CA1124721A - Azabicyclohexanes, methodes d'utilisation et de preparation - Google Patents

Azabicyclohexanes, methodes d'utilisation et de preparation

Info

Publication number: CA1124721A
Authority: CA; Canada
Prior art keywords: hexane; azabicyclo; tolyl; group; process according
Prior art date: 1976-09-15
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

CA285,206A

Other languages

English (en)

Inventor

William J. Fanshawe

Corris M. Hofmann

Lantz S. Crawley

Sidney R. Safir

Joseph W. Epstein

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.)

Wyeth Holdings LLC

Original Assignee

American Cyanamid 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.)

1976-09-15

Filing date

1977-08-22

Publication date

1982-06-01

1977-06-23 Priority claimed from US05/809,339 external-priority patent/US4131611A/en

1977-08-22 Application filed by American Cyanamid Co filed Critical American Cyanamid Co

1982-06-01 Application granted granted Critical

1982-06-01 Publication of CA1124721A publication Critical patent/CA1124721A/fr

Status Expired legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 60
238000002360 preparation method Methods 0.000 title abstract description 42
150000001875 compounds Chemical class 0.000 claims abstract description 126
239000002253 acid Chemical class 0.000 claims abstract description 25
150000003839 salts Chemical class 0.000 claims abstract description 15
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 281
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 145
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 134
239000000203 mixture Substances 0.000 claims description 112
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 71
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 54
-1 nitro, amino, acetamido Chemical group 0.000 claims description 44
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 42
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 38
229910000041 hydrogen chloride Inorganic materials 0.000 claims description 38
239000001257 hydrogen Substances 0.000 claims description 37
229910052739 hydrogen Inorganic materials 0.000 claims description 37
230000008569 process Effects 0.000 claims description 33
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 32
238000006243 chemical reaction Methods 0.000 claims description 31
150000004678 hydrides Chemical class 0.000 claims description 27
JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical compound [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 claims description 24
239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 claims description 24
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 21
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 21
239000004202 carbamide Substances 0.000 claims description 19
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
229910052736 halogen Inorganic materials 0.000 claims description 17
150000002367 halogens Chemical class 0.000 claims description 17
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 16
230000009467 reduction Effects 0.000 claims description 16
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 13
239000002904 solvent Substances 0.000 claims description 13
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 12
125000001309 chloro group Chemical group Cl* 0.000 claims description 12
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
239000000010 aprotic solvent Substances 0.000 claims description 10
239000003638 chemical reducing agent Substances 0.000 claims description 10
239000000126 substance Substances 0.000 claims description 10
150000003951 lactams Chemical class 0.000 claims description 8
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 7
231100000252 nontoxic Toxicity 0.000 claims description 7
230000003000 nontoxic effect Effects 0.000 claims description 7
239000012279 sodium borohydride Substances 0.000 claims description 7
229910000033 sodium borohydride Inorganic materials 0.000 claims description 7
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 6
239000012280 lithium aluminium hydride Substances 0.000 claims description 6
229910000029 sodium carbonate Inorganic materials 0.000 claims description 6
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 5
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 5
125000004849 alkoxymethyl group Chemical group 0.000 claims description 5
239000011230 binding agent Substances 0.000 claims description 5
229910052802 copper Inorganic materials 0.000 claims description 5
239000010949 copper Substances 0.000 claims description 5
