JPS5946222B2 - グアニジン化合物の製法 - Google Patents
グアニジン化合物の製法Info
- Publication number
- JPS5946222B2 JPS5946222B2 JP50106459A JP10645975A JPS5946222B2 JP S5946222 B2 JPS5946222 B2 JP S5946222B2 JP 50106459 A JP50106459 A JP 50106459A JP 10645975 A JP10645975 A JP 10645975A JP S5946222 B2 JPS5946222 B2 JP S5946222B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- production method
- guanidine compound
- present
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- ZRALSGWEFCBTJO-UHFFFAOYSA-N anhydrous guanidine Natural products NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 title claims description 7
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 title claims description 5
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 title claims description 5
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- -1 guanidine compound Chemical class 0.000 title claims description 4
- 229910001385 heavy metal Inorganic materials 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 3
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 4
- JEOZNMMOIBLWLV-UHFFFAOYSA-N 2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethanamine Chemical compound CC=1N=CNC=1CSCCN JEOZNMMOIBLWLV-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 150000001718 carbodiimides Chemical class 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 229910001961 silver nitrate Inorganic materials 0.000 description 3
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- MHGGQXIPBPGZFB-UHFFFAOYSA-N methyl n-cyano-n'-methylcarbamimidothioate Chemical compound CSC(=NC)NC#N MHGGQXIPBPGZFB-UHFFFAOYSA-N 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 101100073357 Streptomyces halstedii sch2 gene Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910052793 cadmium Inorganic materials 0.000 description 1
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000027119 gastric acid secretion Effects 0.000 description 1
- 150000002357 guanidines Chemical class 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002541 isothioureas Chemical class 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229960002523 mercuric chloride Drugs 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/61—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/68—Halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/46—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/02—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/26—Radicals substituted by sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
