DK2563790T3 - PROCESS FOR quaternary ammonium salt - Google Patents
PROCESS FOR quaternary ammonium salt Download PDFInfo
- Publication number
- DK2563790T3 DK2563790T3 DK11775164.4T DK11775164T DK2563790T3 DK 2563790 T3 DK2563790 T3 DK 2563790T3 DK 11775164 T DK11775164 T DK 11775164T DK 2563790 T3 DK2563790 T3 DK 2563790T3
- Authority
- DK
- Denmark
- Prior art keywords
- compound
- group
- formula
- mole
- methyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 64
- 150000003242 quaternary ammonium salts Chemical class 0.000 title claims description 59
- 150000001875 compounds Chemical class 0.000 claims description 243
- -1 1,2-benzisothiazol-3-yl Chemical group 0.000 claims description 70
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 53
- 239000011541 reaction mixture Substances 0.000 claims description 47
- 238000006243 chemical reaction Methods 0.000 claims description 40
- 238000004519 manufacturing process Methods 0.000 claims description 30
- 239000002904 solvent Substances 0.000 claims description 30
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 27
- 239000007787 solid Substances 0.000 claims description 25
- 150000007529 inorganic bases Chemical class 0.000 claims description 22
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 18
- 125000002950 monocyclic group Chemical group 0.000 claims description 16
- 125000002947 alkylene group Chemical group 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 13
- 125000002619 bicyclic group Chemical group 0.000 claims description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 8
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 8
- 125000004104 aryloxy group Chemical group 0.000 claims description 7
- 239000013078 crystal Substances 0.000 claims description 7
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 6
- 125000005110 aryl thio group Chemical group 0.000 claims description 5
- 125000004465 cycloalkenyloxy group Chemical group 0.000 claims description 5
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 3
- 125000005947 C1-C6 alkylsulfonyloxy group Chemical group 0.000 claims description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
- 125000005366 cycloalkylthio group Chemical group 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000003158 alcohol group Chemical group 0.000 claims description 2
- 150000003863 ammonium salts Chemical class 0.000 claims description 2
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000005948 methanesulfonyloxy group Chemical group 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 4
- 125000001931 aliphatic group Chemical group 0.000 claims 1
- 150000001450 anions Chemical class 0.000 claims 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 171
- 239000000203 mixture Substances 0.000 description 51
- 239000006227 byproduct Substances 0.000 description 39
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 36
- 235000011181 potassium carbonates Nutrition 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 239000000243 solution Substances 0.000 description 19
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 15
- 229910052799 carbon Inorganic materials 0.000 description 14
- 230000035484 reaction time Effects 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 11
- 238000004811 liquid chromatography Methods 0.000 description 11
- 125000000041 C6-C10 aryl group Chemical group 0.000 description 10
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 10
- 239000002585 base Substances 0.000 description 9
