• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    1455728 Benzimidazole-2-carbamates SYNTEX (USA) Inc 13 Dec 1973 [29 Dec 1972 21 Nov 1973] 57925/73 Heading C2C The invention comprises novel compounds (I) where R is a lower alkyl group having 1 to 4 carbon atoms; R<SP>1</SP> is -SOR<SP>2</SP>, -SO 2 R<SP>2</SP>, -SCN, -SR<SP>5</SP>, -OR<SP>5</SP>, or M<SP>1</SP>(CH 2 ) n MR<SP>7</SP> where M and M<SP>1</SP> are independently O, S, R<SP>7</SP> is lower alkyl having 1 to 4 carbon atoms or aryl, and n is 1-4; R<SP>2</SP> is lower alkyl having from 1 to 6 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, lower alkenyl or lower alkynyl having 3 to 6 carbon atoms, or aralkyl or aryl; and R<SP>5</SP> is lower alkenyl, lower alkynyl, or aralkyl; the R<SP>1</SP> substitution being at the 5(6)- position; or a pharmaceutically acceptable salt thereof. They are made by utilizing the compounds shown in the following reaction schemes: (Z is R<SP>2</SP>SO or R<SP>2</SP>SO 2 and M is O or S). Pharmaceutical compositions having anthelmintic and antifungal actions contain (I) as active ingredient; administration is, e.g. orally.
    公开号:SU727143A3
    申请号:SU731980901
    申请日:1973-12-28
    公开日:1980-04-05
    发明作者:К. Бирд Колин；А. Эдвардс Джон；Х. Фрид Джон
    申请人:Синтекс /Ю.С.А/Инк. (Фирма)；
    IPC主号:
    专利说明:

    Bbiuje, to the corresponding sulfonyl or sulfonyl soybean, and not f9P rs are 1, where it is SOR, SOgP or M (CHg) ;, MFr ,. where at least one. from M or M is SO or .K-, R. and n is defined above ,, and its condition is in free form or in the form of salt ,.
    PR and EL-1o 175 g of sulfate S - methyl isothiouroch in 1 liter of water is smoothed to, add g of methyl chloroformate and then a solution of 250 potassium hydroxide in 750 ml of water at 0-5 ° C. Crude extraction product, a) t benzene, an extract of high sting, evaporated, the residue recrystallized Occur from methanol to give 1; 3 - bis (methoxycarbonyl) -3-methylisothiourea.
    Similarly, using ethyl; propyl and butyl chloroform-1at instead of methyl: crrapfop and ita, respectively, get 1, 3 - bis (ethoxycarbonyl) -, 1, 3-bis (propoxycarbonyl) and 1,3-bis (butoxycarbonyl) -B-motilisothiourea.
    Example 2, 2 g of 1-aminO 2 Nitro-4 -thiocyanatobenzene smes; 12 g of tin dichloride in b ml of concentrated hydrochloric acid are added dropwise to a dropwise m-solution, and 5 to 20 m-g are kept at 15–20 Cp. product filtered: Vagot and 12 Mj; 6 k, salt KVSClot. After treatment with 25 ml of a saturated solution of bicarbonate balsa and extraction} slor Formog-.1, a free base is obtained. Recrystallization from benzene separates 1,2-diamino-4 thiodianatobenzene
    A solution of 1.3 g of 1 ,, 2 diamino 4-thiocyanatobenzene and 1.1 g of 1,3-bis (methoxycarbonyl) -S-methyl isothiomychevine in 20 4 liters of ethanol and 20 ml of water are treated with O p 5 ml of acetic ACID, heated 1 , 5 hours under reflux, cooled and the filter; / s. The solid product is recrystallized from methanol-chloroform to give 5 (6} -t and they are anatObomethoxyg; cobene1-1-dazole, t, de 250 ° C
    Similarly, using 1,3-bis (ethoxycarbonyl) -, 1,3-bks - (propoxycarbonkl) - n 1, 3-bis- (butoxycarbonyl) -3-metipxothiourea instead of 1,3-bis- (methoxycarbonyl) -S ™ Methylisotio yuchevinYp receive the corresponding 5 (6) -thiocyanato-2-carboethoxy, 5 (b) -thioganato-2-carbopropoxy- and 5 (6) -thiocyanato-2 carbobut oxy ciaminoben 3 and and yes 3 about l.
    -L - :; ivi er 3. 5 g of 1-acetamido - / -; -IL -. :: os - --T - Opantobenzene in 70 ml of V: -prsiapol d ;, containing; ka; gidroikmsk Kylm; -:., and 2, G g of n-propyl bromide is ideal and the flow at l5--20 Cf with le 1 is hydrated with water and extracted with chloroform. Dried extracts are evaporated in vacuo, the remaining dye oil is dissolved in 25 ml of acetic acid. A few drops of sulfuric acid are introduced;
    Jh at 2025 ° C, acetate is added.
    Sodium and Wiar are evaporated under vacuum. The residue is treated with water, the precipitate is filtered off and recrystallized from methanol to give 1-acetamido-2-nitro-4-n-propylthio benzene.
    This intermediate can be obtained directly by alkylation; and 1 - acetate 1 / shdo-2 nctroT iOL-i-iaHazo6ev 3Ojja n-propyl bromide in dimethylformamide (DMF) in the presence of sodium sulfidoid,
    3; 8 -L-1-adetam; to-2 - nitro 4-n Prog. Ethylthiobenzene e 35 u chloroform is treated at (-20) - (-15) ° C with solution 3. About O 40% peracetic acid in 3 ml of methanopao Heated to 20 Cp at C stirred for 1 h, about 1 h; from solutions of bisulfite and sodium bicarbonate. After removal of the chlorofor. I leave the resin, which is treated on a steam bath. 15g. 5 n. sodium hydrooxy for 1 h, cooled, extracted with chloroform and the solvent removed. The crude product percrystalline α-from benzene to obtain 1-amino-2-nitro-4-n-propylsulfinclebenzene.
    If 14 g of 1-amino-2-nitro 4 n-propyl sulfide; -H1 :; .1-benzene E 100 ml of methanol at a pressure of 1 atm in the presence of 1 g of catalyst - 5% palladium on coal is treated with hydrogen until stopped, the latter. The catalyst is distilled off, the filtrate is evaporated, the resulting resin is treated with 12 g of 1,3-bis- (methoxycarbonyl) -8 - methylisothiourea and 0.3 U / t of vinegar kg in a boiling civiecH 10 MP and 10 / “l of water. After 3 hours, it is compacted, filtered, and the precipitate is crystallized from ethanol to give 5 (6) n-propylsulfk n and l-2-a b a. and VK and angry j t. Sq. 1E 7 С (decomp.)
    In the same way, using methyl-- or ethyl iodide, isopropyl-, butyl--, isobutyl-, pentyl-, hexyl-, cyclogropyl- ;. cyclopentyl-- and cyclohexylb omcd instead of n-propyl bromide receive 1-amino-2-NITRO-4-alkyl or i-amino-2-nitro-4 -cc-, respectively; oalkylsulfinylbenzene, 5 (6) -alkylsulfinyl-2 -carbomethoxyaminobanzimidazole and 5 (6) - cycloapkylsulfkl-2-benzim "dazole, including 5 (6) cyclopenilol --- t, mp, 2.95-298 ° C (decomp); 5 (6) -methyl-, t. square
    (rael.); 5 (6) -ethyl-, m.p. 285С (dec,); 5 (6) -isopropyl-, mp 200 (decomp.), And 5 (6) -n-butylsulfinyl-2-carbomethoxyaminobenzimidazole, m.p. (different).
    As a result of the interaction of 1-amino-2-nitro-4-alkylsulfinyl benzene and 1-amino-2-nitro-4-cycloalkylsulfinylbenzene with 1,3-bis- (methoxycarbonyl-, 1,3-bis- (ethoxycarbonyl) -, 1 , 3-bis- (propoxycarbonyl) - or 1,3-bis- (butoxycarbonyl) -S-methylisothiourea, respectively, 5 (6) -alkylsulfinyl or 5 (6) -cycloalkylsulfinyl-2-car-balkoxyaminobenzimidazolr where R is methyl, ethyl, propyl or. butyl,
    Example 4. 5g of 1-acetamido-2-nitro-4-thiocyanatobenzene 1.7 ml of methyl iodide are introduced into a solution of 4.8. g of potassium hydroxide in 70 ml of ethanol, incubated overnight at room temperature, diluted with water and filtered, 1-amino-2 nitro.-4-methylthiobenzene.
    To a solution of 3.7 g of 1-amino-2-nitro-4-methylthiobenzene in 37 ml of acetic anhydride, a few drops of concentrated sulfuric acid are added and kept at. at room temperature for 1-2 hours, treated with a slight excess of sodium acetate and evaporated. Water is then added, filtered and 1-acetamido-2-nitro-4-methylthiobenzene is separated.
    4.0 g of 1-acetamido-2-nitro-4-methylthiobenzene is treated in 40 ml of chloroform 12 ml of 40%. naduksuenoj acid at room temperature, incubated. 1.5 h, the product is filtered off, washed with methanol and receive 1-acetamido-4-methylsulfonyl-2-nitrobenzene.
    .4 g of 1-acetamido-4-methylsulfonyl-2-nitrobenzene is treated with 40 ml of concentrated hydrochloric acid on a steam bath for 1 h, cooled and diluted with water, filtered and 1-amino-4-methylsulfonyl-2-nitrobenzene is isolated .
    2 g of 1-amino-4-methylsulfonyl 2-nitrobenzene are treated in 200 ml of methanol with hydrogen at a pressure of 4 atm in the presence of Rene nickel. The catalyst is filtered off, the filtrate is evaporated and get 1,2-diamino-4-methylsulfonylben 3ol,
    0.5 g of 1,2-diamino-4-methylsulfonylbenzene, 0.6 g of 1,3-bis- (methoxycarbonylamino) -S-methyl-isothiourea and 0.2 ml of acetic acid are heated under reflux in 10 mp of ethanol and 10 ml of water within 4 hours, cooled,., filtered, the product is recrystallized from a mixture of methanol / chloroform and 5 (6) -methylsulfonyl-2-carboxymethyaminobenzimidazole are obtained, decompose without melting.
    Similarly, using ethyl iodide, propyl, butyl, pentyl, hexyl, cyclopentyl, or cyclohex. instead of methyl iodide, semi-VOT, 1, 2-diamino-4-alkylthiobenzene, .1,2-diaminocycloalgylthiobenzene, 5 (b) -alkylsulfonyl, 5 (b) -cycloalkylsulfonyl-2-carboxy-methoxyaminobenzimidazole, respectively.
