SK69899A3 - Process for making 2-amino-2-imidazoline, guanidine, and 2-amino-3,4,5,6-tetrahydropyrimidine derivatives - Google Patents

Process for making 2-amino-2-imidazoline, guanidine, and 2-amino-3,4,5,6-tetrahydropyrimidine derivatives Download PDF

Info

Publication number: SK69899A3
Authority: SK; Slovakia
Prior art keywords: amino; methyl; imidazoline; methylene group; ethyl
Prior art date: 1996-11-25

Application number

SK698-99A

Other languages

English (en)

Slovak (sk)

Inventor

Michael Godlewski

Sean R Klopfenstein

Screenivasa R Mundla

William L Seibel

Original Assignee

Procter & Gamble

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.)

1996-11-25

Filing date

1997-11-25

Publication date

2000-01-18

1997-11-25 Application filed by Procter & Gamble filed Critical Procter & Gamble

2000-01-18 Publication of SK69899A3 publication Critical patent/SK69899A3/sk

Links

238000000034 method Methods 0.000 title claims abstract description 48
230000008569 process Effects 0.000 title claims abstract description 29
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 title claims description 26
DISXFZWKRTZTRI-UHFFFAOYSA-N 4,5-dihydro-1h-imidazol-2-amine Chemical compound NC1=NCCN1 DISXFZWKRTZTRI-UHFFFAOYSA-N 0.000 title claims description 19
PEHDFSFYZKSKGH-UHFFFAOYSA-N 1,4,5,6-tetrahydropyrimidin-2-amine Chemical class NC1=NCCCN1 PEHDFSFYZKSKGH-UHFFFAOYSA-N 0.000 title claims description 16
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 title claims description 13
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 title claims description 13
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims abstract description 59
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 27
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 27
125000000217 alkyl group Chemical group 0.000 claims abstract description 22
125000003545 alkoxy group Chemical group 0.000 claims abstract description 13
229910052736 halogen Inorganic materials 0.000 claims abstract description 12
150000002367 halogens Chemical class 0.000 claims abstract description 12
125000001424 substituent group Chemical group 0.000 claims abstract description 12
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 11
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 11
125000003367 polycyclic group Chemical group 0.000 claims abstract description 11
125000003342 alkenyl group Chemical group 0.000 claims abstract description 10
239000001257 hydrogen Substances 0.000 claims abstract description 10
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 10
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 9
125000004414 alkyl thio group Chemical group 0.000 claims abstract description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 7
125000005842 heteroatom Chemical group 0.000 claims abstract description 7
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 7
229920006395 saturated elastomer Polymers 0.000 claims abstract description 7
229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 5
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 125
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 65
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 60
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 48
238000006243 chemical reaction Methods 0.000 claims description 46
150000003839 salts Chemical group 0.000 claims description 46
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 42
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 26
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 25
238000002360 preparation method Methods 0.000 claims description 22
-1 amino, carboxyl Chemical group 0.000 claims description 21
239000003795 chemical substances by application Substances 0.000 claims description 18
GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 claims description 14
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 14
XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 claims description 14
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 13
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 12
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 12
229910000027 potassium carbonate Inorganic materials 0.000 claims description 12
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 12
239000002168 alkylating agent Substances 0.000 claims description 11
229940100198 alkylating agent Drugs 0.000 claims description 11
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 claims description 11
MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical class C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 claims description 11
150000007524 organic acids Chemical class 0.000 claims description 11
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 claims description 11
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
150000001409 amidines Chemical class 0.000 claims description 9
150000001412 amines Chemical class 0.000 claims description 9
FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 claims description 9
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 9
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 8
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 7
230000010933 acylation Effects 0.000 claims description 7
238000005917 acylation reaction Methods 0.000 claims description 7
150000002148 esters Chemical class 0.000 claims description 7
