm l &lt; Production Example 23 &gt; ^-(Production of 2-pyridylmethylacetamido-3-nitrobenzopyramine) &gt; Ethyl chloride in an ice bath Rhenium (1.25g) was added dropwise to a solution of 4-ethanesulfonylamino-3-nitrobenzoic acid (1,000g) and N, N-dimethylformamidine (0.20g) in dipyridine (15ml). Then, the mixture was stirred at room temperature for 1 hour. The reaction solution was concentrated, and diisopropyl ether was added to crystallize. This crystal was added with 2-aminofluorenyl group. Bipyridine (0.483 g) and triethyl A solution of amine (0.35 g) in dioxane (15 ml). After stirring at room temperature for 1 hour, the organic layer was washed with water (100 ml x 2 times) and washed with an aqueous sodium hydrogen carbonate solution (iQ 0 ml). Concentrated There is a paper ruler Guan Jiapi (CNS) A4 specification (210X29 '^) 548272 A7 B7 V. Description of the invention (10¾ machine layer and N- (2-. Than methyl) -4-acetamido -3-Shithosylbenzofluorenamine (0.99g). [Physical properties of the compound] 'H-NMR (CDCl3, δ): 2.33 (3H, s), 4.76 (2H, d5 J = 4.8Hz), 7.25 (1H, dd, J = 5. 〇 and 7.2Ηζ), 7.34 (1Η, d, J = 7.9Hz), 7.71 (1H, dt ”J = 1.8 and 7.8Hz), 7.8 4 (1H, s) 5 8 · 14 (1Η5 dd, J = 2.1 and 8.8Hz), 8.58 (1Η, d, J = 4 · 9Ηζ), 8.77 (1H, d, J = 2.1Hz), 8.90 (1Η, d, J = 8.0Hz), 10 · 47 (1Η, s). &Lt; Production Example 24; Production of N- (2-pyridinyl) -4-acetamido-3-aminobenzobenzoamide &gt; Add 5% carbon / carbon (2.53g) to a solution of N- (2-α specific amidino) -4-acetamido-3-nitrobenzopyramine (10.Og) in methanol (150ml). , Stir for 15 hours at 60 ° C in a hydrogen ambient gas. Filter out the solid and purify the residue from the concentrated filtrate by silica gel column chromatography (eluent: ethyl acetate / methanol = 7/3) to obtain N- (2-Pyridinyl) -4-acetamido-3_aminobenzobenzopyrene (8.02g) was obtained. [Physical properties of the compound] lH ~ NMR (DMS0-d6, δ): 2.06 (3H, s), 4.52 (2H, d, J = 5.9Hz), 5.09 (2H, s), 7. 10 (1H, dd, J = 1.9 and 8 · 2Ηζ), 7.22-7 · 30 (3Η, m), 7.38 (1Η, d, J = 8.2Hz), 7.75 (1H, dt, JJ1.7 and 7.6Ηζ), 8.50 (1H, d, J = 4.6Hz), 8.84UH, t, J = 5.8Hz), 9.19 (1H, s). 〈Production Example 25; N- (2-pyridylmethyl) -4-acetamido-3- (4-benzyloxybenzylamino) benzopyrene Manufacture &gt; Add 4-benzyloxybenzyl chloride (1.31g) and sodium bicarbonate (i.i8g) to N- (2-pyridinyl) -4-acetamido-3_aminobenzofluorene Amine (〇.80g) of N, N-II: ---- uu__ This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) (read the precautions on the back before filling this page)-Order Ψ A7 548272 B7 V. Description of the invention (10j (Read the precautions on the back before filling this page) In a solution of fluorenylamine (10ml), stir at 90 ° C for 2 hours. Trichloromethane and water were added to the reaction solution, and extraction was performed using chloroform. The organic layer was washed with water, concentrated, and purified by silica gel column chromatography to obtain N- (2-pyridinyl) -4_acetamido_3_ (4_benzyloxybenzylamino) benzene. Amine (0.434 g). [Physical properties of compounds] lH-NMR (DMS0-d6, δ): 2.07 (3H, s), 4.30 (2H, d, J = 5.6Hz), 4.51 (2H, d, J = 5 • 9Hz), 5 · 07 (2Η, s), 5.68 (1Η, t, J 2 5.6Ηζ), 6.97 (2H, d, J = 8.6Hz), 7.14 (2H, m), 7.25 (2H, dd, J 2 3 · 4 and 7. · 4Ηζ), 7.32UH, t, 7.5Hz), 7.38 (2Η, t3 J 2 7 • 1Hz), 7.44 (2Η, d, J 2 7 · 2Ηζ), 7.72 ( 1Η, dt, J 2 1.8 and 7 · 7Ηζ), 8 · 49 (1Η, dd, J = 1.9 and 5.3Hz), 8.89 (1Η, t, J = 5.9Hz), 9 · 28 (1Η3 s). &lt; Production Example 26; Production of N- (2-pyridylmethyl) -4-acetamidinyl-3- (3,4-methoxydioxybenzylamino) benzopyramine &gt; Central 榀 ^ -Λθ 5 Consumption Hezhu II Yinfu added 3,4-dimethoxybenzyl chloride (.962g) and sodium bicarbonate (0.71〇g) to N- (2-pyridylmethyl) _4_Ethylamido-3_ (4-benzyloxybenzylamino) benzopyramine (0.80g) in a solution of N, N-dimethylformamide (10ml), stirred at 80 ° C for 4 hour. Trichloroarsine and water were added to the reaction solution, and extraction was performed using trigas methane. The organic layer was washed with water, concentrated, and purified by silica gel column chromatography (eluent: ethyl acetate / methanol = 9/1) to obtain N- (2-pyridinyl) -4-acetamido -3- (3,4-methoxydioxybenzylamino) benzylamine (0.49 g). [Physical properties of the compound] INMIUDMSO-de, d): 2.08 (3Η, s), 4.29 (2Η, s), 4.52UH, d, J: 5.9Hz), 5.27 (1H, s), 5.97 (2Η, s), 6.84-6 · 88 (2Η, m) 5 6.96 (1Η, s), 7.10 (1H, d, J2 1.3) This paper standard applies to the Chinese National Standard (CNS) A4 specifications (21 OX 297 mm) 548272 A7 __ ____B7__ 5. Description of the invention (ioi Ηζ), 7 · 13 (1 (, dd, J = 1.6 and 8.2Hz), 7.25-7 · 32 (3Η, m) , 7.76 (1Η, dt, J2 1.2 and 7.6Hz), 8.51 (1Η, d, J2 4.8Ηζ), 8.90 (1Η, J2 5.8Ηζ), 9.28 (1Η, s). &Lt; Production Example 27; N- (2-pyridylmethyl) -4-acetamido-3- [4 · (1,2,3-thiadiazol-4-yl) benzyl Propylamino] Manufacture of benzopyramine &gt; 4- (4-Bromomethylphenyl) -1,2,3-thiadiazole (1.08 g) and sodium bicarbonate (0.710 g) were added to N- (2-α-pyridinylmethyl) -4-acetamido-3_aminobenzylidene (0.800 g) in a methanol solution (10 ml), and stirred at 70 ° C. for 1 hour. The reaction solution was concentrated, And purified by silica gel column chromatography (eluent: ethyl acetate / acetol = 9/1) to obtain N- (2-pyridinyl) -4-acetamido- 3- [4- (1,2,3-thiadiazol-4-yl) benzylamino] benzofluorenamine (0.830 g). [Physical properties of the compound] ^ -NKRiCDCh, δ): 2.1K3Κ, s), 4.43-5.56 (2H, m) 3 5.92 (1H, t, J = 5.9Hz) 5 7.5U1H, d, J 2 1. 4Ηζ), 7 · 15 (1Η, dd5 J 2 1.6 and 8 · 1Ηζ), 7.22 (2Η, dd, J 2 1.9 and 8.1Ηζ), 7.33 (1Η, d, J 2 8.1Ηζ), 7.57UH, d, J = 8.1Hz), 7 69 (1Η, dt, J 2 1.8 and 7 · 7Ηζ), 8.09 (2H, d, J 2 8.2Ηζ), 8.47 (1Η, dd, J 2 1.9 and 5. 2Ηζ) 3 8 · 89 (1Η3t, J = 5.9Ηζ), 9.34 (1Η, s), 9.58 (1Η, s). &lt; Manufacturing Example 28; Production of N-benzenesulfonyl-4-ethylamido-3-nitrobenzimidamine &gt; Zhong Rong of the Ministry of Economic Affairs «. 卑 ΛΜ: τ *; / ί 贽 合 竹淞 印 来 (诮 Please read the notes on the back before filling in this page) Add Ν, Ν'-Weiji Diwei saliva (14.45g) to 4-acetamido-3-nitrobenzoic acid (l.OOg) In a solution of N, N, -dimethylformamide (300 ml), search and stir at room temperature for 1 hour. Next, benzamidine (14.03 g) and diazabicycloundecene (13.58 g) were added and stirred at 10 (rc for 72 hours. Trichloromethane and water were added to form a layer, and then The organic layer was concentrated to obtain a residue, which was subjected to silica gel column chromatography (eluent: ethyl acetate / methanol = 4 / 丄) ________106 This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) 1 ~ 548272 A7 '----------------- B7 ______ V. Description of the invention (refined by 103) to obtain N-benzenesulfonyl-ethenylamino group_3_ nitrate Benzofluorenamine (12.67g). (谙 Please read the precautions on the back before filling in this page) [Physical Properties of Compounds] W-NMmDMSO-d6, (5) ·· 2.08 (3H, s), 7.39-7 · 47 (3Η, m), 7.65 (1Η, d, J: 8.5Hz), 7.84 (2H5 dd, J: 1.4 and 7.7Hz), 8.11 (1Η, dd, J = 1.9 and 8.4 · ζ) , 8.38 (iH, d, JL), ι · 34 (1 Η, s). &Lt; Production Example 29; Production of N-benzylsulfonyl-4-ethylfluorenamino-3-aminobenzofluorenamine &gt; Dissolve N-benzenesulfonylacetamidinyl 3-nitrobenzofluorenamine (12.67g) in methanol (200ml) and water 30 (ml), and add potassium bicarbonate ( 7.59g). The catalyst was hydrogenated under a hydrogen ambient gas at 40% for 5 hours using a 5% palladium / carbon (2.53g) catalyst. The solid was filtered off and the filtrate was concentrated to give a residue 'by silica gel column chromatography. (Eluent: ethyl acetate / methanol = 4/1) was purified to obtain N-benzylsulfonyl-4-ethylamido-3-aminobenzobenzoamide (6.72g). [Compound of Physical properties] W-NMMDMSO-d6, (5): 2 · 06 (3Η, s) 3 7 · 07 (1Η, dd, J 2 1.8 and 8 · 3Ηζ) 3 7.17 (1H, d3 J = 1.8Hz) 3 7.44 (1H5 d, J = 8.3Hz), 7.61 (2H3 t), 7.68 (1H, t) 3 7.96 (2H, d, J = 7.5Hz), 9.19 (1Η, s) IR (Nujol): 1682cm丨. Manufacture Example 30; Production of N-benzylsulfonyl_4_acetamido_3_ (2-nitrobenzylamino) benzopyramine &gt; According to the method of Production Example 32, N was used -Benzenesulfonyl-4-ethylamido-3-aminobenzylideneamine (0.6 mg and 2-nitrobenzyl bromide (0522 g) to give ------ 1. 7 _____ This paper size applies Chinese National Standard (CNS) A4 size (2K) 'x297 mm) 548272 A7 ___________ B7 V. Description of the invention (104 N-benzylsulfonyl-4-acetamido-3- ( 2-nitrobenzylamino) benzofluorene (〇.79g) 〇 [Physical properties of the compound] (Please read the precautions on the back before filling this page) A-NMlUDMSO-de ， ά): 2.08 (3Η, s), 4.72 (2H, d, J = 5.0Hz), 5.92 (1Η, s), 6.86 (1H, s), 7.13 (1H, d, J: 8.1Hz), 7.31 (1Η, d5 J: 8.0Hz), 7.49-7 , 58 (3H, mh 7.60 (2H3 d3 J = 7.6Hz) 3 7.66 (1H3 t5 J = 7.4Hz) 3 7.86 (2H3 d, J = 7.7Hz), 8.11 (1H, d, J = 8.3Hz), 9 · 37 (1Η, s). &lt; Production Example 31; Production of N-benzenesulfonyl-4-ethylamido-3-benzylaminobenzylamine &gt; According to the method of Production Example 32, N-benzenesulfonyl · 4 was used _Ethylamino-3-aminobenzobenzylamine and benzyl bromide (0.47 g) to give N-benzyl-4-benzylamino-3-benzylaminobenzylamine (0.38g). [Physical properties of compound] INMR (DMSO-d6, d): 2.07 (3H, s), 4.35 (2H, d, J = 5.5Hz), 5.73 (1Η, s), 7.06 (1Η , S), 7 · 14 (1Η, d, J 2 8.3Ηζ), 7 · 21-7 · 28 (2Η, m), 7 · 32 (2Η, t, J 2 7.3 Hz), 7 · 37 (2Η, d, J 2 7.6Ηζ), 7.53 (2Η, t, J = 7.4Hz), 7.59 (1Η, t, J: 7.0 Hz), 7 • 88 (2H, d , J: 7.7 Hz), 9 · 29 (1Η, s), 12 · 34 (1Η, s). &lt; Production Example 32; Production of N-benzenesulfonamido-4-ethylamidoamino-3- (2,4-difluorobenzylamino) benzopyramine &gt; At 60 ° C, N-benzenesulfonyl-4-ethylamido-3-aminobenzamine (0.60g), 2,4-difluorobenzyl bromide (0.656g), and potassium bicarbonate (0.423g) The methanol (7 ml) solution was stirred for 1 hour. The reaction solution was concentrated, and purified by silica gel column chromatography (eluent: ethyl acetate / methanol = 9/1) to give N-phenylphenethyl-4-ethylammonyl-3- (2, 4-Difluorobenzylamino) benzene -------108___ This paper size applies to the Chinese National Standard (CNS) A4 (210X297 mm) 548272 A7 ________________________ B7_ V. Description of the invention (105) Amine (0.370 g). [Physical properties of compounds] (Read the precautions on the back before filling in this page} lH-NMR (DMS0-d63 δ): 2.05 (3H, s), 4.34 (2H, d, J = 5.5Hz), 5.60 (1H , s), 7. 〇2 (lH, t3 J-8.0Hz), 7.06 (1H, s), 7.16-7.27 (3H, m), 7.38-7.51 (411, m), 7.8 2 (ZH, d, J-7.2Hz), 9,27 (1H, s) 3 1Z.35 (1H, s) 0 &lt; Production Example 33; N-benzenesulfonyl-4-ethylamido-3- (4-nitrate) Benzylamino) Benzofluorenamine Production> According to the method of Production Example 32, N-benzenesulfonamido-4_acetamido-3-aminobenzophenamine (0.50 g) and 4 were used. -Nitrobenzyl bromide (0.436 g) to give N-benzenesulfonyl-4-ethylamido-3- (4-nitrobenzylamino) benzofluorenamine (0.52 g). [ Physical properties of compound] ^ -NMRiDMSO-dG, δ): 2.09 (3H, s), 4.54 (2H, d, J = 5.0Hz), 6.10 (1H, s), 6. 89 (1H, d, J = 1.8 Hz), 7 · 14 (1Η, dd, J = 1.8 and 8.2Hz), 7.39UH, d ...) = 8 · 2Ηζ), 7.58-7.65 (4Η, m), 7.68 (1Η, t, J = 7.6Hz), 7.92 (2Η, dd, J = 1.4 and 7.4Hz) 3 8.20 (2H, d, J = 8.7Hz), 9.36 (1H, s), 12.28 (1H, s). <Manufacturing Example 34; Production of N-benzenesulfonamido-4-ethylamidoamino-3- [4- (l, 2,3-thiadiazol-4-yl) benzylamido]] benzopyrene &gt; According to the method of Production Example 32, N-benzenesulfonyl-4-ethylaminoamino-3-aminobenzofluorenamine (0.50 g), 4- (4-bromomethylphenyl)- 1,2,3-thiadiazole (0.45 g) to give N-benzenesulfonyl-4-ethylamidino-3- [4- (l, 2,3-thiadiazol-4-yl ) Benzylfluorenamine] Benzofluorenamine (0.38 g). [Physical properties of compounds] iH-NMR (DMS (Hi6, (5): 2.HK3H, s), 4.46 (2H, d, J: 5.3Hz) · 5.96 (1Η, s), 7. ______IM_____ Paper Zhang scale is applicable to Chinese National Standard (CNS) A4 specification (210X297 mm) 548272 A7 ___________________ B7 V. Description of the invention (1 06) ~~ 03 (1H, s), 7.14 (1H, dd, J = 1.7 and 8 · 2Ηζ), 7.40 (1Η, d, J = 8 · 0Ηζ), 7.52-7. 61 (411, in), 7.65 (1H, t, J-7.1Hz), 7.93 (2H, d5 J-7.6Hz ), 8.10 (2H, d, J = 8.2 Hz), 9.35 (1H, s), 9.58 (1Η, s), 12.31UH, s) 〇 (诮 Please read the notes on the back before filling this page) & lt Production Example 35; Production of 3-amino-2-nitrobenzoic acid ethyl g &gt; Stir 3-acetamido-2-nitrobenzoic acid (20.2 g), 97% sulfuric acid ( 11.4 g) and a mixture of ethanol (300 ml) for 23 hours. After distilling 100 ml of ethanol and cooling to room temperature, the reaction solution was poured into ice water (200 ml) containing sodium bicarbonate (19.5 g). The precipitated crystals were filtered off and washed with water. Next, the crystals were dispersed in a mixed solution (30 ml) of ethyl acetate and hexane 1.2, and the crystals were filtered, washed with hexane, and dried. Thereby, 3-amino-2-stone-shokylic benzoate (18.0 g) was obtained. [Physical properties of compound] 'H-NMRiCDCh, δ): 1.39 (3H, t, J-7.1Hz), 4.37 (2H, q, J = 7.1Hz), 6.41 (2H? Br s), 6.83 (1H, d , J = 8.7Hz), 8.00UH, dd, J = 1.8 and 8.7Ηζ), 8.85 (1H, d, J = 1.8Hz). &lt; Manufacturing Example 3 6; Production of 3-ethylethylamino-2-stone-shoky benzoic acid ethyl ester &gt; Under an ice bath, ethyl It-chloride (13 ml) was dripped into 3-amino-2_stone-shoky benzoin In a solution of ethyl acetate (2.98 g) and N, N-dimethylaniline (20 ml), the mixture was stirred at room temperature for 48 hours. 10% hydrochloric acid was used to make the reaction solution acidic, extraction was performed twice with ethyl acetate, and the organic layer was washed three times with water. Hexane was added to the residue obtained by distilling off the solvent under reduced pressure to crystallize it. By filtration, washing with hexane, and drying to obtain 3-acetamidonitro nitroamphenicol paper, the size of the paper is suitable for China National Standard (CNS) A4 (21QX2 = thin) 548272 A7 B7 V. Invention Explanation (10) 7 Ethyl benzoate (3.30g). [Physical properties of compounds], (¾Read the precautions on the back before filling this page) W-NMIUCDCI3, (5): 1.42 (3Η, t), 2.33 (3Η, s), U2 (2H, q ), 8.27 (1Η3 dd3 J 2 1.9 and 8.9Hz), 8.89 (1Η, d, J: 1.9Hz), 8.91 (1Η, d, J = 8.9Hz), ι54 · 1 (1Η , Br s) 〇 &lt; Production Example 37; Production of 4-Ethylamido-3_aminobenzoic acid ethyl ester &gt; 3-Ethylamino-2-nitrobenzoic acid was produced under a hydrogen atmosphere. A mixture of ethyl acetate (149.4 g), 5% palladium / carbon (14.9§), and ethanol (1500 ml) was stirred for 15 hours. The solid was filtered off, the residue obtained by concentrating the filtrate was dissolved in a small amount of ethanol, and diisopropyl ether was added. The precipitated crystals were filtered and dried to obtain 'ethyl ethylamino-3 -aminobenzoate (114.4 g). [Physical properties of compound] fNMRiDMSO-dG, (5): 1.27 (3Η5 t), 2.G5 (3H3 s), 4.23 (2H, q), 5.19 (2Η, s), 7.13UH, d, J = 8.2Hz), 7,35 (1Η, s) 5 7 · 47 (1Η, d, J = 8.2Hz), 9.19 (ίΗ, s) &lt; Example 24; 1- (2-chloro Synthesis of benzyl) -6-ethoxycarbonyl-2-methylbenzimidazole (92) &gt; Ethanol (20 ml), acetic acid and reduced iron (3.07 g) were added to 3- [N- (2-Azobenzyl) acetamido] -4-nitrobenzoate (2.07 g) and refluxed for 4 hours. The solid was filtered off and washed with ethanol. After the filtrate was evaporated, the sodium bicarbonate aqueous solution was added to the residue and extracted with ethyl acetate. After drying, distilled under reduced pressure to remove the solvent, and the essence of Shi Xijiao color method (dissolving solution: hexane / ethyl acetate g purpose: = 100/0 ~ 70/30) ------ nj___ The size of this paper is / 1] Chinese National Standard (CNS) A4 specification (210X297 Gongchu) 548272 A7 B7_ V. Description of the invention (108) to obtain 1- (2-Azobenzyl) -6_B Oxocarbonyl_2-fluorenylbenzimidazole (92) (1.46g). (Xu first read the precautions on the back before filling in this page) [Physical properties of compound (92)] 1H-NMR (CDCl3, δ): 1.39 (3H t 7 ih ?, 9 0 w, J-7 · 1Ηζ), 2.57 (3H, s), 4.37 (2Η, q, J27.1

Hz), 5.46 (2H3 s) 3 6.4K1H, d, J, 7.8Hz) 3 7.10 (1H5 t, J = 7.8Hz), 7.25 (111, t) 5 7.47 (1H5 d3 J, 8.0Hz) 3 7.75 ( 1H3 d5 J = 8.4Hz) 3 7.94 (1H, s) 3 8.00 (1H3 dd, J 2 1.5 and 8 · 4Ηζ). &lt; Example 25; Synthesis of 6-ethoxycarbonyl-1-fluorenyl-2-n-propylbenzimidazole (93) &gt; According to the method of Production Example 14, 3-butanylamino-4-benzoin was used Ethyl acetate (1000 g) and methyl iodide (0 843 g) to give 3- (N-fluorenbutylamido) -4-nitrobenzoate as a crude product (100 g) . The method of Example 24 was then used to obtain 6-ethoxycarbonyl-; 1-methyl-n-propylbenzimidazole (93) (0.56 g). [Physical properties of compound (93)] H-NMR (CDCl3, δ): 1.08 (3H, t, J = 7.4Hz), 1.43 (3H, t, J = 7.0 Hz), 1.89-L9 7 (2H, m), 2.89 (2Η, t, J: 7.7Hz), 3.79 (3Η, s), 4.38-4.44 (2H, E), 7_71UH, d, J: 8.4Hz), 7.96 (1H, dd5 J: 8.4 and 1.5 Η ζ,), 8.05 (1 Η, d, J: 1.4 Hz). &lt; Example 26; Synthesis of 1-n-butyl-6-ethoxycarbonyl-2-n-propylbenzimidazole (94) &gt; At room temperature, 3-butylamido-4-nitro A solution of ethyl benzoate (186 g) in N, N-dimethylformamide (10 mi) was dropped into 60% sodium hydroxide (0.428 g) and N, N-dimethylformamide (1 g). The slurry consisting of ml) was stirred at room temperature for 30 minutes. Then drip n, N-dimethyl iodide of n-butyl iodine (i.97g) ____ This paper is suitable for 7/5 ^ standard (CNS) A4 size (210x2m shame) ------ 548272 ^ 沪 ' ^ | Zhong Jue ^^-and ', only diazepam ^ ^ printed 113 A7 B7 V. Description of the invention (1 () 9) ~ ~ Methylamine (10ml), heated at 50 for 13 hours. The reaction solution was poured into a mixed solution of dilute hydrochloric acid (70 g) and ethyl acetate (70 g) for extraction. The organic layer obtained was washed with water (twice), dried, and concentrated under reduced pressure to obtain a crude product of ethyl 3- (N-n-butylbutylamino) -4-nitrobenzoate (2.59 g). Next, the method of Example 24 was used to obtain 1.n-butyl-6-ethoxycarbonyl-2-n-propylbenzimidazole (94) (0.81 g). [Physical Properties of Compound (94)]

(CDCl33 δ): 0.98 (3H5 t3 J = 7.4Hz) 5 1.08 (3H, t3 J-7.4Hz); 1.43 (3H &gt; t, J = 7.1Hz), 1.75-1.83 (2H, m), 1.91-1.98 (2H5 m) 5 2.88 (2H) t, J = 7.6Hz), 4.15 (2Η, t, J = 7.5Hz), 4.42 (2H, q5 J, 7.2Hz), 7.73 (lHj d, J, 8.4Hz) 5 7.96 (1H, dd, J = 8.5 R i.5Hz) j 8 &lt; 06 (1Hj dj J = L4Hz) 〇 &lt; Example 27; 1-(3-chlorobenzyl) _6_ethoxy Synthesis of carbonyl_2-n-propylbenzimidazole (95) &gt; According to the method of Production Example 14, 3-butyramidinyldongkuyl benzoic acid ethyl acetate (1.86g) and 3-chlorochlorobenzyl ( 1.64g) to obtain a crude product of 3- [n_3_chlorobenzyl) butyramidinyl] -4-nitrobenzoate. Without re-refining, the method of Example 24 can be used to obtain (3_ oxobenzyl) -6-ethoxycarbonyl · 2-n-propylbenzimidazole (95) (〇 57§). [Physical properties of compound (9 ^)] 'H-NMR (CDCl3, c5): 1.02 (3H, t, J, 7.4Hz), 1.39 (3H, t, J = 7.1 Hz), 1.85-1.9 2 (2H M), 2.80 (2Η, t, J 7.5Hz), 4.38 (2H, q, J: 7.mz), 5.37 (2Η, s), 6.86 (1H5 d3 J ^ 4Hz) 3 7.04 (1H, s), 7.21-7.29 (2H, m) 3 7.77 (1H, d, J = 8.4Hz) 3 7.96 (1H, d, J = 1.2Hz), 7.99 (1Η, dd, J : 8.5 and 1.5HZ). &lt; Example 28; q-based · 6 · ethoxypropyl-n-propylbenzimidazole M-scale scale / fl China National Standard (CNS) A4 specification (210X297 mm) (Read the precautions on the back first (Fill in this page again)

548272 A7 B7 was eliminated by cooperation of the Ministry of Justice i? ^ R ^ mT. 5. Synthesis of the description of the invention (110) (96) &gt; According to the method of Manufacturing Example 14, 3-butanylamino-4 was used. -Ethyl nitrobenzoate (1.86 g) and benzyl bromide (1.36 g) to give 3- [N-benzylbutyramido] -4-nitrobenzoate ethyl. Without further refining, the method of Example 24 was used to obtain Benzyl-6-ethoxycarbonyl-n-propylbenzimidone (96) (0.97 g). [Physical properties of compound (96)] JH-NMR (CDCl35 5): 1.0K3H, t3 J, 7.4Hz) 3 1.39 (3H5 t3 L83, L9 K2H5 m) 5 2.8K2H, t5 J = 7.5Hz) 3 4.37 (2H5 q5 5.40 (2H, s) 5 7.03 (1H, d, J = 6.4Hz), 7.28-7.33 (3Η, ffl), 7.76 (1Η, d, j: 8 • he), 7.98⑽, ^ 8.4 and 1 · 2Ηζ) 3 8 · 00 (1Η, s). '-&Lt; Example 29; Synthesis of 1- (4-chlorobenzyl) _6_ethoxycarbonyl_2_n-propylbenzimidazole (97) &gt; According to the method of Production Example 14, 3_ Butylamino-4_nitrobenzoate ethyl ester (1.86g) and 4-chlorobenzyl bromide (1.64g) to give 3_ [ν · (4-Azobenzyl) butylamidoamine] _4 _ Ethyl nitrobenzoate. Without further refining, according to the method of Example 24, __ (4-chlorobenzyl) -6-ethoxyquinyl-2-n-propylbenzo sigma (97) (1 · 〇 6β). [Physical properties of compound (97)] INMMCDCh, 6): 1.02 (3Η, t, J: 7.4Hz), 1.39 (3H, t, J = 7.1Hz), 1.83-1 9 2 (2H, m ), 2.80 (2Η, t, J: 7.8Hz), 4.38 (2Η, q, J = 7.5Hz), 5.36 (2Η, s), 6.96 (2H, d, J: 8.2Hz) , 7.29 (2H, d, J: 8.3Hz), 7.76 (1H, d, J: 8.4Hz), 7.96 (1H, d J = 1.2Hz), 7.99 (1H, d, J: 8.3Hz) 1.2Hz). &lt; Example 30; 6-ethoxycarbonyl-2-methyltrifluorofluorenyl) --------- #! (谙 Please read the notes on the back before filling in this page j, a'll Φ— 548272 A7 B7 V. Description of the invention (111) Synthesis of benzyl] benzimidazole (98) &gt; (Read the precautions on the back before filling this page) According to the method of Example 24, use 4-nitro -3- [N- [2- (trifluoromethyl) benzyl] acetamido] ethyl benzoate (1.82g) to give 6-ethoxycarbonyl-2-methyl-1- [2 -(Trifluoromethyl) benzyl] benzimidazole (98) (1.32 g). [Physical properties of compound (98)] iH-NMR (CDCh, 6): 1.38 (3Η, t, J 2 7 · 1Ηζ), 2.53 (3Η, s), 4_37 (2H, q, J 7.1 Hz), 5.58 (2H, s), 6.47 (1Η, d, J = 7.7Hz), 7.36 ( 1Η3 t, J = 7.5Hz), 7.41 (1H, t, J 2 7.5Ηζ), 7.75-7.97 (2H, m), 7.94 (1Η, d, J 2 1.0Ηζ), 8.02 (1H, (dd, J. 1.6 and 8.6 Hz). &lt; Example 31; Synthesis of 6-ethoxycarbonyl-2 · fluorenyl-l- [4- (trifluoromethyl) benzyl] benzimidazole (99) &gt; According to the method of Example 24, 4-nitro-3- [N- [4- (tridecylmethyl) benzyl] acetamido] an Ethyl benzoate (1.52g) to give 6-ethoxydiyl-2-methyl-1- [4- (trifluoromethyl) benzyl] benzo η σ σ (99) (1.22g [Physical properties of compound (99)] ^ -NMRiCDCh, δ): L39 (3H, t, J-7.1Hz), 2.58 (3H, s), 4.38 (2H, q, J = 7.1 Hz), 5.44 ( ZH ^ s), 7.15 (ZH, d, J = 8.2Hz), 7.59 (2H, d, J = 8.ZHz), 7.75 (1H, d, J = 8.3Hz), 7.97 (1Η, s) , 8.00 (1H, dd, J 2 1.5 and 8.5Hz). &lt; Example 32; Synthesis of l- (3,4-digaso-benzyl) -6-ethoxycarbonyl-2-methylbenzimidazole (100) &gt; According to the method of Production Example 14, 3- Acetylamino-4-nitrobenzoic acid ethyl ester (1.50g) and 3,4-dichlorobenzyl (1.74g) to obtain 3- [N- 115 This paper is applicable to Chinese National Standards (CNS) A4 specification (210X297 mm) 548272 A7 B7 V. Description of the invention (112) (3,4-di-gasoyl) acetamido] -4-nitrobenzoic acid ethyl g. Without further purification, the method of Example 24 was used to obtain i_ (3,4-dichlorobenzyl) -6-ethoxyepi-2-methylbenzobenzoal (100) (0.76 g). [Physical properties of compound (100)] 'H-NKR (CDCh, ά): 1.40 (3Η, t3 J 2 7.1Ηζ), 2.58 (3Η, s), 4.39 (2Η, q, J = 7.2 heart), 5.33 (2Η, s), 6.84 (1Η, dd, J 2 8.4, and 2.3 Hz) 5 7 · 16 (2H, d, J 2 2.0 Hz), 7.39 (1H, d, J = 8.3Hz), 7.74 (1H, d, J = 8.4Hz), 7.96 (1H, d, J = 1.2Hz), 8.00 (1 H, dd, J = 8.4 and 1.5Hz). <Example 33; Synthesis of 1- (bibenz-4-methyl) -6-ethoxyquinyl-2-methylbenzimidazole (101)> According to the method of Production Example 14, 3-acetamidine was used Ethyl-4-nitrobenzoate (1.51g) and 4-chloromethylbiphenyl (1.46g) to give 3- [N- (biphenyl-4-fluorenyl) acetamido ] -4-Shishiki Benzoic acid ethyl g crude refined product (1.44g). Then, the method of Example 24 was used to obtain 1- (biben-4-methyl) -6-ethoxyweilyl-2 -fluorenylbenzometer (101) (1.13 g). [Physical properties of compound (101)] ^ -NMRiCDCh, δ): 1.39 (3Η5 t3 J = 7,1Hz) 3 2.62 (3H, s) 3 4.38 (2H, q3 J = 7.1 Hz) 5 5.42 (2H, s) , 7.1K2H, d, J = 8.2Hz) 5 7.34 (1H, m), 7.42 (2H, m), 7.54 (4 In the Ministry of Commerce, ii ^ f- ^ m 5 eliminates the need for H, m), 7.74 (1Η, d, J = 8.4Hz), 7.99UH, dd, J 二 1.5, and 8.4Ηζ), 8.06 (1Η, d, J = 1.5Hz). &lt; Implementation Example 34; Synthesis of 6-ethoxycarbonyl-2-methyl-1- (2-methyl) benzimidazole (102) &gt; According to the method of Production Example 14, 3-acetamido-4- Ethyl nitrobenzoate (1.50g) and 2-methylbenzyl bromide (1.65g) to obtain 3- [N- (2- This paper scale follows the China National Standards (CNS) A4 specification (210X 297 mm) 548272 A7 __________________________ B7 V. Description of the invention (113) 'monomethylbenzyl) acetamido] -4-nitrobenzoic acid ethyl alcohol. According to the method of Example 24 without purification, 6-ethoxycarbonyl-2-methyl'-1- (2-methylyl) benzimidal (102) (0 81 g) was obtained. (诮 Please read the precautions on the back before filling this page) [Physical properties of compound (102)] lH-NKR (CDCl35 6): 1.38 (3H, t, J = 7,2Hz) 3 2.43 (3H, s) 3 2.54 (3H3 s) 3 4 36 (2H, q, J: 7.2Hz), 5.33 (2H, s), 6.35 (1Η, d, J: 7.7Hz) 5 7 · 03 (1Η, j: 8,2Hz ), 7.18-7.25 (2H, m), 7.75 (1H, d, J = 8.5Hz), 7.91 (1H, d, J = 1.2Hz), 7.98 (ih, dd, and 1.5Hz). &lt; Example 35; Synthesis of 6-ethoxycarbonyl (fluorenylbenzyl) -2-methylbenzimidazole (103) &gt; According to the method of Production Example 14, 3-acetamidonitrobenzoin was used Ethyl acetate (1.16g) and 2-fluorenylbenzyl chloride (1.44g) to give 3: [n_ (2-methoxybenzyl) acetamido] -4_nitrobenzoate Coarse refined product. Then, according to the method of Example 24, 6 • ethoxycarbonyl, fluorenyloxy) -2-methylbenzimidal (103) (1.18 g) was obtained. [Physical Properties of Compound (103)]

HiMEXCDCh, 6) · 1.39 (3H, t, J: 7.2Hz), 2.60 (3Η, s), 3.90 (3Η, s) 4 37 (2Η, q, J = ?. 2Hz), 5 · 36 (2Η, s), 6.61 (1Η, d, J: 7.4Hz), 6.82 (1Η, t, J = 7 5Hz) 3 6.92 (1H, d3 J-8-3Hz), 7.27 (1H , m), 7.71 (1H, d, J = 8.4Hz), 7.96 (1H dd J2 1.5 and 8.4Ηζ), 8.03 (1Η, d, J: 1.3Hz). &lt; Example 36; Synthesis of 6-ethoxyquinyl-i- (4-methoxybenzyl) -2-methylbenzimidazole (104) &gt; According to the method of Production Example 14, 3-acetamidine was used _4_Nitrobenzoate (1.60g) and 4-methoxybenzyl gas (1.49g) to obtain 3_ [n_ (4_ __ _... 117. This paper is in accordance with the Chinese National Standard of CNS (CNS ) A4 specification (210X297 mm) ---- * ---- 548272 A7 _______ B7 V. Description of the invention (114) Methoxybenzyl) acetamido] -4-nitrobenzoic acid ethyl ester Thing. (^ Please read the notes on the back before filling this page) Then follow the method of Example 24 to get 6-ethoxycarbonyl-1- (4-methoxypentyl) -2-fluorenylbenzyl. Sit (104) (1.27g). [Physical properties of compound (104)] W-NMiUCDChJ): 1.40 (3H, t, J 27.1Ηζ), 2.59 (3Η, s), 3.77 (3Η, s), 4.38 (2Η, q, J = 7.1Hz) 3 5 · 31 (2Η3 s), 6.84 (2Η, m) 5 7 · 0〇 (2Η, ιη) 3 7 · 71 (1Η, d, J: 8.4 Hz), 7 · 97 (1Η, dd, J = 1.4 and 8.4Ηζ), 8.03 (1Η, d, J = 1.3Hz). &lt; Example 37; Synthesis of 1- [2- (benzenesulfonylmethyl) benzyl] -6-ethoxycarbonyl-2-fluorenylbenzimidazole (105) &gt; According to the method of Production Example I4, 3-Ethylamido-4-nitrobenzoic acid ethyl ester (1,000 g) and 2- (benzenesulfonylmethyl) benzyl bromide (1.93 g) to give 3- [N- [2- ( Phenylmethyl) benzyl] ethylammonium] -4-nitrobenzoate. According to the method of Example 24 without further refining, 1 &lt; 2- (benzenesulfonyl) benzyl] -6-ethoxycarbonyl-2-methylbenzimidazole (105) (0.89 g) . [Physical properties of compound (105)] ^ -NMRiCDCh, δ): 1.37 (3H, t, J-7.1Hz), 2.57 (3H, s) 5 4.36 (2H3 q3 J-7.1

Hz), 4.50 (2Η, s), 5.60 (2H, s), 6.38 (1Η, d, J: 6.7Hz), 6.88 (1Η, dd, J = 1.5 and 7.3Hz), 7 · 10-7 · 18 (2Η, m) 5 7 · 57 (2Η, t, J = 7.6Hz), 7.69-7 · 78 (2Η3 m), 7 • 79 (1H, dd, J = 0.8 and 8 · 1Ηζ), 7.92 (1Η, d3 J: 1.2Hz), 7.99 (1Η, dd5 J: 1.5 and 8.4Hz). &lt; Example 38; Synthesis of l- (2-cyanobenzyl) -6- (2-cyanobenzyloxycarbonyl) -2-methylbenzimidazole (106) &gt; A method according to Example 24 Using 3- [N- (2-cyanobenzyl) acetamidine This paper is sized to the Chinese National Standard (CNS) A4 (210X297 mm) 548272 A7 B7 V. Description of the Invention (115) Amine] 2-oxybenzyl nitrobenzoate (3.33g) to give 1- (2-cyanobenzyl) -6_ (2_cyanobenzyloxycarbonyl) -2-methylbenzimidazole (106) (1.75g). (翱 Please read the precautions on the back before filling this page) [Physical properties of compound (106)]

H-leg (CDCh, d): 2.60 (3Η, s), 5_55 (2H, s), 5.6QUH, s), 6.68 (1H, d, J = 7.3Hz), 7.41-7.48 (3H3 m) 5 7.61 (2H, m), 7.72 (1H5 d3 J = 7.6Hz), 7.76 (1H, d, J = 7.6Hz) 3 7.77 (1Η, d3 J: 8.6Hz) 3 8 · 02 (1Η, s ) 3 8.05 (1H, dd, J: 8.4 and 1.5 Hz) &lt; Example 39; 1- (biphenyl-2-methyl) -6-ethoxycarbonyl-2-methylbenzimidazole (107 ) Synthesis> According to the method of Production Example 14, ethyl 3-acetamido-4-nitrobenzoate (1,000 g) and 2-bromomethylbiphenyl (1.47 g) were used to obtain 3 -[N_ (biphenyl-2-fluorenyl) ethenylamino] _4-nitrobenzoate. Without further refining, 1- (biphenyl-2-methyl) -6-ethoxycarbonyl-2-methylbenzimidone was obtained according to the method of Example 24. Sit (107) (1.3 lg). [Physical properties of compound (107)] 'H-NMRiCDCh, ά): 1.41 (3Η5 t, J-7.3Hz), 2.39 (3H, s), 4.38 (2H, q, J-7.3

Hz), 5.27 (2Η, s), 6.68 (1Η, d, J 2 7.9Ηζ) 5 7 · 21 (1Η, dt, J 2 9.0 and 2.1 Hz), 7.32-7 · 39 (4Η, m), 7.43 (1Η, dd5 J = 7.3 and 1.9Ηζ), 7.46-7 · 51 (2Η, m) 3 7 · 68 (1Η, d, J 2: 8 · he ), 7.87 (1Η, d3 J = 1.3Hzh 7.95 (1Η, dd, J = 8.4 and 1.5Η) &lt; Example 40; 1-Benzyl-6-ethoxycarbonyl-2-methylbenzene Synthesis of Benzimidazole (108) &gt; According to the method of Production Example 14, 3-acetamido-4-nitrobenzoic acid ethyl acetate (1.00 g) and benzyl bromide (102 g) were used to obtain 3_ ( N_benzylacetamide The size of this paper is suitable / 1] Bamboo touch standard ((: milk) 44 size (21 () \; 297 mm) 548272 A7 __ B7 V. Description of the invention (116) '' ~ & quot Based on M-stone benzoic acid ethyl vinegar. According to the method of Example 24 without further refining can be obtained 丨 Buddenyl ethoxy-2-yl-2-methylbenzimidazole (108) (0.71g); (Read the precautions on the back before you fill in this page) [Physical properties of compound (108)] (CDCh, (5): 1.39 (3Η, t, J: 7.1Hz), 2.58 (3Η, s ), 4 · 38 (2Η, q, J 2 7.1, 5.38 (2Η, s) 3 7 · 05 (2Η, dd, J. 2 · 3 and ΐ · 8Ηζ), 7.28-7.33 (3H, m), 7.72, d, J = 8.4Hz), 7.98 (1Η, dd, J: 8.4 and Hz), 8.02 (1H, d , J: 1.2 Hz) &lt; Example 41; Synthesis of 1- (4-third butylbenzyl) _6_ethoxycarbonyl_2_fluorenylbenzo salivary (109) &gt; Method: 3-ethylammonium aminonitrobenzoate (1,000 g) and 4-third butylbenzyl bromide (35 g) were used to obtain 3- [N- (4-third butylbenzyl ) Acetaminophen 4- 4-nitrobenzoic acid acetamidine can be obtained according to the method of Example 24 without further refining, and 1- (4-third butylbenzyl) -6-ethoxycarbonyl_2_ Crude refined product of methylbenzimidazole (109) (1.60 g). &Lt; Example 42; 6-ethoxycarbonyl-2-methyl-1- (2-naphthylmethyl) benzimidazole (110 ) Synthesis> According to the method of Production Example 14, 3-ethylacetamido-4-nitrobenzoate (1,000 g) and 2-naphthylmethyl bromide (h32g) were used to obtain 3- [ N- (2naphthylmethyl) acetamidinyl] -4-acrylic acid ethyl ester. Without further purification, 6-ethoxycarbonyl-2-methyl-1- (2-naphthylmethyl) benzimidazole (28 g) was obtained according to the method of Example 24. &lt; Example 43; 1- (biphenyl-4-methyl) _6_ethoxycarbonyl_2 · ethylbenzene paper standard ^ 7 ^^ standard (CNS) A4 specification (210/29 ^ ¾ ^- -548272 A7-~ One B7 V. Description of the invention (117) Synthesis of benzimidazole (111) &gt; (Read the precautions on the back and then write this page) According to the method of manufacturing example 14, use 4-nitrate Ethyl-3-propanamidinyl benzoate (2.00g) and 4-chlorofluorenylbiphenyl (2.28g) to give 3- [N- (biphenyl_4-methyl) propanamido ] -4-Ethyl benzoate benzoate. Without further refining, 1_ (biphenyl_4-methyl) -6-ethoxycarbonyl-2-ethylbenzimidazole ( 111) (2.07g). [Physical properties of compound (111)] 1H-NMR (CDCl33 δ): 1.39 (3Η5 t, J-7.2Hz), 1.45 (3H, t, J-7.5Hz), 2.90 (2H5 ^ J = 7.5Hz), 4.38 (2Η, q, J = 7.2Hz), 5.43 (2H3 s), 7.10 (2Η, d, J: 8,3Hz), 7.33-7 · 36 (1Η3 m), 7.43 (2Η, t, J: 7.4Hz) 3 7.5 Bu 7.56 (4Η, m), 7,79 (1H, d, J 2 8 • 5Hz), 7.80 (1Η, dd , J = 1.5 and 8.4 Hz) 5 8 · 05 (1Η3 d5 J = 1.3 Hz). &Lt; Example 44; 1- (2-chlorobenzyl) -5-ethoxycarbonyl-2 -Synthesis of methyl benzimidazole (112) &gt; According to the method of Production Example 14, ethyl 4-acetamido-3-sonylbenzoate (3.15 g) and 2-air benzyl bromide (3.85) were used. g) to obtain 4- [N_ (2--Arylidene) ethynylamino] -3 -nitrobenzoate. 142-chlorine can be obtained according to the method of Example 24 without further refining. Benzyl) -5-ethoxycarbonyl-2-methylbenzimidazole (112) (2.54 g). [Physical properties of compound (Π2)] 'H-NKRiCDCh, d); 1.4K3H, t, J = 7.1Hz), 2.59 (3Η, s) 5 4.40 (2H, q5!

Hz), 5.43UH, s), 6.43 (1Η, d, J = 7.8Hz), 7.KK1H, t, ": 7.5Ηζ), 7.19UH, d, J = 8.5Hz), 7.25 (1Η, m) 3 7 · 46 (1Η, d, J: 8.1Hz), 7.95UH, dd, J: 1.4 and .4Hz), 8.47 (1H3 s). <Example 45; 1- (2,6 -Dichlorobenzylethoxycarbonyl_2 • A paper size standard (CNS) A4 specification (21G X2 $ i%) — '&quot; 548272 A7 ______________ _ B7 V. Description of the invention (118) Synthesis of benzimidazole (113) &gt; (Read the precautions on the reverse side before filling in this page) According to the method of Production Example 14, use 3-ethylamido-4-chlorobenzoate ethyl ester (1.50g) And 2,6-dibenzimidazole bromide (2.14g) to give 3_ [N- (2,6-monochlorofluorenyl) acetamidinyl] _4_ shishothyl benzoate ethyl ester. No further purification required According to the method of Example 24, ι_ (2,6-monogasofluorenyl) -6-ethoxyquinyl-2 -fluorenylbenzo sigma (113) (0.91g) can be obtained. [Compound ( 113) Physical properties] H-NMR (CDC13, d): 1.38 (3Η, t, J = 7.1Hz), 2.64 (3Η, s), 4.34 (2H, q3 J: 7.iHz), 5 61 (2Η, s), 7.30 (1H, dd, J: 7.6 and 8.5Ηζ), 7. 40 (2H, d, J: 8.0Hz), 7.66 (1H, d, J = 8.4Hz), 7.87 (1Η, d, J = 1.1Hz) 3 7.91 (1H, dd, J 2: 8 · 4 and 1.5

Hz) &lt; Example 46; Synthesis of 6-ethoxycarbonyl-2-n-propyl-1-isopropylbenzimidazole (114) &gt; 4-amino-3- (N-isopropyl Ethyl butylammonium benzoate (0.06 g) was added to acetic acid (2 ml) and stirred at 90 ° C. for 14 hours. The reaction solution was concentrated under reduced pressure to obtain 6-ethoxycarbonyl-2-n-propyl-1-isopropylbenzimidazole (114) (0.05 g). [Physical Properties of Compound (114)]

il-NMRiCDCh, δ): 1.07 (3Η, t5 J = 7.4Hz), 1.43 (3H, t, J-7.0Hz), 1.69 (6H, d, J = 6.9Hz) 3 1.85-1.92 (2H3 m), 2.91 (2H, t, J = 7.7Hz), 4.41 (2H, q, J = 7.3H z), 4.67-4.76 (lH, m), 7.72 (1H, d, J = 8.3Hz), 7.9 ^ (1H , dd, J = 8.7 ^ 1.5Hz), 8.25 (1H, d, J = 1.2Hz) &lt; Example 47; 2-benzyl-6-ethoxycarbonyl-1-methylbenzimidazole (115 Synthesis of) ______122_____ This paper is suitable for Chinese national standard (CNS> A4 size (210X297mm)) 548272 A7 V. Description of the invention (丨 19) Add 60% sodium hydroxide (〇. 166g) in an ice bath In a solution of 4-nitro_3-phenylethylamidoaminobenzoic acid ethyl ester (.924 g) in N, N-dimethylformamide (10 ml), stir at room temperature for one hour. Then add Methyl ethyl ether (0.50ml), stirred for an additional hour at room temperature. The reaction solution was poured into cooled 1N hydrochloric acid and extracted twice with ethyl acetate. The organic layer was washed with 1N hydrochloric acid, washed with water, and dried. 2. Distillate the solvent to obtain the residue. Purify by silica gel column chromatography (eluent: ethyl acetate / hexane to obtain 2-benzyl-6-ethoxycarbonyl-1-methylbenzimidazole (115 ) (0. 090g). [Physical properties of compound (115)]

HNMR (CDC13, ό): 1.41 (3Η, t, J: 7.1Hz), 3.63 (3Η, s), 4,32 (2H5 s), 4 40 (2Η3 q3 α = 7 · 1Ηζ) 3 7 · 21-7 · 26 (3Η3 m) 3 7 · 27-7 · 32 (2Η, m) 3? .72 (iH, d, J14H z), 7.98 (1Η, dd, J: 1.5 and 8 · He), 8.03 (1ϋ3 d, J: 1.3 Hz). &lt; Example 48; Synthesis of l- (2,4-dichlorobenzyl) _6_ethoxycarbonyl_2_methylbenzimidazoline (116) &gt; Amino_4-nitrobenzoate ethyl ester (1.50g) solution of n, N-diamidinofluorenamine (8ml) was dripped with 60% sodium hydroxide (0.357g) and N, N-dimethyl In a slurry consisting of methylamine (8 ml), stir 30 minutes. Then, a solution of 2,4-dichlorobenzyl chloride (1.74 g) in N, N-methylformamide (8 ml) was added dropwise and stirred for 30 minutes. The reaction solution was poured into a mixed solution of 50 g of dilute sodium hydroxide and ethyl acetate (60%), and the obtained organic layer was washed twice with water (5 called). The organic layer was concentrated under reduced pressure to obtain [^ 2 ' 4 One-generation benzyl) acetamido] -4-nitrobenzoate + 3.5g of fine clothing. Dissolve it in ethanol A4 (210x297 mm) without further refining (诮 Read the precautions on the back before filling this page) This paper ruler 548272 A7 B7 V. Description of the invention (丨 2〇) (23ml ), Acetic acid (12 ml), followed by adding reduced iron (3.32 g), and heating to reflux for 6 hours. A filtering aid was used to remove solids, and the filtrate was concentrated under reduced pressure. Ethyl acetate (60 ml) and dilute hydrochloric acid (50 ml) were added to the obtained residue to form a layer. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution (50 g), washed twice with water (50 g), and concentrated under reduced pressure to obtain a residue. The residue was purified by silica gel column chromatography (eluent ·· hexane / ethyl acetate = 4/1 ~ 1/1) to produce (2,4_dichlorobenzyl) ethoxylated -2-Azobenzobenzoate. Sitting (116) (0.94 g). [Physical properties of compound (116)] W-NMIUCDCh, 6): 1.40 (3Η, t, J 2 7.1Ηζ) , 2.56 (3Η, s), 4.38 (2H, q, J 2 7.1 Ηζ), 5.41 (2Η, s), 6.34 (1Η, d, J = 8.4Hz) 3 7 · 09 (1Η , Dd, J2 8.4 and 2.00Ηζ), 7.49 (1Η, d, J2 2.00Ηζ), 7.75 (1Η, d, J2 8.4Ηζ), 7.92 (1Η, s) : 8.00 (1Η, dd5 8.5 and 1.4Ηζ) &lt; Example 49; Synthesis of 6-carboxy-1- (4-chlorobenzyl) -2-n-propylbenzimidazole (117) &gt; 10% sodium hydroxide aqueous solution (3.57g), ethanol (5mi) and water (3.57g) were added to i- (4-gasbenzyl) _6_ethoxycarbonyl-n-propylbenzimidazole (1.06g) , Heated to reflux for 1 hour, 10% hydrochloric acid was used to make the reaction solution form pH 6. Ethanol was added to the residue obtained by concentration under reduced pressure, and the inorganic salt was filtered off. The filtrate was concentrated under reduced pressure to obtain 0.80 g of a residue. The residue was purified by silica gel column chromatography (eluent: ethyl acetate / methanol = 4/1) to obtain 6-carboxy-1- (4-gaso benzyl) _2_n-propylbenzimidazole (117 ) (0.63 g). [Physical properties of compound (117)] Standards for this paper (CNS) A4 · (21GX2 = Dong) &quot; ~~ ----- 548272 Α7 Β7 V. Description of the invention (121) (Fill in this page) ^ 'NMRiDMSO-dG, δ): 0.96 (3H, t, J = 7.3Hz), 1.76-1.88 (211, m), 3.10-3.23 (2H, rn), 5.83 (2Η, s ), 7.27 (2Η, d, J: 8.4Hz), 7.44 (2Η, d, J: 8.4Hz), 7.89 (1 H, d, J: = 8.4Hz), 7.89 (1Η, d, J 2: 8 · 5Ηζ), 8.28 (1H, s). &lt; Example 50; Synthesis of 6-Weiyl-1-methyl-2-n-propylbenzyl sigma (ns) &gt; According to the method of Example 49, 6-ethoxycarbonylmethyl_2 was used -N-propylbenzimidazole (0.5 6 g) to give 6-carboxy-1-fluorenyl-2-n-propylbenzyl salicylate (118) (0.46 g). [Physical properties of compound (118)] ^ -NMRiDMSO-dG, 6): 1.00 (3H, t3 J = 7,3Hz), 1.79-1.93 (2H3 m) 3 3.06 (3H, t, J = 7.4Hz), 3 · 92 (3Η, s) 5 7 · 76 (1Η, d, J = 8.4Hz), 7.97 (1H, d, J = 8.4Hz), 8.3.1 (1H5 s). 〈Example 51; 6 -Synthesis of -carboxy-2-n-propyl-1-isopropylbenzimidazole (119) &gt; According to the method of Example 49, 6-ethoxycarbonyl-2-n-propyl-1-isopropyl was used Benzimidazole (0.045 g) to give 6-carboxy-2-n-propyl-1-isopropylbenzimidazole (119) (0.045 g). [Physical properties of compound (119)] ^ -NMRiCDaOD, .5): 0.98 (3H5 t, J = 7.4Hz), 1.61 (6H, d5 J-6.9Hz), L74-1.8 2 (2H3 m), 2.89 (2H , t3 J = 7.5Hz), 3.21-3.24 (2H5 m), 4.78-4.83 (1H, m), 7.51 (1H, d, J two 8.3Hz), 7.84 (1H, dd, J = 8.4 and 1.5 · ζ ), 8.26 (1Η, s). &lt; Synthesis of Example 52,1-n-butyl-6-Weiyl-2-n-propylbenzyl sigma (120) &gt; According to the method of Example 49, 1_n-butyl_6 was used -Ethoxyoxyl ---------- L15_ This paper size is in accordance with China State Standard (CNS) A4 (210X297 mm) ~-548272 Α7 Β7 5. Description of the invention (122) -2- n-propyl Benzimidazole (0.81 g) to give n-butyl-6-carboxy_2-n-propylbenzimidazole (120) (0.60 g). (诮 Please read the precautions on the back before filling this page) [Physical properties of compound (120)] .41 (2H, m) 5 1.70-1.77 (2H3 m) 7 1.85-1.93 (2H5 m) 5 3.07 (2H, t , J = 7.6Hz), 4. 42 (2H, t, J: 7.4Hz), 7.78 (1Η, d, J: 8.5Hz), 7.99 (1H, dd, J: 8.5 and 1.0Hz), 8.35 (1H, s) 5 13.13 (1H5 s) 0 &lt; Example 53; Synthesis of 6-carboxy-1- (2-fluorobenzyl) -2-fluorenylbenzimidazole (121) &gt; Ethanol ( (80ml) and 10% aqueous sodium hydroxide solution (37g) were added to (2-oxofluorenyl) -6-ethoxykyl-2-fluorenylbenzo sigma (10.〇g) for 4 hours It is heated under reflux. After the reaction solution was cooled, it was adjusted to pH 6 with 10% hydrochloric acid. The collected precipitate was washed with water and dried under reduced pressure to obtain 6-carboxy-1- (2-chlorobenzyl) -2-methylbenzimidazole (12m). &lt; Example 54; Synthesis of 6-carboxy-l- (2,6-dichlorobenzyl) -2-fluorenylbenzimidazole (122) &gt; According to the method of Example 53, l- (2 , 6-dichlorobenzyl) -6-ethoxycarbonyl-2-methylbenzimidazole (0.90 g) to give 6-carboxy-1- (2,6-dichlorobenzyl) _2.methylbenzimidazole (m) (0.72g). [Physical properties of compound (122)] 'H-NKRiDMSO-dG, δ): 2.60 (3H, s), 0.71 (2H3 s), 7.46 (1Η, t, J = 7.9Hz)? 7. 57 (3H , T, J 2 8 · 2Ηζ), 7.73 (2Η, m), 12.57 (1H, s). &lt; Example 55; Synthesis of 6 · carboxy-2-methyl-l- [2- (trifluorofluorenyl) benzyl] benzimidazole (123) &gt;-____—_-_— \ Ύί \ The size of this paper is China State Standard (CNS) A4 (210X297 mm) 548272 A7 _____________________ B7 V. Description of the invention (123) ^ ^ ~~ '(邡 Please read the notes on the back before filling this page} According to the example 53 method, using 6_ethoxycarbonyl_2 • methyl_1- [2- (difluoromethyl) benzyl] benzimidazole (117g) to obtain 6_carboxyl-fluorenyl-1- [2- (trifluorofluorenyl) benzyl] benzimidazole (123) (0 98 g). [Physical properties of compound (123)] iNMIUDMSO-de, (5): 2.49 (3Η, s), 5.7Q (2H, s), 6.46-6.51 (1Η, π), 7,5] (2H, porphyrin 7.65 (1Ηί d, buckle 8 • him), 7.81 (1η, 虮 J = 14 and 8 · 4Ηζ), H, m), 7.91 (1Η3 s). &Lt; Example 56; 6-carboxy-2-methyl-l- [4- (trifluoromethyl) benzyl] benzene Synthesis of Benzimidazole (124) &gt; According to the method of Example 53, 6-ethoxycarbonyl-2-methyl_1- [4- (trifluoromethyl) benzyl] benzimidazole (22 g) was used to obtain 6_carboxy_2_ fluorenyl-1- [4_ (trifluorofluorenyl) benzyl ] Benzimidazole (124) (1.07 g). [Physical properties of compound (124)] ^ -NMRiDMSO-dG, d): 2.85 (3H3 s), 5.92 (2H, s) 3 7.50 (2H, d, J, 8.1Hz), 7. 74 (2H, d, J-8.1Hz) 5 7.88 (1H, d, J = 8.5Hz), 8.07 (1H, d? J = 8.5Hz), 8.31 (1H, s), 13.3 (1Η, br s). '&lt; Example 57; Synthesis of 6-carboxy-l- (3,4-dichlorobenzyl) -2-methylbenzimidazole (125) &gt; According to the method of Example 53, 1- ( 3,4-Dioxobenzyl) -6-ethoxycarbonyl-2-methylbenzimidazole (0.76 g) to give 6-carboxy-1- (3,4- ^ mono-gas-fluorenyl)- 2-Amidinobenzopyrene (125) (0.55g). [Physical Properties of Compound (125)] NMR (DMS0-d6,6): 2.56 (3Η, s), 5.61 (2H, s), 6.98 (1H, dd, J = 8.4 and 1.9Hz), 7.46 (1Η, d, J = 1.9Hz), 7.59 (1Η, d, J 2 8.3Ηζ), 7.63 (111, d, J 2 8.4Ηζ), 7.81 (1Η, dd, J 2 8 · 4 and 1.4 Hz), 8,07 (1H, s), 12 · 76 (1Η, s). The size of this paper is / 1] Chinese National Standard (CNS) A4 specification (210X2 ^ 1 centimeter) '' 548272 A7 B7 V. Description of the invention 24) &lt; 实施 例 58; 1-Benzyl_6_carboxyl · 2_ Synthesis of n-propylbenzimidazole (126) &gt; 10% sodium hydroxide aqueous solution 61g), ethanol (5ml), water (3ml) were added to 1-benzyl-6-ethoxycarbonyl-n-propylbenzimidazole ( 〇97g), heating and refluxing was performed for 1 hour, and the reaction solution was adjusted to pH 6 using 10% hydrochloric acid. Ethanol was added to the residue obtained by concentration under reduced pressure, and the inorganic salt was filtered to obtain 1-benzyl-6-carboxyl-n-propylbenzimidazole (126) (0.85 g). [Physical properties of compound (126) ] ffmiUDMSO-d6, d): 0.94 (3Η, t, J: 7.4Hz), 1.73-1.81 (2Η, m) 3 2.85 (2H, 1, J-7, 3Hz), 5.59 ( 2Η, s), 7.07 (2H, dd, J: ll and 8.3Hz), 7.27 (1H, t, J: 7. · 3Ηζ), 7.33 (2Η, t, J: 7.4Hz), 7.65 (1H, d, J = 8.4Hz), 7.79 (1Η, dd, J: 1.5 and 8. he), 8.04 (1Η, s). &lt; Example 59; Synthesis of 6-carboxy-1- (3-fluorobenzyl) -n-propylbenzimidazole (127) &gt; According to the method of Example 58, using __ (3_chloro Benzyl) ethoxycarbonyl-2-n-propylbenzimidazole (0.57g) to give 6-carboxyl_1- (3-gasobenzyl) -2-n-propylbenzimidazole (127) (0. 35 @). [Physical properties of compound (〖27)] fNMMDMSO-de, d): 0.94 (3H, t, J = 7.3Hz), 1.70-1 · 79 (2Η, m), 2.83 (2Η, t, J = 7.4Hz), 5.59 (2H5 s), 6.94 (1H, s), 7.15 (1H? S), 7.34 (211, d, J = 4.4Hz), 7.59 (lH, d, J = 8.4Hz), 7.81 (lH, d, J = 8.1 Hz), 8.02 (lH, s). &lt; Example 60; Synthesis of 6-carboxy-2-methyl-1- (2-nitrobenzyl) benzimidazole (128)> This paper size is applicable to China National Standard (CNS) A4 (210X297 mm) ) (掮 Please read the notes on the back before filling this page)

1T 548272 A7 B7 V. Description of the invention (125) According to the method of Example 58, ethoxycarbonyl-2-methyl-1_ (2-nitrobenzyl) benzimidazole (0.61g) was used to obtain 6 Carboxy_2-methylonitrobenzyl) benzimidazole (128) (0.35 g). [Physical properties of compound (128)] ^ -NMRiDMSO-dG, δ): 2.5K3Η, s), 5.96 (2H, s), 6.33 (1H, d, J = 7.0Hz) 7 7. 55-7 · 62 ( 2Η, m), 7.66 (1H, d3 J = 8.3Hz), 7.81 (1H, d, J = 8.4Hz) 8 06 (1H s) 8 · 24 (1Η3 d, J = 7 · 0Ηζ), 12 · 66 (1Η, s). &lt; Example 61; Synthesis of 6-carboxy-1- (2-chlorobenzyl) _2-fluorenylbenzimidazole (121) &gt; Ethanol (15 ml) and a 5% aqueous sodium hydroxide solution (1. .6 g) was added to (2-chlorobenzyl) -6-ethoxycarbonyl-2-fluorenylbenzimidazole (1456 g), and it was refluxed for 1 hour. After the reaction solution was cooled, it was adjusted to pH 6 using 10% hydrochloric acid. The sink was collected, washed with water, and dried under reduced pressure to give 6-carboxychlorobenzyl) -2-methylbenzimidazole (121) (0.645 g). &lt; Example 62; Synthesis of 6-carboxy-1- (2,4-dichlorobenzyl) -2-methylbenzimidazole (129) &gt; A 10% aqueous solution of sodium hydroxide (3.10 g) and ethanol (10ml) Add 1- (2,4-dioxobenzylethoxycarbonyl-2-fluorenylbenzimidazole (0.94g) in the prostitutes department. First read the precautions on the reverse side and fill in this page), and let it heat to reflux for 1 hour. Adjust the reaction solution to pH 6 with 10% hydrochloric acid. The crystals precipitated are dried by filtration to obtain the carboxyl 4- (2,4_ Monobenzyl) -2-methylbenzimidal (129) (0.68g). [Physical properties of compound (129)] mMiUDMSQ-dG, d) ·· 2.52 (3H, s), · 61 (2Η , S), 6,54 (1H, d, J: 8.4Hz), 7.33 (1H, dd, J = 8.4 and 2.1Hz), 7.64 (1H, d, J: 8.4Hz), 7. · 74 (1H, d, J: 2.1 Hz), 7.81UH, dd, J = 8.4 and 1.51ζ), 7.98 (1Η, s), 12.72UH, s).