- C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
- C07D285/135—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】
本発明は薬効を有するグアニジン化合物の改良された製
法に関する。
法に関する。
本発明者らは、ドイツ国特許公開明細書第２、３４４、
７７９号において、式： ／ ＣＨ３肖ＣＨ２ＳＣＨ２ＣＨ２ＮＨ−Ｒ＿１印＼ク〔式
中、Ｒ＿１はメチルのような低級アルキルを意味する〕
で示されるグアニジン化合物およびその製法を開示して
いる。
７７９号において、式： ／ ＣＨ３肖ＣＨ２ＳＣＨ２ＣＨ２ＮＨ−Ｒ＿１印＼ク〔式
中、Ｒ＿１はメチルのような低級アルキルを意味する〕
で示されるグアニジン化合物およびその製法を開示して
いる。
本発明はこれらの化合物の改良された製法を提供するも
のである。
のである。
本明細書において「低級アルキル」なる語は炭素数１〜
４のアルキルを意味する。本発明によれば、式： ／／ＮＣＮ Ｒ＿ＩＮＨ−Ｃ〔旧 ＼ 〔式中、Ｒ＿１およびＡは同一または異なつて、各各、
メチルのような低級アルキルを意味する〕で示されるイ
ソチオウレアを適当な重金属塩および式：で示されるア
ミンで処理して式〔ｌ］の化合物を得る。
４のアルキルを意味する。本発明によれば、式： ／／ＮＣＮ Ｒ＿ＩＮＨ−Ｃ〔旧 ＼ 〔式中、Ｒ＿１およびＡは同一または異なつて、各各、
メチルのような低級アルキルを意味する〕で示されるイ
ソチオウレアを適当な重金属塩および式：で示されるア
ミンで処理して式〔ｌ］の化合物を得る。
適当な重金属塩とは、銀、水銀、鉛またはカドミウムの
ような重金属の塩を意味し、好ましくは硝酸銀または塩
化第二水銀である。好ましくは、反応を促進するために
炭酸カリウムやトリエチルアミンのような塩基を加える
。これらの塩基は反応当初から存在させておくことが好
ましい。生成した重金属メルカプチドは容易に淵去でき
る。本発明の反応はピリジンまたはジメチルホルムアミ
ドのような適当な溶媒中で行なうことができ、また、室
温で行なうことができる。従つて、この製法は、重金属
塩を用いず、昇温させ、および／または反応時間をのば
す必要のある従来法に比べて反応速度の点で非常に有利
である。マツカーテイら〔ＭｃＣａｒｔｙら、Ｊ．Ｏｒ
ｇ．Ｃｈｅｍ．３５巻、２０６７頁（１９７０年）〕に
よれば、式〔〕のようなタイプのイソチオウレアを塩基
の存在下に重金属塩で処理すると、反応系内に式：Ｒｌ
Ｎ−Ｃ−ＮＣＮ〔〕〔式中、Ｒ１は前記式〔１〕と同じ
である〕で示されるカルボジイミド中間体が形成される
ことが証明されている。
ような重金属の塩を意味し、好ましくは硝酸銀または塩
化第二水銀である。好ましくは、反応を促進するために
炭酸カリウムやトリエチルアミンのような塩基を加える
。これらの塩基は反応当初から存在させておくことが好
ましい。生成した重金属メルカプチドは容易に淵去でき
る。本発明の反応はピリジンまたはジメチルホルムアミ
ドのような適当な溶媒中で行なうことができ、また、室
温で行なうことができる。従つて、この製法は、重金属
塩を用いず、昇温させ、および／または反応時間をのば
す必要のある従来法に比べて反応速度の点で非常に有利
である。マツカーテイら〔ＭｃＣａｒｔｙら、Ｊ．Ｏｒ
ｇ．Ｃｈｅｍ．３５巻、２０６７頁（１９７０年）〕に
よれば、式〔〕のようなタイプのイソチオウレアを塩基
の存在下に重金属塩で処理すると、反応系内に式：Ｒｌ
Ｎ−Ｃ−ＮＣＮ〔〕〔式中、Ｒ１は前記式〔１〕と同じ
である〕で示されるカルボジイミド中間体が形成される
ことが証明されている。
従つて、本発明はまた、対応する前駆体から反応系内で
生じさせた式〔酌のカルボジイミドを式１〕のアミンと
反応させて式〔１〕の化合物を得る製法も包含する。式
〔〕のカルボジイミドの好ましい前駆体は式〔〕のイソ
チオウレアであるが、これに限定するものではない。
生じさせた式〔酌のカルボジイミドを式１〕のアミンと
反応させて式〔１〕の化合物を得る製法も包含する。式
〔〕のカルボジイミドの好ましい前駆体は式〔〕のイソ
チオウレアであるが、これに限定するものではない。
本発明（こおいて得られる化合物および出発物質として
用いられる化合物は酸付加塩の形で存在しうる。
用いられる化合物は酸付加塩の形で存在しうる。
本発明者らの英国特許明細書第１，３３８，１６９号に
記載したとおり、式〔１〕の化合物（本発明の製法によ
つて得ることができる）は例えばヒスタミンＨ２一拮抗
剤〔Ｎａｔｕｒｅｌ２３６巻、３８５頁（１９７２年）
参照〕のごとき薬効を有し、例えば胃酸分泌の抑制剤と
して有用である。
記載したとおり、式〔１〕の化合物（本発明の製法によ
つて得ることができる）は例えばヒスタミンＨ２一拮抗
剤〔Ｎａｔｕｒｅｌ２３６巻、３８５頁（１９７２年）
参照〕のごとき薬効を有し、例えば胃酸分泌の抑制剤と
して有用である。
投与用ｌこは、もちろん該化合物を適当な医薬土許容さ
れる単位投与形とすることができる。つぎに実施例をあ
げ、本発明をさらに詳しく説明するが、これらに限定さ
れるものではない。
れる単位投与形とすることができる。つぎに実施例をあ
げ、本発明をさらに詳しく説明するが、これらに限定さ
れるものではない。
実施例 １Ｎ−シアノ−Ｎ′，Ｓ−ジメチルイソチオウ
レア０．８１９お上び硝酸銀１．０６９のピリジン１０
０ｄ溶液を２−（（５−メチル−４−イミダゾリル）メ
チルチオ）エチルアミン１．０７９、無水炭酸カリウム