- WLDMPODMCFGWAA-UHFFFAOYSA-N 3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione Chemical compound C1CCCC2C(=O)NC(=O)C21 WLDMPODMCFGWAA-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- 238000011088 calibration curve Methods 0.000 description 7
- 150000002430 hydrocarbons Chemical group 0.000 description 7
- 230000009466 transformation Effects 0.000 description 7
- 125000003545 alkoxy group Chemical group 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 230000003287 optical effect Effects 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 5
- 125000004414 alkyl thio group Chemical group 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 150000003949 imides Chemical class 0.000 description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 4
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 4
- 150000008041 alkali metal carbonates Chemical class 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 4
- 125000005368 heteroarylthio group Chemical group 0.000 description 4
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 3
- KRDOFMHJLWKXIU-UHFFFAOYSA-N ID11614 Chemical compound C1CNCCN1C1=NSC2=CC=CC=C12 KRDOFMHJLWKXIU-UHFFFAOYSA-N 0.000 description 3
- 150000004945 aromatic hydrocarbons Chemical group 0.000 description 3
- 150000001924 cycloalkanes Chemical class 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 3
- 125000001841 imino group Chemical group [H]N=* 0.000 description 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 201000000980 schizophrenia Diseases 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000020925 Bipolar disease Diseases 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 206010029333 Neurosis Diseases 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- SVGOMVDLLKZDBF-UHFFFAOYSA-N O=C1C2C(C3)CCC3C2C(=O)N1CC1CCCCC1CN(CC1)CCN1C1=NC=CC=N1 Chemical compound O=C1C2C(C3)CCC3C2C(=O)N1CC1CCCCC1CN(CC1)CCN1C1=NC=CC=N1 SVGOMVDLLKZDBF-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- 150000001338 aliphatic hydrocarbons Chemical group 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 2
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 125000005587 carbonate group Chemical group 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
- LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 2
- 239000001095 magnesium carbonate Substances 0.000 description 2
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 208000015238 neurotic disease Diseases 0.000 description 2
- 125000006574 non-aromatic ring group Chemical group 0.000 description 2
- 239000003444 phase transfer catalyst Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 description 2
- 239000011736 potassium bicarbonate Substances 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 229910052717 sulfur Inorganic materials 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
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- IACVNURSTUDTFC-UHFFFAOYSA-N (2-hydroxy-3-methylsulfonyloxypropyl) methanesulfonate Chemical compound CS(=O)(=O)OCC(O)COS(C)(=O)=O IACVNURSTUDTFC-UHFFFAOYSA-N 0.000 description 1
- RIVOBMOBWMOLDJ-RNGGSSJXSA-N (3ar,4s,7r,7as)-hexahydro-1h-4,7-methanoisoindole-1,3(2h)-dione Chemical compound O=C1NC(=O)[C@@H]2[C@H]1[C@]1([H])C[C@@]2([H])CC1 RIVOBMOBWMOLDJ-RNGGSSJXSA-N 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- HOCRXQDESXBOIC-UHFFFAOYSA-N 1'-[[2-[[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]methyl]cyclohexyl]methyl]spiro[bicyclo[2.2.2]octane-3,3'-pyrrolidine]-2',5'-dione Chemical compound C1=CC=C2C(N3CCN(CC3)CC3CCCCC3CN3C(=O)C4(C5CCC(CC5)C4)CC3=O)=NSC2=C1 HOCRXQDESXBOIC-UHFFFAOYSA-N 0.000 description 1