229940102396 methyl bromide Drugs 0.000 claims description 7
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 7
VBXZSFNZVNDOPB-UHFFFAOYSA-N 1,4,5,6-tetrahydropyrimidine Chemical class C1CNC=NC1 VBXZSFNZVNDOPB-UHFFFAOYSA-N 0.000 claims description 6
JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 claims description 6
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 6
GZDFHIJNHHMENY-UHFFFAOYSA-N Dimethyl dicarbonate Chemical compound COC(=O)OC(=O)OC GZDFHIJNHHMENY-UHFFFAOYSA-N 0.000 claims description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 6
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 6
125000002837 carbocyclic group Chemical group 0.000 claims description 6
JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 claims description 6
FFYPMLJYZAEMQB-UHFFFAOYSA-N diethyl pyrocarbonate Chemical compound CCOC(=O)OC(=O)OCC FFYPMLJYZAEMQB-UHFFFAOYSA-N 0.000 claims description 6
DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 claims description 6
229940008406 diethyl sulfate Drugs 0.000 claims description 6
235000010300 dimethyl dicarbonate Nutrition 0.000 claims description 6
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 claims description 6
PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 claims description 6
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 6
235000019260 propionic acid Nutrition 0.000 claims description 6
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 6
150000003573 thiols Chemical class 0.000 claims description 6
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 6
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 claims description 5
229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 4
230000002378 acidificating effect Effects 0.000 claims description 4
BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 claims description 4
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 4
239000011976 maleic acid Substances 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 claims description 4
239000001384 succinic acid Substances 0.000 claims description 4
238000007039 two-step reaction Methods 0.000 claims description 4
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 3
PCMHJJOKHSAPFF-UHFFFAOYSA-N 4-ethyl-1h-benzimidazol-5-amine Chemical compound CCC1=C(N)C=CC2=C1N=CN2 PCMHJJOKHSAPFF-UHFFFAOYSA-N 0.000 claims description 3
239000005711 Benzoic acid Substances 0.000 claims description 3
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 3
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 3
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 3
239000012346 acetyl chloride Substances 0.000 claims description 3
230000002152 alkylating effect Effects 0.000 claims description 3
238000005804 alkylation reaction Methods 0.000 claims description 3
235000010233 benzoic acid Nutrition 0.000 claims description 3
229960005215 dichloroacetic acid Drugs 0.000 claims description 3
235000019253 formic acid Nutrition 0.000 claims description 3
239000001530 fumaric acid Substances 0.000 claims description 3
RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 claims description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
239000011975 tartaric acid Substances 0.000 claims description 3
235000002906 tartaric acid Nutrition 0.000 claims description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
230000029936 alkylation Effects 0.000 claims description 2
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 claims description 2
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 claims description 2
NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 claims description 2
HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 claims description 2
238000005859 coupling reaction Methods 0.000 claims description 2
229960003750 ethyl chloride Drugs 0.000 claims description 2
239000003960 organic solvent Substances 0.000 claims 2
PGZVFRAEAAXREB-UHFFFAOYSA-N 2,2-dimethylpropanoyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC(=O)C(C)(C)C PGZVFRAEAAXREB-UHFFFAOYSA-N 0.000 claims 1
ZFTFAPZRGNKQPU-UHFFFAOYSA-N dicarbonic acid Chemical compound OC(=O)OC(O)=O ZFTFAPZRGNKQPU-UHFFFAOYSA-N 0.000 claims 1
150000001875 compounds Chemical class 0.000 abstract description 15
125000002950 monocyclic group Chemical group 0.000 abstract description 8
125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 5
125000003118 aryl group Chemical group 0.000 abstract description 4
125000003396 thiol group Chemical class [H]S* 0.000 abstract 1
239000011541 reaction mixture Substances 0.000 description 64
239000000203 mixture Substances 0.000 description 52
239000000047 product Substances 0.000 description 40
239000000243 solution Substances 0.000 description 31
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
230000015572 biosynthetic process Effects 0.000 description 25
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
239000002904 solvent Substances 0.000 description 22
238000001914 filtration Methods 0.000 description 21
229960000583 acetic acid Drugs 0.000 description 19
239000000543 intermediate Substances 0.000 description 19
239000007787 solid Substances 0.000 description 18
238000003756 stirring Methods 0.000 description 18
238000003786 synthesis reaction Methods 0.000 description 13
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
239000000706 filtrate Substances 0.000 description 12
