WO1998038180A1 - Process for the preparation of benzothiazolone compounds - Google Patents
Process for the preparation of benzothiazolone compounds Download PDFInfo
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- WO1998038180A1 WO1998038180A1 PCT/SE1998/000274 SE9800274W WO9838180A1 WO 1998038180 A1 WO1998038180 A1 WO 1998038180A1 SE 9800274 W SE9800274 W SE 9800274W WO 9838180 A1 WO9838180 A1 WO 9838180A1
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- formula
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- 238000000034 method Methods 0.000 title claims abstract description 21
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- BXQNSPXDWSNUKE-UHFFFAOYSA-N 1,3-benzothiazole 1-oxide Chemical class C1=CC=C2S(=O)C=NC2=C1 BXQNSPXDWSNUKE-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 45
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 21
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 7
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 6
- -1 2-aminobenzothiazole compound Chemical class 0.000 claims description 5
- 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 5
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 4
- 230000002140 halogenating effect Effects 0.000 claims description 4
- BSQLQMLFTHJVKS-UHFFFAOYSA-N 2-chloro-1,3-benzothiazole Chemical compound C1=CC=C2SC(Cl)=NC2=C1 BSQLQMLFTHJVKS-UHFFFAOYSA-N 0.000 claims description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 3
- 239000012346 acetyl chloride Substances 0.000 claims description 3
- MMCPOSDMTGQNKG-UHFFFAOYSA-N anilinium chloride Chemical compound Cl.NC1=CC=CC=C1 MMCPOSDMTGQNKG-UHFFFAOYSA-N 0.000 claims description 3
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- CPEKAXYCDKETEN-UHFFFAOYSA-N benzoyl isothiocyanate Chemical compound S=C=NC(=O)C1=CC=CC=C1 CPEKAXYCDKETEN-UHFFFAOYSA-N 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- QXDAKFBVTWGQHQ-UHFFFAOYSA-N 2-nitroacetamide Chemical compound NC(=O)C[N+]([O-])=O QXDAKFBVTWGQHQ-UHFFFAOYSA-N 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- 230000000802 nitrating effect Effects 0.000 claims description 2
- 239000007800 oxidant agent Substances 0.000 claims description 2
- 239000000543 intermediate Substances 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- 239000007787 solid Substances 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 4
- 229960004592 isopropanol Drugs 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- LTPVSOCPYWDIFU-UHFFFAOYSA-N 4-methoxyphenylethylamine Chemical compound COC1=CC=C(CCN)C=C1 LTPVSOCPYWDIFU-UHFFFAOYSA-N 0.000 description 3
- 0 COc(ccc(CC*)c1)c1[N+]([O-])=O Chemical compound COc(ccc(CC*)c1)c1[N+]([O-])=O 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- UHGULLIUJBCTEF-UHFFFAOYSA-N 2-aminobenzothiazole Chemical compound C1=CC=C2SC(N)=NC2=C1 UHGULLIUJBCTEF-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- ZFMBBERGVABIIK-UHFFFAOYSA-N 4-(4-methoxy-3-nitrophenyl)butanamide Chemical compound COC1=CC=C(CCCC(N)=O)C=C1[N+]([O-])=O ZFMBBERGVABIIK-UHFFFAOYSA-N 0.000 description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 2
- 229910021592 Copper(II) chloride Inorganic materials 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 229940043265 methyl isobutyl ketone Drugs 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- JEYVGOXHPJRQET-UHFFFAOYSA-N 2-(1-oxo-1,3-benzothiazol-7-yl)ethanamine Chemical class NCCC1=CC=CC2=C1S(=O)C=N2 JEYVGOXHPJRQET-UHFFFAOYSA-N 0.000 description 1
- VBHLGXLPPGNNIE-UHFFFAOYSA-N 4-(4-methoxyphenyl)butanamide Chemical compound COC1=CC=C(CCCC(N)=O)C=C1 VBHLGXLPPGNNIE-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- SOIFLUNRINLCBN-UHFFFAOYSA-N ammonium thiocyanate Chemical compound [NH4+].[S-]C#N SOIFLUNRINLCBN-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- DQMWMUMCNOJLSI-UHFFFAOYSA-N n-carbamothioylbenzamide Chemical compound NC(=S)NC(=O)C1=CC=CC=C1 DQMWMUMCNOJLSI-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/16—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
- C07C233/17—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/18—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/34—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups
- C07C233/35—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/36—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C335/04—Derivatives of thiourea
- C07C335/16—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C335/20—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C335/04—Derivatives of thiourea
- C07C335/24—Derivatives of thiourea containing any of the groups, X being a hetero atom, Y being any atom
- C07C335/26—Y being a hydrogen or a carbon atom, e.g. benzoylthioureas
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D277/82—Nitrogen atoms
Definitions
- the present invention relates to a process for the preparation of benzothiazolone compounds and to novel intermediates in the process of the invention.