    In the interaction of the obtained 1,2-diamino compounds with 1,3-bis- (ethoxy0 carbonyl) -, 1,3-bis- (propoxycarbonyl) - or If 3-bis- {butoxycarbonyl) -S-methylisothiourea, respectively, 5 (6) are obtained -alkylsulfonyl 5 (6) cycloalkylsulfonyl-2-car5 balkoxyaminobenemidazole, where R is ethyl, propyl or butyl.
    Example 5. 5.85 g of 1-amino-2-nitro-4-thiocyanatobenzene in 20 ml of D1-1FA. treated under nitrogen atmosphere 1, -14 g sodium borohydride at a temperature not higher. The mixture is stirred at 15–20 ° C for 1 hour, treated with 5 ml of allylene bromide at 20–25 ° C. After 3 hours water is added, the product is extracted with chloroform, dried
    5, the extract is passed through a column filled with silica gel to remove minor amounts of polar impurities and pure 1-amino-2-NITRO-4- (prop-2-in-1-ylthio) -ben sol is recovered.
    4.8 g of 1-amino-2-nitro-4- (prop-2-yn-1-ylthio) -benzene in 14 ml of concentrated hydrochloric acid treatment 5 with a solution of 24 g of tin dichloride in. 14 ml of concentrated hydrochloric acid at 20 -30 ° C. After 30 minutes, neutralized with a saturated solution of 5: kgshi carbonate, add
    0 x poroform, filtered, the chloroform layer is separated, dried and evaporated to give 1,2-diamino-4- (prop-2-IN-1-ILTIO) benzene. Obgtion yield 75%.
    4.0 g 1,2-diamino-4- (prop-2-in-1
    5 -thylthio) -benzene in 25 ml of ethanol, and 25 ml of water are treated with 4.9 g of 1,3-bis- (methoxycarbonyl) -S-methyl-isothiomyochine and 1.5 ml of acetic acid under heating with reverse refrigeration for 3 h, cooled, 5 (6) (prop-2-in-1-ylthio) -2-carbomethoxyaminobenzimidazole is filtered off and, if desired, recrystallized from methanol-chloroform, mp.
    5 212.5С; yield 92%.
    1.31 g of 5 ((prop-2-in-1-ylthio) -2-carbomethoxyaminobenzimidazole is dissolved in a mixture of 65 ml of acetic acid and 65 ml of chloroform; a solution of 1.02 g of m-chloroperbenzoic acid is added
    0 acid in 20 ml of chlorofor (and at (-20) -15, slowly heated to, hold; 6 h at this temperature, evaporated in vacuum and the residue is treated with sodium bicarbonate solution.
    5 5 (6) - (Prop-2-in-1-ylsulfinyl) -2-carbomethoxyaminobenzimidaeol is filtered off and, if desired, recrystallized from a mixture of methanol / chloroform, so pl. (decomp.) Mass spectrum: m / e 277 (M), the peak being 216. Similarly, using 2-pr penyl-, 2-butenyl-, 3-butenyl-, 2-pentenyl-, 2-hexenyl-, 2-butynyl3-butynyl-, 2-pentenyl- or 2-hexyl ylbromide instead of allylene bromide, respectively, 5 are obtained (6 ) -alkini, 5 (b) -alkenylsulfinyl- and 5 (6) -a lki-nil sul lfi u and l - arbometo to si-aminobenzimidazole, including b (6) - {prop-2-en- 1-ilthio) -2, m.p. 201-201, 5 ° C and; 5 (6) - (prop-2-en-1 -ylsulfinyl) -2-carbomethoxyaminobenzimidazole, m.p. 213s (decomp.) In the same way, using 1,2-daamino-4-alkenyl- or. 1, 2-diam Lno -; 4-alkynylthiobenzene and 1, 3-bis- (this sicarbonyl) -, 1, 3-bis- (propoxy.sycarbonyl) - or 1,3-bis-butoxycarbonyl-S-methylthiourea, get therefore, 5 (6) -alkenylthio, 5 (6) -alkynylthio, 5 (b) -alkenylsulfonyl, or 5 (6) -alkynylsulfinyl-2-carb; alkoxyaminobenzimidazole, where R is these propyl or. butyl. Example b. 1 mol of 5 (6) alkenylthio or 5 (6) alkynylthio-2-carbalkoxyaminobenzimidazole is treated with 2 moles of the peracid (for example, m-chloroperbenzoic or peracetic, as in Example 3 or 4, but for a longer time) and get 5 (6) -alkenyl- or 5 (6) -alkynylsulfonyl-2-carbapkoxy-1 1o benzimidazole. These compounds can be prepared analogously to example 4 of 5 (6) -alkenyl or 5 (b) -alkynylsulfinyl-2-carbalkoxy-aminobenzimidazole. Example 7. 1.0 g of 1-acetamido -2-nitro-4-benzylthiobenzene is treated with 2 ml of 5N. sodium hydroxide and 6 MP of methanol on a steam bath for 15 minutes, diluted with water, and 1-amino-2-nitro-4-benzylthiobenzene is filtered off. 0.9 g of 1-amino-2-nitro-4-benzylthiobenzene in 5 ml of concentrated hydrochloric acid is treated with 4.5 g of dichloride, tin on a steam bath for a very short time, cooled, the liquid decants the resinous product washed with 5 1 l of cold bn hydrochloric acid is treated with potassium bicarbonate solution and 1,2-diamino-4-benzylthiobenzene is obtained, which is separated by extraction with chloroform and purified by recrystallization from cyclohexane. Similarly, receive 5 (6) -benzylthio-2-carbomethoxyaminobenzimidazole, so pl. (dec) In a similar way, using p-chlorobenzyl, p-methylbenzyl and p-methoxybenzyl bromide, 1,2-diamino-4- (substituted benzylthio) -benzene and 5 (6) - (substituted benzylthio) -2, respectively, are obtained -carbomethoxyaminobenzimidazole. When interacting 1,2-diamino- (4-substituted benzylthio) -benzene with 1,3-bis- (ethoxycarbonyl) -, 1,3-bis- (propoxycarbonyl) - or 1,3-bis- (butoxycarbonyl) -S -methyl isothiourea get 5 (6) - (substituted benzylthio) -2-carbalkoxyaminobenzimidazole, where R is ethyl, propyl or butyl. Example 8. 2.37 g of 1-acetamido-2 nitro-4-thiocyanatobenzene in 10 ml of DMF are treated under a nitrogen atmosphere with 0.38 g of sodium borohydride at 20-25 ° C. After 1 h, 2.4 ml of benzyl bromide was added, aged for 2 hours, diluted with water, filtered, the precipitate was washed with cyclohexane, recrystallized from methanol and 1-acetamido-2-nitro-4-benzylthiobenzene was obtained. 2.42 g of 1-acetamido-2-nitro-4-benzylthiobenzene in 25 ml of chloroform at (-20) - (-15) ° C are treated with 1.6 g of 40% peracetic acid in 2 ml of methanol, slowly heated to room temperature, incubated at room temperature for 6 hours, washed with solutions of bisulfite and sodium bicarbonate, dried, evaporated, the residue is recrystallized from methanol and 1-acetamido-2-nitro-4-benzylsulfinylbenzene is obtained. 2.14 g of 1-acetamido-2-nitro-4-benzylsulfinylbenzene is treated with 4 g of 5N. Yaatri hydroxide and 12 ml of methanol on a steam bath for 30 minutes, diluted with water and filtered to obtain 1-amino-2-nitro-4-benzylsulfinylbenzene. 1.8 g of 1-amino-2-nitro-4-benzylsulfinylbenzene are treated in 120 ml of methanol and 30 ml of water 1.8 g of powdered iron and 0.9 g of ferrous sulfate (hereinafter FeS04) with heating under reflux for 4 hours, filtered, the filtrate is evaporated in vacuo, the residue is extracted with chloroform, the extract is evaporated, the residue is recrystallized from a mixture of methylene chloride-benzene and 1,2-diamino-4-benzylsulfinylbenzene is obtained, total yield 60-70%. 0.55 g of 1,2-diamino-4-benzylsulfinylbenzene, 0.44 g of 1, 3-bis- (methoxycarbonyl) -S-methylisothiourea, 0.15 MP of acetic acid in 20 ml of ethanol and 20 mp of water are heated for 4 hours reflux, filter and recrystallize the precipitate from ethanol to give .5 (6) -benzylsulfinyl-2-carboxometrobenzene idazol, m, rf, 224.5-226 ° C; yield 85%.
    In the same way, using p-chlorobenzyl, p-methylbenzyl and p-methoxybenzyl bromide instead of benzylbro. Foreign Ministry, receive, respectively, 1,2-diamino-4- (substituted benzylsulfinyl) benzene and 5 (6) - (substituted benzylsulfinyl) -2-carbomethoxyaminobenzimidazole,
    As a result of the interaction of 1,2-diamino-4- (substituted benzylsulfinyl) benzene with 1,3-bis- (ethoxycarbonyl) -, 1,3-bis- (propoxycarbonyl) or 1,3-bis- (butoxycarbonyl) -S -methyl isothiourea get 5 (6) - (substituted benzylsulfinyl) -2-carbalkoxyaminobenzimidazole, where R is ethyl propyl or butyl.
    Example 9. 1-Acetamido-2-nitro-4-benzylthiobenzene or 1-acetamido-2-nitro-4- (substituted benzylthiobenzene) is treated with an excess of peracetic acid and 5 (6) -benzylsulfonyl or 5 (bJ- (substituted benzylsulfonyl) is obtained) -2-carbalkoksnaminobenzimidazole.
    These compounds can also be prepared from 5 (6) -benzylsulfinyl or 5 (6) - (substituted benzylsulfonyl) -2-carbalkoxyaminobenzimidazole.
    EXAMPLE 10 5 g of 2-amino-4-chloro-1-nitrobenzene is added to a solution of sodium phenyl mercaptide prepared under a nitrogen atmosphere from 2.53 g of 57% sodium hydride and 6.2 ml of thiophenol in 20 ml of DMF, together with After washing with 10 ml of DMF, the mixture is stirred for 3 hours under nitrogen at 20-30 ° C, diluted with water, the crude product is washed with water and hexane, recrystallized from methanol and 2-amino-4-phenythylthio-1-nitrobenzene is obtained.
    6, O g of 2-amino-4-phenylthio-1-nitrobenzene is dissolved in 80 ml of acetic anhydride and a few drops of sulfuric acid are added, kept for 2 hours at 20-30 ° C, some sodium acetate is added, evaporated in a vacuum, the residue treated with water, filtered and recrystallized from methanol to give 2-acetamido-4-phenylthio-1-nitrobenzene,
    This product can be obtained from 2-acetamido-4-chloro-1-nitrobenzene and sodium phenylmercaptide.
