CA2493244A1 - A method of preparing enantiomers of indole-2,3-dione-3-oxime derivatives - Google Patents
A method of preparing enantiomers of indole-2,3-dione-3-oxime derivatives Download PDFInfo
- Publication number
- CA2493244A1 CA2493244A1 CA002493244A CA2493244A CA2493244A1 CA 2493244 A1 CA2493244 A1 CA 2493244A1 CA 002493244 A CA002493244 A CA 002493244A CA 2493244 A CA2493244 A CA 2493244A CA 2493244 A1 CA2493244 A1 CA 2493244A1
- Authority
- CA
- Canada
- Prior art keywords
- butyrolactone
- gamma
- alpha
- enantiopure
- isoquinolin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 49
- LNMAXZZQNSPQSR-UHFFFAOYSA-N 3-(hydroxyamino)indol-2-one Chemical class C1=CC=CC2=NC(=O)C(NO)=C21 LNMAXZZQNSPQSR-UHFFFAOYSA-N 0.000 title claims abstract description 20
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 title abstract description 10
- 239000000203 mixture Substances 0.000 claims description 13
- 150000001875 compounds Chemical class 0.000 claims description 12
- 239000007795 chemical reaction product Substances 0.000 claims description 11
- GIIQUGGTGRRQEN-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinolin-8-amine Chemical compound C1CNCC2=C1C=CC=C2N GIIQUGGTGRRQEN-UHFFFAOYSA-N 0.000 claims description 10
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 9
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 claims description 8
- 230000002255 enzymatic effect Effects 0.000 claims description 7
- BUQTYVUSGLJSKS-UHFFFAOYSA-N tert-butyl n-hydroxy-n-[(2-methylpropan-2-yl)oxycarbonyl]carbamate Chemical compound CC(C)(C)OC(=O)N(O)C(=O)OC(C)(C)C BUQTYVUSGLJSKS-UHFFFAOYSA-N 0.000 claims description 7
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical class C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 claims description 6
- 238000011084 recovery Methods 0.000 claims description 6
- 239000007858 starting material Substances 0.000 claims description 6
- XHVFZTFICFJHJR-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonyl]-n-phenylmethoxycarbamate Chemical compound CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)OCC1=CC=CC=C1 XHVFZTFICFJHJR-UHFFFAOYSA-N 0.000 claims description 6
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical class CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 claims description 5
- 229940126062 Compound A Drugs 0.000 claims description 5
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 5
- 238000006640 acetylation reaction Methods 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- GKFUMDRWFRXOPA-UHFFFAOYSA-N n,n-dimethyl-4-(8-methyl-2,3-dioxo-1,6,7,9-tetrahydropyrrolo[3,2-h]isoquinolin-5-yl)benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N(C)C)=CC=C1C(C=1CCN(C)CC=11)=CC2=C1NC(=O)C2=O GKFUMDRWFRXOPA-UHFFFAOYSA-N 0.000 claims description 5
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 claims description 4
- 229960002327 chloral hydrate Drugs 0.000 claims description 4
- 238000005984 hydrogenation reaction Methods 0.000 claims description 4
- CFJRSKULEDUDKL-FQEVSTJZSA-N (2s)-2-[[5-[4-(dimethylsulfamoyl)phenyl]-8-methyl-2-oxo-7,9-dihydro-6h-pyrrolo[3,2-h]isoquinolin-3-yl]amino]oxy-4-hydroxybutanoic acid Chemical compound C1=CC(S(=O)(=O)N(C)C)=CC=C1C1=CC2=C(NO[C@@H](CCO)C(O)=O)C(=O)N=C2C2=C1CCN(C)C2 CFJRSKULEDUDKL-FQEVSTJZSA-N 0.000 claims description 3
- JWKBIWVJEDVHFE-UHFFFAOYSA-N 2-hydroxyimino-n-(1,2,3,4-tetrahydroisoquinolin-8-yl)acetamide Chemical compound C1CNCC2=C1C=CC=C2NC(=O)C=NO JWKBIWVJEDVHFE-UHFFFAOYSA-N 0.000 claims description 3