150000002902 organometallic compounds Chemical class 0.000 claims description 5
RIDXNPOAOROPNF-UHFFFAOYSA-N 1-(4-methylphenyl)cyclopropane-1,2-dicarboxylic acid Chemical compound C1=CC(C)=CC=C1C1(C(O)=O)C(C(O)=O)C1 RIDXNPOAOROPNF-UHFFFAOYSA-N 0.000 claims description 4
NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 claims description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
239000007818 Grignard reagent Substances 0.000 claims description 3
150000004795 grignard reagents Chemical class 0.000 claims description 3
230000007062 hydrolysis Effects 0.000 claims description 3
238000006460 hydrolysis reaction Methods 0.000 claims description 3
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 claims description 3
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 2
235000019253 formic acid Nutrition 0.000 claims description 2
VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical group [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 claims description 2
125000005948 methanesulfonyloxy group Chemical group 0.000 claims description 2
DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 claims description 2
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 claims 24
OFYVIGTWSQPCLF-UHFFFAOYSA-N 1-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane Chemical compound C1=CC(C)=CC=C1C1(CNC2)C2C1 OFYVIGTWSQPCLF-UHFFFAOYSA-N 0.000 claims 10
238000004519 manufacturing process Methods 0.000 claims 9
VLWYROJLUFPLPC-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-azabicyclo[3.1.0]hexane Chemical compound C1=CC(Cl)=CC=C1C1(CNC2)C2C1 VLWYROJLUFPLPC-UHFFFAOYSA-N 0.000 claims 6
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 4
KUPJXVOZSLVPEB-UHFFFAOYSA-N 1-(4-chlorophenyl)cyclopropane-1,2-dicarboxylic acid Chemical compound OC(=O)C1CC1(C(O)=O)C1=CC=C(Cl)C=C1 KUPJXVOZSLVPEB-UHFFFAOYSA-N 0.000 claims 3
239000007858 starting material Substances 0.000 claims 3
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 2
MHTCLHUZDMHGFC-UHFFFAOYSA-N 3-(4-methylphenyl)-2,5-dihydro-1h-pyrrole Chemical compound C1=CC(C)=CC=C1C1=CCNC1 MHTCLHUZDMHGFC-UHFFFAOYSA-N 0.000 claims 2
IYVOFPIRCZBAEI-UHFFFAOYSA-N 3-methyl-1-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane Chemical compound C1N(C)CC2CC21C1=CC=C(C)C=C1 IYVOFPIRCZBAEI-UHFFFAOYSA-N 0.000 claims 2
UHQOPDGATRGDDD-UHFFFAOYSA-N 3-azabicyclo[3.1.0]hexane-2,4-dione Chemical compound O=C1NC(=O)C2CC12 UHQOPDGATRGDDD-UHFFFAOYSA-N 0.000 claims 1
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims 1
FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 claims 1
230000000202 analgesic effect Effects 0.000 abstract description 4
150000005228 3‐azabicyclo[3.1.0]hexanes Chemical class 0.000 abstract 1
239000002249 anxiolytic agent Substances 0.000 abstract 1
230000000949 anxiolytic effect Effects 0.000 abstract 1
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 240
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 117
229940076134 benzene Drugs 0.000 description 92
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 90
239000000243 solution Substances 0.000 description 73
230000002829 reductive effect Effects 0.000 description 56
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 54
239000003921 oil Substances 0.000 description 53
235000019198 oils Nutrition 0.000 description 53
239000013078 crystal Substances 0.000 description 49
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 46
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 46
239000000047 product Substances 0.000 description 41
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 40
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 38
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 34
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 32
235000011121 sodium hydroxide Nutrition 0.000 description 30
229940083608 sodium hydroxide Drugs 0.000 description 30
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
229910052757 nitrogen Inorganic materials 0.000 description 27
239000007788 liquid Substances 0.000 description 26
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 23
239000007787 solid Substances 0.000 description 23
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 20
150000003949 imides Chemical class 0.000 description 20
229960003390 magnesium sulfate Drugs 0.000 description 19
229910052943 magnesium sulfate Inorganic materials 0.000 description 19
235000019341 magnesium sulphate Nutrition 0.000 description 19
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
239000012044 organic layer Substances 0.000 description 18
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 17
