公开(公告)号：JPH1087624A

公开(公告)日：1998-04-07

申请号：JP24183896

申请日：1996-09-12

Applicant: SAGAMI CHEM RES

Inventor： TERAJIMA ATSURO ,  KAJIYASHIKI TSUYOSHI ,  HASHIMOTO MASARU

IPC: C07D213/61

Abstract: PROBLEM TO BE SOLVED: To industrially and inexpensively produce 2-chloro-5- chloromethylpyridine useful as a producing intermediate of a medicine or an agrochemical by chlorinating 2-alkoxy-5-methylpyridines. SOLUTION: The objective 2-chloro-5-chloromethylpyridine of the formula II is obtained by affecting a molecular chlorine to 2-alkoxy-5-methylpyridines of the formula I [R is a lower alkyl, a (substituted) lower alkenyl, etc.] and affecting an acid chloride and/or phosphorus chloride. The starting material of the formula I is obtained by producing 5-methyl-2-sulfonylpyridines by reacting sulfonylcyanide of the formula III with 1-acyloxy-2-methyl-1,3-butadiene of the formula IV and affecting an alcoholic salt.

公开(公告)号：JPH05247043A

公开(公告)日：1993-09-24

申请号：JP8138392

申请日：1992-03-04

Applicant: SAGAMI CHEM RES

Inventor： TERAJIMA ATSURO ,  HASHIMOTO MASARU ,  YAMADA KAORU

IPC: A61K31/40 ,  A61K31/396 ,  A61P35/00 ,  C07D207/20 ,  C07D487/04 ,  C07F7/18

Abstract: PURPOSE:To obtain a new compound useful as a carcinostatic agent having strong cell toxicity. CONSTITUTION:A compound of formula I (R and R are 1-5C alkyl or aralkyl) such as (S)-5-(t-butyldiphenylsilyloxy)methylpyrrolidine-2-thione. The compound of formula I is obtained by silylating (S) or (R)-5-hydroxymethylpyrrolidin-2-one of formula II as a starting substance, successively carrying out conversion of carbonyl group, reaction with a halogenomalonic diester and elimination of silyl group to give a compound of formula III, then sulfonylating the hydroxyl group of the compound of formula III and treating with a base (e.g. potassium hydroxide).

公开(公告)号：JPH05163232A

公开(公告)日：1993-06-29

申请号：JP33487591

申请日：1991-12-18

Applicant: DAIICHI SEIYAKU CO ,  SAGAMI CHEM RES

Inventor： KAMATA MASAHIRO ,  HAYAKAWA ISAO ,  AKIBA TOSHIFUMI ,  TERAJIMA ATSURO ,  TAMURA OSAMU ,  KOBAYASHI YUKO ,  HASHIMOTO MASARU ,  KATO TADASHI ,  NAKATANI KAZUHIKO

IPC: C07C209/88 ,  C07C211/37 ,  C07C269/06 ,  C07C271/24

Abstract: PURPOSE:To obtain (1R*,2S*)-2-fluorocyclopropylamine useful as a raw material for producing quinolone derivatives which are excellent antimicrobial agents in an extremely short step by passing an N-vinylcarbamate derivative as a starting raw material through a specific intermediate. CONSTITUTION:A compound expressed by formula 2 (Y is alkyl having 1-3 aryl groups at the 1-position or 4-10C trialkylmethyl) is subjected to addition reaction with a monofluorocarbene to provide an N-[(1R*,2S*)-2- fluorocyclopropyl]carbamate derivative expressed by formula 1. The alkoxycarbonyl group of the compound is then removed to afford the objective (1R*,2S*)-2-fluorocyclopropylamine, having the cis-configuration and expressed by formula 3. The removal of the alkoxycarbonyl group is carried out by hydrolysis when Y is the alkyl and treatment with a strong acid when Y is the trialkylmethyl.

公开(公告)号：JPH083133A

公开(公告)日：1996-01-09

申请号：JP14050394

申请日：1994-06-22

Applicant: SAGAMI CHEM RES

Inventor： TERAJIMA ATSURO ,  HASHIMOTO MASARU ,  YAMADA KAORU

IPC: C07D487/04 ,  A61K31/396 ,  A61K31/40 ,  A61P35/00 ,  C07D207/24 ,  C07F7/18

Abstract: PURPOSE:To obtain the subject new compound, capable of manifesting strong cytotoxicty and useful as a carcinostatic agent. CONSTITUTION:This 2-(1-aclamio-1-carbamoyl)methylidenepyrrolidine derivative is expressed by formula I [R and R are each a 1-5C alkyl, a (substituted) aralkyl or a (substituted)aryl; R and R are each a (substituted)aralkyl], e.g. 2-(1-benzoylamino-2-(1-methylethyl)amino-2-oxo)ethylidene-1-aza-3,4-bi sbenzy1 oxybicyc1o[3.1.0]hexane. The compound of formula I is obtained by passing a compound of formula IT (R to R are each same as R and R ) as a starting raw material through a 2-(5-oxo-DELTA -oxazolin-4-ylidene)pyrrolidine derivative of formula III, etc., which is an intermediate for producing the compound of formula I.

