HRP970567A2 - Nicotinic agents in addiction therapy - Google Patents

Info

Publication number

HRP970567A2

HRP970567A2 HR60/028,804A HRP970567A HRP970567A2 HR P970567 A2 HRP970567 A2 HR P970567A2 HR P970567 A HRP970567 A HR P970567A HR P970567 A2 HRP970567 A2 HR P970567A2

Authority

HR

Croatia

Prior art keywords

pyrido

hexahydro

methane

diazocin

boc

Prior art date

1996-10-30

Links

• Espacenet
• Global Dossier
• Discuss

• 206010012335 Dependence Diseases 0.000 title claims description 9
• 238000002560 therapeutic procedure Methods 0.000 title description 6
• 239000000181 nicotinic agonist Substances 0.000 title 1
• 229940027564 cytisine Drugs 0.000 claims description 119
• 150000001875 compounds Chemical class 0.000 claims description 102
• 239000000203 mixture Substances 0.000 claims description 60
• -1 hydroxy, hydroxymethyl Chemical group 0.000 claims description 57
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 48
• 229910052739 hydrogen Inorganic materials 0.000 claims description 43
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 35
• 239000001257 hydrogen Substances 0.000 claims description 35
• 125000003118 aryl group Chemical group 0.000 claims description 30
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 28
• 229910052794 bromium Inorganic materials 0.000 claims description 25
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 24
• 150000003839 salts Chemical class 0.000 claims description 24
• 238000000034 method Methods 0.000 claims description 23
• 125000001072 heteroaryl group Chemical group 0.000 claims description 22
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
• 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 20
• 125000005843 halogen group Chemical group 0.000 claims description 17
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
• 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 13
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 12
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
• 208000035475 disorder Diseases 0.000 claims description 12
• 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 11
• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 11
• 241000124008 Mammalia Species 0.000 claims description 11
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 11
• 239000000460 chlorine Substances 0.000 claims description 11
• 229910052801 chlorine Inorganic materials 0.000 claims description 11
• 150000002431 hydrogen Chemical class 0.000 claims description 11
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
• 208000012902 Nervous system disease Diseases 0.000 claims description 10
• 208000025966 Neurological disease Diseases 0.000 claims description 10
• 241000208125 Nicotiana Species 0.000 claims description 10
• 235000002637 Nicotiana tabacum Nutrition 0.000 claims description 10
• 206010057852 Nicotine dependence Diseases 0.000 claims description 10
• 208000025569 Tobacco Use disease Diseases 0.000 claims description 10
• 239000002253 acid Substances 0.000 claims description 10
• 230000006949 cholinergic function Effects 0.000 claims description 10
• 230000007423 decrease Effects 0.000 claims description 10
• 230000000926 neurological effect Effects 0.000 claims description 10
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
• 208000020016 psychiatric disease Diseases 0.000 claims description 10
• 125000001424 substituent group Chemical group 0.000 claims description 10
• 125000003342 alkenyl group Chemical group 0.000 claims description 9
• 125000000217 alkyl group Chemical group 0.000 claims description 9
• 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 9
• 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 9
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 9
• 229910052757 nitrogen Inorganic materials 0.000 claims description 8
• 229920002554 vinyl polymer Polymers 0.000 claims description 8
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 7
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 6
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 6
• 150000001412 amines Chemical class 0.000 claims description 6
• 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
• 230000006999 cognitive decline Effects 0.000 claims description 6
• 208000010877 cognitive disease Diseases 0.000 claims description 6
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
• 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
• 229910052736 halogen Inorganic materials 0.000 claims description 6
• 150000002367 halogens Chemical group 0.000 claims description 6
• 125000005241 heteroarylamino group Chemical group 0.000 claims description 6
• 239000000651 prodrug Substances 0.000 claims description 6
• 229940002612 prodrug Drugs 0.000 claims description 6
• 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 6
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 6
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
• 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 6