--------— τ 2Q Speed of this paper / 1] Chinese National Standard (CNS) A4 specification (210X2 ^ 7 mm)-548272 A7 B7 V. Description of the invention (126) &lt; Example 63; 1- (Synthesis of 4-benzyl-4-methyl &gt; 6-carboxy-2-methylbenzimidazole (130) &gt; (Read the precautions on the back before filling in this page) The method according to Example 53 , Using (biphenylmethylethoxycarbonyl-2-methylbenzimidazole (ii0g) to obtain (biphenyl_4_fluorenyl) _6-branzyl-2-methylbenzo1 [1 Misa (13〇) (〇.838). [Physical properties of compound (130)] iH-NMIUDMSQ-ciG, d): 2,53 (3H3 s) 3 5.61 (2H3 s) 5 7.18 (2H, d, J : 8.2Hz), 7 34 (1H3 m) 3 7 · 43 (2Η, m) 3 7 · 62 (5Η3 m) 3 7,79 (1H, dd, J = 1.6 and 8.5Ηζ), 8.09 (1H, d, J = 1.0 Hz) 3 12 · 72 (1Η3 br s). &Lt; Example 64; 1- (4- 3rd butylbenzyl) -6-carboxy-2-methylbenzimidazole Synthesis of (131) &gt; According to the method of Example 53, 1- (4- 3rd butyl benzyl) -6-ethoxycarbonyl-2-fluorenylbenzimidazole (1.34 g) was used to obtain i- (4-third butylbenzyl) -6-carboxy-2-methylbenzimidazole (i31) (〇e55g). [Physical properties of compound (131)] HN MR (DMSQ-d6, ά): H (9H, s), 2.57 (3Η, s), 5.52 (2Η, s), 7.Q3 (2H, d, J-8.2Hz), 7. · 35 (1Η, d, J: 8.3Hz), 7.60 (1Η, d, J: 8.4Hz), 7.78 (1Η, dd, J = 8 4 and 1.5Ηζ), 8.06 (1Η, s), 12.71 (1Η, s). &lt; Example 65; Synthesis of 6-carboxy-2-methyl-1- (2-fluorenylbenzyl) benzimidazole (132) &gt; According to the examples Method 53 using 6-ethoxyquinyl-2-fluorenyl-1- (2-methylbenzyl) benzimidazole (0.81g) to give 6-carboxyfluorenylmethylmethylbenzyl) benzene Benzimidazole (132) (0.49 g). [Physical properties of compound (132)] This paper size applies Chinese National Standard (CNS) A4 specification (210X 297 mm) 548272 A7 ____ B7 V. Description of the invention (127) (谙 Please read the precautions on the back before filling in this page) inm ^ DMSO-d6, 6) 2.41 (3 ·, s), 2.48 (3Η, S), 5.55 (2Η, s), 614 (1H, d, J: 7.6Hz), 7 · 02 (1Η, t, J: 7.4Hz), 7.miH, t, J: 7.3Hz) 5 7 26 (this d, j: 7 4 Hz), 7.65 (1H, d, J-8.4Hz ), 7.81 (1H, dd, J1 ^ · 4 and 14Hz) 7 97 (1H d J = 1.1 Hz), 12.71 (1H, s). &lt; Example 66; Synthesis of 6-carboxy-1- (2-methylbenzyl) -2-methylbenzimidazole (133) &gt; According to the method of Example 53, ethoxycarbonyl group was used. 2-methylbenzyl) -2-methylbenzimidazole (1.63 g) to synthesize 6-weilylmethylfluorenyl) -2-methylbenzyl saliva (I33) (1.00 g). [Physical properties of compound (133)] Dirty (DMSO-d6,0) U5 (3H, s), 3.81 (3Η, s) 3 5 · 42 (2Η, s), 6.77 (1Η, m), 6.85 (1Η, in), 7.G5UH, m), 7.28 (1Η, m), 7,58 (1Η, ιη), 7.76 (1Η, ιη), 7.99 (1H, s), 12 · 65 (1Η, br s) 〇 Example 67; Synthesis of 6-carboxy-1- (4-fluorenylbenzyl) _2-methylbenzimidazole (134)> According to the method of Example 53, 6-ethoxyweilyl-1- (4-methylbenzyl) -2-methylbenzimidazole (1.27 g) was used to give 6-carboxyfluorenylbenzyl) -2-fluorenylbenzimidazole (134) (0.99 g). [Physical properties of compound (L34)] W-NM ^ DMSQ-de, ά): 2.86 (3H, s), 3.71 (3Η, s), 5.69 (2Η, s), 6.92 (2Η, d3 J 2: 8 · 4Ηζ), 7.27 (? Η, d, J = 8.4Hz), 7.84 (1Η, d, J = 8.5Hz) 3 8.〇4 (1Η, d, J = 8 · 5 Hz), 8 · 33 (1Η, s), 13 · 25 (1Η, br t). &lt; Example 68; Synthesis of 6-carboxy-2-methyl-l- [2- (benzenesulfonylmethyl) benzyl] benzimidazole (135) &gt; The paper size applies the Chinese National Standard (CNS ) A4 specification (210X297 mm) \ Ί 5. Description of the invention (128) According to the method of Example 53, 6-ethoxycarbonyl_2_methyl_ 1- [2- (benzenesulfonylmethyl) benzyl [Yl] benzimidazole (〇89g) to get the carboxyl (read the notes on the back before filling out this page} group-2-methyl-1- [2- (benzenesulfonylmethyl) benzyl] Benzimidazole (135) (0.74g). [Physical properties of compound (135)] H-NMR (DMS0-d6, δ): 2.44 (3H, s) 5 4.99 (2H, s), 5.71 (2H3 s), 6 08 (1H d

J-6.5Hz), 7.12-7 · 20 (3Η, m), 7.64-7 · 70 (3Η, m), 7,77-7 · 83 (2Η, in), 7 89 (2H, s) 3 7.90 (1H, s), 12.71 (1H3 s). &lt; Example 69; Synthesis of 6-carboxy-: u (2-cyanobenzyl) _2-methylbenzimidazole (136) &gt; According to the method of Example 53, i_ (2-cyanobenzyl ) _6_ (2_cyanobenzyloxycarbonyl) -2-methylbenzimidazole (2.04g) to give 6-quinyl_1β (2_cyanobenzyl) _2_methylbenzimidazole (136 ) (1.14g). [Physical properties of compound (136)] ^ -NMRiDMSO-dB, δ): 2.54 (3H, s), 5.80 (2H, s) 5 6.78 (1H, d, J == 7.8Hz), 7 51 (1H, t , J = 7.4Hz), 7.61 (1Η, dt, J: 7.8 and 1.2Hz), 7.64 (m, d, J: 8.4Hz) ，, 7.80 (1Η, dd, J = 8.4 and 1.5Hz ), 7.94 (1H, d, J: 6.7Hz), 8.00UH, d, J: 1.1Hz), 1Z.70 (1H, s) 〇 Example 70 Synthesis of benz-2-fluorenyl) -2-fluorenylbenzoxazole (137) &gt; According to the method of Example 53, ι_ (biphenylmethyloxycarbonyl-2-methylbenzimidazole ( l.31g) to obtain 6-carboxyl_ 丨 _ (biphenyl-2_fluorenyl) -2-methylbenzimidazole (137) (1.07g). [Physical properties of compound (137)] ___U2_ This paper is suitable for this paper Sichuan China National Standard (CNS) A4 specification (210X297 mm) '548272 A7 B7 V. Description of the invention (129) 1 Bandit (DMS0-d6, (5) · 2.32 (3Η, s), 5.45 (2H, s), 6.61 (1H, d, J: 7.7Hz), 7.26 (1H, dt, J = 7.7 and i.4Hz), 7.31UH, dd, J: 7.5 and 1.3Hz), 7.36 (1H, d (麴 Please read the notes on the back before filling in this page t, J: 7.5 and 0.7 Hz), 7.40-7.46 (lH, m), 7.46-7.52 (4H, id), 7.57 (1H, d, J) 8 · 4Ηζ), 7.76 (1H, dd, J-7.9 and!. 5Hz), 7,86 (1H, d, 1.2Hz), 12.72 (1H, s). &Lt; Example 71; 1-benzyl- Synthesis of 6-carboxy-2-fluorenylbenzimidazole (138) &gt; According to the method of Example 53, ι_benzyl-6_ethoxyepimethylbenzimidazole (0.71g) was used to obtain the benzyl group _6_carboxy_2_methylbenzimidazole (138) (0.59g). [Physical properties of compound (138)]

, 1T W-NMR (DMSQ-d6, ά): 2.556 (3Η, s) 5 5.57 (2Η, s), 7.11 (1H, d, J = 8.GHz), 7.27 (1Η3 t , J: 7.2 Hz), 7.32-7.35 (2Η, m), 7.61 (1Η, d, J: 8.3Hz), 7.79 (1Η, dd, J = 8.4, and 1.3Ηζ) , 8.06 (1Η, s), 12.75UH, s). &lt; Example 72; Synthesis of 6-carboxy-2-methyl-1- (2-naphthylmethyl) benzimidazole (139) &gt; According to the method of Example 53, 6-ethoxycarbonylmethyl was used 1- (2-naphthylmethyl) benzimidazole (1.28§) to give carboxy-2-methyl-^ (2-naphthylfluorenyl, benzyl) benzimidazole (139) (0.80g) . [Physical properties of compound (139)] ^ leg (DMSO-j6, d): 2.61 (3H, s), 5.74 (2Η, s), 7.29 (1Η, d, J: 8.6Hz), 7. 46 7.52 (2Η, m), 7.59 (1H, s), 7.63 (1Η, d, J: 8.3Hz), 7.78-7 · 92 (4Η, m), 8.0 9 (! H, s) , 12,68 (1H, s). &lt; Example 73; l- (biphenyl-4-methyl) -6-fluorenylethylbenzimidazole —-------- L3-3 _____ This paper is compliant with Sichuan National Standards (CNS) A4 specifications (210X 297 mm '548272 A7 _______ B7 V. Description of the invention (131) [Physical properties of compound (142)] (Read the precautions on the back before filling in this page) W-NMRiDMSO-de, ά): 2 · 49 (3Η, s) 5 5.9K2H, s) 3 6 · 36 (1Η, pyridine J = 7 2 and 1.8Hz), 7.52 (1Η, d, J: 8.5Hz), 7.55-7 · 62 ( 2Η, m), 7.77 (1h, machine J = 85 and} • 5HZ), 8. H, d, machine 3 „z), 8.2, dd, ㈣ 4 and i 6Hz) i2 69 (n) 〇 & lt Example 76; Synthesis of 2-benzyl-5-carboxy-substituted benzyl) benzimidazole (143) &gt; 14. According to the method of Example 53, a 2-benzyl-substituted benzyl group) -5- Ethoxycarbonyl benzimidazole (0.635 g) to give 2-benzylcarboxyl 1- (2-chlorobenzyl) benzobenzyl (143) (0.488 g). [Physical Properties of Compound (143)] ^. (DMSO-de, (5): 4.27 (^ s), 5.57 (2H, S), 6.27 (1Η, d, J = 7 1Hz), 7〇6 (lH, t), 7.1〇- 7.29 (6H5 m), 7.39 (1H, d, J = 8.6Hz), 7.47 (1H, d, J, 7.9Hz), 7. Low dd, J = 1.4 and 8 , 8.21 (1Η, d, J = 12Hz), i2 &amp; s). &Lt; Example 77; 2-benzyl-6-carboxyl- (2-chlorobenzyl) benzimidazole (144) Synthesis> According to the method of Example 53, 2-benzyl-1β (2-oxobenzyl) -6-ethoxycarbonylbenzimidazole (1.00 g) was used to obtain 2_ Benzylsulfonyl_ 1-0 chlorofluorenyl) benzimidazole (144) (0.780g). [Physical properties of compound (144)] ^ -NMRiDMSO-dG, d): 4.29 (2H, s), 5.63 ( 2H, s) 5 6.28 (1H, d, J = 7.8Hz), 7 07 (1H, t, J: 7.6Hz) 5 7 · 15 (1Η, in), 7.19-7 · 29 (5Η, ffl ), 7.49 (1η, d, j: 7 4Hz), 7.70 (1Η, d, J = 8.4Hz), 7.81UH, d, J = 8.4Hz), 7.91 (1Η, s), 12 · 73 (1Η, br) 〇, this paper size Tongzhou Chinese National Standard (CNS) A4 specification (210X 297 mm) 548272 A7 B7 V. Description of the invention (132) &lt; Example 78; 2-section base_5_ Synthesis of benzimidobenzyl) benzimidazole (145) &gt; According to the method of Example 53, fluorenylbenzyl-4,2, 'dioxobenzyl) -5-ethoxycarbonylbenzimidazole ( 0.50 g) to give fluorenylbenzylcarboxy-1- (2,4-dichlorobenzyl) benzimidazole (145)[Physical properties of compound (14 5)] H ~ NMR (DMS0-d65 δ); 4.28 (2H s) 5 55 (? Η \ ^ 〇〇〇? 7iRH, v 〖, S), 5_55 (2H, s), 6.19 (1Η, d, J: 8. he), 7. ⑽-7.22 (6H, m), 7.4ί (1Η, d, J: 8 4Hz) 7 ^ T. 4 calls, 7.62 (1H, d, 2.2Hz), 7.79 (1H, dd, 1.5, and 8.6 · ζ), 8.22 (1Η3 s), 12.72UH, br s). &lt; Example 79; Synthesis of 2-benzylcarboxy-le (2, 'digaso-benzyl) benzimidazole (146) &gt; According to the method of Example 53, fluorenylbenzyl-1- (2 , 'Digasobenzyl) -6-ethoxycarbonylbenzimidazole (0.48g) to give 1benzylcarboxyl-1-(2,4-, monomurinofluorenyl) 146) (0.35 g). [Physical properties of compound (146)] lH-NMR (DMS0-d6? Ά): 4.30 (2H? S), 5.61 (2H7 s), 6.19 (111, d? J = 8.4Hz), 7. 09 7.22 (6H , M), 7.64 (1Η, d, J = 2, lHz), 7.71 (1H, d, J: 8.4Hz), 7.82 (1H, dd, J2, 1, 5 and 8. he), 7 · 94 (1Η, d, J: 1.2 Hz), 12.78 (1Η, br s) (&lt; Example 80; l- (biphenyl-4-fluorenyl) -6-carboxy-2-trifluoromethyl Of Benzobenzimidazole (147) &gt; According to the method of Example 53, 1- (bibenzyl-4-methyl) -6-ethoxycarbonyl-2-trifluorofluorenylbenzimidazine (〇. 690g) to obtain 1- (biphenyl-4-fluorenyl) -6-carboxy-2-trifluoromethylbenzimidazole (i47) (0.483g). [Physical properties of compound (147)] State National Standard (CNS) M specifications (210 X 297 mm) Λ beat bei 'in the jealous department ,; 1.τ eliminate the combination of bamboo and fir seal 54 548272 A7 B7 5. Description of the invention (133) 1 leg (DMSQ-d6, ά) 5.87 (2Η, s), 7.18 (2Η, d, J: 8.2Hz), 7.35 (1Η, t, J 2 7 • 4Hz) 3 7.44 (2H3 t3 J-7.5Hz) 3 7.60-7.67 (4H, m) 3 7.98 (2H, d5 J = 0.7Hz), 8.3 2 (1H3 s) 3 13.15 (1H, s) 〇 &lt; Example 81; l- (Biphenyl-4-methyl) -5-carboxy Synthesis of 2-trifluoromethylbenzimidazole (148) &gt; According to the method of Example 53, 1- (biphenyl-4-methyl) -5-ethoxycarbonyl-2-trifluoromethylbenzene was used Benzimidazole (0.38 g) to give 1_ (biphenylmethyl) -5-carboxy-2-trifluoromethylbenzimidazole (148) (0.270 g). [Physical properties of compound (148)] lH-dirty ⑽S0-d6,0): 5.80UH, s), 7.19UH, d, J: 6.3Hz), 7.35 (1Η3 t, J: 7 • 2Hz), 7.43 (2Η, t, J: 7.3Hz ) 3 7 · 82 (1Η, d, J = 8.7Hz), 8.Q4UH, d, J: 8.7Hz), 8.45 (1H3 s) 〇 Example 82; 5-ethoxycarbonyl-2-methyl Synthesis of Benzimidazole (149) &gt; Added reduced ethyl iron (6.64g), ethanol (48ml) and acetic acid (24ml) to ethyl ethyl 3-nitro-4-nitrobenzoate Medium, heated to reflux for 1 hour. A filtering aid was used to remove solids, and the filtrate was concentrated under reduced pressure. Ethanol (100 ml) and 35% hydrochloric acid (5.2 g) were added to the residue, and the mixture was heated under reflux for 5 hours. The reaction solution was neutralized with sodium bicarbonate (63 g), and the filtrate obtained by filtration was concentrated under reduced pressure. Ethyl acetate (70 ml) and water (70 ml) were added to the obtained residue to separate the layers. The organic layer was washed three times with water, and the aqueous layer was extracted three times with ethyl acetate. The obtained organic layer was concentrated under reduced pressure to obtain a 5-ethoxycarbonyl-2-methylbenzimidazole (149) powder (1.53 g). (Read the notes on the back before filling in this page}

| 548272 A7 __ 一 B7 V. Description of the invention 134 [Physical properties of compound (149)]

Η-orbital (CDCh, d) · 1.41 (3H, t, J: 6.9Hz), 2.67 (3Η, s), 4.40 (2Η, q, J 2 7.1 Ηζ), 7.55 (1Η3 d, J 2 8.4Ηζ), 7.96 (1Η, dd, J: 8.4 and 1.5Ηζ), 8.27 (1Η, d, J = 1.4Hz). &lt; Example 83; Synthesis of 2-benzyl-5-ethoxycarbonylbenzimidazole (50) &gt; Ethyl 3-nitro-4-phenylacetamidoaminobenzoate (3.60g) under reflux A mixture of ethanol (47 ml), acetic acid (23 ml) and reduced iron (6.4 g) was used for 4 hours. The solid was filtered off and the filtrate was concentrated. Ethanol (501111) and 35/0 hydrochloric acid (5 g) were added to the residue, and stirred under heating and refluxing for 40 hours. Neutralize with sodium bicarbonate and extract with trichloromethane. The organic layer was concentrated under reduced pressure and purified by silica gel column chromatography to give 2-benzyl-5-ethoxycarbonylbenzimidazole (150) (2.30 g). [Physical properties of compound (150)] ^ -NMRiCDCh, δ): 1.39 (3H5 t, J = 7.1Hz), 4.26 (ZH3 s), 4.37 (ZH, q3 J = 7.1

Hz), 7.22-7 · 36 (5Η, m), 7.50 (1Η, d, J = 8.6Hz), 7.94 (1Η, dd, J = 1.5 and 8.6

Hz), 8.23 (1.33 d3 J = 1.3 Hz) &lt; Examples 84, 85; 6-ethoxycarbonyl-2-methyl-1- (2-nitrobenzyl) ^ y,-^ 1 ^^^ 1,; ^^ 消 于 合 竹 ^ 印 ^ (谙 Please read the precautions on the back before filling this page) Benzimidazole (151) and 5-ethoxycarbonyl-2-methyl-1- (2 -Nitrobenzyl) Benzimidazole (152) Synthesis> N, N-dimethylformamide (1 plus 1), 2-nitrobenzyl bromide (1.59g) and sodium bicarbonate (1.23 g) Add 5-ethoxycarbonyl-2-methylbenzimidazole (1000 g) and heat at 60 ° C for 1 hour. After adding 70 ml of ethyl acetate and water (70 ml) to the reaction solution for layer separation, the organic layer was washed with water. 3 The paper size is in accordance with China National Standard (CNS) A4 (21 ^ 297 ^ 1) ~ --- 548272 A7 ------------------- B7 V. Description of the invention (135) --- Human Asia uses ethyl acetate for 3 times to extract the water layer. The organic layer obtained by concentration under reduced pressure was used to obtain 6-ethoxyquinyl heptamethyl-fluorenyl "shawyl" benzimidin ^ ethoxy-2-yl small (2-nitrobenzyl) ) The mixture of benzoic saliva was purified by medium pressure silica gel column chromatography (eluent: hexane / ethyl acetate 1/4 ~ 0/100) to obtain buethoxyquinyl-2-methyl small ( 2-Azylbenzyl) benzimidazole (151) (0.6Mg) and 5-ethoxycarbonyl-2-fluorenyl-K2-nitrobenzyl) benzimidazole (152) (0.259g). [Compound (15 1) Physical properties] H_ (CDCh, 6) · 1.38 (3Η, t, J: 7.2Hz), 2.56 (3Η, s), 4.37 (2H, q, J = 7.1 Hz) , 5.84 (2H, s), 6.41 (1Η, d, J: 6.8Hz), 7.44-7.53 (2H, m), 7.78 (1H, d, J: 8.6Hz), 7.88 (1H, s), 8 · 02 (1Η, dd, J: 8.3 and 1.5Ηζ), 8.30UH, dd, J = 7.9 and 1,5Hz) q [physical properties of compound (152)] tfiMIUCDCla ， ά): 1.42 (3Η, t, J: 7.0 Hz), 2.56 (3Η, s), 4.40 (2H, q, J: 7.0 Hz), 5.80 (2Η, s), 6.43 (1H, dd, J: 7.6 and Hz) , 7.14ΠΗ, j: 8.3Hz) i 7.45-7.53 (2Η, m), 7.95 (1H, dd, J: 8.4 and 1.5Hz), 8.27 (1H, dd, J: 8.0 and 1.7Hz ), 8.48 (1H3 d, J-1.2 Hz) &lt; Examples 86, 87; 2 · Benzyl-l- (2-chlorobenzyl) -6-ethoxycarbonylbenzimidazole (l53) and 2-benzyl-1_ (2_ Synthesis of gasified benzylethoxycarbonylbenzimidazole (154) &gt; According to the method of Examples 84 and 85, 2-benzyl-5-ethoxycarbonylbenzimidazole (2.37g) and 2-chlorobenzyl were used Bromide (3.94g) to give 2-fluorenyl-1- (2-chlorobenzyl) -6-ethoxyepibenzobis (153) (1.06g) and 2-fluorenyl-1- (2-Azoyl) 5-Ethoxybenzoyl benzophenone sigma paper size of this paper applies Chinese National Standard (CNS) A4 specification (210X 297 mm) (Read the precautions on the back before filling in this 548272 A7 B7 V. Description of the invention (136 ^ (154) (0.640g). [Physical properties of compound (153)]

Hz), 5.36 (2H, s), 6.23 (1Η, d, J: 7.8Hz), 6.97 (1Η, t, J: 7.6Hz), 7.1b 7 45 (7H, m) 5 7, 85 (1H, d3 J: 8.5Hz), 7.91 (1H, s), 8.02UH, dd, J: i.2 & δ 6Hz) [Physical properties of compound (154)]

^ -NMRiCDCla, δ): 1.41 (3Η3 t3 J-7.1Hz) 3 4.25 (2H3 s), 4.41 (2H, q3 j ^ A Hz), 5.33 (2Η3 s), 6.22 (1Η3 d5 J 6.9Hz), 6.97 (1H, t, J = 7 · 6Ηζ) 3 7.12 ~ 7.28 (7H5 m) 3 7.40 (1Η? D5 J = 8.0IIz) t 7.95 (1H, dd5 J ^ i.6 R 8.6 Hs); 8.60 (lH d, J 2: 1 · he). &lt; Examples 88 and 89; 2-benzyl-l- (2,4-dichlorobenzyl) -6-ethoxycarbonylbenzimidazole (I55) and 2-benzyl-l- (2,4- Synthesis of dichlorobenzyl) _5_ethoxycarbonylbenzimidazole (156) &gt; According to the method of Examples 84 and 85, 2-benzyl-5-ethoxyquinylbenzimidazole (2.37g) and 2,4-Dioxobenzyl bromide (4.45g) to give 2_benzyl-1- (2,4-dichlorobenzyl) _6 · ethoxycarbonylbenzimidyl salivate in the middle part of y? . ^-^ h 3 Consumers' private seal (Read the precautions on the back before filling in this page j (155) (0.49g) and 2_benzyl small (2,4-dioxobenzyl)) _% Ethoxybenzylbenzimidazole (156) (0.52g). [Physical properties of compound (155)] ^ -NMRiCDCh, d): L39 (3H3 t), 4.24 (2H, s), 4.37 (2H, q ) 5 5.32 (2HS s), 6.08 (1Η, d, J = 8.3Hz), 6.90 (1Η, d, J = 8.4ilz), 7.12-7 · 24 (5Η, m), 7.41 (ih s), 7.84 (1Η, i J: 8.4Hz), 7.88 (1Η, s), 8.G3 (1H, d, J: 8.4Hz). [Physical properties of compound (156)] This paper is suitable for the national standard (CNS) A4 size (210x29m) ----- ------ 548272 A7 __ B7 V. Description of the invention (137) lH-NMR (CDCl3 , δ): 1.42 (3H, t5 J-7.1Hz) 5 4.25 (2H, s), 4.4i (2H, qj Hz), 5.28 (2Η, s), 6.07 (1Η, d, J = 8.4Hz), 6.90 (1Η, dd, J2 1.9 and 8 4Hz) 7.08-7 · 28 (6Η, m), 7 · 40 (1Η, d, J2 2.12ζ), 7 96 (1Η, dd, J 2 1.3 and 8 3Ηζ) 8.56 (1Η, d, J = 0.9Hz). &lt; Example 90; Synthesis of 5-ethoxycarbonyl-2-trifluoromethyl benzimidazole (157)> 5% / stone (0.50 g) was added to 3-amino-4-nitro-benzoin In a solution of ethyl acetate (4.00 g) in methanol (100 ml), under hydrogen atmosphere, stir at 5 (rc for 16 hours. The solid was filtered, and the filtrate was concentrated to obtain 3,4-diaminobenzoic acid ethyl ester. Trifluoroacetic acid (20 ml) was added thereto and stirred at 60 ° C. for 2 hours. The reaction solution was concentrated, and the crystals precipitated by adding trifluoromethane were filtered and dried to obtain 5-ethoxycarbonyl-2- Trifluoroimethylbenzimidazole (l57) (4.46g). [Physical properties of compound (157)] 1NMR (DMS0-d6, (5): 1.36 (3Η, t3 J: 7.0Hz), 4.36 (2Η, q3 J: 7.0Hz), 7 82 (1 H3 d, J: 8.5Hz), 7.99 (1Η, dd, J = 1.5 and 8.7Ηζ), 8.33 (1Η, s). OK浐 中 中 ^; i? Quasi ^ hJr. Consumption and Bamboo 卬 f (诮 Please read the precautions on the back before filling in this page) &lt; Examples 91, 92; 1- (biphenyl-4-fluorenyl)- Of 6-ethoxycarbonyl-2_trifluoromethylbenzimidazole (158) and 1- (biphenyl-4-amidino) -5-ethoxychiyl_2_trifluoromethyl polyimidazole (I59) Synthesis> Basis In the method of Examples 84 and 85, 5-ethoxycarbonyltrifluoromethylbenzimidazole (2.00 g) and 4-bromofluorenylbiphenyl (100gg) were used to obtain 1- (biphenyl-4 -Methyl) -6-ethoxycarbonyl-2-trifluoromethylbenzimidazole (158) (0.69g) and 1- (biben-4-methyl) -5-ethoxycarbonyl-2-trifluoro Pyridyl benzimidazole (159) (0.38g). This paper size is applicable to the Chinese National Standard (CNS) A4 (210X297U ^) ----- 548272 kl B7 The middle part of the noodles is humble, ^^ 消竹 合 竹 ^ 印 掣 5. Description of the invention (13θ [physical properties of compound (158)] Xing (CDCh, 0): 1.39 (3H, t), 4.38 (2Η, q), 5.64 (2H, s), 7.18 (2H, d3 J 2: 8.2Ηζ), 7.34 (1H, t, J: 7.4Hz), 7.42 (2Η, t, J = 7.4Hz), 7.52-7 · 57 (4Η, m) , 7 • 95 (1H, d, J = 8.8Hz), 8.09 (2Η, dd, J = 1.4 and 8.8Ηζ), 8.14 (1H, d, J = MHz) 〇 [Compound (159) Physical properties]

4-wake (CDC13, 6): 1.40 (3Η, t), 4.40 (2Η3 q), 5.59 (2Η, s), 7.16 (2H, d, J = 8.1Hz) 3 7.34 (2H3 t3 J = 6.2Hz) 3 7.41 (2H3 t3 J-7.5Hz) 3 7.53 (4H3 m) 3 8.08 (1 H, dd, J = 1.3 and 9.1Hz), 8.65 (1Η, s). &lt; Production Example 38; Production of 1- (2-chlorobenzyl) -6-hydroxymethyl-2-methylbenzimidazole &gt; The 1- (2- Chlorobenzyl) -6-ethoxycarbonyl-2-methylbenzimidazole (2.66g) in tetrahydrofuran (20ml) was added to a solution of potassium hydride (1.54g) in tetrahydroσfuran (20ml). . Then, it was stirred at room temperature for 1 hour. 30 ml of tetrahydropyran was added to dilute the reaction solution. A saturated aqueous sodium sulfate solution was added to decompose and solidify the potassium hydride, thereby separating the tetrahydrocaran layer. The solvent was distilled off and purified by silica gel column chromatography (eluent: trichloromethane / methanol = 9/1) to obtain i_ (2-chlorobenzyl) _ 6-¾ylmethyl-2 -fluorenyl Stupid spider σ sitting (145 g). [Physical properties of compound] ^ -NMRiCDCla, δ): 2.53 (3Η3 s), 4.77 (2H3 s) 5 5.39 (2H, s) 3 6.40 (1H, d3 J = 7.7Hz), 7.08 (1Η, t, J 2 7 · 7Ηζ), 7.20-7 · 28 (3Η, m) 3 7 · 45 (1Η, d, J 2 7.9 · ζ), 7.70 (1H, d, JH = 8.2 Hz). &lt; Manufacturing Example 39,1-(bibenzylmethyl) _6-Methylbenzyl-2-methylbenzol This paper is sized for China National Standards (CNS) A4 (2H) x 297 meters) (Please Read the precautions on the back before filling in this page), \ ί 口. 91. Μ ^., Δ1 in ^ i? ^-^ H, T ^) Feizhu * 1print t 548272 A7 B7 V. Description of the invention (139). Production of the seat> According to the method of Production Example 38, using 1-xylbiphenyl-4-methylethoxycarbonyl-2-methylbenzimidazole (5.30 g) and potassium aluminum hydride (2.17 g) to obtain 1 -(Biphenyl-4-methyl) -6-hydroxymethyl-2-methylbenzimidal (3.72 g). [Physical properties of compound]

H-NMR (CDC1: 3,5) · 2.59 (3Η, s), 4.78 (2Η, s), 5.37 (2Η, s) 3 7.11 (2H, d, J -8 · 3 ζ) 3 7.24 (1Η, d, J ~ 8.3Hz), 7.30 ~ 7.37 (2Η, in), 7.42 (2Η, t), 7 51 ~ 7 56 (4Η, m), 7.70 (1Η, d, J = 8.2Hz). &lt; Production Example 40; Production of l- (2-chlorobenzyl) -6-gasmethyl-2-methylbenzimidazole hydrochloride &gt; Gasified thionyl chloride (5ml) was added to 1- (2-Azobenzyl) -6-methyl-2-methylbenzimidazole (3.56g), stirred at room temperature, 2 (TC, 80 ° C) for 20 minutes. Distilled under reduced pressure to After removing the excess thionyl chloride, the residue was dissolved in trichloromethane (10 ml), and hexane was added to crystallize it. The crystals were filtered out, washed and dried to obtain 1_ (2-chlorobenzyl) -6-chlorofluorenyl-2-fluorenylbenzimidazole hydrochloride 4.07 g. [Physical properties of the compound] lH-NMR (CDCl35 δ): 3.0K3Η, s) 3 4.68 (2H, s), 5.61 (2H, s) 5 6.71 (1H3 d5 J 2 7.5Ηζ), 7.24-7 · 29 (1Η, m) 3 7 · 38 (1Η, t, J: 7.7Hz) , 7.44 (1H, s), 7.52 (2H, d, J = 8.2Hz), 7.92 (1H, d, J = 8 · 4Ηζ). <Manufacturing Example 41; Production of 1- (biphenyl-4-fluorenyl) -6-chlorofluorenyl-2-fluorenylbenzimidazole &gt; Add thionyl chloride (2ml) at room temperature to 1- (Biben-4-methyl) _ 6-¾fluorenyl-2-methylbenzimidazole (3.62g) in trichloromethane solution (30mi) The paper size is applicable to China National Standard (CNS) A4 specifications ( 210X 297 mm) (Read the precautions on the back before filling this page)

548272 A7 B7

V. Description of the invention (14〇) -S, stir at 60 C for 1 hour. An aqueous sodium hydrogen carbonate solution was added to stop the reaction, and the trichloromethane layer was dried and washed with water. After removing the solvent by distillation under reduced pressure, ethyl acetate was added to crystallize. The crystals were filtered, washed with ethyl acetate, and dried to obtain 2.04 g of (biphenyl-4-methyl) -6-chloromethyl-2-fluorenylbenzimidazole. [Physical properties of the compound] lH-NMR (CDCl33 δ): 2.67 (3H, s) 3 4.71 (2H5 s), 5.40 (2H3 s), 7.12 (2H, d, J 8.2Hz), 7 · 31_7 · 38 ( 3Η, m), 7.43 (2Η, t), 7.52-7 · 58 (4Η, m), 7.75 (1H, d, &gt; 8 · 2Ηζ) 〇 &lt; Manufacture example 42; 1- (2 -Chlorobenzyl) -6-methylamino-2-fluorenylbenzimidazole &gt; Manganese dioxide (3.46g) was added to 1- (2-chlorobenzyl) -6-hydroxymethyl- A solution of 2-fluorenylbenzimidazole (3.46 g) in toluene (100 ml) was dehydrated with molecular sieve 4A while heating and refluxing for 3.5 hours. The solid was filtered and washed with chloroform. The filtrate was concentrated to give 3.35 g of 1- (2-chloroimidyl) -6-fluorenyl-2-fluorenylbenzimidazole. [Physical properties of compound] 'H-NMRiCDCh, 6): 2.61 (3H, s) 5 5.48 (2H, s), 6.42 (1H, d, J = 7.8Hz), 7 * U (1H, t, J = 7.6 Hz), 7 · 27 (1Η, t), 7.48 (1H, d, J = 8 · 0Ηζ), 7.76 (1Η, s), 7 * 81 (1 H, dd, &lt; M · 4 and 8 · 3Ηζ), 7.86 (1Η, d, J 2 8.3Ηζ), 10 · 02 (1Η, s). IR (KBr): 1676 (^ 0 mp: 124.1-125.2 ° C. &Lt; Production Example 43; Production of 1- (2-Gasoxybenzyl) -2-fluorenylbenzimidazole-6-acetonitrile &gt; The paper size applies the Chinese National Standard (CNS) A4 specification (210/29711). (The first note on the back is to fill in this animal.)

1T Φ1. 548272 A7 __________________B7 V. Description of the invention (141) ^ — Add potassium cyanide (0.450g) and 18-crown ether-6 (0.450g) to 1- (2-chlorobenzyl) -6-chloroform The solution was stirred in room temperature for 18 hours in a solution of ketosmethylbenzimidazole 0.20 dimethylsulfoxide (10 ml). Add chloroform, water, and a small amount of ammonia, and extract. The organic layer was concentrated to obtain a residue, and the residue was purified by silica gel column chromatography (eluent: trifluoromethane / methanol = 20/1) to give 1_ (2_gaso benzyl) -2-methylbenzo. Imidazole-6-acetonitrile (500 g). [Physical properties of compound] ^ -NMRiCDCh, δ): 2.52 (3H3 s), 3.80 (2H5 s), 5.37 (2H3 s), 6.40 (1H, d, J = 7.6Hz), 7.09 (lH, t), 7.10 -7.19 (2H, m), 7.23 (lH, t), 7,44 (lH, d, J = 7.9Hz) 3 7.70 (1H3 d3 J-8.2Hz) 〇 &lt; Production Example 44; 6-carboxyl-1 -Production of (2-chlorobenzyl) benzimidazole &gt; 98% of formic acid (0.5ml) was added to 4-amino_3- (2- Benzyl) aminobenzoic acid (0.490 g) was refluxed for 1 hour. The solid precipitated in the reaction solution was collected. After washing with water and drying to obtain 0.468 g of 6-carboxy-1- (2-chlorobenzyl) benzoacetone. [Physical properties of compound] W-NMiUDMSO-dG, 6): 5.69 (2Η, s), 7.02 (1H, dd, J: 1.5 and 7.7Hz), 7.30 (1H, t, J = 7.5Hz), 7 · 36 (1Η5 dt, J = 1.7 and 7.5Hzh 7.53 (1Η, dd, J = 1.3 and 7.9Hz), 7.75 (1Η, d5 J = 8 · 4Ηζ), 7.83 (1Η, dd, J = 1.5 and 8.4Ηζ), 8.09 (1H, s), 8.54 (1H, s), 12.8 (1H, br s) 〇 &lt; Example 93; l- (2-chlorobenzyl) -6- Synthesis of ethoxycarbonyl-2-methylbenzimidazole (92) &gt; 2-Gas benzyl bromide (100 g) was added to 4-acetamido-3-amino-benzoate ----- --14S ___ This paper size applies Chinese National Standard (CNS) A4 (210X297 mm) (Please read the precautions on the back before filling this page), 11 548272 A7 ------------- ------- B7 V. Description of the invention (142) '' &quot; &quot; ~ · — 一 'Ethyl benzoate (86.0g) and calcium carbonate (37 3g) in ethanol (75〇mi) solution Stir at 60 ° C for 14 hours. Filter the solids, reduce the mash to 500ml under reduced pressure. Add 35% hydrochloric acid (38 7g), and stir at 60 ° C for 2 hours. Filter the solids and pass through carbonic acid. After neutralization with sodium hydrogen, ethanol was distilled off under reduced pressure. Ethyl acetate and water were added for extraction (three times). After washing with water and drying the organic layer, the solvent was distilled off until the organic layer was 300 mi. The precipitated crystals were filtered and recrystallized from ethanol to obtain丨 _ (2_ chlorobenzyl) -6-ethoxycarbonyl_2_methylbenzimidazole 54 3g. Also, all the filtrate was collected, and the crystals obtained by recrystallization from ethanol were concentrated to obtain 1- (2-Gas-benzyl) -6-ethoxycarbonylmethylbenzimidazole (92) 18.lg [Physical properties of compound (92)], 57 (3, s) 5, 37 (2H3 q3 ,, , '5 5,46 (2H3 S), 6-41 (1H5 di J =?-8HZ ^ 7-l0 (lH3 t3 J, 7.8Hz) 3 7.25 (1H3 .7.47 (1H, d5 J, 8.0Hz) 3 7.75 (1H5 d, J, 8.4Hz) 5 7.94 (1H3 s), 8.00 (1H3 dd, J2 1.5 and 8. 4Ηζ). Mp: 126.0 —127 · 0 Τ. &Lt; Peipalladium Example 94; 6-carboxyl Synthesis of -1- (2-chlorobenzyl) -2-methylbenzimidazole (121) &gt; 10 /. An aqueous solution of sodium hydroxide (240 g) and ethanol (200 ml) were added to 1- (2-chlorobenzyl) -6-ethoxycarbonyl-2-methylbenzimidazole (600 g), Heat to reflux for 2 hours. After cooling, the reaction solution was adjusted to pH 6 with 10% hydrochloric acid, and the precipitated crystals were dried to obtain 6-endyl-1- (2-chlorobenzyl) · 2-methylbenzimidazole 021). (54.7g). National paper standard (CNS) A4 size (21Gxl ^^ (Read the precautions on the back before filling this page) 1 Ding Feng 548272 A7 B7 V. Description of the invention (143) [Physical properties of compound (121) ] Old-dirty_0_ (16,6): 2.51 (3Η, s), 5.62 (2Η, s), 6.54 (1d, d, J: 7.7Hz) 3 7 · (Please read first Note on the back page: 23 (1H3 t, J: 7.5Hz), 7.33 (1Η, t3 J: 7.7Hz), 7.55 (1Η, d, J: 8.z), 7.63 (1Η, d5 J = 8.4Hz) 3 7.79 (1H, d5 J = 8.4Hz), 7.95 (1H, s) 〇inp: 300.8-303.0oC 〈Example 95; l- (2-chlorobenzyl ) Synthesis of 2-methylbenzimidazole-6-acetic acid (160) &gt; Add 10 ° /. Hydrochloric acid to 1- (2-chlorobenzyl) -2-methylbenzimidazole_6-acetonitrile ( 0.500g), heated to reflux for 15 hours, neutralized with a saturated sodium bicarbonate aqueous solution, and extracted with chloroform. The organic layer was concentrated by silica gel column chromatography (eluent: chloroform / methanol = 9/1 ~ 4/1) and 11 were refined to obtain 1- (2-chlorobenzyl) -2-methylbenzimidazole-6-acetic acid (160) (0.170 g). [Physical properties of compound (160)] ^ -NMRCCDCh, 6): 2.42 ( 3H, s), 3.56 (2H, s) 3 5.15 (2H3 s) 3 6.33 (1H5 d) 3 6.96 (1Η, t), 7.03 (1Η, s), 7.13 (2Η, m ), 7.35 (1Η, d, J: 7.9Hz), 7.62 (1Η, d), 8.90 (1Η, br s) 0 &lt; Example 96; 1- (2-chlorobenzyl ) Synthesis of 2-methylbenzimidazole-6-acrylic acid ethyl ester (161) &gt; Triphenylphosphonium acetoacetate (4.49 g) was added to 1- (2-chlorobenzyl) A 6-fluoren-2-fluorenylbenzimidazole (2.73 p-dioxane (50 ml) solution was 'stirred under heating and refluxing for 6 hours. After cooling the reaction solution, the solvent was distilled off' by silica gel column chromatography (Dissolved liquid: three gas methane / methanol = 9/1) refined residue to get H2-gaso benzyl) _2_methylbenzimidazole_6_Acrylic paper scales (CNS) Α4 gauge; (ΓΠΓ0 × 297)) 548272 A7 B7 V. Description of the invention (144) ^ — crude refined product of methyl ester (161) 743g. This crude refined product is directly used in the following reaction. (Please read the precautions on the back before reading) (Fill in this page) &lt; Example 97; Synthesis of 1- (2-chlorobenzyl) -2-methylbenzimidazole acrylic acid (162) &gt; Add 1- (2-chlorofluorenyl) _2_methyl The crude refined product of methyl benzoyl sialic acid (161) 3.29§ was dissolved in ethanol (20 mi), and a 5% aqueous sodium hydrogen solution (10.lg) was added and refluxed for 2 hours. The reaction solution was neutralized with an aqueous hydrochloric acid solution, and the residue obtained by concentrating the solvent under reduced pressure was purified by silica gel column chromatography (eluent ·· trichloromethane / methanol = 9/1 ~ 6/1) to obtain ^ 〇 chloro Benzyl) 2-methylbenzimidazole-6-acrylic acid (162) i 10 g. [Physical properties of compound (162)] 4- earning S0-d6, ά): 2.56 (3 (, s), 5.65 (2Η, s) 3 6.54 (1Η, d, # 15 · 9Ηζ), 6 • 62 (1H, d, J: 7'Hz), 7.25 (1Η, t), 7.35 (1Η, t), 7.56 (1Η, d, J: 8.1Hz), 7 6 -7.7G (3H, m), 7.99 (1Η, s), 12.35 (1H, br s). &lt; Example 98; Synthesis of 6-benzylaminocarbamoyl-based benzyl) -2-fluorenylbenzyl salivary (163) &gt; Iced into a solution of dioxanyl (2-oxobenzyl) -2-methylbenzimidazole (45.0g) in N, N-dimethylformamide (95ml), and stirred at room temperature 1 hour. Next, sparbenamine (471 g) and diazabicycloundecene (35.0 g) were added and stirred at 100 ° C. for 70 hours. The reaction solution was cooled, and the solvent was distilled off under reduced pressure. Water (300 ml) and methanol (200 ml) were added to the residue, followed by 35% hydrochloric acid (607 g) to adjust the solution to pH 5.5. The precipitated crystals were filtered out, washed with a mixture of methanol and water (1/1) (200ml), and dried to obtain 6 • benzylsulfonylamino. This paper is sized to the Chinese National Standard (CNS) A4. (210x ^ 97 ^ 1) — 548272 A7 B7 V. Description of the invention (14 women (诮 first read the notes on the back and then fill out this page) 醯 + + (2-chlorobenzyl) 丄 methyl benzimidazole 38 々. In addition, water was added to the filtrate, and the precipitated crystals were filtered, washed with water, and dried to obtain 13.3 g. The above 2 crystals were added together, and acetone (⑺00) and water (900 ml) were added, and heated to make Its dissolved. The solvent 200 mi was distilled off under heating, and it was cooled. The precipitated crystals were filtered off, and dried to obtain 33.8 g of 6-benzylsulfanylmethanylmethyl (+ 2-chlorobenzyl) -2-methylbenzimidazole (163). [Physical Properties of Compound (163)]-Legs «0-d6,: 2.53 (3H, s), 5.46 (2H, s), 6.34 (1H, d, hours), 7, J-8.6Hz) 5 7.90 (1H3 m) 7,60 (1H5 7.69 (lH3d ».09 (2H5 m) 3 8.11 (1H3 s), 11.84 (1H5 br s)) IR (KBr): 1684, 1448CDT1.

