CA1039308A - Halophenylacetamidines et benzamidines substituees en n,n' - Google Patents

Halophenylacetamidines et benzamidines substituees en n,n'

Info

Publication number: CA1039308A
Authority: CA; Canada
Prior art keywords: formula; hydrochloride; reaction; temperature; salt
Prior art date: 1974-10-02
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

Application number

CA230,932A

Other languages

English (en)

Other versions

CA230932S (en

Inventor

James R. Mccarthy (Jr.)

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Dow Chemical Co

Original Assignee

Dow Chemical Co

Priority date (The priority date 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 date listed.)

1974-10-02

Filing date

1975-07-07

Publication date

1978-09-26

1974-11-29 Priority to US05/527,989 priority Critical patent/US3972931A/en

1975-07-07 Application filed by Dow Chemical Co filed Critical Dow Chemical Co

1975-07-07 Priority to CA230,932A priority patent/CA1039308A/fr

1975-07-24 Priority to GB3105675A priority patent/GB1466047A/en

1975-07-29 Priority to NL7509033A priority patent/NL7509033A/xx

1975-07-30 Priority to BE158783A priority patent/BE831934A/fr

1975-07-30 Priority to DE19752534038 priority patent/DE2534038A1/de

1975-07-31 Priority to FR7523921A priority patent/FR2319335A1/fr

1975-08-01 Priority to JP50094106A priority patent/JPS5219636A/ja

1975-08-01 Priority claimed from JP50094106A external-priority patent/JPS5219636A/ja