239000003586 protic polar solvent Substances 0.000 description 12
238000005406 washing Methods 0.000 description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
PDQAZBWRQCGBEV-UHFFFAOYSA-N Ethylenethiourea Chemical compound S=C1NCCN1 PDQAZBWRQCGBEV-UHFFFAOYSA-N 0.000 description 9
125000004429 atom Chemical group 0.000 description 9
229960004592 isopropanol Drugs 0.000 description 9
239000003880 polar aprotic solvent Substances 0.000 description 9
238000010992 reflux Methods 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
239000012043 crude product Substances 0.000 description 8
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
229910000041 hydrogen chloride Inorganic materials 0.000 description 8
GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 7
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 7
150000001242 acetic acid derivatives Chemical class 0.000 description 7
239000000556 agonist Substances 0.000 description 7
239000003153 chemical reaction reagent Substances 0.000 description 7
230000000694 effects Effects 0.000 description 7
239000012362 glacial acetic acid Substances 0.000 description 7
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
102000030484 alpha-2 Adrenergic Receptor Human genes 0.000 description 6
108020004101 alpha-2 Adrenergic Receptor Proteins 0.000 description 6
229960002896 clonidine Drugs 0.000 description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 5
238000000605 extraction Methods 0.000 description 5
238000001556 precipitation Methods 0.000 description 5
125000004399 C1-C4 alkenyl group Chemical group 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
238000004821 distillation Methods 0.000 description 4
239000004210 ether based solvent Substances 0.000 description 4
150000002357 guanidines Chemical class 0.000 description 4
150000003254 radicals Chemical class 0.000 description 4
238000000935 solvent evaporation Methods 0.000 description 4
229910052717 sulfur Inorganic materials 0.000 description 4
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
LLXOATMJZSVSII-UHFFFAOYSA-N 2-[[1-(4-hydroxy-3-iodophenyl)-3-oxopyrrolidine-2-carbonyl]amino]ethyl 2,6-dimethyl-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate Chemical group CC=1NC(C)=CC(C=2C(=CC=CC=2)C(F)(F)F)C=1C(=O)OCCNC(=O)C(C(CC1)=O)N1C1=CC=C(O)C(I)=C1 LLXOATMJZSVSII-UHFFFAOYSA-N 0.000 description 3
DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 3
206010013654 Drug abuse Diseases 0.000 description 3
208000018522 Gastrointestinal disease Diseases 0.000 description 3
206010020772 Hypertension Diseases 0.000 description 3
208000019695 Migraine disease Diseases 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
208000013521 Visual disease Diseases 0.000 description 3
KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 3
239000002253 acid Substances 0.000 description 3
239000005557 antagonist Substances 0.000 description 3
239000012267 brine Substances 0.000 description 3
238000010511 deprotection reaction Methods 0.000 description 3
201000010099 disease Diseases 0.000 description 3
208000035475 disorder Diseases 0.000 description 3
238000001035 drying Methods 0.000 description 3
208000001780 epistaxis Diseases 0.000 description 3
239000007789 gas Substances 0.000 description 3
125000001072 heteroaryl group Chemical group 0.000 description 3
150000002430 hydrocarbons Chemical group 0.000 description 3
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
239000000463 material Substances 0.000 description 3
206010027599 migraine Diseases 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
208000011309 nasal bleeding Diseases 0.000 description 3
125000004433 nitrogen atom Chemical group N* 0.000 description 3
239000004031 partial agonist Substances 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
208000023504 respiratory system disease Diseases 0.000 description 3
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
208000011117 substance-related disease Diseases 0.000 description 3
238000001308 synthesis method Methods 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
OTPDWCMLUKMQNO-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrimidine Chemical compound C1NCC=CN1 OTPDWCMLUKMQNO-UHFFFAOYSA-N 0.000 description 2
BYLGOOAQHWOIGZ-UHFFFAOYSA-N 1,2-dimethyl-1-(8-methylquinolin-7-yl)guanidine Chemical compound C1=CC=NC2=C(C)C(N(C)C(N)=NC)=CC=C21 BYLGOOAQHWOIGZ-UHFFFAOYSA-N 0.000 description 2
FLHWLBNLXDWNJC-UHFFFAOYSA-N 4,5-dihydroimidazole-1-sulfonic acid Chemical compound OS(=O)(=O)N1CCN=C1 FLHWLBNLXDWNJC-UHFFFAOYSA-N 0.000 description 2
GONXJTJRZCPBLD-UHFFFAOYSA-N 6-(4,5-dihydro-1h-imidazol-2-ylamino)-7-methyl-3h-benzimidazole-4-carbonitrile Chemical compound C1=C(C#N)C=2N=CNC=2C(C)=C1NC1=NCCN1 GONXJTJRZCPBLD-UHFFFAOYSA-N 0.000 description 2
UCIWJBLQGSHKFP-UHFFFAOYSA-N 6-(4,5-dihydroimidazol-1-ylamino)-7-methyl-1h-indole-3-carbonitrile Chemical compound C1=CC=2C(C#N)=CNC=2C(C)=C1NN1CCN=C1 UCIWJBLQGSHKFP-UHFFFAOYSA-N 0.000 description 2
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/38—Nitrogen atoms
- 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
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
- C07D233/44—Nitrogen atoms not forming part of a nitro radical
- C07D233/50—Nitrogen atoms not forming part of a nitro radical with carbocyclic radicals directly attached to said nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Quinoline Compounds (AREA)