Mass (FAB): m / e 440 (M + 1). That is: 273.5-274.30C. <Example 99; 6-benzylsulfonylaminofluorenyl-1- (biphenyl-4-fluorenyl)- Synthesis of 2-ethylbenzimidazole (164) &gt; 4. According to the method of Example 98, 1- (biphenyl-4-fluorenyl) _2_ethyl-6-carboxybenzimidazole (0 600§), Ν, Ν, carbonyldiimidazole (0546g), benzylsulfonamide (0.529g), diazabicycloundecene (〇512) to give 6 • benzenesulfonylcarbamidine -1- (Biphenyl Ifluorenyl) _2-ethylbenzimidazole (164) (0,473g). [Physical properties of compound (164)] lH ~ NMR (DMS0-d63 δ): 1.29 (3H, t, J = 7.4Hz) 3 2.88 (2H, q3 J-7.4Hz), 5.59 (2 H, s) 3 7.16 (2H3 d5 J = 8.2Hz), 7.33-7.37 (1H, m), 7.44 (2H, t, J = 7.5Hz), 7.5

9-7.71 (8H, m), 7.74 (1Η, dd, J: 8.4 and 1.4Hz), 7.98-8 · 02 (2Η, m), 8.21 (1H 5 s), 12.43 (1H5 s) .IR (KBr): 1684cm-1〇mp: 149,5-157.0 ° C. The paper size is suitable-Jiaxian County (CNS-) A ^ T (210X29 ^^ 7 548272 A7 B7 V. Description of the invention (146) &lt; Implementation Example 100; Synthesis of 5-benzenesulfonylaminoaminofluorenyl-; ι_ (2-chlorobenzyl) -2-methylbenzimidazole (165) &gt; (Read the precautions on the back before filling in this Page) According to the method of Example 98, 5-carboxy-1- (2-chlorobenzyl) -2-fluorenylbenzimidazole (0.450 g), N, N'-carbonyldiimidazole (0.485 g), Phenyl S &amp; amine (0.470g), diazabicycloundecene (0.4456g) to give 5-benzenesulfonylaminofluorenyl-1- (2-chlorobenzyl) -2-fluorene Benzimidazole (165) (0.480 g). [Physical properties of compound (165)] W-NMIUDMS◦-d6, d): 2.53 (3Η, s) 3 5.61 (2H3 s), 6.57 (1Η) , D, J 2 7 · 4Ηζ), 7.22 (1H, t) 3 7 · 33 (1Η, t), 7.50 (1 (, d, J = 8.6Hz), 7.54 (1 (, dd, JII 7.9 and 0.9Ηζ), 7.63 (2Η, t), 7.71 (2H, m), 8.00 (2Η, d, J = 7.3Hz) 8.21 (1Η, d, J = 1.4H z) 5 12.50 (1H, br s) 〇IR (KBr): 1685cm 'mp: 137.0-138.5oC &lt; Example 101; 5- (4-Gasbenzene) Synthesis of sulfonylaminofluorenyl) -1- (2-chlorobenzyl) _2.methylbenzimidazole (166) &gt; According to the method of Example 98, 5-carboxy-1- (2- Chlorobenzyl) -2-methylbenzimidazole (0.450 g), N, N'-carbonyldiimidazole (0.485 g) &gt; 4-chlorobenzenesulfonamide (0.573 g), diazepine Ene (〇.456g) to give 5- (4-Gabenzenesulfenylcarbamoylmethyl) -1- (2-gasobenzyl) -2-fluorenylbenzimidazole (166) (0.520g) . [Physical properties of compound (166)] 1H-NMR (DMS0-d6,6): 2.49 (3H, s), 5.58 (2H, s), 6.51UH, d, J: 7.6Hz), 7.t), 7 · 32 (1Η, t), 7.45 (1Η, d, J = 8.6Hz), 7.53 (1Η, d, J = 7.8Hz), 7.69 This paper size applies the Chinese National Standard (CNS) A4 specification ( 21 (^ 297 ^ 1) 548272 A7 ____ B7 V. Description of the invention (147) (3H, d, J = 8.6Hz), 7.99 (2Η, d, J: 8.6Hz), 8.18 (1Η, s ), 12.58UH, br s). iR (KBr): 1619cm- 丨. (Read the precautions on the back before filling in this page) That is: 261.5-263.0oCo &lt; Example 102; l- (2-chlorobenzyl) -2-methyl-5_ (2-naphthalenesulfonium Synthesis of Benzylaminofluorenyl) Benzimidazole (167) &gt; According to the method of Example 98, 5-carboxy-1- (2-chlorobenzyl) -2-methylbenzimidazole (0.450 g) was used ), N, N, -carbonyl diamnidazole (.485g), 2-naphthylbenzenesulfonamide (0.620g), diazabicycloundecene (0_456g) to give 1- (2_ Gaso-benzyl) -2-methyl-5_ (2-naphthylsulfonylcarbamoyl) benzimidazole (167) (0.352 g). [Physical properties of compound (167)] 1H-NMR (DMS0-d6, δ): 2.48 (3H, s) 3 5.56 (2H, s), 6.49 (1H3 d, J-7.7Hz), 7. 20 (1H, t5 J = 7,6Hz), 7.3K1H, t3 J = 7.7Hz) 3 7.44 (1H, d, J = 8.6Hz), 7.52 (1H,

d, J = 8.0Hz), 7.66-7.75 (3H, m) 5 7.97 (1H, d, J = 8.8Hz), 8.04 (1Η, d, J = 8.0H z) 5 8.14 (1H, d, J-8.8Hz), 8.19 (1H, s) 5 8.23 (1H, d, J-8.0Hz), 8.68 (1H, s), 1Z.55 (1H, br s), IR (KBr): 1685cm-1 . mp: 236.5-238.0 ° C &lt; Example 103; Synthesis of 1- (2-chlorobenzyl) -6-fluorenylsulfonylaminomethylfluorenyl-2-fluorenylbenzimidazole (168) &gt; basis The method of Example 98 was performed using 6-carboxy-1- (2-chlorobenzyl) -2-methylbenzoxyl saliva (0.500 g), N, N,-prison-based rice noodles (0.539 g) Methanesulfonylamine (0.316g), diazabicycloundecene (0506g) to give 1- (2-chlorobenzyl) -6-methanesulfonylaminofluorenyl_2_ The paper size of fluorenylbenzo is applicable to Chinese National Standard (CNS) A4 (210X297 mm) 548272 A7 B7 V. Description of the invention (148) Imidazole (168) (0.564g). [Physical properties of compound (168)] (Please read the precautions on the back before filling in this page)! Η-orbital (DMS〇-d6, d): 2.49 (3Η, s), 3.35 (3Η, s ), 5.60 (2Η, s), 6.43UH, d, J 2 7.8Ηζ), 7.23 (1Η, t), 7.34 (1Η, t, J = 7.7Hz), 7.57 (1Η, d, J = 8.0Hz), 7.68 (1H, d, J = 8.5Hz), 7.81 (1Η, dd, J = 1.7 and 8.5Hz), 8.13 (1H, d, J = i.5Hz), 11.94 (1H3 br s) 〇IR (KBr): 1670cm—, mp: 302 · 30—303.0 ° C— &lt; Example 104; 6- (l-butanesulfonylcarbamoylamino benzyl)- Synthesis of 2-methylbenzimidazole (169) &gt; According to the method of Example 98, using 6-carboxychlorobenzyl) -2 · fluorenylbenzimidazole (0.500g), N, N'-carbonyldi Oral saliva (0.539g), 1-butanesulfonamide (0.456g), diazabicycloundecene 506g) to give 6- (1-butanthanthenylaminofluorenyl) -1- ( 2-Azobenzyl) -2-methylbenzimidazole (169) (0.595g). [Physical properties of compound (169)] 1H-NMR (DMS0-d63 δ): 0.84 (3H, t, J = 7.4Hz), 1.38 (2H, m), L65 (2H, m), 2. 49 (3H, s), 3.49 (2Η, m), 5.60 (2Η3 s), 6.44 (1H, d, J = 7.6Hz), 7.23 (1Η, t, J = 7.6Hz), 7.35 ( 1Η, t), 7.56 (1Η, d, J: 8.0Hz), 7.68 (1Η, d, J: 8.4Hz), 7.80 (1H, dd, J: 1.6 and 8.4Ηζ), 8 · 11 (1Η, d, J: 1.4Hz), 11 · 86 (1Η, br s). IR (KBr): 1684cm'l0mp: 214.0-217.0 ° C (&lt; Example 105; 1- (2-Atomylbenzyl) -2-methyl-6-octylsulfonylcarbamoylmethyl) Synthesis of benzimidazole (170) &gt; According to the method of Example 98, 6_carboxyl 1- (2_chlorobenzyl) was used. The paper size applies the Chinese National Standard (CNS) A4 (210x 297 mm) 548272 A7 ___ B7 V. Description of the invention (149) (Read the precautions on the back before filling in this page) Base) -2-Azobenzimidazole (0.4〇g), N, N'-carbonyldiimidazole (0.431g) , 1-octanesulfonamide (0.406g), diazabicycloundecene (0.404g) to give 1- (2-chlorobenzyl) -2-methyl-6- (1-octanesulfonate Amidinocarbamoyl) benzimidazole (170) (0.309 g). [Physical properties of compound (170)] (DMSQ-d63 (5): 0.82 (3Η, t, J: 7.3Hz), 1.13-1.28 (8Η, m), 1.32-1.41 (2Η3 m ), 1.62-1.7Κ2Η, m) 3 2.50 (3H, s), 3.50 (2H5 t3 J-8.5Hz), 5.61 (2H, s), 6.45 (1Η, d3 J 2 7 · 7Ηζ), 7 · 24 (1Η, t, J, 27.5Ηζ), 7.35 (1Η, t, J = 7.5Hz), 7,58 (1H, d, J = 8.0Hz), 7.69 (1Η, d, J = 8.4Hz), 7.81 (1Η, d3 J: 8.5Hz), 8.12 (1Η, s) 3 11.86 (1H, s). IfUKBr): 1674CHT1. nip: 180.0 — 183.0 ° C. <Example 106; Synthesis of l- (2-chlorofluorenyl) -2 · methyl-6- (2-propanthazinylaminocarbamyl) benzimidazole (171) &gt; Basis The method of Example 98 uses 6-carboxy-1- (2-fluorobenzyl) -2-fluorenylbenzimidazole (0.400 g), N, N, carbonyldiimidazole (0.431 g), and 2-propanesulfonic acid. Fluorenamine (0.328g), diazabicycloundecene (0.404g) to give 1- (2-gasofluorenyl) -2-fluorenyl-6- (2-propanthazolylcarbamate) Alkyl) benzimidazole (171) (0.417 g). [Physical properties of compound (171)] 1H-NMR (DMS0-d6, δ): 1.30 (6H, d, J = 6.9Hz), 2.50 (3H, s), 3.81-3.87 (1H, m), 5.62 (2H3 s), 6.46 (1Η5 d, J 2 7.7Ηζ), 7.25 (1H3 t, J 2 7.5Ηζ), 7.35 (1Η, t, J = 7.5Hz), 7.62 (1Η, d , J = 7.9Hz), 7.69 (1Η, d, J 2 8.5Ηζ), 7.81 (1Η, d, J 2 8.6Η z), 8 · 12 (1Η, s), 11 · 83 (1Η, s). —-- IS3__ _ This paper is a Chinese standard (CNS) A4 size (210X297 mm) 548272 A7. 5. Description of the invention (5q) IR (KBr): 1670 ^^ 0 mp: 215 · 0-217.5 ° Co. Example 107 Synthesis of 1- (biphenyl-4-methyl) -6- (1-butanesulfonylaminofluorenyl) -2-methylbenzimidazole (172) &gt; Basis The method of Example 98 uses 1- (biphenyl-4-methyl) -6-carboxy-2-methylbenzimidazole (0.300 g), N, N'-carbonyldiimidazole (0.323 g), 1- Butylsulfonamide (0.273 g) and diazabicycloundecene (0.303 g) to obtain di (biphenyl-4-methyl) -6- (1-butane yellow base, aeroylmethytyl ) _2_Aminobenzobenzoate (172) (0.349g) 〇 [Physical properties of compound (172)] lH-dirty (DMS (H16, d): G.85 (3H, t, # 7 · 4Ηζ) , 1.36_1 · 43 (2Η, m), 1.63-1 · 72 (2H, m), 2.57 (3H, s), 3.52 (2H, t, J: 7.7Hz) 35.60 (2H3s) 37.21 (2H3d , J: 8. 2Ηζ), 7.35 (1Η, t, J = 7.3Hz), 7.44 (2Η, t, J: 7.5Hz), 7.60-7 · 68 (5Η, m), 7 · 81 (1Η, dd, J = 1.6 and 8.4Ηζ), 8.26 (1Η, d, J = 1.4Hz), 11.97 (1Η, s). IR (KBr): 1676cm-1. Mp : 219.5-222.5 ° C &lt; Example 108; 6- (1-Butanesulfonylcarbamoyl) -l- (2,4-dichlorobenzyl) -2-fluorenylbenzimidazole (173 ) Synthesis &gt; The central part of the warp section «: rate ^ $ τ, eliminate the private seal of the bamboo ¾ (read the precautions on the back before filling this page) According to the method of Example 98, use 6-carboxy-1- (2,4-dichlorobenzyl) _2-fluorenylbenzofluorene (0.40 g), Ν, Ν, quinone disigma (0-431 g), 1-butanesulfonamide ( .364g), diazabicycloundecene (0.404g) to give 6- (1-butanesulfonylcarbamoamido) -l- (2,4-dichlorobenzyl) · 2-methylbenzimidazole (173) (0.459g). [Physical properties of compound (173)] W-NMR (DMS0-d6, ά): 0.85 (3Η3 t, J = 7.3Hz), 1.36 -1 · 42 (2Η, m), 1.63-1, 70 (This paper size applies to Chinese National Standard (CNS) A4 specifications (210 x 297 male 4) 548272 A7 B7 V. Description of the invention (15) Please fill in this page again for the matters needing attention) 2H, m), 2.50 (3Η, s), 3.51 (2Η, t, J: 7.7Hz), 5.59 (2Η, s) 3 6.45 (1Η5 d, J 2: 8 · he), 7.33 (1H, dd3 J: 2.1 and 8. 4Ηζ) 3 7 · 6 9 (1Η3 d5 J: 8.4Hz) 3 7.76 (1Η, d, J = 2.0Hz), 7.81 (1Η, dd, J: L7 and 8.5Ηζ), 8.11 (1Η, d, J : 1.3 Hz) 3 11 · 90 (1Η 3 s). IR (KBr): 1670 cm-. H2.0-223.0oCo &lt; Example 109; 1- (Biphenyl-4-methyl) -6- (1-butanesulfonylaminomethylamidino) -2-ethylbenzimidazole (174) Synthesis &gt; According to the method of Example 98, 1- (biphenyl-4-methyl) -6-carboxy-2-ethylbenzowow (0.300 g), N, N'-jikylobiazepine was used Saliva (.340g), sulfasalazine (0.300g), diazabicycloundecene (0.320g) to give 1- (biphenyl-4-methyl) -6- (1-butyric acid (Carbamoyl) -2-ethylbenzimidazole (174) (0.300 g). [Physical properties of compound (174)] 4-NMR (DMS0-d6, 6): 0.85 (3H, t3 J-2 7.3Ηζ), 1.30 (3Η, t, J-2 7.5Hz), 1.35-1 • 44 (2H, m), 1.64_1 · 72 (2Η, m), 2.9G (2H, q, J = 7.4Hz), 3.52 (2Η, t, J = 7.7Hz), 5.61 (2H, s), 7 · 19 (2Η, d, J 2 8.3Ηζ), 7,35 (1H, t, J 2 7.3Ηζ), 7.44 (2Η, t, J 2 7.5Ηζ), 7 · 61-7 · 67 (4Η, m), 7.71 (1Η, d, J = 8.5Hz), 7.82 (1Η, dd, J = 1.6 and 8. · 5Ηζ), 8.27 &lt; 1Η, d, J 2: 1.3Ηζ), 12.01 (1 (, s). IR (Nujol): 1687, 1682cni 1 mp: 171.8-173.0oC 0 &lt; Example 11; 6-benzenesulfonylcarbamoyl-1- (biphenyl-4-fluorenyl) -2-trifluoro Synthesis of methylbenzimidazole (175) &gt; According to the method of Example 98, 1- (biphenyl-4-methyl) -6-carboxy-2-trifluorofluorenylbenzimidazole (0.483 g), N, N'-carbonyldiimidazole ^ --------- tss ---- The paper size is Yaozhou Chinese National Standard (CNS) A4 (210X 297 mm) 548272 A7 B7 V. Description of the invention (15j ( 〇.396g), sulfasalazine (0.383g), diazabicyclo eleven dilute (〇.371g) (谙 Please read the precautions on the back before filling this page) to get 6-benzoxanthinamine amino -1- (bibenzylidene) trifluoromethylbenzimidazole (175) (0.508g). [Physical properties of compound (175)] lH-NMR (DMS0-d6, δ): 5.81 (2H3 s) 3 7.15 (2H, d3 J = 8.3Hz), 7.35 (1H, t, J-7 .5Hz), 7.44 (2H, t, J = 7.5Hz), 7.60-7.66 (6H, m), 7.70 (1H, t , J = 7.4Hz), 7.9 1 (1H, dd, J = 8.7 and 1.4Hz), 7.96-8.01 (3H, m), 8.42 (1Η, s), 12 · 65 (1Η, s) (IR (KBr): nip: 164.5 to 167. (TC0 &lt; Example 111; 5-benzothiazinoyl Synthesis of methylmethylfluorenyl_i_ (biphenyl_cardiacyl) -2-trifluorofluorenylbenzimidazole (176) &gt; According to the method of Example 98, 1_ (biphenylmethyl) -5-Wei Syl-2-trisitinobenzobenzoic acid (0.270g), N, N '· kisyl bisalamine (0.221g), benzylsulfonamide (0.214g), diazabicycloundecene 0.207 g) to give 5-benzoxanthenylcarbamoyl-1- (biphenyl-4-methyl) -2-trifluorofluorenylbenzimidazole (176) (0.286 g). [Physical properties of compound (176)] INMlUDMSiH ^, 6): 5.79 (2Η, s) 5 7 · 15 (2Η, d, J: 8.1Hz), 7.35 (1Η, t, J = 7 · 5Hz ), 7.43 (2Η, t3 J = 7.5Hz), 7.59-7 · 67 (6Η, m), 7.72 (1Η, t, J: 7.6Hz), 7.8 3 (1H, d, J = 8.8Hz), 7.94 (1Η, d, J = 8.9Hz), 8.02 (2Η, d, J: 7.4Hz), 8.49 (1H, s), 12.69 (1H3 s). IR (KBr): 1699cm-, mp: 248.5-251.0oC &lt; Example 112; 6-benzenesulfonylaminoaminofluorenyl-2-cyclopropyl-1- (2-fluorobenzyl) benzo Synthesis of imidazole (177) &gt; -------- This paper size applies Chinese National Standard (CNS) A4 (210X 297 mm) 548272 呔 呔 呔, ^ ^ Bamboo II f A7 B7 V. Description of the invention (15j According to the method of Example 98, 6-carboxy-2-cyclopropyl-1- (2-fluorobenzyl) benzimidazole (0.993 g) was used , N, N, -Ichizodiazole (〇.972g), sulfenamide ((K942g), diazabicycloundecene (.906g) to give 6-benzenesulfonylcarbamidine Phenyl-2-cyclopropyl-1- (2-fluorobenzyl) benzimidazole (177) (0.730 g). [Physical properties of compound (17 7)] 1H-NMR (DMS0-d63 δ): 1.04 ( 4H3 m) 3 2.15 (1H, m), 5.70 (2H5 s), 6.85 (1 H, t3 J: 7.5Hz), 7 · 12 (1H, t, J = 7.5Hz>, 7.22-7 · 38 (2H, twist), 7.54-7.70 (5H, m), 7.99 (2H, d, J = 7.5Hz), 8.11 (1H, s). White powder. &Lt; Example 113 ; N-benzenesulfonyl-3- [1 · (2-chlorobenzyl) _2_methylbenzimidazole-6-yl] acrylamide 178) Synthesis> According to the method of Example 198, 1- (2-Gastilbyl) _2-methylbenzimidazole-6-acrylic acid (liOg), N, N, and bis-diimidazole ( (109g), benzylsulfonamide (1.06g), diazabicycloundecene (1.02§) to give N-benzenesulfonyl-3_ [1- (2-chlorobenzyl) -2- Methylbenzimidazole-6-yl] propenamide (178) (1.05g) 〇 [Physical properties of compound (178)]-Earn (DMSO-d6, cS): 2.47 (3H, s) 3 5,55 ( 2H, s), 6.46-6.S5UH, m), 7.22 (1 H, t, J = 7.6Hz), 7.32 (1Η3 t, J: 7.7HZ), 7.40 (1Η, d, J: 8.4 Hz), 7.52-7.66 (6Η, m), 7.69 (1Η, t), 7.93 (2Η, d, J = 7.9Hz), 12 · 17 (1Η, br s ) IR (KBr) · 1687cm— !.

Mass (FAB): m / e 466 (M + l) 〇 jap: 243.1 — 244.3 ° C 〇 This paper standard Chinese National Standard (CNS) A4 specification (21〇χ29 ^^ --- (Read the note on the back first Please fill out this page again for the matter}, 1T ^ 548272 A7 B7 V. Description of the invention (15j &lt; Example 114; N-benzenesulfonyl-2-_2- [1- (2-chlorobenzyl) _2-methylbenzyl) Synthesis of fluoren-6-yl] acetamide (179) &gt; According to the method of Example 98, ι_ (2-chlorobenzyl) &gt; 2-methylbenzimidazole-6-acetic acid (0.170§), Team: ^,-carbonyldiimidazole (0.1758), benzylsulfonamide (0.170 g), diazabicycloundecene (0.164 g) to obtain N-benzoxanthanyl-2- [1- (2-chlorobenzyl) -2-fluorenylbenzimidone-6-yl] ethynylamine (179) (0.09 g). [Physical properties of compound (179)] ^ -NMRiDMSO-dG, δ): 2.44 (3H, s) 3 3.57 (2H, s), 5.46 (2H, s), 6.41 (1H3 d, J = 7.7Hz), 6.96 (1Η, d, J: 7.0Hz), 7.16 ( 1Η, s) 3 7.20 (1H, t), 7.32 (1Η3 t) 3 7 · 47 (1Η, d3 J = 8Iz), 7.52-7 · 59 (3Η, m), 7.67 (1Η , T, J: 7.5 Hz) 3 7.84 (2 Η, d 3 J-7.4 Hz) 5 12.28 (1H, br s) IR (KBr) 1719 cm-10 mp: 236.2-237.8 ° C. &lt; Example 1 15; l- (2,4-dichlorobenzyl) -2-methylpyridylmethyl) aminofluorenyl] benzimidal (180) &gt; Only τ, eliminate cooperation * print? Water (please read the precautions on the back before filling this page) Add dioxane (150ml) and a few drops of Ν, Ν-dimethylphosphonium amine to 6-end Base-1- (2,4-digasocarbyl) -2-fluorenylbenzo (η) (9.00 g), ice-cold. Drop into the gasified ethylenedifluorene (6.48 g) and stir for a few minutes. After stirring at room temperature for 1.5 hours, it was concentrated under reduced pressure to a volume of about one-third. The precipitate was collected and 2-aminopyridine (2.69 g) and triethylamine ( 7.34g) in a solution of dichloromethane (200ml). After stirring for 15 hours, the reaction solution was washed three times with water, and then washed with a saturated sodium bicarbonate aqueous solution. The organic layer was concentrated under reduced pressure, and ethyl acetate was used to To make it crystallize. Feng paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 548272 Μ B7 V. Description of the invention (15j transition out of crystalline 'dry surplus to pay 1- (2,4 -dichloro section) Base) -2-fluorenyl-6_ [(2-0 Specific σ 疋 曱 group) Gasomethyl] benzo sigma (i80) 4.35g. (Read the precautions on the back before you fill in this page) [Physical properties of compound (180)] H NMR (CDCl35 δ): 2.56 (3H3 s), 4.76 (2H3 d3 J = 4.8Hz) 3 5.40 (2H3 s), 6.33 (1H 'd, J: 8, 4Hz), 7.07 (1Η3 dd, J: 8.4 and 2.00Ηζ), 7.22 (1Η, dd, J = 7.4 and 4.9Hz), 7.33 (1H, d , J: 7, 9Hz), 7.48 (1Η, d3 J: 2.1Hz) 3 7.62_7 · 79 (4Η, ιη), 7.86 (1Η, d, J = l.lHz) 8.57, (1H , D, J: 4.9 Hz). IR (KBr): 1645cm l0: 204.5-206,5oC &lt; Example 116; 1-methyl · 2-n-propyl-6-[(2-pyridylmethyl) carbamoyl] benzimidazole Synthesis of (181) &gt; According to the method of Example 115, 6-carboxyl-fluorenyl-n-propylbenzimidazole (0.402 g), ethylene dichloride (0.468 g), and 2-amino group were used. Methylpyridine (0.199g), triethylamine (0.559g) to give 1-fluorenyl-2-n-propyl-6-[(2-.pyridinylmethyl) aminofluorenyl] benzimidazole (181) (0.213 §). [Physical properties of compound (181)] 1H-NMR (CDCl3, δ): 1.08 (3H3 t3 J = 7.4Hz) 1.92 (2H, m) 2.88 (2H, m) 3.76 (3H, s) 4.80 (2Η, d, J = 4.8Hz), 7 · 22 (1Η, dd, J = 2.5 and 7. · 5Ηζ), 7.35 (1H, d, J = 7.8Hz), J.67-7.77 (4H, m), 7 · 80 (1Η, s), 8.58 (1Η, dd, &lt; M · 9 and 0.9 Hz) IR (KBr): 1647cm_1mp: 140.5 -141-50C. <Example 117; 1- (2- Synthesis of chlorobenzyl) -2-fluorenyl-6-[(2-pyridylmethyl) aminomethylfluorenyl] benzimidazole (182) &gt; This paper is compliant with China National Standard (CNS) Α4 specification (21 × 297 mm) 548272 After the final decision «. 绛 and only T, consumption Hezhu private printing A7 B7 V. Description of the invention (15g according to the method of Example 115, using 6-carboxy-1- (2 -Azobenzyl:)-2-methylbenzimidazole (0.300g), ethylenedifluoride chloride (0.253g), 2, aminomethylpyridine (0.108g), triethylamine (0.302g) to This gives 1- (2-chlorobenzyl) -2-methyl-6-[(2-α-pyridinylmethyl) carbamoyl] benzimid. (182) (0.164 g). [Compound (Physical properties of (182)] lH-NMR (CDCl33 δ): 2.56 (3H3 s) 5 4.76 (2H3 d3 J = 4.8Hz), 5.45 (2H3 s) 3 6.4 (1H, d, J = 7.8Hz), 7.08 (1Η, t, J 2 7.6Ηζ), 7.20-7 · 27 (2Η, m), 7.33 ( 1Η, d, j = 8Ηζ), 7.45 (1Η, dd, J = 0.9 and 8.1Ηζ), 7.64 (1H3 s) 3 7,65-7 · 69 (1Η, m), 7 • 72 (1H, dd, J 2 1.5 and 8. 4Ηζ), 7.77 (1Η, d, J = 8.4Hz), 7.88 (1Η, d, Jq, 2Hz) 3 8.56 (1H5 d, J- 4.7Hz) IR (KBr): 1646cffl_1. Mp: 156.5-157.50C0 &lt; Example 1118; 2-n-propyl-1-isopropyl-6-[(2-pyridylmethyl) carbamoyl] Synthesis of Benzo sigma (183) &gt; According to the method of Example 115, 6-carboxy-2-n-propylisopropylbenzo saliva (0.095 g) and ethylene chloride (〇 · ΐ) were used 〇g), 2-aminomethylpyridine (0.039g), triethylamine (0.097g) to give 2-n-propyl-1-isopropyl-6-[(2-, ) Aminofluorenyl] benzimidazole (183) (0.020 §). [Physical properties of compound (183)] W-NMR (CDC13, (5): 1.08 (3Η, t, J 二 7.4Ηζ), 1.69 (6H, d, J = 7.1Hz), 1.87-1.9 3 ( 2H, m), 2.90 (2Η, t, J = 7.8Hz), 4.69-4.75 (1H, m), 4.80 (2Η, d, J: 4.9Hz), 7.23 (1Η, dd, J = 7.3 and 2.1Hz), 7.37 (1H, d3 J = 7.7Hz), 7.62-7 · 77 (4Η, m), 8.21 (1Η, s), 8.58 (1Η, d, J II 4 · 5Ηζ). _____ ι ^ ο _______ The paper size is appropriate / 1] Chinese National Standard (CNS) A4 specification (210X297 mm) '--- (Read the precautions on the back before writing this page j-, may 548272 A7 B7 V. Description of the invention (15) IR (KBr): Ιθβίοιη ^ nip: 155.0-156.9 ° C &lt; Example 119; 1-n-butyl-2-n-propyl-6-[(2-pyridine Synthesis of fluorenyl) aminofluorenyl] benzimidazole (184) &gt; According to the method of Example 115, 1-n-butyl-6-carboxy-2-n-propylbenzimidazole (0.500 g), Ethylenediamine (0.487 g), 2-aminomethylpyridine (0.208 g), and triethylamine (0.582) to give 1-n-butyl-2-n-propyl-6-[(2- Fluorenyl) Amino acyl donkey] Stupid and Mimic σ sitting (184) (0.283 g) [Physical properties of compound (184)] W-NMR (CDC133 (5): 0.97 (3Η3 t5 J: 7.3Hz), 1.08 (3Η, t, J: 7 · other), 1,37- 1.4 6 (2H, m), 1.76-1,83 (2Η, m), 1.92-2 · 00 (2Η, m) 3 2.86 (2Η3 t, J: 7.8Hz) 5 4 · 15 (2H, t, J: 7.6Hz), 4.81 (2Η, d5 J, 2 · 8Ηζ), 7.23 (1Η, dd, J: 7.3 and 2.4Hz), 7.36 (1Η, d, J = 7.8Hz), 7.63-7 · 76 (4Η, m), 8.02 (1Η3 s), 8.58 (1Η, d, J: 4.7Hz) IR (KBr): 1631cm1. Mp: 105.8-107.2 〈〈 Example 120; Synthesis of 1- (3-Azobenzyl) -2-n-propyl-6-[(2-pyridylmethyl) aminomethylamidino} benzoyl salivary (185)〉 According to the method of Example 115, using 6-carboxy-1- (3-fluorobenzyl) -2-n-propylbenzimidazole (0.580 g), ethylene dichloride (0.407 g), 2- Aminomethylpyridine (.173g), triethylamine (0.486) to give 1- (3-chlorobenzyl) -2-n-propyl-6-[(2- ° to fluorenylmethyl) amino Methylfluorenyl] benzobispyrene (185) (0.311 g). [Physical properties of compound (185)] ---— _161 —__ This paper is suitable for size / fl Chinese National Standard (CNS) A4 (210X297 mm) (Please read the precautions on the back before filling this page}-Ding, -5 口 Ψ 548272 Α7 Β7 V. Description of the invention (15 sessions (read the precautions on the back before filling this page) 'H-NMRCCDCb, 6): 1.03 (3H, t3 J = 7.4Hz) 3 1.85-1.93 ( 2H, m), 2.80 (2H, t3 &gt; 7. · 5Ηζ), 4.77 (2Η, d3 J = 4.8Hz), 5.36 (2Η, s), 6.86 (1H, d, J = 7 · he ), 7.02 (1H, s), 7.20_7 · 28 (3Η, m), 7.33 (1Η, d, J: 7.8Hz), 7.63-7.73 (3H, m), 7.79 (1 H, d, J: 8.4 Hz), 7.91 &lt; 1Η, d3 J 2 1.3Ηζ), 8.57 (1Η, d, J = 4.7Hz). IR (KBr): 1643cm-1. mp: 157.7-158.80C. <Consistent Example 121; Synthesis of 1-fluorenyl-2-n-propyl-6-[(2-0 ratio σ-determined methyl) aminomethylfluorenyl] benzimidazole (186) &gt; According to the method of Example Π5, 1-benzyl-6-carboxy-2-n-propylbenzimidazole (0.850 g), ethylene dichloride (0.949 g), and 2-aminomethylpyridine were used. (0.404g), triethylamine (1.132g) to give 1-benzyl-2-n-propyl-6-[(2.pyridylmethyl) aminofluorenyl] benzimidazole (186) (0, 35 Og). [Physical properties of compound (186)] W-NMiUCDCh ， ά): 1.01 (3Η, t, J = 7.4Hz), 1,83] · 2H, m), 2.82 (2Η, t, J2) 7 · 6Ηζ), 4.77 (2Η, d, J = 4.8Hz), 5.4G (2H, s) 3 7.G3 (2H, d, J = 6.5Hz), 7.21 (1H, dd, J : 7.1 and 2.1Ηζ), 7.18-7 · 34 (4Η, m), 7.60 (1Η3 s), 7.65-7 · 72 (2Η, m), 7.78 (1Η, d, J: 8.4 Hz), 7.94 (1Η, d, J = 1.2Hz), 8.56 (1Η, M = 4 · 2Ηζ). IR (KBr): 1642cffi-l0mp: 121.9-123.10C. <Example 122; l- (4-Azobenzyl) _2_propyl_6-[(2-. Specific fluorenyl) carbamate Fluorenyl] Synthesis of benzimidazole (187) &gt; According to the method of Example 115, 6-carboxy-1J4-chlorobenzyl) -2-propylbenzimidazole (0.547 g) and ethylenedifluorene chloride were used. (〇384g), 2-aminopyridylpyridine (〇.163g), triethylamine (0.458g) to get ι_ (deduction of gas generation _____ _L £ 2 ___) This paper rule Z national standard (CNS) A4 specifications (210X297 Gongchu) '' '^ Hubuzhong ^ ir-^-^ h 3 Eliminate the combination of bamboo and impression 548272 A7 ________ ____ B7_____ V. Description of the invention (15 $ benzyl) -2-propyl-6- [ (2-Pyridylmethyl) carbamoyl] benzimidazole (187) (0.089 g). [Physical properties of compound (187)] tNMIUCDCh, (5) ··· 02 (3Η, t, J: 7.4 Hz ), 1.84_1.92 (2Η, m), 2.77-2.83 (2H, m), 4.76 (2Η, d, J = 4.8Hz), 5.36 (2Η, s), 6.96 (2H, d , J 2: 8 · 3Ηζ), 7.22 (1H, dd, J = 6.4 and 0.4Ηζ), 7.27 (2 (3 dd, J: 8.3 and 1.31ζ), 7.33 (1Η, d, J 2: 7 8 Ηζ) 5 7.62-7.73 (3Η3 ιπ) 5 7.78 (1Η3 d3 J-8. 4Hz), 7.91 (1Η3 d3 J = 0.9Hz) 5 8.56 (1Η, dd, J = 4.9 and 0 · 8Ηζ). IR (KBr): 1643cm-1〇mp: 158.8-161.0oC. &Lt; Examples 123; Synthesis of 2-benzyl-1-methyl-6-[(2-pyridylmethyl) carbamoyl] benzimidazole (188) &gt; According to the method of Example 115, 2-benzyl- 6-carboxy-1-methylbenzimidazole (0.310g), ethylenedichloride (0.295g), 2-aminomethylpyridine (0.108g), triethylamine (0.303g) to give 2 -Benzyl-1-fluorenyl-6-[(2-pyridinyl) aminofluorenyl] benzimidazole (188) (0.17 lg). [Physical properties of compound (188)] 1H-NMR (CDCl3) δ ): 3.66 (3H, s), 4.35 (2H, s), 4380 (2H3 d, J = 4.8Hz), 7.21 -7 · 37 (7Η, π), · 7 · 66 (1Η, br t), 7 · 67-7 · 73 (2Η, m), 7.78 (1H, d, J = 8 · 4Ηζ), 7.98 (1H, s), 8.58 (1Η, d3 J = 4.9Hz) IR (KBr) : 1632 cm10 mp: 168.5-169.50C. <Example 124; l- (2,6-dichlorobenzyl) -2-methyl-6-[(2-pyridinyl) carbamoyl] benzene Synthesis of Benzimidazole (189) &gt; This paper is suitable for Chinese National Standard (CNS) A4 size (210X 297 mm) (Please read the back first Note: Please fill in this page again) 548272 A7 __ B7 V. Description of the invention (16g according to the method of Example 115, using 6-carboxy-fluorene- (2,6 · digaso-benzyl) -2-fluorenylbenzimidazole (〇.600g), ethylene dichloride (0.472 §), 2-aminomethylpyridine (0.201 §), triethylamine (0.188 §) to give 1- (2,6 · Mono-amorphous fluorenyl) -2-methyl-6-[(2-σ than fluorenyl) carbamyl] benzimidazole (189) (0.040 g). [Physical properties of compound (189)] ^ -NMRCCDCh, δ): 2.62 (3H, s) 3 4.76 (2H3 d3 J-4.7Hz), 5.62 (2H, s) 3 7.23 (1H, dd, J = 7.1 and 2 · 2Ηζ), 7.28 (1Η, d, J = 7.8Hz), 7.32 (1Η, d, J: 7.9Hz), 7-39 (2H, d3 J = 8.1Hz), 7.54 (1H3 s) 3 7.66-7.71 (3H5 m) 3 7.78 (1H5 s) 5 8.60 (1 d, J = 4.6Hz). IR (KBr): 1635cm-lmp: 225.7-226.9 ° C &lt; Example 125; 2-fluorenyl-6-[(2-pyridylmethyl) carbamoyl] -1- [2_ (tri Synthesis of fluoromethyl) benzyl] benzozal (190) &gt; According to the method of Example 115, 6-carboxy-2-methyl-1- [2- (trifluorofluorenylbenzyl] benzo) was used. Imidazole (0970g), ethylenedichloride (0.736g), 2-aminomethylpyridine (0.261g), triethylamine (0.726g) to give 2-methyl-6 _ [(2 " Pididylmethyl) carbamoyl]-[[2- (trifluorofluorenyl) benzyl] benzimidazole (190) (0.713g). [Physical Properties of Compound (190)] ^ -NMRiCDCla, δ): 2,54 (3H, s), 4.76 (2H3 d3 J ^ 4.8Hz), 5.59 (2H, s), 6,45 (1H, d, J = 7.9Hz), 7.22 (1H, t, J-5.8Hz ), 7.34 (2H, t, J = 8.8Hz) 5 7.40 (1H, t, J = 7.55Ηζ), 7.62 (1Η, br s), 7.68 (1Η, dt, J: 1.7 and 7 · 7Ηζ), 7.72-7 · 82 (3Η, m), 7.87 (1H, s), 8.56 (1H, d3 J = 4.9Hz). The paper size is in accordance with China National Standard (CNS) A4 specifications (210X297). (Mm) (Please read the precautions on the back before filling this page), 1T 548272 Α7 Β7 V. Description of the invention (16j IR (KBr): 1648cm-1. Mp: 172 —174 ° C (Read the precautions on the back before filling this page) &Example; Example 126; 2-Methyl-6-[(2-pyridinyl) carbamoyl] -1- [4- (trifluorofluorene Group) benzyl] Synthesis of benzoyl salivary (191) &gt; According to the method of Example 115, 6-carboxy-2-methyl_1- [4- (trifluoromethylbenzyl] benzimidazole ( 0.997 g), ethylene dichloride (0.736 §), 2-aminofluorenyl toxidine (0.261 §), triethylamine (0.7268) to give 2-methyl- 6-[(2-αbipyridylmethyl) carbamoyl] "-μ · (trifluoromethyl) benzyl] benzimidazole (191) (0.194g). [Physical Properties of Compound (191)] ^ -NMRiCDCh, δ): 2.59 (3H3 s) 3 4.77 (2Η, d, J-4.7Hz) 3 5.45 (2H, s) 3 7,15 (2H, d, J = 8.2Hz), 7.23 (1Η3 m) 3 7 · 33 (1Η, d3 J = 7.9Hz), 7.58 (2Η, d, J: 8.2Hz ^) 5 7.63 (1H, br s), 7.67-7.74 (2H3 m), 7.77 (1H, d5 J = 8.3Hz), 7.93 (1H, s), 8.57 (1Η, d, J = 4.9Hz) IR (KBr): 1637cm'l0nip: 188.5-190.0oC. <Examples l27; l- (3,4-dioxobenzyl) -2-methyl-6-[(2-pyridinyl) carbamoyl] benzimidazole (192) Synthesis &gt; According to Example 115 Method to make 6-carboxy-l- (3,4-dioxobenzyl) -2-methylbenzimidazole (0.500 g), ethylenedichloride (0.393 g), 2-aminomethylpyridine (〇 ”67g), triethylamine (0.469g) to give 1- (3,4-digaso-benzyl) -2-fluorenyl-6-[(2-pyridylmethyl) aminofluorenyl] Benzimidazole (192) (0.264 g). [Physical properties of compound (192)] ----- L4S- This paper is suitable for Chinese National Standard (CNS) A4 specification (210X297 mm) 548272 A7 B7 V. Description of the invention (16i W-NMlUCDCh, 6): 2 58 (3Η, s), 4.77 (2H, d, J: 4.8Hz), 5.33 (2H, s) 3 6.85 (111, (1 (1, # 8.3 and 2.2 this), 7.14 (1 [1, ( 1, pay .1 call, 7.22 (111, (1 (15 deduction 7.3 and 5. 6Ηζ), 7.33 (1Η, d, J: 7.8Hz), 7.38 (1Η, d, J: 8.3Hz) , 7.65-7 · 77 (4Η, m), 7.92 (1H, d, J 二 1.2 · ΗΗζ), 8.57 (1H, d, J 二 4 · 8Ηζ). IR (KBr): 1638cm-lmp ··· 219.0-220.7 ° C. &Lt; Example l28; Synthesis of 2-fluorenyl-l- (2-fluorenylbenzyl) _6 _ [(2_2 pyridylmethyl) carbamoyl] benzimidazole (193) &gt; According to the method of Example 115, using 6-endyl-2-methyl-1- (2-fluorenylbenzyl) benzozine (0.453 g), ethylene dichloride (〇41 lg), 2 -Aminopyridine (0.175g), triethylamine (0.490g) to give 2-fluorenyl-1- (2-fluorenylbenzyl) -6-[(2-2methylmethyl) carbamate Fermentation group] Benzo flavor (193) (0.100 g) 〇 [Physical properties of compound (193)] H -_ (CDCh, cn: 2.42 (3H, S) 2.54 (3Η, S), 4.75 (2Η, d, J: 4.9Hz), 5.32 (2H, s), 6.33 (1Η, d, J-7 · 8Ηζ), 7.01 (1Η , T, J: 7.8Hz), 7,17-7 · 24 (3Η, m), 7.33 (1H, d5 J.7.8HZ), 7.60 (1H, s) 3 7.63-7.73 (2H5 7.76 (1H , d5 J-8.4Hz), 7.84 (1H3 d, J: 1.4Hz), 8.56 (1Η, d, J = 4.9Hz). The middle part of the warp «.- ^-^ 1, only τ-consumption Sealed with bamboo (please read the precautions on the back before filling this page) IR (KBr): 1635cm ~ 10 namely: 154.0-157.0 ° C. &Lt; Example 129; 1- (2-methoxybenzyl) ) Synthesis of 2-methyl-6-[(2-methylamino) aminofluorenyl] benzimidazole (194) &gt; According to the method of Example 115, 6-carboxy-1 _ (2_ Methoxybenzyl) · 2-fluorenyl benzimidal (0.997g), ethylene dichloride (〇.858g), 2- --- 16 ^ ___ This paper size applies to China National Standard (CNS) A4 (210X 297mm) 548272 A7 B7 V. Description of the invention (16) Aminopyridine (0.309g), triethylamine (1.02g) to obtain] μ (2-methoxybenzyl)- 2-methyl-6-[(2-. Pididylmethyl) carbamoyl] benzimidazole (194) (0.918g). [Physical properties of compound (194)] 4-ug (CDCh, d): 2.60 (3Η, s), 3.89 (3Η, s), 4.77 (2Η, d, ㈣8Hz), 5 36 UH, s), 6.60 (1Η, d, j: 7.4Hz), 6.79 (1Η, J = 08 and 7 • deleted, 6.9ι (ι, d, J-7.4HZ), 7.20-7.28 (2Η3 m), 7.34 (1Η3 d, J = 7.9Hz), 7.56 (1H, br t), 7.6 6-7.75 (3H, m) 5 7.95 (1H, m), 8.57 (1H, d, J-4.9 Hz) 〇IR (KBr): 1652cm- ^ mp: 136-138.5 ° C. <Example 130; 1- (4-fluorenyloxybenzyl) _2_fluorenyl_6 _ [(2-pyridylmethyl) aminofluorene Synthesis of benzimidazole (195) &gt; According to the method of Example 115, 6-carboxymethoxybenzyl) -2-methylbenzomime (0.985g), gasified ethylene distillate (〇85 gg ), 2-aminopyridinylpyridine (0.309g), triethylamine (i.02g) to give 1- (4_fluorenylbenzyl) -2-fluorenyl-6-[(2-this pyrimidinyl ) Aminofluorenyl] benzimidazole (195) (0.697 g). [Physical properties of compound (195)] 1H-NMR (CDCl35 ^): 2.59 (3Η, s) 3 3.76 (3H3 s) 5 4.78 (2H, d, J = 4.8Hz), 5.32 (2H, s) 3 6.83 ( 2H3 m) 5 7.00 (2H5 m) 3 7.22 (1H, dd3 J, 5.l * 6.8Hz) 5 7.34 (1H3 d, J-7.8Hz), 7.60 (1H, br t), 7.67-7.76 (3H, m) 3 7.97 (1H, d3 J = 1.2Hz) 5 8 · 57 (1Η, d, J = 4.9Hz). IR (KBr): 1652cm-lOmp: 191.5-192.20. . _____t (si The size of this paper is / 1] Chinese National Standard (CNS) A4 specification (210X 297 mm) (Read the precautions on the back before filling this page) Order ^ ewi. 548272 A7 B7 V. Description of the invention (16 "&Lt; Example 131; 1- [2- (benzenesulfonylmethyl) benzyl] -2-methyl-6 _ [(2 · leaf bite methyl) carbamoyl] benzimidal (196 ) Synthesis> According to the method of Example 115, 1- [2- (benzenesulfonylmethyl) benzyl] -6-carboxy-2-methylbenzowow (0.74 g), ethyl chloride Distillate (0.45g), 2-aminopyridylpyridine (0.19g), and triethylamine (0.53g) to give 1-[2-(this stone page ii & methyl) fluorenyl] · 2 -Methyl-6-[(2-σ fixed methyl) carbamoyl] benzimidazole (196) (0.64g). [Physical properties of compound (196)] a-NM ^ CDCh, (5): 2 · 57 (3Η, s), 4.50 (2Η, s), 4.74 (2H, d, J = 4.9Hz), 5.59 (2H, s), 6.63 (1Η, d, J = 7 · 7Ηζ) , 6.87 (1Η, d, J = 7, 4 and 1.5Ηζ), 7.09-9-7ΐ9 (3Η, m), 7.31 (1Η, d, J = 7.8Hz), 7 · 53_7 · 61 (3Η, m) 5 7 · 64 (1Η3 dt, J: 7.6 and 1.6Ηζ), 7.68-7 · 79 (5Η, m) 7.84 (1Η, s), 8.52 (1Η, d, J = 4.8Hz), IR (neat) 1646CHT1. Liquid. <Example l32; l- (2-cyanobenzyl) -2_ Synthesis of methyl-6-[(2-pyridylmethyl) carbamic acid group] benzo saliva (197)> According to the method of Example 115, 6-carboxy-1- (2-cyanobenzyl)- 2-methylbenzimidazole (1.14g), ethylenedifluoride chloride (.998g), 2-aminopyridinium pyridine (0.425g), triethylamine (1.19g) to obtain i- (2-cyanobenzyl) -2-fluorenyl-6-[(2-methylpyridinyl) aminofluorenyl] benzimidazole (197) (1.03g) 〇 [Physical properties of compound (197)] Used -Leg (CDCh, 6): 2.58 (3Η, s), 4.76UH, d, J = 4.8Hz), 5.59 (2Η, s), 6.64 (1Η, d, J = 7. He), 7 · 21 (1Η, dt, J: 5.6 and 1.8Ηζ), 7 · 33 (1Η, d, J: 7.9Hz), __ 16 «_ This paper is in accordance with China National Standards (CNS) A4 specifications ( 210X 297 mm) '~ (Read the precautions on the back before writing this page), == 548,272 A7 B7 V. Description of the invention (16 · 39 ~ 7 · 47 (2Η, m), 7 · 65-7.79 (5Η, m), 7.89 (1Η, s), 8.56 (1Η, dd, J 4.9 and 0.9Hz) IR (KBr): 2223, 1642cnT1. That is: 150.5-151.4. . . &lt; Example 133; Synthesis of 1- (biphenyl-2-methyl) _2 · methyl-6-[(2-pyridinyl) carbamoyl] benzimidazole (198) &gt; According to Examples Method 115, using 丨 _ (biphenyl_2_methyl) _6_ carboxy-2-methylbenzimidazole (1.07g), ethylene dichloride (〇796g), and amidomethylpyridine (0.339g ), Triethylamine ((K950g) to give 丨 _ (biphenyl_ 2-methyl) -2-methyl-6 _ [(2_pyridylmethyl) aminomethylamidino] benzimidazole (198) ( 0.672g) 〇 [Physical properties of compound (198)] lH-NMR (CDCl3, δ): 2.380H, s), 4.78 (2H3 d3 J-4.8Hz) 5 5.27 (2H3 s) 3 6.64 (1H, d, J : 8.0Hz), 7.17-7 · 24 (2Η, m), 7.29-7 · 43 (6Η, in), 7.48 (2Η5 t3 J: 5.5H z), 7.49UH, s), 7.57_7 · 73 (3Η, m), 7.80 (1Η, d, 8.58 (1Η, d, J = 4.9 Hz). IR (KBr): 1630, 1619cm-1. Mp: 179.8-180.8 oC〇 Via the central part of the crotch ii .- ^-^ h 3 Consumption of Hezhu Bamboo (read the precautions on the back before filling this page) Example 134; 1-benzyl-2-methyl-6- [ Synthesis of (2-pyridylmethyl) carbamoyl] benzimidazole (199) &gt; According to the method of Example 115, 丨 _benzyl_6-carboxyl was used Methyl benzimidazole (0.59 g), ethylene dichloride (0.56 g), 2-aminomethyl. Pyridine (0.24 g), triethylamine (0.67 g) to give 1 · benzyl · 2 _Methyl-6 _ [(2_pyridylmethyl) carbamoyl] benzimidazole (199) (0.66g). —__ ____L6J2___ This paper size applies to China National Standard (CNS) A4 (210X297 mm) 548272 A7 B7 V. Description of the invention (16g [physical properties of compound (199)] lH-NMR (CDCl33 δ): 2.58 (3Η5 s), 4.76 (ZH5 d, J ^ 4.9Hz) 3 5.36 (2H3 s) 3 7.02 -7.06 (2Η, melons), 7.21 (1Η, dd, J = 6.9, and 5.0Ηζ), 7.27-7.35 (4H, m), 7.65-7.7 5 (4H3 m) 3 7.96 ( 1Η, d3 is 0 · 8Ηζ) 3 8 · 56 (1Η, d3 J 2 · 4Η8Ηζ). IR (KBr); 1640cm'1〇 That is: 124.0-124.90C0 &lt; Example 135; 1- (4 -Synthesis of 3rd butylbenzyl) -2-methyl-6-[(2-pyridylmethyl) aminofluorenyl] benzo (° 00) &gt; According to the method of Example 115, use 1- (4- 3rd butylbenzyl) -6-benzyl-2-methylbenzo miso (0.544 g), vaporized ethylene difluorene (0.428 g), 2-aminomethylpyridine (0.183g), triethylamine (0.511g) to get 1- (4-brother 3 Butylfluorenyl) -2-fluorenyl-6-[(2-0 specific methyl) aminomethyl] benzimidazole (200) (0.477g). [Physical properties of compound (200)] 1H-NMR (CDCl33 δ): 1.27 (9H3 s) 3 2.60 (3H3 s) 3 4.77 (2H, d? J = 4.9Hz)? 5.34 (2H, s), 6.98 (2Η, d, J = 8.3Hz), 7 · 21 (1Η, dd, J 2 7.3 and 5 · 1Ηζ), 7 · 29-7 · 35 via the central part of the quasi-MT, eliminate Seal ^ (Read the precautions on the back before filling in this page) (3Η, m), 7.62 (1Η, br s) 3 7,65-7 · 75 (3Η5 m) 3 7 · 96 (1Η, d, J 1.1Hz), 8.57 (1Η, d, J 二 4 · 7Ηζ) 〇IR (KBr): 1646cm · 10mp ·· 140.4-142.8 ° C. &lt; Example 136; Synthesis of 2-methyl-1- (2-theylmethyl) -6-[(2-σΛσdefinitemethyl) aminomethylamidino] benzimidazole (201) &gt; The method of Example II5 uses 6-carboxy-2-fluorenyl-1- (2-naphthylfluorenyl) benzimidazole (0.80 g), vaporized ethylene difluorene (0.64 g), and amine group. ____ U10-- This paper is in accordance with China ’s National Standard (CNS) A4 size (210X297 mm) 548272 A7 B7 V. Description of the invention (1 Methyl σ ratio 唆 (0.27g), triethylamine (0.77g) to get 2_methyl small (2_naphthylmethyl) _6-[(2- ° specific bite methyl) carbamyl] benzo-flavored saliva (read the precautions on the back before filling in this page) (201) (〇.47g). [Physical properties of compound (201)] lH ~ NMR (CDCl35 δ): 2.60 (3H, s) 5 4.75 (2H3 d3 J = 4.9Hz), 5.52 (2H3 s) 5 7.17 -7′3 (2H, m), 7.31 (lH, d, J: 7.8 Hz), 7.38 (lH, s), 7.43-7.48 (2H, in), 7.60-7 · 82 (7Η, m), 8.00 (1Η , D, J = 1.0 Hz), 8.53 (1.33 d, J: 4.7 Hz). IR (KBr): 1640 cm- 10 Ye: 143.0-144.5 ° C. &Lt; Example 137; 1- ( Biphenyl-4-methyl) _2-ethyl-6-[(2-. Specific fluorenyl) carbamyl] benzimidyl Synthesis of azole (202) &gt; According to the method of Example 115, 1- (biphenylmethyl) -6-carboxy-2 · ethylbenzimidazole (0.500 g), ethylene dichloride (0 356 g), 2-Aminomethyl σ is better than fluorene (0.15 lg) and triethylamine (0.424g) to give 1_ (biphenyl_ 4-fluorenyl) -2-ethyl-6-[(2-leaf b bite nail Group) carbamoyl] benzimidal (202) (0 ″ 04g) ° [physical properties of compound (202)] ^ -NMRiCDCh, δ): L45 (3H3 t3 J-7,7Hz), 2.90 ( 2Η3 q, J-7.4Hz), 4.77 (2H5 d, J = 4.7Hz), 5.43 (2H, s), 7.10 (2H, d, J = 8.2Hz), 7.20 (1H3 dt, J2 4.9 and 7. · 7Ηζ), 7.33 (2Η, t, J = 7.4Hz), 7.42 (2Η, t, J = 7.5Hz), 7.49-7 · 55 (4Η3 m), 7 • 61 (1H, br t), 7.67 (1Η, dt, J = 7.8 and 1.8 · ζ), 7.72 (1Η, d, J = 8 · 4Ηζ), 7.8.1 (1Η, d, J: 8.4Hz), 7.99 (1Η, s), 8.56 (1Η3 d, J: 4.9Hz). IR (KBr): 1640cm1. mp: 123 · 0 —124.0oC. This paper size is suitable for China National Standard (CNS) A4 size (210X297 mm) 548272 A7 ~~ _______________ B7______ 5. Description of the invention (16) <Example I38; 1- (2- Synthesis of Benzyl) _6_ [2_ (pyridylmethyl) carbamoyl] benzimidazole (203) &gt; (Please read the precautions on the back before filling this page) According to the method of Example 115, use Weyl 4- (2-chlorobenzyl) benzimidazole (0.461 g), ethylene dichloride (0.728 g), 2-aminomethylpyridine (0.1 Mg), triethylamine (0.1 468 g) to give 丨 -fluorenylbenzyl) -6 · [2 decapyridylmethyl) carbamoyl] benzimidazole (203) (〇u〇g). [Physical Properties of Compound (203)]

Shijiu ..., 6): 4.78 (2Η, d3 J: 4'Hz), 5.51 (2Η, s), 6.92 (1Η, d, J: 6.5 Ηζ), 7.17-7 · 31 (3Η, m), 7.34 (1Η, d, J = 7.8Hz), 7.45 (1Η, dd, J: li and 8.0 Ηζ), 7.69 (1Η, dt, J = 1.8, and 7.7Ηζ ), 7.67-7 · 73 (1Η, br s), 7.76 (1Η, dd, J -1 · 5 and 8.4Ηζ), 7.87 (1Η, d, J = 8.4Hz), 8.05 (2Η, s), 8.57 (1Η, d, J: 4.9Hz) 〇IR (KBr): 1646 cm10 mp: 144.0-145.0 ° C. &lt; Executive Example 139; Synthesis of 2-methyl-1-(2-stone-sweetyl benzyl) _6 _ [(2_σ than fluorenyl) aminofluorenyl] benzimidazole (204) &gt; j Bamboo Seal | ____ 172_ The paper size is / 1] Chinese National Standard (CNS) A4 size (210X297 mm) According to the method of Example 115, 6_Retarder j-methyl-1- (2- Nitrobenzyl) benzimidazole (0.367 g), ethylene dichloride (0.29%), 2-aminomethyl, pyridine (0.217 g), triethylamine (0.360 g) to obtain 2-methyl-1- (2-nitrobenzyl) -6-[(2-.pyridinylmethyl) carbamoyl] benzazole (204) (0.241 g) 〇 [Compound (204) Physical properties]

^ -NMRiCDCh, δ): 2.56 (3H, s), 4.75 (2H, d3 J = 4.8Hz), 5.83 (2H, s) 5 6.41 (1H, d, J = 7.8 and 1.2 · ζ), 7.22 (1Η, dt, J 2 5.0 and 1. 7ΗZ), 7 · 32 (1Η, d, J 548272 A7 B7 V. Description of the invention (16) 9 (Read the precautions on the back before filling this page) 2 7 · 9Ηζ), 7.43-7 · 52 (2Η, m), 7.64 (1Η, s), 7.68 (1Η, dt, J = 7.6 and 1.7Hz), 7 • 75 (1H, dd , J 2 8 · 4 and 1.5 5Ηζ), 7,80 (1H, d, J 2 8,4 Hz), 7.82 (1Η, d, J = 1.3Hz), 8.28 (1Η, dd, J 8.0 and 1. 7Ηζ), 8.56 (1Η, d3 J = 4.9Hz). IR (KBr): 1645CHT1. nip: 194.8 —196.7 ° C. &lt; Example 14〇; Synthesis of 2-methyl-1- (2-stone-sweetylbenzyl) -5-[(2- ^ 1 to 0-determined methyl) aminomethylamino] benzimidazole (205) According to the method of Example 115, 5. · carboxy-2-methyl-1- (2-nitrobenzyl) benzimidazole (0.096 g), vaporized ethylene difluorene (0.078 g), 2- Aminomethylpyridine (0.048g), triethylamine (0.093g) to give 2-methyl-1- (2-nitrobenzyl) -5-[(2-this pyridylmethyl) carbamidine Group] benzimidazole (205) (0.079 g). [Physical properties of compound (205)] iH-NMlUCDCh, (5): 2.57 (3Η, s), 4.80 (2Η, d, J: 4.7Hz), 5.80 (2Η, s), 6. · 43 (1Η, d, J: 7.4 and 0 · 8Ηζ), 7 · 17 (1Η, d, J = 8.4Hz), 7.22 (1Η, dt, J: 5.5 and 1.81ζ), 7.35 ( 1Η, d, J: 7.8Hz), 7.44_7.52 (2Η, m), 7.67 (1Η, s), 7.69 (1Η, dt, J: 7.8 and 1.9Ηζ), 7.82 (1Η, dd, J: 8.4 and 1.5Ηζ), 8.27 (1Η, dd, J2 8.0 and 1.6Ηζ), 8.28 (1Η, d, J ^ UHz), 8.56 (1Η, d, J: 4.9 Hz). IR (KBr): 1645CHT1. mp: ~ 96T (decomposed by 奁). &lt; Example 141; Synthesis of 1- (2-chlorobenzyl) _2_methyl-6_ (2-naphthalenesulfonylcarbamoyl) benzo 17 m pyrene sodium salt (206) &gt; N , N'-Jijiji. Misal (0.541g) was added with 6-Weiji-1- (2-chlorobenzyl) -2-methylbenzimidazole (0.500g) of N, N-dimethylamidamine (20ml) ________ 173_ This paper size is in accordance with Chinese National Standard (CNS) A4 (210X297 mm) 548272 A7 _____________ B7 V. Description of the invention (17) t) Stir for 1 hour at room temperature in the solution. Next, 2-naphthalenesulfonamide (0.689g) and a solution of diazabicycloundecene (0550 N, N-dimethylformamide (5ml) were added, and stirred at 100t for 48 hours. .Cool the reaction solution and distill off the solvent under reduced pressure. Add water and chloroform to the residue and add 丨 0% hydrochloric acid until the water layer becomes acidic. Extraction with chloroform is performed.) 'Saturated aqueous sodium bicarbonate solution Add the obtained organic layer and stir it. The precipitated crystals were filtered out, dissolved in a small amount of methanol, and ethyl acetate was added to crystallize. The crystals were filtered off and dried to give 0.508 g of 1- (2-gaso-benzyl) -2-methyl-6- (2-naphthalenesulfonamidocarbamoyl) benzimidazole sodium salt (206). [Physical properties of compound (206)] 6): 2.46 (3Η, s) 3 5.51 (2Η, s), 6.38 (1Η, d, J = 7.9Hz), 7.17 (1H, t , J = 7.5Hz), 7 · 30 (1Η, t) 3 7 · 45 (1Η, d, J = 8.5Hz), 7.51-7 · 57 (3Η, in), 7.77-7 · 93 (5Η, m), 7.99 (1H, ιη), 8.35 (1Η3 s). IR (KBr): 1594cm1.

Mass (FAB): m / e 512 (M + 1). mp: 352.0-354.50C. The third part of the ministry's cooperation and private printing rewards (read the precautions on the back before filling this page) &lt; Example l42; l- (2-Azobenzyl) (Synthesis) _2_methyl-6_ (1-naphthalenesulfonylcarbamoyl) benzimidazole sodium salt (207) &gt; According to the method of Example 141, 6-carboxy-1- (2-gas Substituted base) -2-fluorenylbenzomethyl. Sit (0.600g), N, N'-Chichi. Mesalazine (0.647g), 1-naphthalenesulfonamide (0.829g), and diazabicycloundecene (0.608g) to give 1- (2-chlorobenzyl) -2-methyl 6- (1-naphthalenesulfonylcarbamoyl) benzimidazole sodium salt (207) (0.390 g). ______174____ The paper size is in accordance with China State Standard (CNS) A4 (210X297 mm) 548272 A7 ___ B7 V. Description of the invention (17 \ [physical properties of compound (207)] (诮 Please read the precautions on the back before filling this page ) lH ~ NMR (DMS0-d63 δ): 2.46 (3H3 s) 3 5.49 (2H, s) 5 6.39 (1H3 d3 J = 7.8Hz), 7. 16 (1H3 t, J 2 7 · 5Ηζ), 7 · 31 (1Η, t, J 2 7.3Ηζ) 5 7.36 (1H, t), 7.40-7.45 (2Η, m), 7.50 (1Η3 J 2 7.7 · ζ), 7.54 (1Η, d3 J 2 8.0Ηζ), 7.75-7 · 81 (2Η, in), 7.87 (1Η, d, J 2 7.9Ηζ), 7.93 (1Η, d, J 2 8.2Ηζ), 8.09 UH, d, J 2 7. 3Ηζ), 8.86 (1H, d, J = 8.5 Hz). IR (KBr): 1633 cm1.

