FI111162B - Förfarande för framställning av N-metyl-3-(1-metyl-4-piperidinyl)-14-indol-5-etansulfonamid - Google Patents
Förfarande för framställning av N-metyl-3-(1-metyl-4-piperidinyl)-14-indol-5-etansulfonamid Download PDFInfo
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- FI111162B FI111162B FI961378A FI961378A FI111162B FI 111162 B FI111162 B FI 111162B FI 961378 A FI961378 A FI 961378A FI 961378 A FI961378 A FI 961378A FI 111162 B FI111162 B FI 111162B
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- Prior art keywords
- formula
- methyl
- compound
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- 238000000034 method Methods 0.000 title claims description 25
- 238000002360 preparation method Methods 0.000 title claims description 9
- -1 1-methyl-4-piperidinyl Chemical group 0.000 title description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 98
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 72
- 150000001875 compounds Chemical class 0.000 claims description 62
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 53
- 239000000203 mixture Substances 0.000 claims description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 14
- 239000003054 catalyst Substances 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- 229910052763 palladium Inorganic materials 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 229910003445 palladium oxide Inorganic materials 0.000 claims description 7
- JQPTYAILLJKUCY-UHFFFAOYSA-N palladium(ii) oxide Chemical compound [O-2].[Pd+2] JQPTYAILLJKUCY-UHFFFAOYSA-N 0.000 claims description 7
- 238000011946 reduction process Methods 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 6
- 150000001408 amides Chemical class 0.000 claims description 5
- 229910000510 noble metal Inorganic materials 0.000 claims description 5
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 230000002829 reductive effect Effects 0.000 claims description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical group COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- 235000019253 formic acid Nutrition 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 239000002815 homogeneous catalyst Substances 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 239000000852 hydrogen donor Substances 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- 239000007868 Raney catalyst Substances 0.000 claims description 2
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 230000003197 catalytic effect Effects 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 230000001035 methylating effect Effects 0.000 claims description 2
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 claims description 2
- 229910052697 platinum Inorganic materials 0.000 claims description 2
- 229910003446 platinum oxide Inorganic materials 0.000 claims description 2
- QBERHIJABFXGRZ-UHFFFAOYSA-M rhodium;triphenylphosphane;chloride Chemical group [Cl-].[Rh].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 QBERHIJABFXGRZ-UHFFFAOYSA-M 0.000 claims description 2
- OXUVAWYNYBDHFN-UHFFFAOYSA-N n-methyl-2-[3-(1-methyl-3,6-dihydro-2h-pyridin-4-yl)-1h-indol-5-yl]ethenesulfonamide Chemical compound C12=CC(C=CS(=O)(=O)NC)=CC=C2NC=C1C1=CCN(C)CC1 OXUVAWYNYBDHFN-UHFFFAOYSA-N 0.000 claims 1
- 229910052703 rhodium Inorganic materials 0.000 claims 1
- 239000010948 rhodium Substances 0.000 claims 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
- 239000000706 filtrate Substances 0.000 description 20
- 239000000725 suspension Substances 0.000 description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 19
- 239000000543 intermediate Substances 0.000 description 17
- 239000012065 filter cake Substances 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- 239000000047 product Substances 0.000 description 14
- 239000002585 base Substances 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 10
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 10
- JOXWSDNHLSQKCC-UHFFFAOYSA-N ethenesulfonamide Chemical compound NS(=O)(=O)C=C JOXWSDNHLSQKCC-UHFFFAOYSA-N 0.000 description 9
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 8