1976-02-11 Priority to US05/657,335 priority patent/US4029703A/en

1978-09-26 Application granted granted Critical

1978-09-26 Publication of CA1039308A publication Critical patent/CA1039308A/fr

Status Expired legal-status Critical Current

Links

150000003937 benzamidines Chemical class 0.000 title 1
238000000034 method Methods 0.000 claims abstract description 26
-1 amidine compounds Chemical class 0.000 claims abstract description 11
230000008569 process Effects 0.000 claims abstract description 8
125000001475 halogen functional group Chemical group 0.000 claims abstract description 6
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
239000001257 hydrogen Substances 0.000 claims abstract description 5
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract 2
238000006243 chemical reaction Methods 0.000 claims description 20
150000003973 alkyl amines Chemical class 0.000 claims description 15
150000002825 nitriles Chemical class 0.000 claims description 11
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 7
UQPRCNDNKRPGDM-UHFFFAOYSA-N 2-(4-chlorophenyl)-n,n'-dimethylethanimidamide;hydrochloride Chemical compound Cl.CNC(=NC)CC1=CC=C(Cl)C=C1 UQPRCNDNKRPGDM-UHFFFAOYSA-N 0.000 claims description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 4
150000001408 amides Chemical class 0.000 claims description 4
SESUZOLXSAPAIT-UHFFFAOYSA-N 3,4-dichloro-n,n'-dimethylbenzenecarboximidamide;hydrochloride Chemical compound Cl.CNC(=NC)C1=CC=C(Cl)C(Cl)=C1 SESUZOLXSAPAIT-UHFFFAOYSA-N 0.000 claims description 3
238000009835 boiling Methods 0.000 claims description 3
IVYMIRMKXZAHRV-UHFFFAOYSA-N 4-chlorophenylacetonitrile Chemical compound ClC1=CC=C(CC#N)C=C1 IVYMIRMKXZAHRV-UHFFFAOYSA-N 0.000 claims description 2
NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 claims description 2
RXAOGVQDNBYURA-UHFFFAOYSA-N (4-chlorobenzenecarboximidoyl)azanium;chloride Chemical compound Cl.NC(=N)C1=CC=C(Cl)C=C1 RXAOGVQDNBYURA-UHFFFAOYSA-N 0.000 claims 1
KUWBYWUSERRVQP-UHFFFAOYSA-N 3,4-dichlorobenzonitrile Chemical compound ClC1=CC=C(C#N)C=C1Cl KUWBYWUSERRVQP-UHFFFAOYSA-N 0.000 claims 1
GJNGXPDXRVXSEH-UHFFFAOYSA-N 4-chlorobenzonitrile Chemical compound ClC1=CC=C(C#N)C=C1 GJNGXPDXRVXSEH-UHFFFAOYSA-N 0.000 claims 1
BAVYZALUXZFZLV-UHFFFAOYSA-O Methylammonium ion Chemical compound [NH3+]C BAVYZALUXZFZLV-UHFFFAOYSA-O 0.000 claims 1
125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
150000003839 salts Chemical class 0.000 abstract description 30
150000001875 compounds Chemical class 0.000 abstract description 29
239000000203 mixture Substances 0.000 abstract description 20
230000000694 effects Effects 0.000 abstract description 11
239000000935 antidepressant agent Substances 0.000 abstract description 5
229940005513 antidepressants Drugs 0.000 abstract description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 3
238000002360 preparation method Methods 0.000 abstract description 3
230000000049 anti-anxiety effect Effects 0.000 abstract description 2
239000002249 anxiolytic agent Substances 0.000 abstract description 2
239000003795 chemical substances by application Substances 0.000 abstract description 2
230000001914 calming effect Effects 0.000 abstract 1
229910052736 halogen Inorganic materials 0.000 abstract 1
150000002367 halogens Chemical class 0.000 abstract 1
239000000047 product Substances 0.000 description 21
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 13
239000000376 reactant Substances 0.000 description 13
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
241000699670 Mus sp. Species 0.000 description 12
150000001409 amidines Chemical class 0.000 description 12
239000012458 free base Substances 0.000 description 12
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 8
LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 8
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238000007912 intraperitoneal administration Methods 0.000 description 8
BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 8
229960003147 reserpine Drugs 0.000 description 8
MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
238000001704 evaporation Methods 0.000 description 7
230000008020 evaporation Effects 0.000 description 7
229910052757 nitrogen Inorganic materials 0.000 description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
206010015995 Eyelid ptosis Diseases 0.000 description 6
238000007792 addition Methods 0.000 description 6
230000000875 corresponding effect Effects 0.000 description 6
230000003389 potentiating effect Effects 0.000 description 6
201000003004 ptosis Diseases 0.000 description 6
239000012429 reaction media Substances 0.000 description 6
239000007858 starting material Substances 0.000 description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
210000003169 central nervous system Anatomy 0.000 description 5
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 4
230000001154 acute effect Effects 0.000 description 4
230000006399 behavior Effects 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
239000007928 intraperitoneal injection Substances 0.000 description 4
238000002844 melting Methods 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
239000000243 solution Substances 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
238000005406 washing Methods 0.000 description 4
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
PDLBFUDXXCCCBP-UHFFFAOYSA-N 4-chloro-n,n'-dimethylbenzenecarboximidamide;hydrochloride Chemical compound Cl.CNC(=NC)C1=CC=C(Cl)C=C1 PDLBFUDXXCCCBP-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
239000002253 acid Substances 0.000 description 3
150000001450 anions Chemical class 0.000 description 3
230000001430 anti-depressive effect Effects 0.000 description 3
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000000605 extraction Methods 0.000 description 3
125000005843 halogen group Chemical group 0.000 description 3
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
229910000041 hydrogen chloride Inorganic materials 0.000 description 3
239000007788 liquid Substances 0.000 description 3
230000008018 melting Effects 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
ZHDPSMHSXOOZDE-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-n,n'-diethylethanimidamide Chemical compound CCNC(=NCC)CC1=CC=C(Cl)C(Cl)=C1 ZHDPSMHSXOOZDE-UHFFFAOYSA-N 0.000 description 2
MUWLVPGPXLREOW-UHFFFAOYSA-N 2-(4-bromophenyl)-n,n'-diethylethanimidamide;hydrochloride Chemical compound Cl.CCNC(=NCC)CC1=CC=C(Br)C=C1 MUWLVPGPXLREOW-UHFFFAOYSA-N 0.000 description 2
