FI74954C - PROCEDURE FOR FRAMSTATION OF N-METHYL-N'-CYANO-N '' - / 2 ((4-METHYLIMIDAZOL-5-YL) METHYLTHIO) ETHYL / GUANIDINE. - Google Patents
PROCEDURE FOR FRAMSTATION OF N-METHYL-N'-CYANO-N '' - / 2 ((4-METHYLIMIDAZOL-5-YL) METHYLTHIO) ETHYL / GUANIDINE. Download PDFInfo
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- FI74954C FI74954C FI783990A FI783990A FI74954C FI 74954 C FI74954 C FI 74954C FI 783990 A FI783990 A FI 783990A FI 783990 A FI783990 A FI 783990A FI 74954 C FI74954 C FI 74954C
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- methyl
- cyano
- ethyl
- methylimidazol
- guanidine
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/39—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
- C07C323/43—Y being a hetero atom
- C07C323/44—X or Y being nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C329/00—Thiocarbonic acids; Halides, esters or anhydrides thereof
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D203/00—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom
- C07D203/04—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D203/06—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D203/16—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with acylated ring nitrogen atoms
- C07D203/20—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with acylated ring nitrogen atoms by carbonic acid, or by sulfur or nitrogen analogues thereof, e.g. carbamates
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
frus^n KUULUTUSJULKAISU n a nc Λ jjSfe [βΗ11) UTLÄQQNINQSSKRIFT 7495 4 C mk) --1. 7.; ui;: t-ty 1- .. j. .l ,t ^ 7 ^ i ^ 34 1 JQ3 (51) Kv.lk.Vlnt.Cl* C 07 D 233/6^+frus ^ n ADVERTISEMENT n a nc Λ jjSfe [βΗ11) UTLÄQQNINQSSKRIFT 7495 4 C mk) --1. 7 .; ui ;: t-ty 1- .. j. .l, t ^ 7 ^ i ^ 34 1 JQ3 (51) Kv.lk.Vlnt.Cl * C 07 D 233/6 ^ +
SUOMI-FI N LAN DSUOMI FINLAND
(Fl) (21) Patenttihakemus - Patentansökning 783990 (22) Hakemispäivä - Ansökningsdag 27-12.78(Fl) (21) Patent application - Patentansökning 783990 (22) Application date - Ansökningsdag 27-12.78
Patentti- ja rekieterihellitue (23) Alkupäivä - Giitighetsdag 27.12.78Patent and racket support (23) Start date - Giitighetsdag 27.12.78
Patent- och registerstyreleen (41 j Tullut jU|kiseksj_Bhvjt 0ffentijg 08.06.80 (44) Nähtäväksipanon ja kuul.julkaisun pvm. - 31.12 87Patent- och registerstyreleen (41 j Tullut jU | kiseksj_Bhvjt 0ffentijg 08.06.80 (44) Date of dispatch and of publication - 31.12 87
Ansökan utlagd och utl.skriften publicerad (86) Kv. hakemus - Int. ansökan (32)(33)(31) Pyydetty etuoikeus - Begärd prioritet 07-12.78 Sveitsi-Schweiz(CH) 12477/78 Toteennäytetty-Styrkt (71) Laboratoires OM S.A., 22, rue du Bis-du-Lan, Meyrin, Kanton Genf, Sveitsi-Ansökan utlagd och utl.skriften publicerad (86) Kv. application - Int. trap (32) (33) (31) Privilege claimed - Begärd priority 07-12.78 Switzerland-Switzerland (CH) 12477/78 Proven-Styrkt (71) Laboratoires OM SA, 22, rue du Bis-du-Lan, Meyrin, Canton Geneva, Switzerland
