WO2004087623A2 - An improved process for the preparation of (r) (-) tamsulosin hydrochloride - Google Patents
An improved process for the preparation of (r) (-) tamsulosin hydrochloride Download PDFInfo
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- WO2004087623A2 WO2004087623A2 PCT/IN2004/000054 IN2004000054W WO2004087623A2 WO 2004087623 A2 WO2004087623 A2 WO 2004087623A2 IN 2004000054 W IN2004000054 W IN 2004000054W WO 2004087623 A2 WO2004087623 A2 WO 2004087623A2
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- Prior art keywords
- process according
- tamsulosin
- anyone
- hydrochloride
- base
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 57
- DRHKJLXJIQTDTD-OAHLLOKOSA-N Tamsulosine Chemical compound CCOC1=CC=CC=C1OCCN[C@H](C)CC1=CC=C(OC)C(S(N)(=O)=O)=C1 DRHKJLXJIQTDTD-OAHLLOKOSA-N 0.000 title claims abstract description 37
- 229960003198 tamsulosin hydrochloride Drugs 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 239000002904 solvent Substances 0.000 claims abstract description 20
- 150000001875 compounds Chemical class 0.000 claims abstract description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000002585 base Substances 0.000 claims description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 27
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 27
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 14
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 13
- 239000003054 catalyst Substances 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 8
- 239000011736 potassium bicarbonate Substances 0.000 claims description 8
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 8
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 8
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 8
- 229940086066 potassium hydrogencarbonate Drugs 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 4
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 claims description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 125000001931 aliphatic group Chemical group 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 239000008096 xylene Substances 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 235000009518 sodium iodide Nutrition 0.000 claims description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 2
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 claims description 2
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 2
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- -1 alkaline earth metal carbonates Chemical class 0.000 claims description 2
- 235000012538 ammonium bicarbonate Nutrition 0.000 claims description 2
- 239000001099 ammonium carbonate Substances 0.000 claims description 2
- 238000006482 condensation reaction Methods 0.000 claims description 2
- 150000003983 crown ethers Chemical class 0.000 claims description 2
- 229940113088 dimethylacetamide Drugs 0.000 claims description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 2
- 229930195733 hydrocarbon Natural products 0.000 claims description 2
- 150000002430 hydrocarbons Chemical class 0.000 claims description 2
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 claims description 2
- 229910052808 lithium carbonate Inorganic materials 0.000 claims description 2
- 150000007530 organic bases Chemical class 0.000 claims description 2
- XSXHWVKGUXMUQE-UHFFFAOYSA-N osmium dioxide Inorganic materials O=[Os]=O XSXHWVKGUXMUQE-UHFFFAOYSA-N 0.000 claims description 2
- 239000003444 phase transfer catalyst Substances 0.000 claims description 2
- 150000004714 phosphonium salts Chemical group 0.000 claims description 2
- 239000002798 polar solvent Substances 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 235000011181 potassium carbonates Nutrition 0.000 claims description 2
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 claims description 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 2
- 239000003352 sequestering agent Chemical group 0.000 claims description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 229940086542 triethylamine Drugs 0.000 claims description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims 2
- 238000000634 powder X-ray diffraction Methods 0.000 claims 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims 1
- 239000003513 alkali Substances 0.000 claims 1
- 239000007789 gas Substances 0.000 claims 1
- 150000004679 hydroxides Chemical class 0.000 claims 1
- 150000004694 iodide salts Chemical class 0.000 claims 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims 1
- DRHKJLXJIQTDTD-UHFFFAOYSA-N 5-(2-{[2-(2-ethoxyphenoxy)ethyl]amino}propyl)-2-methoxybenzenesulfonamide Chemical compound CCOC1=CC=CC=C1OCCNC(C)CC1=CC=C(OC)C(S(N)(=O)=O)=C1 DRHKJLXJIQTDTD-UHFFFAOYSA-N 0.000 abstract description 8
- 239000012467 final product Substances 0.000 abstract description 7
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 abstract description 4
- 208000004403 Prostatic Hyperplasia Diseases 0.000 abstract description 4
- 239000000356 contaminant Substances 0.000 abstract description 3
- 230000000903 blocking effect Effects 0.000 abstract description 2
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 2
- 230000002349 favourable effect Effects 0.000 abstract description 2
- 231100001261 hazardous Toxicity 0.000 abstract description 2
- 230000001077 hypotensive effect Effects 0.000 abstract description 2
- 239000011541 reaction mixture Substances 0.000 description 10
- IOYHGBZPUZBUTJ-UHFFFAOYSA-N 1-(2-bromoethoxy)-2-ethoxybenzene Chemical compound CCOC1=CC=CC=C1OCCBr IOYHGBZPUZBUTJ-UHFFFAOYSA-N 0.000 description 6
- ZZIZZTHXZRDOFM-UHFFFAOYSA-N 2-(2-ethoxyphenoxy)ethyl-[1-(4-methoxy-3-sulfamoylphenyl)propan-2-yl]azanium;chloride Chemical compound Cl.CCOC1=CC=CC=C1OCCNC(C)CC1=CC=C(OC)C(S(N)(=O)=O)=C1 ZZIZZTHXZRDOFM-UHFFFAOYSA-N 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 0 CC(C)(Cc(cc1*)ccc1OC)NC(COc(cccc1)c1O)=C Chemical compound CC(C)(Cc(cc1*)ccc1OC)NC(COc(cccc1)c1O)=C 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 229960002613 tamsulosin Drugs 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- GDZWGGUGMFJABZ-UHFFFAOYSA-N 2-(2-ethoxyphenoxy)acetyl chloride Chemical compound CCOC1=CC=CC=C1OCC(Cl)=O GDZWGGUGMFJABZ-UHFFFAOYSA-N 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000003638 chemical reducing agent Substances 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
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 150000004820 halides Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
- C07C303/40—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/37—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered 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
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Definitions
- the present invention relates to a process for the preparation of (R)(-) Tamsulosin hydrochloride [(R)(-)-5-[2-[[2-(o-ethoxy-phenoxy)ethyl]amino]-2-methylethyl]-2- methoxybenzenesulfonamide hydrochloride] of formula (HI),
- the (R)(-) Tamsulosin hydrochloride of formula (III) produced by the process has an alpha-adrenergic blocking action and possesses a hypotensive activity and is used mainly for the treatment of benign prostatic hyperplasia (BPH).