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
241000700159 Rattus Species 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
BLGXFZZNTVWLAY-CCZXDCJGSA-N Yohimbine Natural products C1=CC=C2C(CCN3C[C@@H]4CC[C@@H](O)[C@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-CCZXDCJGSA-N 0.000 description 2
230000016571 aggressive behavior Effects 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
BLGXFZZNTVWLAY-UHFFFAOYSA-N beta-Yohimbin Natural products C1=CC=C2C(CCN3CC4CCC(O)C(C4CC33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-UHFFFAOYSA-N 0.000 description 2
RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 2
125000001309 chloro group Chemical group Cl* 0.000 description 2
238000004821 distillation Methods 0.000 description 2
239000012065 filter cake Substances 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
239000011521 glass Substances 0.000 description 2
PIPZGJSEDRMUAW-VJDCAHTMSA-N hydron;methyl (1s,15r,18s,19r,20s)-18-hydroxy-1,3,11,12,14,15,16,17,18,19,20,21-dodecahydroyohimban-19-carboxylate;chloride Chemical compound Cl.C1=CC=C2C(CCN3C[C@@H]4CC[C@H](O)[C@@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 PIPZGJSEDRMUAW-VJDCAHTMSA-N 0.000 description 2
208000013403 hyperactivity Diseases 0.000 description 2
239000011261 inert gas Substances 0.000 description 2
230000009191 jumping Effects 0.000 description 2
231100000225 lethality Toxicity 0.000 description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
239000011976 maleic acid Substances 0.000 description 2
239000001630 malic acid Substances 0.000 description 2
238000002156 mixing Methods 0.000 description 2
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 2
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238000000746 purification Methods 0.000 description 2
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238000003756 stirring Methods 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
239000001384 succinic acid Substances 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
229960000317 yohimbine Drugs 0.000 description 2
BLGXFZZNTVWLAY-SCYLSFHTSA-N yohimbine Chemical compound C1=CC=C2C(CCN3C[C@@H]4CC[C@H](O)[C@@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-SCYLSFHTSA-N 0.000 description 2
AADVZSXPNRLYLV-UHFFFAOYSA-N yohimbine carboxylic acid Natural products C1=CC=C2C(CCN3CC4CCC(C(C4CC33)C(O)=O)O)=C3NC2=C1 AADVZSXPNRLYLV-UHFFFAOYSA-N 0.000 description 2
229960000949 yohimbine hydrochloride Drugs 0.000 description 2
HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
BYIMJLNPEUMZDE-UHFFFAOYSA-N 2-(3,4-dibromophenyl)-n,n'-dipropylethanimidamide;hydrobromide Chemical compound Br.CCCNC(=NCCC)CC1=CC=C(Br)C(Br)=C1 BYIMJLNPEUMZDE-UHFFFAOYSA-N 0.000 description 1
PAVPURABCCEXIP-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-n,n'-diethylethanimidamide;hydrochloride Chemical compound [Cl-].CCNC(=[NH+]CC)CC1=CC=C(Cl)C(Cl)=C1 PAVPURABCCEXIP-UHFFFAOYSA-N 0.000 description 1
OSCAZEOYRIBZFR-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-n,n'-dimethylethanimidamide;hydrochloride Chemical compound Cl.CNC(=NC)CC1=CC=C(Cl)C(Cl)=C1 OSCAZEOYRIBZFR-UHFFFAOYSA-N 0.000 description 1
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JTZHLMRKALGOFS-UHFFFAOYSA-N 2-(3-bromophenyl)-n,n'-di(propan-2-yl)ethanimidamide;hydrochloride Chemical compound Cl.CC(C)NC(=NC(C)C)CC1=CC=CC(Br)=C1 JTZHLMRKALGOFS-UHFFFAOYSA-N 0.000 description 1
CAWURYSHSNCQQB-UHFFFAOYSA-N 2-(4-bromo-3-chlorophenyl)-n,n'-diethylethanimidamide;hydrobromide Chemical compound Br.CCNC(=NCC)CC1=CC=C(Br)C(Cl)=C1 CAWURYSHSNCQQB-UHFFFAOYSA-N 0.000 description 1
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LTADIWWYTXOETE-UHFFFAOYSA-N 2-(4-chlorophenyl)-n-methylacetamide Chemical compound CNC(=O)CC1=CC=C(Cl)C=C1 LTADIWWYTXOETE-UHFFFAOYSA-N 0.000 description 1
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238000004566 IR spectroscopy Methods 0.000 description 1
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238000005481 NMR spectroscopy Methods 0.000 description 1
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230000037396 body weight Effects 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
210000000748 cardiovascular system Anatomy 0.000 description 1
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
230000000857 drug effect Effects 0.000 description 1
238000000921 elemental analysis Methods 0.000 description 1
WCQOBLXWLRDEQA-UHFFFAOYSA-N ethanimidamide;hydrochloride Chemical compound Cl.CC(N)=N WCQOBLXWLRDEQA-UHFFFAOYSA-N 0.000 description 1
239000002024 ethyl acetate extract Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
VNWHJJCHHGPAEO-UHFFFAOYSA-N fluoroboronic acid Chemical compound OB(O)F VNWHJJCHHGPAEO-UHFFFAOYSA-N 0.000 description 1
238000009472 formulation Methods 0.000 description 1
239000007789 gas Substances 0.000 description 1
150000002431 hydrogen Chemical class 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
229910001412 inorganic anion Inorganic materials 0.000 description 1
229910001503 inorganic bromide Inorganic materials 0.000 description 1
229910052806 inorganic carbonate Inorganic materials 0.000 description 1
229910001504 inorganic chloride Inorganic materials 0.000 description 1
229910001506 inorganic fluoride Inorganic materials 0.000 description 1
229910001505 inorganic iodide Inorganic materials 0.000 description 1
229910052920 inorganic sulfate Inorganic materials 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
238000000622 liquid--liquid extraction Methods 0.000 description 1
230000005291 magnetic effect Effects 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
239000000463 material Substances 0.000 description 1
229940041669 mercury 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
AFVFQIVMOAPDHO-UHFFFAOYSA-N methanesulfonic acid Substances CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
210000000653 nervous system Anatomy 0.000 description 1
238000010915 one-step procedure Methods 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000002891 organic anions Chemical class 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
150000003864 primary ammonium salts Chemical class 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
238000000926 separation method Methods 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000007787 solid Substances 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
238000003419 tautomerization reaction Methods 0.000 description 1
238000011282 treatment Methods 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)