公开(公告)号：JPH07109280A

公开(公告)日：1995-04-25

申请号：JP27600493

申请日：1993-10-08

Applicant: SAGAMI CHEM RES

Inventor： TERAJIMA ATSURO ,  KATO TADASHI ,  KIRIHARA MASAYUKI ,  HASHIMOTO MASARU ,  MATSUMOTO MIYOKO

IPC: C07D491/107 ,  A01N43/90

Abstract: PURPOSE:To extremely simply obtain the compound, a substance having a strongly herbicidal activity through one process by reacting D-isoascorbic acid with urea. CONSTITUTION:D-Ascorbic acid of formula I is reacted with urea of formula II preferably in a solvent-free state at 60-160 deg.C to obtain (+)-hydantocidin of formula III and (-)-5-epihydantocidin of formula IV. The molar ratio of the compound of formula I: the compound of formula II is 1:10 to 10:1, preferably 1:1. The reaction is performed in a solvent such as water or methanol in the presence of a catalyst (e.g. zinc chloride, triethylamine) or in the absence of the catalyst. The raw materials are inexpensive and easily available.

公开(公告)号：JPH07149764A

公开(公告)日：1995-06-13

申请号：JP31918993

申请日：1993-11-26

Applicant: SAGAMI CHEM RES

Inventor： TERAJIMA ATSURO ,  HASHIMOTO MASARU ,  MATSUMOTO MIYOKO ,  YAMADA KAORU

IPC: C07D487/04 ,  A61K31/396 ,  A61K31/40 ,  A61K31/4025 ,  A61P35/00 ,  C07D405/12

Abstract: PURPOSE:To obtain the derivative of a specific formula useful as a new carcinostatic agent, having strong cytotoxicity. CONSTITUTION:This derivative is expressed by formula I [R and R are each a l-5C alkyl, a (substituted) aralky] or a (substituted) aryll such as (2R,2'S,3' S)-2-{1-ethoxycarbonyl-1[2'-(3''-methoxy-5''-methyl-1''-naphthalenecar bonyl)-3',4'- epoxy-3'-methylbutanoylamino]}methylidene-5-(t-butyldiphenylsilyloxyme thyl) pyrrolidine. The derivative is preferably obtained by firstly acylating 3,4- epoxy-1-(4-methoxybenzyloxy)-3-methylbutan-2-ol of formula II, etc., as a starting substance.

公开(公告)号：JPH05163212A

公开(公告)日：1993-06-29

申请号：JP33487791

申请日：1991-12-18

Applicant: DAIICHI SEIYAKU CO ,  SAGAMI CHEM RES

Inventor： KAMATA MASAHIRO ,  HAYAKAWA ISAO ,  AKIBA TOSHIFUMI ,  TERAJIMA ATSURO ,  TAMURA OSAMU ,  KOBAYASHI YUKO ,  HASHIMOTO MASARU ,  KATO TADASHI ,  NAKATANI KAZUHIKO

IPC: C07C209/88 ,  C07C209/26 ,  C07C209/62 ,  C07C211/37 ,  C07C269/00 ,  C07C269/04 ,  C07C269/06 ,  C07C271/04 ,  C07C271/12 ,  C07C271/24

Abstract: PURPOSE:To produce (1R,2S)-2-fluorocyclopropylamine salt as an synthetic intermediate of quinolone derivatives used as an excellent antifungal, through a novel intermediate safely, inexpensively and readily. CONSTITUTION:N-[(1R)-arylalkyl]-N-(1R*, 2S*)-2-fluorocyclopropylcarbamate derivative of formula 7 (Ar is phenyl or naphthyl both of which may be optionally substituted) is subjected to dehydrative condensation reaction with acetaldehyde to give a compound of formula 6. The product is allowed to react with phosgene in the presence of a base to form N-(1-arylalkyl)-N-vinylcarbamic acid chloride derivative of formula 3, which is allowed to react with a compound of formula Y-OM (Y is alkyl bearing 1 to 3 aryl groups in the 1-position; M is alkali metal) to give a compound of formula 2. Then, monofluorocarbene is added to the product to give N-(1-arylalkyl)-N-[(1R*, 2S*)-2- fluorocyclopropyl]-carbamate derivative of formula 1. Then, the product is hydrogenolyzed into(1R*, 2S*)-2-fluorocyclopropylamine of formula 4. The compounds of formula 1 through formula 3 are novel.