０．４４９および無水ジメチルホルムアミド４７ＴＬ１
の撹拌混合液に加える。
レア０．８１９お上び硝酸銀１．０６９のピリジン１０
０ｄ溶液を２−（（５−メチル−４−イミダゾリル）メ
チルチオ）エチルアミン１．０７９、無水炭酸カリウム
０．４４９および無水ジメチルホルムアミド４７ＴＬ１
の撹拌混合液に加える。
この混合液を室温で１８時間撹拌し、濾過する。濾液を
蒸発乾固し、残渣をシリカゲルカラムクロマトグラフイ
一に付し、イソプロピルアルコール一酢酸エチル（１：
４）、ついでイソプロピルアルコール一酢酸エチル（１
：３）で溶出してＮ−シアノ−Ｎ′−メチル−Ｖ−〔２
−（（５−メチル−４−イミダゾリル）メチルチオ）エ
チル〕グアニジン０．７１ｆ１を得る。融点１３９〜１
４１℃実施例 ２ Ｎ−シアノ−ＮＺＳ−ジメチルイソチオウレア０．８１
９、硝酸銀１．０６９、無水炭酸カリウム０．４４９お
よびピリジン１００ｍ１を混合し、室温で１８時間撹拌
し、濾過する。
蒸発乾固し、残渣をシリカゲルカラムクロマトグラフイ
一に付し、イソプロピルアルコール一酢酸エチル（１：
４）、ついでイソプロピルアルコール一酢酸エチル（１
：３）で溶出してＮ−シアノ−Ｎ′−メチル−Ｖ−〔２
−（（５−メチル−４−イミダゾリル）メチルチオ）エ
チル〕グアニジン０．７１ｆ１を得る。融点１３９〜１
４１℃実施例 ２ Ｎ−シアノ−ＮＺＳ−ジメチルイソチオウレア０．８１
９、硝酸銀１．０６９、無水炭酸カリウム０．４４９お
よびピリジン１００ｍ１を混合し、室温で１８時間撹拌
し、濾過する。
濾液を蒸発乾固し、２−（（５−メチル−４−イミダゾ
リル）メチルチオ）エチルアミン１．０７９のジメチル
ホルムアミド４ｍ１溶液で処理し、室温で１８時間放置
する。この混合液を蒸発乾固し、残渣をシリカゲルクロ
マトグラフイ一に付し、イソプロピルアルコールー酢酸
エチル（１：３）で溶出してＮ−シアノ−Ｎ′−メチル
−Ｎ″一〔２−（（５−メチル−４−イミダゾリル）メ
チルチオ）エチル〕グアニジンを得る。実施例１の生成
物との混融試験の結果は該化合物であることを示してい
る。実施例 ３ Ｎ−シアノ−Ｎ′，Ｓ−ジメチルイソチオウレア０．４
１３９（３．２ミリモル）、トリエチルアミン２ｍ１お
よび２−（（５−メチル−４−イミダゾリル）メチルチ
オ）エチルアミン０．５４７９（３．２ミリモル）を順
次ジメチルホルムアミド１００７ｎ１に溶解する。
リル）メチルチオ）エチルアミン１．０７９のジメチル
ホルムアミド４ｍ１溶液で処理し、室温で１８時間放置
する。この混合液を蒸発乾固し、残渣をシリカゲルクロ
マトグラフイ一に付し、イソプロピルアルコールー酢酸
エチル（１：３）で溶出してＮ−シアノ−Ｎ′−メチル
−Ｎ″一〔２−（（５−メチル−４−イミダゾリル）メ
チルチオ）エチル〕グアニジンを得る。実施例１の生成
物との混融試験の結果は該化合物であることを示してい
る。実施例 ３ Ｎ−シアノ−Ｎ′，Ｓ−ジメチルイソチオウレア０．４
１３９（３．２ミリモル）、トリエチルアミン２ｍ１お
よび２−（（５−メチル−４−イミダゾリル）メチルチ
オ）エチルアミン０．５４７９（３．２ミリモル）を順
次ジメチルホルムアミド１００７ｎ１に溶解する。
Claims (1)
- 【特許請求の範囲】 １ 式： ▲数式、化学式、表等があります▼ 〔式中、Ｒ＿１およびＡは同一または異なつて、各各、
低級アルキルを意味する〕で示されるイソチオウレアを
重金属塩および式：▲数式、化学式、表等があります▼
で示されるアミンと反応させることを特徴とする式：▲
数式、化学式、表等があります▼ 〔式中、Ｒ＿１は前記と同じである。 〕で示されるグアニジン化合物の製法。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB38258/74A GB1531231A (en) | 1974-09-02 | 1974-09-02 | Process for the production of cyanoguanidine derivatives |
| GB3825874 | 1974-09-02 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5154562A JPS5154562A (ja) | 1976-05-13 |
| JPS5946222B2 true JPS5946222B2 (ja) | 1984-11-10 |
Family
ID=10402299
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP50106459A Expired JPS5946222B2 (ja) | 1974-09-02 | 1975-09-01 | グアニジン化合物の製法 |
| JP59099672A Granted JPS6023370A (ja) | 1974-09-02 | 1984-05-15 | グアニジン化合物の製法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59099672A Granted JPS6023370A (ja) | 1974-09-02 | 1984-05-15 | グアニジン化合物の製法 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US4049671A (ja) |
| JP (2) | JPS5946222B2 (ja) |
| BE (1) | BE832664A (ja) |
| CA (1) | CA1064037A (ja) |