Schwe i z(CH) (72) Pierre Baudet, Veyrier, Kanton Genf, Jean-Paul Ricard, St-Cergue, Kanton Waadt, Adrian Schulthess, Begnins, Kanton Waadt, Sveitsi-Schweiz(CH) (74) Oy Koi ster Ab (54) Menetelmä N-metyyli-N 1-syano-N11-/2((4-metyyli- imi datsol~5~yy1i)metyyli t io)-etyyli/guanidiinin valmistamiseksi - Förfarande för f ramstäiIning av N-metyl--N1-cyano-N11-/2((4-metylimidazol-5~y1)mety11 io)-etyl/guanidinSchwe iz (CH) (72) Pierre Baudet, Veyrier, Canton of Geneva, Jean-Paul Ricard, St-Cergue, Canton of Vaud, Adrian Schulthess, Begnins, Canton of Vaud, Switzerland-Switzerland (CH) (74) Oy Koi ster Ab ( 54) Process for the preparation of N-methyl-N1-cyano-N11- [2 ((4-methylimidazol-5-yl) methylthio) ethyl] guanidine - Preparation of N-methyl-N1 -cyano-N11- [2 ((4-methylimidazol-5-yl) methyl) ethyl] guanidine
Keksinnön kohteena on menetelmä N-metyyli-N’-syano-N"-^((4-metyyli-imidatsol-S-yylijmetyylitio)etyyl!7guanidiinin valmistamiseksi, jonka kaava on NHCH,The invention relates to a process for the preparation of N-methyl-N'-cyano-N "- N - ((4-methylimidazol-5-yl) methylthio) ethyl] guanidine of the formula NHCH,
^CH2-S-CH2-CH2-NH-C^ CH2-S-CH2-CH2-NH-C
n ~J ^N-C = N (J) H 3n ~ J ^ N-C = N (J) H 3
Keksinnölle on tunnusomaista, että sellaisen imidatsolin hydro-kloridi, jonka kaava onThe invention is characterized in that the hydrochloride of an imidazole of formula
N-—η-CH_SHN - η-CH_SH
I (II) U J CH,I (II) U J CH,
HB
2 74954 saatetaan reagoimaan atsiridiinin kanssa, jonka kaava on NHCH-j [x 3 [>-cv (III)2 74954 is reacted with aziridine of the formula NHCH-j [x 3 [> -cv (III)
^NC = N^ NC = N
vesipitoisessa väliaineessa NaOH:n läsnäollessa inertissä atmosfäärissä.in an aqueous medium in the presence of NaOH under an inert atmosphere.
Useista firman Smith Kline & French patenttijulkaisuista esimerkiksi DE-2 344 779:stä, DE-2 344 833:sta ja US-4 013 678:sta tunnetaan sellaisten yhdisteiden valmistusmenetelmiä, joilla on terapeuttisesti arvokkaita, varsinkin vatsahaavaa vastustavia ominaisuuksia toimiessaan histamiini-H2-reseptorien salpaajina ja joiden kaava on NHR.Several patent publications from Smith Kline & French, such as DE-2 344 779, DE-2 344 833 and US-4 013 678, disclose processes for the preparation of compounds which have therapeutically valuable properties, in particular antiulcer properties, in the treatment of histamine H2 receptor blockers of the formula NHR.
/ 1/ 1
Het-(CH„) -S-CH„-CH0-NH-C: ^ m 2 2. \ ^N-R2 jossa Het on imidatsoliryhmä, joka voi olla substituoitu, m on luku 1 - 4, R^ on vetyatomi tai 1-4 hiiliatomia sisältävä alkyyliryh-mä ja R2 on -C=N tai -NC>2. Missään SKF:n patenteissa ei kuitenkaan ole esitetty edellä esitetyn kaavan I mukaisen yhdisteen valmistusta saattamalla kaavan II mukainen yhdiste reagoimaan kaavan III mukaisen yhdisteen kanssa. Kaavan I mukainen yhdiste saadaan keksinnön mukaisesti valmistettaessa suurin saannoin.Het- (CH 2) -S-CH 2 -CHO-NH-C: m 2 2. N 2 R 2 wherein Het is an imidazole group which may be substituted, m is a number from 1 to 4, R 1 is a hydrogen atom or An alkyl group having 1 to 4 carbon atoms and R 2 is -C = N or -NC> 2. However, none of the SKF patents disclose the preparation of a compound of formula I as described above by reacting a compound of formula II with a compound of formula III. The compound of formula I is obtained according to the invention in the highest yields.