- WO 02/068382A1 describes the process for 'the preparation of (R)(-)-Tamsulosin hydrochloride III by the condensation of I with 2-ethoxy phenoxyacetyl chloride IV to give 2-(2-ethoxy-phenoxy)-N-[2-(4-methoxy-3-sulfamoyl-3-phenyl)-l- methylethyl] acetamide ( V ) which on .reduction with lithium aluminium hydride yielded R-(-) Tamsulosin hydrochloride (III), (Scheme-I).
- Another object of the present invention is to provide a process of manufacture of [(R)(-)-5-[2-[[2-(o-ethoxy-phenoxy)ethyl]amino]-2-methylethyl]-2- methoxybenzenesulfonamide hydrochloride] which would avoid unreacted contaminants in the final product and provide for isolating and obtaining the final product with good yield and purity.
- Yet another objective of the invention is to provide a process for the preparation of (R)(-) Tamsulosin Hydrochloride that would not require the handling of hazardous reagents, such as LAH.
- a further objective of the invention is to provide a process of manufacture of [(R)(-)-5-[2-[[2-(o-ethoxy-phenoxy)ethyl]amino]-2-methylethyl]-2- methoxybenzenesulfonamide hydrochloride] that, would involve selective mild reaction conditions.
- a further object of the invention is to provide a process of manufacture of [(R)(- )-5-[2-[[2-(o-ethoxy-phenoxy)ethyl]amino]-2-methylethyl]-2- methoxybenzenesulfonamide hydrochloride] that would be industrially favourable in that the same would use less amount of solvent, hence increase the plant capacity and will also require less manpower.
- a further object of this invention is to provide the method of purification which would be industrially feasible for large scale preparation of [(R)(-)-5-[2-[[2-(o- ethoxy-phenoxy) ethyl] amino]-2-methylethyl]-2-methoxy benzene sulfonamide hydrochloride].
- the present invention provides a process for the preparation of (R)(-) Tamsulosin Hydrochloride [(R)(-)-5-[2-[[2-(o-ethoxyphenoxy) ethyl] amino]-2-methylethyl]- 2-methoxybenzenesulfonamide hydrochloride] (III) comprising reacting R-(-)-5- [(2-amino-2-methyl)ethyl]-2-methoxy benzenesulfonamide hydrochloride (I) with the compound of formula (II) wherein X represents F, CI, Br, I, OS0 CH 3 , OS0 2 CF 3 , OTs, OBs, ONs or any other suitable leaving group in the presence or absence of a suitable catalyst, a suitable base, in a organic solvent.
- the present invention relates to a process for the preparation of (R)(-) Tamsulosin Hydrochloride [(R)(-)-5-[2-[[2-(o-ethoxyphenoxy) ethyl] amino]-2-methylethyl]-2- methoxybenzenesulfonamide hydrochloride] (III) comprising the reaction of R-(-)-5-[(2- amino-2-methyl)ethyl]-2-methoxybenzenesulfonamide hydrochloride (I) with the compound of formula (II)
- X is halides such as CI, Br, I, or sulphonates such as OSO 2 CH 3 , OS0 2 CF 3 , OTs, OBs, ONs or any other suitable leaving group in the presence or absence of a suitable catalyst, a suitable base, in a organic solvent to give (R)(-) Tamsulosin base which is further crystallised with suitable solvent and converted into hydrochloride salt by suitable method and may be purified from water or polar solvents or mixtures thereof.