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238000006722 reduction reaction Methods 0.000 description 15
238000003756 stirring Methods 0.000 description 15
101100536354 Drosophila melanogaster tant gene Proteins 0.000 description 14
150000002431 hydrogen Chemical group 0.000 description 14
238000010992 reflux Methods 0.000 description 14
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 13
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239000000706 filtrate Substances 0.000 description 12
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DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 11
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210000002683 foot Anatomy 0.000 description 10
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125000000217 alkyl group Chemical group 0.000 description 9
238000001704 evaporation Methods 0.000 description 9
230000008020 evaporation Effects 0.000 description 9
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
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QLFNUXTWJGXNLH-UHFFFAOYSA-N bis(2-methoxyethoxy)alumane Chemical compound COCCO[AlH]OCCOC QLFNUXTWJGXNLH-UHFFFAOYSA-N 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 7
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 7
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239000003795 chemical substances by application Substances 0.000 description 7
230000005021 gait Effects 0.000 description 7
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241000212342 Sium Species 0.000 description 6
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 6
125000001246 bromo group Chemical group Br* 0.000 description 6
230000000694 effects Effects 0.000 description 6
239000000284 extract Substances 0.000 description 6
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
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235000011118 potassium hydroxide Nutrition 0.000 description 6
238000012360 testing method Methods 0.000 description 6
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 5
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 5
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UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 5
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OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 4
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125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
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DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 4
125000001153 fluoro group Chemical group F* 0.000 description 4
HJLHTTJLVALHOP-UHFFFAOYSA-N hexane;hydron;chloride Chemical compound Cl.CCCCCC HJLHTTJLVALHOP-UHFFFAOYSA-N 0.000 description 4
239000000843 powder Substances 0.000 description 4
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
238000000746 purification Methods 0.000 description 4
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VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
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VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
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OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 3
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CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
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239000009937 cyclo 3 Substances 0.000 description 1
125000004981 cycloalkylmethyl group Chemical group 0.000 description 1
125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
229960002944 cyclofenil Drugs 0.000 description 1
125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
FDKLLWKMYAMLIF-UHFFFAOYSA-N cyclopropane-1,1-dicarboxylic acid Chemical compound OC(=O)C1(C(O)=O)CC1 FDKLLWKMYAMLIF-UHFFFAOYSA-N 0.000 description 1
238000010908 decantation Methods 0.000 description 1
238000004042 decolorization Methods 0.000 description 1
238000007033 dehydrochlorination reaction Methods 0.000 description 1
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BSMNRYCSBFHEMQ-UHFFFAOYSA-N dov-216,303 Chemical compound C1=C(Cl)C(Cl)=CC=C1C1(CNC2)C2C1 BSMNRYCSBFHEMQ-UHFFFAOYSA-N 0.000 description 1
238000010828 elution Methods 0.000 description 1
150000002081 enamines Chemical class 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
239000012259 ether extract Substances 0.000 description 1
ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
SLNHJHHDMDGTGB-UHFFFAOYSA-N ethyl 2-(3-chlorophenyl)acetate Chemical compound CCOC(=O)CC1=CC=CC(Cl)=C1 SLNHJHHDMDGTGB-UHFFFAOYSA-N 0.000 description 1
DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 1