- QSPPRYLTQFCUCH-UHFFFAOYSA-N n-methylethanesulfonamide Chemical compound CCS(=O)(=O)NC QSPPRYLTQFCUCH-UHFFFAOYSA-N 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 229940124530 sulfonamide Drugs 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- AMKVXSZCKVJAGH-UHFFFAOYSA-N naratriptan Chemical compound C12=CC(CCS(=O)(=O)NC)=CC=C2NC=C1C1CCN(C)CC1 AMKVXSZCKVJAGH-UHFFFAOYSA-N 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- VXWVFZFZYXOBTA-UHFFFAOYSA-N 5-bromo-1h-indole Chemical compound BrC1=CC=C2NC=CC2=C1 VXWVFZFZYXOBTA-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 238000007069 methylation reaction Methods 0.000 description 4
- HUUPVABNAQUEJW-UHFFFAOYSA-N 1-methylpiperidin-4-one Chemical compound CN1CCC(=O)CC1 HUUPVABNAQUEJW-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 230000011987 methylation Effects 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 150000002940 palladium Chemical class 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 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 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 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 2
- 239000012429 reaction media Substances 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 150000003456 sulfonamides Chemical class 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 description 1
- OXUVAWYNYBDHFN-JXMROGBWSA-N (e)-n-methyl-2-[3-(1-methyl-3,6-dihydro-2h-pyridin-4-yl)-1h-indol-5-yl]ethenesulfonamide Chemical compound C12=CC(/C=C/S(=O)(=O)NC)=CC=C2NC=C1C1=CCN(C)CC1 OXUVAWYNYBDHFN-JXMROGBWSA-N 0.000 description 1
- VLEXLKUZOJOXOJ-UHFFFAOYSA-N 2-[3-(1-methyl-3,6-dihydro-2h-pyridin-4-yl)-1h-indol-5-yl]ethanesulfonamide Chemical class C1N(C)CCC(C=2C3=CC(CCS(N)(=O)=O)=CC=C3NC=2)=C1 VLEXLKUZOJOXOJ-UHFFFAOYSA-N 0.000 description 1
- VKXJACAFAISRGF-UHFFFAOYSA-N 4-(5-bromo-1h-indol-3-yl)-1-methylpiperidin-4-ol Chemical compound C1CN(C)CCC1(O)C1=CNC2=CC=C(Br)C=C12 VKXJACAFAISRGF-UHFFFAOYSA-N 0.000 description 1
- IRJNNZSKGXPISD-UHFFFAOYSA-N 5-bromo-3-(1-methyl-3,6-dihydro-2h-pyridin-4-yl)-1h-indole Chemical compound C1N(C)CCC(C=2C3=CC(Br)=CC=C3NC=2)=C1 IRJNNZSKGXPISD-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- CVSVTCORWBXHQV-UHFFFAOYSA-N anhydrous creatine Natural products NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 229960003624 creatine Drugs 0.000 description 1
- 239000006046 creatine Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 150000001993 dienes Chemical class 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- ZCRZCMUDOWDGOB-UHFFFAOYSA-N ethanesulfonimidic acid Chemical compound CCS(N)(=O)=O ZCRZCMUDOWDGOB-UHFFFAOYSA-N 0.000 description 1
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 description 1
- 229910002094 inorganic tetrachloropalladate Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000003446 ligand Substances 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
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000015096 spirit Nutrition 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Claims (15)
1. Förfarande för framställning av en förening med formeln I, ΛιΛ CHNHSO.CHCH.v^^ XXj H 5 eller ett sait därav, kännetecknat av, att man reducerar en förening med formeln (II) C^NHSO^CH^ ^ A J (,,) H eller ett sait därav. 10
2. Förfarande enligt patentkrav 1, känneteck nat av, att reduceringsprocessen utförs i närvaro av väte och en ädelmetallkatalysator.
3. Förfarande enligt patentkrav 1, kännetecknat av, att ädelmetallkatalysatorn är palladium, palla- 15 diumoxid, Raney nickel, platina, platinaoxid eller rodium, som valfritt har koi som bärare.
4. Förfarande enligt patentkrav 3, kännetecknat av, att ädelmetallkatalysatorn är palladiumoxid pä koi. 20
5. Förfarande enligt patentkrav 4, känneteck nat av, att ädelmetallkatalysatorn är 10-%:ig palladiumoxid pä koi. 111162
6. Förfarande enligt patentkrav 5, känneteck-n a t av, att palladiumoxid sätts tili reaktionskärlet i form av vät pasta.
7. Förfarande enligt patentkrav 1, känneteck-5 n a t av, att reduceringsprocessen utförs i närvaro av väte och en homogen katalysator.