- Benzothiazolone compounds are known.
- WO 93/24473 describes 7-(2- aminoethyl)-benzothiazolone compounds of general formula
- X and Y independently represent -S(O) n - or -O-, n represents 0, 1 or 2, p, q and r independently represent 2 or 3,
- Z represents phenyl optionally substituted by halogen, -OR , NO2 or NR R ; or a 5- or
- R , R and R independently represent hydrogen or 1 and pharmaceutically acceptable derivatives thereof.
- the compounds of WO 93/24473 may be prepared by any of several methods, for example by alkylation of the benzothiazolone compound of formula I
- the present invention relates in particular to a novel process for the synthesis of compound I.
- the compound of formula II is novel and may be prepared by halogenating the 2- aminobenzothiazole compound of formula III, for example using copper (II) chloride and copper (I) chloride and optionally ethanol, in HC1, e.g., 20% HC1 to which is added sodium nitrite:
- the compound of formula III is novel and may be prepared from a thiourea of formula IV,
- a halogenating/oxidising agent for example N-bromosuccinimide, bromine or N- chlorosuccinimide in an acidic solvent, e.g., a mixed acid solvent e.g. MeSO 3 H/AcOH.
- the compound of formula IV is novel and may be prepared by hydrolysis of a compound of formula V
- NHCOPh for example in water using a base such as K 2 CO 3 or an alkali metal hydroxide, e.g. NaOH or KOH.
- a base such as K 2 CO 3 or an alkali metal hydroxide, e.g. NaOH or KOH.
- the compound of formula V is novel and may be prepared by reacting an aniline hydrochloride of formula VI
- benzoylisothiocyanate for example in acetone or methylisobutylketone (MIBK).
- the compound of formula VI is novel and may be prepared by hydrogenating a nitroacetamide of formula VII and treating with HC1
- the compound of formula VII is novel and may be prepared by nitrating an acetamide of formula VIII
- the compound of formula VIII may be prepared from a compound of formula IX:
- the present invention provides a process for the preparation of compounds of formula I, comprising (i) converting a compound of formula IX into a compound of formula VIII, for example using acetic anhydride or acetyl chloride, either as solvent and reagent, or in the presence of dichloromethane and triethylamine, and (ii) converting the compound of formula VIII into the compound of formula I, for example by the stepwise preparation of compounds VII, VI, V, IV, III and II as described above.
- the process of the present invention provides an easy process for the preparation of compound II, without the need to use undesirable starting materials, and giving the product compound in good yield.
- the present invention also provides the novel compounds of formulae II, III, IV, V, VI and VII.
- the reaction mixture was poured into iced water (2.7L) forming a precipitate/ suspension.
- the product oiled out on stirring at room temperature.
- the mixture was extracted with dichloromethane (2xlL).
- a sample of the extract was washed with NaHCO3 dried and concentrated for analysis.