SK698-99A 1996-11-25 1997-11-25 Process for making 2-amino-2-imidazoline, guanidine, and 2-amino-3,4,5,6-tetrahydropyrimidine derivatives SK69899A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US3431896P	1996-11-25	1996-11-25
PCT/US1997/021646 WO1998023595A1 (fr)	1996-11-25	1997-11-25	Procede de fabrication de derives 2-amino-2-imidazoline, guanidine, et 2-amino-3,4,5,6-tetrahydropyrimidine

Publications (1)

Publication Number	Publication Date
SK69899A3 true SK69899A3 (en)	2000-01-18

Family

ID=21875679

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK698-99A SK69899A3 (en)	1996-11-25	1997-11-25	Process for making 2-amino-2-imidazoline, guanidine, and 2-amino-3,4,5,6-tetrahydropyrimidine derivatives

Country Status (21)

Country	Link
EP (1)	EP0944603B1 (fr)
JP (1)	JP2001506605A (fr)
KR (1)	KR20000069132A (fr)
AR (1)	AR008920A1 (fr)
AT (1)	ATE232851T1 (fr)
AU (1)	AU732056B2 (fr)
BR (1)	BR9713296A (fr)
CA (1)	CA2272690C (fr)
CO (1)	CO4910165A1 (fr)
CZ (1)	CZ183599A3 (fr)
DE (1)	DE69719210T2 (fr)
DK (1)	DK0944603T3 (fr)
ID (1)	ID22896A (fr)
IL (1)	IL130095A0 (fr)
NO (1)	NO312721B1 (fr)
PE (1)	PE28099A1 (fr)
SK (1)	SK69899A3 (fr)
TR (1)	TR199901484T2 (fr)
TW (1)	TW472043B (fr)
WO (1)	WO1998023595A1 (fr)
ZA (1)	ZA9710581B (fr)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2196792A1 (fr)	1994-08-04	1996-02-15	Yoon T. Jeon	Nouveaux derives de benzimidazole
US6495583B1 (en)	1997-03-25	2002-12-17	Synaptic Pharmaceutical Corporation	Benzimidazole derivatives
US20040167194A1 (en)	2003-02-20	2004-08-26	Randall Jared Lynn	Methods of making 6-[(4,5-Dihydro-1H-imidazol-2-yl)amino-]-7-methyl-1H-benzimidazole-4-carbonitrile and its preferred salt form
US11077053B2 (en)	2018-08-21	2021-08-03	Allergan, Inc.	Alpha-2-adrenergic receptor agonists for treatment of presbyopia, visual glare, visual starbursts, visual halos and night myopia