8. Förfarande enligt patentkrav 7, känneteck- n a t av, att den homogena katalysatorn är tris(tri- fenylfosfin)rodiumklorid. 10
9. Förfarande enligt nägot av de föregaende pa- tentkraven, kännetecknat av, att reduceringsprocessen utförs i ett lösningsmedel, som innehäller vat-ten eller alkohol, eter, ester eller amid eller en bland-ning av dessa. 15 10. Förfarande enligt patentkrav 9, känne tecknat av, att lösningsmedlet är vatten, metanol, etanol, dioxan, etylacetat, dimetylformamid eller en blandning av dessa.
11. Förfarande enligt nägot av de föregaende pat- 2. entkraven, kännetecknat av, att reduceringsprocessen utförs vid en temperatur av 10 - 50 °C.
12. Förfarande enligt patentkrav 1, kännetecknat av, att reduceringsprocessen utförs vid betingelser för katalytisk överföring av väte. 25 13. Förfarande enligt patentkrav 12, känne tecknat av, att reduceringsprocessen utförs under användning av palladium i närvaro av en vätedonor.
14. Förfarande enligt patentkrav 13, kännetecknat av, att vätedonorn är myrsyra eller ett 30 sait därav.
15. N-metyl-2-[3-(1,2,3,6-tetrahydro-l-metyl-4-metyl- 4-pyridinyl)-lH-indol-5-yl]etensulfonamid och salter därav.
16. Förfarande för framställning av N-metyl-2-[3-(1,2,3,6-tetrahydro-l-metyl-4-pyridinyl)-lH-indol-5-yl]eten- 35 sulfonamid och salter därav, kännetecknat av, att man ' I I 10/ (A) kondenserar en förening med formeln (III) rV^CH3 >k J (HI) χχτ*' H eller ett salt därav, där R1 är en hydroxigrupp och R2 är väte eller R1och R2 tillsammans bildar en dubbelbindning, 5 X är en avgäende grupp, sasorn en halogenatom, till exempel en bromatom, eller en avgäende grupp, till exempel en tri-flatgrupp (CF3S03) , med en N-metylvinylsulfonamid, som har formeln (IV)
10 CH2=CHS02NZCH3 (IV) där Z är väte eller en aminoskyddsgrupp, och val-fritt, om sä behövs eller önskas, avlägsnar skyddet frän det sä erhällna skyddade derivatet; 15 (B) metylerar en förening med formeln (VII) c^nhsq2ch=ch^^ m XXX H (C) kondenserar en förening med formeln (X), JO LSC^CH^CH^ (X) 20 2 H 111162 där L är en lämplig avgäende grupp, med metylamin; (D) avlägsnar vatten frän en förening med formeln (XII) p* /v84 CHjNHSO^CH^^ J XXji ” j H 5. närvaro av en syra eller en bas; (E) omsätter en förening, som har formeln (VIII) C^N~tSO,CH=C|-k H med en förening, som har formeln (VI); 10 eller (F) avlägsnar vatten frän en förening med formeln (XVI) r^^NMe H° j WeNHSO?^ ^ XXf N H (XVI)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB939320115A GB9320115D0 (en) | 1993-09-29 | 1993-09-29 | Process |
| GB9320115 | 1993-09-29 | ||
| EP9403216 | 1994-09-27 | ||
| PCT/EP1994/003216 WO1995009166A1 (en) | 1993-09-29 | 1994-09-27 | Process for the preparation of n-methyl-3-(1-methyl-4-piperidinyl)-14-indole-5-ethanesulphonamide |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI961378A FI961378A (sv) | 1996-03-26 |
| FI961378A0 FI961378A0 (sv) | 1996-03-26 |
| FI111162B true FI111162B (sv) | 2003-06-13 |