- MKIIBHAVKKVAKM-UHFFFAOYSA-N 1,2-bis(bromomethyl)cyclohexane Chemical compound BrCC1CCCCC1CBr MKIIBHAVKKVAKM-UHFFFAOYSA-N 0.000 description 1
- GRZUMRMUCBCYHV-UHFFFAOYSA-N 1,2-bis(bromomethyl)cyclopentane Chemical compound BrCC1CCCC1CBr GRZUMRMUCBCYHV-UHFFFAOYSA-N 0.000 description 1
- KIHQZLPHVZKELA-UHFFFAOYSA-N 1,3-dibromopropan-2-ol Chemical compound BrCC(O)CBr KIHQZLPHVZKELA-UHFFFAOYSA-N 0.000 description 1
- DEWLEGDTCGBNGU-UHFFFAOYSA-N 1,3-dichloropropan-2-ol Chemical compound ClCC(O)CCl DEWLEGDTCGBNGU-UHFFFAOYSA-N 0.000 description 1
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- PYUFUUDEYQJLPV-UHFFFAOYSA-N 1-(1-benzofuran-5-yl)piperazine Chemical compound C1CNCCN1C1=CC=C(OC=C2)C2=C1 PYUFUUDEYQJLPV-UHFFFAOYSA-N 0.000 description 1
- KFVKNZPFYQDNAE-UHFFFAOYSA-N 1-(1-benzofuran-7-yl)piperazine Chemical compound C1CNCCN1C1=CC=CC2=C1OC=C2 KFVKNZPFYQDNAE-UHFFFAOYSA-N 0.000 description 1
- VNICFCQJUVFULD-UHFFFAOYSA-N 1-(1-naphthalenyl)piperazine Chemical compound C1CNCCN1C1=CC=CC2=CC=CC=C12 VNICFCQJUVFULD-UHFFFAOYSA-N 0.000 description 1
- MRBFGEHILMYPTF-UHFFFAOYSA-N 1-(2-Pyrimidyl)piperazine Chemical compound C1CNCCN1C1=NC=CC=N1 MRBFGEHILMYPTF-UHFFFAOYSA-N 0.000 description 1
- VNZLQLYBRIOLFZ-UHFFFAOYSA-N 1-(2-methoxyphenyl)piperazine Chemical compound COC1=CC=CC=C1N1CCNCC1 VNZLQLYBRIOLFZ-UHFFFAOYSA-N 0.000 description 1
- VHFVKMTVMIZMIK-UHFFFAOYSA-N 1-(3-chlorophenyl)piperazine Chemical compound ClC1=CC=CC(N2CCNCC2)=C1 VHFVKMTVMIZMIK-UHFFFAOYSA-N 0.000 description 1
- XPDSXKIDJNKIQY-UHFFFAOYSA-N 1-cyclohexylpiperazine Chemical compound C1CCCCC1N1CCNCC1 XPDSXKIDJNKIQY-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- VWGYXCCHJRYCRU-UHFFFAOYSA-N 2,3-bis(bromomethyl)-7-oxabicyclo[2.2.1]hept-5-ene Chemical compound O1C2C=CC1C(CBr)C2CBr VWGYXCCHJRYCRU-UHFFFAOYSA-N 0.000 description 1
- RJJGLGWMQBORFA-UHFFFAOYSA-N 2,3-bis(bromomethyl)bicyclo[2.2.1]heptane Chemical compound C1CC2C(CBr)C(CBr)C1C2 RJJGLGWMQBORFA-UHFFFAOYSA-N 0.000 description 1
- YLBIXCWPQYQTNF-UHFFFAOYSA-N 2-[[2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]cyclohexyl]methyl]-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione Chemical compound O=C1C2CCCCC2C(=O)N1CC1CCCCC1CN(CC1)CCN1C1=CC=CC=N1 YLBIXCWPQYQTNF-UHFFFAOYSA-N 0.000 description 1
- KDXGOAOXIFWEPO-UHFFFAOYSA-N 2-[[2-[(4-pyrimidin-2-ylpiperazin-1-yl)methyl]cyclohexyl]methyl]-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione Chemical compound O=C1C2CCCCC2C(=O)N1CC1CCCCC1CN(CC1)CCN1C1=NC=CC=N1 KDXGOAOXIFWEPO-UHFFFAOYSA-N 0.000 description 1
- DFOATGAIVVNLEX-UHFFFAOYSA-N 2-[[2-[[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]methyl]cyclohexyl]methyl]-3a,4,5,6,7,7a-hexahydro-octahydro-1h-4,7-epoxyisoindole-1,3-dione Chemical compound C1=CC=C2C(N3CCN(CC3)CC3CCCCC3CN3C(=O)C4C5CCC(O5)C4C3=O)=NSC2=C1 DFOATGAIVVNLEX-UHFFFAOYSA-N 0.000 description 1
- QXHXQIYZHOLROU-UHFFFAOYSA-N 2-[[2-[[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]methyl]cyclohexyl]methyl]-3a,7a-dimethyl-4,5,6,7-tetrahydroisoindole-1,3-dione Chemical compound C1=CC=C2C(N3CCN(CC3)CC3CCCCC3CN3C(=O)C4(C)CCCCC4(C3=O)C)=NSC2=C1 QXHXQIYZHOLROU-UHFFFAOYSA-N 0.000 description 1
- SGLNWXAAUCPKHN-UHFFFAOYSA-N 2-[[2-[[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]methyl]cyclohexyl]methyl]-4,5,6,7-tetrahydroisoindole-1,3-dione Chemical compound O=C1C(CCCC2)=C2C(=O)N1CC1C(CN2CCN(CC2)C=2C3=CC=CC=C3SN=2)CCCC1 SGLNWXAAUCPKHN-UHFFFAOYSA-N 0.000 description 1