- base is selected from the group comprising of metal carbonates; metal bicarbonates; alkali metal hydroxides, alkaline metal hydroxide or organic bases.
- the preferred base is selected from the group comprising of Potassium hydrogen carbonate, Sodium hydrogen carbonate, Sodium carbonate, Potassium carbonate, Lithium carbonate, Ammonium bicarbonate, sodium hydroxide or potassium hydroxide or tert-amines such as tri ethyl amine.
- the organic solvent is selected from the group comprising of acetonitrile, propionitrile, acetone, methyl ethyl ketone, methyl isobutyl ketone, dimethyl formamide, dimethyl acetamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone, tetrahydrofuran, toluene, benzene, xylene, t dichloro ethane, diisopropyl ether, polyethylene glycol or mixtures there of.
- the catalyst is selected from potassium iodide, sodium iodide, tetrabutyl ammonium iodide, or a phase transfer catalysts like crown ethers, quaternary ammonium salts, quaternary phosphonium salts or sequestering agents.
- the preferred catalyst is potassium iodide.
- the amount of catalyst is used 0 to 2 equivalents of R (-)-5-[(2-amino-2-methyl) ethyl] -2-methoxy benzenesulfonamide hydrochloride.
- the above condensation reaction is carried out at a temperature range of 20 to 120°C.
- the preferable temperature range is 60 to 90°C.
- reaction is carried'' out for 30 minutes to 48 hours.
- reaction is carried out for 18 to 30 hours and most preferably 24 hours.
- the suitable solvent for the crystallisation of (R)(-) Tamsulosin base is selected from the group comprising of hydrocarbons, alcoholic solvent, ketonic solvent, aliphatic esters or mixtures thereof.
- the preferred solvent is selected from the group comprising of toluene, xylene, methanol, ethanol, isopropanol, acetone, methyl ethyl ketone, methyl isobutyl ketone, ethyl acetate, butyl acetate or mixtures there of.
- IR (cm "1 ) : 3354, 3082, 2981, 2811, 2744, ⁇ 608, 1589, 1498, 1455, 1414, 1392, 1338, 1282, 1251, 1215, 1159, 1128, 1072, 1045, 1018, 915, 897, 819, 749, 718, 677, 602, 577, 514.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
A process for the preparation of (R)(-) Tamsulosin hydrochloride [(R)(-)-5-[2-[[2-(o-ethoxy-phenoxy)ethyl]amino]-2-methylethyl]-2-methoxybenzenesulfonamide hydrochloride] of formula (III), The (R)(-) Tamsulosin hydrochloride of formula (III) produced by the process has an alpha-adrenergic blocking action and possesses a hypotensive activity and is used mainly for the treatment of benign prostatic hyperplasia (BPH). The process is directed to be high yielding, cost effective, easy to operate at industrial scale and does not involve the use of moisture sensitive, pyrophoric compounds. Importantly, the process would avoid unreacted contaminants in the final product and provide for isolating and obtaining the final product with good yield and purity. Advantageously, the process would not require the handling of hazardous reagents, such as LAH. The process is also selective, industrially favourable in that the same would use less amount of solvent, hence increase the plant capacity and will also require less manpower.
Description
AN IMPROVED PROCESS FOR ΪHE PREPARATION OF (R) (-) TAMSULOSIN HYDROCHLORIDE
TECHNICAL FIELD:
The present invention relates to a process for the preparation of (R)(-) Tamsulosin hydrochloride [(R)(-)-5-[2-[[2-(o-ethoxy-phenoxy)ethyl]amino]-2-methylethyl]-2- methoxybenzenesulfonamide hydrochloride] of formula (HI),
HI
The (R)(-) Tamsulosin hydrochloride of formula (III) produced by the process has an alpha-adrenergic blocking action and possesses a hypotensive activity and is used mainly for the treatment of benign prostatic hyperplasia (BPH).
BACKGROUND OF THE INVENTION:
WO 02/068382A1 describes the process for 'the preparation of (R)(-)-Tamsulosin hydrochloride III by the condensation of I with 2-ethoxy phenoxyacetyl chloride IV to give 2-(2-ethoxy-phenoxy)-N-[2-(4-methoxy-3-sulfamoyl-3-phenyl)-l- methylethyl] acetamide ( V ) which on .reduction with lithium aluminium hydride yielded R-(-) Tamsulosin hydrochloride (III), (Scheme-I).
IV
Y= CI, OR, OC(=O)R (R'= Et)
V (R'= Et)
Lithium aluminium hydride
Ill
(R'= Et)
Scheme I
The main disadvantage of this process is the use of lithium aluminium hydride as reducing agent, which is extremely moisture sensitive and pyrophoric hence, difficult to use at industrial scale.
