NZ519079A - Process of preparing tolterodine and analogues and intermediates prepared in the process - Google Patents
Process of preparing tolterodine and analogues and intermediates prepared in the processInfo
- Publication number
- NZ519079A NZ519079A NZ519079A NZ51907900A NZ519079A NZ 519079 A NZ519079 A NZ 519079A NZ 519079 A NZ519079 A NZ 519079A NZ 51907900 A NZ51907900 A NZ 51907900A NZ 519079 A NZ519079 A NZ 519079A
- Authority
- NZ
- New Zealand
- Prior art keywords
- compound
- formula
- enantiomerically enriched
- pct
- salt
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 36
- OOGJQPCLVADCPB-HXUWFJFHSA-N tolterodine Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(C)C=2)O)=CC=CC=C1 OOGJQPCLVADCPB-HXUWFJFHSA-N 0.000 title claims abstract description 23
- 229960004045 tolterodine Drugs 0.000 title claims abstract description 20
- BDIAUFOIMFAIPU-UHFFFAOYSA-N valepotriate Natural products CC(C)CC(=O)OC1C=C(C(=COC2OC(=O)CC(C)C)COC(C)=O)C2C11CO1 BDIAUFOIMFAIPU-UHFFFAOYSA-N 0.000 title claims abstract description 20
- 239000000543 intermediate Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 87
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 9
- 239000001257 hydrogen Substances 0.000 claims abstract description 9
- -1 methoxy, hydroxy, hydroxymethyl Chemical group 0.000 claims abstract description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 8
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 7
- 150000002367 halogens Chemical class 0.000 claims abstract description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 7
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- 238000006220 Baeyer-Villiger oxidation reaction Methods 0.000 claims abstract description 6
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 5
- 230000008707 rearrangement Effects 0.000 claims abstract description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 150000001412 amines Chemical class 0.000 claims description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 claims description 6
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 6
- 150000002596 lactones Chemical class 0.000 claims description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 5
- 150000002440 hydroxy compounds Chemical class 0.000 claims description 5
- 230000002829 reductive effect Effects 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- SUHIZPDCJOQZLN-ZDUSSCGKSA-N (4s)-6-methyl-4-phenyl-3,4-dihydrochromen-2-one Chemical compound C1([C@@H]2CC(=O)OC3=CC=C(C=C32)C)=CC=CC=C1 SUHIZPDCJOQZLN-ZDUSSCGKSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 229940043279 diisopropylamine Drugs 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 238000007363 ring formation reaction Methods 0.000 claims description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 3
- JGRSOLBFAHJDTL-KNVGNIICSA-N (4s)-6-methyl-4-phenyl-3,4-dihydro-2h-chromen-2-ol Chemical compound C1([C@@H]2CC(O)OC3=CC=C(C=C32)C)=CC=CC=C1 JGRSOLBFAHJDTL-KNVGNIICSA-N 0.000 claims 2
- AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 claims 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N diisobutylaluminium hydride Substances CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 claims 1
- 238000001914 filtration Methods 0.000 claims 1
- 238000005984 hydrogenation reaction Methods 0.000 claims 1
- 239000002585 base Substances 0.000 abstract description 5
- 239000012458 free base Substances 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 5