- UGUROFMSHXLSRO-UHFFFAOYSA-N 2-[[2-[[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]methyl]cyclohexyl]methyl]isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1CC1C(CN2CCN(CC2)C=2C3=CC=CC=C3SN=2)CCCC1 UGUROFMSHXLSRO-UHFFFAOYSA-N 0.000 description 1
- XAGLOCYWGDAVKJ-UHFFFAOYSA-N 2-[[2-[[4-(1,2-benzoxazol-3-yl)piperidin-1-yl]methyl]cyclohexyl]methyl]-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione Chemical compound C1=CC=C2C(C3CCN(CC3)CC3CCCCC3CN3C(=O)C4CCCCC4C3=O)=NOC2=C1 XAGLOCYWGDAVKJ-UHFFFAOYSA-N 0.000 description 1
- LVYDVAKVOSIHPF-UHFFFAOYSA-N 2-[[2-[[4-(1-benzofuran-5-yl)piperazin-1-yl]methyl]cyclohexyl]methyl]-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione Chemical compound C1=C2OC=CC2=CC(N2CCN(CC2)CC2CCCCC2CN2C(=O)C3CCCCC3C2=O)=C1 LVYDVAKVOSIHPF-UHFFFAOYSA-N 0.000 description 1
- LYFHCJRRQKLAOD-UHFFFAOYSA-N 2-[[2-[[4-(1-benzofuran-7-yl)piperazin-1-yl]methyl]cyclohexyl]methyl]-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione Chemical compound O=C1C2CCCCC2C(=O)N1CC1CCCCC1CN(CC1)CCN1C1=CC=CC2=C1OC=C2 LYFHCJRRQKLAOD-UHFFFAOYSA-N 0.000 description 1
- QPCOLNXTMARMBL-UHFFFAOYSA-N 2-[[2-[[4-(2-methoxyphenyl)piperazin-1-yl]methyl]cyclohexyl]methyl]-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione Chemical compound COC1=CC=CC=C1N1CCN(CC2C(CCCC2)CN2C(C3CCCCC3C2=O)=O)CC1 QPCOLNXTMARMBL-UHFFFAOYSA-N 0.000 description 1
- KGQUIUQNTRAXBN-UHFFFAOYSA-N 2-[[2-[[4-(3-chlorophenyl)piperazin-1-yl]methyl]cyclohexyl]methyl]-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione Chemical compound ClC1=CC=CC(N2CCN(CC3C(CCCC3)CN3C(C4CCCCC4C3=O)=O)CC2)=C1 KGQUIUQNTRAXBN-UHFFFAOYSA-N 0.000 description 1
- LMVKVIQZWVRGGM-UHFFFAOYSA-N 2-[[2-[[4-(4-fluorophenoxy)piperidin-1-yl]methyl]cyclohexyl]methyl]-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione Chemical compound C1=CC(F)=CC=C1OC1CCN(CC2C(CCCC2)CN2C(C3CCCCC3C2=O)=O)CC1 LMVKVIQZWVRGGM-UHFFFAOYSA-N 0.000 description 1
- PFIDYHKBPFTRBJ-UHFFFAOYSA-N 2-[[2-[[4-(4-fluorophenyl)sulfanylpiperidin-1-yl]methyl]cyclohexyl]methyl]-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione Chemical compound C1=CC(F)=CC=C1SC1CCN(CC2C(CCCC2)CN2C(C3CCCCC3C2=O)=O)CC1 PFIDYHKBPFTRBJ-UHFFFAOYSA-N 0.000 description 1
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000005979 2-naphthyloxy group Chemical group 0.000 description 1
- RMFUECWROCQIPI-UHFFFAOYSA-N 3,3-dioxo-3lambda6-thia-4-azatricyclo[5.2.1.02,6]decan-5-one Chemical compound C1CC2C3C(=O)NS(=O)(=O)C3C1C2 RMFUECWROCQIPI-UHFFFAOYSA-N 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- PJPJVTSCAFZBGN-UHFFFAOYSA-N 3-piperazin-1-ylisoquinoline Chemical compound C1CNCCN1C1=CC2=CC=CC=C2C=N1 PJPJVTSCAFZBGN-UHFFFAOYSA-N 0.000 description 1
- SJBJFVTZXSLBFK-UHFFFAOYSA-N 3-spiro[1,3,3a,4,7,7a-hexahydroisoindol-2-ium-2,4'-1,4-diazinan-4-ium]-1'-yl-1,2-benzothiazole Chemical compound C1=CC=C2C(N3CC[N+]4(CC3)CC3CC=CCC3C4)=NSC2=C1 SJBJFVTZXSLBFK-UHFFFAOYSA-N 0.000 description 1
- CIFFBTOJCKSRJY-UHFFFAOYSA-N 3α,4,7,7α-tetrahydro-1h-isoindole-1,3(2h)-dione Chemical compound C1C=CCC2C(=O)NC(=O)C21 CIFFBTOJCKSRJY-UHFFFAOYSA-N 0.000 description 1
- SSGSIZPVBPNHOX-UHFFFAOYSA-N 4'-(1-benzofuran-7-yl)spiro[1,3,3a,4,5,6,7,7a-octahydroisoindol-2-ium-2,1'-1,4-diazinan-1-ium] Chemical compound C1C2CCCCC2C[N+]1(CC1)CCN1C1=CC=CC2=C1OC=C2 SSGSIZPVBPNHOX-UHFFFAOYSA-N 0.000 description 1
- CNHFVDKWWMVECQ-UHFFFAOYSA-N 4'-(2-methoxyphenyl)spiro[1,3,3a,4,5,6,7,7a-octahydroisoindol-2-ium-2,1'-1,4-diazinan-1-ium] Chemical compound COC1=CC=CC=C1N1CC[N+]2(CC3CCCCC3C2)CC1 CNHFVDKWWMVECQ-UHFFFAOYSA-N 0.000 description 1