- the extract was washed with saturated Na2CO3 solution (2xlL), causing the extract to become saturated with water.
- the extract was diluted slightly with dichloromethane ( ⁇ 100 ml), then dried over anhydrous MgSO_ ⁇ , filtered and concentrated, in vacuo.
- Ammonium thiocyanate (12.35 g) was dissolved in acetone (AR grade, 120 ml) and benzoylchloride (17.3 ml) was added drop wise with stirring over 2 mins. The temperature rose from 22° C to 38° C over the addition and a white precipitate formed. The reaction was stirred at room temperature for a further 75 mins and then filtered, and washed with acetone (20 ml) to give a solution of benzoylisothiocyanate. This was added dropwise with stirring to the amine solution, over 40 mins. The temperature rose from 23° C to 36° C during the addition. A thick cream precipitate formed. The reaction was allowed to stir at room temperature for 16 hours and then the product was collected by filtration, washed with water (30 ml), sucked dry and then dried in vacuo at 60° C.
- the mixture was cooled to room temperature with the aid of a cold water bath and then acidified to pH 7-8 using hydrochloric acid ( ⁇ 4N, 80 ml).
- the mixture was cooled further in an ice bath - internal temp to 5° C, stirred cold for 15 mins and the product collected by filtration, washed with water (50 ml) and sucked dry. Dried in vacuo at 50° C.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
Description
Claims
Priority Applications (18)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP98908361A EP0970064A1 (en) | 1997-02-27 | 1998-02-17 | Process for the preparation of benzothiazolone compounds |
JP53756798A JP2001513770A (en) | 1997-02-27 | 1998-02-17 | Method for producing benzothiazolone compound |
SK1114-99A SK111499A3 (en) | 1997-02-27 | 1998-02-17 | Process for the preparation of benzothiazolone compounds |
NZ336877A NZ336877A (en) | 1997-02-27 | 1998-02-17 | Process for the preparation of benzothiazolone compounds |
IL13112198A IL131121A0 (en) | 1997-02-27 | 1998-02-17 | Process for the preparation of benzothiazolone compounds |
CA002280010A CA2280010A1 (en) | 1997-02-27 | 1998-02-17 | Process for the preparation of benzothiazolone compounds |
EEP199900373A EE9900373A (en) | 1997-02-27 | 1998-02-17 | Process for the preparation of benzothiazolone compounds |
AU66407/98A AU724616B2 (en) | 1997-02-27 | 1998-02-17 | Process for the preparation of benzothiazolone compounds |
HU0000766A HUP0000766A3 (en) | 1997-02-27 | 1998-02-17 | Process for the preparation of benzothiazolone derivatives |
PL98334901A PL334901A1 (en) | 1997-02-27 | 1998-02-17 | Method of obtaining benzothiazolones |
BR9807785-6A BR9807785A (en) | 1997-02-27 | 1998-02-17 | Process for the preparation of the compound, e, compound |
US09/029,831 US6087508A (en) | 1997-02-27 | 1998-02-17 | Process for the preparation of benzothiazolone compounds |
IS5162A IS5162A (en) | 1997-02-27 | 1999-08-23 | Process for producing compounds from benzothiazolone |
NO994131A NO994131L (en) | 1997-02-27 | 1999-08-26 | Procedure for the preparation of benzothiazolone compounds |
US09/410,066 US6194614B1 (en) | 1997-02-27 | 1999-10-01 | Process for the preparation of benzothiazolone compounds |