- ABWVHMGKBDSGFT-UHFFFAOYSA-N 6,7,8,9-tetrahydro-1h-pyrrolo[3,2-h]isoquinoline-2,3-dione Chemical compound C1CNCC2=C1C=CC1=C2NC(=O)C1=O ABWVHMGKBDSGFT-UHFFFAOYSA-N 0.000 claims description 3
- 102000004190 Enzymes Human genes 0.000 claims description 3
- 108090000790 Enzymes Proteins 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 3
- 230000000397 acetylating effect Effects 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- 238000005342 ion exchange Methods 0.000 claims description 3
- 230000002366 lipolytic effect Effects 0.000 claims description 3
- XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000001117 sulphuric acid Substances 0.000 claims description 3
- 235000011149 sulphuric acid Nutrition 0.000 claims description 3
- UJRFQKXRABWQKT-NSHDSACASA-N (2s)-4-hydroxy-2-[(2-oxo-6,7,8,9-tetrahydropyrrolo[3,2-h]isoquinolin-3-yl)amino]oxybutanoic acid Chemical compound C1CNCC2=C1C=CC1=C2NC(=O)C1=NO[C@@H](CCO)C(O)=O UJRFQKXRABWQKT-NSHDSACASA-N 0.000 claims description 2
- SFVFCARLPJZFLQ-UHFFFAOYSA-N 4-(8-amino-2-methyl-3,4-dihydro-1h-isoquinolin-5-yl)-n,n-dimethylbenzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N(C)C)=CC=C1C1=CC=C(N)C2=C1CCN(C)C2 SFVFCARLPJZFLQ-UHFFFAOYSA-N 0.000 claims description 2
- FUUZAPBTVAFEGN-UHFFFAOYSA-N n-[5-[4-(dimethylsulfamoyl)phenyl]-2-methyl-3,4-dihydro-1h-isoquinolin-8-yl]-2-hydroxyiminoacetamide Chemical compound C1=CC(S(=O)(=O)N(C)C)=CC=C1C1=CC=C(NC(=O)C=NO)C2=C1CCN(C)C2 FUUZAPBTVAFEGN-UHFFFAOYSA-N 0.000 claims description 2
- FWIBCWKHNZBDLS-GSVOUGTGSA-N (3r)-3-hydroxyoxolan-2-one Chemical compound O[C@@H]1CCOC1=O FWIBCWKHNZBDLS-GSVOUGTGSA-N 0.000 claims 2
- FWIBCWKHNZBDLS-VKHMYHEASA-N (3s)-3-hydroxyoxolan-2-one Chemical compound O[C@H]1CCOC1=O FWIBCWKHNZBDLS-VKHMYHEASA-N 0.000 claims 2
- FWIBCWKHNZBDLS-UHFFFAOYSA-N 3-hydroxyoxolan-2-one Chemical compound OC1CCOC1=O FWIBCWKHNZBDLS-UHFFFAOYSA-N 0.000 claims 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 claims 2
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 76
- 229930188620 butyrolactone Natural products 0.000 description 38
- 239000011541 reaction mixture Substances 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 17
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- 239000002244 precipitate Substances 0.000 description 14
- 229910052739 hydrogen Inorganic materials 0.000 description 13
- 239000001257 hydrogen Substances 0.000 description 13
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- 125000000217 alkyl group Chemical group 0.000 description 11
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical class C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 6
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 239000008363 phosphate buffer Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- UFNDNNCDEFJCHU-RMKNXTFCSA-N (2e)-2-hydroxyimino-n-phenylacetamide Chemical compound O\N=C\C(=O)NC1=CC=CC=C1 UFNDNNCDEFJCHU-RMKNXTFCSA-N 0.000 description 3
- XXIJFHJUUXTXIX-UHFFFAOYSA-N 3-nitroso-1H-indol-2-ol Chemical compound Oc1[nH]c2ccccc2c1N=O XXIJFHJUUXTXIX-UHFFFAOYSA-N 0.000 description 3
- 239000004367 Lipase Substances 0.000 description 3
- 102000004882 Lipase Human genes 0.000 description 3
- 108090001060 Lipase Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- -1 hydroxy lactones Chemical class 0.000 description 3
- 235000019421 lipase Nutrition 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 239000011343 solid material Substances 0.000 description 3