US patent 4731478 describes the synthesis of (R)(-) Tamsulosin
III
scheme - II
hydrochloride (III) by condensing R(-)-5-[(2-amino-2-methyl)ethyl]-2-methoxy benzenesulfonamide (I) with 2-(2-ethoxy phenoxy) ethyl bromide (II) in ethanol (Scheme-II). The process described therein yields the Tamsulosin hydrochloride in a very poor yield (37%). Moreover, in the process described therein, (R)(-) Tamsulosin hydrochloride (III) purification is proposed using column chromatography which is expensive, time consuming and impractical at industrial scale.
Importantly, it is found that in the above process of US '478, the base compound of Formula I, which is used as a free base' and reacted with the compound of Formula II resulted in a final product (Tamsulosin Base) with contaminants of
unreacted compound of Formula I. This lead to difficulties in isolating the final product and also loss in yield of Tamsulosin Hydrochloride alongwith problems of purity.
OBJECTS OF THE INVENTION
It is thus the basic object of the present invention to provide a process for the preparation of (R)(-) Tamsulosin Hydrochloride, which would be high yielding, cost effective, easy to operate at industrial scale and would not involve the use of moisture sensitive, pyrophoric compounds.
Another object of the present invention is to provide a process of manufacture of [(R)(-)-5-[2-[[2-(o-ethoxy-phenoxy)ethyl]amino]-2-methylethyl]-2- methoxybenzenesulfonamide hydrochloride] which would avoid unreacted contaminants in the final product and provide for isolating and obtaining the final product with good yield and purity.
Yet another objective of the invention is to provide a process for the preparation of (R)(-) Tamsulosin Hydrochloride that would not require the handling of hazardous reagents, such as LAH.
A further objective of the invention is to provide a process of manufacture of [(R)(-)-5-[2-[[2-(o-ethoxy-phenoxy)ethyl]amino]-2-methylethyl]-2- methoxybenzenesulfonamide hydrochloride] that, would involve selective mild reaction conditions.
A further object of the invention is to provide a process of manufacture of [(R)(- )-5-[2-[[2-(o-ethoxy-phenoxy)ethyl]amino]-2-methylethyl]-2- methoxybenzenesulfonamide hydrochloride] that would be industrially favourable in that the same would use less amount of solvent, hence increase the plant capacity and will also require less manpower.
A further object of this invention is to provide the method of purification which would be industrially feasible for large scale preparation of [(R)(-)-5-[2-[[2-(o- ethoxy-phenoxy) ethyl] amino]-2-methylethyl]-2-methoxy benzene sulfonamide hydrochloride].
SUMMARY OF THE INVENTION:
The present invention provides a process for the preparation of (R)(-) Tamsulosin Hydrochloride [(R)(-)-5-[2-[[2-(o-ethoxyphenoxy) ethyl] amino]-2-methylethyl]- 2-methoxybenzenesulfonamide hydrochloride] (III) comprising reacting R-(-)-5- [(2-amino-2-methyl)ethyl]-2-methoxy benzenesulfonamide hydrochloride (I) with the compound of formula (II) wherein X represents F, CI, Br, I, OS0 CH3, OS02CF3, OTs, OBs, ONs or any other suitable leaving group in the presence or absence of a suitable catalyst, a suitable base, in a organic solvent.
The reaction scheme followed is as shown in Scheme III hereunder :
Scheme
DETAILED DESCRIPTION OF THE INVENTION:
The present invention relates to a process for the preparation of (R)(-) Tamsulosin Hydrochloride [(R)(-)-5-[2-[[2-(o-ethoxyphenoxy) ethyl] amino]-2-methylethyl]-2- methoxybenzenesulfonamide hydrochloride] (III) comprising the reaction of R-(-)-5-[(2- amino-2-methyl)ethyl]-2-methoxybenzenesulfonamide hydrochloride (I) with the compound of formula (II)
wherein X is halides such as CI, Br, I, or sulphonates such as OSO2CH3, OS02CF3, OTs, OBs, ONs or any other suitable leaving group in the presence or absence of a suitable catalyst, a suitable base, in a organic solvent to give (R)(-) Tamsulosin base which is further crystallised with suitable solvent and converted into hydrochloride salt by suitable method and may be purified from water or polar solvents or mixtures thereof.
According to the present invention base is selected from the group comprising of metal carbonates; metal bicarbonates; alkali metal hydroxides, alkaline metal hydroxide or organic bases. The preferred base is selected from the group comprising of Potassium hydrogen carbonate, Sodium hydrogen carbonate, Sodium carbonate, Potassium carbonate, Lithium carbonate, Ammonium bicarbonate, sodium hydroxide or potassium hydroxide or tert-amines such as tri ethyl amine.
The organic solvent is selected from the group comprising of acetonitrile, propionitrile, acetone, methyl ethyl ketone, methyl isobutyl ketone, dimethyl formamide, dimethyl acetamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone, tetrahydrofuran, toluene, benzene, xylene,t dichloro ethane, diisopropyl ether, polyethylene glycol or mixtures there of.
The catalyst is selected from potassium iodide, sodium iodide, tetrabutyl ammonium iodide, or a phase transfer catalysts like crown ethers, quaternary
ammonium salts, quaternary phosphonium salts or sequestering agents. The preferred catalyst is potassium iodide.