    7.0 g of 2-acetamido-4-phenylthio-1-nitrobenzene are dissolved in 70 ml of chloroform and treated at (-20) - (-15) C with a solution of 5.0 g of 40% peracetic acid in 10 ml of methanol heated to 2Q ° C, stirred for 4 hours, extracted with sodium bisulfite solution, then sodium bicarbonate solution, dried and evaporated. A resinous product, which is 2-acetamido-4-phenylsulfinyl-1-nitrobenzene, is treated with 20 ml of 5N. sodium hydroxide and 40 mg of methanol at 20-25c for 1 h.
    dooaaaaaa water and almost completely pure 2 a vKHO-4 - phenylsulfinyl-1-n-trobezol is filtered off. Pro, the product can be recrystallized without benzene,
    5, 4 g of 2-amnno-4-fe1-: ylsulfinyl-1-nitrobenzene booster and poured under hydrogen pressure tm in 500 ml of methanol in the presence of 5 g of 5% pa: ala, gti on coal until the absorption of hydrogen ceases , filtered, the filtrate is evaporated in vacuo, the residue is recrystallized from methanol-benzene to give 1,2 diamino-4 sulfinyl benzene,
    5.5 g 1 g 2 - diam15No-4-phenol 5lsulfinyl5 benzene, 5,. 3 g of 1, (methoxycarbonyl) -3-metm.gtizotiourea and 1.2 MP of acetic acid in 100 hp of ethanol and 100 ml of water are heated .4 h with o6paTHbnvi cold; flax; m cooled
    0 and almost absolute number 5 (b) -phenylsulfinyl-2 carbomethoxyaminobenzimidazole is filtered and washed with methanol; it can be recrystallized from methanol-chloroform, so pl. (dec),; output 95; Overall
    5 yield 80-85%.
    Using 1, 3-bis - (ethoxycarbop 5l) -, .1, 3-bis- (propoxycarbonyl) or 1; 3-bis (butoxycarbonyl) -S-me; i ln 3 o t and oh-th che vin y, and k. b. c gi h no
    0 get 2-carbalkoksam1SHO-5 (6) -phenylsulfonylbenzimnlazol, where
    R is zhil. Poo, or butyl (with R, butyl, mp, 127, 5-132, 5 C).
    Using sodium aft-2 ormerc5 tkd instead of sodiumfenklmerkiptida, get 5 (b) -naft-2-ylsulfinyl-2-to a.z 5o iviaT o to siiminobenndaol, v-pl, 300C,
    (), mainframe and cc of fct: p / e 365
    0 plc 317 ,.
    g 2-aminoG; pmimep 1 1 „2.5 - i - clap -1 -nitrobenzene, 3.6 g p-thiocresol and 4.2 g sodium carbonate in 20 ml DMFL are stirred overnight at room temperature The temperature is mixed with water. After recrystallizing from pn methanol, 2-amino-4 - (p-methylphenylthio) -1-nitrobenzene is obtained.
    3.35 g of 2-α-4Mn-4- (p-methylphenylthio) -1-nitrobenzene in 16 br of concentrated hydrochloric acid and 16 ml of acetic acid are treated with 16 g of tin dichloride on a steam bath for 1 h, cooling; ; give, treat with excess potassium bicarbonate and
    5 extrahiryyut chloroform. After evaporation, 1,2 diamno-4- (p-methyl en lthio) -benzene is obtained, the total yield is 50%.
    2, - 5 g 1 f 2-, cri- aNT5-5HO 4- (pietylphenylthio) -benzene 2.35 g 1,3-bis- (meto toxicum carbonyl) -3 markers of urea and Of 75 mt acetic acid in 50 ml in, oy and 50 MP of ethanol are cooked for 3 hours with reverse malt on 1-5 grams, filtered
    5 and the product is recrystallized from
    methanol-chloroform mixtures to give 5 (b) - (p-methylphenylchio) - 2-carbomethoxy-aminobeneimidazole, t, pl. 22b ° C (decomp.); yield 90%.
    1.88 g of 5 (6) - (p-methylphenylthio) -2-carbomethoxyaminobenzimidazole is dissolved in a mixture of 150 ml of acetic acid and 150 ml of chloroform, a solution of 1.22 g of m-chloroperbenzoic acid in 20 ml of chloroform npiH {-15 ) - (- 10) ° C and slowly heating K1t to 20-25 ° C. After b h, the solvent is removed in vacuum at 20-30 C, the octopus is treated with sodium bicarbonate solution, filtered and recrystallized from methanol / chloroform, to give 5 (6) -methylphenylsulfinyl-2-carbomethoxybenzimidazole, t, pl. 265-267 s (decomp.); yield 90%.
    Using p-chloro, p-methoxy- and p-fluorophenylmercaptide instead of p-thiocresol, 5 (6) -p-chlorophenylsulfinyl-2-carbometoxyaminobenzimidazole are obtained, m.p. 292 ° C (decomp.), 5 (6) -n-methoxyphenylsulfinyl-2-carbomethoxyaminobenzimidazole, so pl. 275 ° C (decomp.), 5 (b) -n-fluorophenylsulfonyl-2-carb toxiaminobenzimidazole, so pl. 273 C (decomp.).
    Similarly, using the obtained 1,2-diamino compounds and 1f3-bis- (ethoxycarbonyl) -, 1,3-bis- (propoxycarbonyl) - or 1,3-bis- (butoxycarbonyl) -S-methylisothiourea, get 5 (6) -p-methyl-, 5 (6-p-chloro, 5 (6) -p-methoxy-, and 5. (6) -n-fluorophenylsulfinyl-2-carbalkoxyaminobenzimidazole, where R is ethyl, propyl, or butyl.
    Example 12. 2.0. g of 2-amino-4-HLOR-1-nitrobenzene and 5.0 g of sodium benzene sulfinate in 20 mp DMF are heated for 3 hours under reflux, cooled, diluted and filtered 2-amino-1-nitro-4-phenylsulfonylbenzene,
    1.9 g of 2-amino-1-nitro-4-phenylsulfonylbenzene in methanol is treated with hydrogen at a pressure of 4 atm per syringe) The presence of Rene nickel for 2 hours. The catalyst is filtered off, the filtrate is evaporated in vacuo, the residue is recrystallized and I get 1, 2- diamino-4-phenylsulfonylbenzene.
    0.75 g 1, 2-diamine 6-4-phenylsulfonylbenzene, 0.68 g 1,3-bis- (methoxycarbonyl) -S-methylisothiourea and Of 2 ml of acetic acid in 10 ml of ethanol and 10 ml of water are heated under reflux within 4 hours, the product is filtered off, recrystallized from methanol-chloroform and 5 (6) -phenylsulfanal-2-carbomethoxyaminobenzimidazole, m.p. 320 ° C.
    Mass spectrum: m / e 331 (M), main peak 143.
    Similarly, using 1,3-bis- (ethoxycarbonyl) -, 1,3-bis- (propoxycarbonyl) - or. 1,3-bis- (butoxycarbonyl) -S-methylisothiourea, get 5 (6) -phenylsulfonyl-2-carbalkoxyaminobenzimidazole, where R is ethyl, propyl or butyl.
    Example 13. 5 (6) - (p-substituted phenylthio) -2-carbalkoxyaminobenzimidazoles are treated with an excess of m-chloroperbenzoic acid and 5 (6) - (p-substituted phenylsulfonyl) -2-carbalkoxyaminobenzimidazoles are obtained, which can also be synthesized from 5 (6 ) - (p-substituted phenylsulfinyl) -2-carbalkoxyaminobenzimidazoles.
    Example 14. 2.94 g of 1-acetamido-4-hydroxy-2-nitrobenzene, 5.13 g of benzyl bromide and 4.2 g of anhydrous potassium carbonate are heated under reflux overnight in acetone with stirring, evaporated to dryness, the excess benzyl bromide is removed In vacuo, water is added, the mixture is extracted with methylene chloride and 1-acetamido-4-benzyloxy-2-nitrobenzene is obtained.
    1-Acetamido-4-benzyloxy-2-nitrobenzene is treated with sodium hydroxide in methanol, quickly heated on the steam bath for 40 minutes before the reaction stops, diluted with water, extracted with methylene chloride and get 1-amino-4-benzyloxy-2-nitrobenzene,
    2.44 g of 1-amino-4-benzyloxy-2-nitrobenzene is stirred in 10 ml of methanol and. 100 ml of 20% hydrochloric acid with 1.0 g of powdered iron at room temperature for 2 h, poured into an excess of ammonium hydroxide, the precipitate is extracted with chloroform, filtered under nitrogen, dried over magnesium sulfate, filtered again, evaporated to dryness and get 1,2-diamino-4-benzyloxybenzene.
    5 g of 1,2-diamino-4-benzyloxybenzene, 5 g of 1,3-bis- (methoxycarbonyl) -S-methylthiomethurene and 1.8 g of acetic acid are dissolved in 50 ml of ethanol and 50 ml of water, heated for 3 h. cooler, cool, 5 (6) -benzyloxy-2-carbomethoxyaminobenzimidazole is filtered off and washed with methanol, so pl. (different); yield 70%.
    Similarly, using p-chloro-, p-methyl- and p-methoxybenzyl bromide instead of benzyl bromide, I get 1,2-diamino-4- (substituted benzyloxybenzene) and 2-carbomethoxyamino-5 (6) - (substituted benzyloxybenzimidazole)
    When interacting 1,2-diamino-4-. (Substituted benzyloxybenzene) with i, 3-bis- (ethoxycarbonyl) -, 1,3-bis- (propoxycarbonyl) - or 1,3-bis- (butoxycarbonyl) -S- methyl xothiourea
    receive 2-carbalkoxyamino-5 (6) - (substituted benzyloxybenzimidazole), where R is ethyl, propyl or butyl.
    Example 15. 1-Acetamido-4-hydroxy-2-nitrobenzene is treated with alkenyl or alkynyl halides to give 5 (6) -alkenyloxy-2-carbalkoxybenzimide aols, including 5 (6) - (prop-2-en-1-yloxy) - 2-carbomethoxyaminobenzimidazole, m.p. 217 ° C (decomp.), Or 5 (6) -alkynyloxy-2-carbalkoxybenzimidazoles.