Mass (FAB): m / e 512 (M + 1). mp: ~ 265 ° C (decomposition 奁 Companion 3). &lt; Example 143; Synthesis of 6- (4-fluorobenzenesulfonylaminofluorenyl) -1- (2-fluorobenzyl) -2-methylbenzimidazole sodium salt (208) &gt; The method of Example 114 uses 6-carboxy-1- (2-chlorobenzyl) -2-fluorenylbenzimidazole (0.400 g), N, N'-carbonyldiimidazole (0.4328), and 4-benzene Benzamine (0.5108) and diazabicycloundecene (0.404 @) to give 6- (4-chlorobenzylsulfonylaminocarbamyl) -1- (2-chloro Benzyl) -2-methylbenzimidazole sodium salt (208) (0.270 g). [Physical properties of compound (208)] ^ -NMRiDMSO-de, δ): 2.46 (3H3 s) 3 5.52 (2H, s) 3 6.38 (1H5 d3 J = 7.4Hz) 3 7. 19 (1H, t, J = 7.6Hz), 7.31 (1Η, t, J = 7.6Hz), 7.39 (2Η, d, J = 8.5Hz), 7.45 (1Η, d, J = 8.9Hz), 7.54 ( 1Η, d, J = 8.0Hz), 7.76-7 · 82 (4Η, m). IR (KBr): 1592cm-- 、

Mass (FAB): m / e 496 (M + l) 〇 mp: 360—362 ° C (decomposed). &lt; Example 144; 6- (3-Gasbenzenesulfonylcarbamoyl) -1- (2-chloro) This paper is sized for China National Standard (CNS) A4 (210X 297 mm) 548272 A7 V. Description of the invention Synthesis of (17j benzyl) _2-methylbenzimidazole (209) &gt; According to the method of Example 丨 4 丨, 6_fluorenyl_K2 chlorobenzyl) -2- 曱 is used Benzimidazole (0.450 g), ν, N, -carbonyldiisocyanate (0.486 g), 3-chlorobenzenesulfonamide (0.573 g), diazabicycloundecene (〇456 g) to obtain 6- (3-Gassulfenylcarbamoylcarbamyl ^^-chlorobenzyl) _2_fluorenylbenzimidazole sodium salt. This was dissolved in a mixed solution of methanol and water, and adjusted to pH 5 to 6 using 10% hydrochloric acid. The precipitated crystals were filtered out, and dried to give 6- (3-airbenzenesulfonylaminocarbamyl) _1- (2_oxobenzyl) -2-methylbenzimidazole (209) (0.420g) . [Physical properties of compound (209)] 'H-NMEaMSO-d6, (5): 2.51 (3Η, s) 3 5.63 (2H, s), 6.48 (1Η, d, J = 7.7Hz), 7 22 (1H, t, J: 7.6Hz), 7.34 (1Η, t, J = 7.7Hz), 7.56 (1H, t, J = 8.0Hz), 7.64 (1Η3 t5 ^ 8 · 0Ηζ) , 7,68 (1H, d, J = 8.5Hz) 3 7,78 (2H, t, J = 8.6Hz), 7.91 (1H, d, J = 7.6Hz), 7.95 (1Η, d, J = 1.6Hz), 8.10 (1H, s). IR (KBr): 16870111 ^ 0 Mass (FAB) ·· m / e 474 (M + 1). mp · 254.5-257.5 ° C (decompose left companion 3). &lt; Example 145; Synthesis of 5-benzylaminocarbamoyl benzyl-i_ (2_ oxobenzyl) benzimidazole (210) &gt; According to the method of example 144, 2-benzyl- 5-carboxy-1- (2-chlorobenzyl) benzimidazole (0.466 g), N, N, carbonyl diimidosulfan (0.401 g), benzodiazepine (0.389 g), diazabicyclo Eleven dilute (0 77g) to give 5-benzenesulfonylcarbamoylbenzyl-l- (2.chlorobenzyl) benzimidazole (210) (0.447g). ____—- 176 —__________ This paper is suitable for Chinese National Standard (CNS) A4 (210X297 mm) (诮 Please read the notes on the back before filling in this page)

1T 548272 A7 B7 V. Description of the invention (17i [Physical properties of compound (210)] lH-NMR (DMS0-d6, δ): 4.28 (2H3 s) 3 5.57 (2H? S) 5 6.23 (1H, d, J = 7.6Hz), 7.〇4 (lH, t, J = 7.6Hz), 7.10-7 · 26 (6Η, m), 7.40 (1Η, d, J = 8 · 6Ηζ), 7.46 ( 1H, d, J = 8.0Hz), 7.61-7 · 73 (4Η, m), 8.00 (2Η, d, J: 7.6Hz), 8.23 (1Η, s), 12.43 (1H, br s) 0 IR (KBr): 1685cm-10mp: 152.0-155.0 ° C. &lt; Example 146; 6-benzenesulfonylaminofluorenyl-2-benzyl-1- (2-fluorobenzyl) ) Synthesis of benzimidazole (211) &gt; According to the method of Example I44, 2-benzyl-6-carboxy-1- (2-chlorobenzyl) benzimidazole (0.776 g), N , N, -carbonyldiimidazole (0.654g), benzylsulfonamide (0.634g), diazabicyclo-ene (0.614g) to give 6-benzenesulfonylcarbamoylbenzyl-l -(2-Azobenzyl) benzimidazole (21 1) (0.803g). [Physical properties of compound (211)] W-NMIUDMSiHlG, c5): 4.41 (2H, s), 5.71 (2Η, s ), 6.32 (1H, d, J: 7,7Hz), 7.06 (1H, t, J = 7.7Hz), 7.14-7 · 30 (6Η, m), 7.50 (1Η, d, ㈣.GHz), 7 62 (2Η, t), 7.70 (1Η, t), 7.81 (1Η, d, J = 8.6Hz), 7.87 (1H, d, J = 8.5Hz), 7.97 (2H, d, J = 8 · 2Ηζ), 8 · 16 (1Η, s), 12 · 60 (1Η, br s). IR (KBr): 1704cm-10 mp: 143.0-144.5 ° C. &lt; Example 147; Synthesis of 1- (2,4-digaso-benzyl) _2_methyl-6 _ [(2 · pyridinyl) aminomethylfluorenyl] benzimidazole (180) &gt; Drop of N, N-dimethylmethanamine was added to the base group (2,4_ 二 气 代 _______ Λ22 ___ This paper is used in China National Standard (CNS) Λ4 specification (210X297 ^ 3 ---- (Please (Please read the notes on the back before filling this page)-口 ψ. .. 浐.. ^-^-Consumer cooperation ^ ^ 548272 Α7 Β7 5. Description of the invention (17j ~ section base) -2-methyl In benzimidazine (0.627 g), ice-cooled. Ethylene chloride (0.493 g) was added dropwise and stirred for several minutes. After stirring at room temperature for 丨 hours, it was concentrated under reduced pressure to remove gasified ethylene dichloride. Alas, the residue was dissolved in trichloromethane (10ml). This solution was dripped into amidinomethyl under ice-cooling. Pyridine (0.1678) and diethylamine (0.4698) (51111) solution. After being stirred for 1 hour, the reaction solution was washed 3 times with water, and then washed with a saturated sodium bicarbonate aqueous solution. The organic layer was concentrated under reduced pressure, and thin-layer silica gel chromatography (expansion> cereal media) C-diethyl ether = 1/1) refined Then dissolve in ethyl acetate (5ml), add hexane (2ml) to crystallize it. The crystals are decanted and dried to give 1- (2,4-dichlorobenzyl) _2_yl. _6 _ [(2-Pyridinyl) aminoamino] benzimidazole (180) 0.359 g. [Physical properties of compound (180)] 4-NMR (CDC13, (S): 2.56 (3Η, s) , 4.76 (2H, d3 5.4G (2H, s), 6.33 (1H, d, J = 8,4Hz), 7.07 (1Η, dd, J = 8.4 and 2.00 · ζ), 7.22 ( 1Η, dd, J: 7.4 and 4.9Ηζ), 7.33 (1H, d, J = 7.9Hz), 7.48 (1Η, d, J = 2.1Hz), 7.62_7 · 79 (4Η, m), 7.86 (1Η, d, J = 1.lHz), 8.57, (1H, d, J: 4.9Hz). IR (KBr): 1645cm &quot; 10mp: 204.1-206.3 ° C. &Lt; Example 148 Synthesis of 1- (biphenyl-4-fluorenyl) -2-fluorenyl-6-[(2-a ratio. Fixed methyl) aminomethylfluorenyl] benzimidazole (212) &gt; Gasified ethylenedifluoride (0.655g) was added with 1 · (biphenylmethyl) -6-enyl-2-methylbenzo. Mizidine (0.866g) and N, N-dimethylformamide (1 drop) of a solution of dioxane (13 ml) and stirred at room temperature for 15 hours. The precipitated crystals transitioned out, washed with digas methane, and dried under reduced pressure. Two. — ------- 1 7 Λ This paper size applies to the Chinese National Standard (CNS) Α4 specification (21〇X2 ^ H) '' ^ (It is necessary to read the precautions on the back before filling this page) Order Φ 548272 Μ ________________B7 V. Description of the invention (17 $ (诮 Please read the notes on the back before filling this page) Add this crystal to 2-aminofluorenyl group under ice cold. Specific bite (0.235g) and triethylamine (0.635 g) Digas methane (i5mi) solution, stirring for i hours. Water was added to the reaction solution to stop the reaction. After washing with water (twice) and saturated sodium bicarbonate aqueous solution, the organic layer was dried and the solvent was reduced. The solution was concentrated under pressure. The residue was recrystallized from a mixed solvent of ethyl acetate and ethanol to obtain 1- (biphenyl-4-methylmethyl-6-[(2-σ than pyridylmethyl) carbamoyl). ] 0.774 g of benzimidazole (212). [Physical properties of compound (212)] H-NMR (CDCh3 δ): 2.62 (3H3 s) 3 4.77 (2H3 d5 J = 4.8Hz), 5.42 (2H, s), 7.12 (2H5 d3 J ^ 8.5Hz), 7.21 (1H3 m) 3 7.34 (2H5 m) 5 7.42 (2H3 m) 3 7.51-7.55 (4H, m), 7.62 (1Η, br t), 7.67 ( 1Η3 dt, J = 1.7 and 7 · 7Ηζ), 7 · 71 (1Η, dd, J: 1.6 and 8.4Hz) 5 7.76 (1H3 d3 J = 8.4Hz) 3 8.00 (1H3 d3 J = 1.2Hz), 8.56 (1H5 d3 J-4.8 Hz) IR (KBr): 1642CET1. Mp: 205.0-206.5 ° C. &Lt; Examples 149; 6-benzenesulfonamidoaminofluorenyl-1- (2-chlorobenzyl) -2-methylbenzimid. Synthesis of (163) &gt; N, N'-carbonyldiimidazole ( 0.973 g) was added to a solution of 6-carboxyl-hexyl 2-chlorobenzyl) -2-methylbenzimidazole (0.90 g) in N, N-dimethylformamide (20 ml), Stir at room temperature for 1 hour. Next, add a solution of benzenesulfonamide (.943g) and diazabicycloundecene (0.99g) in N, N-difluorenylamine (5ml). Stir at 100 ° C for 70 hours. Cool the reaction solution and distill off the solvent under reduced pressure. Add water and chloroform to the residue and add 10% hydrochloric acid until the water layer becomes acidic. Extraction with chloroform (2 times ), The size of the paper is suitable for the Chinese National Standard ([?) 8 4 specifications (210 &gt; &lt; 297 mm) 548272 A7 B7 5. Description of the invention (17g and the organic layer obtained by washing with sodium bicarbonate aqueous solution, in The solvent was distilled off under reduced pressure. The residue was dissolved in a small amount of trichloromethane, and ethyl acetate was added to crystallize it. The crystals were filtered off and dried to give 0.667 g of 6-benzenesulfonylcarbamoylchlorobenzyl) _2 · methylbenzimidazole (163). &lt; Example 150; Synthesis of 6-benzenesulfonylaminocarbamyl group 丨 丨 (biphenyl-4-methyl) -2-methylbenzimidazole sodium salt (213) &gt; According to Example 141 Method, using 6-carboxyl; μ (bibenzylmethyl) -2-fluorenylbenzimidazole (〇j37g), benzylsulfonamide (0.516g), diazabicycloundecene (0.500g) to This gives 6-benzenesulfonylcarbamoyl-1- (biphenylfluorenyl) -2-fluorenylbenzimidazole sodium salt (213) (0.365 g). [Physical properties of compound (213)] W-NMBXDMSO-d6,6): 2.52 (3Η, s), 5.52 (2Η, s), 7.13 (2Η, d, J: 8.1Hz), 7 · 3 Bu 7.37 (4Η, m), 7.39-7 · 45 (3Η, m), 7.58-7 · 63 (4Η, in), 7.78-7 · 82 (3Η, m) , 7.97 (1H, s). IR (Nujc) l): 1591CET1. Melon P: 289.0 — 290.0 ° C (decomposed 奁 with 弋). &lt; Example 151; Synthesis of 6-benzenesulfonamidoaminofluorenyl-1- (2-chlorobenzyl) -2-methylbenzimidazole (163) &gt; Dimethyl Jun (5.41g) was added with 6-alkyl-1- (2-Azobenzyl) -2-fluorenylbenzimidazole (502g) of n, N-dimethylformamide (110ml) The solution was stirred at room temperature for 1 hour. Next, a solution of bensulfenamide (5.24 g) and diazabicycloundecene (5.08 g) in N, N-diamidinofluorenamine (20 ml) was added and stirred at 100 ° C for 70 hours. The reaction solution was cooled, and the solvent was distilled off under reduced pressure. Add water and trifluoromethane to the residue and add it while mixing. The paper size applies the Chinese National Standard (CNS) A4 (210X297 mm) --------- ^ ------ 1T- ----- (诮 Please read the precautions on the back before filling this page) 548272 A7 B7 V. Description of the invention (17) Add hydrochloric acid until the water layer becomes acidic. Extraction was carried out using tri-gas methylbenzene (twice), and the obtained organic layer was washed with a saturated sodium bicarbonate aqueous solution, and the-part of the solvent was removed under reduced pressure. The precipitated crystals were filtered, and the 6-benzenesulfonylcarbamoamidinyl group "-(, oxobenzylmethylbenzyl) was found to be dried. (163) 4.96g., &Lt; Example 152; H2-Azobenzyl) Synthesis of 2_methyl_6_trifluoromethanesulfonylaminomethylbenzylbenzoyl sialic hydrochloride (214) &gt; N, N'-carbonyldiimidazole ( 0.647g) added n-n-dimethylformamidine (20ml) / § ^ solution of p-carboxyl-i_ (2-chlorobenzyl) -2-methylbenzimidazole (0.600 g) The mixture was stirred at room temperature for 1 hour. Next, trifluorosulfonamide (0.596 g) and diazabicycloundecene (0.609 N, N_: fluorenylformamidine (5 ml) were added. The solution was stirred at 10 ° C for 72 hours. The reaction solution was cooled, and the solvent was distilled off under reduced pressure. Water and chloroform were added to the residue, and 100 /% hydrochloric acid was added while mixing until the aqueous layer became acidic. The precipitated crystals were washed with a mixed solvent of ethanol (25 ml) and methanol (25 ml). The crystals were dried to obtain 1- (2-chlorobenzyl) -2-methyl-6-trifluorofluorenylsulfonyl. 0.420 g of aminoamidobenzimidazole hydrochloride (214) [Physical properties of compound (214)] WN MR (DMSQ-d6,6): 2.84 (3H, s), 5.82 (2Η, s), 7.G8 (1H, d, J = 7.5Hz), 7.30 (1H5 t) 3 7.40 (1H3 t, J = 7.7Hz), 7.58 (1H, d, J = 8.0Hz), 7.79 (1H, d, J ^ 8,6 Hz), 8.07-8.13 (2H5 m), IR (KBr): 1634cm1.

Mass (CI): m / e 432_-HCl). Mp: 332-335 ° C (decomposition of accompany 3). The size of this paper is in accordance with Chinese National Standard (CNS) Α4 specification (210X297 mm)

1T 548272 A7 ___ ~ V. Description of the invention (17 $ &lt; Examples 153, 154; 6-benzenesulfonylaminocarbamoyl-1- (2,4-monoatomyl) -2-methylbenzene Benzosial hydrochloride (215) and 6-benzylpyridylaminomethyl &amp; &amp; yl-1- (2,4 -monogasoyl) -2-methylbenzomethylpyridine (216) Synthesis &gt; According to the method of Example 152, 6-alkyl-1- (2,4-dichlorobenzyl) -2-methylbenzimidal (0.460 g), N, N, -Chlorodistilbene (0.445 g), benzylsulfonamide (0.431 g), and diazabicycloundecene (0418 g) to give 6-benzenesulfonylcarbamoyl-i- (2, 4-Dichlorobenzyl) -2-methylbenzimidazole hydrochloride (215) 0.540§. [Physical properties of compound (215)]. LH-NMR (DMS0-d63 δ): 2.71 (3H3 s) 3 5.74 (2H, s) 5 6.83 (1H, d, J ^ 8.4Hz), 7.33 (1H, dt J 2 2.0 and 8.4Hz), 7.63 (21 t), 7.71 (1H3 t), 7.78 ( 1H, d, J = 2.0 Hz), 7.86 (1Η, d, J-8.7Hz), 7.95 (1Η, dd, J = 1.4 and 8.7Ηζ), 7.99 (2Η, in) , 8 · 29 (1Η, s) 〇IR (KBr): 1686cm-1. Mp: 236.0-238.0 ° C. It was dissolved in a mixed solution of sodium bicarbonate aqueous solution and methanol. 10% hydrochloric acid was used to adjust the pH to 5 ~ 6. The precipitated crystals were collected, washed with water, washed with methanol, and dried to obtain 6-benzylsulfonylcarbamoamidinyl_ 1- (2,4_ 1-kilocarboxyl) _2-methylbenzimid. Sitting (216). Physical properties of compound (216)] 1 who _80- (16, (5): 2.48 (3Η, s), 5.58 (2H , s), 6.42UH, d, J: 8.4Hz), 7.31 (1H, dd, J: 2.2 and 8.4Ηζ), 7.60-7 · 75 (6Η, m), 7.99 (2Η , D, J 2 7 · 4Ηζ), 8 · 〇6 (1Η, s), 12 · 40 (1Η, s). The size of this paper conforms to the Family Standard (CNS) A4 specification (2Euro 29 ^)- -(Read the notes on the back before filling in this page)

1T 548272 A7 V. Description of the Invention (i7) IR (KBr): 1540cm ~ 10mp ·· 238 · 2 · -239.9〇C〇 (Read the precautions on the back before filling this page) &lt; Example 155 ; Synthesis of l- (2-Azobenzyl) _6_ (4-methoxybenzenesulfonylaminocarbamyl) -2-methylbenzimidazole (217) &gt; N, N'-Chloroyl Imidazole (0.431 g) was added with 6-carboxyl (2-chloroammonyl) -2-methylbenzomethylbenzoate (0.400 g) of n, N-dimethylformamide (15 ml) ) The solution was stirred at room temperature for 1 hour. Next, a solution of each oxybenzamide (0.0498 g) and diazabicycloundecene (0.405 g) in N, N-dimethylamidamine (5mi) was added at 1.0. Stir for 67 hours. The reaction liquid was cooled, and the solvent was distilled off under reduced pressure. Add water and three gas methane to the residual water. While mixing, add 10% hydrochloric acid until the water layer becomes acidic. Extraction was performed using trigas methane (twice), and the obtained organic layer was washed with a saturated sodium bicarbonate aqueous solution, and the solvent was distilled off under reduced pressure. Purified by silica gel column chromatography (eluent ·· trichloromethane / methanol = 1 00/2 ~ 100/1/10). After concentration, the mixture was crystallized using a mixed solution of ethyl acetate and diethyl ether. . The crystals were filtered and dried to give 0.450 g of tris (chloromethoxybenzyl) -6- (4-methoxybenzenesulfonylaminomethylamidino) -2-fluorenylbenzimidazole (217). [Physical properties of compound (217)] 4-earning_30- (16, d) ·· 2.46 (3H, s), 3.83 (3Η, s), 5.58 (2Η, s) 3 7.12 (2H3 d J 2 9 · 0Ηζ), 7.21 (1Η, t, J = 7.3Hz), 7.33 (1Η, t), 7.56 (1Η, d, J = 7.GHz), 7.63 (1H, d , J = 8.5Hz), 7.71 (1Η, dd, J = 1.6 and 8. · 5Ηζ), 7.91 (2Η, d, war ·), 8.05 (1Η, d, &gt; 1. · 3Ηζ) . IR (KBr) · 1683cm1.

Mass (FAB): m / e 470 (M + l) o mp: 271.0-274.0 ° C 〇The paper size is suitable for China National Standards (CNS) (-----_ 548272 A7 B7 V. Description of the invention (180 &lt; Example 156; Synthesis of 1- (2_fluorobenzyl) -2_fluorenyl_6_ (α-methylbenzite fluorenylaminofluorenyl) benzimidazole (218) &gt; According to Example 155 Methods: 6-Carboxycarbatobenzyl) -2-methylbenzimidazole (0.450 g), Ν, Ν, -carbonyl disalanilide (.485 g), α-toluene scutamine (0.05. (512g), diazabicycloundecene (0.456g) to give 1- (2-chlorobenzyl) -2-fluorenyl-6- (α-methylbenzylfluorenylaminofluorenyl) benzo 0.350 g of imidazole (218). [Physical properties of compound (218)] iH-NMIUDMSO-dG, (5): 2.48 (3Η, s), 4.36 (2Η, s), 5.53 (2 3 s) 3 6 · 40 (1Η3 d, J-6 · 8Ηζ), 7 · 15-7 · 28 (6Η, m), 7.32 (1Η, t), 7.49 (1Η, d, J: 8.3Hz) 3 7 · 55 (1Η, d), 7.83-7 · 87 (2Η, m) 0 IR (KBr) ·· 1593CHT1.

Mass (FAB): m / e 454 (M + 1). Mp: 193-196 ° C (bubble). &lt; Example 157; of 1- (2-chlorobenzyl) -6- (2,5-dimethylbenzenesulfonylmethylaminomethyl) -2-methylbenzopyrene (219) Synthesis> According to the method of Example 155, using 6-carboxy-1- (2-chlorobenzyl) -2-methylbenzimidazole (0.500 g), n, N, -carbonyldiimidazole® λ «· Guide to find 3 consumer cooperation (please read the precautions on the back before filling in this page) (〇.539g), 2,5-xylene sulfonamide (〇.616g), Cycloundecene (0.506 g) to give 1- (2-chlorobenzyl) -6- (2,5-dimethylbenzenesulfonylaminocarbamyl) -2-methylbenzimidazole (219) 0.490 g. [Physical properties of compound (219)] ^ -NMRiDMSO-dG, δ): 2.35 (3H, s), 2.48 (3H, s), 2.5K3H, s) 3 5.58 (2H, s), 6.45UH, d, J = 7.5Hz), 7.20-7 · 27 (2Η, m), 7.31-7 · 39 (2Η, m), 7.56 (1Η, d, J = 8,0Hz), 7.64 (1H, d, J = 8.5Hz), 7.75 (1H, d, J = 8.5Hz), 7.82 (1H, s), 8.06 (---—____ ISA___ This paper is suitable for Sichuan National Standard (CNS) A4 specifications (210X297) (%) 548272 A7 &gt; —-----—--------------__ B 7 V. Description of the invention (18 j-iH, s), 12 · 45 (1Η, br s). IR (KBr): 1690cm '(Read the precautions on the back before filling this page)

Mass (FAB): m / e 468 (M + 1). mp: 266.5-267.5 ° C. &lt; Conjugate Example 158; l- (2-chlorobenzyl) _2-methyl-6_ (4-nitrobenzenesulfonylaminofluorenyl) benzimidazole (22 〇) Synthesis &gt; N, N, carbonyldiimidazole (0.432g) was added to the carboxyl- 丨-^-oxobenzyl) -2-methylbenzimidazole (040,00N, N In a solution of dimethylformamide (15ml), and stirred at room temperature for 1 hour. Then, add nitrobenzidine (0.538g) and diazabicycloundecium (0405g) N, N-dimethylformamide (5 ml) solution, stirred at 10 (rc for 84 hours. The reaction solution was cooled, and the solvent was distilled off under reduced pressure. Trichloromethane and hydrochloric acid were added to the residue and stirred to precipitate Crystals. The crystals were filtered and dried to give 1- (2-chlorobenzyl) -2-methyl-6- (4-nitrobenzenesulfonylaminocarbamyl) benzimidazole (220) 0.300 g. [Physical properties of compound (220)] -NMR (DMS0-d6, 6): 2.56 (3Η, s), 5.65 (2Η, s), 6.54 (1Η, d, J: 7.6 Hz), 7.23 (1H, t, J = 7.6Hz), 7.34 (1Η, t, J: 7.6Hz), 7.56 (1Η, t, J: 8.0Hz), 7.68 (1Η , D, J = 8.5Hz) 3 7 · 83 (1Η, d, J: 8.3Hz) 8 · 07 (1Η, s) 3 8.16 (2M, J = 8.7Hz), 8.3 7 (2H, d, J two 8 · 7Ηζ) square IR (KBr): 1621CHT1.

Mass (FAB): m / e 485 (M + 1). Melon · · 330 —332 ° C. &lt; Example l59; l- (2_fluorobenzyl) _2_methyl-6-['(trifluorofluorenyl) ___ ^ -—__ This paper is in accordance with China National Standard (CNS) A4 specification (210X297 (Mm) 548272 The central part of the Ministry of Economic Affairs ^ quasi ^ B, τ Consumer cooperation private printing t A7 __________________ B7_ V. Description of the invention (183 ~ benzenesulfonylcarbamoyl) synthesis of benzimidazole (221) &gt; The method of Example 158 uses 6-carboxy-1- (2-chlorobenzyl) -2-methylbenzimidazole (0.450 g), N, N, -carbonyldiimidazole (0.486 g), 4- (trifluoromethyl) benzite baicaleamine (0676 g), diazabicycloundecene (0.457 g) to give 1- (2-fluorobenzyl) -2-fluorenyl-6- [ 4- (trifluoromethyl) benzenesulfonylaminocarbamyl] benzimidazole (221) 0.39 (^. [Physical properties of compound (221)] Η-ugly (DMS0-d6, 6): 2.52 ( 3Η, s), 5.62 (2Η, s), 6.47 (1Η, d, 7.27Z) 22 (1Η, t, J: 7.5Hz), 7.34 (1Η, t), 7.56 (1Η, d, H = 8.GHz), 7.66 (1Η, d, 8 5), 7.78 (1Η, d), 7.97 (2Η3 d, J = 8.3Hz), 8.06 (1H, s), 8.15 (2H, d, J: 8.3 as) o IR (KBr): 1620 (^ -1.

Mass (FAB): m / e 508 (M + 1) Onip: 288.0-292.0 ° C 0 '&lt; Example 160; 6- (2-Gasylsulfonylaminoamidino) -Bu (2- Synthesis of Benzyl) -2-Methylbenzimidazolium Ammonium Salt (222) &gt; Add N, N-^ Anidol ^ Blind Sigma (0.485g) to 6-Weiyi-1- (2-Gas A solution of benzyl) -2-methylbenzimidazole (0.450 g) in N, N-dimethylformamidine (15 ml) was stirred at room temperature for 1 hour. Next, a solution of trifluoromethanesulfonamide (0.575 g) and diazabicycloundecene (0.457 g) in N, N-dimethylamidamine (5 ml) was added, and the mixture was stirred at 100 ° C. 72 hours. The reaction solution was cooled, and the solvent was distilled off under reduced pressure. Water and ethyl acetate were added to the residue, and 10% hydrochloric acid was added while mixing until the water layer became acidic. The precipitated crystals were filtered off. Dissolve the crystals in ethanol and add ammonia to adjust to I paper size. Applicable to household standards (CNS) A4 specifications (210X29 ^^

(Read the notes on the back before filling in this page J

548272 A7 B7 V. Description of the invention (18 $ PH7, then adding diisopropyl ether, filtering out the precipitated crystals, and drying, it is known that 6- (2-chlorobenzenesulfonylaminofluorenyl) &gt; 1_ (2_ 0.360 g of chlorobenzylbuthylmethylbenzimidazole ammonium salt (222). [Physical properties of compound (222)] 'H-plane (DMS0-d6,: 2.47 (3H, s), 5.51 (2H, s) , 6 43 (ih, &amp; j = 7 5Hz) 7 12 (4H, br s), 7.19 (1H, t, J = 7.6Hz), 7.28-7.38 (4 «, m), 7.46 (1H5 d, J = 8.3HZ), 7.53 (1H, d, J: 7.9Hz), 7.78-7.82 (2H, m), 7.97 (1Η m) IR (KBr): 1590cm-1. '

Mass (FAB): π / e 474 (M + 1-NH3). mp: 264.0 —267.0cC. &lt; Example ΐόΐ; 6-aminomethylfluorenyl- 丨 _ (2, 'di-gas benzyl) _2_ fluorenyl benzimidazole (223) Synthesis &gt; Ethyl hydrazone chloride (0.437 g ) Add 6-carboxy_H2,4-di-aminobenzyl) -2-methylbenzoxazone (0.49 g) and n, N-dimethylmethyl MM central central rate ^ mT consumption combined Bamboo II (read the precautions on the reverse side and then fill out this page) In a solution of ammonium amine (1 drop) in gasified ethylene dichloride (gml), stir at room temperature for I] hours. Water and emulsified ethylenediamine were added to the reaction solution for extraction. The organic layer was concentrated, and the precipitated crystals were collected and dried to give 0.240 g of 6-carbamoyl-1- (2,4-dichlorobenzyl) -2-methylbenzimidazole (223). [Physical properties of compound (223)] 4-leg (DMSO-d6, (5): 2.48 (3Η3 s), 5.54 (2Η, 3), 6.41 (1Η, d, J = 8.4Hz) , 7.21 -8 · 02 (3Η, m), 7.31 (1Η, dd, private 2 and 8.4Ηζ), 7.60 (1H, d, J: 8.4Hz), 7.75 (1H, m) , 7.93 (1H, s). This paper size is applicable to Chinese National Standard (CNS) A4 (210x297 mm) 548272 Ministry of Economic Affairs decided «.- Jujube and find -T consumption cooperation seal ^ A7 B7 V. Description of the invention (18j IR (KBr): 1666cm-10 mp · 112.0-114.0 ° C &lt; Example 162; 6-benzenesulfonylcarbamoamido-2-decyl_; μ (2,4-monogas Synthesis of fluorenyl) benzoyl salivary (224) &gt; N, N'-carbonyldiimidazole (0.248g) was added to 2-benzyl &lt; · carboxyl · (2-oxobenzyl) benzimidazole ( 0.315§) in N, N-diamidinofluorenamine (5ml) / cereal solution was stirred at room temperature for 1 hour. Then, benzylsulfonamide (0.224g) and A solution of azabicycloundecene (0.233 g) in N, N-dimethylamidamine (4 ml) was stirred at 100 C for 62 hours. The reaction solution was cooled, and the solvent was distilled off under reduced pressure. Water and three Add chloromethane to the residue and mix while At the same time, 10 ° /. Hydrochloric acid was added until the water layer became acidic. Extraction was performed using trisfane (2 times), and the resulting organic layer was washed with a saturated sodium bicarbonate aqueous solution, and a part of the solvent was distilled off under reduced pressure. Methanol (4mi) and 20% potassium hydrogencarbonate aqueous solution (4ml) were added to the residue, and the pH was adjusted to 5 to 6 with 10% hydrochloric acid. The precipitated crystals were filtered and dried to obtain 6-benzenesulfonylcarbamoamido. 2_benzyl-Bu (2,4-monofluorofluorenyl) benzimid. Sitting (224) 0.31 (^. [Physical properties of compound (224)] | H-Luo⑽s0-d6, w: 4.32 (1H, s), 5.61 (2H, s), 6.16 (1H, d, Sunda), 7 09 (1H, dd, J: 8, 4 and UHz), 7.18_7 · 1〇 (5Η, π), 7.82 7 58 (6h, '7 97 (2 H, d, J = 7.6Hz), 8.10 (1Η, s), 12.43 (143, br s). IR (KBr): 1703 ^^ 0 mp: 236.0-238.0 ° C. &Lt; Example 163; Synthesis of 5-benzenesulfonylaminocarbamoylbenzyl-Bu (2,4-a ^ amino substituted fluorenyl) Benzosalamine (225) &gt; (Please read the notes on the back before filling this page), 1T contention, 548272 by the Ministry of Shanghai ^ Jujube ^ only workers eliminate cooperation ^ printed «A7 B7 V. Description of the invention (18 $ according to The method of Example 152 was carried out using 2-benzyl-5-carboxy-1 · (2,4-dichlorobenzyl) benzobis (嗤 .385g), Ν, Ν, glutaimide (. .304g), benzylsulfonamide (0.294g), and diazabicycloundecene (〇285g) to give 5-benzenesulfonylcarbamoylmethylbenzyl_1- (2,4-dichloro Benzyl) 0.270 g of benzimidazole (225). [Physical properties of compound (225)] tNMROiMSO-d6, d): 4.28 (2Η, s), 5.52 (2Η, s) 5 6.14UH, d, J = 8 · he), 7.2 and 7 · 06 (6Η, m), 7.42 (1Η, d, J = 8.6Hz), 7.76-7 · 57 (5Η, m) 3 8.05-7 · 95 (2Η, m), 8.24 ( 1Η, s), 12 · 43 (1Η, br s). IR (KBr): 1691 cm ′! 〇 That is: 107.0-110.co &lt; Example 164; 6-benzenesulfonylcarbamoyl (biphenyl-4-methyl) -2-hydroxybenzo Synthesis of imidazole (226) &gt; Tetramethoxyoxane (0.220g) was added to N-benzenesulfonyl-4-amino-3- (biphenyl-4-fluorenylamino) benzoxamine ( In 400 g) of an acetic acid solution (5 ml), it was stirred at 80 ° C for 2 hours. The reaction solution was concentrated, and a 20% aqueous solution of calcium bicarbonate was added to make it alkaline, and then adjusted to pH 5 to 6 using 10% hydrochloric acid. The precipitated crystals were collected, and methanol (10 ml), 10% hydrochloric acid (0.50 g), and 35% hydrochloric acid (0.35 g) were added thereto, followed by stirring at 60 ° C for 15 hours. After adding a 20% aqueous solution of calcium bicarbonate to make it alkaline, the pH was adjusted to 5 to 6 using 10% hydrochloric acid. The precipitated crystals were filtered and dried to obtain 0.219 g of 6-benzenesulfonylcarbamoyl-1- (biphenyl-4-methyl) -2-hydroxybenzimidazole (226). [Physical properties of compound (226)] ^ -NMRiDMSO-dG, δ): 5.07 (2H, s), 7.08 (1H3 d3 J = 8.2Hz), 7,33-7.39 (3H, ni ------- ---—______ I flQ_ _____ This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) n Order '(Read the precautions on the back before filling this page) 548272 A7 B7 V. Description of the invention (18g 7.44 (2H, t5 J = 7.5Hz) 3 7.60-7.65 (7H, m) 3 7.66-7.72 (2H5 m) 3 7.96-7.80 (2 H, 11.46 (1Η3 s), 12.34 (11 s).

IiUKBr): i7〇4, 1686cm—, (诮 Read the precautions on the back before filling in this page)

Mass (FD): m / e 483 (M). That is: 268 · 7—273 · 9 ° C. &lt; Example 165; Synthesis of 6-benzenesulfonylcarbamoyl (biphenylmethyl) -2-mercaptobenzimidazole (227) &gt; Carbon disulfide (2ml) was added to N-benzylsulfonylcarbamyl In a solution of fluorenyl-4-amino-3- (biphenyl-4-fluorenylamino) benzofluorenamine (0.800 g) in methanol (10 ml), stir at 50 ° C for 70 minutes. hour. Add chloroform and water, and dry the precipitated crystals to obtain 6-benzylaminocarbamyl-1- (biphenyl-4-methyl) -2-sulfobenzimidazole. (227) 0.719 g. [Physical properties of compound (227)] iH-NM ^ DMSO-d6,6): 5.55 (2Η, s), 7.28 (1Η, d, J 2 8.4Ηζ), 7.35 (1Η, t , J 2 6 • 3 Hz), 7.39-7.47 (4Η, m), 7.61-7 · 65 (6Η, m), 7.69 (1Η, t, J: 7.4Hz), 7.78 (1Η, dd, J = 8.4 and 1.4 ζ), 7.87 (1 Η, s), 7.81-7 · 98 (2 Η, m), 12.5K1H, s), 13.29 (1 Η, s), IR (KBr) : 1701cm 〖. mp: 320.0 — 321.0 ° C. &lt; Example 166; Synthesis of 6-benzenesulfonylaminocarbamoyl-1- (biphenyl-4-methyl) -2-methoxybenzimidazole (228) &gt; Tetramethoxymethane (0.250 g) was added to a solution of N-benzenesulfonyl-4-amino-3 ((biphenyl-4-methylamino) benzopyramine (0.400 g) in acetic acid (3 ml) at 80 ° C Stir for 2 hours. Add methanol to the reaction solution and collect -------------- Lift ------. This paper size applies Chinese National Standard (CNS) A4 (210X297 mm) 548272 A7 B7 5 Description of the invention (18) Crystals precipitated. A mixed solvent of acetone (1 ml) and methanol (8 ml) was used to wash and crystallize, and filtered and dried to obtain 6-benzenesulfonylcarbamoyl-1- (biben-4-methyl) -2- Benzoxybenzimidazole (228) 0.280 g. [Physical properties of compound (228)] lH-NMR (DMS0 ~ d6, δ): 4.17 (3H3 s), 5.33 (2H, s), 7.30 (2H, d, J = 8.2Hz) 5 7. 35 (1H5 t5 J = 7.4Hz), 7.44 (2H5 t, J-7.5Hz) 5 7.50 (1H, d, J = 8.4Hz), 7.60-7.6 5 (6H3 m) 3 7 · 68-7 · 72 (2Η, m) , 7 · 98-8 · 01 (2Η, m) 3 8 · 05 (1Η3 d, J: 1.5Hz), 8.18 UH, s) 3 12 · 50 (1Η, s), IR (KBr): 1690cm ~! 〇 That is: 136.0-138.5 ° C. &lt; Example 167; Synthesis of 6-benzenesulfonylaminocarbamoyl-i- (biphenyl-4-methyl) _2-carboxybenzimidazole (229) &gt; Triethylamine (0.080g) and Methylethanedichloride (o.HSg) added N, N-benzenesulfonyl-4-amino-3- (biphenyl-4-fluorenylamino) benzofluorenamine (0.400g) -In a solution of dimethylformamide (3 ml), stir for 2 hours at room temperature. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: ethyl acetate / formamidine = 9/1) to give 6-benzenesulfonylcarbamoyl (biphenyl-4-methyl) -2 -Crude refined product of carboxybenzimidazole. This was dissolved in acetic acid (1 ml) and methanol (5 ml), and stirred at 60 ° C for 1 hour. It was neutralized with an aqueous potassium hydroxide solution, and the precipitated crystals were filtered and dried to obtain 6-benzenesulfonylaminofluorenyl-i- (biphenyl_4-methyl) -2-carboxybenzimidazole ( 229) 0.245 g. [Physical properties of compound (229)] ^ -NMRiDMSO-de, δ): 5.44 (2H3 s), 7.23 (1H, d, J = 8.4Hz) 3 7.36 (1H, t3 J-7 .6Hz), 7.4K2H, d3 J = 8.1Hz), 7.45 (2H, t, J = 7.5Hz), 7.58 (2H3 t, J = 7.8Hz) (Read the precautions on the back before filling this page) Order

548272 A7 B7 V. Description of the invention (188) 7.60-7.71 (7Η, m) 3 7.94 (2Η, d, J: 8.3Hz), 12 · 38 (1Η, s) 3 12.52 (1H , S). IR (KBr): 1670cm-1. mp: 247 · 5-250.0 ° C. &lt; Example 168; 6-benzenesulfonylaminocarbamoyl (biphenyl-4-methyl) -2-methylamino group benzoyl sigma (230) Synthesis &gt; Stir N-benzenesulfonylaminofluorenyl-4-amino_3_ (¼ben-4-methylamino) benzanoic acid amine (0.300g), methyl at room temperature A mixture of isothiocyanate (0.200 g), methanol (5 ml) and acetone (5 ml) for 12 hours. Then, 97% sulfuric acid (1 ml) was added, and the mixture was stirred at room temperature for 43 hours. After adding a 20% potassium hydrogen carbonate aqueous solution to the reaction solution to make it alkaline, it was concentrated, and ethyl acetate and water were added to extract the residue. Concentrate the organic layer, dissolve it in chloroform, add hexane to precipitate crystals, filter and dry to obtain 6_benzoxanthanylaminopyreno_ι_ (biphenylmethyl) _2_methylamine 0.140 g of benzimidazole (230). [Physical properties of compound (230)] H NMR (DMS0-d6, δ): 2.98 (3H, d, J = 4.4Hz) 3 5.34 (2H, s) 3 7.22 (2H, d5 J = 8 «. ^-Λmember 5 Consumption Hezhu Private Printing Fan (诮 Please read the precautions on the back before filling this page)

• 2 Hz), 7.26 (1Η, d, J = 8.4Hz), 7.34 (1Η3 t, J = 7.3Hz), 7.44 (2Η, t, J: 7.5Hz), 7.57 (2Η , T, 4 = 7 · 6Ηζ) 3 7 · 59-7 · 68 (6Η, m), 7.76 (1Η, s), 7.95 (2Η, d, J: 7.4H z), 12 · 28 (1Η, s) .IR (KBr): 1672cm-1.

Mass (FAB): m / e 497 (M + 1). Mp: 225.0-228.0 ° C. &lt; Example 169; 2-Amino-6-benzylsulfonylaminofluorenyl-i_ (biphenyl. _L22____) This paper size applies Chinese National Standard (CNS) A4 (210X297 mm) 548272 A7 —__ B7 V. Description of the invention Synthesis of (18j ~ -4-methyl) benzimidazole (231) &gt; (Please read the notes on the back before filling this page) Methanol (10ml), acetone (10ml), Cyanobromide (.395g) was added to N-benzenesulfonylcarbamoyl-4-amino-3- (biphenyl-4-methylamino) benzofluorenamine (1.500g), and Stir at room temperature for 10 hours, then at 5 ° C for 30 hours. Add chloroform and water for extraction. The organic layer was washed with water (6 times), concentrated, and subjected to silica gel column chromatography (eluent: acetic acid). Ethyl acetate / methanol = 9/1) refined residue to give 2_amino-6_benzoxanthan fluorenylaminomethylmethyl-1- (biphenyl-4-methyl) benzo sigma (231) 0.i35g [Physical properties of compound (231)]

(5) ·· 5.32 (2H, s), 6.77 (2Η3 s), 7.05 (1Η, d, # 8 · 8Ηζ) 5 7. 21 (2H, d, J = 8.3Hz), 7 · 31-7 · 38 (4Η, m), 7.43 (2Η, t, J: 7.5Hz), 7.58-7.65 (6H, m), 7.79-7 · 82 (2Η, m). IR (KBr): 1684cm ~ 10 Mass (FAB): m / e 483 (M + 1) 0mp: 352.5-355, 0 ° C 0 &lt; Example 170; 6-benzenesulfonylaminofluorenyl _ 丨 _ (Synthesis of 2-benzyl) -2-n-propylbenzimidazole potassium salt (232) &gt; Triethylamine (0.060g) and butane gas (0.084g) were added to N • benzenesulfonate In a solution of fluorenyl-4-amino-3- (biphenyl-4-methylamino) benzofluorenamine) (0,300 g) in N, N &lt; fluorenylformamidine) (2ml), Stir at room temperature for 15 hours. The reaction solution was directly purified using a silica gel column chromatography to obtain threonylsulfonium_3_ (biphenyl_4-fluorenylamino) -4-butanamide benzopyreneamine (0e25 g). Methanol (5 ml) and 35% hydrochloric acid (0.50 g) were added and stirred at 60 for 3 hours. 20% potassium hydrogen carbonate was added to stop the reaction, and ethyl acetate and water were added for extraction. This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) v548272 A7 V. Description of the invention (193 'Concentrated organic layer, dissolve the product in a small amount of chloroform, add ether to make it θθ. . Filter and dry the crystals to get 6-benzenesulfonate (read the precautions on the back of the word before filling out this page) fluorenylaminofluorenyl-1- (bibenzylmethyl) _2_n-propylbenzimidazole Potassium salt (232) (0.157g). [Physical properties of compound (232)] Dirty (DMS0-d6, (5): G.95 (3H, t, deduction of 7. other), 1.77 (2Η, q3 Mura · 5Ηζ), 2.82 (2H, t, J = 7.5Hzh 5.55 (2Η, s), 7.11 (2Η3 d3 J: 8.2Hz), 7.32-7.38 (4H, m), 7.43 (2H, t, J: 7.5Hz) 3 7 · 47 (1Η, d, J = 8.4Hz), 7.58-7 · 64 (4Η, m), 7 · 79-7 · 83 (3Η, 7 · 96 (1Η, s). IR (Nujol) · 1592CHT1.

Mass (FAB) · m / e 548 (M + 1). mp: 279.0-282.0 ° C. &lt; Example 171; Synthesis of 6-benzenesulfonylaminocarbamyl group 丨 丨 (biphenyl_4-methyl) -2-n-heptylbenzimidazole (233) &gt; Method according to Example 170 Benzenesulfonyl-4-amino-3- (biphenyl-4-fluorenylamino) benzofluorenamine (0.400 g) and triethylamine (0.080 g) were used. (0. 17 g) to give 6-benzenesulfonylcarbamoyl-1- (biphenyl-4-methyl) -2-n-heptylbenzimidazole (233) 0.232 lum. I?. · ^-^ In the crotch part to find τ, eliminate the compound of the bamboo buckle [physical properties of compound [233]] lH-NMR (DMS0-d63 δ): 0.79 (3H, t, J = 7.3Hz ), L12-1.24 (6H, m), 1.24-1.31 (2H, m), 1.66-1.73 (2H, m) 3 2-84 (2H5 t3 J-7.6Hz) 3 5.58 (2H5 s) 5 7.14 (2H , d, J = 8.1Hz), 7.34 (2H, t, J = 7.6Hz), 7.43 (2Η, t, J = 7 · 4Ηζ), 7.52-7 · 66 (7Η, m), 7 75 (1Η, d, J 2 8.8Ηζ), 7.95 (2Η, d, J 2 7.6Ηζ), 8.15 (1Η, s), 12 · 45 (1Η, s). IR (KBr): 1688cm-1〇 ^ mp ·· 112.0- 117.5 ° C〇 —— _ 1 Qd____ This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) 548272 A7 B7 V. Description of the invention ( 19ί &lt; Example 172; Synthesis of 6-benzenesulfonylaminoaminofluorenyl-1- (biphenyl-4-methyl) -2-aminomethylbenzimidazole (234) &gt; (Please read the back first (Notes on this page, please fill in this page) According to the method of Example 170, N-benzenesulfonyl-4-amino-3- (biphenyl-4-methylamino) benzofluorenamine (0.300 g), Triethylamine (0.060g) and acetylacetonyl chloride (0.102g) to give 6-benzenesulfonylaminocarbamoyl-1- (biphenyl-4-fluorenyl) -2-chlorofluorenylbenzene 0.193 g of benzimidazole (234). [Physical properties of compound (234)] ^ -NMRiDMSO-dG, δ): 5.10 (2H3 s) 3 5.71 (2H3 s), 7.23 (2Η, d3 J = 8.3Hz) 5 7. 35 (1H, t, J = 7.3Hz), 7.44 (2H, t, J: 7.5Hz), 7.60-7.66 (6H, m), 7.69 (1Η, t, J 2 7.5Ηζ), 7.75-7.81 (2Η, in) 5 7.98-8 · 01 (2Η3 m), 8,16 (1H, s), 12.52UH, s) 〇IR (KBr) ·· 1700cm—, mp: 220.5-223.5 oC &lt; Example 173; 6-benzenesulfonylcarbamoamidin-1- ( Synthesis of Phenyl-4-fluorenyl) -2-ethoxymethylbenzobenzo (235) &gt; According to the method of Example 170, N-benzenesulfonyl-4-amino-3- (diphenyl Phenyl-4-fluorenylamino) benzofluorenamine (0.400 g), triethylamine (0.115 g), methyl ethyl fluorenyl chloride (0.131 g) to give 6-benzenesulfonylaminocarbamyl- 0.183 g of 1- (biphenyl-4-fluorenyl) -2-ethoxymethylbenzimidazole (235). [Physical properties of compound (235)] lH-NMR (DMS0-d6, ό '): 3.31 (3H5 s) 5 4.72 (2H3 s), 5.63 (2H, s), 7.23 (2H, d3 J = 8.3Hz), 7.35 (1Η, t, J: 7.4Hz), 7.44 (2Η, t5 J: 7.5Hz), 7.60-7.65 (6H, m), 7.70 (1H3 t, J-7.5Hz), 7.72-7.79 (2H, m), 7.98-8.0K2H, ffl), 8.18 (1H5 s), 12.50 (1H, s) 〇 ______ IQ 岑 —____ This paper is suitable for China National Standard (CNS) A4 specification (21〇X297) 5%) 548272 A7 B7 ir V. Description of the invention (IR (KBr): ΙβθΟοιη ^ mp: 195.0-198.0 ° C 〇 &lt; Example 174; 6-benzenesulfonylaminocarbamoyl group_ 丨 _ (biphenyl_ Synthesis of 4-methyl) -2-isopropylbenzimidazole potassium salt (236) &gt; According to the method of Example m, N_benzite lutetyl cetylamido_3- (biphenyl-4-methyl Amine) Benzofluorenamine (04000), triethylamine (0. _g), isobutylammonium chloride ((U i2g) as raw materials for the reaction-dissolve the crude product in methanol and 20% In a mixed solvent of aqueous potassium hydrogen carbonate solution, the pH was adjusted to 7 with 10% hydrochloric acid. The crystals precipitated were benzenesulfonylcarbamoyl-1- (biphenyl-4-methyl) _2-isopropylbenzimidazole. Potassium salt (236) 0.167 g. [Physical properties of compound (236)] U-d6, w: L26 (6H, d, ㈣ · 8Ηζ), 3.25_3 · iron ih, 虼 5.58 (2η, s ), 7.09 (2Η, d, J = 8.3Hz), 7.32-7 · 37 (4Η3 m), 7.43 (2H3 t3 J = 7.5Hz), 7.48 (1Η, d, J: 8.4Hz ), 7.58-7 · 64 (4Η, m) 5 7 · 79-7 · 83 (3Η, m) 3 7.95 (1Η, s) IR (Nujol): 1592cmΛ Mass (FAB): m / e 548 (M + 1). That is: 310.1-312.7 ° C &lt; Example 175; 6-benzenesulfonylaminoaminofluorenyl_ 丨 _ (biphenyl_4_fluorenyl) -2-fluorenylsulfide Of Benzylbenzimidazole (237) &gt; 20% potassium hydroxide aqueous solution (0323g) and water (2ml) were added to benzodiamidinocarbamoyl-1- (biphenylmethylfluorenylbenzimidazole) (0.310 g) of a methanol (5 ml) solution, followed by addition of fluorenyl bromide (0123 g), and stirred at room temperature for 2 hours. It is adjusted to ph5 ~ 6 with 10% hydrochloric acid, filtered, and the paper size is suitable for family care standards (CNS) A4 (2lGx29m) (Please read the precautions on the back before filling this page) &quot; 口 1 «.