The amount of catalyst is used 0 to 2 equivalents of R (-)-5-[(2-amino-2-methyl) ethyl] -2-methoxy benzenesulfonamide hydrochloride.
The above condensation reaction is carried out at a temperature range of 20 to 120°C. The preferable temperature range is 60 to 90°C.
The above mentioned reaction is carried'' out for 30 minutes to 48 hours. Preferably the reaction is carried out for 18 to 30 hours and most preferably 24 hours.
The suitable solvent for the crystallisation of (R)(-) Tamsulosin base is selected from the group comprising of hydrocarbons, alcoholic solvent, ketonic solvent, aliphatic esters or mixtures thereof. The preferred solvent is selected from the group comprising of toluene, xylene, methanol, ethanol, isopropanol, acetone, methyl ethyl ketone, methyl isobutyl ketone, ethyl acetate, butyl acetate or mixtures there of.
The crystal structure of the Tamsulosin hydrochloride thus prepared has the endotherm in DSC at 235.8°C (Figure I) and the XRD (Figure II) reported as below d-spacing
16.10, 7.99, 6.06, 5.62, 5.29, 5.06, .4.62, 4.26, 3.98, 3.86, 3.75, 3.66, 3.52, 3.36, 3.29, 3.23, 3.01, 2.97, 2.85, 2.72, 2.55, 2.42
The process of the present invention is described by the following examples, which are illustrative only and not be construed so as to limit to the scope of the invention in any manner.
Examples:
Example: 1
A mixture of R (-)-5-[(2-amino-2 -methyl) ethyl]-2-methoxy benzenesulfonamide hydrochloride (5 g), 2-(2-ethoxy phenoxy) ethyl bromide (4.3 g), potassium hydrogen carbonate (3.5 g), potassium iodide as catalyst (0.6 g) and Acetonitrile (100 ml) was refluxed for 24 hrs. The solvent was distilled off under vacuum. Water(100 ml) was added in the reaction mixture. Stirred the reaction mixture for 1 hr. The separated solid was filtered and dried to give crude (R)(-) Tamsulosin Base (7.2 g).
The crude (R)(-) Tamsulosin base was crystallized from toluene to get pure (R)(-) Tamsulosin base. The base was dissolved in methanol (5 volume) and adjusted pH 2 by isopropanolic HC1 to get (R)(-) Tamsulosin HC1. This may be crystallized from water (20 volumes) or methanol (50 volumes) to remove polar impurities. [HPLC Purity 99.5%, [ α]24 D -3.8° (c=0.35, Methanol),M.P. 230-232°C]
1H-NMR (DMSO-de); δ (ppm) = 9.5(bs,2h),' 7.62 (d, lH), 7.45 (dd, lH),
7.17(d, lH) 7.08 (s,2H), 6.93 (m,4H), 4.33 (t,2H), 4.0 (q, 2H), 3.88 (s,3H0, 3.54
(b, lH), 3.40(b,2H), 3.31(d, lH),2.66(t, lH), 1.25(t, 3H), 1.16 (d,3H).
13C-NMR (DMSO-d6); δ(ppm) = 155.7, 149.52, 148.14, 135.28, 132.03, 129.10, 123.1 1, 121.55, 116.09, 114.39, 113.70, 65.90, 64.53, 56.95, 55.53, 43.81, 38.05, 15.58, 15.43.
IR : (cm"1) : 3354, 3082, 2981, 2811, 2744, Ϊ608, 1589, 1498, 1455, 1414, 1392, 1338, 1282, 1251, 1215, 1159, 1128, 1072, 1045, 1018, 915, 897, 819, 749, 718, 677, 602, 577, 514.
Example: 2
A mixture of R (-)-5-[(2-amino-2 -methyl) ethyl]-2-methoxy benzenesulfonamide hydrochloride (5 g), 2-(2-ethoxy phenoxy) ethyl bromide (4.3 g), potassium hydrogen carbonate (3.5 g), potassium iodide as catalyst (0.6g) and DMF (100 ml) was refluxed for 24 hrs. The solvent was distilled off under vacuum. Water (100 ml) was added in the reaction mixture. Stirred the reaction mixture for 1 hr. The separated solid was filtered and dried to give crude (R)(-) Tamsulosin Base (5.0 g).
It was purified and converted into hydrochloride salt by process as described in example 1.
Example: 3
A mixture of R (-)-5-[(2-amino-2 -methyl) ethyl]-2-methoxy benzenesulfonamide hydrochloride (5 g), 2-(2-ethoxy phenoxy) ethyl bromide (5 g), potassium hydrogen carbonate (3.5 gm), potassium iodide as catalyst (0.6 g) and Acetonitrile (100 ml) was refluxed for 24 hrs. The solvent was distilled off under vacuum. Water (100 ml) was added in the reaction mixture. Stirred the reaction mixture for 1 hr. The separated solid was filtered and dried to give crude (R)(-) Tamsulosin Base (6.0 g).