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
• 125000004429 atom Chemical group 0.000 claims description 5
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 5
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
• 229910052731 fluorine Inorganic materials 0.000 claims description 5
• 239000011737 fluorine Substances 0.000 claims description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
• 230000002285 radioactive effect Effects 0.000 claims description 5
• 208000024891 symptom Diseases 0.000 claims description 5
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
• 125000000172 C5-C10 aryl group Chemical group 0.000 claims description 4
• 208000012661 Dyskinesia Diseases 0.000 claims description 4
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
• 208000023105 Huntington disease Diseases 0.000 claims description 4
• 206010020651 Hyperkinesia Diseases 0.000 claims description 4
• 208000000269 Hyperkinesis Diseases 0.000 claims description 4
• 208000015592 Involuntary movements Diseases 0.000 claims description 4
• 206010026749 Mania Diseases 0.000 claims description 4
• 208000005314 Multi-Infarct Dementia Diseases 0.000 claims description 4
• 208000002193 Pain Diseases 0.000 claims description 4
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
• 201000004810 Vascular dementia Diseases 0.000 claims description 4
• 230000032683 aging Effects 0.000 claims description 4
• 125000001769 aryl amino group Chemical group 0.000 claims description 4
• 229910052799 carbon Inorganic materials 0.000 claims description 4
• 210000003169 central nervous system Anatomy 0.000 claims description 4
• 230000001684 chronic effect Effects 0.000 claims description 4
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
• 206010015037 epilepsy Diseases 0.000 claims description 4
• 125000005842 heteroatom Chemical group 0.000 claims description 4
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
• 230000007774 longterm Effects 0.000 claims description 4
• 230000017311 musculoskeletal movement, spinal reflex action Effects 0.000 claims description 4
• 229910052760 oxygen Inorganic materials 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims description 4
• 201000000980 schizophrenia Diseases 0.000 claims description 4
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Chemical class OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 4
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 3
• 208000024827 Alzheimer disease Diseases 0.000 claims description 3
• 208000008589 Obesity Diseases 0.000 claims description 3
• 208000018737 Parkinson disease Diseases 0.000 claims description 3
• 206010039966 Senile dementia Diseases 0.000 claims description 3
• 208000000323 Tourette Syndrome Diseases 0.000 claims description 3
• 208000016620 Tourette disease Diseases 0.000 claims description 3
• 125000002252 acyl group Chemical group 0.000 claims description 3
• 239000000654 additive Substances 0.000 claims description 3
• KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 3
• 239000004327 boric acid Substances 0.000 claims description 3
• 206010009887 colitis Diseases 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 235000020824 obesity Nutrition 0.000 claims description 3
• 235000019505 tobacco product Nutrition 0.000 claims description 3
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 claims description 2
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
• NTOIKDYVJIWVSU-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(4-methylbenzoyl)butanedioic acid Chemical compound C1=CC(C)=CC=C1C(=O)C(O)(C(O)=O)C(O)(C(O)=O)C(=O)C1=CC=C(C)C=C1 NTOIKDYVJIWVSU-UHFFFAOYSA-N 0.000 claims description 2
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 2
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
• 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 2
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 claims description 2
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Chemical class OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 2
• 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 2
• 150000007513 acids Chemical class 0.000 claims description 2
• 230000000996 additive effect Effects 0.000 claims description 2
• 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
• CODNYICXDISAEA-UHFFFAOYSA-N bromine monochloride Chemical compound BrCl CODNYICXDISAEA-UHFFFAOYSA-N 0.000 claims description 2
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical class O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims description 2
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
• OQQXGCLLMDQESN-UHFFFAOYSA-N cyclohexylcarbamic acid Chemical group OC(=O)NC1CCCCC1 OQQXGCLLMDQESN-UHFFFAOYSA-N 0.000 claims description 2
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
• 239000001530 fumaric acid Chemical class 0.000 claims description 2
• 125000002541 furyl group Chemical group 0.000 claims description 2
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 2