- DMVLSFDXZGKZBK-UHFFFAOYSA-N 4'-(3-chlorophenyl)spiro[1,3,3a,4,5,6,7,7a-octahydroisoindol-2-ium-2,1'-1,4-diazinan-1-ium] Chemical compound ClC1=CC=CC(N2CC[N+]3(CC4CCCCC4C3)CC2)=C1 DMVLSFDXZGKZBK-UHFFFAOYSA-N 0.000 description 1
- UWTMJUVZYJGVMX-UHFFFAOYSA-N 4'-[bis(4-fluorophenyl)methylidene]spiro[1,3,3a,4,5,6,7,7a-octahydroisoindol-2-ium-2,1'-azinan-1-ium] Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)=C1CC[N+]2(CC3CCCCC3C2)CC1 UWTMJUVZYJGVMX-UHFFFAOYSA-N 0.000 description 1
- ZQYAMDRPUMINCV-UHFFFAOYSA-N 4'-isoquinolin-3-ylspiro[1,3,3a,4,5,6,7,7a-octahydroisoindol-2-ium-2,1'-1,4-diazinan-1-ium] Chemical compound C1=CC=C2C=NC(N3CC[N+]4(CC3)CC3CCCCC3C4)=CC2=C1 ZQYAMDRPUMINCV-UHFFFAOYSA-N 0.000 description 1
- WNUSZPVTPWMFIV-UHFFFAOYSA-N 4'-naphthalen-1-ylspiro[1,3,3a,4,5,6,7,7a-octahydroisoindol-2-ium-2,1'-1,4-diazinan-1-ium] Chemical compound C1=CC=C2C(N3CC[N+]4(CC3)CC3CCCCC3C4)=CC=CC2=C1 WNUSZPVTPWMFIV-UHFFFAOYSA-N 0.000 description 1
- KQABHRHRXCAIKK-UHFFFAOYSA-N 4'-quinolin-8-ylspiro[1,3,3a,4,5,6,7,7a-octahydroisoindol-2-ium-2,1'-1,4-diazinan-1-ium] Chemical compound C1=CN=C2C(N3CC[N+]4(CC3)CC3CCCCC3C4)=CC=CC2=C1 KQABHRHRXCAIKK-UHFFFAOYSA-N 0.000 description 1
- YUJCWMGBRDBPDL-UHFFFAOYSA-N 4,4-dimethylpiperidine-2,6-dione Chemical compound CC1(C)CC(=O)NC(=O)C1 YUJCWMGBRDBPDL-UHFFFAOYSA-N 0.000 description 1
- DVVDZCQWTCVCFD-UHFFFAOYSA-N 4,5-bis(bromomethyl)cyclohexene Chemical compound BrCC1CC=CCC1CBr DVVDZCQWTCVCFD-UHFFFAOYSA-N 0.000 description 1
- AFYALJSDFPSAAZ-UHFFFAOYSA-N 4-(4-fluorophenyl)piperidine Chemical compound C1=CC(F)=CC=C1C1CCNCC1 AFYALJSDFPSAAZ-UHFFFAOYSA-N 0.000 description 1
- OZONPSQNTUHWGJ-UHFFFAOYSA-N 4-(4-fluorophenyl)sulfanylpiperidine Chemical compound C1=CC(F)=CC=C1SC1CCNCC1 OZONPSQNTUHWGJ-UHFFFAOYSA-N 0.000 description 1
- JTJAFXFVXLEYQT-UHFFFAOYSA-N 4-[4-(4-phenylpiperazin-1-yl)butyl]-4-azatricyclo[5.2.1.02,6]decane-3,5-dione Chemical compound O=C1C2C(C3)CCC3C2C(=O)N1CCCCN(CC1)CCN1C1=CC=CC=C1 JTJAFXFVXLEYQT-UHFFFAOYSA-N 0.000 description 1
- KNNQGZBGAQFPCY-UHFFFAOYSA-N 4-[bis(4-fluorophenyl)methylidene]piperidine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)=C1CCNCC1 KNNQGZBGAQFPCY-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- CGSWRHKBLLDUHO-UHFFFAOYSA-N 4-piperazin-1-ylquinoline Chemical compound C1CNCCN1C1=CC=NC2=CC=CC=C12 CGSWRHKBLLDUHO-UHFFFAOYSA-N 0.000 description 1
- GGRZCCWFABLKCX-UHFFFAOYSA-N 5-fluoro-3-piperidin-4-yl-1,2-benzoxazole Chemical compound C12=CC(F)=CC=C2ON=C1C1CCNCC1 GGRZCCWFABLKCX-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- DCUZDOXGNVJQQL-UHFFFAOYSA-N 8-piperazin-1-ylquinoline Chemical compound C1CNCCN1C1=CC=CC2=CC=CN=C12 DCUZDOXGNVJQQL-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- LENAGFDTLKPUEP-UHFFFAOYSA-N C1=C2OC=CC2=CC(N2CCN(CC2)CC2CCCCC2CN2C(=O)C3C4CCC(C4)C3C2=O)=C1 Chemical compound C1=C2OC=CC2=CC(N2CCN(CC2)CC2CCCCC2CN2C(=O)C3C4CCC(C4)C3C2=O)=C1 LENAGFDTLKPUEP-UHFFFAOYSA-N 0.000 description 1
- XCJPWESGFBNLJW-UHFFFAOYSA-N C1=CC(F)=CC=C1OC1CCN(CC2C(CCCC2)CN2C(C3C4CCC(C4)C3C2=O)=O)CC1 Chemical compound C1=CC(F)=CC=C1OC1CCN(CC2C(CCCC2)CN2C(C3C4CCC(C4)C3C2=O)=O)CC1 XCJPWESGFBNLJW-UHFFFAOYSA-N 0.000 description 1
- KTRSBLRKQBZDGV-UHFFFAOYSA-N C1=CC(F)=CC=C1SC1CCN(CC2C(CCCC2)CN2C(C3C4CCC(C4)C3C2=O)=O)CC1 Chemical compound C1=CC(F)=CC=C1SC1CCN(CC2C(CCCC2)CN2C(C3C4CCC(C4)C3C2=O)=O)CC1 KTRSBLRKQBZDGV-UHFFFAOYSA-N 0.000 description 1
- VONMXAXGNGYKPP-UHFFFAOYSA-N C1=CC=C2C(C3CCN(CC3)CC3CCCCC3CN3C(=O)C4C5CCC(C5)C4C3=O)=NOC2=C1 Chemical compound C1=CC=C2C(C3CCN(CC3)CC3CCCCC3CN3C(=O)C4C5CCC(C5)C4C3=O)=NOC2=C1 VONMXAXGNGYKPP-UHFFFAOYSA-N 0.000 description 1