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 229910000085 borane Inorganic materials 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000012973 diazabicyclooctane Substances 0.000 description 3
- QNXSIUBBGPHDDE-UHFFFAOYSA-N indan-1-one Chemical compound C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 3
- QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 description 2
- QVCUKHQDEZNNOC-UHFFFAOYSA-N 1,2-diazabicyclo[2.2.2]octane Chemical compound C1CC2CCN1NC2 QVCUKHQDEZNNOC-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- SUHIZPDCJOQZLN-UHFFFAOYSA-N 6-methyl-4-phenyl-3,4-dihydrochromen-2-one Chemical compound C12=CC(C)=CC=C2OC(=O)CC1C1=CC=CC=C1 SUHIZPDCJOQZLN-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- PUPAWTXNPAJCHR-UHFFFAOYSA-N oxazaborole Chemical compound O1C=CB=N1 PUPAWTXNPAJCHR-UHFFFAOYSA-N 0.000 description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000758 substrate Substances 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- WEKSEMHQTYUZNT-INIZCTEOSA-N (1s)-5-methyl-3-phenyl-1h-inden-1-ol Chemical compound C([C@H](O)C1=CC=C(C=C11)C)=C1C1=CC=CC=C1 WEKSEMHQTYUZNT-INIZCTEOSA-N 0.000 description 1
- SBTVLCPCSXMWIQ-UHFFFAOYSA-N (3,5-dimethylphenyl) carbamate Chemical compound CC1=CC(C)=CC(OC(N)=O)=C1 SBTVLCPCSXMWIQ-UHFFFAOYSA-N 0.000 description 1
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
- MZFIOCKXBSMAKY-UHFFFAOYSA-N 3-(3-phenylprop-2-enoyl)-1,3-oxazolidin-2-one Chemical compound C1COC(=O)N1C(=O)C=CC1=CC=CC=C1 MZFIOCKXBSMAKY-UHFFFAOYSA-N 0.000 description 1
- VDQMHHMZXNDCBD-UHFFFAOYSA-N 5-methyl-3-phenylinden-1-one Chemical compound C12=CC(C)=CC=C2C(=O)C=C1C1=CC=CC=C1 VDQMHHMZXNDCBD-UHFFFAOYSA-N 0.000 description 1
- JGRSOLBFAHJDTL-UHFFFAOYSA-N 6-methyl-4-phenyl-3,4-dihydro-2h-chromen-2-ol Chemical compound C12=CC(C)=CC=C2OC(O)CC1C1=CC=CC=C1 JGRSOLBFAHJDTL-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- YZDJYAKELHSKKK-UHFFFAOYSA-N COC1=CC=C(C)C=C1[Mg] Chemical compound COC1=CC=C(C)C=C1[Mg] YZDJYAKELHSKKK-UHFFFAOYSA-N 0.000 description 1
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 229910002666 PdCl2 Inorganic materials 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 150000002238 fumaric acids Chemical class 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 150000002689 maleic acids Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- BDOLXPFAFMNDOK-UHFFFAOYSA-N oxazaborolidine Chemical compound B1CCON1 BDOLXPFAFMNDOK-UHFFFAOYSA-N 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 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
- 230000002485 urinary effect Effects 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/20—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 hydrogenated in the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/46—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/46—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C215/48—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by hydroxy groups
- C07C215/54—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by hydroxy groups linked by carbon chains having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/143—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C35/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring
- C07C35/22—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring polycyclic, at least one hydroxy group bound to a condensed ring system
- C07C35/23—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring polycyclic, at least one hydroxy group bound to a condensed ring system with hydroxy on a condensed ring system having two rings