Landscapes

Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Hydrogenated Pyridines (AREA)

CA230,932A 1972-08-10 1975-07-07 Halophenylacetamidines et benzamidines substituees en n,n' Expired CA1039308A (fr)

Priority Applications (9)

Application Number	Priority Date	Filing Date	Title
US05/527,989 US3972931A (en)	1972-08-10	1974-11-29	N,N'-Disubstituted benzamidines
CA230,932A CA1039308A (fr)	1974-10-02	1975-07-07	Halophenylacetamidines et benzamidines substituees en n,n'
GB3105675A GB1466047A (en)	1974-10-02	1975-07-24	Substituted amidine compounds
NL7509033A NL7509033A (nl)	1974-10-02	1975-07-29	Werkwijze voor de bereiding van gesubstitueerde amidineverbindingen.
BE158783A BE831934A (fr)	1974-10-02	1975-07-30	Amidines substituees, leur preparation et leur emploi
DE19752534038 DE2534038A1 (de)	1974-10-02	1975-07-30	Substituierte amidine, verfahren zu deren herstellung und diese verbindungen enthaltende arzneipraeparate
FR7523921A FR2319335A1 (fr)	1974-10-02	1975-07-31	Composes acetamidine substituee
JP50094106A JPS5219636A (en)	1974-10-02	1975-08-01	Production of substituted amizine compound
US05/657,335 US4029703A (en)	1972-08-10	1976-02-11	N,N'-disubstituted halophenylacetamidines

Applications Claiming Priority (7)

Application Number	Priority Date	Filing Date	Title
US51095574A	1974-10-02	1974-10-02
CA230,932A CA1039308A (fr)	1974-10-02	1975-07-07	Halophenylacetamidines et benzamidines substituees en n,n'
GB3105675A GB1466047A (en)	1974-10-02	1975-07-24	Substituted amidine compounds
NL7509033A NL7509033A (nl)	1974-10-02	1975-07-29	Werkwijze voor de bereiding van gesubstitueerde amidineverbindingen.
DE19752534038 DE2534038A1 (de)	1974-10-02	1975-07-30	Substituierte amidine, verfahren zu deren herstellung und diese verbindungen enthaltende arzneipraeparate
FR7523921A FR2319335A1 (fr)	1974-10-02	1975-07-31	Composes acetamidine substituee
JP50094106A JPS5219636A (en)	1974-10-02	1975-08-01	Production of substituted amizine compound