It was purified and converted into hydrochloride salt by process as described in example 1.
Example: 4
A mixture of R (-)-5 -[(2 -amino-2 -methyl) ethyl]-2-methoxy benzenesulfonamide hydrochloride (5 g), 2-(2-ethoxy phenoxy) ethyl bromide (5.0 g), potassium hydrogen carbonate (3. 5 g), potassium iodide as catalyst (0.6 g) and 2-Butanone (100 ml) was refluxed for 24 hrs. The solvent was distilled off under vacuum. Water (100 ml) was added in the reaction mixture. Stirred the reaction mixture for 1 hr. The separated solid was filtered and dried to give crude (R)(-) Tamsulosin Base (6.4 g).
It was purified and converted into hydrochloride salt by process as described in example 1.
Example: 5
A mixture of R (-)-5 -[(2 -amino-2 -methyl) ethyl]-2-methoxy benzenesulfonamide hydrochloride (5 g), 2-(2-ethoxy phenoxy) ethyl mesylate (4.3 g), potassium hydrogen carbonate (3. 5 g) potassium iodide (0.69) and Acetonitrile (100 ml) was refluxed for 24 hrs. The solvent was distilled off under vacuum. Water (100 ml) was added in the reaction mixture. Stirred the reaction mixture for 1 hr. The separated solid was filtered and dried to give crude (R)(-) Tamsulosin Base (6.4 g).
It was purified and converted into hydrochloride salt by process as described in example 1.
To demonstrate the comparative advantages of the process of the invention i.e. involving the use of hydrochloride salt of Formula I as the βtarting material instead of the use of the compound of Formula I as base as initial reactant (US '478) to react with the compound of Formula π, the following example was carried out following the process as that of US '4731478 as detailed hereunder :
Example 6
In 120ml of ethanol were dissolved 2.4 g of (R)(-)-5-[(2-amino-2-methyl)ethyl]-2- methoxybenzenesulfonamide and 1.2 g of 2-( -ethoxyphenoxy)ethyl bromide and the mixture was refluxed under heating. The solvent was distilled away.
The reaction conditions followed under Examples 1 to 5 (in accordance with the invention) and that under Example 6 (of US 4731478) and the yield obtained are detailed in TABLE I hereunder :
Table - 1
It would be apparent from the above comparative study results of the process of the invention vis-a-vis the process of US'478 that the process of the invention which involves the use of salt of compound of Formula I instead of its base form as proposed in US'478 achieves higher yield of the final product (Tamsulosin Base )and serves as a selective industrially applicable process for the manufacture of Tamsulosin hydrochloride of Formula III.
Claims
1. A process for the preparation of (R)(-)Tamsulosin hydrochloride (III) comprising of reacting R(-)-5-[(2-amino-2-methyl)ethyl]-2-methoxy benzenesulfonamide hydrochloride (I) with the compound of for ula (II) wherein X represents F, CI, Br, I, OSO2CH3, OS02CF3, OTs, OBs, ONs or any other suitable leaving group in presence of a suitable base and an organic solvent to give (R)(-) Tamsulosin base, which is isolated and crystallized from a suitable solvent and converted into the hydrochloride salt , optionally, purifying the said hydrochloride salt from any one or more of water, polar solvents and mixtures thereof.
III
2. A process for the preparation of (R)(-)Tamsulosin hydrochloride (III) as claimed in claim 1 wherein said condensation reaction of the compound of Formula I with the compound of Formula II is carried out in the presence of a catalyst.
3. Process according to anyone of claims 1 or 2 wherein the base is selected from the group comprising of alkali or alkaline earth metal carbonates, bicarbonates or hydroxides or organic bases.
4. Process according to anyone of claims 1 to 3 wherein base is preferably selected from the group comprising of Potassium hydrogen carbonate, Sodium hydrogen carbonate, Sodium carbonate, Potassium carbonate, Lithium carbonate, Ammonium bicarbonate, sodium hydroxide, potassium hydroxide and tert-amines preferably triethyl amine.
5. Process according to claim 4, wherein base is more preferably Potassium hydrogen carbonate.
6. Process according to any one of claims 1 to 5 wherein the amount of base used is 1 to 4 equivalents, preferably 1 to 3 equivalents.
7. Process according to anyone of claims 1 to 6 wherein the organic solvent is selected from the group comprising of acetonitrile, propionitrile, acetone, methyl ethyl ketone, methyl isobutyl ketone, dimethyl formamide, dimethyl acetamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone, aliphatic esters, tetrahydrofuran, dioxane, toluene, benzene, xylene, dichloroethane, diisopropyl ether, polyethylene glycol or mixtures thereof.
8. Process according to claim 7, wherein the organic solvent is preferably Acetonitrile.
9. Process according to any one of claims 1 to 8 wherein the amount of the organic solvent used is between 0.5 to 100 volumes, preferably 10 to 30 volumes.