- C07C35/32—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring polycyclic, at least one hydroxy group bound to a condensed ring system with hydroxy on a condensed ring system having two rings the condensed ring system being a (4.3.0) system, e.g. indenols
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/511—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of singly bound oxygen functional groups to >C = O groups
- C07C45/512—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of singly bound oxygen functional groups to >C = O groups the singly bound functional group being a free hydroxyl group
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/65—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
- C07C45/74—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups combined with dehydration
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
- C07C49/82—Ketones containing a keto group bound to a six-membered aromatic ring containing hydroxy groups
- C07C49/835—Ketones containing a keto group bound to a six-membered aromatic ring containing hydroxy groups having unsaturation outside an aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Urology & Nephrology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrane Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9904850A SE9904850D0 (sv) | 1999-12-30 | 1999-12-30 | Novel process and intermediates |
| PCT/SE2000/002662 WO2001049649A1 (en) | 1999-12-30 | 2000-12-22 | Process of preparing tolterodine and analogues there of as well as intermediates prepared in the process |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ519079A true NZ519079A (en) | 2004-02-27 |
Family
ID=20418365
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ519079A NZ519079A (en) | 1999-12-30 | 2000-12-22 | Process of preparing tolterodine and analogues and intermediates prepared in the process |
Country Status (29)
| Country | Link |
|---|---|
| US (1) | US6310248B2 (enExample) |
| EP (2) | EP1496045A3 (enExample) |
| JP (1) | JP2003519207A (enExample) |
| KR (1) | KR20020062669A (enExample) |
| CN (1) | CN1209342C (enExample) |
| AR (1) | AR027138A1 (enExample) |
| AT (1) | ATE282019T1 (enExample) |
| AU (1) | AU782796B2 (enExample) |
| BR (1) | BR0016785A (enExample) |
| CA (1) | CA2392832A1 (enExample) |
| CZ (1) | CZ20022255A3 (enExample) |
| DE (1) | DE60015799T2 (enExample) |
| DK (1) | DK1242361T3 (enExample) |
| EE (1) | EE200200325A (enExample) |
| ES (1) | ES2228658T3 (enExample) |
| HU (1) | HUP0203816A3 (enExample) |
| IL (1) | IL150275A0 (enExample) |
| MX (1) | MXPA02006415A (enExample) |
| MY (1) | MY118906A (enExample) |
| NO (1) | NO20023189L (enExample) |
| NZ (1) | NZ519079A (enExample) |
| PE (1) | PE20011123A1 (enExample) |
| PL (1) | PL355947A1 (enExample) |
| PT (1) | PT1242361E (enExample) |
| SE (1) | SE9904850D0 (enExample) |
| SK (1) | SK9392002A3 (enExample) |
| TW (1) | TWI225476B (enExample) |
| WO (1) | WO2001049649A1 (enExample) |
| ZA (1) | ZA200204066B (enExample) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0957073A1 (en) * | 1998-05-12 | 1999-11-17 | Schwarz Pharma Ag | Novel derivatives of 3,3-diphenylpropylamines |
| US6703504B2 (en) | 2002-02-11 | 2004-03-09 | Clarke Slemon | Conformationally constrained compounds as dendrimer cores |
| WO2003064501A1 (en) * | 2002-01-31 | 2003-08-07 | Clarke Slemon | Conformationally restricted compounds as dendrimer cores |