| CH (1) | CH608233A5 (ja) |
| GB (1) | GB1531231A (ja) |
| IE (1) | IE41651B1 (ja) |
| NL (1) | NL7510334A (ja) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4170652A (en) * | 1974-03-12 | 1979-10-09 | Smith Kline & French Laboratories Limited | Heterocyclic-methylthioalkyl-guanidines |
| US4109003A (en) * | 1974-03-12 | 1978-08-22 | Smith Kline & French Laboratories Limited | Pharmacologically active compounds |
| GB1496787A (en) * | 1974-03-12 | 1978-01-05 | Smith Kline French Lab | Heteroalkylthioalkyl amidine derivatives |
| NZ184893A (en) * | 1976-09-21 | 1980-11-28 | Smith Kline French Lab | Pure crystalline form of cimetidine a(n-methyl-n-cyano-n-(-2-(5-methyl-4imidazolyl) methylthio) ethyl)-guanidine andpharmaceutical compositions containing it |
| US4165378A (en) | 1977-04-20 | 1979-08-21 | Ici Americas Inc. | Guanidine derivatives of imidazoles and thiazoles |
| NZ186965A (en) | 1977-04-20 | 1980-02-21 | Ici Ltd | Guanidino derivatives and pharmaceutical compositions |
| NZ187376A (en) * | 1977-06-03 | 1981-05-29 | Bristol Myers Co | N-cyano-n-(2-(4-methyl-5-imidazolyl)methylthio)ethyl)-n-alkynyl guanidines intermediates pharmaceutical compositions |
| IL56265A (en) * | 1977-12-28 | 1982-08-31 | Om Lab Sa | Process for preparing imidazolyl methylthio guanidine derivatives and a novel intermediate therefor |
| GR65283B (en) * | 1977-12-30 | 1980-08-01 | Crc Ricerca Chim | Method for the alkyliosis of 4(5)-merka ptomethyl-imidazoles with aziridin derivatives |
| YU40332B (en) * | 1978-04-26 | 1985-12-31 | Lek Tovarna Farmacevtskih | Process for preparing n-cyano-n'-methyl-n''-((2-((4-methyl-5-imidazolyl)-methylthio)ethyl)-guanidine |
| ATE1353T1 (de) | 1978-05-24 | 1982-08-15 | Imperial Chemical Industries Plc | Anti-sekretion thiadiazol-derivate, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische zusammensetzungen. |
| US4200760A (en) * | 1978-09-26 | 1980-04-29 | Bristol-Myers Company | Imidazolylalkylthioalkylamino-ethylene derivatives |
| US4276421A (en) * | 1978-11-18 | 1981-06-30 | Societe De Recherches Et De Syntheses Organiques S.A. | Cyano-guanidine geometrical isomers |
| US4242351A (en) * | 1979-05-07 | 1980-12-30 | Imperial Chemical Industries Limited | Antisecretory oxadiazoles and pharmaceutical compositions containing them |
| US4220654A (en) * | 1979-06-04 | 1980-09-02 | Merck & Co., Inc. | Cyclic imidazole cyanoguanidines |
| JPH0192664A (ja) * | 1987-10-03 | 1989-04-11 | Ngk Insulators Ltd | 線路用検電装置 |