Tiolin ja atsiridiinin välinen reaktio /3-aminoalkyylijohdannaisten valmistamiseksi on tunnettu julkaisusta Heterocyclic compounds with three- and four-membered rings, Part 1, 1964, Interscience Publishers, New York-London-Sidney, page 554. Tämän julkaisun mukaan ei ole ilmeistä, että simetidiiniä ja vastaavia yhdisteitä voitaisiin valmistaa käyttämällä lähtöaineena atsiridiiniä. Aikaisemmin ei ollut mahdollista aavistaa keksinnön mukaisen menetelmän erinomaista saantoa.The reaction between thiol and aziridine to prepare β-aminoalkyl derivatives is known from Heterocyclic compounds with three- and four-membered rings, Part 1, 1964, Interscience Publishers, New York-London-Sidney, page 554. According to this publication, it is not apparent that cimetidine and the like could be prepared using aziridine as the starting material. Previously, it was not possible to imagine the excellent yield of the process according to the invention.
Koska kaavan II mukainen merkaptojohdannainen on erittäin epästabiili ja herkkä happeen nähden, täytyy käyttää suojakaasua. Näin toimittaessa kulkee yhdisteen II reaktio yhdisteen III kanssa vesi-liuoksessa NaOHrn läsnäollessa huoneen lämpötilassa käytännöllisesti katsoen kvantitatiivisesti. On suositeltavaa lisätä NaOH typen vir- 3 74954 ratessa ja säilyttää inertti kaasukehä koko reaktion ajan. Kuten esimerkissä 5 on kuvattu saadaan hyvälaatuinen kiteinen tuote.Since the mercapto derivative of formula II is very unstable and sensitive to oxygen, a shielding gas must be used. In doing so, the reaction of compound II with compound III in aqueous solution in the presence of NaOH at room temperature is practically quantitative. It is recommended to add NaOH under a stream of nitrogen 3 74954 and to maintain an inert atmosphere throughout the reaction. As described in Example 5, a good quality crystalline product is obtained.
Kaavojen II ja III mukaiset yhdisteet saadaan esimerkeissä 1 -3 (yhdiste II) ja esimerkissä 4 (yhdiste III) kuvatun menetelmän mukaisesti. 4-metyyli-5-metyyli-merkapto-imidatsoli valmistetaan kolmessa vaiheessa.Compounds of formulas II and III are obtained according to the procedure described in Examples 1-3 (Compound II) and Example 4 (Compound III). 4-Methyl-5-methyl-mercapto-imidazole is prepared in three steps.
Lähtöaine on etoksi-ditioformyyli-2,3-diketo-butaani, joka muutetaan 4-metyyli-5(etoksi-ditioformyyli)-imidatsoliksi, joka muutetaan 4-metyyli-5-metyyli-merkapto-imidatsoliksi.The starting material is ethoxydithioformyl-2,3-diketo-butane, which is converted to 4-methyl-5- (ethoxydithioformyl) imidazole, which is converted to 4-methyl-5-methyl-mercaptoimidazole.
Seuraavat esimerkit kuvaavat keksintöä.The following examples illustrate the invention.
Esimerkki 1Example 1
Etoksi-ditioformyyli-2,3-diketobutaani Jäähauteella jäähdytettyyn liuokseen, joka sisältää 74,4 g (0,465 mol) kaliummetyyliksantogenaattia 200 ml:ssa metanolia lisätään tipoittain koko ajan sekoittaen 76,7 g (0,465 mol) 1-bromi-butaani- 2,3-dionia. 16 tunnin kuluttua erotetaan liukenematon KBr suodattamalla ja liuotin poistetaan alennetussa paineessa, otetaan jäännös talteen petrolieetterillä, suodatetaan ja haihdutetaan liuotin - nestemäinen jäännös, 97,7 g kiehuu 98 - 100 °C:ssa 0,1 T. Saantotisla-uksen jälkeen 90 g (0,436 mol) = 94 %.Ethoxydithioformyl-2,3-diketobutane To a solution cooled in an ice bath containing 74.4 g (0.465 mol) of potassium methylxanthate in 200 ml of methanol is added dropwise, with stirring, 76.7 g (0.465 mol) of 1-bromo-butane-2, 3-dione. After 16 hours, the insoluble KBr is filtered off and the solvent is removed under reduced pressure, the residue is taken up in petroleum ether, filtered and the solvent-liquid residue is 97.7 g, boiling at 98-100 ° C for 0.1 T. After distillation, 90 g ( 0.436 mol) = 94%.