• 125000002883 imidazolyl group Chemical group 0.000 claims description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
• 229960002510 mandelic acid Drugs 0.000 claims description 2
• 229940098779 methanesulfonic acid Drugs 0.000 claims description 2
• 125000001624 naphthyl group Chemical group 0.000 claims description 2
• 235000006408 oxalic acid Nutrition 0.000 claims description 2
• 125000002971 oxazolyl group Chemical group 0.000 claims description 2
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 2
• 229910052698 phosphorus Inorganic materials 0.000 claims description 2
• 125000003386 piperidinyl group Chemical group 0.000 claims description 2
• 230000002265 prevention Effects 0.000 claims description 2
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
• 125000004076 pyridyl group Chemical group 0.000 claims description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
• 229960004889 salicylic acid Drugs 0.000 claims description 2
• 229910052717 sulfur Inorganic materials 0.000 claims description 2
• 239000011975 tartaric acid Substances 0.000 claims description 2
• 235000002906 tartaric acid Nutrition 0.000 claims description 2
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
• 125000000335 thiazolyl group Chemical group 0.000 claims description 2
• 125000001544 thienyl group Chemical group 0.000 claims description 2
• 125000001425 triazolyl group Chemical group 0.000 claims description 2
• HIOSTWNYLIZTIU-UHFFFAOYSA-N (3z,7z)-1h-1,5-diazocin-2-one Chemical compound O=C1NC=CC=NC=C1 HIOSTWNYLIZTIU-UHFFFAOYSA-N 0.000 claims 5
• 239000003550 marker Substances 0.000 claims 4
• 208000019901 Anxiety disease Diseases 0.000 claims 2
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 2
• 230000036506 anxiety Effects 0.000 claims 2
• 208000013403 hyperactivity Diseases 0.000 claims 2
• 125000001153 fluoro group Chemical group F* 0.000 claims 1
• 230000006870 function Effects 0.000 claims 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 204
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 168
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 129
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 95
• 229940093499 ethyl acetate Drugs 0.000 description 67
• 235000019439 ethyl acetate Nutrition 0.000 description 67
• 238000006243 chemical reaction Methods 0.000 description 62
• 239000011541 reaction mixture Substances 0.000 description 59
• 239000002904 solvent Substances 0.000 description 59
• 238000001819 mass spectrum Methods 0.000 description 57
• 239000000243 solution Substances 0.000 description 54
• ANJTVLIZGCUXLD-BDAKNGLRSA-N (-)-Cytisine Natural products C1NC[C@@H]2CN3C(=O)C=CC=C3[C@H]1C2 ANJTVLIZGCUXLD-BDAKNGLRSA-N 0.000 description 50
• ANJTVLIZGCUXLD-UHFFFAOYSA-N ent-cytisine Natural products C1NCC2CN3C(=O)C=CC=C3C1C2 ANJTVLIZGCUXLD-UHFFFAOYSA-N 0.000 description 50
• ANJTVLIZGCUXLD-DTWKUNHWSA-N cytisine Chemical compound C1NC[C@H]2CN3C(=O)C=CC=C3[C@@H]1C2 ANJTVLIZGCUXLD-DTWKUNHWSA-N 0.000 description 49
• 229930017327 cytisine Natural products 0.000 description 49
• 239000000047 product Substances 0.000 description 49
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 43
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
• 238000005160 1H NMR spectroscopy Methods 0.000 description 42
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 42
• HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 41
• 229910001868 water Inorganic materials 0.000 description 41
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 38
• 239000012267 brine Substances 0.000 description 37
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 35
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
• 229960002715 nicotine Drugs 0.000 description 31
• 238000010992 reflux Methods 0.000 description 31
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
• SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 29
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 29
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
• 239000000741 silica gel Substances 0.000 description 28
• 229910002027 silica gel Inorganic materials 0.000 description 28
• 239000012074 organic phase Substances 0.000 description 26
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 22
• 229910052763 palladium Inorganic materials 0.000 description 22
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
• 239000003153 chemical reaction reagent Substances 0.000 description 21
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 21
• 239000002585 base Substances 0.000 description 20
• 229910052740 iodine Inorganic materials 0.000 description 17
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 17
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
• 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 15
• 125000006239 protecting group Chemical group 0.000 description 15
• 238000012360 testing method Methods 0.000 description 15
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 14
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