Publications (1)

Publication Number	Publication Date
CA1039308A true CA1039308A (fr)	1978-09-26

Family

ID=27560877

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA230,932A Expired CA1039308A (fr)	1972-08-10	1975-07-07	Halophenylacetamidines et benzamidines substituees en n,n'

Country Status (5)

Country	Link
CA (1)	CA1039308A (fr)
DE (1)	DE2534038A1 (fr)
FR (1)	FR2319335A1 (fr)
GB (1)	GB1466047A (fr)
NL (1)	NL7509033A (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1587945A (en) *	1977-07-20	1981-04-15	Aron Sa	Benzamidine derivatives

1975
- 1975-07-07 CA CA230,932A patent/CA1039308A/fr not_active Expired
- 1975-07-24 GB GB3105675A patent/GB1466047A/en not_active Expired
- 1975-07-29 NL NL7509033A patent/NL7509033A/xx not_active Application Discontinuation
- 1975-07-30 DE DE19752534038 patent/DE2534038A1/de not_active Withdrawn
- 1975-07-31 FR FR7523921A patent/FR2319335A1/fr active Granted

Also Published As

Publication number	Publication date
FR2319335A1 (fr)	1977-02-25
GB1466047A (en)	1977-03-02
FR2319335B1 (fr)	1978-11-10
NL7509033A (nl)	1977-02-01
DE2534038A1 (de)	1977-02-17

Publication	Publication Date	Title
US3660423A (en)	1972-05-02	2-(substituted benzyl)methyl-2-imidazolines
US3995039A (en)	1976-11-30	Pyrazolo [1,5-a] [1,3,5] triazines
Lancini et al.	1966	A new synthesis of alkyl and aryl 2‐aminoimidazoles
US3988345A (en)	1976-10-26	Imidazoline derivatives and the preparation thereof
HERBST et al.	1951	The synthesis of 5-aminotetrazole derivatives
US2948724A (en)	1960-08-09	Halogenated derivatives of tetrahydro-1-naphthyl cyclic amidines
AU611235B2 (en)	1991-06-06	Process for preparing bis(3,5-dioxpiperazinyl) alkanes or alkenes
US3254120A (en)	1966-05-31	N-(tertiaryaminoalkoxy-benzoyl) anilides
CA1055960A (fr)	1979-06-05	Naphthaleneacetamidines disubstitues en n,n'
US3972931A (en)	1976-08-03	N,N'-Disubstituted benzamidines
US3178446A (en)	1965-04-13	Oxyethylation of imidazole compounds
US2450386A (en)	1948-09-28	Manufacture of compounds containing amidine groups
HAUSER et al.	1949	Substitutions at the α-or γ-POSITIONS in pyridyl ring systems by basic REAGENTS1
US3073826A (en)	1963-01-15	3-pyrrolidylmethyl-4-quinazolones
US3449357A (en)	1969-06-10	2-((2,6-substituted)phenoxymethyl)-2-imidazolines
US3256278A (en)	1966-06-14	N-hydroxy ethyl-ortho acetyl and carbalkoxy amino phenyl-glyoxamides and process formaking 2-orthoamino phenyl-morpholines
US4029703A (en)	1977-06-14	N,N'-disubstituted halophenylacetamidines
US3388130A (en)	1968-06-11	1-hydrazino or 1-amino isoquinolines
Haruki et al.	1968	Some reactions of N-haloamidines
US4194044A (en)	1980-03-18	Process for preparing 3-phenoxy morphinans
US2942001A (en)	1960-06-21	Piperazo-pyridazines
US2733244A (en)	1956-01-31	G-tetrahydropyrimidine and imidaz-
US2998421A (en)	1961-08-29	Guanroevo compounds and method of
US3296263A (en)	1967-01-03	2-alkyl-4-alkylamino-6-alkoxy-s-triazines
US3211789A (en)	1965-10-12	Aralkylaminoalkylene guanidines