C7H10O3S2 (206) laskettu C 40,77 H 4,85 S 31,06 % saatu C 40,83 H 4,96 S 31,05 % IR (kalvona): 1710, 1660, 1440, 1410, 1350, 1230, 1200, 1150, 1110, 1060, 1035, 930, 845, 760 cm-1C7H10O3S2 (206) calcd. C 40.77 H 4.85 S 31.06% found C 40.83 H 4.96 S 31.05% IR (as film): 1710, 1660, 1440, 1410, 1350, 1230, 1200 , 1150, 1110, 1060, 1035, 930, 845, 760 cm-1
Esimerkki 2 4-metyyli-5-(etoksi-ditioformyyli)-imidatsoliExample 2 4-Methyl-5- (ethoxydithioformyl) imidazole
Liuos, joka sisältää 13,2 g etoksiditioformyyli-2,3-diketo-butaania, 1,66 g heksametyleeni-tetramiinia, 32 g ammoniumasetaattia 200 ml:ssa jääetikkaa, kuumennetaan 50 °C:seen 7 tunniksi. Liuotin haihdutetaan alennetussa paineessa, otetaan jäännös talteen kloroformilla. Suodattamisen jälkeen liuos uutetaan 2 kertaa liuoksella, joka sisältää 15 ml 12 N kloorivetyhappoa 250 mlsssa vettä. Vesifaa-si neutraloidaan natriumvetykarbonaatilla ja uutetaan sitten kloroformilla. Orgaaninen liuos kuivataan vedettömällä natriumsulfaatilla. Liuottimen haihdutusjäännös on kiinteä kiteinen aine, joka kiteytetään uudelleen asetonista. S.p. = 139-141°C. Saanto 10,8 g (0,5 mol) = 78 %.A solution of 13.2 g of ethoxydithioformyl-2,3-diketo-butane, 1.66 g of hexamethylene tetramine, 32 g of ammonium acetate in 200 ml of glacial acetic acid is heated to 50 ° C for 7 hours. The solvent is evaporated off under reduced pressure, the residue is taken up in chloroform. After filtration, the solution is extracted twice with a solution of 15 ml of 12 N hydrochloric acid in 250 ml of water. The aqueous phase is neutralized with sodium hydrogen carbonate and then extracted with chloroform. The organic solution is dried over anhydrous sodium sulfate. The solvent evaporation residue is a solid crystalline substance which is recrystallized from acetone. Mp = 139-141 ° C. Yield 10.8 g (0.5 mol) = 78%.
74954 C8H12N2OS2 *216^ laskettu C 44,44 H 5,55 N 12,96 S 29,71 % saatu C 44,48 H 5,63 N 12,99 S 29,62 % IR (nujol): 1610, 1410, 1280, 1260, 1220, 1110, 1045, 960, 850, 820, 740, 670 cm"1 Esimerkki 3 4-metyyli-5-metyyli-merkapto-imidatsolin hydrokloridi Keitetään palauttaen typpivirrassa 6 tunnin ajan liuosta, joka sisältää 8,7 g 4-metyyli-5-(etoksi-ditioformyyli)-imidatsolia 100 ml:ssa 12 N kloorivetyhappoa. Liuotin poistetaan alennetussa paineessa ja kiteytetään kiinteä jäännös kylmänä 2-butanolista, uudelleen kiteytys 2-butanolista, s.p. = 208 - 210 °C. Saanto 5,13 g (31 mmol) = 78 %.74954 C8H12N2OS2 * 216 ^ calculated C 44.44 H 5.55 N 12.96 S 29.71% found C 44.48 H 5.63 N 12.99 S 29.62% IR (nujol): 1610, 1410, 1280, 1260, 1220, 1110, 1045, 960, 850, 820, 740, 670 cm -1 Example 3 4-Methyl-5-methyl-mercaptoimidazole hydrochloride Boil under reflux for 6 hours a solution containing 8.7 g 4-methyl-5- (ethoxydithioformyl) imidazole in 100 ml of 12 N hydrochloric acid, the solvent is removed under reduced pressure and the solid residue is crystallized cold from 2-butanol, recrystallized from 2-butanol, m.p. = 208-210 ° C. , 13 g (31 mmol) = 78%.