    Example 16, 2.37 g of 1-acetamido-2-nitro-4-thiocyanatobenzene in 10 MP of DMF at 20-25 ° C in a nitrogen atmosphere is treated with 0.38 g of sodium borohydride, after 1 h, 1.61 ml of chloromethyl methyl is added ether, incubated for 3 hours at 20-30 ° C, water is added and the mixture is filtered and recrystallized from cyclohexane with 1-acetamido-2-nitro-4-methoxymethylthiobenzene.
    1,4 g of 1-acetamido-2-nitro-4-methoxymethylthiobenzene is treated with 3 ml of 5N. sodium hydroxide and 6 ml of methanol on a steam bath for -15 min, evaporated in vacuo, the residue is extracted with chloroform. The dried extracts are evaporated and 1-amino-2-nitro-4-methoxymethylthiobenzene is obtained as red crystals.
    1.3. g 1-amino-4-nitro-4-methoxymethylthiobenzene in 80 ml of methanol and 20 MP of water is heated under reflux under nitrogen with 0.7 sulphate of iron and 2.8 g of iron (added in two portions) for 4 hours filtered, evaporated in vacuo, the residue is recrystallized from cyclohexanch to obtain 1,2-diamino-4-methoxymethylthiobenzene.
    0.85 g of 1,2-diamino-4-methoxymethylthiobenzene and 1.0 g of 1,3-bis- (methoxycarbonyl) -S-methylisothiourea in 25 ml of ethanol and 25 ml of water are heated under reflux with 0.7 ml of acetic acid after 1 h, cooled, filtered and get 5 (6) -methoxymethylthio-2-carbomethoxyaminobenzimidazole, which can be recrystallized from a mixture of methanol / chloroform, so pl. 200-201.5 ° C; output at the last stage 75%; Obl. Yield / V 75%.
    Similarly, using hloretil-, hlorpropil-, hlorbutilmetilovy ether hlormetilztilovy, hlormetilpropilovy or hlormetilbutilovy ester instead of chloromethyl methyl ether to give 1,2-diamino-4-alkoksialkiltiobenzol and 5 (6) 2--alkoksalkiltio karbometoksiaminobenzimidazol including 5 (6) - methoxypropyl-2-carbomethoxyaminobenzimidazole, so pl. 171.5-174 C. Using 1,3-bis- (ethoxycarbonyl) -, 1,3-bis- (propoxycarbonyl) - or 1,3-bis- (butoxycarbonyl) -S-methylisothiourea, is obtained. 5 (6) -alkoxyalkylthio-2-carbalkoxyaminobenzimidazole, where R is ethyl, propyl or butyl.
    Example 17, 5.85 g of 1-amino-2-nitro-4-thiocyanatobenzene is treated in 20 ml of DMF under a nitrogen atmosphere at 20-25 0 1.14 g of sodium borohydride for 1 h, 10 ml of methylthiomethyl chloride are added for overnight, diluted with water and extracted with chloroform. The dried extract is passed through a column filled with silica gel, evaporated to dryness and 1-amino-2-nitro-4-methylthiomethylthiobenzene is obtained as a red solid.
    2.5 g of 1-amino-2-nitro-4-methyl5 thiomethylthiobenzene in 160 ml of methanol (i 40 ml of water is heated under reflux for 5 hours with 1.25 g of ferrous sulfate and 5 g of powdered iron (added in two portions) Filtered, evaporated
    0 the filtrate, the oily residue, containing 1,2-diamino-4-methylthiomethylthiobenzene, extracted with chloroform, washed, dried and evaporated the extract.
    five
    1.8 g of 1,2-diamino-4-methylthiomethylthiobenzene, 1, 9 .g 1, 3-bis- (carbonyl si-marks) -S-methylthioisothiourea and O, 3 ml of acetic acid in 20 ml of ethanol and 20 ml of water heat up
    0 under reflux for 5 h, cooled and filtered. 5 (6) -methylthiomethylthio-2-carbomethoxyaminobenzimidazole is recrystallized from methanol-chloroform,
    5 m.p. 208-210.5 ° C; total yield of 20%.
    In the same way, using ethyl-, propyl-, butiltiometilhlorid, metiltioetil-, metiltiopropil-, methylthiobutyl, ethylthioethyl or etiltiotsropilhlorid obtained dyami0 1,2-but-4-alkiltioalkiltiobenzol and 5 (6) 2--alkiltioalkiltio karbometoksiaminobenzimidazol including 5 (6) methylthioethylthio, m.p. 209C (decomp.), And 5 (6) -ethylthioethylthio-2-carbomethoxyamino5 benzimidazole, m.p. 197 ° C (decomp.) ..
    As a result of the interaction of 1,2-diamino-4-alkylthioalkylthiobenzenes with 1,3-bis- (ethoxycarbonyl) -, 1,2-bis- (propoxycarbonyl) -. or 1.30-bis- (butoxycarbonyl) -S-methylisothiourea; get 5 (6) -thhylthioalkylthio-2-carbalkoxyaminobenzimidazole, where R is ethyl, propyl or butyl.
    five
    Example 18.6g of 1-acetamido-4-hydroxy-2-nitrobenzene is mixed with 200 ml of acetone containing 25 g of potassium carbonate and 6 ml of chloromethylmethyl sulfide, heated for 1 hour under reflux and filtered. The acetone is removed and 1-acetamido-4 is obtained -methylthiomethoxy-2-nitrobenzene as a gummy product, which is purified by column chromatography.
    5 5.7 g of 1 acetamido-4-methylthiomethoxy-2-nitrobeneol are added to the mixture 12 ml of 5N. sodium hydroxide and 60 ml of methanol, heated for 15 min Ma steam bath, poured into 500 ml of water and extracted with methylene chloride. The extract is dried over sodium sulfate, evaporated, 1-amino-4-methylthiomethoxy-2-nitrobenzene is obtained in a resinous product mix, which is dissolved In a mixture of 5 ml of acetic acid and 95 ml of methanol, 8 g of powdered iron are added and the mixture is heated under reflux for 2 hours. Methanol and acetic acid are discarded, the residue is extracted with 200 ml of hot tetrahydrofuran (THF), sieved and evaporated to give 1,2-diamino-4-methylthiomethoxybenzene as a gummy product, which is purified by column chromatography, 4.1 g 1, 2-diamino-4-methylthiomethoxybenzene, 5 g of 1,3-bis- (methoxycarbonyl) -S-methylthiourea and 1 g of the acid, are dissolved in 50 ml of ethanol and 50 ml of water, heated to reflux for 3; h, cooled and 5 (b) -methylthioteas with C-2-carbomethoxyaminobenzimidazole is filtered off and washed with methanol. Can . recrystallize the pr from a mixture of methanol-chloroform ,, T:. pl. 215-217 ° C (decomp.). Thus, using chloroethyl, chloropropyl-, chlorobutylmethylsulfide, chloromethylethyl-, chloromethylpropyl- or chloromethylbutylsulfide, 1.2 diamino-4-alkylthioalko-sibenzene and 5 (6) -alkylthioalkoxy-2-alkylmethylobenzimidazole and 5 methylthioethoxy-2-carbobo-mutoxyaminobenzimidazole, m.p. 214 217 ° C (decomp.). As a result of the interaction of 1 ,, 2-diamino-4-alkylthioalkoxybenzene, 1,3-bis-ethoxycarbonyl) -, 1,3-bis- (propoxycarbonyl) - or 1 |, 3-bis- (butoxycarbonyl) -S-methylisothiomeo chevine 5 (6) -alkylthio-2-carbalkoxyaminobenzimidazole, where R is ethyl, propyl or butyl. Example 19. 1-Acetamido-4-hydroxy-2-nitrobenzene is treated with chloromethyl, chloroethyl, chloropropylchlorobutylmethyl ether, chloromethyl ethyl, chloromethylpropyl, methyl chlorine butyl, chloroethyl ethyl, and chloroethylpropyl ether to give 5% alkyloxy, chloromethyl ethyl, methyl chlorofluoromethyl ether, chloromethyl ethyl chlorine, chloromethyl propyl chloroformate including the 5 (6) -me current of the si-2 k-2 ball of the coca amino 5 (6) - (2-ethoxyethoxy) 2-carbomethoxy-aminobenzimidazole, m.p. 206 (dec) Example 20: 2.4 g of 100% sodium hydride are dissolved in 120 ml of 2-methoxyethanol, 12 g of 2-nitro-5-chloroaniline are added, heated in reverse for 4 hours, cooled and mixed with water. The resulting 2-nitro 5- (2-methoxyethoxy) -aniline is filtered off. 11 g of 2-nitro-5- {2-methoxyethoxy) -aniline, 220 ml of methanol, 460 ml of water, 40 g of sodium carbonate and 60 g of sodium bisulfite are heated for 15 minutes under reflux, evaporated, diluted with water and extracted with chloroform. After evaporation, 1,2-diamino-4- (2-methoxyethoxy) benzene is obtained as an oily product of almost absolutely pure, suitable for subsequent synthesis. A mixture of 1.8 g of 1,2-diamino-4- (2-methoxyethoxy) benzene, 2.2 g of 1,3-bis- (methoxycarbonyl) -S-methylisothiourea, 0.8 ml of acetic acid in 20 ml of ethanol and 20 ml of water are heated under reflux for 4 hours, cooled, filtered and 5 (6) - (2-methoxyethoxy) -2-carbomethoxyaminobenzimidazole is obtained, which can be recrystallized from methanol / chloroform, mp. 213-215c, Example 21, 5g of 2-nitro-5-chloroaniline and 7.5 g of sodium sulfide monohydrate in 25 ml of ethanol and 25 ml of water are heated under reflux for 1 hour, diluted with water to ml, filtered, the filtrate treated with 2.5 acetic acid 2-nitro-5-mercaptoaniline is filtered off. A solution of 3.4 g of 2-nitro-5-mercaptoaniline in 20 ml of DMF is treated with 0.5 g of 100% sodium hydride, 2.2 g of chloromethyl ethyl ether are added, the mixture is kept at 20-25 ° C for 30 minutes, diluted with water and extracted chloroform. After removal of chloroform, 2 nitro-5- (ethoxymethylthio) -aniline is obtained as an oily product. The oily product obtained is treated for 15 minutes in a boiling mixture of 50 ml of methanol, 50 ml of water, 12 g of sodium carbonate and 12 g of sodium bisulfite, evaporated, diluted with water and extracted with chloroform. After evaporation of the extract, 1,2-diamino-4-ethaxymethylthiobenzene is obtained as an oily product, 2.6 g of an oily product, 2.6 g of 1,3-bis (methoxycarbonyl) -S-methylisothiourea and 1 ml of acetic acid is treated with 40 50 ml of an aqueous solution of ethanol boiling under reflux for 4 hours is cooled and filtered to obtain 5 (6) -ethoxymethylthio-2-carbomethoxyaminobenzimidazole, which can be recrystallized from methanol-chloroform, mp. 199-201 C. 0.84 g of 5 (6) -ethoxymethylthio-2-carbomethoxyaminobenzimidazole is dissolved in a 50 ml mixture. chloroform and 10 ml
    acetic acid, treated at (-30) - {- 20C) with a solution of 0.62 g of m-chloroperbenzoic acid in 15 ml of chloroform, slowly heated to room temperature. After 15 minutes, the solvent was removed in vacuo, the residue was treated with dilute potassium bicarbonate solution. The crude 5 (6) -ethoxymethylsulfinyl-2-carbomethoxyaminobenzimidazole is filtered off and recrystallized from methanol-chloroform, mp. 200 ° C (decomp.)
