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
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- 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
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- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (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 (enExample) |
| EP (1) | EP2563790B1 (enExample) |
| JP (1) | JP5820821B2 (enExample) |
| DK (1) | DK2563790T3 (enExample) |
| ES (1) | ES2594709T3 (enExample) |
| HU (1) | HUE030294T2 (enExample) |
| WO (1) | WO2011136383A1 (enExample) |
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 |
| US9409899B2 (en) | 2012-02-13 | 2016-08-09 | Cadila Healthcare Limited | Process for preparing benzisothiazol-3-yl-piperazin-1-yl-methyl-cyclo hexylmethanisoindol-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 |
| EP3242876A4 (en) * | 2015-01-08 | 2019-01-02 | 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 |
| BRPI0413081B8 (pt) | 2003-07-29 | 2021-05-25 | Dainippon Sumitomo Pharma Co | processo para produzir o cloridrato do composto imida |
| 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 |
| DE602006021437D1 (de) | 2005-08-30 | 2011-06-01 | Honeywell Int Inc | Verfahren zur synthese von quaternären ammonium-spirosystemen |
| 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 JP JP2012549043A patent/JP5820821B2/ja active Active
- 2011-04-25 EP EP11775164.4A patent/EP2563790B1/en active Active
- 2011-04-25 DK DK11775164.4T patent/DK2563790T3/en active
- 2011-04-25 ES ES11775164.4T patent/ES2594709T3/es active Active
- 2011-04-25 HU HUE11775164A patent/HUE030294T2/en unknown
- 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 |
|---|---|
| EP2563790A1 (en) | 2013-03-06 |
| US8921551B2 (en) | 2014-12-30 |
| US9309255B2 (en) | 2016-04-12 |
| US20110263847A1 (en) | 2011-10-27 |
| EP2563790B1 (en) | 2016-09-14 |
| US20150087830A1 (en) | 2015-03-26 |
| ES2594709T3 (es) | 2016-12-22 |
| JP5820821B2 (ja) | 2015-11-24 |
| EP2563790A4 (en) | 2014-02-19 |
| JP2013525264A (ja) | 2013-06-20 |
| HUE030294T2 (en) | 2017-04-28 |
| WO2011136383A1 (en) | 2011-11-03 |
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