- DRDVJQOGFWAVLH-UHFFFAOYSA-N tert-butyl n-hydroxycarbamate Chemical compound CC(C)(C)OC(=O)NO DRDVJQOGFWAVLH-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QKCPMZKDZBRKDB-UHFFFAOYSA-N 4-[3-(hydroxyamino)-8-methyl-2-oxo-7,9-dihydro-6h-pyrrolo[3,2-h]isoquinolin-5-yl]-n,n-dimethylbenzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N(C)C)=CC=C1C(C=1CCN(C)CC=11)=CC2=C1NC(=O)C2=NO QKCPMZKDZBRKDB-UHFFFAOYSA-N 0.000 description 2
- 229940006015 4-hydroxybutyric acid Drugs 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 208000033962 Fontaine progeroid syndrome Diseases 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 229920001429 chelating resin Polymers 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000013058 crude material Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000009509 drug development Methods 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical group 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 150000002596 lactones Chemical group 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000001226 reprecipitation Methods 0.000 description 2
- MZNBNPWFHGWAGH-UHFFFAOYSA-N tert-butyl n-phenylmethoxycarbamate Chemical compound CC(C)(C)OC(=O)NOCC1=CC=CC=C1 MZNBNPWFHGWAGH-UHFFFAOYSA-N 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- CFJRSKULEDUDKL-UHFFFAOYSA-N 2-[[5-[4-(dimethylsulfamoyl)phenyl]-8-methyl-2-oxo-7,9-dihydro-6h-pyrrolo[3,2-h]isoquinolin-3-yl]amino]oxy-4-hydroxybutanoic acid Chemical class C1=CC(S(=O)(=O)N(C)C)=CC=C1C1=CC2=C(NOC(CCO)C(O)=O)C(=O)N=C2C2=C1CCN(C)C2 CFJRSKULEDUDKL-UHFFFAOYSA-N 0.000 description 1
- NXZLTPQEYLXQCH-UHFFFAOYSA-N 2-hydroxyiminoacetamide Chemical compound NC(=O)C=NO NXZLTPQEYLXQCH-UHFFFAOYSA-N 0.000 description 1
- ASNHGEVAWNWCRQ-UHFFFAOYSA-N 4-(hydroxymethyl)oxolane-2,3,4-triol Chemical compound OCC1(O)COC(O)C1O ASNHGEVAWNWCRQ-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 1
- 239000012223 aqueous fraction Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003257 excitatory amino acid Substances 0.000 description 1
- 230000002461 excitatory amino acid Effects 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002431 hydrogen Chemical group 0.000 description 1
- RBLWMQWAHONKNC-UHFFFAOYSA-N hydroxyazanium Chemical compound O[NH3+] RBLWMQWAHONKNC-UHFFFAOYSA-N 0.000 description 1
- WCYJQVALWQMJGE-UHFFFAOYSA-M hydroxylammonium chloride Chemical compound [Cl-].O[NH3+] WCYJQVALWQMJGE-UHFFFAOYSA-M 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- BVSPJPNNLDIUFE-UHFFFAOYSA-N n,n-dimethylbenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=CC=C1 BVSPJPNNLDIUFE-UHFFFAOYSA-N 0.000 description 1
- HYDZPXNVHXJHBG-UHFFFAOYSA-N o-benzylhydroxylamine;hydron;chloride Chemical compound Cl.NOCC1=CC=CC=C1 HYDZPXNVHXJHBG-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- KVCGISUBCHHTDD-UHFFFAOYSA-M sodium;4-methylbenzenesulfonate Chemical compound [Na+].CC1=CC=C(S([O-])(=O)=O)C=C1 KVCGISUBCHHTDD-UHFFFAOYSA-M 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 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 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/02—Oxygen as only ring hetero atoms
- C12P17/04—Oxygen as only ring hetero atoms containing a five-membered hetero ring, e.g. griseofulvin, vitamin C
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
- C12P41/003—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions
- C12P41/004—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions by esterification of alcohol- or thiol groups in the enantiomers or the inverse reaction
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Analytical Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA200201237 | 2002-08-22 | ||
| DKPA200201237 | 2002-08-22 | ||
| PCT/DK2003/000539 WO2004018466A2 (en) | 2002-08-22 | 2003-08-13 | A method of preparing enantiomers of indole-2,3-dione-3-oxime derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2493244A1 true CA2493244A1 (en) | 2004-03-04 |
Family
ID=31896777
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002493244A Abandoned CA2493244A1 (en) | 2002-08-22 | 2003-08-13 | A method of preparing enantiomers of indole-2,3-dione-3-oxime derivatives |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US7632948B2 (https=) |
| EP (1) | EP1532146B1 (https=) |
| JP (1) | JP2006503011A (https=) |
| CN (1) | CN1296372C (https=) |
| AT (1) | ATE318815T1 (https=) |
| AU (1) | AU2003250323A1 (https=) |
| CA (1) | CA2493244A1 (https=) |
| DE (1) | DE60303825T2 (https=) |
| DK (1) | DK1532146T3 (https=) |
| MX (1) | MXPA05002056A (https=) |
| NZ (1) | NZ537810A (https=) |
| WO (1) | WO2004018466A2 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008144931A1 (en) * | 2007-05-30 | 2008-12-04 | Painceptor Pharma Corporation | Compositions and methods for modulating gated ion channels |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1183025T3 (da) | 1999-05-19 | 2009-05-04 | Painceptor Pharma Corp | Hæmmere af proton-styrede kationskanaler og deres anvendelse til behandling af iskæmiske lidelser |
| GT200600180A (es) * | 2005-04-29 | 2006-11-22 | Proceso para preparar isatinas con control de formacion de subproductos | |
| WO2007059608A1 (en) | 2005-11-23 | 2007-05-31 | Painceptor Pharma Corporation | Compositions and methods for modulating gated ion channels |
| CA2652307A1 (en) * | 2006-04-10 | 2007-10-18 | Painceptor Pharma Corporation | Compositions and methods for modulating gated ion channels |
| AU2016359230B2 (en) | 2015-11-25 | 2020-04-23 | Ligachem Biosciences Inc. | Conjugates comprising self-immolative groups and methods related thereto |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2542941B2 (ja) * | 1990-02-02 | 1996-10-09 | チッソ株式会社 | 光学活性ヒドロキシラクトン類の製造方法 |
| JP2939646B2 (ja) * | 1990-07-17 | 1999-08-25 | チッソ株式会社 | ４―置換―２―ヒドロキシブタン酸エステルおよび製造法 |
| JP3789951B2 (ja) * | 1993-11-25 | 2006-06-28 | 三共アグロ株式会社 | Ｏ−ｎ結合を有する糖誘導体及び製造方法 |
| UA54403C2 (uk) * | 1996-10-01 | 2003-03-17 | Н'Юросерч А/С | Похідні індол-2,3-діон-3-оксиму, фармацевтична композиція, спосіб лікування розладу чи захворювання ссавців, у тому числі людини та спосіб одержання похідних індол-2,3-діон-3-оксиму |
| EP1066037B1 (en) * | 1998-03-31 | 2004-12-29 | Neurosearch A/S | Use of indole-2,3-dione-3-oxime derivatives as ampa antagonists |
| WO2001018231A2 (de) * | 1999-09-08 | 2001-03-15 | Lonza Ag | VERFAHREN ZUR HERSTELLUNG VON (R)- ODER (S)-HYDROXY-η-BUTYROLACTON |
-
2003
- 2003-08-13 DE DE60303825T patent/DE60303825T2/de not_active Expired - Lifetime
- 2003-08-13 DK DK03792147T patent/DK1532146T3/da active
- 2003-08-13 AT AT03792147T patent/ATE318815T1/de not_active IP Right Cessation
- 2003-08-13 JP JP2004529729A patent/JP2006503011A/ja active Pending
- 2003-08-13 AU AU2003250323A patent/AU2003250323A1/en not_active Abandoned
- 2003-08-13 NZ NZ537810A patent/NZ537810A/en unknown
- 2003-08-13 CA CA002493244A patent/CA2493244A1/en not_active Abandoned