- WKZXRDCHUAEPEL-UHFFFAOYSA-N C1=CC=C2C(N3CCN(CC3)CC3CCCCC3CN3C(=O)C4C(C5CCC4C=C5)C3=O)=NSC2=C1 Chemical compound C1=CC=C2C(N3CCN(CC3)CC3CCCCC3CN3C(=O)C4C(C5CCC4C=C5)C3=O)=NSC2=C1 WKZXRDCHUAEPEL-UHFFFAOYSA-N 0.000 description 1
- JPVVKPNPQOUZMP-UHFFFAOYSA-N C1=CC=C2C(N3CCN(CC3)CC3CCCCC3CN3C(=O)C4C(C5CCC4CC5)C3=O)=NSC2=C1 Chemical compound C1=CC=C2C(N3CCN(CC3)CC3CCCCC3CN3C(=O)C4C(C5CCC4CC5)C3=O)=NSC2=C1 JPVVKPNPQOUZMP-UHFFFAOYSA-N 0.000 description 1
- YOROGQBABBFSKT-UHFFFAOYSA-N C1=CC=C2C=NC(N3CCN(CC3)CC3CCCCC3CN3C(=O)C4C5CCC(C5)C4C3=O)=CC2=C1 Chemical compound C1=CC=C2C=NC(N3CCN(CC3)CC3CCCCC3CN3C(=O)C4C5CCC(C5)C4C3=O)=CC2=C1 YOROGQBABBFSKT-UHFFFAOYSA-N 0.000 description 1
- PZMVCMMRTNSERU-UHFFFAOYSA-N COC1=CC=CC=C1N1CCN(CC2C(CCCC2)CN2C(C3C4CCC(C4)C3C2=O)=O)CC1 Chemical compound COC1=CC=CC=C1N1CCN(CC2C(CCCC2)CN2C(C3C4CCC(C4)C3C2=O)=O)CC1 PZMVCMMRTNSERU-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- ZOYDOOFPPXKVMK-UHFFFAOYSA-N ClC1=CC=CC(N2CCN(CC3C(CCCC3)CN3C(C4C5CCC(C5)C4C3=O)=O)CC2)=C1 Chemical compound ClC1=CC=CC(N2CCN(CC3C(CCCC3)CN3C(C4C5CCC(C5)C4C3=O)=O)CC2)=C1 ZOYDOOFPPXKVMK-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 241000283986 Lepus Species 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- DMADELJYOZEJCQ-UHFFFAOYSA-N O=C1C2C(C3)CCC3C2C(=O)N1CC1CCCCC1CN(CC1)CCN1C1=CC=CC2=C1OC=C2 Chemical compound O=C1C2C(C3)CCC3C2C(=O)N1CC1CCCCC1CN(CC1)CCN1C1=CC=CC2=C1OC=C2 DMADELJYOZEJCQ-UHFFFAOYSA-N 0.000 description 1
- HYMWWRVZGXFNNY-UHFFFAOYSA-N O=C1C2C(C3)CCC3C2C(=O)N1CC1CCCCC1CN(CC1)CCN1C1=CC=CC=N1 Chemical compound O=C1C2C(C3)CCC3C2C(=O)N1CC1CCCCC1CN(CC1)CCN1C1=CC=CC=N1 HYMWWRVZGXFNNY-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- JIHKCHWEXXZTOU-UHFFFAOYSA-N [2-(methylsulfonyloxymethyl)cyclohexyl]methyl methanesulfonate Chemical compound CS(=O)(=O)OCC1CCCCC1COS(C)(=O)=O JIHKCHWEXXZTOU-UHFFFAOYSA-N 0.000 description 1
- RPVVUZPLCARFKW-UHFFFAOYSA-N [2-(methylsulfonyloxymethyl)cyclopentyl]methyl methanesulfonate Chemical compound CS(=O)(=O)OCC1CCCC1COS(C)(=O)=O RPVVUZPLCARFKW-UHFFFAOYSA-N 0.000 description 1
- HZSKYVAPSHVKKF-UHFFFAOYSA-N [3-(methylsulfonyloxymethyl)-2-bicyclo[2.2.1]heptanyl]methyl methanesulfonate Chemical compound C1CC2C(COS(=O)(=O)C)C(COS(C)(=O)=O)C1C2 HZSKYVAPSHVKKF-UHFFFAOYSA-N 0.000 description 1
- 229940022663 acetate Drugs 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- YRTHJMQKDCXPAY-UHFFFAOYSA-N azaspirodecanedione Chemical compound C1C(=O)NC(=O)CC11CCCC1 YRTHJMQKDCXPAY-UHFFFAOYSA-N 0.000 description 1
- OSNDUYDDOHEKEE-UHFFFAOYSA-N azepane-2,7-dione Chemical compound O=C1CCCCC(=O)N1 OSNDUYDDOHEKEE-UHFFFAOYSA-N 0.000 description 1
- 208000028683 bipolar I disease Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 150000001925 cycloalkenes Chemical class 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- ZXIJMRYMVAMXQP-UHFFFAOYSA-N cycloheptene Chemical compound C1CCC=CCC1 ZXIJMRYMVAMXQP-UHFFFAOYSA-N 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229940049920 malate Drugs 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
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 1
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229940039748 oxalate Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 1
- 229940085991 phosphate ion Drugs 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- KNCYXPMJDCCGSJ-UHFFFAOYSA-N piperidine-2,6-dione Chemical compound O=C1CCCC(=O)N1 KNCYXPMJDCCGSJ-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- GZRKXKUVVPSREJ-UHFFFAOYSA-N pyridinylpiperazine Chemical compound C1CNCCN1C1=CC=CC=N1 GZRKXKUVVPSREJ-UHFFFAOYSA-N 0.000 description 1