    Example 22: A solution of 2.37 g of 1-acetamido-2-nitro-4-thiocyanatobenzene in 10 ml of DMF is treated under nitrogen at 20-30 ° C with 0.38 g of sodium borohydride, and after 1 h, 1.61 ml of chloromethyl methyl is added. ether at 20-30 ° C, after another 3 hours, diluted with water and filtered. Crude 1-acetamido-2-nitro-4-methoxymethylthiobenzene is recrystallized from cyclohexane.
    1.4 g of 1-acetamido-2-nitro-4-methoxymethylthiobenzene are treated in 6 ml of methanol 3 ml of 5N. sodium hydroxide and heated under reflux for 15 minutes, the solvent is removed in vacuo, the residue is diluted with water and 2-nitro-4-methoxymethioaniline is isolated as reddish crystals.
    1.4 g of the obtained compound is treated in a refluxing mixture of 80 ml of methanol and 20 ml of water, 1.4 g of powdered iron and 0.7 g of ferrous sulfate. After 2 hours, another 1.4 g of iron powder is added. After another 1-2 hours, it is filtered, the filtrate is evaporated in vacuo, and 1,2-diamino-4-methoxymethylthiobenzene is recrystallized from cyclohexane.
    1.7 g of 1,2-diamino-4-methoxymethylthiobenzene are treated in 50 ml of a 50% aqueous solution of ethanol boiling under reflux with 2.0 g of 1, 3-bis- (methoxycarbonyl) -S-methylisothiourea and 0 , 7 ml of acetic acid for 4 h, cool and filter 5 (b) -methoxymethylthio-2-carbomethoxyaminobenzimidazole, which can be recrystallized from methanol-chloroform, so pl. 200-201.5s (decomp.).
    0.53 g of the obtained substance is dissolved in a mixture of 50 ml of chloroform and 50 ml of acetic acid at -15 ° C, a solution of 0.41 g of m-chloroperbenzoic acid in 10 ml of chloroform is added at (-15) - (- 10) ° C and heated to 20-25 seconds. After 10 hours at 20-25 ° C, the solvent is removed in vacuo, the residue is thoroughly treated with dilute sodium bicarbonate solution (pH 7), filtered and recrystallized from methanol: Poropoform, resulting in 5 (b) methoxymethylsulfinyl 2-carbomethoxyaminobenemidazole, m.p. 300s
    Mass spectrum: m / e 283 (M), main peak 45
    Example 23 A mixture of 4 g of 4-hydroxy-6-nitroacetamide, 17 g of potassium carbonate, and 4 g of chloromethyl methyl ether in 50 ml of acetone is heated under nitrogen at reflux for 4 hours. The hot mixture is diluted with 200 ml of hot acetone and
    0 filtered. The filtrate is evaporated to give 2-nitro-5-methoxymethoxyacetanilide as a red oily product.
    4.5 g of 2-nitro-4-methoxymethoxy5 acetanilide is heated for 30 minutes with 10 ml of 5N. sodium hydroxide and 60 ml of methanol, cooled, diluted with water and filtered, 2-nitro-4-methoxymethoxyaniline,
    0
    3.5 g of 2-nitro-4-methoxymethoxyaniline in the absence of 1 g of 5% palladium on charcoal and 120 ml of methanol are reduced by hydrogen until the absorption is completely stopped: the last one is filtered, evaporated
    5 filtrate and get 1,2-diamino-4-methoxymethoxybenzene.
    3.0 g of 1,2-diamino-4-methoxymethoxybenzene in 15 ml of ethanol, 15 ml of water and 0.5 ml of acetic acid are treated with 3.0 g of 1,3-bis (methoxycarbonyl) -3-methyl-iso-echevin when heated under reflux for 4 h, cooled, filtered and recrystallized
    5 precipitate, from methanol-chloroform, to obtain 5 (6) -methoxymethoxy-2-carbomethoxyaminobenzimidazole, m.p. 216218 ° C (dec,).
    Example 24. b g of 4-oxy-60-nitroacetanide, 25 g of potassium carbonate, 5 g of chloromethyl sulfide in 200 ml of acetone are heated under reflux for 4 hours under nitrogen atmosphere. The hot mixture is diluted with 300 ml of hot acetone and filtered. The filtrate is evaporated, the oily residue is passed through a column filled with silica gel, eluted with chloroform to obtain pure 2-nitro-4-methylthiomethoxyacetanilide.
    0
    5.7 g of 2-nitro-4-methylthiomethoxyacetanilide are treated with 12 ml of 5 n. sodium hydroxide and 60 ml of methanol, heated for 30 minutes, cooled, diluted with water and extracted with chloroforum. The extract was dried over sodium sulfate and evaporated to give 2-nitro-4-methylthiomethoxyaniline.
    4.5 g of 2-nitro-4-methylthiomethoxyaniline in 95 ml of methanol and 5 ml
    3 g of powdered iron are processed with acetic acid, heated for 4 hours under reflux. The hot solution is filtered, the filtrate is evaporated, the residue is treated with hot THF, filtered, evaporated and
    5 get 1,2-diamino-4-methylthiomethoxybenzene. 3.9 g of 1,2-diamino-4-methylthiotoxy benzene in 25 ml of ethanol, 25 rvin of water and 0.6 ml of acetic acid are treated with 5.0 g of 1,3-bis (methoxycarbonyl) -8 methylisothiourea under heating with reflux for 4 hours, cool, filter, and the precipitate is recrystallized from THF to give 5 (6) -methylthiomethoxy-2-carbomethoxyaminobenzimidazole, m.p. 216-217 C (decomp.). Example 25. 2.5 g of 4-hydroxy-6-nitroacetanilide, 2.1 g of 2-bromo; of ethyl ethyl acetate and 3.6 g of potassium carbonate in 25 ml of daF are heated to 11 under nitrogen for 16 hours, cooled, diluted with water and 4- (2-ethoxyethoxy) -2-nitroacetanilide is filtered, 2.3 g of 4- ( 2-ethoxyethoxy) -2-nitro-acetanilide is heated for 30 minutes with 5 ml. 5 n. sodium hydroxide and 30 ml of methanol, cooled, diluted with water and 4- (2-ethoxyethoxy) -2-nitroaniline filtered 1.8 g of 4- (2-ethoxyethoxy) -2-nitroaniline in the presence of 5% palladium on charcoal and 200 mp of methanol is reduced by hydrogen until the absorption of the latter is stopped, filter -and 1,2-diamino-4- (2 ethoxyethoxy) -benzene is obtained by evaporation of the filtrate, 1.6 g of 1,2-diamino-4- (2-ethoxyethoxy) -benzene in 12 ml of ethanol ,. 12 m of water and O, 3 ml of acetic acid are treated with 2 g of 1, 3-bis- (methoxycarboNIL-) -S-methylisothiourea by heating under reflux for 4 h, cooled, filtered, the precipitate is recrystallized from methanol-chloroform and 5 (6) - (2-ethoxyethoxy) -2-carbomethoxyam nobenzimidazole is obtained, m.p. 20b-208 s (decomp, yield 65%. Similarly, using 2-bromoethylphenyl ether, 5 (6) - (2 -phenoxyethoxy) -2-carbomethox aminobenzimidazole, mp 221-223 C (decomp.); yield 50%. Example 26. 6 g of 1-amino-2-nitro-4-thiocyanatobenzene in 20 m: and DMF is treated in the atmosphere Sphere of nitrogen 1.17 g of sodium borohydride in 10 ml of DMF at a temperature not higher than 30 ° C, stirred for 1 hour at 15-20 ° C, treated with 5 g of 2-bromoethyl ethyl ether at (-20) - (- 25) C, heated to 100 for 2 hours, cooled and diluted with water. Extraction is carried out with chloroform (5 grams, the extract is dried over sodium sulfate, evaporated. And the mixture is obtained la. IHO-2-nitpo-4- (2-ethoxyethylthio) benzene. 6.4 g 1 -amino-2-nitro-4- (2-ethoxy ethylthio) -benzene in 100 ml of methanol and 50 ml of water are treated with 16 ml of sodium dithionate and 14 g of sodium carbonate at reflux under nitrogen for 3 0 min, the methanol is distilled off, diluted with 100 ml of water and extracted with chloroform. The extract is dried over sodium sulfate, evaporated and get 1,2-diamino-4 (2-ethoxyethylthio) -benzene, 4f8 g of 1,2-diamkno-4- (2-ethoxyethylthio) -benzene in 25 ml of ethanol, 25 ml of water and 1 ml of acetic acid is treated with 7.5 g of 1,3-bis- (methoxycarbonyl) -S-methylisothiourea by heating under reflux for 4 hours, cooled, filtered and the residue is recrystallized from methanol-chloroform, to give 5 (6) - (2-ethoxyethylthio) -2-carbomethoxyaminobenzimidazole, mp, 185-ISS C (decomp.). Using 2-bromoethyl methyl ether, 5 (6) - (2-methoxyethylthio) -2-carbomethoxy-aminobenzimidazole, similarly, is obtained. (dil,), Example 27 ,, 4.4 g of 1-amino-2-nitro-4-thiocyanatobenzene in 10 mp DMF is treated under nitrogen at a concentration of 0.85 g of sodium borohydride in 10 ml of DMF at a temperature not higher than and stirred at 15 -20 ° C for 1 h, treated with 5 g of 1,1,1-trifluoro-2-bromoethane at 20–25 ° C, heated to 100 ° C for 3 h, cooled and diluted with water. Extraction is carried out with chloroform, the extract is dried over sodium sulfate, evaporated and 2-NITRO-4- (2, .2, 2-trifluoroethylthio) -aniline is obtained, 4.2 g of 2-NITRO-4- (2,2,2-trifluoroethylthio) β-aniline in 60 ml of methanol and 12 ml of water are treated with 1.25 g of ferrous sulfate and 3.3 g of powdered; iron under reflux for 2 hours, 1.25 g of ferrous sulfate and 3.3 g of powdered iron are added, heated for another 4 hours, transferred to 600 ml of hot THF and filtered. 1,2-diamino-4 (2,2,2-trifluoroethylthio) -benzene is obtained from the filtrate after evaporation. 3.4 g of 1,2-diamino-4- (2,2,2-trifluoroethylthio) -benzene in 17 ml of ethanol, 17 ml of water and 1 ml of acetic acid are treated with 3.5 g of 1,3-bis- (methoxycarbonyl) -S-methylisothiourea by heating under reflux for 4 hours, cooled, filtered and the resulting product was recrystallized from methanol-chloroform to give 5 (6) - (2,2, 2-trifluoroethylthio) -2-carbomethoxyaminobenzimidazole. 1.2 g of 5 (6) - (2,2,2-trifluoroethylthio) -2-carbomethoxyamino benzyl dazole in 480 ml of chloroform, 120 ml of methanol and 2 g of acetic acid are treated with 0.75 g of 85% m-chloroperbenzoic Acidic acid O C, stirred. 1 4f extracted with saturated sodium bicarbonate solution and water. The chloroform layer of BbicyLjTiQaioT is over sodium sulfate and evaporated, the residue is recrystallized from methanol and 5 (6) - (, 2-trift orethyl sulfide fi NIL) is obtained - a carbonate about ciagli. nobenzimidazole, tpl,
    The mass spectrum of S t / e 321 () is the suspicious peak 206. In a similar way, using .5 (6) methylthiomethoxy-2-carboxome / inobenzig, ldazol. 5 (b) -methylsul are obtained (Leonyl ketoxy-2-carbomethoxyaminobenzigethadazole f m.p., 208-210 C (decomp.),
    EXAMPLE 28, 1.8 g 5 (6) -2- {2-ethoxyethylthio) -2-carbomethoxy-1-c-gcobenzimidazole in 200 ml of hporoorma and 1 ml of acetic acid of the treatment tube; 1.55 g of 30% peracetic acid in a solution of acetic acid at 1 hour and evaporate. Evaporate the residue. The residue is mixed with ether, the solid is filtered off and recrystallized from methanol / chloroform gives 5 (6) -2 -. {2-ethyl acetate-2-2-carbomethoxyamic benzimidazolg m.p. 167-170 ° C (decomp.); yield 60%
    Similarly, from 5 (6) -2- (2-methoxy ethylthio) -2-carbomethoxybenzoimidazole, 5 (b) -2- (2 methoxyethylsulfinyl) -2-carbomethoxya.fs- is obtained: cobenzimidazole, mp. 19 7-200 ° With (decomp.) Yield 70%.