C5H8N2S,HC1 (164'5) laskettu C 36,47 H 5,47 N 17,02 S 19,45 Cl 21,58 % saatu C 36,69 H 5,63 N 16,99 S 19,41 Cl 21,43 % IR (nujol): 3070, 2700, 2620, 1625, 1520, 1310, 1270, 1220, 1180, 1095, 980, 940, 920, 830, 730 cm"1 Esimerkki 4 1-(NH-metyyli-N1-syano-karboksamidiino)-atsiridiini Liuokseen, joka sisältää 15,8 g merkurikloridiligandiatsiridii-niä (1:1) 60 ml:ssa dimetyyliformamidia, liuotetaan 3,1 g N-syano-N',S-dimetyyli-isotioureaa ja kuumennetaan 55°C:een lämpötilaan 5 tunniksi, suodatetaan, liuotin haihdutetaan alennetussa paineessa. Jäännös otetaan talteen vesiliuokseen, joka sisältää 184,4 mmoolia etylee-ni-diamino-tetra-etikkahappoa ja 737,6 mmoolia NaOH. Tämä liuos uutetaan 6 kertaa kloroformilla. Liuottimen haihdutusjäännös kiteytetään tetrahydrofuraanista ja uudelleen etyyliasetaatista, s.p. = 133 -135°C.Saanto 6,0 g eli 70 %.C 5 H 8 N 2 S, HCl (164-5) calculated C 36.47 H 5.47 N 17.02 S 19.45 Cl 21.58% obtained C 36.69 H 5.63 N 16.99 S 19.41 Cl 21, 43% IR (nujol): 3070, 2700, 2620, 1625, 1520, 1310, 1270, 1220, 1180, 1095, 980, 940, 920, 830, 730 cm-1 Example 4 1- (NH-methyl-N1- cyano-carboxamidino) -aziridine To a solution of 15.8 g of mercuric chloride ligandiaziridine (1: 1) in 60 ml of dimethylformamide is dissolved 3.1 g of N-cyano-N ', S-dimethylisothiourea and heated to 55 ° C. The residue is taken up in an aqueous solution containing 184.4 mmol of ethylenediaminetetraacetic acid and 737.6 mmol of NaOH, and this solution is extracted 6 times with chloroform. from tetrahydrofuran and again from ethyl acetate, m.p. = 133-135 ° C. Yield 6.0 g or 70%.
C5HgN4 (124) laskettu C 48,38 H 6,45 N 45,16 % saatu C 48,20 H 6,48 N 44,99 % IR (kalvona): 3220, 3100, 3050, 2160, 1580, 1540, 1410, 1270, 1190, 1160, 1090, 1060, 1030, 945, 930, 885, 850, 820, 735 cm"1 5C 5 H 9 N 4 (124) calculated C 48.38 H 6.45 N 45.16% found C 48.20 H 6.48 N 44.99% IR (as film): 3220, 3100, 3050, 2160, 1580, 1540, 1410 , 1270, 1190, 1160, 1090, 1060, 1030, 945, 930, 885, 850, 820, 735 cm -1
Esimerkki 5 7 4 9 5 4 N-metyyli-N*-syano-Nn-Z?-((4-metyyli-imidatsol-5-yyli)-metyylitio)etyyli?guanidiini 16,45 g (0,1 mol) 4-metyyli-5-metyyli-merkapto-imidatsolin hydrokloridia ja 12,4 g N-(N'H-metyyli-N"-syano-amidiino)-atsiri-diiniä 100 ml:ssa tislattua vettä, lisätään typen samalla virratessa 4,4 g (0,11 mol) NaOH ja pidetään yllä inertti kaasukehä koko reaktion ajan. 20 tunnin kuluttua erotetaan suodattamalla huoneen lämpötilassa tuotteen kiteinen faasi, joka kiteytetään uudelleen asetonitriilistä, s.p. 142-143°C. Saanto 23,9 g (0,095 mol) = 95 %.Example 5 7 4 9 5 4 N-methyl-N * -cyano-Nn-Z - ((4-methylimidazol-5-yl) methylthio) ethyl] guanidine 16.45 g (0.1 mol) 4 -methyl-5-methyl-mercaptoimidazole hydrochloride and 12.4 g of N- (N'H-methyl-N "-cyanoamidino) -aziridine in 100 ml of distilled water are added under a stream of nitrogen at 4.4 g (0.11 mol) of NaOH and maintaining an inert atmosphere throughout the reaction After 20 hours, the crystalline phase of the product is filtered off at room temperature and recrystallized from acetonitrile, mp 142-143 [deg.] C. Yield 23.9 g (0.095 mol) = 95%.