| EP1424079A1 (en) * | 2002-11-27 | 2004-06-02 | Boehringer Ingelheim International GmbH | Combination of a beta-3-receptor agonist and of a reuptake inhibitor of serotonin and/or norepinephrine |
| DE10315917A1 (de) * | 2003-04-08 | 2004-11-18 | Schwarz Pharma Ag | Hochreine Basen von 3,3-Diphenylpropylaminmonoestern |
| ITMI20031354A1 (it) * | 2003-07-02 | 2005-01-03 | Istituto Di Chimica Biomolecolare D El Cnr Sezione | Sintesis enantioselettiva di composti enantiomericamente arricchiti. |
| ES2235648B1 (es) * | 2003-12-22 | 2006-11-01 | Ragactives, S.L. | Procedimiento para la obtencion de tolterodina. |
| ITMI20040616A1 (it) * | 2004-03-30 | 2004-06-30 | Dinamite Dipharma S P A In For | Processo per la preparazione di tolterodina e suoi intermedi |
| EP1629834A1 (en) | 2004-08-27 | 2006-03-01 | KRKA, D.D., Novo Mesto | Sustained release pharmaceutical composition of tolterodine |
| ITMI20041920A1 (it) * | 2004-10-11 | 2005-01-11 | Chemi Spa | Processo per la preparazione di n, n-diisopropil-3-2-idrossi-5-metilfenil-3-fenil-propabammina |
| JP4513535B2 (ja) * | 2004-12-03 | 2010-07-28 | 住友化学株式会社 | トルテロジンの製造方法 |
| US20080045602A1 (en) * | 2004-12-24 | 2008-02-21 | Casar Renata T | Process for Preparation of 3-(2-Hydroxy-5Methylphenyl)-N, N-Disopropyl-3-Phenylpropylamine |
| US7528267B2 (en) * | 2005-08-01 | 2009-05-05 | Girindus America, Inc. | Method for enantioselective hydrogenation of chromenes |
| ES2268987B1 (es) | 2005-08-05 | 2008-02-01 | Ragactives, S.L. | Procedimiento para la obtencion de 3,3-difenilpropilaminas. |
| KR100647068B1 (ko) | 2005-09-15 | 2006-11-23 | 하나제약 주식회사 | 라세믹ｎ,ｎ-디이소프로필-3-(2-히드록시-5-메틸페닐)-3-페닐프로판아민의 제조방법 |
| KR100686351B1 (ko) * | 2006-01-12 | 2007-02-22 | 주식회사 카이로제닉스 | 톨테로딘 라세미체의 제조방법 |
| ATE480531T1 (de) | 2006-05-24 | 2010-09-15 | Pfizer Ltd | Verfahren zur herstellung von benzopyran-2- olderivaten |
| KR101488740B1 (ko) | 2006-06-12 | 2015-02-03 | 유씨비 파마 게엠베하 | 새로운 키랄 중간체, 그 키랄 중간체의 제조방법 및 톨테로딘, 페소테로딘 또는 그 활성대사물질의 제조에서 그키랄 중간체의 사용 |
| KR100717361B1 (ko) * | 2006-08-07 | 2007-05-11 | 주식회사 카이로제닉스 | 톨테로딘 라세미체 및 이의 중간체의 제조방법 |
| US8871275B2 (en) | 2007-08-08 | 2014-10-28 | Inventia Healthcare Private Limited | Extended release compositions comprising tolterodine |
| MX2011001341A (es) | 2008-08-19 | 2011-03-29 | Xenoport Inc | Prodrogas de metil hidrogeno fumarato, sus composiciones farmaceuticas, y metodos de uso. |
| RU2478616C2 (ru) | 2008-12-24 | 2013-04-10 | Дайити Санкио Компани, Лимитед | Циклические аминосоединения |
| NZ593676A (en) | 2008-12-24 | 2012-06-29 | Daiichi Sankyo Co Ltd | Calcium-sensing receptor antagonists |
| KR101275984B1 (ko) * | 2010-10-18 | 2013-06-18 | 경기대학교 산학협력단 | 광학활성을 갖는 크로만계 유도체 및 이의 제조방법 |
| EP2639216B1 (en) * | 2010-11-09 | 2018-07-11 | Kaneka Corporation | Halogenated indenones and method for producing optically active indanones or optically active indanols by using same |
| WO2012098044A1 (en) | 2011-01-17 | 2012-07-26 | Cambrex Profarmaco Milano S.R.L. | Process for the preparation of n,n-diisopropyl-3-(2-hydroxy-5-methylphenyl)- 3-phenyl propylamine and its salts starting from a novel intermediate |
| EP2476665A1 (en) | 2011-01-17 | 2012-07-18 | Cambrex Profarmaco Milano S.r.l. | Process for the preparation of N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)- 3-phenyl propylamine and its salts starting from a novel intermediate |
| LT3135656T (lt) | 2011-06-20 | 2019-04-25 | H. Lundbeck A/S | Deuterinti 1-piperazin-3-fenilindanai, skirti šizofrenijos gydymui |
| CN103159657B (zh) * | 2011-12-08 | 2016-06-29 | 重庆华邦胜凯制药有限公司 | 一种定向合成不饱和共轭醇的方法 |