公开(公告)号：JPH05163211A

公开(公告)日：1993-06-29

申请号：JP33487691

申请日：1991-12-18

Applicant: DAIICHI SEIYAKU CO ,  SAGAMI CHEM RES

Inventor： KAMATA MASAHIRO ,  HAYAKAWA ISAO ,  AKIBA TOSHIFUMI ,  TERAJIMA ATSURO ,  TAMURA OSAMU ,  KOBAYASHI YUKO ,  HASHIMOTO MASARU ,  KATO TADASHI ,  NAKATANI KAZUHIKO

IPC: C07C209/62 ,  C07C209/88 ,  C07C211/37

Abstract: PURPOSE:To produce (1R,2S)-2-fluorocyclopropylamine salt as an synthetic intermediate of quinolone derivatives used as an excellent antifungal, through a novel intermediate readily, inexpensively and safely. CONSTITUTION:N-[(1R)-arylalkyl]-N-(1R*,2S*)-2-fluorocyclopropylcarbamate derivative of formula 3 (Ar is phenyl or naphthyl both of which may be optionally substituted; Y is alkyl having 1 to 3 aryl groups in the 1-position) is subjected to partial hydrogenolysis in the presence of an acid of XH selected from sulfonic acid, phosphoric acid, carboxylic acid and hydrohaloic acid to give a novel N-[(1R)-1-arylalkyl]-N-(1R*,2S*)-2-fluorocyclopropylamine salt derivative of formula 1. Then, the compound is subjected to fractional recrystallization to give the compound of formula 1a, which is hydrogenolyzed to (1R,2S)-2-fluorocyclopropylamine salt derivative of formula 2.

公开(公告)号：JPH04327580A

公开(公告)日：1992-11-17

申请号：JP9535891

申请日：1991-04-25

Applicant: DAIICHI SEIYAKU CO ,  SAGAMI CHEM RES

Inventor： TERAJIMA ATSURO ,  NAKATANI KAZUHIKO ,  TAMURA OSAMU ,  HASHIMOTO MASARU ,  KATO TADASHI ,  KOBAYASHI YUKO ,  KAMATA MASAHIRO ,  HAYAKAWA ISAO

IPC: C07C211/37 ,  C07D263/22

Abstract: PURPOSE:To provide a novel (1R,2S)-2-fluorocyclopropylamine useful as production raw material for an antibacterial quinolone derivative. CONSTITUTION:The (4R,5S)-3-[(1R,2S)-2-fluorocyclopropyl]-4,5-diphenyl-2- oxazolidinone of formula I (Ph is phenyl). The compound of formula I can be produced by reacting (4R,5S)-4,5-diphenyl-3-vinyl-2-oxazolidinone of formula II or its antipode with monofluorocarbene.

公开(公告)号：JPH07149750A

公开(公告)日：1995-06-13

申请号：JP31919093

申请日：1993-11-26

Applicant: SAGAMI CHEM RES

Inventor： TERAJIMA ATSURO ,  HASHIMOTO MASARU ,  MATSUMOTO MIYOKO ,  YAMADA KAORU

IPC: C07D303/46 ,  A61K31/335 ,  A61K31/336 ,  A61P35/00

Abstract: PURPOSE:To obtain a carcinostatic agent having strong carcinostatic action and capable of expecting excellent treating effect. CONSTITUTION:This carcinostatic agent contains a 3-methoxy-5- methylnaphthalene-1-carboxylic acid enter derivative of the formula as an active ingredient. Since the carcinostatic agent has strong carcinostatic activity equivalent to adriamycin in proliferation-inhibiting activity test to a mouse lymphatic leukemic cell (P388), excellent treating effect by this agent is expected. Although the compound is isolated together with atinomycins A and B which are strong carcinostatic antibiotics from Streptomyces grisreofuscus S42227, it is synthesized using an allyl-4-methoxybenzyl ether obtained by reacting p-anisic alcohol with an allyl bromide as a starting raw material.