I 548272 A7 B7 Ψ 'it in the A part f: He Zhu Yin 5. Description of the invention (19 $-6_benzenesulfonylaminoamino group obtained by drying the precipitated crystal_ 丨 _ (Lianbenjia Group) -2-methylthiobenzimidazole (237) 0.28 lg. [Physical properties of compound (237)] 'h -__ 6, w: 2.75 (3H, s), 5 ._, s), 7.25 (2Η, d, warfare), 7.35 (1H, t, J-7.4Hz), 7.44 (2H, t, J = 7.5Hz), 7.60-7.66 (7H, m), 7.68-7.75 (2H, m), 7.82-7.99 (2H, E), 8.19 (1H, d, J = i6Hz), i243 (ih, s). IR (KBr) · 1685cm-1. fflP: 218.8-22 (K40C. &lt; Example 176; 6-benzenesulfonylaminocarbamyl group ;; μ (biphenylmethyl) -2-ethylthiobenzimidazole (238) synthesis &gt; basis The method of Example 175 was performed using 6-benzenesulfonylcarbamoyl-1- (biphenyl-4-methyl) -2-sulfobenzimidazole (0.240 g) and ethyl bromide (0.117 g ) To obtain 0.225 g of 6-benzenesulfonylcarbamoyl (bibenzylidene) -2-ethylthiobenzimidazole (238). [Physical properties of compound (238)] H-NMR (DMS0-d6 , 6): 1.39 (3Η, t, J: 7.3Hz), 3.37 (2Η, q, J: 7.3Hz), 5.47 (ίH, s) 3 7 · 24 (2Η, d, J = 8.1Hz) 3 7 · 35 (1Η, t, J: 7.1Hz), 7.44 (2Η, t, J: 7.6Hz) 3 7 · 57-7.68 (8 (, m), 7.75 (1H3 d, J: 8.4Hz), 7.98 (2Η3 d3 J: 7.5Hz), 8.15 (1Η, s), 12e43 (lH, _s). IR (KBr): 1686cm—, mp: 125.5-12S.50C. &lt; Example 177; Synthesis of 6-benzylsulfonylaminofluorenyl 4- (biphenylfluorenyl) -2-n-propylthiobenzimidazole (239) &gt; According to the method of example 175, 6 was used -Bensulfonylaminoamino (Shun first read the notes on the back before filling out this page) Order I Q7 State Chinese National Standard (CNS) A4 specification (210X 297 mm) in the Ministry of Light Technology-Ai? Bei ^ BJT eliminates the combination of bamboo and W ^ 548272 A7 B7

V. Description of the invention (194 S-I-1- (biphenyl-4-fluorenyl) -2-sulfenylbenzimidazole (0.220 g) and n-phenyl molybdenum (0.117 g) to obtain 6-benzite stilbene 0.156 g of carbamate_1_ (biben_4 • methyl) -2-n-propylthiobenzyl (239). [Physical properties of compound (239)] H-NMR (DMS0-d6, 6) : 〇.97 (3H, t3 J: 7.4Hz), 1.76 (2H, q5 J: 7.2Hz), 3 29 3 .36 (2H3 ni) 3 5.48 (2H, s) 5 7.24 (2H, d3 J-8.3 Hz), 7.35 (1H3 t3 J ^ 7,3Hz)? 4 (2H, t, &gt; 7 · 4Ηζ), 7.58-7 · 71 (8Η, m) 3 7,74 (1H3 dd3 J = 8.5 and 1? Hz) 9 (2H, d, J-7.7HZ), 8.17 (1H, s), 12.43 (1H3 s) .z '7.9 IR (KBr): 1690cm-1〇mp: 106.0-111.5 ° C. &lt; Example 178; Synthesis of 6-benzenesulfonylaminocarbamyl (bibenzylmethyl) -2-n-hexylthiobenzimidal (240) &gt; According to the method of Example 175, use 6-Benzyl luteol carbamoyl-1- (biphenyl-4-methyl) -2-weilyl benzosulfazone (0.25g) and n-hexyl (0.166g) were filled to give 6-benzene Sulfonylaminofluorenyl-1 Xinglianbenzylmethyl) -2-n-hexylthiobenzophenone (240) 0.212 @. [Physical properties of compound (240)] IMlUDMSiHlG, (5): 0 · 82 (3Η3 t, J = 7.9Hz), 1.19-1.33 (however m) 5 1.33-1 44 (2H, ιη), 1.68_1 · 75 (2Η, m), 3.3G-3.43 (2H, ιη), 5.48 (2Η, s), 7.23 (2Η, d3 J = 8 • 2Hz), 7.35 (1Η, t, J: 7.1 Hz), 7.44UH, t, J: 7.6Hz), 7.60-7 · 75 (9Η, m) 3 8 0 (2H, d, J = 7.7hz), 8.19 (1H, s), 12.44 (1H3 s ) IR (KBr): 1688CDT1. mp: 139.5 —141.0 ° C (decomposed). &lt; Example 179; 6-benzenesulfonylaminocarbamyl-1- (bibenzylmethyl) (诮 Please read the precautions on the back before filling out this page), 11 This paper size applies the national standard of I7 country ( CNS) A4 specification (210X297 public envy) '' 548272 A7 B7 V. Description of the invention (Synthesis of benzo-spit (241) &gt; (诮 Please read the precautions on the back before filling this page) Stir N at 90 ° C -Benzenesulfonyl-4-amino-3- (biben-4-ylamino) benzofluorenamine (0.400 g) and formic acid (2 ml) for 3 hours. The reaction solution was concentrated, and methanol was added to Crystals were precipitated, and filtered and dried to obtain 6-benzenesulfonylcarbamoyl-i- (biphenyl-4-methyl) benzimidazole (241) 0.243 g. [Physical properties of compound (241)] 4-leg (DMSO-d6, (5): 5.60 (2Η, s), 7.35 (1Η, t3 J = 7.2Hz), 7.39 (2Η, d, J: 8 • 2Hz), 7 · 44 (2Η, t, J: 7.6Hz) 3 7 · 61-7 · 77 (9Η, m), 8 · 00 (2Η, d, J = 7.7HZ), 8 · 2 6 (1H, s), 8.66 (1Η, s), 12.5 (1H3 s). IR (KBr): 1683cm '! 〇mp: 141.5-143.60C. <Example 18o; l- (4-benzyloxybenzyl) _2_ Fluorenyl-6-[(2-pyridylmethyl) carbamate Synthesis of Benzo] benzo miso (2 42) &gt; Add acetic acid (4 ml) and ethanol (8 ml) to N- (2-α specific methyl) -4-acetamidoamino_3- (4-section In oxybenzylamino) benzopyramine (0.434 g), it was stirred at 90 ° C for 7 hours. It was concentrated under reduced pressure to obtain a residue, and ethyl acetate and diethyl ether were added thereto to crystallize it. By filtration 1. Dry the crystals to give 1_ (4-benzyloxybenzyl) _2_methyl-6 _ [(2-pyridylmethyl) aminomethylamidino] 0.375 g of benzimidazole (242). [Compound (242) Physical properties] * H-NMR (CDCl3, c5): 2.59 (3H, s), 4.78 (2H, dj J = 4.8Hz)) 5.〇1 (2H3 s), 5.31 (2H, s), 6.89 (2H, d, ㈣. service), 6.99 (2H, d, ㈣ ·), 7 2i (ih, this, pay.i

And 7.4Hz), 7.29-7.42 (6H, m), 7.62 (1H, br t), 7.65-7.75 (3H, m), 7.98 (1H

____1 QO A paper conforms to the Chinese National Standard (CNS) A4 specification (210X297 mm) 548272 A7 _____________________ B7_ 5. Description of the invention (19g ~~, s), 8.57 (1Η, d, J: 4 · 1Ηζ). IR (KBr): 1640cm-1. mp: 169.0-170.0oC (read the precautions on the back before filling this page) &lt; Example 181; 2-Methenyl-: ^ 3,4 · methoxydioxybenzyl) _6-[(2_ Synthesis of pyridylmethyl) aminofluorenyl] benzimidazole (243) &gt; Add acetic acid (2ml) and methyl alcohol (5ml) to N- (2-pyridylmethyl) _4_ethylfe &amp; c group In 3- (3,4-fluorenedioxybenzylamino) benzamine (0,490 g), it was stirred at 70 C for 8 hours. The residue was concentrated under reduced pressure to obtain a residue. The residue was purified by column chromatography (eluent: ethyl acetate / methanol = 9/1) and crystallized by ethyl acetate. The crystals were filtered and dried to give 2-methyl-l- (3,4-methyldioxybenzyl) -6-[(2-pyridylmethyl) aminomethylamidino] benzimidazole (243) 0.270§. [Physical properties of compound (243)] H-NMR (CDCl3, &lt; 5): 2.59 (3Η, s), 4.78 (2Η, d, J: 4.8Hz), 5.28 (2Η, s), 5.93 (2H, s), 6.51 (1Η, d, J = 1.6Hz), 6.55 (1Η, dd, J = 1.4 and 7.9Hz), 6.72 (2H, d, J = 8 · 0Ηζ), 7 · 22 (1Η, dd, J = 6.7 and 5.0Ηζ), 7.34 (1Η, d, J: 7.7Hz), 7.62 (1H, br t), 7.67_7 · 75 (3Η, m), 7.96 (1Η, d, J: l.lHz), 8.58UH, d, J = 4.9Ηζ) IR (KBr): 163 and cnT1. mp: 190 · 5-192 · 0ο0〇 &lt; Example 182; 2-methyl-6-[(2-pyridylmethyl) aminomethyl}-1- [4_ (1,2,3_Janji Synthesis of sial-4-yl) fluorenyl] benzofluorene (244) &gt; According to the method of Example 180, N-[(2-pyridylmethyl) -4-acetamido-3- [4 -(l, 2,3-thiadiazol-4-yl) benzylamino] benzimidazole ____im___ This paper is suitable for Chinese National Standard (CNS) A4 (210X297 mm) 548272 A7 ____________________ B7 ___One five 2. Description of the invention (19) (0.50 g) to obtain 2-methyl-6-[(2-pyridinyl) carbamoyl] -1- [4- (I, 2,3 · thiadiazole_ 4-yl) benzyl] benzimidazole (244) 033 g. (Read the precautions on the back and fill in this page. [Physical properties of compound (244)] H NMR (CDCh3 δ): 2.58 (3H, s), 4.58 (2H, d, J-5.9Hz), 5.62 (2H, s) 3 7.24 (1H, dd, J: 7.3 and 5.0 Ηζ), 7.28-7.33 (3H, ni), 7.64 (1 Η, d, J: 8.4 Hz), 7.73 (1H3 dt3 J: 7.7 and 1 · 6Ηζ), 7.81 (1Η, pyridine 8 4 and h3Hz), 81〇 (1H, J-8.2Hz) 3 8.13 (1H, s) 3 8.49 (1H3 d3 J = 4.2Hz) 3 9.04 (1H5 t, J = 5.9Hz), 9.58 (1H, s). IR (KBr): 1642cm_1. That is: 216,0-217.0oC. &lt; Example 183; 6-benzenesulfonylaminoamidino_i_ ( Synthesis of 2,4-difluorobenzyl) -2-methylbenzimidazole (245) &gt; The N-benzylbenzyl_4_ethynamine_3_ (2,4_difluorobenzylamine) Benzylpyridine (0.370g) was dissolved in a mixed solvent of 10% hydrochloric acid (3.3g), methanol (6ml), and water (4ml), and then 35% hydrochloric acid (0.5g) was added and stirred at 60 ° C. 3 hours. After adding 20% potassium bicarbonate aqueous solution to make the reaction solution alkaline, the pH was adjusted to 5 to 6 using 10% hydrochloric acid. The precipitated crystals were filtered and dried to obtain 6-benzenesulfonylaminofluorene. -L- (2,4-difluorobenzyl) -J2-fluorenylbenzo 245) 0.1 82 g. [Physical properties of compound (245)] ^ -NMIwDMSO-de, δ): 2.53 (3H3 s) 3 5.56 (2H, s) 3 6.95-7.0K1H, m) 3 7.04 (1 H, dt, J = 8.7 and 1. · 4Ηζ), 7.32 (1H, dt, J = 1 (K7 and 2.1Hz), 7.59-7 · 66 (3Η3 m), 7.68-7 · 74 (2Η, m) 3 8 · 00 (2Η, d, J: 8.1Hz) 3 8.13 (1H, s), 12.43 (1H, s). IR (KBr): 1686cm-1. Mp: 234.5-235.5eC (decomposition of 奁 companion * 5) ---------- xw ----- This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X297 mm) 548272 A7 V. Description of the invention (19g &lt; Bei Bi case 184; 6- Synthesis of benzenesulfonylaminocarbamyl (biphenyl_4-methyl) -2-phenylbenzimidazole (246)> Triethylamine (0.115g) and phenylphosphonium chloride (0.200g) are added to N- Benzenesulfonyl 4-amino-3- (biben-4-methylamino) benzodonamine (0.500 g) in a solution of N, N_-methylphosphonium amine (5 ml), After stirring at room temperature for 15 hours, an aqueous potassium hydrogen acid salt was added to stop the reaction. The solvent was distilled off under reduced pressure, and the residue was dissolved in a mixed solution of water and methanol, and adjusted to pH 5 to 6 with 10% hydrochloric acid. The precipitated crystals were collected and dried to obtain a crude product (0.393 g) of N-benzenesulfonamido-4-phenylamidoamino (biphenylmethylamino) benzamidoamine. By the method of Example 183, &amp; benzenesulfonylaminomethyl-1- (biphenyl-4-methyl) -2-phenylbenzimide was obtained. Sit (246) 0.270g. [Physical properties of compound (246)] 1 ⑽ S〇-d6,: 5.7Q (2H, s), 〇07⑽, d, ㈣ · 2Hz), 7 32-7 37⑽, m) 5 7.43 (2H) t, J = 5.7HZ), 7.53-7.58 (2H, m), 7.58-7.65 (^, ffl), 7.68-7.72 (1 H 'm), 7.77 (2H, dd, J = 7.5 and 1.5Hz), 7 · 81-7, 83 (2Η, m), 7.98-8.02 (2H, ^), 8.22 (1Η, s), 12,47 (1H, s). IR (KBr): 1690cm '! 〇mp: 138.5-139.5 ° C &lt; Example 185; 6-benzenesulfonylcarbamoylmethylsulfonium-methylmethyl el_ (2-nitrobenzyl) benzimidazole (247) Synthesis> According to the method of Example 183, benzenesulfenylacetamidinyl-3- (2-nitrobenzylamino) benzofluorenamine (0.79 g) was used to obtain 6- Phenylsulfonylaminocarbamyl-2-fluorenyl-1- (2-nitrobenzyl) benzophenone U12. (Read the precautions on the back before filling this page) This paper is applicable to China Standard (CNS) A4 specification (210X297 mm) 548272 A7 B7___ 5. Description of the invention (id (247) 0.237g. [Physical properties of compound (247)] (Please read the precautions on the back before filling this page) H-NMR (DMS0-d6, δ): 2.48 (3H, s) 3 5.01 (2H, s), 5.93 (2H, s), 6.28-6.30 (1 m), 7.55-7.62 (4H, m), 7.64 ~ 7.74 ( 3H, m), 7.97 (2H, d, J = 8.0i ^), 8.10 (1H, s), 8.22-8 · 28 (1Η, m) 5 12.39 (1H, s). IR (KBr): 1686cm_, 〇mp: 269-5, 272-5 (decomposition $: companion). &Lt; Example 186; 6-benzenesulfonylaminoamidino-2-methyl-1-benzylbenzimidazole (248) Synthesis &gt; Method according to Example 183 N-benzenesulfonyl-4-ethylamido-3-fluorenylaminobenzylamine (0.38g) was used to obtain 6-benzylaminomethylamino-2, fluorenyl- 0.222 g of 1-benzyl benzo saliva (248). [Physical properties of compound (248)] 'H-NMRiDMSO-dG, δ): 2.54 (3H5 s) 5 5.55 (2H3 s) 3 7.12 (2H, d3 J = 7.9Hz) 5 7. 28 (1H, t, J = 7.3Hz), 7.34 (2Η, t, J: 7,0Hz), 7.61-7 · 66 (3Η, m), 7.69 -7.76 (2Η, m), 8.00 (2Η, d, J: 7.9Hz), 8.18 (1Η, s), 12.43UH, s). IR (KBr): 1695cm] nip: 260.0-262.0 ° C (decomposition of accompany 〇). &lt; Examples 187, 188; 6-benzylsulfonylaminofluorenyl-2-methyl-1- (4-nitrofluorenyl) benzo (°) (249) and 6-benzene Of carbamoyl-2-methyl-1- (4-nitrocarbyl) benzoxalate salt (250) &gt; According to the method of Example 183, N-benzenesulfonyl-4 -Ethylamine- 3- (4-nitrocarboxamino) benzophenamine (0.505g) to give 6-benzenesulfonylaminofluorenyl-2-methyl-1- (4-Nitrobenzyl) benzimidazole ____24U___ This paper size applies to Chinese National Standard (CNS) A4 (210X 297 mm) 548272 A7 B7 V. Description of the invention (20d (249) 0.255g crystal. Furthermore, 0.136 g of 6-benzenesulfonylcarbamoyl-2-methyl-1- (4-nitrobenzyl) benzimidazole potassium salt (250) was obtained by concentrating the filtrate. [Compound (Physical properties of (249)] ^ -NMRiDMSO-dG, d): 2.50 (3H5 s) 5 5.70 (2H, s), 7.30 (2H5 d, J, 8.7Hz), 7 52 (2H, t, J: 7.6Hz ), 7.57 (2Η3 d3 J 2 8.3Ηζ), 7.76 (1Η, pyr Jr: 8 4 and Gong. He), 7.92 (2Η, d, J: 7, 3Hz), 8.05 (1Η, s), 8 · 20 (2Η, d, J: 8.7Hz), 12 · 43 (1Η, s) o IR (KBr): 1686cm'10mp: 164.5-167.0oC. [Physical properties of compound (250)] 1H-NMR (DMS0-d63 δ): 2.51 (3Η3 s) 3 5,68 (2Η3 s), 7.28 (2Η, d3 J -8.5Hz), 7 • 32-7.41 (3H , M), 7.46 (1Η, d, J = 8.4Hz), 7.78-7 · 86 (3Η, m), 7.91 (1Η, s), 8.20 (2H, d, J = 8,5Hz). IR (KBr): 15940111- ^ mp: 326.0 -328.0 ° C (decomposed with "5"). &lt; Example 189; Synthesis of 6-benzylsulfenylaminofluorenyl group-Xingren benzyloxybenzyl) _2-fluorenylbenzimidazole (251) &gt; In the Ministry of Chemistry ^-^ Μ .τ 消 贽 合 竹 ii imprinted (that is, read the precautions on the back before filling this page) Stir N-benzylsulfonyl-3-amino-4-acetamidobenzopyrene at 90 ° C Amine potassium salt (0.50 g), 4-benzyloxybenzyl bromide (0.470 g), 20% aqueous potassium hydrogen carbonate solution (0.925 g) and N, N-dimethylformamide (3 ml) for 1 hour . The reaction solution was concentrated and purified by silica gel column chromatography (eluent: ethyl acetate / methanol-9 / 1) to obtain N-benzite yellow ethyl-4-ethyl ethylamine-3- (4-fluorene oxygen Crude benzylamino) benzylamine. According to Example 183 -----— _2Π4 ___________— The paper size is in accordance with the Chinese National Standard (CNS) A4 specification (210X 297 mm) 548272 A7 B7 V. Description of the invention (20j) The method is obtained through cyclization 6_benzenesulfonylaminocarbamyl_1_ (4-benzyloxybenzyl) _2_methylbenzimidazole (251) 0.16 (^. [Physical properties of compound (251)] (read first on the back) Please fill in this page again) fNMlUDMSQ-de ,: 2.54 (3 2, s), 5.Q5 (2H, s), 5.44 (roll sh 7 q9 (2h, d, J 2 8.7Ηζ) , 7.32 (2Η, d, J: 7.QHz) 3 7 · 29-7 · 44 (5Η, in), 7.58-7 · 67 (3Η, ffl), 7.6 8-7 · 75 (2Η, m), 7.79-8 · 02 (2Η, m), 8.18 (1H, s), 12.46 (1Η, s). IR (KBr): 1685cm-1. °-mp: 111.0- 114.0oC. &Lt; Example 190; Synthesis of 2-methyl-5-[(2-pyridinyl) carbamoyl] benzimidazole (252) &gt; 5% palladium / carbon (0.10 g) was added In a mixture of N- (2-pyridylfluorenyl) -4-acetamidinyl-3-pentylbenzofluorenyl crude product (1.0.§) and acetic acid (8mi) and methanol (12ml), Stir under water ambient gas, 8 ° C for 7 hours. Filter out the solid By drying, 0.57 g of 2-methyl-5 [[2-pyridylmethyl] carbamoyl] benzimidazole (252) was obtained. [Physical properties of compound (252)] 1 orbital (CDC13, &lt; 5): 2.52 (3Η, s), 4.59 (2H, d, J: 5.9Hz), 7.26UH, dd, J2 7.1 and 5.1Hz), 7_33UH, d, J = 7.8Hz), 7 · 50 (1Η, d, J = 8.4Hz), 7.72-7 · 78 (2Η, m) 5 8.08 (1H, s), 8.5K1H, d, J = 4.8Hz), 9.04 (1H, t5 J = 5.8Hz), 12.44 (1H, s) 〇IR (KBr): 1641cm ′ mp: 212.0-215.0 ° C. &lt; Examples 191, 192; 1-benzenesulfonyl-2-methyl-6-[(2-pyridinemethyl ________ 9 0S_ This paper size applies to the Chinese National Standard (CNS) A4 specification (21 × 297 mm) ) 548272 A7 V. Description of the invention (20i group) aminofluorenyl] benzimidazole (253) and ^ benzenesulfonyl-2-methyl-5 _ [(2-pyridinyl) carbamoyl] Synthesis of benzimidazole (254) &gt; (Read the precautions on the reverse side before filling out this page} Add dioxane (10ml) and triethylamine (0760g) to ^ methyl_5-a [(2-pyridine Methyl) carbamoyl] benzimidazole (100 §), and then benzylsulfenyl chloride (0.994 g) was added dropwise. After stirring for 3 hours, the reaction solution was washed with water (3 times), and then with carbonic acid. Wash with aqueous sodium hydrogen solution. The organic layer was concentrated under reduced pressure, and purified by silica gel column chromatography (eluent: ethyl acetate / methanol = 9/1) to obtain 1-benzenesulfonyl-2-methyl-6_ [(2-Turadinylmethyl) carbamoyl] benzimidazole and 1-benzenesulfonyl-2-methyl-5-[(2-epiridinyl) carbamoyl] benzimidazole The mixture was 1.38 g. Then, it was subjected to medium pressure silica gel column chromatography (eluent ·· ethyl acetate / methanol = ^ 00/3). This mixture was refined to give 1-benzylsulfonyl-2-methyl-6-[(2-α-pyridinylmethyl) carbamoyl] benzimidazole (253) as an oil, 0.55 g, as an oil. 0.540 g of 1-benzenesulfonyl-2-methyl-6-[(2-pyridine α-methyl) aminopyrene] (25 4). The oil was dissolved in dichloromethane (1.5 ml), diethyl ether was added to crystallize it. [Physical properties of compound (253)] lH-fmR (CDCh, 6) ··· 2,84 (3H, s), 4.81UH, d, J: 4.8 Hz), 7.24UH, dd, J: 5.1 and 7. 3Ηζ), 7.37 (1Η, d, J: 7.7Hz), 7.53 (2H, dd, J = 7.9 and 7.5Hz), 7.6 3- 7.74 (2H, m) "7.85 (lH, dd, J = 8.4 &amp; 1.2Hz), 7.97 (2H, dd, J: 9.6 ^ 1 • 1Hz) 5 8.58-8.6K2H, m) IR (KBr): 16360111 ^ nip: 163.4-164.30C〇 [Physical properties of compound (254)] ______206 This paper size applies Chinese National Standard (CNS) to specifications (2H) x 297 mm) 548272 Δ7 A7 B7

V. Description of the invention (20S ^ -NMRiCDCh, d): 2-83 (3H, s) 3 4.78 (2H3 d, J = 4.7Hz), 7.23 (1H3 dd, J = 4.9 and 8.6Ηζ), 7 · 34 (1Η, d, J = 7.9Hz), 7.53 (2Η3 dd, J = 7.5 and 8.4Ηζ), 7.64-7 · 75 (3Η, m), 7.91-7.96 (3Η, m), 8.10 (lH, d, J = 9 · 1Ηζ), 8.14 (1Η5 d3 J = 1 · 3Ηζ), 8.56 (1Η, dd, J = 4.9 and 1.0 Hz). IR (KBr): 1657cm ~ 10: 88.3 — 91 · 30C〇 <Conductive Examples 193, 194; 2-Methyl-l- (4-Shotosylbenzyl) -6 _ [(2_11 ratio fluorenyl) carbamate Synthesis of fluorenyl] benzimidazole (255) and 2-fluorenyl-1_ (4-nitrobenzyl) -5-[(2-αpyridinylmethyl) aminofluorenyl] benzimidazole (256) &gt; Add N, N-dimethylformamide (10 ml), 4 · nitrobenzyl bromide (3.24 g) and sodium bicarbonate (2.52 g) to 2-methyl-5-[(2- Beta ratio: methyl) carbamoyl] benzimidazole (3.56 g), heated at 80 ° C. for 2 hours. Water and chloroform were added to the reaction solution to separate the layers. The organic layer was concentrated under reduced pressure, and purified by column chromatography on silica gel (eluent ·· ethyl acetate / methanol = 4/1) to obtain 2-methyl-1- (4 · nitrobenzyl) -6- [(2-Pyridylmethyl) carbamyl] benzimidazole and 2-methyl-^ (4-nitrobenzyl) -5 · [(2-pyridylmethyl) carbamoyl] benzimidazole Of a mixture. Then use medium pressure silica gel column color 5 Jin (eluent: ethyl acetate / methanol = 85/15) to separate the positional isomers, and then recrystallize by using a mixture of trichloromethane and diethyl ether. And 2-methyl-1- (4-nitrobenzyl) -6-[(2-pyridylmethyl) aminomethyl] benzimidazole and 2-methyl-1- (4-nitro Group> 5-[(2- &quot; pyridinyl) carbamoyl] benzimidazole (256) 1.19 g. [Physical properties of compound (255)] H-NMR (CDC13, 6): 2.59 (3H , s), 4.77 (2H, d, J-4.8Hz), 5.48 (2H, s) 3 7,09 This paper size ㈣1 &quot; (2ΐ〇χΐ9 ^ ¥ Τ (Please read the notes on the back before copying Page) Order 548272 A7 B7 V. Description of the invention (20j (2H3 d, J = 8.7Hz), 7.22 (1Η, dd, J = 7.2 and 4 · 9Ηζ) 3 7.33 (1H, d, J: 7 』Hz ), 7.66-7 · 70 (2Η, m), 7.73 (1Η, dd, J: 8.4 and 1.5Ηζ), 7.78 (1Η, d, J: 8.4Hz), 7.9K1H, d , J = 1.2Hz), 8.15-8.19 (2H, m) 3 8.56 (1H3 d3 J = 4.6Hz) 〇IR (KBr): 1652cm—, nip: 116.1 —119.100C〇 [Physical properties of compound (256)] W-NMlUCDCh, 6): 2.59 (3Η, s), 4.79 (2Η, d, J 2 4.8Ηζ ), 5.46 (2H, s) 3 7 · 17 -7.24 (4H, m) 3 7 · 35 (1Η, d, J 2 7 · 8Ηζ) 3 7 · 69 (2Η3 dt, J 2 7 · 6 and 1 · 7Ηζ), 7.83 (1Η, d, J 2 8.4Ηζ), 8.19 (2Η, d, J 2 8.6Ηζ), 8.26 (1Η, d, J = 1.3Hz), 8.57 (1Η, d, J = 4.8Hz) 〇IR (KBr): 1634CET1. Mp: 203,7-206.3 ° C 〇Beijing Zhong Rong Dabei AM T, eliminate the combination of bamboo: Yin 1 '! (翱Read the precautions on the back before filling this page) &lt; Examples 195, 196; 2-methyl-1- (2-phenethyl) -6-[(2-pyridinyl) aminofluorenyl] benzene Synthesis of benzimidazole (257) and 2-fluorenyl-1- (2-phenethyl) -5-[(2-α than pyridylmethyl) aminomethylfluorenyl] benzimidazole (258)> According to the Examples The method of 193 and 194, using 2-methyl-5-[(2-dipyridylmethyl) aminofluorenyl] benzimidazole (2.0 g) and phenethyl iodide (15.0 g) to obtain 2-methyl-1- (2-phenethyl) -6-[(2-αbipyridinyl) aminofluorenyl] benzimidazole (257) (0.30g) and 2-fluorenyl-1- (2-Phenethyl) -5-[(2-pyridinyl) carbamoyl] benzimidazole (25 8) (0.23 g). [Physical properties of compound (257)] ^ -NMRiCDCla, δ): 2.17 (3Η5 s), 3.10 (2H, t, J = 6.8Hz) 3 4.35 (ZH, t, J = 6.8 Hz), 4-82 (2H , d, J = 4.8Hz), 6.92-6.97 (2H, m) 3 7,21-7.28 (4H, m), 7.38 (1H, d, J-7-SHz), 7.78 (1H, br t), 7.68-7.73 (3H, m), 7.98 (1H, d, J-0.9Hz), 8.6 -----_? N «_ This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) A7 548272 ________________ B7 V. Description of the invention (20i 0 (1H, dd, J 2 1.0 and 4. 9K · ζ). IR (neat): 1633cm_10 Liquid. (Permit reading the precautions on the back before filling in this page) [Physical properties of compound (258)] ^ -NHRCCDCla, δ): 2.19 (3H, s), 3.08 (2H, t, J = 6.8Hz), 4.35 (2H, t3 J = 6.8 Hz), 4.8K2H, d3 J = 4.8Hz), 6.91-6.96 (2H, m), 7.19-7.26 (4H, m), 7.31 (1H, d, J: 8.4Hz), 7.36 (1H, d, J: 7.8Hz), 7.64 -7 · 73 (2Η, m), 7.85 (1H, &lt; ld, J = 1.7 and 8.4Ηζ), 8.19 (1Η, d, J 2 1.3Ηζ), 8.58 (1Η, d, J: 4.0Hz). IR (neat): 1643cm-1. liquid. &lt; Examples 197, 198; 1- (2,4-difluorobenzyl) _2-fluorenyl-6-[(2- this pyridylmethyl) carbamoyl] benzimidazole (259) and i_ Synthesis of (2,4-difluorobenzyl) -2-methyl-5-[(2-pyridinofluorenyl) aminofluorenyl] benzimidazole (26) &gt; According to Examples 193, 194 As a method, 2-methyl-5-[(2-exomethyl) carbamate] benzo is used. Sit (100g) with 2,4-dioxobenzyl bromide (1000g) to give 1- (2,4-difluorobenzyl) _2_fluorenyl-6-[(2- Pyridinyl) aminoamino] benzimidazole (259) 0.25g and 1- (2,4-difluorobenzyl): 2-fluorenyl-5 · [(2-pyridinylmethyl) carbamoyl Fluorenyl] benzimidazole (260) 0.25 g ° [physical properties of compound (259)] H-NMR (CDC13, d): 2.62 (3Η, s), 4,78 (2H, d, J: 4.7Hz ), 5.38 (2H, s), 6.73 to 6.79 (2Η, m), 6.88 (1Η, t, J: 10 Hz), 7.24 (1H, dd, J: 7.3 and 5 · 1Ηζ), 7.3 5 (1H, d, J = 7.8Hz), 7.67-7 · 76 (4Η, m), 7.97 (1Η, s), 8.58 (1Η, d, J = 4.4 Hz). ___ 209___ This paper size is applicable to China National Standards (CNS) A4 specification (210X297 mm) 548272 In the head of the Ministry of Economic Affairs i ?. quasi-only-T eliminates the seal of the woman ¾ A7 ______ B7 V. Description of the invention (2 ^^ IR (KBr): 1642cm- 丨. That is: 98 · 0 — 104 · 0 ° C. [Physical properties of compound (260)] ^ -NMRCCDCh, δ): 2.62 (3H3 s) 5 4.79 (2H, d3 J-4.7Hz) 5 5.35 (2H5 s), 6.72-6 · 81 (2Η, m), 6.89 (1Η3 t, J = 9.8Hz), 7 · 22 (1Η, t, J = 6.2Hz), 7 · 28 (1Η, d3 8.4Hz), 7.34 (1H, d, J = 7.8Hz), 7.63-7.71 (2H, m), 7.83 (1H3 d, J = 8.4Hz), 7. 97 (1H5 s) , 8.57 (1H, d, J = 4.7Hz) .IR (KBr0: 1647cm1. Mp: 143.5-144.0 ° C. · <Examples 199, 20o; 1-(4-aminobenzyl) _2_ Methyl-6-[(2-pyridylmethyl) carbamoyl] benzimidazole (261) and 1- (4-aminobenzyl) _2-fluorenyl-5-[(2-.pyridine (Synthesis) Carbamidyl] Synthesis of Benzimidazole (262) &gt; Methanol (30ml) and 5% palladium / carbon (0.20g) were added to 2-methyl_1- (4-nitrobenzyl)- 6-[(2-Pyridylmethyl) carbamoyl] benzimidazole and 2-methyl-1- (4-nitrobenzyl) -5-[(2-α ratio Pyridinyl) carbamoyl] benzimidal mixture (2.32g), stirred at room temperature under hydrogen atmosphere until the raw materials disappeared. The solid was filtered, and the filtrate was concentrated to obtain a residue. Purification by silica gel column chromatography (eluent: ethyl acetate / methanol = 85 / 丨 5) to separate into 1- (4-aminobenzyl) -2-methyl-6-[(2-α Methyl) carbamoyl] benzimidazole and 1- (4-aminobenzyl) -2-methyl-5-[(2-pyridinyl) carbamoyl] benzimidazole. Trichloro A mixed solvent of methylbenzene and diethyl scale is used to crystallize. ^ (4-aminobenzyl) -2-methyl-6-[(2-pyridylmethyl) amino is obtained by filtering and drying the crystals. Formamyl] 0.354 g of benzimidazole (26l) and 1_ (4_aminobenzyl) _2 · fluorenylpyridylmethyl) ammonia paper standard Shizhou Chinese National Standard (CNS) A4 size (210X297 mm) (Please read the precautions on the back before filling out this page) Order 548272 A7 B7 V. Description of the invention (20) Base fluorenyl] benzimidazole (262) 0.33 (^. [Physical properties of compound (261)] 'H-NMRiCDCL ·, δ): 3.00 (3R, s) 3 4.98 (2H3 s) 3 5.88 (2H, s), 7.55 (2H3 d, J 2 8.6Ηζ) 3 7.69 (2H, d, J: 8.6Hz), 7.90 (1H, d3 J = 8.6Hz), 7.96 (1Η, dt, J 2 7.1 and 0.6Hz), 8 · 12 (1Η3 J: 8.0Hz ) 3 8,18 (1H, dd3 J: 8.5 and 1. he), 8,55 (1H, dt, J 2 8.0 and l_7 Hz) 3 8.62 (1H, d, J 2 1.1 Hz), 8.77 (1Η, dd, J 二 5.9 and 1.1Ηζ) 0 IR (KBr): 1643cm-1. mp: 180.0 —181.0 ° C. · [Physical properties of compound (262)] lH-NMR (CDCl33 δ): 3.00 (3H, s) 3 5.01 (2H3 s) 3 5.83 (2H, s), 7.47 (2H, d, J = 8 · 5Ηζ) 3 7.78 (2H, d3 J2 8.5Ηζ), 7.78 (1H, d, J2 8.98ζ), 7.97 (1H, dt, J2 7.2 and 0.77Ηζ), 8.13 (1Η5 J = 8.1Hz) , 8.15 (1Η, d, J = 8.9Hz), 8.51UH, s), 8.55 (1H, dt3 J = 7.9 and 1.6Ηζ), 8.77 (1H, d3 J = 5.8Hz). IR (KBr): 1639, 1612 (^ 0 mp: 168.0-171.0QC. &Lt; Example 201; l- [4- (benzenesulfonylamino) benzyl] _2-fluorenyl-6-[(2 -Synthesis of pyridylmethyl) carbamoyl] benzimidazole (263) &gt; Triethylamine (0.185g) and benzenesulfonium (0.221g) were added; aminobenzyl) -2- In a solution of fluorenyl-6-[(2-pyridylfluorenyl) aminofluorenyl] benzimidazole (0.340 g) in chloroform (10 ml), it was stirred at room temperature for 8 hours. Water was added to stop the reaction, and extraction was performed using trichloromethane. The organic layer was washed with water (three times), dried and concentrated, and then the residue was purified by silica gel column chromatography (eluent · ethyl acetate / formase = 1〇〇 / 〇〜4 / 1) to obtain ι_ [4_ (Benzene 2 \ This paper size applies to Chinese National Standard (CNS) A4 specifications (210X 297 mm) (Read the precautions on the back before filling in this page)

Order 548272 Air quasi-h consumer cooperation in the Ministry of Economic Affairs II India A7 B7 V. Description of the invention (Table 20 sulfoamidoamino) benzyl] -2-methyl «(2-pyridylmethyl) carbamoyl] Benzimidazole (263) 0.300 g. [Physical properties of compound (263)] H'NHR (CDCl33 δ): 2.53 (3H3 s) 5 4.78 (2H3 d3 J-4.8Hz), 5.28 (2H, s) 3 6.90 (2H, t3 J = 8.6Hz), 6.99 (2H, d3 J: 8.5Hz) 3 7 · 11 (1Η, s), 7.23UH, dd, J: 5.5 and 7.2Hz), 7.34 (1Η, d, J: 7.7Hz) 3 7,40 (2H, J = 81Hz) 3 7 5〇 (m, t, J = 7 • 5Hz) 3 7.66-7.74 (6H, m), 7.92 (1H, s) 5 8.56 (1H3 d3 J = 4.8Hz) (KBr): 1642cm-10, that is, 204.4-206.5oC &lt; Example 202; 6-benzylsulfonamidoaminomethyl _] μ (2-Gas benzyl) 2-methylbenzimidazole (264) Synthesis> At room temperature, 60% sodium hydroxide (0.127 g) was added to a solution of ammonium besylate (0.667 g) in N, N-monoammonium formate (5 ml) and stirred for 1 hour . Next, 1- (2-chlorobenzyl) -6-chloromethylmethylbenzimidazole hydrochloride (0.648 g) was added, and the mixture was stirred at room temperature for 18 hours. Water was added to the reaction solution to stop the reaction, and the solvent was distilled off under reduced pressure. Ethyl acetate and water were added to the residue for extraction. The organic layer was concentrated and purified by silica gel column chromatography (&gt; Valley Liquid: Ethyl Acetate) to give 6_benzenesulfonylaminomethyl-1- (2-gaso benzyl) _2_form Base benzimidazole (264) 0 240 g. [Physical properties of compound (264)] 1H-NMR (DMS0-d6, d): 2.42 (3H5 s) 3 4.02 (2H3 m) 3 4.02 (2H, m) 3 5.44 (2H, s), 6.36 (1Η , D, J: 7.7Hz), 7.03 (1Η, d, J: 8.4Hz) 5 7.18 (1H, s), 7.21 (1Η, t), 7.33 (1H, t), 7.59-7.43 ( 5H, m), 7.73 (2H3 d3 J, 7.5Hz), 8.08 (1H, s), IR (KBr): 1522cm-1. mp: 164.5-167.0oC〇217 No ... ruler and Chinese National Standard (CNS) A4 specification (210X 297 male shame) (Please read the precautions on the back before filling this page), \ ν'ί &gt; Γ 548272 kl B7 V. Description of the invention (20 in combination <Beijing Example 203; 1- (biben-4-methyl) -2-methyl-6-[(2-glutidinylmethyl) aminomethyl] benzyl Synthesis of Benzimidazole (265) &gt; (Read the precautions on the back before filling this page) Add 2-Aminopyridylpyridine (〇372g) to (Biphenyl_4 • fluorenyl) _2_methyl-6 -A solution of chloromethyl-2-methylbenzimidazole (0.597 g) and potassium carbonate (0350 g) in N, N-dimethylformamide (3 ml) and stirred at 60.0 2 Hours. Water and ethyl acetate were added for extraction, and the organic layer was washed with water (twice). The solvent was removed under reduced pressure to obtain a residue, which was purified by silica gel column chromatography (eluent: trichloromethane / methanol = 9/1). In order to obtain 丨 · (biphenyl-4_fluorenyl) _2_fluorenyl-cardio [(2-pyridylmethyl) aminomethyl] benzimidazole (265) 0300 g. [Compound (265) Physical properties] [H-NMR (CDC13, c5): 2.57 (3H, s) 3 3.91 (2H, s), 3.93 (2Η, s), 5.35 (2Η, s), 7.08-7 · 14 (3Η, m), 7.23 (2Η, d3 J: 7.3Hz), 7.30-7, 35 (2H, m), 7.41 (2Η, t) 3 7 · 50-7 · 55 (4Η, m), 7.57 (1Η, dt, J = 1.8 and 7.6Ηζ) 3 7 · 68 (1Η, d, J: 8,1Hz) 5 8 .53 (1Η, d3 J = 4.9Hz) IR (KBr): 1618cm1〇 That is: 104.5-106.0oC. <Example 204; N-benzenesulfonyl-3- [1 ((2-fluorobenzyl) -2-methyl) Of benzimidazol-6-yl] propanamide (266) &gt; Add palladium / carbon (0.500 g) to N-benzenesulfonyl small (2-gaso-benzyl) -2- In a solution of methyl benzimidazole-6-propenylamine (0.607 g) in ethanol (150 mi), stir at room temperature for 43 hours under hydrogen atmosphere. The solid was filtered off, and the filtrate was concentrated and dissolved in 20 In a mixed solution of a potassium potassium carbonate aqueous solution and methanol, the pH was adjusted to 5 to 6 with 100/0 hydrochloric acid. The precipitated precipitate was filtered off, and the residue was dried to obtain N · benzenestone yellow brewing group-3- [1-(2 · Chlorination Festival —-—_ 213 _ This paper size is suitable for China National Standard (CNS) A4 specification (210X297 mm) &quot;-548272 A7 ___________________B7__ V. Description of the invention (2 1¾ basis) -2 -Methylbenzo -6-yl] amine propionate (2 66) 0.25 Og. [Physical properties of compound (266)] 4-dirty_50- (16,6): 2.45 (3Η, s), 2.52 (2H, t), 2.78 (2Η, t), 5.37 (2Η , S), 6.88 (1Η, d, J: 8.4Hz), 7.08 (2Η, d, J: 7.4Hz), 7.22-7 · 34 (3Η, melon), 7.36 (1Η , T, J = 8.1Hz), 7.55 (2Η, t), 7.67 (1Η, t), 7.84 (2Η3 d, J = 7 · 6Ηζ), 12 · 04 (1Η, br s) .IR (KBr): 1715 cm. Mass (FAB): m / e 468 (M + 1). mp: 229.8 —233.0 ° C. <Example 205; 6-Benzylpyridinylcarbamyl-2-methyl-l- [4- (I, 2,3-thiadiazol-4-yl) benzyl] benzimidazole ( Synthesis of 267) &gt; According to the method of Example 18 3, N-benzyl-4-acetamido-3- [4- (l, 2,3-thiadiazol-4-yl) benzyl was used Aminoamino] benzofluorenamine (0.382g) to give 6-benzite yellow aminoaminopyrenyl-2-methyl-l- [4- (1,2,3-thiadiazole-4- (Benzyl) benzyl] benzimidazole (267) 0.279 g. [Physical properties of compound (267)] 1H-NMR (DMS0-d6, δ): 2.56 (3H, s), 5.62 (2H, s), 7.28 (2H, d, J = 8.2Hz), 7. 58-7 · 63 (3Η, m) 3 7 · 67 (1Η, t, J 2 · 7Η3Ηζ), 7.74 (1Η, dd, J = 8.5 and 1.2Ηζ), 7 · The meridian is interposed MT dismisses the impression of bamboo shoots (read the precautions on the back before filling this page) 99 (2H3 dd, J2 S.4 and 1.2Hz), 8 · 10 (2Η, d, J2 8 · 2Ηζ), 8.19 (1Η, s) 3 9 · 58 (1Η, s), 12.47 (1Η5 s), IR (KBr): 1617, 1556cm, mp: 258.5-260.0 ° C (decomposition of 奁 companion 0). &lt; Example 206; Synthesis of 1- (2-chlorobenzyl) _2-methyl-6- (8-fluorolinesulfonylaminocarbamyl) benzimidazole sodium salt (268) &gt;- ----- 204 ----- This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 548272 A7 B7 V. Description of the invention (21 j (#Read the precautions on the back before filling this page) ) According to the method of Example 141, 'Using 6-benzyl-1_ (2-chlorobenzyl) -2-methylbenzimidazole (0.450 g), N, N'-carbonyldiazole (0.485§), 8-biting leaching 1 blueamine (0.625§), diazabicycloundecene (0.457g) to give 1- (2-chlorobenzyl) -2-methyl-6- (8-leaching 0.400 g of luteinylcarbamoyl) benzimidazole sodium salt (268). [Physical properties of compound (268)] ^ -NMRCDMSO-dG, δ): 2.4Z (3H3 s), 5.48 (2H, s) 3 6.32 (1Η, d5 J = 7.7Hz) 5 7. 17 (1H, t, J = 7.5Hz), 7.30 (1H, t3 J = 7.7Hz), 7.42 (1Η, d, J = 8.4Hz) , 7.48 (1Η, dd, J = 4.2 and 8.2Ηζ) 3 7.53 (1H, d3 J 2: 8.0Ηζ), 7.64 (1Η3 t, J 2: 7.7Ηζ), 7.79 (1H, d, J = 8.5Hz), 7.88 (1Η, s), 8.04 (1Η, d, J: 8.1Hz), 8.33-8 · 37 (2Η, m), 8 • 85 (1H, dd). IR (KBr): 1594cm1. . ·

Mass (FAB): m / e 513 (M + 1). mp: 348 — 352 ° C (decomposition of accompaniment 3). &lt; Example 207; of 6- (4-Third-butylbenzenesulfonylaminofluorenyl) _1- (2-gasobenzyl) -2-methylbenzimidyl salivary sodium salt (269) Synthesis> According to the method of Example 141, 6-carboxy-1- (2-chlorobenzyl) -2-fluorenylbenzyl rice was used. Sit (0.450g), N, N'-Weiji diwei saliva (0.486g), 2-third butylsulfonamide (0.640g), diazabicycloundecene (0.657g) to get 0.280 g of 6- (4- 3rd butylbenzenesulfonylcarbamoyl) -1-ochlorobenzyl) -2-methylbenzimidazole sodium salt (269). [Physical properties of compound (269)] 1H-NMR (DMS0-d6, 6) 1.25 (9H, s) 5 2.46 (3H3 s) 3 5.51 (2Η, s), 6.37 (1Η3 d, J: 7 · 7Ηζ ), 7 · 18 (1Η, t), 7.31 (1Η, t), 7.34 (2Η, d, J = 8.4Hz), 7.44 (1Η, d, J 2 8 China National Standard (CNS) A4 specification (210X297 mm) 548272 The central part of the warp is printed ^-^ m η Consumption Bamboo Shirt ^ A7 B7 V. Description of the invention (21i • he), 7.54 (1Η, d, J: 8.0 Hz), 7.69 (2Η3 d, J: 8.5Hz), 7.78-7 · 82 (2Η, in). IR (KBr): 1596cm1 Mass (FAB): m / e 518 (M + l) 〇mp: 359.5-362 ° C 〈Example 208; 6-Bentylsulfonylcarbamoylmethyl group “— [′ (difluoromethyl) fluorenyl] benzylimide group (270 ) Synthesis &gt; According to the method of Example 32, N-benzenesulfonylacetamidinyl-3-aminobenzofluorenamine (0.5% and 4- (trifluoromethyl) benzyl bromide (0.5%) 418 to obtain a crude product of N-benzenesulfonyl-4-acetamido-3_ [4- (trifluoromethyl) benzylamino] benzidine (0.30g), which was dissolved in In methanol, it is left to precipitate crystals. After filtering, the crystals are dried to obtain 6-benzene 0.160 g of fluorenylcarbamoyl-2-methyltrifluoromethyl) benzyl] benzimidazole (270). [Physical properties of compound (270)] ilHiMlUDMSO-dG, ¢): 2.51 (3Η, s ), 5.66 (2H, s), 7.28 (2Η, d, J = 8.1Hz), 7.59-7.65 (3H, m), 7.67-7 · 75 (4Η, m), 7.99 (2Η, d, J = 7.5Hz), 8 · 14 (1Η, d, 0Hz), 12.43 (1H, s), IR (KBr): 1618, 1550CDT1. Mp ·· 278.5 —280 · 0 ° C. & Lt Example 209; Synthesis of 2-benzyl-6-carboxy-1_methylbenzimidazole hydrochloride (271) &gt; 1 A 5% sodium hydroxide aqueous solution (28g) was added to 2-benzyl-6_ In a solution of ethoxycarbonyl-1-fluorenylbenzimidazole (0.340 g) in ethanol (4 ml), heat to reflux for 1.5 hours. Make it acidic with 1N hydrochloric acid, and concentrate under reduced pressure (read the notes on the back of the reading first) Please fill in this page for matters) Order Φ ·. 548272 A7 B7 V. Description of Invention (2l) Ethanol was added to the residue to extract organic matter, and ethanol was distilled off under reduced pressure to obtain 0.300 g of 2-benzyl-6-carboxy-1-methylbenzimidazole hydrochloride (271). (Read the precautions on the back before you fill in this page) [Physical properties of compound (271)] H ^ NMR (DMS0-d63 δ): 4.00 (3H3 s), 4.62 (2H, s), 7.33 (1H5 m), 7.35-7.45 (4 H, '7.83 (1Η, d, J: 8.4Hz), 8.06 (1Η, d, J: 8.4Hz), 8.42 (1Η, s), 13.3 (1H, br s) 0 &lt; Example 210; Synthesis of 5-benzenesulfonylaminofluorenylmethylbenzimidazole (272) &gt; Stir N-benzenesulfonyl-4-ethylamidoamine at 60 C- 3-Aminobenzofluorenamine (0.50 (^), 350/0 hydrochloric acid (3.9§), methanol (15010), and water (121111) mixture for 1 hour. Use an aqueous potassium hydrogen carbonate solution to neutralize it, The precipitated crystal was filtered and dried to obtain 0.404 g of 5-benzenesulfonylcarbamoylmethyl-2-methylbenzylpyrene (272). [Physical properties of compound (272)] Η- fmR (DMS0-d6,5): 2.79 (3Η, s), 7.64-7 · 68 (2Η, m), 7.72-7 · 76 (1Η, m), 7.81 (1Η, d, J: 8.7 Hz), 7.94 (1Η, dd, J = 1.6 and 8.7Ηζ), 8.02-8 · 05 (2Η, m), 8 determined by the Ministry of Justice ^. ^-And 0 3 Private Ownership 30 (1Η, s) 〇IR (KBr): 1701cml 〇mp: 223.0-227.5 ° C 〇 &lt; Real Example 45; Production of 3-methoxyethylamido-4_nitrobenzoate ethyl ester> According to the method of Production Example 12, 3_amino_4-nitrobenzoate ethyl ester (15.0g) was used And methoxyacetamidine (15 g) to obtain hong methoxyacetamidine -------- 217 This paper is sized to China National Standard (CNS) A4 ^ i7Ti〇297mm) ~ ----- 548272 A7 B7 V. Explanation of the invention (21 &gt; Ethyl-4-nitrobenzoate g (1 8.7g). [Physical properties of compound] (翱 Please read the precautions on the back before filling this page ) W-ugly (CDCh, 6): 1.42 (3Η, t, 7.2Hz), 3.58 (3H, s), 4.1K2H, s), 4.43 (2H, q, j: 7.2Hz), 7 · 85 (1Η, dd, J: 1.6 and 8.7Ηζ), 8.27 (1Η, d, J: 8.7Hz), 9.44 (1H, d, J = 1.6Hz), 11 · 15 (1Η, s). &lt; Example 211; Synthesis of 1- (biphenyl-4-methyl) -6-ethoxycarbonyl-2-methoxymethylbenzimidazole (273) &gt; According to the method of Production Example 14, 3- Ethyl methoxyacetamido-4-nitrobenzoate (2.OOg) and 4-biphenylmethyl bromide (2.98g) to give 3-[N- (biphenyl-4-methyl) methyl Ethoxyacetamido] _4_shishothiobenzoate Crude refined product (2.02g). Then, according to the method of Example 24, 1.44 g of a crude product of 1- (biphenyl-4-methyl) -6-ethoxycarbonyl-2-oxomethylbenzimidazole (273) was obtained. <Example 212; Synthesis of 1- (biphenyl-4-methyl) -6-carboxy-2-methoxymethylbenzimidazole (274)> According to the method of Example 53, (biphenylmethyl ) _6_ethoxy.yl-2-methoxyoxyfluorenyl crude refined product (U4g) to give 丨 _ (bibenzyl) -6-carboxy-2-methoxyfluorenyl Benzimidazole (274) 0.864 g. [Physical properties of compound (274)] Η-NMR (DMS0-d6, ό): 3.35 (3Η, s), 4.77 (2Η, s) 5 5,68 (2H, s), 7.25 ( 2Η, d, J-8, 3Hz), 7.35 (1H3 t, J = 7.4Hz), 7.44 (2H, t, J = 7.5Hz), 7.61-7.66 (4H, m) 5 7 · 74 (1Η, d , J = 8.6Hz), 7 · 83 (1Η, dd, J = 1.6 and 8. · 5Ηζ), 8.08 (1H, d3 J = 1.2

Hz), 12.83 (1H, s) 〇 _____ 218 This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 548272 A7 B7 V. Description of the invention (21 husband &lt; Example 213; 1- (biphenyl Synthesis of 4-methyl) -6- (1-butanesulfonylaminomethylamidino) -2-methoxymethylbenzimidazole (275) &gt; According to the method of Example 98, 1-( Biphenyl-4-methyl) -6-Weiyl-2-methoxymethylbenzoxyl salivary (0.400 g), N, N'-kisyl diisocyanine (0.348 g), 1- Butanite amine (0.294 g) and diazabicycloundecene (0.327 g) to give 1- (biphenyl-4-methyl) -6- (1-butanesulfonylcarbamidine) Group) 0.429 g of 2-methoxymethylbenzimidazole (275). [Physical properties of compound (275)]% -NMR (DMS0-d63 6): 0.84 (3Η, t, J = 7.4 Hz) , 1.35-1 · 42 (2Η, m), 1.62-1.70 (2Η, m) 3 3.33 (3Η, s), 3.51 (2Η, t, J = 7.6Hz), 4.74 ( 2Η, s), 5.65 (2Η, s) 3 7 · 2 6 (2H, d3 J = 8,3Hz), 7.35 (1H, t, J = 7.3Hz), 7.44 (2H, t, J = 7.5Hz) , 7.62-7.67 (4H, m), 7.78 (1Η, d3 J = 8.6Hz), 7.84 (1Η, dd, J 2 1.5 and 8.4Ηζ), 8.24 (1Η, d3 J = 1. 5Hz) 3 12.0K1Η, s) 〇IR (KBr): 1684cm-that is: 176.0-178.5 ° C. &lt; Example 214; 1- (4 · benzyloxybenzyl) -6-ethoxycarbonyl fluorenyloxy fluorene Synthesis of Benzylbenzimidazole (276) &gt; ^ Shanghai Ministry of Justice «Beijing and PT Consumption Hezhu * India ^ (Read the precautions on the back before filling this page) According to the method of manufacturing example 14, using Ethoxyethylaminoaminonitrobenzoate (2.00g) and 4-benzyloxybenzyl gas (3.30g) to give 3- [N- (4-benzyloxybenzyl) Crude refined product of ethyl methoxyacetamido] nitrobenzoate (2.14 g). Then according to the method of Example 24 to obtain a crude product (1.66 g) of 1- (4-benzyloxybenzylethoxycarbonylmethoxymethylbenzidine (276). &Lt; 贝 施 例 215; 1- (4-benzyloxybenzyl) carboxyl_2_ 曱 oxyfluorenyl ----- 219_ This paper is suitable for 1] Chinese National Standard (CNS) A4 specification (210X297 mm) '一 &quot; &quot; '--- 548272 A7 B7

V. Description of the invention (2A Synthesis of benzimidazole (277) &gt; According to the method of Example 53, using Benzene (read the precautions on the back before filling this page) ethoxycarbonyl-2-methoxy Crude refined product of methyl benzimidazole (3 75 g) to give 1- (4- ¥ oxybenzyl) -6-isopropyl-2-methoxymethyl benzimidazole (277) 2.64 g. [Physical properties of compound (277)]! -NMR (DMS0-d6, ά): 3.34 (3Η, s) 5 4.74 (2Η, s), 5.05 (2Η, s), 5.53 (2Η, s), 6.97 (2Η, d, J = 8.7Hz), 7.15 (2Η3 d, J = 8.7Hz), 7.31 (1Η, t, J = 7.2 · 2Ηζ), 7.41 (2Η, d, J ^ .ZHz), 7.71 (1Η, d, ιϋ. ^ ΙΗζ), 7.81 (1Η, dd3 J: 1.5 and 7. · 4Ηζ), 8.04 (1Η, d, J2 · 1 · 1Ηζ), 12 · 81 (1Η, s). &Lt; Example 216; 1- (4-benzyloxybenzyl) -6- (1-butanesulfonylcarbamoyl) -2-fluorenyloxymethyl Synthesis of benzimidazole (278) &gt; According to the method of Example I55, 1- (4-benzyloxybenzyl) -6-weiyl-2-fluorenylbenzyl benzimidyl α was used ( 0.400 g), n, N, -kisyl di-taste. Sit (〇.322 g), 1-butanesulfonamide (0.272 g), diazabicyclo Undecene (0.302g) to give 1- (4-benzyloxybenzyl) -6_ (l-butanesulfonylaminomethylamidino) _2-methoxyfluorenylbenzimidazole (278) 0.32lg [Physical properties of compound (278)] ^ -NMRiDMSO-dp, δ): 0.86 (3H3 t3 J = 7.4Hz) 3 1.37-1.44 (2H, m), 1.65-1.71 (2 H, in), 3.32 (3Η, s), 3.52 (2Η, t, J 2 7.6Ηζ), 4.71 (2Η, s), 5.05 (2H, s), 5.51 (2H, s), 6.98 (2Η, d, J: 3.7 Hz), 7.15 (2Η, d, J = 8.3Hz), 7.31 (1Η, t, J 2 7.2Ηζ), 7.37 (2Η, t, J = 7.2Hz) , 7.41 (2Η, d, J = 7.1Hz), 7.74 (1Η, d3 J = 8.5Hz), 7.8 2 (1H, dd, J = 1.5 and 8.5Hz), 8.21 (1Η, s ), 1L98 (1H, s). IR (KBr): 1685CHT1. mp: 72.0-74.0 ° C. ______220 _ This paper size is in accordance with China National Standard (CNS) A4 (210X297 mm) 548272 A7 B7 V. Description of the invention (&lt; Example 217; 1- (2,4-dichlorobenzyl) -6_ Synthesis of ethoxycarbonyl · 2 · methoxymethylbenzimidazole (279) &gt; According to the method of Production Example 14, 3-ethoxyethylamidoaminonitrobenzoate (2.00 g) and 2, deaminium benzyl chloride (2.08 to obtain 3- [N- (2,4-dichlorobenzyl) methoxyethylamidoamino] _4-nitrobenzoate ethyl ester The crude product was purified according to the method of Example 24 to obtain the crude product of 1- (2,4-dioxobenzyl) -6-ethoxycarbonyl-2-methoxymethylbenzimidazole (2) 3.15 g of purified product. &Lt; Example 218; Synthesis of 6-carboxy-1- (2,4-dichlorobenzyl) -2-methoxymethoxybenzimidazole (280) &gt; Method 53, using 丨 _ (2,4_dichlorobenzyl) _ 6-ethoxycarbonyl-2-methoxyoxybenzyl benzimidazole crude product (315g) to obtain 6-carboxyl- 1- (2,4-dichlorobenzyl) _2_methoxyoxybenzyl benzimidazole (280) 1.46 g. [Physical properties of compound (280)] 4 ~ NMR (DMS0-d6, ά): 3 · 23 (3Η, s), 4.70 (2Η, s), 5.68 (2Η, s), 6.54UH, d, J = 8.5Hz), 7.31 (1Η, dd, J: 2.2 and 8 · 5Ηζ), 7.73 (1Η, d, J: 2.1liz), 7.76 (1Η, d, J 2: 8.5Ηζ), 7.86 (1Η, dd, J 2: 1.5, and 8.5Ηζ ), 8 · 〇〇 (1Η, d, 12 · ^ tooth, central part &quot;-rate ^ only 3 consumer Hezhu private seal ^ (read the precautions on the back before filling in this page) MW. 85 (1Η, s) ○ Example 219; 6- (1. Butanesulfonylaminocarbamyl phenyl ^ -rendichlorocarbyl) -2-methoxymethyl benzo saliva (2 81) Synthesis> According to the method of Example 98, 6-carboxy_1- (2,4-dichlorobenzyl) -2-methoxymethylbenzimidazole (0.400 g), N , N, -carbonyldiimidazole (0.355g), 1-butanesulfonamide (0.300g), diazabicycloundecene (〇333g) The scale is applicable to China National Standard (CNS) A4 specifications (210 / 29¾1 Xian) 548272 A7 B7 V. Description of the invention (to get 6- (1-butanesulfonylaminomethylamidino) -i- (2,4-dichlorobenzyl) _ 2-methoxymethyl Benzimidazole (281) 0.430 g. (Read the precautions on the back before filling this page) [Chemicals (Physical properties of (281)] 2H? M), 3.21 (3H, s), 3.51 (2H, t3 J = 7.6Hz) 3 4.68 (2H, s), 5.65 (2H, s), fi.4 6 (1H, d, J 2: 8.5Ηζ), 7.31 (1Η, dd, J2 2.0 and 8.4Ηζ), 7.75 (1Η, d3 J: 2.1Hz), 7.80 (1Η, d, J: 8.5 Hz), 7.86 (1Η, dd, J: 1.7 and 8.6Ηζ), 8.14 (1Η, d, J 2: 1.2

Hz), 12.00 (1Η3 s). IR (KBr): 1694cm-1. mp: 168.5 —170.5 ° C. &lt; Example 220; Synthesis of l- (2-chlorobenzyl) -2-methyl-6- (1-butanesulfonylcarbamoyl) benzimidazole (282) &gt; According to Example 98 Method, using 6-carboxy-1- (2-chlorobenzyl) -2-methylbenzoxyl salivary (0.400g), N, N'-I carbon-based disulfal salivary (0.431g), 1- Butanesulfonamide (0.328g) and diazabicycloundecene (0.404g) to give 1- (2-chlorofluorenyl) -2-methyl-6- (1-butyrate yellow Benzylcarbamoyl) benzimidazole (282) 0.459 §. [Physical properties of compound (282)] β, τ digestion and bamboo shirt printing through the central part of the crotch ^ -NMRCDMSO-dG, 6): 0.98 (3H, t, J = 7.4Hz), 1.67-1.75 ( 2H5 m) 5 2.50 (3H, s), 3.49 (2Η, t, J = 7.7Hz), 5.61 (2Η5 s), 6.45 (1Η, d, 7.0Hz), 7.24 (1H, dt, J 2 0 · 8 and 7.8Ηζ), 7.35 (1Η, dt, J 2 1.4 and 7.4Ηζ), 7.63 (1Η, dd, J: 0.9 and 7.9Ηζ), 7 · 69 (1Η, d, J = 8.5Hz), 7.81 (1Η, dd, J = 1.6 and 8.5Ηζ), 8.12 (1H, d, J = 1.66Ηζ), 11 · 90 (1Η, s ). IR (KBr): 1676cm-1. mp: 217.5-218.5〇C〇 _____-- 242 ........ This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) 548272 A7 B7 5. Description of the invention (&lt; Examples 221; 6-Ethylsulfonylaminofluorenylchlorobenzyl) -2-methylbenzimidazole (283) Synthesis> According to the method of Example 98, 6-carboxy-ip-chlorobenzyl was used ) -2-methylbenzo. Sit (0.400g), N, N'-Carbonyl diu miwa (0.431g), ethanesulfonamide (0.290g), diazabicycloundecene ((M04g) to get 6-ethyl Permethrinyl-1-(2-Azobenzyl) _2-fluorenylbenzimidazole (283) 0.459 g. [Physical properties of compound (283)] iH-NMIUDMSO-dG, 6): 1.23 (3Η, t, J: 7.3Hz), 2.5G (3H, s), 3.50 (2Η, q, J 2 7. 3Ηζ), 5.61 (2Η, s), 6.45 (1Η, d , J = 6.7Hz), 7.24 (1Η, dt, J = 0.9. And 7.5Ηζ), 7.35 (1Η, dt, J = 1.4 and 7.5Ηζ), 7.58 (1Η, dd, J = 1.0 and 8.0Ηζ), 7.69 (1Η, d, J = 8.5Hz), 7.81 (1Η, ddv J = 1.6 and 8. he), 8.13 (1Η, d, J: 1.5Hz), 11. 86 (1H3 s) IR (KBr): 1673cm-1. mp: 256.5 — 258.5 ° C. &lt; Example 222; 6- (propanesulfonamide-1-carbonyl) -1- (2-chlorobenzyl &gt; Synthesis of 2-fluorenylbenzimidazole (284) &gt; Hit ^-^ m 5 Consumer Cooperation ii 卬 5? (诮 Please read the notes on the back before filling this page) According to the method of Example 98, use 6-carboxy-1- (2-chlorobenzyl) -2- Methyl benzimidazole (0.400 g), N, N, -carbonyldiimidazole (0.431 g), 1- (3-gasopropyl) sulfonamide (0.420 g), diazabicycloundecene ( 0.0404 g) to give 6- (propanesulfonamido-1-carbonyl) -1- (2-fluorobenzyl) -2-fluorenylbenzimidazole (284) 0.323 @. [Compound (284) Physical properties] lH ~ NMR (DMS0-d6, δ): 2.27-2 · 33 (2Η, m), 2.52 (3H, s), 3.52 (2H, t, J-7.0Hz) This paper is applicable to Chinese national standards ( CNS) A4 specification (210X297 mm) 548272 A7 B7 V. Description of the invention (22 ^)), 3.87 (2H, t, J = 6.6Hz), 5.59 (2H, s), 6.57 (1H, d, J = 7.7 Hz), 7.23 (1H, t, J = 7.6Hz), 7.34 (1H, t5 J = 6.4Hz) s 7.53-7.58 (2Η, m) &gt; 7.67 (1H, d, J = 8.4Hz), 7.79 ( 1H, d, J = 1.1 Hz) IR (KBr): 1648CDT1. Mp: 165.5-166.60C &lt; Example 223; 6-Bentylsulfonylcarbamoyl group q Synthesis of biphenyl_4-methyl) -2-cyclopropylbenzimidazole potassium salt (285) &gt; According to the method of Example 170, N-phenylphenanthino-4_amino group-3- ( Biphenyl-4-methylamino) benzamidine (400 g) and cyclopropylcarbonyl chloride (0.110 g) to give N-phenylsulfonyl (bibenzylmethylamino) Cyclopropylaminobenzyl S &amp; fe 'is used to give 6-benzoflavinylaminofluorenyl-1- (biphenyl-4-methyl) -2-cyclopropylbenzimidazole Salt (285) 0.196 g ° [physical properties of compound (285)] ilHiMIUDMSiHIG, 6): 1.0--1.15 UH, m), 2.23-2 · 31 (1Η, m), 5.66 (2H, s) , 7.21 (2Η, m, J = 9.1Hz), 7.32_7 · 45 (7Η, m), 7.59-7 · 63 (4Η, m), 7.78-7 · 83 (3Η, m) , 7.97 (1Η, s) 〇IR (Nujol): 1540cm-1〇 After the middle of the 榀 ^-and 6_-1 eliminate the combination of bamboo and private printing (read the precautions on the back before filling this page )