| AR094054A1 (es) * | 2012-12-19 | 2015-07-08 | H Lundbeck As | 6-cloro-3-(fenil-d₅)-inden-1-ona y uso de la misma |
| KR101380982B1 (ko) | 2013-04-29 | 2014-04-10 | 경기대학교 산학협력단 | 광학활성을 갖는 크로만-2-올 유도체 및 이의 제조방법 |
| WO2017137955A1 (en) | 2016-02-14 | 2017-08-17 | Celestis Pharmaceuticals Pvt. Ltd. | Novel (r) and rac 3-(2-(allyloxy)-5-methylphenyl)-n,n-diisopropyl-3- phenylpropan-1-amine and its use for synthesis of (r) and rac-2-(3- (diisopropylamino)-1-phenylpropyl)-4-(hydroxymethyl)phenol |
| WO2018013739A2 (en) * | 2016-07-12 | 2018-01-18 | Chromocell Corporation | Compounds, compositions, and methods for modulating sweet taste |
| CN113056457B (zh) | 2018-12-03 | 2025-06-20 | H.隆德贝克有限公司 | 用于治疗cns疾病的前药 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE8800207D0 (sv) * | 1988-01-22 | 1988-01-22 | Kabivitrum Ab | Nya aminer, deras anvendning och framstellning |
| SE9203318D0 (sv) * | 1992-11-06 | 1992-11-06 | Kabi Pharmacia Ab | Novel 3,3-diphenylpropylamines, their use and preparation |
| ZA969363B (en) | 1995-11-08 | 1997-11-18 | Smithkline Beecham Corp | An improved process for preparing aromatic ring-fused cyclopentane derivatives. |
| KR20000057548A (ko) * | 1996-12-13 | 2000-09-25 | 알프레드 엘. 미첼슨 | 광학적 전송물질 및 결합재 |
| EP0957073A1 (en) * | 1998-05-12 | 1999-11-17 | Schwarz Pharma Ag | Novel derivatives of 3,3-diphenylpropylamines |
-
1999
- 1999-12-30 SE SE9904850A patent/SE9904850D0/xx unknown
-
2000
- 2000-12-20 MY MYPI20005976A patent/MY118906A/en unknown
- 2000-12-22 DK DK00990151T patent/DK1242361T3/da active
- 2000-12-22 EP EP04014454A patent/EP1496045A3/en not_active Withdrawn
- 2000-12-22 IL IL15027500A patent/IL150275A0/xx unknown
- 2000-12-22 EP EP00990151A patent/EP1242361B1/en not_active Expired - Lifetime
- 2000-12-22 CN CNB008180067A patent/CN1209342C/zh not_active Expired - Fee Related
- 2000-12-22 PT PT00990151T patent/PT1242361E/pt unknown
- 2000-12-22 AT AT00990151T patent/ATE282019T1/de not_active IP Right Cessation
- 2000-12-22 NZ NZ519079A patent/NZ519079A/en unknown
- 2000-12-22 WO PCT/SE2000/002662 patent/WO2001049649A1/en not_active Ceased
- 2000-12-22 MX MXPA02006415A patent/MXPA02006415A/es active IP Right Grant
- 2000-12-22 PL PL00355947A patent/PL355947A1/xx not_active Application Discontinuation
- 2000-12-22 ES ES00990151T patent/ES2228658T3/es not_active Expired - Lifetime
- 2000-12-22 KR KR1020027008466A patent/KR20020062669A/ko not_active Withdrawn
- 2000-12-22 CA CA002392832A patent/CA2392832A1/en not_active Abandoned
- 2000-12-22 SK SK939-2002A patent/SK9392002A3/sk unknown
- 2000-12-22 CZ CZ20022255A patent/CZ20022255A3/cs unknown
- 2000-12-22 AU AU27190/01A patent/AU782796B2/en not_active Ceased
- 2000-12-22 EE EEP200200325A patent/EE200200325A/xx unknown
- 2000-12-22 BR BR0016785-1A patent/BR0016785A/pt active Search and Examination
- 2000-12-22 JP JP2001550189A patent/JP2003519207A/ja active Pending
- 2000-12-22 DE DE60015799T patent/DE60015799T2/de not_active Expired - Lifetime
- 2000-12-22 HU HU0203816A patent/HUP0203816A3/hu unknown
- 2000-12-22 US US09/748,042 patent/US6310248B2/en not_active Expired - Fee Related
- 2000-12-27 PE PE2000001404A patent/PE20011123A1/es not_active Application Discontinuation
- 2000-12-28 AR ARP000106999A patent/AR027138A1/es unknown
- 2000-12-28 TW TW089128081A patent/TWI225476B/zh active
-
2002
- 2002-05-22 ZA ZA200204066A patent/ZA200204066B/en unknown
- 2002-07-01 NO NO20023189A patent/NO20023189L/no not_active Application Discontinuation
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