- 125000005554 pyridyloxy group Chemical group 0.000 description 1
- 125000005030 pyridylthio group Chemical group N1=C(C=CC=C1)S* 0.000 description 1
- XRXDAJYKGWNHTQ-UHFFFAOYSA-N quipazine Chemical compound C1CNCCN1C1=CC=C(C=CC=C2)C2=N1 XRXDAJYKGWNHTQ-UHFFFAOYSA-N 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- XCFVUJRNGIESJC-UHFFFAOYSA-N spiro[bicyclo[2.2.2]octane-3,3'-pyrrolidine]-2',5'-dione Chemical compound O=C1NC(=O)CC11C(CC2)CCC2C1 XCFVUJRNGIESJC-UHFFFAOYSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- BGRJTUBHPOOWDU-UHFFFAOYSA-N sulpiride Chemical compound CCN1CCCC1CNC(=O)C1=CC(S(N)(=O)=O)=CC=C1OC BGRJTUBHPOOWDU-UHFFFAOYSA-N 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- C07D417/04—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 directly linked by a ring-member-to-ring-member bond
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US32780910P | 2010-04-26 | 2010-04-26 | |
| PCT/JP2011/060570 WO2011136383A1 (en) | 2010-04-26 | 2011-04-25 | A process of a quaternary ammonium salt |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2563790T3 true DK2563790T3 (en) | 2016-10-24 |
Family
ID=44816340
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK11775164.4T DK2563790T3 (en) | 2010-04-26 | 2011-04-25 | PROCESS FOR quaternary ammonium salt |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US8921551B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP2563790B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP5820821B2 (cg-RX-API-DMAC7.html) |
| DK (1) | DK2563790T3 (cg-RX-API-DMAC7.html) |
| ES (1) | ES2594709T3 (cg-RX-API-DMAC7.html) |
| HU (1) | HUE030294T2 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2011136383A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5820822B2 (ja) | 2010-04-26 | 2015-11-24 | 大日本住友製薬株式会社 | リン酸塩を用いる第四級アンモニウム塩の製造法 |
| WO2013121440A1 (en) | 2012-02-13 | 2013-08-22 | Cadila Healthcare Limited | Process for preparing benzisothiazol-3-yl-peperazin-l-yl-methyl-cyclo hexyl-methanisoindol-1,3-dione and its intermediates |
| CN103450172A (zh) * | 2012-05-30 | 2013-12-18 | 广州药源生物医药科技有限公司 | 一种抗精神病药物鲁拉西酮的制备方法 |
| CN102863437A (zh) * | 2012-09-04 | 2013-01-09 | 济南百诺医药科技开发有限公司 | 一种鲁拉西酮的制备方法 |
| CN102827157A (zh) * | 2012-09-20 | 2012-12-19 | 北京哈三联科技股份有限公司 | 一种制备鲁拉西酮的方法 |
| CN102936243B (zh) * | 2012-11-16 | 2015-08-05 | 上海伯倚化工科技有限公司 | 一种鲁拉西酮的合成方法 |
| CN103864774B (zh) * | 2012-12-14 | 2016-09-28 | 成都弘达药业有限公司 | 一种鲁拉西酮的制备方法 |
| ITMI20130262A1 (it) * | 2013-02-22 | 2014-08-23 | Edmond Pharma Srl | Procedimento per la preparazione di lurasidone cloridrato |
| ITMI20131737A1 (it) | 2013-10-17 | 2015-04-18 | Procos Spa | Processo per la sintesi industriale di lurasidone |
| JP6594351B2 (ja) | 2014-06-16 | 2019-10-23 | ジョンソン、マッセイ、パブリック、リミテッド、カンパニー | 新規中間体を含むアルキル化アリールピペラジン及びアルキル化アリールピペリジン化合物の製造方法 |
| WO2016059649A1 (en) * | 2014-10-14 | 2016-04-21 | Jubilant Generics Limited (Formerly Jubilant Life Sciences Division) | An improved process for the preparation of lurasidone hydrochloride |
| WO2016110798A1 (en) | 2015-01-08 | 2016-07-14 | Piramal Enterprises Limited | An improved process for the preparation of lurasidone and its intermediate |
| CN106146486A (zh) * | 2015-04-21 | 2016-11-23 | 上海医药集团股份有限公司 | 一种制备高纯度高收率鲁拉西酮的方法 |
| CN106946872A (zh) * | 2017-03-20 | 2017-07-14 | 常州工程职业技术学院 | 一种制备鲁拉西酮关键中间体的方法 |
| CN107936007B (zh) * | 2017-11-28 | 2021-05-25 | 常州寅盛药业有限公司 | 一种盐酸鲁拉西酮的合成方法 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4351939A (en) * | 1980-10-16 | 1982-09-28 | Mead Johnson & Company | Spiro-quaternary ammonium halides and N-(2-pyrimidinyl)piperazinylalkylazaspiroalkanedione process |