Mass (FAB): m / e 546 (M + 1) -mp: 220.8-224.8 ° C &lt; Example 224; 1- (2-chlorobenzyl) -2-fluorenyl-6- (1 -Synthesis of Pentylsulfonylcarbamyl) benzimidazole (286) &gt; According to the method of Example 98, 6-carboxy-1- (2-fluorobenzyl) _2 · methylbenzimidazole ( 〇.4.0〇g), N, N, -carbonyldiimidazole_ 224______ This paper size applies Chinese National Standard (CNS) A4 specification (210X29? Mm) 548272 A7 B7 V. Description of the invention (22i (read the first Note: Please fill in this page again) (0.431g), 1-pentanesulfonamide (0.42g), and diazabicycloundecene (0.404g) to pay 1- (2-gasoyl) -2-Methyl-6- (1-pentanite yellow aminocarbamoyl) benzimidazole (286) 0.49 lg. [Physical properties of compound (286)] W-NM ^ DMSO-c ^, d): 〇 · 81 (3Η, t, j = 7.2Ηζ), 1.23-1 · 28 (2Η, m), 1.32-1.37 (2H, in), 1.65-1.69 (2H, m), 3 · 50 (2Η, t, J = 7 · 8Ηζ), 5.61 (2Η, s), 6.45 (1Η, d, J = 7.5Hz), 7.24 (lH3t, J: 7.6Hz), 7.35 (lH , T, J = 7.5Hz), 7.57 (lH, d, J = 7.9 Hz), 7.69 (1 (, d, J: 8.5Hz), 7.81 (1Η3 dd , J: 1.7 and 8.4 Hz), 8.12 UH, d, J (1.2 2Ηζ), 12 · 25 (1Η, s). IR (KBr): 1684CDT1. mp: 173 · 3-179 · 8ο0〇 Example 225; l- (2-chlorobenzyl) -2-methyl-6-[(3-methylbutyl) sulfonamidocarbamoyl] benzene Synthesis of Benzimidazole (287) &gt; According to the method of Example 98, 6-carboxy-1- (2-chlorobenzyl) -2-methylbenzyl rice was used. Sit (0.300g), N, N'-Geryl two-mouthed saliva (0.323g), 1- (3-methyl) butanesulfonamide (0.302g), diazabicycloundecene (0.303 g) to give 0.284 g of 1- (2-fluorobenzyl) -2-fluorenyl-6-[(3-fluorenylbutyl) sulfonamidoaminofluorenyl] benzimidazole (287). [Physical properties of compound (287)] 'H-NMRlDMSO-dG, δ): 0.84 (6H, d5 J = 6.5Hz), 1.52-1.59 (2H, m), 1.61-1.7 0 (1H, m), 3.44 ( 2H, t, J-7.9Hz) 3 5.60 (2H, s), 6.45 (1H, d5 J = 7: 8Hz) 5 7.24 (1H, t, J: 7.6Hz), 7.35 (1Η3 t, J: 7.4Hz), 7.57 (1Η, d, J = 7.9Hz), 7.66 (1H, d, J = 8.5Hz), 7.81 (1Η3 dd, J: 1.6 and 8.6Hz), 8.09UH, s) , 11.87 (1Η, s). IR (KBr): 1682CHT1. mp: 201.0-204.1oC〇 ----- 225__ This paper is suitable for China National Standard (CNS) A4 specification (210X297 mm) 548272 A7 B7 V. Description of the invention (22i &lt; Example 226; l- (2 -Chlorocarbyl) -6- (1-Hexite yellow carbamoylcarbamyl) -2-methylbenzimidazole (288) &gt;(#Read the precautions on the back before filling this page) According to the method of Example 98, 6-carboxy-1- (2-chlorobenzyl) -2-methylbenzimidazole (0.300 g), N, N, -carbonyldizolidazole (0.323 g), 1_ Hexylsulfonamide (0.335g) and diazabicycloundecene (0.303g) to give 1- (2-gasocarbyl) -6- (1-hexoflavinylaminopyrene) _2_methylbenzimidazole (288) 0.379 g. [Physical properties of compound (288)] ^ -NMRiDMSO-dG, δ): 0.81 (3Η, t5 J-7.0Hz) 5 L18-L28 (4H, m ) 3 1.32-1.41 (2H, m), 1.63-1.71 (2H, m), 2.53 (3Η, s), 3.50 (2Η, t, J = 7.7Hz), 5.64 (2Η, s ), 6.51 (1Η, d, J: 7.7Hz), 7.25 (1Η, dt, J = 1.2 and 7.8Ηζ), 7.36 (1Η, dt, J = 1 • 4 and 7.7Ηζ ), 7.58 (1Η, dd, J: 1.0 and 8.0Ηζ), 7.72 (1Η, d, J: 8.5Hz), 7.84 (1Η, dd, J: 1.6 and 8. · 5Ηζ), 8.15 (1Η, d, J = 1.3Hz), 11.87 (1Η, s). IR (KBr): 1682CHT1. mp: 141.2-143.5 ° C. &lt; Example 227; 6-Synthesis of 3rd-butoxycarbonylamino-1- (2-chlorobenzyl) -2-methylbenzimidazole (289) &gt; According to the method of Example 18, 6-carboxy-1 · (2-chlorobenzyl) -2-methylbenzimidazole (1.0g), diphenylphosphonium amine (imi), and diisopropyl were used. Ethylamine (1ml) and 3rd Butanol (25ml) to give 6- 3rd Butoxycarbonylamino-1- (2-chlorobenzyl) -2-fluorenylbenzimidazole (289) 0.760 g. [Physical properties of compound (289)] W-Xing (CDC13, 6): 1.49 (9Η, s), 2.47 (3Η, s), 5.37 (2Η, s), 6.41 (1Η, d3 J 2: 7.5Ηζ), 6.55 (1Η, br s), 6.93 (1Η, dd, J: 1.9 and 8.6Ηζ), 7.08 (1Η, t, J = 7.5Hz), 7.22 (1H, t), 7.44 (1H, d, J = 8-0Hz), 7.62 (2H, d, J = 8,6Hz) 〇116 _ This paper size applies to China National Standard (CNS) A4 (210X297 mm) ) 548272 A7 B7 V. Description of the invention (223 &lt; Example 228; Synthesis of 6-amino-1- (2-chlorobenzyl) -2-methylbenzazole (290) &gt; The method of Example 22, using 6-th 3rd-butoxyweilylamino-1- (2-gaso-benzyl) -2-methylbenzantene (0.760g) to obtain 6-amino_1 -(2-Azobenzyl) -2-fluorenylbenzimidazole (290) 0.42 (^. [Physical properties of compound (290)] lH-NMR (DMS0-d6, δ): 2.37 (3H, s) 3 4.83 (2H, br s) 5 5.32 (2H? S), 6.33 (1H5 d, J = 1.9Hz), 6.42 (1Η, d5 J = 7.7Hz), 6.46 (1H, dd, J2 1.9 and 8 · 5Ηζ), 7.19 ~ 7.24 (2H, m), 7.31 (1Η, t), 7.53 (1Η, d3 J = 7.9Hz). <Example 229; 6- (l-Butanesulfonylamine) ) -1- (2-Azobenzyl ) Synthesis of 2-fluorenylbenzimidazole (291) &gt; According to the method of Example 20, 6-amino-1- (2-fluorobenzyl) -2-methylbenzimidazole (0.1%) was used. 300g), 1-butanesulfonyl chloride (0.216g), triethyl fe (0.130g) to pay 6- (1-butanthylamino) -1- (2-chlorobenzyl)- 0.230 g of 2-fluorenylbenzimidazole (291). [Physical properties of compound (291)] W-NMR (DMS0-d6, (Ϊ): 0.74 (3Η, m), 1.23 (2Η, m) , 1.5.5 (2Η, m), 2.50 (3Η, s), 2.89 (2Η, m), 5.47 (2Η, s), 6.58 (1Η, d3 J = 7.4Hz) 7 · 02 (1Η, d, J: 8.5Hz), 呔. 卑 ^ 1,; 13 in the consumer department (诮 Read the precautions on the back before filling this page) 7 · 10 (1Η , S), 7.23 (1Η, t), 7.33 (1Η, t), 7.52 (2Η, m), 9.55 (1Η, s). IR (KBr): 1629CDT1. mp: 149.5-151.0 ° C. &lt; Production Example 46; Production of 2- [N- (2,4-dichlorobenzyl) acetamidol · 3.nitronitrobenzoate &gt; According to Production Example The method of 14 uses 2-acetamido-3-nitrobenzyl _ — 227________ This paper is suitable for China National Standard (CNS) A4 specification (210X 297 mm) 548272 A7 _____ B7 V. Description of the invention (22j ~ Acetate (1,000 g) and 2,4-dichlorobenzyl (.985 g) to give Ml (2,4-dioxobenzyl) acetamido] -3 -nitrobenzoic acid Formazan purpose 0.250 g 〇 (Read the precautions on the reverse side before filling in this page) [Physical properties of compounds] π-NMR (CDC13, ¢): 1.99 (3H, s), 3.71 (3Η, S), 4 85 (1Η, d, J 2 4.5 5Ηζ), 4.98 (1Η, d, J: 4.5Hz), 7.17-7 · 22 (2Η, m), 7.46 (1Η, d3 J: 7.9Hz ), 7.63 (1Η, t, J 2 7.9Ηζ), 7.98 (1Η, d, J = 8.0Hz), 8.09 (1Η, d, J 2 7.9Ηζ). &Lt; Example 23〇; Synthesis of 1- (2,4-dioxobenzyl) -7-ethoxycarbonyl · 2-methylbenzimidazole (292) &gt; According to the method of Example 24, 2- [N- (2,4-dichlorobenzyl) acetamido] -3- Benzyl nitrobenzoate (6.50 g) to give 1- (2,4 · digasofluorenyl) -7-ethoxyepi-2-methylbenzoxyl (292) 5.15 @. [ Physical properties of compound (292)] ^-NMRiCDCla, δ): 2.53 (3H, s), 3.70 (3H, s), 5.72 (2Η, s), 6.26 (1H3 d3 J = 8 · 4Ηζ), 7 · 04 (1Η, dd, J = 2, 0 and 8.4Ηζ), 7 · 28 (1Η, t, J = 7 · 9Ηζ), 7.45 (1Η, d, J = 2.0Hz), 7.75 ( 1Η, d5 J = 7.8Hz), 7.93 (1Η, d, J = 7 · 9Ηζ). &lt; Example 231; Synthesis of 7-carboxy-l- (2,4-dioxobenzyl) -2-methylbenzimidazole (293) &gt; According to the method of Example 53, 1- (2, 4-dichlorobenzyl) -7-ethoxyweilyl-2-methylbenzoxyl salivary (2.00 g) to give 7-weilyl-1- (2,4-dioxobenzyl) _2_fluorenyl benzimidazole (293) 1.76 g. [Physical properties of compound (293)] 1H-NMR (DMS0-d6, δ): 2.49 (3H, s), 5.81 (2H, s) 3 6.09 (lH5 d, J-8.4Hz) 3 7. 21-7.28 ( 2H, m), 7.62 (1Η, d, J = 7.8Hz), 7.67 (1Η, d, J: 2.2Hz), 7.83 (1Η, d, J = 8.0Hz), 13 -04 (1H, br s) 〇 ___ __— 22 ^ ________—— This paper size applies to China National Standard (CNS) A4 (21 OX 297 mm) 548272 A7 B7 V. Description of the invention (2 2 j &lt; Example 232; Synthesis of 7- (l-butanesulfonylcarbamoyl) -l- (2,4-dichlorobenzyl) -2-methylbenzimidazole (294) &gt; (Please first Read the notes on the back and fill in this page again) According to the method of Example 98, using 7-carboxyl-l- (2,4-dichlorobenzylmethylbenzimidazole (0.463g), N, N'-carbonyl Diimidazole (0.448 g), 1-butanidine (0.379 g), and diazabicycloundecene (0.421 g) to pay 7- (1-butanite fc-based gas-based donkey base)- 1- (2,4-dichlorobenzyl) _2-methylbenzimidazole (294) 0.325 § [Physical properties of compound (294)] 1H ~ NMR (DMS0-d63 6): 0.84 (3H, t , J = 7.3Hz), 1.33 (2H3 m), 1.44 (2H, m) 3 2. 53 (3H, s), 3.16 (2H, m), 5.64UH, s), 6.0 3 (1H3 d, J = 8.4Hz), 7.25 (1H, dd, J = 2.1 and 8.4Ηζ), 7.30 (1Η, t, J = 7.8Hz), 7.44 (1 (, d, J 7.4Hz), 7.68 (1Η, d, J = 2.1Ηζ), 7.87 (1H, d, J = 7.8Hz), 12.18 (1Η, br s). IR (KBr): 1690cm-1 mp: 98.5-102.0 ° C. &lt; Example 233; 1- (2-chlorobenzyl) _2-fluorenyl-6- [l- [3- (trimethyl alcohol) propanyl] carbosulfanylcarbamate Alkyl] Synthesis of Benzene (295) &gt; According to the method of Example 149, 6-carboxy-1- (2-fluorobenzyl) -2-methylbenzimidazole (0.4.00) was used. g), N, N, -carbonyldiimidazole (0.431 g), 1- [3- (triethylfluorenyl) propyl] sulfonamide (0502 g), diazabicycloundecene ( 0.44 g) to give 1- (2-fluorobenzyl) -2-fluorenyl (trimethylfluorenyl) propyl] sulfonylcarbamoyl] benzimidazole (295) 0.604 g. Physical properties of compound (295)] Shi Zang Zhi Ru-He, Qi Qi, s), Q 6i (2h, t, Qi Yu), 1 66 1 73 Ji, this paper size applies the Chinese National Standard (CNS) A4 specifications- 548272 A7 B7 V. Description of the invention (22g m), 2.50 (3Η, s), 3.51 (2Η, t3 J: 7.7Hz), 5.61 (2Η, s), 6.46 (1Η, d, J: 7.8Hz), 7.24 (1Η, t3 J = 7.6Hz), 7.35 (1Η, t, J: 7.6Hz), 7.57 (1Η, dd, J = 7.9 and 0.9Hz), 7.70 (1Η, d, J: 8.5Hz), 7.81 (1Η, dd, J: 1.5 and 8.5Ηζ ) 3 8.12UH, d,

J-1.4Hz) 3 1L98 (1H3 s) 〇IR (KBr): 1688cm-, mp: 197.0-203H &lt; Example 234; 4-ethoxycarbonyl-2-methylbenzimidazole (296) Synthesis &gt; Heat a mixture of 2-ethylethylamino-3-stone-shoky benzoate methyl vinegar (8.03g), reduced iron (18 · 8 g), acetic acid (20ml), and acetic acid (40 m 1) Reflux for 18 hours. After the solvent was concentrated, three gas methane and 10% hydrochloric acid were added to the residue 'for extraction. A saturated sodium bicarbonate aqueous solution was added to the residue to form a test, and then trichloromethane was used for extraction. Trifluoromethane was removed under reduced pressure to give 1.61 g of 4-ethoxycarbonyl-2-fluorenylbenzimidazole (296). [Physical properties of compound (296)] (H-NMR (CDC133 (5): 1.43 (3Η, t), 2.66 (3Η, s), 4.45 (2Η, q), 7.24-7 · 28 (1Η, m), 7.84-7.89 (2Η, m), 10 · 26 (1Η, br s). Zhong Rong Department of Economics «.- ^-^^ &gt; (Please read the precautions on the back before filling out this page) 〈Example 235; l- (2,4-Dioxobenzyl) -4-ethoxycarbonyl-2-fluorenylbenzimidazole (297 ) &Gt; Synthesis of 4-ethoxycarbonyl-2-methylbenzimidazole (1.61g), 2,4-digas benzyl gas (3.08g), potassium iodide (1.51g), potassium carbonate (l .05g), a mixture of N, N-dimethylformamide (4ML) was stirred at 80 ° C for 16 hours. Trichloromethane and water were added for extraction. Washing, drying, and concentration of trichloromethane paper Applicable to China National Standard (CNS) A4 specification (210X297 mm) 548272 A7 Five invention descriptions (22) '(Read the precautions on the back before filling this page) Burn the layer to get the residue' by Shi Xisheng column chromatography (Eluent ·· Hexane / Ethyl Acetate 4/8) was refined to obtain 0.73 Og of (2,4_digaso-benzylethoxycarbonyl-2-fluorenylbenzimidazole (297). [ Physical properties of compound (297)] Η-orbital (CDCh, d): 1.47 (3Η, t J: 7 1H7)? ΊΠΠΗ, 5 ί · 1Ηζ) 3 2.63 (3Η3 s) 5 4.52 (2Η, q, J = 7.1 Ηζ), 5.39 (2Η 'S), 6.30 (1Η, d, J = 8. He), 7.06 (m, dd, J = 21 and 8 others) 7. Position t, Ke Huan, 7 • Warplane Machine 0 and 7 9Hz) 7 48 (m ζ), 7.93 (1Η, dd, J = 1.0 and 7.7 Hz). &Lt; Example 236; 4-carboxy-; u (2,4-dichloro Synthesis of benzyl) -2-methylbenzimidazole (298)> According to the method of Example 53, 1- (2,4-dichlorobenzyl) _4-ethoxycarbonyl-2-fluorenyl Benzimidazole (0.730 g) to give 4-carboxyl- (2,4-dichlorobenzyl) -2-fluorenylbenzimidazole (298) 0.575 g. [Physical properties of compound (298)] W -NMR (DMS〇-d6, ά): 2.65 (3Η, s), 5.67 (2H, s), 6.73 (1Η, d, J = 8.3Hz), 7.33 (1H, dd, J 2 · 2 and 8 · 4Ηζ), 7.39 (1Η, t, J = 7.9Hz), 7.74 (1Η, d, J = 2.2Hz), 7.76 (1Η, d, J = 8.2Hz ), 7.85 (1Η, d, J = 7.5Hz). &lt; Example 237; Synthesis of 4- (l-butanesulfonylcarbamoamidinyl)-; i_ (2,4-digaso benzamidine) -2-methylbenzimidazole (299) &gt; The method of Example 98 was performed using 4-carboxy-1- (2,4-dioxobenzyl) -2-methylbenzimidazole (0.350 g), N, N, -carbonyldiimidazole (0.333 g) ), 1-butanesulfonamide (0.287g), diazabicycloundecene (0.318g) to give 4- (1-butanesulfonylcarbamoyl) -1- (2,4-di 0.275 g of 2-methylbenzimidazole (299). This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 548272 Printed by the central sample rate of the Ministry of Economic Affairs and printed by Zhengong Consumer Cooperative B7 ___________ B7 V. Description of the invention (22g [Physical properties of compound (299)] iH-fiMlUDMSO- d65 (5): 0.86 (3Η5 t, J: 7.3Hz), 1.42 (2H, m), 1.73 (2Η, m), 2, 61 (3H5 s), 3.61 (2H, m) 3 5.65 (2H3 s), 6.67 (1H5 d3 J = 8.4Hz), 7.32 (1H5 dd, J2 2.1 and 8.4Hz), 7.39 (1Η3 t, J = 7.9Hz), 7.73 (1Η, d, J = 2.1Hz), 7.78UH, d, J = 8 · 0Ηζ), 7.91 (1Η, d, J: 7.7Hz) 3 12.66 (1H, br s). IR (KBr): 1699cm-1. Melon p: 180.7 —183.6 ° C. &lt; Example 238; Synthesis of l- (4-benzyloxybenzyl) _6_ethoxycarbonyl_2_fluorenylbenzimidazole (300) &gt; According to the method of Production Example 14,% acetamidamine was used 4-N-nitrobenzoic acid ethyl ester (2.00g) and 4-benzyloxybenzyl gas (36%) to give 3_ [N- (4-benzyloxybenzyl) acetamidoamine 4_ Crude refined product of ethyl nitrobenzoate. Then, according to the method of Example 24, a crude refined product of benzyloxybenzyl) -6-ethoxycarbonyl-2-methylbenzimidazole (300) was 4.09 g. &Lt; Example 239; 1 -(4-Benzyloxybenzyl) _6_carboxy_fluorenylmethylbenzimidazole (301) Synthesis> According to the method of Example 53, 1_ (4_benzyloxynyl) _6_ethoxycarbonylfluorene Methyl benzimidazole (4.09 g) to give 0.1- (4-benzyloxybenzyl) -6-carboxy-2-methylbenzimidazole (301). [Physical properties of compound (301)] A-NMiUDMSO-dG, 6): 2.57 (3Η, s), 5.05 (2Η, s), 5.48 (2Η, s), 6.97 (2Η d J = 8.6Hz), 7 · 08 (2Η, d, J = 8.5Hz), 7 · 28-7 · 43 (5Η, m), 7 · 60 (1Η, d, J = 8 3Hz) 7 · 78 ( 1Η, d, J = 7.5Hz), 8.07 (1H, s), 12.72 (1H, s) 〇232 Qin paper size applies to China National Standard (CNS) A4 specification (21 OX 297 mm) (Please read the back Please fill out this page again) Order-Φ. «In HI n · 548272 A7 B7 V. Description of the invention (22j &lt; Example 24〇; 1- (4-benzyloxybenzyl) _6 · (1-butanesulfonate Synthesis of fluorenylaminofluorenyl) -2-fluorenylbenzimidazole (302) &gt; According to the method of Example 149, 6-carboxy-1- (4-benzyloxybenzyl) -2-methyl was used Benzimidazole (0.300 g), N, N, -carbonyldiimidazole (0.242 g), 1-butanidine (0.204 g), and diazabicycloundecene (〇227 g) to give 1- (4_ Benzyloxy) -6_ (1.butyric acid carbamoyl) _2_methylbenzimidazole (302) 0.206 g. [Physical properties of compound (302)] lH-NMR (DMS0-d6, δ): 0.87 (3H, t, J = 7.3Hz), 1.38-1.43 (2H, m), 1.64-1.71 (2H, m), 2.54 ( 3Η, s), 3.49 (2Η, t, J = 6.8Hz), 5.05 (2Η, s), 5.45 (2H, s), 6.9 8 (2H3 d, J = 8.7Hz) 3 7.10 (2H , d, J = 8,7Hz) 5 7.31 (1H, t, J = 7.2Hz), 7.37 (2Η, t, J = 7.2Hz), 7.41 (2Η, d, J: 7.3Hz), 7.62 (1H, d, J: 8.5Hz), 7.79 (1Η, dd, J = 1.5 and 8.4Ηζ), 8.23 (1Η3 s), 11.93 (1Η, s)., IR (KBr): 1684cffl-l0mp: 132.4-137.70C0 &lt; Example 241; 6-ethoxycarbonyl-l-[(2, -cyanobiphenyl-4-yl) methyl] -2- Synthesis of methyl benzimidazole (303) & printed by the Central Laboratories of the Ministry of Economic Affairs and printed by Zhengong Consumer Cooperative (please read the precautions on the back before filling out this page) Use 3-acetamidine according to the method of manufacturing example 14 4-nitrobenzoate (1.0 g) and 4, -bromomethyl-2-cyanobiphenyl (1.30g) to give 3_ [Ν · [(2'_cyanobiphenyl (4-yl); fluorenyl;] ethylamido]-4-nitrobenzoic acid ethyl ester crude product (0.750 g). Next, according to the method of Example 24, 6 • ethoxycarbonyl-1-[(2, · cyanobiphenyl_4-yl) methyl] -2 · methylbenzimidazole (303) 0.410 was obtained. g. [Physical properties of compound (303)] This paper size applies the Chinese National Standard (CNS) A4 specification (210x297 mm). The central sample rate of the Department and the Zhengong Consumer Cooperatives Co., Ltd. printed 548272 A7 _________B7 V. Description of the invention (230 ~ 1-4 -Look (CDCI3, ά): 1.40 (3Η, t), 2.63 (3Η, s), 4.39 (2H, q), 5.46 (2h, s) 7.17 (2H, d), 7.40- 7.66 (5Η, m), 7.73-7 · 78 (2Η, m), 8.0 () (1Η, dd, J = 1 5 and '8 · 5Ηζ), 8.05 (1Η, d , J 11 · 2Ηζ). &Lt; Example 242; 6-carboxyl-l-[(2, _cyanobiphenyl_4-yl) methyl] -2-methylbenzimidazole (304) Synthesis> According to the method of Example 53, using 6-ethoxycarbonyl_i _ [(2, _aminobiphenyl-4-yl) fluorenyl] -2-methylbenzobenzoic acid (0.41 〇g) to give 6 carboxy-M (2'-cyanobiphenyl-4-yl) methyl] _2-methylbenzyl salicylic acid (304) 0.190 g ° [physical properties of compound (304)] ^ -NMRCDMSO-dG, δ): 2.59 (3H, s), 5.67 (2H3 s) 3 7.24 (2H, d, J = 8.1Hz), 7 53-7, 64 (5H, m), 7.75 (1H, t , J = 7.7Hz), 7.80 (1Η, d), 7.92 (1H3 d, J = 7 7jjz) 8.12 (1Η, s) 3 12.74 (1H, br s) 〇 Example 243; 6 -(l-Butanesulfonyl Synthesis of carbamate) _1-[(2, _cyanobiphenyl-4-yl) methyl] -2-methylbenzoxazone (305) &gt; According to the method of Example 155, use 6-carboxy-1-[(2, -bibenzyl-4-yl) fluorenyl] -2-methylbenzimidazole (0.187 g), N, N, · carbonyldiisotriazole (0.160 g), 1 -Butylsulfamethoxamine (0.135g), diazabicycloundecene (0.150g) j and refined by silica gel column chromatography (eluent: trigas methane / methanol = 20/1) to get 6 · ( 1-Butylsulfonylcarbamoyl) -1-[(2, -cyanobiphenyl-4-yl) fluorenyl] -2-methylbenzoxan (305) 0.155 g. [Physical properties of compound (305)] 'H-NMRiDMSO-dG, δ): 0.83 (3H, t, J-7.4Hz), 1.34 (2H, m), 1.60 (2H, m), 2.56 (3H, s), 3.27 (2Η, m), 5.62 (2Η, s), 7.23 (2Η, d, J = 8.2Hz), 7.53-7.57 (_____ 234 ______ (Please read the notes on the back first (Fill in this page again) The size of the paper is applicable to the Chinese National Standard (CNS) A4 (210X297 mm) 548272 A7 B7 V. Description of the invention (23)

4H, m), 7.60 (1H3 d, J = 7.8Hz), 7.75 (1Η, dt, J = 1.0 and 7. · 8Ηζ), 7.83 (1H, dd, J = 1.5 and 8. · 4Ηζ), 7. · 92 (1Η, d), 8.13 (1H, s), 11 · 92 (1H, br s). IR (KBr): 2223cm-1〇mp: 115-1180C〇 * &lt; Production Example 47; Production of 2-fluoro-4'-fluorenylbiphenyl &gt; 1.6M n-butyllithium hexane solution (30ml ) Tetrahydrodecane (30 ml) cooled to -78 ° C under a nitrogen atmosphere was added, followed by a solution of 4-bromotoluene (8.33 g) in tetrahydrofuran (30 ml), and stirred at -78 ° C for 1 hour. After heating and melting under reduced pressure, a solution of dehydrated zinc chloride (6.64 g) in tetrahydrodecane (30 ml) was added at -78 ° C, and stirred at room temperature for 1 hour. A tetrafluorofuran (30 ml) solution of 2-fluoroiodotoluene (7.22 g) and tetrakis (triphenylphosphine) palladium (0.52 g) was added to the aforementioned solution at room temperature and stirred for 1 day. The reaction solution was diluted with ethyl acetate (300 ml), and 10% hydrochloric acid was added for extraction. The organic layer was washed with saturated brine, dried, and then concentrated. The residue was purified by silica gel column chromatography (eluent: hexane) to obtain 2-fluoro-4'-fluorenylbiphenyl (6.05 g) as an oil. [Physical properties of compound] INMlUCDClh 6): 2.39 (3Η, s), 7.10-7.30 (5Η, m), 7.39-7.49 (3Η, m). Printed by the Central Standard of the Ministry of Economic Affairs and Cooperative Consumer Cooperative (read the precautions on the back before filling out this page) &lt; Example 48 of Fluoride; 2_Manufacture of Fluoro-4'-fluorenylbiphenyl bromide &gt; Will 2- Fluoro-4 '· methylbiphenyl (8.70g), N-bromopropanamide (8.32g), 2,2'-azobisisobutyronitrile (0.10g), carbon tetrachloride (150ml) The mixture was heated at reflux for 5 hours. The reaction solution was washed with water, and the residue obtained by concentrating the organic layer was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 9/1) to obtain a crude product of 2-fluoro-4'-methylbiphenyl bromide. . Use hexane to make the knot _7 ^^ _ This paper size applies the Chinese National Standard (CNS) A4 (210X297 mm) Central Standard of the Ministry of Economic Affairs and the cooperation of shellfish consumer printing 548272 A7 __________B7 V. Description of the invention (233 crystals To obtain 2-fluoro-4, -methylbiphenyl bromide (4.93g). [Physical properties of the compound] lH-NMR (CDCl3,6): 4.55 (2Η, s), 7.13-7 · 23 ( 2Η, m), 7.33 (1Η, m), 7.43 (1Η, m) 5 7.47 (ZH5 d3 J-8.1HZ), 7.54 (2H, d, J-8.1Hz) ○ Manufacturing Example 49 ; Production of 3- [N-[(2'-fluorobiphenyl-4-yl) methyl] ethylamido] -4-nitrobenzoate &gt; According to the method of Production Example 14, use 3-Ethylamido-4-nitrobenzoate ethyl ester (1.54g) and 2-fluoro-4, -fluorenylbiphenyl bromide (2.26g) to give 3- [N-[(2'_fluoro Substituted biphenyl-4-yl) methyl] acetamidinyl] -4-ethyl stilyl benzoate (1.90 g). [Physical properties of the compound] ^ -NMRCCDCla, 6): L33 (3H, t3 J = 7.1 Hz), 1.92 (3H, s) 3 4.36 (2Η, m) 3 4.44 (1Η, d, J = 4.4Hz) 3 5.32C1H, d3 J = 4.4Hz), 7.13 (1H, m), 7.18- 7.22 (3H, m) 3 7 • 31 (1H, m), 7.40 (1Η, dt, J = L6 and 7.7Ηζ), 7.44 (2Η3 d) , 7.67 (1Η3 d, J = 1 • 6Hz), 7.94 (1Η, d, J = 8.4Hz), 8.15 (1Η, dd, J: 1.8 and 8 · 4Ηζ). &lt; Example 244; Synthesis of 6-ethoxycarbonyl-l-[(2 '· fluorobiphenyl-4-yl) fluorenyl] -2-methylbenzimidazole (306) &gt; According to Examples Method 24, using 3- [N-[(2, _fluorobiphenyl-4-yl) methyl ~ yl] acetamido] -4 · nitronitrobenzoate (1.90g) to obtain 1.53 g of 6-ethoxycarbonyl-1-[(2'-fluorobiphenyl-4-yl) methyl] -2-fluorenylbenzo (306). [Physical properties of compound (306)] ^ -NMRiCDGL ·, δ): 1.40 (3H, t, J = 7.1Hz) 3 2.62 (3H, s), 4.38 (2H, q3 Jrr7 l

Hz), 5.43 (2Η, s), 7.10-7 · 17 (3Η, m), 7.19 (1Η, dt, J = 1.0 and 7. · 5Ηζ), 7.3i ____ ___________ This paper size is applicable China National Standard (CNS) A4 specification (210X297 mm) '~ (Please read the precautions on the back before filling this page) ii m I mi ml ϋ— i I ϋϋ ml —ϋ m in —ϋ n —ϋ am — ϋI ^ i I— —Mu I m nn In —Mm— It ml — ^ ϋ 1 ^ 1 11 —ϋ tmmm— ^ nw im 548272 A7 B7

V. Description of the invention (23S (1H, m), 7.38 (1Η, dt, J 2 1.8 and 7.8Ηζ), 7.50 (2Η, dd), 7.74 (1Η, d, J = 8.5 Ηζ), 8.00 (1Η, dd, J = 1.4 and 8.4Ηζ), 8.06 (1Η, s). 〈Example 245; 6-Weiji-ΐ-[(2'-fluorinated Synthesis of Phenyl_4-yl) methyl] -2-methylbenzosalan (307) &gt; According to the method of Example 53, 6-ethoxycarbyl_1 __ [(2, _ Biphenyl-4-yl) fluorenyl] -2-methylbenzimidazole (i.50 g) to give 6_carboxyl [[2'-fluorobiphenyl-4-yl) methyl Group] -2-methylbenzimidazole (307) 1.24 g 〇 [Physical properties of compound (307)] A-NMR (DMS0-d63): 2.59 (3H3 s), 5.63 (2Η, s) 3 7 · 19 (2Η, d, J 2: 8.1Ηζ), 7.24 ~ 7 · 31 (2Η, m), 7.39 (1Η, ιη), 7.46-7 · 53 (3Η, recognize 7.62 (1Η3 d, J = 8.4Hz), 7.80 (1H, dd, J = 1.3 and 8.4Ηζ), 8.10 (1Η3 s). &Lt; Example 246; 6- (l-ethanesulfonate) Synthesis of carbamoylcarbamidine 丨 7?,-Fluorobiphenyl-4-yl) fluorenyl] -2-methylbenzimidazole (308) &gt; Central Consumer Bureau of Ministry of Economic Affairs (Read the note on the back first Please fill in this page again.) According to the method of Example 98, 6-carboxyl 1-[(2, -fluorobiphenyl-4-yl) methyl] -2-methylbenzimidazole (0.455 g) was used. ), Ν, Ν'-carbonyldiimidazole (0.409 g), 1-butanesulfonamide (0.346 g), diazabicycloundecene (0.384 g) to give 6- (1-ethanesulfonyl Carbamidyl) -1-[(2, -fluorobiphenyl-4-yl) methyl] -2-fluorenylbenzo miso (308) 0.340 g. [Physical properties of compound (308)] ^ -NMRiDMSO-dG, δ): 0.84 (3H, t, J = 7e3Hz), 1.39 (1H, m)-, 1.67 (1H, m), 2. 57 (3H, s), 3.5K1H, t), 5.60 (2H, s), 7.21 (2H, d, J = 8.0Hz), 7.24-7.30 (2H, in), 7.39 (1H, m) 3 7.48 (1H, t), 7.52C2H, d, J = 8.0Hz ), 7.66 (iH, d, J = 8.5Hz), 7.80 (1Η, d, J = 8.5Hz), 8.25 (1Η, s), 11.93 (1Η, br s). —---- 22a__ This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm). The Central Ministry of Economic Affairs and the Consumers' Cooperative Press 548272 A7 B7 V. Description of the invention (23j &lt; Manufacturing Example 50; Production of 3-fluoro-4-methylbiphenyl &gt; A 1.6M n-butyllithium hexane solution (30ml) was added to tetrahydrofuran (30ml) cooled to -78 ° C under a nitrogen atmosphere, and then 4- A solution of bromo-2-fluorotoluene (9.21g) in tetrahydrofuran (30ml) was stirred at -78 ° C for 1 hour. After heating and melting under reduced pressure, dehydrated zinc chloride (-78 ° C) was added 6.64 g) of tetrahydrofuran (30 ml) solution, stirred at room temperature for 1 hour. At room temperature, a solution of iodobenzene (6.63 g) and tetrakis (triphenylphosphine) palladium (0.52 g) in tetrahydrofuran (30 ml) was added. The solution was stirred for 1 day. The reaction solution was diluted with ethyl acetate (300 ml), and 10% hydrochloric acid was added for extraction. The organic layer was washed with saturated brine, dried, and then concentrated. Silica gel column chromatography (eluent: hexane The residue was purified to obtain 3-fluoro-4-methylbiphenyl (6.00 g) as an oil. [Physical properties of the compound] 1H-NMR (CDCl35 ): 2.31 (3H, d3 J = 1.8Hz), 7.2〇-7.28 (3H5 m), 7.34 (1H, m), 7.43 (2Η, t) 3 7.55 (2Η, d) 〇 &lt; Manufacture Example 51; Production of 4-bromomethyl-3-fluorobiphenyl &gt; 3-fluoro-4_fluorenylbiphenyl (6.00g), N-bromopropylamidamine (5.73g), 2, The mixture of 2'-azobisisobutyronitrile (0.075g) and tetragasified carbon (120ml) was heated and refluxed for 5 hours. The reaction solution was washed with water and subjected to column chromatography on silica gel (eluent: hexane / ethyl acetate = 9 / 1) The residue obtained by concentrating the organic layer was purified to obtain 4-benzylmethyl-3-fluorobiphenyl (8.30 g) as an oil. [Physical Properties of Compound] ^ -NMRiCDCh, δ): 4.57 (2H , s), 7.30 (1H, d, J = 11.0Hz) 3 7.34-7.40 (2H, m), 7.45 (3Η, m), 7.56 (2Η, d). _ This paper size applies to China National Standard (CNS) A4 (210X297 mm) (Please read the precautions on the back before filling this page)

1T 548272 A7 B7 V. Description of the invention (239 <Manufacturing Example 52; 3- [N-[(3-Fluorobiphenyl-4-yl) methyl] acetamido] -4-nitrobenzoic acid Production of ethyl esters> According to the method of Production Example 14, ethyl 3-acetamido-4-nitrobenzoate (1.54 g) and 3-fluoro-4-methylbiphenyl bromide (2.26 g) were used. A crude product of ethyl 3- [N-[(3-fluorobiphenyl-4-yl) methyl] acetamido] -4-nitrobenzoate (2.68 g) was obtained. 247; 6-Ethoxycarbonyl-1 — [(3-fluorobiphenyl-4-yl) methyl] -2-methylbenzimidazole (309) Synthesis> According to the method of Example 24, A crude purified product of ethyl 3- [N-[(3-fluorobibenzyl-4-yl) methyl] acetamido] -4-nitrobenzoate (2.68 g) was used to obtain 6- Ethoxycarbonyl-l-[(3-fluorobiphenyl-4 · yl) methyl] -2-methylbenzophenone (309) 1.34§. [Physical properties of compound (309)] 喟 -NMR ( CDC13, d): 1.40 (3Η, t, J = 7.1Hz), 2.65 (3Η, s), 4.39 (2Η, q, J 7.1 Ηζ), 5.46 (2Η, s) , 6.79 (1Η, t, J = 8.0Hz), 7.25 (1Η, m) 3 7.34-7 · 40 (2Η3 m) 3 7 · 41-7 · 47 (2Η, m), 7.50 -7 · 54 (2Η3 m), 7.74 (1Η, d, J = 8.5Hz), 7.99 (1Η, dd, J = 1.5 and 8.4Ηζ), 8.07 (1Η, d, J = 1.3Hz). &lt; Example 248; 6-Carboxy-1-[(3-fluorobiphenyl-4-yl) methyl] _ Central sample of the Ministry of Economic Affairs, Ze Zeyong only Consumer Cooperatives, India Fan (Please read the notes on the back first Fill out this page again) Synthesis of 2-fluorenylbenzimidazole (3 10) &gt; According to the method of Example 53, 6-ethoxycarbonyl-1 _ [(3_ is biphenyl-4-yl) 曱Methyl] -2-methylbenzobis (1,34g) to give carboxyl-l-[(3-fluorobiphenyl-4-yl) methyl] -2-fluorenylbenzyl ( 310) 1.15g. [Physical properties of compound (310)] ______212_ This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 548272 A7 B7 V. Description of the invention (23) 2.59 (3Η, s), 5.64 (2H, s), 7.03 (1H, t, J = 8.0Hz), 7. 37 (1H, t, J = 7.3Hz ·), 7.42_7 · 48 (3Η , M), 7.56-7 · 68 (4Η, m), 7.79 (1H, dd, J = 1 • 4 and 8.4Hz), 8 · 11 (1Η, s) 3 12 · 7 (1Η, br s ). &lt; Example 249; 6- (l-Butanesulfonylcarbamoyl) -i _ [(3-fluorobiphenyl-4-yl) fluorenyl] -2-methylbenzimidyl ( Synthesis of 3 π) &gt; According to the method of Example 98, 6-carboxyl-l-[(3-fluorobiphenyl-4-yl) methyl] -2-fluorenylbenzimidazole (0.390 g) was used. ), N, N, -carbonyldiimidazole (0.351g), 1-butanesulfonamide (0.297g), diazabicycloundecene (0.329g) to give 6- (1-butanesulfonyl Carbamate) -i-[(3-fluorobiphenyl-4-yl) methyl] -2-methylbenzobis (3 11) 0.236 g. [Physical properties of compound (311)] ^ -NMRiDMSO-dG, δ): 0.84 (3Η3 t), 1.38 (2H, m), 1.65 (2H, m), 2.57 (3H, s), 3. · 48 (2Η, m), 5.63 (2Η, s), 6.93 (1H, t, J = 8,1Hz), 7.37 (1Η, m) 3 7.42-7.47 (3H, m), 7.60 ( 1Η, dd, J = 1.7 and 11.8 Hz), 7.62-7 · 68 (3Η, m), 7,80 (1H, dd, J = 1.5 and 8. · 4Ηζ), 8 · 21 (1Η, d, J = 1.3Hz), 11 · 90 (1Η, br s). IR (Nujol): 1681CBT1. mp: 227-230 ° C. Printed by the Central Standards Bureau of Zhenggong Consumer Cooperative (please read the notes on the back before filling this page) &lt; Example 250; l- (2-chlorobenzyl) -6-[(2- 甲Synthesis of oxyethyl) sulfofluorenylmethylamino-methyl] -2-fluorenylbenzoisocyanate (312) &gt; According to the method of Example 98, 1- (biphenyl-4-methyl) was used ) -6-benzyl-2_ethylbenzyl miso (0.300 g), Ν, Ν'-Chichi two-mouth rice noodles (0.272 g), (2-ethoxyethyl) confirmation Amine (.258g), diazabicycloundecene (0.256g) to give 1- (2-chlorobenzyl) -6-[(2-methoxyethyl) sulfonamidocarbamoyl ] -2-methylbenzimidazole (312) 0.149 §. This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 548272 A7 B7 V. Description of the invention (23) [Physical properties of compound (3 12)] lH-NMR (DMS0-d6, δ): 0.87 (3H , t3 J = 6.9Hz), 1.30 (3H, t, J = 8.0Hz), 2.89 (2 H, q, J-7.6Hz), 3,25-3.35 (2H, m) 5 3.63 ~ 3.74 (2H3 m ), 5.59 (2H, s) 3 7.17 (2H, d3 J = 8.1Hz) 3 7.34 (1H, t3 J-7.0Hz) 3 7.44 (2H, t, J = 7.6Hz), 7.58-7.68 (5H, m ) 5 7.82 (1H, d5 J = 8.4Hz), 8.23 (1H, s), 11.88 (1H, s). IR (Nujol): 1681cm-'mp: 78-8rC. &lt; Example 25l; Synthesis of l- (2,4-digaso-benzyl) -6- (1-benzenesulfonylaminocarbamyl) benzimidazole (313) &gt; According to the method of Example 98, use 6_carboxyl_1- (2,4_dikistilbyl) _2_methylbenzimidal (0.300g), N, n, -kisyldiisobutyric (0.323g), 1-pentasulfenylamine (0.301g), diazabicycloundecene (0303g) to give l- (2,4-dichlorobenzyl) -6- (1-benzylsulfonyl) Carbamidyl) Benzimidazole (313) 0.196 g. [Physical properties of compound (313)] Consumers' cooperatives printed by the Central-Ministry Central Laboratories (please read the precautions on the back before filling this page) 6): 0 · 81 (3Η, t, J = 7.3Hz ), 1.22-1 · 30 (2Η, m) 3 1.32-1 · 39 (2Η, m), 1.64-1.71 (2Η, m) 5 2.50 (3Η, s), 3.50 (2Η, t, J = 7-8Hz), 5.59 (2Η, s), 6.45 (1Η, d, J = 8.4Hz), 7.33 (1Η, dd, J = 2.2 and 8.5Hz), 7.69 ( 1Η, d, J = 8.5 Hz), 7.76 (1Η, (1, J = 2.1Hz), 7.80 (1Η, dd, J: 1.6 and 8.5Ηζ), 8.10 (1Η, s ), 1L89 (1H, s), IR (Nujol): 1682cm mp: 213.2-214.6 ° C (Example 252; 1- (biphenyl-4-methyl) -2-ethyl · 6-〇 [3 · (Methylthio) c] Synthesis of fluorenylaminocarbamyl] benzo sial (314) &gt; ---- 244_____ This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) 548272 A7 B7 V. Explanation of the invention (23g according to the method of Example 98, using 6-carboxy-1- (biphenyl-4-methyl) _2-ethylbenzimidazole (0.300g), N, N, -carbonyldi Imidazole (0.272g), 1-[(3-fluorenylthio) propyl] sulfonamide (0.285g), diazabicycloundecene (0-256g) to obtain 0.178 g of 1- (biben-4-methyl) -2-ethyl-6- [1- [3- (methylthio) propyl] sulfonamidoaminofluorenyl] benzimidazole (3 14). [Physical properties of compound (314)] W-NMMDMSO-d6,6): 1.30 (3H, t, J = 7.5Hz), 1.9Η · 99 (2Η, ιη), 1.97 (3Η, s), 2 · 58 (2Η, t, J = 7.2Hz), 2.90 (2Η, q, J = 7.6Hz), 3.55 ~ 3.61 (2Η, m) 3 5 · 60 (2Η, s), 7.18 (2Η, d, J = 8.2Hz), 7.35 (1Η, t, Jf: 7.3Hz), 7.44 (2H, t, .J: 7.5Hz), 7.60-7 · 66 (4Η, m) , 7.69 (1Η, d, J = 8.5Hz), 7.82 (1H, dd, J: 1.8 and 8.5Ηζ), 8.24 (1H, s), 11.98 (1H, s) (I_jol): 1671cm1. That is: 89.9-91.2 ° C. &lt; Example 253; Synthesis of 1- (4-biphenylfluorenyl) -2-ethyl-6- (1-benzenesulfonylaminofluorenyl) benzimidazole (3 15) &gt; Central Ministry of Economic Affairs Standard and printed by employee consumer cooperatives (please read the notes on the back before filling out this page) According to the method of Example 98, 6-carboxy-1- (4 · biphenylmethyl) -2 • ethylbenzo is used Rice millet (0.300g), Ν, Ν'-Dikei rice millet (0.272g), 1-pentasulfonamide (0.254g), diazabicycloundecene (0.2256g) to obtain J- (4-biphenylmethyl) -2-ethyl-6- (l-benzenesulfonylcarbamoyl) benzimidazole (315) 0.258 g. [Physical properties of compound (315)] 'FHiMiUDMSO- dG ， ά): 〇 · 87 (3Η, t, J: 7.2Hz), 1.22-1 · 39 (4Η, m), 1.30 (3Η, t, J = 7.5Hz), 1.66-1.73 ( 2Η, m), ZZ.90 (2Η, q, J ^ 7.4Hz), 3.51 (2H, t, J = 7.7Hz)

, 5.60 (2Η, s), 7.18 (2Η, d, J = 8.2Hz), 7.34 (1Η, t, J = 7.4Hz), 7.44 (2Η, t, J _ Ύ1Ύ ____________ This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 548272 A7 B7 V. Description of the invention (23 $ = 7 · 6Ηζ), 7 · 60-7 · 67 (4Η, m), 7.71 ( 1Η, d, J = 8.4Hz), 7.81 (1Η, dd, J = 1.6 and 8.4Hz), 8.27 (1H, d, Jl.lHz), 11.92 (1H3 s), IR (Nujol): 1682CHT1. mp: 175.3-178.4 ° C. &lt; Example 254; 6- (l-butanesulfonylcarbamoamido) _1- (2,4-digasofluorenyl) -2-ethylbenzyl sigma Synthesis of (3 16) &gt; According to the method of Example 98, 6-carboxydioxobenzyl) -2-ethylbenzimidazole (0.300 g), N, N, -carbonyldiimidazole (0.258 g ), 1-butanesulfonamide (0.217g), diazabicycloundecene (0.262§) to give 6- (bubutsulfonylaminocarbamyl) -1- (2,4- Dioxoyl)-2-ethylbenzo. Mi 0 sits (316) 0.253g. [Physical properties of compound (316)] 1 dirty »0% d): 0.85 (3 (, t, J: 7.4Hz), 1.27 (3Η, t, J = 7.4Hz) 3 1.35-1 • 43 ( 2H, m), 1.63-1 · 70 (2Η, m) 3 2.81 (2Η, q, J = 7.4Hz), 3.51 (2Η, t, J: 7.7Hz), 5.59 ( 2Η, s), 6.41 (1Η3 d, J = 8.4Hz) 3 7.32 (1H, dd3 J = 2.0 and 8.4Hz), 7,7 3 (1H3 d, J 二 8 · 4Ηζ), 7.76 ( 1Η, d, J = 2.0Hz), 7.81 (1Η, dd3 J = 1.5 and 8.5Hz), 8.12 (1H, d3 J = 1.6Hz), 11 · 87 (1Η, s). The Central Ministry of Economic Affairs and the Consumers' Cooperatives, India Fanfan (Please read the precautions on the back before filling this page)

IR (Nujol): 1694cm_1. mp: 175.7-176.9 ° C &lt; Example 255; Synthesis of l- (4-biphenylmethyl) -2-ethylmethyl) butanesulfonylcarbamoyl] benzimidazole (317) &gt; According to the method of Example 98, 1- (4-bibenzylmethyl) -6-branzyl-2-ethylbenzo miso (0.300 g), N, N'-Dynyl saliva (〇272 g) were used. , 1_ (3-methyl) butanite kappaamine (.254g), one mouse, two ring and eleven dilute (.256g) to --J43__ This paper size applies Chinese National Standard (CNS) A4 specification (210X297) %)-548272 A7 B7 V. Description of the invention (240 gives 1- (4-biphenylfluorenyl) -2-ethyl-6- [l- (3-fluorenyl) butylsulfonylcarbamyl ] Benzimidal (3 17) 0.273 g. (Please read the precautions on the back before filling this page) [Physical properties of compound (317)] 4-NMR (DMS0-d6, ά): G.85 (6H, d5 J: 6.5Hz), 1J (3H, t, J: 7.4Hz), 1.55-1 • 62 (2H3 m), 1.63-1 · 70 (1Η, m), 2.90 (2Η, q3 J : 7.4Hz), 3.52 (2H, t, J = 7.9Hz), 5.61 (2Η, s), 7.19 (2Η, d, J = 8.3Hz) 3 7 · 35 (1Η, t3 J = 7.4 Hz), 7.44 (2H, t, J 2 7.5Ηζ), 7.61-7.66 (4Η, m), 7.71 (1Η, d, J 8 · 5Ηζ), 7.81 (1Η, dd, J: 1.6 and 8.4Ηζ), 8.27 (1Η, s), 11.95 (1Η, s). IR (Nujol): 1682cm— mp: 102 8-104.5 ° C &lt; Example 256; Synthesis of l- (2,4-dioxobenzyl) -5-ethoxycarbonyl-2-fluorenylbenzimidazole (318) &gt; According to Production Example 14 This method uses 4-ethylamido-3-nitrobenzoic acid ethyl ester (1.525 g) and 2,4-digaso-benzyl chloride (1.42 g) to obtain 4- [N- (2,4 -Digas benzyl) acetamidinyl] -3_nitrobenzoate. The method according to Example 24 was used to convert to ι_ (2,4-dichlorobenzyl) -5 -ethoxydaiyl -2-methylbenzyl miso (3l8) 1.476 g. [Physical properties of compound (318)] 1H-NMR (CDC13j d): 1.42 (3H, t, J = 7.1Hz), 2.57 (3H, s) 3 4.41 (2H3 q3 J-7.1