- 2003-08-13 WO PCT/DK2003/000539 patent/WO2004018466A2/en not_active Ceased
- 2003-08-13 MX MXPA05002056A patent/MXPA05002056A/es active IP Right Grant
- 2003-08-13 EP EP03792147A patent/EP1532146B1/en not_active Expired - Lifetime
- 2003-08-13 CN CNB03818396XA patent/CN1296372C/zh not_active Expired - Fee Related
- 2003-08-13 US US10/524,441 patent/US7632948B2/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008144931A1 (en) * | 2007-05-30 | 2008-12-04 | Painceptor Pharma Corporation | Compositions and methods for modulating gated ion channels |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2006503011A (ja) | 2006-01-26 |
| DK1532146T3 (da) | 2006-07-03 |
| US20060178391A1 (en) | 2006-08-10 |
| EP1532146A2 (en) | 2005-05-25 |
| ATE318815T1 (de) | 2006-03-15 |
| US7632948B2 (en) | 2009-12-15 |
| CN1671704A (zh) | 2005-09-21 |
| MXPA05002056A (es) | 2005-06-08 |
| NZ537810A (en) | 2006-10-27 |
| CN1296372C (zh) | 2007-01-24 |
| DE60303825D1 (de) | 2006-04-27 |
| DE60303825T2 (de) | 2006-08-17 |
| WO2004018466A3 (en) | 2004-03-25 |
| EP1532146B1 (en) | 2006-03-01 |
| WO2004018466A2 (en) | 2004-03-04 |
| AU2003250323A1 (en) | 2004-03-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1546149B1 (en) | Modified pictet-spengler reaction and products prepared therefrom | |
| AU2020365314A1 (en) | Process for producing acyloxymethyl esters of (4S)-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridin-3-carboxylic acid | |
| AU2009204476A1 (en) | Method of synthesizing tetrahydrobiopterin | |
| ITMI20090332A1 (it) | Sintesi di (4as, 7as)-ottaidro-1h-pirrolo[3,4-b]piridina | |
| CA2493244A1 (en) | A method of preparing enantiomers of indole-2,3-dione-3-oxime derivatives | |
| JP2003502325A (ja) | シス−８−ベンジル−７、９−ジオキソ−２、８−ジアザビシクロ［４．３．０］ノナン対掌体の分離法 | |
| AU730064B2 (en) | Enzymatic resolution of benzodiazepine-acetic acids from esters with a lipase | |
| US8471016B2 (en) | Process for the preparation of chiral beta amino carboxamide derivatives | |
| RU2049778C1 (ru) | Способ получения производного 8-хлорхинолона | |
| US5587481A (en) | Preparation of (S)-decahydroisoquinoline-3-carboxylic acid t-butylamide | |
| JP2006503011A5 (https=) | ||
| PL188634B1 (pl) | Sposób wytwarzania potasowej soli kwasu klawulanowego | |
| US6861525B2 (en) | Process for the preparation imidazo[1,2-A]pyridine-3-acetamides | |
| US5723667A (en) | Method of producing optically active tert-leucinol and its use | |
| US20080234508A1 (en) | Process for the Preparation of N(5)-Ethylglutamine | |
| JPH09124595A (ja) | 光学分割剤およびそれを用いた光学活性３−アミノピロリジン誘導体の製造法 | |
| JPH05279326A (ja) | 光学活性３−ヒドロキシピロリジンの製法 | |
| EP0320898A2 (en) | Processes and compounds useful for resolving 1-methyl-3-phenylpropylamine | |
| JP2001514901A (ja) | シス−およびトランス−ピロロピペリジンの生化学的ラセミ分割法 | |
| WO2010019469A2 (en) | Preparation of (s)-2-aminobutyric acid | |
| JPH08322591A (ja) | 光学分割により光学的に純粋な１，２，３，４−テトラヒドロキノリン−２−酢酸エステル類を得る方法 | |
| US20020193591A1 (en) | Process for producing 5-amino-8-alkylquinolonecarboxylic acid derivative and intermediates in the production thereof | |
| CA2488324A1 (en) | Optical resolution of n-acetyl-indoline-2-carboxylic acid with phenylglycinol | |
| US6495694B2 (en) | Efficient separation of enantiomers of piperidone derivatives by precipitation of the desired eantiomer during in situ racemization of the unwanted enantiomer | |
| JPH07103099B2 (ja) | 光学活性３−ヒドロキシピロリジンの製法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued | ||
| FZDE | Discontinued |
Effective date: 20100813 |