C10H16N6S <252) laskettu C 47,60 H 6,35 N 33,33 S 12,69 % saatu C 47,53 H 6,48 N 33,28 S 12,72 % IR (kalvona): 3270, 3100, 2160, 1610, 1580, 1490, 1400, 1300, 1280, 1235, 1205, 1150, 1070, 950, 840, 800, 760, 680, 670 cm-·*·.C 10 H 16 N 6 S <252) calculated C 47.60 H 6.35 N 33.33 S 12.69% found C 47.53 H 6.48 N 33.28 S 12.72% IR (as film): 3270, 3100, 2160 , 1610, 1580, 1490, 1400, 1300, 1280, 1235, 1205, 1150, 1070, 950, 840, 800, 760, 680, 670 cm -1.
Claims (1)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1612677 | 1977-12-28 | ||
| CH1612677A CH626353A5 (en) | 1977-12-28 | 1977-12-28 | Process for the preparation of a guanidine |
| CH1247778 | 1978-12-07 | ||
| CH1247778A CH636348A5 (en) | 1978-12-07 | 1978-12-07 | Process for the preparation of guanidine derivatives |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI783990A FI783990A (en) | 1979-06-29 |
| FI74954B FI74954B (en) | 1987-12-31 |
| FI74954C true FI74954C (en) | 1988-04-11 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI783990A FI74954C (en) | 1977-12-28 | 1978-12-27 | PROCEDURE FOR FRAMSTATION OF N-METHYL-N'-CYANO-N '' - / 2 ((4-METHYLIMIDAZOL-5-YL) METHYLTHIO) ETHYL / GUANIDINE. |
Country Status (12)
| Country | Link |
|---|---|
| JP (2) | JPS5827792B2 (en) |
| CS (1) | CS208770B2 (en) |
| DE (1) | DE2855836A1 (en) |
| ES (1) | ES476707A1 (en) |
| FI (1) | FI74954C (en) |
| IL (1) | IL56265A (en) |
| IT (1) | IT1102776B (en) |
| NL (1) | NL184832C (en) |
| PL (1) | PL115042B1 (en) |
| RO (1) | RO76087A (en) |
| SU (1) | SU1077570A3 (en) |
| YU (1) | YU41138B (en) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL56265A (en) * | 1977-12-28 | 1982-08-31 | Om Lab Sa | Process for preparing imidazolyl methylthio guanidine derivatives and a novel intermediate therefor |
| NO784350L (en) * | 1977-12-30 | 1979-07-03 | Crc Ricerca Chim | PROCEDURE FOR ALKYLATION OF 4 (5) -MERCAPTOMETHYL-IMIDAZOLES WITH AZIRIDINE 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 |
| LU81178A1 (en) * | 1978-05-12 | 1979-09-10 | Crc Ricerca Chim | NEW THIOLD DERIVATIVES OF IMIDAZOLE |
| US4222845A (en) * | 1978-12-13 | 1980-09-16 | Gulf Oil Corporation | Integrated coal liquefaction-gasification-naphtha reforming process |
| US4383115A (en) * | 1979-02-14 | 1983-05-10 | Baudet Pierre J | Imino-alkyl and amino-nitrile cyano-guanidines |
| CH642068A5 (en) * | 1979-03-14 | 1984-03-30 | Rech Syntheses Organ | THERAPEUTICALLY ACTIVE CYANO-UREA AND CYANO-THIOURAE. |
| PT72320B (en) | 1980-01-08 | 1982-07-23 | Glaxo Group Ltd | Process for preparation of a furan derivative |
| YU41689B (en) * | 1980-01-14 | 1987-12-31 | Lek Tovarna Farmacevtskih | Process for preparing imidazole derivatives |
| DE3014353A1 (en) * | 1980-04-15 | 1982-01-21 | Bayer Ag, 5090 Leverkusen | TRISUBSTITUTED CYANGUANIDINE, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE AS FUNGICIDES |
| JPS5888366A (en) * | 1981-11-19 | 1983-05-26 | Fujimoto Seiyaku Kk | Preparation of guanidine derivative |
| JPS59130273A (en) * | 1983-01-14 | 1984-07-26 | Tokawa Tetsuo | Preparation of imidazole compound |
| JPS6170789U (en) * | 1984-10-16 | 1986-05-14 | ||
| GB8502446D0 (en) * | 1985-01-31 | 1985-03-06 | Smith Kline French Lab | Preparing aziridine derivative |