US09/410,042 US6124468A (en) | 1997-02-27 | 1999-10-01 | Process for the preparation of benzothiazolone compounds |
US09/411,162 US6147219A (en) | 1997-02-27 | 1999-10-01 | Process for the preparation of benzothiazolone compounds |
US09/410,069 US6114578A (en) | 1997-02-27 | 1999-10-01 | Process for the preparation of benzothiazolone compounds |
Applications Claiming Priority (2)
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SE9700706A SE9700706D0 (en) | 1997-02-27 | 1997-02-27 | Process for the preparation of benzothiazoline compounds |
SE9700706-6 | 1997-02-27 |
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US09/029,831 Continuation US6087508A (en) | 1997-02-27 | 1998-02-17 | Process for the preparation of benzothiazolone compounds |
US09/410,068 Division US6232498B1 (en) | 1998-01-30 | 1999-10-01 | Process for the preparation of benzothiazolone compounds |
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PCT/SE1998/000274 WO1998038180A1 (en) | 1997-02-27 | 1998-02-17 | Process for the preparation of benzothiazolone compounds |
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US (6) | US6087508A (en) |
EP (1) | EP0970064A1 (en) |
JP (1) | JP2001513770A (en) |
KR (1) | KR20000075720A (en) |
CN (1) | CN1083447C (en) |
AU (1) | AU724616B2 (en) |
BR (1) | BR9807785A (en) |
CA (1) | CA2280010A1 (en) |
EE (1) | EE9900373A (en) |
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IS (1) | IS5162A (en) |
NO (1) | NO994131L (en) |
NZ (1) | NZ336877A (en) |
PL (1) | PL334901A1 (en) |
SE (1) | SE9700706D0 (en) |
SK (1) | SK111499A3 (en) |
TR (1) | TR199902057T2 (en) |
WO (1) | WO1998038180A1 (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7700782B2 (en) | 2006-12-20 | 2010-04-20 | Astrazeneca Ab | Compounds 569 |
US7709511B2 (en) | 2005-08-09 | 2010-05-04 | Astrazeneca Ab | Benzothiazolone derivatives |
US7951954B2 (en) | 2006-03-14 | 2011-05-31 | Astrazeneca Ab | Bezothiazol derivatives as Beta2 adrenoreceptor agonists |
US8017602B2 (en) | 2008-06-18 | 2011-09-13 | Astrazeneca Ab | N-(2-(2-(5-hydroxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethylamino)ethyl)-3-(phenethoxy)propanamide derivatives, processes for their preparation, pharmaceutical compositions containing them and their use in therapy |
US8058294B2 (en) | 2007-02-08 | 2011-11-15 | Astrazeneca Ab | Pharmaceutical salts of N-[2-(diethylamino)ethyl]-N-(2-{[2-(4-hydroxy-2-oxo-2,3-dihydro-1,3-benzothiazol-7-yl)ethyl]amino}ethyl)-3-[2-(1-napthyl)ethoxy]propanamide |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7158870B2 (en) * | 2002-01-24 | 2007-01-02 | Ford Global Technologies, Llc | Post collision restraints control module |
US7270805B1 (en) * | 2006-03-30 | 2007-09-18 | Conopco, Inc. | Skin lightening agents, compositions and methods |
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- 1998-02-17 NZ NZ336877A patent/NZ336877A/en unknown
- 1998-02-17 IL IL13112198A patent/IL131121A0/en unknown
- 1998-02-17 ID IDW990871A patent/ID22430A/en unknown
- 1998-02-17 PL PL98334901A patent/PL334901A1/en unknown
- 1998-02-17 AU AU66407/98A patent/AU724616B2/en not_active Ceased
- 1998-02-17 CN CN98802761A patent/CN1083447C/en not_active Expired - Fee Related