    Example 29. 5g of 1-amino-2-nitro-4 thiocyanatobenzene in 20 ml of daFA is heated in a nitrogen atmosphere with 0.97 g of borohydride:; at 20 4gg DM FA at a temperature not higher than 30 ° C is stirred at for 1 h, processed .6 g 1-iodine-2, 2 ,, 3, 3-tetrafluoropropane,. heat to 100 ° C for 4 hours, cool and dilute with water. It is extracted with chloroform, the extract is evaporated, the remaining oily red product is passed through a column filled with silica gel, and 2-nitro-4- (2,2,3,3-tetrafluoropropylthio) -ainine is obtained.
    4 g of 2-nitro-4- (2,2.3, 3-tetra-fluoropropylthio) -aniline are treated with 24 g of tin dichloride in 25 ml of concentrated hydrochloric acid, stirred for 30 minutes, podflavlachvuyut P1 hydroxide of ammonium and extracted with chloroform. The extract is filtered / dried, dried over sodium sulfate, evaporated and 1, 2-diaGN-4- (2, 2, 3,3-tetrafluoropropyl-type) -benzene is obtained.
    3.5 g of 1,2-daamino-4- (2, 2,3,3-tetrafluoropropylthio) -benzene in 20 ml of ethanol, 20 h of water and 0.8 ml of acetic acid are treated with 4.5 g 1.3 -bis- (methoxycarbonyl) -5-methyliso-thiourea under reflux for 4 hours,
     icJOT, filtered and recrystallized -; - jo) precipitate from methanol, obtaining (2-2,3,3-tetrafluoropropylthio) -2-, ifiTOKCK and picobekzide dazole. r 5 (6) - (2 J, 2, 3, 3-tetrafluoropro :: o) - 2 - to the armament of the co: a NE and a bee and In. oastzorenogo in 10 KP vinegar, about
    zloty, processing.tva} from at 20 C
    -jn; .. „- on and on, y, kusnuskmslot in yoy: ZORA uk suskoy acid, mix 30 and dilute 150 p liter, filter: comfort, solid, g (b1 is the product uninstalled from methanol and take into account 5 {6; - (2;. 2,. 3, 3-tetrafluoroprosulfonic) -Z-KapooMeTOKcHaMKHO znmgdazol, t, pl, 31СР C.
    - -1 T, -; --- Sr, - (-iv -.-; g -i-r-T TTJ / l O i G l M O R
    J. -, - - -. , 1 with:: L jV / i. / v) J-i / Ch. l-rf ri t Jt
    Pich 276,
    : p v; P: p 30, Apply, 1 - IODINE, 3 J 3, 3-penta.fluoropropane, g dp vos: o; lennya 100 ml of methanol, 10 ml of vCHOH acid and 10 g of iron powder, from 4.1 g to 1.2 dymi4 2 f 2, 3, 3 (. 3-pentafluoropropylthio) neol, 5 g 1, 3-bis- (methoxycarbose) -S-methyl ester-juchevine, 30 ml xHOjia, 30 MP water, d and 1 ml acetic acid
    5 get -5 (6) - (2,2, 3,3,3 ntafluoropropyl-1-thio) - to 516) {2,2,3, -tect of atoropropylsulphyl nyl) -2. Ibomethoxyamicobenzimidazole, l. ,
    D Mass-spektr: gp / e 371 (M), founding-to 69,
    P P and 1 h er 3. 6.0 kg} -am eno; -; itro-4 Chlorbekzol and 7.2 kg of potassium bonate from 25 l D. MFD processing 4, 0 kg of thiophenol in the atmosphere pereiksvayit 2 h, cooled 140 l ice water. :: - pci.; eiiEi3aiOT 1 h: n 1-amino-2 5-phen: 1LbiobenOl filter-1, 5 kg 1-amino 2-nitro-5-f.nylthioog;: - yola in 60 l of methanol and 30 l water - 8.0 kg sodium dithionate is refined; t: 2 ,. About a kg of sodium carbonate, in an aeote atmosphere when heated with a reverse:. S;: o, with a slice for 2 hours, distilled off, the mixture is distilled, the mixture is cooled and the extract; p, me: ilen chloride, the extract of Fg-l-shrub, . they are sulphate over with% g of lp; atri, upar11Bayug and get 1, 20-d11ag-4-phenylthiobenzene.
    3.25 kg 1, 2 - diamino 4 phenylthio be ;; ash in 45 l of ethanol - 45 l of water and 2 l of acetic acid are treated, 3 kg 1, 3-bis (methoxycarbonyl) -S5-methyl-n-thiourea with Kag: with a refrigerator for 4 hours, cool and 5 (b) -phenylthio-2-to-a r bsmet about: si a bk but without it and MI yes, from the filter,
    0
    3, 26 kg of 5 (6) -phenylt; -1O-2-carbo; etoksiaa.shnobyzyzim idazolova in 30-l of acetic cyst treated with 2.70 kg 30 gn-on, cus-acetic acid in solution: acetic-acid, alternated for 1 hour, diluted there are 30, l of water and 5 (b) phen5 nilsulfinyl-2-carbomethoxyaminobe zimidaeol, m.p. 253 C (Rael.), From the filter. Example 32, 5g of 1-amino-2-nitro-4-thiocyanatobenzene in 15 1 g of DMF treated in the aTN SOsphere, nitrogen 0.97 g of sodium borohydride in 10 ml of DMF at a temperature not higher, peremenyvayut 1 hour at 15-20 C, treated with 4, 5 g of 3-propionitrile P1ei 20-25 ° C, heated to 3 hours, cooled and diluted with water. Extracted with chloroform, the extract is dried over sulfate. sodium, evaporated and get 1-amine -2-NITRO-4- (2-cyanoethylthio) -benzene, 2.3 g of 1-amino-2-nitro-4- (2-cyano ethylthio) -benzene in 30 ml of methanol and 6 ml of water is treated with 2.5 g of iron sulphate and 3.3 g of powdered iron are heated with an opposite condenser for 2 hours, 1.5 g of iron sulphate and 3.3 g of powdered iron are added and heated for 4 hours. The mixture is added to 600 m Echer bringing THF and filtered. 1,1-Diami no-4- (2-cyanoethylthio) benzene is obtained after evaporation of the filtrate .. 1.9 g of the obtained compound in 10 m of water and 1 ml of acetic acid are treated with 2.1 g of 1,3-bis- (methoxycarbonyl) -S-methylisothiourea by heating under reflux for 4 hours, cooled, (} 1ltruct1t and the residue is recrystallized from methanol-chloroform, to give 5 (6) - (2-cyanoethylthio) -2-carbomethox aminrbenzimidazole, 1, 2 g of 5 (6) - (2-cyanoethylthio) -2-carbomethoxy-aminobenzimidazol in 400 ml of chloroform, 10 ml of methanol and 2 ml of acetic acid per treatment from 0.85 g of 85% m-chlornadben zoic acid at, stirred for 1 h, extracted with saturated sodium bicarbonate solution and water.The chloroform layer is dried over sodium sulfate, evaporated, the residue is recrystallized from methanol and get 5 (6) - (2-cyanoethylsulfinyl) -2-carbomethoxyaminobenzimidazole, so pl. 227-228c (decomp.). Example 33. 4.4 g of 1-amino-2-nitro-4-thiocyanatobenzene in 10 ml of DMF are treated in aTMOciJepe of nitrogen with 0.85 g of sodium borohydride in 10 ml of DMF at a temperature of not Biioiie 30 С , stirred at 15-2 ° C for 1 h, treated with 5 g of hporacetonitrile at 20-25 ° C, kept in flow ue overnight shei room t perature and smeishvayut with water. After filtration and recrystallization from methanol, 1-amino-2-nitro-4-cyanomethylthiobenzene is obtained. 4.1 g of 1-amino-2-nitro-4 cyanomethylthiobenzene in 60 ml of methanol and 12 ml of water are treated with 1.25 g of ferrous sulfate and 3.3 g of powdered iron with heating under reflux. After 2 hours, 1.25 g of ferrous sulfate and 3.3 g of powdered iron are added and heated for another 4 hours. The mixture is transferred to 60 ml of hot THF and filtered. After evaporation of the filtrate, 1,2-diamino-4-cyanomethylbenzene is obtained. 2.4 g of 1,2-diamino-4-cyanomethylthiobenzene in 17 ml of ethanol, 17 mp of water and 1 ml of acetic acid are treated with 3.5 g of 1; 3-bis- (methoxycarbonyl) -S-methylisothiourea by heating with reverse the refrigerator for 1 h, cooled, filtered, the precipitate is recrystallized from a mixture of methanol-chloroform and get 5 (b) cyanomethylthio-2-carbomethoxyaminobenzimidazole. 1.2 g of 5 (6) -cyanomethylthio-2-carbomethoxyamnobenzimidazole in 480 ml of chloroform, 120 ml of methanol and 2 ml of acetic acid are treated with 0.75 g of 85% m-chloroperbenzoic acid at 0 ° C, stirred for 1 hour, extra1 Route with saturated sodium bicarbonate and water. The chloroform layer is dried over sodium sulfate, evaporated, and after recrystallization of the residue from methanol, 5 (6) -cyanomethylsulfinyl-2-carbomethoxyamino benzimidazole is obtained, m.p. -325с. Mass spectrum: m / e 278 (M); main peak 206. Example 34. A mixture of 5 g of 2-nitro-5-chloroaniline and 7.5 g of sodium sulfide monohydrate in 25 ml of ethanol and 25 ml of water is heated for 1 hour with a reverse fridge, diluted with water to a volume of 150 ml and filtered from a small the amount of insoluble impurities. The filtrate is treated with 2.5 ml of acetic acid and 2 nitro-5-mercaptoaniline is filtered off. A solution of 3.4 g of 2-nitro-b-mercapto-aniline in 20 ml of DMF is treated with 0.5 g of 100% sodium hydroxide solution, 2.2 g of chloromethyl thiocyanate are added, and the mixture is kept for 30 minutes at 20-25 ° C. It is diluted with water and the chloroform is extracted. After removal of chloroform, 1-amino-2-nitro-5- (thiocyanatomethylthio) benzene was isolated. The 1-amino-2-nitro-5- (thiocyanatomethylthio) -benzene is treated for 15 minutes with a boiling mixture of 50 ml of methanol, 50 ml of water, 12 g of sodium carbonate and 12 g of sodium bisulfite, evaporated, diluted with water and extracted with chloroform. After removal of chloroform, 1,2-diamino-4g- (thiocyanatomethylthio) -benzene is obtained. A mixture of 2.6 g of the obtained compound, 2.6 g of 1,3-bis- (methoxycarbonyl) -S-methylisothiourea and 1 ml of acetic acid is treated with 40 ml of an ethanol solution boiling under reflux for 1 (, cooled, filtered to 5 (6) -thiocyanatomethylthio-2-carbomethoxyaminobenzig. 1 isedol is obtained, which can be recrystallized from methanol-chloroform.