10. Process according to anyone of claims 2. to 9 wherein the reaction is carried out in the presence of a catalyst selected from Iodide salts preferably
Potassium iodide, sodium iodide, a phase transfer catalysts preferably crown ethers, quaternary ammonium salts preferably tetrabutyl ammonium iodide, quaternary phosphonium salts, and sequestering agents, polyethylene glycols.
11. Process according to claim 10, wherein the catalyst used is preferably Potassium iodide or sodium iodide.
12. Process according to anyone of claims 2 to 11, wherein the amount of catalyst used is between 0 to 2 equivalents more preferably 0.05 to 1 equivalent, most preferably 0.2 equivalents.
13. Process according to anyone of claims 1 to 12 wherein the reaction is carried out at temperature of 20°C to 120°C, preferably 60°C to 90°C.
14. Process according to anyone of claims 1 to 13 wherein the reaction is carried out for 30 minutes to 48 hours, more preferably 18 to 30 hours, and most preferably 24 hours.
15. Process according to anyone of claims 1 to 14 wherein the ratio of (R)(-)-5- [(2-amino-2-methyl)ethyl]-2-methoxy benzenesulfonamide hydrochloride of formula (I) to compounds of formula (II) wherein X represents F, CI, Br, I, OS02CH3, OS02CF3, OTs, OBs, ONs or any other suitable leaving group) is 0.5 to 1.5 equivalents, more preferably 0.8 to 1.2 equivalents, most preferably 1 equivalent.
16. Process according to anyone of claims 1 to 15 wherein the (R)(-) Tamsulosin base is crystallised from suitable solvents selected from the group comprising of hydrocarbons, alcoholic solvent, ketonic solvent, aliphatic esters, other aliphatic solvents and mixtures thereof.
17. Process according to claim 16, wherein the (R)(-) Tamsulosin base is crystallised from suitable solvents selected from the group comprising of
toluene, benzene, xylene, methanol, ' ethanol, isopropanol, acetone, methyl ethyl ketone, methyl isobutyl ketone, ethyl acetate, butyl acetate or mixtures there of.
18. Process according to anyone of claims 16 to 17 wherein the (R)(-) Tamsulosin base is preferably crystallised from toluene.
19. Process according to anyone of claims 1 to 18 wherein the crude (R)(-) Tamsulosin base is converted to hydrochloride salt in solvent preferably selected from acetone, methanol, ethanol, propanol, water, using gaseous hydrogen chloride gas, its solution in methanol, ethanol, isopropanol and water.
20. Process according to anyone of claims 1 to 19, wherein the crude (R)(-) Tamsulosin base is dissolved in methanol and acidified with isopropanolic hydrogen chloride to obtain (R)(-) Tamsulosin hydrochloride.
21. Process according to anyone of claims 1 to 20 wherein the (R)(-)-Tamsulosin hydrochloride is recrystallized from water or methanol to give a polymorph having the following d-spacing values jn powder XRD, 16.10, 7.99, 6.06,
5.62, 5.29, 5.06, 4.62, 4.26, 3.98, 3.86, 3.75, 3.66, 3.52, 3.36, 3.29, 3.23, 3.01, 2.97, 2.85, 2.72, 2.55, 2.42 (Figure II) and an endotherm in DSC at 235.8°C (Figure I).
22. A polymorph of R(-)Tamsulosin Hydrochloride having the following d- spacing values in powder XRD, 16.10, 7.99, 6.06, 5.62, 5.29, 5.06, 4.62, 4.26, 3.98, 3.86, 3.75, 3.66, 3.52, 3.36, 3.29, 3.23, 3.01, 2.97, 2.85, 2.72, 2.55, 2.42 (Figure II) and an endotherm in DSC at 235.8°C (Figure I).
23. A process for the preparation of (R)(-) Tamsulosin Hydrochloride (III) and a polymorph thereof substantially as herein described and illustrated with reference to the accompanying examples and figures.