- 1998-02-17 SK SK1114-99A patent/SK111499A3/en unknown
- 1998-02-17 US US09/029,831 patent/US6087508A/en not_active Expired - Fee Related
- 1998-02-17 BR BR9807785-6A patent/BR9807785A/en not_active IP Right Cessation
- 1998-02-17 KR KR1019997007789A patent/KR20000075720A/en not_active Application Discontinuation
- 1998-02-17 EE EEP199900373A patent/EE9900373A/en unknown
- 1998-02-17 TR TR1999/02057T patent/TR199902057T2/en unknown
- 1998-02-17 CA CA002280010A patent/CA2280010A1/en not_active Abandoned
- 1998-02-17 EP EP98908361A patent/EP0970064A1/en not_active Withdrawn
- 1998-02-17 HU HU0000766A patent/HUP0000766A3/en unknown
- 1998-02-17 WO PCT/SE1998/000274 patent/WO1998038180A1/en not_active Application Discontinuation
- 1998-02-17 JP JP53756798A patent/JP2001513770A/en active Pending
-
1999
- 1999-08-23 IS IS5162A patent/IS5162A/en unknown
- 1999-08-26 NO NO994131A patent/NO994131L/en not_active Application Discontinuation
- 1999-10-01 US US09/410,069 patent/US6114578A/en not_active Expired - Fee Related
- 1999-10-01 US US09/410,066 patent/US6194614B1/en not_active Expired - Fee Related
- 1999-10-01 US US09/410,042 patent/US6124468A/en not_active Expired - Fee Related
- 1999-10-01 US US09/410,067 patent/US6118024A/en not_active Expired - Fee Related
- 1999-10-01 US US09/411,162 patent/US6147219A/en not_active Expired - Fee Related
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7709511B2 (en) | 2005-08-09 | 2010-05-04 | Astrazeneca Ab | Benzothiazolone derivatives |
US7951954B2 (en) | 2006-03-14 | 2011-05-31 | Astrazeneca Ab | Bezothiazol derivatives as Beta2 adrenoreceptor agonists |
US7700782B2 (en) | 2006-12-20 | 2010-04-20 | Astrazeneca Ab | Compounds 569 |
US8058294B2 (en) | 2007-02-08 | 2011-11-15 | Astrazeneca Ab | Pharmaceutical salts of N-[2-(diethylamino)ethyl]-N-(2-{[2-(4-hydroxy-2-oxo-2,3-dihydro-1,3-benzothiazol-7-yl)ethyl]amino}ethyl)-3-[2-(1-napthyl)ethoxy]propanamide |
US8017602B2 (en) | 2008-06-18 | 2011-09-13 | Astrazeneca Ab | N-(2-(2-(5-hydroxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethylamino)ethyl)-3-(phenethoxy)propanamide derivatives, processes for their preparation, pharmaceutical compositions containing them and their use in therapy |
Also Published As
Publication number | Publication date |
---|---|
IS5162A (en) | 1999-08-23 |
IL131121A0 (en) | 2001-01-28 |
EP0970064A1 (en) | 2000-01-12 |
NO994131D0 (en) | 1999-08-26 |
AU6640798A (en) | 1998-09-18 |
KR20000075720A (en) | 2000-12-26 |
HUP0000766A2 (en) | 2000-10-28 |
CN1083447C (en) | 2002-04-24 |
US6114578A (en) | 2000-09-05 |
SE9700706D0 (en) | 1997-02-27 |
BR9807785A (en) | 2000-02-22 |
ID22430A (en) | 1999-10-14 |
CN1248252A (en) | 2000-03-22 |
HUP0000766A3 (en) | 2001-12-28 |
NO994131L (en) | 1999-08-26 |
US6118024A (en) | 2000-09-12 |
US6124468A (en) | 2000-09-26 |
EE9900373A (en) | 2000-04-17 |
US6194614B1 (en) | 2001-02-27 |
US6147219A (en) | 2000-11-14 |
CA2280010A1 (en) | 1998-09-03 |
JP2001513770A (en) | 2001-09-04 |
NZ336877A (en) | 2001-07-27 |
AU724616B2 (en) | 2000-09-28 |
SK111499A3 (en) | 2000-05-16 |
PL334901A1 (en) | 2000-03-27 |
TR199902057T2 (en) | 2000-02-21 |
US6087508A (en) | 2000-07-11 |
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