    0.84 g of 5 (6) -thiocyanatomethylthio-2-carbrmethoxyaminobenzimidazole is dissolved in a mixture of 50 ml of chloroform and 10 ml of acetic acid, treated at (-30) - (- 20) With a solution of 0.62 g of m-chloroperbenzoic acid in 15 ml of chloroform, allowed to warm to room temperature after 15 minutes, evaporated in vacuo, the residue is treated with a dilute solution of potassium bicarbonate and the resulting 5 (6) thiocyanatomethylsulfinyl-2-carbomethoxyaminobenzimidazole is filtered and recrystallized from methanol-chloroform.
    Similarly receive
    5 (6) -ethylsulfinyl ethylthio-, so pl. 190C (dec),
    5 (6) -methylsulfonylethoxy-, so pl. 225-22bs (decomp.)
    5 (6) -methylthioethylsulfinyl-, so pl. 172 ° C (decomp.)
    5 (b) ethylsulfinyl ethylsulfinyl. Mp. 169 ° C (decomp.)
    5 (6) -phenylthioethylthio, m.p. 210-210 ° C
    5 (6) -phenylsulfinyl ethylthio, m.p. 18b-188 ° C,
    5 (6) -prop-2-en-1-yloxy-, i.e. 217 ° C (decomp.)
    5 (6) -3-phenoxypropylthio, m.p. 196 ° C (decomp.)
    5 (6) -3-phenoxypropylsulfinyl, so pl. 189 ° C (decomp.), A mixture of 5 (6) -p-chlorophenylthiomethylsulfinyl- and
    5 (6) -p-chlorophenylsulfinylmethylthio-, so pl. 174 ° C (decomp.)
    5 (6) -phenoxybutylthio, m.p. 189 (decomp.), 5 (b) - (2-phenylsulfinylethoxy), m.p. 230 ° C (decomp.)
    and 5 (b) - (2-phenylthioethoxy) -carbomethoxyaminobenzimidazole, m.p. 210 (decomp.)
    权利要求:
    Claims (2)
    [1]
    Invention Formula
    The method of obtaining 2-carbalkoxyaminobenzimidazole derivatives of the general formula
    H
    -lI-COOR -yy /
     / i
    where R is alkyl C. R is SOR, SCN, S-R, ORZ or MKGH2) nMR, where each of the M & K is O, S, SO or SOi, R is apkyl. or phenyl, both of which may be substituted by halogen, methyl or methoxy; P -
    1-4; R is alkyl, possibly substituted by halogen or cyano group.
    sing, cycloalkyl, alkenyl Cg-Cg or alkynyl Cj-C, benzyl, naphthyl or phenyl, optionally substituted by alkyl, alkoxy or halogen; R-alkenyl Cz-C, possibly substituted with halogen, alkynyl Cd-C, benzyl or phenethyl, possibly substituted with halogen, alkyl. or alkoxy, and R is in the 5 (6) position, or salts thereof, characterized in that the 1,2-diaminobenzene of the general formula is reacted.
    five
    where R is as indicated above, with 1,3-bio- (alkoxycarbonyl) -S-alkyl iso-urea of the general formula
    BOOC-y C-WHCOOR
    0 I SB
    where R is as indicated above, in boiling the reaction mixture, with isolation of the irradiated compound of formula I
    5 or with the subsequent oxidation of a compound of the formula I, where R is M (CH2) nMR, M and M are as defined above and at least one of M and M is S or SO; R, R
    0 and n are defined as vvky,. oxidized to the corresponding sulfinyl or sulfonyl compound of formula I, where R SOR, S02.R or M (MR, where at least one of M or M
    5 SO or SOg., And R, R f R - as indicated above, and its isolation in free form or in the form of a salt.
    Convention priority by prints:
    0
    29.12.72 with R - alkyl R - SOR, SCN, SRf OR or M (CH) n where each of M and - O or Sr R - alkyl Cy-C is possible. substituted with halogen, methyl or 5 methoxy; n - 1-4; alkyl C — C optionally substituted with halogen or cyano; cycloalkyl alkenyl Cj-Cg or alkynyl Cd-C benzyl, naphthyl or phenyl. (possibly substituted by alkyl or halogen-
    0 nom; alkenyl, possibly substituted with halogen, alkynyl benzyl or phenethyl, possibly substituted with halogen, alkyl C-04 or alkoxy, and R
    5 is in position 5 (6).
    . 11/21/73 with R-alkyl R M (CH2) fi MR, where each of M and M O or B is SO or SO; R is phenyl, possibly substituted by halogen, me-0 tyl or methoxy, and in the case when R is alkyl, possibly substituted by halogen, methyl or methoxy, at least one of M and M -.SO or SO2, while the other - O or S, SO or SC) ;. j p -
    five
    2 72714328
    1-4, with R being in position-1. US patent No. 2933504,
    SRI 5 (6) .kl. 260-309.2, published 1960
    Information sources,
    [2]
    2. Elderfield R. Heterocyclic
    “Mr in attention when examining the compounds. M., I.L., 1961, p. 217.