Family
ID=10742727
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI961378A FI111162B (sv) | 1993-09-29 | 1996-03-26 | Förfarande för framställning av N-metyl-3-(1-metyl-4-piperidinyl)-14-indol-5-etansulfonamid |
Country Status (32)
| Country | Link |
|---|---|
| US (2) | US5659040A (sv) |
| EP (1) | EP0721453B1 (sv) |
| JP (1) | JP3411284B2 (sv) |
| CN (2) | CN1132509A (sv) |
| AP (1) | AP529A (sv) |
| AT (1) | ATE228124T1 (sv) |
| AU (1) | AU682219B2 (sv) |
| CA (1) | CA2170645C (sv) |
| CO (1) | CO4290351A1 (sv) |
| CZ (1) | CZ287581B6 (sv) |
| DE (1) | DE69431759T2 (sv) |
| DK (1) | DK0721453T3 (sv) |
| ES (1) | ES2187534T3 (sv) |
| FI (1) | FI111162B (sv) |
| GB (1) | GB9320115D0 (sv) |
| HK (1) | HK1004218A1 (sv) |
| HR (1) | HRP940613B1 (sv) |
| HU (1) | HU226828B1 (sv) |
| IL (1) | IL111071A (sv) |
| IS (1) | IS1877B (sv) |
| MY (1) | MY117934A (sv) |
| NO (1) | NO309324B1 (sv) |
| NZ (1) | NZ274159A (sv) |
| PE (1) | PE18195A1 (sv) |
| PL (1) | PL178456B1 (sv) |
| PT (1) | PT721453E (sv) |
| RU (1) | RU2143428C1 (sv) |
| SG (1) | SG49322A1 (sv) |
| SI (1) | SI0721453T1 (sv) |
| SK (1) | SK282234B6 (sv) |
| WO (1) | WO1995009166A1 (sv) |
| ZA (1) | ZA947516B (sv) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6673827B1 (en) | 1999-06-29 | 2004-01-06 | The Uab Research Foundation | Methods of treating fungal infections with inhibitors of NAD synthetase enzyme |
| US6861448B2 (en) * | 1998-01-14 | 2005-03-01 | Virtual Drug Development, Inc. | NAD synthetase inhibitors and uses thereof |
| WO1999036422A1 (en) | 1998-01-14 | 1999-07-22 | The Uab Research Foundation | Methods of synthesizing and screening inhibitors of bacterial nad synthetase enzyme, compounds thereof, and methods of treating bacterial and microbial infections with inhibitors of bacterial nad synthetase enzyme |
| WO2006010079A2 (en) * | 2004-07-08 | 2006-01-26 | Dr. Reddy's Laboratories Ltd. | Process for preparing naratriptan hydrochloride |
| WO2006010078A2 (en) * | 2004-07-08 | 2006-01-26 | Dr. Reddy's Laboratories Ltd. | Polymorphic form of naratriptan hydrochloride |
| CN1315821C (zh) * | 2004-12-16 | 2007-05-16 | 上海美通生物科技有限公司 | 制备n－甲基－3－(1－甲基－4－哌啶基)－1,4－吲哚－5－乙硫胺的改进法 |
| WO2007050381A2 (en) * | 2005-10-24 | 2007-05-03 | Janssen Pharmaceutica, N.V. | 3-piperidin-4-yl-indole orl-1 receptor modulators |
| WO2009118753A2 (en) * | 2008-03-07 | 2009-10-01 | Usv Limited | Process for preparation of naratriptan hydrochloride |
| CN101676283A (zh) * | 2008-09-17 | 2010-03-24 | 北京德众万全药物技术开发有限公司 | 一种那拉曲坦的制备方法 |
| US8735589B2 (en) | 2009-08-20 | 2014-05-27 | Cipla Limited | Process for the synthesis of naratriptan |
| CN101792411B (zh) * | 2010-03-26 | 2012-05-30 | 常州晟永光电材料有限公司 | 一种合成乙磺酰胺的方法 |
| CN103073484B (zh) * | 2013-01-28 | 2014-10-22 | 山东诚创医药技术开发有限公司 | 一种甲哌卡因及其光学对映体的制备方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8719167D0 (en) * | 1987-08-13 | 1987-09-23 | Glaxo Group Ltd | Chemical compounds |