| SI8710091A8 (en) * | 1987-01-23 | 1996-06-30 | Lek Tovarna Farmacevtskih | Process for obtaining crystalline cimetadine (n-cyano-n'-methyl-n"- (2/(5-methyl-1h-imidazole-4-yl)methylthio/ethyl)-guanidine |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE36050B1 (en) * | 1971-03-09 | 1976-08-04 | Smith Kline French Lab | Ureas thioureas and guanidines |
| GB1533380A (en) * | 1974-09-02 | 1978-11-22 | Smith Kline French Lab | Process for the preparation of heterocyclic substituted thioureas and h-cyanoguanidines |
| GB1531231A (en) * | 1974-09-02 | 1978-11-08 | Smith Kline French Lab | Process for the production of cyanoguanidine derivatives |
| JPS5817511B2 (en) * | 1975-10-03 | 1983-04-07 | 積水化学工業株式会社 | Setuchiyakuzaisoseibutsu |
| MW5076A1 (en) * | 1975-12-29 | 1978-02-08 | Smith Kline French Lab | Pharmacologicalle active compounds |
| JPS5440547A (en) * | 1977-09-07 | 1979-03-30 | Seikosha Kk | Device for adjusting output frequency of frequency divider |
| IL56265A (en) * | 1977-12-28 | 1982-08-31 | Om Lab Sa | Process for preparing imidazolyl methylthio guanidine derivatives and a novel intermediate therefor |
| JPS5742068A (en) * | 1980-08-27 | 1982-03-09 | Ricoh Co Ltd | Solvent recovering device for wet type electronic copying machine |
| JPS6011994B2 (en) * | 1981-08-10 | 1985-03-29 | 池田 博美 | Liquid fuel for gasoline engines |
| JPS5888366A (en) * | 1981-11-19 | 1983-05-26 | Fujimoto Seiyaku Kk | Preparation of guanidine derivative |
-
1978
- 1978-12-20 IL IL7856265A patent/IL56265A/en unknown
- 1978-12-22 DE DE19782855836 patent/DE2855836A1/en active Granted
- 1978-12-22 ES ES476707A patent/ES476707A1/en not_active Expired
- 1978-12-27 FI FI783990A patent/FI74954C/en not_active IP Right Cessation
- 1978-12-27 YU YU3084/78A patent/YU41138B/en unknown
- 1978-12-27 CS CS788968A patent/CS208770B2/en unknown
- 1978-12-28 RO RO7896094A patent/RO76087A/en unknown
- 1978-12-28 IT IT7831392A patent/IT1102776B/en active
- 1978-12-28 NL NLAANVRAGE7812600,A patent/NL184832C/en not_active IP Right Cessation
- 1978-12-28 JP JP53164401A patent/JPS5827792B2/en not_active Expired
- 1978-12-28 SU SU782704652A patent/SU1077570A3/en active
- 1978-12-28 PL PL1978212223A patent/PL115042B1/en unknown
-
1983
- 1983-07-14 JP JP58129273A patent/JPS5962572A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| IL56265A (en) | 1982-08-31 |
| JPS5827792B2 (en) | 1983-06-11 |
| JPS6140667B2 (en) | 1986-09-10 |
| YU308478A (en) | 1983-01-21 |
| PL212223A1 (en) | 1979-08-27 |
| JPS54130566A (en) | 1979-10-09 |
| ES476707A1 (en) | 1979-06-01 |
| PL115042B1 (en) | 1981-03-31 |
| IT7831392A0 (en) | 1978-12-28 |
| RO76087A (en) | 1981-02-28 |
| IL56265A0 (en) | 1979-03-12 |
| NL7812600A (en) | 1979-07-02 |
| NL184832C (en) | 1989-11-16 |
| DE2855836A1 (en) | 1979-07-12 |
| FI783990A (en) | 1979-06-29 |
| CS208770B2 (en) | 1981-09-15 |
| YU41138B (en) | 1986-12-31 |
| DE2855836C2 (en) | 1989-09-28 |
| FI74954B (en) | 1987-12-31 |
| IT1102776B (en) | 1985-10-07 |
| SU1077570A3 (en) | 1984-02-29 |
| JPS5962572A (en) | 1984-04-10 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: LEK-TAVARNA FARMACEVTSKIN IN KEMICNIH |