| JP2800953B2 (ja) | 1990-07-06 | 1998-09-21 | 住友製薬株式会社 | 新規なイミド誘導体 |
| JP3775823B2 (ja) * | 1995-06-09 | 2006-05-17 | 大日本住友製薬株式会社 | 新規なイミド誘導体 |
| JP4175800B2 (ja) * | 2001-11-27 | 2008-11-05 | 住友化学株式会社 | イミド誘導体の製造方法 |
| CA2538265C (en) | 2003-07-29 | 2012-10-02 | Dainippon Sumitomo Pharma Co., Ltd. | Process for producing imide compound |
| JP4708012B2 (ja) * | 2004-12-15 | 2011-06-22 | 大日本住友製薬株式会社 | 第四級アンモニウム塩の製造法 |
| JP2006169154A (ja) * | 2004-12-15 | 2006-06-29 | Sumitomo Chemical Co Ltd | 第四級アンモニウム塩の製造方法 |
| WO2007027649A1 (en) | 2005-08-30 | 2007-03-08 | Honeywell International Inc. | Method for synthesizing spiro quaternary ammonium systems |
| US20110003994A1 (en) * | 2009-07-02 | 2011-01-06 | Dainippon Sumitomo Pharma Co., Ltd. | Cycloalkane derivative |
| JP5820822B2 (ja) * | 2010-04-26 | 2015-11-24 | 大日本住友製薬株式会社 | リン酸塩を用いる第四級アンモニウム塩の製造法 |
-
2011
- 2011-04-25 WO PCT/JP2011/060570 patent/WO2011136383A1/en not_active Ceased
- 2011-04-25 ES ES11775164.4T patent/ES2594709T3/es active Active
- 2011-04-25 HU HUE11775164A patent/HUE030294T2/en unknown
- 2011-04-25 JP JP2012549043A patent/JP5820821B2/ja active Active
- 2011-04-25 DK DK11775164.4T patent/DK2563790T3/en active
- 2011-04-25 EP EP11775164.4A patent/EP2563790B1/en active Active
- 2011-04-26 US US13/093,927 patent/US8921551B2/en active Active
-
2014
- 2014-11-07 US US14/536,118 patent/US9309255B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| US20150087830A1 (en) | 2015-03-26 |
| US9309255B2 (en) | 2016-04-12 |
| US20110263847A1 (en) | 2011-10-27 |
| JP2013525264A (ja) | 2013-06-20 |
| WO2011136383A1 (en) | 2011-11-03 |
| EP2563790B1 (en) | 2016-09-14 |
| EP2563790A4 (en) | 2014-02-19 |
| EP2563790A1 (en) | 2013-03-06 |
| US8921551B2 (en) | 2014-12-30 |
| HUE030294T2 (en) | 2017-04-28 |
| JP5820821B2 (ja) | 2015-11-24 |
| ES2594709T3 (es) | 2016-12-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK2563790T3 (en) | PROCESS FOR quaternary ammonium salt | |
| EP2563791B1 (en) | A process of a quaternary ammonium salt using phosphate | |
| JP4175800B2 (ja) | イミド誘導体の製造方法 | |
| JP4708012B2 (ja) | 第四級アンモニウム塩の製造法 | |
| JP2006169154A (ja) | 第四級アンモニウム塩の製造方法 | |
| US20140256939A1 (en) | Process of preparing a quaternary ammonium salt using phosphate | |
| AU2011336871B2 (en) | Processes for the preparation of enamines | |
| KR101558015B1 (ko) | 키랄 α,β-에폭시 케톤의 제조 방법 | |
| JP7011242B2 (ja) | ハロゲンコーティングメタセシス触媒及びその方法 | |
| WO2014075648A1 (en) | A method of preparing apixaban | |
| RU2310654C1 (ru) | Способ получения производного 1,8-нафтиридин-3-карбоновой кислоты | |
| CN105636938A (zh) | 制备3-烷硫基-2-溴吡啶的方法 | |
| AU2011336873B2 (en) | Processes for the preparation of enamines | |
| Sosnovskikh et al. | Structure of reaction products of 3-cyanochromones with ethylenediamine | |
| JP2013543841A5 (cg-RX-API-DMAC7.html) | ||
| WO2024249252A1 (en) | Methods of using apol1 inhibitors | |
| TWI545120B (zh) | ３，４－二氫異喹啉衍生物之製造方法及此等衍生物之製造中間體 | |
| Kończyk et al. | Efficient One‐Pot Synthesis of a Densely Functionalized Tetrahydropyridine in the Presence of [1, 1′‐Binaphthalene]‐2, 2′‐diol/Indium (III) Chloride (binol/InCl3) or Simple Brønsted Acids as Catalysts | |
| Aly et al. | Stereospecific non-decarboxylative 1, 3-dipolar cycloaddition as a potential route to proline derivatives, part III. | |
| JPH09216886A (ja) | トリアゾロピリダジン誘導体の製造法 | |
| HK1033128B (en) | Benzo[c]quinolizine derivatives and their use as 5 alpha-reductases inhibitors |