| PT88255B (pt) * | 1987-08-13 | 1995-03-01 | Glaxo Group Ltd | Processo para a preparacao de derivados do indole |
| GB8819024D0 (en) * | 1988-08-10 | 1988-09-14 | Glaxo Group Ltd | Chemical compounds |
| GB8903036D0 (en) * | 1989-02-10 | 1989-03-30 | Glaxo Group Ltd | Chemical compounds |
-
1993
- 1993-09-29 GB GB939320115A patent/GB9320115D0/en active Pending
-
1994
- 1994-09-26 IS IS4212A patent/IS1877B/is unknown
- 1994-09-26 PE PE1994251470A patent/PE18195A1/es not_active Application Discontinuation
- 1994-09-27 EP EP94928825A patent/EP0721453B1/en not_active Expired - Lifetime
- 1994-09-27 SG SG1996009269A patent/SG49322A1/en unknown
- 1994-09-27 DE DE69431759T patent/DE69431759T2/de not_active Expired - Lifetime
- 1994-09-27 CN CN94193590A patent/CN1132509A/zh active Pending
- 1994-09-27 HR HR940613A patent/HRP940613B1/xx not_active IP Right Cessation
- 1994-09-27 ZA ZA947516A patent/ZA947516B/xx unknown
- 1994-09-27 MY MYPI94002565A patent/MY117934A/en unknown
- 1994-09-27 NZ NZ274159A patent/NZ274159A/en not_active IP Right Cessation
- 1994-09-27 US US08/600,932 patent/US5659040A/en not_active Expired - Lifetime
- 1994-09-27 CA CA002170645A patent/CA2170645C/en not_active Expired - Fee Related
- 1994-09-27 WO PCT/EP1994/003216 patent/WO1995009166A1/en active IP Right Grant
- 1994-09-27 CZ CZ1996768A patent/CZ287581B6/cs not_active IP Right Cessation
- 1994-09-27 CO CO94043932A patent/CO4290351A1/es unknown
- 1994-09-27 PL PL94313740A patent/PL178456B1/pl not_active IP Right Cessation
- 1994-09-27 DK DK94928825T patent/DK0721453T3/da active
- 1994-09-27 RU RU96108268A patent/RU2143428C1/ru not_active IP Right Cessation
- 1994-09-27 JP JP51011095A patent/JP3411284B2/ja not_active Expired - Lifetime
- 1994-09-27 SK SK406-96A patent/SK282234B6/sk not_active IP Right Cessation
- 1994-09-27 AT AT94928825T patent/ATE228124T1/de active
- 1994-09-27 AU AU78101/94A patent/AU682219B2/en not_active Expired
- 1994-09-27 HU HU9600814A patent/HU226828B1/hu not_active IP Right Cessation
- 1994-09-27 PT PT94928825T patent/PT721453E/pt unknown
- 1994-09-27 ES ES94928825T patent/ES2187534T3/es not_active Expired - Lifetime
- 1994-09-27 SI SI9430433T patent/SI0721453T1/xx unknown
- 1994-09-28 IL IL11107194A patent/IL111071A/en not_active IP Right Cessation
- 1994-09-28 AP APAP/P/1994/000676A patent/AP529A/en active
-
1996
- 1996-03-26 FI FI961378A patent/FI111162B/sv not_active IP Right Cessation
- 1996-03-28 NO NO961252A patent/NO309324B1/no not_active IP Right Cessation
-
1997
- 1997-03-19 US US08/820,833 patent/US5786473A/en not_active Expired - Lifetime
-
1998
- 1998-04-24 HK HK98103467A patent/HK1004218A1/xx not_active IP Right Cessation
-
2000
- 2000-07-12 CN CN00120229A patent/CN1332166A/zh active Pending
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Legal Events
| Date | Code | Title | Description |
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| MM | Patent lapsed |