MJEMIOXXNCZZFK-UHFFFAOYSA-N ethylone Chemical compound CCNC(C)C(=O)C1=CC=C2OCOC2=C1 MJEMIOXXNCZZFK-UHFFFAOYSA-N 0.000 description 1
239000010685 fatty oil Substances 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
125000006332 fluoro benzoyl group Chemical group 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
229960004279 formaldehyde Drugs 0.000 description 1
235000019256 formaldehyde Nutrition 0.000 description 1
230000002538 fungal effect Effects 0.000 description 1
238000003304 gavage Methods 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
QKGYJVXSKCDGOK-UHFFFAOYSA-N hexane;propan-2-ol Chemical compound CC(C)O.CCCCCC QKGYJVXSKCDGOK-UHFFFAOYSA-N 0.000 description 1
210000000548 hind-foot Anatomy 0.000 description 1
235000001050 hortel pimenta Nutrition 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
229910000043 hydrogen iodide Inorganic materials 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
SIAPCJWMELPYOE-UHFFFAOYSA-N lithium hydride Chemical compound [LiH] SIAPCJWMELPYOE-UHFFFAOYSA-N 0.000 description 1
229910000103 lithium hydride Inorganic materials 0.000 description 1
210000003141 lower extremity Anatomy 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
NCBZRJODKRCREW-UHFFFAOYSA-N m-anisidine Chemical compound COC1=CC=CC(N)=C1 NCBZRJODKRCREW-UHFFFAOYSA-N 0.000 description 1
239000000391 magnesium silicate Substances 0.000 description 1
229910052919 magnesium silicate Inorganic materials 0.000 description 1
235000019792 magnesium silicate Nutrition 0.000 description 1
RDPLOLUNEKBWBR-UHFFFAOYSA-L magnesium;sodium;sulfate Chemical compound [Na+].[Mg+2].[O-]S([O-])(=O)=O RDPLOLUNEKBWBR-UHFFFAOYSA-L 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
OHZZTXYKLXZFSZ-UHFFFAOYSA-I manganese(3+) 5,10,15-tris(1-methylpyridin-1-ium-4-yl)-20-(1-methylpyridin-4-ylidene)porphyrin-22-ide pentachloride Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Cl-].[Mn+3].C1=CN(C)C=CC1=C1C(C=C2)=NC2=C(C=2C=C[N+](C)=CC=2)C([N-]2)=CC=C2C(C=2C=C[N+](C)=CC=2)=C(C=C2)N=C2C(C=2C=C[N+](C)=CC=2)=C2N=C1C=C2 OHZZTXYKLXZFSZ-UHFFFAOYSA-I 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
KHBWTRFWQROKJZ-UHFFFAOYSA-N methyl 2-(2-chlorophenyl)acetate Chemical compound COC(=O)CC1=CC=CC=C1Cl KHBWTRFWQROKJZ-UHFFFAOYSA-N 0.000 description 1
YWMCHHGKDMGQPQ-UHFFFAOYSA-N methyl 2-bromo-2-(3-methoxyphenyl)acetate Chemical compound COC(=O)C(Br)C1=CC=CC(OC)=C1 YWMCHHGKDMGQPQ-UHFFFAOYSA-N 0.000 description 1
ALQXBMLSBSWCJQ-UHFFFAOYSA-N methyl 2-hydroxy-2-(3-methoxyphenyl)acetate hydrochloride Chemical compound COC(C(O)C1=CC(=CC=C1)OC)=O.Cl ALQXBMLSBSWCJQ-UHFFFAOYSA-N 0.000 description 1
OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
APVPOHHVBBYQAV-UHFFFAOYSA-N n-(4-aminophenyl)sulfonyloctadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(=O)NS(=O)(=O)C1=CC=C(N)C=C1 APVPOHHVBBYQAV-UHFFFAOYSA-N 0.000 description 1
IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
SEEYREPSKCQBBF-UHFFFAOYSA-N n-methylmaleimide Chemical compound CN1C(=O)C=CC1=O SEEYREPSKCQBBF-UHFFFAOYSA-N 0.000 description 1
OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
239000004533 oil dispersion Substances 0.000 description 1
239000007968 orange flavor Substances 0.000 description 1
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
HCTVWSOKIJULET-LQDWTQKMSA-M phenoxymethylpenicillin potassium Chemical class [K+].N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)COC1=CC=CC=C1 HCTVWSOKIJULET-LQDWTQKMSA-M 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 1
239000006187 pill Substances 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
229940093956 potassium carbonate Drugs 0.000 description 1
235000011181 potassium carbonates Nutrition 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
238000005932 reductive alkylation reaction Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
238000012216 screening Methods 0.000 description 1
239000002002 slurry Substances 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
125000005425 toluyl group Chemical group 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
230000009466 transformation Effects 0.000 description 1
UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
229910052721 tungsten Inorganic materials 0.000 description 1
239000010937 tungsten Substances 0.000 description 1
235000012431 wafers Nutrition 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000009637 wintergreen oil Substances 0.000 description 1
CRUISIDZTHMGJT-UHFFFAOYSA-L zinc;dichloride;hydrochloride Chemical compound Cl.[Cl-].[Cl-].[Zn+2] CRUISIDZTHMGJT-UHFFFAOYSA-L 0.000 description 1