Hz), 5.38 (2Η, s), 6.35 (1Η, d, J: 8.4Hz), 7.09 (1H, dd, J = 2.0 and Ting 8.4Ηζ), 7 · 16 (1Η, d, J: 8.9Hz), 7.49 (1ϋ d, J: 2.0Hz), 7.96 (1Η, dd, J: 1.5 and Sha 8.5H z), 8.46 (1H, s); &lt; Example 257; Synthesis of 5-carboxy-1- (2,4-dichlorobenzyl) -2-fluorenylbenzimidazole (319) &gt; _ 244 This paper size applies to China National Standard (CNS) A4 (210X297) ) 548272 A7 B7 V. Description of the invention (24ί According to the method of Example 53, i- (2,4-dichlorobenzyl) _5-ethoxyquinyl-2-fluorenyl was used. Sit ( 1.465 g) to obtain 1.195 g of 5-weiyl-1 ((2,4-dioxobenzyl) -2-fluorenylbenzimidazole (319). [Physical properties of compound (319)] 1H-NMR ( DMS0-d65 δ): 2.48 (3H3 s) 5 5.56 (2H, s) 3 6.53 (1H, d, J = 8.4Hz)? 7. 32 (1H, dd, J2 2.1 and 8. · 4Ηζ), 7 · 44 (1Η3 d, J 2 8.4Ηζ), 7.73 (1Η, d, J 2 2.2Ηζ), 7.78 (1Η, dd, J 2 1.5 and 8.4Ηζ), 8.15 (1Η, d, J = 1.3 Hz). &lt; Example 258; 5- (1-Butanesulfonylaminofluorenyl) _fluorene- (2,4-dichlorobenzyl) _2_methylbenzimidazole (32 〇 ) Synthesis> According to the method of Example 98, using 5-carboxyl-1- (2,4-dioxobenzyl) -2-fluorenylbenzimidazole (0.565g), N, N, -carbonyldi Imidazole (0.504 g), 1-butanesulfonamide (0.427 g), diazabicycloundecene (.473 g) to give 5- (1-butanesulfonylcarbamoyl) -1- (2,4-Dioxobenzyl) -2-methylbenzimidazole (320) 0.690 y. [Physical properties of compound (320)] W-NMR (DMS (H16, 6): 0.87 (3Η, t, J: 7.3 Hz), L41 (2H, m), 1.68 (2Η, m), 2.49 (3Η, s), 3.52 (2Η, m), 5.58 (2Η, s), 6.53 (1Η, d, J = 8.4Hz), 7.33 (1Η, dd, J 2 2.1 and 8.4Ηζ), 7.50 (1Η, d, J 2 8.5Ηζ), 7.73 (1Η , D3 J 2 2. 1Ηζ) 3 7.78 (1H, in the Ministry of Good Debris ^ humble ^ Volunteers eliminate cooperation ^ seal ^ (Please read the precautions on the back before filling out this page) dd, J-1.5 and 8. 5Ηζ ), 8 · 24 (1Η, s), 11 · 97 (1Η, br s). IR (Nujol): 1674cm-, namely: 135.4-139.2 ° C. &lt; Example 259; Synthesis of 1- (4-biphenylmethyl) -5-ethoxycarbonyl-2-ethylbenzimidazole (321) &gt; According to the method of Production Example 14, 4-propanamidin was used Benzyl-3-nitro ---- --- --- _ One paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 548272 A7 ----------------- --B7 V. Description of the invention (24i '一 ^ (Please read the notes on the back before filling this page) Ethyl benzoate (1.50g) and 4-bromomethylbiphenyl (1.67g) to get 4_ [n_ (4-Biphenylfluorenyl) propanamidonitronitrobenzoate. It was converted to biphenylmethyl according to the method of Example 24) _5_ethoxycarbonyl_2_ ethylbenzimidazole (321 ) 1.23§. [Physical properties of compound (321)] ^ Bake ⑽ ..., 6): 1.40 (3Η, t3 J: 7.1Hz), 1.45 (3Η, t, J: 7.6Hz), 2.90 (2Η, 1 J: 7.6 Hz), 4.39 (2Η, q, J: 7 ″ Hz), 5 · ton 2H, s), 7.09 (2Η3 d, ㈣2Ηζ), 7 · 27 (1Η, d3 J = 8.8Hz), 7.34 (1H, m), 7.42 (2H, t), 7.55-7.51 (4H, m) 3 7.97 (1 H, dd, J: 1.5 and 8.4Ηζ), 8.52 (1Η, d , J 2: 1.2Ηζ). &lt; Example 260; Synthesis of 1- (4-bibenzylidene) -5-carboxy-2-ethylbenzimidazole (322) &gt; According to the method of Example 53, 1- (4-biphenyl Fluorenyl) _5 · ethoxy-2-ethylbenzoyl salicylate (1.00 g) to give ι_ (4-biphenylmethyl) _5_ retyl-2-ethylbenzobenzoic ( 322) 0.870§. [Physical properties of compound (322)] 'H-NMRiDMSO-dG, δ): L30 (3H5 t, J = 7.4Hz), 2.90 (2H, q, J-7.4Hz) 5 5.57 (2 H, s) 5 7.17 (2H3 d3 J = 8.3Hz), 7.33 (1H, m), 7.4Z (2H3 t), 7.63-7.57 (5H, m) 5? 81 (1Η, dd, J 2 1.6 and 8.6Ηζ) , 8.18 (1H, d, J = 1.3Hz), 12.67 (1H, br s). Central Ministry of Economic Affairs «.- Rate is only -T-Consumer Cooperation Private Seal ^ &lt; Example 261; l- (4-bibenzylidene) -5- (1-butanesulfonylcarbamoyl) -2 -Synthesis of ethylbenzimidazole (323) &gt; According to the method of Example 98, using 1- (4-biphenylmethyl) -5-carboxy-2-ethylbenzimidazole (0.400 g), N, N, carbonyldiimidazole (0.364 g), 1-butanesulfonamide (0.308 g), diazabicycloundecene (0.342 g) to give 10-biphenylfluorenyl-5--5- Butylsulfonylaminocarbamyl) -2-ethylbenzimidazole ___ 246 _____ i Paper size applies to Chinese national standard (CNS> A4 specification (210'〆297 Gongchu) &quot; one 548272 Α7 Β7 V. Invention Explanation (24) azole (323) 0.305g ° [physical properties of compound (323)] (Please read the precautions on the back before filling in this page) m-NMlUDMSO-d6 ， ά): 0 · 86 (3Η, t, J Two 7 · 4Ηζ), 1.30 (3Η, t, J 2 7.5Ηζ), 1.41 (2 Η, m), 1.68 (2Η, m), 2.91 (2Η, q, J = 7.4Hz), 3.52 (2Η, m), 5.59 (2Η, s), 7.16 (2Η, d, J 2 8.2Ηζ), 7.34 (1Η, t, J 2 7.4Ηζ), 7.43 (2Η3 t), 7.59-7 · 65 (5Η, π), 7.80 (1Η, dd, J = 1.6 and 8 · 6Ηζ), 8 · 24 (1Η, d, J = 1.6Ηζ), 11 · 97 (1Η, br s). IR (Nujol): 1682cm-l. mp: 142.9-144.4 ° C. &lt; Example 262; Synthesis of 1- (4-biphenylmethyl) -2-ethyl-6- (2-methoxyethylide yellow aminocarbamoyl) benzimidal (324) &gt; According to the method of Example 98, using benzimidazole (0.513 g), N, N'-carbonyldiimidazole (0.464 g), 2-methoxyethanesulfonamide (0.420 g), and diazabicyclo Undecene (0.438 g) to give 1- (4-biphenylmethyl) -2-ethyl. 6- (2-methoxyethylsulfonylaminofluorenyl) benzimidazole (324) 0.487 g. [Physical properties of compound (324)] 1-_0-d6, (5): ΐ · 30 (3Η, t3 j: 7.5Hz), 2 9_, q, Fu ·), &amp; H, s), 3 · 70-3 · 77 (4Η, π), 5.60 (2Η, s) 7.18 (2Η, d, J 2 8.28ζ), 7.35 (1Η t J -7 · 1Ηζ), 7 · 44 &lt; 2Η, t, J: 7.5Hz), 7.60-7 · 67 (4Η, π), 7.70 (1Η, d, J: & 5Hz) 7 · 80 (1Η, dd, J = 7.4 and 1 · 3Ηζ), 8 · 25 (1Η, s), 11 · 97 (1Η, s). IR (Nujol): 1684cm— *. mp: 94.6-97.2 ° C &lt; Example 263; Synthesis of 6-ethoxycarbonylethyl-l- [4- (4-fluorobenzyloxy) benzyl] benzimidazole (325) &gt; _____ Ύάΐ_ 本Paper size applies to Chinese National Standard (CNS) A4 specification (210 × 297 mm) ^ h_x eliminates the combination of bamboo ^ India 548 272 A7 __________ B7 V. Description of the invention (24j — Stir at 75 ° C 4-Propanamidin-3-aminobenzoic acid ethyl acetate (0.534 g), potassium carbonate (0.374 g), 4- (4-fluorobenzyloxy) benzyl (0.800 g), ethyl acetate (5mi) and water (3ml) for 16 hours. Ethanol and 36% hydrochloric acid (0.46 g) were added to the residue obtained by concentrating the organic layer, and stirred under heating and refluxing for 2 hours. After adding potassium carbonate for neutralization, The solvent was concentrated under reduced pressure, and ethyl acetate and water were added for extraction. The organic layer was concentrated under reduced pressure, and purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/8) to obtain 6- 0.228 g of ethoxycarbonyl-2-ethyl-1_ [4-gas 4-fluorobenzyloxy] benzyl] benzimidazole (325). [Physical properties of compound (325)] 'H-NMRiCDCla, δ): 1.40 (3H, J = 7.1Hz), 1.42 (3H, t3 J = 7.5Hz), 2.86 (2H, q3 J-27.5 · 5Ηζ), 4.38 (2H, q, J = 7.1Hz), 4.97 (2H, s), 5.32 (2H, s), 6.88 (2H3 d, J = 8.7Hz), 6.98 (2Η, d, J = 8.7Hz), 7 · 05 (2Η, t, J = 8.7Hz), 7.37 (2Η, m), 7.76 (2H, d, J = 8.4Hz), 7.98 (1Η, dd, J 2 1.5 And 8 · 5Ηζ), 8 · 02 (1Η, s). <Example 264; Synthesis of 6-tether-2-ethyl-1- [4- (4-fluorobenzyloxy) benzyl] benzimidazole (326) &gt; According to the method of Example 53, use 6-ethoxycarbonyl-2-ethyl-1- [4_ (4-fluorobenzyloxy) benzyl] benzozine (0.225g) to give buweiyl-2-ethyl, yl-1- [4- (4-fluorobenzyloxy) benzyl] benzimidazole (326) 0.175 g. [Physical properties of compound (326)] 1H-NMR (DMS0-d6, δ): 1.28 (3H, t5 J = 7.4Hz) 3 2.89 (2H, q, J-7.4Hz), 5.01 (2 H, s), 5.47 (2H, s), 6.95 (2Η, d), 7.03 (2H, d), 7.18 (2Η, t), 7.45 (2Η, m), 7.62 (1H, d3 J-8.4Hz ), 7.77 (1H, d, J = 8.4Hz), 8.05 (1H, s) 〇; Paper size is suitable / fl towel Guan Jiaxian (CNS) A4 size (210X29 ^ 54) &quot; ~ Order (read first read Note on the back, please fill out this page again) 548272 A7 V. Description of the invention (&lt; Example 265; 6- (l-Butylsulfonylaminofluorenyl) -2-ethyl [4- (4-fluorobenzyl Synthesis of oxy) benzyl] benzimidazole ammonium salt (327) &gt; According to the method of Example 98, using carboxy-2-ethyl-4-444- (4-fluorobenzyloxy) benzyl] benzimidazole (0171g), N, N, -carbonyldiimidazole (0.137g), butanesulfonamide (oj 16g), diazabicycloundecene 129g) to give 6- (1-butanesulfonyl) as an oil Carbamate) _2_ethyl _〗 _ ['(4-fluorobenzyloxy) benzyl] benzimidazole. This was dissolved in ethyl acetate 'and ammonia water was added. The precipitated solid was filtered out and dried to give 6- (1-butanesulfonylaminocarbamyl) -2_ethyl-; μ [4_ (4-fluorobenzyloxy) benzyl] benzene 0.140 g of benzimidazole ammonium salt (327). [Physical properties of compound (327)] tNM ^ DMSO-dG, 6): 0.83 (3Η, t) 3 1.25 (3Η, t), 1.35 (2Η, ιη), 1.61 (2Η, m), 2.84 (2Η, q), 3.27 (2Η, m), 5.01 (2Η3 s) 3 5.42 (2Η, s), 6.95 (2Η, d, J-7.8Hz), 7.02 (2Η, d, J = 7.8Hz), 7.17 (2Η, t), 7.44 (2Η, m), 7.57 (1Η, d, J: 8.1Hz) 3 7.82 (1H5 d3 J-8.1Hz) 3 8.12 (1H3 s) 〇IR (Nujol): 1614cm10 mp: 105-115 ° C 〇 Shumi's 呔 i ?. quasi ^ BJT elimination of bamboo: India ^ &lt; Example 266; 1-[4- Synthesis of (3,4-dichlorobenzyloxy) benzyl] -6_ethoxycarbonyl-2-ylbenzimidazole (328) &gt; According to the method of Example 263, 4-propanamidin_3_ Ethyl benzoate (l.Slg) and 4- (3,4 · dichlorobenzyloxy) benzyl (3 · ΐ8 ^ to give 1- [4- (3,4-dichlorobenzyloxy) (Benzyl) ethoxycarbonylethyl benzimidazole (328) 2.Olg. [Physical properties of compound (328)]

244L (Read the precautions on the back before you fill in this page) The paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) 548272 A7 B7_ V. Description of the invention (24 ^^-NMRiCDCh, δ): 1.40 ( 3H, t3 J-7.1Hz) 3 1.42 (3H3 t5 J-7.5Hz) 3 2.86 (2H3 q, J 2 7.5Ηζ), 4.38 (2Η3 q3 J = 7.1Hz), 4.97 (2Η, s ), 5.33 (2Η, s), 6.87 (2H3 in), 6.98 (2H, a), 7.22 (1H, dd, J 2.0 and 8.38ζ), 7.44 (1Η, d, J 2 8 · 3Ηζ), 7.50 (1H, d, J = 2.00Ηζ), 7.76 (1Η, d, J: 8.6Hz), 7.97 (1Η, dd, J: 1.6 and 8.6Ηζ), 8.0 (1Η, d3 J = 1.3 Hz). <Example 267; Synthesis of 6-carboxyl-l- [4- (3,4-dioxobenzyloxy) benzyl] -2-ethylbenzimidazole (329) &gt; Method according to Example 53 , Using 6-ethoxycarbonyl-2-ethyl-1-[4- (4-I-benzyloxy) benzyl] benzimidium η (2 · 〇ig) to get & carboxy-1- [ 4- (3,4-dichlorobenzyloxy) benzyl] · 2-ethylbenzimidazole (329) 1.82 g. [Physical properties of compound (329)] ^ -NMRiDMSO-dG, δ): 1.28 (3HS t), 2.88 (2H, q), 5.05 (2H, s) 3 5.47 (2H5 s), 6.96 (2Η, d ), 7 · 04 (2Η, d), 7.39 (1Η, m), 7.68-7 · 59 (3Η3 m) 3 7 · 78 (1Η3 d, J = 8 · 4Ηζ), 8 · 06 (1Η, s). In the Ministry of Economic Affairs, we must be stubborn and consume 5 Chinese characters (please read the precautions on the back before filling this page) &lt; Example 268; 6- (l-Butylsulfonylaminocarbamidine * h_ [ Synthesis of 4_ (3,4_ mono-gas benzyloxy) benzyl] ethylbenzimidamidin alpha succinic ammonium salt (33〇) &gt; According to the method of Example 98, 6-carboxyl group; μ [心 (3, Each dichlorobenzyloxy) benzyl] ethylbenzimidazole (0.500 g), N, N, -kisyl disalylamine (0.356 g), butanidine (0.301 g), diazonium Bicyclic eleven dilute (0334g) to give 6- (1-butanesulfonylaminocarbamyl) β1_ [4 · (3,4-dichlorobenzyloxy) benzyl] ethyl as an oil Benzimidazole. Dissolve it in ethyl acetate and add ammonia. The precipitated solid is filtered off and dried to give 6- (1-butanesulfonylcarbamoyldichlorobenzyloxy). This paper size is applicable to Chinese National Standard (CNS) A4 (210X 297 cm) 548272 A7 ___ B7 V. Description of the invention (24) Benzyl] -2-ethylbenzimidazole ammonium salt (330) 0.5 lg. [Compound (330) Properties] (Please read the precautions on the back before filling this page)! H-dirty (DMS0-d 6, (5): G.82 (3H3 t, J = 7.3Hz), 1.26 (3Η3 t, J = 7.4Hz), 1.31 (2 H, m), 1.54 (2Η3 m) 3 2 · 84 (2Η, q, J: 7 · he), 3.07 (2Η, m) 3 5.05 (2Η3 s), 5.41 (2H, s), 6.95 (2Η, d, J = 8.7Hz) , 7.00 (2Η, d, J 2 8.7Ηζ), 7.41 (1Η3 d, J = 8.2Hz), 7.46 (1H, d, J 2: 8. he), 7.62 (1Η, d3 J : 8.2Hz), 7.68 (1Η, s), 7.81 (1Η, d, J = 8.4Hz), 7.97 (1H, s), IR (Nujol): 1540cm'10, mp: 99 · 5- 101.5oC &lt; Example 269; Synthesis of l- (4-biphenylmethyl) -6- (n-butylaminomethyl) -2-ethylbenzimidazole (331) &gt; According to Example 15 The method uses i- (4-biphenylmethyl) -6-chlorocarbonyl-2-ethylbenzimidazole hydrochloride (0.400 g), n-butylamine (0.2338), and triethylamine. (0.2158) to give 0.295 g of 1- (4-biphenylmethyl) -6- (n-butylaminomethylmethyl) -2-ethylbenzobenzene (33 1). [Compound (33 1 ) Physical properties) ^ -NMRiDMSO-dG, c5): 0.95 (3H, t5 J = 7.3Hz) 3 1.37-1.48 (2H, m) 3 1.45 (3H, t, J = 7.4Hz) 5 1.57-1.63 (2H5 m), 2.90 (2H3 q3 J = 7.5Hz), 3.46 (2H, -q5 J-7.1Hz), 5.42 (2Η, s ), 6.16 (1Η, br s), 7.10 (2Η, d, J: 8.1Hz), 7.34 (1Η, t, J-2, 7Hz), 7.42 (2H3 t, J = 7.5 Hz), 7.48-7.57 (5H, m), 7,87 (1H, d, J = 8.4Hz), 7.91 (1 H, s). IR (Nujol): 1621cm mp: 170.5-173.0 ° C. &lt; Example 270; l- (4-biphenylfluorenyl) -2-ethyl each (canconazole_2-amino paper size, Shizhou Chinese National Standard (CNS) A4 specification (2ι〇, χ297 attack) 548272 A7 B7 V. Description of the invention Synthesis of (24 ^ methyl ethyl) benazepine (332) &gt; According to the method of Example 15, 1- (4-biphenylmethyl) -6-oxoyl 2-ethylbenzimidazole hydrochloride (0.400 g), 2-aminobenzidine (0.318 g), and triethylamine (0.215 g) to give 1- (4- Biphenylmethyl) -2-ethyl-6- (thiazole-2-carbamoyl) benzimidazole (332) 0.179 g. [Physical properties of compound (332)] lH-NMR (DMS0-d6, δ) : 1.48 (3H3 t5 J = 7.5Hz), 2.95 (ZH, q5 J-7.5Hz), 5.41 (2 H, s), 6.94 (1Η, d, J = 3.66Ηζ), 7.06 (2H, d , J = 8.1Hz), 7.26 (1Η, d3 J = 3.6Hz), 7.32 (1H3 t3 J = 7.4Hz), 7.39 (2H3 t5 J = 7.3Hz), 7.47-7.51 (4H3 m) 3 7.87 ( 2H, s), 8.03 (1Η, s), 11 · 15 (1Η, s), IR (Nujol): 1652cm-lmp, 225.5-227.7 ° C. &Lt; Example 271; 1- ( Synthesis of 4-biphenylmethyl) -2-ethyl-6- (2-pyridylaminofluorenyl) benzimidazole (333) &gt; According to Example 98 Method using 1- (4-biphenylmethyl) -6-carboxy-2-ethylbenzimidazole (0.300 g), N, N'-carbonyldiimidazole (0.272 g), and 2-amino σ ratio Bite (0 · 15 8g), diazabicyclopyrene-dilute (0.256g) to get 1-the rate of entrapment in the warp section and the private seal of K-worker cooperation ^ (Please read the notes on the back before filling This page) (4-Biphenylfluorenyl) -2-ethyl-6- (2-.pyridinylcarbamyl) benzimidazole (333) 0.116 g 〇 [Physical properties of compound (333)] 1 leg (CDCh, d): 1.47 (3Η, t3 J: 7.6Hz), 2.93 (2Η, q, J = 7.4Hz), 5.45UH, s), 7.06 (1Η, dd, J = 7.4 And 4 · 9Ηζ), 7 · 10 (2Η, d, J: 8.1Hz), 7_34 (1H, t, J 2 7.4Ηζ), 7.42 (2Η, t, J: 7.6Hz), 7.50 -7 · 55 (4Η, m), 7.75 (1Η, t, J: 7.9Hz), 7 • 79 (1H, d, J 二 8 · 4Ηζ), 7.86 (1H, d, J 二 8 · 4Ηζ ), 7 · 98 (1Η, s), 8 · 30 (1Η, d, J 2 6 · __ 252_____ This paper size is applicable to China National Standard (CNS) A4 (210X 297 mm) 548272 Α7 ___ Β7 5 Description of the invention (24d 2Hz), 8.38 (1H, d3 J = 8.4Hz), 8.62 (lH) S) 〇IR (Nujol): 1661cm'1 * mp : 160.9-164.5 ° C. (Please read the precautions on the back before filling in this page) &lt; Example 272; 6- (n-butylaminomethyl) digas benzyl) _2-methylbenzimidazole (334) Synthesis &gt; According to the method of Example 15, 6-chlorocarbonyl-b-methyl, 4-dichlorobenzyl) -2-ethylbenzimidazole hydrochloride (0.300 g), triethylamine (0.181 g) N-butylamine (0.196 g) to give 6- (n-butylaminofluorenyl) -1- (2,4-dichlorobenzyl) _2-methylbenzimidazole (334) 0.156 Yap. [Physical properties of compound (334)] 'H-NMRiCDCla, δ): 0,96 (3H, t, J = 7.3Hz), 1.37-1.43 (2H, m), 1.55-1.62 (2H, m), 2 · 56 (3Η, s), 3.46 (2Η, q, J = 7.0Hz), 5.40 (2Η, s), 6.15 (1Η, br s), 6. 32 (1H, d, J: 8.5Hz), 7.07 (1Η, d, J = 8.4Hz), 7.48 (1Η, d3 J: 2.GHz), 7.55 (1Η, d3 J = 8.4Hz) 3 7.74 (1H, d , J = 8.4Hz), 7.79 (lH, s). IR (Nujol) · 1636cm-1. mp: 146.6-147.5 ° C. &lt; Production Example 53; Production of 3- [2 (2,4-digasophenethyl) amino] -4-nitrobenzoate &gt; 3-Fluoro-4-nitrobenzoate A solution of (0.877 g) and 2 (2,4-dichlorophenylethyl) amine (2.25 g) in toluene (5 ml) was heated under reflux for 15 hours. After the solvent was distilled off, the residue was purified by silica gel column chromatography to obtain a crude product of 3- [2 (2,4-dichlorobenzylethyl) amino] -4-nitrobenzoic acid. Ethanol (80 ml) and 97% sulfuric acid (3.0 g) were added thereto, and heated under reflux for 4.5 hours. After distilling off the ethanol under reduced pressure, add three gas methane and saturated sodium bicarbonate water __232______ — This paper is suitable for China National Standard (CNS) A4 specification (210X297 mm) 548272 A7, ------- --- 一 _____ B7 —— __ 5. Description of the invention (25 ^ solution for extraction. After drying the organic layer, it is purified by silica gel column chromatography (eluent · hexane / 1 ethyl acetate = 2/1) The obtained residue was concentrated under reduced pressure to give 3- [2 (2,4-dichlorobenzylethyl) amino] -4-nitronitrobenzoate (1.16g). [Physical properties of the compound] 1 Dirty (CDCh, ά): i.35 (3H, t, J: 7.mz), 1.64 (3Η, d5 J: 6.6Hz), 4.30 (2Η, q3 J = 7.1Hz) 3 5.16 (1H3 m) 3 7.18-7.31 (4H, m), 7.43 (1H, d, J ^ Z.OHz), 8.21 (1d, J: 8.8Hz), 8.34UH, d, J: 5Hz). &lt; Production Example 54; Production of 4-amino group [2 (2,4_di-gasophenethyl) amino] ethyl benzoate &gt; 3- [2 (2,4-digasoline Phenethyl) amino] 4-nitrobenzoate (1.14 g), reduced iron (0.60 g), ethanol (10 ml) and a mixture of acetic acid (5rnl) were heated under reflux for 3 hours. The solid was filtered off, and the residue obtained by concentrating the filtrate was extracted with chloroform and 10% hydrochloric acid. The organic layer was washed with a saturated sodium bicarbonate aqueous solution, and the solvent was distilled off under reduced pressure. Residue obtained by refining on Shixi gel column chromatography (eluent: hexane / ethyl ester = 2/1) to obtain 4-amino_3_ [第 2 (2,4-dichlorophenethyl) (Amino) amino] ethyl benzoate (0.920 g). [Physical properties of compound] t dirty (CDCh, 6): 1.31 (3Η, t, J = 7.1Hz), 1.52 (3Η, d, J 2 6.7Ηζ), 3.56UH, br s), 3 79 (2Η, br s), 4.23 (2H, q, J: 7.1Hz), 4.96 (1H, q, J: 6.7Hz), 6.68 UH, d, J = 8.0Hz), 7.03 (1H, d3 J2 1.7Ηζ), 7 ″ 5 (1H, dd, J2 2.1 and 8. He), 7.35 (1Η, d3 J = 8.4Hz), 7.39-7.43 (2Η, m) 〇 &lt; Implementation Example 273; 1- [No. 2 (2,4-dichlorophenethyl)]-6-ethoxycarbamidine Paper size / 适] Chinese National Standard (CNS) A4 Specification (210X29 * 7 mm) (Read the precautions on the back before you fill in this page), 1T Qin · 548272-· ——_________— _B7 ^ _____ V. Description of the invention (25) &quot; Synthesis of 2--2-benzylbenzimidazole (335)> Acetyl chloride (0.243 g) was added dropwise at room temperature to 4-amino-3- [2 (2,4-dioxophenethyl) amino] benzoic acid ethyl ester (0.90 g) The ratio is 2.0% of pyridine (2.0ml) / cereal. After stirring at room temperature for 1 hour, acetic acid and an excess of 10% hydrochloric acid are added for extraction. The organic layer is washed with a saturated sodium bicarbonate aqueous solution and decompressed. The solvent was distilled off to obtain 4-4-acetamido-3- [ The crude product of mono (2,4-dichlorobenzylethyl) amino] ethyl benzoate. Immediately dissolved in ethanol (20ml), added 36% hydrochloric acid (0.4ml) and heated under reflux for 2 hours. Added hydrogen carbonate After neutralizing with sodium, the solvent was distilled off under reduced pressure. Ethyl acetate and water were added to extract the residue. The organic layer was concentrated and subjected to silica gel column chromatography (eluent: hexane / ethyl ester = 20/1). ) To obtain 0.700 g of 1- [2 (2,4-dichlorophenethyl)]-6-ethoxycarbonyl-2-methylbenzimidazole (335). [Compound (335) Physical properties] limiUCDCla, (5): 1.38 (3Η, t, J: 7.2Hz), 2.01 (3Η, d5 J: 7.2Hz), 2.63 (3Η, s), 4.29-4 · 40 (2Η, ffl), 5.89 (1Η, q, J = 7) z), 7.37 (1Η, dd, J: 2.2 and 8.4

Hz), 7.40 (1H, d, J = 2.0Hz), 7.52 (1H3 d, J = 8.4Hz), 7.67 (1H, d3 J = 8.4Hz) 3 7 • 86 (1H, s), 7.91 ( 1Η, dd, J: 1.4 and 8.4Hz). &lt; Example 274; 6-carboxy-1- [Synthesis of 2 (2,4-di-gas-substituted phenylethyl) l-2-fluorenylbenzimidazole (336) &gt; According to the method of Example 53, Using 1- [2 (2,4-dichlorophenethyl)] · 6-ethoxyepi-2-methylbenzoxyl salivary (0.690g) to obtain &amp; No. 2 (2,4-dichlorophenethyl)]-2-methylbenzimidazole (336) 0.447g ° This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) (Please read the precautions on the back before filling this page) 548272 A7 B7 V. Description of the invention (25i [Physical properties of compound (336)] (Read the precautions on the back before filling out this page) H ^ (DHS0-d63 δ ): 1.88 (3H, d5 J = 6.8Hz), 2.57 (3H, s), 6.01 (1H, q) 5 7. 55 (1H, d) 5 7.60-7.67 (3H, m), 7.71 (1H? D ) 3 7.89 (1H, d) 5 12.65 (1H, br s) &lt; Example 275; 6- (l-Butylsulfonylaminocarbamyl)] _ [Second (2, 'digasophenethyl) )] Synthesis of 2-methylbenzimidazole (337) &gt; According to the method of Example 98, 6_carboxy_ 丨 _ [2 (2,4-dichlorophenethyl)]-2 was used -Fluorenylbenzimidazole (0.433g), N, N, -carbonyldizolidazole (0.412g), butanesulfonium Amine (.348g), diazabicyclo-ene (0.386g) to give 6- (1-butanesulfonylaminocarbamyl [second (2,4-mono-gas-substituted ethyl)]- 2-Methylbenzyl η (337). [Physical properties of compound (337)] 1 fiMR (DMS (H163 ¢): 0.84 (3Η, t, J: 7.3Hz), 1.34 (2Η, ιη), 1.57 (2Η, m), 1.89 (3Η, d, J = 7.0Hz), 2.49 (3H3 s) 3 3.07 (ZH3 m) 3 5.954 (1H, q3 J = 7.0Hz), 7.4 1 (1H, d, J = 8.7Hz), 7.56 (1Η, dd, J = 2, l and 8.5Ηζ), 7.61 (1H, d, J: 2.1Hz), 7.74-7.79 (3H M) &lt; Example 276; Synthesis of 1- (4-biphenylmethyl) _2-ethyl-6- (phenylaminomethyl) benzimidazole (338) &gt; According to Example 15 Method: ι_ (4-biphenylmethyl) -6-chlorocarbonylethylbenzimidazole hydrochloride (0.300 g), triethylamine (0.243 g), and aniline (0.224 g) were used. 0.195 g of 1- (4-biphenylmethyl) -2-ethyl-6- (phenylaminofluorenyl) benzimidazole (338) was obtained. [Physical properties of compound (338)] 1H-NMR (CDCl3, 6): 1.47 (3H, t5 J = 7.5Hz), 2.93 (2H, q, J-7.5Hz), 5.44 (2H, s), 7.1K2H, d, J = 8.2Hz), 7 · 14 (1Η, t, J 二 7 · 4Ηζ), 7.32-7 · 38 (3Η, ni), 7.42 (This paper is suitable for Chinese National Standard (CNS) A4 Specifications (210X297 mm) 548272 A7 B7 V. Description of the invention (25i 2H, t, J 2 7.4 Hz), 7.51-7 · 54 (4Η, m), 7.63 (2Η, d, J 2 7 · 8Ηζ) , 7.69UH, dd5 J 2: 8 · 4 and 1. 6Ηζ), 7.84 (1Η, d, J2 8.4Ηζ), 7.88 (1Η, br s), 7.97 (1H, d, J 2 1 5Ηζ) IR (Nujol): 16470111 ^ 0 mp: 171 · 7-172 · 1. . . &lt; Example 277; Synthesis of l- (4-biphenylmethyl) -2-ethyl-6- (l, 3,4-thiadiazole-2-aminomethylamidino) benzimidazole (339) &gt; According to the method of Example 98, 1- (4-biphenylmethyl) -6-weilyl-2-ethylbenzyl flavor was used (Sat (0.300g), N, N'-Weiji Diweiwa (〇, 272g), 2-amino-1,3,4-thiadiazole (0.170g), diazabicycloundecene (0.256§) to give 1- (4-biphenylmethyl) ) -2-Ethyl-6- (1,3,4-thiadiazole-2-carbamic acid group) benzo saliva (339) 0.234 yup. [Physical properties of compound (339)] ^ -NMRiCDCla, ^): 1.45 (3H3 t3 J-7.5Hz) 3 2.90 (2H, q3 J-7.5Hz), 5.53 (2H, s), 7.07 (2H, d3 J = 8.3Hz), 7.33 (1H, t, J = 7.5Hz), 7.40 (2H, t3 J = 7.3Hz), 7.5 2 (4H, d, J = 8 · z), 7.89 (1Η, d, J = 8.5Hz), 8 · 08 (1Η, dd, J = 8.5 and 1.6Ηζ), 8.34 (1Η, d, J = 1.2Hz) 3 7 · 60 (1Η, s), 12 · 26 ( 1Η, s). The middle section of the Ministry of Economic Affairs «. ^-And 01 Consumption Hezhu Private Seal f (Read the precautions on the back before filling this page) IR (Nujol): 1654CHT1. mp: 230.1-233.4 ° C &lt; Example 278; 1- (4-biphenylmethyl) -2-ethyl-6- (tetrazole-5-aminomethylamidino) benzimidazole (340) Synthesis> According to the method of Example 98, 1- (4-bibenzylmethyl) -6-carboxy-2-ethylbenzimidazole (0.300 g), N, N'-carbonyldiimidazole (. 272g), 5-amino group &quot; tetrasial (0.143g), diazabicycloundecene (0.256g) to get 1-257 This paper size applies Chinese National Standard (CNS) A4 specifications (210X297 (Mm) 548272 A7 B7 5. Description of the invention (25j (4-biphenylfluorenyl) -2-ethyl-6- (tetrazole-5-aminomethylfluorenyl) benzimidazole (340) 0.135 g. [Compound (Physical properties of (340)] 4- Look_30- (16,6): 1.32 (3Η, t, J = 7.5Hz), 2.93 (2H, q, J: 7.5Hz), 5.61 (2H, s) 5 7 · 23 (2Η, d, J = 8 · 1Ηζ) 3 7 · 34 (1Η, t, J = 7.4Hz), 7.44 (2Η, t, J = 7.6Hz), 7.60-7.67 (4H, m), 7.76 (1Η, d, J: 8.5Hz), 7.98 (1Η, d, J = 8.6Hz), 8.46 (1H, s), 12.30 (1Η, s) 3 15.95 (1H , S). IR (Nujol): 1667C0T1. That is: 273.1-276.0oC. &Lt; Implementation Example 279; 1-(4-biphenylmethyl) -2-ethyl-6- (1 Synthesis of 3,4-triazolyl-3-aminofluorenyl) benzimidazole (341) &gt; According to the method of Example 98, 1- (4-biphenylfluorenyl) -6-carboxy-2- Ethylbenzimidazole (0.300g), N, N'-carbonyldiimidazole (0.272g), 3-amino-1,3,4-triazole (0.141g), diazabicycloundecene (0.256 g) to obtain 0.224 g of 1- (4-biphenylmethyl) -2-ethyl-6- (l, 3,4-triazol-3-carbamoyl) benzimidazole (341). [ Physical properties of compound (341)] After the sample was removed from the crotch, the workmanship was eliminated. (Please read the precautions on the back before filling this page) 'H-NMRiDMSO-dG, c5): 1.33 (3H , t3 J-7, 4Hz) 3 2.93 (2H3 q, J-7.4iiz) 3 5.63 (2H, s), 7.17 (2Hy d, J = 8.3Hz), 7.35 (1Η, t, J: 7.4Hz ), 7.44 (2Η, t, J: 7.5Hz), 7.60-7 · 65 (4Η, m) 3 7.78 (1Η, d3 J 2 7.4Ηζ), 7.83 (1Η, dd , J = 8.4 and 1.51ζ), 8.17 (1Η, s), 8.77 (2Η, s), 12.04 (1Η, s), IR (Nujol): 1675cm1. mp: 263.4-266.20C0 &lt; Example 280; l- (4 · biphenylmethyl) -2-ethyl-6- (l, 3,4-triazole-2- __________ This paper size applies to China Standard (CNS) A4 specification (210X297 mm) 548272 A7 B7. 5. Description of the invention (25 $ &quot; mono ~ aminoamido) benzimidazole (342) synthesis &gt; (Read the precautions on the back before reading (Fill in this page) According to the method of Example 98, ΐ- (4 · bibenzylmethyl) _6_weiyl-2-ethylbenzimidazole (0.300 g), N, N, -carbonyl disalizol ( .272g), 2-amino-1,3,4-difluorene (0.141g), diazabicycloundecene (0256g) to be produced 1- (4-biphenylmethyl) -2-ethyl -6- (l, 3,4-tris-2-carbamic acid group) Benzimidazole (342) 0.215 @. [Physical properties of compound (342)] ^ -NMRiDMSO-de, δ): 1.31 (3H5 t5 J = 7.4Hz), 2.92 (2H3 q3 J-7.4Hz), 5.60 (2 H, s), 7.23 (2Η, d5 J: 7.8Hz), 7.34 (1Η, t, J = 7.2Hz) 3 7 · 44 (2Η, t, J: 7.6Hz), 7.60-7 · 66 (4Η, m), 7.72 (1Η, d, J = 8.3Hz), 7.78 (1Η3 s), 7.95 (1Η, d, J 8.3H z), 8.43 (1Η, s), 11.85 (1Η, s), 13.5 7 (1Η, s). IR (Nujol): 1659 cm &quot; 10 mp: 306.0 ° C (decomposed). &lt; Example 281; Synthesis of 1- (4-biphenylfluorenyl) -2-ethyl-6- (3-pyridylaminomethylfluorenyl) benzimidazole (343) &gt; According to the method of Example 98, Use 1- (4-biphenylfluorenyl) _6_Weiji-2-ethylbenzo miso (0.300g), N, N'-Weiji diwei saliva (0.272g), central part It is only green, and it consumes 3-amino 17 ratio fluorene (0.1588) and diazabicycloundecene (0.2568) to obtain 1- (4-biphenylmethyl) -2- 0.229 g of ethyl-6- (3-turidinecarbamoyl) benzimidazole (343). [Physical properties of compound (343)] ^ -NMRiCDCh, δ): 1.47 (3H, t, J = 7.6Hz), 2.93 (2H, q3 J = 7.4Hz) 3 5.45 (2H, s), 7.10 (2H, d , J 2 8.1Ηζ), 7.29-7.36 (2H, m), 7.42 (2Η, t, J 2 7.4Hz), 7.53 (4H, d, J = 8.0Hz), 7.71 (1H, d , J = 8.5Hz), 7.86 (1H, d, J = 8.4Hz), 7.97 (1H3 s) ________ This paper size applies to China National Standard (CNS) A4 specification (21〇X297 mm) 548272 Α7 Β7 V. Invention Explanation (25g, 7.98 (1Η, s), 8.27 (1Η, d, J 2 8.4Ηζ), 8.38 (1Η3 d, J = 4.7Hz), 8.68 (1Η, d, J (2 · 5Ηζ). IR (Nujol): 1644cm-1. Inp: 124.4-125.60C0 &lt; Example 282; l- (2,4-dichlorobenzyl) -2-methyl-6- ( Synthesis of 2-pyridylaminofluorenyl) benzimidazole (344) &gt; According to the method of Example 98, 6-carboxy-l- (2,4-dioxobenzyl) _2_methylbenzimidazole was used (0.300g), N, N, -carbonyldiimidazole (0.290g), 2-aminopyridine (0.168g), diazabicycloundecene (0.273g) to pay 1_ (2,4-di Chlorofluorenyl) -2-fluorenyl-6- (2- ° specific carbamate) benzimidazole (344) 0.152 yup. Physical properties of compound (344)] ^-NMRiCDCh, δ): 2.59 (3H, s), 5.43 (2H, s) 3 6.33 (1H, d, J = 8.4Hz), 7.06 -7.10 (2H, m), 7.50 (1Η, d, J 2 2.1Ηζ), 7.77 (1Η, dt3 J 2 7.8 and 1.9Ηζ), 7.83 (2Η, s), 7.88 (1Η, s), 8 · 30 (1Η, d, J = 3.7Hz), 8.39 (1Η, d, J = 8.3Hz), 8.78 (1Η, s), IR (Nujol): 1666cm 10m, · 157.4-159.20C 〇 Via the Central Committee of the Ministry of Shanghai «.- ^-^ β-τ 消 贽 Cooperation # 卬 5? (Read the precautions on the back before filling in this page) &lt; Example 283; 1- (4-Biphenylmethyl) Synthesis of 2-ethyl-6- (4-pyridylaminomethylmethyl) benzimidazole (345) &gt; According to the method of Example 98, 1- (4-biphenylmethyl) -6-carboxyl- 2-ethylbenzimidazole (0.300 g), N, N, -carbonyldiimidazole (0.272 g), 4-aminopyridine (0.158 g), diazabicycloundecene (〇j56 g) This gives 1- (4-bibenzylmethyl) -2-ethyl-6- (4-. Than biting carbamate) Benzo rice n _____ 260 This paper size applies Chinese National Standard (CNS) A4 specification (210 × 297 mm) 548272 A7 B7 V. Description of the invention (2 5 Today (345) 0.153g [Physical properties of compound (345)] (Please read the precautions on the back before filling this page) lH-NMR (CDCl3, δ): 1.48 (3H5 t5 J = 7.4Hz), 2.94 (2H, q5 J = 7, 4Hz), 5.45 (2H, s), 7.10 (2H, d, J = 8.1Hz), 7.35 (1Η, t, J: 7 · he), 7.42 (2Η, t, J: 7.4Hz) , 7.50-7.60 (6Η, m), 7.691 (1Η, d, J: 7.8Hz), 7.86 (1Η, d, J: 8_3Hz), 7.95 (1Η, s), 7,99 (1H, br s), 8.54 (2Η, dd, J 2 1.5, and 4.7Ηζ). IR (Nujol): 1663cm-1〇mp: 123.8-124.7 ° C. &Lt; Production Example 55; Production of N- (1-butanesulfonyl) -4-acetamidinyl-3-nitrobenzimidamine &gt; According to the method of Production Example 28, 4-acetamidinyl 3-nitrobenzoin was used Acid (lO.Og), N, N'-carbonyldiimidazole (9.40g), 1. butanesulfonamide (7.92g), one nitrogen and one percent eleven fines (8.83g) to obtain N- (1- Butyl yellow brewing group) _4_Ethylamino-3-nitrobenzofluorenamine (i.75g) [Physical properties of compound] 'H-NMlUDMSQ-de, (5): 〇87 (3Η, t, J: 7.4Hz), 1,37-1 · 44 (2Η, m), 1.64-1 · 71 (2Η3 m), 2.12 (3Η, s), 3.52 (2Η, t, J: 7.7Hz), 7.83 (1Η, d, J: 8.6Hz), 8.21 (1Η, dd, J : 8.6 and 2.1Ηζ), 8.54 (1Η, d, J = 2.2Hz), 10.56 (1Η, s), 12 · 32 (1Η, s) 〇 &lt; Production Example 56; N- ( Production of 1-butanesulfonyl) -3-amino-4-acetamidobenzylidene &gt; According to the method of Production Example 29, N- (l-butanesulfonyl) -4-acetamidine was used Amine-3-nitrobenzofluorenamine (i.75g) to give N- (1-butanesulfonyl) -3-amino-4-acetamidobenzophenamine (3. 〇 4g).-261 This paper size applies Chinese National Standard (CNS) A4 specification (210 × 297 mm) 548272 A7 B7 V. Description of the invention (25) [Physical properties of compound] (诮 Please read the precautions on the back before filling this page) 4-NMR (DMS0-d6, 6): 0.86 (3Η, t3 J = 7.3Hz), 1.33-1 · 43 (2Η, m), 1.59-1 · 67 (2H, m), 2 · 07 (3Η, s), 3 · 37-3 · 43 (2Η, t), 5 · 12 (2Η, br s), 7 · 13 (1Η, dd, J = 8 2 and 2 · 0Ηζ), 7 · 28 (1Η, d, J: 1.9Hz), 7.40 (1H, d, Jt3Hz), 9.09 (1Η, s). &lt; Manufacturing Example 57; Production of N- (1-butanesulfonyl) _4-acetamidoamino_3- [4- (2-pyridinyl) benzylamino] benzobenzamine &gt; According to manufacture The method of Example 32, using N_ (1-τsulfofluorenyl) _3-amino-4-ethylaminobenzodonylamine (400 g) and 2-[(4-molyl) phenyl ] ° ratio σ 疋 (0.477g) to get N- (l-butytazine) -4-ethylamidoamino_3- [4 · (2_σbipyridine) benzylamino] Crude product. Use it directly in the response below. &lt; Example 284; Synthesis of 6- (1-butanesulfonylcarbamoamidinyl) benzyl] -2-methylbenzimidazole (346) &gt; According to the method of Example 183, the above-mentioned N- ( The crude product of l-butanesulfonyl) -4-acetamidinyl-3- [4 ((2-pyridyl) benzylamino] benzobenzylamine to directly obtain 6- (1-butanesulfonyl Carbamoylpyridine) benzyl] methylbenzimidazole (346) 0.330 g. [Physical properties of compound (346)] H-T is eliminated in the M part, and h_T is eliminated. NMR-DMSO-dG, δ): 0.82 (3H, t) 3 1.37-1.46 (2H, m) 5 1.54- 1.6K2H, m), 2 • 54 (3H, s), 3.10 (2Η, t, J = 7,8Hz), 5.57 (2Η, s), 7.19 (2H, d, J = 7.5Hz) , 7.3 3 (1H, t, J 邛 · 2Ηζ), 7.49 (1Η, d3 J J2 · 4Ηζ), 7.82-7.87 (2H, m), 7.90 (1H, d, J = 8 · 0Ηζ), 8.0 Bu 8.04 (3Η, m), 8.63 (1Η, d, J = 4.2Hz). IR (Nujol): 1722cm-10 mp: 292.4-298.4 ° C. ___________ Zή2_ This paper is suitable for Chinese National Standard (CNS) A4 specification (210X297 mm) 548272 Λ7 B7 V. Description of the invention (25 $ &lt; Example 285; 5-Chlorosulfonyl · W24 — one f ^ ^ ϋ ^ (347) ^ 6. ^ § §i ^ group) Synthesis of 2-methylbenzimidazole (348) &gt;-Milky hydrazone in ice solution, H2,4_dichlorobenzyl) _2_ A (4. 00 g) was added to Chlorine 0, and stirred at room temperature for two hours: stirring under thief for 5 hours. The reaction solution was added to ice water, and borrowed; the precipitated gelatinous Solid 'to give 5_chlorosulfofluorenyl] _', r- ^ r / radical ^ _2_f-based benzofluorene (347) and 6_chlorocontinuyl-1- (2,4-digas Benzyl)) 2-methylbenzo is called a mixture. It was directly used in the following reaction .: Example 286; 5-Aminosulfonyl_ (2,4_dioxobenzyl) ) _2_methylbenzimidazole (349) and 6-aminosulfonamido_ 丨 ((2,4_dichlorobenzyl) -2-methylbenzo). Synthesis of (35〇) & gt Treating 5-chlorosulfosulfanyl 1- (2, fluorenyldichlorobenzyl) · 2-fluorenyl with Example 25 using 25% aqueous ammonia (iomi) under hydration; A mixture of benzimidazole and 6-chlorosulfofluorenyl 'dichlorobenzyl) -2-methylbenzimidazole for 1 hour. The solid was filtered to obtain 5-aminosulfonyl-1_ (2, A 1/1 mixture of dichlorobenzyl) -2-methylbenzimidazole (349) and 6-aminosulfofluorenyl 1-methylammonium) -2-methylbenzo miso (350) ( 2.68 g;). [Physical properties of a mixture of compound (349) and compound (350)] NMR (CD3OD3 (5): 2.52 (3 / 2H, s), 2.54 (3 / 2H, s), 5.54 (2H, s), 6.55 (1Η, d3 J = 6.9Hz), 7.17 (1Η, d, J: 8.GHz), 7.52 (1Η, s), 7.65-7 · 78 (2Η , M), 7.82 (1 / 2Η3 s), 8.11 (1 / 2Hj s) 0-24J- This paper size applies to China National Standard (CNS) A4 (210X 297 mm 548272 kl B7) V. Description of the invention ( 26ί) (Please read the precautions on the back before filling out this page) &lt; Example 287; 6- (n-Amylaminosulfonyldichlorobenzyl) -2-methylbenzimidazole (351) and 5_ (n-fluorenylaminosulfofluorenyl) _ 1- (2,4- &gt; synthetic fluorenyl) -2-methylbenzo miso (352) Synthesis &gt; Digas methylbenzene (lml ), Triethylamine (0.56ml), n-youji Chlorine (0.326§) is added to the above 5-aminosulfonyl-1- (2,4-dichlorobenzyl) _2_ hydrazone (349) and 6-aminophenoxy-1- (2 In a mixture (500 g) of 1,4-dioxobenzyl) -2-methylbenzimidazole (350), the mixture was stirred at room temperature for 48 hours. Water was added to stop the reaction. Trichloromethane was added for extraction. The organic layer was dried, concentrated, and purified by silica gel column chromatography (eluent: chloroform / methanol = 95/5) to obtain 6_ (n-pyridylaminostilbenzyl) -1- (2, A mixture of 4-dichlorobenzyl) -2-methylbenzimidazole and 5- (n-fluorenylaminosulfonyl'dichlorobenzyl) _2 • methylbenzimidazole (0.360 g). Then, it is purified by medium pressure silica gel column chromatography (eluent ·· hexane / ethyl ester = 1/1 ~ 1/4) to obtain 6_ (n-fluorenylaminosulfonyl) -1-( 2,4-dichlorobenzyl) _2_fluorenylbenzimidazole (351) (0.95§) and 5- (n-benzylaminomethyl) _1_ (2,4_dichlorobenzyl)- 2-methylbenzimidazole (352) (0.45 g). [Physical properties of compound (351)] ^ -NMRiDMSO-de, ¢): 0.74 (3H, t, J = 7.3Hz), 1.09 (ZH5 m) 3 1.31 (2H5 m), 2. 10 (ZH, t, J-7.3Hz), 2.53 (3H, s) 3 5.63 (2H, s), 6.60 (1H3 d, J = 8 4Hz) 3 7 32 (1H, d, J = 8.3Hz), 7.67- 7.77 (3Η, m), 7.93 (1Η, s). IR (KBr): 1726cm-l0mp: 207,5-210.0oC〇Mass (FD): m / e 454 (M + l) 〇_264 This paper size applies to China National Standard (CNS) A4 specification (21 OX 297 mm) 548272 A7 B7___ V. Description of the invention (26! [Physical properties of compound (352)] (You may read the precautions on the back before filling in this page) lH-NMR (DMS0-d65 δ): 0.75 (3H3 t, J = 7.3Hz), 1.11 (2H, m) 3 1.34 (2H, m) 3 2. 13 (2H, t3 J = 7.4Hz), 2.51 (3H3 s), 5.59 (2Η, s) 3 6 · 57 (1Η, d, J 2: 8.5Ηζ), 7.32 (1H, dd, J 2.2 and 8.4Ηζ), 7.57 (1Η, d, J 2: 8.6Ηζ), 7.67 (1Η, dd , J = 1.6 and 8. · 6Ηζ), 7.73 (1Η, d, J = 2 · 1Ηζ), 8.08 (1Η, d, J · 2 · 6Ηζ). IR (KBr): 17060111 ^ mp: 213.0 —216.0 ° C. &Lt; Example 288; Synthesis of 2,4-difluorenyl-6-fluorenyloxybenzimidazole &gt; According to the method described in Journal of Medicinal Chemistry 1993, 36, 4040-4051, use 4-Amino-3-methylbenzoic acid methyl ester to give 4-acetamido-5-amino-3-methylbenzoic acid methyl ester. Then heated under reflux in acetic acid for 2 hours to give 2, 4-dimethyl-6-methoxycarbonyl Benzo at 17 m 11. [Physical properties of compounds] lH-NMR (CDCl3, δ): 2.55 (3H, s), 2.62 (3H3 s) 3 3.91 (3H5 s), 7.74 (1H5 s) 3 8 · 07 ( 1Η, s), 10.65 (1H, br s). &Lt; Example 289; 1- (2,4-dioxobenzyl) -2,4-dimethyl-6-methoxycarbonylbenzimidazole ( Synthesis of 353) &gt; Stir 2,4-dimethyl-6-oxobenzoylbenzoxazone (0.900g), 2,4-dioxobenzyl gas (1.20g), iodine at 80 ° C A mixture of sodium chloride (0.200g), potassium carbonate (0.610g), and N, N-dimethylamidamine (4ml) for 16 hours. After removing the organic solvent under reduced pressure, ethyl acetate and water were added for extraction. Concentrate the organic layer, add hexane to crystallize it. Filter out the crystals, ___165___ This paper is suitable for Jfl Chinese National Standard (CNS) A4 specification (210X297 mm) 548272 A7 B7 V. Description of the invention (26h after drying to obtain 1.08 g of (2,4_dichlorobenzyl) · 2,4_dimethyl-6_methoxycarbonylbenzimidazole (353). [Physical properties of compound (353)] (Read the precautions on the back before filling this page) 'H-KMR (CDCl3, d): 2.58 (3H, s), 2.71 (3H, s), 3.90 (3H, s ) j 5.39 (2H, s) 6.30UH, d, ㈣, he), 7.07 (1H, pyr J = 8 4 and 20 Hz), 7 49 (ih, d, ruler such as Z), 7.75 (1H, s ), 7.81 (1H, S). &lt; Bex Example 29〇; 6-Ikisyl-l- (2,4-dioxobenzyl) · 2,4-dimethyl-6-methoxycarbonylbenzimidazole (354) Synthesis> Basis The method of Example 53 uses di (2,4-dichlorobenzyl) -2,4-dimethyl-6-methoxycarbonylbenzimidazole (0501 g) to obtain 6-carboxyl-1 -(2,4 · Dichlorobenzyl) _2,4-difluorenyl-6-fluorenyloxycarbonylbenzimidazole (354) 0.435 g 〇 [Physical properties of compound (354)] fNMiUDMSO-d6, d) ·· 2.51 (3Η, s), 2.55 (3Η, s), 5.57 (2Η, s), 6.49 (1Η, d, J = 8.4Hz), 7.31 (1Η3 dd3 J: 8.4 And 2 · 2Ηζ), 7.62 (1Η, s), 7.72 (1Η, d, J = 2.0Hz), 7.78 (1Η, s), 12.64 (1H3 br s). &lt; Example 291; Synthesis of 6- (1-butanesulfonylaminofluorenyl) _1- (2,4_dichlorobenzyl) _2,4_difluorenylbenzimidal (355) &gt; According to the method of Example 98, using 6-carboxy-: u (2,4-dichlorobenzyl) -2,4-dimethyl-6-methoxycarbonylbenzimidazole (0435g), N, N, _ carbonyldiimidazole (0.290g), 1-butanesulfonamide (0246g), diazabicycloundecene (0.273g) to give the heart (1 · butanesulfonylcarbamoamidinyl dichloride Benzyl) -2,4-difluorenylbenzimidazole (355) 04688. [Physical properties of compound (355)] ------— 266___ This paper size applies to Chinese National Standard (CNS) A4 specification (210X297). 548272 A7 ________________ B7 V. Description of the invention (26) Please fill in this page again for attention) Η-NMR (DMSQ-d6, ά): G.84 (3H, t, J = 7.4Hz), L38 (2H, m), 1.64 (2Η, m), 2 · 49 (3H, s), 2.56 (3Η3 s), 3.48 (2Η, t), 5.55 (2H, s), 6.40 (1Η, d, J = 8.5Hz), 7.31 (1Η3 dd3 J = 2.1 and 8 · 4Ηζ), 7.64 (1Η, s), 7.75 (1Η, d, J: 2.1Hz) 3 7 · 90 (1H3 s), 11 · 79 (1Η, br s) IR (Nujol): 16820111 ^ 0 mp: 180.0-181.5 ° C. &Lt; Production Example 58; Production of 4-phenoxybenzyl alcohol &gt; Sodium borohydride (0.48 g) was added to 4-benzyloxy In a solution of benzoxaldehyde (4 96 g) in ethanol (20 ml), stir at room temperature for 15 hours. After concentration, '3 butyl methyl ether and water are added for extraction. The organic layer is concentrated to give 4-phenoxy Benzyl alcohol (4.84 g). [Physical properties of the compound] W-fiMIUCDCh, 6): 4 ·· 67 (2Η, d, J = 5, 7Hz), 6.99_7 · 01 (4Η, m), 7 · 1 〇 (1Η, t5 J 2 7.4Ηζ ), 7.32-7.35 (4Η, melon). &lt; Production Example 59; Production of 4 · phenoxybenzyl chloride &gt; Thionyl chloride (13.34 g) was added to 4-phenoxybenzyl alcohol (4 06 g), and the mixture was stirred at 80 C for 3.5 hours. . After concentration, ethyl acetate and water were added for extraction. The organic layer was concentrated to give 4-phenoxybenzyl chloride (4.31 g). [Physical properties of the compound] T-boat (CDC13, 6): 4. · 58 (2Η, s), 6.96-7 · 03 (4Η,…, 7_u-77 1H, porphyrin 7 32-7 · 37 ( 4Η, m) &lt; Example 292; Synthesis of 6-ethoxycarbonyl-2-methyl-1- (4-phenoxybenzyl) benzimidazole (356) &gt; According to the method of Example 263, use 4-Ethylamido-3-aminoamino ----- 267___ This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 548272 A7 B7 V. Description of the invention (26) 乙酯 Ethyl benzoate (0.56g), sodium carbonate (0.33g), sodium iodide (0.12g), 4-phenoxybenzyl gas (0.66g) to give 4-acetamido-3 _ [(4-benzene Oxygen) benzylamino] ethyl benzoate (0.49g). Then convert it to 6-ethoxyquinyl-2-methyl small (4-benzyloxybenzyl) benzimidazole (3 56) (0.44 §). [Physical properties of 4-ethylamidoamino-3-[(4-benzyloxy) benzylamino] ethyl benzoate] ^ -NMRiCDCla, δ): 1.37 (3H, t3 J = 7.1Hz), 2.04 (3H3 s), 4.18 (1H3 br s), 4.3.1-4 · 36 (4Η, m), 6.98-7.G2 (4H, m), 7.09-7.12 (lH, m), 7.27- 7.51 (8Η, m). [Physical properties of compound (356)] 屮 leg ⑽⑴, (Π ·· 1 · 40 (3Η, t3 J: 7.1Hz), U1 (3H, s), 4 · 39 (2Η, q, J 2 7.1 Hz ), 5.35 (2H, s), 6.92-6.95 (2Η, m), 6.97-7 · 〇〇 (2Η, m), 7.02 (2H, d, J = 8.7

Hz), 7.09-7.13 (1H3 a), 7.31-7.34 (2H, m) 3 7.72 (1H, d3 J-8.6Hz) 5 7.98 (1H3 dd, J = 1.5 and 8.4Ηζ), 8.04 (1Η , D, J 1.2Hz). &lt; Example 293; Synthesis of 6-carboxy-2-methyl-l- (4-phenoxybenzyl) benzimidazole (357) &gt; According to the method of Example 53, 6-ethoxycarbonylmethyl was used _ 1- (4-phenoxy) benzylbenzimidazole (〇44§) to give 6_carboxy_2_fluorenyl_1_ (4-benzyloxybenzyl) benzimidazole (357) 0.37 g. [Physical properties of compound (357)] 'H-NMR (DMS0-d6),); 2.57 (3H) s) &gt; 5.54 (^^? ^. 13⑽, π), 7,33_7.37⑽, 7 6〇 ( iH, d, j = 8 4 Hz), 'π⑽, ^, sunda), 8.07 (1Η, s), 12.72 (1Η, br s). &lt; Synthesis Example 294; Synthesis of 6- (1-butanxanthenylaminofluorenyl) _2_methyl-bu (4-benzyloxybenzyl) benzimidazole (358) &gt; Method, using 6_carboxymethyl_ 丨 _ (4_benzene paper size applicable to Chinese National Standard (CNS) A4 specification (210X 297 mm) 548272 A7 B7 5. Description of the invention (oxybenzyl) benzimidazole (0.36 g), N, N, -carbonyldiimidazole (0.24 g), 1-butanesulfonamide (0.21 g), diazabicycloundecene (0.23 g) to give 6- (1_ butanesulfonyl Carbamate) -2-methyl-1- (4-phenoxybenzyl) benzimidazole (358) 0.19 g. [Physical properties of compound (358)] 1H-NMR (DMS0-d63 δ): 0.85 ( 3H, t, J 2 7. 4Ηζ), 1.40 (2Η, m), 1.68 (2Η, m), 2.54 (3Η, s), 3.52 (2Η, t, J 2 7 · 87ζ) , 5.51UH, s), 6.96-6 · 98 (4Η, m), 7.11 (1Η, t, J 2 7.4Ηζ), 7.17 (2Η, d, J 2 8.6Ηζ), 7.34 -7 · 37 (2Η, m), 7.64 (1Η, d, J = 8.5Ηζ), 7.79 (1Η, dd, J = 1.5 and 8.5Ηζ), 8.24 (1Η, s) , 11 · 92 (1Η, br s). m (Nujol): 1632CDT1. mp: 183.4 — 184.4 ° C. &lt; Example 295; Synthesis of 6-ethoxycarbonyl-2-methyl-1- (2-pyridylmethyl) benzimidazole (359) &gt; According to the method of Example 263, 4-acetamidoamino group was used Ethyl-3-aminobenzoate (0.600 g), sodium carbonate (0.445 g), hardened sodium (22 g) and 2-chloropyridylpyridine (0.413 g) to give 6-ethoxy Carbonyl-2-methyl-1- (2-leaf b-methyl) benzo-flavin (3 5 9) 0.65 6 g. It was used directly in the reaction described below. The Ministry of Economic Affairs has worked hard to eliminate the cooperation private seal ^ (Read the precautions on the back before filling this page) 〈例-例 296; 6-carboxy-2-methyl-1- (2- Synthesis of pyridylmethyl) benzimidazole (360)> According to the method of Example 53, 6-ethoxyweilyl_2_methyl_1- (2-αbipyridylmethyl) benzimidazole ( 〇656g) to obtain 6_carboxy_2_methyl_1- (2- ° specific bite methyl) benzoacetone (360) 0.532g. [Physical properties of compound (360)] This paper is suitable for Chinese National Standard (CNS) A4 specification (210X297 mm) 548272 A7 B7 V. Description of the invention (2 to 1H ~ NHR (DMS0-d6, δ): 2.56 (3H , s), 5.56 (2H, s) 3 7.22 (1H, d, J = 7.9Hz), 7. 28 (1H, dd3 J = 5.0 and 7.1Hz), 7.45 (1Η3 d3 J: 8.3Hz), 7.74-7.79 (2Η, m), 7.95 (1H, s), 8.48 (1Η, d, J = 8.5Hz) &lt; Example 297; 1- (butylsulfonylamino) Synthesis of methylmethyl) -2-methyl-1_ (2-pyridylmethyl) benzimidazole (361) &gt; According to the method of Example 98, 6-carboxy-2-methyl-1- (2-17 Pyridinyl) benzimidazole (0.500 g), n, N, -carbonyldizolidazole (0.394 g), 1-butanesulfonamide (0.334 g), diazabicycloundecene (〇37. g) 0.142 g of 1- (butytazinemethylcarbamoyl) -2-amidino-1-(2-σ specific methyl) benzimidazole (361). [Physical properties of compound (361)] lH-NMR (DMS0-d6, δ): 0.83 (3Η, t, J = 7.3Hz), 1.28-L36 (2H3 m) 3 1.52-1.58 (2H, m), 2.55 (3Η, s) 3 3 · 06 (2Η, t, &lt; I = 7 · 9Ηζ) 3 5 · 56 (2Η, s), 7.17 (1H, d, J 2 7 • 8Hz), 7.29 (1H, dd, J = 4.2 and7 · 3Ηζ), 7 · 43 (1Η, d5 J, 2 · 4Ηζ), 7.77 (1Η, dt, J = 1.8 and 7.7Ηζ), 7.81 (1Η, dd3 J = 1.4, and 8.48ζ ), 7.96 (1Η, s), 8.50 (1Η, d3, 4.7Hz) m (Nujol): 1674cm-1. Πιρ ·· 139 ° C (decomposed) · <Solution. Example 298; 6-B Synthesis of oxycarbonyl-2-methyl-1- (4-nitrobenzyl) benzimidazole (362) &gt; According to the method of Example 263, 4-ethylamidoamino-3-aminobenzoic acid ethyl Ester (0.67 g), calcium carbonate (0.39 g), sodium iodide (0.14 g), and 4-nitrobenzyl bromide (0.78 g) to give 6-ethoxycarbonyl-2-methyl- : 1- (4-nitrobenzyl) benzimidazole (362) 0.5 lg. ____ 3 minutes ---- This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) ------ --- f (Read the precautions on the back before filling in this page)