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE1670807A1 (de) *	1967-02-17	1971-03-11	Bayer Ag	Verfahren zur Herstellung von cyclischen Guanidinen
DE2854659A1 (de) *	1978-12-18	1980-07-10	Boehringer Sohn Ingelheim	Neue 3,4-disubstituierte 2-phenylimino-imidazolidine, deren saeureadditionssalze, diese enthaltende arzneimittel und verfahren zu deren herstellung

1997
- 1997-11-25 CA CA002272690A patent/CA2272690C/fr not_active Expired - Fee Related
- 1997-11-25 AU AU74021/98A patent/AU732056B2/en not_active Ceased
- 1997-11-25 CZ CZ991835A patent/CZ183599A3/cs unknown
- 1997-11-25 PE PE1997001068A patent/PE28099A1/es not_active Application Discontinuation
- 1997-11-25 WO PCT/US1997/021646 patent/WO1998023595A1/fr not_active Ceased
- 1997-11-25 TR TR1999/01484T patent/TR199901484T2/xx unknown
- 1997-11-25 BR BR9713296-9A patent/BR9713296A/pt unknown
- 1997-11-25 DE DE69719210T patent/DE69719210T2/de not_active Expired - Lifetime
- 1997-11-25 SK SK698-99A patent/SK69899A3/sk unknown
- 1997-11-25 KR KR1019997004620A patent/KR20000069132A/ko not_active Ceased
- 1997-11-25 EP EP97949622A patent/EP0944603B1/fr not_active Expired - Lifetime
- 1997-11-25 ID IDW990413A patent/ID22896A/id unknown
- 1997-11-25 DK DK97949622T patent/DK0944603T3/da active
- 1997-11-25 JP JP52482898A patent/JP2001506605A/ja active Pending
- 1997-11-25 AR ARP970105531A patent/AR008920A1/es not_active Application Discontinuation
- 1997-11-25 ZA ZA9710581A patent/ZA9710581B/xx unknown
- 1997-11-25 CO CO97068899A patent/CO4910165A1/es unknown
- 1997-11-25 IL IL13009597A patent/IL130095A0/xx unknown
- 1997-11-25 AT AT97949622T patent/ATE232851T1/de not_active IP Right Cessation
1998
- 1998-03-07 TW TW087103342A patent/TW472043B/zh active
1999
- 1999-05-25 NO NO19992501A patent/NO312721B1/no unknown

Also Published As

Publication number	Publication date
CO4910165A1 (es)	2000-04-24
ZA9710581B (en)	1998-06-12
IL130095A0 (en)	2000-02-29
TW472043B (en)	2002-01-11
AU7402198A (en)	1998-06-22
PE28099A1 (es)	1999-03-31
ATE232851T1 (de)	2003-03-15
CA2272690C (fr)	2004-07-13
TR199901484T2 (xx)	1999-09-21
DK0944603T3 (da)	2003-06-16
JP2001506605A (ja)	2001-05-22
DE69719210D1 (de)	2003-03-27
EP0944603A1 (fr)	1999-09-29
WO1998023595A1 (fr)	1998-06-04
NO312721B1 (no)	2002-06-24
CZ183599A3 (cs)	1999-10-13
ID22896A (id)	1999-12-16
EP0944603B1 (fr)	2003-02-19
AR008920A1 (es)	2000-02-23
NO992501L (no)	1999-07-22
KR20000069132A (ko)	2000-11-25
CA2272690A1 (fr)	1998-06-04
DE69719210T2 (de)	2004-02-12
BR9713296A (pt)	1999-10-26
NO992501D0 (no)	1999-05-25
AU732056B2 (en)	2001-04-12

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