Landscapes

Indole Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

CA285,206A 1976-09-15 1977-08-22 Azabicyclohexanes, methodes d'utilisation et de preparation Expired CA1124721A (fr)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US72340276A	1976-09-15	1976-09-15
US723,402		1976-09-15
US809,339		1977-06-23
US05/809,339 US4131611A (en)	1975-07-31	1977-06-23	Azabicyclohexanes

Publications (1)

Publication Number	Publication Date
CA1124721A true CA1124721A (fr)	1982-06-01

Family

ID=27110807

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA285,206A Expired CA1124721A (fr)	1976-09-15	1977-08-22	Azabicyclohexanes, methodes d'utilisation et de preparation

Country Status (3)

Country	Link
CA (1)	CA1124721A (fr)
ES (1)	ES462388A1 (fr)
SU (1)	SU786891A3 (fr)

1977
- 1977-08-22 CA CA285,206A patent/CA1124721A/fr not_active Expired
- 1977-09-14 SU SU772524809A patent/SU786891A3/ru active
- 1977-09-15 ES ES462388A patent/ES462388A1/es not_active Expired

Also Published As

Publication number	Publication date
ES462388A1 (es)	1979-07-16
SU786891A3 (ru)	1980-12-07

Legal Events

Date	Code	Title	Description
1999-06-01	MKEX	Expiry

Publication	Publication Date	Title
US4131611A (en)	1978-12-26	Azabicyclohexanes
US4161538A (en)	1979-07-17	Substituted phenylacetic acid derivatives and process for the preparation thereof
AU677644B2 (en)	1997-05-01	Piperazine derivatives
US5637593A (en)	1997-06-10	Tryptamine analogues as 5-ht1-like agonists
US4435419A (en)	1984-03-06	Method of treating depression using azabicyclohexanes
US4231935A (en)	1980-11-04	1-Phenyl-3-azabicyclo[3.1.0]hexanes
US4261895A (en)	1981-04-14	Alkanoyl-proline derivatives and homologues thereof
HU217433B (hu)	2000-01-28	Pirrolidinszármazékok, azokat tartalmazó gyógyszerkészítmények, és eljárás előállításukra
IE912224A1 (en)	1992-01-01	"New 4-aminobutyric acid compounds, process for the preparation thereof and pharmaceutical preparations containing them"
US4196120A (en)	1980-04-01	Azabicyclohexanes, method of use and preparation of the same
US4476307A (en)	1984-10-09	Heteroylidene indolone compounds
Tomaszewski et al.	1992	Benzofuran bioisosteres of hallucinogenic tryptamines
CA1255664A (fr)	1989-06-13	Nouvelles pyrrolidinones substituees, procede de preparation et composes pharmaceutiques les contenant
HU177531B (en)	1981-11-28	Process for producing azabicyclohexanes
JPH0812649A (ja)	1996-01-16	新規な（チア）シクロアルキル〔ｂ〕インドール類、それらの製造法及びそれらを含む医薬組成物
EP0140070A1 (fr)	1985-05-08	Dérivés du pyridoindole, procédé pour leur préparation et leur application
EP0954521B1 (fr)	2003-05-14	Derives du 4- (thien-3-yl)methyl]-imidazole ayant une activite agoniste vis-a-vis de l'adrenorecepteur alpha2
EP0286515B1 (fr)	1992-04-29	Nouvelles amines tricycliques dérivées du tétrahydro-5,6,7,8 naphto [2,3b] dihydro-2,3 furanne, et du tétrahydro-6,7,8,9 5H-benzocyclohepta [2,3b] dihydro-2,3 furanne, leurs procédés de préparation et les compositions pharmaceutiques qui les contiennent
CA1124721A (fr)	1982-06-01	Azabicyclohexanes, methodes d'utilisation et de preparation
Ermili et al.	1965	Products from Attempted Vilsmeier-Haack Acylations of Pyrroles with Select Amides1a, b
US4705807A (en)	1987-11-10	Amine derivatives
EP0434070B1 (fr)	1995-08-09	Dérivés de pyrrolaldéhyde
HU202222B (en)	1991-02-28	Process for producing thiophene derivatives and pharmaceutical compositions comprising same as active ingredient
CY1431A (en)	1988-09-02	3,3-dialkyl-and,3,3-alkylene-indoline derivatives,processes for their production and pharmaceutical compositions,comprising them
US3741980A (en)	1973-06-26	1,1-disubstituted-2-alkyl isoindolines