1T 548272 A7 --___________________________ B7_ V. Description of the invention (26) [Physical properties of compound (362)]

lH-NMR (CDCl33 δ): L39 (3H5 t, J = 7.1Hz), 2.59 (3H, s), 4.38 (2H, q3 J = 7.1H (诮 Please read the precautions on the back before filling this page) z) 3 5.49 (2Η, s), 7.2G (2H3 d, J: 8.6Hz), 7.76 (1Η, d, J: 8.5Hz), 7.94 (1Η, d, JHHz), 8.01 (1Η, dd3 J: 1.4 and 8.5Hz), 8.20 (2Η5 d5 J: 8.6Hz) ·) Physical properties 3

'H'NMRiCDCL ·, δ): 1.39 (3H5 t, J-7.1Hz), 2.59 (3H, s), 4-38 (2H5 q, J = 7.1H z), 5.49 (2Η, s), 7 · 20 (2Η, d, J = 8 · 6Ηζ), 7.76 (1Η, d3 J = 8.5Hz), 7.94 (1Η, d, J = l.lHz), 8.01 (1Η, dd , J: 1.4 and 8. · 5Ηζ), 8.20 (2Η, d, J: 8.6Hz) ·) Physical properties] lH -_ (CDC13, (5): 1.39 (3Η3 t, J = 7.1Hz), 2.59 (3H, s), 4.38 (2Η, q, J = 7.1H z) 3 5.49 (2H3 s) 3 7.20 (2H, d, J = 8.6Hz) 3 7.76 (1H, d3 J-8.5Hz) , 7.94 (1H3 d3 J = 1.1 Hz), 8.01 (1Η, dd, J: 1.4 and 8.5Hz), 8.20 (2H, d, J: 8.6Hz) &lt; Example 299; 1- (4 -Aminobenzyl) -6-ethoxycarbonyl-2-methylbenzo &quot; Synthesis of 7-million (363) &gt; ethanol (6ml) and acetic acid (0.8ml) were added to 1- (4-nitro Base group) _6_ ethoxy 1 ^ analyl-2-methylbenzyl sigma (0.50 g), reflow iron (0.57 g), reflux for 4.5 hours. Add water, ethyl acetate for the purpose Extraction. The organic layer was washed with water, dried, and concentrated under reduced pressure to obtain 0.46 g of 1- (4-aminobenzyl) -6-ethoxycarbonyl-2-fluorenylbenzimidazole (363). Central Ministry of Foreign Affairs and Consumer Cooperation Sugiyin ^ [Physical properties of compound (363)] ΐ-ugly (CDCL ·, (5): 1.40 (3Η, t, J: 7.2Hz), 2.59 (3Η, s), 4.38 (2H, q3 J: 7.2 H z), 5.25 (2Η, s), 6.61 (2Η, d, J 2 8.6Ηζ), 6.87 (2Η, d, buckle 8.6Ηζ), 7.71 (ιη, d, J = 8.3Hz), 7.96 (1Η3 dd5 J 2 1.5 and 8 · He), 8.05 (1Η, d, J: i. 3Hz). &Lt; Example 300; l-[(4-Benzene Amine) benzyl] Synthesis of 6-ethoxyquinylmethyl benzimidazole (364) &gt; ------- 2J4 --_____ The paper size is in accordance with China National Standard (CNS) A4 size (210X297 (Mm) 548272 A7 B7 V. Description of the invention (26g) (Read the precautions on the reverse side and fill in this page) Add a solution of phenylhydrazine (0.25g) in chloroform (4ml) to 1- (4 -Aminobenzyl) -6-ethoxycarbonyl-2-methylbenzimidazole (0.45 g) and a pyridine (0.155 g) in a solution of trichloromethane (8 ml), and stirred at room temperature for 16 hour. Water and chloroform were added for extraction. The organic layer was concentrated under reduced pressure to give 1-[(4-benzylamine) benzyl] -6-ethoxycarbonyl-2-fluorenylbenzimidazole (364) 0.33 g of [Compound (364) Physical properties) ^ NMRiCDCL ·, δ): L40 (3H, t, J-7.1Hz) 3 2.59 (3H, s), 4.38 (2H3 q3 J-7.1H z), 5.37 (2H, s), 7.06 (2H3 d3 J = 8.5Hz), 7.46-7.50 (2H, m), 7.53-7.57 (1H, m), 7.61 (2Η, d, J = 8.5Hz), 7.72 (1Η, d, J: 8) Hz), 7.84-7 · 86 (2Η, m), 7.89 (1 H, br s), 7.98 (1Η, dd, J = 1.5 and 8. · 5 · ζ), 8.03 (1H, s) · & lt Example 301; Synthesis of l-[(4 · Benzamidine) benzyl] -6-carboxy-2-methylbenzimidazole (365) &gt; According to the method of Example 53, 1-[(4 -Benzylamine) benzyl] -6-ethoxycarbonyl-2-methylbenzimidazole (0.31 g) to give 1-[(4-benzylamine) fluorenyl] -6-weiyl-2- 0.28 g of methyl benzo saliva (365). [Physical properties of compound (365)] Ή-NMR (DMS0-d6,6): 2.58 (3Η, s), 5.52 (2Η, s) 3 7 · 12 (2Η, d, J: 8,5Hz ), 7.48-7.52 (2Η, m), 7.54-7 · 58 (1Η, m), 7.61 (1Η, d, J = 8 · he), 7.73UH, d, J 8. 6Hz), 7.79 (1Η3 dd, J = 1.5 & 8.4Ηζ) 57 · 90-7 · 92 (2Η, ιη), 8.07 (1Η, (13ΐM · 2Hz ;, 10 · 26 ( 1Η, s), 12 · 73 (1Η3 br s) · &lt; Example 302; l-[(4-phenylamidino) benzyl] -6- (1-butanesulfonylaminofluorenyl)- Synthesis of 2-methylbenzimidazole (366) &gt; According to the method of Example 98, using 1-[(4-benzylamine) benzyl] -6- ---------- Ύ1Ύ ___________ Paper size applies to Chinese national standard (CNS> A4 specification (210X297 mm) A7 548272 B7 V. Description of the invention (26 $ Weiji-2-methyl Benzo miso (0.26g), N, N'_ 罗 炭 基 二Taste saliva (〇 ”7g), (Read the precautions on the back before filling in this page) Pubusulfonamide (0.14g), diazabicycloundecene (0.16g) to get the [[4- Phenylamino) benzyl] -6- (1-butanesulfonylcarbamoyl) -2-methylbenzopyrene (366) 0.14 g. [Compound (366) Properties] Ή-NMR (DMS0-d6, d): 0.85 (3Η, t, J 二 7.4Ηζ), 1.40 (2Η5 m), 1.68 (2Η, in), 2.56 (3Η3 s) 3 3 · 52 (2Η, t3 J: 7.8Hz) 3 5 · 50 (2Η, s), 7 · 15 (2Η, d, J: 8.6Hz), 7 · 5

0 (2H3 t3 J-7.5Hz), 7.55-7,59 (1H3 m), 7.64 (1H, d3 J = 8,5Hz) 3 7.74 (2H3 d3 J two 8.6Ηζ) 3 7.79 (1Η, dd , J: 1.6 and 8.5 Hz), 7.90-7 · 92 (2Η, m), 8 · 24 (1Η, d, J = 1.3Ηζ), 10 · 27 (1Η, s), 11.92 (1H3 br s) IR (Nujol): 1693cm-1. Mp: 267.5-268.1 ° C. <Cut Example 203; 6-ethoxydienyl-2-methyl-l- [4- (2-phenylethenyl) benzyl Synthesis of benzimidazole (367) &gt; According to the method of Example 263, 4-ethylamidoamino-3-aminobenzoic acid ethyl ester (0.405 g), calcium carbonate (0.253 g), and iodination were used. Sodium (0.082g) and 4-chlorofluorenylstilbene (0.500g) to give 6-ethoxycarbonyl-2-methyl-1- [4- (2-styryl) benzyl] benzyl Imidazole (367) 0.32 g. [Physical properties of compound (367)] NMRiCDCL ·, δ): 1.40 (3H3 t, J = 7.2HJz), 2.6 (3H, s), 4.38 (2H, q, J = 7.1H z), ό · 38 ( 2Η, s), 7 · (Π-7 · 09 (4Η3 m), 7.26 (1H, t, J 2 7.4Ηζ), 7.35 (2Η, t, J 2 7 • 5Hz), 7.45 (2H, d, J = 8.2Hz), 7 · 49 (2Η, d3 J = 7 · 5Ηζ), 7 · 73 (1Η, d, J = 8.5Hz) 3 7 · 99 (1Η, dd, J = 1.5 and 8 · 4Ηζ), 8 · 30 (1Η, d, J = 1.2Hz) &lt; Example 304; 6-ethoxycarbonyl-2-fluorenyl-l- [4- (2-phenethyl) _____273___ Paper size Tong J1] Chinese National Standard (CNS) A4 specification (21 OX 297 mm) 548272 Passed by the central ministry of Shanghai Ministry i?: ^-^ HT-elimination cooperation cooperation printed ¾ A7 5. Description of the invention (27j ~-benzyl) Synthesis of benzimidazole (368)> Add 5% palladium-carbon to 6-ethoxycarbonylmethyl 1- [4- (2-styryl) benzyl] benzimidazole (0,32) under nitrogen atmosphere. g) in ethanol (10 ml), and stirred under a hydrogen atmosphere for 23 hours. The solid 2 was filtered off, and the filtrate was concentrated to give 6-ethoxycarbonyl-2-methylphenethyl) benzyl] benzyl. Benzimidazole (368). It was used directly in the following reaction. &Lt; Besch Example 305; 6-Diene Synthesis of fluorenyl_1- [4- (2_benzylethyl) benzyl] benzimidazole (369)> According to the method of Example 53, 6_ethoxycarbonyl_2_methyl_1 · [ 4- (2-phenethyl) benzyl] benzimidazole (〇283g) to give 6-carboxy-2_fluorenyl-1- [4- (2-phenethyl) benzyl] benzimidazole ( 369) 0242 g. [Physical properties of compound (369)] HNMR (DMS0 d6, (5): 2.56 (3Η, s), 2.82 (4Η, s), 5.51 (2Η3 s), 7. · 02 (2Η, d, J 8 · 1Ηζ), 7.1, 7.27 (7Η, m) 3 7 · 61 (1Η, d, J = 8.4Hz), 7 · 78 (1Η, dd, J = 1.5 and 8 · 〇4 (1Η, s), 12.72 (1Η, s). <Example 306; 6- (l-butanesulfonylcarbamoamido) -2-methyl- [4- (2-benzene Ethyl) benzyl] Synthesis of benzimidazole (37〇) &gt; According to the method of Example 98, 6-carboxy-2-fluorenyl-l- [4- (2-benzylethyl) &gt; Benzimidazole (0.225 g), N, N ,. jidizodiazole (1.214 g), 1-butanesulfonamide (〇el67 g), diazabicycloundecene (〇185 g) to give 6 -(1-butanesulfonylcarbamoyl) -2-methyl- [4- (2-phenethyl) benzyl] benzimidazole (370) 0.249 g. [Physical properties of compound (370)] II-NMR (DMS0-d6, &lt; 5) ·· 86 · (3Η, t, J = 7.4Hz), 1.35-1 · 42 (2Η, m), 1 · 63-1 · 71 (The paper size is suitable / 1) Chinese National Standard (CNS) A4 size (210X297mm) (Read the precautions on the back before filling this page)

1T 548272 A7 B7 V. Description of the invention (27i 2H, m) 3 2.53 (3H, s) 3 2.83 (4H3 s) 3 3.52 (2H, t3 J-7.7Hz), 5.49 (2H, s), 7. 04 (2H, d, J-8.0Hz), 7.12-7.25 (7H3 m) 3 7.64 (1H3 d, J = 8.4Hz), 7.79 (1H3 dd, (Read the precautions on the back before filling this page) J = 1.7 and 8. · 5Ηζ), 8.22 (1Η, d3 J: 1.3 Hz), 11.92 (1Η, s) · IR (Nujol): 1682cm-l. Mp: 95.4-99.0 ° C. &Lt; Manufacturing Example 6; Production of 4-benzylbenzyl bromide &gt; According to the method of Production Example 48, 4-methylbenzylbenzene (3.92 g), N-bromopropylamidamine (4.28 g) and 2,2 were used. , -Azobisisobutyronitrile (0.40 g) to give 4-phenylhydrazone benzyl bromide (5.28 g). [Physical properties of compound] 'H-NMIUCDCL · ， ά) ··· 54 (2Η, s), 7.47-7 · 52 (4Η, in), 7.58_7 · 62 (1Η, m) 3 7.77- 7.82 (4Η, m). &Lt; Example 307; Synthesis of 1 _ [(4-phenylfluorenyl) benzyl] -6-ethoxycarbonyl-2-methylbenzimidazole (371) &gt; The method of Example 263 uses ethyl 4-acetamido-3-aminobenzoate (0.56 g), sodium carbonate (0.33 g), sodium iodide (0.11 g), and 4-benzylbenzyl bromide. (0.83 g) to give 1-[(4-phenylfluorenyl) benzyl] -6-ethoxycarbonyl-2-fluorenylbenzimidazole (371) (0.70 g). [Physical properties of compound C371] Ή-NMR (CDCl ·, (5): 1.40 (3Η3 t, J = 7.2Hz), 2.61 (3Η3 s), 4.39 (2Η3 q, J = 7.2H ζ), 5.47 (2Η, s), 7.14 (2Η, d, J: 8.2Hz), 7.45-7 · 48 (2Η, m), 7.5fi-7.60 (lh, m), 7.74 -7 · 77 (5Η, m), 7.99-8 · 02 (2Η, m) · &lt; Example 308; l-[(4-phenylhydrazone) benzyl] -6-carboxy-2-methyl Synthesis of benzimidazole (372) &gt; 275_ This paper size is applicable to Chinese National Standard (CNS) A4 (210X 297 public directors) 548272 Ministry of Economic Affairs ^-^ h_T Elimination cooperation Sugihara A7 B7 V. Description of the invention (27 $ According to the method of Example 53, ^ [(4-phenylfluorenyl) benzyl 6-ethoxycarbonyl-2-fluorenylbenzimidazole (0.68 g) was used to obtain [[4 -Phenylhydrazone) benzyl] -6-carboxy-2-fluorenylbenzilide (372) (0.55g). [Physical properties of compound (372)] Η-NMR (DMSGU) ····· 57 (3Η, s), 5.71 (2Η, s), 7.25 (2Η, d, J: 8.2Hz), 7 • 52 (2H, t, J = 7.7Hz) 3 7 · 62-7 · 66 (2Η, m) 3 7 · 68-7 · 72 (4Η, m), 7 · 80 (1Η, dd, J 2 1.3 and 8.4Ηζ), 8 · 08 (1Η, d, J: l) Hz), 12,72 (1H, br s) &lt; Example 309; l- [ (4-Benzamidine) benzyl] -6- (1-butanesulfonylcarbamoyl) -2-methylbenzimidazole (373) &gt; According to the method of Example 98, 1- [ (4-Phenylhydrazine) benzyl] -6-carboxy · 2-fluorenylbenzofluorene (0.52g), N, N'-Weiyldiimidofluorene (0.34g), 1-butanesulfonamide ( 0.29 g), and diazabicycloundecene (0.32 g) to give i-[(4-phenylhydrazone) benzyl] -6- (1-butanesulfonylaminocarbamyl) -2- 0.13 g of methyl benzimidazole (373). [Physical properties of compound (373)] 1H-NMR (DMS0-d6, δ): 0.84 (3H, t5 J-7.4Hz) 3 1.38 (2H, m) 3 1.66 ( 2H, m) 3 2 • 54 (3H, s), 3.48 (2Η, t, J = 7.7Hz), 5.67 (2H, s), 7.27 (2Η, d, J = 8.2Hz), 7.5 1-7 · 55 (2Η, melon), 7.63-7 · 73 (6Η3 m), 7.81 (1Η3 dd, J 1.6 and 8.5Ηζ), 8 · 21 (1Η, d, J = 1.4 Hz) IR (Nujol): 1660cm-l.mp: 111.0-112.4 ° C.

Mass (FAB): m / e 490 (M + 1). &Lt; Example 310; Synthesis> __________ 276 This paper size applies Chinese National Standard (CNS) A4 (210X 297 mm) '' '(Please read the precautions on the back before filling this page)

1T 548272 A7 B7 V. Description of the invention (according to the method of Example 53, 6-ethoxycarbonyl-2-methyl-1-[4- (2-styryl) benzyl] benzimidazole (0.500g ) To obtain 0.237 g of 6-endyl_ 2-fluorenyl- [4- (2-styryl) benzyl] benzimidazole (374). [Physical properties of compound (374)] $ -NM (DMS0- d6,6): 2.59 (3H, s), 5.58 (2Η, s) 3 7,12 (2H, d, J = 8.2Hz) 3 7. 21 (2H, s) 3 7 · 26 (1Η, t, &gt; 7.4Ηζ), 7.36 (2Η, t, J: 7.6Hz), 7.57 (4Η3 d3 J 2 8.0 Hz), 7.62 (1Η, d3 J = 8.4Hz), 7.79 ( 1H, dd3 J = 1.5 and 8 · 4Ηζ), 8 · 07 (1Η, d, J = 1 · 2Ηζ), 12 · 73 (1Η, s). &Lt; Example 311; 6- (1-butylsulfonium Synthesis of aminocarbamoyl) -2-methyl- [4- (2-styryl) benzyl] benzimidazole (375) &gt; According to the method of Example 98, 6-carboxy-2-methyl was used -[4- (2-styryl) benzyl] benzimidazole (0.237 g), N, N'-carbonyldiimidazole (0.209 g), 1-butanesulfonamide (0.176 g), diazonium Bicycloundecene (0.15 g) to give 6- (1-butanesulfonylcarbamoyl) -2-methyl- [4- (2-styryl) benzyl] benzimidazole ( 375) 0. 239g. [Physical properties of compound (375)] Jinglai-Jiangzhong sample-like jujube 杓 Η Η 贽 · # 印 繁 (Please read the precautions on the back before filling this page) Ή-NMR (DMS0-d6, 6 ): 〇 · 86 (3Η, t, J = 7.4Hz), 1.35-1 · 43 (2Η, m), 1.63-1 · 70 (2Η, m) 3 2 · 56 (3Η, s) , 3.52 (2Η, t3 J = 7.6Hz), 5.55 (2Η, s), 7.15 (2Η, d3 J 2 8 • 2Hz), 7.22 (2Η, s) 3 7 · 26 (1Η, t, J = 7.4Hz), 7 · 36 (2Η, t, J = 7.6Hz) 3 7 · 57 (1Η, d, J = 7 · 3Ηζ), 7 · 58 (1Η, d, J: 8.2Hz) , 7.66 (1Η, d, J: 8.5Hz), 7.80 (1Η, d, J 2 8.4Ηζ), 8.24 (1Η, s), 11 · 93 (1Η3 brs). IR (Nujol ): 1680cm-l. Mp: 140.3-143.4 ° C. &Lt; Example 312; l- (dibenzofuran-2-methyl) -6-ethoxycarbonyl-; _____777 _______ This paper size applies to Chinese national standards (CNS) A4 specification (210X297 mm) 548272 A7 B7 Printed by the Ministry of Economics and Trade and co-operation private printing V. Description of the invention (274 Synthesis of 2-methylbenzimidazole (376) &gt; According to Example 263 Method, using ethyl 4-acetamido-3-aminobenzoate (0.480 g), Sodium carbonate (0.274 g), moth sodium (0.097 g) and 2-bromomethyldibenzofuran (0.56 g) to give l- (dibenzoαfuran-2-yl) ) -6-Ethoxydiyl-2-fluorenylbenzoacetone (376) 0.47g. [Physical properties of compound (376)] NMRiCDCL ·, δ): 1.38 (3H, t, J = 7.1Hz), 2.62 (3H, s) 5 4.36 (2H, q5 J = 7.1H z), 5.54 ( 2Η, s), 7.19 (1H, dd, J = 1.6 and 8.5Ηζ), 7.32 (1Η, t, J = 7.6Hz), 7 • 43-7 · 59 (4Η, m) 3 7 · 76 (1Η, d, J = 8.4Hz), 7.85 (1Η, d, J = 7.1Hz), 8.00 (1Η, dd, J = 1.3 and 8.4Ηζ), 8.07 (1Η, d, J = 1.2Hz). &Lt; Example 313; Synthesis of 6-carboxyl- (dibenzofuran_2_fluorenyl) -2-methylbenzimidazole (377) &gt; Method according to Example 53 , 6-ethoxycarbonyl-2-methylbenzimidazole (0.46g) was used to obtain 6-carboxy-1- (dibenzopyran-2-fluorenyl) -2-fluorenylbenzimidazole (377 ) 0.336g. [Physical properties of compound (377)] MMIUDMSO-d6,6): 2.63 (3Η, s), 5.71 (2Η, s), 7.27 (1Η, d, J = 8 · 5Ηζ), 7. · 36 (1H, t5 J = 7.5Hz), 7.50 (1H, t), 7,61-7.68 (3H, m) 3 7.78 (1H3 d, J = 8-3Hz), 7-97 (lH, s) ^ 7.07-8-11 (2H, m). &Lt; Example 314; l- (dibenzo.furan_2-methyl) -6- (1-butyxanthenylaminofluorenyl) -2-methyl Of Benzobenzimidazole (378) &gt; According to the method of Example 98, 6-carboxy-1_ (dibenzofuran-2-methyl) -2-methylbenzimidazole (0.255 g), N, N, -carbonyldiimidazole (0.197g), busulfenylamine (0.167g), diazabicycloundecene (〇i85g)

2JLS The size of this paper applies Chinese National Standard (CNS) A4 (210x297 mm) (Read the precautions on the back before filling this page) Order 548272 A7 B7 V. Description of the invention (27¾ to get 1- (dibenzo Furan-2-methyl) -6- (1-butanesulfonylcarbamoyl) -2-methylbenzimidazole (378) 0.249 g. [Physical properties of compound (378)]

Ή-NMR (DMS0-d6, tf): 0.81 (3Η, t, J: 7.4Hz), 1.36 (2Η, m), 1.65 (2Η, m), 2.60 (3H, s ), 3.50 (2Η, t, J: 7.7HZ), 5.69 (2Η, s), 7.29 (1H, dd, J: 1.96 and 8 • 7Hz), 7.34-7 · 38 (1Η, m), 7.48-7.52 (1Η, m), 7.63-7 · 68 (3Η, m), 7.81 (1Η3 dd, J = 1.7 and 8.5Ηζ), 8.00 (1Η , D, 8.94 (1Η, d, J: 7.1Hz), 8.28 (1H, d3 J = 1.4Hz), 12.70 (1H, br s). IR (Nujol): 1682cm ~ l. Mp: 224.1-229.8 ° C. &Lt; Production Example 61; Production of N-1-butanesulfonyl-3-ethylamido-4-nitrobenzopyramine &gt; According to the method of Production Example 28, 3-acetamidine was used. 4-nitrobenzoic acid (5.15g), N, N'-carbonyldiimidazole (5.59g), 1-butanesulfonamide (4.73g), diazabicycloundecene (5.25g) to obtain N_1-Butylsulfonyl-3-acetamido-4-nitrobenzopyrene (6.30g). [Physical Properties of Compounds] The Ministry of Economic Affairs is involved in 榀 ^-and only the consumer cooperation cooperates with India (please (Please read the precautions on the back before filling this page) lH-NMR (DMS0-d6, 6): 0.87 (3H, t, J = 7.4Hz), 1.40 (2H, m), L68 (2H, m) 3 Z. 07 (3H, s), 3.51 (2Η, t ), 7.83 (1H, dd, J = 1.8 and 8.5Ηζ), 8.03 (1Η, d, J = 8.5Hz), 8.07 (1H, d, J = L8Hz), 10,43 (1H, s ), 12,64 (1H, br s). &Lt; Production Example 62; Production of N-1-butanesulfonyl-3-amino-4-nitrobenzopyramine &gt; Stir N at room temperature -1-Butylsulfonyl-3-ethylamidoamino_4-nitrobenzofluorenamine (6.30g), 10% aqueous sodium hydroxide solution, ethanol (300mi), and water_ 279 Applicable to paper size Chinese National Standard (CNS) A4 specification (210X297 mm) 548272 A7 B7 V. Description of the invention (27i (please read the precautions on the back before filling this page) (200ml) mixture for 4 hours, then stir at 50 ° C for 3 hours After about 1/2 volume of the solvent was distilled off, it was adjusted to pH 2 using 10% hydrochloric acid. The precipitated crystals' were collected and dried under reduced pressure to obtain N-1-butanthino-3-amino-4-nitrobenzofluorenamine (5.22 g). [Physical properties of compound] H-NMR (DMS0-d6, δ): 0.87 (3H5 t3 J = 7.4Hz), L40 (2H3 m) 3 1.66 (2H, m), 3. 49 (2H, m), 6.99 ( 1H, dd3 J = 1.8 and 9 · 0Ηζ) 3 7 · 49 (1Η, d, cM.8Hz), 7.55 (2Η, br s), 8 · 04 (1Η3 d, J = 9.0Hz), 12 · 28 (1Η, br s) · <Production Example 63; Production of N-1-butanesulfonyl-3- (2,4-dichlorobenzylamino) -4-nitrobenzoate &gt; Stir N-1-butanesulfonyl-3-amino-4-nitrobenzofluorenamine (1.10g), sodium iodide (0.273g), calcium carbonate (1.54g), and 2, at 60 ° C. A solution of 4-dichlorobenzyl chloride (2.17 g) in methanol (10 ml) for 24 hours. Then, 2,4-a-gasofluorene-based gas (2.00 g) was added and heated at 60 ° C for 36 hours. Ethyl acetate and a saturated aqueous sodium bicarbonate solution were added to the reaction solution to extract N-1-butanesulfonyl-3- (2,4-dichlorobenzylamino) -4-nitrate in the aqueous layer. Benzyl benzamine. The organic layer was concentrated to obtain N-1-butanesulfonyl-3- (2, 'di-gaso benzylaminonitrobenzofluorenamine (0.885 g). [Physical properties of the compound] Ή-NMR (DMS0-d6, 6): 0 · 81 (3Η, t, J = 7.3Hz) 3 1 · 29 (2Η, m), 1 · 49 (2Η, m), 2 97 (2H3 m), 4.66 (2Η, d, J = 6.0Hz), 7.22 (1Η, d, J = 8.9Hz), 727 (1H, s), 7.31 (1H, d, J = 8.4Hz), 7.37 (1H, d3 J = 8.3Hz), 7.65 (1Η, s), 8.04 (1Η, d5, 8.9ΗZ), 8.57 (1Η, t), &lt; Production Example 64; N-1-butane Fluorenyl-4-amino-3_ (2,4-dioxobenzyl ________ 280 ___ — this paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) 548272 A7 B7 V. Description of the invention (27 &gt; Production of Amine) Benzofluorenamine &gt; N-1-butanesulfonyl-3- (2,4-dioxobenzylamino) -4-nitrobenzoic acid amine ( 0.505 g) was added to a mixture of sodium bisulfite (1.32 g), ethanol (1 ml), tetrahydropyran (1 ml) and water (1 ml). Heated to reflux for 40 minutes. The solvent was distilled off under reduced pressure, and the water Add to the residue, collect the precipitated solid, and dry it. Then add methanol (10 ml) and water (3 ml) The mixed solution was washed, and dried to obtain N-1-butanesulfonyl-4-amino-3- (2,4-monogasofluorenylamino) benzamine (0.220 g). [ Physical properties of the compound] $ -⑽⑽S0-d6,6): G.93 (3H, t3 J = 7.4Hz), 1.45 (2Η, m), 1.83 (2Η, m), 3.57 (2Η , M), 5.45 (2Η, s), 6.36 (1Η, d, J = 8.2Hz), 7.11 (1Η, d, J = 8.3Hz), 7.51 (1H, s), 7 · 75 (1Η, d) 3 7 · 79 (1Η, d), 7 · 88 (1Η, s) · &lt; Example 315; 6- (1-Butanesulfonylcarbamoamido) _1- ( Synthesis of 2,4-dioxobenzyl) _2-hydroxybenzimidazole (379) &gt; stirred at 60 ° C for N-1-butanesulfonyl-4-amino-3- (2,4- A mixture of digas-benzylamino) benzofluorenamine (0.2220 g), tetramethoxymethane (0.31m) and acetic acid (2.0 ml) for 4 hours. The acetic acid was distilled off under reduced pressure, and tri-gas sintering was used. Extract with water. Concentrate the three-layer gas-fired layer to obtain the residue. Remove the sample from the central sample of the Ministry of Economic Affairs -T to eliminate the bamboo private seal f (Please read the precautions on the back before filling this page) ( 4.0ml) and 36% hydrochloric acid (4 drops) force α into the residue at 60. Stir for 2 hours. Neutralize with a saturated aqueous sodium bicarbonate solution, wash with water, and dry the precipitated crystals to obtain 6- (1-butanesulfonylaminofluorenyldichlorobenzyl) _2_hydroxybenzimidazole (379) 0.207g . [Physical properties of compound (379)] H-NMRiDMSO-dB, δ): 0.83 (3H, t, J = 7.3Hz), L36 (2H, m) 3 1.61 (2H, m), 3. —. .. ._______ 281 Paper Ruler (CNS) A4 Specification (210X297,1 ") _- '&quot; I ----- 548272 A7 B7 Central Ministry of Economic Affairs and Consumer Cooperatives, India. Description of the invention (27¾ 40 (2H, m), 5.08 (2Η, s), 6.94 (1Η, d5 J = 8.3Hz), 7 · 11 (1Η, d, J: 8 · Shi), 7, 36 (1H, dd, J: 2.0 and 8. he), 7.58 (1H, s) 3 7.68-7.73 (2 (, m), 11.47 (1H, br s), 11.77 (lH, brs). IR (Nujol): 1689cm-l. Mp: 254-256 ° C.

Mass (FD) ·· m / e 455 (M). &Lt; Example 316; Synthesis of 6-ethoxycarbonyl-2-methyl-1- (2-fluorinomethyl) benzimidazole (380) &gt; According to the method of Example 263, ethyl 4-acetamido-3-aminobenzoate was used (2.22 g), sodium carbonate (1.27 g), sodium iodide (0.45 g), and 2-bromomethyl Perylene (2.28 g) to give 0.87 g of 6-ethoxycarbonyl-2-methyl-1- (2-fluorinomethyl) benzimidazole (380). [Physical properties of compound (380)] lH-NMR (DMS0-d6, δ): 1.27 (3H, t3 J = 7.1Hz), 2.62 (3H3 s), 4.26 (2H, q? J-7 .1Hz), 5.85 (2H, s), 7.35 (1Η, d, J = 8.5Hz), 7.58 (1H, m) 3 7.63 (1H, d, J = 8.4)

Hz), 7.73 (1Η, m), 7.78 (1Η, dd, J = 1, 3, and 8.4Ηζ), 7.86 (1Η, d, J = 8.4Ηζ), 7.95 ( 1Η, d, J: 8.0 Hz), 8.14 (1Η, s), 8.36 (1Η, d, J = 8.5Hz). &Lt; Example 317; 6-carboxy-2-methyl- (2 -Synthesis of fluorenylmethyl) benzimidazole (381) &gt; According to the method of Example 53, 6-ethoxycarbonyl-2-methyl-1- (2-fluorinolinemethyl) benzimidazole (. 85 g) to give 6-carboxymethyl- (2-amylmethyl) benzimidazole (381). [Physical properties of compound (381)], H-NMR (DMS0-d6J c ^): 2.62 (3H, s), 5.83 (2H, s), 7.35 (1H, d3 J = 8.5Hz), 7. --- ------ _ 7 7 _______- one paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) --------- Φ—, (Read the notes on the back before filling (This page), 1T-line one 548272 The middle of the warp «. ^-^ A Industrial and consumer cooperation cooperation A7 B7 V. Invention description (27 in 57 (1H, m), 7.60 (1H, d, J = 8.5Hz), 7.72 (1H5 t, J = 7.6Hz) 3 7.77 (1H, d3 J-8.4 Hz), 7.86 (1Η, d, J 2 8.4Ηζ), 7.94 (1Η, d, J 8.1Hz), 8.11 (1Η, s), 8.35 (1Η, d, J = 8.5Hz) &lt; Example 318; 6- (1-Butanesulfonylcarbamoamido) -2 -Methyl-i_ (2-pyridinomethyl) benzimidazole (382) Synthesis> According to the method of Example 98, 6-carboxy-2-methyl- (2-pyridinomethyl) benzo was used Imidazole (0.222 g), N, N'-carbonyldiimidazole (0.195 g), 1-butanesulfonamide (0.165 g), and diazabicycloundecene (0.183 g) to give 6_ (1_ 0.088 g of butanesulfonylcarbamoyl) -2-methyl-1- (2-fluorinomethyl) benzimidazole (382). Physical properties of matter (382)] Ή-ΝΜΕχϋΜ30- (16, ά): 0 · 82 (3Η, ΐ, &lt; 1: 7 · 3Ηζ), 1.36 (2Η, ιη), 1.64 (2Η, ιη) ) 32 · 61 (3H, s) 3 3.48 (2H, t, J = 7.4Hz), 5.82 (2H3s), 7.32 (lH, d5 J-8.5Hz), 7.58 (1H, m), 7.65 (1Η , D, J = 8.5Hz), 7.73 (1Η, t, J: 7.6Hz), 7.78 (1Η, m), 7.87 (1H, d, J = 8.5Hz), 7′5 (lH, d, J = 8, lHz), 8.23 (1Η, s), 8.37 (1Η, d, J = 8.5Hz) 5 11.86 (lH5brs). IR (Nujol): 1684cm-l. mp: 185.5- 187.5 ° C. &Lt; Production Example 65; Production of 4-amino_3_ (2,4-dichlorobenzylamino) benzoic acid ethyl ester &gt; According to the method of Production Example 63, 3- (2, 4-Dichlorobenzylamino) ethyl 4-nitrobenzoate (1.40 g) and sodium bisulfite (4.50 g) to give 4-amino-3- (2,4-digas A crude product of benzylamino) ethyl benzoate. It was used directly in the following reaction. __283 This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) (Please read the precautions on the back before filling this page) -1 mouth

I 548272 A7 B7 produced by the central sample guide of negative M-T consumer cooperation ii. Description of the invention (28 &amp; &lt; Example 319; 1- (2,4-dichlorobenzylamino) -2- Synthesis of hydroxy-6-ethoxycarbonylbenzimidazole (3 83) &gt; According to the method of Example 3 15 and using the method of Example 65, 4-Amino-3- (2,4-dioxobenzylamine) was obtained. Base) ethyl benzoate and tetramethoxymethane (2.60 g) to give 1- (2,4-dichlorobenzylamino) -2-hydroxy-6-ethoxycarbonylbenzimidazole (3 83 ) 0.40 (^. [Physical properties of compound (383)] Ν-ΝΜΕ (ϋΜ80-ά63 δ): 1.27 (3H, t, J = 7.1Hz), 4.24 (2H, q, J = 7.1Hz), 5.12 (2 H, s), 7.04 (1Η, d, J 2 8.4Ηζ), 7.12 (1H, d, J 2 8.2Hz), 7.37 (1H, dd, J = 2.1 and 8.4Ηζ), 7.51 (1Η, s), 7.67_7 · 72 (2Η, m), 11 · 37 (1Η, br s) &lt; Example 320; 6-ethoxycarbonyl-2-methyl-1- [3- (4_ Synthesis of bromoisoxoline) methyl] benzimidazole (384) &gt; According to the method of Example 263, ethyl 4-acetamido-3-aminobenzoate (0.87 g), sodium carbonate ( 0.53g), sodium iodide (0.18g), and 4-bromo-3-bromomethylisokhalin ( 87g) to give 6-ethoxyweilyl-2-methyl-1- [3- (4-bromoisomaine) methyl] benzimidazole (384) 0.3 (^. [Compound (3 84 ) Physical properties] H-NMIUDMSO-dG, 6): 1.26 (3H, t, J: 7.GHz), 2.59 (3Η, s), 4.24 (2Η, q3 J = 7 • 0Ηζ), 5 · 93 (2Η, s), 7. · 61 (1, d, J = 8.4Hz), 7.75-7.8G (2H, m) ·· 99 (1Η, m), 8.03 (1Η, s), 8 · 13 (1Η, d, J: 8.1Hz), 8 · 23 (1Η, d, J = 8.5Ηζ), 9 · 12 (1Η, s). &Lt; Example 321; 6-carboxy-2- Synthesis of methyl- [3- (4-bromoisofluorinyl) methyl] benzimidazole (385) &gt; According to the method of Example 53, 6-ethoxyamidofluorenyl_ 1- [3- (4-Bromoisopyridinyl) fluorenyl] benzimidazole (〇29〇g) to obtain the paper standard This paper applies the China Standard (CNS) A4 · (210 / 297¾) '--(Please (Read the notes on the back before filling out this page)

, 1T 548272 A7 B7 V. Description of the invention (28 fluorenyl-2-methyl- [3- (4-mo-isoisocyanate) methyl] benzo 17 m σ (385) 0.1 18 g. Use it directly below (Please read the precautions on the back before filling out this page) &lt; Example 322; 6- (1-Butanesulfonylaminofluorenyl) -2-methyl-1- [3- ( Synthesis of 4-bromoisoxolinoline) methyl] benzimidazole (386) &gt; According to the method of Example 98, 6-carboxy-2-methyl- [3_ (4-bromoisoxorimidine) 曱 was used Yl] benzimidazole (0.11 lg), N, N, -carbonyldiimidazole (0.097 g), 1-butanesulfonamide (0.082 g), diazabicycloundecene (0.091 g ) To give 6- (1-butanesulfonylcarbamoyl) -2-methyl-l- [3- (4-bromoisosnophyl) fluorenyl] benzo. ) 0.075 g. [Physical properties of compound (386)] H-NMR (DMS0-d6, (5): 0.81 (3Η, t3 J: 7.4Hz), 1.35 (2Η, m), 1.62 ( 2Η, in), 2. 54 (3Η, s), 3.46 (2Η3 t, J: 7.5Hz), 5.91 (2Η, s), 7.63 (1Η, d, J: 8.5Hz), 7.76 (1H, dd3 J = 8.5 and 1.41ζ), 7.79 (1Η, t, J = 7.6Hz), 8.00 (1Η, t, J = 7.9Hz), 8.08 (1Η t, J: l.lHz), 8.13 (1Η, d, J: 8.2Hz), 8.24 (1Η, d, J: 8.5Hz), 9.11 (1 H, s), 11.8K1H, brs) IR (Nujol): 1678cm-l. Mp: 258-259 ° C.

Mass (FAB): m / e 515, 517 (M + 1). Representative compounds are selected from the compounds of the present invention for testing of pharmacological properties. &lt; Experimental Example 1; Accumulation of triglyceride (TG) accumulation in 3T3-L cells (pre-adipocytes) &gt; Test compound 6_benzenesulfonylcarbamoamidine_2_cyclopropyl_ 丨 _ ( 2_Fluorobenzyl) Benzimid --____ 285 This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 548272 A7 B7 V. Description of the invention (28i mouth sitting machine (please read the note on the back first) (Fill in this page again)

1. Centrifuge: TOMY LC-122 2. Incubator: ESPECBNA-121D 3. Mixer: Automatic Labo-Mixer 4. Hot water tank: TAITEC PERSONAL-11 5. Spectrophotometer: Shimadzu UV visible spectrophotometer UV- 160A

6. · 24-well plate: GLASS CORNING made by Iwaki. Test medium: 1. Medium: Dulbecco's minimum medium (MEM) + 5% calf fetal serum (FCS) 2. PBS (-): a solution with the following composition

NaCl 0.8g / l KC1 0.2

Na2HP04 1.15 KH2P〇4 0.2 3. EDTA-trypsin solution: 0.02% EDTA + 0.25% trypsin / PBS (') 4. · dexamethasone ··· IGB by Sigma (3-isobutyl-1) -Methylxanthine): SIGMA 6. Insulin: SIGMA 7. DMSO (dioxin): Made by Wako Pure Chemicals 8. Kit for TG measurement This paper applies Chinese national standard (CNS) μ specifications (210X297) 548272 A7 B7 V. Description of the invention (283 triglyceride-test kit (acetamidine-acetone method): Wako Pure Chemicals 9. · 0.1N NaOH solution: Dilute IN NaOH solution to 10 times the volume with distilled water 10. Bio-Rad protein quantitative analysis reagents ·· BIO-RAD 11. Bovine albumin: SIGMA test method 3T3-L1 cell preparation Prepare 3T3-L1 cells in a F75 flask to reach a dense state. Remove the culture medium, Wash 2 times with 5ml PBS (-), peel off the cells with EDTA-trypsin solution. Add 10ml culture medium to form a suspension. Place the suspension in a 50ml centrifuge tube and centrifuge at 1000rpm for 5 minutes to allow the cells to pellet , Remove the supernatant. Then suspend the cells in 20ml of medium, calculate the fine It was prepared at 6 X 104 cells / ml, and 1 ml and 1 ml were injected into a 24-well plate. In this state, the cells were cultured in an incubator (37 ° C, 5% C02) for 2 days. Dexamethasone and IBMX Mix and add the central rate of the ministry and work only for private consumption (please read the precautions on the back before filling this page). Use DMSO to prepare ImM Dexamethasone + 500mM IBMX. Then, dilute the solution with the medium 1000 times to prepare 1 μM, dexamethasone + 0.5 mM IBMX. At the same time, DMSO was diluted with the medium to prepare a 0.1% DMSO solution. Then, a 24-well plate containing the cultured 3T3-L1 cells was removed from the incubator. After confirming that the cells have formed a thick state using an inspection microscope, the medium was aspirated. Then, 0.1% DMSO solution was put into 2 wells of a 24-well plate, and 1 μM dexamethasone + 0.5mM IBMX was put into other 22 holes. _2 &amp; 2_ This paper size applies to Chinese National Standard (CNS) A4 (210X297mm) 548272 A7 B7 V. Description of the invention (28 'In this state, in the insulation box (37 ° C, 5% C02 ). The test agent and insulin are adjusted and added with DMSO. Test agent diluted to 1 X 10 · 2,1 X 1 (T3,1 X 1〇-4Μ, then diluted 500-fold to prepare a concentration 2Χ10 · 5,2Χ 10_6,2Χ 1 (Τ7Μ. At the same time, a 0.2% DMSO solution was prepared. 100 μM insulin (0.2% bovine serum albumin (BSA) and 3 mM HCl) was prepared in advance, stored at 80 ° C, and then thawed naturally. The medium was diluted to 50000 times to prepare 2 nM insulin. Next, the 24 wells in which dexamethasone and IBMX were added the day before were taken out of the incubator, and using an inspection mirror to confirm that the cells had undergone morphological changes based on the addition of dexamethasone and IBMX, the medium was aspirated. Next, 500 μ1 of 0.2% DMSO solution was added to 2 wells in which 0.1% DMSO solution was added the previous day (to determine the state of the cell at that time). For the other 22 wells (wells with dexamethasone and IBMX), add 0.2% DMSO solution to 2 of them, 500 μ1 of the test agent to 20 of them, and then add 500 μ1 of insulin solution to each of the 22 wells. In this state, culture in an incubator (37 ° C, 5% C02) for 4 to 5 days. Determination of triglyceride (TG) and protein After the central part of the cymbal sounds, only eliminate the cooperation private printing (Please read the precautions on the back before filling in this page)

After adding the test agent and insulin solution for 4 to 5 days, remove the 24-well plate from the incubator, tilt the plate to remove the medium, and then remove the remaining medium with tissue paper to completely remove the medium. Then, extraction was performed twice with isopropyl alcohol, and TG measurement was performed using a TG measurement kit (acetamidine-acetone method) (measurement wavelength: 410 nm). Next, after the isopropanol-extracted plate is removed, isopropyl alcohol is added, and O.INNaOH _ikk_ is added to each plate hole. This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 548272 A7 B7 V. Invention Instructions (28 go (read the precautions on the back and then fill out this page). Solution 400μb is left at room temperature for 30 days to lyse the cells. Then, 50μ1 solution is sampled into each test tube. Then, 2.5ml of quilt Bio-Rad protein quantitative analysis reagent diluted 5 times with distilled water was added to each test tube. After sufficient stirring, the protein was measured using a spectrophotometer (measurement wavelength: 595 nm). Result The control compound PiOglitazone (1 × 10-6M) The promotion effect of TG accumulation was taken as 100%, and the insulin (+) at the time of the drug was taken as 0% to obtain the promotion effect (%) of TG accumulation of the test compound. The results are shown in Table 1 below. ___ ^ 1_ Concentration ( M) TG accumulation promoting effect (%) _lxl0 · 5 _38.2% _ &lt; Experimental Example 2; Blood glucose lowering effect in db / db mice &gt; Test compound 6-Benzofluorenylcarbamoyl-2-cyclo Propyl-1- (2-fluorobenzyl) benzimidyl (177) 6-This stone sheet is based on methyl carbamoyl-1-(2-lactofluorenyl) -2 -methylbenzoxyl ° (163) '1- (biphenyl-4-methyl ) -6- (1-Butylfluorenylcarbamoyl) -2-fluorenylbenzimidazole (172) C57BL / KsJ-dbm db + / db +, C57BL / KsJ_dbm + m / + m Female rats at the age of 5 weeks, after 2 ~ 3 ____ 2 &amp; 9 ___ This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 548272 A7 B7 5. Description of the invention (28g weeks for domestication for experiment. I Material preparation (please read the precautions on the back before filling out this page) Use a mortar to mix the specimen and powder bait (CE-2, CREA). This ratio is based on the food intake of rats, and the ratio is above 〇〇 0.1 ° / 〇 at mg / kg, 0.03% at 30 mg / kg, and 0.001% at img / kg. Feed bait twice a week, record the amount of bait and the amount of residual bait. The difference was used to calculate the amount of recording. The test procedure was based on body weight, blood glucose, and triglyceride concentration in plasma. Female db / db mice were grouped and fed with a drug bait for 14 days (the experimental period was 8 weeks to 10 weeks old). ). Day 7 and day 14 in the morning, so that application of heparin (heparin) process of glass capillaries for blood collection orbital venous plexus through, the blood collected was centrifuged to obtain plasma. The measurement items were blood glucose levels, triglyceride concentration in plasma, plasma insulin concentration on day 0 and 14 days, blood glucose level on day -7, and triglyceride concentration in plasma. The body weight was measured on days 0, 7, and 14. When the final blood collection was completed, he was killed using CO2 gas. Using 10 to 15 μ1 of plasma, and measuring the blood glucose level by the glucose oxidase method (glucose CL1 · test kit, Wako Pure Chemical Industries, Ltd.). Use 10 ～ 15μ1 plasma and measure GPO-p-phenol method (triglyceride g_ test kit) or GPO-DAOS method (triglyceride g-E test kit) Triglyceride concentration. The above measurement was performed as soon as possible after blood collection. 20 μ1 of plasma (can be stored at -20 ° C) was used to measure it by the antibody method (Phadeseph RIA kit, Kabi Pharmacia). This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 548272 A7 B7 V. Description of the invention (28) Results (Read the precautions on the back before filling this page) Compare the control group of db / db mice with The difference between the blood glucose level of the mouse and the triglyceride concentration in the plasma was regarded as 100%, and the reduction rate (%) of the blood glucose level and the triglyceride concentration in the plasma of the test group were determined. The results are shown in Table 2 below. Table 2 Dosage (mg / kg) Blood glucose lowering effect (%) Compound (177) 30 34.5 Compound (163) 30 72 Compound (172) 10 70 ～ 80 The present invention provides a novel benzimidazole derivative or can be used for Used as salts of the benzimidazole derivative in medicine. These compounds and their salts have blood glucose-lowering activity or PDE5 inhibitory effects, and can be used as glucose tolerance disorders, diabetes (type II diabetes), diabetic comorbidities (diabetic nephropathy, diabetic neurological disorders, diabetic omentosis, etc.) , Insulin resistance syndrome (insulin receptor abnormality, Robson-Mendenhall syndrome, Leprechaunism, Kobberling-Dunnigan syndrome, Seip syndrome, Lawrence syndrome, Cushing 'syndrome, megacephaly, etc.), high-moment bloodemia, atherosclerosis Disease, cardiovascular disease (arrhythmia, insufficiency, etc.), hyperglycemia (such as those with abnormal glucose metabolism and other characteristics), or hypertension, or autism, hypertension, pulmonary hypertension, congestion Arrhythmias, glomerular diseases (such as diabetic glomerulosclerosis, etc.), urinary tubulointerstitial diseases (such as kidney disease caused by FK506, cyclosporine, etc.), --- 24M --- This paper Standards are in accordance with Chinese National Standard (CNS) A4 specifications (210X297 mm) 548272 A7 B7 V. Description of invention (28 ^ Renal insufficiency Atherosclerosis, vascular stenosis (_ the latter), terminal seminal vascular disease, cerebral hemorrhage, = sloping arterial slope reversible occlusive disease (e.g., bronchitis, asthma (chronic asthma, allergic gas embolism = sensitive Rhinitis, measles, glaucoma, characterized by intestinal motility: two common diseases (such as allergic bowel syndrome), impotence (such as organ impotence, sperm = sexual impotence, etc.), diabetic complications (such as diabetic gangrene) , Diabetic arthritis, diabetic glomerulosclerosis, diabetic skin abnormalities, diabetic neurological abnormalities, diabetic cataracts, diabetic omentosis, etc.), nephritis, malignant cancer, or restenosis after PCTA, etc. (Please read the notes on the back before filling this page)

、 1T line The Ministry of Economics and the Ministry of Economics and the Ministry of Economic Affairs and the Ministry of Economic Affairs only print 5 papers for cooperation and private printing. 292 The paper size applies to China National Standard (CNS) A4 (210X297 mm)

Claims (1)

548272 ^ as No. 86100149 Application for revision of patent scope g Proof date: 92.6.18 6. Scope of patent application ... · 1 · A benzimidazole derivative or a pharmaceutically acceptable salt of the benzimidazole derivative The benzimidazole derivative is represented by the following formula (IX): 28 R 〇 ^ 〇γ · R- 29 27 ⑽ k Member of the Intellectual Property Bureau of the Ministry of Economic Affairs X. Consumer Cooperative's printed formula (IX) 'R27 is a hydrogen atom, a lower alkyl group, a halogen lower alkyl group, an arylsulfonyl group, an aryl lower alkyl group, or a pyridine lower alkyl group , Quinoline lower alkyl, _isoquinoline lower alkyl; the aromatic ring of the aryl lower alkyl can be selected from the II atom, lower alkyl, halogen lower alkyl, cyanoaryl, amine, lower alkyl Oxy, nitro, cyano, aryl, haloaryl, arylsulfonyl lower alkyl, arylsulfanylamino, aryl lower alkoxy'aryl lower alkyl, thiadiazolyl , Pyridyl, aryloxy, arylcarbenyl, arylcarbenylamino, or one or two of aryl lower alkyloxy substituted with one or two _ prime atoms; R28 is Hydrogen atom, lower alkyl, lower alkyl, lower alkoxy lower alkyl, lower cycloalkyl, aryl, aryl lower alkyl, lower alkylamino, lower alkoxy, lower alkylthio, Hydroxyl, fluorenyl, amine or carboxyl; R25 is an alkyl group having up to 8 carbon atoms, a lower alkyl group, a tri-lower alkyl silyl group Alkyl, lower alkoxy lower alkyl, lower alkylthio lower alkynyl, aryl, quinolinyl, aryl lower alkynyl, or thoryl lower radical; this aryl group can use i element atom, lower alkynyl Base, halogen low-grade burning base, low 293 This paper size applies to Chinese National Standard (CNS) A4 specification (210 X 297 mm) (Please read the precautions on the back before filling this page) A8B8C8D8 548272 Oxygen or nitro substituted; R26 is a hydrogen atom or a lower radical; when R25 and R26 are lower fluorenyl groups, they can be combined with each other to form a ring; Y is a carbofluorenyl or a lower alkylene group; A represents early Pure bond or lower alkylene group or lower dilute volatile group; R29 is a hydrogen atom or a lower alkyl group; and in the above definition, the lower alkyl group has a carbon number of 1 to 6; the carbon number of the lower cycloalkyl group 3 to 7; aryl is phenyl or naphthyl. 2. The benzimidazole derivative or the pharmaceutically acceptable salt of the benzimidazole derivative as described in item 1 of the scope of the patent application, wherein R27 is an aryl lower alkyl group, and the aryl lower alkyl group is The aromatic ring can be selected from _ prime atom, lower alkyl group, i lower alkyl group, cyanoaryl group, amino group, lower alkoxy group, nitro group, cyano group, aryl group, haloaryl group, and aryl group. Alkyl, arylsulfonylamino, aryl lower alkoxy, aryl lower alkyl, thiazolyl, pyridyl, aryloxy, arylcarbamyl, arylcarbamylamino, or via One or two of the aryl lower alkoxy groups substituted with one or two prime atoms; Y is a carbofluorenyl group; and A is a single bond. 3. The benzimid sigma derivative or the salt of the benzimidal derivative as described in item 2 of the scope of patent application, wherein R27 is an aryl lower alkyl group, and the aryl group The aromatic ring of lower alkyl can be substituted by one or two of free atom or aryl group; R28 is an alkyl group having a carbon number of up to 7 or a cycloalkyl group, and R25 is an alkyl group having a carbon number of up to 8 Or aryl. 4. The benzimidazole derivative or the salt of the benzimidazole derivative as described in item 1 of the scope of the patent application is free to choose 6_benzenesulfonate. The paper size applies the Chinese National Standard (CNS) A4 Regulations X 9〇8 pairs (please read the notes on the back before filling in this page) # ·-线. Consumer Cooperation of Intellectual Property Bureau of the Ministry of Economic Affairs 钍 printed 294 548272 as ___ gg _ Aminocarbamoyl-fluorenyl. Chlorobenzyl) _2_methylbenzoxyl, benzo (biphenyl-4-methyl) -6- (1-butanesulfonylcarbamoyl) _2_ 曱Benzimidazole, 1 (such as benzene-4-methyl) _6_ (1-butanesulfonylcarbamoyl) &gt; 2-ethylbenzimidyl, 6-benzylfluorenylaminofluorenyl · 2-ring Θ group-1- (2-fluorobenzyl) benzimidazole, 6-benzylaminocarbamoyl small (M: chloro 1-yl) · 2 · methylbenzo2azole, 6 -Benzenesulfonylaminocarbamyl small (2,4-difluorobenzyl) _2_fluorenylbenzimidazole, 6_d-butanesulfonylcarbamoyl) -1-[(3-fluorobiphenyl -4-yl) methyl] 2-methylbenzofluorene, pyrene, di-gasofluorenyl) _2_fluorenyl (pentylaminomethyl) methyl σ m and σ sat groups were composed of 1 _ (4_ biphenylcarbonitrile-yl) -2-ethyl-6- (1-pentanesulfonamide acyl acyl carbamoyl) benzimidazole. 5. · A pharmaceutical composition for the prevention and treatment of glucose tolerance disorders, diabetes, diabetic comorbidities, insulin resistance syndrome, hyperlipidemia, atherosclerosis, cardiovascular disease or hyperglycemia, which contains The compounds described in the scope of patent application No. 1, 2, 3 or 4 or the pharmaceutically acceptable salts are used as active ingredients and have blood glucose lowering activity. (Please read the precautions on the back before filling out this page) Order:-· Line-Consumer Cooperation of Intellectual Property Bureau of the Ministry of Economic Affairs ♦ Society prints appropriate ruler (21 rule 4) AS) N (C quasi-standard family Male 97