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| IN248/MUM/2003 | 2003-03-07 | ||
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Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006061549A1 (en) * | 2004-12-06 | 2006-06-15 | Hovione Inter Ltd. | Process for the preparation of tamsulosin and intermediates thereof |
| WO2006019358A3 (en) * | 2004-08-16 | 2006-12-07 | Scinopharm Singapore Pte Ltd | Process for preparing tamsulosin |
| EP1734036A1 (en) * | 2005-06-14 | 2006-12-20 | Well-being Biochemical Corp. | Process for preparation of tamsulosin and its derivatives |
| WO2006134212A2 (en) * | 2005-06-15 | 2006-12-21 | Fermion Oy | Preparation of tamsulosin hydrochloride from tamsulosi |
| JP2007015975A (en) * | 2005-07-07 | 2007-01-25 | Well Being Biochemical Corp | Production method for tamusulosin and relating allyl derivative |
| WO2007031823A1 (en) * | 2005-09-12 | 2007-03-22 | Aurobindo Pharma Limited | An improved process for preparing tamsulosin hydrochloride |
| US7282606B2 (en) * | 2005-07-13 | 2007-10-16 | Well-Being Biochemical Corp. | Process for preparation of tamsulosin and its aralkylamine derivatives |
| WO2007119110A2 (en) * | 2005-10-28 | 2007-10-25 | Medichem, S.A. | Process for the preparation of tamsulosin and related compounds |
| CZ299493B6 (en) * | 2005-04-20 | 2008-08-13 | Zentiva, A. S | Method of making analysis, particularly determination of active substance content and purity thereof |
| WO2008152653A2 (en) * | 2007-06-11 | 2008-12-18 | Matrix Laboratories Ltd | An improved process for the preparation of tamsulosin hydrochloride |
| EP2098503A1 (en) * | 2006-11-30 | 2009-09-09 | Jiangsu Hansen Pharmaceutical Co., Ltd. | 5-[(2r)-[2-[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl]amino]propyl]-2-methoxybenzenesulfonamide |
| CN102898336A (en) * | 2012-10-16 | 2013-01-30 | 北京悦康科创医药科技有限公司 | Preparation method of tamsulosin hydrochloride |
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| US5447958A (en) * | 1980-02-08 | 1995-09-05 | Yamanouchi Pharmaceutical Co., Ltd. | Sulfamoyl-substituted phenethylamine derivatives, their preparation, and pharmaceutical compositions, containing them |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US5447958A (en) * | 1980-02-08 | 1995-09-05 | Yamanouchi Pharmaceutical Co., Ltd. | Sulfamoyl-substituted phenethylamine derivatives, their preparation, and pharmaceutical compositions, containing them |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006019358A3 (en) * | 2004-08-16 | 2006-12-07 | Scinopharm Singapore Pte Ltd | Process for preparing tamsulosin |
| US7332621B2 (en) | 2004-08-16 | 2008-02-19 | Scinopharm Taiwan Ktd. | Process for preparing Tamsulosin |
| US8017803B2 (en) | 2004-12-06 | 2011-09-13 | Hovione Inter Ltd. | Process for the preparation of tamsulosin and intermediates thereof |
| WO2006061549A1 (en) * | 2004-12-06 | 2006-06-15 | Hovione Inter Ltd. | Process for the preparation of tamsulosin and intermediates thereof |
| CZ299493B6 (en) * | 2005-04-20 | 2008-08-13 | Zentiva, A. S | Method of making analysis, particularly determination of active substance content and purity thereof |
| EP1734036A1 (en) * | 2005-06-14 | 2006-12-20 | Well-being Biochemical Corp. | Process for preparation of tamsulosin and its derivatives |
| WO2006134212A2 (en) * | 2005-06-15 | 2006-12-21 | Fermion Oy | Preparation of tamsulosin hydrochloride from tamsulosi |
| WO2006134212A3 (en) * | 2005-06-15 | 2007-02-22 | Fermion Oy | Preparation of tamsulosin hydrochloride from tamsulosi |
| JP2007015975A (en) * | 2005-07-07 | 2007-01-25 | Well Being Biochemical Corp | Production method for tamusulosin and relating allyl derivative |
| US7282606B2 (en) * | 2005-07-13 | 2007-10-16 | Well-Being Biochemical Corp. | Process for preparation of tamsulosin and its aralkylamine derivatives |
| WO2007031823A1 (en) * | 2005-09-12 | 2007-03-22 | Aurobindo Pharma Limited | An improved process for preparing tamsulosin hydrochloride |
| US8273918B2 (en) * | 2005-09-12 | 2012-09-25 | Avrobindo Pharma Ltd. | Process for preparing tamsulosin hydrochloride |
| WO2007119110A2 (en) * | 2005-10-28 | 2007-10-25 | Medichem, S.A. | Process for the preparation of tamsulosin and related compounds |
| WO2007119110A3 (en) * | 2005-10-28 | 2008-02-28 | Medichem Sa | Process for the preparation of tamsulosin and related compounds |
| EP2098503A1 (en) * | 2006-11-30 | 2009-09-09 | Jiangsu Hansen Pharmaceutical Co., Ltd. | 5-[(2r)-[2-[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl]amino]propyl]-2-methoxybenzenesulfonamide |
| EP2098503A4 (en) * | 2006-11-30 | 2010-02-10 | Jiangsu Hansen Pharmaceutical | 5-[(2r)-[2-[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl]amino]propyl]-2-methoxybenzenesulfonamide |
| WO2008152653A3 (en) * | 2007-06-11 | 2010-04-29 | Matrix Laboratories Ltd | An improved process for the preparation of tamsulosin hydrochloride |
| WO2008152653A2 (en) * | 2007-06-11 | 2008-12-18 | Matrix Laboratories Ltd | An improved process for the preparation of tamsulosin hydrochloride |
| CN102898336A (en) * | 2012-10-16 | 2013-01-30 | 北京悦康科创医药科技有限公司 | Preparation method of tamsulosin hydrochloride |
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