    类似技术:
    公开号 | 公开日 | 专利标题
    SU727143A3|1980-04-05|Method of preparing 2-carbalkoxyaminobenzimidazole derivatives or their salts
    EP0560177B1|2003-01-08|Imidazole derivatives having biphenylsulphonylurea or biphenylsulfonylurethane side chains, process for their production and use thereof
    CA2355470C|2008-09-30|Benzoheterocycles and their use as mek inhibitors
    EP0503162B1|1998-04-22|Azole derivatives, process for their preparation and their application
    PT91623B|1995-05-31|PROCESS FOR THE PREPARATION OF ANTI-HYPERTENSIVE AGENTS OF GLUTARAMIDE REPLACED WITH CYCLOALKYL
    WO2015103142A1|2015-07-09|5-fluoro-4-imino-3-|-1- |-3,4-dihydropyrimidin-2|-one and processes for their preparation
    US4002640A|1977-01-11|5|-Benzene ring substituted benzimidazole-2-carbamate derivatives having anthelmintic activity
    DE2820375C2|1991-01-17|
    CN1101815C|2003-02-19|3 -amidochromanylsulfonyl | ureas, processes for their preparation, their use, and pharmaceutical preparations comprising them
    US3965113A|1976-06-22|5|-Benzene ring substituted benzimidazole-2-carbamate derivatives having anthelmintic activity
    DE4342024A1|1995-06-14|Combination preparations containing a quinoxaline and a nucleoside
    CA1059136A|1979-07-24|Anthelmintically active 2-carbalkoxyamino benzimidazolyl-5 | sulfonic acid phenyl esters and process for their manufacture
    EP1097140B1|2004-03-03|Biphenylsulfonyl-substituted imidazole derivatives, their preparation process, their use as a drug or diagnostic agent and drug containing them
    EP1097141B1|2007-05-23|Imidazole derivatives with biphenylsulfonyl substitution, method for preparing them and their use as a drug or diagnostic agent
    US3996368A|1976-12-07|Anthelmintically active 2-carbalkoxyamino-5|-phenyl sulfonyloxy benzimidazoles
    US4086336A|1978-04-25|Phosphonothioureide anthelmintics
    DE2230543A1|1974-01-17|BENZENE SULFONYL URUBE AND METHOD FOR MANUFACTURING IT
    US3882229A|1975-05-06|Composition and method for shrinking mucous membranes
    EP0857724A1|1998-08-12|Sulfonamide substituted compounds, process for their preparation, their use as medicine or for diagnostic purpose
    EP1076651A1|2001-02-21|Substituted sulphonyl cyanamides, method for producing same and their use as medicament
    AR029401A1|2003-06-25|IMPROVED PROCEDURE FOR THE PREPARATION OF SUITABLE BENCIMIDAZOL DERIVATIVES AS ANTIULCEROUS PHARMACOS, PARTICULARLY OMEPRAZOL OR PANTOPRAZOL
    DE2110227A1|1972-10-26|Process for the preparation of five- or six-membered heterocycles
    CA1056828A|1979-06-19|Preparation of 2,1,4-benzothiadiazine derivatives
    DE1182656B|1964-12-03|Process for the preparation of N-benzenesulfonyl-N&#39;-cyclohexyl-ureas
    IL33776A|1973-05-31|Process for the production of o,o-dimethyl-thionophosphoric acid |)ester
    同族专利:
    公开号 | 公开日
    IL43860A|1977-05-31|
    FR2212150B1|1977-01-28|
    JPS5939428B2|1984-09-22|
    DE2363351A1|1974-07-11|
    JPS505518A|1975-01-21|
    IT1046097B|1980-06-30|
    AR216037A1|1979-11-30|
    PL95987B1|1977-11-30|
    YU36706B|1984-08-31|
    ES421927A1|1977-01-01|
    FR2212150A1|1974-07-26|
    NL7317797A|1974-07-02|
    US3929821A|1975-12-30|
    IE40046B1|1979-02-28|
    DE2366069A1|1977-11-10|
    DE2363351C2|1987-03-12|
    BR7310296D0|1974-09-24|
    HU169272B|1976-10-28|
    MY8000273A|1980-12-31|
    HK8280A|1980-03-14|
    DK137329C|1978-07-24|
    NL169738B|1982-03-16|
    NL169738C|1982-08-16|
    YU337173A|1981-11-13|
    SE414402B|1980-07-28|
    DK137329B|1978-02-20|
    AR221816A1|1981-03-31|
    RO67150A|1980-12-30|
    ES445257A1|1977-10-01|
    GB1456497A|1976-11-24|
    IN138644B|1976-03-06|
    AT332883B|1976-10-25|
    IE40046L|1974-06-29|
    DE2366070C2|1987-06-11|
    YU64180A|1983-04-30|
    YU40868B|1986-06-30|
    ATA1075173A|1976-02-15|
    CH613955A5|1979-10-31|
    CH608006A5|1978-12-15|
    AU6367473A|1975-06-19|
    GB1455728A|1976-11-17|
    CS187390B2|1979-01-31|
    DE2366069C2|1987-06-11|
    IL43860D0|1974-03-14|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US2933502A|1958-02-12|1960-04-19|Du Pont|Benzimidazolone derivatives|
    US2933504A|1959-08-10|1960-04-19|Du Pont|Derivatives of polyalkoxycarbonyl imine|
    US3010968A|1959-11-25|1961-11-28|Du Pont|Process for manufacture of certain alkyl esters of benzimidazole carbamic acids|
    FR4648M|1964-08-04|
    US3506767A|1965-08-06|1970-04-14|Geigy Chem Corp|Benzimidazole compositions and methods of use|
    US3401171A|1966-03-11|1968-09-10|Smithkline Corp|2-amidobenzimidazoles|
    CH456236A|1966-05-06|1968-07-15|Agripat Sa|Process for protecting textile keratinous fiber materials from insect damage and means for carrying out this process|
    US3480642A|1967-03-22|1969-11-25|Smithkline Corp|Process for producing 2-carbalkoxyaminobenzimidazoles|
    CH490010A|1967-10-26|1970-05-15|Ciba Geigy|Pesticides|
    US3562290A|1967-11-07|1971-02-09|Du Pont|Process for making 2-benzimidazolecarbamic acid alkyl esters|
    FR2059938A1|1969-03-14|1971-06-11|Aries Robert|1-haloalkyl sulphenyl-2-aryloxycarbon-yl -|
    US3657267A|1969-06-20|1972-04-18|Janssen Pharmaceutica Nv|Benzimidazole carbamates|
    US3714180A|1970-08-12|1973-01-30|Squibb & Sons Inc|Sulfonyl benzimidazoles|
    US3694455A|1970-11-19|1972-09-26|Smith Kline French Lab|Acyloxyalkyl amidobenzimidazoles|
    US3720686A|1971-04-01|1973-03-13|Squibb & Sons Inc|Mercaptobenzimidazole derivatives|US4002640A|1972-12-29|1977-01-11|SyntexInc.|5-Benzene ring substituted benzimidazole-2-carbamate derivatives having anthelmintic activity|
    US4258198A|1973-05-29|1981-03-24|Smithkline Corporation|5-Cycloalkyl thio- and oxy-2-carbalkoxyaminobenzimidazoles|
    DE2441202C2|1974-08-28|1986-05-28|Hoechst Ag, 6230 Frankfurt|2-Carbalkoxyamino-benzimidazolyl-5-sulfonic acid-phenyl ester, process for their preparation and anthelmintic compositions containing them|
    DE2441201C2|1974-08-28|1986-08-07|Hoechst Ag, 6230 Frankfurt|2-Carbalkoxyamino-5-phenyl-sulfonyloxy-benzimidazoles and process for their preparation|
    US4086235A|1976-04-12|1978-04-25|SyntexInc.|5 -Benzene ring substituted benzimidazole-2-carbamate derivatives having anthelmintic activity|
    USRE30990E|1976-07-16|1982-07-06|E. R. Squibb & Sons, Inc.|Benzimidazole derivatives, compositions thereof and method of use as anthelmintics|
    US4046908A|1976-07-16|1977-09-06|E. R. Squibb & Sons, Inc.|Benzimidazole derivatives, compositions thereof and method of use as anthelmintics|
    JPS5341436A|1976-08-13|1978-04-14|Wellcome Found|Antiiparasite composition|
    DE2736508A1|1976-08-13|1978-02-16|Wellcome Found|ANIMAL PREPARATIONS AGAINST HELMETS|
    FR2362116B1|1976-08-20|1981-12-24|Oreal|
    US4093732A|1977-02-17|1978-06-06|E. R. Squibb & Sons, Inc.|Sulfoxide derivatives of benzimidazoles|
    IT1076022B|1977-04-20|1985-04-22|Montedison Spa|ANTIELMINTIC BENZIMIDAZOLCARBAMMATES|
    IT1107749B|1977-10-06|1985-11-25|Montedison Spa|BENZIMIDAZOLCARBAMMATE PARTICULARLY ACTIVE AGAINST GASTROENTERIC AND PULMONARY PARASITES|
    US4152522A|1978-01-03|1979-05-01|Ethyl Corporation|Process for the preparation of 2-benzimidazole carbamates|
    US4156006A|1978-01-09|1979-05-22|E. R. Squibb & Sons, Inc.|Vinyl sulfide derivatives of benzimidazoles|
    US4136174A|1978-01-18|1979-01-23|E. R. Squibb & Sons, Inc.|Benzimidazolecarbamates and method|
    JPH0135343B2|1978-02-03|1989-07-25|Nippon Denso Kk|
    US4145431A|1978-02-16|1979-03-20|E. R. Squibb & Sons, Inc.|Method of treating helminthiasis by parenteral administration of sulfide- and sulfoxide-derivatives of benzimidazoles|
    US4154846A|1978-06-16|1979-05-15|E. R. Squibb & Sons, Inc.|Substituted thio-, sulfinyl-, and sulfonyl-alkyl benzimidazole carbamates|
    US4174400A|1978-09-13|1979-11-13|Merck & Co., Inc.|Anthelmintic benzimidazoles|
    DE2845537A1|1978-10-19|1980-04-30|Bayer Ag|BENZIMIDAZOLYLCARBAMID ACID ESTER, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE AS MEDICINAL PRODUCTS|
    NL7908719A|1978-12-06|1980-06-10|Montedison Spa|BENZIMIDAZOLE CARBAMATES.|
    IT1100788B|1978-12-06|1985-09-28|Montedison Spa|Benzimidazole-carbamates|
    US4198422A|1979-05-17|1980-04-15|E. R. Squibb & Sons, Inc.|Substituted 2,3-naphthimidazole carbamates and method|
    EP0028455A1|1979-10-12|1981-05-13|Imperial Chemical Industries Plc|5-Phenylselenobenzimidazole derivatives, their preparation and anthelmintic or fasciolicidal compositions containing them|
    HU182763B|1979-10-19|1984-03-28|Chinoin Gyogyszer Es Vegyeszet|Process for preparing 5/6/-alkylthio-benzimidazolyl-alkyl-carbamates|
    IL61232A|1979-10-19|1985-09-29|Chinoin Gyogyszer Es Vegyeszet|Process for the preparation of 2-amino-5-thiocyanatobenzimidazole derivatives|
    US4599428A|1979-10-19|1986-07-08|Chinoin Gyogyszer Es Vegyeszeti Termekek Gyara Rt|Process for the preparation of 5-thio substituted benzimidazoles|
    US4299837A|1979-12-05|1981-11-10|Montedison S.P.A.|Anthelmintic benzimidazole-carbamates|
    DE3719783A1|1987-06-13|1988-12-22|Hoechst Ag|METHOD FOR PRODUCING 5-PHENYLSULFINYL-1H-2-- BENZIMIDAZOLE|
    GB9205368D0|1992-03-12|1992-04-22|Pfizer Ltd|Benzimidozole anthelmintic agents|
    US6593466B1|1999-07-07|2003-07-15|Isis Pharmaceuticals, Inc.|Guanidinium functionalized nucleotides and precursors thereof|
    EP1913009B1|2005-07-28|2010-05-12|Intervet International BV|Novel benzimidazolecarbamates with antiparasitic activity and the synthesis thereof|
    AU2007345301A1|2006-06-12|2008-07-31|Smith And Nephew Inc|Systems, methods and devices for tibial resection|
    KR101403135B1|2006-06-14|2014-06-19|인터벳 인터내셔널 비.브이.|A suspension comprising benzimidazole carbamate and a polysorbate|
    CN102241635A|2011-04-28|2011-11-16|江苏宝众宝达药业有限公司|Preparation method for anthelmintic benzimidazole fenbendazole|
    CN102863392A|2012-10-18|2013-01-09|江苏宝众宝达药业有限公司|Method for greatly reducing amount of solvent usage in production process of oxfendazole|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US31929972A| true| 1972-12-29|1972-12-29|
    US417963A|US3929821A|1972-12-29|1973-11-21|5 -Benzene ring substituted benzimidazole-2-carbamate derivatives|
    [返回顶部]