| JPH01123159A (ja) * | 1987-11-06 | 1989-05-16 | Ngk Insulators Ltd | 線路用検電装置 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1397436A (en) * | 1972-09-05 | 1975-06-11 | Smith Kline French Lab | Heterocyclic n-cyanoguinidines |
-
1974
- 1974-09-02 GB GB38258/74A patent/GB1531231A/en not_active Expired
-
1975
- 1975-08-12 IE IE1798/75A patent/IE41651B1/en unknown
- 1975-08-20 CA CA233,789A patent/CA1064037A/en not_active Expired
- 1975-08-20 US US05/606,268 patent/US4049671A/en not_active Expired - Lifetime
- 1975-08-22 BE BE159394A patent/BE832664A/xx not_active IP Right Cessation
- 1975-08-26 CH CH1105075A patent/CH608233A5/xx not_active IP Right Cessation
- 1975-09-01 JP JP50106459A patent/JPS5946222B2/ja not_active Expired
- 1975-09-02 NL NL7510334A patent/NL7510334A/xx not_active Application Discontinuation
-
1984
- 1984-05-15 JP JP59099672A patent/JPS6023370A/ja active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| BE832664A (fr) | 1976-02-23 |
| CA1064037A (en) | 1979-10-09 |
| GB1531231A (en) | 1978-11-08 |
| NL7510334A (nl) | 1976-03-04 |
| JPS5154562A (ja) | 1976-05-13 |
| JPS6023370A (ja) | 1985-02-05 |
| IE41651L (en) | 1976-03-02 |
| CH608233A5 (ja) | 1978-12-29 |
| US4049671A (en) | 1977-09-20 |
| JPS6140668B2 (ja) | 1986-09-10 |
| IE41651B1 (en) | 1980-02-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPS5946222B2 (ja) | グアニジン化合物の製法 | |
| JPS5949225B2 (ja) | 化合物の製造方法 | |
| JPS5949221B2 (ja) | ３−アシルアミノ−４−ホモイソツイスタンの製造法 | |
| JPH061776A (ja) | 置換ピラジンカルボニトリルの製造方法 | |
| JPH06509562A (ja) | ジベレリン分離法 | |
| JPS62286968A (ja) | 新規ニコチン酸アミド誘導体 | |
| JPS62249963A (ja) | Ｎ−（スルホニルメチル）ホルムアミド類の製造法 | |
| JPS6111956B2 (ja) | ||
| JPS6360969A (ja) | イミダゾ−ル誘導体の製造方法 | |
| JPS5910346B2 (ja) | チオウレアの製法 | |
| JP2671401B2 (ja) | α‐アミノチオアセトアミド誘導体およびその製造法 | |
| KR800001451B1 (ko) | 1, 3, 5-트리치환 벤젠 유도체의 제법 | |
| JPS6039671B2 (ja) | ２−（７−インデニルオキシメチル）モルホリンの酸付加塩の製法 | |
| US4772735A (en) | Coordination complexes of platinum with amides | |
| JPH10287650A (ja) | １−クロロカルボニル−４−ピペリジノピペリジンまたはその塩酸塩の製造方法 | |
| JPH01313471A (ja) | Ｎ−スルフアモイルアミジン化合物の製造法 | |
| JPS63216886A (ja) | ピリミドピリミジン誘導体およびその製造法 | |
| JPH0285235A (ja) | 光学活性アミノアルコール類の製法 | |
| JPS6263568A (ja) | １，３，４，５−テトラヒドロベンズ〔ｃｄ〕インド−ル誘導体の製造方法 | |
| JPS5813553B2 (ja) | シンキナピリド （ ４，３−ｄ ） ピリミジンジオンユウドウタイノセイゾウホウ | |
| JPS63192747A (ja) | ホルムアミジンのギ酸塩 | |
| JPH0827148A (ja) | ジチアゾリウム塩の製造方法 | |
| JPS6249276B2 (ja) | ||
| JPS59122474A (ja) | イミダゾ−ル誘導体の製造法 | |
| JPS6129340B2 (ja) |